Yellow Fever: Clinical Features, Diagnosis, Management and Prevention
Clinical Medicine Year 3 • an African arboviral disease with hepatic, renal and haemorrhagic complications
Why yellow fever matters
Yellow fever is an acute mosquito-borne viral haemorrhagic disease caused by yellow fever virus, a flavivirus. It ranges from an asymptomatic or mild febrile illness to a toxic phase with jaundice, coagulopathy, shock, renal failure, encephalopathy and death. Because early yellow fever can look like malaria, viral hepatitis, dengue or sepsis, the diagnosis is often missed unless the clinician asks about mosquito exposure, travel, vaccination and outbreaks.
The word “yellow” refers to jaundice from hepatic injury. The disease is not spread by ordinary casual contact, but a patient with circulating virus can infect a mosquito that later bites another person. Early mosquito precautions therefore protect both the patient and the community.
Learning outcomes
- Describe the virus, vectors, reservoirs and jungle, intermediate and urban transmission cycles.
- Explain the clinical phases from incubation through acute and toxic disease.
- Recognise jaundice, bleeding, shock, renal failure and encephalopathy as danger signs.
- Choose appropriate laboratory tests and distinguish yellow fever from malaria, hepatitis, dengue and other severe febrile diseases.
- Provide safe supportive management and explain vaccination, mosquito control and outbreak response.
Definition and virology
Yellow fever virus is an enveloped, positive-sense single-stranded RNA virus in the genus Flavivirus. It is an arbovirus because it is transmitted by arthropods. The virus has a strong tropism for hepatocytes, reticuloendothelial cells and other tissues. Viral replication, apoptosis and inflammatory injury can produce midzonal hepatic necrosis, cholestasis, coagulopathy and multiorgan dysfunction.
Epidemiology and transmission cycles
Yellow fever remains endemic in tropical parts of Africa and South America. Uganda is within the African risk zone, so a febrile jaundiced patient with mosquito exposure or an outbreak connection requires serious consideration of yellow fever alongside malaria and viral hepatitis.
| Cycle | Reservoir and vector | Clinical/public-health meaning |
|---|---|---|
| Sylvatic (jungle) | Non-human primates and forest mosquitoes; humans enter the cycle when they work or travel in forest | Occupational and travel-related cases; primate deaths may precede human cases |
| Intermediate (savannah) | Forest-edge mosquitoes infect monkeys and humans in rural or semi-rural areas | Can cause rural outbreaks and bridge infection toward towns |
| Urban | Infected humans and peridomestic Aedes mosquitoes, especially Aedes aegypti | Rapid explosive outbreaks where population immunity is low |
An infected mosquito becomes capable of transmission after an extrinsic incubation period. Humans are most infectious to mosquitoes around the early viraemic days of illness. A person does not normally infect another person directly by touch, coughing or sharing food.
Risk factors
- Living in or visiting a yellow-fever-endemic area without vaccination.
- Forest work, farming, hunting, logging, fishing or outdoor night/day exposure depending on the vector.
- Low community vaccine coverage, urban crowding and abundant breeding sites.
- Immunosuppression or advanced age, which may increase the risk of severe vaccine adverse effects or severe natural disease.
- Pregnancy and young infancy require careful vaccine-risk decisions in a travel or outbreak context.
Pathophysiology
- After a mosquito bite, virus replicates locally and enters lymphatic tissue.
- Viraemia disseminates virus to the liver, spleen, lymph nodes, kidney and bone marrow.
- Hepatocyte injury causes jaundice, raised aminotransferases, impaired clotting-factor synthesis and hypoglycaemia.
- Systemic endothelial injury, cytokines and coagulation abnormalities produce bleeding, capillary leak and shock.
- Acute kidney injury results from shock, direct injury and pigment/volume effects; encephalopathy may reflect hepatic failure, shock or metabolic derangement.
Clinical course
1. Incubation phase
Symptoms commonly begin about 3–6 days after an infective mosquito bite. The patient is usually well during incubation.
2. Acute febrile phase
This phase usually lasts several days and may include sudden fever, chills, severe headache, backache, myalgia, arthralgia, nausea, vomiting, photophobia, weakness and facial flushing. Conjunctival injection and relative bradycardia may be present. Laboratory findings can include leukopenia, thrombocytopenia, raised transaminases and mild proteinuria.
3. Remission phase
Many patients improve after the initial fever. A short remission does not always mean cure; clinicians must warn patients to return if jaundice, bleeding, severe abdominal pain, reduced urine, confusion or recurrent fever appears.
4. Toxic phase
A minority progress to severe disease, often after apparent improvement. Findings include:
- Jaundice, dark urine, pale stool and tender hepatomegaly.
- Persistent vomiting, epigastric or right-upper-quadrant pain.
- Bleeding from gums, nose, gastrointestinal tract, injection sites or uterus; petechiae and ecchymoses.
- Hypotension, narrow pulse pressure, cold extremities, oliguria and metabolic acidosis.
- Acute kidney injury, haematuria and reduced urine output.
- Hypoglycaemia, agitation, drowsiness, seizures or hepatic encephalopathy.
- Myocarditis, arrhythmias, respiratory failure, disseminated intravascular coagulation and multiorgan failure.
Bedside danger signs
Jaundice plus bleeding, persistent hypotension, altered mental state, oliguria, hypoglycaemia, severe abdominal pain, rapidly rising INR, severe thrombocytopenia or worsening creatinine should be treated as toxic yellow fever until proven otherwise.
