Small group Flashcards
Yellow Fever Summary
Flavivirus. Vector: Aedes aegypti – bites different people to get a full meal, day-biting, very hardy mosquito. South America and Africa. Majority get asymptomatic disease, 20-30% will develop symptoms, most of the illnesses are self-limiting viral illness (fever, chills, myalgia), small number have severe disease with mortality 20-50% with no treatment – jaundice, haemorrhagic disease, DIC
Yellow Fever Vaccine Summary
Live. Recognised potential serious adverse events: 1 Viscerotropic yellow fever disease post-vaccination ~1/200,000 regardless of immune function. 2 - Anaphylaxis 1/1,000,000 3 - Neurotropic yellow fever disease post-vaccination ~1/200,000 and is completely reversible.
Yellow Fever Vaccine Contraindications
Contraindications: - Absolute: Immunocompromised, HIV if CD4<200, athymus. - Relative: Young infant 6-9m, pregnant and elderly(>60) 1/50,000 patients. Indications for use:
Yellow Fever Vaccine indications
Travel to endemic areas: Protecting the country not the traveller, ensuring there is no cases brought into the country
Yellow Fever Strategies
Different strategies in protecting the traveller vs programmatic vaccination vs outbreak situation. Individual: DEET, clothes covering. Vaccination in endemic countries – at the same time as MMR ~12m, if vaccine before 2yo, there is an indication for re-vaccination to make the duration lifelong. Outbreak situation: Difficult to make the vaccine, need eggs to produce, cold chain, only certain amount. Give 20% of the dose to give more people a shorter cover
Dengue Summary
Flavivirus, 4 serotypes. Vector: Aedes aegypti. Epi: Widespread along equator. Most infections are asymptomatic, some fever, rash, severe dengue thrombocytopaenia, capillary leakage. Recognised potential serious adverse events: Secondary infection with the same serotype, Antibody enhancement reaction. Third and fourth infection are usually mild. Immunity is lifelong for the serotype, so greatest risk is with the second exposure
Dengue Vaccine
Dengvaxia – single dose, YF backbone, Qdenga 2 doses, dengue backbone with cover for 4 serotypes, Countries like Brazil are trying to cover the country with vaccination
Zika Summary
Flavivirus. Vector: Aedes aegypti. Majority asymptomatic. South America Brazil outbreak of MTC with congenital disease. Prevention: avoid bites, no vaccine. If planning pregnancy: don’t travel to endemic area. Avoid pregnancy for 2m if only woman travelled, 3m if both/male partner travelled. If already pregnant: use barrier contraception. If living in an endemic country - mosquito avoidance
Diarrhoea Rainy season transmission
Possible increased transmission in rainy season: vector borne diseases where vector uses surface water for breeding (malaria, dengue). Diseases of inundation (leptospirosis). Faecal-oral transmission (risk of overwhelming sanitary facilities). Diseases of fresh water contact (Schistosomiasis)
Diarrhoea Leptospirosis Philippines
Seasonal peak during the rainy season. Thousands of people displaced and housed in emergency evacuation centres during typhoon
Diarrhoea Epidemic curves
Point source (up then down - ie hepatitis A, norovirus - vast majority of cases occur within a single incubation period), Continuous source (up then plateau ie water pump contamination). Person to person (up then down, then up with more, then down, then up with even more - although in reality, these often coalesce)
Diarrhoea Occurrence over 2 weeks period
Suggests either: a long and variable incubation period (unlikely as diarrhoeal illnesses typically have short incubations). A common, contaminated source for transmission (possible), ongoing person-to-person transmission (most likely)
Diarrhoea Stool microscopy
Inflammatory cells (red and white cells). One case has cysts of E histolytica ?significant
Diarrhoea Causes of diarrhoea with blood
Bacteria (Salmonella, Shigella, Campylobacter, E coli, Yersinia, Plesiomonas, C difficile), Protozoa (E histolytica, Balantidium coli, Malaria), Helminths (v heavy Trichuris), intestinal Schistosomiasis. Viruses (VHF esp Lassa, Marburg), Non-infectious (Inflammatory bowel disease, ischaemic colitis, radiation colitis, bowel cancer, vasculitis - all very unlikely to cause 150 cases in 2 weeks)
Diarrhoea Person-to-person spread causes
Shigella, E coli (sometimes) VHF
Diarrhoea Case management
Triage and prioritise: A send home with ORS, B at extreme risk admit, resuscitate and isolate (exclude malaria), C concerning, may be septic, resuscitate. Need an effective treatment
Diarrhoea Issues in case management
Identify high risk patients (malnourished, extremes of age, seriously ill, dehydrated, or septic), continue feeding/breastfeeding. Correct dehydration with ORS. Give an effective antimicrobial in appropriate doses. Avoid antdiarrhoeals (they are harmful), arrange to review. If an effective antimicrobial is in short supply, it may need to be reserved for high risk patients, such as those with severe or complicated disease, and milder cases managed with supportive care alone. If an effective antimicrobial is given it is reasonable to expect improvement within two days.
Diarrhoea Resistant Shigella
Resistant to all available antibiotics in LMIC except gent, however gent is typically ineffective even when Shigellae are sensitive to it, likely because of poor intracellular penetration. Quinolones such as ciprofloxacin are likely to be effective. Third generation cephalosporins (CRO) are widely used and relatively cheap (but concerns re AMS) Nalidixic acid is the cheapest quinolone regimen which is likely to be effective, but resistance has emerged rapidly under these circumstances. The story given suggests a large scale epidemic of dysentery in an LMIC setting. The main cause of these epidemics is Shigella dysenteriae type 1 which in recent years has affected Central America, South Asia and central and southern Africa. Most LMICs are at risk. The other Shigella serogroups (S flexneri, S sonnei, and S boydii), in contrast, cause milder disease are less often associated with fatal complications, are not associated with large scale epidemics and are less likely to exhibit antimicrobial resistance, although recently there has been MDR S flexneri epidemic in MSM
Diarrhoea E histolytica cysts
The finding of entamoeba cysts during episodes may lead to incorrect diagnosis and treatment. E histolytica trophozoites containing ingested RBC indicate amoebic invasion, typically amoebae do not elicit an inflammatory response and so WBCs are usually not seen in the stool in amoebic dysentery. E histolytica cysts in stool of patients with blood diarrhoea in an epidemic indicate neither that E histolytica is causing the epidemic nor that it is causing dysentery in the individual. Historically this finding led to confusion about the cause of dysentery epidemics and the treatment of dysentery cases with metronidazole which is ineffective against Sd1 and resultant continued transmission and excess mortality
Diarrhoea Shigella complications
The hazards are invasive disease leading to sepsis, dehydration (especially in children and those who are vomiting), intestinal perforation and local and remote effects of toxin (eg haemorrhagic colitis, renal failure, DIC). Febrile convulsions may occur in children. Potassium depletion may be quite severe in shigellosis, though marked dehydration is quite unusual. Hypokalaemia can be prevented by replacing faecal losses with ORS solution, and giving potassium-rich foods, such as bananas or green coconut water.
Diarrhoea HUS
Haemolytic uraemic syndrome may follow infection with Sd1 or E coli O157:H7. The classic triad of symptoms is haemolytic anaemia, thrombocytopaenia and renal failure. HUS may be mild, with rapid recovery, or severe, with kidney failure. Haemodialysis may be required if available. Clotting abnormalities can cause bleeding, and the red blood cell count may be low. Transfusions of whole blood or platelets may be needed in severe cases. With adequate treatment, many HUS patients never recovery fully. HUS should be suspected when a dysentery patient develops easy bruising and has little or no urine output. The diagnosis of HUS can be made by the following: 1 a low haematocrit 2 a blood smear showing fragmented RBC 3 a low platelet count, or platelets not seen on the blood smear, or 4 raised urea or creatinine (unavailable in many rural settings). If HUS is diagnosed, stop giving potassium-rick foods or fluids, including ORS solution, and refer the patient for hospital management if facilities are available.
Diarrhoea Shigella and E coli
Recent genomic studies suggest that shigellae should probably be classified as pathogenic strains of E coli. Extremely similar genetically. They share an invasion phenotype with EIEC. Share a large virulence plasmid Pinv A or B acquired by horizontal transfer. Shigella and EIEC evolved from the same ancestor and form a single pathovar within E coli. Biochemical differences between strains induced by minor genetic variants. Shigella strains are nonmotile as a result of minor changes - deletion in the fliF operon (flagellar coding region) or an ISI insertion mutation in the flhD operon. Shigella is an E coli…
Diarrhoea Priorities
Prevent transmission in the health centre. Educate staff and patients. Combat fear and rumour. Use local politics/structure for health education messaging.
