DTMH Flashcards

Question

Critical diagnostic test for RHD

Answer 1

Echocardiogram

Answer 2

Secondary prophylaxis for prevention of ARF

Answer 3

Secondary Abx prophylaxis with penicillin Trial: GOAL, NEJM No prophylaxis vs IM Pen 4 weekly Pen group had 10 times less echo progression of latent disease at 2 years

Answer 4

INVICTUS study, RCT NEJM Rivaroxaban was associated with more stroke, emboli, MI, death compared to Vit K antagonist eg warfarin (24 countries)

Answer 5

South America and Africa Aedes mosquito

Answer 6

- Taxonomic group of single-celled organisms with a nucleus (ie. Eukaryotes) that are non-photosynthetic

Answer 7

Taxonomic group of single-celled eukaryotes including Protozoa, algae and slime moulds

Answer 8

Direct * Passed directly from one infected host to another by some physical means eg faecal contamination of food or water Via intermediate host or vector * Very common amongst parasites * Sometimes just mechanical transfer, but usually one or more essential life-cycle stages take place here Definitive host: stage where the sexual stages of the life cycle take place * May or may not be the human

Answer 9

- Direct ○ Passed directly from one infected host to another by some physical means eg faecal contamination of food or water - Via intermediate host or vector ○ Very common amongst parasites ○ Sometimes just mechanical transfer, but usually one or more essential life-cycle stages take place here ○ Definitive host: stage where the sexual stages of the life cycle take place § May or may not be the human

Answer 10

Disease spread from humans to humans Eg smallpox, malaria

Answer 11

Any disease which can be transmitted to humans from animals - E.g. East African sleeping sickness - These animals form reservoir hosts, which can greatly complicate control or elimination

Answer 12

- a general, rather ill-defined term for the feeding, growing and dividing stage of a protozoan - Note that many organisms have specific names for life-cycle stages that could be described as trophozoites

Answer 13

- A microscopic, resistant form shed into the environment and responsible for transmission (e.g. Entamoeba) In the tissue, a distinct walled off cavity containing multiple organisms, often important in transmission (e.g. Trichinella, Toxoplasma). Related to general clinical usage.

Answer 14

Toxoplasma gondii Cryptosporidium Acanthamoeba species Balamuthia madrillaris

Answer 15

Pneumocystis jirovecii Encephalitozoon intestinalis - microsporidiosis

Answer 16

Giardia intestinalis Entamoeba histolytica Babesia microti

Answer 17

- Mutualism: both benefit - Neutralism: neither incur cost or benefit - Commensalism: one benefits but at no cost to the other - Parasitism: one benefits at the cost of the other ○ All pathogens now fit in here

Answer 18

Host immunocompetence Symbionts Ectopic infection Presence of other organisms Microbiome Coinfections ?theory of dysbiosis

Answer 19

Platyhelminthes (flatworms) Nematoda (round worms)

Answer 20

Trematoda - flukes Cestoida - tapeworms

Answer 21

Schistosomiasis

Answer 22

Multicellular eukaryotic animal eg parasitic helminths

Answer 23

Complex metazoan Most multicellular but some can be intracellular Many are zoonosis -> control is more difficult - Infection is by: ○ Ingestion of eggs/cysts on/in food (e.g vegetables, meat, fish etc) ○ Penetration of skin by infective larval stages (directly or via biting insect) - Larvae grow, moult, mature to adult and then produce offspring (eggs or larvae) which are voided from the host to infect new hosts

Answer 24

Parasite requires one host to complete its life cycle

Answer 25

parasite requires TWO or MORE HOSTs to complete its life cycle

Answer 26

Host harbouring the sexually mature adult worm

Answer 27

Host harbouring the larval stages

Answer 28

Level and duration of exposure ie cumulation Worm burden determines clinical disease

Answer 29

Schistosomiasis - hepatosplenomegaly + peri-portal fibrosis Hydatid cyst Filariasis - elephantiasis Onchocerciasis Hookworm -anaemia

Answer 30

Leaf-shaped flatworms - no body cavity, oral and ventral suckers for attachment and sucking nutrients, blind sac-like gut ‘Flukes’ Found in various tissues All belong to sub-class Digenea ‘digenetic trematodes’ ○ Means 2 or more generations in different hosts to complete the life cycle

Answer 31

Schistosomes (blood fluke) • Paragonimus (lung fluke) • Opistorchis/Clonorchis (liver fluke) • Fasciola (liver fluke) • Fasciolopsis (intestinal fluke)

Answer 32

Freshwater snail

Answer 33

Schistosomes - Morphologically adapted to live inside blood vessels and dioecious (separate sexes) - Below = Schistosoma spp. = blood fluke ○ Causes Schistosomiasis ○ Affects ~250mill people worldwide ○ Eggs become lodged in tissues -> immune reaction generate granulomas and fibrosis

Answer 34

Taenia saginata (beef tapeworm) • Taenia solium (pork tapeworm) (larval infection=cysticercosis) • Dihyllobothrium spp (fish tapeworm) • Echinococcus spp (dog and fox tapeworms) (larval infection=hydatid cyst)

Answer 35

Segmented ribbon-like (tape) flatworms - All species of cestodes are parasitic - Adult worms live in the small intestine of vertebrate animals (definitive host) Larval stages live in tissues of vertebrates and invertebrates (intermediate host)

Answer 36

Cysticercosis

Answer 37

Intestinal nematodes: • Hookworms • Ascaris • Trichuris • Strongyloides Tissue nematodes: • Wuchereria/Brugia (Lymphatic filariasis)

Answer 38

Most dangerous + most deaths Pre-erythrocytic stage: 5.5-7 days Incubation period of 9-14 days

Answer 39

ovale and vivax

Answer 40

Knowlesi Malaysia Macaques natural host Pre-erythrocytic 8-9 days Erythrocytic: 24 hr cycle Incubation period: 9-12 days Fastest growth of all human infecting plasmodium

Answer 41

Fever Spikes correspond to erythrocyte cycle and syncronisation of developmental stages

Answer 42

Endemicity, transmission intensity and age of patient

Answer 43

Fever that recurs every third day, ie after 48hrs Falciparum Vivax Ovale

Answer 44

Fever that recurs every fourth day, ie after 72hrs malariae

Answer 45

Erythrocytes infected with trophozoites and schizonts Sequestration intravascularly, especially in capillaries Rosetting (infected RBCs bind to uninfected RBCs) Microvascular obstruction (due to RBCs becoming less deformable)

Answer 46

P falciparum erythrocyte membrane protein 1 Mediates cytoadherence Exported to the surface of infected RBCs Interacts with molecules on endothelial cells including ICAM-1 Different subsets determine pathophysiology and clinical features

Answer 47

About 60 genes called var. Each parasite can switch on and off specific var genes -> produces functionally different protein to evade host's immune system

Answer 48

- Its partial and sterile - gradual acquisition can result in people living in endemic areas due to repeated exposure to parasites -> they lose this when they leave - Two types of immunity in parallel: anti-parasite + anti-disease - Age and exposure independently impact on development of immunity -> kids in moderate/high transmission settings develop immunity faster as transmission increases

Answer 49

Anti-parasite: ability to control parasite density Anti-disease: ability to tolerate higher parasite densities without fever

Answer 50

Insecticide treated nets

Answer 51

— COVID-related disruptions — Climate change — Humanitarian crises — Limited funding — Insecticide & artemisinin resistance — Invasion of An stephensi — Health systems challenges

Answer 52

Vaccines Longer lasting insecticides (non-pyrethroid? -> growing resistance) Vector tools to address outdoor biting Single-dose preventive therapies (monoclonal Abs) Diagnostic tools for latent P.vivax infection New drugs to mitigate ACT resistance Single-dose chemoprevention therapies

Answer 53

The defined no. of secondary cases arising from a single primary case in a fully susceptible human population

Answer 54

Total no. of potentially infectious bites that arises from all the mosquitoes biting a single perfectly infectious human on a single day

Answer 55

Stable transmission Each new case gives rise to a single further case – Total number of cases remains the same

Answer 56

Cases increase until entire population is infected

Answer 57

Cases decline until infection disappears

Answer 58

R0 = ma2pn/-r(logeP) * m = mosquito density (number of female mosquitoes per person) * a = the frequency with which each female bites a human (vs animal) * p = survival rate (probability of mosquito surviving a full day after being infected) * n = length of sporogonic (extrinsic) cycle * r = recovery rate of humans

Answer 59

Fever or hx of fever in past 24h OR palmar pallor plus 1 or more: - Unable to eat or drink or breastfeed - Vomiting everything - Multiple convulsions - Lethargy - Unconsciousness - Stiff neck - Chest indrawing or stridor

Answer 60

Fever or hx of fever in past 24h plus 1 or more: - Very weak or unable to stand - Convulsions - Lethargy - Unconsciousness - Stiff neck - Resp distress - Severe abdominal pain

Answer 61

One + of below with P falciparum asexual parasitaemia in absence of alternative cause: - Impaired conciousness - Prostration - Multiple convulsions - Acidosis - Hypoglycaemia - Severe anaemia - Renal impairment - Jaundice - Pul oedema - Significant bleeding - Shock - Hyperparasitaemia

Answer 62

At least 3 diagnostic tests over 24-48hr

Answer 63

Histidine rich protein 2 Plasmodium lactate dehydrogenase (pLDH) Both can increase through trophozoite development

Answer 64

ACT: eg artemether + lumefantrine (AL), or artesunate + amodiaquine (AS + AQ)

Answer 65

Can result from re infection or recrudescence (eg treatment failure) - ?drug resistance - Suboptimal dosing - Poor adherence or vomiting - Substandard or fake medicines Need to confirm recurrence with microscopy (not RDTs) May not be possible to distinguish recrudescence from infection in individual patients -> need PCR for genotyping Re infection very common in high risk areas

Answer 66

Within 28 days: alternative ACT After 28 days: consider as new infection and treat with first line ACT Note: do not retreat with AS+MQ (artesunate + mefloquine) -> increased risk of neuropsychiatric reactions

Answer 67

1. Malarone (atovaquone-proguanil), weight based, OD, 3 days 2. Quinine + doxycycline, Q 8hrly + doxy daily, 7 days 3. Quinine + clindamycin, Q 8hrly + clinda 8hrly, x7days

Answer 68

1st trimester: artemether-lumefantrine 2/3rd trimesters: treat with ACT

Answer 69

Hypoglycaemia

Answer 70

Primaquine Tetracyclines eg doxy

Answer 71

Primaquine (0.5mg/kg/day) for 7 days for children and adults NOT if pregnant or breastfeeding

Answer 72

Weekly chemoprophylaxis with CQ until delivery and breastfeeding are completed If then G6PD ok -> primaquine

Answer 73

Primaquine base at 0.75mg/kg bw once a week for 8 weeks (with close medical supervision)

Answer 74

CQ - treatment dose for two days then weekly suppression whilst pregnant and breast feeding Once stopped BF then check G6PD level and if ok -> for 7 days primaquine

Answer 75

Alternative standard dose -> shortened course regimen to 0.5mg/kg/day for 7 days rather than treating for 14 days Was made as shorter regimen could lead to better adherence and to fewer relapses

Answer 76

Kills mature (stage V) gametocytes

Answer 77

Single dose of primaquine + ACT (Not in pregnant/BF women, infants <6mths, or older infants with unknown G6PD status)

Answer 78

Mum: either mefloquine if no hx of MH issues and if grandmother is paternal, otherwise don't go Son: Malarone (or mefloquine) Daughter: mefloquine Grandmother: Malarone (or doxy)

Answer 79

– Sleep under an insecticide treated bednet, – Cover up between dusk and dawn – Repellants with 30-50% DEET

Answer 80

Coma/convulsions ARDS **AKI Shock/hypoglycaemia Hyperparasitaemia

Answer 81

**Coma/convulsions AKI Shock/hypoglycaemia **Severe anaemia Respiratory distress secondary to acidosis Hyperparasitaemia

Answer 82

WHO: >10% UK: >2%

Answer 83

Motor: Localises painful stimulus 2 Withdraws limb from pain 1 Non-specific or absent response 0 Verbal: Appropriate cry 2 Moan or inappropriate cry 1 None 0 Eyes: Directed/following 1 Not directed 0

Answer 84

Disease for which a high prevalent level of infection begins early in life and affects most of the child population, leading to a state of equilibrium such that the adult population shows evidence of the disease much less commonly than do children

Answer 85

Persistent, high levels of disease occurrence

Answer 86

An endemic disease with a moderate rate of infection. This term is often used to describe the prevalence of malaria in a local area, with 10 to 50% of children showing evidence of prior infection being considered a moderate level for that disease.

Answer 87

A disease that is constantly present at a low incidence or prevalence and affects a small proportion of individuals in the area. A term commonly used in malaria literature to refer to regions with low transmission.

Answer 88

Areas of low transmission: cerebral malaria Areas of high transmission: severe anaemia

Answer 89

Sequestration Microvascular obstruction Organ dysfunction

Answer 90

– Impaired consciousness (multiple factors) – Presence of retinopathy (highly suggestive) – Convulsions common (but can be sub-clinical) – Increased ICP (in > 80% of children, NL in adults) – Cerebral oedema (more common in children)

Answer 91

- Retinal whitening (macular or peripheral) - Discolouration of retinal vessels (white or orange) Non specific: - Retinal haemorrhages, especially with white centres - Papilloedema

Answer 92

Haemoglobin < 5g/L in children, < 7g/dL in adults

Answer 93

– Spleen filters both infected & damaged uninfected cells – Intravascular haemolysis – Bone marrow suppression – *Repeated malaria infection*

Answer 94

HIV, bacterial infections, hookworm, deficiency of B12 & Vitamin A

Answer 95

Kids: acidosis + pneumonia Adults: ARDS, pul oedema, pneumonia

Answer 96

non-typhi Salmonella

Answer 97

Base deficit >8mmol/L Coma Uraemia (Bun?20mg/dL) Underlying chronic illness

Answer 98

High parasite density Presence of schizonts on **peripheral** blood smear Pigment in the neutrophils

Answer 99

Both showed in African and South Asian setting artesunate>quinine for severe malaria SEQUAMAT showed even better in those with high parasite counts as brings counts down in 2 days whereas quinine takes 7

Answer 100

1. Admit 2. IV/IM artesunate for a minimum of 24hrs (2.4mg/kg at 0,12,24 hrs then 24hrly, if <20kg then 3mg/kg) 3. Stepdown to ACT 3 days 4. Consider primaquine if vivax/ovale or low transmission area for falciparum ALSO CONSIDER GIVING EMPIRICAL ABx eg CEFFTRIAXONE

Answer 101

Risk of delayed haemolysis Rapidly kills ring-stage parasites which are then taken out of red cells by the spleen These RBCs then return to circulation but with shortened life span -> haemolysis Occur often 1 week after treatment: patient with s/s anaemia and dark urine (bilirubin) Worse in patients with hyperparasitaemia and non-immune travellers

Answer 102

Need smaller volumes for IM injection In kids >5 and adults may be superior to quinine

Answer 103

Where complete treatment of severe malaria is not possible, but injections are available, adults and children should be given: ○ A single IM dose of artesunate & referred to an appropriate facility for further care ○ If IM artesunate is not available, give IM artemether or, if that is not available, IM quinine Where IM injection of artesunate is not available: ○ Children < 6 years should be treated with a single rectal dose (10mg/kg bw) of artesunate & referred immediately to an appropriate facility for further care ○ Rectal artesunate should not be used in older children and adults

Answer 104

Resolve within 6 mth: Hypotonia, ataxia, tremors, cortical blindness, aphasia Persist: Motor deficits Worsen: SAL(T) + cognitive deficits Develop: behavioural disorders, epilepsy

Answer 105

First pregnancy then reduction in risk -> can acquire Abs against CSA-binding iRBCs and resistance to placental malaria IUGR Preterm labour LBW SGA Stillbirth

Answer 106

- Sequestration in intervillous space of placenta - Cytoadherence via chondroitin sulphate A First time mothers: lack immunity to CSA-binding parasites so highly susceptible to parasitaemia and chronic infection SO important reservoir for infection

Answer 107

Women living in endemic areas develop anti-malarial immunity from lifelong exposure to falciparum parasites -> controls infection

Answer 108

Intermittent preventitive treatment of malaria during pregnancy. Given: Curative dose of an effective antimalarial drug (currently sulfadoxine-pyrimethamine) to all HIV-negative pregnant women in areas of moderate to high malaria transmission without testing whether infected or not Usually given at each antenatal visit

Answer 109

– In high transmission settings, transfuse children if Hb < 5 g/dL (Hct < 15%) – In low transmission settings, Hb < 7 g/dL (Hct < 20%)

Answer 110

increases malaria severity - Higher parasite densities (in partially immune) - Risk of severe malaria & death (in less immune) - In pregnant women, ↑adverse effects of placental malaria

Answer 111

Efavirenz increases AQ exposure & risk of toxicity Avoid artesunate and sulfadoxine if taking co-trimoxazole Avoid artesunate and amodiaquine if being treated with efavirenz or zidovudine

Answer 112

Severe anaemia Respiratory distress (especially in children) Acute renal failure

Answer 113

Defined as for falciparum but with two differences – Hyperparasitaemia = parasite density > 100,000/µL – Jaundice & parasite density > 20,000/µL Associated with high parasite densities, treat as for falciparum

Answer 114

Treat with artesunate and CQ together Repeat films after course of treatment

Answer 115

Drug resistance Insecticide resistance (pyrethroids) P falciparum lacking HRP2/3 (RDTs don't pick up parasite) Anopheles stephensi

Answer 116

Prevent infection, progression of disease especially pulmonary, prevent reinfection and reactivation Better TB vaccine for neonates/infants compared to BCG (aim to be safer in immunocompromised) + more sustainable to produce Vaccine to improve TB treatment outcomes -> prevent re-infection, increase proportion of survivors to cure, shorten and simplify drug treatment regimens (ie vaccine in addition to treatment)

Answer 117

- Infectiousness of index case - Age of child - Proximity to and duration of contact with index cases - Immune status of child - Children of families living with HIV - Other illnesses eg HIV, pertussis, malnutrition, post-measles etc

Answer 118

1. Persistent unremitting cough >2-3 weeks 2. Intermittent fever 3. Weight loss/failure to gain weight

Answer 119

Young children <5 - High risk of LN and disseminated disease - Clinical diagnosis more common Kids >15 years - Higher risk of adult type disease - Bacteriological confirmation of TB is common

Answer 120

Immaturity of immune system Less resident macrophages and existing ones more immature

Answer 121

1. 50-90% -> containment with granuloma leading to latent infection (more likely the older child is) 2. Primary progressive pulmonary disease -> disseminated disease (military TB, TB meningitis)

Answer 122

1. Immune based tests – Tuberculin Skin T est; Interferon-γ Release Assay 2. Radiology – X ray, CT scan 3. Sputum samples collection 4. Pathogen detection tests: i. Microbiological tests – culture ii. Molecular / Nucleic acid amplification test – GeneXpert, Truenat 5. Histological tests – FNAB/FNAC 6. Biomarkers – futuristic, subject of intense research

Answer 123

Delayed-type hypersensitivity reaction to PPD; heterogenous mix of mycobacterial proteins § Positive TST suggests M.tb infection or sensitization to M.tb Ag - results do NOT indicate or rule out TB disease Impacted by prior BCG vaccination (false positive), NTM exposure, HIV

Answer 124

§ Sub-optimally sensitive in children + in immunosuppression Indeterminate results common in young children

Answer 125

Hilar lymphadenopathy Pulmonary effusion Paratracheal lymphadenopathy Miliary TB Adult type disease if older eg dense alveolar consolidation, cavities

Answer 126

Spontaneous sample: older children or adolescents § Sputum induction (<7 years) § Gastric washings (<6mths) BAL § Not necessary if induction can be done Personnel need to be trained, hospital admission needed with overnight fasting

Answer 127

Childhood TB is paucobacillary: 95% of TB cases in children <12 years are smear negative Culture-positive: 4.2% (<5yo), 5% (5-9 yo) and 21% (10-14yo) Culture positivity in kids rarely exceeds 30%

Answer 128

Clinical features +/- radiology

Answer 129

Enlarged, non-tender LNs (esp cervical) Painful swelling of joint or bone, which has slowly arisen over time Angular deformity of spine Abdominal swelling - hard, painless (+/- free fluid)

Answer 130

1) TB in children mimics other common childhood diseases 2) Childhood TB is paucibacillary in nature 3) CXR changes often non-specific; inter-reader variability 4) TST / IGRA of limited value in TB-endemic settings

Answer 131

Elevated opening pressure Cells (?mononuclear, can be some neutrophils, variable no.) Elevated protein Low glucose Xpert ultra and culture ~50% (no single test can rule out TBM)

Answer 132

Diabetes is associated with active TB -> 3.6 fold higher TB risk

Answer 133

Latent - Asymptomatic - Sputum does not contain enough bacteria -> can't culture it - CXR would be negative Subclinical - No symptoms and don't feel ill - But TB prevalent and active - Ie if given a sputum pot they can produce some and TB can be grown - Might have some CXR changes

Answer 134

Resistance to rifampicin and isoniazid

Answer 135

Screened for disease but no investigations

Answer 136

Diagnosed with disease but not started on treatment

Answer 137

Daily isoniazid 6-9 months (most programmes go for 6 months)

Answer 138

Weekly rifapentine and isoniazid for 3 months - issues with regulation and rolling out OR Daily isoniazid plus rifampicin for 3 months OR (conditional recommendation) 1 month regimen of daily rifapentine + isoniazid or 4 months of daily rifampicin 2024 update: levofloxacin daily for 6 months for people exposed to multidrug- and rifampicin-resistant TB

Answer 139

Daily rifampicin and isoniazid for 3 months

Answer 140

TB ○ Increase political will ○ Diagnosis based on quality-assured sputum testing: "passive case finding" ○ Uninterrupted standard 6 months treatment course ie uninterrupted drug supplies ○ Patient support (DOT - directly observed therapy) ○ Systematic reporting % cure

Answer 141

- Treatment success: Cured + Treatment completed cases - Failed treatment - LTFU - Died - Not evaluated

Answer 142

1. Field based ○ Microscopy ○ RDTs 2. Molecular methods ○ qPCR (quantitative PCR/real time PCR) ○ PCR (eg nested PCR methods) Genome sequencing (eg field-based Nanopore sequencing)

Answer 143

Parasites found to lack HRP2 and HRP3 - Method of resistance to evade diagnostics ie gene deletion

Answer 144

Can replicate/survive at lower temperatures - Can be transmitted by lots more mosquito species - More transmissible to mosquitoes and make them earlier on in infection - ?day biting so nets less effective Traditionally less efficient at invading Duffy negative RBCs but this is now changing

Answer 145

malariae low parasitaemia quartan fever pattern slowest erythrocytic cycle

Answer 146

SE Asia esp Malaysia Mosquito presence Macaques prevalence

Answer 147

Curtisi Wallikeri

Answer 148

- Species? - Parasite density? - Is it original infection or relapse? - Any drug resistant genotypes?

Answer 149

Lots of gametocytes -> sicker patient Parasite starts accelerating sexual reproduction for onward transmission

Answer 150

○ Pan-plasmodium LDH ○ P.falciparum-specific HRP2 ○ P.falciparum-specific LDH

Answer 151

No Only species detection

Answer 152

qPCR or rtPCR

Answer 153

○ Species ○ Drug resistance markers ○ Multiplicity of infection (clonal/polyclonal -> ie are there multiple strains of species infecting patient) ○ Original infection/relapse ○ Origin of infection

Answer 154

- Drop TB cases (reduce incidence 90%) - Drop deaths from TB (reduce by 95%) - Drop catastrophic costs due to TB By 2035 (Goals made in 2014) SDG targets by 2030 - reduce incidence by 80% - reduce deaths by 90% - reduce catastrophic costs to 0

Answer 155

Adult men = 55%

Answer 156

1. Digital CXR + Computer Aided Diagnostics then sputum PCR at primary care ○ Convenience screening +/- symptoms CAD since 2022 being recommended for first time as alternative to human interpretation 2. Urine-LAM (TB antigen) screening for all hospitalized HIV+ medical patients ○ New LAM tests may expand this remit 3. Community interventions with evidence for affordable impact - Digital CXR-based - Symptom + smear microscopy-based

Answer 157

- Red cells NOT enlarged - Rings appear fine and delicate and there may be several in one cell - Some rings can have two chromatin dots - Presence of marginal or applique forms - Unusual to see developing forms in peripheral blood films - Gametocytes: crescent shape appearance ○ Do not appear in peripheral blood in first few weeks of infection Maurer's dots may be present

Answer 158

- RBCs containing parasites usually enlarged - Schuffer's dots in red cells - Mature ring form large and coarse - Developing forms frequently present

Answer 159

- People can be infected for long periods before symptomatic - Incubation 18-40 days - Quartan fever pattern - Slowest growth => longest erythrocytic cycle - Associated with rare kidney pathologies and fatalities - Frequently low parasitaemias

Answer 160

- Ring forms can have a squarish appearance - Can also be bulls eye -> ie centralised in cell - Trophozoites can be band form or compact - Mature schizonts -> daisy head appearance with 8-10 merozoites - Red cells NOT enlarged (parasite likes old cells) Chromatin dot may be on inner surface of ring

Answer 161

- Red cells enlarged - Comet forms common - Rings large and coarse - Schuffner's dots - Can have fimbriae -> jagged edge - Mature schizonts - Similar to those of P malariae but larger and more coarse

Answer 162

Atopic Haematological Rheumatological Drugs Infection - most commonly parasites

Answer 163

Loa loa Gnathostoma Sparganum

Answer 164

In patients with high microfilarial counts eg >20,000 treatment with Ivermectin can result in large inflammatory reaction eg encephalopathy due to body reaction in response to worms being killed Can use DEC but can face similar issue

Answer 165

Yeast in the beast Mould in the cold eg histoplasma

Answer 166

Albendazole or Ivermectin (but not IVM for loa loa)

Answer 167

Beta D glucan Galactomannan Serology (less helpful in immunocompromised patients eg HIV, as can't mount a proper response) If particular suspected cause, then specific test eg Histoplasma urinary Ag

Answer 168

Amphotericin B (ambisome is liposomal form)

Answer 169

Itraconazole

Answer 170

Histoplasma Blastomyces Coccidioides Paracoccidiodes Sporothrix Penicillum = Talaromyces Containment level 3

Answer 171

Candida eg albicans or non-albicans Cryptococcus neoformans

Answer 172

Cryptococcus neoformans

Answer 173

Histoplasmosis Common in bat faeces

Answer 174

Reticuloendothelial involvement Skin nodules Mouth ulcers Renal, bone, CNS, liver lesions Adrenal involvement (hypo) Uveitis, panophthalmitis

Answer 175

Madura foot eg Eumycetoma pedis Prolonged course of antimicrobial eg Itraconazole or Voriconazole - Difficult as need levels and monitoring

Answer 176

Tumour - growth Tracts - body's attempt to drain and get pus out Grains - release of grainy liquid of fungal colonies

Answer 177

Madurella mycetomasis - a environmental soil mould - hot spot in Sudan

Answer 178

Actinomycosis Podoconiosis TB Non-tuberculosis mycobacterium Bacterial osteomyelitis

Answer 179

Fasciola (big) Opisthrochis Clonorchis

Answer 180

Triclabendazole 10mg/kg/PO 2 doses 12-24 hours apart

Answer 181

Liver flukes eg trematodes Central and east Asia eg Kazakhstan, Siberia, eastern Russia Eating raw or undercooked fish Treat with praziquantel Cholangiocarcinoma

Answer 182

Eating watercress

Answer 183

Acute infection § Eosinophilia § May have positive serology (6-8 weeks for Ab to develop) § Negative OCP (not early enough to get eggs in stool) Chronic § Positive serology § May have eosinophilia § Intermittent eggs in stool

Answer 184

Bacterial Amoebic (singular, big, ring-enhancing) Echinococcosis

Answer 185

- Molluscum contagiosum - Cytomegalovirus - Cryptococcus neoforms - Dimorphic fungi: histoplasmosis/talaromycosis - Syphilis - TB - Trichoepitheliomas - Tuberous sclerosis

Answer 186

Talaromycosis caused by Talaromyces marneffei Management: - Severe: ○ Induction: Ambisome 7-14 days or Amphotericin B IV (0.7mg/kg/day) at least 14 days ○ Consolidation therapy: Itraconazole PO BD for next 10 weeks Mild/moderate: Itraconazole If HIV positive then secondary prophylaxis with itraconazole until CD4+ count of >100 cells for at least 6 months (suggestion)

Answer 187

Dimorphic fungus Bamboo rats are reservoir Associated with HIV and poverty Infectious mould spores inhaled from soil Skin lesions only present in around 50% of patients (usually late stage infection) Symptoms: weight loss, prolonged fever, fatigue, diarrhoea Signs: hepatosplenomegaly, anaemia, lymphadenopathy CXR: chest signs common, may see diffuse reticulonodular or alveolar infiltrates

Answer 188

P ~/= ID Treatment increases -> duration of disease to rise + incidence to fall - HIV prevalence should continue to rise or be stable for time to come Means need to consider its role in aetiology and management of other conditions

Answer 189

1987, more in 1990s and 2000s

Answer 190

95 95 95 * First 95: 95% of PLHIV know their status * Second 95: 95% of PLHIV on treatment * Third 95: 95% of PLHIV on treatment achieved viral suppression

Answer 191

Middle income countries eg - West Africa - South America - Asia

Answer 192

West Africa and places with ties to WA

Answer 193

Sexual - Transmission through semen, vaginal fluid, blood, anal mucus - Heterosexual transmission is main mode of spread globally Parenteral - Transmission through skin or via blood/blood products Mother-child transmission During pregnancy, labour or through breastfeeding

Answer 194

- Treatment ○ Treatment as prevention (U=U) - HIV combination prevention ○ Behaviour change including consistent condom use ○ Biomedical interventions: eg Voluntary medical male circumcision, Pre-exposure prophylaxis (PrEP) ○ Supportive political and health care environment - Prevention of mother-to-child transmission (PMTCT) HIV testing for access to treatment and some prevention

Answer 195

R0 = c x ß x D R0: Basic reproductive number C: Exposure rate --Influencing factors: Norms around multiple partnerships, sexual violence ß: Probability of HIV transmission --Influenced by: Ability to negotiate condom use, age at first sex, availability of PrEP D: Duration of infectious period --Influenced by: Access to treatment

Answer 196

HIV has spread rapidly in one or more defined subpopulation but is not well established in the general population. Numerical proxy: HIV prevalence is consistently over 5% in at least one defined subpopulation but is less than 1% among pregnant women in urban areas.

Answer 197

HIV is firmly established in the general population. - Numerical proxy: HIV prevalence consistently exceeding 1% among pregnant women. Most generalized HIV epidemics are mixed in nature, in which certain (key) subpopulations are disproportionately affected.

Answer 198

People are acquiring HIV infection in one or more subpopulations and in the general population. Mixed epidemics are therefore one or more concentrated epidemics within a generalized epidemic.

Answer 199

Five key populations in 2016 WHO guidelines 1. Sex workers* 2. People who inject drugs 3. Men who have sex with men (MSM) 4. People in prisons or other closed settings 5. Transgender people Also region- or country-specific populations at elevated risk - Migrant populations - Occupational groups: fisherfolk, truck drivers, miners Adolescents*

Answer 200

- Biological vulnerability: higher per-act risk of sexual transmission, higher STI prevalence, anatomical development - Behavioural vulnerability, including risky sexual behaviour - Social and structural vulnerability: gender-based violence, lack of access to services increase risk and decrease access to PrEP and other HIV prevention

Answer 201

- Retroviridae family - Lentivirus - HIV-1 and HIV-2 species Single stranded, sense RNA

Answer 202

- Gp41 and Gp120 bind onto CD4 cell using CCR5 or CXCR4 co-receptor - Fusion with membrane - Expels capsid into cell cytoplasm - Capsid makes way to nucleus via nuclear import (using microtubules) - Then viral RNA exposed - Reverse transcription - Integration of proviral DNA into human genome -> stays there forever in that cell - Transcription to make proteins eg enzymes, viral particles - Nuclear export - Assembly of new virus with utilisation of cell membrane -> budding - Release of new virion Maturation

Answer 203

- Local infection of mucosal tissues ○ Can't detect virus in blood in this stage - Death of mucosal memory CD4+ T cells - Infection established in lymphoid tissues eg LNs - Viraemia after infection in blood - Spread through body - Immune response -> but is incomplete and dysfunction ie partially control viral replication ○ Abs can't completely neutralise virus ○ Cytotoxic T lymphocytes - Due to widespread dissemination of HIV in lymphoid tissue -> clinical latency due to reservoir ○ Chronic + concentrated low-level viral production in lymphoid tissues ○ Inflammation associated with viraemia § Cytokine storms § CV disease § Metabolic issues - Eventually increased viral replication - AIDs -> destruction of lymphoid tissues + depletion of CD4+ T cells

Answer 204

Two tests: 4/5th generation assays ○ Ie get two positive results Then immunotyping 4/5th generation include: p24Ag + Abs combined OR separate p24 Ag and Ab components (p24 is protein in viral caspid) Window period 45 days for Ab/Ag assays, 90 for POCT

Answer 205

- Immune selection pressure --> escape mutants --> quasispecies created - 1-10 mutations per replication cycle, with production of 1 billion virions a day - Older infection = more diverse - Drug selection pressure

Answer 206

- Failure of ART to reduce viral load WHO can define as viral load >1000 copies on ideally two tests - Need to do genotypic resistance test: Protease and integrase are standard Can result from archive mutations -> means can re-emerge if patient re-started on treatment having been incompletely treated in the past (which may be unknown to healthcare provider)

Answer 207

HIVDR detected in individuals initiating ART regardless of prior antiretroviral (ARV) drug exposure(s) (e.g. prior ART followed by default from care ie stopped taking it or lost to f/u, pre‐exposure prophylaxis (PrEP), post‐exposure prophylaxis (PEP)) Means archive mutations can re-emerge when ART is started IE: PDR may either be transmitted at time of initial infection or acquired by prior exposure to ARV drugs

Answer 208

- Mixed population including drug-resistant minority variants - Subtherapeutic drug levels e.g. adherence issues - Selection pressure -> resistant variants flourish - Usually not “fitter” than wild-type - Take away drug (ART cessation/onward transmission) ○ wild-type takes over again - Archived resistance - Compartmentalisation e.g. CNS

Answer 209

- Origin West Africa - More indolent - Slower progression - Slower CD4 decline - VL lower - Intrinsic NNRTI resistance

Answer 210

CD4 count at baseline Two components: 1. Number of CD4 T cells 2. Differences in phenotype and function of pathogen-specific CD4 T cells

Answer 211

CD4<200 cells/mm3 OR WHO stage 3 or 4 event Children<5 years old with HIV

Answer 212

1. Primary HIV infection ○ Acute viral illness or asymptomatic 2. Chronic viral infection: direct viral effects and inflammation ○ Adenopathy, haematological, skin disorders ○ Higher risk of non-HIV cancers, cardiovascular disease, osteoporosis ○ HAND, wasting syndrome, HIVAN 3. Opportunistic infections and cancers: impaired cellular immunity ○ Many pathogens; related to CD4 count 4. ART-associated effects eg IRIS, toxicity

Answer 213

Immune reconstitution syndrome - High mortality in first 12 months of starting ART - Usually 4-6 weeks after starting ART Two forms: ○ Paradoxical IRIS ○ Unmasking IRIS

Answer 214

TB (TB - IRIS) Syphilis Lymphoma KS/Castlemans NTM

Answer 215

Nocardia Dimorphic fungi infection eg hits, emergomycosis, talaromycosis, sporotrichosis Cryptococcus

Answer 216

1. Herpes zoster 2. Papular pruritic eruption (PPE) 3. Molluscum contagiosum 4. Apthous ulcer 5. Oropharyngeal candidiasis 6. Oral hairy leukoplakia

Answer 217

Papular pruritic eruption ○ Eosinophilic folliculitis ○ Occurs at any CD4 count ○ ++ discomfort; can lead to scarring ○ No specific treatment: § Antihistamines, symptomatic ○ Easily confused with dimorphic fungal infection --> always biopsy if CD4 <100 or constitutional symptoms

Answer 218

§ Cryptococcosis § Histoplasmosis, talaromycosis § Mpox

Answer 219

§ Early HIV § Lymphoma and KS § Herpesviruses: HSV, CMV § Other infections § Tuberculosis § Syphilis § Deep fungal infection § Leishmaniasis § Rheumatologic diseases and IBD

Answer 220

Ascus forms (cystic) Transmissible form Thick cell wall containing beta-glucans Contains cholesterol (not ergosterol, so can't be targeted by traditional anti-fungals) Immune stimulus Trophic forms (trophozoite) Replicative form (more abundant in lungs) Wall-less -> biofilm Contains cholesterol (not ergosterol, so can't be targeted by traditional anti-fungals) Immune evasive DIAGNOSING IT" § Gold standard bronchoscopy: not available § Sputum-based tests not accurate enough § Most patients started on empiric therapy qPCR: good rule out test on induced sputum and oral wash B-D-Glucan: After a negative test: Rules out PCP with 95% certainty up to a pre-test probability of 50% After a positive test: Increases chance of PCP to ~70% for any HIV- associated pneumonia (prevalence of PCP ~25%)

Answer 221

Co-trimoxazole 21 days high dose TMP-SMX = trimethoprim-sulfamethoxazole, used both for PCP prophylaxis and treatment

Answer 222

Bacteria (especially pneumococcal disease) TB and PTLD Resp viruses NTM

Answer 223

PCP KS Lymphoma

Answer 224

Cryptococcus Dimorphic fungi CMV

Answer 225

EBV - No treatment You can do tongue scrapings on candida throat/tongue, not on OCL

Answer 226

TB Lymphoma Mycobacteria Dimorphic fungi Cryptococcus Nocardia

Answer 227

* TB * Bacterial * KS * Cryptococcosis * Lymphoma (KSHV-related)

Answer 228

Treat toxoplasmosis with co-trimoxazole

Answer 229

* TBM * Cryptococcal meningitis * Viral meningitis * Bacterial meningitis (pneumococcus and meningococcus) * Listeria * Syphilis

Answer 230

* TB * Toxoplasmosis * Nocardia * Pyogenic brain abscess * Lymphoma * Cryptococcus * Syphilis

Answer 231

1. Opportunistic diseases - TB, NTM, lymphoma, deep fungal, leishmaniasis 2. HIV wasting syndrome 3. GI pathology - Painful oral/oesophageal lesions - Severe chronic diarrhoea 4. Other malignancy 5. Depression – very common & often unrecognized 6. Lack of financial resources to buy food

Answer 232

Toxoplasmosis CMV PML Cryptococcal meningitis TBM Bacterial meningitis Viral meningitis VZV Primary CNS lymphoma

Answer 233

○ Stains (Gram, AFB, India Ink) ○ Bacterial, mycobacterial and fungal culture ○ Cryptococcal antigen (CrAg) test (close to 100% sensitivity and specificity) ○ Xpert Ultra MTB/Rif ○ Pneumococcal Ag tests ○ Viral and bacterial PCRs (multiplex) ○ Toxoplasma serology

Answer 234

- Blood tests ○ Malaria film, FBC, U&E ○ Blood cultures ○ HIV test and CD4 count - LP ○ Opening pressure ○ Appearance ○ Cell count & differential ○ Protein & glucose Only real contraindication to LP in LMICs where scanning is not possible is focal neurological deficit (excluding CN palsies) suggesting mass lesions

Answer 235

CrAg tests (close to 100% sensitivity and specificity), india ink staining (ring enhancing), culture

Answer 236

Single high-dose liposomal amphotericin based regimen for treatment of HIV-associated Cryptococcal meningitis ○ Novel single dose treatment was both safer and more effective Now being used in Botswana, Eswatini, Malawi, Zimbabwe, Uganda

Answer 237

Induction treatment: Single-dose Liposomal Amphotericin B* 10mg/kg plus Flucytosine (5FC)100mg/kg/day (4 divided doses) & Fluconazole 1200mg/day for 2 weeks; then Consolidation treatment: Fluconazole 800mg/day for 8 weeks; then Maintenance treatment: Fluconazole 200mg/day until CD4 > 200 cells/µL and virally suppressed on ART - Do not give steroids -> worsen outcomes Start ART 4-6 weeks after starting anti fungal to avoid IRIS

Answer 238

- Renal impairment, K+/Mg2+ wasting, anaemia, thrombophlebitis - Give 1L N. Saline + 20mEq K+, 2 Slow-K Tablets (16 mEq) twice daily, 2 Slow-Mag Tablets (143mg Mg2+) Alternate day creatinine + electrolytes, twice weekly Hb

Answer 239

No - worsens outcomes

Answer 240

Start ART at 4-6 weeks after initiating antifungal therapy to avoid immune reconstitution syndrome

Answer 241

Common ≈ 75 %, can occur at initial presentation, on treatment, IRIS Communicating hydrocephalus Headache, Visual/hearing loss, CN palsies, depressed GCS, confusion Management is with therapeutic lumbar punctures - daily LP’s until OP <25cm H20

Answer 242

Individuals with CD4<100 Ideally offer LP if available Treat patients without evidence of CNS disease with high dose fluconazole 1200mg for 2 weeks, then standard consolidation and maintenance therapy If LP positive then manage as cryptococcal meningitis

Answer 243

- Chronic headache + meningism - Cryptococcal investigation negative - CSF compatible - Routine bacterial cultures negative - Evidence of TB elsewhere (TB on CXR: 44% in HIV+ TBM) Often CD4 count may be >100-200

Answer 244

- Standard quadruple therapy (RIPE), 9-12 months duration - Steroids: maybe but benefit in HIV-infected subset not clear - currently evidence suggesting no benefit nor in TB pericardial disease -ART: data on timing not clear, most would delay initiation until around 9-12 months after initiation of TB treatment and give steroid cover TB medication may help prevent TBM in HIV positive individuals. Give BCG in kids.

Answer 245

CD4 <100cells/microL

Answer 246

Initial therapy: - Pyrimethamine 200mg OD loading then 75mg OD plus Sulfadiazine 6-8g/daily divided QDS Or - Clindamycin 450mg pd QDS Increasingly used: Co-trimoxazole (high dose) much more widely available Secondary prophylaxis: - Initiate ART without delay (low risk of IRIS) Long term co-trimoxazole prophylaxis until sustained (>6m) response to ART with CD4 count >200 cells/µl Don't give steroids -> can confuse therapeutic trial

Answer 247

Cervical cancer Kaposi's sarcoma Lymphomas esp Non-hodgkin's lymphoma Castlemann's disease

Answer 248

- Pulmonary TB - Upper lobe infiltrates with cavities - EPTB less common - Mild immunosuppression (eg CD4 >350) is similar VS - Thoracic lymphadenopathy and pleural effusions more common - Extrapulmonary disease more common with declining CD4 counts - Disseminated disease * Post-mortem have shown dissemination in 90% - Lower zone nodules, non-cavitating or normal CXRs - Very severe: * Sepsis with bacteraemia + organ dysfunction * ~25% admitted with sepsis have TB. Microbacteraemia in 40-50%

Answer 249

Microscopy - sputum smear for AFB Culture - gold standard Molecular techniques - PCR eg GeneXpert Antigen detection eg urinary LAM (only can use in HIV) Can do urine Xpert Ultra (high specificity but lower sensitivity) and stool Xpert Ultra

Answer 250

1. WHO 4 symptom screen (cough, fever, weight loss, night sweats) 2. CRP, cut-off >5 mg/L 3. Chest X-ray (+CAD) 4. WHO recommended molecular diagnostic (medical inpatients) Screen with IGRA or TSTs Screen at every visit to a health facility

Answer 251

PLHIV -Signs /symptoms of TB -Advanced HIV -Seriously ill -Positive screening test Do: - urinary LAM - Sputum Low complexity molecular testing eg geneXpert

Answer 252

-Signs /symptoms of TB -Positive screening test Do Respiratory sample -> Low complexity molecular testing eg geneXpert Stool Low complexity molecular testing eg stool Xpert ultra

Answer 253

Use USS as POC to look at 6 points to look for: - Pleural fluid - Pericardial fluid - Ascites - Focal liver lesions - Focal splenic lesions

Answer 254

Start ART as soon as possible within two weeks of initiating TB treatment regardless of CD4 cell count among people living with HIV Exception: TBM (start 4-8 weeks after)

Answer 255

- Started TB treatment and newly go on to start ART - Then clinical deterioration - Usually happens within weeks of ART Paradoxical as patients should get better and not worse

Answer 256

- Not on TB treatment - Newly started on ART - After a couple of weeks -> deteriorate and new S/S + new diagnosis of HIV associated TB

Answer 257

RI for 6 months PE for 2 months + pyridoxine

Answer 258

Hepatitis Rash Arthropathy (pyrazinamide) Optic neuritis (ethambutol) Peripheral neuropathy (isoniazid)

Answer 259

Rifampicin - potent CYP450 Many HIV drugs metabolised by CYP450 1. Atripla: efavirenz + lamivudine + tenofovir ○ But issues with resistance 2. Dolutegravir + Tenofovir + lamivudine + dolutegravir 50mg ○ Ie give with rifampicin but need to double dose of dolutegravir so give extra tablet top up

Answer 260

Steroids eg PO Prednisolone

Answer 261

- 8% have paradoxical IRIS after starting ART - Usually worsening pulmonary infiltrates / enlarging LNs - 25% hospitalized, 2% mortality - Prednisolone reduces severity /hospitalization / need for procedures Risk factors: ○ Low CD4 count / high viral load ○ Extrapulmonary TB ○ Early ART (but mortality lower) ○ Prophylactic prednisolone reduces IRIS by 30%

Answer 262

○ Low CD4 count / high viral load ○ Extrapulmonary TB ○ Early ART (but mortality lower) ○ Prophylactic prednisolone reduces IRIS by 30%

Answer 263

Drug resistance Multiplication rate Invasion pathways Cytoadherence Rosetting Antigenic polymorphism Antigenic variation via PfEMP-1 Malaria toxin

Answer 264

Immunity Proinflammatory cytokines Genetics eg SCT, thalassaemia, ovalocytosis, CD36, TNF-a, ICAM-1 etc Age Pregnancy

Answer 265

Access to treatment Cultural and economic factors Political stability Transmission intensity -> seasonality, infectious bites per year, epidemics

Answer 266

Schizont rupture - release of parasite proteins eg immunogenicity materials triggering immune response Malaria toxins eg Haemozoin, Parasite DNA, GPI (Glycophosphatidylinositol) causes pro-inflammatory cytokine release Splenic clearance of iRBC via activation of splenic macrophages -> cytokine storm -> systemic inflammation over activation

Answer 267

1. Mechanical hypothesis = vascular obstruction by parasitised erythrocytes ○ Evolutionary basis of cytoadherence to brain endothelial cells § To avoid clearance of parasitised erythrocytes by the spleen § For optimal development condition: low O2 pressure found in post-capillary venules 2. Immunopathology hypothesis = effector function of immune cells ○ Endothelium activation and damaging § Up-regulation of parasite, platelets and monocytes receptors (cell accumulation within microvessels) § Endothelial shrinking, induction of apoptosis

Answer 268

CD36 - Parasites sequester in microvessels via CD36 -> avoid clearance by the spleen ○ CD36 is a scavenger host endothelial cell receptor which is widely distributed Over 75% of encoded PfEMP1s have a binding domain for this receptor

Answer 269

- Cytoadherence - Rosetting - Clumping Impair blood flow leading to anaerobic glycolysis, acidosis and tissue damage

Answer 270

1. Preterm delivery (<37wks) ○ Associated with malaria parasitaemia and anaemia 2. Foetal growth restriction ○ Chronic infection and placental insufficiency ○ Lack of nutrients to foetus ○ TNF, IFN-Y, IL-1 and IL-2 production elevated § High TNF linked to fetal growth restriction and preterm delivery IFN-Y related to low birth weight

Answer 271

- iRBCs accumulate and aggregregate in placental intervillous spaces - RBC use the VAR2CSA type of PfEMP-1, which binds to chondroitin sulfate A (CSA) - The sequestration blocks the transfer of nutrients from mother to embryo - VAR2CSA found during pregnancy that are absent in men and non-pregnant women - Women with PAM remain afebrile - suggesting local pathology - with some aspects of acquired immunity remaining unaffected by placental parasitisation - Elevated type 1 pro-inflammatory responses in placentas of malaria-infected mothers - Sequestration of infected erythrocytes -> inflammatory environment -> release of C&C -> recruitment of monocytes and macrophages into intervillous space ○ TNF, IFN-Y, IL-1 and IL-2 production elevated § High TNF linked to fetal growth restriction and preterm delivery IFN-Y related to low birth weight

Answer 272

- VAR2CSA found during pregnancy that are absent in men and non-pregnant women - Women with PAM remain afebrile - suggesting local pathology - with some aspects of acquired immunity remaining unaffected by placental parasitisation

Answer 273

1. Loss of infected RBCs: lysis or phagocytosis ○ Haemolytic anaemia ○ Misconception: SMA arises simply from the lysis of infected RBC. ➔ Lysis of infected RBCs is not the most significant cause of SMA ○ Minor loss, parasitaemia < 1% 2. Loss of uninfected RBCs ○ Phagocytosis, phosphatidylserine and other markers involved as 'eat me' signal ○ ~12 uninfected RBC are lost for every iRBC during malaria infection 3. Suppression of BM erythropoiesis -> prevention of replacement

Answer 274

Changes in plasma membrane of uninfected RBCs during malaria infection targets them for destruction: ’eat me’ signal * Phosphatidylserine externalization * Oxidation * Reduced deformability Binding of immune components to the surface of uninfected RBCs also targets cells for destruction * Binding of malaria RSP-2 (ring surface protein 2) on the surface facilitates recognition * Immune complexes and IgG (specific for parasite material that may stick to uninfected RBC) promotes phagocytosis * Complement binding Destruction of uninfected RBCs generally mediated by splenic red pulp macrophages

Answer 275

- Haemozoin (a breakdown product of haemoglobin produced by the parasite) inhibits erythropoiesis - Suppressive cytokines: ○ TNF inhibits all stages of erythropoiesis ○ IFN-Y inhibits erythroid cell growth, differentiation and survival - Hepcidin is released by the liver and blocks iron availability for incorporation into haemoglobin - MIF (migration inhibitory factor) inhibits erythropoiesis by direct effects on erythroid precursors and bone marrow rather than modulation of TNF production

Answer 276

PfEMP1 - Prevention of parasite from establishing its own actin cytoskeleton within the host cell - Impaired vesicular transport - Distorted trafficking of PfEMP1; less in the surface - Reduced cytoadherence - Data limited to HbS and HbC

Answer 277

Comes from proximal tubules of mammals so high in animal urine eg rats outbreaks when floods

Answer 278

Point source: - Questions typically refer to weddings eg outbreak of vomiting after cream puffs at a wedding - Should settle after exposure is over - Most cases within same incubation period Extended common-source: - The continual exposure means continue cases - If you stop the exposure, ie break the water pump, then the cases should stop Propagated source: - Transmission occurs from person to person rather than a common source - Can have multiple waves - Cases in one peak can be sources for cases in a subsequent peak - May have progressively taller peaks (if incubation period and infectiousness period similar) Intermittent source - Multiple peaks - Length bears no relation to incubation period -> reflects intermittent times of exposure - eg contaminated food source

Answer 279

1. Prepare for field work -> identify an investigation team, mobilise appropriate resources 2. Establish the existence of an outbreak/epidemic 3. Verify diagnoses of cases 4. Establish a working case definition 5. Systematic case finding to identify additional cases 6. Conduct descriptive epidemiological studies (time, place, person) 7. Develop hypotheses 8. Evaluate hypotheses (often with case control study) 9. If required, reconsider/refine hypotheses and do additional studies to test them 10. Implement control and prevention measures (as early as possible) 11. Communicate findings 12. Institute surveillance

Answer 280

- Proven/confirmed ○ Usually are symptomatic ○ Are within suspected incubation period ○ Have positive test: ie serology, culture, PCR etc - Probable/suspected ○ ?live in epidemic area ○ Symptomatic - Possible ○ Milder symptoms ○ ?Not necessarily in traditional incubation period ○ ?Might have had contact with proven or probable case in preceding given amount of time

Answer 281

Cysts (can sit/lay dormant for a while) Trophozoites (cause active infection)

Answer 282

- IBD - Ischaemic colitis - Radiation colitis - Bowel cancer - Vasculitis

Answer 283

VHF esp Lassa, Marburg, ebola -CMV if CD4 low

Answer 284

- Shigella (p to p spread) - E coli (p to p spread) - Campylobacter - Salmonella Other - C difficle - Yersinia enterocolitia - Plesiomonas shigelloides

Answer 285

- Schistosomiasis ○ Intestinal -> eggs in mesenteric veins -> portal spread -> portal HTN and varices § Can distinguish from other liver diseases as liver function quite preserved - Amoeba (E histolytica) - Balantidium coli - Malaria - Helminths - Very heavy trichuris (but tends to be due to rectal prolapse)

Answer 286

Hypokalaemia

Answer 287

PPE Hand-washing Sanitation Incineration Clean surfaces Identify common sources for spread Prevent iatrogenic infections

Answer 288

NRTI: nucleoside reverse transcriptase inhibitors - Pretend to be nucleotides - Drug class associated with most toxicities - ?secondary to introduction of them into cell - Risk of mitochondrial toxicity NNRTI: non-nucleoside reverse transcriptase inhibitors - Bind to reverse transcriptase and cause confirmational change so doesn't work as well INSTI: integrase (strand transfer) inhibitors PI: protease inhibitors Capsid inhibitor (lenacapavir): 6 monthly subcut injection, not yet licensed, could be gamechanger Other drugs that aren't really used: CD4 inhibitor: ibalizumab - Withdrawn in Europe, only available in USA - IV every 2 weeks - Very expensive CCR5 inhibitor: maraviroc - Rarely used Fusion inhibitor: enfuvirtide BD subcut injections

Answer 289

- TBM: after at least 4 weeks, but start within 8 weeks of anti-TB treatment ○ Consider adjuvant steroids - After TB treatment started: within 2 weeks - Cryptococcal meningitis ○ Increased mortality with immediate ART ○ Defer until 4-6 weeks after CM treatment start

Answer 290

Until 1996: NRTI 1996 - 1999: PI + NNRTI 2000+: INSTI + new (2 NRTI + 1 other)

Answer 291

Dolutegravir (II) Lamivudine (NRTI)

Answer 292

First line: Tenofovir-DF (TDF) + emtricitabine or lamivudine + dolutegravir (TLD = Teno/Lamni/Dolu is 1 pill but not available in UK yet) Alternative first line: TDF + lamivudine + efavirenz 400 Don't use efavirenz if country has resistance rates of >10% if DTG not available then boosted PI should be used Consider TAF instead of TDF if pre-existing bone disease or renal impairment

Answer 293

Tenofovir disoproxil fumarate = old tenofovir = TDF, TDX (same drug but different salts) - These are old tenofovir Biggest SEs: renal impairment and reduction in bone mineral density Can consider new tenofovir: TAF = Tenofovir-alafenamide or another drug

Answer 294

Monitor viral load Don't monitor CD4 count Now in London/?UK once CD4>350 stop monitoring it If viral load testing not available then use CD4 cell count with clinical monitoring

Answer 295

>1000 copies/ml Same as for plasma

Answer 296

Creatinine Not indicative of renal disease

Answer 297

Resistance testing if available Otherwise, according to WHO guidelines if Viral load >1000 on NNRTI then switch as pre-treatment resistance common in many countries Switch to 2nd line after single VL >1000 reduces mortality & transmission & is cost-effective (at $500 DALY threshold)

Answer 298

§ Midazolam § Amiodarone § Rivaroxaban § Fluticasone

Answer 299

INSTI + 2NRTIS - TAF + emtricitabine + bictegravir (Biktarvy) - Abacavir/lamivudine/dolutegravir (if HLAB5701 negative, 10-year CV risk <10%) - Dolutegravir + TAF/TDF + lamivudine or emtricitabine OR INSTI + 1 NRTI - Dolutegravir + lamivudine ○ No baseline lamivudine resistance ○ Baseline VL <500,000 ○ Baseline CD4>200 ○ No need to include tenofovir for hep B treatment/prevention

Answer 300

Male circumcision

Answer 301

Emtricitabine

Answer 302

Tenofovir disoproxil fumarate

Answer 303

Tenofovir-alafenamide

Answer 304

Raltegravir

Answer 305

- Up to 72 hour after exposure - POCT negative - Tenofovir/emtricitabine and raltegravir OD for 28 days - Vaccinate for hepatitis/assess risk for other STIs - Emergency pregnancy prevention - Follow up testing for HIV ○ Minimum 45 days after completion of PEP course ○ If 28 day PEP course is completed this is 73 days (10.5 weeks) post-exposure

Answer 306

- Truvada OD (can be on it long term) = FTC/TDF (for anyone at risk) OR Descovy (FTC/TAF) OD for men and transgender women - Cabotegravir IM injection every 8 weeks

Answer 307

Cisgender adolescent and young women

Answer 308

Emtricitabine/tenofovir alafenamide

Answer 309

VL: at 6M, 12M then yearly CD4 every 6M until established on ART Ideally also check Creat & eGFR for TDF Pregnancy test for women of child bearing potential

Answer 310

Creat & eGFR for TDF HBV surface Ag before switching drugs if not done at baseline or negative and not-vaccinated If >50-<1000 copies/ml VL: enhanced adherence counselling and repeat VL testing at 3 months -> if above >1000 then switch, if <50 then maintain, IF still >50-<1000 copies/ml VL then maintain ART, enhanced adherence counselling and repeat VL testing at 3 months -> if still high then switch If VL>1000copies/ml and on NNRTI based ART -> switch (high risk of resistance)

Answer 311

Enhanced adherence counselling and repeat VL testing at 3 months IF still >50-<1000 copies/ml VL then maintain ART, enhanced adherence counselling and repeat VL testing at 3 months -> if still high then switch, if <50 then maintain

Answer 312

Inhibits OCT2, a renal transporter Highest in first 4 weeks Not harmful to kidneys nor reflective of renal disease

Answer 313

Jaundice + transaminitis on ART -> associated with worse mortality Switch the most likely culprit ○ Eg AZT to TDF ○ 3rd agent to another 3rd agent ○ Atazanavir = PI § Not really used anymore § Can cause jaundice § Risk of renal impairment

Answer 314

Only if jaundiced + transaminitis Atazanavir alone causes unconjugated hyperbilirubinemia

Answer 315

- At enrolment to care/initiation of ART - At treatment failure/switching ART regimen - At re-engaging following care interruption

Answer 316

Switch away from NNRTI at 1st detectable VL - Pre-treatment resistance common in many countries - Resistance common at virological failure - Although many will resuppress, outweighed by risk of more resistance + consequences of treatment failure - Switch to 2nd line after single VL >1000 reduces mortality & transmission & is cost-effective (at $500 DALY threshold)

Answer 317

If non-DTG regimen is failing: - DTG in combination with optimised NRTI backbone If DTG-based regimens are failing: - Boosted PIs with optimised NRTI backbone

Answer 318

1. Human/intestinal hookworm ○ Humans are definitive hosts § Ancyclostoma duodenale § Necator americanus 2. Animal hookworm ○ Humans are accidental host ○ Multiple species ○ Can invade and parasitise humans ○ Ancyclostoma ceylanicum ○ Ancyclostoma braziliense ○ Ancyclostoma caninum

Answer 319

Hookworm infection - ‘Skin-worm-moving’ - Intensely pruritic - Creeps along for days “serpinginous” - Track – due to an inflammatory, allergic response to the microscopic larva - Represents IgE-mediated response to filariform larval migration → histamine release → itchy ++ - Secondary bacteria infection can occur - Gradually will self-resolve once larvae enter circulation and migrate to the lungs

Answer 320

- Usually asymptomatic - Less commonly → eosinophilic pneumonitis - IgE-mediated immune response to larvae in the lungs - Leads to transient cough, wheezing, chest pain and haemoptysis - Lobar infiltrate on a CXR can mimic bronchopneumonia - “Loeffler’s syndrome”

Answer 321

1) Widespread distribution 2) Walking barefoot on soil contaminated with human faeces 3) Mostly asymptomatic or low grade GI disturbance 4) Auto-infection cycle for decades 5) Serpiginous rash of larva currens 6) Beware small bowel obstruction (duodenal aspirate) 7) Hyper-infection syndrome, normal eosinophils 8) Cellular immuno-suppression including HTLV-1 9) Travellers and migrants are different 10) Eosinophilia, serology, microscopy and charcoal culture

Answer 322

Strongyloides

Answer 323

○ Histoplasma ○ Talaromyces = penicillium ○ Blastomyces ○ Coccidioides ○ Paracoccidioides ○ Sporothrix (rose gardening one)

Answer 324

Talaromycosis

Answer 325

- Severe: ○ Induction: Ambisome (ie liposome amphotericin) 3-5mg/kg/day IV for 10-14 days OR Amphotericin B IV (0.7mg/kg/day) at least 14 days ○ Consolidation therapy: Itraconazole PO BD for next 10 weeks - Mild/moderate: ○ Itraconazole 200mg BD for 8-10 weeks - Maintenance therapy: Itraconazole 200mg OD lifelong or until CD4>100 for 6 months while on ART

Answer 326

Talaromyces marneffei Thermally dimorphic geographically restricted fungi * Rainy seasons soil exposure (inhalation of conidia) * Bamboo rats enzootic reservoir * 3rd commonest opportunistic infection in advanced HIV in endemic areas (SE Asia- Thailand, Vietnam and China) * Mortality 97-100% without treatment * Delay in diagnosis doubles mortality 24-50% * Newer diagnostics: PCR, metagenomic next-generation sequencing Severe: liposomal Amphotericin B or amphotericin B for 14 days Then consolidation: itraconazole BD for 10 weeks Mild: itraconazole BD for 8-10 weeks Maintenance: itraconazole lifelong or until CD4>100 for 6 months on ART

Answer 327

Zidovudine (AZT), Lamivudine (3TC), Abacavir (ABC), Tenofovir disoproxil fumarate (TDF), emtricitabine (FTC)

Answer 328

- Efavirenz (EFV) - Rilpivirine (RPV) - Doravirine (DOR)

Answer 329

- Dolutegravir (DAG) - Raltegravir (RAL) - Bictegravir (BIC)

Answer 330

- Ritonavir (RTV) - Lopinavir (LPV) - Atazanavir (ATV) - Darunavir (DRV)

Answer 331

Caspid inhibitor Shown promise for HIV -> only given 6monthly subcut injections but not licensed yet

Answer 332

4-6 weeks after CM treatment has started due to increased mortality with immediate ART

Answer 333

After at least 4 weeks but within 8 weeks of anti-TB treatment and consider adjuvant steroids

Answer 334

- RCT on starting ART - Delayed (until CD4>350 or AIDS related symptoms) vs start immediate group Better for immediate group * faster viral suppression * lower mortality * lower AIDs related events

Answer 335

Hep B = Need tenofovir

Answer 336

Cabotegravir

Answer 337

WHO: enhanced adherence counselling + repeat VL at 3M * Many people will resuppress * Resistance emergence uncommon 07/2024 VL undetectable Consistent with data from ADVANCE (1st line DTG vs EFV) which shows most participants resuppress on continued DTG

Answer 338

Adherence: - Secure drug supplies - Longer drug supplies - Education - Simple dosing - Adherence tools - Aim for longer acting medication Attendance: - COVID lessions - Virtual care - Transport support - REACH study

Answer 339

- NADIA trial looked at dolutegravir or darunvair in combination with lamivudine plus either zidovudine or tenofovir for second line treatment of HIV - Showed dolutegravir is non-inferior to darunavir but is at greater risk of resistance in second line therapy Also tenofovir should be continued in second-line therapy rather than being switched to zidovudine

Answer 340

Amoebae Flagellates Sporozoa Ciliates

Answer 341

Entamoeba Naegleria

Answer 342

Leishmania Giardia Trichomonas

Answer 343

Plasmodium Toxoplasma

Answer 344

Balantidium

Answer 345

Cestodes (tapeworm) Trematodes (flukes) Nematodes (roundworm)

Answer 346

Taenia saginata Taenia solium Hymenolepsis nana Diphyllobothrium latum Echinococcus sp

Answer 347

Liver flukes eg Fasciola, Clonorchis, Opisthorchis Lung flukes Tissue flukes Blood flukes eg schistosomiasis

Answer 348

Geohelminths Filariae

Answer 349

Ascaris Trichuris Hookworm Strongyloides Toxocara Trichenella Enterobius

Answer 350

Lymphatic filariasis Loa loa Onchocerca Dracunculus

Answer 351

"Giant roundworm" Crenelated eggs Adult worms 200-350mm in size Large bowel location Soil to mouth Clinical features: - Asymptomatic Loeffler's GI obstruction Cholangitis Peritonitis Distinct feature: lung migration Eosinophilia only if in lungs Treatment: albendazole

Answer 352

Disease in which eosinophils accumulate in the lung in response to a parasitic infection

Answer 353

"Whipworm" Bulb-ended eggs Adult worms 50mm in size Large bowel location Soil to mouth Clinical features: Asymptomatic GI upset Stunting Rectal prolapse Distinct feature: overlap with ascaris Often eosinophilia Treatment: albendazole

Answer 354

"Hookworm" Thin-walled eggs Adult worms 10mm in size Small bowel location Skin penetration Clinical features: Asymptomatic CLM Loeffler's GI upset Anaemia VERY ITCHY Distinct feature: lung migration Eosinophilia can be high Treatment: albendazole or ivermectin

Answer 355

"Threadworm in USA" Ellipsoid eggs with larva Adult worms 1mm in size Small bowel location Skin penetration Clinical features: Asymptomatic Larva currens GI upset Hyper-infection Distinct feature: auto-infection Eosinophils common but not in hyper infection Treatment: Ivermectin

Answer 356

Pinworm (Or called threadworm in the UK) Eggs are flat on one side Adult worms 1-2mm in size Located in rectum Transmitted faecal to mouth Clinical features: Asymptomatic Pruritis Vaginal discharge Distinct feature: Family clusters/sellotape test Eosinophilia: unusual Treatment: albendazole

Answer 357

Early illness: - Larva migration in the skin -> cutaneous larva migrans - Larva migration in the lungs -> coughing, wheeze Late illness: - Correlates with worm burden in the GI tract - Adults bite on intestine and suck blood -> anaemia

Answer 358

- Often asymptomatic - Adults rarely pass spontaneously - worms hold on tight and only 1cm long - Two adults sit and sexually reproduce in GI tract + blood suck -> can last for years - Nausea, abdominal pain + diarrhoea - Late infections - Hookworm anaemia -> major concern in endemic areas - Each adult: 0.03-0.2ml blood/day - May contribute to growth restriction in heavily-infected children

Answer 359

Eggs in faeces Rhabditiform larva hatches Development to filariform larva in environment Filariform larva penetrates skin Larvae can be developmentally arrested and dormant in tissues Reactivated larvae may enter the small intestine If they get into lung circulation -> exit -> coughed up and swallowed Eggs in faeces

Answer 360

Skin penetration via larvae through skin BUT animals definitive hosts Adults in small intestine Eggs in faeces of animal definitive host Hatched rhabditiform larva develops in environment Rhabditiform larva develops into infectious filariform larva

Answer 361

Hookworm Person lies on beach that dogs have been running on etc (ie there faeces have been in contact with beach) Get rash wherever their faeces touched -> clinical diagnosis of cutaneous larva migrans Treat with ivermectin or albendazole

Answer 362

Hands carry infective ova from soil contained with human excreta/dust/veg etc Larvae penetrate mucosa Enter lymphatics and venules Migration to right heart and lungs -> into alveoli -> moult twice Ascend resp tree -> descend oesophagus to mature in intestine Maturation in humans 2 months Adults live around 1 year and make 100,000 eggs a day Eggs leave body and complete cycle -> have to complete in soil before affecting the next person

Answer 363

1. Kill the worms ○ Albendazole ○ Mebendazole ○ Pyrantel pamoate 2. Manage the complications ○ Surgery for obstruction ○ ERCP for pancreatitis 3. Break the cycle ○ Better sanitation ○ Hand hygiene ○ MDA

Answer 364

Early infection: - Asymptomatic Can get lung migration and Loeffler's syndrome -> IgE mediated response to larvae in lungs -> transient wheezing, coughing, chest pain, haemoptysis May see Charcot Leyden crystals on microscopy Late infection: GI worm burden related -> can be asymptomatic Nausea/abdominal pain/diarrhoea Malnutrition GI complications eg bowel infection /perforation -> peritonitis Ectopic infection -> migration up biliary tree causing pancreatitis, biliary sepsis and peritonitis

Answer 365

Strongyloides

Answer 366

- Usually asymptomatic - Larval invasion of the GI tract → Abdominal pain, intermittent diarrhoea - Larval penetration → petechial haemorrhages and pruritis at site of entry (eg peri-anal skin) - Larval migration → Rash → cutaneous larva currens - Larval invasion of the lungs → cough, wheezing, chronic bronchitis

Answer 367

Filariform larvae in soil penetrate skin Larvae move via venous system into lungs Larvae swallowed and develop into adult females in GI tract -> eggs produced by asexual reproduction Eggs hatch into rhabditiform larvae -> excreted in stool Some rhabditiform larvae transform to filariform larvae and reinvade gut wall -> reinfection The rhabditiform larvae outside of the body develop and mate ie adult males and females reproduce sexually and develop into filariform larvae

Answer 368

Cutaneous larva currens - Intensely pruritic - Moves linearly for hours (faster moving, shorter duration than hookworm’s cutaneous larva migrans) - Represents IgE-mediated response to filariform larval migration - Resolves quickly when larvae enter circulation

Answer 369

- Usually asymptomatic - Less commonly → eosinophilic pneumonitis - IgE-mediated immune response to larvae in the lungs - Transient cough, wheezing, chest pain and haemoptysis - Lobar infiltrate on chest x-ray may mimic bronchopneumonia Ie “Loeffler’s”

Answer 370

· Immunosuppressed individuals – T-lymphocyte depletion ○ HTLV-1, HIV ○ Malnourished ○ Iatrogenic immunosuppression (steroids, chemotherapy, transplant patients etc) · Leads to a faster reproduction cycle · Migration to ectopic sites · Spread of faecal bacteria to normally sterile sites · Can → recurrent gram negative bacteremia, CNS involvement, granulomas, abscesses…

Answer 371

- Usually eosinophilia - up to 80% ○ Check over a time period as can have periods of high and of normal -> depends on movement of worm - Faecal ova, cysts and parasites – but low sensitivity – worms are difficult to detect as usually few in number. NPV 50% - Serology (ELISA IgG) if immunocompetent ○ Can stay positive for long time -> don't use it as indicator of cure but can use it to diagnose in chronic infection ○ Cross reactivity for other parasitic diseases eg schiso - Test to do: ○ Charcoal stool but not routine In hyper-infection: - Suspect the diagnosis and try to find the worms - Gram negative rod sepsis, bacteraemia, pneumonia, meningitis - Eosinophilia - rare - Serology rarely helpful -> slow turnaround, poor NPV - Look for larvae in stool and the sputum

Answer 372

Ivermectin>albendazole Screen and treat before planned immunosuppression (ie if risk factors then before chemo/radio etc)

Answer 373

Whipworm Embryonated eggs are ingested larvae hatch in small intestine adults move to caecum unembryonated eggs pass in faeces eggs develop in soil -> become embryonated

Answer 374

eg trichuris Severity = correlates with burden of worms Light infections: ○ Abdo pains Heavy infections (800+ worms): ○ Dysentry ○ Growth stunting ○ Associated with anaemia (0.005ml blood/worm/day, unlikely causal, likely multifactorial) ○ Rectal prolapse due to tenesmus Lots of inflammation -> higher intraabdominal pressure -> need to open bowels a lot

Answer 375

Eggs in stool OCP? Adults are visible on colonoscopy Treat with albendazole > mebendazole

Answer 376

Normal eosinophil count

Answer 377

Migrants more likely to have positive serology but negative symptoms Travellers less likely to have symptoms but positive serology

Answer 378

Migrants more likely to have positive serology but negative symptoms Travellers less likely to have symptoms but positive serology

Answer 379

Venom ophthalmia Caused by spitting cobras

Answer 380

1. Immediate irrigation with any clean bland fluid 2. Pain killing eye drops: 1% adrenaline or tetracaine (LA) 3. Fluorescein staining/slit-lamp examination to exclude corneal abrasion 4. Topical Abx eg tetracycline/chloramphenical 5. Topical cycloplegic eg atropine +/- eye pads

Answer 381

Acute conjunctivitis Hypopyon Panopthalmitis Anterior uveitis

Answer 382

Skip lesions Venom comes out of front of fangs Can inject venom into lymphatics Leads to extensive scarring, can need extensive debridement and can end up with contractures Also can get superimposed staph infection on top or marjolin's ulcer

Answer 383

- Growing and ageing populations - Success in preventing and treating communicable disease - Success in preventing childhood disease - Urbanisation and globalisation - Change in RFs eg ETOH, tobacco, diet, physical activity

Answer 384

Aim for 25% reduction in mortality by 2025 Four priority diseases 1. CVD 2. Diabetes 3. Cancer 4. Chronic respiratory diseases Update: 5. Mental and neurological conditions Five priority interventions: 1. Tobacco control 2. Salt reduction 3. Improved diets and physical activity 4. Reduction in hazardous alcohol intake 5. Essential drugs and technologies Update: address air pollution

Answer 385

1. Prevention 2. Primary healthcare 3. Equitable access to medicines 4. Sustainable financing and investments 5. Engaged and empowered communities

Answer 386

Acute and chronic CVD mx Clinical based RF control, smoking cessation, BP control Lipid and diabetes mx Improving medical education Healthcare financing Policies for smoking, diet, physical activity modulation Tackle social determinants of health

Answer 387

Healthy lifestyle counselling Evidence based protocols Access to essential medicines Risk based CVD management Team based care Systems for monitoring

Answer 388

- Black Africans have lower BMI (eg 27) and lower age (51.5) + less co-existing hypertension and more hyperglycaemia HbA1c 9% vs 7.1% (in white Europeans)

Answer 389

Insulin - Insulin injection - Intermediate acting insulin - Long-acting insulin analogues Oral hypoglycaemic - Metformin - Empagliflozin - Gliclazide

Answer 390

Analogue - Rapid or long acting Soluble - Regular - Short - SC or IV Isophane - NPH insulin (Neutral protamine Hagedorn) - Intermediate acting Lente insulin - Zinc suspension Intermediate - long mode of action

Answer 391

Thrifty phenotype diagnosis Also lots of high sugar food/processed etc in LMICs eg South Africa

Answer 392

Rapid acting: - Insulin lispro - Aspart - Glulisine Short acting: - Regular insulin Intermediate acting: - NPH insulin (Neutral protamine Hagedorn) Long acting: - Insulin glargine - Insulin detemir

Answer 393

Dolutegravir can increase conc of metformin by 200 times

Answer 394

Blood Pressure: The integrated care model showed a significant increase in the proportion of patients achieving target blood pressure levels compared to standard care. Glycemic Control: There was a notable improvement in HbA1c levels among diabetic patients in the integrated care group. Quality of Life: Patients reported higher quality of life scores in the integrated care model. Adherence: Higher adherence rates were observed in the integrated care group, indicating better management and follow-up. Hospitalization: There was a reduction in hospitalization rates for chronic disease-related complications.

