Yellow Fever
Summary
Yellow Fever is a high-consequence mosquito-borne viral haemorrhagic fever caused by a Flavivirus. It is endemic to tropical areas of Africa and Central/South America. The clinical course is classically biphasic: an initial "viremic" phase of flu-like symptoms, followed by brief remission, and then a "toxic" phase (in ~15% of cases) characterized by hepatic failure (Jaundice = Yellow), renal failure, and coagulopathy. Mortality in the toxic phase exceeds 50%. Prevention is via the highly effective 17D live-attenuated vaccine. Diagnosis relies on travel history and PCR/Serology, but differentiating from Malaria and Leptospirosis is critical. [1,2]
Key Facts
- Vector: Aedes aegypti (Urban cycle) and Haemagogus spp. (Jungle/Sylvatic cycle).
- Faget's Sign: A classic sign where the pulse is relatively slow (bradycardia) despite a high fever. (Also seen in Typhoid).
- Councilman Bodies: Eosinophilic apoptotic hepatocytes seen on liver biopsy (pathognomonic, though biopsy is contraindicated due to bleeding risk).
- The "Yellow Card": An International Certificate of Vaccination or Prophylaxis (ICVP) is mandatory for entry into certain countries to prevent importation of the virus.
Clinical Pearls
The "Period of Intoxication": If a patient survives the first 10-14 days without entering the toxic phase, they will usually recover completely without sequelae.
Vaccine-Associated Viscerotropic Disease (YEL-AVD): A rare but fatal complication where the vaccine virus replicates wildly, mimicking wild-type Yellow Fever. Risk factors: Age >60, History of Thymus disease (Thymoma/Myasthenia).
Egg Allergy: The vaccine is cultured in chick embryos. Severe egg allergy is a contraindication.
Zero Asia: Curiously, Yellow Fever has never established itself in Asia, despite the presence of Aedes mosquitoes and dengue. This mystery protects billions of people.
Geography
- Africa: 90% of global cases (West/Central/East Africa).
- South America: Amazon basin (Brazil, Peru, Colombia).
- Asia: No transmission.
Cycles
- Sylvatic (Jungle): Monkey-to-Mosquito-to-Human (logger/forest worker).
- Intermediate: Savanna (Africa only).
- Urban: Human-to-Mosquito-to-Human. Epidemic potential.
Mechanism
- Entry: Mosquito bite -> Lymph nodes -> Replication.
- Viremia: Disseminates to Liver, Spleen, Kidney, Bone Marrow.
- Hepatic Damage: Direct viral injury to mid-zonal hepatocytes -> Apoptosis -> Jaundice + Loss of clotting factors.
- Renal: Acute Tubular Necrosis (Direct viral + Hypotension).
- Bleeding: Thrombocytopenia + Clotting factor consumption (DIC).
Incubation
Phase 1: Acute (Viremic)
Phase 2: Toxic (15% of cases)
- General: Toxic, agitated. Jaundiced (sclera).
- Skin: Petechiae, Ecchymoses.
- Abdomen: Epigastric tenderness (Liver). Hepatomegaly.
- Vitals: Hypotension (Shock). Relative bradycardia.
Specific
- RT-PCR: Blood. Diagnostic in first 3-4 days.
- Serology (IgM): Detectable from Day 5 onwards. (ELISA/PRNT).
- Cross-reactivity with Dengue/Zika is a problem.
General
- FBC: Leucopenia (early) then Leucocytosis (late). Severe Thrombocytopenia.
- LFTs: AST and ALT > 1000-5000. (AST usually > ALT, unlike viral hepatitis). Bilirubin high.
- Coagulation: PT/APTT prolonged (Liver failure + DIC).
- Renal: Creatinine rising (ATN).
- Urinalysis: Proteinuria (Albuminuria).
Management Algorithm
SUSPECTED YELLOW FEVER
(Fever + Travel + Jaundice)
↓
ISOLATE PATIENT
(Under mosquito net)
↓
SUPPORTIVE CARE
(ICU usually required)
↓
┌─────────────┼──────────────┐
COAGULOPATHY RENAL SHOCK
↓ FAILURE ↓
FFP / Vit K Dialysis Fluids /
Platelets Vasopressors
1. Supportive Care
- No specific antiviral treatment.