Diarrhoea Control of Sd1 epidemics
Sd1 is an exclusively human pathogen acquired through contact with an infected case, or through eating or drinking contaminated food and water. Measures such as handwashing with soap, breastfeeding, food safety, safe drinking water, treatment of stored or piped water, safe disposal of human excreta, disinfection of clothing and safe disposal of bodies, fly screens, may be usefully promoted in health education messages. Prophylactic antimicrobials are not indicated. There is a useful document from the WHO website called ‘Guidelines for the control of Shigellosis, including epidemics due to Shigella dysenteriae type 1’
Diarrhoea VIP latrine
Ventilated improved pit latrine. Pipe doubles the cost. Flyscreen at the top, cannot get out of vent pipe. Two important features: need to be on a mound of earth so it does not flood when it rains. For the air to circulate properly, need to face the prevailing wind. Do not have a seal at the bottom and it should sink away.
Diarrhoea Water
if not fortunate, you go to the well to fill up your container of water. Water storage container can become a common contaminated source. One drop of commercial bleach can work - not enough to taste or harm people. Water and sanitation practices - modifiable and vulnerability to outbreak can be improved
Transient migratory lesions Differential diagnosis of Eosinophilia
Parasites, chronic allergy, haematological malignancy, autoimmune, vasculitidies, fungal (cocci)
Transient migratory lesions Differential diagnosis
Loa loa, gnathostoma, sparganum, another lost parasite
Transient migratory lesions Loa loa
Classically eye, Calibar swellings (esp wrists and ankles - it gets stuck at bony prominences) Geographically limited distribution: Central Africa - Equatorial Guinea, Cameroon, Central African Republic, Gabon, Congo. Transmission: Chrysops
Transient migratory lesions Gnathostoma
Ingestion of rare fish/reptiles or paratenic host. Rapid onset of symptoms. Painful hot red migratory lesions. Short and stubby worm ~2cm with a crown of spikes that can burrow through muscle tissue. Can cause eosinophilia and muscle necrosis. Global distribution
Transient migratory lesions Cutaneous larva migrans
Hook worm, including A braziliensis/A canis (zoonotic ones that get stuck in dermis of humans)
Transient migratory lesions Investigations
Filaria and gnathostoma serology, day and night bloods, US or MRI of lesion. Caution using ivermectin in loa loa endemic regions. Serology unreliable - lots of cross-reaction. Filarial films (night Wb Bm, Day Ll)
Histoplasmosis Epidemiology
Geographical distribution: East coast of Northern and South America, Sub-Saharan Africa, SE Asia, East Australia.
Histoplasmosis Diagnosis
Culture slow (need CL3 lab), Microscopy: looks like WW1 sea mines. BDG and AspAg will be positive. Serology - less useful in HIV/disseminated disease. Ag testing in blood/urine may be available. Often mistaken for TB, and can be disseminated in advanced HIV.
Histoplasmosis Treatment
Disseminated: Amphotericin. Localised, pulmonary: Itraconazole
Histoplasmosis Differential diagnosis
Talaromyces (SE Asia), Blastocystis (Nth America). In South East America, cases of histoplasmosis in advanced HIV are more common than TB
Fasciola Summary
Worldwide distribution. Zoonosis - cattle parasite (big and designed for cattle) Humans are accidental host - ingest cercariae on unwashed salad vegetables (water cress). Move through liver parenchyma causing damage, but generally not further due to large size. Acute infection: usually have eosinophilia, may have positive serology, negative OCP. Chronic infection: usually have positive serology, may have eosinophilia, intermittent eggs in stool. Treatment: triclabendazole (with buscopan and analgesia as it can be uncomfortable)
Fasciola Amoebic liver abscess
Mexico, Indian subcontinent, can cause acute dysentery, may cause an acute liver abscess. Usually circumscribed, can be massive. Rx metronidazole (melt away)
Fasciola Opisthorchis
Kazakhstan, Eastern Europe, much smaller ~1cm, much smaller operculum
Fasciola Clonorchis
East Asia, Siberia, Vietnam, SE Asia (more common) - fewer symptoms as much smaller, associated with undercooked fish
Fasciola Opisthorcis/clonorchis
Chronic biliary inflammation -> risk factor for cholangiocarcinoma (diagnosed late with very poor outcome), risk in China. Rare to present with acute symptoms as the smaller worms cause much less damage.
Mycetoma Summary
Chronic barefoot exposure, soil is packed with fungi. Microabrasions, microinoculations accumulate over a period of time. Mycetoma belt: North and South America, Central/West/East Africa, South Asia. Triad of signs: tumour (swelling), tracts, grains. Complications: disfiguring, social isolation, economically and socially disadvantages the poor. Treatment: months-to-years of Itraconazole, voriconazole (levels/monitoring challenging), surgery often ineffective (tends to relapse due to microabscesses left behind). Most ‘tropical’ diseases are diseases of poverty
Mycetoma Differential diagnosis
Madurella mycetomatis (single most common fungal cause of mycetoma), Actinomycosis (actinomycetoma), podoconiosis, TB, bacterial OM, cutaneous leishmaniasis. NTM
Malaria Diagnostics
Blood films: speciation, parasitaemia estimation. RDTs: sensitivity comparable to blood film, don’t need to be an expert, semi-speciation
Malaria Child assessment
Take ABCDE approach: A airway, B RR & SaO2, C HR BP, D GCS & signs of seizure, E check for other signs of severe malaria
Malaria Severe malaria criteria
CNS: coma/convulsions, Lungs: ARDS (adults), Respiratory distress or acidosis (children) Kidney: AKI, Shock, Hypoglycaemia (previously SE of quinine), Severe anaemia (children), Hyperparasitaemia 10% in WHO guidelines (2% in HIC settings)
Malaria Blantyre coma score
Motor: 2 localises pain, 1 withdraws from pain, 0 no/abnormal response. Verbal: 2 normal cry, 1 abnormal cry, 0 no cry. Eyes: 1 normal (tracking), 0
Malaria ACTs
ACT = Artemisinin Combination Therapy. Two (or maybe now 3) drugs in a single tablet. Main drug = an ‘artemisinin’ (artemether, artesunate, dihydroartemisinin) with combination drug = there to protect the artemisinin (mefloquine, piperaquine, lumefantrine) - first line drug for immediate treatment of all species of malaria. Artemisinins reduce parasitaemia very rapidly - everyone clears their parasitaemia by day 3. They kill more blood stages of the parasite and is probably why they are more effective. Quinine takes day 4 for 50% clearance, day 7 for complete clearance
Malaria Severe malaria features
Schizonts not usually seen in peripheral blood as is usually stuck to a capillary. If capillaries are full and schizonts leaking into blood, there is generally a severe infection. Sequestration, predominantly though to be mediated by PfEMP1 (Pf erythrocyte membrane protein) mediate binding in different parts of the body - if bind in brain -> cerebral malaria, if bind in bone marrow - anaemia, lung -> ARDS (but these are not well understood outside of brain and placenta) Malaria is more severe in first pregnancy, then slowly develop antibodies to the antigen that mediate binding to the placenta (gross simplification). Noone has ever shown that any drug that targets any of the putative mechanisms of cerebral malaria have any adjunctive benefit (and some increase mortality).
Malaria Treatment of severe
Artesunate and Ceftriaxone. Artesunate is the mainstay drug (can be given IV or rectally or IM but absorption not good). This has replaced quinine as the drug of choice. SEAQUAMAT and AQUAMAT demonstrated mortality benefit of artesunate compared with quinine. After initial artesunate switch to an ACT to finish treatment, PLUS careful fluids, strongly consider empiric antibiotics. Bacterial infections - classic association with non-typhoidal Salmonella, in severe disease often given broad spectrum Abx alongside antimalarials
Malaria Fluids
FEAST trial shows excess mortality with bolus-based fluids in children. High lactate/lowish BP is pretty common. Much of this is due to sequestration not classical hypotension. Giving fluids therefore doesn’t really help. Excess fluids plus endothelial dysfunction = BAD
Malaria Haemolysis post-artesunate
1-3 weeks after artesunate, 7-22% incidence. Haemolysis of previously infected RBC. Proportional to parasitaemia. At 2-3 week Hb check if >10%. With quinine it takes several days to work, this gives the spleen time to clear damaged RBC as opposed to artesunate - salvage more cells, but they can haemolyse later. Lose the same amount of blood with artesunate as quinine - but it happens more slowly in quinine.