Answer 395

Low awareness and access to screening Unaffordable drugs, lack of willingness/motivation to engage with services, social norms Lack of retention due to lack of clinicians, poor understanding of conditions, fear of side effects/long term effects and competing priorities Low screening and inaccurate measurements Poor use of guidelines/understanding of diagnosis and management amongst healthcare staff

Answer 396

- Untreated HTN - Infection ○ HIV (southern and central Africa), stroke mimics/CNS infections - SCD

Answer 397

SOL - Tuberculoma - Cryptococcoma - Primary CNS lymphoma HIV associated Ois - Toxoplasmosis - PML Meningitis complications - Acute bacterial meningitis - TB meningitis

Answer 398

Infection: - Risk of stroke, 1-3 days higher risk but can persist for 90 days - Pre-existing risk increased in infections Remodelling: - Especially in HIV - Inflammatory process or latent infection causing vasculopathies eg Moyamoya or RSCV Vasculitis: - Eg TB/VZV/Syphilis - Vasotropism -> attacking of blood vessels and wall inflammation - Endarteritis obliterans - Post-infective inflammatory vasculitis Hypercoagulability - Eg COVID Cardioembolic - RHD - Chagas

Answer 399

- Hypoglycaemia - Migraine - Todd's paresis - Non-HIV associated CNS malignancies - Autoimmune/inflammatory CNS lesions

Answer 400

- Investigations: ○ brain imaging, electrocardiogram, echocardiogram, blood test (FBC, U&Es, LFTs, CRP, HIV, VDRL), Lumbar puncture if indicated - Medications ○ low-cost medication available for management of complications ○ Aspirin ○ Insulin/anti-diabetics ○ Antihypertensives ○ Common oral agents : thiazide, amlodipine, nifedipine, atenolol, enalapril ○ Common IV agents: hydralazine, labetalol ○ Antibiotics/antivirals ○ Variable availability: thrombolytic agents (+/- access to confirmatory imaging) - Rehabilitation ○ Physios usually available but few staff may not meet patient needs ○ Other rehab specialties + equipment may not be available ○ Limited resource for long term / intensive rehab ○ Limited capacity for providing professional care and home f/u

Answer 401

A seizure is a sudden burst of electrical activity in the brain that can affect how a person behaves, moves, or senses things for a short time.

Answer 402

A chronic neurological disorder characterized by a predisposition to recurrent, unprovoked seizures. Key features of epilepsy include: · Recurrent seizures: A person is diagnosed with epilepsy after having two or more unprovoked seizures that occur at least 24 hours apart. · Unprovoked: Seizures are not triggered by immediate, dentifiable causes such as fever, alcohol withdrawal, or acute brain injury. Varied seizure types: Seizures can vary in type and severity. They may involve convulsions (tonic-clonic seizures), brief periods of altered awareness (absence seizures) or focal neurological symptoms (focal seizures).

Answer 403

A neurological emergency characterized by prolonged or repeated seizures without the person regaining consciousness between episodes. It is defined by either of the following criteria: 1. Continuous seizure activity lasting 5 minutes or longer without interruption. 2. Two or more discrete seizures between which there is incomplete recovery of consciousness. Status epilepticus can be divided into two main types: 1. Convulsive Status Epilepticus (CSE): The more common and severe form, where there are continuous tonic-clonic seizures, which can lead to brain injury if untreated. 2. Non-Convulsive Status Epilepticus (NCSE): Characterized by altered mental status and seizure activity without the obvious physical convulsions.

Answer 404

Diazepam Phenobarbital Phenytoin

Answer 405

· Potential interactions between antiretroviral therapy for HIV and antiepileptic drugs · Greatest concern relates to the P450 system enzyme induction effects of several older-generation antiepileptic drugs (e.g. phenobarbital, carbamazepine, phenytoin), which might lower the effective dose of non-nucleotide reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), metabolized by the P450 system. · Consequences include treatment resistance for HIV-infected patients; alternative treatment for seizures needs to be used in epilepsy patients with HIV

Answer 406

- Adult female mosquito mates soon after emergence from pupa and stores spermathecae (the sperm from male mosquitoes) to fertilise batches of eggs. - After the female mosquito blood feeds, egg development starts - Female searches for appropriate quality of water for egg laying - Different species of mosquito make different choices as where to lay their eggs - Larvae may hatch soon after eggs are laid or after some time depending on conditions - 4th instar metamorphoses into pupa - Pupa swims and breathes are but do not feed - Pupa metamorphoses into adult mosquito which emerges at the water surface, stretches its wings and flies away - Both sexes of adult obtain energy from sugary plant juices Only the adult female feeds on blood to get proteins to feed her young

Answer 407

1. Anophelinae 2. Culicinae 3. Toxorhynchitinae (don't like humans)

Answer 408

Never - Japanese - Loa Loa - Lassa, Ebola - HAT - Schistosoma haematobium Very rarely - Onchocerciasis - Schistosoma mansoni

Answer 409

Parts of Latin America have Biomphalaria snail for mansoni but no snail for haematobium (bulinus)

Answer 410

- Trypanosoma cruzi ○ esp in HIV -> causes neurological disease that looks like toxoplasmosis - Endemic mycoses ○ Histoplasmosis esp in HIV ○ Coccidioidomycosis ○ Paracoccidioidomycosis - Leishmaniasis ○ Generally cutaneous, wet ulcers, non-healing wet ulcers Other - Carrion's disease (Oroya fever) -> Bartonella - Bolivian haemorrhagic fever - Oropouche

Answer 411

Testes and Eye Men can transmit in semen months after being sick, whilst being asymptomatic -> can prompt new outbreak

Answer 412

Valley fever eg Coccidioidomycosis

Answer 413

Histoplasmosis Leishmaniasis Actinomycosis TB Lymphoma Paracoccidioidomycosis

Answer 414

Paracoccidioidomycosis

Answer 415

Mexico in north to northern regions of Argentina -> think poor male farm workers Typically asymptomatic pulmonary infection with lymphatic spread -> subsequent immune control leads to granuloma formation -> clearance In children/young adults -> can get disseminated disease via reticuloendothelial dissemination 80/90% who get disease in adulthood -> reactivation of latent foci months-years after initial infection Looks like TB!

Answer 416

Pulmonary infiltrates (77%) and upper respiratory mucosal lesions (>50%). In the upper respiratory tract, the mouth is most commonly affected, with lesions typically appearing as painful ulcers with ragged borders and areas of haemorrhage. Involvement of the skin, lymph nodes, CNS and adrenal glands are also well-described but any organ system can be involved and occult disease is common. Disease is multifocal in 75% of cases.

Answer 417

Histopathological tissue examination with Grocott or periodic acid-Schiff stains is highly sensitive (>95%), but more invasive. The size and multiple-budding appearance of the Paracoccidioides yeasts is distinguishing from other endemic mycoses, with ‘ships wheel’ or ‘Mickey Mouse’ structures considered pathognomonic. Culture => can take a month and is affected by site and burden of infection Serology -> risk of cross-activity with other endemic mycosis, sensitivity of around 80%

Answer 418

Mild/moderate: Itraconazole Severe/CNS: Amphotericin B induction therapy then itraconazole

Answer 419

Valley fever -> lots in Latin America but can be in Arizona or surrounding states Symptoms: - Fatigue - Fever + night sweats - Weight loss - Cough, CP, dyspnoea - Haemoptysis - Headache - Arthralgia - Looks like TB Clinical - Erythema nodosum (25% of pulmonary) - Erythema multiforme Can also have dissemianted form with extensive cutaneous involvement and multisystem involvement CXR - Pulmonary infiltrates - Hilar adenopathy Pleural effusions -> can mimic TB

Answer 420

Symptoms: - Incubation 3-10 days - High fever + headache + myalgia/arthralgia + rash ~25% - Severe: neurological eg meningoencephalitis, haemorrhagic eg gingival bleeding, epistaxis, petechiae - ?Biphasic -> ~60% have relapse type picture and get sick again - Low case fatality rate Ddx: - Arboviruses eg dengue, Chik, Zika Vectors: Culicoides paraensis = biting midges + Culex quinquefasciatus, Coquillettidia venezuelensis, and Aedes serratus mosquitoes

Answer 421

Oropouche virus

Answer 422

Virus: Machupo virus Animal: Calomys callosus eg large vesper mouse Epi: - Range of reservoir and human movement Treatment: ribavirin

Answer 423

Ebola -> west, tropical rainforest Marburg -> drier forest or savannah in East

Answer 424

Microvascular instability with capillary leak + impaired haemostasis +/- DIC Fever/headache/asthenia/hepatosplenomegaly but no lymphadenopathy/possible early maculopapular rash/N&V&D/bleeding eg from gums, conjunctival haemorrhage, rectum

Answer 425

Fruit bats Human infection likely occurs due to exposure to infected bat excreta or saliva Miners/forest workers/spelunkers at high risk, esp for Marburg -> have they been into a cave or mine?

Answer 426

Nonhuman primates esp gorillas and chimps and other wild animals -> humans come into contact with their blood and bodily fluids Esp through hunting or butchering

Answer 427

Female sandflies -> Tunga penetrans -> burrows into epidermis of humans, often in feet to lay eggs Pale nodule with dark centre that develops into brown/black with crust, slow growing nodules on feet (periungal regions/interdigital), systemically otherwise well. Due to contact with contaminated soil. Ix: Look for parasite and eggs in tissue samples and histopathological specimens Clinical diagnosis Mx: - Check they have received tetanus injection/booster - Remove flea with sterile needle, disinfect

Answer 428

ITN = insecticide treated nets

Answer 429

Need to target outdoor stage, ie most interventions currently aimed at within the home which is unrealistic - Financing - Drug resistance - Vector resistance ○ Biochemical ○ Behaviour - Diagnostic resistance - Organisational - Climate change

Answer 430

Anopheles - gambiae - funestus - arabiensis

Answer 431

Egg Stage: Larval Source Management (LSM) Larval Stage: Larval Source Management (LSM) Pupal Stage: Larval Source Management (LSM) Adult Stage: Insecticide-Treated Nets (ITNs) Indoor Residual Spraying (IRS) Space Spraying Personal Protection Measures Feeding Stage: Personal Protection Measures Genetic Control: Genetic approaches (e.g., genetically modified mosquitoes)

Answer 432

1. Insecticide resistance 2. Invasive vectors eg Anopheles stephensi 3. Climate change 4. Diminished access, use and durability of insecticide treated nets (ITNs 5. Funding 6. Outdoor transmission (residual transmission) * Increase in vectors biting outdoors -> reducing efficiency of indoor vector control tools like ITNs and IRS 7. Natural disasters, conflict situations and demographic changes

Answer 433

· Warmer temperatures can alter vector survival, abundance and increase the geographical spread of malaria vectors · Extensive rainfalls and floods can create more breeding sites extending malaria transmission seasons. · Changes in weather can alter mosquito composition, resulting in higher densities of more efficient vectors. · Weather changes can affect human behaviour facilitating habits that expose them to vectors e.g sleeping outside in hot weather · Temperature changes accelerate changes in vector behaviour, enabling them to escape traditional vector control interventions · Temperature and humidity changes can affect the efficacy of some vector control products

Answer 434

- Historically Asian vector eg India, Iran, Pakistan and Arabian penninsula - Efficient vector of urban malaria (plasmodium falciparum and vivax) - Breeds in domestic and other artificial water containers, man made pits etc -> urban settings -> current management not build to handle this - Can resist high temperatures so can sustain transmission in dry seasons - Vector difficult to target with standard vector control What can be done? * Increased vector surveillance * Increase collaboration between different sectors * Bye laws on water storage especially in urban settings * Increase vector control strategies that can target the vector e.g larviciding * On-going coordination meetings led by WHO

Answer 435

* Bait stations (attractive targeted sugar baits) * Spatial repellents * Systemic insecticides and endectocides * Genetic manipulation, including gene drive and self-limiting systems * Topical repellents * Insecticide treated clothing * Housing modification * Lethal house lures (EaveTubes)

Answer 436

1. Dual ITNs (Pyrethroids + new Insecticide) 2. New IRS eg Pirimiphos-methyl, Clothianidin, eg Broflaniline WP ( Vectron T500, under evaluation)

Answer 437

Administration of a full therapeutic courses of antimalarial treatment to a population at risk, whether infected or not, at defined time points separated by periods without drug exposure people living in endemic areas

Answer 438

Administration of an anti-malarial drug to an at risk population in such a way as to achieve protective blood levels over the whole of the period of risk sub-therapeutic doses primarily used by non-immune travelers to malaria endemic areas

Answer 439

1. Intermittent preventive treatment of malaria in pregnancy (IPTp) - give from 13 weeks gestation onwards, at least 3 doses during pregnancy, give at antenatal visits, allow 1 month between treatment times 2. Perennial malaria chemoprevention (PMC), previously known as intermittent preventive treatment in infants (IPTi) - From 10 weeks of age onwards up to 24 months - Sulfadoxine-Pyrimethamine normally used, with ACT now being considered 3. Seasonal malaria chemoprevention (SMC) previously known as intermittent preventive treatment in children (IPTc) - Door to door/community based intervention - Use Sulfadoxine-Pyrimethamine and Artesunate Combination Therapy (SPAQ) 4. Intermittent preventive treatment in school aged children (IPTsc) 5. Post-discharge malaria chemoprevention (PDMC)

Answer 440

Sulfadoxine-Pyrimethamine and Artesunate Combination Therapy

Answer 441

1. RTS,S/ASO1E (Mosquirix ®): Oct 2021 2. R21 /Matrix M : Sep 2023

Answer 442

Circumsporozoite protein

Answer 443

RTS,S/ASO1E (Mosquirix ®) - 3 primary vaccinations were given prior to the season followed by an annual booster dose until children reached 5 years of age - Compared with and to seasonal chemoprevention - RCT showed non-inferior to seasonal chemoprevention alone, even higher efficacy when combined - Reduction in incidence, hospital admissions and deaths R21 /Matrix M - RCT - Reduction in time to first episode and all episodes, seasonal > standard by ~5% - Efficacy held at all and seasonal sites at 24 months

Answer 444

Intermittent preventative treatment in pregnancy Seasonal malaria chemoprevention

Answer 445

Anopheles Culex Aedes Mansonia

Answer 446

Culex (tritaeniorhynchus)

Answer 447

Culex (pipiens)

Answer 448

Aedes, Haemagogus, Sabethes

Answer 449

Dengue Zika Chikungunya Lymphatic filariasis Yellow fever

Answer 450

- Adult female mosquito mates soon after emergence from pupa and stores spermathecae (the sperm from male mosquitoes) to fertilise batches of eggs - After the female mosquito blood feeds, egg development starts - Female searches for appropriate quality of water for egg laying - Different species of mosquito make different choices as where to lay their eggs - Larvae may hatch soon after eggs are laid or after some time depending on conditions - Larvae swim, feed, breathe air and develop through 4 larval stages called instarts - 4th instar metamorphoses into pupa - Pupa swims and breathes are but do not feed - Pupa metamorphoses into adult mosquito which emerges at the water surface, stretches its wings and flies away - Both sexes of adult obtain energy from sugary plant juices -Only the adult female feeds on blood to get proteins to feed her young

Answer 451

Endophagic Exophagic

Answer 452

Endophilic or exophilic

Answer 453

anthropophilic, exophagic and exophilic

Answer 454

anthropophagic, endophagic, endophilic bites late at night after people are asleep

Answer 455

Each individual/each household etc has equal probability of being included Can use random cluster sample if large population and homogenous distribution of disease

Answer 456

- Number of cases of disease in a defined population at a given point in time - Is affected by duration o Ie if you increase duration of illness then it can drive up prevalence because you capture more people with the illness at that time of disease, but incidence is unaffected

Answer 457

- The number of new cases of disease in a defined population ‘those at risk’ over a specified period of time o Population at risk should not only be those people but how much time they spend at risk

Answer 458

- Number of new cases that arise in population and divides them by the number of people who started off at risk - Counts all people at start, then at end of period of observation tells you how many people got ill during that period o Irrespective of whether they were all at risk at that period of time o Easier to calculate than incidence rate, as you just count how many people you start with and how many have developed outcome disease at the end o But becomes inaccurate if you lose people to follow up as you can’t verify them so your numerator lacks accuracy Defined as: number of new cases in specified period/population of those disease free at start of period of observation If they are not within the numerator then they can’t be within your denominator

Answer 459

Number of new cases that arise in population in specified period/sum of length of time during which each person in the population is at risk - Denominator: person-time at risk - So take every individuals person time at risk over given period of time and add them all together - If you lose people to follow up, the numerator will still lack accuracy If a disease only gives you partial immunity eg Covid, then you can be part of the numerator again when you become at risk again

Answer 460

Adv: rapid sharing of new info about rare occurrences and useful in hypothesis generation Dis: one experience, ?coincidental, lack of comparison group

Answer 461

o A representative sample of a population is studied to quantify a disease, an exposure or both o ‘Snapshot’ of population at a single point in time o Exposure and disease assessed simultaneously § Eg surveys § Trends over time can be examined using repeated cross-sectional surveys eg polling before elections Adv: quick and relatively easy, can measure prevalence, can measure prevalence of RF, can measure demand for service (for health service planning), hypothesis generation Dis: prevalence subject to singular point in time, can’t measure incidence, can’t determine causality

Answer 462

o People with disease (case) and people without the disease (control) are compared by looking at past exposure of each group to potential causes § Retrospective o Adv: Can be useful for investigating causation, particularly if disease is rare or long ‘incubation’ period after exposure (when cohort studies impractical), quick and inexpensive, can examine multiple exposures o Dis: selection bias (ensuring case population is representative of larger control population apart from outcome is hard), impractical if exposure is rare, not always certain that exposure preceded disease, cannot measure disease incidence OR: yes/no for cases compared to yes/no for controls for given exposure

Answer 463

o Study people with a risk factor to see if they develop particular diseases o Can do descriptive or analytic cohort studies o Recruit people free from disease, classify participants at baseline as exposed or unexposed, follow both to determine outcome, compare incidence of outcome between exposed and unexposed o Usually prospective o Adv: can measure incidence, useful for prognosis and causation, useful for rare exposures, can examine multiple outcomes, can show exposure comes from disease, can measure exposure and outcome data directly so more accurate and less risk of bias o Dis: expensive & time consuming, impractical/efficient if outcome is rare, vulnerable to losses to follow up o Retrospective cohort § Construct cohort based on past records § Efficient if accurate outcome data § Problematic if poor data on outcome Nested case-control At end of cohort study when outcomes have occurred, you can select cases (participants who developed outcome of interest during follow-up) and controls (participants who did not develop outcome during follow-up)

Answer 464

o Pre-specify an outcome o Investigator allocates exposure o Randomisation: enables two groups to be balanced for factors/characterisations which could influence the outcome, so you isolate the effect of only the intervention you want (treatment or prevention) o Adv: strongest evidence of effect of intervention, can examine more than one outcome, prospective, eradicates effect of bias o Dis: expensive, time consuming, if not properly planned then can be too small or too short, not always practical (ie if no. of patients needed is prohibitively high, if randomisation is unethical), trials do not necessarily reflect what happens when intervention is delivered routinely ie in real life

Answer 465

Hepatitis ABCE Leptospirosis Arboviruses: Yellow fever virus (AST>ALT) VHF: Lassa fever Herpes viruses: CMV, EBV Malaria

Answer 466

Faecal oral transmission, incubation 4-8 weeks - Children esp <6 ~70% asymptomatic, but spreaders, >6 70% jaundiced - Adults: jaundice, fulminant hepatitis +/- liver necrosis, risk of failure if pre-existing liver disease - If symptoms then can be symptomatic for months - Spontaneous resolution over 1-2 weeks - No chronic HAV Diagnosis: serology IgM/IgG Vaccine ○ Effective in 95% cases, immunity for 20 years Can't give to kids <6 months -> need anti-hepA immunoglobulin

Answer 467

Transmission: blood borne, bodily fluids Incubation: 2 weeks - 6 months Who: - (IVDUs/haemophiliacs issue/needles/tattoos/dialysis) - 15-25% spontaneous clear - 75-85% chronic infection S/S: - <30% symptomatic - Liver failure 1/2% Diagnosis: hep C total Ab +/- Hep C RNA - Ab can persist for whole life - If immunocompromised or high risk (ie might not mount full immune response or slow one) then just do hep C RNA directly - Some Ag tests available Mx: DAAs upon diagnosis (based on detectable HCV RNA) Vaccine: none, reinfection common esp in high risk groups

Answer 468

- Sporadic acute jaundice ○ Genotypes 3/4 ○ Consumption of undercooked or raw pork/game meat and shellfish ○ High income countries - Acute jaundice in Africa and Asia ○ Genotypes 1/2 ○ Faecal contamination of drinking water ○ Humanitarian crises

Answer 469

Hepatitis A, so most people will have Abs

Answer 470

- Treat child with tenofovir or TAF from week 30 to week 4 post-partum - HBV vaccine and HBIG on first day of life HBIG not really available outside high income countries

Answer 471

Acute infection, if persists >6 months then = chronic infection

Answer 472

Ingest cyst Swallow cysts Pass through stomach as resistance to acid Exist/hatch in small intestine Release of trophozoite Multiplication Cysts form Hatching in stool -> infect others

Answer 473

AST to Platelet Ratio Index

Answer 474

Adult males no sex differences in Amoebic dysentry

Answer 475

· Wet-film microscopy (but note cannot distinguish between E. histolytica and E. dispar) ○ Concentrated, fixed and stained faecal samples · Serology - Relatively cheap. Usually strongly positive in ALA, can persist · Tissue biopsies - likely histolytica if seen in tissue · Antigen detection – Not all distinguish Eh/Ed. Reliable? · Nucleic acid methods – Real-time PCR, LAMP, metagenome · Diagnosis of ALA – Imaging, symptoms

Answer 476

- Invasive amoebiasis is almost exclusively treated with metronidazole or other 5-nitroimidazole drugs (equally but no more effective) - Should be followed by a luminal amoebicide– choice depends on what is licensed locally - Paromomycin is most effective for luminal E. histolytica

Answer 477

Small intestine

Answer 478

Large intestine

Answer 479

- Malabsorption of glucose, water, Na+ - Diffuse microvillus shortening - Loss of epithelial barrier function -> increased intestinal permeability - Apoptosis of enterocytes

Answer 480

1. Wet film microscopy of faecal samples ○ Cysts easy to recognise, so specificity is high but sensitivity low 2. Direct fluorescence Ab staining of cysts 3. Ag detection (ELISA/card; slightly less sensitive than DFA) 4. Conventional, multiplex & real time PCR

Answer 481

- Food, water, person to person - Infectious dose is very small ~10 cysts - Cysts are resistant to chlorine and other disinfectants - Efficacy of conventional wastewater treatment processes at removing cysts is limiting - Cysts remain viable for weeks in cold water - Animal reservoirs of some genotypes

Answer 482

Metronidazole (1, avoid in first trimester) / Tinidazole (seems to be slightly better) / Nitazoxanide Paromomycin appears to be effective and is regarded as safe in pregnancy Treatment failures with nitroimidazoles are not uncommon. Drug resistance is a growing problem.

Answer 483

1. Trichomonas vaginalis 2. Trichomonas tenax 3. Pentatrichomonas hominis

Answer 484

- Still largely by wet-film examination - Culture will detect 10-30% more but takes longer - Rapid antigen detection kits provide the speed of wet film & better sensitivity than culture - PCR and other nucleic acid amplification tests (NATS) probably the most sensitive but not yet in routine use

Answer 485

Sexually transmitted Linked to low birthweight and also higher risk of HIV acquisition and transmission

Answer 486

Most common signs and symptoms in women:* - Purulent vaginal discharge - Vaginal and vulvar erythema - Urethra commonly infected causing dysuria In men: - Urethral discharge and/or dysuria - Spontaneous loss of infection seems to be quite frequent The overwhelming majority of infections are asymptomatic (98.5% in men, 73.3% in women)

Answer 487

1. Single 2g dose of metronidazole (MTZ) 2. Tinidazole -> sig more effective but 10x more expensive (also avoid in pregnancy) 3. The most recent CDC STI treatment guidelines now recommend metronidazole 500mg PO BD (women); single 2g dose (men) Metronidazole resistance is a rare but real problem

Answer 488

- Amoeboid appearance but is related to trichomonads - Pathogenicity is controversial and certainly variable - Reported symptoms are non-specific (e.g. diarrhoea, abdominal pain) - The trophozoite will not be found by light microscopy unless specimens are rapidly fixed and stained - If use PCR, infection rate is high in the general population Treatment: - Metronidazole (not particularly effective) - Clioquinol - more effective in reliving symptoms - Tetracycline - also used - Secnidazole - may be the best

Answer 489

Balantioides coli - Both cyst and trophozoite are much larger (> 50 μm) than other gut protozoa - Very common in pigs, but rare in humans - A large bowel parasite - Frequently asymptomatic but can occasionally invade like E. histolytica and cause colitis, dysentery and death - Metronidazole seems to be effective but few recent reports available - Cysts and nucleus are huge

Answer 490

Resistance to 1. Isoniazid (INH) and Rifampicin (RIF), the two most powerful first-line TB drugs (this is what defines multidrug-resistant TB, or MDR-TB). 2. Fluoroquinolones, a class of antibiotics that are key second-line drugs. 3. At least one of the injectable second-line drugs, such as amikacin, kanamycin, or capreomycin.

Answer 491

- Rif resistance +/- isoniazid resistance + resistance to fluoroquinolone (mof/levofloxacin)

Answer 492

- Combo of isoniazid and rifampicin resistance - Unusual to have Rif resistance without isoniazid resistance

Answer 493

Key Goals of DOT: Ensure Adherence Prevent Drug Resistance Monitor Side Effects: Support Patients Types of DOT: In-person DOT: Patients visit a clinic or a healthcare worker comes to the patient's home to observe them taking the medication. Electronic DOT (eDOT): Patients record themselves taking their medication via video, which is reviewed by healthcare workers remotely. This method is increasingly being used where in-person observation is not feasible.

Answer 494

Used for MDR and XDR, treat for 6 months (prior regimens used 9-18 months) Only for adults, no CNS/disseminted/ MDR you can use BPaLM: bedaquiline (B), pretomanid (Pa), and linezolid (L) + moxifloxacin (M) BPaL: bedaquiline (B), pretomanid (Pa), and linezolid (L)

Answer 495

Drop FBC Eye toxicity Peripheral neuropathy

Answer 496

Prolong QTc -> risk of sudden death Hepatitis N&V&Arthralgia

Answer 497

Very expensive

Answer 498

Only use if suspecting TB in HIV Only approved for patients with low CD4 count Only looks for active disease, ie not passive

Answer 499

Rule out active disease Give preventative treatment to children under 5 and HIV positive individuals/high risk

Answer 500

Empirical 6 months levofloxacin

Answer 501

Cutaneous leishmaniasis - localised painless ulcer with raised edges Sporotrichosis -> Sporothrix schienckii Cutaneous TB Balamuthia mandrillaris (amoeba) Francisella tularensis (Tularaemia) -> northern hemisphere only Cutaneous anthrax - but will appear dark

Answer 502

Its the form leishmania takes in the vertebral host otherwise = protist cell that does not have visible external flagella or cilia

Answer 503

Balamuthia mandrillaris

Answer 504

Sporothrix schenckii - dimorphic fungi Found in soil/on plants Enters skin through direct inoculation eg thorny plants/animal scratch Papule -> tender ulcer Lesions can spread along draining lymphatic vessels ?farmer/gardener Hyperendemic in parts of Andes -> children, facial lesions

Answer 505

Protozoa = genus Leishmania Anthroponotic or zoonotic (reservoir small animals) Transmission: sandflies - Lutzomyia (New World) - Phlebotomus (Old World) Incubation period: weeks to months Clinical: depends, most common is localised Old world (Africa/Asia/Europe): >50% heal spontaneously New world (Latin America): <20% heal sponteanously Treatment: OW/NW (but not L.Viannia-complex): intralesional pentavalent antimonial eg sodium stibogluconate SSG, paramomycin cream +/- cryotherapy or thermotherapy Systemic tx: Pentavalent Antimonials (e.g., Sodium Stibogluconate or Meglumine Antimoniate) injections 20-28days OR Miltefosine OR Azoles 2nd LINE: Amphotericin B OR ambisome L.guyanensis: pentamidine

Answer 506

1. Skin scrapping and Giemsa staining -> amastigotes 2. Culture on FNA/biopsy samples 3. Montenegro or Leishmania skin test -> test for delayed immune response

Answer 507

Oculomotor damage -> innervates the levator palpebrae superioris - Lesions can result in complete ptosis Sympathetic damage eg Horner's -> partial ptosis via superior tarsal muscle

Answer 508

Streptococcus pneumonia Neisseria meningitides Streptococcus suis (Asia) Rapid onset, high fever, meningism, CN involvement less common CSF: cloudy, high leucocyte count, polymorphs, low glucose

Answer 509

Mycobacterium TB Hx of several days of illness, slightly less abrupt, CN involvement common CSF: clear, high CSF protein and low glucose

Answer 510

Cryptococcus neoformans Hx: subacute onset, severe headache, CN involvement CSF: normal in at least 25% of cases

Answer 511

- Hepatitis surface Ag (HbsAg) to have hep B, >6 months = chronic - Hepatitis B core Ag (HbcAg) generally means acute infection - Isolated hep B total core Ab (HbCAb) can mean prior infection - Core IgM Ab = acute infection

Answer 512

Transmission: body fluids, blood etc Incubation: 1-6 months Who: * Acquiring as child -> MUCH higher risk of CHRONIC infection, worse if vertical transmission ○ <1 year: usually asymptomatic ○ >1 year: symptomatic infections * 30% symptomatic, 95% adult cases will resolve, 1% liver failure · 5-10% of adults get chronic infection · Only need a small amount of exposure to blood with high viral load Diagnosis: - Hepatitis surface Ag (HbsAg) to have hep B, >6 months = chronic - Hepatitis B core Ag (HbcAg) generally means acute infection - Serology for HBV Core IgM Vaccine: Recombinant HbsAg - 3 doses - 95% effective in healthy people

Answer 513

Transmission: Faecal-oral, domestic pigs/deers Incubation: 4-8 weeks, often preceded by prodrome and diarrhoeal illness Who: - Sporadic acute jaundice ○ Genotypes 3/4 ○ Consumption of undercooked or raw pork/game meat and shellfish ○ High income countries - Outbreaks of acute jaundice in Africa and Asia ○ Genotypes 1/2 ○ Faecal contamination of drinking water ○ Humanitarian crises - Mortality in pregnant women can be up to ~20% S/S: - Mild or symptomatic - Typically resolves spontaneously over 1-2 weeks - Liver failure rare except in pregnancy (acute liver failure in 20%), chronicity recognised in immunocompromised Diagnosis: - Serology (IgM/IgG) and molecular testing (HEV RNA) Vaccine: Licensed in China, global trials ongoing in women of child bearing age

Answer 514

- RCTs have not demonstrated efficacy but are safe - Lamivudine/entecavir/tenofovir if 2 of ○ Hepatic encephalopathy ○ Bilirubin >10mg/dL (171micromol/L) ○ INR>1.6

Answer 515

- 7.4% globally - Much more likely to develop chronic HBV 30% - HIV/HBV coinfection indication for treatment with ART against HBV (tenofovir/emtricitabine or lamivudine backbone) - Without treatment -> progression to cirrhosis can be rapid - Treatment does not totally stop disease progression

Answer 516

1. Acute inflammation -> carcinogenic properties of virus directly -> HCC ○ Uncontrolled hep B can cause liver cancer due to integration into host genome 2. Acute inflammation -> Fibrosis -> cirrhosis 20% (30% decompensated) -> HCC 1-4% annually

Answer 517

Nucleot(s)ide reverse transcriptase inhibitors (NRTI) suppress viraemia eg TDF But CANNOT get rid of DNA in nucleus of hepatocytes due to cccDNA forming minichromosome that remains despite therapy Means virus can reactivate later in life eg if immunosuppressed - Treat ○ Functional cure -> does not rule out risk - Minimise superimposed risks ○ No etoh ○ Lower infection risk ○ Control metabolic syndrome ○ Behaviour -> eg avoid groundnuts, cooking equipment with led etc

Answer 518

- Reduction to zero of the incidence of a disease in a defined geographical area - Continued interventions required to present re-introduction Eg Polio in the Americas

Answer 519

- Permanent reduction of worldwide incidence to zero of infection caused by specific agent - Continued interventions required to present re-introduction Eg Polio in the Americas

Answer 520

- An effective intervention is available to interrupt transmission - Surveillance: Practical diagnostic tools of sufficient sensitivity and specificity to detect levels of infection that can lead to transmission are widely available - No animal reservoir - The disease must be widely recognised to be of public health importance - Elimination must be perceived as a worthy goal by all levels of society - A technically feasible intervention must have been field-tested and found effective - Political commitment must be obtained at the highest levels (WHA resolution) - Advocacy plan must have been prepared

Answer 521

Resolved to sustain, expand and extend programmes that ensure the necessary supply of drugs and other interventions to help eradicate Guinea worm disease, and help eliminate by 2020 lymphatic filariasis, leprosy, human African trypanosomiasis and blinding trachoma

Answer 522

* Yaws * Guinea worm

Answer 523

* Onchocerciasis in South America * Human African trypanosomiasis due to T.b.gambiense * Schistosomiasis – in China, Eastern Mediterranean, Caribbean, Indonesia, Mekong basin – In the Americas and Western Pacific Region * Chagas disease through blood transfusion (2015); intra-domiciliary * Rabies in SE Asia and Western Pacific

Answer 524

* Blinding Trachoma * Leprosy * Visceral leishmaniasis in the Indian sub-continent * Lymphatic filariasis

Answer 525

- Large numbers of people, vectors or intermediate hosts may need to be sampled ○ Tests should be high throughput ○ Pooling can save time and money ○ Tests do not necessarily need to be at the point of care - Sensitivity should be high - False positives must be kept to a minimum - Tests must be highly specific

Answer 526

○ Annual or twice yearly MDA with single dose ivermectin and albendazole, plus DEC in regions where there is no onchocerciasis – reduces microfilaraemia but does not kill adult worms

Answer 527

- Zero Grade 2 disability (G2D) among paediatric leprosy patients - Reduction of new leprosy cases with G2D to less than one case per million population - Confirmed absence of children with leprosy for 5 consecutive years - Zero countries with legislation allowing discrimination on basis of leprosy

Answer 528

T. brucei gambiense - Insidious onset (“sleeping sickness”) - No confirmed animal reservoir - POC screening test available (lateral flow HAT Sero-K-SeT) T. brucei rhodesiense - Acute onset - febrile illness - Zoonosis - Blood film usually positive

Answer 529

– Until 2019 * Stage 1: Pentamidine IM * Stage 2: Nifurtimox + eflornithine IV – Now * Fexinidazole is an effective oral treatment for stage 2 T. gambiense

Answer 530

Now: Fexnidaxole PO for both stages Old guidelines ○ Stage 1: Suramin IV (stage 1) ○ Stage 2: Melarsoprol IV + prednisone (stage 2)

Answer 531

- 90% reduction in the number of people requiring interventions against NTDs - 100% of population at risk protected from out of pocket health payments due to NTDs - 100 countries have eliminated at least 1 NTD - 2 NTDs have been eradicated - DALYs lost to NTDs reduced by 75%

Answer 532

1. Flies 2. Fomites 3. Fingers Within Family or among close Friends 5Fs

Answer 533

- Initially tetracycline ointment BD for 6 weeks - Trial by Prof Bailey RCT, single-blinded in 2 Gambian villages showed single dose PO Azithromycin (20mg/kg) showed better adherence and treatments were equivalent Reinfection was common Now also - Surgery - Facial cleanliness + hygiene

Answer 534

Baseline survey: - 5 years MDA where TF ≥30% in 1-9 year-olds - 3 years MDA where TF 10-29.9% - 1 round of MDA where TF 5-9.9% Impact surveys: - 1-5 years after SAFE interventions began Surveillance surveys: At least two years after an impact survey has shown the TF prevalence to be <5% in 1-9 year olds

Answer 535

Chlamydia trachomatis - Bacterium - Intracellular organism (biphasic developmental cycle) Infects mucosal epithelial cells of genital tract and conjunctiva

Answer 536

- Serological ○ TPPA (treponema pallidum partial agglutination test) § Stays positive for life ○ RPR/VDRL § Titres fall following treatment § Less specific - eg low level false positives from malaria - Molecular PCR can differentiate sub-species

Answer 537

Treponema pallidum pertenue Found in warm/humid environment ○ West Africa ○ South America ○ Pacific ○ South-East Asia Children = main reservoir of siease Transmission ○ Skin to skin contact ○ ?Flies

Answer 538

Primary: § Painless ulcer or nodule (>1cm, raised, solid) in trop world known as papillomas § More papillomas in West Africa as proportion of cases § These particular lesions heal within a few weeks Secondary Then spread of bacteria -> general illness, disseminated § Destructive lesions of skin/soft tissue § Face, nasal mucosa, bones of lower limbs § No neuro involvement/no CVS disease Tertiary § Asymptomatic between stages § Can become latent at any stage § No clinical signs of disease § Latent cases -> important source of reinfection and onward transmission § Ratio latent : clinical between 6-10:1

Answer 539

India and Equador

Answer 540

Dual Path Platform (DPP) Syphilis Screen and Confirm Test: - Detects treponemal and non-treponemal Abs - Can differentiate between an active infection (non-treponemal antibodies present) and a past infection (treponemal antibodies alone) Treponemal-Specific Rapid Diagnostic Tests: treponemal Abs only so can't distinguish between active and past infection

Answer 541

YAWS3 trial One round of MDA, followed by targeted treatment of active cases and their contacts VS Three rounds of MDA at six-month intervals before transitioning to targeted treatment. ○ Three rounds of mass azithromycin administration for yaws eradication ○ Multiple rounds of treatment enable opportunity to address treatment reservoir in addition to acute cases A single round of MDA significantly reduced the prevalence of yaws, it was insufficient to eliminate transmission in the long term. Reintroductions of yaws occurred due to untreated latent cases or people who missed the MDA. In contrast, the strategy of three rounds of MDA was more effective in maintaining lower prevalence and reducing the risk of re-emergence. Additionally, the trial highlighted the need to monitor for potential macrolide resistance, as azithromycin-resistant strains of Treponema pertenue had been detected in some cases

Answer 542

Poor data on epi + serological same amongst different species of treponema Limited funding MDA with azithromycin creating resistance (de-novo mutations) Potential for animal reservoirs -> similar infections in non-human primates

Answer 543

– Mapping to identify current foci – Mass treatment with azithromycin (likely with multiple rounds) – Surveys to identify cases & contacts – Mop-up Treatment – Integrate with other skin NTDs

Answer 544

T.pallidum ssp pallidum -> Syphilis T.pallidum ssp pertenue -> Yaws T.pallidum ssp endemicum -> Bejel T.carateum -> Pinta

Answer 545

- T.carateum - Found in warm, humid environments ○ Restricted to Latin America - Active cases in young adults are main reservoir of infection Transmission: skin to skin contact

Answer 546

- "Endemic syphilis" - T.p.endemicum ○ Found in dry environements eg § The gulf § The sahel - Children = main reservoir Transmission via ○ Skin to skin contact ○ Indirect contact via utensils

Answer 547

What could help with success? - Easily identifiable disease - Relatively simple and vulnerable life-cycle - Cheap, easy interventions - Community focused interventions - Vertical health programme - Political and economic support Obstacles to success? - Insecurity (political etc) - Population movement - Donor fatigue - Community fatigue - Atypical transmission (dogs get infected by paratenic host) - Pseudo-presentation

Answer 548

Guinea worm 60cm large nematode

Answer 549

An organism that harbors a parasite but is not necessary for the parasite's development to its adult or infective stage. In other words, the parasite can survive and remain infective within the paratenic host, but it does not undergo any further development there. The host simply acts as a temporary "carrier" or "reservoir" for the parasite until it reaches its definitive host, where it will complete its life cycle.

Answer 550

- Lives for 10-14 months as worm in human host - 14 days as larvae in water - 14 days developing as larvae in vector until it can infect a human again

Answer 551

1. Yaws 2. Leprosy (Hansen’s disease) 3. Onchocerciasis 4. Lymphatic filariasis (lymphoedema and hydrocele) 5. Buruli ulcer 6. Cutaneous leishmaniasis 7. Mycetoma, chromoblastomycosis, and other deep mycoses ( including sporotrichosis) 8. Post-kala-azar dermal leishmaniasis 9. Scabies 10. Tungiasis

Answer 552

Mycobacterium ulcerans WHO - Poor inhabitants, remote rural areas, limited access to healthcare services - All ages and socioeconomic groups - Africa ~50% aged <15 years - Australia: adults mostly affected TRANSMISSION - Trauma -> introduction of mycobacterium to skin - Occurs in people living close to lakes, rivers, marshy areas, mining, deforestation or flooding - Inoculation into skin by ○ Aquatic insects ○ Mosquitoes

Answer 553

Buruli ulcer toxin called mycolactone Variants driven by chemical modification of side chain of toxin: ○ A/B: African strains ○ C: Australia ○ D: Asia Pathogenesis driven by toxin? ○ Low concs of toxin cause suppression of dendritic cells, macrophages, T-cell function abrogating cytokine and chemokine secretion in response to mitogens Downregulation of inflammatory mediators, lipid metabolism Early lesions: - Clumps extracellular mycobacteria - Subcutaneous fat necrosis Sparse inflammatory infiltrate Late lesions: - Areas of acute and chronic inflammation including: * few mycobacteria granulomatous inflammation

Answer 554

Incubation: 32-264 days (mean 4.5 months) No constitutional symptoms associated Lesions appear on all parts of body but predominantly on the limbs (up to 85%) Bones involvement (6-25% of lesions in Benin) Active disease: - Non-ulcerative (papule, nodule, plaque, oedema) - Ulcerative forms and osteomyelitis - Painless, NO LN involvement (usually) - firm, immobile If not treated: Ulceration -> necrosis -> sloughing - indurated/undermined edges, painless

Answer 555

* Abscess---------------------------Painful * Lipoma----------------------- Mobile * Ganglion-------------------------Close to joints * Tuberculous lymphadenitis----Constitutional symptoms * Onchocerciasis nodule----------Painless, long history * Subcutaneous infections such as fungal infection * Tropical phagedenic ulcers * Arterial and venous insufficiency * Diabetic ulcers * Sickle cell ulcer * Cutaneous leishmaniasis * Extensive ulcerative yaws * Haemophilus ducreyi ulcers Non Buruli ulcers are often painful

Answer 556

1. Swab ○ Get under the undermined edge of ulcerative lesions 2. FNA ○ For non-ulcerative lesions eg nodules/papules/oedema/some ulcerative lesions 3. Biopsy in case of surgery GOLD standard: PCR (sensitivity 98%) Other: - Culture (sens 49%) - Histopathology (sens 82%) - Microscopy for AFB (sens 42%)

Answer 557

Rifampicin 10mg/kg + Clarithromycin 15mg/kg DAILY for 8 WEEKs In Australia: sometimes use Rif + Moxifloxacin *but no RCT ALSO: - Enhance wound healing: nutrition, wound care, skin grafting - Disability prevention - Rehabilitation § <2% patients § Skin rash (Rifampicin) § Anorexia/nausea/abdo pain/jaundice/renal failure (Rif) § Nausea/altered taste/jaundice/hepatitis (Clari) § Tendonitis, rash (Moxifloxacin)

Answer 558

Paradoxical reaction - Multiple nodular lesions 2 weeks after start of Abx - Inflammatory reaction that, prior to antibiotic treatment, is suppressed by mycolactone, the M. ulcerans toxin. - As the organisms are killed by antibiotics, mycolactone production ceases and its suppressive effect is lost causing a rebound of inflammation - Associated with high bacterial load Can consider steroids but should heal on its own Cover lesions with vaseline gauze + control lymphoedema with short stretch bandages +/- grafting

Answer 559

- Contractures - Cancer - Amputation - Eye complications - Severe mental distress and reduced QOL - Burden on caregivers - Stigmatising

Answer 560

Steadily progressive foot and leg swelling (lymphoedema), often confused with lymphatic filariasis Caused by triad of: - Exposure to irritant soil - Genetic susceptibility (link to SNPs in HLA Class II locus (particularly HLA DQA1) in Wellcome funded study) - Foot vulnerability (lack of shoe-wearing and foot hygiene) + long term exposure Rare in children, more common at higher altitudes and with Smectite in soil, farming communities + barefoot

Answer 561

- Clinical ○ Hx, physical O/E, Ag and Ab tests to rule out lymphatic filariasis - Early signs ○ Itching, burning, splaying of forefeet, reversible plantar oedema, hyperkeratosis - Later signs ○ Persistent oedema, inter-digital maceration, nodules, 'mossy' changes, 'waterbag' or 'fibrotic' swelling

Answer 562

Podoconiosis Lymphatic filariasis Onchocerciasis Leprosy Protein-energy malnutrition in children

Answer 563

- Sea level: Podo>1500m, LF<1000m - Diagnosis: LF field ICT blood test, Podo clinical - First symptom site: LF not food, Podo toes/foot - LN attacks: LF precede swelling of limb, Podo follow swelling of limb - Chief site of swelling: LF above/below knee, Podo below knee - Prevention: LF mosquito nets/MDA, Podo: footwear/coverings/foot washing - Treatment: LF 2 drugs (albendazole/DEC) + foot hygiene, Podo: foot hygiene, bandages, socks etc

Answer 564

- Bacterial co-infection (high rates of drug-resistance organisms found, mix gram neg + gram positive Bac) - Acute episodes (ADLA) characterized by malaise, fever, chills, diffuse inflammation and swelling of the limb, lymphangitis, adenitis and skin peeling ○ Require analgesia (e.g. paracetamol), fluids and antibiotic such as penicillin - Ulcer not responding to care -> refer to a surgeon for biopsy (?SCC/BCC) - Deep fungal infection. Additional swelling, on which small black dots may be visible -> refer to surgeon - Psychosocial and MH burden

Answer 565

Hygiene - BD, room-temp washing of limbs Skin care - Wash + dry + rub ointment/emollients, if breakages then washing + antibac/fungal creams, cover with sterile gauze for fly protection Bandaging - To reduce swelling, from toes to knee, V design, 5cm above upper limit of swelling (give people 2, one to wash and one to use) Elevation and exercise - Raise affected limb at night, ankle circles Footwear - Clean socks + feet, clean between toes, avoid tight shoes + low heel Treatment of acute attacks - Rest& elevate affected limb - Coldwater immersion/cold soaked towels - Anti-histamines + analgesia - Encourage fluids - Abx if no improvement in 24hrs - Refer if pregnant, rigors, high fever, vomiting, confusion - ?Associated diseases DON'T: exercise, warm/heat on skin, open/cut blister or skin, bandage, rub herbs etc, use scarification

Answer 566

Rapidly acting orofacial gangrene Affects kids aged 2-5 years old 14,000 cases yearly but now focused in South America, Africa and parts of Asia Opportunistic infectioninte Range of organisms found but not consistently (Fusobacterium necrophorum, Prevotella intermedia, Klebsiella, Streptococcus, Porphyromonas gingivalis, Campylobacter rectus, Treponema denticola) Risk factors = No care access + socio-demographics + comorbidities - Aged 2-5 years - Chronic malnutrition - Comorbidities - Lack of access to quality healthcare including childhood vaccinations - Not being breastfed - Poor oral hygiene practices - Low socioeconomic status of the family High no. of previous pregnancies in mother

Answer 567

0: Simple gingivitis - Bleeding when touched or during brushing - Red or purplish red gum - Swelling gum 1: Acute necrotising gingivitis (indefinite duration) - Spontaneous bleeding - Painful ulceration of gum - Ulceration with 1+ interdental papillae - Fetid breath or halitosis - Excessive salivation 2: Oedema (1-2 weeks) - Rapid extension of gingival ulceration and mucosal tissue - Fetid breath or halitosis - Facial swelling or oedema - Painful cheek - High fever - Excessive salivation - Mouth soreness - Difficulty eating - Anorexia - Lymphadenopathy 3: Gangrene (Progresses in 1-2 weeks) - Excessive destruction of intraoral soft and hard tissue - Lesion with well demarcated perimeter surrounding blackened necrotic centre - Separation of slough -> leaves hole in face often around cheeks or lips - Difficulty eating - Perforation of cheek + exposition of teeth/denuded bones - Progressive drying of facial gangrene, anorexia, apathy 4: Scarring - Trismus (depending on lesion location) - Sequestration of teeth and exposure of bones 5: Sequelae - Disfiguring - Trismus - Teeth loss/displacement/dental anarchy - Feeding + speech difficulties - Fusion of maxilla and mandible bones - Nasal regurgitation

Answer 568

> Tooth abscess > Cellulitis > Animal bites > Burn injuries > Syphilitic yaws > Buruli ulcer > Leprosy > Oral cancer > Chemical burns Noma: will be quick destruction of facial tissue in a child with comorbidities, with well defined perimeter

Answer 569

Abx -> typical antibiotic regimen often includes: Metronidazole (for anaerobes) Penicillin or Amoxicillin (for aerobic bacteria) Gent if gram neg Wound debridement Nutritional support Reconstructive surgery Physiotherapy Psycho-social support

Answer 570

Cirrhosis -> treat with tenofovir or entecavir, if a child then with entecavir No cirrhosis? Basically persistently abnormal ALT + high VL -> treat If VL <20,000 then defer and monitor If ALT not that abnormal and/or lower VL -> defer and monitor Should get regular screening for HCC/treatment response/toxicity (renal esp)

Answer 571

HDV suppresses both HBV and HCV replication (DNA/RNA levels do not predict outcome)

Answer 572

- Single stranded RNA - Can only infect with HBV (takes 3 proteins for viral envelope) - Transmission: blood/body fluids (MTCT is rare) - Epidemiology: 5% of HBsAg carriers (high seroprevalence in Middle East, Central Asia and South America and high-risk groups: IVDU, MSM, SW (a/w HCV, HIV) - up to 80%) - Incubation: up to 3/12 - Course: usually found in screening of acute hepatitis or progressive chronic liver disease - Co-infection: acute self-limiting; chronicity rare - Superinfection: 5% acute liver failure; 80-100% chronicity; rapid progression (up to 80% cirrhosis in <10 years) - HDV suppresses both HBV and HCV replication (DNA/RNA levels do not predict outcome) - Diagnosis: serology (IgM/IgG) or molecular testing (RNA); guidelines for testing inconsistent (EASL: low HBV DNA and high ALT) Treatment: IFN𝛼 <30% SVR at 6/12

Answer 573

DAAs usually 8-12 weeks, for all serotypes so genotypic testing not required eg Sofosbuvir/Velpatasvir Glecaprevir/Pibrentasvir Good SVR (sustained virologic response) >95%: measured as virus is no longer detectable in the blood 12 weeks after completing therapy If uncompensated cirrhosis may need longer course

Answer 574

1. Eclipse phase ○ Infection of mucosal tissue 2. Viral stage I (viral RNA) ○ Viraemic ○ Test still negative 3. Early Ag ○ P24 Ag 4. HIV-specific Ab response ○ ELISA ○ Western blots ○ Partial control of viraemia but not complete ○ Chronic infection ○ Early chronic infection stage

Answer 575

Time between infection and test at which 99% of infections should be identified 4th/5th Gen: 45 days (4th gen median 18 days, IQR 13 - 24) POCT/self-tests: 90 days

Answer 576

Send pro viral DNA

Answer 577

* Drug resistance mutations in HIV usually come at a cost to the virus, making it less "fit" in the absence of the drug. These resistant strains may replicate more slowly or less effectively compared to the wild-type virus. * When the selective pressure from the antiretroviral drugs is removed (for example, if the patient discontinues treatment), the wild-type virus can outcompete the drug-resistant strain because it is generally more fit. * As a result, the virus reverts to its original, drug-sensitive form. Importance of Reversion to Wild Type: * Clinical Implications: Reversion to wild type can be beneficial in terms of restoring sensitivity to the original drug, meaning that the same ART regimen may become effective again if resistance had previously developed. * However, even though reversion occurs, archived resistance mutations can still persist in the viral reservoir and may re-emerge if the same drug is used again.

Answer 578

Primary HIV (CD4 ~ 350 - 500 cells/mm3) - Asymptomatic, acute retroviral syndrome Clinical stage 1 (CD4 ~ 350 - 500 cells/mm3) Asymptomatic Persistent generalised lymphadenopathy Clinical stage 2 (CD4 ~ 350 - 500 cells/mm3) Lots but Herpes zoster Angular cheilitis Recurrent oral ulceration Papular pruritic eruptions (eosinophilic folliculitis) Weight loss but less than 10% BW Clinical stage 3 (CD4 ~ 200 – 350 cells/mm3) Severe WL >10% BW Persistent oral candidiasis Oral hairy leukoplakia Pulmonary tuberculosis Severe bacterial infections (pneumonia etc) Ulcerative stomatitis Clinical stage 4 (CD4 <200 cells/mm3) HIV wasting syndrome Pneumocystis pneumonia Oesophageal candidiasis Extrapulmonary tuberculosis Kaposi’s sarcoma CNS toxoplasmosis Extrapulmonary cryptococcosis Disseminated non-TB mycobacterial infection Chronic cryptosporidiosis Chronic isosporiasis Disseminated mycosis (dimorphic fungal)

Answer 579

* TB * Lymphoma * Dimorphic fungal * Cryptococcosis * Nocardia * NTM

Answer 580

WHO now provisionally recommend screening all individuals with a CD4 count < 200 cells/µL Treat patients without evidence of CNS disease with high dose fluconazole 1200mg for 2 weeks, followed by standard consolidation and maintenance therapy

Answer 581

6th nerve palsy Inward deviation of the eye (esotropia): The affected eye turns inward toward the nose because the lateral rectus muscle is weakened or paralyzed, while the opposing medial rectus (which pulls the eye inward) is unopposed. Diplopia (double vision): Patients often experience horizontal double vision, particularly when looking toward the side of the affected eye. This occurs because the two eyes are misaligned. Limited outward movement: There is a marked reduction or inability to move the affected eye outward (abduction). For example, if the left 6th nerve is palsied, the left eye won’t move fully to the left. Head turning: To compensate for the double vision, patients may turn their head toward the side of the affected nerve (the side of the weakened lateral rectus muscle). This helps align the eyes and reduce double vision.

Answer 582

Difficult to differentiate between other causes. Headache/meningism/fever/focal neurology/abnormal mental status.

Answer 583

Adults: strep pneumoniae Kids: Hemophilus influenzae, Strep pneumoniae, GNRs eg E coli/Klebsiella

Answer 584

Appearance: Clear/cloudy Opening pressure: raised WCC: raised (normally <500), lymphocytes Protein: greatly raised Glucose: low Serum to glucose ratio: v low

Answer 585

Appearance: Clear Opening pressure: normal/mildly raised WCC: raised (normally <1000), lymphocytes Protein: mildly raised, 0.5-1 Glucose: normal or slightly low Serum to glucose ratio: normal or slightly low

Answer 586

Appearance: turbid/cloudy/purulent Opening pressure: raised WCC: raised, neutrophils Protein: raised, >1 Glucose: low Serum to glucose ratio: very low

Answer 587

CANDIDA Treat but a lack of response should prompt endoscopy to investigate for: * Cytomegalovirus * Major aphthous ulceration * Deep fungal infections * Malignancy

Answer 588

Cryptosporidium parvuum * Zoonosis, contaminated water * Most common cause of chronic diarrhoea * No other treatment than ART Cystoisospora belli - Widespread in environment - Can cause refractory disease - Treat with cotrimoxazole (or ciprofloxacin)

Answer 589

* Cryptosporidium * Isosporiasis * Mycobacterium tuberculosis * Non-tuberculous mycobacteria – MAC * Cytomegalovirus * Microsporidiosis * Deep fungal infection eg cryptococcus, histoplasma * Lymphoma

Answer 590

Small: - Bloating + abdominal pain - Watery and large volume * Cryptosporidium * Isospora * NTM * HIV enteropathy * Microsporidiosis - Ix: Endoscopy and biopsy Large: - Small volume, blood/mucus/WBCs - Tenesmus - CMV, TB, Amoebiasis, Schisto

Answer 591

First 3 months of ART and if not on ART. Salmonella (typhoidal and non-typhoidal), Pneumococcus, E Coli.

