Micro - Specific Groups Affected Flashcards
Congential Rubella
- Blueberry muffin rash
- Sensorineural deafness, cataracts
- PDA/ASD/VSD
- Microcephaly/psychomotor retardation
- Worse outcomes if infected earlier in pregnancy
- Rare (MMR) - rubella eliminated in the UK in 2015 and removed from routine antenatal screening in 2016
Congenital HSV
Blistering rash –> babies become septic
- SEM disease (45%) - localised to skin/eyes/mouth
- CNS disease +/- SEM (30%). Can present late - 10days-4 weeks postnatally
- Disseminated (25%) - multiple organs (CNS, lungs, liver, adrenals, skin, eyes, mouth). High mortality. >20% won’t have skin lesions.
IV aciclovir ASAP
Congenital Parvovirus B19
Seroprevalence in pregnant women in 50-60%
Baby only affected if mother infected <20wks (transplacental transmission approx 33%)
Virus destroys RBC precursors:
- Slapped Cheek Syndrome = Erythema Infectiosum = Fifth Disease
- Transient aplastic crisis
- Arthralgia
- Foetal anaemia –> cardiac failure –> non-immune hydrops fetalis
Treatment: human immunoglobulin
- Referral to specialist foetal medicine unit
- Intrauterine blood transfusion
- Some cases resolve spontaneously
- If infant survives the hydropic state, long-term prognosis is usually favourable
Congenital CMV
- DNA virus
- Detection of CMV from body fluids or tissues within 21 days of birth
- Commonest congenital infection (can also get vertically and horizontally - salivary contact)
- Primary infection or reactivation of maternal CMV (reactivation = lower risk)
- 12.7 % congenitally infected babies born with sx. 75% of these will have CNS involvement.
- Of those who are asymptomatic, 10% have abnormalities on follow up.
- Sensorineural deafness, microcephaly
- Treatment: IV ganciclovir
Other issues include:
Eyes - Chorioretinitis
Heart - Myocarditis
Neurological - Encephalitis
Lung - Pneumonitis
Liver- Hepatitis, Jaundice, Hepatosplenomegaly
Other- IUGR, Thrombocytopenia +/- anaemia
Neonatal Early Onset Sepsis (<3 days)
Group B strep (mainly), E. coli, listeria
Ix: FBC, CRP Blood cultures --> lumbar puncture if +ve cultures Deep ear swab Surface swabs
Rx - benzylpenicillin and gentamycin (plus supportive - ventilation, circulation, nutrition etc)
Neonatal Late Onset Sepsis (>3 days)
Coagulase-negative staph (epidermis, saprophyticus = from skin)
Ix: FBC, CRP Blood cultures --> lumbar puncture if +ve cultures Deep ear swab Surface swabs
Rx
1st line - Cefotaxime and Vancyomycin
2nd line - meropenem
Community acquired late onset neonatal infections: cefotaxime, amoxicillin +/-gentamicin
Congenital Infection - things we screen for and those we don’t but are able to
Current screening: Hep B HIV Rubella Syphilis
Not screening: CMV Toxoplasmosis Hep C Group B Streptococcus
Congenital Toxoplasmosis
Cat faeces. Undercooked meat.
May be asymptomatic at birth – 60% but may still go on to suffer long term sequelae e.g. deafness, low IQ, microcephaly
40% symptomatic at birth
- Choroidoretinitis
- Microcephaly/hydrocephalus
- Intracranial calcifications
- Seizures
- Hepatosplenomegaly/jaundice
Congenital chlamydia infection
- Causes neonatal conjunctivitis, or rarely pneumonia
- Treated with erythromycin
Neonatal Group B Strep Infection
Gram positive coccus Catalase negative Beta-haemolytic Lancefield Group B In neonates: - Bacteraemia - Meningitis - Disseminated infection e.g. joint infections
Neonatal E.coli Infection
Gram negative rod In neonates: - Bacteraemia - Meningitis - UTI
RFs for Early Onset Neonatal Sepsis
Maternal:
- PROM/prem. Labour
- Fever
- Foetal distress
- Meconium staining
- Previous history
Baby:
- Birth asphyxia
- Resp. distress
- Low BP
- Acidosis
- Hypoglycaemia
- Neutropenia
- Rash
- Hepatosplenomegaly
- Jaundice
Other organisms causing late onset neonatal sepsis
Coagulase negative Staphylococci (CoNS) is the main one. Others include:
Group B streptococci E. coli Listeria monocytogenes S. aureus Enterococcus sp. Gram negatives – Klebsiella spp. /Enterobacter spp. /Pseudomonas aeruginosa/Citrobacter koseri Candida species
Childhood Strep Pneumonia Infection
- Leading cause of morbidity and mortality esp. in < 2y.o.