Malaria HRP2 deletion
Most RDTs detect an antigen called ‘histadine rich protein 2’. This is the P falciparum specific antigen. This has generated considerable selection pressure on P falciparum > deletions of this gene are now emerging globally (ie Eritrea and Peru >20%). WHO says if ?5% should switch, btu unclear what to really do
Malaria Treatment failure
Causes: poor compliance, counterfeit drugs, drug resistance, another diagnosis. Delayed parasite clearance common in parts of SE Asia. Associated with pf13k (kelch)mutations. Increasing in Africa. This is a ‘reduced effect’ rather than a true resistance - the response slows out to the clearance time associated with quinine - the drug still works, but just need to give it for longer. What to do: treat for longer, dihydroartemisinin-piperaquine, watch out for recrudescence, triple artemisinins…
Malaria Pregnancy
WHO now recommends ACTs in pregnancy in ALL trimesters.
Malaria P vivax
Initial treatment of ALL species is with an ACT. P vivax infection -> hypnozoites in the liver. Without specific treatment these lead to recurrence. Only 2 effective drugs: primaquine and tafenoquine. Both drugs can cause haemolysis. Need to assess G6PD prior to treatment.G6PD is not a single disease, there are different levels, and if you have >30% G6PD activity then primaquine is pretty safe. Tafenoquine is long-acting primaquine - the issue is that in most parts of the world it is difficult to access G6PD level, and at least with short-acting primaquine, if someone starts haemolysing you can stop it. Study looking at clearance in high Pv setting. In those who had primaquine - 10% change of infection, in those with placebo 50% - which shows that the vast majority of vivax in this context are recurrences from liver.
Malaria Summary
Management of malaria relies on: assessment of the patient for markers of severe disease, RDTs/blood films for speciation +/- assessment of parasitaemia, ACTs are the first line drug for all individuals and all species with non-severe malaria. Artesunate (+/- antibiotics) is the first line for individuals with severe malaria. Drug resistance is emerging, esp in SE Asia. Pv and Po treatment is also needed for hypnozoites with assessment of G6PD activity. Remember you do not need to have hyperparasitaemia to have severe malaria - the percentage is just one measure of severity, don’t forget the clinical features
NTDs Assessing a child
What else would you like to know: has he received treatment elsewhere, immunisations and growth chart, is the mother well? Any other illness in the family?
NTDs Measles
Mouth: Koplik’s spots. Hepatosplenomegaly. Lymphadenopathy. Desquamating rash after measles. Complications: bacterial pneumonia, malnutrition (may be severe = Kwashiorkor), blindness. Management: Vitamin A (time to discharge and mortality significantly lower if given), antibiotics (reduced incidence of pneumonia and conjunctivitis, greater weight gain after one month). Measles mortality is 100x higher in Africa compared with Europe due to malnutrition, lack of access to care for secondary infections, overcrowding
NTDs Sickle cell
Sickle cell disease with hand-foot syndrome. Sickle crisis can cause painful necrosis of hand and feet. HbF protects from this initially, often present after 6m. Management: keep warm, analgesics, oral fluids++, antibiotics to cover S pneumo, H influenzae, non-typhoidal Salmonella, folic acid, immunisations (S pneumo, H influenzae), long term penicillin and antimalarias, education for parents. Repeated infarctions of the small bones causes significant deformity. Hydroxyurea reduces the incidence of vasoocclusive events, infections, malaria, transfusions and death in sub-Saharan Africa
NTDs TB adenitis
Painless swelling of neck, Scrofula, Diagnosis: LN aspirate and direct smear. Probably from drinking cattle milk (unpasteurised)
NTDs Congenital syphilis
Was responsible for 50% stillbirths in Mwanza, where prevalence of syphilis was about 6% in ANC attenders. Rash on palms of hands is syphilis until proven otherwise. More babies in Africa die from syphilis than those that die from HIV. Can be prevented with a single dose of benzathine penicillin delivered before third trimester. One of the most cost-effective health interventions. Symptoms: blistering rash, hepatosplenomegaly, chronic nasal discharge, palmar rash, osteitis (periosteal inflammation - responds to penicillin). Management: healthy infants born to seropositive mothers should receive benzathine penicillin 50,000 units/kg IM stat. Infants born with signs of congenital syphilis should receive procaine penicillin 50,000 units/kg daily IM x10.
NTDs Burkitt’s lymphoma
B cell lymphoma, associated with malaria and HIV. B lymphocytes proliferate to EBV, in setting of malaria T cell function is impaired, and the B cells proliferate for longer, mutation in the B cell causes the malignancy. Diagnosis confirmed by needle aspirate. Management - single dose of cyclophosphamide, vincristine and methotrexate IV, intrathecal methotrexate, beware of tumour lysis syndrome. Repeat every 2-3 weeks for at least 2 courses beyond clinical remission
NTDs Tumbu fly
Cutaneous myiasis. Vaseline suffocates the maggot - it sticks its head out, and then is removed. Prevent by ironing sheets and clothes - flies may maggots on the washing hanging on line
NTDs Cutaneous larva migrans
Hookworm - Ancylostoma canimus, self-limited. Cat and dog hookworm cannot get through the human dermis
NTDs Mycetoma (Madura foot)
Caused by either Bacteria (actinomycetes) or Fungi (Madurella mycetomatis). Starts as a painless subcutaneous nodule, progresses to multiple discharging sinuses. Black grains in the pus suggest fungal infection, red grains suggest actinomycetes. Diagnosis confirmed by microscopy or culture.
NTDs Melioidosis
Burkholderia pseudomallei, humans are infected by inoculation or contamination of wounds or mucosal surfaces by infected soil or water. Clinical features: may be a long latent period, may be localised to the lung and mimic TB, or cause osteomyelitis or abscesses in a wide variety of organs. May cause a severe sepsis syndrome with high mortality. Diabetes, renal impairment and cirrhosis are risk factors for severe disease (HIV is not). Diagnosis: culture (or serology). Treatment IV ceftazidime for 2 weeks followed by oral SXT 3-6 months
NTDs Borderline lepromatous leprosy
Treatment: Rifampicin monthly, Clofazimine 300mg monthly and 50mg daily, Dapsone 100mg daily. Patients should be warned about possible reactions and told to return immediately if they develop new neurological symptoms
NTDs Human African Trypanosomiasis
T brucei rhodesiense (acute onset, zoonosis, blood film usually positive). T brucei gambiense (insidious onset ‘sleeping sickness’, no confirmed animal reservoir, POC screening test available)
NTDs African Tick Typhus
Rickettsia africae, transmitted by cattle ticks (Amblyomma sp). Clinical features: eschar, rash (50%), regional lymphadenopathy. Diagnosis: PCR or serology. Treatment: Doxycycline 5d
NTDs Loa loa
Vector: Chrysops flies. Diagnosis: history, blood film for microfilaria. Treatment according to microfilarial load: low DEC for 3 weeks, moderate: ivermectin stat, then DEC 3 weeks. High :albendazole 3w with initial steroid cover, then DEC 3 weeks.
NTDs African Histoplasmosis
Histoplasma capsulatum var duboisii. Isolated from LN aspirate from a Belgian man in Congo with cervical and axillary lymphadenopathy. Clinical features differ from those caused by H capsulatum capsulatum - lung involvement uncommon, may cause localised or disseminated disease, characteristic skin lesions, bone an dLN commonly involved, unlike Hc capsulatum, it is not associated with HIV. In culture morphologically and antigenically identical to H capsulatum. Treatment: Itraconazole or Amphotericin, significant risk of relapsing disease.
NTDs Meningococcus
Major epidemics every few years in the ‘meningitis belt’. Always in the dry season. Can be treated with a single dose of CRO or long-acting oily chloramphenicol. Very high prevalence of nasal carriage. Traditionally caused by N meningitidis serogroup A, but recent outbreaks due to other serotypes. Conjugate vaccines are highly effective.