Answer 592

TBM -> if HIV negative / if SOL TBM -> consider if HIV positive Inflammatory pericarditis Severe and neurological TB IRIS

Answer 593

You can’t. Would need micro. Toxo treat with co-trimox.

Answer 594

Consider CNS lymphoma Brain biopsy for definitive diagnosis Treat with chemo/radio/ART

Answer 595

· Caused by JC virus, insidious onset, occurs at CD4 counts <100 cells/µL · Progressive focal neurology (mainly motor) · Normal CSF (JC virus PCR usually positive), MRI is diagnostic No known effective treatment, give ART

Answer 596

* Progressive disseminated infection * Fever, fatigue, weight loss, and hepatosplenomegaly * Cough, chest pain, and dyspnea in ~ 50% of patients * CNS, GI, and cutaneous manifestations in a smaller * percentage of patients If CD4 counts >300 cells/mm3, histoplasmosis is often limited to the respiratory tract with cough, pleuritic chest pain, and fever Ix: - Microscopy - characteristic 2 to 4 µm in diameter budding yeast - Culture (lysis-centrifugation technique) blood, bone marrow, respiratory secretions - PCR Antigen detection (blood or urine) by EIA or LFA Mild: itraconazole Severe/CNS: induce with ambisome then itraconazole maintenance (can be lifelong eg for AIDS pts)

Answer 597

Disseminated or localized end-organ disease in individuals who have very advanced HIV disease (CD4 <50 cells/µL) – Retinitis, colitis, pneumonitis, encephalitis Diagnose with PCR Treat with valganciclovir

Answer 598

- Cervical cancer - Kaposi's sarcoma ○ Mortality at 8 months after KS -> poor outcomes - Lymphomas (NHL) - Castleman's disease (Lymphoproliferative disorder, unicentric vs multicentric)

Answer 599

○ Less CD4+ ○ Alteration in macrophage activation (less IFN-Y production and in turn, granuloma formation) ○ Alteration to neutrophils, less epithelioid cells, less Langhans cells ○ Less effective granuloma formation ○ Altered adaptive cell populations + altered phenotypes of cells Advanced: increased necrosis + increased neutrophils + increase Mtb => granulomas poorly organised or absent

Answer 600

2000: DOTs Mid 2000s: HIV control 2005ish: HIV/TB Collaboration activities 2010ish: 3 'I's (intensive case finding/IPT/infection control) 2012: HIV/TB policy updates eg early ART, WHO endorsed Xpert 2014ish: End TB strategy, UNAIDS 90-90-90, WHO test can treat 2020: UNAIDs 95-95-95

Answer 601

LMICs - Bacterial LRTI is important differential for pulmonary TB - Assumption that LRTI improves with short course of Abx ○ PTB will not improve with antibiotics ○ Widely used intervention (especially low resource settings) ○ Recommended in several TB diagnosis guidelines ○ Little consensus on which Abx/duration Sensitivity ~70%, Specificity ~77%

Answer 602

Rifapentine based 4 month regimens are in WHO guidelines for CD4 counts >100 (only 8% of trial participants PLHIV)

Answer 603

Rifampicin: Shorter half-life, used daily, preferred for active TB treatment. Rifapentine: Longer half-life, used weekly or biweekly in latent TB treatment or intermittent regimens, with fewer dosing requirements. Both can cause orange discolouration of body liquids. Both inhibit RNA polymerase.

Answer 604

Rifabutin - Less potent CYP450 inhibitor - Can cause Uveitis

Answer 605

1. People living with HIV (PLHIV), due to their significantly higher risk of developing TB. 2. Close contacts of active TB cases, especially children under 5 and immunocompromised individuals. 3. Immunocompromised individuals, such as those on immunosuppressive drugs, or organ transplant recipients. 4. People with silicosis, as this condition increases TB risk. 5. Children under 5 years old, who are at high risk after exposure to TB. 6. Healthcare workers and other high-risk populations, such as prisoners or people in homeless shelters. Issues: resistance/poor adherence/pill burden/availabiltiy Examples: 1st: Isoniazid/Rifapentine weekly 3 months OR Isoniazid/Rifampicin daily for 3 months 2nd: Monotherapy eg Isoniazid daily for 6-9 months

Answer 606

Oocyst ingested Asexual reproduction leads to schizogony repeated OR Sexual reproduction leads to gamete formation Release of oocyte Resistent oocytes (ie with outer coat) are shed in faeces Oocyte maturation (sporulation, sporogony) normally outside the body

Answer 607

Sporocyst Sporozoites Residual body

Answer 608

* Oocyst Stage (Infective Stage): The Cryptosporidium parasite starts as a resistant oocyst (a spore-like form) in contaminated food, water, or surfaces. These oocysts are ingested by a host, such as a human or animal. * Excystation in the Intestine: Once inside the host’s stomach or small intestine, the oocyst releases infectious forms called sporozoites. This process is called excystation. * Invasion of Intestinal Cells: The sporozoites attach to and invade the epithelial cells of the intestinal lining. Inside these cells, they undergo asexual reproduction, forming meronts. * Asexual and Sexual Reproduction: Type I meronts release merozoites which invade new cells for further asexual reproduction, type II meronts release merozoites which undergo sexual reproduction to form microgamonts (male gametes) and macrogamonts (female gametes). These gametes fuse to form a zygote. Formation of New Oocysts: The zygote develops into a new oocyst, if its thin-walled it can stay inside the host -> autoinfection. If thick walled it exists host, shed in faeces.

Answer 609

- Wide ranging s/s: asymptomatic (common) -> life threatening - Watery diarrhoea is most frequent symptom ○ + dehydration, WL, abdo pain, fever, N&V - Immunocompetent lasts 1-2 weeks ○ Immunity to reinfection is incomplete -> risk of multiple episodes - Chronic and more severe in immunocompromised -> infection spreads from intestine to hepatobiliary and pancreatic ducts -> cholangiohepatitis, cholecystitis, choledochitis or pancreatitis - Risk of respiratory cryptosporidiosis? ○ Known in immunocompromised ○ New data suggesting in immunocompetent children in Malawi via cryptosporidial diarrhoea and unexplained cough, transfer via aerosolised droplets or contact with fomites contaminated by coughing Long term morbidity (up to 10 years) Symptoms can persist following infection eg weight loss, blood in stool, chronic diarrhoea - IBS like symptoms

Answer 610

Cryptosporidiosis interacts in a complex way with malnutrition and the intestinal microbiome to cause long-term harm to young children in less-developed countries * A change in intestinal cell kinetics, leading to fewer mature enterocytes and impaired nutrient uptake, may be one significant reason (Wallbank et al. 2024) Other associations with bowel cancer -> higher rates of infection in BC compared to controls

Answer 611

* Light microscopy of faecal specimens - staining with Ziehl–Neelsen, Auramine or Safranin (last not quite so good) - MUST measure (5-5.5 µm) and check bright red (Z-N) * Direct FAT and immunochromatographic RDTs available and widely used - But note: the mean sensitivities of the three best kits tested, by species, was C. parvum 73.5%; C. hominis 80.8%, other species 27.7% (Agnamey et al. 2011) - The sensitivity and specificity of 3 antigen detection kits, Auramine and Immunofluoresence were good and all were better than modified Ziehl–Neelsen (Chalmers et al. 2011a) * PCR for diagnosis and genotyping PCR based methods appear to have the highest sensitivity and specificity - for a comparison of four commercial and four in-house protocols (including performance with some of the less-common species) see Costa et al (2021)

Answer 612

5micrometers, cherry red

Answer 613

Cryptosporidium: 5micrometers, cherry red Cyclospora: 5-8micrometre ie bigger, can be red, acid-fast behaviour

Answer 614

Criteria for identifying oocysts: – Usually round – Small, normally about 8μm diameter – Dark, refractile wall, thicker than most other gut protozoan cysts – “Broken glass” contents

Answer 615

solid transplant recipients and autoimmune inflammatory diseases These patients tend to have a sudden acute onset and worse survival outcomes than HIV+ patients -> ie HIV patients have higher fungal loads but poor immune system so less mortality, whereas organ transplant patients etc have lower fungal loads but better immune system so mount more fatal responses

Answer 616

Organism adheres to Type 1 pneumocytes lining alveoli Seems to be immune component involved

Answer 617

Pneumocystic cysts -> Grocott Silver stain

Answer 618

1. Co-trimoxazole ○ High incidence of SEs in HIV+ patients ○ Mutations in sulphonamide target enzyme might reduce effectiveness (conflicting evidence) 2. Other ○ Pentamidine ○ Dapsone-trimethoprim ○ Clindamycin-primaquine ○ Atovaquone

Answer 619

- Need to distinguish between colonisation and actual PCP - BAL (best sample) ○ Invasive but more sensitive than induced sputum ○ Staining (silver; direct FAT more sensitivie) ○ PCR better than microscopy ○ Metagenomic sequencing - Quantitative PCR using oral wash samples - Some DNA has been detectable in *plasma* of AIDs/PCP patients but no method really used - Detection of (1,3)-beta-D-Glucan: less invasive ○ Sensitivity high but not as good as PCR, especially when used alone ○ Specificity: same polysaccharide present in cell walls of other fungi/serum of patients who have had certain procedures etc Performs worse if lower fungal load

Answer 620

- Host-specific ie human parasite - Airborne transmission - Transplacental transmission - rabbits, maybe humans - Very widespread in air -> ie most kids colonised before school - Probable later attacks of PCP in immunocompromised are NEW infections not reactivation

Answer 621

- Staining and light microscopy (speciation difficult or impossible) - Electron microscopy (define species) - Nucleic acid amplification methods (increasingly important) - In situ hybridisation

Answer 622

Mycobacterium leprae and Mycobacterium lepromatosis - Intracellular organism - Not possible to culture - Long incubation period

Answer 623

- Unclear - ?similar to TB, ie aerosol spraying into nasopharyngeal tract, coughing etc ○ Bacilli found in nasal droplets of highly infected people and thought to enter body through upper resp tract - Affinity for cooler sites of body -> peripheral nerves and skin - More rarely: eyes, mucous membranes, testes, bones and viscera - Disease: ○ Long incubation period, 3-5 years, may vary from 6 months to 20 years ○ Progress of disease depends on immunological status of person - Animal reservoirs: ○ Armadillo? ○ Some monkeys/squirrels - Has been found in soil and can survive in it - ? Environmental pathogens

Answer 624

- Numbness /loss of function in hands and feet - Deformities in hands and feet - Painless ulcers or burns (but might smell) - Nasal stuffiness - Weakness in eyelids - Reaction presentation: fever, joint pains, inflammed skin - Skin lesions - 95% patients Skin lesions: ○ Tuberculous end lesions are asymmetrical and well defined but there is some anaesthesia ie loss of sensation ○ Lepromatous lesions more symmetrical, widespread, at worst -> nodules and infiltration

Answer 625

Skin lesions: ○ Tuberculous end lesions are asymmetrical and well defined but there is some anaesthesia ie loss of sensation ○ Lepromatous lesions more symmetrical, widespread, at worst -> nodules and infiltration - Enlarged nerves - Dryness in hands and feet - Loss of sensation in hands and feet - Painless ulcers and wounds - Weakness in motor function in hands and feet (progression to motor nerves being affected) - Deformities in hands and feet

Answer 626

- Slit skin smear for AFB ○ Suspected lesions and sites commonly affected eg forehead, eyebrows, ear lobes) are sampled - No useful serological or skin test - Skin and nerve biopsy -> granumolas? Bacteriological index - ZN staining of smears made from skin slits - Read on logarithmic scale 0-6 - Useful in lepromatous cases and unusual skin lesions - Can start treatment where clear-cut skin and/or nerve lesions are present before skin slit smears results available - Negative skin-slit smears do not exclude diagnosis

Answer 627

Definite loss of sensation in a skin lesions consistent with leprosy Thickening or one or more peripheral nerves Skin smear or biopsy positive for AFB If these then start Tx

Answer 628

- Paucibacillary = 5 lesions or less - Multibacillary = 6 lesions or more If skin smear positive -> patient automatically classified as MB regardless of no, of patches

Answer 629

PB - 6 months treatment - 2 drugs: ○ Rifampicin once a month ○ Dapsone daily MB - 12 months treatment - 3 drugs: ○ Rifampicin once a month ○ Dapsone daily ○ Clofazimine daily NOW WHO recommends to give ALL patients the 3 drug packet but 6 months vs 12 months according to two groups. Enables just a single packet to be given. Patients don't like it as Clofazimine causes hyperpigmentation so if they have PB then why are they taking drug? SIDE EFFECTS Dapsone: - Anaemia - Hypersensitivity syndrome (fatal in 10%) Clofazimine - Hyperpigmentation - Ichthyosis (dry scaly skin) Rifampicin - Orange urine/tears: 1-2 days only Safe in: pregnancy, breast feeding, HIV

Answer 630

- Increased risk of developing leprosy -> need prolonged contact with person and they probably need high BI - WHO recommend chemoprophylaxis with single dose of rifampicin to contacts ○ Household ○ Household and neighbours ○ Communities - Screened for evidence of clinical leprosy and TB Now new drugs being considered for contacts eg adding clarithromycin and treating for a couple of months. - Brazilian ministry of health recommends all household contacts be given two doses of BCG

Answer 631

Type 1 reactions Features: Can occur at any point in journey Skin and nerve acute inflammation Typically effects pre-existing skin lesions Presents as large skin lesions/Scaling/Oedema/Annular lesions Associated with facial and peripheral oedema Nerve inflammation may lead to permanent loss of nerve function ENL Multisystem disorder -> can occur anytime and can be recurrent or chronic Can present with any systemic inflammatory symptoms eg fever/malaise/oedema/any -itis type Effective treatment: Thalidomide (but issues with access/restriction/banning etc) so patients often given other drugs eg prednisolone, Clofazimine, Azathioprine Silent neuropathy Lucio's phenomenon -> Widespread ulcerative lesions in patients with high bacillary load who likely are not on treatment or who have been under-treated. Start MDT immediately Consider steroids or other anti-inflammatories Wound care/Abx if secondary infections

Answer 632

- Lipodystrophy - Infections particularly strongyloidiasis - Hypertension - DM - Peptic ulceration - Mood disturbance - Osteoporosis - Cataracts

Answer 633

- Type 1 reactions -> Nerve inflammation may lead to permanent loss of nerve function - Nerve enlargement -> Increased risk of entrapment + compression - Vascular effect - Direct effect of mycobacterium on nerve tissue

Answer 634

Lucio's phenomenon Start MDT immediately Consider steroids or other anti-inflammatories Wound care/Abx if secondary infections

Answer 635

Hand/feet: Primary Loss of sensation, sweat Muscle weakness Secondary Claw fingers/toes/wrist/foot drop -> Contracture Ulceration Loss of digits Eyes: Primary Lagophthalmos Corneal anaesthesia Secondary Exposure keratitis Corneal ulcer Blindness

Answer 636

1. Early case detection Helps also pick up paediatric cases and G2D. Allow for reliable burden estimation, district prioritisation and identifying populations at risk. 2. Self-care practice Skin care, wound care, exercise, footwear, health education + peer support groups 3. Footwear 4. Psychosocial support (PSS) 5. Reconstructive Surgery need nerve assessments to find patients at risk ie muscle strength, sensation and sweating correct wrist/foot drop, decompress nerves, collapse nose, eye surgery

Answer 637

Only 5% infected with leprosy bacilli will develop the disease Indeterminate: detectable but no clinical manifestations Tuberculoid: strong immunity, few bacteria Lepromatous: weak immunity, many bacteria - Generalised -> nerves, skin + other tissue - Macrophages ingest but don't digest the bacilli due to lack of cell mediated immunity (CMI) -> convenient host - Multiplication of bacilli and transport by macrophages to other parts of body Upgrading towards tuberculoid end = not necessarily a good thing as over activity of T cells -> inflammation -> tissue damage

Answer 638

TT Tuberculoid leprosy: well defined (asymmetrical, definite anaesthesia) BT Borderline Tuberculoid: ill-defined satellites (asymmetrical, definite anaesthesia) BB Borderline borderline: circinate (asymmetrical, definite anaesthesia) BL Borderline lepromatous: hypoesthetic patches (symmetrical + variable lesion anaesthesia) LL Lepromatous: Nodules and infiltration (symmetrical + variable lesion anaesthesia) RIDLEY JOPLING CLASSIFICATION is the 5 things Now use WHO criteria instead

Answer 639

○ Lagophthalmos ○ Decreased corneal sensation ○ Acute/chronic iritis ○ Cataract

Answer 640

Supraorbital Great auricular Cervical Radial Median Ulnar Radial cutaneous Common peroneal Posterior tibial

Answer 641

Eyes/Hands/Feet Grade 0,1,2 Grade 2 disability suggests visible functional disabilities in the person and he will not only be economically affected by these but also more at risk of stigmatisation

Answer 642

History Full examination of skin, nerves, deformities, ulcers, wounds ST (sensory testing) VMT (voluntary muscle testing) Disability grading including eyes Skin slit smears/biopsy

Answer 643

1. Viperidae ○ Vipers (eg western Russell's viper, pit viper), adders, pit-vipers, moccasins, rattlesnakes ○ Relatively short thick body, short tail, distinctive dorsal pattern, slow-moving ambush predators but strike like lightening 2. Elapidae ○ Cobras, king cobras, kraits, mambas, coral snakes, all Oceanian/Australian venomous snakes and sea-snakes ○ Relatively long thin body, long tail, uniformly coloured (except corals), fast, some spread good

Answer 644

○ Phospholipases A2 ○ Metalloproteases ○ Serine proteases ○ Three-finger toxins (neuro, cyto toxins)

Answer 645

- Depends on interaction with snakes and their readiness to strike - Meteorology: heats, rains, flooding - Cycles of diurnal and seasonal activity: ○ Snake: nocturnal hunting + mating season ○ Human: occupational (agriculture, pastoralism), building projects, travel - Sleeping on the ground ○ Nocturnal krait bites in South Asia - Intentional snake handling ○ Restaurants/leather ○ Performance ○ Religion/Science

Answer 646

- Cause puncture marks on skin indicating penetration by teeth or fangs - BUT results in no evidence of local or systemic envenoming over next 24hr (no venom injected) - Incidence varies with snake species: ○ Saw-scaled vipers (Echis): <10% bites are dry ○ Australian brown snakes (Pseudonaja): >80% of bites are dry Mechanism unknown (?mechanical disadvantageous defensive strike, ?snake-controlled metering)

Answer 647

ACE-I: jacaraca snake in Brazil GLP-1: Toxin from North American Gila monster

Answer 648

LOCAL Cytotoxicity (some cobras and most vipers) - Local swelling - Bruising - Necrosis - Risk of bacterial infection Systemic Haemotoxicity (vipers and oceanic/australian elapids) - Coagulopathy - Bleeding - Extravasation Neurotoxicity (elapids, a few vipers) - Descending flaccid paralysis CVS toxicity (vipers) - Arrhythmias - Myocardial damage - Capillary leak - Hypovolaemia - Shock Myo-toxicity - Generalised rhabdomyolysis - Hyperkalaemia Nephro-toxicity - AKI - Pigment nephropathy - Microangiopathic haemolysis - Thrombotic microangiopathy

Answer 649

- Hypovolaemia from extravasation into bitten limb - Generalised increase in capillary permeability - Direct myocardial toxicity

Answer 650

Anxiety -> hyperventilation, conversion disorders Pre-hospital treatment Pre-existing medical conditions and regular medical conditions Secondary bacterial wound infections eg tetanus, necrotising faciitis, septicaemia Secondary hypoxic damage resulting from delayed resuscitation of venom - induced shock or respiratory failure Then finally envenoming

Answer 651

WHOLE BLOOD CLOTTING TEST - Bedside test for 20mins for coagulopathy - Few ml of venous blood in new, clean, dry (soda) glass vessel - Leave undisturbed for 20mins at ambient temp - Tip once - Positive -> non-clotting, incoagulable blood if blood remains liquid like water - Negative -> clotting, coagulable blood if blood clots - Repeat with normal control if result inconsistent with clinical status

Answer 652

Aim to compress veins and lymphatics in immediate vicinity of bite -> draining depot of injecting venom

Answer 653

FIRST AID 1. Remove from danger and reassure 2. Immobilise whole body, especially bitten limb (need to prevent muscle contraction) 3. Remove anything tight eg bracelets, anklets etc from limb 4. Apply pressure-pad-immobilisation immediately 5. Prevent shock, airway obstruction and resp failure in transmit, oxygen (?atropine + neostigmine for cobra bite paralysis) 6. Discourage traditional treatment 7. Get to hospital Treatment 1. ABCDE + oxygen intubation 2. Admit all proven or suspected snakebite cases for min of 24hr observation to cover late evolution of symptoms of envenoming 3. Assess for signs of local and systemic envenoming (including bedside test for coagulopathy) ?ANTIVENOM (SAME DOSE for kids and adults) 4. Try to diagnose species of snake 5. Analgesia - paracetamol/acetaminophen 6. Tetanus toxoid booster to all cases (all bites are penetrating injuries and injection provides reassurance) 7. Watch for secondary bacterial wound infections (potentially fatal tetanus, nec fasc, septicaemia) 8. Consider IVF/intubation + ventilation/RRT ANTIVENOM indications: - Shock - Spontaneous systemic bleeding +/- incoagulable blood - Neurotoxicity (ptosis or more) - Black urine (haemoglobin or myoglobin) - Rapidly progressive local swelling (especially bites on digits)

Answer 654

Monovalent: cover one species Polyvalent: cover multiple medically important species in the region eg Indian Polyvalent ASVs cover for big 4

Answer 655

SAME INITIAL DOSE

Answer 656

- Drain abscesses - Aspirate large tense blisters using fine needles - Debride/amputate necrotic tissue early (beware of nec fasc) and apply skin grafts - AVOID fasciotomy (s/s of raised compartmental pressure not accurate in snake bite - Encourage early rehab

Answer 657

Treatment of local pain: Infiltration/digital block with 1% lignocaine or something similar Treatment of systemic envenoming: Rare severe cases: may require ICU/CV/resp monitoring for minimum 24hr (ECG/echo) Antivenom for: - Any systemic symptoms/signs not explained by pain/anxiety alone, especially in small children - Administration: slow IV injection/infusion Use UV light to show them

Answer 658

Local: - Intense pain, tissue necrosis, secondary marine/aquatic bacterial infections (Staph, Strep, Vibrio vulnificus, Mycobacterium marinum, Aeromonas hydrophila) Systemic: - N&V, fever, hypotension, bradycardia, other cardiac arrhythmias, reps distress, pulmonary oedema, delirium, convulsions, autonomic stimulation, paralysis - Rare cardiac arrest - reef stonefish Synanceia verrucosa is most dangerous

Answer 659

- Stone fish (Synanceia) - Scorpionfish (Scorpaenidae) - Lionfish - Catfish - Toadfish - River ray - Sting ray (Potamotrygon) - Dogfish

Answer 660

Echinoderms eg star fish or sea urchins Cnidarians (Coelenterates) eg jellyfish etc

Answer 661

STAR FISH OR SEA URCHINS ○ Venomous spines and grapples (pedicellaria) ○ Severe local pain, redness, swelling, blue/violet staining ○ Vomiting, rare systemic effects (weakness, paraesthesia, cardiac arrhythmias) ○ Marine bacterial wound infection

Answer 662

○ Surface of cnidarians (esp tenticles) are studded with millions of cnidocytes ○ Contain explosive nematocysts extruding stinging tubes for predation ○ Deadly jellyfish for example: § Australian box jellyfish (Chironex fleckeri) "sea wasp" - up to 3m long □ Features: ® Intense local pain ® Cough, N&V, abdominal colic, diarrhoea, rigors ® Severe MSK pains ® Syncope, profuse sweating, cyanosis, generalised convulsions, pul oedema, rapid death § Nomura's jellyfish (Nemopilema (Stomolophus) nomurai § Irukandji (Malo kingi) - around 1cm long, has lots of stinging tubes □ Features: ® Minimal local signs ® Delayed (5-50mins) severe low back, "boring" ® Muscle pain/cramps limbs, trunk - in waves ® Chest tightness ® Sweating, restlessness, anxiety, resp distress, pul oedema, potentially fatal acute Takotsubo-like cardiomyopathy ® HTN causing fatal intracerebral haemorrhage ® ?hypercatecholaminaemia § Look out for local pain, wheals (indiagnostic patterns), swelling, erythema, vesiculation, necrosis

Answer 663

Kinetoplastid parasitic disease -> flagellate protozoa

Answer 664

L. donovani

Answer 665

Visceral leishmaniasis a.k.a kala azar Leishmania donovani Leishmania infantum Post Kala azar Dermal Leishmaniasis (PKDL) Leishmania donovani

Answer 666

Cutaneous leishmaniasis * ”localised” L. major, L. tropica, L.mexicana, L. braziliensis * Mucosal lesions L. aethiopica * Diffuse (DCL) L. mexicana, L aethiopica * Recidivans L. tropica * Mucocutaneous leishmaniasis L. Viannia sub-genus

Answer 667

about 2-4 months after infection at least 2 weeks of fever (rule out Malaria) enlarged spleen and liver Ⓒ spleno- or Ⓓ hepato- megaly) weight loss (cachexia) Anaemia +ve test (non-invasive)

Answer 668

1. Infection of Sandfly (Promastigote Stage): * Female sandfly takes blood meal -> ingests macrophages that contain the amastigote form of the Leishmania parasite * Inside the sandfly midgut, the amastigotes transform into promastigotes, which are the motile, flagellated form of the parasite * Promastigotes divide + multiply in the sandfly's midgut + eventually migrate to the fly’s proboscis (the biting mouthpart) 2. Transmission to Humans: * When the infected sandfly bites a human, it injects the promastigotes into the skin. * The promastigotes are then phagocytosed (engulfed) by macrophages in the human's skin. 3. Amastigote Stage in Humans: * Inside the macrophages, the promastigotes transform into amastigotes, the non-motile, intracellular form of the parasite. * The amastigotes multiply within the macrophages, causing the cells to rupture and release new amastigotes into the bloodstream or nearby tissues, where they infect more macrophages. 4. Infection of New Sandflies: When a sandfly bites an infected human or animal, it ingests macrophages filled with amastigotes, and the cycle begins again.

Answer 669

- Seen in East Africa and South Asia when a VL infection has been clinically cured (eg L.donovani) - Can also occur after L.infantum VL infection - Parasites are localised in the skin, within lesions which range in appearance from slight to severe - Some differences in PKDL presentation between East Africa and South Asia - RESERVOIR for infection -> ie sandflies can bite the skin - South Asia ○ Macular ○ After VL: 10-30% ○ 0-3 years after VL - E Africa ○ Papular ○ After VL: 50-60% ○ 0-13 months after VL

Answer 670

CUTANEOUS - Localised or simple CL - Eg L.major, L.tropica, L.mexicana, amazonensis - Single or limited number of discrete lesions - Self culture in months-years - DTH+ - Disfiguring MUCOSAL - Mostly L.aethiopica infections - Also seen with L.infantum, L.major and L.tropica - Surface lesions of oral mucosa - Not structurally destructive

Answer 671

L. aethiopica and some L. m. amazonensis infections Multiple, coalesced lesions. Non-ulcerative, +++amastigotes, (“anergy”) +++Leishmania antibodies General T cell hypo-responsiveness (DTH –ve) * No macrophage activation to clear parasites or induction of cell-mediated immunity * Absence of IFN-γ allows multiplication and progression of lesions Poor prognosis as highly refractory to treatment, immunotherapy +conventional treatment more successful

Answer 672

- Rare - Relapsing L. tropica, L major or L. braziliensis - Develops after an LCL infection has been resolved, months to years later. Close to the original lesion or at site of trauma (LATENCY) - Amastigotes very sparse - PCR diagnosis - Difficult to treat

Answer 673

HIV - two exacerbate eachother -> VL if HIV+ promotes progression of HIV/AIDS - Asymptomatic or latent VL will recrudesce on HIV infection ↓CD4 cells leads to ↓IFN-Ɣ leading to ↓ cell-mediated response TB More patients presenting with TB + VL Exacerbate each other (Some TB+VL+HIV) HELMINTHS Worm infections induce a regulatory immune response → control of Leishmania (Murine model of S. mansoni and L. donovani and L. major) PREGNANCY * Associated reduced cellular immunity may result in VL exacerbation. * Reports of transplacental transmission * Pregnancy has a higher risk of early VL relapse. * Newborns infected with Leishmania can have delayed symptoms

Answer 674

- Digenetic single-celled organism ie exists in 2 forms - ~1-2 um diameter - No flagellum - Obligate intracellular amastigote in humans ○ Parasitophorus vacuole pH 5.5 ○ Amastigotes can survive in their vacuole -> have own protein pumps etc ○ Macrophages don't "see" parasite, ie parasites can hide in cell, divide, multiply then burst - Survive & divide within cells of the reticuloendothelial system, e.g. macrophages of the liver, spleen, bone marrow and skin Amastigotes reside with a phagolysosomal vacuole a.k.a. parasitophorous vacuole, not free in the cytoplasm Amastigotes survive and multiply within the macrophage by modifying innate pathogen-killing mechanisms such as Inhibiting the generation of free radicals and down-regulating IL-12 and suppressing Th1 cell activation. Promoting the production of immunosuppressive molecules In sand fly vector = flagellated promastigote

Answer 675

Parasitology -> Microscopy (+/- culture) Eg LN puncture (lowest sensitivity), Splenic (best sensitivity) then BM aspiration, lesion biopsy for CL Immunodiagnosis IFAT/ELISA DAT (direct agglutination test) rK39 Ag-based (ELISA and dipstick format) -> now a dipstick and almost universally used as part of diagnostic algorithm for VL Katex (Ag detection) DNA probes and PCR Kinetoplast DNA (minicircle) 16-18s rDNA gene- species specific

Answer 676

Parasitology - Near 100% specificity - Only way to diagnose non-response/relapse Splenic aspirate is the most sensitive - Diagnose primary VL (if borderline DAT) - Assess post-treatment efficacy - Diagnose VL relapse rK39 RDT - South Asia - All formats perform well - East Africa – level of sensitivity is insufficient to rule out VL; sensitivity sufficient if case-definition is respected; best tool for decentralised diagnosis DAT - More sensitive that rK39 RDTs - Should be used in pts with a –ve rK39 RDT where clinical suspicion of VL is still high VL+HIV patients: rK39 + DAT combination, plus biopsy East African setting: rK39 + biopsy

Answer 677

L.donovani or L.infantum

Answer 678

- Phlebotomus spp. - Europe, Africa, S. Asia - Lutzomyia spp. - South America Unique sand fly – Leishmania species pairings Ph. sergenti & L. tropica; Ph. papatasi & L. major L. longipalpis & L. infantum

Answer 679

L.infantum

Answer 680

L.mexicana L.major

Answer 681

- Reappearance of previously resolved L.Viannia sub-genus: ○ L.V.braziliensis (1-10%) Others also possible: L. V.panamensis, L.V.peruviana, L.V.guyanenis months to years - Initial skin lesion that may spontaneously heal --> mucosal involvement months to years later Eg ulceration, destruction of nasal and oral tissues, disfigurement Risk factors: ○ Male>female, age, nutritional status, # of LCL lesions above waist, inadequate Rx, immune status - ~10% will develop MCL, trigger unknown - Tissues of soft palate are infected, decrease amastigotes Can be called immune-mediated inflammatory reaction -> Th1 cells producing IFN-γ (interferon-gamma), which helps activate macrophages to kill the parasites but causes tissue damage disproportionate to tissue load Destructive and difficult to treat

Answer 682

Leishmaniasis disease works on spectrum - Hypersensitivity ○ MCL ○ DL ○ ~LCL, LR ○ Th1 cells release IFN-Y, greater response than Th2 cells releasing IL-10 ○ Means immune-system mediated damage is large component of pathology - Moderate: PKDL - Hyposensitivity ○ ADCL Greater Th2 response + release of IL-10 than Th1 response with release of IFN-Y Disease control occurs due to - Ag presentation and activation of macrophages - Proinflammatory cytokines and chemokine response - Ab production - Decrease in lesion size and parasite no. - ROS and NO production - Cure is associated with reduction in IL-10 and IL-13 in VL and increased IFN-Y and CD4 T cell response in CL Disease progression associated with - Reduced Ag presentation - Increased IL-10 and TGF-beta - Non-productive Ab, increase in lesion size and no. of parasites - ROS inhibition

Answer 683

Acutely: Conjunctivitis - Vitamin A deficiency induced by measles ○ Drying of cornea ○ Keratomalacia ○ Corneal ulcers and ulcerative keratitis ○ Optic neuritis

Answer 684

syphilis until proven otherwise secondary

Answer 685

- Lack of access to affordable healthcare and effective treatment - Demographic factors eg lots of young people in Africa + no. of partners - Rural to urban migration - Migrant labour - Commercial sex - Different patterns of sexual networks (eg younger women with older men)

Answer 686

R0 = beta x c x D R0: basic reproductive number beta: probability of STI transmission given exposure c: Exposure rate of susceptible to infectious partners (eg rate of sexual partner change) D: duration of infectious period (eg HIV is v long) ________________________________________________ Efficiency of transmission (β): – infectivity of the organisms (viral or bacterial load) – biological interactions with other organisms (HIV & STIs) – sexual behaviours which increase or decrease risk (condom use, anal vs vaginal vs oral sex vs non penetrative) Behavioural parameters (c): – rate of partner change – patterns of sexual mixing (gender, age, assortative/disassortative mixing) Duration of infection (D): – infectious period of the organism – treatment-seeking behaviour ________________________________________________ On β (=reducing efficiency of transmission) - Treat - treat cofactors (e.g. treat STIs to reduce HIV shedding) - condoms & safer sex practices - male circumcision On c (=reducing the rate of exposure) - rate of partner change - contact with high-risk partners - concurrent partnerships On D (=reducing the duration of infectiousness) - implement prompt STI diagnosis and effective case management - promote early treatment-seeking (through education / IEC)

Answer 687

Partner notification and management Clinical goal: to provide concurrent antibiotic treatment to the sexual partner(s) to eradicate the STI and prevent reinfection Public health goal: to interrupt the chain of transmission and reduce spread Little evidence of effectiveness in LMIC & potential harmful effects (violence, incomplete treatments)

Answer 688

1 Partner notification 2 Female condoms 3 Microbicides 4 Voluntary medical male circumcision (VMMC)

Answer 689

Clinical aetiological diagnosis: Clinical features, clinical acumen, reproducibility, self- medication Laboratory aetiological diagnosis: Diagnose specific pathogens via multiple methods Syndromic approach: Consistent group of symptoms and clinical signs => target ALL treatable pathogens that can cause the syndrome (ie give treatment for all possible causes)

Answer 690

Syndromic approach, 3 syndromes: - Urethral Discharge & Cervical Discharge - Vaginal Discharge - Genital Ulcer Treat for all possible causes of whichever syndrome you treat with Diagnosis + treatment +: + the “4 Cs”: Compliance Counselling Condoms Contacts

Answer 691

- Neisseira gonorrhoeae - Chlamydia trachomatis - Trichomonas vaginalis - Mycoplasma genitalium

Answer 692

If you can do molecular assays and can get result back on same day then do that Otherwise treat for chlamydia and gonorrhoea + offer test for HIV and syphilis * Gram stain is rapid but only 50% sensitive for Ng in women * Culture is the reference standard for Ng but requires a microbiology laboratory * Near patient lateral flows & microscopy available for Trichomonas * NAATs may be used to diagnose all infections using self-administered vaginal swabs Treatment: GC: Ceftriaxone 250mg AND Azithromycin 1gm CT: Doxycycline 100mg BD 14/7 OR Azithromycin 1gm (NB Only if not given azithromycin for GC) TV: Metronidzole 2gm OD – OR – 400mg BD for 7 days MG: Complicated & only routinely done in a limited number of high- income countries (Azithromycin 1st line)

Answer 693

Trichomonas vaginalis Candida albicans Bacterial vaginosis Chlamydia trachomatis Neisseira gonorrhoeae DIAGNOSIS Molecular assay often not available No good lateral flow for chlamydia Could maybe do speculum Otherwise: - Treat for NG + CT - Consider treating for BV/TV if abnormal vaginal discharge or micro/molecular results Consider treating for candida if symptomatic TREATMENT Candidiasis (thrush): Clotrimazole pessary STAT – or - Miconazole pessary - or - Fluconazole 150mg p.o. STAT TV: Metronidazole 2.0g STAT or 400mg BD for 7 days BV: Metronidazole 400 or 500mg bd daily for 7 days

Answer 694

Herpes Simplex Virus Treponema pallidum (Syphilis) Haemophilus ducreyi (Chancroid) Klebsiella granulomatis (Donavanosis) Lymphogranuloma venereum If ulcer vesicular or hx of recurrent ulcers in same site -> treat for HSV, if not then treat for HSV and syphilis If NO hx of recent syphilis treatment (past 3 months) -> treat for syphilis Diagnosis: Ideally have molecular assay eg NAAT, if not * Clinical diagnosis is unreliable * Dark field microscopy is effective for primary syphilis but requires a microbiology laboratory * Culture is possible (but difficult) for chancroid * NAATs may be used to diagnose all infections

Answer 695

Herpes simplex virus type 2 or type 1 - Lifelong infection with clinical recurrences - Symptoms are self-limiting - Symptoms more severe and of longer duration if immuno-compromised Treatment: Acyclovir 400mg tds for 5-10d - Not necessary in most cases - Suppressive treatment can prevent recurrences - Long term Rx may be needed in immuno-compromised patients

Answer 696

Haemophilus ducreyi Multiple painful ulcers with regional lymphadenopathy Mainly seen in core groups (i.e FSW) -> hard to maintain outside of this as lesions are painful so people seek treatment Asymptomatic infection rare Treatment = Azithromycin

Answer 697

Cause: Chlamydia trachomatis, L1,2, 3 Clinical features: Primary: Small, transient genital ulcer or proctitis Secondary: - Lymphadenopathy -> (inguinal or retroperitoneal), usually unilateral - Continuing proctitis - Fever, rigors, weight loss, erythema nodosum Tertiary: Fibrosis, lymphoedema, rectal stricture Treatment: Azithromycin OR Doxycycline (better)

Answer 698

Klebsiella (formerly Calymmatobacterium) granulomatis Possibly still prevalent in India, PNG, Brazil, Guyanas Clinical features: * Beefy red genital/anal ulcers, usually painless * Inguinal lesions – bubo, ulcer * Lymphoedema, fibrosis, autoamputation of penis Treatment: Azithromycin

Answer 699

- PID ○ Endometritis ○ Salpingitis ○ Peritonitis, perihepatitis - Infertility - Ectopic pregnancy

Answer 700

Gonococcal opthalmia neonatorum Treatment: CLEAN EYES IMMEDIATELY after delivery - Single dose IM ceftriaxone 125mg is highly Alternatives - Kanamycin 25mg/kg IM stat (max 75mg) OR - Spectinomycin 25mg/kg IM stat (max 75mg) Prevention: * 1% tetracycline ointment is as good as 1% silver nitrate * 2.5% povidone-iodine is more effective than 1% silver nitrate or * 0.5% erythromycin NB: ophthalmia neonatorum -> can lead to corneal ulceration and blindness in 24 hours (remember to also screen for Chlymydia)

Answer 701

1. Increased Susceptibility to HIV: Biological factors: inflammation + disruption to mucosal barrier in the genital and rectal tracts due to STIs -> entry points for HIV -> easier for the virus to infect cells Immune response: STIs recruitment of immune cells, including CD4+ T cells (which HIV targets), to the site of infection -> increases the concentration of target cells for HIV, facilitating its transmission 2. Increased Transmission of HIV: Higher viral load: STI can increase HIV viral load in genital secretions -> more infectious to others Ulcerative STIs: STIs that cause open sores eg syphilis or herpes -> direct access for the HIV virus to enter or leave the body -> amplifying the risk of transmission. 3. Co-infection and Disease Progression: STIs can accelerate HIV disease progression by continuously activating the immune system, which HIV exploits to replicate. Persistent STIs can lead to a faster depletion of CD4+ T cells, advancing the course of HIV more rapidly. Can we treat STIs to reduce HIV? Three major RCTs were conducted in 1990s-early 2000s * Mwanza – Syndromic STD management - Reduced rate of new HIV within those communities * Rakai– Mass STD treatment every 10 months - Did not work * Masaka– Information, education & communication plus syndromic STD management - Did not work Differences - ?reflect different stages of HIV epidemic and different burdens of STIs in population

Answer 702

Treponemal * Lab and POCT * Highly specific * Stay positive for life Non-treponemal * VDRL & RPR (rapid plasma reagin test) * Less specific * Titres rise & fall with treatment

Answer 703

Primary, secondary and early latent – Benzathine penicillin G 2.4 million units IM stat Late latent – Benzathine penicillin G 2.4 million units IM weekly x3 No RCT evidence underpinning different treatment for Late Latent

Answer 704

Transmission believed to occur in-utero Risk varies by stage – Primary 60% – Secondary 90% – Early 40% – Late Latent <10% Associated with spirochetaemia Most vertical transmission is in women with latent syphilis -> as most women are in this stage

Answer 705

- 30-40% stillbirth, fetal demise, hydrops fetalis or preterm birth if mother untreated - In inadequately/untreated mothers: meningitis, snuffles, hepatosplenomegaly, osteochondritis, periostitis, rash, haemolytic anaemia, thrombocytopenia >2 years old, ie late symptoms: developmental delay, sensorineural hearing loss, interstitial keratitis, hutchinson's teeth, saber skins, clutton joints

Answer 706

* >95% of antenatal clinic attenders screened * >95% of seropositive women treated * Incidence of congenital syphilis <50 per 100,000 births (including stillbirths)

Answer 707

Serology eg high RPR titre more likely to represent active infection More associated with still birth and poor birth outcomes

Answer 708

- Proved to be most cost effective ○ Ie despite the fact it will remain positive for life, even if a person comes back and receives repeat treatment its cheaper to treat than to prove they actually have a repeat infection Dual tests are too expensive

Answer 709

Early Syphilis: 1 dose IM Benzathine Benzylpenicillin Late or UNKNOWN: 3 weekly doses IM Benzathine Benzylpenicillin Issues: * Most women don’t know duration = recommend 3 doses * Good completion for first dose in many settings BUT poor completion all 3 doses * Some data suggests this might be ok -> ie 1 dose is enough to prevent all the v severe outcomes like stillbirth/LBW etc but still don't know whether this would actually be the case for women who have latent/long infection

Answer 710

Complex algorithms depending on if infant is “High” or “Low” risk High Risk: - Infants with signs of congenital syphilis - Positive body fluid / placenta by Darkfield of PCR - Infant RPR 4* or higher than mother - RX: Procaine Penicillin or Benzylpenicillin for 10 Days Medium Risk: - The mother was ‘inadequately treated’ - RX: Procaine Penicillin or Benzylpenicillin for 10 Days OR IM Benzathine Low Risk: - The mother was ‘adequately treated’ Rx: Nil or Single Dose Benzathine Penicillin

Answer 711

Centralised laboratory testing * High throughput, highly sensitive and specific PCR platforms (+) * Multiplex capabilities (+) * Robust laboratory system/network required (-) Point-of-care testing * Reduced time to treatment (+) * All activities complete on same day (+) * Supply chain complexity (-) * Quality assurance more difficult to monitor (-)

Answer 712

* Real time connectivity * Ease of specimen collection * Affordable * Sensitive * Specific * User-friendly * Rapid & Robust * Equipment-free and Environmentally friendly * Deliverable to end-users

Answer 713

- Syphilis ○ >50% of pregnancies in women with syphilis will result in adverse birth outcome - Trichomoniasis - Chlamydia - Gonorrhoea

Answer 714

Strategy for integration of POC diagnostics for STIs into antenatal care in Zimbabwe. Only 8% of ANC attendees could be approached for enrolment but did find STI in 31% of asymptomatic pregnant women (most common CT), 98% of which were treated on same day. Issues with study provision in terms of environment, getting staff involved, device limitations and client willing to wait.

Answer 715

Wantaim study - Aimed to see if POC testing and immediate treatment of CT, Gon., Trich. Or BV in pregnancy ?lead to reduction in preterm birth +/- LBW compared with standard antenatal care - Big study (n>4000), Papua new guinea - No sig difference between two arms - No impact among women who had chlamydia or trichomonas at enrolment - 39% had CT/Gon./Trich at enrolment in intervention arm CT prevalence in control group dropped -> ?due to malaria prophylaxis standard of care which can have some effect in treating CT ?Jury is out as to impact of POC testing for STIs on birth outcomes -> new trials planned in Zim and Botswana

Answer 716

Social innovation: a community-engaged process that sees the wisdom of communities and impacts social and health outcomes Prosocial interventions: one example of social innovation that encourage voluntary actions to help others -> One prosocial intervention is pay-it-forward which provides a financial nudge (zero cost health service) and a social nudge (handwritten postcard) to increase uptake of services

Answer 717

- 90% of girls fully vaccinated with HPV vaccine by 15 years of age - 70% of women are screened with high-performance test by 35 and 45 years of age - 90% of women identified with cervical disease (precancer or cancer) received treatment and care

Answer 718

HPV - double-stranded DNA within a spherical shell (capsid), composed of - structural proteins L1 and L2 * current vaccines target L1 - Viral proteins E1, E2, E4, E5, E6, E7 40 genotypes infect the genital area, 15 high-risk (HR) oncogenic types, => 2 types (HPV16/18) linked to 70% of invasive cervical cancer => 7 types (HPV16/18 + 31/33/45/52/58) linked to >90% of invasive cervical cancer HPV6 & 11 linked to anogenital warts (AGW) HPV is the most common sexually transmitted infection, 50-80% of women will acquire HPV in their lifetime - Most infections will clear; median duration of new infection is approx. 8 month - Although new infections decrease with age, risk of persistence increases with age - HR-HPV persistence increases risk of precancerous lesions and cancer

Answer 719

~ 50% of women develop no measurable antibody response following HPV infection In women who have detectable antibody levels following natural infection, levels of antibodies are low (compared to post vaccination levels) Low levels of antibodies are less likely to protect against re-infection

Answer 720

- HPV is RF for HIV acquisition (x2) - HIV increases HPV incidence (x2) and decreased HPV clearance - Increase multiple HR infection and broader range - HIV increases cervical cancer (x6) - HIV increases anal cancer in MSM (x10) and women (x7-10) - Increase AGW prevalence, incidence and persistence Impact of ART? - Women on ART have 17% reduced risk of HR-HPV prevalence - Reduction in SIL incidence and progression - Decrease in ICC incidence - Risk is lower if initiated early (higher nadir CD4) + prolonged ART duration, good adherence & effective treatment etc

Answer 721

· Primary prevention -> HPV vaccine · Secondary prevention -> HPV DNA, visual inspection, cytology "pap" smear · Treatment precancer -> ablation/excision · Treatment cancer -> surgery, radio, chemo

Answer 722

Decreasing in HIC, Europe/North America, South America and Oceania, Asia: * Successful screening and treatment programmes * HPV vaccination * Changes in disease risk factors Increasing in Eastern European and Sub-Saharan Africa: * Shorter duration and quality of screening programmes * Fewer vaccination programmes * Changes in disease risk factors * Impact of HIV

Answer 723

General population of women: Screen and Treat OR Screen, Triage and Treat * HPV DNA as primary screening test * Starting at age 30 * Every 5 to 10 years screening interval For women living with HIV: Screen, Triage and Treat * HPV DNA as primary screening test * Starting at age 25 * Every 3 to 5 years screening interval * Where HPV DNA testing is not yet operational, use a regular screening interval of every 3 years when using VIA or cytology as the primary screening test among WLHIV * Use either provider or self-collected samples

Answer 724

Low specificity for high grade lesions

Answer 725

Virus-like particle (VLP) vaccines * 2-valent: 16/18 (GSK Biologicals; Innovax) * 4-valent: 6/11 + 16/18 * 9-valent: 6/11 + 16/18 + 31/33/52/58 & 45 Use 4/9 in gender non-discriminative settings to help prevent ano-genital warts Prevent HPV acquisition, persistence and neoplasia development (vaccines are prophylactic, NOT therapeutic) * Type specific protection++ * Some cross protection (eg. 31/33/52 & 45) Vaccines MOST effective when introduced PRIOR to exposure Ie prior to sexual debut >80% effective in preventing invasive cervical cancer

Answer 726

141 countries have HPV vaccine in national programme - 40% LMICs vs 88% HIC - 1st dose coverage greater in LMICs than HIV but lower for 2nd dose -> drop out 53% (75/141) of country HPV vaccine programs were gender neutral Challenges: Costs of vaccine and costs of delivery Political will & support Competing priorities Perception of cervical cancer prevention as a public health priority Vaccine hesitancy Appropriate delivery strategies Vaccine supplies COVID-19

Answer 727

Option: *1*-dose schedule for 9 to 20-year-olds Prioritize the vaccination of Immunocompromised/HIV+ populations – also at ages beyond primary target - with at least2 doses, ideally 3

Answer 728

* Toxoplasma gondii * Neurocysticercosis/ Taenia solium * Trypanosoma brucei spp. (African trypanosomiasis/Sleeping sickness) * Plasmodium falciparum (Cerebral malaria)

Answer 729

Herpes simplex virus Varicella zoster virus Enteroviruses HIV Arboviruses: Japanese encephalitis virus, Dengue virus, Chikungunya virus Rabies virus Herpes B virus Nipah virus

Answer 730

Strep pneumoniae Neisseria meningitidis Haemophilus influenzae Listeria monocytogenes (Young/Old/Immunosuppressed/Pregnant) Mycobacterium tuberculosis Mycoplasma pneumoniae Streptococcus suis Burkholderia pseudomallei Orientia tsutsugamushi (Scrub typhus) and Rickettsia spp. Spirochaetes: Treponema pallidum, Borrelia spp. (Lyme, Relapsing fever) Bacterial Toxins

Answer 731

* Dengue virus infection * Rickettsial disease ( esp. Scrub typhus) * Enterovirus infection * Chikungunya virus infection * Leptospirosis * Cryptococcal meningoencephalitis

Answer 732

Gold standard: Seroneutralisation - Rise in anti-JEV Iggs as measured by haemagglutination inhibition Issues with serology due to cross-reactivity CSF or serum IgM antibody detection (by ELISA) is the primary diagnostic method - MAC ELISA, problems with specificity - Often can't get CSF then relying on serum sample -> reduces specificity even further PCR tests may also be used, especially early in infection

Answer 733

1. JEV IgM antibody in cerebrospinal fluid (CSF) or serum, as detected by anti-JEV IgM-capture ELISA (MAC-ELISA) 2. Detection of JEV antigens in tissue by immunohistochemistry 3. JEV genome in serum, plasma, blood, CSF or tissue by reverse transcriptase polymerase chain reaction or an equally sensitive and specific nucleic acid amplification test 4. x4/> rise in anti-JEV Igs as measured by haemagglutination inhibition (HI) or plaque reduction neutralization assay (PRNT) in serum collected during the acute and convalescent phase (>14 days later) and tests performed in parallel with other confirmatory tests to prevent cross-reactivity. NB: *MAC ELISA is WHO recommended reference standard*. This is the test used in endemic countries. Problem: needs lab, time, skilled workers, CSF, etc Has poor field sensitivity and reduced specificity when using serum so ideally need CSF.

Answer 734

4 main types: inactivated MB, inactivated VC, live-attenuated, Chimeric - Inactivated JE vaccine (e.g., JE-VAX) for adults and children over 1 year - Inactivated MB: 2 doses in endemic areas or 3 doses non-endemic + booster, concern regarding potential link with ADEM and reduced supply - Inactivated VC: one used in UK - Live attenuated vaccine (e.g., SA 14-14-2) used in some endemic areas; provides longer-lasting immunity - JE-YF chimeric vaccine Immunity should be life long

Answer 735

* JEV is an arbovirus (Culex sp.) and a flavivirus (like dengue, zika, yellow fever, west nile virus…) * Chief identified cause of acute CNS infections in Asia * JE mainly occurs in rural areas; Humans are accidental hosts; 1/300 develop clinical disease; mainly children affected in endemic areas * The clinical presentation is typically acute encephalitis syndrome (fever, headache, reduced GCS, seizures, movement disorders) * No treatment but JEV vaccine recommended by WHO and supported by GAVI as part of childhood immunisation programme in endemic countries * 24 endemic countries; 15 are now vaccinating, but limits in diagnostic capacity affect our true understanding of the burden and evaluate vaccination, and there are ongoing problems with vaccine coverage * JEV is a zoonosis and vaccination will not eradicate disease

Answer 736

(short for arthropod-borne viruses) - broad group of viruses transmitted by arthropods such as mosquitoes, ticks, and sandflies Includes: - flaviviruses eg Dengue, Zika, West Nile, yellow fever - Togaviridae eg Chikungunya - Bunyaviridae eg rift valley fever

Answer 737

Causative Agent Caused by Japanese encephalitis virus (JEV), a flavivirus related to West Nile, Zika, and dengue viruses Transmission Primarily transmitted by Culex mosquitoes (especially Culex tritaeniorhynchus), which breed in rice paddies and standing water - Pigs = amplifying hosts - Human/horses = dead-end reservoir Endemic Regions Found mainly in Asia and parts of the Western Pacific. Countries with significant risk include India, Nepal, Thailand, and Vietnam Incubation Period Typically 5-15 days after the mosquito bite Symptoms Many infections are asymptomatic. Symptomatic cases often have: - Initial symptoms: Fever, headache, vomiting. - Neurological signs: Seizures, altered mental status, tremors, stiffness, which can lead to coma. - Severe cases may progress to brain inflammation and long-term neurological damage. Mortality Rate Case fatality rate is approximately 20-30% in symptomatic cases; up to 50% of survivors have permanent neurological or psychiatric issues

Answer 738

1. Infection via: broken skin, intact mucous membrane, tissue transplant 2. Incubation, usually 20-90 days (can be weeks to years) 3. Virus enters nerve endings, evades immune surveillance, centripetal retrograde axonal transport to brain 4. CNS infection: transsynaptic spread, viral replication, inclusion (Negri) body formation, neurons intact but dysfunctional 5. Clinical signs of encephalomyelitis begin +/- immune response Centrifugal neuronal transport to salivary glands (viral excretion), virus carried to skin, heart, muscle, tongue eg but no viraemia

Answer 739

Vampire bat 99% of human transmission is from dogs Can come from other animals eg seals, bats, racoons human to human -> organ transplantation from donors who died of unknown neurological illness

Answer 740

*Post-vaccinal encephalomyelitis *Paralytic poliomyelitis *Flavivirus myelitis *Herpes simiae (B virus) encephalomyelitis So provide full Rx, until diagnosis of rabies made

Answer 741

Itchiness - ? due to rabies virus reaching dorsal root ganglion

Answer 742

Furious -> die quickly * Phases of arousal and lucid intervals * Cranial nerve lesions III,VII, VIII * Autonomic stimulation: secretions, temp control * Cardiac arrhythmias * Coma * Paralysis * Priapism * Axonal neuropathy Paralytic -> die slowly * Ascending paralysis, loss of tendon reflexes * Fasciculations * Sphincter dysfunction * Fever, sweating, gooseflesh * Bulbar / respiratory paralysis * (hydrophobia) * Survive < 30 days

Answer 743

Hydrophobia * Provoked by drinking / draught of air (aerophobia) * Reflex forceful jerky inspiratory muscle spasms * With inexplicable terror * Violent inspiratory gasps- contraction of diaphragm * Generalized extensor response → opisthotonos, convulsion, cardiac/ respir. arrest → pneumothorax, oesophageal tears * Later on - provoked by minor stimuli ? due to virus wanting to remain in head and neck nerves and avoid GI distribution etc

Answer 744

Heart: arrhythmias, hypotension, cardiac failure Lungs: asphyxiation, pneumonia, pneumothorax respiratory arrhythmias: inspiratory spasms periodic breathing- cluster breathing, Cheyne-Stokes ARDS, respiratory failure CNS: Convulsions, hypo-/ hyper-pyrexia, diabetes insipidus, inappropriate ADH secretion Gut: Bleeding, stress ulceration

Answer 745

NO only encephalitis syndrome

Answer 746

Skin biopsy (NUCAL BIOPSY FOR HAIR FOLLICLES) = GOLD STANDARD * Immunofluorescence: Ag (skin punch biopsy) * RT-PCR * Detect Ag detection and viral RNA detection Saliva, tears, CSF (need multiple, 2-3 a day, sequential) - Tissue culture, mouse innoculation - RT-PCR - Virus isolation Serum, CSF - Neutralising Ab - Serology

Answer 747

Rabies Bodies in cytoplasm of neuronal cells

Answer 748

Attempt ICU only if 1) American bat virus implicated 2) Early appearance of Ab 3) ITU facilities available

Answer 749

Benefits - No need for post-exposure Rabies Immunoglobulin - Decreases number of post-exposure vaccinations required - Helps in cases where post-exposure treatment is delayed - Might provide protection against inapparent rabies exposure cases Who * Those who live in highly endemic areas * Rabies virus laboratory workers* * Those who handle animals in/from endemic areas eg. dog catchers, wildlife workers, zoos, ports.** * Travellers to, or residents of, dog rabies enzootic areas, especially children. * Hospital staff likely to care for rabies patients – Very low risk but overcomes fear *need antibodies checked (>0.5IU/L) every 1-2 years and booster if low ** need antibodies checked (>0.5IU/L) every 2 years and booster if low

Answer 750

- IM (deltoid) ○ 1 dose = 1 vial ○ If delayed vaccination should be resumed, not restarted ○ A change in route is acceptable if unavoidable -> restarting course is not necessary ○ Vaccine cold chain required 2-8 degrees ○ Standard regimen in high resource countries BUT too expensive for most LMICs - ID ○ Improves availability, accessibility and affordability ○ More immunogenic because dermal dendritic cells convey vaccine Ag to reticulo-endothelial system ○ 1 dose =0.1 mL (irrespective of WHO recommended vaccine brand) ○ Store opened vial up to 6 h ○ Site: deltoids, thighs or suprascapular ○ Appropriately trained health care staff essential ○ Vaccine failure if given IM/SC instead WHO say 2 dose schedule on DAY 0 and 7: but in UK and other countries 3rd dose is given as WHO could provide no evidence as to immunogenicity without 3rd dose

Answer 751

2 dose schedule on DAY 0 and 7: Rabies vaccine*: 1 dose intramuscular (IM) or intradermal (ID) 2 sites at each visit but in UK and other countries 3 dose is given as WHO could provide no evidence as to immunogenicity from 3 doses, 3rd dose given at 28 days In immunocompromised patients ideally check neutralising Ab checked at 2-4 weeks if feasible

Answer 752

Post-exposure prophylaxis (PEP): * Meticulous wound cleaning * Irrespective of their rabies vaccination status: * 5 doses of vaccine: days 0, 3, 7, 14 and 28-30 AND * RIG for all Category 2 and 3 cases

Answer 753

NO If they have been vaccinated then even if cat 2 or 3 exposure they still don't need RIG just - wash wound with soap for 15mins - vaccinate

Answer 754

* Mass dog vaccination/contraception programs. * Educate children to avoid mammal interaction * Vigorous washing of all bite wounds immediately with soap * Human vaccination: Rabies vaccines are outstandingly effective, no one should die of dog-transmitted infection

Answer 755

* Rabies is caused by zoonotic, neurotropic Lyssa viruses transmitted through saliva of an infected mammals. Incubation period 2-3 months (range days to years) * Dog rabies accounts for 99% human infections worldwide. * The combination of pre- and post-exposure vaccination has proved 100% successful in preventing human infection * Rabies is an acute, progressive viral encephalomyelitis that is almost universally fatal. Virus is already widely disseminated by the time of onset of clinical symptoms. * Pre-exposure prophylaxis means you do not need post-exposure rabies immunoglobulin (passive immunisation) (unless immunocompromised) * Intensive care treatment may be appropriate if infected by a bat in the Americas or if antibody is present. Otherwise, compassionate palliative care is the best management of rabies patients * Control of canine rabies is the most economical method of preventing human rabies.

Answer 756

Trypanosoma cruzi Transmitted by inoculation of contaminated faeces of a triatomine vector Transmission: - Vector - Vertical (transplacental) - Transfusion - Transplantation - Oral ingestion ○ On the rise Eg juice like acai juice, higher burden of parasite and higher mortality rates Vectors: - Triatoma infesters, Rhodnius prolix, Triatoma dimidiata Acute: - Self-limiting syndrome 4-8 weeks - Fever, malaise, lymphadenopathy, heptosplenomegaly, myocarditis - Chagoma may occur at entry site - Rare case presenting as orbital cellulitis (eye acts as another portal of entry) = Romana's sign Rarely, meningoencephalitis Indeterminate (2/3), Chronic/determinate (1/3) - Arrhythmias (BBB, SN disruption, AV block) - Myocardial abnormalities (segmental wall motion abnormalities, dilated cardiomyopathy) - Aneurysms (LV, RV) - Thromboembolism (stroke>systemic) Treatment - Benznidazole (or nifurtimox) - Named patient order to WHO outside of endemic areas - 60 days -> poorly tolerated Objectives - Effective for parasitological clearance - Effect upon clinical endpoints unproven - Prevents vertical transmission TRIALS - BENEFIT -> did not show evidence in patients with early cardiomyopathy that treatment with Benznidazole did not affect progression but patients did clear parasites (?relevance) BENDITA trial - Looked at benznidazole alone and in combination with fosravuconazole - Similar rates of seroconversion in BZN shorter dose in 2 weeks compared to 8 weeks - So should we be treating for shorter courses than 60 days MULTIBENZ - No differences in sustained negativity by qPCR between control with Benz, low-dose and short treatment - Can we shorten treatment to 2 weeks Marked low response to treatment in Brazil site -> not explained by genotype

Answer 757

- HIV -> SOL (mimics cerebral toxo), meningocencephalitis (ring enhancing lesions) - Transplant recipients -> fever, rash, myocarditis

Answer 758

Romana's sign Chagas

Answer 759

Serology (need 2x tests) - ELISA - IFAT - In indeterminate phase titre is unhelpful, response to therapy variable -> ie can't use as marker of disease or therapy PCR - Parasite DNA detection - Only performed if sero-positive - May be positive in indeterminate phase - Conversion seen with therapy but not necessarily sustained neither reflective of preventing disease progression - Used for congenital infection Microscopy (blood/buffy coat) only useful in acute infection (<1% diagnosed) and congenital (50% sensitivity)

Answer 760

TRIALS - BENEFIT -> did not show evidence in patients with early cardiomyopathy that treatment with Benznidazole did not affect progression but patients did clear parasites (?relevance) BENDITA trial - Looked at benznidazole alone and in combination with fosravuconazole - Similar rates of seroconversion in BZN shorter dose in 2 weeks compared to 8 weeks - So should we be treating for shorter courses than 60 days MULTIBENZ - No differences in sustained negativity by qPCR between control with Benz, low-dose and short treatment - Can we shorten treatment to 2 weeks Marked low response to treatment in Brazil site -> not explained by genotype

Answer 761

NO - treat after breast feeding has stopped 1. vertical transmission occurs in 5% of pregnancies in women with T. cruzi infection 2. without maternal testing this transmission is invisible until the development of disease in young adult life 3. anti-parasitic treatment of infants is highly effective so early detection and treatment is critical 4. anti-parasitic treatment during pregnancy is contra-indicated, but future pregnancies can be protected by treatment of mother after breast-feeding ceases 5. pre-conception anti-parasitic treatment prevents almost all vertical transmission

Answer 762

Girls and women from endemic countries of Latin America should be offered testing (only needed once) 1. Offer screening (ideally pre-conception) to all women of child-bearing age 2. Offer antenatal screening to all women from Latin America 3. Test and follow-up infants born to T. cruzi seropositive mothers, treating those with confirmed infection Babies will have positive serology from mum so need to take PCR

Answer 763

· Zoonotic spillover to humans : activities of infected animals/vectors and humans overlap · Unpredictable combination of factors: ○ shedding patterns, ○ land use change, social/economic conditions, ○ wrong place wrong time · human-vector interface: animal husbandry, household environment · Exception ‘human reservoirs’ : where viable virus persists in survivors after recovery, e.g. EV sexual transmission · Person to person transmission drives outbreaks ○ R0: estimates from 1.34 to 4.71 but limited data ○ Direct contact with contaminated body fluids or objects through broken skin or mucous membranes ○ High potential for exposure in households due to caring practices, and late presentation to healthcare due to fear ○ Super-spreading events: funeral ceremonies, markets, cultural obligations ○ Increased population movement: shift into more dense urban environments changes exposure risk ○ Nosocomial transmission due to poor IPC, undetected cases, slow diagnosis of suspect cases *Exception Ongoing exposure to a common zoonotic transmitter – can resemble person to person spread (e.g. Lassa)

Answer 764

People in contact with potential transmitting vector eg animal faeces, insects etc Household members and close contacts Nosocomial infection

Answer 765

Asymptomatic − Ebola 2.6-6.5%; CCHF ~70%; Lassa 80%; Marburg 0%? − Difficulty of identifying due to non- specific common symptoms and case definition − Unlikely to transmit due to lack of body fluids & low viral load Pauci-symptomatic − Transmission potential may depend on type of symptoms (“dry”/ “wet”) − Increasing viral load linked to onset of more florid symptoms Symptomatic − extent of exposure to a symptomatic case, and whether that case is dry or wet is strongly associated with risk of infection − Ebola - many contacts with high exposure do not become infected.