- Gram positive diplococcus – alpha haemolytic streptococcus
- Meningitis, bacteraemia, pneumonia
- > 90 capsular serotypes
- Increasing penicillin resistance
Pneumococcal Conjugate Vaccines
Conjugated vaccine immunogenic in children from 2 months.
- Prevenar introduced in U.K. in 2006 (7 serotypes, individually conjugated to a carrier, then mixed
- These 7 serotypes are responsible for approx 80% of IPD in the UK in 2006
- Vaccine serotypes were almost eradicated since introduction of PCV7
- BUT still seeing much IPD (invasive pneumococcal disease) in children
- ? Due to replacement phenomenon i.e. serotype replacement
- ?Could this lead to change in disease phenotype e.g. HUS (serotype 19a), empyema (serotype 1)
- Introduction of Prevenar 13 in UK in 2010
Meningitis at Different Ages
<3/12: N. meningitidis; S. pneumoniae; (H. influenzae (Hib) if unvaccinated); GBS; E. coli; Listeria sp.
3/12 - 5 years:N. meningitidis; S. pneumoniae; (Hib if unvaccinated)
> 6 years: N. meningitidis; S. pneumoniae
Bacterial RTI Causes and Rx in children
- S. pneumoniae (pneumococcus) is the most important bacterial cause
- Most UK strains remain sensitive to penicillin or amoxicillin
- Mycoplasma pneumoniae tends to affect older children (>4 years) – Macrolides are treatment of choice e.g. Azithromycin
Mycoplasma Pneumoniae
Acquired by droplet transmission person to person.
Epidemics occur every 3-4 years. Occurs in school age children and young adults.
Incubation period 2-3 weeks.
Many asymptomatic Classically presents: - Fever - Headache - Myalgia - Pharyngitis - Dry cough
DDx if fails to respond to treatment: whooping cough, TB (inc MDRTB, XDRTB)
Mycoplasma Pneumoniae - Extrapulmonary Manifestations
Haemolysis
- IgM antibodies to the I antigen on erythrocyte
- Cold agglutinins in 60% patients
Neurological (1% cases)
- Encephalitis most common
- Aseptic meningitis, peripheral neuropathy, transverse myelitis, cerebellar ataxia
- Aetiology unknown ?antibodies cross react with galactocerebroside
Cardiac
Polyarthralgia, myalgia, arthritis
Otitis media and bullous myringitis
UTIs in children
Common
Up to 3% girls and 1% boys by age 11
Diagnosis:
- Symptoms – if child old enough to give clear history
- Pure growth >105cfu/ml
- Pyuria – pus cells on urine microscopy
N.B. Get sample before starting treatment
Organisms: E.coli, proteus, klebsiella, enterococcus, coagulase -ve staph (Staph saprophyticus)
Recurrent/persistant infections in children
May be a sign of immunodeficiency – either congenital or acquired – e.g. HIV, SCID
Warrants investigation by Paediatric Infectious Diseases doctors
Congenital Rubella Syndrome - Mechanism
Mechanism:
- Mitotic arrest of cells –> Necrotic change in placental cells due to viral replication –>
- Infected placental endothelial cells desquamate into vessels causing transport of virus-infected ‘emboli’ to foetus (antipathy) –>
- Viral infection of foetal cells during organogenesis –> Viral mediated apoptosis –> Interference with development of key organs (growth inhibitor effect)
Diagnosis of Rubella (in the mother) and Rx
Clinical:
- Maculopapular rash
- Lymphadenopathy
- Fever
- Lesions on soft palate
- Headache
Lab: Rubella serology (IgM and IgG), detection of virus (molecular diagnosis - PCR of secretions)
Rx - none available (but vaccinated against in MMR)
Maternal Diagnosis of CMV
Lab: virus and serology
Detection of virus (blood, urine, respiratory secretions)
- Cell culture
- Detection of Early Antigen Fluorescent Foci
- DEAFF – accelerated cell culture system
- CMV DNA (Polymerase Chain Reaction)
CMV Serology - IgM, IgG seroconversion, IgG avidity
Foetal/Neonatal Diagnosis of CMV
Pre-natal:
Detection of CMV DNA in amniotic fluid at 21 weeks gestation
Post-natal:
- CMV detection within 21 days of life. (Positive result beyond that time will NOT make a diagnosis of congenital infection) - Urine/Salivary swab/blood for CMV PCR
- CMV Serology - CMV IgM (low sensitivity)
Prevention and Treatment of CMV
Vaccine
None at present – in development
Prevention
“universal precautions”
Antiviral treatment: - Not used during pregnancy – toxicity Congenital CMV with end organ disease - Valganciclovir / Ganciclovir for 6/12 - Audiology review until age 6 - Ophthalmology review
Classification of maternal HSV infection and associated risk of neonatal infection
First episode, primary infection - 57%
First episode, non-primary infection - 25%
Recurrent infection - 2%
Symptomatic/Asymptomatic
Highest risk = Maternal primary HSV infection in the third trimester.
