Yellow fever

Classification and Structure

• Family: Flaviviridae

• Genus: Flavivirus

• Genome: Single-stranded positive-sense RNA (~11 kb)

• Structure: Enveloped, spherical, icosahedral capsid, ~50 nm in diameter

• Closely related to dengue, Zika, and West Nile viruses

Transmission

• Vector-borne: Transmitted by Aedes aegypti mosquitoes in urban settings and Haemagogus and Sabethes mosquitoes in jungle cycles

• Transmission cycles:

  • Sylvatic (jungle): Mosquitoes transmit the virus between non-human primates; humans are infected when they enter forested areas

  • Intermediate (savannah): Semi-domestic mosquitoes infect both monkeys and humans

  • Urban: Mosquitoes transmit between humans, leading to outbreaks in cities

• No documented human-to-human transmission outside of vector route, except rarely via blood products or organ transplantation

Epidemiology

• Endemic in tropical regions of Africa and South America

• Not naturally present in Asia despite presence of competent vectors

• WHO estimates ~200,000 cases annually worldwide, with high mortality in severe disease

• Historically caused devastating urban epidemics in the Americas, Africa, and Europe

Pathogenesis

• Virus enters skin via mosquito bite → infects dendritic cells → spreads to lymph nodes and bloodstream

• Targets liver, kidneys, and myocardium

• Causes hepatocellular injury with midzonal necrosis, leading to jaundice and coagulopathy

• Induces cytokine release and capillary leakage contributing to multi-organ failure

Clinical Manifestations

• Incubation period: 3–6 days

• Illness phases:

  1. Infection phase (3–4 days)

     • Sudden onset fever, chills, headache, myalgia (especially back pain), nausea, vomiting, conjunctival injection

  2. Remission (hours to a day)

     • Temporary improvement in symptoms

  3. Toxic phase (15–25% of cases)

     • Recurrence of fever, jaundice, abdominal pain, vomiting (may be bloody)

     • Hemorrhagic signs: epistaxis, hematemesis ("black vomit"), melena

     • Oliguria, proteinuria, acute kidney injury

     • Delirium, seizures, coma in severe cases

• Complications: Acute liver failure, disseminated intravascular coagulation (DIC), shock, death

Diagnosis

• Molecular: RT-PCR for viral RNA (most useful in early infection)

• Serology: IgM and neutralizing antibody detection (cross-reactivity with other flaviviruses possible)

• Laboratory findings: Leukopenia, thrombocytopenia, elevated liver enzymes (AST often higher than ALT), prolonged prothrombin time, proteinuria

• Differential diagnosis: Malaria, viral hepatitis, leptospirosis, other viral hemorrhagic fevers

Treatment

• No specific antiviral therapy available

• Supportive management is critical

• Measures include:

  • Hospitalization for moderate to severe cases

  • Fluid replacement and electrolyte correction

  • Antipyretics (paracetamol/acetaminophen); avoid NSAIDs and aspirin due to bleeding risk

  • Blood transfusion for severe hemorrhage

  • Dialysis for renal failure if needed

  • Intensive care support for multi-organ failure

• Avoid unnecessary injections to reduce bleeding risk

• For severe hepatic involvement: monitor coagulation, provide plasma products if indicated

Prevention and Control

• Vaccination:

  • Live attenuated 17D yellow fever vaccine

  • Single subcutaneous dose provides immunity within 10 days; likely lifelong protection

  • Recommended for residents or travelers to endemic areas (required by International Health Regulations for entry into certain countries)

  • Contraindicated in infants <6 months, people with severe egg allergy, immunosuppressed patients, and pregnant women unless at high risk

• Vector control: Eliminate breeding sites, apply larvicides, indoor residual spraying

• Personal protection: Insect repellents (DEET, picaridin), long clothing, bed nets

• Outbreak response: Rapid vaccination campaigns, mosquito control, travel advisories