- Hydration: Aggressive IV fluids to prevent renal failure, but careful of pulmonary oedema.
- Coagulopathy: FFP for bleeding. Gastric protection (PPI) to reduce risk of GI bleed.
- Dialysis: Often required for metabolic acidosis/anuria.
2. Isolation
- In endemic areas, patients must be kept under bed nets during the viremic phase (first 5 days) to prevent local mosquitoes biting them and sparking an urban outbreak.
3. Vaccination (Prevention)
- Stamaril (17D strain): One of the most effective vaccines ever made.
- Schedule: Single dose. Immunity within 10 days. Lifelong protection (WHO removed 10-year booster requirement in 2013).
- Contraindications:
- Egg Hypersensitivity (Anaphylaxis).
- Immunodeficiency (HIV CD4 less than 200, Thymus disorder).
- Infants less than 9 months (Encephalitis risk).
- Caution in >60 years (Viscerotropic risk).
- Hepatorenal Syndrome: Combined liver/kidney failure.
- Myocarditis: Arrhythmias.
- Secondary Bacterial Infection: Pneumonia / Sepsis.
- Mild cases: 100% recovery.
- Toxic cases: 50% Mortality. Death usually occurs within 7-10 days of onset.
- Survivors: No chronic carrier state. Lifelong immunity. Liver usually heals without cirrhosis.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Yellow Fever | WHO / CDC | Vaccination is the only effective control measure. Single dose lifelong. |
| Vaccine Safety | NaTHNaC | Strict risk assessment for >60s. Absolute contraindication for Thymus history. |
Landmark Knowledge
1. Walter Reed Commission (1900)
- Discovery: Proved mosquito transmission (debunking "fomite" theory).
- Impact: Allowed control of the disease during Panama Canal construction through mosquito control.
2. Theiler (1937)
- Discovery: Developed the 17D vaccine strain.
- Impact: Nobel Prize 1951. Still the same vaccine strain used today.
What is Yellow Fever?
It is a severe virus spread by mosquitoes in Africa and South America. It attacks the liver, causing jaundice (yellow skin) and bleeding.
Is it dangerous?
Yes. About 15% of people get the severe form. Of those, half will die. There is no cure once you catch it.
The Vaccine
The vaccine is extremely effective. One shot protects you for life.
- Why do I need a certificate? Some countries require proof of vaccination ("Yellow Card") not to protect you, but to protect their mosquitoes from catching it from you if you arrived sick.
Side Effects
The vaccine is a live virus. It can cause mild flu symptoms. In very rare cases (especially in older people or those with thymus problems), it can cause serious illness. We will do a careful risk assessment before giving it.
Primary Sources
- World Health Organization. Yellow fever. Fact sheet.
- Monath TP. Yellow fever: an update. Lancet Infect Dis. 2001;1:11-20. PMID: 11871403.
- Gardner CL, Ryman KD. Yellow fever: a reemerging threat. Clin Lab Med. 2010;30:237-260.
Common Exam Questions
- Travel Medicine: "Contraindications to YF Vaccine?"
- Answer: Egg allergy, Thymectomy/Thymoma, Immunosuppression, Age less than 6 months.
- Infectious Disease: "Faget's Sign?"
- Answer: Pulse-Temperature dissociation (Bradycardia with Fever).
- Pathology: "Liver biopsy findings?"
- Answer: Councilman Bodies (apoptotic hepatocytes). Mid-zonal necrosis.
- Virology: "Type of virus?"
- Answer: Flavivirus (ssRNA).
Viva Points
- YEL-AND vs YEL-AVD:
- AND: Associated Neurotropic Disease (Encephalitis).
- AVD: Associated Viscerotropic Disease (Multi-organ failure mimicking YF).
- Why no YF in Asia?: Theories include cross-immunity from Dengue or lower vector competence of Asian Aedes.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.