- particularly within 6 weeks of delivery: continuing viral shedding , birth before development of protective maternal antibodies. C-section recommended.
Factors influencing neonatal transmission in HSV
Type of maternal infection
Maternal antibody status (neutralizing Ab)
Duration of rupture of membranes
Integrity of mucocutaneous barriers (eg use of foetal scalp electrodes)
Mode of delivery (caesarean section versus vaginal)
Highest risk of transmission is in the permpartum(perinatal period) - 85% (as opposed to 5% in utero and 10% postpartum).
Diagnosis and Treatment HSV
- Decrease the time to diagnostic consideration (mum&baby)
- Early initiation of antiviral therapy
- Prompt collection of specimens for diagnosis - HSV cultures/PCR, liver transaminase levels (suggest disseminated HSV infection)
Rx:
- High dose aciclovir at 60 mg/kg/day IV in three divided daily doses
- Continute for 21 days in CNS/disseminated, 14 in SEM
- Continue acyclovir until PCR -ve
- Monitor neutrophil count and renal function
VZV in Pregnancy
- DNA virus - HHV3
- Droplet transmission
- 90% women of childbearing age immune
- Spread through local nerves with latency in the sensory dorsal root ganglia
- Zoster (shingles) - no risk to the foetus
Foetus - risk of transmission:
- Congenital varicella syndrome
- Neonatal varicella
- Herpes zoster in early childhood
Mother: pneumonitis, encephalitis, sepsis
Congenital Varicella Syndrome
Eyes:
- Chorioretinitis
- Cataracts
Neurological:
- Microcephaly
- Cortical atrophy
Musculoskeletal/Skin:
- Limb hypoplasia
- Cutaneous scarring
Other:
- IUGR
Maternal infection during 13-20 weeks’ gestation = highest risk (2%)
Neonatal Varicella Infection
Newborn is vulnerable when maternal infection occurs within 7 days prior to delivery or 7 days post-partum - No time for passive transfer of VZV antibodies
Manifestations of infection may include
- Mild course of infection
- Disseminated skin lesions
- Purpura fulminans
- Visceral infection
- Pneumonitis
20% mortality untreated
Diagnosis: clinical or VZV PCR of lesion
Varicella Prevention in Pregnancy
Vaccine:
Live virus vaccine available (give preconception)
Avoidance of exposure in pregnancy if susceptible
Post-exposure prophylaxis:
- Varicella-zoster immunoglobulin (given with 10 days of exposure) up to 20/40
- Antiviral chemotherapy: Aciclovir 800mg x4/day from day 7-14 post exposure after 20/40
Parvovirus B19 - Pathophysiology
- Unique tropism for rapidly dividing erythrocyte precursors
- Virus requires theP blood antigen receptor (globoside) to enter the cell
- Suppression of erythrogenesis
- No reticulocytes are available to replace aging or damaged erythrocytes as they are cleared by the reticuloendothelial system
- Virus crosses the placenta and destroys red cell precursors
- Foetal anaemia –> high output congestive heart failure –> hydrops fetalis
- Virus also directly infects and injures myocardial cells
Diagnosis of Parvovirus - Mother and Foetus
Maternal Infection:
- Parvovirus DNA PCR from blood (and respiratory samples)
- Serology - IgM, IgG, seroconversion
Foetal Infection:
- Foetal blood and amniotic fluid for serology and Parvovirus PCR
Measles in Pregnancy
Rare in pregnant women in UK:
- Foetal loss (miscarriage, IUD)
- Preterm delivery
- Increased maternal morbidity
- No congenital abnormalities to foetus
In susceptible pregnant woman in contact with suspected/confirmed measles:
- Measles Immunoglobulin attenuates illness
- No evidence it prevents IUD or preterm delivery
- MMR cannot be given post exposure in pregnancy (live vaccine)
Zika Virus in Pregnancy (inc congenital zika syndrome)
- 80% of infections asymptomatic
- Miscarriage/stillbirth/microcephaly
