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Updated: Dec 21 2016

Yellow Fever

Snapshot
  • A 43-year-old female presents to the ED with a six day history of fever, chills, headache, and severe backache. She returned from Gambia on a missions trip 10 days prior to onset of illness. She had been taking antimalarial prophylaxis but did not receive any immunizations prior to the trip. Temperature is 102.8°F (39°C). Physical exam reveals an ill-looking woman with pallor and scleral icterus.Her epigastrium is markedly tender to palpation. Complete blood count shows a hematocrit of 30%, platelets of 75,000/mm3, and leukocyte count of 3,200/mm3. Coagualtion panel revealed an INR of 5.3 and PT of 29 secs. Total bilirubin was 3.3 mg/dL, AST 950 U/L, and ALT 350 U/L. Blood, CSF, and urine cultures were negative. No Plasmodia were detected on peripheral blood smear. Patient was presumptively treated for malaria and serology for IgM ELISA is pending.
Introduction
  • Classification
    • linear, enveloped (+) ssRNA flavivirus
      • yellow fever virus
  • Acute viral hemorrhagic fever spread by infected mosquitos
    • flavi = yellow, jaundice
  • Epidemiology
    • incidence
      • 200,000 illnesses per year
      • 30,000 deaths per year
    • risk factors
      • residing in Africa
        • 90% of infections take place in Africa
      • the unvaccinated population
    • location
      • common in Africa and South America
  • Transmission
    • 3 types 
      • sylvatic (or jungle)
        • occurs in tropical rainforests
        • infected monkeys pass virus to other mosquitos that feed on them
        • these mosquitos bite and infect humans in the forest (think loggers)
      • intermediate
        • occurs in humid savannahs of Africa
        • small-scale epidemics in rural villages
        • semi-domestic mosquitos infect both monkey and human hosts
        • increased contact between man and infected mosquito
      • urban
        • large explosive epidemics
        • travellers from rural areas introduce virus into highly populated areas
        • mosquito can carry virus from person to person
    • via Aedes aegypti mosquito 
    • virus has monkey or human reservoir
  • Pathogenesis
    • virus replicates in lymph nodes
    • infects dendritic cells in particular
    • find their way to the liver where they infect hepatocytes
      • eosinophilic degradation and cytokine release
      • necrotic masses (Councilman bodies) are found in the cytoplasm of hepatocytes
Presentation
  • Symptoms
    • incubation period of virus is approximately 3-6 days
    • mild (lasts approximately 3-4 days)
      • fever
      • headache
      • nausea
      • vomiting 
      • myalgias
      • anorexia
    • possible subsequent toxic phase 
      • recurring fever
      • liver damage leading to jaundice and/or death
      • bleeding daithesis
      • bloody vomitus 
      • affects 15% of those with a primary infection
      • fatal in 20% of cases
Evaluation
  • Biopsy
    • liver
      • can verify inflammation, necrosis, and viral antigens
      • only consider bx post-mortem b/c of bleeding tendency of yellow fever patients
  • Diagnosis
    • clinical diagnosis
      • relies on history, symptomatology, and incubation time
    • viral genome amplification via RT-PCR (reverse transcription polymerase chain reaction)
      • cannot be confirmed until 6-10 days after illness began
    • viral growth in cell culture
      • takes 1-4 weeks
    • ELISA 
      • IgM against yellow fever virus
      • can cross-react with other flaviviruses
Differential
  • Other viral hemorrhagic fevers (Ebola, Marburg, and Lassa)
    • not usually associated with jaundice
  • Viral hepatitis A and B
  • Leptospirosis
Treatment
  • Supportive care
    • no specific treatments have been developed yet
    • hospitalization as needed
Prognosis, Prevention, and Complications
  • Prognosis
    • mortality 
      • 20-60% in developing countries (mainly unvaccinated population)
  • Prevention
    • vaccines
      • YF-VAX
        • live, attenuated
          • induces humoral and cell-mediated immunity
        • q10 years PRN
        • needed for travel to affected areas
    • vector control
      • insect repellant
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