Answer 766

Reduce exposure, break transmission, speed care for infected, reduce severity & fatality __ Active case detection : reduce delay from onset to isolation, speed care provision Earlier and more rapid isolation & care: improve outcome, reduce exposure Triage & suspect management: avert undetected cases in routine services; also confidence in safety in healthcare setting Faster, more frequent testing: reduce time to care, better management of suspect & quarantine IPC healthcare facilities: prevent transmission, avert amplification IPC household: human and animal: prevent/ reduce exposure “IPC” community: adapt public health measures - avert exposure Contact tracing: early detection, break transmission Quarantine: reduce time to detection, reduce unwitting transmission but risk of opposite effect

Answer 767

Genus orthoebolavirus has 6 different species associated with it (only top 3 associated with : - Zaire/Ebolavirus (highest mortality rate) - Sudan ebolavirus virus - Bundibugyo ebolavirus - Tai forest ebolavirus - Reston ebolavirus - Bombali ebolavirus

Answer 768

- Targets mononuclear phagocyte system -> affects dendritic cells (inhibition of RIG-I and aberrant maturation) and macrophages - Rapidly replicates in the cytoplasm + disseminates to nearby tissues - Immune system dysregulation -> B and T cell dysregulation - Cytokine storm - Vascular leakage, third spacing and coagulopathy (haemorrhage), damage to endothelium, low BP - Liver: transaminitis, reduced clotting factor production, hypoalbuminaemia, hypoglycaemia - GI: V&D, fluid and electrolyte loss, disrupted acid-base balance, hypoproteinaemia - Spleen: cytokine dysregulation and death of lymphocytes - Kidney: AKI, oliguria, anuria, electrolyte abnormalities - Skeletal muscle: injury + elevated CK

Answer 769

Cycle of transmission - Single pass from animal to human eg via bat faeces etc - Amplification in humans, human to human transmission Epi Major outbreaks include the 2014-2016 West Africa outbreak and periodic outbreaks in the DRC. - Guinea, Liberia, Sierra Leone High case fatality rate (often 50% or higher), with outcomes heavily impacted by healthcare access. Ebola's severe impact on public health emphasizes the need for rapid response, strong healthcare measures, and international collaboration. Transmission Animal-to-Human: Likely spread from infected wild animals, such as fruit bats, through direct contact or consumption Human-to-Human: Direct contact with bodily fluids (blood, saliva, sweat, etc.) or contaminated surfaces and materials Non-Airborne: Ebola does not spread through air, water, or casual contact Pathogenesis - Targets mononuclear phagocyte system -> affects dendritic cells (inhibition of RIG-I and aberrant maturation) and macrophages - Rapidly replicates in the cytoplasm + disseminates to nearby tissues - Immune system dysregulation -> B and T cell dysregulation - Cytokine storm - Vascular leakage, third spacing and coagulopathy (haemorrhage), damage to endothelium, low BP Clinical presentation Incubation Period: 2-21 days - Only symptomatic patients can spread the disease and remain infectious until virus is not in blood Early phase: day 0-1 fever, muscle pain, headache, sore throat, fatigue (non-specific, eg could look like Malaria) Day 2-4: some diarrhoea, hiccups, feel worse etc Progressive Symptoms (GI phase): day 4-9: Vomiting, diarrhoea (can be bloody), abdominal pain, rash, kidney/liver impairment Cardiovascular compromise, weak/fast pulses, less ambulation of patients Different phenotypes e.g. renal, encephalopathy, hypoglycaemia Terminal phase: Internal/external bleeding, organ failure Day 10-12, confusion and delirium worsen, oliguric, anuric, death (both gradual and sudden) For those who survive, they may still be shedding -> transmission risk Lab diagnosis Gold standard: RT-PCR Other: RDTs (used as initial test, often need PCR to confirm): - OraQuick Ebola ELISA Viral culture (rarely used), high biosafety risk) Other: - Elevated transaminases - Raised CRP tracked with fevers - Raised WCC and thrombocytopenia Treatment Supportive Care: - IVF aggressively - Electrolyte abnormalities correction - Septic shock physiology -> IVF, monitor for third spacing - Symptomatic mx - Prophylactic Abx use due to concerns about bacterial gut translocation - Nutrition etc Experimental Treatments: Antivirals and monoclonal antibodies - Inmazeb = REGN-EB3 = 3 Ab targeting Ebola glycoproteins to get entry - Ebanga = mAb114 = single Ab targeting - more effective it administered early Vaccine: rVSV-ZEBOV vaccine (licensed 2019) protects against Zaire Ebola strain, given in outbreak zones. Prevention PPE: Essential for healthcare workers and those handling deceased. Safe Burial Practices: Reduces transmission from deceased individuals. Public Health Measures: Quarantine, isolation, contact tracing help contain outbreaks. Vaccine Deployment: Targeted in high-risk areas to prevent spread. Case management Shift from isolation unit to Ebola treatment unit - Trace - Isolate - Treat

Answer 770

Remdesevir MBP134 (monoclonal Ab targeting SUDV glycoprotein)

Answer 771

1. Suspected case Any individual presenting with one or more of the following: Malaise, fever, headache, sore throat, cough, nausea, vomiting, diarrhoea, myalgia, chest pain, Hearing loss, and either a. History of contact with excreta or urine of rodents b. History of contact with a probable or confirmed Lassa fever case within a period of 21 days of onset of symptoms OR Any person with inexplicable bleeding/hemorrhage. 2. Confirmed case A suspected case with laboratory confirmation (positive IgM Antibody, PCR or virus isolation) 3. Probable case A suspected case (see definition above) who died or absconded without collection of specimen for laboratory testing

Answer 772

Virus Arenaviridae family Lassa virus RNA virus with high mutation rates Transmission Most due to contact with rodent excreta (urine, feces, blood) from infected Mastomys natalensis rats - Ingestion of contaminated food - Handling, killing, ingesting rodents - Inhalation of aersolized virus (eg during sweeping or cleaning surfaces) Human-to-human transmission can occur via direct contact with bodily fluids, sexual transmission (persistence up to 12 months) Nosocomial Vertical + breastmilk Endemic Areas Found mainly in West Africa, especially in Nigeria, Sierra Leone, Liberia, Guinea, and Benin Some seasonal trends Highest in Nigeria, outbreaks Dec-May Some imported cases -> fatality higher due to delays in diagnosis (secondary transmission from these v rare) Approximately 100,000–300,000 cases per year Incubation Period Typically 1-3 weeks after exposure Asymptomatic Early symptoms: Fever, malaise, sore throat, sorethroat, myalgia (similar to Malaria) Severe symptoms: Bleeding, facial swelling, shock, and multi-organ failure Complications: Renal, neurological (seizures, encephalitis), bleeding, resp, pregnancy (termination, abortions, eclampsia) Mortality Rate Generally 1% for all cases Up to 15–20% in severe hospitalized cases Higher risk of death in late-stage pregnancy (up to 80%) Diagnosis RT-PCR on blood samples, sometimes on CSF from children ELISA for antigen or antibody detection Virus isolation in specialized labs RDT being evaluated Treatment Ribavirin (antiviral) is effective if given early Supportive care: IVF, renal support, blood products, resp support Prevention No licensed vaccine currently available Prevention relies on rodent control, proper food storage, and protective measures for healthcare workers (e.g., PPE) Public Health Impact Significant impact on healthcare systems in endemic regions; outbreaks pose high risks due to human-to-human transmission in healthcare settings

Answer 773

Vision * To be able to reduce death and morbidity from CCHF through safe and affordable effective treatments informed by rapid, reliable, simple-to-use and easily accessible diagnostics by 2023 (missed) and * To be able to prevent or mitigate CCHF disease through deployment of safe, affordable and effective vaccines or other preventive measures by 2030

Answer 774

Crimean-Congo Hemorrhagic Fever virus (CCHFV) Nairovirus genus in the Bunyaviridae family RNA virus Priority pathogen by WHO 2014 Transmission Tick-borne zoonosis -> Hyalomma ticks Maintained in nature -> enzoonotic tick-vertebrate eg camels/cows-tick cycles Primary human infection: via tick bite OR direct contact with blood or tissues of infected ticks or viraemic vertebrates including wild animals and livestock - High risk due to unsafe slaughter of animals Secondary human to human transmission: direct contact with blood, bodily fluids/tissues of infected (not extensive, hospital worse spread) High transmission risk when providing direct patient care or handling dead Concern transfer in migratory birds into Spain/Europe (carry ticks with them) Epidemiology Found in parts of Africa, Asia, Eastern Europe, and the Middle East - Turkey, Iraq, AFG, Iran, Pakistan Areas with high tick populations, especially rural and farming regions, are at higher risk. Incubation Period Typically 1-13 days, 3-4 days time to presentation/hospital admission, hospitalisation for 8 days, median age 50 years Typically 1-3 after tick bite Depends on transmission route (shorter with tick bites, longer with exposure to fluids) Symptoms Classified by fever, thrombocytopenia, haemorrhage -> VHF that 'bleeds' Children: - Fever, anorexia, N&V, Abdo pain -> not death, milder disease Initial symptoms: - Fever (not that high), headache, muscle aches, nausea, and abdominal pain - Transaminitis and bleeding, very low platelets BUT patient initially may have NEWs0/1 and look otherwise well, apart from thrombocytopenia and bleeding (different to ebolavirus) Progressive symptoms can include severe bleeding, shock, and organ failure Prognostic indicators + scoring criteria Fatal outcome associated with: - Elevated APTT, ALT, LDH, Plts <20 Criterias: - Swanepoel - SGS scores - SSI parameters Mortality Rate Varies between 10–40%, with higher rates in untreated severe cases. Diagnosis RT-PCR (blood, v little from urine) - Development of portable real-time PCR ELISA for CCHFV antigen or antibody detection Virus isolation in specialized laboratories (high risk) RDT: CCHF prototype 001 in development Gn Mab: BH14, JE12 Treatment Supportive care Ribavirin: Cochrane review showed low quality evidence, some benefit Favipiravir mAb development -> 2 selected with broad-neutralising activity (being taken from recovered patients and also lab based) Prevention One health approach essential No licensed vaccine is available - Anti-tick and Anti-CCHFV (DNA vaccines) showing promising results Prevention Relies on tick control measures, use of protective clothing, insect repellents, and avoiding animal contact in endemic areas Public Health Impact High impact in endemic areas; CCHF can cause outbreaks in healthcare settings due to person-to-person transmission. Special precautions are needed in hospitals to prevent spread

Answer 775

* Eggs in Environment: The life cycle starts when adult Echinococcus tapeworms residing in the intestines of definitive hosts release eggs into the environment through the host’s feces. * Ingestion by Intermediate Hosts: Intermediate hosts, including livestock (sheep, cattle, pigs) or accidental human hosts, ingest these eggs via contaminated food, water, or soil. * Larval Development in Intermediate Host: Once ingested, the eggs hatch in the intestines, releasing oncospheres(larvae) that penetrate the intestinal wall and migrate through the bloodstream to various organs, primarily the liver and lungs. Here, they develop into cysts (hydatid cysts in E. granulosus or alveolar cysts in E. multilocularis), which grow slowly and produce infectious protoscolices (immature tapeworms). * Definitive Host Infection: Carnivores become infected when they consume the organs of intermediate hosts containing these cysts. The protoscolices attach to the intestinal lining of the definitive host, mature into adult tapeworms, and complete the cycle by producing more eggs. * Human Infection: Humans act as accidental intermediate hosts. If they ingest Echinococcus eggs, the larvae form cysts, primarily in the liver and lungs, causing cystic or alveolar echinococcosis, which can be life-threatening if untreated.

Answer 776

* Cystic lesion in the liver * Simple cyst * Haematoma * Abscess * Cystadenoma * Cystadenocarcinoma * Necrotic liver mets

Answer 777

Viable cysts Transitional cysts DO NOT need to treat non-viable cysts

Answer 778

Depends on 1) Type, 2) Size, 3) Position Includes: - Conservative - Medical: albendazole, praziquantel - Interventional: PAIR, PEVAC - Surgical General principles · Albendazole alone: cysts <5cm · PAIR + ABZ: cysts >5cm without daughter cysts or solid areas · Surgery ○ Cysts > 5cm with daughter cysts or solid areas ○ Complex cysts invading other structures or the biliary tree ○ Lung cysts

Answer 779

The diagnosis of NCC should be based on neuroimaging and supported by specific serological tests. Assays of choice are LLGP-EITB for antibodies and mAb-based ELISA for antigen detection Imaging -> ideally both CT (for calcifications) or MRI (better image resolution and for intraventricular cysts) to detect cysts - Establish diagnosis - Define characteristics of infection Serological tests (e.g., Western blot, ELISA) for antibodies - Small amounts of Ag produced by parasite - Western blot almost 100% sensitive with 2 or more parasites - Not good for follow up - For Ag may be helpful in follow up Molecular - PCR on serum, CSF, urine Works in EP NCC but sensitivity unknown in PNCC

Answer 780

Pros: Rapid disappearance of cysts. * Severe cases are seen less frequently now. * Series of ABZ or PZQ-treated patients have better clinical evolution (have less seizures) than not-treated patients seen at the same centers. * Less residual calcifications.(?) Cons: NCC becomes symptomatic after several years, when the parasite dies. Anti-parasitic treatment causes severe, acute, unnecessary brain inflammation. Treatment-induced inflammation or stroke can kill the patient.

Answer 781

Caused by Taenia solium (pork tapeworm) Humans ingest tapeworm eggs from contaminated food, water, or direct contact with infected individuals Epi South America, Sub-Saharan Africa, South East Asia, also North Asia - Major cause of neurological disease Life Cycle 1. Ingestion of infected pork, poorly cooked Taeniasis -> faecal contamination 2. Eggs ingested by humans develop into larvae (cysticerci) that migrate through the bloodstream 3. Larvae encyst in tissues, especially muscles and the brain 4. Simultaenous ingestion of T.Solium eggs or proglottids -> porcine cysticercosis Transmission Fecal-oral route through contact with infected feces or contaminated food/water Autoinfection (self-infection) can occur if a person ingests tapeworm eggs from their own intestines Types Cysticercosis: Larval cysts in various body tissues, such as muscles, skin, eye Neurocysticercosis: Larval cysts in the brain, causing neurological symptoms - Intraparenchymal: cyst -> granuloma -> calcification (or disappearance) ○ Variable evolution ○ Other: massive infections - Extra-parenchymal: ○ Subarachnoid "racemose" cysts ○ Not quite associated to seizures and epilepsy: intracranial HTN, hydrocephalus ○ Significant mortality ○ Uncontrolled growth of cystic membrane Symptoms Cysticercosis: Often asymptomatic but may cause lumps under the skin or muscle pain Neurocysticercosis: Seizures (PNCC), headaches, intracranial HTN (NPNCC) - Can present as any neurological system as can get cysts anywhere in brain

Answer 782

Treatment Antiparasitic drugs (e.g., albendazole, praziquantel) to kill larvae - In general beneficial, need to identify type of CC, prioritise symptomatic management, its never an emergency (ie don't give acutely) - BUT in some people causes extensive brain inflammation -> stroke/inflammation can kill patient - BUT seems to reduce seizure incidence Corticosteroids to reduce inflammation in neurocysticercosis - Indication and dose not yet certain Antiepileptic drugs for seizure management. Surgery may be required for certain cases Prevention Proper cooking of pork to kill tapeworms Improved sanitation and hand hygiene to prevent egg ingestion Education on safe food practices and avoiding contaminated water or food sources Public Health Impact Significant in regions with poor sanitation and where pork is commonly consumed, such as Latin America, sub-Saharan Africa, and parts of Asia Leading cause of acquired epilepsy in endemic areas

Answer 783

Leptospira spp. = spirochaetes Free living and aerobic, motile Divided into serogroups based on serology not on DNA Transmission: ZOONOSIS Proximal tubules of mammals (primary reservoir) -> direct or indirect contact with animal urine Rodents are most important for maintaining transmission Survives for weeks in fresh water Spirochaetes invade skin and mucus membranes RFs: Occupational or recreational exposure to contaminated water/soil, cuts/abrasions, inadequate footwear, farming, sewerage workers Epi: Tropical and temperate regions, worse in rainy season, men>women, 1 million cases, 3rd commonest infectious cause of life threatening disease in returning travellers

Answer 784

Pathophysiology: Inoculation -> haematogenous spread and dissemination –> sepis syndrome/cytokine storm (IL6 and IL10) Severity related to innoculum dose and host factors Organ damage from direct pathogen insult and host response Haemorrhage can occur -> endothelial damage, capillary fragility and thrombocytopenia

Answer 785

Incubation period: 7-14 days, can range from 1-30 BIPHASIC (but manifested in few people in reality) (Most can be mild, self limiting illness) Early phase: leptospiraemia -> non-specific febrile illness lasting 3-9 days, fever chills myalgia OF CALVES, headache, 1/2 patients D&V, 1/3 cough Possible brief period of defervescence but two phases can overlap Immunological phase: IgM in blood, leptospira in urine, complications in 10% WEIL's disease in 5-10%: Fever, Jaundice, AKI, Conjunctival suffusion (develops in first week of illness) Complications: ○ Rhabdomyolysis ○ Jaundice ○ Acute Kidney Injury (with hypokalaemia) ○ Pulmonary haemorrhage (>50% CFR) ○ Myocarditis ○ Aseptic meningitis ○ Multi-organ failure ○ Rarer: ▪ Encephalitis ▪ Peripheral Nervous System: neuritis/radiculitis/optic neuritis Risk of Jarisch-Heixheimer reaction in 20% of patients

Answer 786

Laboratory findings: * Non-specific: ○ Leucocytosis, thrombocytopenia ○ Elevated CRP/Procalcitonin ○ AKI (with hypokalaemia) ○ Elevated conjugated bilirubin (+-transaminitis and ALP rise) ○ +- anaemia ○ NB clotting normal, no DIC Urinalysis: protein/blood/pyuria Diagnosis: * Compatible clinical syndrome * PLUS - Exposure history * PLUS - Detection of leptospira DNA (PCR, blood 1st week, urine 1st week onwards, high specificity, ok sens.) or serological response (IgM) (ELISA) (cross reactivity issue, ok spec/sens) Other diagnostic techniques ○ Dark field microscopy (need at least 10 spirochaetes) ○ Culture of blood (1st week illness, prolonged incubation of 12 weeks and low diagnostic yield) ○ Microscopic agglutination test (MAT) -> serological gold standard Caution with clinical risk/predictor scores e.g. modified Faine’s -> Poor specificity and poor PPV

Answer 787

* OPD vs Inpatient * Majority mild and spontaneously resolve. Standard IPC precautions. * Antibiotics – consider EARLY: ○ B-lactams/cephalosporins: IV Benzyl-penicillin or Ceftriaxone Doxycycline PO (or azithromycin PO or Amoxicillin PO) Cochrane review showed insufficient evidence. Supportive management: ○ Hydrate, correct electrolyte disturbances ○ Early haemo/peritoneal dialysis ○ Ventilation (low tidal volumes, “stiff lungs”) ○ Transfusion ○ Cardiac monitoring ○ No specific evidence based therapy RISK: Jarisch-Herxheimer reaction

Answer 788

Systemic reaction Occurs hours after initial treatment of spirochete infections, such as syphilis, leptospirosis, Lyme disease, and relapsing fever Presents with fever, rigors, hypotension, and flushing Can easily be mistaken for a drug-induced hypersensitivity reaction The underlying mechanism is initiated by antibiotic-induced release of spirochete-derived pyrogens Transient rises in TNF, IL-6, and IL-8 have been detected Reaction lasts 12–24 hours and can be alleviated by aspirin/ibuprofen/prednisone

Answer 789

* Lymphocytic pleocytosis (moderate) * Elevated protein, normal glucose * Imaging: ○ Cortical, midbrain, and rarely subcortical white matter change * Can mimic viral meningoencephalitis * Prognosis: ○ Generally good ○ Can have long term sequelae in severe cases

Answer 790

Sanitation Modifying risks and related behaviours -> provide wellies in wet season Abx prophylaxis: 200mg doxy weekly (debatable) Vacccination 10-15years away for humans Routine for animals - tetravalent vaccine

Answer 791

Parotid abscesses

Answer 792

Burkholderia pseudomallei Gram negative, oxidase positive -> environmental saprophyte - Seasonal, lives in soil -> rain -> increased exposure -> affects rural poor - Long latency (highest reported 28 years) Opportunistic pathogen so need predisposing conditions: - Diabetes mellitus *high risk - ETOH - Renal failure - Steroids - Exposure to ++ innoculum Epi: - Endemic in 45 countries - Found south of equator, issue in SE Asia and Australia (eg Darwin) - Thailand has surveillance programme Transmission: - Innoculation - Inhalation

Answer 793

Variable clinical presentation -> "Sepsis, pneumonia, abscesses anywhere in body" In order of prevalence: 1) Lung: pneumonia, pul abscesses 2) CVS: bacteraemia, pericarditis, aneurysm 3) GI: liver/splenic abscesses (honeycomb appearance) 4) UT: acute pyelo, kidney/prostatic abscess 5) Skin/soft tissue: ulceration, soft tissue abscess 6) Head/neck: parotid abscess (*think kids*), neck abscess, lymphadenitis 7) MSK: septic arthritis, osteomyelitis, myositis 8) CNS: encephalomyelitis, brain abscess Other eg mastitis, mediastinal mass, corneal ulceration, epididymo-orchiotis, scrotal abscess

Answer 794

Staining: safety pin polarity (not exclusive to this pathogen though, also seen in Yersinia pestis etc) Culture = gold standard ○ Est. sensitivity 60% ○ Enhanced if right samples from correctly suspected patients: ie blood, pus if abscess, urine etc Serology ○ Problems with sensitivity (particularly with indirect agglutination test) and specificity ○ Standardisation PCR ○ Not routinely used anywhere Ag detection -> research attempting for RDT

Answer 795

Burkholderia pseudomallei

Answer 796

Hazard group 3/Tier 1 'select agent' -> risk of bioterrorism For * Availability * Intrinsic resistance * Environmental persistence * High mortality * Inhalation transmission * Wide host range Against * Little development of weaponisation * No person to person spread * Less of effect in immunocompetent (inoculum dependent) * Difficult to disseminate (eg not like anthrax in forming spores)

Answer 797

* Intrinsic resistance to early beta-lactams and aminoglycosides * Resistance to co-trimox overcalled by disc diffusion * Acquired resistance to beta-lactams can occur ○ Uncommon ○ Rarely necessitates change in tx * No person to person spread * People get sick from environment not from other people so reduces AMR risk/burden

Answer 798

* Intensive phase: 2+ weeks IV beta-lactam (ceftazidime or carbapenem) * Eradication phase: 12+ weeks PO Co-trimox ○ Essentially all manifestations get 2 weeks minimum of intensive phase management and then depending on manifestations, varying length of treatment for both intensive and then for eradication phase ○ Eg CNS infection can get total treatment course of 3+ months Supportive management: critical to managing the illness

Answer 799

Yersinia pestis, gram negative bacteria 3 main forms: - Bubonic - Septicaemic - Pneumonic Circulates in animal reservoirs -> rodents Epi: Broad-belt across tropics Large burden (>90%) in Africa, eg DRC, Madagascar, Uganda, Tanzania More sporadic in Asian countries -> less contact with reservoir 2017 outbreak in Madagascar Transmission: * Droplet * Direct physical contact eg touching, sexual, unsafe burial * Indirect contact eg touching contaminated soil or surface * Airborne * Faecal-oral * Vector borne - carried by insects eg fleas from infected animals

Answer 800

○ In humans generally occurred by flea bite which was infected by biting rodent carrying the disease ○ Bacteria can multiply inside the flea -> stick together to form biofilm plug -> blocks stomach -> causes it to starve ○ Flea bites host -> continues trying to feed even though it can't quell its hunger -> flea vomits blood tainted with bacteria back into bite wound ○ Bacterium then infects a new victim -> flea dies from starvation ○ Rats die first --> in time then plague outbreak Urban cycle: refers to infected fleas biting rodents, then humans coming into contact with them, or new fleas being infected by them Sylvatic cycle: infected flea infects wild rodent which can then infect humans to again fleas can become infected

Answer 801

* Survival and proliferation within macrophages * Array of toxins and type 3 secretion mechanism: ~2 extra plasmids ○ pMT1: carries ymt -> for biofilm ○ pPCP1: carries pla -> for bubos/invasion at tissue barriers * Molecular typing being used in epidemics

Answer 802

* Buboes ○ Bubo=a tender, enlarged and inflamed lymph node) enlarged smooth tender/painful lymph nodes related to the site of a flea bite or other exposure ○ BUBONIC PLAGUE * Septicaemia with multiorgan failure/DIC -> peripheral gangrene: SEPTICAEMIC PLAGUE ○ Bacteraemia + role of endotoxins ○ N & V & Abdo pain ○ Hypotension + organ failure + DIC + localised areas of tissue/organ death (?black) ○ May be 2nday to bubonic/pneumonic or could be primary presentation ○ High mortality * A rapidly progressive pneumonia: PNEUMONIC PLAGUE ○ Rapidly progressive pneumonia ○ Short incubation - 2-4 days ○ Fever + weakness + nausea ○ Then pleuritic pain, SOB, cough, blood tinged sputum (contains numerous bacilli) ○ CXR: severe pneumonia +/- mediastinal or hilar lymphadenopathy ○ High mortality * Others ○ e.g meningeal involvement following dissemination ○ Pharyngeal and cellulocutaneous kinds All characterised by invasive bacterial infection and then uncontrolled proliferation of Y.pestis

Answer 803

* Short incubation period: 1-7 days * Bubo forms ○ Often singular ○ Common in groin ○ May occur in axilla/cervical region related to site of initial bite/scratch ○ May not be fluctuant or contain pus * Pain may be first feature - ie before swelling appears * Progressive -> rapid onset of sepsis features and dissemination: ○ Chills ○ Malaise ○ High fever eg 39 ○ Muscle cramps ○ Seizures ○ Peripheral gangrene secondary to sepsis

Answer 804

Macrolides

Answer 805

Pneumonic, septicaemia, bubonic In general: Fluoroquinolones (ciprofloxacin, levofloxacin and moxifloxacin) added to the first-line medicines (streptomycin and gentamicin) e.g. Streptomycin or gentamicin Fluoroquinolones 10 days For bubonic -> doxy also Meningitis In general: Floro. with good CNS penetration Moxifloxacin Ofloxacin Chloramphenicol at least 10 days Post-exposure: Floro added to first line of doxy and co-trimox. e.g. Ciprofloxacin Doxycycline Co-trimoxazole 7 days Pre-exposure: Tetracycline Doxycycline Co-trimoxazole

Answer 806

* LN aspirate ○ Culture organisms -> often bubos don't contain pus so can instil small vol of saline and withdraw it again * BCs ○ Can see organisms in blood smears if patient is septicaemic ○ In early course of illness: smears may be negative via microscopy but culture should be positive * Sputum ○ Culture possible from sputum of v ill pneumonic patients ○ Blood usually positive at that time * Bronchial/tracheal washings ○ Can take from pneumonic patients but other bacteria can mask presence of plague * Post-mortem ○ Take lymphoid, spleen, lung, liver or BM via DFA (direct florescent Abx) or PCR * RAPID tets ○ Lateral flow § F1RDT detects F1 capsular antigen (think that makes biofilm and blocks up stomach of flea) of Y.pestis which is present in a large amount of buboes, blood and sputum from infected patients § Performed on sputum from patients with suspected pneumonai plague and on bubo aspirate from patients with suspected bubonic plague Easily interpreted/used

Answer 807

Growth at 22-25oC An irregular or "fried egg" appearance, at 48-72 hours NB: Gram stain shows safety pin appearance (like Burkholderia pseudomallei)

Answer 808

* Reduce likelihood of infected flea bites * Reduce direct contact with infectious tissues and exudates * Reduce resp exposure to pneumonia plague cases * Pest control * Flea control * Wear gloves when handling wildlife * Plague vaccine unreliable, worked for bubonic but not pneumonic, (but new developments) CONTROL * Report * Isolate and treat clothing and baggage to rid of fleas * Disinfect ○ Surfaces contaminated with sputum ○ Flea control in environment * Quarantine in effective ○ Close contact of pneumonic cases -> chemoprophylaxis (tetracyclines or chloramphenicol) and surveillance for 7 days * Investigation of contacts * Specific treatments

Answer 809

Investigate all cases if possible with autopsy and lab tests Communicate to avoid panic Intensive flea control with insecticidal dusts Bodies, clothing, habitats (Reduce/attack rat populations) Contact tracing and prophylaxis Protect field workers (powder and repellents) Possibility of deliberate release an issue (most cases pneumonic? Yp lives in the air for an hour)

Answer 810

a self limiting enterocolitis associated with mesenteric adenitis, ileitis and gut wall granuloma formation

Answer 811

pCD1 - encodes type 3 secretion system, covers bac in needle like projections which inject yersinia outer proteins (yops) into host cells - yops induce apoptosis, inhibit phagocytosis and cytokine production and leukocyte recruitment pMT1 - produces an antiphagocytic slime layer around the bacterium which prevents phagocytosis + blocks flea stomach NB: this is the target of the RDT Ymt, which is required for survival within the midgut of the flea and is therefore important for the ability of Y. pestis to be transmitted by fleas pPCP lasminogen activator protease Pla which is thought to promote bacterial dissemination at the inoculation site by inhibiting the formation of a fibrin clot barrier, inhibiting innate immune cell recruitment, and inactivating antimicrobial peptides

Answer 812

Small enveloped single-positive stranded RNA virus = FLAVIVIRUS Two genotypes: African and Asian Africa: - Enzootic sylvatic transmission cycle, between non-human primates and forest dwelling Aedes mosquitoes with epidemic spillover into humans in peri-urban/urban areas via Aedes - Also human-to-human transmission: sexually, vertically, transplanted blood or tissue Cycle not identified yet in Asia but likely exists

Answer 813

Used to be central/South America during epidemic but NOW from south and SE Asia

Answer 814

50-80%: asymptomatic Symptomatic: Incubation 2-14 days Rash (maculopapular), diffuse, palms and soles +/- pruritis Low grade fever (often self-reported) Arthralgia Conjunctivitis (can help differentiate from dengue) Normally self-limiting illness, 2-7 days, with full recovery NB: prior Zika virus may worsen dengue disease caused by serotypes 2, 3 and 4, but conversely prior dengue infection may protect against zika

Answer 815

PCR Single positive PCR (blood or urine) -> test both - blood often only briefly positive within first week of illness Negative PCR does not rule out illness Serology For Zika-specific IgM and IgG -> available + diagnostically useful - Prone to cross-reacting with other flaviviruses SO caution when interpreting NB: IgM for Zika may not appear in patients with a history of previous dengue infection, an example of ‘original antigenic sin’ Negative serology 2 weeks after the onset of symptoms makes the diagnosis of Zika highly unlikely.

Answer 816

Zika virus demonstrates neurotropism, and neurological complications from infection are well described. The best-known is congenital microcephaly, one of multiple potential neurological complications of congenital Zika infection. Maternal-to-fetal transmission during maternal Zika infection is likely very frequent, but the reported risk of subsequent congenital abnormality is variable, ranging from 6% to 40% for any abnormality and 1% to 5% for microcephaly. Birth defects are exclusively associated with the Asian genotype; it is hypothesised that the more virulent African strain may instead lead to fetal loss. In adults, Zika has also been associated with Guillain-Barré syndrome, meningitis, encephalitis, and transverse myelitis.

Answer 817

Gnathosomiasis caused by Gnathostoma spinigerum Look for: mobile subcut mass, intermittent creeping eruptions, eosinophilia (may have N&D&V, fever, malaise for 2-3 weeks before cutaneous or visceral manifestations) Acquired by eating raw fish and other food items -> most common in SE Asia and Latin America Nematode, zoonotic, foodborne Tx: Albendazole 21 days /Ivermectin 2 days Big risk: migration of nematode to brain or spinal cord -> eosinophilic meningitis, SAH, cranial neuritis, painful radiculomyelitis Ddx: - Strongyloides stercoralis - Sparganosis - Rarer: ectopic fascioliasis, Migratory myiasis

Answer 818

adult worms infect GI tract of felines and canines eggs excreted in faeces get into water first stage larvae hatch -> infect small freshwater crustaceans then other animals become intermediate hosts via heating raw or undercooked meat of intermediate hosts eg freshwater fish, crustaceans, crabs, shrimp, frogs etc

Answer 819

Microscopy for Eggs Stool or Urine Confirms active infection Limited sensitivity; needs egg excretion, ie can NOT always see Ova in chronic infection Serology (Antibody) Blood Early detection, non-endemic cases Cannot distinguish past vs. active Antigen Detection Urine or Blood Indicates current infection Lower sensitivity for some species PCR Blood, Urine, Stool High sensitivity, species-specific Requires specialized lab Tissue Biopsy Tissue (bladder, rectum) Confirms diagnosis in chronic cases Invasive, used selectively Imaging Bladder, Liver, Spleen Assesses organ damage in chronic cases Not diagnostic on its own USS in chronic cases can be investigation of choice -> eg in urogenital cases can demonstrate hydronephrosis and bladder wall abnormalities Also cystoscopy shows sandy patches and uraemia

Answer 820

Granulomatous

Answer 821

Schistosoma haematobium -> causes urogenital schistosomiasis

Answer 822

Granulomatous inflammation of bladder wall and ureteral mucosa Obstructive uropathy Hydronephrosis Recurrent bacterial pyelonephritis End stage renal disease SCC bladder

Answer 823

Ehrlichia Anaplasma Coxiella burnetii = Q fever Rickettsia rickettsii = Rocky Mountain spotted fever

Answer 824

Eschar - rickettsial disease, expect systemic symptoms Cutaneous anthrax Insect bite Folliculitis Myiasis -> infection with fly maggots (slow growth of boil, no lymphadenopathy, no systemic symptoms, localised itch)

Answer 825

Infestation of live humans and vertebrate animals with larvae (maggots) of flies -> feed on host's dead or living tissue, liquid body substance or ingested food Cutaneous -> common manifestation -> red lesion with scab in middle, systemically well Two types: - Africa = caused by larvae of Cordylobia anthropophaga (Tumbu fly or Mango fly) ----> Adult female flies deposit eggs on sandy ground or on damp laundry spread etc -> humans wear contaminated clothes without hot ironing or lie on ground -> larvae hatch and burrow into skin -> over 2/3 weeks developing larvae cause itch and 'blind boil' NB: lesions are usually sterile as larva oozes with antibacterial properties Tx: petroleum over wound -> starves larva of air and eventually comes to surface of skin -> pull it out. Self-limiting regardless as mature larva has to leave host and pupate elsewhere. - Central/South America = Dermatobia hominis (human botfly) ----> Eggs laid directly on exposed skin + ova also deposited on blood-sucking insects eg mosquitoes, flies, ticks -> conveyed to human host

Answer 826

Puff adder (Bitis arietans)

Answer 827

Thiamine Wet beri beri

Answer 828

Thiamine deficiency Causes: Inadequate dietary intake, often in populations consuming polished rice. Increased thiamine demand (e.g., pregnancy, lactation). Malabsorption issues (e.g., gastrointestinal disorders, alcohol dependence). Symptoms: Cardiovascular: Edema (swelling in legs and feet). Rapid heart rate (tachycardia). Low blood pressure (hypotension). Possible heart failure. Neurological: Some patients may experience peripheral neuropathy. Diagnosis: Based on clinical symptoms and dietary history. Laboratory tests can measure thiamine levels but are not always necessary. Treatment: Thiamine Supplementation: Immediate oral or intravenous administration of thiamine. Dietary Changes: Encourage consumption of thiamine-rich foods (whole grains, legumes, nuts). Prevention: A balanced diet rich in thiamine. Education about thiamine's importance, especially in at-risk populations.

Answer 829

The slope of the roof should trap the prevailing wind to allow air to circulate through the latrine The pipe is designed to trap flies and other insects which are attracted to the light and then trapped by the fly screen which you can see at the top of the pipe, as well as reduce smells if the airflow is adequate. Most sources would say that 15m or 50 feet is the lower limit of distance from a water source. The sides of the pit are normally sealed to prevent collapse/undermining by burrowing animals. The bottom is left unsealed so that liquid can seep away- sealing it would cause the latrine to fill up with liquid and flood. Constructing a latrine on a slight mound is preferred so it does not flood easily with rain or groundwater

Answer 830

intracellular Gram negative cocci in pairs (diplococci)

Answer 831

Bartonella is intracellular

Answer 832

Yersinia pestis

Answer 833

scurvy - check for loss of teeth -> feature of the weakening of connective tissue

Answer 834

Handwashing RCOG Antiseptics Antibiotics RCM NHS oxytocin Training Contraception MgSO4 Abortion law Living standards Safer anaesthesia

Answer 835

Direct: As a consequence of a disorder specific to pregnancy e.g. Haemorrhage, pre-eclampsia, genital tract sepsis Indirect: Deaths resulting from previous existing disease, or diseases that developed during pregnancy, and which were not due to direct obstetric causes but aggravated by pregnancy e.g. Cardiac disease, other infections (sepsis) Coincidental: Incidental/accidental deaths not due to pregnancy or aggravated by pregnancy e.g. Road traffic accident Late: Deaths occurring more than 42 days but less than one year after the end of pregnancy

Answer 836

- Severe bleeding (PPH) - Infections (usually after childbirth) - High blood pressure during pregnancy - Delivery complications - Unsafe abortion

Answer 837

1. Health system failures ○ Poor quality of care ○ Insufficient numbers and training of healthcare staff ○ Lack of essential resources/medial supplies ○ Poor accountability 2. Social determinants ○ Income ○ Nutrition ○ Education ○ Race and ethnicity 3. Harmful gender norms ○ Structural and individual 4. External factors Instability of health systems eg conflict, climate, humanitarian crises

Answer 838

1) Delay in decision to seek care 2) Delay in reaching appropriate care 3) Delay in receiving adequate care

Answer 839

- SDGs (2015-2030) - under no.3, target 3.1 to reduce MMR <70 maternal deaths per 100,000 livebirths by 2030 Strategies toward ending preventable maternal mortality WHO 2015 (5 objectives, progress updated 2021)

Answer 840

Address inequities in access to maternal health services. Ensure universal health coverage for comprehensive maternal and reproductive health. Address all causes of maternal mortality and related disabilities. Strengthen health systems to meet the needs of women and girls. Improve measurement, data quality, and use of maternal health data.

Answer 841

Recommended interventions in five categories What? * Antenatal nutrition * Maternal and fetal assessment * Preventive measures * Management of common physiologic symptoms in pregnancy How? * Health system-level interventions to improve the utilization and quality of ANC Eight contacts * One in first trimester * Two in second trimester * Five in third trimester * Tailored to individual country context * What is included at each contact * Who it is provided by * Where it is provided * How it is provided and co-ordinated

Answer 842

- Routine antenatal nutrition * Promote healthy eating and physical activity * Iron and folic acid supplements * Calcium supplements for populations with low dietary intake * Vitamin A supplements or populations with high deficiency rates - Maternal and fetal assessment * Check haemoglobin and urine culture using available methods * Ask about intimate partner violence if provider is trained to ask/respond * Routinely screen all women: for gestational diabetes, tobacco and substance misuse, HIV and syphilis * Screen for TB in high prevalence areas * Assess fetal growth by SFH or abdominal palpation * Provide ultrasound before 24 weeks gestation - Preventative measures * Treat asymptomatic bacteriuria * Provide anti-helminthic treatment in endemic areas * Vaccinate against tetanus * Provide intermittent preventative treatment and insecticide treated nets in malaria endemic areas - Common physiological symptoms of pregnancy * Offer pharmacological and non-pharmacological treatments for common pregnancy symptoms - Health system interventions * Woman-held case notes improve quality of care and pregnancy experience * Midwifery-led continuity of care in settings with robust midwifery programmes * Task-shifting of ANC activities * Support to recruit and retain health workers in rural/remote areas - Community based interventions * Improve communication and support for pregnant women * Increase birth preparedness and complication readiness * Increase use of antenatal services and skilled care at birth * Increase male involvement * Build partnership with traditional birth attendants

Answer 843

1. Tocolysis - 24 – 33+6/40 - CI: PV bleeding, placental abruption, intrauterine infection - To allow antenatal corticosteroids OR transfer to a facility for care of preterm infant - Nifedipine 20mg, followed by 10mg 6 hourly 2. Antenatal corticosteroids - 24-33+6/40 - If high chance of labour within 7 days (PPROM, cervix ≥3cm dilated or ≥75% effaced) - Or planned preterm birth - IM dexamethasone: 6mg, 12 hourly, 4 doses. - IM betamethasone 12mg, 24 hourly, 2 doses. - Maximum benefit after 24 hours to 7 days. 3. Antibiotics for PPROM - Any gestation <37/40 - Erythromycin 250mg, qds, 10 days or until birth - Reduce risk of chorioamnionitis and NEC 4. Magnesium sulphate - 30% reduction in cerebral palsy <32 weeks - 4g loading and 1g/hour maintenance - If delivery anticipated within 24 hours 5. Delayed cord clamping 6. Thermal care Plastic bag/wraps for stabilisation and transfer

Answer 844

Preterm birth * extremely preterm (<28 weeks) * very preterm (28 to 32 weeks) * moderate to late preterm (32 to 37 weeks) * 5-18% of births globally * Increased burden in southern Asia and sub-Saharan Africa * 13.4 million babies in 2020 Leading global cause of perinatal mortality (30%) Causes: * Idiopathic (cause unknown) * Iatrogenic (pregnancy complications eg. PET, growth restriction) * Preterm prelabour rupture of membranes (PPROM) * Infection (intra- and extra-uterine) * Bleeding (APH) * Multiple pregnancy Prevention: * Optimal antenatal care * Nutrition and lifestyle * Identify and treat anaemia, asymptomatic bacteriuria * USS to determine GA and multiple pregnancy * Cervical length monitoring * Progesterone * Cervical cerclage * (Rescue cerclage)

Answer 845

Definition: Hb <110g/l in first trimester <105g/l in second and third trimesters <100g/l postpartum Prevalence: Around 40% globally * Highest in SE Asia and Africa Second leading cause of disability globally Causes: * Pregnancy physiology * Nutritional deficiency (90% of cases) * Parasitic infection * Other infections (TB, HIV, malaria) * Chronic diseases * Acute/chronic blood loss * Haemoglobinopathies Complications: Maternal: * Symptoms (fatigue, irritability, generalized weakness, shortness of breath) * Reduction in immune function (increased susceptibility and severity of infection) * Placental abruption * Post partum haemorrhage * Increased maternal mortality Fetal: - Preterm birth - LBW - Increase in infant mortality Management: Oral iron supplementation * Ferrous sulphate 200mg od * Ferrous fumarate 210mg od * Expect 1g/week Hb increase Parenteral iron * If not tolerating oral or rapid correction of Hb needed * Anaphylaxis, skin staining Blood transfusion * Hb <6g/dL (<8g/dL if PPH risk) Folic acid * 5mg od Vit B12 * IM or oral cyanocobalamin * 250-1000mcg alternate days, 2 weeks

Answer 846

Pre-existing HTN - Essential - Secondary to renal disease - Diabetes - Systemic disease - Cardiac causes Pregnancy induced HTN Pre-eclampsia - Pregnancy specific: HTN + proteinuria - Most common in first pregnancy Pre-eclampsia, eclampsia, HELLP * Any organ system may be affected * Most commonly presents - headache, hypertension, proteinuria * Fitting in pregnancy should be managed as eclampsia until other proven cause Recurrence rate of 10-40% Complications - Super-imposed pre-eclampsia - Preterm birth - Fetal growth restriction - Placental abruption - Perinatal death - Maternal stroke Management: * Prompt and careful control of hypertension * Meticulous fluid balance with avoidance of overload * Seizure prophylaxis with magnesium sulphate * Watch platelets * Renal function * May develop coagulopathy * Planned delivery on the best day is the best way * Stabilisation before any transfer * Postpartum vigilence

Answer 847

- Check BP and urine at every point of contact in pregnancy to screen for pre-eclampsia and manage any pre-existing HTN Reduce risk by low dose aspirin 150mg from 12-36 weeks for women considered high risk HIGH Chronic Hypertension: Pre-existing high blood pressure before pregnancy. History of Preeclampsia: Previous pregnancies complicated by preeclampsia. Autoimmune Disorders: Conditions such as lupus or antiphospholipid syndrome. Kidney Disease: Chronic kidney issues raise the risk of hypertensive complications. Diabetes: Both Type 1 and Type 2 diabetes are risk factors. Multiple Pregnancy: Carrying twins or more increases the risk. LOW First Pregnancy: Higher likelihood in first-time mothers. Age: Being under 20 or over 35. Obesity: Higher BMI increases risk. Family History: Family members with preeclampsia or hypertension. Personal History of Conditions: Previous gestational hypertension or related issues in past pregnancies.

Answer 848

Maternal collapse - Consider uterine manual displacement and peri-mortem C-section Causes: 4H's and 4T's, particularly - Hypovolaemia - Hypoxia - VTE - Toxicity eg LA, MgSO4 Other: - Eclampsia - Pre-eclampsia - Intracranial haemorrhage - Amniotic fluid embolus - High spinal anaesthesia - Peripartum cardiomyopathy - Aortic disection APH RFs: Placental praevia Placental abruption Uterine rupture Mx: ABC Bloods: FBC, X match, Coag, Kleihauer Deliver fetus Prepare for PPH PPH 'Empty uterus does NOT bleed' RFs: * Retained placenta (tissue) * Adherent membranes or placental fragments (tissue) * Uterine rupture (tone and trauma) * Uterine inversion (tone) * Atonic uterus (tone) * Genital tract trauma – cervix or vagina (trauma) * Coagulopathy – PET, abruption, AFE, sepsis (thrombin) Mx: * ABC * Call for help * State nature of emergency * Depends on clinical situation * Uterotonic medications * May need urgent transfer to theatre for manual removal of placenta * Urgent suturing * Intrauterine pressure with balloon * Laparotomy and compression of uterus * Decision for hysterectomy saves lives In general for bleeding at time of C-section: * A contracted empty uterus does not bleed * Empty the uterus * Step-wise approach to atony * Give uterotonic drugs * Pressure, pack, platelets, prayer, patience * Consider B Lynch suture * Intrauterine balloon * Hysterectomy SEPSIS - sepsis 6 Women should not feel flu like after birth + young fit women decompensate late ?GrpA strep Mx * Avoid NSAIDs * IV antibiotics as soon as possible * Full thorough examination ?sepsis source

Answer 849

Breech mx: * Delay pushing until breech is distending the introitus * Lithotomy * Episiotomy * Hands off approach * Do not squeeze fetal abdomen * Pelvic grasp and rotate to aid delivery of arms * When nape of neck appears allow baby to hang down * MSV to flex and deliver head * Forceps if head difficult to deliver – assistant to hold baby UP SD: Recognise early - ?turtle sign/failure to restitute * Call for help * State the nature of the emergency * Discourage pushing * McRoberts manoeuvre to maximise size of pelvic outlet * Routine axial traction * Suprapubic pressure to try to dislodge anterior shoulder * Internal rotational manoeuvres or delivery of posterior arm * Ready for neonatal resuscitation * Prepare for PPH * Debrief the mother Cord prolapse: ELEVATE THE PRESENTING PART RFs: - Malpresentation/unstable lie - Multiparity - Polyhydramnios - Prematurity Mx: * State the nature of the emergency * Is the fetus viable? * Is the cervix fully dilated? * Turn off any oxytocin and consider tocolysis * Manually elevate presenting part * Catheter with 500ml into bladder * All fours * Monitor fetus and transfer for delivery by Caesarean * Release bladder prior to skin incision * Debrief the patient

Answer 850

* Bimanual compression * Give uterotonics * Ensure bladder is empty – indwelling catheter * Consider EUA and intrauterine balloon * Consider laparotomy * Slow 5u IV oxytocin * Ergometrine 0.5mg IM or slow IV (not if hypertension) * Oxytocin infusion * Carboprost 0.25mg IM every 15 mins to maximum 8 doses * 1mg misoprostol (5 tablets) * Tranexamic acid (in context of active bleeding)

Answer 851

Placental praevia Placenta implanted totally or partially in lower segment of uterus - Recurrent bright red bleeding without pain - Fetus not usually compromised unless major blood loss Often high presenting part or malpresentation RFs: More common in multiple pregnancy and C-section Mx: Do NOT do a vaginal examination Think about C-section Entry and haemorrhage control Placental abruption Separation from the placental bed of a normally sited placenta Tender uterus/fetal distress - Unknown cause - Usually presents with pain - Bleeding may or may not be revealed Complications: - Fetal compromise - Maternal shock and DIC Mx: Vaginal delivery not necessarily CI Uterine rupture Occurs in labour Presents with pain, bleeding, fetal distress, maternal collapse RFs: RFs: - VBAC - Multiparity - Obstructed labour - Trauma Mx: ABC Theatre GA if possible C-section with possible hysterectomy

Answer 852

Pregnancy related: o Maternal collapse o Septic abortion/TOP o Miscarriage · Threatened/missed § Closed cervix · Incomplete § Open cervix, Ectopic pregnancy · Heavy menstrual bleeding · Cervical cancer § Rarely present as emergencies but needs to be considered · Trauma: Assault, secondary to unsafe termination, Non-obstetric/gynaecological

Answer 853

· Ectopic pregnancy ○ Salpingectomy -> Usually mini-laparotomy in low resource settings · Sexual assault ○ Assess injuries including non-gynaecological □ Documentation and sampling needs to occur before repair/theatre ○ Risk of pregnancy ○ Emergency contraception ○ STI risk □ HIV PEP □ HBV vaccination □ Consider Abx if no follow-up available ○ Mental health assessment □ Consider admission if needed · Miscarriage ○ Threatened □ Reduce activity --> either threat passes or abortion inevitable □ Consider infectious cause (e.g. malaria, STI) --> treat □ Analgesia ○ Missed □ Uterine evacuation not urgent if no signs of infection, no heavy bleeding □ Uterine evacuation ◊ Misoprostol 600mcg SL or 800mcg PV ◊ Manual vacuum aspiration (MVA) under LA ○ Ongoing/incomplete □ Analgesia □ Remove POC from vagina and cervix ◊ If RPOC may need misoprostol/MVA □ Consider underlying cause □ Iron/folate supplementation ○ Septic □ As above □ Remove foreign bodies □ Expedite uterine evacuation □ Abx · Heavy menstrual bleeding ○ NSAIDs ○ TXA ○ COCP ○ Oral progesterone only ○ Gynaecology specialist referral --> IUD · Sepsis after unsafe abortion ○ Often identified late, fail treatment ○ Examine for foreign body ○ Broad spectrum Abx · PID ○ Indications for admission □ High fever >38 □ HR >110 □ Rebound tenderness □ Palpable pelvic mass □ Non-responsive to treatment or unable to take PO medications ○ US for tubo-ovarian abscess ○ Broad spectrum Abx ○ Contact tracing and treatment ○ HIV testing ○ Advise re: safe sexual practices

Answer 854

An abnormal opening between the vagina and other nearby organs in the pelvis 2million women globally but decreasing incidence Iatrogenic fistulae are on the rise (ie used to be more ischaemic as described below), occur due to: § Hysterectomy, caesarean hysterectomy, caesarean delivery § Gaps in healthcare worker density § Healthcare worker skillset/training § Infrastructure Pathophysiology o Obstetric fistula · Used to be major cause · Usually occurs in second stage · More common in primiparous women · Fetal head compressed between pubic symphysis, sacrum --> oedema of (anterior) vaginal wall --> extreme pressure necrosis § Causes widespread ischaemia of surrounding tissues --> sloughing --> fistula formation § Can occur even if LUSCS performed § Often takes several days after delivery for diagnosis --> may not be diagnosed before discharge · Risk factors § Prolonged or obstructed labour § Late referrals from community settings § Distended bladder § Use of oxytocin in second stage § Failed instrumental § Destructive delivery after prolonged labour § Uterine rupture/pre-rupture (Bandl's Ring) Teenagers eg as in child marriage, are at risk Low education, rural location

Answer 855

Complications · Urinary/faecal leakage · Abnormal vaginal discharge · Tissue damage/irritation · Pyelonephritis · Infertility § Nerve damage --> foot drop § Perineal injury § Urethral loss/stress incontinence · Hydronephrosis, renal failure § Rectal atresia, anal sphincter incompetence § Cervical destruction § Asherman's syndrome --> amenorrhoea § PID § Secondary infertility § Vaginal stenosis § Osteitis pubis § Sociocultural consequences

Answer 856

Preterm birth

Answer 857

· High income countries § Gynaecological surgery · Usually multiple operations § Pelvic malignancy § Complications of RTx · Middle income countries § Iatrogenic § Contribution from cervical cancer, obstructed labour, genitourinary TB · Lower income countries § Relatively high rates of ongoing obstetric fistula but improving · Improving maternal mortality improves morbidity Increasing rates of iatrogenic fistula

Answer 858

Obstetric fistula · Primary prevention § Health promotion § Planned pregnancies · Birth spacing · Contraception, abortion care · Prevention of child marriage · Addressing violence Community awareness · Secondary prevention § Antenatal care § Skilled personnel at birth § Use of partograph § Identification of obstructed labour § Immediate referral § Bladder care during labour · Consider catheterisation if needed · Can consider catheterisation post-partum after obstructed labour · Tertiary prevention § Access to emergency obstetric and neonatal care including safe emLUSCS Iatrogenic fistula: · Requires prevention of surgical error § Reducing non-indicated C-sections § Restricting surgery to authorised, registered and trained surgeons

Answer 859

DIAGNOSIS Methylene blue: via IDC into bladder Vagina packed with gauze, observe ?dye leakage · Only diagnoses vesicovaginal/urethrovaginal fistula Imaging TREATMENT o Leave IDC (silicone) in for 4/52 · Can be observed in community · Weekly review for hydration status, signs of infection · Repeat methylene blue test after 4/52 § If neg -> remove catheter, consider bladder training § If pos -> remove catheter and refer · Don't leave IDC in for >6/52 total o Referral to specialist centre for all vesico/urethrovaginal fistulae · Take details including contact details (including of alternative contact) o Basic hygiene and care advice · Drink 4L/day of water o Offer contraception o If large rectovaginal fistula with severe contamination, irrigation with diluted povidone/betadine after every stool · Treat diarrhoea o If small rectovaginal fistula, may close spontaneously · Sitting baths, regular intimate toileting may prevent infection

Answer 860

· Rural settings § High population number, low density · Low attack rate (0.1-2%) · Slow peak (1-3m) § Lasts 3-6m § Fatality rate <5% · Urban settings/slums § High population number, high density · High attack rate (1-5%) § Peak 2-8 weeks § Duration 2-4m § Fatality rate 2-5% · Closed settings (refugee camps) § Low population number, high density · High attack rate (1-5%) · Rapid peak (2-4w), short duration (1-3m) - Fatality rate <2%

Answer 861

Cause Vibrio cholerae bacteria (serogroups O1 and O139 most common for epidemics) Highly motile, rapidly reproducing Epidemiology Endemic in parts of Africa, South Asia, and Southeast Asia; outbreaks occur after natural disasters or in settings with poor water and sanitation infrastructure Incidence increasing (conflict, climate change (low water stock -> more conc organisms), vaccine shortage) Transmission Primary: Fecal-oral route -> ingested via infected water source Requires large ingestion load to cause illness Secondary: Contaminated water or food Flies Soil Hand hygiene -> food contamination NB - Can have asymptomatic carriers Pathophysiology Ingested --> multiply in stomach --> toxin secretion Massive secretion of water and electrolytes in the intestines Symptoms Incubation: can be convalescent for 14 days Mild: Often asymptomatic or mild diarrhoea Severe: Profuse (up to 15L/day), "rice-water" diarrhoea, vomiting, rapid dehydration, shock, acidosis Diagnosis Clinical: Based on symptoms in endemic areas Laboratory: Stool culture, rapid antigen tests (e.g., dipstick or PCR for V. cholerae detection) Complications Severe dehydration, electrolyte imbalances, shock, acute kidney injury, death if untreated Case fatality highest in pregnancy, in general up to 50% without treatment, <1% with treatment

Answer 862

Rehydration: Primary treatment, ORS or IVF (if severe) Antibiotics: in severe cases to shorten illness duration, consider Doxy, resistance increasing Hygiene: Clean water, sanitation, handwashing Vaccination: Oral cholera vaccines (e.g., Dukoral, Shanchol) available in high-risk areas Evaluation: need to collect data on CFR, weekly incidence rate, attack rate Outbreak management: Case management Isolation and treatment · Decentralisation to keep people in affected communities · Treatment separated from existing healthcare facilities --> remove transmission risk · Cholera treatment centres: large, autonomous, 24/7, offer IV and PO rehydration · Cholera treatment units: simpler, smaller, 24/7, offer IV and PO rehydration · Oral rehydration point: outpatient, in-hours, simple cases, referral pathway to CTU/CTC Training of healthcare workers Use of protocols · Triage and admission: diagnosis, assessment of hydration status, initial treatment · Hydration: compensating for losses, close supervision (every 30min), zinc supplementation for children <5yo · Complementary therapy: Abx, nutritional Early case detection and referral · Active case finding WASH in treatment facilities § Supply of chlorinated water § Adequate sanitation and waste management § Strict IPAC measures § Management of bodies

Answer 863

o Vaccination (oral) § Appropriate >1y, including pregnant women · Low efficacy in children (43% <5yo) § 2 doses, 14d apart · Immunity 7-10 days after 1st dose § Immunity lasts at least 6 months, up to several years (not lifelong) · Protected for 3-5 years after 2 doses § Also reduces transmission in healthy carriers § Should be stored at 2-8 degrees but strict cold chain not required § Still effective after 3-4 days at 40 degrees § Can vaccinate reactively or preventively o Health promotion · Consideration to lack of literacy --> need oral delivery o Hygiene · Hand & household hygiene · Food hygiene (eat immediately --> decrease risk of contamination after cooking by flies) · Safe burial/funeral practices -> avoid touching, disinfection, burial 1.5-2m deep, avoid water sources o Sanitation · Disposal of human waste + waste water o Access to water · 15-20L/person/day -> needs increase with cholera · Chlorination (in line, batch, bucket -> must cover, inactivated in sunlight, aquatabs) o Risk stratification · Ring strategy/case area targeted intervention § Households surrounding cholera cases at increasing risk with increasing proximity to affected household § Implement WASH interventions, disinfection, vaccination to reduce inter-household transmission

Answer 864

First week Esp intra-partum

Answer 865

1 Prematurity 2 LRTI/Pneumonia 3 Intrapartum related eg birth asphyxia 4 Diarrhoea 5 Neontal infection

Answer 866

Family planning

Answer 867

- Assessing gestational age - Providing warmth - Feeding and fluids - Respiratory support - Infection prevention, recognition and treatment - Different exposures; context and care settings - Care largely supportive; the majority do not have access to NICU - Minimal capacity for investigations - Low nursing ratios, minimal monitoring - Risks of compounding brain injury; cooling not universally implemented - Limited access to fit-for-context equipment ie. pumps - Supply chain challenges and drug outages - Inconsistent electricity & water supplies

Answer 868

Child mortality reducing: * 12.6 → 5 million from 1990 to 2020 Newborn deaths still lag: * 2.4 million newborn deaths, ¾ of these in the first week * 47% of all under-5 mortality * Preterm birth and birth complications are the leading causes of death under-5 250 million children –are at risk of stunted growth and poverty and unlikely to fulfil developmental potential An estimated 53 million children with developmental disability

Answer 869

· 'Every Newborn Action Plan’ lays out strategic objectives and ambitious targets to reduce neonatal mortality NMR or <12 per 1000 births · Neonatal conditions are associated with an increased risk of developmental delay and disability · Important to think ‘Beyond Survival’ … to survive AND THRIVE including early intervention for young children with developmental disability

Answer 870

Neonatal conditions

Answer 871

· The highest risk of death is the day of birth, 75% in the first 7 days (highest risk is in first 24 hrs) · Prematurity, birth complications and neonatal infections are the leading causes of neonatal deaths

Answer 872

* Late preterm 34 - <37 weeks * Moderate preterm 32 - 34 weeks * Very preterm 28 – <32 weeks * Extremely preterm <28 weeks

Answer 873

Power, water, space Assessing gestational age Providing warmth Feeding and fluids Infection prevention, recognition, treatment Respiratory support Prevention of apnoea High patient nurse ratio

Answer 874

- Low birthweight, LBW < 2500g - Very low birthweight, VLBW < 1500g - Extremely low birthweight, ELBW < 1000g A lot of women won't know LMP etc so actually can't work out age of babies This weight method is also an issue as a lot of babies in LMICs are low weight for gestational age

Answer 875

- C-section - Born outside hospital - Moderate/Severe hypothermia at admission (highest risk factor) ○ Hypothermia stops surfactant production, increases respiratory distress ○ Use more energy, increasing glucose requirements, can become hypoglycaemic ○ Increased risk apnoea - Bradycardia at admission - Hypoxia at admission

Answer 876

- Dry and cover - Skin to skin (Kangaroo) - Put on hat and nappy - Avoid bathing

Answer 877

RDS Need CPAP

Answer 878

Compared to formula milk, in preterm infants, breast milk reduces the risk of: ○ Sepsis ○ Necrotising enterocolitis ○ Retinopathy of prematurity ○ Feeding intolerance ○ Neurodevelopmental delay * Wherever possible choose early & exclusive breast milk diet How? Use mum's milk expressed into cup every 2 hours -> feed by NG to establish feeds, feed by cup and spoon when stable, off CPAP and gaining wait BUT - Over 40% of preterms in neonatal units in LMICs have insufficient access to mum’s own milk - Preterms are at increased risk of postnatal growth failure (PGF) - PGF increases the risk of neonatal mortality - PGF also increases risk of subsequent neurodevelopmental delay in surviving preterm infants - PGF contributes to the high neonatal mortality rate in Uganda Solutions: - Nutritional support for mothers - Educate/encourage acceptability of donor breastmilk - Lactational support - Low cost, sustainable milk bank

Answer 879

Maternal Risk Factors * Fever (>38C) before or during labour * Foul-smelling or purulent amniotic fluid * Premature rupture of membranes (>18 h) * Multiple unclean vaginal examinations during labor * Prolonged or difficult labor (>24 h) Fetal Factors * low birth weight * Prematurity * perinatal asphyxia

Answer 880

Case definition * History of feeding difficulty * History of convulsions * Movement only when stimulated * Respiratory rate > 60 breaths/min * Severe chest indrawing * Temperature >37·50C, or <35·50C Sequelae: Pregnancy - Still birth Neonatal period - Meningitis - Sepsis - Pneumonia - Tetanus - Death Childhood and adulthood - Impairment - Neurological and neurodevelopmental issues - Hearing issues - Physical and mental health issues

Answer 881

Early onset neonatal sepsis - Occurs within first 72 hours of life (days 0 – 2) - Often caused by pathogens that the baby is exposed to before or during birth - Causative organisms may originate from the maternal genital tract - Unhygienic delivery practices and unclean birth area Risk factors: Maternal Risk Factors * Fever (>38C) before or during labour * Foul-smelling or purulent amniotic fluid * Premature rupture of membranes (>18 h) * Multiple unclean vaginal examinations during labor * Prolonged or difficult labor (>24 h) Fetal Factors * low birth weight * Prematurity * perinatal asphyxia Late onset neonatal sepsis - First 29 days Risk factors: - NICU admission (ie hospital acquired) - Invasive medical procedures (IV cannulations; mechanical ventilation) - Administration of stock solutions during parenteral therapy - Contaminated equipment, IV or enteral solutions - Prolonged hospitalisation For community acquired: - Poor hygiene practices in home setting - Inadequate cord care - Bottle>breast feeding - Lack of exclusive breastfeeding

Answer 882

Early-onset Group B Streptococcus (GBS) Escherichia coli Listeria monocytogenes Enterococci Late-onset Coagulase-negative Staphylococcus Staphylococcus aureus Escherichia coli Klebsiella

Answer 883

Maternally acquired * Intrapartum antibiotics * Penicillin (GBS) * Azithromycin * Maternal vaccines * RSV * Pneumococcus (RCTs) * GBS (in development) Early-onset infections * Handwashing before delivering and handling the newborn * Good basic hygiene & cleanliness during delivery * Avoid unnecessary separation of the newborn from the mother * Appropriate umbilical care * Appropriate eye care Late-onset infections * Exclusive breastfeeding * Strict hand-washing (alcohol rub) protocols for all staff and families * Clean injection practices * Removing IVF when no longer necessary * Strict asepsis for all procedures

Answer 884

1. Detection - Improved lab support and rapid response -> micro culture = GOLD STANDARD - POC diagnostics 2. Antimicrobials - Treatment protocols + IV Abx access - Current local/regional epi - AM stewardship 3. AMR - Vectors of transmission - Surveillance 4. IPC = infection control measures - Environmental and hand hygiene - Context specific guidelines 5. Investment - Resources and research 6. Supportive care - NICU admission - IVF - Temperature control - Euglycemia - Support for oxygen - Blood products

Answer 885

Resistance to WHO-recommended antibiotics (Lancet study:) * β-lactams 68% (614/904 cases) * Aminoglycosides (Gentamicin 26% - 83%; Amikacin 0 – 21%) Resistance to alternative therapeutic options * Fluoroquinolones (14% – 30%) * Carbapenems (0 – 4%) * Piperacillin/tazobactam (7% - 37%) Wide variation in treatment. Frequent switching of antibiotics due to high resistance to treatments.