NTDs Leptospirosis
Zoonotic infection, many animal species infected. Caused by Spirochaetes of genus Leptospira, many species of Leptospira, each with a different animal host. Humans are infected through contact with animal urine. Bacterial can penetrate intact skin. Clinical features: Mild >90% (fever, headache, myalgia - often self-limiting), Moderate ~9% (sudden prostration, muscle tenderness, conjunctivitis, jaundice, pneumonitis), Severe (Weil’s disease, <1%) (almost always L icterohaemorrhagiae, acute hepatic and renal failure, extensive haemorrhage, myocarditis, 10% mortality). Diagnosis Spirochaetes may be seen in urine under dark field microscopy, Serology (microscopic agglutination test), PCR of blood or urine. Treatment: penicillin, amoxicillin, cephalosporins, macrolides, and tetracyclines all effective
NTDs Yaws
Non-venereal treponematosis: Treponema pallidum subsp pertenue, spread by skin to skin contact. Primary, secondary and tertiary stages, mainly affecting skin and bones. Management: benzathine penicillin 50,000 units/kg IM stat, or Azithromycin 30mg/kg (max 2g) stat
NTDs Massive tropical splenomegaly
Differential diagnosis: lymphoproliferative disorder, tropical splenomegaly syndrome (TSS - hyper-reactive malarial splenomegaly), visceral leishmaniasis, portal hypertension due to (Schistosoma mansoni, cirrhosis secondary to chronic HBV), TB, Brucellosis
NTDs Kwashiorkor
Management: warm, insert nasogastric tube, give F75 formula milk 2-hourly (contains vitamin A, folic acid, zinc and copper), ReSoMal (low sodium) oral replacement fluid while diarrhoea continues. Correct electrolyte imbalance (K+ supplements), start a broad spectrum antibiotic. Later management: catch-up feeding (switch from F75 to F100), love, stimulation and play, appropriate discharge planning
South America Diseases not seen
Never: Japanese encephalitis, Loa loa, Lassa, Ebola, HAT, Schistosoma haematobium. Very rarely: Onchocerciasis (only on border of Venezuela and Brazil - Venezuela has government and healthcare issues, the indigenous population of the region are not covered by public health), Schistosoma mansoni (only in a few areas of East Coast, mainly Brazil)
South America Usual tropical diseases seen
Arboviruses (Dengue, Zika, Chikungunya, Yellow fever), HIV, TB (think MDR), Leptospirosis, Brucellosis, Enteric fever, Hantavirus, Amoebic dysentery and ALA (patients can be quite toxic and unwell, and often don’t have preceding dysenteric illness), Fascioliasis (common in rural communities in high Andes 60-70% seropositive), Giardiasis, Buruli ulcer (Amazon basin), Leprosy (Brazil)
South America What’s special about Central and South America
Trypanosoma cruzi (esp in HIV or immunosuppressed - present like cerebral toxo), Endemic mycoses (Histoplasmosis esp in HIV, Coccidiodomycosis, Paracoccidiodomycosis), Leishmaniasis (mostly cutaneous, visceral is rare). Rare: Carrion’s disease (Oroya fever - Peruvian warts), Bolivian haemorrhagic fever, Oropouche
South America Bolivian haemorrhagic fever
Machupo virus. Vector: large vesper mouse (corn rat). Epidemiology determined by range of reservoir and human movement, and is affected by humans encroaching on reservoir habitat (building road). Sudden high rate of death in HCW, exposure to body fluids, suspect person-to-person ie VHF. Rx Ribavirin (local MO believes it works)
South America Oropouche
Vector: Culicoides paraensis and Culex. Mild dengue-like disease (fever, myalgia, arthralgia, headache, rash), probably has been misidentified as dengue previously. More awareness = more testing = more diagnoses. Probably also affected by three RNA segment rearrangement
South America Endemic mycoses
May be overlooked because rare in immunocompetent. Systemic fungal infections are uncommon (1 infection often occurs in endemic areas, 2 most infections are asymptomatic or self-limiting, 3 in immunocompromised hosts, infections are more fatal). Infection requires a large inoculum and a susceptible host - natural immunity is high, physiologic barriers include 1 Skin and mucus membranes, 2 Tissue temperature - fungi grow better at less than 37oC, 3 Redox potential - in vivo conditions too reducing for most fungi. As these are in the environment they are impossible to eliminate. Even with a vaccine 100% effective with 100% coverage, it is unlikely to be eliminated due to constant exposure. Habitat in soil - outbreaks seen associated with natural disasters, building and construction work, farming
South America Coccidiodomycosis
Coccidioides immitis (Epi: Southern USA, Northern Mexico) “Valley fever” Symptoms: fatigue, fever and night sweats, weight loss, cough, chest pain, dyspnoea, haemoptysis, headache, arthralgia. Clinical: erythema nodosum, erythema multiforme. CXR: pulmonary infiltrates, hilar adenopathy, pleural effusions (can mimic TB)
South America Paracoccidiodomycosis
Paracoccidioides brasiliensis (Epi: Brazil). Prolonged soil contact (disease of rural poor, farmers. No significant person-to-person transmission). HIV (no demonstrated increased risk, but more severe disease, and increased risk of relapse). Clinical: fever, lymphadenopathy, hepatosplenomegaly, skin and oral mucosal lesions. Complications: respiratory, adrenal, neurological. Lung biopsy: ‘pilot wheel’ appearance of budding yeast. Treatment: Itraconazole. Complications: Significant residual pulmonary impairment (fibrosis in 50% treated patients), Adrenal involvement in 90% at autopsy (15-50% adrenal dysfunction, 5% Addisonian), Neurological disease associated with significant sequelae (raised ICP, epilepsy)
South America Chromoblastomycosis
Subcutaneous mycoses secondary to inoculation injury
South America Summary
Most of the usual suspects are found in tropical Latin America: Arboviral disease (YF, Chik, Dengue, Zika), leptospirosis, brucellosis, TB, leprosy, Buruli ulcer, Hantavirus, HIV, Amoebic disease, Fascioliasis, Giardia. But also think of: Endemic mycoses (coccidioides, paracoccidiodomycosis, histoplasmosis esp in HIV), Cutaneous leishmaniasis (crucial to speciate), Carrion’s disease (Bartonella bacilliformis), Chagas disease (Trypanosoma cruzi), and Bolivian haemorrhagic fever etc
TB Care Epidemiology/DR surveillance
9/30 countries with highest burden of MDR-TB are within European region: Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Republic of Moldova, Russian Federation, Tajikistan, Ukraine and Uzbekistan. Region has highest prevalence of new and retreated cases of MDR-TB: 16% of new TB and 48% of previously treated TB. XDR-TB is on the rise (?1 in 4 DR cases), but under-reported. ‘Chronic TB’ ‘Seasonal treatment’
TB Care Guidelines and SOPs
There are lots of guidelines. Example: 100 practitioners from single city in India asked to write a standardised prescription for TB. 80 different prescriptions. 6 judged as consistent with TB guidelines.
TB Care Active case finding
WHO recommendations: 1 general population prevalence >=0.5%, and 2 among subpopulations with structural risk factors (poor communities, homeless communities, communities in remote or isolated areas, indigenous populations, migrants, refugees, internally displaced persons and other vulnerable or marginalised groups with limited access to health care. 3 PLHIV should be systematically screened for TB at each visit. 4 Household contacts and other close contacts of individuals with TB, 5 Prisons and penitentiary institutions, 6 Current and former workers in workplaces with silica exposure, 7 In settings where the TB prevalence in the general population is 100/100,000 or higher, systematic screening for TB may be conducted among people with a risk factor for TB who are either seeking healthcare or who are already in care. 8 People with an untreated fibrotic lesion seen on CXR
TB Care TB preventive treatment
People with HIV (after active TB excluded). Household contacts of people with TB, Other people at risk (anti-TNFa, dialysis, organ/haem transplant, silicosis), consider for prisoners, HCWs, immigrants from endemic areas, homeless people, and people who use drugs. Test with TST or IGRA. Treatment options: 6-9m Isoniazid, 3m weekly rifapentine plus isoniazid, or 3m HR (daily), or 1m daily rifapentine plus isoniazid, or 4m daily rifampicin. In contacts exposed to MDR or Rif-resistant TB, 6m daily levo should be used
TB Care Clinical assessment
Sx and duration. Previous treatments. Contacts of drug-resistant TB. Comorbidities: malnutrition, HIV, DM, HBV/HCV. Medications (?any interactions), allergies. Pregnancy/breastfeeding status, birth control. EtOH, Social and financial situation. Treatment counselling. Weight.