- Associated predominantly with travel to Caribbean/Central/South America (Antigua, Barbados, Grenada, Jamaica, St Lucia & Trinidad & Tobago)
Congenital Zika Syndrome:
- Severe microcephaly + skull deformity
- Decreased brain tissue, subcortical calcification
- Retinopathy, deafness
- Talipes, contractures
- Hypertonia
Current Advice:
- Bite avoidance
- Avoid travel to all areas with current transmission
- Avoid conception 3 months after travel (prolonged viral shedding in semen)
- Testing only in symptomatic or abnormalities identified on antenatal USS
- Abnormalities commonly detected in late 2nd or 3rd trimester
HIV in African Children - Epi
- Of the 35.3 million people living with HIV in Dec 2012, 1/10 are children
- Large impact of AIDS on under 5 mortality in African countries
- HIV accounts for 35% of deaths of children <5 in SSA. Trend however is towards increasing proportion of deaths in teenagers with perinatally acquired HIV.
- HIV in children: >90% is due to mother-to-child transmission but child sexual abuse or exchanging sex for food/shelter = risk factors for vulnerable children (i.e. orphaned etc)
- 1/3 of babies born to mothers with HIV who did not know their diagnosis, born by normal vaginal delivery and breast fed for 1 year/18 months will be infected (on a population level)
HIV in African Children - Clinical Features
- Progressive encephalopathy - basal ganglia calcification, white matter changes, atrophy (v large ventricles), vasculopathy/strokes. Neurotrophic virus.
- Anaemia
- Frequent nose bleeds
- Severe oral thrush
- Suppurative ear infections
- Enlarged parotids
- Failure to thrive
- Lymphadenopathy
- Severe pneumonia - TB, VZV, pneumocystis carinii, LIP (lymphoid interstitial pneumonitis - CXR looks like TB but child clinically much more well. Lymphoid tissue between airways contracts –> airway stretched –> bronchiectasis –> chronic suppurative lung disease and clubbing as result)
- Hepatosplenomegaly
- Clubbing
- Severe nappy rask
- Recurrent or persistent diarrhoea
- Easy bruising (thrombocytopenia)
- Herpes zoster infection - worry if in more than one dermatome. Trigeminal shingles is almost pathopneumonic of HIV in an endemic area.
- Molloscum very common
- Spinal TB - Pott’s disease
- CMV –> blindness (spread perinatally)
- Kaposi’s (most die or something else before they die of malignancy)
HIV in African Children - Mother to Child Transmission
- Vertical transmission: breast feeding, in utero, perinatal. % transmission increases significantly with increasing maternal plasma viral load.
- A healthy placenta is an effective barrier to transmission of HIV from mother to baby (Also Hep B and C)
- Most transmission occurs towards the end of of pregnancy when the placenta is getting tired alongside maternal uterine contractions –> microhaemorrhages allow maternal blood to get into foetal circulation.
- Birth canal plays key role. –> first born twin has double the risk of being infected, as it’s born it clears the birth canal of cervico-vaginal secretions, also more susceptible to ascending infections once the waters have broken.
- Elective C section halves risk of transmission
- 16% increased with breast vs formula feeding
HIV in African Children - Rx
All pregnant and BF women should initiate triple ARVs
- Fixed dose combination Tenofovir+3TC+efavirenz
- BF infants should receive daily NVP for 6 weeks
Maintain ARVs for duration of MTCT risk
Maintain ARVs lifelong with those meeting Rx eligibility (CD4< 500) (strong recommendation)
Maintain ARVs lifelong in all for programmatic reasons (conditional recommendation)
Uninfected infants should exclusively BF for 6 months and continue to BF until atleast 12 months
In developing countries where access to HRT is not as easy, bigger focus on prevention/reducing transmission etc.