Answer 886

* Klebsiella pneumoniae * Serratia marcescens * Klebsiella michiganensis * Escherichia coli * Enterobacter cloacae complex

Answer 887

BARNARDs Showed 4 commonly prescribed Abx combinations for neonatal sepsis: * Ampicillin–gentamicin, * Ceftazidime–amikacin, * Piperacillin–tazobactam–amikacin * Amoxicillin Clavulanate–amikacin

Answer 888

Grp B strep Strep pneumoniae Staph aureus

Answer 889

1st line: Gentamicin + Penicillin/Ampicillin 2nd line: Cephalosporin eg ceftriaxone or cefotaxime

Answer 890

Large observational study on neonatal sepsis in Bangladesh/India/South Asia Key causative organisms were: * RSV - 5.39 * Ureaplasma - 2.38 * Klebsiella pneumoniae - 1.49 * Escherichia coli - 1.43

Answer 891

Crusted scabies - sacroptes scabiei Can get superimposed skin infection eg staph aureus or strep pyogenes, also gram negative eg pseudomonas aeruginosa Ddx: Skin based eg psoriasis, tinea corporis, skin malignancies eg T cell lymphoma, Sezary syndrome Nutrition deficiencies eg pellagra, pemphigus, lepromatous leprosy, secondary syphilis Treat with: - IV Abx if superimposed bacterial infection - Ivermectin / benzyl benzoate / keratolytic cream - Treat family with topical permethrin

Answer 892

CT guided percutaneous vertebral or paravertebral aspiration In endemic settings usually: hx + epi + X-rays *if available On Spinal radiograph: - Focal areas of erosions - Osseous destruction in anterior corners of vertebral bodies - Involvement of adjacent disc or vertebral body - Wedging - Gibbus deformity - Paraspinal abscess formation

Answer 893

Compressive: - Potts disease (subacute, +/-bladder) - Metastases (acute/subacute +/-bladder) - Degenerative spinal disease eg slipped disc Non-compressive: - Transverse myelitis (acute, often non-progressive, bladder involvement common) - Schistosomiasis (acute/subacute, often flaccid paresis, bladder involvement common) - HIV associated vacuolar myelopathy

Answer 894

Herpes simplex - usually painful - can have multiple lesions - usually self-healing (after a few days) in immunocompetent but may be more severe/persist in immunocompromised -> consider tx with aciclovir Syphilis - usually single lesion and painless = chancre - treat with IM BenPen - serology can be negative in early infection Chancroid - Haemophilus ducreyi - multiple, painful lesions - common in sex workers/people who go to them - gram stain not sens/spec -> need to culture at 33 degrees from swabs - inherently resistant to penicillins, also lots resistant to tetracyclines and sulphonamides - Tx with azithromycin OR erythromycin OR Ciprofloxacin

Answer 895

Non-typhoidal salmonellae (iNTS) HIV seems to provide some protection against typhoid fever (weirdly)

Answer 896

Epi: v common S/SE Asia, medium incidence Latin American and Africa CANNOT DISTINGUISH Salmonella typhi and paratyphi clinically Typhoid fever is exclusively human disease -> no animal reservoir. Advise people to wash hands, clean food etc Incubation Typhoid fever: 10-20 days (range 3-56) Paratyphoid: 1-10 days Clinically: Non-specific eg fever, frontal headache, abdominal pain, constipation (rarely foul-smelling diarrhoea), dry cough At worse: confusion, myocarditis, toxaemia, intestinal perforation, haemorrhage Labs: leukopenia + (normocytic anaemia) + thrombocytopenia + slightly elevated transaminases

Answer 897

Isolation from stool or urine indicates carrier state -> does NOT prove disease Ideally need bacteria isolated from BCs or BM Serological lacks specificity Start on ABX depending on resistance patterns eg fluoroquinolone like cipro as they have v high intracellular concentrations. If resistance eg in SE Asia then use azithromycin or 3rd gen cephalosporins If resource constrained setting consider: chloramphenicol, amoxicillin, co-trimoxazole Treat between 1-2 weeks

Answer 898

Both produce protection of only 70-80% - parenteral Vi-capsular polysaccharide Ag vaccine - oral live attenuated vaccine

Answer 899

Reduce stimulation -> quiet, dark environment Abx: IV Penicillin +/- metronidazole Antitoxins - tetanus antitoxin human/equine Sedative -> chlorpromazine/phenobarbitone anti-spasmodic -> diazepam etc Magnesium to reduce spasms

Answer 900

Yes = infection does not provide immunity

Answer 901

Onset of weeks Discomfort around wound Rigidity Pain Weakness Increased deep tendon reflexes Can develop into generalised tetanus

Answer 902

Incubation period of days Lower cranial nerve muscles Facial palsy/stiffness Trismus Pharyngeal spasms Laryngeal spasms, dysphagia, neck stiffness Paresis of IX/X/III

Answer 903

Faeces (sanitation) - Fluids - Fingers - Flies - Fields (safe water) (hygiene and hand washing) Food (hygiene and hand washing) New host

Answer 904

Sanitation: the safe disposal of excreta and human faeces to protect the health and contamination of the environment Sanitation chain: the safe containment, transport, treatment and disposal/re-use of human excreta

Answer 905

SAFELY MANAGED Use of improved facilities which are not shared with other households and where excreta are safely disposed in situ or transported and treated off-site BASIC Use of improved facilities which are not shared with other households eg pit latrines, dry pit latrines LIMITED Use of improved facilities shared between two or more households UNIMPROVED Use of pit latrines without a slab or platform, hanging latrines or bucket latrines OPEN DEFECATION Disposal of human faeces in fields, forests, bushes, open bodies of water, beaches and other open spaces or with solid waste

Answer 906

Worse in central Africa - 46% of people do not have safely managed services WW ~20% (1.7 billion) people lack basic sanitation services

Answer 907

Pit filling Pit emptying (or not): manually or mechanically Transport Waste disposal Treatment or not Last two can include: drying beds, anaerobic digestion for biogas production, turn waste into fuel

Answer 908

1. Health benefits - Can reduce risk of diarrhoea by up to 25% - Reduced risk of: Ascaris, hookworm, Strongyloidiasis, Chlamydia, Trachoma, Schistosomiasis, Nutrition - Best is sewered system compared to improved - Barreto study 2007: city-wide sanitation intervention reduced childhood diarrhoea by 43% in high risk areas but no effect in low risk areas ○ High risk: high baseline prevalence of diarrhoea and lower initial sanitation coverage ○ Big investments eg sewer systems are what's really needed 2. Privacy, convenience, time, cleanliness and smell 3. Increases school attendance 4. Don't have to withhold food/drinks 5. Prevent imprisonment by daylight 6. Protection from harassment and rape

Answer 909

SAFELY MANAGED Drinking water from an improved water source that is located on premises, available when needed and free from faecal and priority chemical contamination BASIC Drinking water from an improved source, provided collection time is not more than 30 minutes for a round trip, including queuing LIMITED Drinking water from an improved source for which collection time exceeds 30 minutes for a round trip, including queuing U N I M P R O V E D Drinking water from an unprotected dug well or unprotected spring SURFACE WATER Drinking water directly from a river, dam, lake, pond, stream, canal or irrigation canal Note: Improved sources include: piped water, boreholes or tubewells, protected dug wells, protected springs, and packaged or delivered water.

Answer 910

A source that by nature of its construction or through active intervention, is protected from outside contamination, in particular from contamination with fecal matter

Answer 911

IMPROVED Piped water into dwelling In general: network & tap Piped water to yard/plot Public tap/ Public standpost Tubewell/Borehole/Hand pump Often with a handpump Protected Dug well/spring Protected Spring Rainwater UNIMPROVED (Collected) Surface water Unprotected dug well Unprotected spring Tanker truck/Cart with tank

Answer 912

30mins More water -> more likely to practice hygiene If only 10-20L per day -> less likely to use for hygiene eg hand washing, will prioritise it for food, drinking etc Minimum for “basic” access according to WHO: Improved source & available within 30 minutes (round-trip)

Answer 913

- Chlorination -> residual effect to continue disinfection, does not get rid of Crypto - Boiling -> expensive and requires fuel - Filtration: slow sand filters - UV disinfection (SODIS -> solar) -> Fill up to 2L, corrugated roof to reflect UV back and maintain temp of water With user methods difficult to know how effective methods are ie were cans left in sun long enough, was enough Cl put in etc

Answer 914

Transmission Route, Description, Example Water-borne You drink it Cholera Improve drinking water quality Improve sanitation Water-washed Person-to-person transmission due to inadequate personal and domestic hygiene Trachoma, conjunctivitis, louse- borne typhus Increase quantity of water Improved hygiene by increasing access and availability of water Water-based Transmission of infections via an obligatory aquatic host (e.g., snail) Schistosomiasis, guinea worm Decrease contact with contaminated water Control aquatic animals Reduce excreta entering environment Water-related insect vector Transmission by insects which breed in (or bite near) water Malaria, dengue, yellow fever, African Trypanosomiasis, filariasis Eliminate breeding sites Netting, repellent Keeping people away from breeding sites

Answer 915

The conditions and practices that help maintain health and prevent spread of disease

Answer 916

Basic: availability of handwashing facility with soap and water at home Limited: availability of handwashing facility lacking soap and/or water at home No facility: no handwashing facility on premises

Answer 917

Use running water + temperature does not matter 1min with piped water can use up about 5-10L Most people wash their hands for 10 seconds so this is about 0.5-2L  Water scarce settings: eco-friendly devices claim to be able to facilitate handwashing with about less than 100ml of water  Rinsing hands with water and scrubbing thoroughly is better than not handwashing at all and could reduce pathogens by up to 77%

Answer 918

GEMS study: aimed to assess the population-based burden of diarrhoeal disease in children living in sub-Saharan Africa and South Asia Key pathogens: - Rotavirus - Cryptosporidium - Shigella - Enterotoxigenic E Coli

Answer 919

- Inhibits nutrient absorption → malnutrition, even if sufficient nutrition is consumed - Reduces resistance to infections - Early childhood development, including stunting and wasting - Cognitive development (e.g. language, memory) - Lifelong consequences, such as productivity or ability to learn

Answer 920

Inadequate WASH leads to exposure to enteric pathogens Leading to - Soil transmitted helminth infections - Environmental enteric dysfunction (inflammation of small intestine, marked by alternations in gut lining) - Diarrhoeal diseases All leading to poor nutritional status BUT NO EVIDENCE suggesting WASH influences actual nutritional outcomes eg weight for age/height etc

Answer 921

Clostridium tetani Anaerobic Gram-positive bacillus Hardy ubiquitous environmental organisms

Answer 922

Disrupts release of inhibitory neurotransmitters, causing Trismus Risus sardonicus Opisthotonos

Answer 923

Neonatal tetanus (NNT) Encephalitis/meningitis Rabies TMJ disease Cerebral malaria Strychnine poisoning

Answer 924

Climate Conflict Covid Chaotic/Corrupt/incompetent leaders, systems

Answer 925

4.9 million child under 5 deaths per year -> under nutrition contributed to 45% of these deaths Global nutrition report 2020 - 1 in 9 people hungry/undernourished -> increase since 2015 - 1 in 3 people overweight/obese

Answer 926

Marasmus = wasting: - Generally wasted - Thin arms (MUAC) - Thin face, “old man” - Ribs visible - Sunken eyes - Lack of skin turgor - (NB assessment hydration!) Kwashiorkor = oedematous malnutrition: - Bilaterally pitting oedema - Apathetic - Sparse, discoloured hair - Dermatosis - Enlarged liver - Angular chelitis

Answer 927

Any condition in which deficiency, excess or imbalance of energy, protein or other nutrients adversely affects body function and/or clinical outcome How to measure: 1) ‘RAW’ measurements (weight, length/height, MUAC) 2) COMBINE to form an INDEX - Eg height for age, weight for age or BMI 3) COMPARE against a ‘reference’ - Growth curves using age and BMI Wasting (thinness / marasmus) = acute malnutrition, = low weight-for-height / MUAC Stunting = chronic malnutrition = low height-for-age Underweight = acute & chronic malnutrition = low weight-for-age Micronutrient malnutrition (+/- specific clinical signs) NB: MUAC only between 6 months to 5 years

Answer 928

Socioeconomic reasons for malnutrition. Includes failures such as: ○ Production based eg reduced harvest ○ Trade based (import bottlenecks) ○ Labour based (poverty, unemployment) ○ Transfer based (late delivery of food aid, profiteering)

Answer 929

Normal range Weight for height +2 to -2 SDs from median score = Z score Acutely malnourished includes: Moderate acute (MAM) -2 to -3 Z scores or MUAC<125mm (moderate wasting) No oedema Can manage supplementary feeds as outpatient Severe acute (SAM) <-3 Z scores or MUAC<115mm -> marasmus Oedema Yes -> kwashiorkor Tends to need inpatient stabilisation NB: any bilateral oedema is then classified as severe acute even if weight or height is ok If a patient slowly deteriorates along the spectrum then their anthropometric status may be worse than their clinical status If fast deterioration in nutrition then might get matching fast deterioration in clinical status 2008 MAM uncomplicated -> outpatient supplementary feeds SAM uncomplicated -> outpatient therapeutic feeds SAM complicated -> inpatient stabilisation 2023 Wasting and oedematous malnutrition

Answer 930

Metabolism - Reduction in metabolic rate and protein synthesis Heart/CVS - Output reduced, anaemia (decreased production and increased RBC loss) Kidneys - GFR reduced, reduced Na excretion Liver - Fatty liver (esp in kwashiorkor, a little in marasmus), decreased endogenous glucose production Pancreas - Decreased beta cell function and enzyme production Hormonal - Decreased thyroid function and cortical, growth hormone responses Gut - Atrophy, decreased nutrient absorption, chronic inflammation, microbiome changes Skin - Decreased barrier role, subcut fat, decreased insulation, decreased collagen/protein reserve Immune function - Greater vulnerability to infection - Atypical () response to infection - Atypical manifestations of infection - Poorer outcomes from infection CNS - Relatively protected so worrying sign of late stage - Lethargy, irritability, decreased appetite and interaction with environment

Answer 931

Appetite -> helps differentiate between complicated vs complicated and helps determine phase progression during treatment

Answer 932

- Assume infection -> all get 1st line Abx eg co-trimoxazole - Sick or not improving -> 2nd line Abx eg ampicillin and gent - Very sick or worsening fast -> 3rd line Abx eg cef or 3rd gen cephalosporins

Answer 933

Usual signs DO NOT APPLY: May (or may not) indicate dehydration: - Skin turgor (loss subcut fat?) - Sunken eyes (loss retrorbital fat?) - Dry mouth / eyes (atrophied glands?) Following ARE USEFUL: - Recent changes in above - Input / output history (+charts) ? Urine or watery stool? - Weight changes (use SAME accurate scales!) - (Thirst) - (Conscious level) TREAT WITH GREAT CARE!: - Risk of heart failure / worsening - Oral / NGT whenever possible - Specially forumulated solutions - Monitor response closely - e.g ‘High dependency’ beds) - reweigh (wt up but not too fast) - vitals better? (pulse; rr; CRT) - passing urine - more alert - PAUSE / SLOW FLUIDS IF WORSENING ➔ Prevention better (early feeds / ORS / breastfeeding)

Answer 934

Phase 1 = stabilisation - Small volumes (total and per feed) - Frequent feeds eg 2/3hrly - Light/easy to digest and metabolise -> PO whenever possible - May need NG tube if not tolerating PO Transition phase Phase 2 = 2 rehabilitation - Large volumes (total and per feed) - Less frequent - Nutrient dense Offer breast milk before feeds ie don't stop it

Answer 935

- Direct effect on CNS - Weak, sick -> do not crawl or explore environment - Do not engage with adults - Poor homes Treat - As essential as Abx etc - Environment stimulating - Structured play 15-30min/day - Engage with carer eg exercise

Answer 936

Good for patients - Prefer home treatment Decrease: - Nosocomial infection - Abx resistance (also population benefit) - Hospital costs Good for carers - Time for other children and home duties - Increased early presentation and less absconders Good for staff - Less pressure on ward based care Good for communities - Empower them, improve impact, begin to address root causes

Answer 937

1. Hypoglycaemia: IV/NG dextrose 2. Hypothermia: skin-2-skin, warm fluids 3. Dehydration + shock: ReSoMal (ORS), ?fluid bolus, transfuse if Hb<4 4. Electrolytes - TNa IK: ReSoMal or F75 5. Infection: all SAM → Abx, consider specific infections (malaria, worms, candiasis) 6. Micronutrients: Vitamin A (eyes), Zn, Fe (but not early) 7. Feeding: <6 months: encourage breastfeeding before formula >6 months: F75, monitor for appetite 8. Catch-up growth: F100 2-3 days/plumpynut, fortified local foods 9. Stimulate and support: play to encourage development 10. Follow-up: immunisations, social work, nutrition Remember: classical signs of dehydration do not apply in malnutrition Monitor UO, weight trend and level of consciousness NB: MUAC will respond to treatment -> don't always need weight MUAC only relevant between 6 months to 5 years

Answer 938

Severe 3+ oedema Unable to sit up Hypothermia Vomiting Metabolic disturbance Severe infection Open skin lesions Failed appetite test

Answer 939

Short-term (morbidity, mortality) vs long-term (adult height, cognition, economic performance, reproductive performance, obesity, CVS + metabolic disease) First 1000 days of life issues Underlying causes: household food security, inadequate care + feeding practices, access to healthcare + household environment Basic causes: quantity + quality of resources (land, education, employment, £$, technology), financial/human/physical/social capital, and social/economic/political context

Answer 940

Corynebacterium diptheriae Aerobic, Gram-positive rods with club shaped morphology Transmission by respiratory droplets and close contact and communicable for 2-6w without antibiotics, 48h with antibiotics

Answer 941

Patho: Exo-toxin mediated disease Death of mucosal epithelial cells > formation of grey fibrinous pseudo-membranes Lymphatic and haematogenous spread > disseminated disease, shock and multiorgan involvement SYMPTOMS 2-5 day incubation period Pharyngitis or laryngitis Gross lymphadenopathy -> ”bull neck” Adherent pseudomembranes **Respiratory failure due to airway obstruction or aspiration of pseudomembranes** Initially isolated spots of grey/white, coalesce to form membrane that bleeds on contact Examine: uvular, palate, oropharynx and nasopharynx Simple: one area only Extensive: >1 area COMPLICATIONS Myocarditis (2-7 weeks) Neuropathy and paralysis (1-3 months) Renal failure

Answer 942

ANTITOXIN Indications: tonsillar plaques, pseudomembranes, shock or systemic signs Contraindications: >7 days symptoms, unresponsive, intractable shock or airway compromise Risks: anaphylaxis (<1%), febrile reaction (4%), serum sickness (8%) Dose according to severity of disease ABx Severe: IM/IV benzylpenicillin or erythromycin Mild-moderate: PO penicillin V, erythromycin or azithromycin VACCINATION Vaccinate by age: Pentavalent (if 6w – 6y) or Td if (>7y) CLOSE CONTACTS Prophylactic antibiotics: single dose IM benzathine penicillin or azithromycin or erythromycin PO for 7 days Vaccination by age

Answer 943

Death (high mortality rate) Small head circumference Microencephaly Other cognitive/developmental impacts eg hand to eye coordination tasks, lower summated developmental score Neurological abnormalities Behavioural problems

Answer 944

1. Clean delivery practices - hands/delivery surface/cord care 2. Tetanus toxoid protects both mother and child Un-immunised pregnant women: 2 doses tetanus toxoid - 1st dose as early as possible in pregnancy - 2nd dose at least one month later/3 weeks before delivery. 3. Infection does not provide natural immunity -> need to vaccinate

Answer 945

Highest in Africa and South Asia World Health Organization estimate shows is 25,000 deaths from NNT in 2018, which means an 88% reduction from since 2000. Maternal tetanus and NNT have not yet been eliminated (July 2019) in 12 countries

Answer 946

Tetanus Strychnine poisoning Narcotic withdrawal Hypocalcaemic tetany Neuroleptic malignant syndrome Phenotiazine dystonic reaction Rabies Stiff-person syndrome

Answer 947

Support Airway -> Tracheostomy Muscle spasm control 1st Benzodiazepines (Diazepam up to 20mg/kg/day) 2nd Chlorpromazine 3rd Vecuronium Magnesium sulphate Environment control Minimise light, sounds, any stimulus that can cause spasms Turn off toxin Neutralise toxin -> Human hyperimmune globulin or Anti-tetanus globulin (equine) Source control -> surgical debridement Antibiotic -> Metronidazole 500mg TDS IV 7-10 days Complications Autonomic dysfunction -> Labetolol or esmolol, Magnesium sulphate infusion* Prevention Give tetanus toxid vaccination -> No natural immunity derived from infection, therefore need immunisation course

Answer 948

DTaP/IPV/Hib/HepB then DTaP 4 in 1: 3 years and 4 6 in 1: 8, 12 and 16 Tdap for preteens 3 in 1: age 14 Td Every 10 years

Answer 949

Elimination defined as <1 NNT case per 1000 live births in every district per year

Answer 950

Trismus, ricus sardonicus, opisthotonos

Answer 951

Recent measles Deficient

Answer 952

The occurrence of disease episodes in greater numbers than would be expected at a particular time and place

Answer 953

Acute bacterial infection eg staph aureus, strep pyogenes, Haemophilis influenzae Neonates -> gram neg HIV -> Strep pneumoniae Endemic regions eg Laos/rice farming -> Burkholderia pseudomallei If unvaccinated -> mumps (but not suppurative and becomes bilateral in majority of cases) Other viruses: CMV EBV Influenza A Parainfluenza Enteroviruses

Answer 954

* Road traffic accidents account for 23% of injury related deaths PA globally Exacerbation/complications of chronic illness & motor vehicle accidents are the leading causes of death and severe disability in travellers >95% of travel associated illness is not vaccine preventable

Answer 955

○ Things to check: ▪ Age ▪ Comorbidities ▪ Risk threshold ▪ With whom ▪ Reason for travel * What do they plan to do, where and with whom? ▪ Country ▪ Area ▪ Mode of travel ▪ Accommodation ▪ What is going on * How long are they going for, what is the season? ▪ Length of stay Seasonality 1. Malaria prevention 2. Vaccines 3. Non-vaccine preventable infections 4. Other: sexual health/altitude/DVT/Trauma/Security/Insurance 5. Patient education

Answer 956

DARN Desire, ability, reasons, need 1. Ask permission to start agenda 2. What does patient think about their health 3. Ask questions to find out what they already know 4. Tell the patient information in a way that’s easy to understand 5. What is the patient's understanding

Answer 957

1st trimester * Concern for mother * Miscarriage * Ectopic * Bleeding * Retained products * N&V * DVT * Infection 2nd trimester * Concern for mother * Congenital abnormalities * Anaemia * DVT * Gestational diabetes * HTN * Infection 3rd trimester * Concern for mother and baby * Premature labour * Stillbirth * Post-partum haemorrhage * DVT * HTN/Pre-eclampsia/Infection

Answer 958

Fetal USS to look for heartbeat Once heartbeat is seen the risk of miscarriage<5% Can also look for - congenital abnormalities - position of fetus - fetal growth - position of placenta

Answer 959

* flights/journeys > 4hrs * Older age * previous clot * family history * additional clotting disorder * Obesity * severe oedema * Immobility * Other medical conditions REDUCE VIA * Compression stockings * Hydration * Mobilization * Isle seat * No ETOH, sleeping medication * LMH safe * UK all get pertussis vaccine 16-32 weeks * RSV vaccine from 28 weeks (Aug 24 UK) * Flu & COVID recommended * No evidence harm from inactivated vaccines * Live; balance risk vs theoretical foetal harm * Inadvertent vaccine administration NEVER indication for termination

Answer 960

INACTIVATED Safe Less robust immune response Multiple doses often needed Waning immunity * Pneumococcus * IFV * Hepatitis * D/T/P * Typhoid LIVE-ATTENUATED Robust immune response Often lifelong immunity BUT Potential vaccine derived infection * MMR * YF * OPV * Zoster

Answer 961

* Early administration ○ Mainly addresses GC-independent memory B-cells * Germinal-center activity persists for weeks to months resulting in more memory B-cells that can be addressed by revaccination * Long term protection ○ Ab persistence above threshold +/- memory cells Rapid clonal expansion on exposure to pathogen RESPONSE * Early Ag specific Ab * Efficacy = avidity + specificity + neutralizing capacity * Long term protection = persistence Ab + memory + rapid clonal expansion Eg B cells and T cells

Answer 962

Primary : Inherited, can affect all areas, usually severe e.g. * SCID * CVID * Di George * IgA deficiency Secondary/acquired : Physiological state, illness or treatment for a condition that reduces your immune function e.g. * HIV * Extremes of age * Pregnancy * Malignancy * Post BMT Medication etc

Answer 963

* Asplenia * Complement deficiencies * Medication * HIV * Pregnancy * IVIG * Post BMT/CART-T

Answer 964

* Measles ○ Give mum MMR if not pregnant ○ 6 month year old -> give early MMR -> but does not count as initial dose of MMR -> needs full repeat when of age * Hepatitis A ○ Mum: might have had exposure, can test but can also just vaccinate ○ Dad: vaccinate ○ 3 year old: immunise due to public health management ○ 6mth old: no, if breast fed then no risk * Typhoid * Dengue * Rabies

Answer 965

Ocreluzemab: * B cell depleting * Severely reduced clonal expansion * Reduced efficacy * Reduced safety * Increased risk of infection, especially intracellular like pneumococcal and skin and soft tissue infections * Increase risk of reactivation of infections, esp HBV so check liver function before starting treatment * Vaccinate against pneumococcal disease prior to starting Ocreluzemab

Answer 966

* Wash wound for 15mins with soap and water * Seek medical attention ASAP * DTP booster if required * May need Abx * Simian HerpesB: Macaque monkeys in SEA, Aciclovir within 5 days for 14 days ○ Rare but >85% mortality * Rabies PEP+/-HRIG

Answer 967

Additional vaccinations * Haemophilus influenza type b * Meningococcal ACWY * Meningococcal B vaccine * Influenza * Pneumococcal Prophylactic/standby Abx * PenV * Consider stand by Abx Other infection risks * Malaria * Babaesiosis Give other advice: * Trousers tucked into socks * Permethrin spray * Tick check and removal

Answer 968

* Men ACWY at least 10 days prior to travel * Polio if travelling from a country with wild-type polio * Yellow fever if travelling from 'at risk country' * Other things to consider: ○ COVID-19 ○ Flu ○ Hep B ○ Rabies ○ MERS-CoV ▪ Close contact with animals eg camels, unpasteurised camel products ○ Diarrhoea

Answer 969

Roads for supply access Water - ?from where - any nearby streams/bore holes? - risk of viral contaminated into ground water/village water supply Electricity (ideally mains) Size and space (12 beds thought to need 2500metres squared) Phone signal Ground water level/flood plain -> ideally need at least 1.5 metres above ground water level Need big buffer zone around ETC If worried about contamination of water supply -> check Cl levels as remain in water, viral levels hard to determine Buildings needed: - ensure ancillary eg lab, pharmacy, morgue, staff areas Ensure potential for holistic care: eg visiting, spiritual needs, children/neonates, survivors, dying Donning and doffing - ideal need mirrors, clocks (35/40mins before need to exit zone), lots of space, well lit - need buddy check and third person - doffing done by someone else based on instructions, need multiple lanes and hygienists WATER - 0.5% chlorine (200L per patient per day) - 0.05% chlorine (150L per patient per day) - drinking water (50L per patient per day) Staff: - hygienists - laundry staff - medics - nurses - logistics - psychologists - rota/record keepers

Answer 970

1. Risk zoning (need No pathogen and pathogen zones, need whole centre to be separated from outside world) 2. Flow -> need patient flow pathway and staff flow pathway which will be different. UNIDIRECTIONAL ONLY Need protocols for case

Answer 971

Gram negative aerobic, pleomorphic, flagellated, motile, coccobacillary INTRACELLULAR

Answer 972

Pyoderma Dermatitis Dementia Vit B3 deficiency

Answer 973

Perifollicular haemorrhages

Answer 974

Neurotoxicity, ptosis, breathing difficulties (eg mambas, cobras, kraits) - they usually warn you before they bite, ie they rear up

Answer 975

Asia NOT Africa

Answer 976

Streptococcus pneumoniae Bacterial will occur in hours to days, TBM/Crypto will be days to weeks Staphylococcus aureus Streptococcus pyogenes Haemophilus influenzae Non-typhoidal salmonella Salmonella typhi Escherichia coli If pregnant - ?Listeria monocytogenes Apart from Listeria, treat with 3rd generation cephalosporin, ideally 14 days but evidence mixed -> also check local resistance patterns

Answer 977

HIV EBV CMV Cutaneous TB Non tuberculosis mycobacterial infections Mollusca contagiosum Melioidosis Bartonella spp. (causing bacillary angiomatosis in severely immunocompromised patients -> usually erythematous lesions) Histoplasmosis Talaromycosis Cryptococcosis Lymphomas HHV-8 castleman's disease

Answer 978

Infectious mononucleosis Hepatosplenomegaly Lymphadenopathy

Answer 979

Fever Eosinophilia Elevated liver enzymes

Answer 980

Malaria -> blood films Katayama syndrome - need urine and stool for Ova and cysts of Schistosoma but these may not appear until 3 months after infection and patients can be infected with different stages of schistosomulae at once

Answer 981

Acute schistosomiasis -> acute hypersensitivity reaction thought to be result of initial egg deposition by adult trematodes Incubation period: 2-12 weeks Fever + urticaria + dry cough +/- dry wheeze CXR: patchy pulmonary infiltrates or micronodular changes in the lower lungs NB: eosinophilia may be delayed, ie not seen after a couple of weeks. In addition, may need to repeat urine/stool tests for ova as may not appear for at least 3 months. Can do PCR if available. Manage with praziquantel after adults have developed as it is not effective against immature flukes. -> may need repeat courses due to infection with many schistosomulae.

Answer 982

Dengue -> aedes aegypti or albopictus -> Asia>Latin America>Africa -> DAY Yellow fever -> aedes -> Africa + LA -> DAY Zika -> aedes -> LA>Caribbean>few African/Asian cases -> DAY Japanese encephalitis -> culex -> Asia -> dawn/dusk/night

Answer 983

Alphavirus Aedes LA,Africa,Asia DAY

Answer 984

Yellow fever -> aedes -> Africa + LA -> DAY Positive single-stranded RNA virus Incubation: 3-6 days, max 15 Life cycle: urban - aedes aegypti biting infected humans then uninfected and circulates sylvatic - aedes africanus biting infected non-human primates and circulates intermediate/savanna - aedes biting non-human primates then humans and circulates * Most asymptomatic * Fever, headache, chills, muscle pain, nausea * Most self-limiting * 1 week * 10-25% haemorrhagic manifestation, kidney and liver damage +/- encephalitis * Case fatality rate of 20-50% Concern regarding its spread as can go with aedes which are found almost everywhere VACCINE - live attenuated Safe ✓Massively used since 1938 ✓Rare complications Efficient ✓Fast neutralizing immune response ✓One dose; long-lasting protection - now thought life-long CONs Production ✓Need for embryonated egg ✓Q/C & batch release time Storage & transport ✓Need for strict cold-chain

Answer 985

Hypersensitivity reaction 1:100.000 doses Vaccine-associated viscerotropic disease (YEL-AVD) 1: 200.000-300.000 doses 1: 40.000-50.000 doses >= 60 years old Vaccine-associated neurotropic disease 1: 150.000-250.000 doses Revaccination has not been associated with serious adverse events.

Answer 986

CIs: * < age 6 months. * Persons with a confirmed anaphylactic reaction to a previous dose of YF vaccine. * Persons with a confirmed anaphylactic reaction to any of the components of the vaccine, including egg * Persons with a history of thymus disorder* or removal of the thymus gland for any reason (thymectomy) including incidental thymectomy (e.g. during cardiac surgery). * Persons with primary or acquired immunodeficiency including symptomatic HIV infection and asymptomatic HIV infection when accompanied by evidence of impaired immune function * Persons who are immunosuppressed * Persons with a first-degree** family history of YEL-AVD or YEL-AND following vaccination that was not related to a known medical risk factor (in case of an unidentified genetic predisposition). * Individuals aged 60 years and older travelling to countries and areas designated by WHO as areas with low potential for exposure to yellow fever virus (see section on people aged 60 years or older). Precautions: * Infants aged six to eight months * Individuals aged 60 years and older * Breastfeeding women * Pregnant women * Those taking low dose steroid or non-biological oral immune modulating drugs * Individuals living with HIV (with a CD4 count greater than 200 and a suppressed viral load) BOOSTER (consider if) - If person is working/living in endemic region or with the virus ie high risk setting and last had vaccine over 10 years ago - If person had original vaccine over 10 years ago and in a slightly immunocompromised state, eg <2 years old, when pregnant, before undergoing BM transplant, when infected with HIV or when immunosuppressed

Answer 987

Protect populations at risk - Mass vaccination campaigns (need 80+% in at risk areas to prevent outbreaks) - Catch up vaccination campaigns - Vaccinate every child - Evaluate risk to prioritise resources **WHO recommendation 2016: YF fractional dose vaccination should be considered in response to an emergency situation in which current vaccine supply is insufficient.** Prevent international spread - Apply the IHR: Monitoring and surveillance, strengthening public health capacity, collaboration and communication, rapid response and containment - Build resilient urban centres Contain outbreaks rapidly - Detect early: strengthen lab and surveillance capacity - Timely and equitable access to vaccine supply - Respond immediately

Answer 988

International Health Regulations (IHR), a legally binding framework established by the World Health Organization (WHO) to strengthen global health security. The IHR (2005) aims to help countries prevent, detect, and respond to public health risks that have the potential to spread internationally, ensuring that outbreaks and other health emergencies are managed effectively to minimize their impact. Involve: Monitoring and surveillance, strengthening public health capacity, collaboration and communication, rapid response and containment

Answer 989

International Health Regulations (IHR), a legally binding framework established by the World Health Organization (WHO) to strengthen global health security. The IHR (2005) aims to help countries prevent, detect, and respond to public health risks that have the potential to spread internationally, ensuring that outbreaks and other health emergencies are managed effectively to minimize their impact. Involve: Monitoring and surveillance, strengthening public health capacity, collaboration and communication, rapid response and containment

Answer 990

Efficacious and safe in SEROPOSITIVE persons: 72-80% against dengue of any severity; >90% against severe dengue DO NOT GIVE TO SERONEGATIVE patients -> increases risk of severe dengue

Answer 991

Dengvaxia - 3 doses over 12 months - check serostatus before giving - 9-45 year olds TAK003/Qdenga (Takeda) - 2 doses (0 and 3 months) - WHO: 6-16 years in endemic settings

Answer 992

Only if they are seropositive (you need to test them)/have had dengue in past, aged 4+ and are travelling to high risk areas, areas with ongoing outbreaks or will come into contact with virus through work Day time biting so use repellant Risk highest during and just after rainy season

Answer 993

Aedes mosquito bite Sexual Blood transfusion Pregnancy S/S: - Asymptomatic 50-80% - Mild disease 20-50% - Complications in <1%

Answer 994

Neurologic eg GB syndrome, transverse myelitis, meningoencephalitis Ocular Thrombocytopenic purpura Transient myocarditis Highest risk of birth defects during 1>2>3 trimester In 20-30% of babies who are infected: Fetal loss Congenital zika with microencephaly Asymptomatic infection including sequelae in baby/child of: * Seizures * Hearing loss * Visual impairment * Dysphagia * Development delay

Answer 995

If male travelling and partner pregnant OR female pregnant and travelling with male then barrier methods for whole pregnancy If female traveller pregnant but male did not travel -> barrier methods for 2 months after last possible exposure If male traveller and partner NOT pregnant OR female traveller not pregnant but male partner also traveller -> avoid conception + barrier methods for 3 months If female traveller not pregnant and male partner did not travel then avoid conception and barrier for 2 months after Zika exposure

Answer 996

Alphavirus, genus Togaviridae Incubation: 2-6 days 90% of patients will have: fever (up to 1 week), myalgia (up to 10 days), polyarthralgia, polyarthritis or both (weeks to months) Rash for 1 week in 50% patients Viraemia will last 5-7 days IgM 3-8days after onset to up to 3 months IgG 4-10 days after onset, persists for years

Answer 997

1 Maternal risk |2 Antenatal risk |3 Perinatal complications Dengue: 1 Increased risk of severe disease and death; more difficult clinical mx of severe dengue 2 Increased fetal losses in the first half of pregnancy (data from multiple cohorts, substantiated by a meta- analysis) 3 Severe neonatal infection with sepsis-like symptoms and acute respiratory distress reported in case report: most other cases mild Zika 1 No increased risk, prolonged viremia 2 Congenital Zika Syndrome 3 No increased risk Chikungunya 1 No increased risk except for pre-term labour 2 Miscarriages documented in three (2%) of 678 participants in one study and no increase in number of stillbirths, prematurity, or malformation 3 Documented transmission rate of 28–49% with severe neonatal infection (encephalopathy) in 53% of newborns in one study; severe neonatal infection with encephalopathy shown in four studies

Answer 998

* Recommended for: ○ 18+ yr olds and travelling to country with outbreak * Consider in: ○ Travelling to non-outbreak place but evidence of chikungunya virus transmission among humans within the last 5 years in people who ▪ Aged >65 years old, esp with medical conditions who are likely to have moderate exposure OR Ppl staying for cumulative period of 6 months or more

Answer 999

* Genus Orthobunyavirus, Peribunyaviridae family * Transmitted by midges (Culicoides paraensis) and mosquitoes (Aedes spp) * Reservoir pale-throated sloths, non-human primates, and birds * Most infection are mild (symptoms similar to dengue) * Approx 4% develop neuroinvasive disease * Report of vertical transmission! Rising cases in Latin America eg Brazil

Answer 1000

The probability that a case will die from the infection being studied

Answer 1001

an error in selecting the study population such that either the people who are selected to participate are not representative of the population of interest or the comparison groups are not comparable Survivorship bias Sampling bias Attrition bias Non-response bias Volunteer bias Undercoverage bias

Answer 1002

Any error in the measurement of exposure or outcome resulting in systematic differences in the accuracy of information collected between groups being compared Occurs - In case-control study: if accuracy of exposure data differs between case and controls - In cohort study: if accuracy of outcome data differs between exposed and unexposed groups Recall bias Observer bias Performance

Answer 1003

- Neonatal disorders - Pneumonia - Diarrhoeal diseases - Congenital defects - Malaria

Answer 1004

Cough + dyspnoea + danger signs: Severe respiratory distress: grunting, very severe chest indrawing · O2 sats <90% in air or central cyanosis · Inability to breastfeed/drink · Reduced LOC/lethargy/convulsions MANAGEMENT Admit · O2 therapy if known low sats, central cyanosis or severe resp. distress · IV antibiotics (local spectrum or IV amp and gent if unknown) · Care with fluid balance · Anti-pyretics if child distressed, bronchodilators if wheeze

Answer 1005

71% of all LRTI due to 10 organisms: RSV, flu, metapneumovirus, rhinovirus, paraflu, s.pneumo, s,aureus, h.influenza, TB, PCP

Answer 1006

High levels of Gram –ve organisms (eg Klebsiella, non-typhoidal haemophilus influenzae E Coli) and Strep pneumonia, in fatal LRTIs

Answer 1007

– Cylinders: produced in manufacturing plants. Need regular refilling. Often means intermittent supply – Concentrators: extract nitrogen from air in the atmosphere to leave O2. Done at the bedside. Can supply up to 5 patients with flow-splitters. Need constant electricity. Need cylinders as back-up in case of power-cuts – Central piped O2: Piped from large O2 source e.g. concentrator. High cost, usually only in central hospitals.

Answer 1008

Can stop if O2 can be disconnected for 10-15mins with no emergency signs or SpO2>90% in air. Monitor for 24hrs as tends to worsen overnight

Answer 1009

Nasal prongs, face-mask, head-box/tent, nasal catheter Nasal prongs recommended as provide ~5cm PEEP to help improve oxygenation and most efficient Flow rates: 0.5-1L/min neonates (<1mth) 1-2L/min infants (<1yr) 1-4L/min pre-school (<5yr) 1-6L/min older children Check for mucous plugging and position 3hourly Humidification needed for flow-rates >4L/min

Answer 1010

Central Cyanosis (bluish discoloration) Decreased consciousness Grunting with every breath Nasal flaring Severe palmar or conjunctival pallor Acute coma or convulsions >15mins Severe chest indrawing Tachypnea (rapid breathing by age) >70/min Head nodding

Answer 1011

1) Do TB symptom screen If positive: 2) Do CXR + molecular diagnostics eg rapid diagnostic test like Xpert MTB/RIF, Xpert Ultra, LAMP or Truenat Samples from: - Sputum/induced sputum - Early morning GA - Stool - NPA - Biopsy samples e.g. of LN - CSF if LP

Answer 1012

Children with non-TB could be treated for 4 months rather than longer standard course of treatment

Answer 1013

‘Nonsevere’ = - non-cavitatory, non-miliary pulmonary TB in one lung lobe - Peripheral LN TB - Intra-thoracic LN TB without airway obstruction - Simple TB pleural effusion Regime = 2 months HRZ(E) 2 months HR

Answer 1014

All asymptomatic household contacts should be offered TPT Children <5 years and PLHIV particularly high risk => target populations for TPT TPT options: 6 months isoniazid 3 months isoniazid and rifampicin 4 months rifampicin 3 months weekly rifabutin and isoniazid 1 month daily rifabutin and isoniazid

Answer 1015

6 month BDLLfxC can be used in all (that have not had >1 month exposure previously to Bdq, Dlm or Lzd) BEAT-TB and endTB trials

Answer 1016

50% of under 5 mortality in 1st month of life – most in the first week * C.1/3rd infections, 1/3rd birth complications, 1/3rd prematurity

Answer 1017

* Fast breathing (respiratory rate ≥60 breaths/minute * Severe chest in-drawing * Fever (temp ≥38˚C) * Hypothermia (temp <35.5˚C) * No movement at all or movement only on stimulation * Feeding poorly or not feeding at all * Convulsions very poor specificity

Answer 1018

Investigations: Blood culture + LP if safe, malaria RDT, BM if available A: support if needed (neutral head position, chin lift) B: O2 (0.5-1L/min) via nasal prongs if seizing/resp distress and available C: NG feeding EBM if not breastfeeding D: Treat low BM (2-5ml/kg 10% dextrose IV or NG) Phenobarbitone for seizures (then phenytoin/benzos if needed) E: Keep warm – hat, KMC Phototherapy for jaundice if available – if not then transfer. If not possible, sunlight. can influence methyl IV antibiotics: Go on local resistance pattern/local guidelines if available If unknown Amp & gent If meningitis concerns add 3rd gen cephalosporin - Ceftriaxone difficult in small baby as displaces bilirubin so makes jaundice worse, cefotaxime better

Answer 1019

Hospitalisation is still the priority in these cases * If not possible then if signs of critical illness: – BD IM ampicillin or benpen, and OD IM gentamicin – OD IM ceftriaxone or procaine penicillin, and OD IM gentamicin “until hospitalisation is possible, up to 7 days” * If severe but not critical illness: – PO amoxicillin BD for 7d with IM gentamicin OD for 7d – PO amoxicillin BD for 7d with IM gentamicin OD for 2d * If fast breathing as only sign of pSBI then oral amoxicillin only BD for 7 days is acceptable

Answer 1020

- Are they severely malnourished? - Are they shocked? - How dehydrated is the child?

Answer 1021

SOME 2 or more of: Restless/irritable Sunken eyes Thirsty/drinks eagerly Skin pinch goes back slowly MANAGE Treatment Plan B (treat at 7.5% fluid deficit): * Oral rehydration in hospital over 4 hours * Home if tolerates * Zinc PO SEVERE 2 or more of: Lethargy or unconsciousness Sunken eyes Unable to drink or drinks poorly Skin pinch goes back v. slowly (≥2secs) MANAGE Treatment Plan C (manage as 10% fluid deficit): * IV or NG rehydration (30ml/kg over 30mins-1hr then 70ml/kg over 2.5-5hrs + 5ml/kg/hr ORS orally when tolerates) * Hospital admission * Zinc PO

Answer 1022

Means signs not meeting some/severe dehydration criteria Treatment Plan A: * Oral rehydration at home 50-100ml/loose stool <1 100-200ml/loose stool >1 * Zinc PO

Answer 1023

Top 5 pathogens for AWD = Rotavirus, shigella, ST-ETEC, cryptosporidium and enteropathogenic E.coli * More recent studies suggest rotavirus still leading cause despite roll-out of rotavirus vaccine

Answer 1024

~ 20 drops/ml clear fluids ~ 15 drops/ml blood

Answer 1025

1. Replace lost fluid and give extra for ongoing loses 2. Feed early and extra (only with-hold food in initial fluid replacement phase) 3. Zinc PO (though limited evidence) 4. Advise when to return (worsening/fever/blood in stool/persistent diarrhoea)

Answer 1026

* Screen for TB and other opportunistic infections and test/treat if present – delay ARVs for as short a time as possible (≤2-8 weeks) following TB/OI treatment commencement * Start ARVs according to national guidelines * Daily co-trimoxazole prophylaxis for all children <1 years (+ older children if CD4 <25%/200, or WHO stage 2,3,4) * TPT if TB contact and not concerned about active TB disease * Baseline bloods and CD4 count for monitoring purposes * Support parents and family

Answer 1027

- Undetectable does not mean untransmissible - PROMISE study with effective maternal ART, the risk of HIV transmission through breastfeeding could be minimized but not eliminated: 1% of kids still got HIV

Answer 1028

* ? Reinfection * ? Treatment failure * ? Persistent antigen but no malaria (if using PfHRP2) - roughly 4 weeks Need microscopy or LDH-based RDT If current infection confirmed WHO suggests: * < 4 weeks from previous infection – assume treatment failure, give 2nd line anti-malarials * If > 4 weeks from previous infection – treat as new infection but consider different oral agent if available * If severely unwell and delay in getting microscopy/LDH RDT treat as severe malaria and other causes e.g. sepsis until results known

Answer 1029

Retinal fundoscopy 1. Patchy retinal whitening 2. Focal changes of vessel colour 3. Retinal haemorrhages - often white centred +/- Papilloedema

Answer 1030

Investigated fluid boluses in African children with severe infection, split children into no hypotension and hypotension groups Trialled in each group, 3 sub-groups: - saline bolus - 5% Albumin bolus - maintenance fluids only (maintenance group not for hypotensive kids only non) 3.3% greater risk of 48hr mortality with any bolus given (p=0.003)

Answer 1031

HIV/STDs Pregnancy complications Unwanted pregnancy Alcohol use Suicidal ideation Depression Attempted suicide Difficulty sleeping Cigarette use

Answer 1032

In most confirmed abuse cases examination will be normal. Some other findings include: - Hymenal bumps, ridges and tags - v-shaped notches (often superior / lateral) not extending to the base of the hymen - vulvovaginitis - labial agglutination - vaginal discharge - acute abrasions, lacerations or bruising of the labia, perihymenal tissues, penis, scrotum, or perineum. - hymenal notch / cleft extending through more than 50% of the width of the hymenal rim, usually in 4 o’clock to 8 o’clock - scarring or fresh laceration of the posterior fourchette - presence of sperm confirmed on microscopy - presence of sexually transmitted disease

Answer 1033

History (patient led, with parent then ideally child alone) Examination 1. Record the findings 2. Report for court/police 3. Referral/liaison with social welfare / counselling / police etc 4. PEP if <72 hours (eg in Malawi ABC/3TC + DTG < 30kg, TDF/3TC/DTG >30kg) 5. STI prophylaxis (eg Malawi – metronidazole, erythromycin, gent, benzathine pen) 6. Emergency contraception <5 days (eg in Malawi Levonorgestrel 1500mcg STAT)

Answer 1034

* Multiple disease-specific and integrated interventions e.g. HIV/malaria prevention & treatment, expanded vaccination, IMCI * Investment in health systems: free/subsidised healthcare for mothers and young children, training, CHW for prevention and basic care, infrastructure, equipment, supply chains, quality standards, data availability and use * Cross-sectoral collaboration: addressing malnutrition, water and sanitation, income * Governance: Sustained, high-level political commitment, stakeholder involvement, partner coordination * Focus on prevention: This age group is ideal for health interventions due to increased independence and lifestyle habit development * Scheduled well child visits: Ensuring scheduled health contacts for older children is key, as they are less likely to seek care when critically ill. * Interventions with potential: Priority interventions for children aged 5-9 include school feeding, micronutrient supplementation, health education, vision screening, deworming, mass drug administration for trachoma, vaccine catch-up, and mental health support. * Delivery platforms: Primary care services + outreach, schools and childcare centres, home and community platforms, child and social protection services, digital platforms

Answer 1035

* Infectious Diseases Prevail: Malaria, diarrhoea, and respiratory infections remain leading causes of death. * Emerging Challenges: Deaths from neoplasms (cancers), traffic accidents, and other injuries are on the rise. * Females: Significant burden of maternal causes * Males: High burden of injuries, particularly road traffic accidents and interpersonal violence. * Substantial burden of NCDs. * Regional variation -> high burden of HIV and TB in Africa.

Answer 1036

Integrated approach: NCDs, mental health, injuries, SRH including maternal care, nutrition, communicable disease and wider determinants Health systems: workforce training to operationalize adolescent friendly services, sufficient space, peer groups, communications campaigns, routine well-child visits etc. Multisector e.g. road safety, school health, marketing regulation * Supply: adolescent health included within paediatric training, centres for adolescent services * Engagement and awareness: communications campaigns, teen clubs, adolescent involvement in policy working groups * Regulation: ban on tobacco advertising * Wider sectors and platforms: developing school health * Further progress: needs political commitment and funding for scale up and comprehensive provision, and integration with social welfare workforce

Answer 1037

1. Absorption ○ Reduced gut motility ○ Increased lung function ○ Increased skin blood circulation 2. Distribution ○ Increased plasma volume, body water and fat deposition affecting volume of distribution (increased circulating volume to around 8L) -> consider eg with ARVs ○ Protein binding -> decreased plasma proteins (interpreting drug concs more difficult as more/less free unbound drug, more or less of a resulting effect) 3. Metabolism ○ Hepatic enzyme activity could be increased (maternal hormones) 4. Excretion ○ Increased glomerular filtration rate ○ Gastric motility reduced

Answer 1038

AVOID Tetracyclines (doxy -> staining, chelating in growing bones and teeth) Streptomycin Debatable Fluoroquinolones Aminoglycosides Co-amoxiclav Trimethoprim (folate agonist, neonatal haemolytic) Other Nitrofurantoin -> avoid at term Metronidazole -> avoid high dose

Answer 1039

- blood level of medicine in mother - characteristics of medicine - amount of medicine passed into breast milk - amount of milk taken by baby per feed Minimise exposure via: * Withhold or delay therapy if possible * Use a drug with poor penetration into milk * Use an alternative route of administration * Avoid nursing at peak drug concentrations * Give drug before infant’s longest sleep * As a last resort- ‘Pump & dump’ milk if short courses or discontinue breastfeeding

Answer 1040

Risk of TB to mother and child outweighs risk of treatment * First-line anti TB drugs cross the placenta but do not appear to be harmful * Second-line anti TB drugs more risky. Avoid streptomycin (ototoxic to fetus) * Continue breastfeeding (low concentrations of anti-TB drugs present) * Avoid streptomycin (and other 2nd line agents) if possible * Safety of pyrazinamide in fetus unknown

Answer 1041

IPTP Sulfadoxine-pyrimethamine - Start as early as possible in second trimester NOT before week 13 - give doses minimum of 1 month apart - give 3 doses in total SP is CI in first trimester of pregnancy as anti-folate

Answer 1042

Artemether-lumefantrine

Answer 1043

Same as non pregnant at least 24hr artesunate IV until they can tolerate oral medication (3 days ACT)

Answer 1044

- Avoid primaquine - Avoid doxycycline

Answer 1045

Absorption * Administration route? * pH * Site of absorption Distribution * Lipophilicity vs hydrophylisity * Volume of distribution * Protein binding Metabolism * Hepatic maturity * Microsomal enzyme processes * Glucuronidation/sulphation Excretion * Renal function * Gastric motility/peristalsis

Answer 1046

Asymptomatic screening Stool - Ova, cysts & parasites microscopy - Giardia PCR Bloods - FBC – anaemia, eosinophilia - LFTs – in case of need TB treatment - Vitamin D - Serology – HIV / hep B / hep C / syphilis - Schistosomiasis serology - Strongyloides serology Urine - NAAT – chlamydia and gonococcus (usually IGRA too)

Answer 1047

Panton-Valentine leukocidin = cytotoxin PVL-SA is highly transmissible, lyses human neutrophils, and may cause recurrent skin and soft tissue infections (SSTIs) despite antibiotic treatment Risk factors: Close contact (eg, contact sports, military recruits) Contaminated items Crowding Cleanliness Cuts and compromised skin integrity.

Answer 1048

PCR IgG (IgM is very unreliable) Diagnosis: serology (IgG) most useful with convalescent serology, PCR, culture, histopathology LN biopsy best for PCR, also if you want tissue for PCR needs to be fresh

Answer 1049

Facultative intracellular bacteria Bite/scratch of infected cat or kittens, exposure to cat fleas, infected cats Globally distributed, most commonly disease of children /young adults Incubation: 3-10 days from exposure to primary inoculation lesion, 7-60 (14) for lymphadenopathy Clinical manifestations: - 85-90% localised cutaneous /LN infection - PUO - Disseminated disease - liver, spleen, eye, CNS (more common in children) Complicaitons - neuroretinitis - encephalopathy, transverse myeltiis, cerebellar ataxia, radiculitis - MSK including osteomyelitis - endocarditis Diagnosis: serology (IgG) most useful with convalescent serology, PCR, culture, histopathology Treatment: Localised disease -> sel resolving or 5 days azithromycin Disseminated: Rifampicin + azithromycin, doxy + azithromycin for neuroreitinitis If you are worried about a child -> can give doxy but ideally short course

Answer 1050

Orthopox virus - 2 clades I and II each with 2 subclades (a and b) Transmission: close contact with lesions, resp droplets (prolonged f2f contact) and fomites, sexual Incubation: 5-21 days (7), infectious 4 days prior to symptoms and until all lesions epithelised Clinical manifestations: - fever, flu like, lymphadenopathy - centrifugal maculopapular rash after 3 days, spreads all over body including palm and soles, vesicles and pustules Complications: encephalitis pneumonitis conjunctivitis secondary bacterial infections CRF: 0-11% (endemic areas) pregnant women -> fetal loss Diagnosis: PCR from vesicle fluid, respiratory samples, blood Treatment: - supportive - tecoviromat - brincidofovir - cidofovir Vaccine: - 3rd gen vaccine MVB-BA not currently licensed for pregnant women or children 3

Answer 1051

Take paired maternal and infant syphilis serology LP including PCR and VDRL PCR on CSF, lesions, secretions Neuroimaging - ?bony abnormalities Audiology Ophthalmology review HIV/Hep B/ Hep C STI screening (and treatment for parents) Other - anaemia, thrombocytopenia, abnormal WCC - deranged LFTs - CXR - serology

Answer 1052

Procaine penicillin or benzyl penicillin 10 day course if symptoms or abnormal investigations Single dose if well -> all normal Ix including CSF if missed doses then restart treatment from day 1 Also treat parents

Answer 1053

- HEEADSSS ○ Home ○ Education ○ Employment ○ Eating ○ Activities ○ Drugs/alcohol ○ Sexuality ○ Self harm and suicide ○ Safety - SSHADES ○ Strengths ○ School ○ Home ○ Activities ○ Drugs/substance use ○ Emotions/eating/depression ○ Sexuality ○ Safety

Answer 1054

Unconjugated Hyperbilirubinemia Haemolytic anaemias, Gilberts, Crigler-Najjar Conjugated Hyperbilirubinaemia Viral: HAV HBV HCV HDV HEV EBV CMV HSV Metabolic: Wilsons, Alpha-1-antitrypsin deficiency, Cystic fibrosis Biliary Tract: stones, cholecystitis, choledochal cyst, sclerosing cholangitis Autoimmune Liver disease: type 1 (anti-SM Ab) type 2 (anti-LKM Ab) Hepatotoxins: Drugs eg COCP, anti-TB, paracetamol, alcohol, organophosphates Vascular: Budd-chiari, Veno-occlusive disease

Answer 1055

1. Vaccination * HAV * HBV * HPV * M Pox * Meningitis B Neisseria meningitidis and Neisseria gonorrhoeae are closely genetically related with between 80 to 90% sequence homology. 2. PrEP and PEPSE 3. Condoms 4. Doxycycline PEP

Answer 1056

Heavy Loa Loa infection Children <5 years old or below height 90cm Pregnancy

Answer 1057

Annual community directed mass treatment with ivermectin yearly in at risk communities

Answer 1058

Onchocerca volvulus = a filarial nematode Vector: simulium species of blackflies EPI: Sub-Saharan Africa by fast flowing rivers, focal disease in Yemen and Latin America Incubation: 1-2 years, up to 4 years Pathogenesis: - Adult females live in subcutaneous tissue + shed living microfilariae - Filariae migrate through skin -> often into eyes - Most pathology caused by reactions to dead and dying microfilariae, and to endosymbiontic Wolbachia Clinical TRIAD - Eyes - Sub-cut nodules - Itchy dermatitis Eyes: pear-shaped pupil, punctate sub epithelial stromal keropathy, sclerosing keratitis, iritis, uveitis, 'flecked retina', scarred choroidoretinal fundus, optic nerve atrophy Sub-cut nodules: mainly over bony prominences Skin: dermatitis, depigmentation of skin, thickening of skin, skin atrophy, itching and deforming

Answer 1059

Diagnosis via - Skin-snips from vicinity of subcut nodule ?microfilariae - Skin-lamp examination of eyes - microfilariae in anterior chamber? in cornea? - Nodulectomy of subcut nodules for adults (not normally done) Serology unhelpful TREATMENT *Ivermectin* -> single dose 150microg/kg PO -> repeat at 3-6 mph regular intervals eg 6 months, 1 year Works by killing microfilariae but has little impact on adult worms apart from reducing embryogenesis -> has to be given repeatedly throughout adult life cycle of worm 10-14 years *Doxycycline* -> 100-200mg/d 4-6 weeks Works by killing wolbachia endosymbionts, permanently sterilises adult worms, blocks embryogenesis, kills ~60% adult worms

Answer 1060

Infections -> ?helminths - HIV - Fungal eg coccidioidomycosis paracoccidioidomycosis Convalescence from any infection Allergies Drug induced Connective tissue disease Idiopathic hypereosinophilic syndromes Leukaemias and lymphomas Paraneoplatis

Answer 1061

Threadworm

Answer 1062

Direct invasion through skin Autoinfection through intestinal mucosa or perianal skin Faecal-oral transmission

Answer 1063

Invasion Larvae migrate to lungs via bloodstream -> exit blood vessels in pulmonary alveoli -> enter airways -> coughed up and swallowed -> reach small intestine -> complete life cycle Then - Asexual reproduction of eggs (parthenogenesis) - hatching of non-infectious rhabditiform larvae that are excreted in the stool OR larvae moult into infective filariform larvae -> penetrate gut wall or perianal skin to enter circulation Outside body - larvae mature into free-living male and female adult worms -> reproduce sexually or transform into infectious filariform larvae ready for re-infection

Answer 1064

GI Swiftly moving cutaneous eruptions eg larva current Asymptomatic If immunocompromised eg steroids/chemo/malignancies etc: - Dissemination - Hyperinfection syndrome

Answer 1065

Detect larvae in stool (false negatives common) Serology but false negatives also common and only positive 4-12 weeks after infection TREATMENT Ivermectin STAT dose If not then Albendazole BD for 3 days

Answer 1066

Where? - Nigeria - Sierra leone - Liberia - Guinea - Benin - Togo - Mali - Cote d'Ivoire - Burkina Faso Animal reservoir: mastomys natalensis (not rat or mouse, its a rodent) Direct contact with infected rodent excreta, tissues, or blood or via inhalation of aerosolized virus Poor sanitation and housing conditions correlate with greatest risk of infection Peridomestic rodents are also part of diet in certain populations Season: Nov and April (dry season) -> may reflect a higher prevalence of mastomys inside houses Incubation: 3-21 days Majority asymptomatic - mild Severe disease: 5-10% CSF amongst hospitalised cases

Answer 1067

Bacillus anthracis Gram positive rod Forms spores under certain environmental conditions

Answer 1068

Bacillus anthracis Gram positive rod Forms spores under certain environmental conditions

Answer 1069

Exposure to infected animals or animal products Also, bioterrorism risk - i.e. exposure to spores

Answer 1070

Exposure to infected animals or animal products Also, bioterrorism risk - i.e. exposure to spores

Answer 1071

95% of cases are cutaneous Begin with painless papule, which develops into central ulcer and bursts - echar with black necrotic centre develops, which can be surrounded by small vesicles The fever may not develop, but there may be fatigue, malaise, headache Gastrointestinal and inhalational anthrax are also possible Hx: Recent exposure to infected animals or contaminated animal products If bioterrorism risk - ?break in skin and systemic symptoms

Answer 1072

95% of cases are cutaneous Begin with painless papule, which develops into central ulcer and bursts - echar with black necrotic centre develops, which can be surrounded by small vesicles The fever may not develop, but there may be fatigue, malaise, headache Gastrointestinal and inhalational anthrax are also possible Hx: Recent exposure to infected animals or contaminated animal products If bioterrorism risk - ?break in skin and systemic symptoms

Answer 1073

Bacterial ecthyma Rickettsial diseases Rat bite fevers Necrotic arachnidism Ulceroglandular tularaemia Bubonic plague

Answer 1074

Gram stain and culture (blood, skin lesion aspirate, pleural fluid) Paired serological testing for antibodies to protective Ag Full thickness punch biopsy from vesicle and eschar (fix in formalin and sent for nuclei acid amplification and immunohistochemistry)

Answer 1075

Gram stain and culture (blood, skin lesion aspirate, pleural fluid) Paired serological testing for antibodies to protective Ag Full thickness punch biopsy from vesicle and eschar (fix in formalin and sent for nuclei acid amplification and immunohistochemistry)

Answer 1076

Treat empirically whilst awaiting results with a quinolone or doxycycline. If disseminated, then multidrug therapy with CNS penetration. If cutaneous than treat for 7 to 10 days. If inhalational or risk of bioterrorism, then treat for 60 days with oral antibiotics

Answer 1077

Malaria Typhoid Leptospirosis Ascending cholangitis Advanced HIV Gram negative sepsis

Answer 1078

Sub acute onset malaise, non-productive cough, progressive exertional dyspnoea +/- fever O/E: desaturation on exertion Chest may be clear on auscultation Complications: - resp failure -pneumothorax Graded as mild, moderate, severe

Answer 1079

Sub acute onset malaise, non-productive cough, progressive exertional dyspnoea +/- fever O/E: desaturation on exertion Chest may be clear on auscultation Complications: - resp failure -pneumothorax Graded as mild, moderate, severe

Answer 1080

BAL specimens - immunofluorescence, Grocott methenamine silver staining (Induced sputum has low sensitivity) Chest x-ray is normal in 40%, and if positive has non-specific findings. You may see ground glass opacities

Answer 1081

BAL specimens - immunofluorescence, Grocott methenamine silver staining (Induced sputum has low sensitivity) Chest x-ray is normal in 40%, and if positive has non-specific findings. You may see ground glass opacities

Answer 1082

Co-trimoxazole, IV if severe, 21 days if HIV positive, 14 days if other immunosuppressive ponds Corticosteroids, if moderate or severe (wean over 20 days) ART asap SEs co-trimox: cytopenias, rash, hepatitis Second line: primaquine + clindamycin or IV pentamidine (lots of SEs) Mild to moderate: dapsone- trimethoprim or atovaquone Secondary prophylaxis: co-trimoxazole until CD>200 for at least 3 months (or dapsone or atovaquone)

Answer 1083

Co-trimoxazole, IV if severe, 21 days if HIV positive, 14 days if other immunosuppressive ponds Corticosteroids, if moderate or severe (wean over 20 days) ART asap SEs co-trimox: cytopenias, rash, hepatitis Second line: primaquine + clindamycin or IV pentamidine (lots of SEs) Mild to moderate: dapsone- trimethoprim or atovaquone Secondary prophylaxis: co-trimoxazole until CD>200 for at least 3 months (or dapsone or atovaquone)

Answer 1084

- Awareness of risk - Bite prevention - Chemoprophylaxis - Diagnose promptly and treat without delay

Answer 1085

Atovaquone-proguanil: causal prophylaxis -> kills liver schizonts (ie pre-erythrocytic cycle) Doxycycline Mefloquine Both suppressive prophylaxis -> kills RBC stage

Answer 1086

Atovaquone/proguanil 1 day before, OD, 7 after Considerations: DDI Renal dose adjustment (eGFR<30 avoid) Take with fatty meal or milk Cannot crush 2nd choice pregnancy or BF SEs: Neuro - dizziness, depression and sleeping problems GI - N&V&D, anorexia Hair loss CI: severe liver disease

Answer 1087

250mg weekly, start 2-3 weeks before travel (to assess tolerability), continue 4 weeks after Considerations: DDI Crushable NOT for psych hx, epilepsy, diving, flying, military, cardiac, CYP3A4 eg warfarin, DOACs etc Can use in pregnancy (unlicensed), simple paediatric administration SEs: Dreams Insomnia Anxiety Depression 2-5x more likely Increased gender differences -> 2x female NB: SEs/symptoms can be seen after only SINGLE dose CIs: - allergy to it, ingredients, quinine, quinidine - PSYCH Hx - NOT IF FIRST DEGREE RELATIVES eg with epilepsy/serious MH disorders - NOT FOR EPILEPTICS - AVOID if serious cardiac arrhythmias Useful in: Babies/Pregnancy/BF Those who can tolerate it Renal failure Lower income Not useful in: Any psychiatric/psychological Hx Long term >1 year Eye issues Anticoagulants Arrhythmias Adventure travel – diving, flying High stress

Answer 1088

Start one day before travel, take OD, continue 4 weeks after Considerations: * Drug-drug interactions (DDI) * Does not reduce efficacy of OCP * Metabolism increased by carbamazepine and phenytoin – can double dose * Possibly reduced efficacy oral typhoid vaccine Can use in severe renal failure Can use moderate liver disease (mixed UK vs US guidance) CI: pregnancy up to 15 weeks, no children, UK – no breastfeeding (unless essential), USA – breastfeeding ok, epilepsy, porphyria SEs: * Oesophagitis/Gastritis * Tooth bone effects after 15/40, teratogen * Photosensitivity * No antacids (make it less effective) * Thrush * recommended to take with food or milk Not safe * In epilepsy if on carbamazepine/phenytoin (can dose adjust) * Porphyria * Sunbather/gastritis/children/long trips/thrush

Answer 1089

- Mefloquine -> yes - Ato/Prog -> probably but lack of data - Doxy -> UK says no, USA yes

Answer 1090

Consider an interval before conception of: * Mefloquine – 3 months * Doxycycline – 1 week * Atovaquone/proguanil – 2 weeks BUT conception on any antimalarials is not an indication for termination Most advice based on lack of data

Answer 1091

* Inform anticoag clinic 2-3 weeks before travel * INR before starting and one week after + intervals during travel Warfarin * Mefloquine-OK * Doxycycline- may increase INR * Atov/Prog- Not known, prog increase INR DOAC * Mefloquine inhibits CYP3A4 and p-glycoprotein, could increase risk bleeding * Atovaquone minor increase CYP3A4 NOT p-glycoprotein

Answer 1092

* doxycycline YES * atovaquone/proguanil YES * chloroquine NO * Mefloquine NO

Answer 1093

* Risk of rapid deterioration * Mefloquine easiest- 5kg and above, weekly * Atov/Proguanil- 5Kg and above with milk/yoghurt, daily * Doxycycline >12 years

Answer 1094

- If eGFR<30 avoid malarone Can use mefloquine and doxy in severe renal impairment

Answer 1095

* All metabolized in the liver Severe * Doxy Yes * Malarone unknown * Mefloquine No Moderate and Mild Can use all 3

Answer 1096

Causal: - Malarone - Tafenaquine - primaquine Suppressive - Doxy - Mefloquine - Chloroquine

Answer 1097

Those taking chemoprophylaxis and visiting remote areas where they are unlikely to be within 24 hours of medical attention 1. Artemether + lumefantrine (4 tablets, 5 further doses of 4 tablets at 8,24,36,28,60 hours) 2. Atovaquone + proguanil (4 tablets OD 3 days) 3rd line or first line for pregnant women in first trimester (otherwise treat with regimen 1): quinine (8hrly 5-7 days) + clindamycin (8hrly, 5 days)

Answer 1098

Additional vaccinations * Haemophilus influenza type b * Meningococcal ACWY * Meningococcal B vaccine * Influenza * Pneumococcal Prophylactic/standby Abx * Pen V * Consider standby Abx Other infection risks * Malaria * Babaesiosis Tuck trousers into socks Permethrin spray Tick check and removal

Answer 1099

Resp: Loeffler's syndrome -> dry cough, interstitial infiltrates, eosinophilia Skin: larva currens GI: abdominal pain, indigestion, heartburn, diarrhoea, bloating Asymptomatic if immunocompromised: - strongyloides hyperinfestation syndrome - severe diarrhoea/paralytic ileum, necrotising pneumonia, gram negative sepsis +/- meningitis

Answer 1100

Middle East, North Africa, Asia L major, L tropica, L infantum, L donovani

Answer 1101

Central and South America L mexicana, L braziliensis, L amazonensis

Answer 1102

Hookworm Ancylostoma caninum and Ancyclostoma braziliense Tx: Ivermectin STAT or albendazole Children -> topical thiabendazole (ivermectin)

Answer 1103

10% - Pulmonary or Extrapulmonary

Answer 1104

Diabetes -> increases progression from latent to active TB HIV -> increases probability of early progression + increases probability of TB reactivation

Answer 1105

Tells you if TB is present Tells you if resistance conferring mutation to rifampicin is present

Answer 1106

LED fluorescence increases sensitivity from 50 to 60%

Answer 1107

2HRZE/4HR (2 months all, 6 months total of iso/rif) OR 2HRZE/4(HR)3 (2 months all, but during next 4 months give "continuation therapy" of iso/rif x3 per week rather than daily) If patients have sputum smear status <2 (milder disease) + lack of cavitation on CXR (~50%) then 4 months treatment is non-inferior to 6 months

Answer 1108

Pulmonary TB Hierarchy = PTB with EP manifestations is classified as PTB

Answer 1109

PTB - Involves lung parenchyma - Includes miliary disease EPTB - Involves any other system - Not involving lung parenchyma - Includes: * Hilar lymphadenopathy * Pleural THINK: 1. Hierarchy = PTB with EP manifestations is classified as PTB 2. For EPTB think HIV 3. Paradoxical reactions 4. Steroids

Answer 1110

- Median time to culture conversion (eg positive to negative): 37 days - 90% achieved culture conversion by day 60 (Fitzwater S et al, Clin Inf Dis 2010) - Effective treatment reduces cough frequency

Answer 1111

- Associated with oncho in population based studies in Africa ○ Onset usually 3-18 years ○ Risk increases with microfilariae load ○ Prevalence can be high eg 18% in south Sudan ○ Risk reduced by biannual ivermectin and vector control - Historically ○ Dwarfism (nakalanga) with associated epilepsy reported from oncho-endemic area of Uganda/DRC historically - ?hypopituitarism ○ ‘nodding disease’ strange form of epilepsy seen in children in oncho-endemic areas of Uganda/South Sudan/Tanzania. ○ Involuntary nodding movements precipitated by food or cold. Aetiology uncertain - ? Cross-reactivity with developing neurones.

