What is Yellow Fever
Yellow fever is a potentially fatal mosquito-borne viral hemorrhagic disease endemic to sub-Saharan Africa and tropical South America that causes an estimated 200,000 clinical cases and 30,000 deaths annually, with severe cases characterized by jaundice, hemorrhagic manifestations, and hepatorenal dysfunction carrying a case-fatality rate of 20-50%. 1, 2
Disease Etiology and Transmission
Yellow fever virus (YFV) is an RNA virus belonging to the genus Flavivirus, antigenically related to West Nile virus, St. Louis encephalitis virus, and Japanese encephalitis virus. 2 The disease is transmitted through three distinct epidemiological cycles:
Transmission Cycles
Jungle (sylvatic) cycle: Transmission occurs between nonhuman primates and forest canopy mosquito species (Haemagogus spp. and Sabethes spp. in South America; Aedes africanus in Africa), with humans infected when they encroach into forested areas during occupational or recreational activities. 3
Urban cycle: Anthroponotic transmission between humans via urban mosquitoes, primarily Aedes aegypti, which can sustain epidemic spread in populated areas. 3
Intermediate (savannah) cycle: Found only in Africa, involving transmission by tree hole-breeding Aedes species to humans living or working in jungle border areas, with virus transmission occurring from nonhuman primate to human or human to human. 3
Geographic Distribution
Yellow fever occurs exclusively in sub-Saharan Africa and tropical South America, with approximately 90% of cases and deaths occurring in Africa. 4 The disease is not endemic to North America, Asia, Australia, or Oceania, though the presence and spread of Aedes aegypti mosquitoes increases the risk of introduction to these regions. 4
Clinical Manifestations and Pathogenesis
Following mosquito inoculation, the virus enters the bloodstream and replicates in target tissues, producing high viremia that peaks shortly before fever onset and persists for 3-5 days. 2 The incubation period ranges from 3-6 days. 2
Disease Spectrum
Asymptomatic or mild disease: The majority of YFV infections remain asymptomatic or produce only mild, undifferentiated febrile illness. 2
Symptomatic disease: Manifests abruptly with fever, prostration, headache, photophobia, lumbosacral pain, extremity pain, epigastric pain, anorexia, and vomiting. 2
Severe disease: Approximately 15% of symptomatic patients progress to severe disease with jaundice (from massive hepatocyte destruction), hemorrhagic manifestations (from thrombocytopenia and coagulopathy), and multisystem organ failure including renal failure. 2 The overall fatality rate is approximately 20%, reaching 20-50% in those with hepatorenal dysfunction. 1, 2
Prevention and Vaccination
The Centers for Disease Control and Prevention recommends yellow fever vaccine for persons aged ≥9 months traveling to or living in areas at risk for YFV transmission in South America and Africa. 1 Vaccination should be administered at least 10 days before travel to ensure immunity. 1
Vaccination Contraindications and Precautions
Absolute contraindications include age <6 months, primary immunodeficiencies, and transplantation. 1 Healthcare providers should carefully consider precautions before administering vaccine to infants aged 6-8 months, adults aged ≥60 years, pregnant women, and breastfeeding women. 1
Additional Preventive Measures
All travelers should use EPA-registered insect repellents containing DEET, picaridin, IR3535, or oil of lemon eucalyptus, wear permethrin-impregnated clothing, and stay in accommodations with screened windows or air conditioning. 1
Treatment and Prognosis
There is no specific antiviral treatment for yellow fever, making management of severe cases extremely problematic and reliant on supportive care. 4 The distinctive property of lifelong immunity after a single dose of yellow fever vaccination makes prevention through routine childhood vaccination in endemic countries the primary strategy to reduce disease burden. 4