Immune reconstruction inflammatory syndrome (IRIS)
other infections can flare up as you start to treat the immune system
Major classes of immunosuppressive agents
- Steroids
- Calcineurin inhibitors (T-cell function) - cyclosporin, tacrolimus
- Antiproliferative agents - azathioprine
- Antibodies - depleting, non-depleting (anti CD-25 receptor ABs, costimulation blockers - belatacept)
Epidemiologic Exposure to opportunistic infections in transplant recipients and prevention of these
Viruses acquired from graft eg HBV
- Serostatus
- Risk assessment
Viral reactivation from the host eg HSV
- Serostatus
- Monitoring
- Prophylaxis
- Pre-emptive therapy
Novel infection from infected individual eg VZV - Isolation-barrier nursing - Advide for family/contacts - PEP - Vaccinating contacts - Control of diet
Diagnostic protocols for opportunistic infections in transplant
Pre-transplant serology: HIV Ag/Ab HBV sAg HBV cTAb HBV sAb HCV Ab EBV IgG CMV IgG HSV IgG VZV IgG HTLV Ab
Post transplant: CMV monitoring or prophylaxis EBV monitoring Adeno monitoring (paeds BMT) HSV prophylaxis if indicated
Opportunistic infections - Rx
Opportunistic viral infections are often more difficult to treat
Often requires
- Early treatment
- higher dose
- longer course
- sometimes drug combinations
Increased risk of antiviral drug resistance
VZV in Immunocompromised
- Acute retinal necrosis (ARN)
- Progressive outer retinal necrosis (PORN)
- VZV-associated vasculopathy
CMV in Immunocompromised - presentation, risk, prevention strategies and treatment
Encephalitis
Retinitis
Pneumonia
Gastroenteritis
In transplant the risk of CMV disease relates to pre-tx serostatus
- solid organ transplant - D+/R- : carries the greatest risk of reactivation
- bone marrow transplant: adoptive immunity - D-/R+ : carries the greatest risk of reactivation
Prevention strategies:
- BM - CMV viral load twice weekly, treat if virus reactivates until suppressed (pre-emptive therapy)
- Solid organ - Valganciclovir prophylaxis for 100 days
Rx: Ganciclovir (IV): bone marrow suppression Valganciclovir: oral Foscarnet (IV) (nephrotoxicity) Cidofovir (nephrotoxicity) IVIg (with another drug for pneumonitis)
EBV in Immunocompromised
Post-transplant lymphoproliferative disease (PTLD)
- Latently infected B cells – polyclonal activation
- Predisposes to lymphoma
- suspicion on rising EBV viral load (> 105 c/ml) and CT scan
- Confirmation with biopsy of lymph nodes
Kaposi’s Rx
HAART, radiotherapy, surgical, INF alpha, chemo
JC Virus - Progressive Multifocal Leukoencephalopathy
- Plyomavirus
- Effective antiretroviral therapy has drastically reduced PML incidence in HIV+ve patient
- Can be seen in other types of immunosupressed hosts: i.e patients on monoclonal antibodies
- Cognitive disturbance, personality change, motor deficits other focal neurological signs
- The main pathological feature of PML
is a demyelination of white matter with
neurological deficits corresponding
to the area(s) of the brain affected - Diagnosis: MRI and PCR on CSF
BK Virus
Polyomavirus
Double stranded DNA
BK cystitis post SCT
BK nephropathy post Renal Tx
Adenovirus in immunocompromised
- Particular problem post-BMT (especially paeds)
- Exogenous infection or reactivation of persistent endogenous infection.
- Fever
- Encephalitis/Pneumonitis/Colitis
- High mortality with disseminated infection.
Resp Viruses in the Immunocompromised - Risk and Rx
Increased risk of complications (pneumonitis) and high mortality associated particularly with:
- Influenza A and B
- Parainfluenza 1, 2, 3 and 4
- Respiratory Syncitial Virus (RSV) infection
- Adenovirus
- Novel coronavirus: MERS coronavirus
Rx: Influenza A and B - Oseltamivir (oral drug) for 5 days - If severely immunosupressed: risk of oseltamivir resistance - zanamivir (inhalation or IV) is an alternative
Other respiratory viruses do not have a standard treatment protocol
Hep B in the Immunocompromised
Two things can happen:
1) Carriers may have flare of disease.