Answer 1112

Simulium damnosum complex

Answer 1113

- Female lays eggs under water - Eggs last 3 days - Usually 7 larval instars, develop over 7-12 days - Have mechanism on top to filter out water - Pupae - 3-5 days -> Pupate under water - Come out of water and fly immediately - Males and females mate immediately, females store sperm, often have more matings in life than need to - Adult females <30 days (between blood meals 3-4 days)

Answer 1114

Skin acute: Massive skin infestations by microfilaria Live mf cause minor symptoms Dying mf create inflammatory reactions which provoke the reactions seen in the skin Acute phase: Severe Itching Secondary skin infections due to scratching Disturbed sleep Poor performance NB. These stages are reversed with ivermectin treatment Skin chronic: Irreversible changes Thickening of the skin (Lizard skin) Atrophy of the skin (The skin looks old even in young adults) Hanging groin (Rare caused by inguinal lymph nodes dragging the atrophied skin down wards creating a large skin fold) Leopard Skin dermatitis (the most common chronic disease) All these conditions are associated with itching which will be relived with ivermectin but skin changes are irreversible.

Answer 1115

Neurological effects Children - Growth retardation (Nakalanga syndrome) ○ Huge community impact ○ Skin disease, blindness, neurological effects and chronic ill health leads to a vicious cycle of poverty - Nodding syndrome - Increased mortality Adults - OAE: onchocerciasis associated epilepsy

Answer 1116

The eye 1. Conjunctiva - Inflammation around dying microfilaria causes pruritis and pigmentation 2. Punctate keratitis - Dying microfilariae in cornea create inflammatory response -> appears as white linear opacity - Develops as more diffuse white spot = 'snowflake/cotton wool keratitis' - As microfilaria are absorbed -> cornea regains normal appearance and transparency - Repeated heavy infections create irreversible changes 3. Sclerosing keratitis - Permanent opacities eg 9 and 3 o'clock - Space between called semi-lunar keratitis - Rest of cornea becomes opaque - Pupil increasingly covered -> vision progressively impaired 4. Chronic anterior uveitis and secondary cataract 5. Chorioretinitis - Inflammatory process provokes increasingly destructive chorioretinitis with loss of vision, most often beginning at periphery 6. Optic atrophy - Inflammatory changes lead to atrophy - Retina: clumping of pigment and atrophy of optic nerve Major causes of blindness - Sclerosing keratitis (difficult to see back of eye if present) - Anterior uveitis (iritis) often associated with glaucoma and secondary cataract - Progressive chorioretinitis - Optic atrophy

Answer 1117

1. Use larvicides for larvae populations concentrated at identifiable points (breeding sites in white-water rapids) in rivers (eg via helicopter) 2. 'Safe' insecticides eg low toxicity to non-target organisms including man, eg emulsion or as particles which larvae will filter and eat (eg Temephos and Bacillus thuringiensis serotype H14) 3. Apply larvicides to rivers above breeding sites and rotate sites to minimise insecticide resistance. Wash insecticide down river through breeding sites -> apply for 10 minutes to ensure lethal dose reaches blackflies, 30minutes needed for S.neavei) ○ Idea is kills multiple breeding sites as insecticide is washed down river ○ Depending on river may need to treat at multiple dosing points Other principles - Repeat dose weekly to kill every generation (S.naevi is slower growing and insecticide can often be applied monthly) - Measure river discharge before every treatment to ensure dilutional effect is correct Measure success of vector control by reduction of biting flies

Answer 1118

WHO roadmap: elimination of onchocerciasis by 2030 in 12 countries. National elimination programmes are long-term programmes and based on multiple ivermectin treatments each year. WHO’s Onchocerciasis Elimination Program for the Americas (OEPA). Onchocerciasis control programme (OCP) = 11 countries in West Africa. African Programme for Onchocerciasis Control (APOC) = 19 countries. - Pioneered community directed treatment so don't need health worker coordination etc African programmes now nationally owned under WHO AFRO ESPEN. Onchocerciasis Control Programme in West Africa major public success (1974-2002) Based on vector control (larviciding initially, later on mass drug treatment with ivermectin) Community directed treatment programmes: 1. Choose a distributor for training 2. Do a census to calculate Mectizan requirements 3. Organise the collection of Mectizan from a Health Centre or other distribution point 4. Organise a distribution method, house to house, fixed point in village etc 5. Help the distributor calculate the dose and distribute the Mectizan 6. Note the treatment statistics and report to the health authorities 7. Participate in community supervision After 5 years communities should be ready to continue treatment alone with minimal help and supervision from the P.H.C. services Equally a mechanism is in place for mass distribution of other medicines

Answer 1119

FROM: CONTROL (Elimination as a Public Health Problem) * Onchocerciasis control (elimination as a public health problem) * Reduction of blindness and skin problems to insignificant levels * Largely achieved except in conflict countries (An APOC success) * However there is a constant risk of recrudescence * Some treatment and surveillance will be needed for decades TO: ELIMINATION (Elimination of transmission) * Elimination is not “business as usual” * The disease must be fully mapped to identify where transmission is ongoing * Treatment strategies will need to be analysed to interrupt transmission as soon as possible

Answer 1120

* Simulium are very mobile and with the winds can travel 400 Km so there is always a risk of reinvasion * Transmission can occur when treatment is not carried out “across the border” (national or provincial) with local vectors * may cross state or national borders and may not include whole health districts

Answer 1121

Pros Reduces transmission particularly in early rounds (Skin microfilaria kept at zero) May speed up the achievement of a “closed system” Has more effect on adult worms May increase overall "annual" coverage Reduces treatment time to 6 - 7 years, therefore easier to proclaim an endpoint and success in elimination Cons Change in CDTI philosophy Distribution times more controlled at central level More control from central level No reduction in transmission after several years of treatment Extra costs - Retraining - Logistics in country More ivermectin needed

Answer 1122

Morbidity * The absence of microfilariae (mf) in the anterior segment of the eye no longer included Transmission * Presence of L3 in flies <0.05% (0.1% in parous flies) * ATP lower than 20 L3 per season * Absence of detectable infection in children <10 yrs and antibody prevalence of <0.1% * No new infections in recent migrants

Answer 1123

1. Infected Blackfly bites human * During the bite, fly deposits infective L3 larvae of Onchocerca volvulus into skin 2. Larval Development in Human Host * L3 larvae migrate into subcutaneous tissue + grow and mature * Over 6–12 months, larvae develop into adult worms. Female worms can grow up to 50 cm in length, while males are smaller, reaching around 4–5 cm. * Adult worms form fibrous nodules or lumps, known as onchocercomas, typically around the bony areas of the skin (e.g., near the joints or skull). 3. Production of Microfilariae * Inside the nodules, adult worms live for 10–15 years and reproduce continuously. Each female can release thousands of microfilariae (larvae) throughout its lifespan. * These microfilariae measure about 200–300 micrometers and migrate from the nodules to various parts of the body, particularly to the skin and eyes. * Microfilariae cause intense itching and inflammation as they travel through the skin, and can invade the eye 4. Re-Ingestion by Blackfly * When an infected human is bitten by another blackfly, the fly ingests the microfilariae present in the blood or skin of the host. * Once inside the blackfly’s gut, microfilariae migrate to the thoracic muscles of the fly. 5. Development of Microfilariae in the Blackfly * Inside the blackfly, the microfilariae undergo two molts over a period of 7–14 days, developing from the ingested microfilariae into the infective L3 larvae. * Once the larvae reach the L3 stage, they migrate from the thoracic muscles to the blackfly’s proboscis (mouthparts), ready to be transmitted to a new human host. 6. Cycle Repeats with New Human Host

Answer 1124

Definition A parasitic disease caused by the filarial worm Onchocerca volvulus; primarily affects skin and eyes. Causative Agent Onchocerca volvulus (a parasitic worm) Vector Blackfly (Simulium species) = females only Breeds near rivers and streams -> white water, fast-flowing (well oxygenated for nutrients for larval requirements) Only bite through skin (not clothes), PAINFUL BITE, outdoors, daytime Geographic Distribution + EPI Mainly found in sub-Saharan Africa (96%); 4% Latin America and Yemen 21 Million WW, 123 million at risk Blindness 270,000 (most commonly SS savanna), vision loss 1 million, skin disease 15 million Transmission Transmitted through repeated bites of infected blackflies; larvae enter skin and develop into adults Major effects in skin necessary for transmission: acute dermatitis, chronic lizard skin, leopard skin, skin atrophy

Answer 1125

Adult worms create nodules in skin: <2cm diam, mobile, firm, well-defined, non-tender or painful, pelvic girdle in Africa, head and shoulders in Guatemala, Mexico and African children Microfilariae drive disease - Early reactions to dead microfilariae in upper dermis: eosinophil and neutrophil infiltration with macrophages – leads to itching and acute skin lesions – reversible inflammatory changes - Neutrophils attracted by endotoxin-like molecules released from symbiotic rickettsial bacteria Wolbachia - Later develop fibrosis, depigmentation and atrophy – leads to irreversible chronic skin lesions - Hyperreactive form of disease Sowda: few microfilariae, high IgE levels, increased inflammatory infiltration, altered Th2 response. Intensely itchy. - Neutrophil attraction to bacterial Wolbachia prevents eosinophil-mediated response to nematode worm: immune evasion. - Transmitted transovarially from worm to worm (vertical transmission) = death of wolbachia (eg with tetracyclines, rifampicin and chloramphenicol) disrupts fertility and worm death

Answer 1126

Sowda few microfilariae, high IgE levels, increased inflammatory infiltration, altered Th2 response. Intensely itchy

Answer 1127

Symptoms DYING MICROFILARIAE cause DISEASE Depend on no. of bites and severity -> related to microfilariae burden Severe itching and acute skin lesions (rash, nodules, depigmentation) - Early reactions to dead microfilariae in upper dermis - Nodules found mostly on bony prominences throughout body, mostly asymptomatic Eye lesions leading to visual impairment and, in severe cases, blindness Consequences Clinical * Visual damage leading to blindness * Itching, acute and chronic skin disease * Increased mortality especially in <20, ?associated with epilepsy * Clinical severity depends on length of exposure to bites and density of microfilariae in the skin. Chronic inflammatory response leads to progressive disease Socio-economic * Stigma + psychosocial consequences, reduced marriage consequences * Personal and family economic impacts * Community desertion of fertile river valleys

Answer 1128

DIAGNOSIS Skin snips to detect microfilariae (normally from iliac crest) Slit-lamp examination for eye infection. Serologic tests in some cases ELISA: Ov16 point of care RDT - IgG in blood -> indicates exposure to infection TREATMENT Ivermectin: kills larvae, alleviates symptoms, and helps prevent transmission (given annually) - Mass treatment every 3-6 months controls transmission as keeps MF amount low - Mass treatment every 12 months stops blindness/clinical manifestations ○ little effect on adult worm mortality – a major drawback Exclusion: pregnant women, lactating women within 1 week of birth, children under 5, co-infection with Loa loa Doxycycline: depletes symbiotic bacteria (Wolbachia) within worms, weakening them (3 weeks causes sterility of adult worms, 4 weeks can kill them) CHALLENGES 1) Loa loa co-infection (loascope can help identify patients with filarial load of 20,000 roughly as cut off -> don't treat those with that or more), consider giving them doxy 2) Ivermectin tolerant parasites

Answer 1129

Onchocerciasis, Wuchereria bancrofti, Ascaris, Strongyloides, head lice and scabies. Even malaria with doses every 3 weeks.

Answer 1130

* Priority for control is communities with high endemicity (eg prevalence over 60% in adults), but need to treat all affected communities for elimination (transmission) * Morbidity: High prevalence → high parasite density → more pathology * Mass distribution (treat everybody in community regardless of infection or disease status) every 12 months for control * Elimination: every 3 or 6 months: reduces transmission as well as clinical benefit (very successful in Latin America) * Community-directed treatment is highly successful * Long-lived adult worms: programme must last 10 years at least (ivermectin kills mf but not adult worms)

Answer 1131

1) Capacity building (public health and lab) 2) Sustainability (length of treatment to finish task, post-treatment surveillance) 3) Conflict (population changes, infrastructure, funding) 4) Loiasis 5) New drugs *ideally want macrofilaricide but not micro, also one to combat parasite evasion 6) Data and specificity if control is being integrated into other elimination/NTD campaigns 7) Country ownership (ESPEN is facilitating national ownership but insufficient domestic funding in many countries) 8) Advocacy (need long term funding and agenda)

Answer 1132

Cestode: tapeworm Spirometra Spirometra infect animals WW, but high incidence in SE and East Asia, especially in (south and east) China (practices to do with eating frogs, snails, snakes or using their undercooked flesh to apply to skin or eyes as remedy) Life cycle: 1) Adult worms live in the intestines of dogs and cats => release eggs into the environment via faeces 2) Eggs embryonate in freshwater, infecting crustaceans 3) develop into procercoid larva within the crustacean, then ingested alongside it by a second intermediate host, namely fish, amphibians, and reptiles. 4) Humans are accidental hosts => ingest the procercoid larvae either by drinking contaminated freshwater, or by eating or topically applying the undercooked flesh of the second intermediate host Incubation period variable eg 1 day to 30 years -> also depends on where the spargana migrate to

Answer 1133

migratory, painful subcutaneous nodule -> like on and off lipoma Ocular and visceral disease can occur Cerebrospinal disease -> uncommon but well described, can affect any part of CNS, presents as seizures, headache, and cognitive decline, or focal neurological symptoms related to disease location. CT: unilateral punctate calcification in white matter with surrounding low-density lesions MRI: multiple nodular ring-enhancing lesions with ‘tunnel sign’ and surrounding oedema; it is more sensitive than CT Definitive diagnosis is histological following surgical removal Spirometra spp. procercoid larva are not distinguishable between one another morphologically and species level identification is often done by PCR or genetic sequencing Serology is not routinely used and cross-reacts with other cestode species.

Answer 1134

Surgical removal -> most effective Where this is not possible, high dose (≥120mg/kg) praziquantel has been used. Observational evidence suggests that this can effect cure in some, but no randomised trial data exist. Lower doses (75mg/kg) seem to be less effective.

Answer 1135

Amberjack Happens in tropics and subtropics - D&V 3-6 hours after ingestion - Neurological abnormalities 3-72 hr after ingestion ○ Paraesthesia, pruritis ○ Metallic taste, painful dentition ○ Painful urination, blurred vision ○ Temp-related dysesthesias (hold-cold allodynia) ○ Paresis, reversible cerebellar dysfunction - CV: hours after ingestion Bradycardia, heart block, hypotension Prognosis - Recovery is usual ○ GI resolves within days ○ Neurological changes within weeks Symptoms may come back/get worse if ETOH, caffeine, nuts, pork

Answer 1136

Due to poorly stored fish and build up of histamine Presents like allergic reaction - Rash - Palpitations - Tachycardia like IgE mediated immune reaction

Answer 1137

Painful Puncture wounds Tattoo appearance irritating CaCO3 spines -> granulomatous inflammation some spines loaded with venom -> localised reaction MANAGE Remove visible spines hot water soak consider tetanus vaccination, Abx Plain X-ray Later - Treat infection eg bacteria, mycobacterial, fungal surgical removal - topical/intra-lesional steroid - cryotherapy - laser ablation - conservative

Answer 1138

Where are lesions? Mucosal involvement? (need systemic tx) Species -> need PCR as American species more aggressive Multiple lesions?

Answer 1139

Local: - nothing - intra-lesional antimony (meglumine) - heating/freezing/surgery Systemic treatment: - oral miltefosine - IV miltefosine (SSG = sodium stibogluconate) (CI: pregnancy) - IV liposomal amphotericin B (ambisome)

Answer 1140

Gnathostoma spinigerum Spargonosis Loa Loa Strongyloides stercoralis Strongyloides fulleborni (animal species) Cutaneous larva migrans Other - Widespread eczema - Phytophotodermatosis - Trichinosis

Answer 1141

Angiostrongylus cantonensis Gnathostoma spinigerum Baylisascaris procyonis

Answer 1142

Presents: - Acute phase: fever, urticaria, GI symptoms - Cutenous: migratory swellings, subcut haemorrhage - Visceral: lung, GI, CNS - 12 years Diagnosis - Clinical, eosinophilia, serology (immunoblot) Treatment Albendazole 400mg BD 12 days

Answer 1143

Leptospirosis Drugs Long lies exertion eg marathon runner

Answer 1144

GBS eg campylobacter, shigella Acute flaccid myelitis (enterovirus D68 infection) Post-infectious myositis Rhabdomyolysis eg exertion like marathon runner HIV, syphilis

Answer 1145

Initial injury or wound -> gain entry Generalized Tetanus: Stiffness (early symptom), lockjaw (trismus), risus sardonicus (spasmodic smile), muscle rigidity, then muscle spasms -> if severe then impact ability to breathe - Then toxin can get into autonomic nervous system -> rapid changes in HR and BP Localized Tetanus: Muscle spasms near wound Cephalic Tetanus: Can be localised to nerves around head and neck Neonatal Tetanus: Generalized rigidity and spasm in newborns, often from umbilical stump infections Modified Ablett score - to grade spasms Grade 1: no spasms Grade 2: Mild short-lived spasms not interfering with Respiration Grade 3: More prolonged muscle spasm interfering with Respiration Grade 4: Grade 3 but autonomic nervous system dysfunction Other features - Voice change -> muscle tension in pharynx and larynx - Spasms -> can be mild in elderly patients - CV instability is early - Pyrexia -> can cause irreversible heat shock Cardiac events common in elderly patients

Answer 1146

Causative Agent Clostridium tetani, an anaerobic, spore-forming bacterium found in soil, dust, and animal feces 'drumstick appearance' - Pore forming toxin = tetanolysin and a collagenase are needed for growth and toxin production Transmission Entry of bacterial spores through open wounds (e.g., punctures, cuts, or burns) Pathophysiology C. tetani spores germinate in anaerobic conditions Pore forming toxin = tetanolysin and a collagenase are needed for growth and toxin production Retrograde transport into CNS along motor nerve + blocks inhibitory GABA neurotransmitters in motor neurons -> unopposed muscle contraction and spasm Incubation Period 3-21 days (average around 8 days); shorter incubation is associated with rapid + more severe disease

Answer 1147

Management 1. Remove toxin: Clean and debride wound to reduce bacterial load 2. Antibiotics: Metronidazole (preferred) or penicillin 3. Antitoxin: Human tetanus immune globulin (TIG) to neutralize circulating toxin 4. Muscle Relaxation: Benzodiazepines (e.g., diazepam) for muscle relaxation and spasm control 5. Supportive Care: Intensive care for respiratory support, sedation for severe cases * Airway ○ Tracheostomy is best option * Spasms ○ Benzo ○ Mg may help reduce requirement for muscle relaxants but not mechanical ventilation ○ Ventilation * Autonomic disturbance ○ Mg may help ○ Cooling if very hot ○ Only use short acting drugs * GI HAI 6. Vaccination 7. rehab -> patients can lose 25% of muscle during illness

Answer 1148

- Very high risk injury - So regardless of vaccination status give booster and passive immunisation

Answer 1149

- Complete vaccination -> no input needed Even if very high risk injury if patient is fully vaccinated then no booster or passive immunisation needed

Answer 1150

- Incomplete vaccination with tetanus prone wound (but not necessarily very high risk) -> give booster

Answer 1151

Tracheostomy and ventilation To control breathing whilst muscle spasms ongoing

Answer 1152

Causative Agent Mpox virus Zoonotic Orthopoxvirus closely related to the smallpox virus (variola) 2 clades: I and II - Clade I in predominantly Central Africa (split into a and b) -> cases increasing - Clade II in predominantly West Africa (split into a and b) Epi DRC highest no. of cases, others in central and West Africa, some WW eg UK, Singapore Clade Ia - More equally distributed amongst men and women, general population, children especially - Less spread outside of central Africa, but cases increasing - Highest case fatality rate in Africa data ~4.6% Clade Ib - Outbreak from September 2023 onwards, started DRC, spread across East Africa and global imported cases - Predominantly high-contact heterosexual networks - Low case fatality <0.5% Clade IIb - Outbreak 2022, men >90%, MSM, men who have had recent STI, men with HIV - Low case fatality rate <0.1% Transmission Animal-to-human: Contact with infected animals (e.g., rodents, primates) via bites, scratches, eating meat or handling infected materials/animal products Person-to-person: Direct contact with skin lesions, rashes, scabs, bodily fluids, respiratory droplets, or contaminated objects (e.g., clothing, bedding -> lower risk), placental spread to fetus Nosocomial infection can occur and via fomites - Data strongest in clade Iib - ?Sexual transmission - Transmission could be different in different clades but might also be about population representation - Some sexual transmission for Clade I -> not good data

Answer 1153

Pathophysiology Virus enters through mucous membranes, respiratory tract, or broken skin Incubates and spreads to lymphoid tissues and blood, causing viremia and systemic symptoms Affects skin, resulting in characteristic rash Incubation Period Typically 3-21 days (average 7-14 days) Typically prodrome first then rash 1-4 days later Clinical Features 1. Prodrome (early symptoms): Fever, headache, muscle aches, fatigue, lymphadenopathy (swollen lymph nodes, differentiating it from smallpox) 2. Rash: Begins 1-2 days into fever; progresses macules -> papules -> vesicles -> pustules -> scabs - (a few to several thousand, lesions appear and evolve simultaneously, centrifugal vs centripetal distribution) 3. Rash typically begins on the face and spreads to other parts of the body, often including palms and soles, could be anus/vagina Diagnosis 1. PCR -> detect viral DNA - Best samples from rash eg skin lesion material/exudate, crusts, deroof lesion and take fluid from it - If skin lesions absent -> oropharyngeal +/- rectal swabs Other tests: Viral culture, serologic tests for antibodies (used less frequently in acute diagnosis)

Answer 1154

Proctitis Genital deformity/abscesses Pharyngitis Lymphadenopathy Bacterial superinfection/secondary infections Encephalitis Pneumonia Higher rates of complications and mortality with HIV

Answer 1155

Differentials Syphilis (1o or 2o) VZV Disseminated cryptococcus HSV Disseminated gonococcal infection Molluscum Other causes of genital/anal ulcer diseases & proctitis eg chancroid, LGV, Behcets/IBD

Answer 1156

Management Assess pain (not all lesions visible o/e) Supportive care (hydration, pain management, fever control, NSAIDs with caution) Oral lesions - mouthwash, salt water, viscous lidocaine Rectal - stool softners, sitz baths, topical lidocaine, avoid opioids Antiviral therapy: Tecovirimat (Tpoxx) recommended in severe cases or for high-risk individuals - Antiviral stockpiled for smallpox preparedness Isolation: Infected patients should be isolated to prevent spread Avoid scratching lesions to reduce secondary infection risk Prognosis - Generally mild in most cases with full recovery within 2-4 weeks - Severe outcomes more likely in young children, pregnant individuals, and those with weakened immune systems

Answer 1157

Prevention Vaccination: JYNNEOS=IMVAMUNE=IMVANEX (safer option) can be used in high-risk individuals or as post-exposure prophylaxis - Live, non-replicating Vaccinia virus, 2 doses 4 weeks apart - CI: Mpox symptoms, allergy to: egg, cipro, gent - Can give to HIV, atopic dermatitis - Fractional dosing (ID) Public Health Measures: Isolation of infected individuals, contact tracing, proper use of personal protective equipment (PPE) for healthcare workers IPC: gloves, gown, N95/FFP2 mask, eye protection, dedicated footwear, cover lesions At home: patients manage own care, dedicated, well-ventilated room separate from others in household, cover lesions, dedicated utensils for individual eg linens, electronic devices etc

Answer 1158

Causative Agent Zika virus, Flavivirus Single-stranded RNA - Two strains: African and Asian - Asian strain responsible for known outbreaks - African strain -> higher transmissibility and pathogenicity Transmitted primarily by Aedes mosquitoes (e.g., Aedes aegypti, Aedes albopictus) Epi 2007 in Macaques + then case reported in man, similar to Dengue but different Large outbreak 2007 Yap island (no monkeys on island, thought spread by travel) 2013 outbreak pacific islands and high cases of GBS and first evidence of perinatal infection + microcephaly 2015/2016 outbreak in Americas, growing evidence on GBS and congenital abnormalities 2016: WHO public health emergency of international concern Few cases of Zika in UK since 2018 -> most of ours were from Americas but last year 2 from Seychelles + more from Thailand 2024: cases in North/Central/South America, some in West Africa and some East Africa, widespread also in South/SE Asia

Answer 1159

Transmission Mosquito bite from infected Aedes aegypti predominantly, day biting + urban environments, some from Aedes albopictus (more widespread geographically) - Major driver in outbreaks - Aedes can lay eggs/replicate in old tyres etc Transplacental Sexual transmission: Virus can persist in semen, vaginal fluids Blood transfusion: Rare, but possible Other: found in breastmilk but no reports of transmission, ?tears and sweat Incubation: 3-12 days

Answer 1160

Clinical Features 80% asymptomatic Rash and fever most common +/- arthralgia/arthritis, myalgia, conjunctivitis (red eyes), headache, back pain Pregnancy complications: Linked to congenital Zika syndrome, which includes microcephaly, brain malformations, and other birth defects - Asian strain linked to CZS, lack of data on African - African in animal models linked to embryonic death rather than live births with neurotropism - Risk decreases from 1st-3rd trimester (8% in first, 3.8% in third)

Answer 1161

Complications Congenital: Microcephaly, pointed occiput, redundant scalp skin, congenital contractures, cerebral calcifications/ventricular megaly on CT Eye: focal retinal mottling and macular scarring, cataracts, glaucoma, optic nerve atrophy Deafness Seizures, tremor, hypertonia, hyperreflexia, irritability Developmental delays, vision/hearing impairments Neurological: Guillain-Barré syndrome (GBS) and other neurological disorders in some infected adults, post-infectious Campylobacter risk of GBS still higher, ie GBS risk is still low Weakness, facial palsy, inability to walk Median onset 6 days from onset of infection to GBS CNS involvement rare eg menin/encep In comparison to Dengue: - Zika: no increased in maternal s/s, Dengue: more severe disease in pregnancy, increased risk of death - Zika: CZS, Dengue: increased risk of foetal loss

Answer 1162

Diagnosis Molecular testing: PCR on blood, urine, or saliva (best within 7 days of symptom onset, viraemia period short, 3-5 days after onset of symptoms) - Pregnant women have longer viraemic period + longer => higher CZV risk - Urine stays positive for long time (eg up to 3 weeks) - Can also use semen, CSF, amniotic fluid, placental, umbilical cord tissue Serology: Detection of Zika IgM antibodies (may cross-react with other flaviviruses) - IgM positive first week after symptom onset + can persist for weeks, may not develop if previous dengue - IgG appears early, may persist for years/life long, if previous flaviviruses/vaccination subsequent exposure to related flaviviruses can cause rapid and brisk rise in IgG against multiple flaviviruses Management Supportive (hydration, pain relief with acetaminophen, rest) Avoid NSAIDS until dengue ruled out -> risk of bleeding complications

Answer 1163

Prevention Mosquito control: Use insect repellent, wear long sleeves and pants, use bed nets, eliminate standing water Travel advisories: Pregnant women advised to avoid travel to Zika-endemic areas Safe sex practices: Use condoms or abstain from sex if partner has traveled to an area with Zika virus for several months Pregnancy advice If planning a pregnancy: - Don’t travel to Zika virus endemic area ideally - Avoid becoming pregnant for 2 months if only woman has travelled - Avoid becoming pregnant for 3 months if both partners/ just the male partner has travelled If already pregnant: - Use barrier contraception if both travelled for the duration of pregnancy If living in an endemic country: - Mosquito avoidance Cross-infection Relationship is asymmetric * Prior Zika infection – can worsen and enhance future dengue infections with Dengue 2, 3 and 4 (but not 1) * Prior dengue infection protective for Zika * May have implications for Zika and dengue vaccinations

Answer 1164

1. Where is the bite? Skin intact? Contamination by saliva? 2. The circumstances of the bite or other contact 3. Species of mammal 4. Behaviour and appearance of the animal - Known rabies reservoir? - Animal sick or acting abnormally? - Bite unprovoked? - Not been vaccinated against rabies? 5. Vaccination history 6. (Laboratory test on animal's brain) CAT1: low risk eg drinking mild from rabid animal or animal licking closed skin CAT2: nibbling of uncovered skin, minor scratches or abrasions without bleeding (treat as CAT3 if bat involved/if innervated areas eg head/neck/face/hands/genitals) CAT3: single/multiple transdermal bites/scratches/contamination of mucous membranes/exposure to bats/eating raw meat of rabid animal

Answer 1165

VACCINATED Cat I: wash wound, no PEP Cat II/III: wash wound, vaccinate 1-2 visits for vaccination UNVACCINATED Cat I: wash wound Cat II: vaccinate Cat III: vaccinate and give RIG If vaccinating ID then 2 sites and 3 vaccinates within 7 days (day 0,3,7) If vaccinating IM then 1 site, 4 times (day 0,3,7,14-28) -> ie 3/4 visits for vaccination

Answer 1166

7 days after administration of first vaccine dose Passive immunisation -> neutralise virus in wound - Infiltrate around wound any remainder inject IM (not in buttocks)

Answer 1167

Vaccinate 3 times - 0,7,21-28 days Check RABV neutralising Ab 2-4 weeks after vaccination to assess whether additional vaccine dose is required

Answer 1168

1. Wash wound for minimum 15 minutes with soap and water 2. Give 5 doses of vaccine at day 0,3,7,14, 28-30 3. Assess risk -> likely CAT II/III in this case so needs RIG within 7 days of first vaccine dose (if CAT I then no RIG)

Answer 1169

95% LMICs · Fluid resuscitation · Warming · Analgesia · Nutrition · Infection control (including tetanus)

Answer 1170

- RTAs - Burns - Congenital malformations (GI>cardiac), cardiac more serious, 50% in general require immediate surgery CHALLENGES - lack of access - lack of timely access - patient factors: nutrition, anaemia, immunosuppression - system factors: access to parenteral nutrition, safe anaesthesia, ICU, blood transfusion, hygiene, technology, Abx

Answer 1171

Type I (Clitoridectomy) Partial or total removal of the clitoris and/or the clitoral hood. Subtypes: Type Ia: Removal of the clitoral hood/prepuce only Type Ib: Removal of the clitoral glans and prepuce Type II (Excision) Partial or total removal of the clitoris and labia minora, with or without removal of the labia majora. Subtypes: Type IIa: Removal of labia minora only Type IIb: Partial or total removal of clitoris and labia minora Type IIc: Partial or total removal of clitoris, labia minora, and labia majora Type III (Infibulation or pharaonic circumcision) Narrowing of the introitus through creation of a covering seal Layer of scar tissue formed by cutting and repositioning inner or sometimes outer labia, with or without removal of clitoral glands and/or prepuce The vaginal opening is narrowed, leaving a small passage for urine and menstrual fluid -> ++ symptoms eg can take long time for urinate Subtypes: Type IIIa, removal and apposition of the labia minora Type IIIb, removal and apposition of the labia majora High prevalence in North-Eastern Africa: Djibouti, Eritrea, Ethiopia, Somalia, Sudan Tx: de-infibulation = opening procedure, can alleviate some physical symptoms but cannot replace tissue that has been removed, can be done under varying anaesthetics Re-infibulation = re-closure of women with type 3 after childbirth, illegal in UK, can happen on and off if giving birth Type IV (Other harmful procedures) All other harmful procedures to the female genitalia for non-medical reasons. Includes pricking, piercing, incising, scraping, and cauterizing the genital area. May include pulling/stretching labia and clitoris or damage during sexual violence/abuse - Stretching creates severe pain and wounds from sticks/weights to stretch labia May be prick or small scratch -> may heal without scar but women remember it

Answer 1172

* Haemorrhage * Severe pain and shock * Urine Retention * Injury to adjacent tissue * Tetanus, HIV, Hep B/C * Fracture or dislocated limbs from being restrained * Death - severe bleeding leading to haemorrhagic shock * Neurogenic shock as a result of pain and trauma * Infection / septicaemia

Answer 1173

* Dysuria, recurrent uti’s, candida infections * Vulvadynia, clitoral pain * Abscesses due to infected cysts/thorns * Dysmenorrhoea * Infertility * Chronic PID, clitoral neuroma and chronic scar formation. * Sexual dysfunction and dyspareunia * Problems in childbirth * Psychological trauma

Answer 1174

* Flashbacks (maybe triggered during pregnancy/childbirth/suturing postpartum) * Sleep disturbances & nightmares * Panic attacks * Sexual dysfunction * Depression & anxiety * Touch / needle phobia * PTSD

Answer 1175

* May not be identified antenatally * Difficulty with VE's, applying FSE/FBS * Scarring & stricture of vaginal canal * Possible obstructed labour * Psychological Trauma, Flash backs * Limited knowledge of birth attendant * Increased risk of C/S, PPH, fetal asphyxia/anoxia & perineal trauma * Women with Type 3 CAN get pregnant

Answer 1176

Oestrial or testosterone cream Physiotherapy - pelvic floor spasms Dilators - to facilitate intercourse Nerve blocks - pain therapy Surgery De-infibulation or reconstruction

Answer 1177

Oocyst ingested Asexual reproduction or sexual reproduction in intestine, asexual leads to schizogony repeated, sexual leads to gametogony Resistant oocytes shed in faeces Oocyte maturation -> normally outside body

Answer 1178

BIG, 2 sporocysts: Cystoisospora Toxoplasma Medium, 2 sporocysts: Cyclospora Small, 1 sporocyst: Cryptosporidium, Sarcocystis

Answer 1179

· Oocyte ingested, release sporozoites which invade gut cells § Small infectious dose (~100 oocytes) · Asexual reproduction cycle in gut cells § Meronts with 8 units will continue in asexual cycle (type I meront) § Meronts with 4 units will proceed to sexual reproduction (type II meront) § Unlimited number of asexual cycles · Male gametes move along gut cells to fertilise females -> microgamont produces microgametes which fertilise macrogamont of female to form zygote Zygote develops into either thick walled or thin walled oocyst -> thin walled can cause auto infection, thin walled exits host · Oocytes burst out of gut cells --> already infectious (allows person-person spread) § 80% exit host § 20% become thin-walled, rupture and release sporozoites --> auto-infection cycle

Answer 1180

o Can be asymptomatic o Watery diarrhoea most common o Dehydration, Weight loss, Fever, Abdo pain, Nausea/vomiting o Usually self-limiting (1-2 weeks) · Chronic, more severe in immunocompromised · Can have persistent symptoms · Can shed oocytes in stool 1 month after symptoms resolve o Respiratory involvement · Particularly in children, immunocompetent or immunocompromised adults · Concern for airborne transmission o Can be severe/life-threatening Issues regarding longevity -> chronic diarrhoea, weight loss, other non-descript symptoms years after infection

Answer 1181

· Primarily water borne § Including swimming pools · Some food borne transmission § Unpasteurised milk · Person-person eg Common in day care § More common in households where index case is <5yo · Zoonosis from domestic/farm animals · Airborne transmission likely

Answer 1182

Light microscopy of faecal specimens -> acid-fast, stain with ZN/Auramine/Safarin BRIGHT RED on ZN staining Direct FAT, immunochromatographic RDTs PCR/genotyping Treatment o No proven beneficial treatment o Supportive care Prevention o Challenges Oocytes very resistant to chlorine Removal/inactivation of oocysts in wastewater difficult Animal reservoirs of some species

Answer 1183

C. parvum and C. hominis

Answer 1184

Information : SV / DV Medical care : HIV PEP : within 72 hours of sexual contact Emergency contraception : within 3 to 5 days (eg coil or medication) Hepatitis B vaccine : within 7 days, 0/7/21 days + booster at 1 year In endemic settings/can be in west etc: Abx eg doxy post-exposure prophylaxis (obviously not doxy if <12 years old) Psycho-social care - Is your patient suicidal? - Anxiety – GAD2 - Depression – PHQ9 - PTSD – PCL5 - Referrals : refuge / counselling / social support Medicolegal - History of events - Documentation - Evidence eg swabs, clothing

Answer 1185

* Anal causes: (fissures/lacerations), constipation, inflammatory bowel disease, worms, trauma * Skin conditions: vulvo-vaginitis, lichen sclerosis, haemangioma * Infections: urinary tract, worms, STIs including HPV, HSV * Labial fusion * Injury – straddle injury * Foreign body * Urethral prolapse * Oestrogen (endocrine) o exogenous - neonatal oestrogen withdrawal o endogenous - ovarian tumour, precocious puberty * Exogenous medications (hormones, anticoagulants) * Bleeding disorders * Sexual abuse

Answer 1186

* Anal – IBD, infection * Vulvovaginitis * Infections – Streptococcus /Staphylococcus – STI * Chlamydia * Gonorrhoea * Trichomonas vaginalis – Candida – Bacterial vaginosis – Threadworm (symptoms) * Foreign body * Poor personal hygiene * Trauma * CSA – Discharge is uncommon if no abuse (seen in <1 – 2% in studies of prepubertal girls selected for non-abuse)

Answer 1187

Penile discharge * Always pathogenic (unless it's not discharge!) o Overgrowth, Hygiene, STI, Other infection o +/- Balanoposthitis or balanitis o Consider if urethral or penile? o Urethral discharge o is assessed by milking the length of the urethra from the base to the tip o indicates STI

Answer 1188

Taenia saginata: 77 million Hymenolepis nana: 75 million Taenia solinum: 10-50 million Diphyllobothrium spp: ~20 million Echinococcus spp: ~3 million Spirometra spp: 1 mill Treatment - Praziquantel for most Niclosamide +/- albendazole for some

Answer 1189

Pseudophyllids Scolex (head): Slit-like grooves (bothria) Uterus: No branching Convoluted uterine tubes forming rosettes Proglottids/eggs: Eggs released from proglottids (proglottids generally remain attached to adult worm). Eggs in stool. Eggs: Operculated; gives rise to ciliated larvae Cyclophyllids Scolex (head): Suckers and/or hooks Uterus: Branching +/- uterine tubes Proglottids/eggs: Proglottids containing eggs are released from adult worms. Both eggs and proglottids in stool. Eggs: Not operculated; do not give rise to ciliated larvae

Answer 1190

Diphyllobothrium latum 1. Definitive host: Humans or fish-eating mammals 2. Eggs passed in feces, hatch into coracidia in water 3. 1st intermediate host: Copepods ingest coracidia, which develop into procercoid larvae 4. 2nd intermediate host: Fresh water fish eat copepods; larvae develop into plerocercoids in fish muscle 5. Human infection: By consuming raw/undercooked fish with plerocercoid larvae

Answer 1191

Clinically: mild GI eg pain and diarrhoea, vit B12 deficiency Diagnose: eggs in stool Mx: Praziquantel + vit B12 Control by cooking or freezing fish

Answer 1192

Hymenolepis nana

Answer 1193

Taenia saginata - Adult worm length: 4-8 metres - Scolex has 4 suckers, but no hooks - Proglottids are broader than long, 5-10 released each day; each segment can produce 80,000-100,000 eggs/day so up to 1million Eggs: not infectious to humans but indistinguishable to T.solinum - Only infective to cattle - Thick striated egg shell - Oncosphere with 6 hooks WW -> wherever cattle raised 1. Definitive host: Humans (intestines) 2. Eggs excreted in feces 3. Intermediate host: Cattle/buffalo/illamas ingest eggs 4. Oncospheres penetrate intestinal wall and form cysticerci in muscle 5. Human infection occurs through consumption of undercooked or raw beef containing cysticerci (ie larvae stage) 2-3 months for adult development in small intestine, life span 10 years+

Answer 1194

Gravid proglottids may crawl out of anal orifice and oviposit on perianal skin -> patient feels moving or sees in underwear Nausea and mild abdominal pain, and anal pruritis Typically asymptomatic or mild symptoms such as abdominal pain, nausea, or weight loss Eggs or proglottids in Stool Praziquantel or Niclosamide Control: Meat inspection of bovine muscle at abattoirs * Cooking meat to 56oC * Hygiene and sanitation: environmental decontamination v. difficult, eggs are very resistant to most environmental conditions and can survive for several years on pastures. Eggs are disseminated widely in the environment by water, sewage effluents, wind, flies and birds

Answer 1195

Pigs and humans

Answer 1196

1. Definitive host: Humans (intestines) 2. Eggs excreted in feces 3. Intermediate host: Pigs or humans. Ingest eggs, which hatch in intestines 4. Oncospheres penetrate pig gut wall, migrate, and encyst in muscles as cysticerci 5. Human infection occurs by consuming undercooked pork containing cysticerci; larvae develop into adult worms in the intestine OR become intermediate hosts via eating contaminated food etc containing the eggs (autoinfection also possible) Adult worm length: 2-8m Lifespan: 25 years

Answer 1197

Symptoms: WHERE are cysts? HOW MANY? Symptoms? o Muscle – expands so no or little disease symptoms o Brain – no ability to expand = disease o Eye – problem usually when treated due to the inflammation Intestinal taeniasis (through ingestion of undercooked pig meat infected with larval form causing intestinal infection with adult worm): Mild symptoms, abdominal discomfort, nausea, or diarrhea Cysticercosis (tissue infection with larval form via ingestion of eggs from environment eg human faeces): If eggs are ingested, larvae can cause cysts in organs, leading to neurological symptoms eg CNS lesions, focal lesions, convulsions, intracranial hypertension (neurocysticercosis) Eggs or proglottids in Stool - Imaging (CT/MRI): For cysticercosis to detect cysts in the brain or tissues - Serology: For antibodies in cysticercosis cases - Praziquantel for intestinal infection - PQ/ Albendazole +/- steroids for neurocysticercosis - Surgery in severe cysticercosis cases Control: Meat inspection of pork meat, cooking meat, hygiene and sanitation, antihelminthic treatment of pigs (oxfendazole), Pig vaccine (TSOL 18, Cysvax®), Good sanitation and hygiene in humans

Answer 1198

Echinococcus granulosus 1. Definitive host: Dogs and other canids eg livestock 2. Intermediate host: Humans (accidental) or livestock (e.g., sheep) ingest eggs from contaminated food or water 3. Oncospheres hatch in intestine, penetrates, migrate to organs (e.g., liver, lungs), forming hydatid cysts 4. Cysts enlarge over time, causing pressure on tissues. 5. Hydatid cysts full of larvae stages -> proliferation of protoscolices from germinal cells inside cysts -> dogs scavenge and ingest cysts 6. Eggs can be dispersed by wind, rain, herbivores and insects. Reported to remain infective for several years, can survive freezing conditions. Wild cycle: ruminant and canid (e.g wallaby and dingo in Australia) Typical transmission: dogs ingest offal, humans accidentally ingest faeces containing eggs eg from dog Risks: associated with sheep farming/sheepdogs or communities living close to their dogs

Answer 1199

* May be asymptomatic for years. * Caused by the developing larval cyst, slow growing (but variable). * Symptoms vary depending on the organ involved. * Most common site is liver (~75% of cases), but can occur anywhere in the body. * Abdominal pain, hepatic mass, bile duct obstruction (liver). * Chest pain, cough, shortness of breath (lungs). * Rupture of cyst (trauma, surgery) may cause severe anaphylaxis. - Imaging (Ultrasound/CT/MRI): Detects cysts - Serology: Detection of antibodies against Echinococcus Site/size/stage dependent * Medical: Benzimidazole (+/- Praziquantel) * Surgical: cyst removal, PAIR (Puncture, Aspiration, Injection (of scolicide), reaspiration) Control: carcass removal to prevent dogs scavenging, cooking dogfood, deworm dogs, controlling stray dog populations

Answer 1200

Echinococcus multilocularis Small, similar to E. granulosus but more invasive 1. Definitive host: Foxes, dogs/cats/coyotes 2. Intermediate host: small rodents or humans (accidental) ingest eggs eg from fox poo 3. Oncospheres penetrate the intestine and form alveolar cysts in organs, mainly liver 4. Cysts grow aggressively, similar to a tumor, invading tissues Typical transmission: Fox and rodents. Human: accidental ingestion of faeces (fox) containing eggs Risk often associated with hunting, and berry and mushroom picking (contaminated by fox faeces). Infection may also establish in domestic dogs and cats

Answer 1201

Pathogenesis similar to E.granulosis but cysts very slow growing, often asymptomatic for 5-15 years Tumour-like cysts, mainly in liver, symptoms: weight loss, abdominal pain, general malaise, hepatic symptoms (jaundice etc) Larval metastases may spread to other organs (lungs, brain, spleen) to form new cysts If untreated -> progressive + fatal - Imaging (Ultrasound/CT/MRI): For cysts - Serology: Detection of antibodies At early stage if cyst is confined: Radical surgery, followed by long term benzimidazole. Later stages very difficult. Control: more difficult than E.granulosis as life cycle involves wild animals. Hygiene: washing of wild berries and mushrooms. Deworming of domestic dogs and cats may help.

Answer 1202

1. By drinking contaminated water in which there is an infected cyclops 2. By eating infected raw or undercooked flesh (fish, frogs, turtle, snakes), containing spargana (plerocercoid larvae) 3. By use of a poultice of raw infected flesh applied to skin, conjunctiva, or mucosa (traditional medicine in Asia). This allows the plerocercoid larvae in the infected flesh to crawl directly into human tissues. Raw frogs and snakes used in this way, or eaten, are the most likely reservoirs for spargana Larvae are believed to be able to survive for up to 20 years in humans

Answer 1203

1. Definitive host: canids and felines eg cats/dogs/other carnivores 2. First intermediate host copepods 3. Second intermediate host: fish, amphibians, reptiles Umembryonated eggs passed in faeces, embryonate in water, coracidia hatch from eggs, ingested by crustaceans, procecoid larvae body in crustaceans, ingestion by second intermediate host, development of larvae into plerocercoid larva, ingestion of second intermediate host by predator, adult develops in small intestine Humans become accidental hosts by ingesting infected water or undercooked meat from intermediate hosts. Larvae migrate within the human host, sometimes to subcutaneous tissues, eyes, or CNS

Answer 1204

Subcutaneous sparganosis: Migrating nodules, swelling, pain Ocular sparganosis: Eye inflammation, oedema, pain Cerebral sparganosis (rare): Neurological symptoms, seizures Symptoms depend on site and activity of larvae: larvae can move around body quite vigorously (“creeping tumour”) (most common form) DIAGNOSIS: Imaging (Ultrasound/MRI/CT): For locating larvae. Biopsy: Identification of sparganum larvae in tissue samples. TREATMENT: Surgical removal of larvae CONTROL: clean water, cooking fish/amphibian/reptile meat, avoid contact with raw amphibian flesh

Answer 1205

Chromoblastocystis - Caused by various pigmented fungi - Chronic infection of skin and subcut tissue, eg hands, feet, lower legs -> painless lesions develop and spread from site of inoculation as veraccous nodules/plaques centripetally by lymphatic or cutaneous dissemination Complications: ulcerations, chronic lymphoedema, elephantiasis, bacterial superinfection Tx: itraconazole PO + terbinafine/flucytosine

Answer 1206

SPASTIC PARAPARESIS - occurs in cassava growing areas in Africa - Abrupt onset of permanent but non-progressive form of spastic paraparesis children/breast feeding mothers - symmetrical - no sensory or genitourinary involvement - <1 week abrupt onset with no other cause - cassava area with other cases usually emerging at same time

Answer 1207

Haemorrhagic fever with renal syndrome Exposure to rodent excreta

Answer 1208

Caused by leptospirosis Cholestatic jaundice AKI Haemorrhagic diathesis

Answer 1209

Microfilariae have ghost sheath In tissues will have max 1/2 adult female worms, two uteruses and be seen in skin

Answer 1210

cardiotoxic can cause endomyocardial fibrosis

Answer 1211

CAUSED BY Non-American: L.infantum L.donovani VECTOR Female Phlebotomus or Lutzomyia sandflies - 1.3-3.5mm in length - Weak flyers - Only females take blood - PAINFUL bite + INDOOR biting + feeds at NIGHT - Peridomestic species - Zoophilic - Rest during day in dark, humid, sheltered sites EPI Globally: mass underreporting but ?up to 300,000 people per year South Asia - Decreasing trend towards elimination -> epidemic wave pattern every 15 years East Africa - No decreasing trends - Epidemic wave pattern every 6-10 years Latin America - In general decreasing - Increasing cases in Paraguay - Brazil carries majority of cases Endemic in parts of South Asia (India, Bangladesh), East Africa (Sudan, Ethiopia), and Latin America (Brazil); occurs sporadically in other tropical and subtropical regions. RISK FACTORS Risk of transmission - Sandfly density - Human parasite reservoir - Proximity to dog-reservoirs - Sandfly infection rate - Human-sandfly interaction Risk of disease - Proximity to VL cases - Poor health/immune status (malnutrition, HIV, TB and other immune-suppressive conditions) LIFE CYCLE 1) Sandfly bite injects promastigote stage of the parasite 2) Promastigotes are phagocytosed by macrophages, transforming into amastigotes 3) Amastigotes multiply within macrophages, spreading to organs like the spleen, liver, and bone marrow

Answer 1212

Past hx of VL -> refer for parasitological diagnosis No past hx -> rK39 RDT - Positive -> treat - Negative -> refer to national guidelines of relevant country If in high HIV prevalence area -> all VL cases test for HIV and all HIV cases in endemic VL areas should be clinically screened for VL GOLD STANDARD -> visualise amastigotes in Giemsa stained smears - Spleen 93-99% sensitive - BM 53-86% - LN 54-65% PCR - but may identify asymptomatic people Ag/Ab tests

Answer 1213

3-100+ weeks Depends on patient clinical status Clinical Signs and Symptoms THINK: Fever>/=2 weeks + splenomegaly +/- weight loss + RFs Case definition: fever >38 for 2 weeks + splenomegaly + rK39 positive Other: wt loss, hepatosplenomegaly, lymphadenopathy, BM hyperplasia, anaemia, leucopenia, thrombocytopenia, hypergammaglobulinaemia, epistaxis, proteinuria, haematuria Mortality: haemorrhages, supra-infections Differential diagnoses: chronic malaria, typhoid, schistosomiasis, TB, hematologic malignancies

Answer 1214

Chronic malaria, typhoid, schistosomiasis, TB, hematologic malignancies

Answer 1215

Indian sub continent, L donovani: 1. Ambisome Stat high dose eg 10mg/kg or dosing to max over 3-5 days 2. Ambisome STAT + miltefosine OD 7 days OR Ambisome STAT + paromomycin OD 10 days OR Milfetosine + paromomycin OD for 10 days 3. Ambisome low dose OD for 15-20 doses 4. Miltefosine - BW dosing for 28 days If L infantum: 1. 3-6 daily ambisome infusions up to total dose 18-21mg/kg East Africa, L.donovani 1. Combination: pentavalent antimonials eg sodium stibogluconate (SSG) M/IV + Paromomycin for 17 days 2. Monotherapy: eg SSG or meglumine antimoniate IM/IV for 30 days 3. Ambisome 6-10 days If L.infantum (all regions) 1. Ambisome 3-6 days up to dose of 18-21mg/kg 2. Pentavalent antimonials IM/IV over 2 days high dose or low dose 20-30 days

Answer 1216

Pregnant women TERATOGENIC need contraceptive cover for 5 months if given for 28 days and 3 months of given for 10 days

Answer 1217

PKDL = post-kala-azar-dermal leishmaniasis - 5-10% of treated cases, particularly in South Asia (does not self heal) and East Africa (can self heal) - Can be years after treatment, patients otherwise well -> main issues: aesthetics and public health - Major reservoir of L.donovani (common in endemic areas for L.donovani) -> need to treat if transmission to be limited - Skin rash after episode of VL - Varying morphologies: macular (symmetrical on both sides), papular (seen on chin), nodular - Diagnose: clinical s/s, ?endemic area, ?hx of VL (10% will lack hx), rk39 (positive test does not confirm diagnosis), GOLD STANDARD: slit skin smear but low sensitivity - DDx: leprosy, fungal - Tx: 12 weeks Miltefosine 100mg/day WHO recommended, need >7 months contraceptive cover for females of childbearing age OR Ambisome low dose over 3 weeks, in East Africa combo treatment with antimonials/paromomycin given

Answer 1218

HIV - Both mutually reinforcing -> HIV ppl susceptible to VL and VL accelerates HIV replication and progression to AIDS - Poor treatment outcomes and higher mortality in co-infected patients regardless of drug used - Co-infected patients frequently relapse -> may act as reservoir for drug resistance parasites - ?'super-spreaders' - Threat to sustained elimination efforts - Presentation with HIV: pulmonary/intestinal/ocular, atypical disseminated, may have no fever at presentation but exaggerated inflammatory reaction once treated - Treatment for VL/HIV: relapse common, poor cell mediated immunity - For both East Africa and South-East Asia: Liposomal amphotericin B + Miltefosine combination therapy recommended TB - 20% of VL-HIV pts co-infected with TB - High mortality - CBNAAT testing in all VL-HIV pts - Low drug resistance TB prevalence but high incidence of fatal IRIS - Poor response to monotherapy - Delay ART>3 weeks; need 6 week admission

Answer 1219

Sub-genus: viannia *Leishmania braziliensis* - Found in South America, especially Brazil; can lead to mucocutaneous involvement with disfiguring lesions on the nose, mouth, and throat. Leishmania guyanensis - Found in the Guyanas and parts of northern South America; causes primarily cutaneous leishmaniasis but can occasionally involve mucosal tissues.

Answer 1220

Diagnosis: MICROSCOPY +/- PCR Microscopy: amastigotes in skin smears or biopsies Histology Culture: Novy-Nicolle-Mc-Neil Molecular Tests: PCR for DNA for species identification -> ideally fresh tissue but can do on fixed Serology: Generally not useful in cutaneous forms, as antibody levels are often low. Treatment Conservative Intra-lesional pentavalent antimonial eg sodium stibogluconate Intravenous or intramuscular pentavalent antimonial - SEs: Malaise and QT prolongation risk Miltefosine (teratogenic and GI effects) - 28 days for CL - teratogenic - n&v - ocular inflammation Intravenous liposomal amphotericin Intravenous or intramuscular pentamidine Paromomycin Imidazole antifungals Cryotherapy Thermotherapy > 50⁰C Surgical Photodynamic therapy Allopurinol

Answer 1221

Causative Species American: L. mexicana, L. braziliensis, L. guyanensis, and L. amazonensis Non-American: Leishmania major, L. tropica, L.aethiopica The species can vary by region, with L. tropica and L. major found mainly in North Africa and the Middle East Epi 1.5 million cases per year - In UK travellers: 60% 'New World', 80% of these have mucosal involvement Transmission Female Phlebotomus sandflies (Old World) and Lutzomyia sandlies (New World). 1. Sandfly bites 2. Parasite enters through skin + promastigotes phagocytised by macrophages 3. Transformation into amastigotes inside macrophages + subsequent multiplication of amastigotes in cells and tissues 4. Transfer via sandfly meal 5. Amastigotes transform into promastigote in midgut -> divide -> migrate to proboscis 6. Animal reservoirs (e.g., rodents, dogs) play a role in transmission in some regions

Answer 1222

Exam style: well circumscribed, central ulcerated lesion with raised borders, may have multiple if tracking along lymphatics Cannot speciate based on lesion - ie they all look different History: Up to 12 weeks after a sandfly bite Enlarging or non-healing skin lesion: ulcer / nodule / keratotic plaque Exposed sites Lack of response to antibacterial treatments Recent travel Localised (LCL) Mucosal (ML) Mucocutaneous (MCL) Disseminated Nodular lymphangitis Lupoid leishmaniasis Leishmaniasis recidivans Diffuse Post-kala-azar dermal leishmaniasis Lesions: Typically begin as small, painless papules that enlarge and ulcerate, forming raised borders and a central ulcer. Types of Lesions: Can be dry, scaly (urban CL) or moist and ulcerative (rural CL). Location: Primarily on exposed skin (e.g., face, arms, legs). Lesions may heal over months but can leave scarring.

Answer 1223

In immunocompetent people: Conservative Intra-lesional pentavalent antimonial * meglumine antimoniate * sodium stibogluconate Miltefosine Intravenous or intramuscular pentavalent antimonial * meglumine antimoniate * sodium stibogluconate Intravenous liposomal amphotericin Intravenous or intramuscular pentamidine Imidazole antifungals Surgical Cryotherapy Thermotherapy > 50⁰C Topical paromomycin Photodynamic therapy Allopurinol

Answer 1224

Intravenous or Intramuscular sodium stibogluconate or meglumine antimoniate 20mg/kg for 21 days Intravenous liposomal amphotericin B 3mg/kg Miltefosine 50 mg three times daily for 28 days Intravenous or intramuscular pentamidine

Answer 1225

Children, leading cause of blindness in LMICs * Vitamin A deficiency disorders (get xerosis = dryness) * Measles infection * Ophthalmia neonatorum * Traditional eye medicines

Answer 1226

White pupil but IRREGULAR ie if you get BILATERAL REGULAR whitening then more likely cataracts

Answer 1227

6 months to 6 years <6 months maternal vit A in between: harder to make children eat vit A containing food malnutrition, also higher risk of malabsorption eg due to diarrhoeal diseases and higher risk of measles infection >6 years then diet normally better

Answer 1228

Do the eyelids open and close normally? Is the white of the eye white? Is the cornea clear? Is the pupil black and circular?