TB Care Diagnostics/Laboratory support
Smear. Access to DST. Molecular (Xpert Ultra MTB/RIF 80min rpoB gene amplified - if not wild type likely to be rif resistant, Xpert MTB/XDR gives resistance to H, FQN, ETO and Amikacin, Line-probe assay (LPA) detects mutations commonly associated with resistance to Rif, H, FQN, injectables, mutation patterns inhA alone likely ok with high dose INH where katG mutation alone or with inhA isoniazid no longer effective). Culture based - phenotypic and WGS. Others: LFTs, renal function, BBV testing. Radiology.. If they are not culture converting - they are not taking it, not absorbing it, or they had become more resistant.
TB Care TB treatments including obtaining them
Drugs and regimens: 6m BPaLM/9M all oral/longer regimens. Consider drug availability, cost, quality, prescription not regulated, expiring drugs, disruptions in supply
TB Care Drug side effects
N&V (prothionamide, paraaminosalicylate, pyrazinamide), Gastritis/reflux (paraaminosalicylate, prothionamide), Diarrhoea (paraaminosalicylate), low potassium (capreomycin, kanamycin), Psychosis (cycloserine, isoniazid, fluoroquinolones, ethionamide, prothionamide). Depression (cycloserine, fluoroquinolones, isoniazid, prothionamide), Hypothyroidism (paraaminosalicylate, prothionamide), Peripheral neuropathy (cycloserine, prothionamide), ototoxicity (injectable agents streptomycin, kanamycin, capreomycin), Optic neuritis (ethambutol), rash (all TB drugs), Renal toxicity (injectable agents streptomycin, kanamycin, capreomycin), Seizures (cycloserine, kanamycin, capreomycin), arthralgias (pyrazinamide, fluoroquinolones), hepatitis (pyrazinamide, rifampicin, prothionamide, paraaminosalicylate)
TB Care Drug-resistant TB treatment
Isoniazid-resistant 6m REZLfx. MDR: BPaLM (not CNS, OM or disseminated)
TB Care Definitions
MDR: resistant to H & R, pre-XDR resistant to R +/- H and at least one FQN, XDR resistant to R +/- H at least one FQN, and at least one other Group A(BDQ or LZD)
TB Care Supporting treatment adherence
DOTS (family member, community volunteer, healthcare worker), digital tools, stigma, treatment duration, adverse events, adherence contract, food packages, financial
TB Care Safety monitoring and management:
Review at baseline, 2w, monthly, end of treatment, 6 and 12 months post-treatment with various combination of Clinical evaluation (clinical, psychosocial, weight/BMI, performance status, peripheral neuropathy screen, visual acuity and colour discrimination screen, assessment and follow up of adverse events), Bacteriological evaluations (sputum smear, culture, drug susceptibility testing), Radiology, ECG and laboratory evaluations (CXR, ECG, FBC, LFTs, and at baseline - electrolytes, Ur/Cr, pregnancy test, BBV (cannot treat, but want to predict DILI), BSL/HbA1c
TB Care Other
Antiretroviral therapy, Mx of failed treatment/palliative care, advocacy
Ebola treatment centre Symptoms
Early dry (fever, chills, myalgia - d8-10 post exposure). Late wet (severe watery diarrhoea, nausea and vomiting - d10-15 post exposure). Advanced disease may have encephalitic picture, but bleeding is quite rare overall. The index case can be really difficult to identify (once outbreak established it’s ok, but initially may be missed -> lots of exposures before diagnosis made) Recent Marburg outbreak in Rwanda 2024 - HCW 80% of cases, an enormous problem when it is not recognised in a healthcare facility.
Ebola treatment centre Principles of infection prevention and control
Chain of infection: infectious agent > reservoir > portal of exit > mode of transmission > portal of entry > susceptible host. Hierarchy of controls: Elimination > Substitution > Engineering controls > Administrative controls > PPE
Ebola treatment centre Key principles of containment facility design
Isolation (physical and behavioural barriers, environmental decontamination). Working practices (operating procedures, rules and behaviours that limit risk throughout the whole system). PPE (provision of proper personal protective equipment (PPE))
Ebola treatment centre Risk zoning
Within the ETC green = no pathogen, red = pathogen
Ebola treatment centre Flow
From green to red. Isolate those at high risk for transmission. The environment around them and belongings may be contaminated. Need to consider how people and things move in and out of the centre. Basic rule is move from lower to higher risk - reduces the risk of suspect patients being infected within the ETC.
Ebola treatment centre Patient flow
Patient -> suspect (if disproved then exist) -> confirmed -> survived vs died
Ebola treatment centre Placement
Size/capacity, space to expand? Near to main road? Phone signal, Electricity, Water supply, Groundwater level/flood plain? Streams, bore-holes. Do not want to be low lying or on a flood plain, do not want to soak into community water supply…
Ebola treatment centre Essential components of an ETC
Patient areas (reception/ambulance dock, screening/triage, suspect/confirmed +/- recovery wards, toilets, exit showers), Staff areas (PPE donning & doffing areas, staff office/rest/eating areas, toilets) and Ancillary areas (laboratory and pharmacy, morgue, burn pit, chlorine tanks/water storage)
Ebola treatment centre Donning and doffing
Buddy system. Well lit, well stocked, big enough so everyone can be assisted by someone else putting on PPE. 4m squared per staff member - mirror to check Ppe, clock on the wall, so know when they are going in. Timing is really important, will start to sweat through all clothing, then will pant as it is the only way to get heat out. Doffing is the highest risk time, tired, may be emotional - someone else will talk you how to get out. Need multiple lanes running at a time so there is not a queue. Some PPE is discarded, some is preserved - need to consider how to decontaminate the PPE that will be used again
Ebola treatment centre WASH and washing
0.5% chlorine – for the environment, surfaces, corpses prior to body bags, spraying on solid and liquid waste prior to disposal – need 200L per bed per day. 0.05% chlorine – for washing hands (final step leaving ETC), laundry of all scrubs in green zone, patients shower in this need 125L per bed per day. Drinking water – need 75L per bed per day. Need engineers to ensure waste is at least 1.5m above water level. Surrogate marker to measure community water for chlorine (cannot waste water test for Ebola, but can test for chlorine)
Ebola treatment centre How to run day to day
Need to have a team – actually is massive – groups of people who can pick up a stretcher – want to preserve clinical staff for clinical care, so need a team of non-clinical staff to carry patients – hygienists/waste manager/stretcher bearers. Always trying to manage the situation – when the patient is coming out of the ambulance, everyone has a role. Need a strategy for how to get things between red and green zone. Need SOPs, rosters, handover infection prevention and control structures
Ebola treatment centre Waste management
Everything in the red zone should stay there, except recovered patients, Liquid – latrine with chlorine poured over. Sharps – sharps pit, backfilled with concrete at the time of decommissioning. Solid – PPE, clothes, put into two bags, sprayed with chlorine, transported to waste management area – may be an incinerator. Burn pit, ideally 20-30m away from staff and patients – needs a cover to stop rain, ideally needs a chimney to channel smoke away.
Ebola treatment centre Pharmacy and Laboratory
Key is to put between green and red zone. Staff are mostly in green zone , but ready access to receive from red zone. Lab needs access point from the road. Calculating weight-based dosing should occur in the green zone, make up cannula packs etc, so that the work in the red zone is as straight forward as possible. Containment hood, so staff can handle specimens in the hood without wearing full PPE. Ebola PCR and Malaria tests are key.
Ebola treatment centre Pregnancy
Can present with pregnancy loss – this is a common thing to happen. No thing to suggest that you are at increased risk of getting ebola, but you are at increased risk of adverse pregnancy outcomes. Someone successfully treated with Ebola, the placenta is a privileged site – the products are likely to be HIGHLY infectious.
Ebola treatment centre Children and neonates
Very common, very high risk of infection due to lots of contact with each other and animals and poor hand hygiene. Facilitating visit with a recovered baby and the mother still in the ETC – ideally isolated. Treatment of coinfection, fluid. Big safeguarding is separate areas, more frequent obs, treatment monitoring, the emotional impact is enormous, 30,000 children lost both parents in the 2014 outbreak.
