Management and Treatment of Yellow Fever
There is no specific antiviral therapy for yellow fever; management is entirely supportive and symptom-based, with treatment intensity determined by the severity of organ system involvement. 1
Immediate Management Approach
Mild to Moderate Disease
- Provide rest, oral fluids, and acetaminophen or NSAIDs for fever and myalgias 1
- Avoid aspirin due to hemorrhagic complications risk 1
- Isolate patients from mosquito exposure (indoors or under mosquito nets) during the first 3-4 days of illness to prevent further transmission 1
Severe Disease with Multisystem Involvement
- Patients with hepatorenal dysfunction, hemorrhagic manifestations, or cardiovascular instability require critical care support 1
- Mechanical ventilation may be necessary for respiratory compromise 1
- Hemodialysis is indicated for renal failure 1
- Monitor for and manage bleeding diathesis, including hematemesis, melena, hematuria, and coagulopathy 1
Diagnostic Confirmation
Early Phase (First 3-4 Days)
- Obtain serum for virus isolation or RT-PCR to detect yellow fever virus or viral RNA 1
- Note that by the time overt symptoms appear, virus is often undetectable, so negative results do not exclude diagnosis 1
Later Phase (After Day 3-4)
- Test for yellow fever-specific IgM antibodies using capture ELISA 1
- Confirm positive results with plaque reduction neutralization test due to cross-reactivity with other flaviviruses (West Nile, dengue) 1
- Document ≥4-fold rise in neutralizing antibody titers between acute and convalescent sera 1
Contact Public Health Authorities
- Healthcare providers should contact their state/local health department and CDC (1-970-221-6400) for diagnostic testing assistance 1
Critical Monitoring Parameters
Laboratory Surveillance
- Monitor for leukopenia (first week) or leukocytosis (second week) 1
- Track coagulation parameters: PT, PTT, platelet count, fibrin-split products 1
- Follow bilirubin levels (may peak at end of first week) 1
- Monitor transaminases (may remain elevated up to 2 months) 1
Clinical Surveillance
- Watch for progression to severe disease in approximately 15% of symptomatic patients, typically occurring within 48 hours after initial 3-day viremic period 1, 2
- Monitor for jaundice, renal insufficiency, cardiovascular instability, and hemorrhagic manifestations 1
Differential Diagnosis Considerations
Yellow fever with jaundice must be differentiated from: 1
- Viral hepatitis
- Malaria
- Leptospirosis
- Congo-Crimean hemorrhagic fever
- Rift Valley fever
- Typhoid, Q fever, typhus
- Drug-induced or toxic jaundice
Yellow fever without jaundice must be differentiated from: 1
- Dengue hemorrhagic fever
- Lassa fever
- Marburg and Ebola virus diseases
- South American hemorrhagic fevers
Prognosis and Expected Outcomes
- Majority of patients with mild disease recover without long-term sequelae 1
- Case-fatality ratio is 20-50% for severe disease with hepatorenal dysfunction 1, 2
- Risk factors for death include: hypotension, shock, renal failure, severe hemorrhage, coma, and convulsions 1
- Convalescence is often prolonged, lasting several weeks 1
- Rare late deaths can occur weeks after recovery due to myocardial damage and arrhythmia 1
- Secondary bacterial infections (e.g., pneumonia) can complicate recovery 1
Common Pitfalls to Avoid
- Do not rely on negative RT-PCR or viral culture to exclude yellow fever, as viremia is typically absent by the time severe symptoms develop 1
- Do not administer aspirin for symptom management due to hemorrhagic risk 1
- Do not delay critical care support in patients showing signs of progression to severe disease 1
- Do not forget mosquito isolation during the viremic period to prevent transmission 1
Experimental Considerations
While multiple drugs have been evaluated empirically, none has demonstrated specific benefit to date 1. One case report describes sofosbuvir use in vaccine-associated yellow fever in an immunocompromised patient, but this remains experimental and unproven 3.