History and examination
| Ask or examine | Why it matters |
|---|---|
| Onset, travel and residence | Links illness to endemic area or a known outbreak and estimates incubation. |
| Vaccination card and prior yellow fever | A documented vaccine or past infection greatly changes probability, but does not replace testing in a compatible outbreak. |
| Mosquito and forest exposure | Identifies sylvatic or urban risk. |
| Malaria tests and treatment | Failure to improve after appropriate antimalarial therapy should prompt a wider differential. |
| Bleeding and urine output | Detects coagulopathy and kidney injury early. |
| Neurologic state and glucose | Encephalopathy and hypoglycaemia are potentially reversible emergencies. |
| Jaundice, hydration, shock, hepatosplenomegaly | Assesses severity and need for admission/critical care. |
Investigations
Initial severity assessment
- Full blood count with platelet count and haematocrit.
- Urea, creatinine, electrolytes, glucose and urinalysis.
- AST, ALT, bilirubin, albumin and alkaline phosphatase.
- PT/INR, aPTT, fibrinogen and lactate where available.
- Blood group and cross-match if bleeding or severe thrombocytopenia is present.
- Malaria microscopy or rapid diagnostic test, blood cultures and targeted tests for other causes of fever.
Confirmatory tests
- RT-PCR or viral RNA testing: most useful early in illness while viraemia is present.
- IgM ELISA: becomes useful after the early days; a positive result supports recent infection but can cross-react with other flaviviruses.
- Neutralisation testing: may help confirm specificity in reference laboratories.
- Post-mortem or tissue testing: immunohistochemistry or molecular testing may be needed in fatal cases.
Collect specimens using appropriate biosafety precautions and coordinate with the national reference laboratory. A negative early test does not always exclude disease; repeat or reference testing may be necessary when clinical suspicion remains high.
Differential diagnosis
| Condition | Clues and tests |
|---|---|
| Severe malaria | Parasitaemia, anaemia, hypoglycaemia, coma or renal failure; can coexist with yellow fever. |
| Acute viral hepatitis | Marked transaminases, exposure history, hepatitis A/E/B tests; does not explain every outbreak pattern. |
| Dengue | Retro-orbital pain, severe myalgia, thrombocytopenia, capillary leak and Aedes exposure. |
| Leptospirosis | Animal/water exposure, conjunctival suffusion, renal injury and jaundice. |
| Ebola/Marburg or other viral haemorrhagic fever | Outbreak contact, severe systemic illness and bleeding; follow isolation and notification procedures. |
| Sepsis, meningococcaemia, Lassa fever | Shock, rash, altered mental state and organ-specific findings. |
Management
Immediate supportive care
- ABC assessment, oxygen for hypoxaemia and frequent monitoring of pulse, blood pressure, respiratory rate, urine output, mental state and glucose.
- Use careful isotonic crystalloid resuscitation for hypoperfusion; reassess frequently because hepatic failure, capillary leak and kidney injury make fluid overload dangerous.
- Give paracetamol only within safe dose limits after considering liver injury. Avoid aspirin, ibuprofen, diclofenac and other NSAIDs because of bleeding and renal risk.
- Correct hypoglycaemia promptly and monitor glucose repeatedly.
- Control nausea, provide enteral nutrition when safe and avoid unnecessary intramuscular injections.
- Use blood products for clinically significant bleeding or procedure-related need, guided by haemodynamics, haemoglobin, coagulation and specialist advice—not by an isolated laboratory number.
- Manage acute kidney injury with fluid balance, electrolyte correction and dialysis when indicated.
- Treat encephalopathy by correcting glucose, hypoxia, shock, electrolytes and infection; protect the airway if consciousness falls.
- Search for and treat secondary bacterial infections, but do not prescribe antibiotics solely because yellow fever is suspected.
Infection-control and mosquito precautions
During the viraemic period, keep the patient in a screened or mosquito-protected area and use bed nets/repellent. Standard precautions apply to routine care; gloves, gowns, eye protection and safe sharps practice are essential when blood, vomit, stool or body fluids may be present. Escalate precautions and laboratory handling according to the suspected viral-haemorrhagic-fever protocol.
Prevention and vaccination
- Vaccination: the live-attenuated 17D vaccine is the most effective preventive measure. A single documented dose generally provides long-lasting/lifelong protection for most people and an international certificate may be required for travel.
- Contraindications and precautions: severe allergy to a vaccine component, significant immunosuppression and very young age require specialist assessment. Pregnancy and breastfeeding usually require a risk–benefit decision during outbreaks or unavoidable travel.
- Vector control: remove standing water, cover containers, improve environmental sanitation, use screens and repellents and reduce indoor/outdoor mosquito exposure.
- Outbreak response: rapid case notification, laboratory confirmation, vaccination campaigns, community education, active case finding and mosquito control are required.
- One Health surveillance: unexplained monkey deaths and clusters of febrile jaundice should be reported because animal and human surveillance can identify transmission early.
Exam-focused pearls
- Yellow fever is an Aedes-transmitted flavivirus with jungle, intermediate and urban cycles.
- The toxic phase can follow a brief remission; apparent improvement does not always mean recovery.
- Jaundice plus bleeding, renal failure or encephalopathy suggests severe disease.
- Test for malaria at the same time; coinfection is possible.
- Avoid NSAIDs, aspirin, unnecessary injections and hepatotoxic medicines.
- Vaccination and mosquito control are the main public-health tools; treatment is supportive.