Ebola treatment centre Holistic care
Spiritual needs are incredibly important in these areas. Isolation is very hard and stigmatising with Ebola. It is not just about fancy drugs and monoclonals, it needs to be about pastural care
Ebola treatment centre Caring for the dying and dead
Mortality can be a significant problem, community can also be traumatised by this. Ministering to the dead can propagate the infection – this is something the community want to do, it is a disconnect between practices to stop transmission contrasting to allowing people to process spiritually what is happening to them and their communities. WHO have since produced helpful guidelines of how to safely care for and provide safe and dignified burials in outbreaks – to allow some of the religious practices. Spray body with chlorine and put in one or two body bags, spray that with chlorine, can use coffin if practiced in the area (or shrouds for Muslim inside body bag) – lighter PPE can be used to carry the coffin. When it is done right, it can make a huge difference – it is so important
Ebola treatment centre Survivors
Two negative ebola PCR required for discharge, 48h apart. Certificate of discharge needed to be signed by three (specific) people. Need clothes for people to wear when they leave, they cannot take their clothes. Local environment at your home may also be decontaminated/destroyed.
Ebola treatment centre Design
WHO: Designing an Ebola Treatment Unit gives clear instructions, but in reality often have a facility that is being repurposed which creates significant challenges
Ebola treatment centre Requirements
Caring for 125 patients = 350 head-to-toe body suits, 6600 gallons water, 2500 gallons bleach. For a centre with 100-200 patients, need 300-600 staff
Ebola treatment centre Key messages
Goals of an ETC: save lives and prevent spread of infection. Risk zoning. Unidirectional flow - staff and patients. Principles same for purpose built/adapting existing facilities. Ancillary buildings: lab, pharmacy, morgue, staff areas. Environmental considerations: site, water, decontamination. Waste management. Holistic care: visiting, spiritual needs, survivors, dying.
Scrub typhus Epidemiology
Over 1 million cases per year in South and SE Asia. Rural scrubland. Bite of infected larval trombiculid/chigger mite. Increasingly cases are reported from outside the triangle
Scrub typhus Clinical
Non-specific presentation (fever, headache, myalgia, lymphadenopathy (regional), rash (sometimes)). Eschar is key (occurs/found in >50%). Mild to severe disease. In adults: AKI, ARDS, hepatitis, shock, meningoencephalitis. In children: bronchopneumonia, hepatitis, meningoencephalitis and haemophagocytic lymphohistocytosis (HLH). CFR 1% (treated) to 6% (untreated). Rare in children <5y
Scrub typhus Diagnostics
Inadequate. RDT: variable performance (geography, comparator population, reference standard), antibody kinetics not well understood. Serology (immunofluorescence assay) ‘Gold standard’ (laborious, 4-fold increase in paired samples at least 14d apart). PCR (47kDA) serology can be negative in first week, buffy coat increases yield, eschars are high yield. Delay associated with worse outcomes (empirical treatment)
Scrub typhus Treatment
Doxycycline is mainstay (covers pathogens with similar presentations, safe in children, no evidence of resistance). Azithromycin first-line in pregnancy. Combination may have role in severe disease. Duration 7 days (response within 48h)
Scrub typhus Summary
Caused by Orientia tsutsugamushi - Gram negative intracellular coccobacilli. Transmitted by the bite of the larval trombiculid/chigger mite, found (predominantly) in the Tsutsugamushi triangle. Major (under recognised) cause of acute undifferentiated fever in Asia (esp rural). Examine the patient thoroughly all over for eschars. Immunofluorescence assay serology is gold standard, but requires convalescent serum. PCR of eschar is high yield diagnostically. Trial of treatment: delay associated with increased mortality. Don’t forget ‘doxycycline deficiency’ (providing safe for patient, not pregnant, and no contraindications. Second line is azithromycin)
Dengue Risk factors for severe dengue
Pregnant women. Patients with comorbidities eg diabetes and uncontrolled hypertension. Patients >60y. Patients with over and under nutrition
Dengue Warning signs
Abdominal pain or tenderness. Persistent vomiting. Clinical fluid accumulation. Mucosal bleed. Lethargy, restlessness. Liver enlargement >2cm. Laboratory increase in HCT concurrent with rapid decrease in platelet count)
Dengue Severe dengue
Severe plasma leakage (shock, fluid accumulation with respiratory distress), severe bleeding, severe organ involvement (liver AST>1000, CNS impaired consciousness, heart and other organs)
Dengue Phases
Febrile d1-3 (fever and viraemia), Critical d4-6 (fever drops, organ impairment shock/bleeding, decreased platelet increased haematocrit, no viraemia, rising IgM/IgG, Recovery d7-> reabsorption/fluid overload, increasing platelets and decreasing haematocrit, rising IgM/IgG
Dengue Management
Warning signs -> consider admission. No warning signs -> educate patient/relatives re-warning signs, follow up. Supportive care: encourage oral fluid intake, regular paracetamol (avoid if transaminases >10x ULN), avoid NSAIDs. Monitor: warning signs, vital signs (BP, HR, Temp), fluid balance (min 4-hourly), bloods: Plt, HCT, Hb), Shock (narrowed pulse pressure <20mmHg or poor perfusion = shock, fluid resuscitation guided by HCT/PCV, reassess frequently-serious risk of overload. Blood products if haemorrhage
Dengue Prevention
Cover tanks, sinks and pools. Turn over containers that can accumulate water and remove any that are not necessary. Keep garbage containers dry and well covered. Clean rain gutters and drains, if they get blocked with leaves and garbage, there will be mosquitoes. change water in vases and flower pots once a week. It is important to clean them in case mosquito eggs are attached to the sides. Protect doors and windows with mosquito netting. Vaccinate
Dengue Summary
Arbovirus - flavivirus (DENV) - 4 serotypes (DENV1-4). Transmission: Female Aedes mosquitoes. Incubation period 3-14d. RF: pregnancy, extremes of age, under/over nutrition, comorbidities. Clinical syndrome: mild febrile illness to haemorrhagic fever and shock syndrome. 60% infections are asymptomatic, know the warning signs. Estimated annual global burden 70-500million infections, 2.1 million severe dengue cases, 21,000 deaths.
Typhus group Epidemiology
Rickettsia typhi worldwide ‘murine typhus or endemic typhus’ Vector: flea faeces. Rickettsia prowazekii worldwide ‘epidemic typhus’ Vector: louse faeces. Symptoms: fever (95%), headache (54%), rash (41%), LFT deranged (26%)
Typhus group Diagnostics
d-4 to 10 PCR, >d6 IgM >d8 IgG, fever d0-14, rash d4-9. Investigations: WBC often normal, thrombocytopaenia in severe disease, elevated transaminases and creatinine. CXR/LP if indicated. Serological testing (4-fold rise) or PCR. Rapid tests? Nb wide geographical variation in performance
Tick typhus Summary
1 R rickettsii, 2 R conorii, 3 R africae. Vector :1 American dog tick 2 Brown dog tick, 3 Amblyomma tick. Any of a few tick-transmitted rickettsial illnesses - 1 Rocky mountain spotted fever, 2 Boutonneuse fever (Mediterranean spotted fever). 3 Africa tick-bite fever. Who gets it: visitors to national parks, grassy areas, dog contact
Epidemic typhus Summary
R prowazekii. Vector: louse faeces. Big outbreaks in overcrowded populations. Must be treated - can recur. Mortality rate 20-80%. Who gets it: Prisons, migrant camps, war/disaster zones
Murine (endemic) typhus Summary
R typhi. Vector: flea faeces. Mild, mortality rate 1-2%. Who gets it: contact with animals likely
Scrub typhus Summary
O tsutsugamushi. Vector: trombiculid chigger mite bite. Mortality 6%. Who gets it: farmers or occupational exposure.