2) Those who have had past infection can reactivate –> The risk of reactivation is particularly important with patients on B-cell depleting therapies (i.e Rituximab)
Prevention:
Nucleoside/nucleotide analogues (eg lamivudine, tenofovir, entecavir) prophylaxis
(Hep E also more common)
HAI
Healthcare associated infections
Timing- onset within a certain period from contact; not present on admission
If not present on admission – possibly acquired in hospital
Categorise- by organism / by syndrome
15-30% likely reversible
How common are HAI in UK
Around 8%
Most common in intensive care
Most common syndrome of HAI
Pneumococcal pneumonia
Most common systems affected by HAI (in order)
GI Urinary tract Pneumonias Surgical site Skin and soft tissues
C Diff
Gram +ve spore forming anaerobe
C. diff colitis associated with abs use
E coli
Grav -ve rod
Risk of surgical site infections determined by
Wound environment
Host defences
Pathogens
CPE stands for
Carbapenemase-producing Enterobacteriaceae e.g. NDM klebsiella pneumoniae
Defining PUO
Petersdorf 1961
- Fever >38.3C
- Lasting > 3 weeks
- Uncertain diagnosis after 7 days in hospital
Durack 1991
- Prescriptive set of mandatory investigations
- 3 days of hospital investigation or 3 OP visits
Knockaert 2003
- Pragmatic
- 3 days of Hospital investigation with no diagnosis
Causes of PUO in pt subgroups - children, HIV, neutropenia
Children –
- 44% infective
- 43% undiagnosed
HIV
- CD4 cell count dependent
- High risk of TB and NTM
- PCP
- Cryptococcal meningitis
- Non-Hodgkin’s lymphoma
Neutropenia
- Underlying disease
- Fungal infections
PUO - Hx and Ex
Hx:
- B-symptoms, localising clues
- Medications - doses and initiation date
- Foreign travel - be exact! What did they do there? Where where they? For how long?
- Unwell contacts, pets / animal exposures, injecting drug use, sexual history
Ex - really thorough top to toe examination, look everywhere you can.
Ix - PUO
Routine Admission Ix:
- FBC
- U&E
- LFTs
- CRP
- CXR
- Blood cultures
- Urine dip
Additional Tests -
- Essential for PUO:
- 2x more blood cultures
- Urine culture
- Stool cultures x3 and OCP (ova, cysts and parasite)
- CMV/EBV serology
- HIV/HBV/HCV
Additional Tests - if indicated/previous set unremrkable:
- CK
- Ferritin
- LDH
- ANA
- ANCA
- RhF
- TFT
- FDG-PET CT (Fluro-D Glucose accumulates in cells with an increased rate of glycolysis e.g. activated leukocytes)
- Echo
- Biopsies
- LPs
- Bone marrow
1/20 false positive –> the more tests you do, the more will be positive by chance so try to use specific/targeted tests
Echo in PUO - TTE vs TOE for potential infective endocarditis
5-10% of IE have negative blood culturess because of antibiotics or Fastidious organisms (HACEK) or Aspergillus, Bartonella, Brucella, Coxiella, Rickettsia, Mycobacteria, Nocardia, Chlamydia
HACEK = Haemophilus, Aggregatibacter, cardiovacterium, Eikenelia, Kingella
Initially do TTE. Unless you are sure it is completely benign on TTE/low clinical suspicion, get TOE as well.
Clinical - Duke’s criteria
PUO - Infective Causes
Viral
- CMV / EBV
- HIV
- Hepatitis A,B,C,D,E
Parasites
- Malaria
- Amoebic liver abcess
- Schistosomiasis
- Toxoplasmosis
- Trypanosomiasis
Fungal
- Cryptococcosis
- Histoplasmosis
- Coccidioides
Bacterial
- Mycobacteria - TB, NTM
- Enteric fevers
- Salmonella typhi
- Zoonoses
Can send off the the panel for certain geographic regions
PUO - Inflammatory Causes
There are loads - all the vasculidities etc
Young patient = Adult onset Stills - salmon pink rash (may be mistaken for drug rash). Ferritin often very high in Adult onset Stills –> Macrophage activation syndrome).
