Yellow fever

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 affected individuals 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 these 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.

• 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.

• Pathogen: yellow fever virus
  • Genus: flavivirus, type of arbovirus
  • Genetics: single-stranded, positive-sense, linear RNA virus
  • Appearance: enveloped, icosahedral
• Transmission
  • Vectors: mosquitoes; (primarily Aedes aegypti )
  • Main reservoir: primates (human and non-human)
  • Different transmission cycles (depending on local circumstances and geography)

References:^[2][3]

• 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 high 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)
       • Hemorrhage (epistaxis, mucosal bleeding, melena, hematuria, black vomiting)
       • Multiorgan dysfunction (e.g., acute kidney and liver failure)
       • Abdominal pain, severe jaundice

Most patients remain asymptomatic or experience only mild symptoms.

References:^[4][5]

• Laboratory tests
  • ↑ ALT/AST
  • Leukopenia
  • In period of intoxication
    • Thrombocytopenia, ↑ PTT
    • Signs of organ failure (see acute liver failure, acute renal failure)
• Virus detection
  • PCR
  • ELISA
• Liver biopsy
  • Used for definitive diagnosis (e.g., postmortem)
  • Must not be done while the patient has an active yellow fever infection
  • May show Councilman bodies (eosinophilic apoptotic globules)

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]

• Influenza
• Viral hepatitis (e.g., hepatitis A)
• Other viral hemorrhagic fevers (e.g., Dengue hemorrhagic fever)
• Malaria

The differential diagnoses listed here are not exhaustive.

• 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:^[5]

• Bacterial superinfections (e.g., pneumonia, sepsis)
• Cardiac disorders (e.g., myocarditis)

We list the most important complications. The selection is not exhaustive.

Vaccination ^[2][6][7]

• The yellow fever vaccine is a live-attenuated vaccine administered subcutaneously.
• Indications: individuals 9 months to 60 years of age ≥ 10 days prior to ^[7]
  • International travel to areas with endemic yellow fever (see “Immunizations before travel”)
  • Handling of yellow fever strains (e.g., in laboratory or research jobs)
• A single lifetime dose is typically sufficient; some individuals may require a booster. ^[7]
• Contraindications include: ^[8]
  • History of anaphylaxis to any vaccine component (e.g., eggs, latex in a prefilled syringe)
  • Age < 9 months ^[7]
    • Absolute contraindication if < 6 months of age (risk of encephalitis)
    • Relative contraindication if 6–8 months of age
  • Contraindications for live vaccines

When contraindications are present, consider the individual's specific risks and benefits and use shared-decision making to decide whether to immunize.

If state supplies of yellow fever vaccine are limited, direct international travelers to the following CDC website (wwwnc.cdc.gov/travel/page/search-for-stamaril-clinics) for US providers of imported, non-FDA approved yellow fever vaccines. ^[7]