• Clinical science

Yellow fever

Abstract

Yellow fever is an acute viral infection caused by the yellow fever virus. Primates are the main reservoir of the virus, which is usually transmitted through bites from infected mosquitoes. Yellow fever is endemic in large parts of South America and Africa. The incubation period is 3–6 days, and the majority of patients remain asymptomatic or experience only mild symptoms. Symptomatic patients initially present with nonspecific symptoms such as sudden-onset fever, malaise, headaches, chills, nausea, and myalgia. Approx. 15% of symptomatic patients progress to the most serious stage of the disease, which can present with life-threatening hemorrhagic fever and organ failure. There is no causal treatment available, making prevention of crucial importance. A single dose of live-attenuated vaccine provides lifelong protection for most individuals.

Epidemiology

  • Yellow fever is endemic in tropical regions of South America and Sub-Saharan Africa.
  • Asia, Europe, North America, and Australia are free of yellow fever (except for occasional imported cases).

Yellow fever is endemic in large parts of South America and Africa!

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

  • Pathogen: yellow fever virus (genus Flavivirus)
    • Genetics: single-stranded, positive-sense, linear RNA virus
    • Appearance: enveloped, icosahedral
  • Transmission
    • Vectors: mosquitoes (primarily Aedes aegypti or Haemagogus spp.)
    • Main reservoir: primates (human and non-human)
    • Different transmission cycles (depending on local circumstances and geography)

References:[2][3][4][5][6]

Clinical features

  • Incubation time: 3–6 days
  • Clinical features
    • The majority of infected individuals remain asymptomatic.
    • In symptomatic patients: classic progression in three stages
      1. Period of infection (3–4 days)
        • Sudden onset of fever (up to 41°C, or 105°F)
        • Headaches, chills
        • Nausea, vomiting
      2. Period of remission (up to 2 days)
        • Easing of symptoms and decline in fever
      3. Period of intoxication (only in ∼ 15% of symptomatic patients)
  • Complications

Most patients remain asymptomatic or experience only mild symptoms!

References:[7][4][8][9]

Diagnostics

May show Councilman bodies in the intermediate zone (zone II)

The best test to rule out yellow fever infection is PCR, particularly in the absence of overt symptoms such as fever, headaches, and chills!

References:[2][4][8][5]

Differential diagnoses

References:[4]

The differential diagnoses listed here are not exhaustive.

Treatment

  • Symptomatic treatment
  • No specific antiviral treatment is available

Avoid NSAIDs that increase the risk of bleeding (e.g., aspirin, ibuprofen, naproxen) in patients with confirmed or suspected yellow fever infection!

References:[9]

Prevention

Vaccination

  • Indication: recommended for individuals (≥ 9 months) traveling to areas where yellow fever is endemic
  • Administration
    • A single dose of live-attenuated vaccine is sufficient for most patients and provides life-long protection (administer at least 10 days before travel).
    • ACIP guidelines nevertheless recommend additional doses for:
      • Women who were pregnant at the time of initial vaccine administration → administer 1 additional dose
      • Individuals who received a hematopoietic stem cell transplant after their last vaccination → repeat vaccination before next travel
      • Individuals who were HIV-positive at the time of the last vaccination → repeat vaccination every 10 years as long as they are exposed to risk of infection
  • Absolute contraindications (also see general contraindications for vaccination)
    • Infants under 9 months of age
    • Individuals with insufficient immune function (e.g., due to HIV infection or immunosuppressive medication)
  • Relative contraindications
    • Individuals over 60 years of age because of the high risk of severe side effects
    • Pregnancy and nursing mothers
  • Side effects
    • Two very rare, but severe side effect syndromes:
      • Particularly in infants: yellow fever vaccine-associated neurologic disease
      • Particularly in older patients: yellow fever vaccine-associated viscerotropic disease

References:[4][5][10]