Older patient = GCA
Involve rheumatologist
Careful interpretation of results
PUO - Malignant Causes
Lymphoma - often advanced diseases with aggressive subtype
Leukaemia
Renal cell carcinoma - 50% present with fever, haematuria can also occur
Hepatocellular carcinoma or other tumours metastatic to the liver
Often identified on Axial imaging
PUO - Miscellaneous Causes
Subacute thyroiditis
Addisons
Dressler syndrome
PE
Habitual hyperthermia - variation in temp in the mentstrual cycle
Drug fever - idiosyncratic reaction or by affecting thermoregulation. Accompanying rash and eosinophilia in 25%
Factitious fever
Take Home Messages - Fever in the Returning Traveller
70% of those returning from Africa had a tropical illness
Risk of tropical infection higher among VFRs (visiting friends and relatives)
Non-tropical were common among returnees from SE Asia (45%) - but enteric fever (34%) and dengue (20%) remain important
FRT - Presentation Syndromes
1) Fever (Systemic Febrile Illness) - Undifferentiated fever, Fever ‘plus’ some localising signs/symptoms
2) Diarrhoea (acute/chronic)
3) Skin Rash (+/- eosinophilia)
4) Respiratory Syndrome
Malaria - Types
P. Vivax P. Ovale P. Malariae P. knowlesi P. Falciparum - Invades erythrocytes of all ages, may be drug resistant and can be life threatening
From female anopheles mosquito
Africa – causes 20% of childhood deaths
African child – 1.6-5.4 episodes in malaria fever each year
Malaria - Symptoms
Fevers – cyclical or continuous with spikes
Malaria paroxysm – chills, high fever, sweats
Severe Malaria:
High parasitaemia or schizont
Altered consciousness with/ without seizures
Respiratory distress or ARDS
Circulatory collapse
Metabolic acidosis
Renal failure, haemoglobinuria (blackwater fever)
Hepatic failure
Coagulopathy +/-DIC
Severe anaemia or massive intravascular haemolysis
Hypoglycemia
Malaria - Blood Film
Falcip – double dotted rings (chromatin dots on some rings)
Vivax – schuffners dots may be present
Malaria – mature schizonts have daisy head appearance. Squarish appearance of ring forms
Ovale – enlarged red cells. Comet forms
Thick and thin blood smears x3
- Field’s or Giemsa stain
- Thick: screen parasites (sensitive)
- Thin: identify species & quantify parasitaemia
Malaria antigen detection tests
- Paracheck-Pf® (detect plasmodial HRP-II)
- OptiMAL-IT (parasite LDH)
Malaria - Rx Non Falciparum
- Chloroquine – 3 days
- Primaquine 30mg for 14 days weeks if G6PD normal
Hypnozoites
Complications in non-falciparum malaria are extremely rare but splenic rupture is well recorded (80% mortality with splenic rupture)
Malaria - Rx Mild Falcpiarum
Not vomiting, Parasitaemia <2%, Ambulant
- Oral Malarone ™ (atovaquone and proguanil) - 4 tablets daily with food for three days
- ACT – artemisinin combination therapies E.g Riamet/ Co-artem – Artemisinin & Lumefantrine
- Oral quinine 600mg tds (salt) - then doxycycline 100mg od for 1 week
Malaria - Rx Severe Falcpiarum
- ABC
- Correct Hypoglycamia
- Cautious rehydration (avoid overload)
- Organ support as necessary
- IV Artesunate in preference to IV Quinine
Quinine side effects: cinchonism, arrhythmias, hyperinsulinaemia - Daily parasitaemia then PO follow on eg with ACT
Dengue
Organism: Dengue Virus (RNA virus) - flavivirus
Transmitted via the Aedes mosquito.
Mostly urban disease
Presents with: fever, headache, myalgia, rash in 50%
3 Phases:
FEBRILE - Day 1-4 – fever, headache, rash
CRITICAL - Day 4-7 – bleeding, shock
RECOVERY – inflammation.
DHF and shock syndromes rare in travellers- Occur in those previously infected with a different Dengue serotype.
Investigations:
- Serology (IgM 5-7 days), PCR.
- Dengue cross reaction with other flavivirus IgG (JE, yellow fever.)
Treatment:
- Identify those at risk of shock. (High Hct, low platelets)
- Supportive - Paracetamol
Thyphoid
Organism: Salmonella Typhi/ Paratyphi
Vaccine only partially protective vs S.typhi, no cover vs S.paratyphi
Symptoms:
- Fever - high and prolonged
- Headaches
- GI symptoms (Payer’s patches) - constipation
- “Rose spots” - rare but specific
- Hepatosplenomegaly
- Dry cough
Investigations: Blood and stool culture. Screen for HIV and malaria.
Treatment:
Empiric Ceftriaxone (2g IV OD) then Azithromycin
500mg BD 7 days
Complications: GI bleeding/ perforation/ encephalopathy
Monospot
Test for EBV - less specific than IgM/IgG