Answer 1229

Acute conjunctivitis (bacterial, viral, allergic) - normal cornea, discharge, usually both eyes - Tx: Abx ointment 8hrly Corneal ulcer - Unilateral, white or grey mark on cornea Green staining with fluorescein If deep may see hypopyon (Can put Abx under conjunctiva eg Gent (around infection) - Tx: hourly intensive topical Abx, antiviral for HSV (5 times a day for 10 days + NO STEROIDS) Iritis - Irregular pupil - Tx: dilate pupil (break adhesions between iris and lens), steroids if sure of diagnosis Glaucoma - hazy cornea, dilated pupil Diamox 500 stat then 250 x 4, may use pilocarpine x4 -> need surgery/laser

Answer 1230

1 Lie flat 2 Local anaesthetic drops on eye 3 Light (dark room with torch on eye) 4 Loupe (magnification) 5 Lift off foreign body (saline wash, corner of card) rub good eye to make bad eye lacrimal

Answer 1231

Foreign body -> anaesthesia + light + remove Hyphaema -> watch + wait, diamox if full to lower pressure Perforation of globe -> refer for surgery

Answer 1232

Refractive error (only one that improves with pinhole) Corneal scar Cataract Chronic glaucoma Retina and optic nerve disease

Answer 1233

Corneal ulceration BILATERALLY if one eye then focus on preserving vision in that eye

Answer 1234

Acute glaucoma

Answer 1235

3 Cs of measles

Answer 1236

Non typhoidal salmonella 1/3 have splenomegaly 30% of patients will have concomitant lower resp tract infection

Answer 1237

Gram negative Intracellular

Answer 1238

Larval trombiculid mite

Answer 1239

1 million cases per year 2 billion at risk Tsutsugamushi triangle: south east Asia, South Asia extending up to south Russia

Answer 1240

* Incubation period 6-21 days * Fever, fatigue, frontal headaches, myalgia, cough * 55% painless eschar * Delayed generalised maculopapular rash * Lymphadenopathy * Pregnancy (stillbirth, prematurity, low birth weight in >40%) * Mortality 1-8% (40% untreated) * Immunity short lived and strain specific Pathogenesis: Widespread vasculitis and perivasculitis, accompanied by infiltration of mononuclear cells into affected organs (can get multi organ dysfunction) - ARDS - Shock - Meningoencephalitis - Hepatitis - Renal failure - Invasive ventilation - CNS dysfunction

Answer 1241

TREATMENT Doxy Azithromycin Chloramphenicol PREVENTION Apply repellents to boots, socks, trousers, skin Avoid sitting/lying directly on ground For high risk people: doxycycline 200 mg weekly (or daily anti-malarial regimen) suppresses disease but may not prevent infection (symptoms may be postponed until after cessation of prophylaxis)

Answer 1242

Dengue Scrub typhus Malaria Leptospirosis Typhoid

Answer 1243

GS: Indirect immunofluorescence assay (IFA) (get Ag of scrub typhus and bind to Ab then fluoresce) Can also do PCR or serology

Answer 1244

TB Typhoid Visceral leishmaniasis Brucellosis Malaria Endocarditis eg staph, strep, enterococcus Q fever - Coxiella burnetti

Answer 1245

Aerobic Intracellular Gram-negative coccobacilli Non-motile Non-spore forming CULTURE FOR LONG EG 6/7 DAYS Brucella suis (pigs) Brucella abortus (associated with cattle, can cause chronic presentations with granulomatous infection) Brucella canis (in dogs)

Answer 1246

Zoonosis - consumption of unpasturised milk/diary products/under cooked meat - contact- mucous membrane/skin penetration (vet/animal care) - aerosolization during butchery – only 10-100 bacteria required to cause infection -Unusual: breast milk, sex, bone marrow transplant, blood transfusion

Answer 1247

Brucellosis >500,000 cases each year for humans

Answer 1248

Cause of brucellosis related to camels (feel well), goats (orchitis or miscarriages), sheep Geographical distribution: Europe: Greece, Spain, Italy, Portugal Latin America: Peru, Argentina, Mexico Arabian Countries: Iraq, Kuwait,” Iran” * Associated with dairy products * Men and women 1:1/Children 20%-25% * Severe clinical disease, fever of unkown origin, hepatosplenomegally, cytopaenias * Rate of familial infection attack: =50% High risk: Mongolia, China High in UK: Somalia

Answer 1249

Inhalation Entry via mucosal membranes Invasion of macrophages, reproduction, circulation in reticuloendothelial system -> lymphadenopathy -> invasion of BM - pancytopenia -> invasion of spleen - splenomegaly CAT 3 pathogen

Answer 1250

1 week to months SYMPTOMS - undulant fever - ARTHRALGIA (migratory, up to 50% patients) - headache - malaise - night sweats - depression in chronic form Complications: HEART/BONES/BALLS Endocarditis Sacroiliitis Epididymo-orchitis Osteomyelitis Spondylodiscitis * Rare <1% Acute neurobrucellosis: Neurologic symptoms and Guillain-Barre syndrome * Immune thrombocytopenic purpura * Rare <2% Skin manifestations * Ocular complications * Pregnancy- abortion/miscarriage Death 2% cases (mainly due to endocarditis)

Answer 1251

CLINICAL - often normal - arthralgia - spleno/hepato megaly - lymphadenopathy BLOODS FBC - neutropenia less often: thrombocytopenia, pancytopenia BIOCHEM - raised LFTs, CRP, ESR, LDH IMAGING Pedro Pon's sign on lumbar x-ray (likes lumbar spine) MICRO *CULTURE* everything you can MOLECULAR PCR (not great) Serum agglutination ELISA (titre >1:160 or 1:320 in endemic area) + clinical features -> ie don't treat positive serology only - seroconversion and evolution of titres can be used for diagnosis Rose Bengal test (another agglutination test) - detects IgM and IgG (high sensitivity, high spec, good screening test in acutely unwell patients, sensitivity lower if previous infection or chronic infection, not useful for B.canis)

Answer 1252

Brucellosis especially Brucella melitensis

Answer 1253

Typhoid -> looks very sick Brucellosis -> looks relatively well and may report sweat smelling funny

Answer 1254

Doxy 100mg BD for 45 days + IV Streptomycin 1g OD for 15 days OR IV Gent 5mg/kg OD for 7-10 days Relapse 5% OR Doxy 100mg BD for 45 days + Rifampicin 15mg/kg/day (600-900mg) 45 days But relapse 5% 2nd line: co-trimoxazole Relapse: usually defined as within 6 months

Answer 1255

* Wear gloves, masks and gowns when working with infected animals * Adequately cooking meat products, and pasteurise dairy products. * There are live attenuated vaccines available for animals (B.abortus and B.melitensis only), but is no human vaccine. * In the event of a laboratory accident or biological attack involving a Brucella species, antibiotic treatment is recommended

Answer 1256

Pre-exposure Post-exposure Therapeutic Candidate: M72/AS01E: but gender and age differences, some promise in reducing progression to active disease in those infected

Answer 1257

Bacillus Calmette-Guerin BCG Protects children from TBM and disseminated forms Non-specific effects Protection from pulmonary TB lowest near equator 3

Answer 1258

Adolescents and adults (especially >15yo) Infants eg <5

Answer 1259

~10% of global cases (as per 2022 rates) = 1.25 million children 0-14 year olds in 2022 Deaths: 214,000 - In HIV negative population 76% of these were kids <5 years - 96% in kids who did not access treatment - 31,000 with co-existent HIV

Answer 1260

U shaped ie high in <2yrs and then low then high in >10 years - 50% <1 yr 25% 1-2 yr 10% >10 years Disseminated TB in children highest in <1yrs (20%)

Answer 1261

TB extensively drug resistance TB eg to first-line and second-line TB drugs, including isoniazid, fluoroquinolones, and second-line injectable drugs (like amikacin)

Answer 1262

Xpert MTB/Rif Xpert Ultra Xpert MTB/XDR Xpert MTB/RIF: Detects Mycobacterium tuberculosis and resistance to rifampicin only. Xpert Ultra: Improved sensitivity over MTB/RIF, detecting lower bacterial loads, useful in HIV co-infections and pediatric cases; still only detects rifampicin resistance. Xpert MTB/XDR: Detects Mycobacterium tuberculosis plus resistance to rifampicin, isoniazid, fluoroquinolones, and injectable second-line drugs—crucial for identifying extensively drug-resistant (XDR) TB.

Answer 1263

TWO SAMPLES ie Concurrent use of molecular testing on respiratory specimens AND stool If HIV +: molecular on resp samples + stool + LF-LAM

Answer 1264

HRZE 2 months HR 10 months TOTAL: 12 months OR 6HRZE (6 month alternative short intensive regimen for TBM treatment)

Answer 1265

2HRZ(E) + 2HR for children 3 months - 16 years (add in ethambutol for children with extensive disease or high prevalence of HIV/INH resistance) Total: 4 months 2HPMZ (isoniazid, rifapentine, moxifloxacin, and pyrazinamide) + 2months HPM for adolescents 12years and over

Answer 1266

Link between TB and diabetes

Answer 1267

Inflammation from TB drives hyperglycaemia but this reverts in some people if TB effectively treated Ideally with screening amongst TB positive people you pick up diabetic individuals only

Answer 1268

Higher odds of MDR-TB Higher mortality risk Higher risk of poor outcome

Answer 1269

* Aimed at reducing short-term and long-term complications (cardiovascular, kidney, eye disease, foot problems) * Lifestyle changes (diet, exercise, smoking, alcohol..) * Glucose control * Cardiovascular risk management

Answer 1270

TB (and other significant co-morbidity): <8% (normally <7%) Issues: DISEASE Active tuberculosis Inflammation leading to: weight loss; loss of appetite; insulin resistance DRUG Side-eﬀects (eg, vomiting); drug–drug interactions; weight gain during treatment HEALTH SYSTEMS Access and aﬀordability of health services; collaboration between tuberculosis and diabetes physicians; laboratory facilities; continuous medicaton supply BEHAVIOUR Variable food intake; physical activity; treatment compliance

Answer 1271

- Main consideration at start of treatment -> secondary prevention Consider need for anti-HTN, statins, anti-plts etc

Answer 1272

1. Vaccine to prevent adult TB 2. Prevention and better management of DM 3. Better mx of combined TB-DM ○ High individual mortality ○ Low population/incidence effect 4. TB preventive treatment for DM/LTBI+ ○ High population impact

Answer 1273

DM-TB ~500 million at risk ~3 fold higher risk of TB More severe pulmonary disease ~2 fold higher mortality and Rif/MDR drug resistance More TB recurrence, PTLD, CVD and deaths post-TB Sensitivity of IGRA/TST not affected DM-HIV ~40 million at risk ~40 fold higher risk of TB but lower with effective ART Fewer cavities and more disseminated disease ~2 fold higher mortality (dependent on CD4 etc) No clear association with drug resistance Less post-TB risk if on effective ART Decreased sensitivity of IGRA/TST (CD4 dependent)

Answer 1274

Allergic disorders: * Allergic disorders * Asthma * Eczema * Hayfever * Drug hypersensitivity Auto-immune: * Auto-immune Churg-Strauss syndrome * Wegener's granulomatosis * Polyarteritis nodosa Haematological * Hodgkin's disease * Eosinophilic leukaemia Dermatological * Bullous pemphigoid * Pemphigus vulgaris Respiratory * Allergic bronchopulmonary aspergillosis * Hypereosinophilic syndrome * Asthma Miscellaneous * Eosinophilia-myalgia syndrome caused by L-Tryptophan * Spanish toxic oil syndrome * Eosinophilic gastroenteritis

Answer 1275

4 pairs ie 8

Answer 1276

Boil for 10 minutes Chlorination doesn’t work

Answer 1277

Treatment: usually metronidazole. Mepacrine and furazolidone are also effective.

Answer 1278

Various mosquitos eg culex, aedes

Answer 1279

Leishmaniasis Mainly new world eg South American rainforests, Brazil

Answer 1280

Clonorchis sinensis Gnathosomiasis Hepatitis A Vibrio parahaemolyticus Paragonimus westermani

Answer 1281

oxidised, denatured bits of haemoglobin found in G-6-PD deficiency for example

Answer 1282

small pieces of nuclear material usually removed from erythrocytes by the spleen so might see them if patient has had a splenectomy

Answer 1283

Usually results in thrombocytosis Asplenic patients are at particular risk of severe pneumococcal infections. They should receive Pneumovax and lifelong prophylactic penicillin. Further, if possible, some splenic tissue should be preserved :-e.g. in the rectus sheath. Asplenic patients also suffer more severe disease following infection with Plasmodium falciparum and Haemophilus influenzae.

Answer 1284

*Beta-heamolytic streptococci *Lupus nephritis *Plasmodium malariae % (especially children 2-8yrs old, may not respond to steroids) Amyloidosis *Schistosoma mansoni % (tx; steroids and cyclophosphamide) * Leprosy (due to secondary amyloidosis) Diabetes Multiple myeloma Filarial worms eg Bancroftian filariasis, onchocerciasis and loiasis Renal vein thrombosis Hepatitis B @ Minimal change glomerulonephritis * = numerically important % due to immune complex deposition @ due to membranous glomerulonephritis

Answer 1285

MMR Oral polio vaccine (OPV)

Answer 1286

Pertussis Diphtheria Parenteral polio Monovalent whole cell typhoid Tetanus Cholera Hepatitis B Haemophilus influensae type b (Hib)

Answer 1287

BCG Yellow fever TY21a (oral typhoid vaccine)

Answer 1288

Severe typhoid Hib meningitis in children Croup Tuberculoid leprosy Severe pneumocystis pneumonia Tuberculous meningitis Tuberculous pericarditis Tuberculous pleural effusion Type 1 lepra reaction Katayama fever VZV encephalitis

Answer 1289

Meningococcal disease Gram negative septicaemia Herpes zoster shingles Cerebral malaria Visceral leishmaniasis

Answer 1290

1 or 2 skin lesions which are well-demarcated, dry, scaly, hypopigmented, anaesthetic and hairless ASYMMETRICAL nerve involvement

Answer 1291

Thrombocytopenia

Answer 1292

Chicken pox: 5 days before rash to six days after last crop Measles: from onset of prodrome until 4 days after onset of rash Mumps: 3 days before until 7 days after salivary swelling Rubella: 7 days before onset of rash until 4 days after onset of rash Bordetella pertussis (whooping cough): 1 week after exposure to 3 weeks after onset of symptoms. The period of infectivity may be shortened by antibiotics Scarlet fever: from appearance of rash until completion of 1 day's penicillin

Answer 1293

Amoebic liver abscess is the most common extra-intestinal manifestation of amoebiasis. All age groups may be affected but occurs most commonly in men aged 20-60 years In approximately 50% of cases there is no previous history of amoebic dysentery. The patient typically presents with fever and right upper quadrant pain of fairly acute onset. Treatment of the fever with chloroquine may modify the clinical presentation. Neutrophilia is usual, NOT eosinophilia. The right hepatic lobe is usually affected. Abscess formation in the left lobe is an indication for drainage.

Answer 1294

dengue fever yellow fever rickettsial infections plague falciparum malaria - the incubation period usually quoted for falciparum is 10-14 days. Occasionally it may be as short as 8 days.

Answer 1295

malaria African trypanosomiasis enteric fever (7-21 days) brucellosis hepatitis A (2-6 weeks)

Answer 1296

brucellosis TB HIV filariasis leishmaniasis amoebic liver abscess hepatitis B (45-160 days)

Answer 1297

Cipro or 3rd gen cephalosporins (due to widespread resistance to penicillins) In severe cases add dexamethasone

Answer 1298

Jaundice (as a result of haemolysis, hepatitis, cholecystitis or cholangitis) Myocarditis (3rd week) Bowel perforation occurs in 5% of cases in the third week and has a high case fatality rate. Surgical intervention is thought to improve prognosis.

Answer 1299

Passive and active immunisation to reduce risk of vertical transmission (additional vaccinations at birth, 4, weeks and 1 year)

Answer 1300

delta virus super-infection. This scenario is especially common in intravenous drug abusers.

Answer 1301

Haemorrhagic colitis Can cause HUS

Answer 1302

nasopharyngeal carcinoma Intra ocular lymphoma Burkitt's lymphoma

Answer 1303

Cholangiocarcinoma

Answer 1304

Squamous cell of bladder

Answer 1305

Good cell mediated immunity to Leish - will be negative in VL but can become positive after treatment

Answer 1306

polyclonal hypergammaglobulinaemia

Answer 1307

Haemophilus influenzae septicaemia

Answer 1308

Erythema infectiosum Fifth's disease Caused by Parvovirus B19 Exanthem = maculopapular rash (face -> trunk -> limbs) after between 4-14 days during which time they are infectious 30% cases asymptomatic, Ab prevalence against infection in UK is high Self-limiting arthritis in adult women can occur

Answer 1309

May cause aplastic crises in sickle cell disease and in other hereditary haemolytic anaemias It may also be responsible for refractory transfusion dependent anaemias in immunocompromised patients

Answer 1310

Known to cause hydrops fetalis (especially in 2nd trimester)

Answer 1311

QuantiFERON-TB Gold (QFT): Measures interferon-gamma released in response to Mycobacterium tuberculosis antigens. A blood sample is incubated with TB antigens, and the response indicates TB exposure. This test requires a lab with specific processing equipment. T-SPOT.TB: Measures the number of immune cells producing interferon-gamma when exposed to TB antigens. It’s especially useful for immunocompromised patients and has a slightly different sensitivity profile.

Answer 1312

Nil tube (grey): ○ Background IFN-Y Mitogen (purple): maximally stimulates T cells to release IFN-Y ○ Positive control TB1 and TB2 -> peptides that are specific for mycobacterium tuberculosis Q1. is mitogen [IFN] above threshold? – YES continue to read TB and control tube – NO INDETERMINATE result STOP Q2. what is TB [IFN] minus control eg nil tube [IFN]? – < 0.35 = IGRA NEGATIVE – ≥ 0.35 = IGRA POSITIVE

Answer 1313

Could indicate an inadequate immune response (e.g., due to immunosuppression or poor sample handling) -> ie person does not generate a good IFN=Y response In such cases, the IGRA test may return an indeterminate result because the IFN-γ response cannot be reliably interpreted, potentially masking a true TB infection status

Answer 1314

Who: - Children - Household contacts - Immunosuppressed What: - Isoniazid for 6-9 months - Rifampicin + Isoniazid for 3 months - Rifampicin for 4 months

Answer 1315

Three Months of Rifapentine (P) and Isoniazid (H) for Latent Tuberculosis Infection Once-weekly RifP + Iso given for 12 weeks compared to OD isoniazid for 9 months RifP/Iso was found to be non-inferior to Iso alone and had better compliance (4 countries, >7000 people) ANOTHER TRIAL: 1HP OD for prevention of HIV-TB -> given Daily HP for 4 weeks v daily H for 36 weeks -> same TB prevalence ie no difference ie non inferior

Answer 1316

Trial to see if 2 month regimen for TB was as effective as standard 6 month regimen 674 patients who were not resistance to rifampicin, treatment length could be extended if necessary 4 strategy groups were trialled but only non-inferiority assessed in 2 Two options both included (isoniazid, pyrazinamide, and ethambutol), varied based on: 1. Bedaquilline + linezolid initial treatment with an 8-week bedaquiline–linezolid regimen was noninferior to standard treatment for tuberculosis with respect to clinical outcomes 2. Rifampicin + linezolid did not meet same success rate Both had similar level of adverse events to standard therapy

Answer 1317

Syphilis HIV TB Neurobrucellosis HTLV-1 Schistosomiasis

Answer 1318

Konzo B12 deficiency Trauma MS Primary lateral sclerosis Familial spastic paraplegia Anterior spinal thrombosis

Answer 1319

Human T-lymphotropic virus-1 7 types, most type A RNA retrovirus, spread by cell-to-cell contact * 5-10M carriers globally. Geographical foci: Japan, Latin America, Caribbean, Africa, Central Australia Transmission: Parenteral: blood transfusion, transfusion of cells, IVDU, solid organ transplant Mother-to child: breastfeeding, rare before and during childbirth Sexual PRESENTATION - most asymptomatic (95%) - means widespread family involvement and easily transmitted Skin effects: - eczema - seborhoeic dermatitis Rheum effects: - sjogrens syndrome - arthropathy - polymyositis Lung effects: - Bronchiectasis - Interstitial pneumonitis DIAGNOSIS Serology EIA/Western blot, Proviral PCR TREATMENT nothing and no vaccine Dermatitis common in kids -> need long term Abx therapy eg co-trimox and consider mild topical steroids + follow up COMPLICATIONS - Most highly ONCOGENIC VIRUS in world -> T cell leukaemia/lymphoma - HTLV-1 associated myelopathy (HAM)/Tropical spastic paraparesis (TSP) INFECTIVE DERMATITIS especially in children PREVENTION - Screen blood/organs - No breast feeding if secured alternatives are in place - Condom use

Answer 1320

PATHOPHYSIOLOGY Abnormal activation of cytokines -> mass inflammatory effect Chronic inflammation of white and grey matter of lower thoracic spinal cord (infiltration of T cells– bystander effect / auto- antibodies) followed by atrophy FEATURES Geographical variation ~0.25% Japan, ~3% elsewhere * Discrepancy striking motor symptoms > mild sensory disturbance (slow, mild, v fast progressors) * Early signs: Lumbar pain, bladder disorders, repeated falls due to “clumsy legs” RFs: Living in endemic country 40-50 years old Genetic predisposition High HTLV-1 provirus load High HTLV1 Ab titres CNS effects: - encephalopathy, leukoencephalitis, low back pain, constipation, unstable bladder Treatment - 1g IV methylprednisolone (3 days) for symptomatic relief but screen first for co-infections eg strongy etc - No role for antiviral therapy or IFN-Alpha - Symptomatic support: antispasmodics, laxatives, physio, secondary infections

Answer 1321

Aggressive proliferation of mature activated CD4+ CD 25+ T-cells Long latency period - can be infected for 20-50 years before presentation Median age 56 years Clinical Presentation: Lymphadenopathies, heptaosplenomegally, visceral lesions Diagnosis: ”Flower cell" on peripheral blood film = acute ATL patient- leukemic cells with multilobulated nuclei Complications: Paraneoplastic hypercalcaemia, opportunistic infections eg TB, strongyloidiasis

Answer 1322

Hb< 12g/dL in women Hb<13g/dL in men

Answer 1323

1. Dietary iron deficiency (at least 40%) 2. Haemoglobinopathies and haemolytic anaemias 3. CKD /Endocrine, metabolic, blood, immune disorders

Answer 1324

- Iron/haematinic deficiencies - consider “trial of treatment” - Haemoglobinopathies/haemolysis - Chronic disease - Infections/infestations - Bleeding – take a good bleeding history, including thorough menstrual history - (Haematological cancers are much less common than all of the above) Assess for other cytopenias/features of haematological disease

Answer 1325

- Transfuse RBC/whole blood - Manage any bleeding - Once patient stable, likely to need additional iron supplementation

Answer 1326

- Oral iron supplementation - Once daily/alternate day dosing - 40-80mg elemental iron likely adequate (NB: more you give it, less you absorb it) - IV iron supplementation (if available) - May be helpful in: - Surgery planned within few weeks - Lack of response to oral - Malabsorption - Dialysis dependent renal disease - Treat for 6 months (and min. 3/12 post normalisation of FBC)

Answer 1327

* Severe symptomatic anaemia * Transfusion has clear risks and complications * Transfuse the minimum amount of blood necessary to improve the clinical condition * Short term fix -> Always aim to correct the underlying cause * Always weigh up risks vs. benefits

Answer 1328

Medical * Haematinic replacement * Anti-fibrinolytics e.g. tranexamic acid * Erythrocyte stimulating agents e.g. erythropoietin Surgical * Cell salvage * Surgical techniques to minimise blood loss

Answer 1329

Anticoagulation * Can prevent potentially fatal PE * Increases risk of bleeding – especially complicated around time of delivery LMWH: * Safest but expensive UFH: * Can be used in pregnancy but needs some APTT monitoring and risk of Heparin-Induced Thrombocytopenia and Thrombosis (HITT) and osteoporosis Warfarin: * Teratogenic in 1st trimester * Increased risk of fetal bleeding throughout pregnancy * Needs stopping at least 2/52 prior to delivery as crosses placenta -> unacceptable bleeding risk for fetus during delivery DOACs * Not enough evidence yet to recommend * Rivaroxaban shows fetal toxicity in animal studies, apixaban does not

Answer 1330

Infective dermatitis (3-15 year olds) * Lesions of the scalp, ears, retroauricular areas, paranasal and perioral areas, neck, axillae, thorax, abdomen, groin, and other sites. * Lesions may be erythematous/scaly, exudative and/or crusted * Chronic, relapsing condition; prompt response to therapy, but recurrence upon discontinuation of antibiotics * Lymphadenopathy * Failure to thrive TREATMENT * Long-term antibiotic therapy (trimethoprim-sulfamethoxazole); * Mild local corticosteroids for severe cases * Follow up

Answer 1331

Mortality: 15-87% Hyperinfection risk: - Recurrent Gram-negative sepsis - Associated with normal eosinophils Lots of other complications eg: - ARDS - Larva currens - Nephrotic syndrome - Small bowel obstruction Diagnosis: direct examination, serology Treatment: Ivermectin

Answer 1332

CHINA Connective tissue disease Helminth ‘Idiopathic’ Neoplastic Allergic

Answer 1333

Leukopenia - Neutropenia - Fever - Infections Thrombocytopenia - Bruising - Bleeding Anaemia - Pallor - Fatigue - Weakness - SOB Leukocytosis - Bone pain - Stroke - CN palsy - Renal failure Extra-medullary sites - Generalised lymphadenopathy - Hepato-splenomegaly B symptoms - Weight loss - Drenching night sweats - Unexplained fever - Bone pain

Answer 1334

Most common between age 5 and 15, almost never under 3yrs Symptoms usually RAPID in onset (<3 months) including: Rapidly growing mass most commonly affecting: * Jaw, retro-orbital, LN’s, Mediastinum, abdomen – liver, LN’s Spleen, Kidney B-symptoms * Night sweats * Bone pain * Weight loss * Unexplained fever CNS/PNS signs * Central nerve palsy * Lower limb weakness * Constipation * Incontinence – urine/stool Signs of bone marrow failure * Anaemia * Neutropenia * leukopenia

Answer 1335

Symptoms tend to be many months (sometimes years before presenting) Symptoms include: Slow growing Mass ▪ Swollen LN (groin, neck, chest,armpit) ▪ Hepatosplenomegaly B-Symptoms: ▪ Night sweats ▪ Bone pain ▪ Weight loss ▪ Unexplained fever Recurrent infections

Answer 1336

Symptoms involving one eye or both include: Leukocoria - white pupil that does not reflect the light Strabismus - eye to become crossed because of loss of vision Painful red eye Decreased vision in one eye Eye swelling or proptosis Most common in infants and young children (almost all diagnoses before age six years)

Answer 1337

Kidney tumour Symptoms/signs include: Child is generally well Abdominal mass +/- pain Haematuria Urinary tract infection Hypertension

Answer 1338

* Persistent headache * New onset seizures * Raised ICP signs/symptoms * Headache and vomiting on waking or early morning * Visual disturbances * Cranial nerve abnormalities, * Gait abnormalities eg Ataxia * Changes in continence * Deteriorating school performance or developmental milestones * Behaviour changes – lethargy, aggression If fast progression -> more likely to be aggressive disease

Answer 1339

Non-Hodgkin's

Answer 1340

aim to improve outcome of treatment of active disease added in to standard drug treatment tough to do as standard treatment already works well

Answer 1341

Infection: H pylori, Giardia, Diphyllobothrium latum Malabsorption: pernicious anaemia Co-morbidities: gastric resection/banding, coeliac, tropical spreue

Answer 1342

X-linked Female carriers have increased resistance to Malaria Variable phenotypes: eg mild in African patients, moderate in Asian, severe in Mediterranean Clinically: - Neonatal jaundice: peaks 2-3 days after birth, variable severity - Acute haemolytic: triggered by anti-oxidant drugs eg primaquine, food, infections - Chronic non-spherocytic haemolytic anaemia

Answer 1343

Immune thrombocytopenia Acquired immune mediated disorder characterised by platelet count <100 and absence of any obvious initiating or underlying disorder can be - newly diagnosed - persistent: 3-12 months - chronic >12 months

Answer 1344

Viral hepatitis

Answer 1345

Yellow fever infection Disseminated herpes simplex (eg in HIV immunocompromised patient)

Answer 1346

CAUSE Yellow fever RNA virus, flavivirus, 7 serotypes (vaccine protective against all) VECTOR Aedes aegypti (widespread across world) Haemagogus in South American jungles EPI Yellow fever belt across mid of Africa and South America

Answer 1347

Transmission Mosquito bites (primarily Aedes spp.); cannot be spread person-to-person directly 1. Sylvatic (Jungle) cycle - Virus transmits between mosquitoes and non-human primates 2. Anthropogenic sylvatic cycle - Humans in forest get disease eg sporadic cases, can transmit back to mosquitoes 3. Village epidemic - Viraemic humans go back to villages eg from forests and mosquitoes pick virus up (small outbreaks) 4. Urban epidemic - Feared due to mass epidemic potential Africa: 1-4 Only 1 and 4 in South America

Answer 1348

INCUBATION PERIOD Typically 3-6 days after mosquito bite, can be longer (<21 days) DISEASE PHASES Many asymptomatic or mild febrile illness 1. Acute phase: fever, muscle pain, headache, chills. 2. Toxic phase (0-8-7.5% progress): jaundice, organ failure, hypotension, shock, haemorrhage, liver failure 30-60% CFR - AST>ALT *only number of infections that can do this, other one is HSV in immunocompromised patients - Little detectable virus but immune complex deposition RFs for mortality based on Brazil study: older (>45 yrs), neutropenia, AST>3500, hyperbilirubinaemia, high RNA levels, renal dysfunction SYMPTOMS Fever, chills, headache, back pain, nausea, vomiting, jaundice (yellowing of skin/eyes), and bleeding

Answer 1349

Haemophagocytic lymphohistiocytosis - cytokine storm + macrophage engulfing of other blood cells IVIG, anakinra (recombinant human IL-1 receptor antagonist), high-dose methylprednisolone

Answer 1350

Diagnosis Serology (IgM ELISA) PCR testing Virus isolation Treatment No specific antiviral; supportive care for dehydration, fever, and organ support if needed Potential new therapy: Galidesivir - Small molecular antiviral, nucleoside (adenosine) analogue - Broad-spectrum in vitro against RNA viruses - Survival benefit in animal models of Ebola, Marburg, Zika, YF - Has been used in cases of YF vaccine with thymectomy Prevention Vaccination (highly effective, typically lifelong immunity) Mosquito control Protective clothing Vaccine Live attenuated vaccine (Yellow Fever 17D strain) - No ability of infect vectors - >90% protection after 10 days, >99% protection after 30 days (likely life-long protection) - Recommended for endemic regions and travellers Needs cold-chain

Answer 1351

Gram neg, facultative intracellular bacteria Bartonella - henselae - quintana - bacilliformis

Answer 1352

¡ Invades endothelial cells and erythrocytes ¡ Induces angiogenesis via VEGF and other growth factors ¡ Avoids immune clearance by intracellular localization ¡ Chronic infection through persistent bacteremia ¡ Subversion of immune system: Inhibition of apoptosis in host cells ¡ Bacterial virulence factors

Answer 1353

Transmission Cat scratches or bites, flea exposure Geographic Distribution Worldwide, especially in areas with high cat populations Symptoms Immunocompetent: CSD: regional lymphadenopathy, fever, fatigue, headache Immunocompromised: bacillary angiomatosis: red vascular skin lesions, also can be in bone/LNs, can be life threatening High-Risk Groups Children, cat owners, immunocompromised individuals

Answer 1354

Cat scratch disease Immunocompromised: bacillary angiomatosis Parinaud's oculoglandular syndrome

Answer 1355

DIAGNOSIS Serology for Bartonella henselae PCR for bacterial DNA Biopsy for angiomatous lesions (Warthin-Starry stain) TREATMENT CSD * Patients with lymphadenitis: 5-day course of azithromycin * Patients intolerant to azithromycin: clarithromycin, rifampin, or trimethoprim-sulfamethoxazole Bacillary Angiomatosis * Macrolides: erythromycin or doxycycline * Patients intolerant to erythromycin or doxycycline: azithromycin or clarithromycin * Mild cutaneous BA can be treated for 12 weeks * If the response is not satisfactory, the duration of therapy can be extended * The duration of therapy has not been determined and most likely longer in cases with invasive disease

Answer 1356

Bartonella bacilliformis - Flagellated, gram-negative, facultative intracellular, aerobic - 2-3 micrometres Carrion’s Disease (Oroya Fever and Verruga Peruana) Vector-borne disease Possible Lutzomyia bites (in Andes regions) No evidence of animal host Geographically confined Endemic to the Andes region (Peru, Bolivia, Ecuador, Colombia) Children in endemic countries most at risk (?lack of immunity from repeated infection)

Answer 1357

* B. bacilliformis infects erythrocytes and endothelial cells * Physical damage and introduction of antigens into the erythrocyte membrane, producing intense erythrophagocytosis Result: **hemolytic anemia** Virulence factors (adhesin, flagellin and hemin): evade the host immune response Acute phase: ⬆ interleukin-10 secretion by erythrocytes, decrease cytokine production → suppresses T helper cells, macrophages, and dendritic cells ¡ favors persistent B. bacilliformis infection and increase the risk of secondary infection

Answer 1358

= Carrion's disease Acute: Oroya fever Chronic: Peruvian wart Biphasic: acute febrile phase (Oroya Fever) - can also be asymptomatic - Fever + haemolytic anaemia - Mortality 44-88% (esp without Abx therapy) - Acute bacteraemia for 60 days (10-210) - Complications include super-infections eg Salmonella, Toxoplasma, Histoplasma, haem, GI, CV !! Eg HF, pericardial effusion, Pul oedema, Neuro later eruptive/chronic phase (Peruvian wart) with red skin lesions - weeks to months after acute phase - classified as: Miliary, mular, diffuse - worse in young patients eg children - ?reservoir of disease Risk factors for mortality in acute phase: age >45 years, history of alcohol use, shock, pulmonary edema, pericarditis, seizures, coma, anasarca, petechiae, and altered mental status

Answer 1359

Acute: Blood smears: low sensitivity Blood culture: >70% culture positive, takes long time (>14 days) PCR Immunological tests: sens + spec - Can reflect persistent humoral immune response - IFA (indirect fluorescence Ab test) Immunoblot-based protocol - Potential for new ELISA Chronic: Clinical +/- skin biopsy Culture: 13-47% positivity (can have asymptomatic or transient bacteraemia)

Answer 1360

Acute: *Ciprofloxacin or chloramphenicol Ceftriaxone (severe cases in children/pregnant women) Co-trimoxazole (uncomplicated cases) Chronic: Azithromycin AMR: rising cipro resistance

Answer 1361

Trench fever Bacillary angiomatosis Endocarditis Incubation 5-20 days Trench Fever: * Cyclical fever (every 5-6 days) * Severe headache, bone pain (especially shins) * Relapsing, chronic form in some cases Immunocompromised Patients: * Bacillary angiomatosis: vascular lesions affecting skin and internal organs * Culture-negative endocarditis Chronic Infection: * Can persist asymptomatically or with mild nonspecific symptoms Endocarditis B. quintana is a more frequent cause of endocarditis than B. henselae Bacillary angiomatosis Occurs in patients with advanced HIV who have CD4 counts less than 100 cells/microL. It is caused by either B. quintana or B.henselae ¡ Patients with infection due to B. quintana may be more likely to have lytic bone lesions than patients with B. henselae Bacillary peliosis hepatitis ¡ Also occurs in patients with advanced HIV-related immunosuppression (CD4 <100 cells/microL) ¡ Patients with this syndrome present with abdominal pain and hepatosplenomegaly, with or without systemic symptoms (eg, fever) ¡ Elevated ALP

Answer 1362

Body louse (Pediculus humanus corporis) No known animal reservoir (primarily human-hosted) WW distribution (US, Europe, Russia, Brazil, East Africa) Associated with homeless populations and poor sanitation - HIV, ETOH, IVDU People in crowded conditions, immunocompromised

Answer 1363

DIAGNOSIS Clinical hx and RFs Blood culture -> difficult due to fastidious growth Bartonella serology eg IgM, IgG PCR Histopathology for vascular lesions TREATMENT Trench Fever: * Doxycycline (100 mg orally every 12 hours) for 28 days + Rifampicin (300 mg orally every 12 hours) for 14 days * rule out endocarditis Bacillary Angiomatosis and Endocarditis: * Prolonged doxycycline or erythromycin, with gentamicin in severe cases. * Treatment of BA depends on the presence of bacteremia and severity of illness

Answer 1364

1. Egg Release Infected humans release eggs of Schistosoma species through urine (S. haematobium) or feces (S. mansoni, S. japonicum). These eggs reach freshwater, where they hatch into free-swimming miracidia. 2. Miracidia in Snails Miracidia penetrate specific species of freshwater snails (intermediate host). Inside the snail, the miracidia develop into sporocysts, which produce thousands of free-swimming cercariae over 4-6 weeks. 3. Cercarial Release Cercariae are released from the snail into freshwater. They are free-swimming and infective to humans, their definitive host. 4. Human Infection Cercariae penetrate the human skin during water contact, shedding their tails and transforming into schistosomula. Schistosomula enter the bloodstream and travel to the lungs and liver for further maturation. 5. Adult Worms Mature schistosomes migrate to their specific venous locations: S. haematobium: Bladder veins S. mansoni: Mesenteric veins of the colon S. japonicum: Mesenteric veins of the small intestine Male and female worms pair and produce eggs. 6. Pathogenesis Eggs released into tissues or excreted cause pathology. Many are excreted into the environment to continue the cycle.

Answer 1365

S.mansoni or S.haematobium - 78 Endemic countries - ~800 million at risk - ~>250 million infected - 90% of cases are in sub-Saharan Africa - ~20 million cases of severe morbidity - ~300,000 deaths per year >90% of cases are S.mansoni or S.haematobium

Answer 1366

* Miracidium infect snail * Mother sporocyst in mantle of snail * Daughter sporocysts move to snail digestive gland * Cercariae develop from daughter sporocyst

Answer 1367

S mansoni ~140 microns

Answer 1368

S haematobium Found in urine ~150 microns

Answer 1369

Penetration of snail host

Answer 1370

Egg production -> eggs and them getting stuck are key causes of pathology

Answer 1371

Around 50% of eggs are retained in the tissues:- (A) Intestinal/hepatic species: (i) In the wall of the intestine (ii) Carried by the blood and lodged in the liver (AIM -> to get out of bowel mucosa and be passed out in stool) (B) Urogenital species: in the walls of the bladder and ureters (AIM S. haematobium, eggs would pass into the bladder lumen and be released in urine) Eggs getting stuck triggers immune response -> pathology

Answer 1372

Cercarial dermatitis (swimmers itch) – commonly caused by animal or bird schistosome cercariae Infection with human species generally only give rise to mild dermatitis (if any)

Answer 1373

* 3-8 weeks post infection (onset of egg production). Up to 90% prevalence following first exposure, more unusual in endemic settings. * Symptoms may include: § Malaise, low grade fever § Head/neck ache § Urticaria § Eosinophilia § Hepatomegaly, splenomegaly § Diarrhoea § Cough and wheeze * Aetiology uncertain - but probably mediated by immune complexes of soluble worm or egg antigens and antibody (hypersensitivity reaction).

Answer 1374

S.mansoni and S. japonicum - Due to eggs getting trapped in pre-sinusoidal vessels of liver Granulomatous response, fibrosis and calcification causes periportal fibrosis => portal HTN and hepatosplenomegaly Also rise in gastric and oesophageal veins -> varices (look for caput medusa) Risk of acute internal bleeding

Answer 1375

* (Cercarial penetration -> dermatitis) * Maturing worms -> Katayama Fever (‘acute schisto’) * Escaping eggs -> haemorrhages in bowel mucosa, inflammation, colitis * Trapped eggs -> granulomas -> periportal (Symmers’) fibrosis -> Portal hypertension ->hepatosplenomegaly ->oesophageal varices ->haematemesis

Answer 1376

90% chronic anaemia and malnutrition (leading to fatigue, growth retardation, loss of cognitive function/development)

Answer 1377

* Haematuria (Passage of eggs →ulceration of bladder wall → haemorrhage) * Fibrosis and calcification of the bladder and ureters * Obstructive uropathy * Hydroureter, hydronephrosis * Bladder cancer

Answer 1378

SQUAMOUS cell carcinoma of bladder

Answer 1379

* (Cercarial penetration -> dermatitis) * Maturing worms -> Katayama Fever (‘acute schisto’) * Escaping eggs -> haematuria, proteinuria, bladder polyps and sandy patches * Trapped eggs in bladder wall -> granulomas -> calcified bladder, bladder cancer * Trapped eggs in ureters -> calcifications -> hydroureter, hydronephrosis, pyelonephritis

Answer 1380

S.japonicum ~3000 eggs produced per day Eggs also small

Answer 1381

1. Lungs - Eggs embolise to pulmonary arterioles -> granulomas pulmonary hypertension -> right ventricular hypertrophy and failure (‘cor pulmonale’) - Occurs in 15% of S.mansoni Symmers’ cases - Also in S.haematobium cases, but rarer in S.japonicum 2. CNS - Eggs ± adults of S.mansoni or S.haematobium in spinal cord -> granulomas -> Paraplegia - Eggs ± adults of S.japonicum in brain -> epilepsy etc 3. Genital tract - Up to 75% of women with S. haematobium have eggs in uterine cervix, vagina and vulva and less commonly in uterus, ovaries. - GS is associated with “sandy patches”, vascularization and contact bleeding - Misdiagnosed as cervical cancer or STIs, GS linked to infertility - Women with GS have up to 3-fold increased risk of having HIV Men: Eggs common in seminal vesicles, prostate, ~50% of egg +ve men have eggs in semen -> Eggs in scrotal lymphatics →hydrocele, elephantiasis

Answer 1382

Degree of symptoms will depend on intensity and duration of infection, and may take years to develop Acute: fever, diarrhoea, abdominal pain, weight loss Chronic: Intestinal/hepatic species: chronic diarrhoea, abdominal pain, anaemia, hepatomegaly, hepatosplenomegaly Urogenital species: Dysuria, frequency, terminal or total haematuria. Chronic disease – obstructive uropathy, bacteriuria, bladder carcinoma, bladder calcification, genital lesions Schisto is a protean (changing) multisystem disease with multiple abdominal symptoms (for both types)

Answer 1383

PARASITOLOGICAL identify eggs in: * sedimented urine, filtrated urine or in semen (Sh) * Direct smear, Kato Katz or formol-ether faecal concentrates (Intestinal species) MORBIDITY MARKERS * Detection of Faecal occult blood (Intestinal species) * Detection of macro/microhaematuria (Sh) (hemastix) IMMUNOASSAYS * Eosinophilia (~45% of patients) * Detection of specific antibody (e.g. to soluble egg antigens by ELISA) (but time to seroconversion often several months) * Detection of antigen in urine (e.g. ‘circulating cathodic antigen’(CCA) by RDT) -> only for S.mansoni

Answer 1384

S.mansoni Urine CCA antigen (RDT) -> "circulating cathodic Ag" -> semi-quantitative assessment of adult worm burden

Answer 1385

40-60 mg/kg p.o, single dose Issues with PZQ * Side effects: abdominal cramps, nausea, diarrhoea, dizziness, vomiting – worse with higher intensity infections * it cannot be used for chemoprophylaxis due to its short half-life, and it is ineffective against migrating schistosomula and juvenile worms * Longstanding availability problems: in 2019 only 44.5% of people requiring treatment globally were reached (WHO) (in 2021 only 29.9% were reached due to the pandemic) NEW - Paediatric formulation coming out which tastes less bitter, water soluble and is smaller

Answer 1386

Transmission sites: Lake, streams (slow flowing), irrigation systems, dams, rice fields S.haematobium - Africa, Middle East - Snail: Bulinus spp - In human: Small venules of the vesical plexus and pelvic plexus and sometimes also the rectal venules S.mansoni - Africa, South America, Caribbean - Snail: Biomphalaria spp. - In human: Mesenteric veins of small and large intestine S.japonicum - Southeast Asia (China, Philippines, etc.) - Snail: Oncomelania hupenis (water and mud) - In human: Mesenteric veins of the small and large intestine (but can be anywhere in mesenterics)

Answer 1387

* Health Education * Safe water supplies * Sanitation * Snail control (by habitat modification and/or molluscicides) * Chemotherapy campaigns

Answer 1388

MORBIDITY CONTROL using praziquantel to prevent build-up of severe fibrosis in individuals living in endemic areas (primarily school age children) Issues - Risk of reinfection high due to - Lack of effect of PZQ on juvenile worms -> individuals still infected and will continuing shedding eggs -> transmission ongoing - High levels of infection prevalence and intensity - Poor or non-compliance of PZQ treatment - Low coverage - Recontact with contaminated water as result of daily activities and seasonal factors

Answer 1389

1. Endemic communities with prevlance of S.spp. >/=10% ANNUAL preventive chemotherapy with single dose of praziquantel at >75% treatment coverage in all age groups 2+ years old (includes adults, pregnant women after the first trimester and lactating women) 2. WHO recommends WASH interventions, environmental interventions (water engineering and focal snail control with molluscicides) and behavioural change as essential methods to reduce transmission

Answer 1390

S. haematobium - Seen in URINE - Terminal spine - 150 microns S.mansoni - See in stool sample - Lateral spine - 140 microns - Production: ~300 eggs per day per female S.japonicum - Small lateral spine, often hard to see - 85 microns - Production: ~3000 eggs per day per female

Answer 1391

Gas gangrene Severe haemolytic anaemia

Answer 1392

Inflammation of choroid (vascular layer) and retina Clinical Features: Visual Symptoms: Progressive reduction in visual acuity or visual field loss, often more severe than anterior uveitis. Painless: Usually no pain unless there is secondary involvement of other eye structures. Floaters: Patients may report seeing spots or shadows due to inflammatory cells in the vitreous. Fundoscopic Findings: Yellowish-white lesions in the retina and choroid, with potential scarring in chronic cases. Retinal hemorrhages or vascular sheathing in severe inflammation.

Answer 1393

Chronic inflammation of cornea -> characterised by scarring and fibrosis Progressive Vision Loss: Typically from peripheral corneal opacification extending toward the central cornea. Photophobia: Sensitivity to light due to corneal involvement. Pain: Mild to moderate eye discomfort due to corneal inflammation. Physical Exam: Opacification or whitening of the cornea, typically starting in the peripheral cornea. In severe cases, vascularization of the cornea (blood vessels invading corneal tissue).

Answer 1394

Tdap-IPV vaccine is a combined inactivated vaccine that protects against tetanus, diphtheria, acellular pertussis, and polio Vaccinate pregnant women between 16 and 32 weeks gestation (ideally fetal anomaly scan at 20 weeks)

Answer 1395

Proportion of those that test positive that genuinely have the disease - increases with higher prevalence - increases the more specific the test

Answer 1396

Proportion of people who have the disease that are correctly identified by the test

Answer 1397

Strongyloides stercoralis

Answer 1398

70% of global TB burden in 8 countries 1. India (27%) 2. Indonesia (10%) 3. China (7%) 4. Philippines (7%) 5. Pakistan (6%) 6. Nigeria (5%) 7. Bangladesh (4%) 8. DRC (3%)

Answer 1399

erythema chronicum migrans

Answer 1400

Neisseria meningitidis group B

Answer 1401

Neisseria meningitidis group A

Answer 1402

gram positive cocci in bunches associated with line infections but can also be floral skin contaminant

Answer 1403

Young children, the elderly and the immunosuppressed may fail to mount an adequate immune response. They are often tuberculin negative in the presence of active disease. In such cases the patients often become tuberculin positive during treatment. can be positive in - tuberculosis pericarditis - in 30% of sarcoid cases

Answer 1404

threadworm = pinworm enterobius vermicularis

Answer 1405

Ascaris lumbricoides

Answer 1406

high p24 Ag low CD4 breast feeding HIV-1 (compared to 2)

Answer 1407

10-21 days from time of bite to chancre

Answer 1408

Viral orf cowpox rabies arboviral infections Bacterial salmonella campylobacter brucella tuleraemia Weil's disease anthrax Protozoal African trypanosomiasis Leishmaniasis giardiasis toxocariasis cryptosporidiosis

Answer 1409

malaria brucellosis typhoid disseminated tuberculosis visceral leishmaniasis

Answer 1410

Streptococcal infection Tuberculosis Sarcoidosis Leprosy Sulphonamides Inflammatory bowel disease

Answer 1411

African pit vipers

Answer 1412

The micro-vasculature is affected by a number of things: 1. Plasma leak 2. Endothelial permeability 3. Thrombocytopenia and bleeding Narrow pulse pressure

Answer 1413

* Environmental management – Elimination of container habitats: * Piped water systems * Mosquito-proofing water-storage containers * Disposal of waste (water-bearing containers) * Chemical control – Larvicides & insecticides – Indoor Residual spraying – Space spraying/fogging (emergency measure) * Biological control: Wolbachia

Answer 1414

Mild - Hypertonic - Hyperalert, starring - Partial primitive reflexes - Irritable, hand clenching - Voracious/poor feeders Moderate - Hypotonic - Lethargic - Don't feed - Absent primitive reflexes - Strong distal flexion - Apnoeas - Seizures Severe - Completely floppy - Comatose - Apnoeic - Decerebrate posturing - Absent reflexes - Full fontanelle

Answer 1415

In babies: eye deviation, flickering of eyes, stereotypical mouth movement, cycling/regular twitching Management: 1) phenobarbitone: loading, starting with 20mg/kg to total 40mg/kg 2) phenytoin 18mg/kg

Answer 1416

Types Quadriplegia: 4 limbs affected Diplegia: lower limbs affected Hemiplegia: arm and leg on one side affected - Spastic: high tone, tight rigid muscles - Hypotonic: low tone (loose muscles and joints) - Athetoid: fluctuating muscle tone and uncontrolled movements - Ataxic: lack of coordination Mixed: combo of 2 or more

Answer 1417

1. Global scales for early development: open access package -> standardized method for measuring development of children up to 36months, creates developmental score (D-score) using short form and long form 2. WHO caregiver skills training: focused largely on autism and behavioural disorders for 2+ year olds, no content on CP Issues: - Stigma, exclusion & discrimination - Gender, equality and empowerment - Poverty and livelihoods - Literacy, language, fidelity

Answer 1418

Inflammation of the cornea

Answer 1419

* Systemic management (antibiotics; rehydration etc) * High dose vitamin A x 3 doses [200,000 IU orally, or IM]* * Examine the eyes, even if child very sick with eyes closed (VAD is painless) * Use fluorescein stain to detect ulceration * Topical antibiotic e.g. tetracycline ointment * Urgent referral to eye unit if concerned about the eyes *Saves sight and lives

Answer 1420

6 stages: 1/2 usually improve and watch + wait, stage 3+ treat, stage 4: retinal detachment, stage 5: total detachment, stage 6: blind

Answer 1421

* Number of worms infecting the host (related to level of exposure, cumulative after repeated exposures) * Duration of infection (long life span of worms) * Immune response to infection (may cause immune-mediated pathology) * Location of worms (migration?) * Age of host (childrens habits make them more likely to be exposed but they may also suffer more from disease, anemia etc) * Sex of host (women may suffer more from helminth-induced anemia)

Answer 1422

Intestinal: direct life cycle, soil-transmitted *eggs need contact with soil to become infective, ?for embroynation but not well understood Filarial: indirect life cycle involving insect or copepod Zoonotic: nematodes of animals that occasionally are transmitted to humans -> humans often dead-end host

Answer 1423

Enterobius vermicularis

Answer 1424

(i) in/on the soil (geohelminths, STH) - Trichuris trichiura (oral) - Ascaris lumbricoides (oral) - Hookworms: Necator americanus, Ancylostoma duodenale (percutaneous) - Strongyloides stercoralis (percutaneous) (ii) without needing contact with soil - Enterobius vermicularis (oral)

Answer 1425

Albendazole Mebendazole Levamisole Pyrantel Prevalence >20%

Answer 1426

Enterobius vermicularis = pinworm/threadworm

Answer 1427

DIAGNOSIS Cellotape test (before showering in mornings, ideally x3) TREATMENT Single dose mebendazole or albendazole (kills adults) Repeat after 2-4 weeks (due to resistant eggs and risk of re-infection), treat whole family

Answer 1428

Cosmopolitan, high and low income countries Playgroups, nurseries, crowded conditions etc Most common helminth infection in the USA and Western Europe ~300 million cases worldwide Prevalence up to 40% in US children Oral (fecal-oral, autoinfection) NOT soil transmitted Found small -> large intestine (cecum, appendix) LIFE CYCLE Ingestion -> infective within hours Eggs hatch in small intestine + larva move to large intestine Penetration and development in mucosa Adult maturation (2-6 weeks) Males die Gravid females migrate to perianal region to lay eggs at night CONTROL Anti-helminths Hygiene, cleaning, washing, clothes, bed linen

Answer 1429

SITEs Epithelium of large intestine (cecum, colon) -> no migration anywhere else Can have adults in rectum and terminal ileum in heavy infection LIFE CYCLE Eggs hatch and produce larvae in small intestine Larvae migrate to colon to mature and embed in mucosa Release unembryonated eggs in stool ~8 weeks after infection Adults live >2 years CONTROL Sanitation Ingestion can occur due to night soil ie use of human faeces as fertiliser then consuming unwashed vegetables WHO recommend mass school-based chemotherapy campaigns if prevalence in the area >20%

Answer 1430

Trichuris trichuria

Answer 1431

CLINICALLY Light -> asymptomatic Mod/heavy -> oedematous, haemorrhagic mucosa "chronic Trichuris colitis" = Trichuris dysentery syndrome - Risk of bacterial infection with Shigella and Salmonella - Risk of invasion by E.histolytica Chronic: sub-clinical effects on physical and cognitive development in children Worms burrow into intestinal epithelium -> feed on cells -> small haemorrhages + inflammation DIAGNOSIS Eggs in stool - Direct smear - Kato Katz thick smear (WHO recommended) - Formol-ether concentration - FLOTAC TREATMENT Albendazole or Mebendazole 100mg BD 3 days Or Oxantel + pyrantel

Answer 1432

EPI - Columbia/Venezuela - West/Central Africa eg Cameroon, Congo, Nigeria - Kazakhstan - South East Asia - Papua TRANSMISSION Oral (fecal-oral) SITE Larval lung migration before adults settle in small intestine LIFE CYCLE Ingest eggs Eggs hatch in duodenum but do not directly develop -> L3 larvae penetrate gut mucosa -> lymphatics or veins -> liver -> heart -> lungs -> penetrate alveoli ascend trachea Swallowed Develop into adults in gut Eggs (females produce ~200,000 a day) released into faeces -> very resistant to desiccation so can survive in environment for 8 years Eggs in stool 9-10 weeks after ingestion Adult worms live 1 year on average

Answer 1433

3 phases 1. Lungs ○ Loeffler's: dry cough at 1-3 weeks, dyspnoea, asthma, substernal pain, haemoptysis, eosinophilia 2. Intestinal ○ Abdo discomfort, acute colicky pain, poor sleep, diarrhoea, malabsorption -> malnutrition ○ Intestinal obstruction -> bolus of worms stuck at ileo-caecal valve ○ Risk of necrosis, gangrene, death 3. Ectopic ○ Migration of adults ○ Promoted by fever, anaesthetics, antihelminth tx ○ Appendix ○ Pancreas -> haemorrhagic pancreatitis ○ Bile ducts ○ Peritoneal cavity ○ Larynx, lungs, urethra, vagina, heart, brain etc DIAGNOSIS Eosinophilia in ~10% Stool microscopy: knobby-surfaced eggs Can also use Kato-Katz preparation TREATMENT Albendazole, Mebendazole, or pyrantel Benzimidazoles cause flaccid paralysis of adults reducing risk of obstruction

Answer 1434

Hookworm = long buccal invagination Strongy = short buccal invagination

Answer 1435

Warm moist climates -> limited by humidity and temp requirements (~23-28 degrees) of infective stages Necator more in Latin America, central/SS Africa and SE Asia Ancyclostoma in SE Asia and North Africa Larvae in environment need moisture, warmth, shade, decaying vegetation Percutaneous (skin penetration by larvae) - often feet Or Oral ingestion of unwashed vegetation (Ancyclostoma>necator) Small intestine Exhibit blood feeding

Answer 1436

retains sheath of L2 sharply pointed tail won't see full larva in 40x magnification

Answer 1437

L3 filariform larva penetrates skin L3 migrate through alveoli-> trachea -> swallowed to intestine L3 -> L4 -> adults which bite onto mucosa of small intestine Eggs in faeces L1 Rhabditiform larva hatches + feeds on bacteria in stool L2 also feeds L3 filariform larva = infective (after 8-10 days), does not feed, lives a few weeks Egg laying around 5-8 weeks post-infection If infection with L3 is oral -> heart-lung migration

Answer 1438

In general: weakness, lethargy, abdominal discomfort, pallor, anaemia, eosinophilia in acute phase 3 organs 1. Skin ○ 1-2 weeks post-exposure ○ L3 larval penetration ○ CML "cutaneous larva migrans" = Serpinginous, erythematous rash, may move 2-5cm/day, can last a few weeks ○ Severity of itch depending on no. of penetrating larvae 2. Lungs ○ 1-2 weeks post-exposure due to L3 migration into alveoli ○ Pneumonitis, bronchitis, pharyngitis ○ Dry cough, wheezing ○ Related to severity of infection 3. Intestine ○ Blood loss due to bite ○ Hookworm pump blood through bodies to feed on erythrocytes ○ Worms move frequently -> persisting haemorrhages due to release of anticoag of worms ○ Heavy infections -> >100ml blood loss/day Long term: cardiac insufficiency, physical and mental stunting due to Fe-deficiency anaemia - More likely chronic than acute, ie due to gradual accumulation - Dependent on inadequate Fe intake (common in most endemic areas) - Anaemia often compensated but upset by slight changes in Fe reserves/intake eg malaria, schiso, menstruation, pregnancy Also get hypoalbuminemia + resulting oedema Can get weight loss due to malabsorption May be fatal at high intensity, esp in children Blood loss and anaemia directly proportional to worm burden

Answer 1439

DIAGNOSE Stool microscopy - Fresh: eggs - Old eg >24hrs: hatched L1 larvae Anaemia on FBC TREAT Albendazole, Mebendazole; iron supplementation CONTROL - avoid walking barefoot in contaminated soil etc - WHO recommends MDA if prevalence >20%

Answer 1440

Asymptomatic Skin: itchy dermatitis, i) non-specific urticarial rash of crops of stational wheals lasting 1-2 days OR ii) larva currens (10cm/hr) ++ itchy Lung: pneumonitis, asthma/allergy s/s, cough, CP (sometimes mistaken for asthma, patients given steroids and then get disseminated disease) Intestine: mucosal damage leading acutely to upper abdo pain mimicking peptic ulcer, diarrhoea, blood/mucus in stool with ++ eosinophilia, chronic: asymptomatic, sometimes chronic colitis, haemorrhage, malabsorption (IgE raised, eosinophilia lower) Eosinophilia, abdominal pain, diarrhea, hyperinfection syndrome in immunosuppressed (can be fatal) Disseminated strongyloidiasis - Not just chemo/severe malnutrition/lymphoma etc - Now due to widespread use of corticosteroids + HTLV-1 - NB: HIV NOT associated with DS - Sometimes treat in absence of positive test based on travel hx + eosinophilia Lung: cough, dyspnoea, wheezing, resp distress + death from resp failure +/- pul haemorrhage Intestine: parasites damage submucosa -> oedematous mucosa/submucosa, mucosal/villous atrophy, sprue like syndrome: steatorrhea, protein losing enteropathy, weight loss, paralytic ileus Ulceration + bacteria carried by larvae -> gram neg bacterial infection -> peritonitis due to bowel perforation, septicaemia, secondary bacterial infections of CNS (brain abscess + meningitis)

Answer 1441

EPI Worldwide but most common in warm moist climates overlapping with hookworm distribution; sporadically in Europe, N. America and Japan TRANSMISSION Percutaneous (skin penetration) SITE Small intestine

Answer 1442

1-4 days in soil Direct life cycle: L3 rhabditiform larvae penetrates skin, undergoes heart-lung migration Swallowed -> small intestine Females reproduce parthenogenetically (without males) L1 rhabditiform larvae release Indirect: L1 rhabditiform larvae released in stool from human host Develop into free living adult males and females Adults mate in stool -> eggs -> hatch into new L1 larvae L1 larvae can either - Independently develop into rhabditiform larvae to continue free-living cycle - OR develop into L3 filariform larvae Self infection: Precocious development of L1->L3 within gut L3 invasion of gut mucosa Internal autoinfection L3 in faeces contaminating perianal regions or following development of L1->L3 on perianal skin can penetrate same host = external autoinfection L3 undergo heart-lung migration -> replicating infection Occurs at low level in normal host -> persisting infections last >50 years In case of severe cellular immunodeficiency -> loads of larvae autoinfect -> adults in gut "hyperinfection syndrome" + disseminated strongyloidiasis (lots of l3 larvae cross capillary bed of lungs to infect all organs)

Answer 1443

DIAGNOSITICS Stool microscopy with serial examinations (due to intermittent larvae excretion) Direct faecal smear* or concentration methods: formol-ether, baermann - Fresh: Observe L1 larvae Culture: charcoal*, nutrient agar plate Baele's string test Duodenal aspirate Disseminated disease: larvae in sputum and sometimes urine Immunodiagnostics: ELISA* with L3 Ag TREATMENT Ivermectin (first line) Albendazole (alternative) Repeat treatment as migrating larvae insusceptible to drugs (+ re-treat immunosuppressed patients)

Answer 1444

Complications - Larva currens (relatively straight) - Nephrotic syndrome - ARDS - Recurrent gram negative bacteraemias (and can't establish source) - Chronic diarrhoea - Bowel obstruction Triggers: - High dose steroids - HTLV-1 - Transplant

Answer 1445

TANKS CRAP MD TB Aspergillus Nocardia Klebsiella Staph/strep Cryptococcus Rodococcus (associated with soil around horse stables) Actinomycosis (can cause mycetoma) Paragonimus Mucor, melioidosis Dimorphic fungi

Answer 1446

BuY PaT - Burkholderia - Yersinia - Pasturella - Tuleraemia

Answer 1447

BAG Bayliscaris procynosis (old racoon poo) Angiostrongylus cantonensis (eat slugs or snails or vegetables they have been moving across) Gnathostoma spinigerum (raw fish)

Answer 1448

Treat or prevent 1. Hypoglycaemia 2. Hypothermia 3. Dehydration 4. Correct electrolyte imbalance 5. Treat infection 6. Correct micronutrient imbalance 7. Begin feeding 8. Increase feeding to recover lost weight (catch up growth) 9. Stimulate emotional and sensorial development 10. Prepare for discharge At a later date then treat helminth infections

Answer 1449

Daytime - Loa loa comes out at lunch

Answer 1450

Bulinus snail

Answer 1451

DEC: diethyl carbamazine targets microfilaria and can kill a proportion of adult worms In small microfilarial counts can use Ivermectin. Albendazole also has some embryo static activity

Answer 1452

Many come from single source eg patient Ring vaccination is effective: contacts and contacts of contacts Babies: test before breast feeding and wear full PPE etc when delivering baby to Ebola mother Infective Ebola virus can be found in various fluids for weeks to months after recovery The high fatality rate was from multi-organ failure and shock rather than from haemorrhage

Answer 1453

Epi India, SE Asia, Pacific Islands, West Africa and Brazil Brugia malayi: India and SE Asia Causative Agents Wuchereria bancrofti (90% of cases) - Humans definitive host - Cosmopolitan Brugia malayi - Periodic and sub-periodic strain - Periodic: mansonia (vector), humans definitive host - Sub-periodic: range of mosquito vectors, range of hosts eg humans, monkeys, domestic casts, forest carnivores Brugia timori Vector transmission Transmitted by mosquitoes: Culex, Anopheles, Aedes, Mansonia Periodicity of larvae -> nocturnal (come out at night due to vector biting habits) - Nocturnal: Wuchereria bancrofti, Brugia malayi - Nocturnal sub-periodic: Brugia malayi - Diurnal periodic: Wuchereria bancrofi, pacific islands Reverse in pattern of periodicity in places where day biting of mosquitoes eg Aedes polynesiensis (in Pacific Islands), bites during day so filariae come out during day

Answer 1454

Infected mosquitoes deposit L3 larvae (which have developed over 2 weeks) Mature into L4 in lymphatics in 2 weeks Mature into adult worms (male and females) in 6-12 months and live in lymphatics (live for ~10 years) Adult worms produce microfilariae that circulate in blood Mosquitoes ingest microfilariae, move to midgut Shed sheath Get into flight muscle cells and moult into L2 Grow then develop into L3 infective larvae in these cells after 10 days

Answer 1455

Acute phase: Fever, skin rashes, lymphangitis, lymphadenitis, epididymoorchitis - Due to death of parasite in lymphatics -> inflammatory reactions Dematolymphangioadenitis stage: constant episodic inflammation +/- secondary bacterial infection, pain, disability Chronic phase: Elephantiasis (limb and genital swelling), hydrocele, chyluria Tropical Pulmonary Eosinophilia (TPE): Cough, wheezing, eosinophilia Affects children + damages their lymphatics but only see clinical manifestations as adults Grade: - Stage 2: unreversible swelling - Stage 3: shallow skin fold - Stage 4: alternation of skin texture, formation of knobs - Stage 5: deep skin folds - Stage 6: mossy lesions - Stage 7: inability to perform work

Answer 1456

These mutualistic endosymbiotic bacteria are essential for: Development * Larval development * Embryogenesis PROPHYLAXIS TRANSMISSION BLOCKING Disease pathogenesis * Inflammatory reactions * Clinical disease CLINICAL CASE MANAGEMENT Adult worm survival (10-14 years) * Adults depleted of Wolbachia die 1-2 years later MACROFILARICIDAL (kills adult worms)

Answer 1457

Diagnosis Thick blood smear for microfilariae (best collected at night due to periodicity) - Wuchereria: nuclei do NOT extend to tip of tail - Brugia: two small terminal posterior nuclei Antigen detection (Immunochromatographic Test for W. bancrofti): IgG4 Ab to BmR1 - But cross reaction with Loa Loa Ultrasound (filarial dance sign) - Helpful to do prior to treatment to "map" where worm nests are then repeat after treatment - Eosinophilia in TPE

Answer 1458

* “Viridans” Streptococci–S.mitis, S.salivarius, S.mutans * Oral anaerobes including Actinomyces sp. * Fusobacterium * S.aureus

Answer 1459

* Streptococcus pneumoniae * Streptococcus pyogenes * Haemophilus influenzae * Mycoplasma pneumoniae * Moraxella sp * Chlamydia pneumophilia * Fusobacterium necrophorum * Neisseria meningitidis * Pseudomonas aeruginosa

Answer 1460

Common * Streptococcus pneumoniae * Haemophilus influenzae * Mycoplasma pneumoniae * Legionella pneumophila * Chlamydia pneumoniae If hx COPD * as above plus: Pseudomonas aeruginosa If aspiration, as above plus: * Anaerobes e.g. Bacteroides sp., Fusobacterium sp Zoonotic: * Chlamydia psittaci If empyema: * Staphylococcus aureus Streptococcus pneumoniae Streptococcus anginosus group Others * Mycobacteria

Answer 1461

Staphylococci sp. –esp S.aureus * Strep.pyogenes * Group C/G streptococcus * Cutibacterium sp. * Corynebacterium sp. Post-op * Pseudomonas * Enterobacterales

Answer 1462

* Oral anaerobes * Staph aureus * Streps * Neisseria sp

Answer 1463

* To reduce by 90% the number of people requiring treatment for NTDs * To eliminate at least one NTD in 100 countries * To eradicate two diseases (dracunculiasis and yaws) * To reduce by 75% the disability-adjusted life years (DALYs) related to NTDs The new road map seeks to promote a paradigm shift in the way NTDs are addressed by; health. 1) Moving away from process driven targets to measures of the impact on public 2) Replacing vertical and siloed disease specific programmes with holistic cross- cutting approaches integrated into national health systems with a people and community centred focus. 3) To transfer programme ownership away from partner support and reliance on donor funding to country ownership with NTDs integrated into national health plans and budgets.