Typhoid Summary
Salmonella typhi. Faecal-oral transmission (no vector). Gram negative bacillus. Completely different to the Rickettsial typhus. Who gets it: poor sanitary conditions
Melioid Summary
Burkholderia pseudomallei. Transmission: inoculation, inhalation, ingestion. Risk factors: Diabetes, chronic renal/lung disease, thalassaemia, malnutrition, not HIV (neutrophil dysfunction), alcohol dependence, occupational exposure. Adults: pneumonia. Children: parotitis. Ubiquitous bacteria across Asia mainly afflicting impoverished rural populations (soil/water contact). Diverse presentations: localising and undifferentiated. Diagnosis requires microbiological capacity and clinician awareness. Extremely high case fatality rate (intrinsic resistance, supportive care, practical difficulties of ensuring adherence)
Melioid Diagnosis
Classic micro: selective media, wrinkled, dry, purplish colonies. Gram negative bacilli (with safety-pin appearance), oxidase positive, non-lactose fermenter. Other options: latex agglutination, distinctive AMR pattern, MALDI-ToF (spectra added), biochemical ID (variable), lateral flow testing
Melioid Therapeutically challenging
Intrinsically resistant to most antibiotics used for the empirical treatment of sepsis. Parenteral phase (10d minimum), eradication phase (12 weeks minimum). Source control. Good quality intensive care. Strong health systems.
Typhoid Summary
Salmonella typhi. Faecal-oral transmission. Incubation 3-60d (usually 7-18d). Symptoms nonspecific. Signs hepatosplenomegaly, relative bradycardia. Investigations low platelets, transaminitis, eosinopaenia. BC: reference standard. BM culture: highest diagnostic yield.
Typhoid Severe complications
10-15% hospitalised patients. Untreated patients in second or third week of illness with continuing fever, increasing weakness, anaemia, weight loss, persistent vomiting, or a clouded mental state (intestinal bleeding, intestinal perforation, encephalopathy, nephritis, hepatitis). CFR 1-4%
Typhoid Epidemiology
Throughout Africa, South and SE Asia. Fluoroquinolone resistance high in many SE Asian countries. XDR in Pakistan. Base treatment on local susceptibilities.
Typhoid Treatment
Uncomplicated: Azithromycin. XDR region complicated: meropenem & azithromycin. Non-XDR region: complicated: CRO
Typhoid Prevention
Vaccination against typhoid fever, drink clean water, keep your hands neat and clean, eat thoroughly cooked food. Wash fruits and vegetables thoroughly
Typhoid Definition
MDR: resistant to chloramphenicol, ampicillin, SXT. FDR = MDR + quinolone resistant. XDR = FDR + CRO resistant
Angiostrongylus Summary
Eosinophilic meningitis. Distribution South, SE Asia, Northern USA and Brazil have all described cases. No data in Africa does not exclude. Clinical: Eye (visual field defects, retinopathy, periorbital oedema), Lung (cough/pneumonitis), CNS (afebrile: severe headache, neck pain/stiffness, nausea, vomiting, convulsions, psychosis, peripheral neuropathy, paraplegia, cranial nerve lesions II/VII, VI, coma)
Angiostrongylus Diagnosis
Larva/worm visualisation - lives in pulmonary artery of rodent host. Neurotropic to CNS, eyes, lungs. CSF PCR. Management steroids +/- albendazole, CFR <1%.
Angiostrongylus Differential diagnosis
Angiostrongyliasis: acute severe headache, no migratory swelling, pain with focal numbness. Peripheral eosinophilia. CSF appears like coconut juice, history of uncooked snails or slugs. Gnathostomiasis: motor weakness, migratory swelling, pain along nerve root. Peripheral eosinophilia. CSF non-traumatic bloody, brain imaging often demonstrates SAH or unusual site ICH, history of uncooked poultry or fish
Eosinophilic meningitis Angiostrongylus cantonensis
Rat lung worm. Migrating larvae inherently neurotropic. SE Asia, Pacific Islands. Humans acquire by eating raw or undercooked snails or slugs, infected animals (crab, shrimp, centipedes), contaminated ground vegetables. Treatment: supportive, advise against antihelminthic agents, which may elicit inflammatory response to dying organism. Most common parasitic cause of eosinophilic meningitis.
Eosinophilic meningitis Baylisascaris procyonis
Migrating larvae inherently neurotropic. Prevalent in US raccoons. Humans acquire by ingesting infective eggs from environment. Often described with young child playing in dirt or sandbox (aka raccoon latrine) or person eating out of contaminated sandbox. Can migrate to variety of tissues (larva migrans), eosinophilic meningitis more rare. Treatment: supportive. Unclear utility of antihelminthic agents.
Eosinophilic meningitis Gnathostoma spinigerum
Migrating larvae in visceral, cutaneous, and/or neural tissues. Endemic in SE Asia, China, Japan, but occurs broadly. Humans acquire by ingesting intermediate hosts (eg fish, frog, snake) containing larvae, or by drinking contaminated water. Possible triad: eosinophilia, migratory cutaneous swellings/nodules, raw fish consumption. Larval penetration into brain usually related to migration along nerve tract, so might have sudden onset radicular pain or headache. Treatment: supportive. Unclear utility of antihelminthic agents with CNS disease. Cutaneous disease can be treated with albendazole or ivermectin as well as surgical excision of worms.
Eosinophilic meningitis Other possible causes
Coccidioidal meningitis; less commonly, cryptococcosis. Toxocariasis, neurocysticercosis, strongyloidiasis, trichinellosis, fascioliasis, Paragonimus westermani, echinococcosis, schistosomiasis, myiasis. Non ID: CNS lymphoma, hypereosinophilic syndromes, adverse drug reactions, presence of VP shunt
Japanese encephalitis Differential diagnosis
Non-malarial febrile illness in Laos: North: Leptospirosis, JEV, Scrub typhus, typhoid. Mid: Dengue, murine typhus. South: Dengue, scrub typhus, malaria.
Japanese encephalitis Summary
Prognosis: 1/3 die, 1/3 disability 1/3 full recovery. Extrapyramidal signs common. Upper/lower motor neuron weakness. Learning difficulties. Vaccine available and effective. Introduced to childhood vaccination schedule in Laos 2013 (9 months). Good 5y protection. Limited long-term data.
Infections India
West: WNV, Q fever, CCHF. North: JE, Visceral leishmaniasis, histoplasmosis. South WNV, JE, ayasunur forest disease, Nipah, Melioid. East: Malaria. Everywhere: Dengue, Scrub typhus, Typhoid, Leptospirosis, TB, Mucormycosis, R conorli
Infections Undifferentiated fever in Asia
30-40% (Undiagnosed). 30-35% (Leptospirosis, Rickettsial infection, Enteric fever, Melioidosis), 25-30% (Dengue, JE, Chikungunya, Zika, Influenza, CCHF), <10% Malaria
RIPL Questions to determine differentials
Contact with sick people, hobbies (particular outdoor), food (particularly unpasteurised), family travel, pets, other social/outdoor activities, sexual contacts, drug/medication use, travel, occupation
RIPL VHF
VHFs are severe and life threatening viral diseases. Endemic in prats of Africa, South America, the Middle East and Eastern Europe. Caused by diverse groups of viruses (Arenaviruses: Lassa, Lujo, new world arenas, Filoviruses: Ebola (Zaire, Sudan, Bundibugyo, Tai Forest), Marburg, Nairoviruses: CCHF). VHFs are of particular public health importance (they can spread readily within a hospital setting, have a high CFR, difficult to recognise and detect rapidly, no effective treatment). Testing in many settings not usually available locally (often via central government/public health laboratories)
RIPL Lassa
Epidemiology: 100-300,000 cases/year (5000 deaths), incubation 3-21d, majority asymptomatic-mild (severe disease 5-10%, CFR amongst hospitalised cases 15-25%). Risk factors: Where (West Africa: Nigeria, Sierra Leone, Liberia, Guinea, Benin, Togo, Mali, Cote d’Ivoire, Burkina Faso, theoretical risk Cameroon, CAR). Animal reservoir (Mastomys natalensis). Direct contact with infected rodent excreta, tissues, or blood or via inhalation of aerosolised virus. Poor sanitation and housing conditions correlate with greatest risk of infection. Peridomestic rodents are also part of the diet in certain populations. Season: November and April (dry season) - may reflect a higher prevalence of mastomys inside houses.
RIPL PPE for possible VHF
Enhanced contact PPE, FFP3 respirator, hood, visor, long rear-fastening fluid-resistant surgical gown, medium thickness apron, inner gloves, middle gloves taped to the gown with microporous tape, outer gloves, wellington boots
Leprosy Assessment Skin
location of lesions (body chart) - types of lesions (patches, plaques, papules, nodules), signs of inflammation in lesions, oedema of the hands and/or feet, mark skin biopsy site.
Leprosy Assessment Nerve palpation
Note thickening and tenderness. Ulnar, median, radial cutaneous, lateral popliteal, posterior tibial
Leprosy Assessment Nerve function
Use MRC Grading system: 5 = full ROM & full resistance, 4 = full ROM & reduced resistance, 3 = full ROM & no resistance, 2 = reduced ROM & some joint movement, 1 = flicker only, 0 = full paralysis. In addition eyelid gap in mm is measured and recorded
Leprosy Assessment Ulnar motor
Little finger abduction, Index finger abduction
Leprosy Assessment Median motor
Thumb abduction
Leprosy Assessment Radial motor
Wrist extension
Leprosy Assessment Lateral popliteal motor
Foot dorsiflexion, Big toe extension, Toe fanning
Leprosy Assessment Facial motor
Close eyes (strong and gentle closure tested)
Leprosy Assessment Sensory
Nylon monofilament - the person’s hand is first tested for sensitivity with eyes closed. Green monofilament 0.05g = normal hand, Blue 0.2g = normal foot. Loss of 4g = loss of protective sensation for hand, loss of 10g = loss of protective sensation for foot
Leprosy Assessment Definition of leprosy
Diagnosed when a patient has one of these modified cardinal signs of leprosy: 1 Presence of skin lesions typical for leprosy, 2 Thickened peripheral nerves, 3 Acid fast bacilli in slit skin smears 4 Histological changes consistent with leprosy in the skin or nerve biopsy. This is a modification of the WHO diagnosis of leprosy by adding in histological features seen in leprosy
Leprosy Assessment Type 1 reaction
Erythema and oedema of skin lesions. There may be accompanying neuritis and oedema of the hands, feet and face
Leprosy Assessment Type 2 reaction (Erythema nodosum leprosum)
Crops of tender subcutaneous skin lesions. There may be accompanying neuritis, iritis, arthritis, orchitis, dactylitis, lymphadenopathy, oedema and fever
Leprosy Assessment Slit skin smears
The bacteriological index (BI) is an expression of the extent of bacterial loads. It is calculated by counting 6-8 stained smears under the 100x oil immersion lens in a smear made by nicking the skin with a sharp scalpel and scraping it; the fluid and tissue obtained are spread fairly thickly on a slide and stained by the ZN method and decolourised (but not completely) with 1% acid alcohol. The results are expressed on a logarithmic scale 1+ 1 bacillus in every 100 fields, 2+ 1 bacillis in every 10 etc to 6+ at least 1000 bacilli in every field. The bacteriological index is valuable because it is simple and is representative of many lesions but is affected by the depth of the skin incision, the thoroughness of the scrape and the thickness of the film. A more accurate and reliable index of the bacillary content of a lesion is given by the logarithmic index of biopsies. These indices help to assess the state of patients at the beginning of treatment and to assess progress.
Ciguatera Summary
Occurs worldwide in tropics and subtropics. Caused by ingestion of ciguatoxin and other toxins from single-celled organisms that grow on coral reefs. Toxin accumulates in large predatory fish that live around coral reefs. Open voltage-gated sodium channels in cell membranes. Maitotoxin results in norepinephrine release. Scaritoxin results in acetylcholine release- both through increased calcium influx. The name ciguatera was given by Don antonio Parra in Cuba in 1787 to intoxication following ingestion of the ‘cigua’, the Spanish trivial name of a univalve mollusc, Turbo pica, reputed to cause indigestion. Diarrhoea and vomiting 3-6h after ingestion. Neurological abnormalities 3-72h after ingestion (paraesthesia, pruritus, metallic taste, painful dentition, painful urination, blurred vision, temperature-related dysaesthesias (hot-cold allodynia), paresis, reversible cerebellar dysfunction). Cardiovascular hours after ingestion (bradycardia, heart block, hypotension). Prognosis recovery is usual (gastroenteritis within days, neurological changes within weeks) Symptoms may come back/get worse if alcohol, caffeine, nuts, pork, chicken, fish consumed
Ciguatera Differential diagnosis
Ciguatera poisoning (diarrhoea, paraesthesia, hot cold allodynia, palpitations), Scombroid fish (rash, palpitations, tachycardia IgE mediated immune reaction), Shellfish (gastrointestinal upset, rapid onset paraesthesia, paralysis), Pufferfish (weakness sodium channel blockade due to teradotoxin), Botulism (gastrointestinal upset, cranial nerve dysfunction, descending paralysis), Guillain-Barre syndrome (paraesthesia, ascending weakness), Multiple sclerosis (paraesthesia, UMN weakness, transverse myelopathy, ataxia), organophosphate poisoning (GI upset, glove and stocking paraesthesia, ascending weakness, cholinergic findings), arsenic poisoning (GI upset, late sensorimotor peripheral neuropathy, rash, acute kidney injury, respiratory failure).
Sea urchin envenomation Summary
Painful, puncture wounds, ‘tattoo’ appearance, irritating calcium carbonate spines -> granulomatous inflammation. Some spines are loaded with venom. Management early (remove visible spines, hot water soak, tetanus vax, abx, XR), late (treat infection (bacterial, mycobacterial, fungal), surgical removal pros & cons, topical/intralesional steroid, cryotherapy, laser ablation, conservative)
Sea urchin envenomation Differential diagnosis
Cellulitis, infected laceration, soft tissue abscess, foreign body, mycobacterial, fungal
Phytophotodermatosis Summary
Acid (lime/lemon juice) poured onto sea urchin injury then exposed to sunlight
Cutaneous leishmaniasis Summary
American (L brasiliensis/vianna subgenus, L mexicana complex), Non-American (L tropica, L major, L aethiopica), Presentation: papules, nodules, ulcers, mucosal disease. Diagnosis: split skin smear (Giemsa stain), biopsy (histology). Treatment (risk of mucosal disease?-> systemic treatment, troublesome skin lesions?) Local (nothing, intralesional antimony (meglumine) or heating/freezing/surgery). Systemic treatment (oral miltefosine, IV miltefosine (sodium stibogluconate), IV LAmB)
Gnathostomiasis Differential diagnosis
Migratory rashes (Strongyloides stercoralis, Strongyloides fulleborni, Cutaneous larva migrans, Gnathostoma spinigerum, Sparganosis, Loa loa) Other (widespread eczema, phytophotodermatosis (no dermographism), trichinosis)
Gnathostomiasis Summary
Gnathostoma spinigerum, mainly SE Asia, increasing in Mexico. Some parts of Africa. Eating undercooked/raw freshwater fish, eels, frogs, birds, reptiles. Ceviche, poke. Human are incidental intermediate host by ingesting L3 larvae in tissue of second intermediate host or paratenic host. Definitive host are dogs/cats/pigs, unembryonated eggs passed in faeces, egg embryonates in water. Egg hatches and releases L1 larvae, first intermediate host crustacean ingests L1 larva, larvae molt twice to early L3 stage, fish, frog etc ingest crustacean, L3 larvae mature in second intermediate host and migrate to tissue. L3 and/or immature adults undergo aberrant migration in the human host causing tissue destruction. Presentation acute (fever, urticaria, GI symptoms), cutaneous (migratory swellings, subcutaneous haemorrhage), visceral (lung, GI, CNS) can live for 12 years. Diagnosis: clinical, eosinophilia, serology (immunoblot). Treatment: Albendazole 400mg bd 21d (>95% cure)
Leptospirosis Differential diagnosis
Acute inflammatory demyelinating polyneuropathy (AIDP)/Guillain Barre syndrome (precedents: Campylobacter, Shigella, Zika, Mycoplasma, influenza [also causes rhabdomyolysis], HIV, COVID-19). Acute flaccid myelitis (enterovirus D68 infection), Post-infectious myositis (leptospirosis, influenza, chikungunya, other viruses), Rhabdomyolysis (leptospirosis, influenza), Trichinella
Leptospirosis Summary
Worldwide distribution. Fresh water exposure. Rodent reservoir. Flooding -> outbreaks. 64 species including Leptospira interrogans, mobile aerobic spirochetes. Presentation acute phase (fever, rigors, myalgia, headache, conjunctival suffusion) immune phase (aseptic meningitis, jaundice, acute kidney injury, rhabdomyolysis, pulmonary haemorrhage), diagnosis (raised CK in 50%, hyponatraemia, hypokalaemia, serology, PCR blood, CSF (early), urine (late). Treatment: Mild po doxycycline or azithromycin. Severe IV penicillin or CRO (doxycycline)