Answer 1464

Adults: * Staph aureus * Strep.pyogenes * Group C/G streptococcus * Strep pneumoniae * Neisseria gonorrhoea Kids: * Staph aureus * Haemophilus influenzae * Strep pyogenes * Strep pneumoniae * Kingella kingae Prosthetic joints: * Staph aureus * Coag neg staph * Corynebacteium * Pseudomonas * Enterobacterales * Cutibacterium

Answer 1465

Common * E. Coli * Shigella * Campylobacter sp * Klebsiella sp. * Pseudomonas aeruginosa * Bacteroides fragilis * Strep. anginosus/constellatus/intermedius * Clostridium difficile * Helicobacter pylori * Salmonella Less common * Vibrio cholerae * Listeria monocytogenes

Answer 1466

Common * Staphylococci –S.aureus –Coagulase neg. Staph * Oral streptococci * Streptococcus gallolyticus * “HACEK” * Enterococcus sp. Less common * Coxiella * Bartonella * Brucella

Answer 1467

Common: * E.coli * Klebsiella sp. * Staphylococcus saprophyticus * Enterococcus sp. * Proteus sp. * Strep.agalactiae (GBS) Other: * N.gonorrhoea * Chlamydia trachomatis * Treponema pallidum

Answer 1468

* Skin * Dental * Ear / mastoid / sinuses * Lung * Gut * Heart valve Other: - TB - Nocardia

Answer 1469

Common * Neisseria meningitidis * Streptococcus pneumoniae Elderly, Pregnant * As above plus: Listeria monocytogenes Unvaccinated * Haemophilus influenzae B Neonates * Streptococcus agalactiae * Listeria monocytogenes * Escherichia coli * Klebsiella sp. * Serratia marcesens CNS instrumentation * Skin flora * Pseudomonas * Gram negatives Other * M.tuberculosis

Answer 1470

Current licensed: Doxy Other candidates: - High dose Rif - Rif + Albendazole Other proof of concept drugs: - Rif - Rifapentine - Moxifloxacine - Minocycline

Answer 1471

TREATMENT Africa: Albendazole + Ivermectin Asia/Americas: Albendazole + DEC - Single dose, annual 2 drug regimen, mass treatment of at-risk populations + interrupts transmission Alternative: - DEC or DEC + Ivermectin for 4-6 years - DEC fortified salt Diethylcarbamazine (DEC): kills both adult worms and microfilariae. Ivermectin: Microfilaricidal. Doxycycline: used to deplete Wolbachia but need to kill >90% of Wolbachia otherwise doesn't work Enhanced self care includes deep breathing exercises, elevation of leg, hygiene for lymphoedema and Abx/anti-inflammatory in acute attacks PREVENTION Vector control (insecticide-treated nets, removing breeding sites) Mass Drug Administration (MDA) Africa: Albendazole + Ivermectin Asia/Americas: Albendazole + DEC - Single dose, annual 2 drug regimen MMDP = morbidity management and disability prevention runs alongside MDA +/- hydrocoelectomy (surgical inversion of tunica vaginalis) Personal protection measures like repellents PUBLIC HEALTH PROGRAMMES GPELF - Global Programme to Elimination of LF launched in 2000, changed to GAELF (Global alliance to eliminate LF) Two key strategies: 1. To stop the spread of infection (MDA) - New WHO strategy with triple therapy IDA = Ivermectin, DEC, Albendazole (as standard tx outside of Africa) - Get sustained suppression of microfilariae for 3 years, so should only need 2x MDA every 3 years 2. To alleviate the suffering (MMDP = morbidity management and disability prevention) - Need six annual treatments with Ivermectin, Albendazole, DEC (these suppress microfilariae for duration of life of adult females, until infection dies out) A.WOL: Aim: to deliver an oral anti-Wolbachia drug effective in ≤7 days Current licensed: Doxy Other candidates: - High dose Rif - Rif + Albendazole Other proof of concept drugs: - Rif - Rifapentine - Moxifloxacine - Minocycline

Answer 1472

BACTERIA Syphilis Bartonella Brucella Coxiella Endocarditis whipples VIRAL CMV HSV VZV HIV SSPE PARASITIC Toxocara sp Toxoplasmosis gondii Baylisascaris procyonis Gnathostomiasis Cystercisosis Onchocerciasis Loiasis etc. MYCOBACTERIAL Tuberculosis FUNGAL Histoplasmosis sp blastomycosis sp coccidiomycosis sp Candida cryptococcosis NON-INFECTIVE Sarcoid connective tissue disorders, vasculitis, lymphoma/leukemia drug induced pregnancy related etc.

Answer 1473

Japan, Canada, Parts of Europe

Answer 1474

High cases in Thailand

Answer 1475

Rat lung worm Eyes and brains -> neurotropic America Vietnam Thailand

Answer 1476

Eschar - preceding symptoms Fever - at day 0/1 Rash - day 4 NB: no Abs in first week, can only get seroconversation after 14 days = GOLD STANDARD Immunofluorescence assay for these infections (IgM and IgG) To diagnose acutely: need PCR

Answer 1477

Indirect immunofluorescence IgG antibody assay of paired serum samples.

Answer 1478

* All spread by arthropods Vectors: fleas, mites, lice, ticks * Often also act as reservoir Reservoir: small mammals / birds * Present all around the world * Worldwide distribution eg murine typhus * Geographically restricted eg scrub typhus * Specific environmental conditions of hosts and vectors * Incubation 6 - 14 days (< 21 days) * Fever, malaise, headache, myalgia * No apparent focus of infection * Eschar? Rash? Severe - vasculitic syndrome * Variable severity Bloods * Normal white cell count * Normal or low platelets * CRP elevated * Normal or slightly elevated ALT/ bilirubin * Renal failure and DIC late

Answer 1479

Fever Rash Headache ?Lymphadenopathy +/- Inoculation eschar (if present then diagnostic) Incubation 6-10 days (<21d)

Answer 1480

R.rickettsia R.conorii Syphilis Enterovirus - hand foot and mouth Mpox Human monocytic ehrlichiosis Drug reaction

Answer 1481

Wear long clothing. * Check for ticks after outdoor activities. * DEET * Promptly/safely remove ticks to prevent transmission of some diseases If you see a tick - grab by mouthpart and pull directly upwards, remove mouthpart fully

Answer 1482

* Rickettsial disease eg scrub typhus * Babesiosis * Borreliosis * Crimean Congo Haemorrhagic Fever * Lyme disease * Tick-borne encephalitis * Tularaemia

Answer 1483

Ticks (Dermacentor variablis/andersoni, Rhipicephalus)

Answer 1484

Tick Rhipicephalus sanguineus

Answer 1485

S: strongy A: ascaris (most common) N: ecator T: oxcara canis A: nyclostoma

Answer 1486

No a significant proportion of healthy individuals will have anti-Leishmania antibodies, either from having past treatment for visceral leishmaniasis or having had subclinical infection, so the presence of antibodies is not diagnostic of active disease

Answer 1487

Profound and prolonged loss of immunological memory

Answer 1488

WHO considers that to maintain the interruption of measles virus circulation, immunization programs must provide measles vaccine to at least 95% of each new birth cohort of infants before the age of 2 years

Answer 1489

USA Rocky Mountain Spotted Fever Tick- Dermacentor variablis American dog tick

Answer 1490

Africa/ Caribbean African tick bite fever Tick- Ambylomma

Answer 1491

Worldwide Europe, Africa, Asia Mediterranean spotted fever Boutonneuse fever Tick Rhipicephalus sanuineus

Answer 1492

Worldwide Rickettsia pox Mite- Liponyssoides sanguinues

Answer 1493

Worldwide Murine typhus Flea faeces- Xenopsylla cehopis

Answer 1494

Worldwide Epidemic typhus Louse faeces- Pediculus humanus corporis

Answer 1495

Orientia tsutsugamushi Worldwide Trombiculid Mite

Answer 1496

Nipah virus

Answer 1497

infective stage cercariae (Schisto)

Answer 1498

amoebiasis

Answer 1499

unit of analysis in this case is at the level of the population/community or group as opposed to the other study designs, for example cross- sectional where individuals are the unit of analysis

Answer 1500

the probability of testing positive if diseased

Answer 1501

the probability of testing negative if not diseased

Answer 1502

The probably of not being diseased if the test is negative

Answer 1503

Typical: migratory loiasis ○ Eye worm migration (1/2 day to 3/4 days) = through bulbar conjunctiva ○ Calabar swelling (dermal migration of adult worm) - transient, erythematous, non-pitting oedema Common but unspecific ○ Asthenia and fatigue ○ Severe headaches, transient nerve palsies ○ Arthralgia, myalgia, transient toothpain ○ Pruritis and rash Rare but important complications ○ Vision loss ○ Encephalitis ○ Nephropathy ○ Cardiomyopathy ○ Pulmonary inflammation ○ Septic arthritis ○ Splenic granulomatous lesions Varying clinical manifestation Asymptomatic, symptomatic, complicated

Answer 1504

Bite of crysops fly Infective L3 larvae develop into adult worms in soft tissue Migration of adult worms around body (lifespan 20 years) Mating and offspring produced -> microfilariae which circulate in blood Crysops take blood meal L1, L2 in thoracic muscles L3 in head and mouthpart

Answer 1505

Spontaneous encephalitis Treatment associated encephalitis * Associated with high microfilarial load * DEC * Ivermectin * (Albendazole) Signs & symptoms: * Palpebral haemorrhages, CRP * Fever, headache, confusion, agitation, coma

Answer 1506

Returning travellers * More often symptomatic * Higher inflammatory response * Higher psychological distress (in patients and doctors…) Less chronic/long term disease

Answer 1507

Adult worm: clinical observation, ?eye migration, calabar swelling (more helpful in travellers) Mf: blood sample (10am-4pm) microscopy, PCR, LAMP, (LoaScope) (may be more helpful in endemic areas but NB: only 1/3 will have positive blood for microfilariae) Serology useful in returning travellers from non-endemic regions but lots of cross reaction due to co-infections in endemic regions

Answer 1508

Identify patients with Loa Loa as part of Oncho treatment programmes to NOT treat them

Answer 1509

Occult: fairly sure they are infected but cannot detect microfilariae in the blood often misdiagnosed as negative blood tests

Answer 1510

Microfilariae (+++) and macrofilariae (++)

Answer 1511

ONLY microfilariae

Answer 1512

some mild activity against macro and microfilariae

Answer 1513

Nothing Loa Loa have no wolbachia so no role of doxy

Answer 1514

Deer fly: Chrysops silacea, C. dimidiata Wood fire, day-biting

Answer 1515

Forest and adjacent savannah regions of Central Africa (parts of W-Africa) ~20 million patients, often life-long infection eg DRC, Gabon Rural populations

Answer 1516

DEC Mazzotti reaction, encephalitis in patients with high mf Contraindication in onchocerciasis indicated in patients with mf<2,000/ml 3-weeks treatment regimen (60%-70% cure rate) (Ivermectin) very rapid and potent activity on mf, no activity on adult worms: Mazzotti reaction, encephalitis in patients with high mf indicated in patients with mf <8,000/ml Single dose; NOT CURATIVE Albendazole very slow activity against mf (probably sterilizing effect), low activity against adult worms Encephalitis? (hasn't been used that much so poor data) indicated if DEC (and IVM) cannot be used 3-5 weeks regimens, cure rate? Tx-algorithm based on microfilaria count; apheresis in hypermicofilaraemia - Several cycles to mechanically remove microfilariae - Lowering mf below 2,000 (8,000)/ml - Consecutive definitive treatment with DEC Risk-benefit analysis? In- versus outpatient?

Answer 1517

Avoidance of fly bites (mosquito nets, clothes, repellents) Very-high-risk travellers: weekly DEC prophylaxis No control prgrammes in endemic countries! Also not a NTD. PERSONAL LEVEL: Avoidance of deer fly bites * Clothing, mosquito net cloths * Repellents? * Citridiol > DEET > Placebo = Icaridin Chemoprophylaxis: * 300mg DEC weekly * 100% protective efficacy * Indication: * selected cases of highest risk * Peace corps, missionaries, military, forest worker __ CONTROL Deforestation and human land-change * Long-term reduction of transmission regions Currently available control-tools are insufficient * MDA-drugs: safety risks and/or not efficacious and/or inappropriate regimens * Vector: no tools available for efficient vector control No control programs implemented in endemic regions Priority for future * Develop new tools for vector control, mass drug administration programs * Distribute knowledge about disease (mode of transmission)

Answer 1518

For CVD in primary care Healthy lifestyle counselling Evidence based protocols Access to essential medicines Risk based CVD management Team based care Systems for monitoring

Answer 1519

Analogue insulin: rapid-acting (eg. lispro) & long-acting (eg. glargine) -> availability limited in LMICs Soluble (regular) insulin: short-acting, suitable for SC or IV administration Isophane (NPH) insulin: intermediate-acting -> cost effective option Lente insulin: intermediate to long-acting -> used when NPH is unavailable

Answer 1520

promote glucose excretion but risk euglycemic ketoacidosis in insulin-deficient patients

Answer 1521

Individual Models (Facility-based): Patients attend facilities individually for care. Individual Models (Community-based): Care provided outside facilities, often closer to homes. Group Models (Healthcare worker-led): Groups of stable patients meet with a health worker for care. Group Models (Patient-led): Patient groups self-manage their care with provider guidance.

Answer 1522

Elimination: Reduce incidence of disease to zero in defined geographical area. Continued interventions required to prevent re-introduction Eradication: Permanent reduction to zero of the worldwide incidence of infection caused by a specific agent

Answer 1523

No animal reservoir Of public health importance Effective intervention Amenable to surveillance

Answer 1524

Hydrocele Acute adenolymphangitis Lymphoedema

Answer 1525

Falsified: medicines that are deliberately and fraudulently produced Substandard: Unintentional errors in production or negligence means medicines of poor quality Degraded: left factory as good quality but deteriorated through not following Good Pharmacy practice in the distribution chain and poor storage ORIGIN 1. Genomic eg environmental DNA 2. Mass spec 3. Social network analysis

Answer 1526

Gnathostoma (12.5mm) Baylisascaris procyonsis (1500-2000 micrometres) Ancyclostoma caninum (500-700 micrometres) Strongyloides stercoralis (600 micrometers) Toxocara canis (400micrometres)

Answer 1527

Zoonotic infection from racoon ascaris Most common: Baylisascaris procyonis Epi: North America, Europe and Japan In animals: - If ingested by other animals then makes them display abnormal behaviour which makes them easier prey for racoons - Not harmful to the raccoons In humans: - Infections rare, only if OLD faeces from racoons ingested (eg >2 weeks - Often asymptomatic but can cause 3 major syndromes 1. Visceral larva migrans: eosinophilia and organ involvement 2. Neural larva migrans - predilection for neural tissue leading to eosinophilic meningitis 3. Ocular larva migrans - DUSN (diffuse unilateral subretinal neuritis)

Answer 1528

Stages of disease: 1. Multi-focal grey white lesions 2. Late stage disease: pigmentation alterations, narrowed retinal vessels, pale optic disc Ideally worm visualisation: 1500-2000 mcm, occurs in approximately 25-40% of cases, size 400-2000mcm

Answer 1529

- Toxoplasmosis - Histoplasmosis - Syphilis choroiditis - Multifocal choroiditis - Serpinginous choroiditis - Acute posterior multifocal placoid pigment epitheliopathy - Multiple evanescent white dot syndrome - Optic neuritis

Answer 1530

Treatment 1. Neurological - Albendazole and praziquantel for prolonged duration +/- steroids - Outcomes poor - High risk exposure: albendazole prevention 10-20 days 2. Ocular (DUSN) - Photocoagulation If not possible -> albendazole +/- scattered photocoagulation

Answer 1531

A. Dividing epimastigotes B. Infective metacyclics C. Excreted infective metacyclics D. Host cell infection E. Circulating trypomastigotes F. Pseudocyst containing dividing amastigotes Ingestion of trypomastigotes by insect vector

Answer 1532

- ELISA - IFAT (indirect immunofluorescence Ab test) - PCR - RAPID tests (immunochromatographic dipstick test eg STATPACK) - Xenodiagnosis In chronic phase need two accordant serological tests for diagnosis In essence: - Acute: PCR or microscopy (rarely positive) or RDT - Chronic: 2x serological test

Answer 1533

Dysplastic lesions of conjunctiva and cornea (ranges from conjunctival intraepithelial neoplasia to invasive SCC of conjunctiva) RFs: HIV (esp in sub saharan Africa) and UV exposure Either treat with topical chemotherapy agents to begin with or if invasive needs surgery which may mean removing whole orbit

Answer 1534

Now estimated 3.8 million deaths from fungal infections

Answer 1535

- Cryptococcus neoformans - Candida auris - Aspergillus fumigatus - Candida albicans

Answer 1536

Histopathology

Answer 1537

Beta-glucan chains eg Caspofungin

Answer 1538

Crytococcus Mucormycosis

Answer 1539

Invasive candidiasis PCP Cryptococcosis Mucormycosis

Answer 1540

- CRAG: very sensitive and specific for cryptococcus - Histoplasma urinary antigen LFA - Aspergillus GM LFA - Coccidioides Ab LFA

Answer 1541

Only yeasts

Answer 1542

Polyenes - Nystatin - Amphotericin B - Liposomal amphotericin B Echinocandins - Caspofungin etc Azoles - Fluconazole - Itraconazole - Voriconazole etc Other - Flucytosine - Terbinafine

Answer 1543

Terbinafine

Answer 1544

Steroid use Diabetes Neutropenia

Answer 1545

TB mimic Massively underdiagnosed especially in African countries due to lack of diagnostics Diagnostic tests: - Culture (slow and needs containment level 3) - BD Glucan and galactomannan will be positive - Serology -> less useful in HIV/disseminated diseases Ag testing in blood and urine (future but not widely available even in rich countries)

Answer 1546

Disseminated: Ambisome/amphotericin Localised, pulmonary: Itraconazole

Answer 1547

Blastomycosis - Pneumonia most common manifestation (60-90%) - Extra-pulmonary manifestations common ○ Myalgia, arthralgia, chills - Dissemination to skin also reported frequently NB: Ontario in Canada world hotspot

Answer 1548

Ontario in Canada

Answer 1549

* Barrier * Immune function * Temperature regulation * Attraction/display * Sensing the environment * Metabolic * Homeostasis of water, electrolytes

Answer 1550

1. Scabies 2. Bacterial skin infection 3. Fungal infection (superficial infection) 4. Eczema 5. Acne 6. HIV-associated skin diseases 7. Pigmentary disorders 8. Wounds

Answer 1551

Causative Agent Sarcoptes scabiei var. hominis Ectoparasitic mite WHO NTD in 2017 Epi 565 million people 4.84 million DALYs Transmission Direct (most common): close physical contact Indirect: - fomites and bedding - outbreak in closed communities

Answer 1552

Clinical Features Symptoms: thought to be due to hypersensitivity to mite, eggs, faeces - Ie continual exposure of mites burrowing into skin causes sensitisation and resulting allergy Intense itching, often worse at night Burrows* (thin, greyish-white, raised lines), typically seen in skin folds Papules, nodules, vesicles, pustules Excoriations Pattern may differ in children and elderly - eg soles of feet in infants Secondary bacterial infections can occur due to scratching

Answer 1553

1. Typical Scabies: Localized skin infestation 2. Crusted Scabies (Norwegian Scabies): Severe, highly contagious form with thick crusts, common in immunocompromised patients eg HIV, HTLV-1 - Hyperkeratosis - Itch may NOT be prominent feature - (esp in elderly and children)

Answer 1554

Clinical: rash and burrows Dermatoscope: delta wing sign Microscopy: mite or eggs No serological, molecular, POC tests Peripheral eosinophilia TREATMENT Practical steps in treating scabies * Information * Diagnosis * Transmission * Fomites Treatment advice * Benzyl benzoate 3 consecutive days concentration determined by age (most available in LMICs) OR TWO treatments 7 days apart of either * Permethrin 5% (esp babies) OR * Ivermectin 200µg/kg Apply creams from neck down (head to toe for infants and elderly) Household contacts treated simultaneously Expectations from treatment and management of post-treatment symptoms (itching won't go away for at least 6 weeks) => post scabies itch and dermatitis Provide psychological support and sexual health screen (to adolescents and adults, including HIV test) For crusted scabies: - Oral: Ivermectin (dosing depending on grading) Topical: permethrin or benzyl benzoate (long course eg weeks) + keratolytic eg urea/lactic acid or salicyclic acid

Answer 1555

WHO informal consultation 2019 * community prevalence of scabies is ≥ 10% * Two doses of oral ivermectin delivered 7–14 days * 3–5 rounds of MDA * Stop if prevalence of scabies falls < 2%

Answer 1556

Secondary bacterial infections (e.g., impetigo, cellulitis) Post-streptococcal glomerulonephritis Bullous disease Erythroderma Widespread skin loss

Answer 1557

Both you are visualising fungi in asexual state In tissue: visualise fungi as hyphae and yeasts In culture: visualise as spores

Answer 1558

Caused by keratophilic moulds Most common causative fungus: Trychophyton rubrum Examples: *Tinea capitis *Tinea faciei Tinea corporis Tinea pedis * roughly 50% caused by non-anthropophilic dermatophytes

Answer 1559

Endothrix: hyphae are within the hair Eg Trichophyton sp. Ectothrix: hyphae outside of the hair Eg Microsporum sp

Answer 1560

Trichophyton indotineae

Answer 1561

Tinea nigra Saprophyte - found in soil, wood, compost Asymptomatic infection of the skin (palms>soles) Rare, adults>children Tx: topical azole eg ketoconazole

Answer 1562

Eumycetoma = fungal - in Africa Actinomycetoma - in Americas

Answer 1563

Madurella mycetomatis - DARK grains - Slow - Walled off - Late invasion - Punched out lesions on XR

Answer 1564

Itraconazole (400mg OD) for years + surgery Recurrence in >1/3 Trial posconazole in refractory disease

Answer 1565

Co-trimoxazole Can use in combo with - amikacin - rifampicin - co-amoxiclav

Answer 1566

rough scales slit like eyes large head short, thick, short-tailed colourful dorsal pattern - like warning signs slow moving but lightening striking

Answer 1567

Puff adders (have repeating V or U pattern on back) Grumpy and won't move but will bite and sting fast

Answer 1568

Bands of colouring No warning signs Can have hoods

Answer 1569

Kraits *part of elapidae

Answer 1570

Biopsy and histopathology or PCR

Answer 1571

Nocardia (asterioides) WHITE grains Mostly feet, trunk and head possible Rapid and spreading infection with unclear margins, inflammation and destruction Rapid spread to bone so hard to treat Mx: - Co-trimoxazole - Often add amikacin or rifampicin

Answer 1572

Bot fly Dermatobia hominis Often need to incise as too big to do just vaseline

Answer 1573

Causative Agent Poliovirus = enterovirus, RNA virus Three serotypes: PV1 (most virulent), PV2 (eradicated), and PV3 1 most virulent > 3 > 2 Transmission Fecal-oral route (primary) or via respiratory droplets Facilitated by poor hygiene and sanitation Case infection ratio low (1/100 to 1/2000) and increases with age + more likely to be paralysed Pathophysiology Virus to mucosa Then to lymphoid tissue then CNS -> acute flaccid paralysis (AFP)

Answer 1574

1. Asymptomatic (90-95%) 2. Minor illness: Fever, malaise, sore throat, headache, and vomiting 3. Non-paralytic poliomyelitis: Aseptic meningitis with neck stiffness, back pain, and muscle spasms 4. Paralytic poliomyelitis: Flaccid paralysis due to anterior horn cell damage; affects limbs asymmetrically; can involve respiratory muscles 5. Post-polio syndrome (PPS): Late-onset muscle weakness and fatigue years after recovery

Answer 1575

as part of Millennium development goals - to eradicate Polio 1. High routine immunisation coverage emphasis on OPV 2. National Immunisation Days (NIDs) OPV to all children under five more than 1 billion doses of OPV per year…. 3. Acute Flaccid Paralysis (AFP) surveillance expect at least 1 per 100,000 under age 15 4. » Mop-up » campaigns house to house

Answer 1576

Oral Polio Vaccine (OPV): Live attenuated vaccine providing intestinal immunity; used in eradication campaigns TRIVALENT to BIVALENT since 2016 - Less expensive, virus builds up in gut to increase antigenic mass = greater enteric immunity (vs infection) - Less expensive than IPV - Transmissible: so immunises > vaccinated (ie virus comes out of faeces as still live in kids who vaccinated so can then be spread and vaccinate whole household but turned out not to be true ie creation of vaccine derived polio vaccines) BUT - Lower seroconversion in tropics ?due to competing organisms in the gut - Causes paralysis approx 1 per million doses - Transmissibility is two edged sword Another issue - OPV is good at stopping clinical disease but not necessarily transmission so when OPV campaigns stopped after coverage given, Type 1 poliovirus found in sewers etc (Israel) suggesting asymptomatic carriage Inactivated Polio Vaccine (IPV): Injected vaccine providing systemic immunity; used in routine immunization schedules

Answer 1577

Diagnosis Clinical Laboratory confirmation via virus isolation from stool, throat swabs, or CSF RT-PCR for viral RNA (Serology does not differentiate between old and new/immunised) Treatment No antiviral treatment available Supportive care: Pain relief, physical therapy, and respiratory support if needed Prevent secondary complications like contractures and infections

Answer 1578

Polioviruses that result from vaccination (esp in areas of low immunisation rates) which take on wild type characterictis and complicated elimination strategy

Answer 1579

Wild type circulating in 2 countries: Pakistan and Afganistan VDPV circulating in 20 countries Endgame challenges: 1. To stop all wild virus circulation 2. To stop all VDPV circulation via NOPV2 (novel oral polio virus vaccine 2 since 2021) 3. Security against reintroduction 4. To stop all vaccination

Answer 1580

Paralysis, which can be permanent Bulbar poliomyelitis leading to respiratory failure Post-polio syndrome with late-onset weakness and fatigue

Answer 1581

3 doses (can give additional birth dose can be referred to as 0, so gives 4 doses) - can have in addition to routine OPV dose to kids up to 5 years old

Answer 1582

Snake bites Hookworm Strongyloides Podoconiasis Tungiasis Venomous bites and stings

Answer 1583

Tunga penetrans Jigger flea --> adults burrow into skin via soil

Answer 1584

○ Treat patients ○ Sealing/spraying floors with insecticide ○ Encourage footwear ○ Treat infected animals owned by infected families

Answer 1585

75% lymphocuteanous Ulcerating nodules, plaques on exposed body sites eg arms and legs 25% fixed cutaneous variable morphology of skin lesions eg papulopustular, nodular, verrucous Can also be non-cutanaeous with localised/systemic form eg ocular, tenosynovitis, CNS

Answer 1586

Sporothrix schenkii Sporothrix braziliensis (from cat scratch eg in Brazil) Sporothrix globosa

Answer 1587

Most commonly: itraconazole (at least 3 months) or terbinafine or potassium iodide Treat until all lesions resolve Consider: Cryotherapy Thermotherapy Photodynamic therapy

Answer 1588

Adult males Agricultural workers Immunocompetent High in Brazil, China, Mexico

Answer 1589

Lobomycosis – Lacazia loboi Central and South America Treat with excision of lesion

Answer 1590

Slow progressing Disfiguring Inoculation or inhalation Sub cut swelling or fibrosis Basidiobolus ranarum - SE Asia, Africa -Limb swelling - Children eg boys Conidiobolus coronatus - Africa, India, West Indies, South America - Facial swelling - Young adults (male)

Answer 1591

Histoplasma duboisii Intracellular parasite, yeast Transmission: inhalation Presentation: bone, LN, skin lesions Do X-rays to look for bone lesions

Answer 1592

Blastomyces dermatitis Blastomyces gilchristii IN soil and organic matter -> INHALATION Agricultural workers Men>women Uncommon in HIV/AIDS PRESENTATION 1) Primary cutaneous -> very rare 2) Pulmonary blastomycosis (eg cavitating lesion, abscess) 3) Disseminated eg widespread skin rash

Answer 1593

Microscopy -> thick-walled, spherical yeasts Culture -> mould at 30degrees, white tan cotton appearance

Answer 1594

Microsopy -> Large sphericals containing endospores Culture -> fast growing white-tan cotton appearance OR thick-walled arthroconidia Treatment - Pulmonary: not always necessary Otherwise: - Itraconazole or fluconazole - Ambisome/Amphotericin Disseminated: complement fixing Abs

Answer 1595

Juvenile form of paracoccidioidomycosis - Lymphadenopathy - Fever - Skin lesions in 50% - Hepatosplenomegaly Adult form Vegetative lesions - Lesions in oral mucosa Macrochelitis - Lesions in nose/eyes - Skin lesions across body

Answer 1596

INVESTIGATIONS Direct visualisation via microscopy: Mickey mouse appearance or sailor ship Culture TREATMENT - itraconazole - ambisome - voriconazole - co-trimoxazole

Answer 1597

Clotrimazole 1% Hydrocortisone Other - Econazole cream - Ketoconazole cream/shampoo

Answer 1598

Betamethasone valerate Hydrocortisone

Answer 1599

Betamethasone Papular pruritic eruption - associated with low CD4 and high VL

Answer 1600

- Classical (old people) - Endemic (was before HIV/AIDs) - HIV/AIDS - Transplant

Answer 1601

ART (may be enough alone if not severe disease) Doxirubicin/Adriamycin Bleomycin Vincristine ABV

Answer 1602

Salicylic acid Podophyllum

Answer 1603

Betamethasone and ART

Answer 1604

Think very low CD4 counts who have started therapy Itraconazole *despite not being fungal disease Permethrin

Answer 1605

<200 Patients get within starting ART ie within 3-6 months VERY ITCHY

Answer 1606

Ulcerated lesions with scalloped borders - Transmission and acquisition in PLWH 4x more likely - Can also genital/perioral transmission Treat with acyclovir NB: aciclovir resistant herpes is 10x more common in immunocompromised -> can present as SCC mimicking

Answer 1607

Low CD4 count May be extensive Often facial involvement

Answer 1608

POLYMORPHIC ERUPTION Pustules Pseudopustules Ulcers

Answer 1609

Prematurity can reduce nephron endowment -> higher risk of CKD Thus, risk of burden in LMICS

Answer 1610

If kidney injury for >90 days

Answer 1611

Abnormalities of kidney structure or function present for >3 months with decreased eGFR (eGFR<60) AND/OR markers of kidney damage (one or more)

Answer 1612

HTN Pruritis Nocturia Dyspnoea Lethargy Vomiting Body swelling Anorexia Restles legs Haematuria

Answer 1613

Urine creatinine to albumin ratio

Answer 1614

Creatinine OR Cystatin C (better in SSA)

Answer 1615

- Sepsis (very common in LMICs) -> Malaria, TB, Bacterial etc - Toxins (nephrotoxins) - Obstruction - Parenchymal kidney disease

Answer 1616

Pediculus (head and clothing/body lice) Pthirus (crab lice) *Pediculus humanus (body lice) - uncommon in developed countries (usually vagrants) *Pediculus capitis (head lice) - world-wide (mostly in children) *Pthirus pubis (crab lice) - mainly in sexually active groups, can occur on beards and eye lashes

Answer 1617

LIFE CYCLE Egg - dark (empty egg =nit is white), laid at scalp where its warmest, nymph (3 instars), adult (9 days longevity) Obligate blood feeders; feed multiple times daily FOUND - Clothing (hems and seams) - Search hair on bed (wet combing with conditioner) - Search coarse hair (pubic, beards and eyelashes/eyebrows)

Answer 1618

P.humanus - Transmit louse-borne relapsing fever, agent is spirochaete Borrelia recurrentis) - Rickettsia prowazekii (typhus): multiples in midgut, passed in faeces (infected for 3 months). Anthroponotic typhus. - Trench fever (Bartonella quintana) Pediculosis = infestation with louse - Pediculosis capitis = head lice, heavy infestations cause irritation, itching & saliva toxic reaction - Pediculosis pubis -> characteristic bluish spots at bite site. Associated with STIs.

Answer 1619

P.humanus Environmental - Replace clothes/isolate for 17+ days - Boil wash clothes - Hot tumble dry (60 degrees for 15mins) Chemical - Insecticide treatment of clothes - If in prision: cleanse prison, shave and dust prisoners with 0.5% permethrin, change beds and clothes P.capitis Chemical - Insecticide resistance to all over-the-counter treatments containing either malathion, permethrin or phenothrin is widespread and ovicidal activity is poor - Dimeticone 4% gel/lotion – prevents respiration (no resistance) Physical - Using wet-combing with conditioner is more effective * Treat all individuals in household with an active infestation. * No need to treat clothing/bedding. Pthirus Eyelashes - Petroleum jelly 2xday for 10 days Pubic hair and beards Water-based insecticide lotions (alcohol-based lotions sting delicate areas)

Answer 1620

How to tell them apart? - Difference in pronotal and gental combs and mesopleural rods - Female: round abdomen, spermathacea - Male: Terminal segments of male abdomen are upturned, Aedeagus – intromittent organ Types: - Xenopsylla (plague flea) ○ No combs ○ Mesopleural rod in second thoracic segment - Pulex irritans (human flea) ○ No combs ○ Sclerotised antennal fossae (like wearing headphones) - Ctenocephalides (cat/dog flea) ○ Genal and pronotal comb ○ Mesopleural rod ○ Antennal fossae are not sclerotized - Tunga penetrans (Jigger flea) ○ Rounder body shape ○ No combs ○ Compressed thoracic segments ○ Head has upturned point ○ Mouthparts are long and serrated

Answer 1621

Egg, larva, pupa, adult ▪Adult longevity 6-12 months (up to 2 years) ▪Female produces 3-25 eggs/day (300-1000/lifetime) ▪Eggs hatch in 2-14 days. ▪Caterpillar-like larvae undergo 2 moults (3 instars) in 2-3 weeks ▪Pupae housed in silk cocoon (2-3 weeks). ▪Adult sheds pupal skin & remains dormant within cocoon (up to one year) until stimulated by a host (vibration). ▪Can copulate immediately after emergence. ▪Eggs laid 1-2 days after bloodmeal BEHAVIOUR Males and females opportunistic blood feeders but can survive for long time without feed Not host specific (but nest/habitat specific) Primary host required to achieve sexual maturity and reproduction Saliva (anticoagulant) injected when mouthparts penetrate

Answer 1622

- Yersinia pestis (plague) via Xenopsylla - Rickettsia typhi (murine typhus) -> Xenopsylla but dried faeces causes disease - Tungiasis via Tunga penetrans - Tapeworms eg Dipylidium caninum, Hymenolepis diminuta via Ctenocephalides spp. (cat/dog flea) -> flea ingested -> give Endogard for dogs (Praziquantel, Pyrantetel, Emonate, Febantel) every 2 weeks until 12 weeks, then every 3 months

Answer 1623

Chemical: - Domestic fleas: insectide tx of houses - Pets (treatment) and other hosts - Reapplication of treatments as reinfestations may appear quickly Environmental: - vacuuming, around edges of carpets, washing floors PPE: shoes, DEET Rodent control + proofing of buildings Mini-smoke generator with insecticide ie permethrin 13.5%

Answer 1624

~3 weeks * 1st instar nymph hatches from an egg and then goes through 4 further nymphal instars, before moulting to become an adult. * Without restrictions due to temperature or host availability, the bed bug life cycle can be completed in 3 weeks. * Peak infestation occurs in around September followed by a decline during the winter and a steady increase throughout the spring and summer months BEHAVIOUR Nocturnal feeders Obligate blood feeders attracted to warmth and CO₂ During day: aggregate within refuges in conspecific groups consisting of all developmental stages and both sexes Check sheets/cabinets etc for faecal spots

Answer 1625

IMPORTANCE - Biting nuisance - Allergic reactions and secondary infections - Anxiety - Economic loss - Potential vector for transmission of trench fever CONTROL * important public health problem * infestations are increasing * pesticide resistance is developing * no passive monitoring device * new approaches are needed – control – monitoring * semiochemicals for odour-baited traps

Answer 1626

DERMATOPHYGOIDES Egg, hexopod larva, 2/3 octopod nympha; stages (protonymph, deutonymph, tritonymph), adult SCABIES Adult lifespan 1-2months Females lay 1-3 eggs per day Eggs hatch in 3-5 days Larvae crawl to surface along burrows Make moulting pocket in skin or hair follicles After 3-4 fays larva moult to protonymph and after another 2-3 days to tritonymph Tritonymph moults to either male or female Male seeks out females Females stay put and only burrow after fertilisation THROMBUCULID MITES -“8-shaped” nymphs & adults live in soil (feed on arthropods & eggs) -Insemination: walk over spermatophores -Eggs laid in damp soil -Larvae (“chiggers”) fall on host and feed on cell tissue fluids through a stylosome

Answer 1627

Dermatophagoides (House dust mite: triggers asthma) Trombiculid mites “chiggers”/harvest mites (transmit scrub typhus) Sarcoptes scabei (causes scabies) Demodex (follicle mite)

Answer 1628

DERMATOPHYGOIDES - Vaccum sampling to assess densities per unit weight - Mitest collector - Simple mite extraction method - Rapid test for mite allergen - ELISA to quantify Ags Control with Physical - Semi-permeable mattress encasings - Removal of domestic habitats/dust eg vaccums, ionisers - Making habitats less favourable for HDM eg de-humidifiers, removing soft furnishings Chemical - Allergen sprays - Fungicides - Acaricides SCABIES - Treat with permethrin 5% cream or benzyl benzoate (whole body below neck, before bedtime, repeat after 7 days) - MDA: If prevalence is >2%, 2 doses of oral ivermectin (200 μg/kg) given 7 to 14 days apart THROMBICULID MITES - Avoid Chigger habitats/mite islands (patchy distribution: need environment with abundant prey, for adults, and with mammals, for larvae) - Spray vegetation with an acaricide (e.g. benzyl benzoate) - Impregnate socks/trousers with repellent (e.g. Diethyltoluamide = DEET). Treatment for scrub typhus: doxycycline (2.2 mg/kg/dose bid PO or IV, maximum 200 mg/day for 7-15 days)

Answer 1629

Dermatophagoides - Faecal pellets can trigger asthma, eczema, perennial rhinitis Sarcoptes scabiei - Itchy, red rash - Especially where skin is thinning eg folds - Diagnose with skin scrapes - Crusting in immunocompromised - Treat with permethrin 5% cream or benzyl benzoate (whole body below neck, before bedtime, repeat after 7 days) - MDA: If prevalence is >2%, 2 doses of oral ivermectin (200 μg/kg) given 7 to 14 days apart Thrombiculid mites 1. Trombidiosis ( or Scrub itch) 20 spp. of chiggers (or harvest mites) can cause intense, itchy dermatitis. - Larvae feed for up to 10 days on host (saliva produces itchy, red lumps found, typically in armpits, leg calves, and pelvic region). 2. Scrub Typhus (or Chigger-borne rickettsiosis) - Orientia tsutsugamushi - Typically confined to rodents/insectivores - Humans typically get infected when they invade “mite islands - Endemic in SE Asia & Australia. - Symptoms: mild fever to fatal multiple-organ failure (1 million cases/year, up to 40 mortality)

Answer 1630

Hard ticks: Ixodidae Soft ticks: Argasidae Control * Avoidance. * Repellents (products with 20%+ DEET). * Clothing (and permethrin impregnated clothing). * Check yourself and pets for ticks. * Safe removal of attached ticks. * Tumble dry clothing on high heat to kill ticks. * Insecticidal treatment of animals. * Insecticidal treatment of breeding sites. Removal - Fine forceps - Grasp close to skin Pull up directly and don't twist -> want to pull with head

Answer 1631

IXODIDAE Arboviruses - Tick-borne encephalitis - CCHF - Colorado tick fever Rickettsiae - Rickettsia rickettsii (Rocky Mountain spotted fever) - Boutonneuse fever (tick typhus) - Queensland tick typhus Spirochaetes - Borrelia burgdorferi (Lyme disease) ARGASIDS * Tick-borne relapsing fever. * Several Borrelia species Ornithodoros species * Man is the sole reservoir of disease (B. duttonii). * Endemic in Africa and southern Asia. * Foci in North America and Europe.

Answer 1632

HARD Female feeds 6-12 days Engorged female drops off host and matures eggs Female lays 1000-10,000 eggs then dies Eggs hatch in 10-20 days or may overwinter 6 legged larvae feeds for 2-6 days 8 legged nymph feeds for 3-8 days Nymph moult into males or females Males feed only briefly Lifecycle 2-3 years for most temperate species SOFT Little sexual dimorphism Females lay several small egg batches 15-100 eggs after each bloodmeal Eggs hatch after 1-3 weeks 1 larval stage Multiple nymphal stages (4-5) each requires bloodmeal Adults can survive for 12 years without bloodmeal Lifecycle: 6-12 months to complete Lifespan 15-20 years

Answer 1633

Blood films - thick and thin CSF

Answer 1634

An infected triatomine insect vector takes a blood meal from a mammalian host and releases trypomastigotes in its feces. Trypomastigotes enter the host through the wound or through mucosal membranes. Inside the host, trypomastigotes invade cells , where they differentiate into intracellular amastigotes. The amastigotes multiply, differentiate into trypomastigotes, and are released into the circulation as bloodstream trypomastigotes. Trypomastigotes infect cells and transform into intracellular amastigotes. The clinical manifestations of acute infection can result from this infective cycle. Replication resumes only when the parasites enter another cell or are ingested by another vector. The triatomine bug becomes infected by feeding on human or animal blood containing circulating parasites. The ingested trypomastigotes transform into epimastigotes. The parasites multiply in the midgut and differentiate into infective metacyclic trypomastigotes in the hindgut. Trypanosoma cruzi can also be transmitted through blood transfusions, organ transplantation, transplacentally, and in laboratory accidents.

Answer 1635

* Prevent drug reaching its target via - Impermeable outer membrane / wall - Efflux pumps - Destroy or modify the compound * Alter the target or its product so that the drug has no effect * Intrinsic resistance e.g. lacks antibiotic target * Acquired resistance * Point mutations * Altered target * Random errors during replication, selected by antimicrobial pressure

Answer 1636

Transmit the organism OR Transmit the resistance gene * Plasmid (circles of DNA that can move between cells) * Bacteriophage (viruses that attack germs and carry DNA from germ to germ) * Other mobile genetic elements e.g. transposons (small pieces of DNA that can move from chromosomes), gene cassettes Mobile genetic elements work via - Transduction (transfer via phages) - Conjugation (via connection of bacteria) - Transformation (picking up resistance genes from nearby germs)

Answer 1637

S.pneumoniae S.aureus E.coli Klebsiella pneumonia Salmonella spp Actinetobacter spp Shigella spp N.gonorrhoeae Mycobacterium tuberculosis

Answer 1638

Reduce use Reduce disease - vaccination - better treatment - better health and sanitation

Answer 1639

* Poor sanitation – increased risk of illness and increased risk of AMR transmission * More adverse consequences when infections do occur * Limited access to 2nd / 3rd line treatment * Limited access to supportive care * Poor infection prevention / control practices increasing dissemination within healthcare settings * And compounded by lack of diagnostics leading to increased use of available agents Same issues in agricultural illness

Answer 1640

- Animal production eg lifestock, aquaculuture - Animal health eg pets and lifestock - Human health eg disease and use of Abx - Food chain - Agriculture - Travel - MDA - Suboptimal rapid diagnostics - Suboptimal vaccination - Environmental contamination

Answer 1641

* Rates of resistant infection eg Hospital and laboratory data * Process indicators eg Antimicrobial use via Point prevalence surveys * Antimicrobial consumption eg Pharmacy records, Import data * Rates of resistance in carriage samples E.g. stool screening, MRSA screening * Proxy markers of resistance eg Environmental sampling

Answer 1642

SCD - Hb SS -> most severe form - Hb Sβ0 thalassemia -> Most prevalent in the eastern Mediterranean region and India (also includes severe β+ with <5%HbA present) - Hb SDpunjab -> Predominant in northern India but occurs worldwide Moderate SCD - Hb SC -> 25-30% of cases of SCD in populations of African origin - Hb Sβ+ thalassaemia -> Most cases found in the eastern Mediterranean region (6-15% HbA present) Mild SCD - Hb Sβ++ thalassaemia -> Mostly in populations in Africa (16-30% HbA present) Very mild SCD - Hb S/HPFH* Group of disorders caused by large deletions of the β-globin gene. Typically, >30% HbF

Answer 1643

- Blood film for sickled cells - Sickle solubility test - Hb electrophoresis - High performance liquid chromatography

Answer 1644

Neuro - Meningitis, stroke Retinopathy - Retinal infarction and glaucoma Pulmonary HTN - ACS - Acute pain event CV - Cardiomegaly - Diastolic heart failure Haem - Anaemia - Leukocytosis - Asplenia -> splenic infarction, sequestration Renal - Papillary necrosis due to albuminuria, isothenuria, substantial kidney injury Liver - Gallstones - Indirect hyperbilirubinaemia Other - Priapism Avascular necrosis

Answer 1645

Complications ACUTE - Acute pain, anaemia, chest syndrome - Infection - Stroke - Priapism - Aplastic crisis - Osteomyelitis - Splenic sequestration - Dactylitis in children CHRONIC - Pain, anaemia - Sickle nephropathy, retinopathy, hepatopathy - Leg ulcers - Pregnancy - Cardiac - PHT - Sickle lung disease

Answer 1646

- Infection - Dehydration - Stress - Hypoxia - Temperature - Physical exertion - Alcohol - Unknown

Answer 1647

May become jaundiced eg eyes may become yellow May be more irritable or tired than usual Numbness or sensation change where pain will be

Answer 1648

- Haem emergency - O2 sats <94% or PO2<9 on AIR - Abx: IV ceftriaxone and PO Clari - High flow oxygen/CPAP - IVF - Incentive spirometry - Thromboprophylaxis - Regular monitoring /discussion with ITU - Exchange transfusion

Answer 1649

Acute chest syndrome 1. S/S of respiratory disease (chest pain, fever, wheeze, SOB, cough) 2. New radiological evidence of consolidation

Answer 1650

- Malaria: increased morbidity and mortality -> give anti-malarial prophylaxis and ITNs in all endemic areas, prompt diagnosis and treatment - Bacterial: encapsulated organisms eg Strep pneumoniae: need Pneumococcal vaccine every 5 years, Hib vaccine, Meningococcal vaccine (A and C), Pen V prophylaxis either until 18 or lifelong - Parvovirus: aplastic anaemia

Answer 1651

SCD children at >200x risk of stroke compared to peers 11% of HbSS have stroke by age 20 Management - Haem emergency - Exchange blood transfusion - Identify precipitating cause - MDT + ICU Prevent Investigate high risk or silent infarcts eg - Transcranial doppler USS - Neuroimaging - Neurocognitive assessment - Psychosocial assessment Prophylactic therapy with hydroxyurea, chronic exchange blood transfusion

Answer 1652

36 countries in SSA ~55 million people at risk - T.brucei gambiense: West Central Africa - T.brucei rhodesiense: East Africa Uganda has overlap between the two Cases coming down due to sustained efforts and screening Disease of rural reas eg Angola, DRC, South Sudan (used to be 30-50% prevalence)

Answer 1653

WHO targeted elimination of HAT “as a public health problem” by 2020 …an annual incidence <1 per 10,000 individuals in 90% of endemic areas …and a global incidence of <2000 per year New target… Elimination of gambiense HAT transmission – zero reported cases by 2030

Answer 1654

1. Infected tsetse fly takes blood meal from mammalian host 2. Injects metacyclic trypomastigotes into skin -> lymphatics -> bloodstream 3. Develop into trypomastigotes and replicate via binary fission, parasites move to other sites 4. Tsetse fly takes meal and ingests trypomastigotes 5. In the fly’s midgut, the parasites transform into procyclic trypomastigotes, multiply by binary fission 6. Leave the midgut, and transform into epimastigotes 7. Epimastigotes reach the fly’s salivary glands continue multiplication by binary fission and transform into met cyclic trypoamastigotes 8. Repeats The cycle in the fly takes approximately 3 weeks. Rarely, T. b. gambiense may be acquired congenitally if the mother is infected during pregnancy.

Answer 1655

50% of people with T.b.rhodesiense will have chancre at bite site

Answer 1656

Two phases 1) Early stage = haemolymphatic stage - T.b.rhodesiense: chancre at bite site in 50% of cases, heals often leaving altered pigmentation - Gambiense: enlarged LNs, spleen, local oedema, cardiac abnormalities, general malaise, headaches, undulating fever ○ Winterbottom's sign = enlarged neck gland 2) Late stage = encephalitic - Parasites invade internal organs including CNS - Gambiense: months/years - Rhodesiense: 1-4 weeks Headaches, altered sleep, personality changes, mental function impaired, weight loss, coma and death

Answer 1657

Direct demonstration of parasite - Blood films eg thick or thin - Chancre or LN if acute infection - Blood concentration techniques eg DEAE anion exchange column, microhaemocrit (buffy coat), quantitative buffy coat LP and CSF examination - Raised WCC in CSF suggest stage 2 Serology - Card agglutination test for trypanosomiasis (CATT) * Drop of blood and antigen (fixed parasites) on plastic card -> blue granular deposits mean infection Only works for T.b.gambiense but V cheap

Answer 1658

Release of ANS mediators = autonomic storm * Parasympathetic (cholinergic) ○ Vomiting, sweating, hypersecretion, pancreatitis, priapism * Sympathetic (adrenergic) ○ Goose bumps/flesh, tachycardia, CV disturbances, myocarditis, pul oedema, hyperglycaemia Neurotoxic effects - Fasciculations - Tonic-clonic spasms "pseudo-convulsions" - Nystagmus - Opsoclonus - Irritability - Paralysis Ptosis

Answer 1659

Wear gloves and don't put fingers in at risk areas, wear long boots and trousers, and socks in sand or undergrowth, shake-out clothes, shoes and backpacks before putting them on, check living spaces with UV light, sleep under perthrin impregnated bed net and off ground

Answer 1660

Loxosceles spider eg american or brown recluse. First 24hr: pain, burning, itching, swelling etc, 48hr: red-white-and-blue sign, blisters, then systemic s/s eg malaise/fever etc, by 7 days necrotic eschar develops sloughing to leave necrotic ulcer which may need surgery/Abx

Answer 1661

Fever, haemolytic anaemia, jaundice, resp distress, collapse and AKI

Answer 1662

Immediate local pain and s/s, then tachycardia, HTN causing stroke, agitation, vomiting, bradycardia, hypotension, arrhythmias, acute pul oedema. Bite may be dry. Death by paralysis or asphyxiation. Give antivenom and supportive care.

Answer 1663

Pain, swellling, persistent + frequent tetanic muscle cramps/spasms in bitten limb then generalised, mild rhabdo

Answer 1664

First Aid: hospital and analgesia (pressure-immobilisation for Sydney funnel-web). Local intense pain: Phoneutria (Brazil) 2% lidocaine then IV dipyrone, Latrodectus (USA): antivenom, Australia: antivenom. Hospital: Antivenoms for Phoneutria, Atrax, Lactrodectus. antivenom has been used for loxosceles but effectiveness uncertain. No evidence for supportive tx but can give eg neurotoxic: Ca gluconate, Necrotic: Abx, steroids, surgery etc

Answer 1665

Protective clothing, footwear and gloves, don't leave gloves or clothing on ground, apply repellent eg DEET to exposed areas of skin, watch out for spiders webs, watch where you put your hands, flick spiders off skin (don’t crush)

Answer 1666

Eg ants, bees, wasps, hornets. Can be fatal anaphylaxis eg in brazil due to acquired IgE-mediated-hypersensitivity. Ix: hx, plasma cell mast tryptase, venom-specific IgE (RAST), molecular allergic diagnostics. Tx: adrenaline if anaphylaxis. Prevent: avoidance, self-injectable adrenaline and allergy bracelet, desensitisation.

Answer 1667

Hairy caterpillars/moths. Eg giant silk worm moth catepillar. PATHOLOGY Venom has anticoagulant effects -> haemorrhage, haemolysis, renal failure (silkworm caterpillar). Local pain, inflammation, blistering (other species). Mx: antihistamines, corticosteroids, analgesia, specific antivenom for silkworm caterpillar.

Answer 1668

Within 6-8 hours: GI upset Then paraesthesias, hot/cold sensation ie cold allodynia/paradoxical dysaesthesia, weakness, ataxia, myalgia CV: hypotension and bradycardia, hypovolaemia Management: IV mannitol early, correct acid-base and electrolyte abnormalities, neuropathic for ongoing symptoms

Answer 1669

Immediate peri-oral tingling/pepper sensation <1hr after ingestion - anaphylactic type symptoms eg rash, pruritic and urticaria, headache, bronchospasm, dizziness and syncope Histamine, taurine release by enteric bacterial histidine decarboxylase from decaying fish flesh (can be potentiated by histaminase inhibitors eg isoniazid) Management: - Adrenaline if anaphylaxis - Histamien H1 and H2 receptor blockers

Answer 1670

If ingestion in 1-2h -> eliminate gut contents Repeated doses of activated charcoal Hypotension -> correct hypovolaemia, atropine for bradycardia

Answer 1671

Paralytic: descending paralysis progressing to fatal resp paralysis Amnesic: short term or permanent amnesia (eg mussel poisoning) NB: tetradotoxins (eg puffer fish) also cause rapid generalised paralysis

Answer 1672

Susceptibility testing * Need universal DST (minimum RIF and INH; FQ if high incidence) Directly observed treatment * DOT for at least 5 days/wk; may not be possible in programmes Pill burden * High (because of rifapentine; no fixed-dose combination) Cost * Higher than RHZE Administration with food * Need to give with at least modest size meal Programmatic considerations * Training of HCW, availability of RPT

Answer 1673

Cryptosporidium parvum Cryptosporidium hominis TREATMENT Most self-limiting in immunocompetent. No current treatment in immunocompromised has been proven to work - paromomycin, nitazoxanide has been trialled.

Answer 1674

Ingestion of Undercooked or Contaminated Meat (contained oocysts) Contact with Contaminated Cat Feces Contaminated Water or Food Congenital Transmission Organ Transplantation or Blood Transfusion Rarely, individuals can become infected by accidentally inhaling oocysts, especially in areas with poor hygiene or heavy cat populations.

Answer 1675

1) Infections in post-natal, immunocompetent persons 2) Congenital infections 3) Severe and very dangerous disseminated infections in immunocompromised

Answer 1676

Across trimesters, risk of transmission increases but risk of symptoms/complications decreases. ie risk of transmission lowest in first trimester but highest risk of miscarriage, stillbirth, congenital malformations. However, in third trimester risk of transmission up to 80% but effects on foetus milder and might not be seen until later in life, eg vision loss or learning difficulties

Answer 1677

Anti-toxoplasma IgG Ag detection via PCR

Answer 1678

Spiramycin OR Pyramethamine + sulphonamide (Not in first trimester) Other: co-trimox

Answer 1679

Mapping of foci • Treatment of whole community • Likely need several rounds • Then mop up with treatment cases & contacts • Once no more cases switch to serological surveillance

Answer 1680

African tick bite fever Rickettsia africae - tick is ambylomma varigatum

Answer 1681

=endemic typhus Obligate intracellular gram-negative bacteria Transmitted by Xenopsylla cheopis ie the rat flea Infection: Occurs via the inoculation of faeces into broken skin -> eschar not found as disease transmitted by faeces, not bites

Answer 1682

Mild illness - presents abruptly after incubation period 7-14 days Triad: fever, headache, rash (in 40% of patients) in most -> PUO Rash: - maculopapular - starts centrally and spreads peripherally sparing the palms and soles GI symptoms in 75% When severe: - pulmonary infiltrates - AKI - altered conciousness - frank shock and DIC - HLH

Answer 1683

DIAGNOSIS - PCR of blood -> insensitive due to low blood rickettsia levels - Serology using indirect fluorescence -> highly sensitive but takes 4 weeks to become reliably positive - On lab features/clinical suspicion -> ALT deranged, thrombocytopenia, anaemia, leukocyte changes TREATMENT - Doxy 100mg BD - second choice is chloramphenicol

Answer 1684

Haemophagocytic lymphohistiocytosis - Macrophage activation syndrome - 3 F's: FEVER, FALLING blood cell COUNTS, hyperFERRITINAEMIA - Can lead to multi-organ failure and death Causes: Primary Secondary: TB, herpesviruses, endemic mycosis, leishmaniasis Diagnosis: Difficult as symptoms overlap with lots of infections anyway Think delayed defervescence or severe disease Can calculate H score Tx often with anakinra but can cause neutropenia

Answer 1685

Suppressed cellular immunity eg people living with HIV Pregnant patients after the first trimester Patients with African or Filipino ancestry CNS disease: young white men disproportionately affected

Answer 1686

Insidious progressive parameningitis => persistent global headache N&V&change in mental status Meningism Hydrocephalus Most occur within 6 months of primary resp infection

Answer 1687

Sickled cells Target cells Howell-Jolly bodies Polychromasia Nucleated red cells

Answer 1688

CMS is caused by damage to the spinal cord segment Th12 to nerve root S5, while CES is caused by damage to nerve roots L3–S5

Answer 1689

Cirrhosis secondary to hepatic pathology Hepatosplenic schistosomiasis Hepatoma Amoebic liver abscess Congestion due to right heart failure

Answer 1690

Pericardial effusion - low BP - distension of jugular veins - muffled heart sounds

Answer 1691

Pulsus paradoxus Tachycardia Syncope Hypotension

Answer 1692

1) Incubation - 6-12 weeks whilst worm makes way to liver (migration through intestinal wall, peritoneal cavity, liver capsule and parenchyma) 2) Acute/invasive - Weight loss - Intermittent fever - Abdominal pain - Malaise - Urticaria - Resp symptoms 3) Latent - Deposition of ova in CBDs ova appear in stool 3-4 months after ingestion of metacercariae Progressive resolution of GI and resp symptoms 4) Chronic/obstructive - Cholangitis - Cholecystitis - Liver abscess - Biliary obstruction - Cholelithiasis

Answer 1693

Stop the cause eg drug Topical antiseptics , IV Abx if systemically unwell IVF +/- electrolyte support Nutrition eg consider NG tube + NaCl mouthwash Pain relief Consider catheter to prevent urethral structures Topical Abx for eyes as conjunctivitis common and early opthal review as can get scaring and blindness

Answer 1694

Avoid consumption of Lathryus sativus ie grasspeas Use metallic cooking utensils rather than clay pots to avoid accrued toxicity from iron-induced oxidation Add anti-oxidant seasonings Soak seeds in lemon water Avoid unripe seeds

Answer 1695

Sensorineural hearing loss Diffuse encephalopathy Rarer: Cerebellar, brain stem, extrapyramidal manifestations eg parkinsonian tremor

Answer 1696

Tuberculous spondylitis Tuberculous spondylodiscitis Epidural and paraspinal abscess OTHER - Tuberculous radiculomyelitis - Tuberculois myelitis - Intramedullary tuberculoma

Answer 1697

Pressure sores -> education and two hourly turning Urinary retention -> catheterisation Contractures -> physio + train guardians Pain -> analgesia Depression -> tx/spiritual care etc Immobilisation -> walking aids/wheelchairs

Answer 1698

Vertebral collapse or dislocation Pus accumulation Caseous granulation tissue accumulation

Answer 1699

Wedging Focal areas of erosion Osseous destruction in anterior corners of vertebrae involvement of adjacent disc or vertebral body gibbus deformity paraspinal abscess formation

Answer 1700

Toxaemia GI haemorrhage Intestinal perforation Myocarditis

Answer 1701

Septicaemia Facial nerve palsy Rupture into Auditory canal Osteomyelitis

Answer 1702

Septicaemia Facial nerve palsy Rupture into Auditory canal Osteomyelitis

Answer 1703

Bacterial: - Burkholderia pseudomallei - strep pyogenes - Staph aureus - H influenzae In neonates: gram neg is a risk In HIV positive: strep pneumoniae Viral - Mumps (usually bilateral) - influenza A - parainfluenza - CMV - EBV - Enterovirus Mycobacterium - TB - M avium intracellulare

Answer 1704

Bacterial: - Burkholderia pseudomallei - strep pyogenes - Staph aureus - H influenzae In neonates: gram neg is a risk In HIV positive: strep pneumoniae Viral - Mumps (usually bilateral) - influenza A - parainfluenza - CMV - EBV - Enterovirus Mycobacterium - TB - M avium intracellulare

Answer 1705

Listeria monocytogenes (is the patient pregnant) S pneumoniae Group A strep Staph aureus Non-typhoidal salmonellae Salmonella typhi E Coli Haemophilus influenzae

Answer 1706

Listeria monocytogenes (is the patient pregnant) S pneumoniae Group A strep Staph aureus Non-typhoidal salmonellae Salmonella typhi E Coli Haemophilus influenzae

Answer 1707

brownish round thick-walled multi-septate sclerotic cells if add KOH -> hyphae more easily visualised

Answer 1708

Ideally multi drug therapy but expensive and long course required Itraconazole + terbinafine or flucytosine 6-12 months minimum Possibly years if extensive and chronic

Answer 1709

Fonsecaea Phialophora Cladophialophora

Answer 1710

fever, anaphylaxis or late serum sickness-like reactions as contains non-human hyperimmunoglobulin

Answer 1711

Contact with urine of infected mammalian hosts, animal abortion products, or contact with contaminated water

Answer 1712

Some directly affected the heart Others can drive eosinophilia which causes endomyocardial fibrosis

Answer 1713

Non-specific urticaria Calabar swellings in loiasis Cysticercosis Larva currens in Strongyliasis Infection with Mansonella perstans More commonly in Asia: Gnathostomiasis Sparganosis

Answer 1714

Small Unsheathed Blunt tail

Answer 1715

May present solely as anaemia

Answer 1716

Need 2/5 1) Follicles on tarsal conjunctiva 2) Conjunctival scarring of upper tarsal conjunctiva 3) Limbal follicles (edge of cornea) or Herbert's pits 4) Fibrovascular pannus mostly affecting upper cornea + ingrowth of fibrovascular tissues 5) Trichiasis on upper lid

Answer 1717

Once started on ART and immune reconstituted- same for other immunocompromised states. If HIV VL high at time of vaccination then immune response may be hampered.

Answer 1718

TB (often can be smear negative) PCP KS (look for skin manifestations) Pulmonary malignancy Pulmonary sarcoidosis

Answer 1719

Mild cough with reduced production Rare to have haemoptysis No cavitation on CXR but may have infiltrates, hilar lymphadenopathy, miliary TB Sputum may be negative Extrapulmonary and disseminated TB is common ie 50%

Answer 1720

Agar plate method Baermann technique for rhabditiform larvae

Answer 1721

Periductal fibrosis Gallstones Cholecystitis Cholangiocarcinoma High in greater Mekong subregion ie Thailand, North Vietnam, Cambodia, Loas Also in Southern China Korea Kazahstan Siberia

Answer 1722

Likely to be infectious TB Bacterial eg Staph aureus, pyogenic and non-pyogenic strep, gram negative bacteria Spinal brucellosis Histoplasmosis Actinomycosis Melioidosis Ix: CT-guided percutaneous vertebral biopsy and subsequent tissue culture and molecular analysis

Answer 1723

Acute: blood culture Chronic/tissue infection: tissue culture

Answer 1724

doxycylin aminoglycoside (streptomycin or genta- micin) plus rifampicin In neurobrucellosis, ceftriaxone doxycyclin rifampicin If contraindications occur, ciprofloxacin and cotrimoxazole may be used. Treatment duration: 6weeks - several months depending upon organ manifestation and severity

Answer 1725

Nonmotile gram negative coccobacillus

Answer 1726

Individuals with high cell-mediated immunity develop tuberculoid leprosy or borderline tuberculoid leprosy with one or a few hypopigmented anaesthetic skin patches and thickened peripheral nerves. Bacteria are usually not seen in the skin biopsies or slit-skin smears of these individuals. Individuals who do not mount a cell-mediated response to M. leprae develop lepromatous leprosy with infiltration of the skin and many skin lesions. These individuals have lots of bacteria in their skin and nasal secretions.

Answer 1727

Streptococcus suis Leading cause of acute bacterial meningitis in Vietnam

Answer 1728

Guillain Barre Syndrome Post-vaccination encephalomyelitis NMDAR antibody-mediated/Autoimmune encephalitis Campylobacter-associated summer paralysis syndrome Cerebral malaria Herpes simplex encephalitis Arthropod-borne encephalitides (e.g. Japanese encephalitis, West Nile Virus encephalitis, etc.) Poliomyelitis B-virus (Cercopithecine herpesvirus 1) encephalomyelitis Tetanus Snake- or Scorpion-envenomation Organophosphate poisoning Illicit drug use, CNS intoxicants Psychiatric disorders

Answer 1729

Cowpox (usually singular lesion and no fever/LN) Varicella (longer incubation ie 14 days + rather than 6-14 days, usually multiple lesions in multiple stages of development and non-uniform, no lesions normally on palms/soles )

Answer 1730

Human to human through - respiratory route - contact with an infected person’s bodily fluids eg saliva and respiratory secretions or contact with exudate or crust material from the skin lesions Risk factors for transmission - sharing a bed or room or using the same utensils as an infected person

Answer 1731

If severe => admit, ICU support for airway protection, diphtheria antitoxin, erythromycin or procaine penicillin 14D Contacts/healthcare workers caring for patient - Erythromycin 7-10D 500mg QDS - Booster of vaccine TadP if needed

Answer 1732

The severity of systemic complications is directly proportional to the extent of local disease and includes myocarditis and neuritis. Myocarditis may present as arrythmias including complex heart blocks, cardiac failure and cardiogenic shock. Neuropathies include paralysis of the soft palate and posterior pharyngeal wall, followed by cranial neuropathies and late onset peripheral neuritis. Cutaneous diphtheria may often present as a shallow ulcerative lesion with a grey-white membrane.

Answer 1733

Ross river virus

Answer 1734

acute febrile illness accompanied by fatigue, myalgia, a maculopapular rash (lasting 5–10 days) and debilitating symmetrical polyarthritis primarily affecting peripheral joints including the wrists, fingers, ankles and knees. Similar to other alphaviral infections, the polyarthralgias characteristically persist for several weeks to months beyond the acute phase of the infection