Yellow Fever

Yellow fever is a viral haemorrhagic fever caused by yellow fever virus, a flavivirus transmitted by Aedes and, in the jungle transmission cycle, Haemagogus mosquitoes. It is endemic to specific regions of sub Saharan Africa and tropical South America.

It has historically been responsible for devastating epidemics and remains a significant cause of morbidity and mortality in endemic, unvaccinated populations.

It is distinguished from most other flaviviral infections by the availability of a highly effective, long lasting vaccine that forms the cornerstone of both individual traveller protection and broader disease control. International vaccination certificate requirements reflect its ongoing public health significance and epidemic potential.

Pathophysiology and transmission cycles

• Two distinct transmission cycles maintain circulation of the virus: the sylvatic (jungle) cycle, involving transmission between non human primates and forest dwelling mosquitoes with incidental human infection during forest activity.
• The urban cycle involves direct human to human transmission via Aedes aegypti in areas of dense human population. The urban cycle carries particular epidemic potential given the efficiency of this specific transmission pattern.
• Following infection, the virus produces direct hepatocellular injury together with systemic vascular endothelial dysfunction, underlying the characteristic combination of severe hepatitis (producing the classical jaundice from which the disease derives its name) and haemorrhagic manifestations in severe disease.

• The majority of infections are asymptomatic or produce a mild, non specific febrile illness.
• Symptomatic disease classically follows a biphasic pattern: an initial phase of fever, headache, myalgia, nausea and relative bradycardia, lasting three to four days. Faget sign is a classically described though inconsistently present finding of a slower pulse rate than would be expected for the degree of fever.
• In a proportion of patients, a brief remission follows before progression to a more severe toxic phase.
• The toxic phase, occurring in approximately fifteen percent of symptomatic infections, is characterised by recurrence of high fever together with jaundice (reflecting severe hepatic involvement), haemorrhagic manifestations (haematemesis, melaena, epistaxis and other bleeding), and progressive renal impairment. This severe presentation carries substantial mortality, historically reported as high as twenty to fifty percent among those developing the toxic phase.
• A relevant travel or residence history in an endemic region of sub Saharan Africa or tropical South America, together with vaccination status, should be specifically established in any compatible febrile illness presentation. Unvaccinated status in a traveller returning from or resident in an endemic area substantially raises clinical suspicion.

• Polymerase chain reaction testing on blood offers sensitive detection during the early viraemic phase, generally within the first several days of illness.
• Serological testing (IgM detection, with confirmatory plaque reduction neutralisation testing given cross reactivity with other flaviviruses) used beyond this early window. It requires careful interpretation in previously vaccinated individuals or those with prior exposure to related flaviviruses given potential cross reactive antibody responses.
• Liver function tests typically show marked transaminase elevation reflecting the severe hepatic involvement characteristic of this infection, together with coagulation studies and renal function supporting assessment of severity in the toxic phase.
• Any suspected case, given the significant public health and outbreak potential of this infection, requires prompt notification to relevant public health authorities, with specialist reference laboratory confirmation typically required given the specific biosafety and public health surveillance considerations associated with this diagnosis.

• There is no specific antiviral treatment available for yellow fever. Management is entirely supportive, comprising careful fluid and electrolyte management, correction of coagulopathy and blood product support for significant haemorrhage, and renal replacement therapy for significant acute kidney injury.
• Care is delivered within an appropriate level of care according to disease severity, up to and including intensive care support for the most severe toxic phase presentations.
• Nonsteroidal anti inflammatory drugs and aspirin should be avoided given the significant bleeding risk associated with this condition, with paracetamol preferred for symptomatic fever and pain management.
• Vaccination represents the single most important preventive intervention. The live attenuated yellow fever vaccine, given as a single dose, provides long lasting, likely lifelong, protective immunity in the great majority of recipients.
• It is recommended for travellers to and residents of endemic regions. Many countries require documented proof of vaccination (via the International Certificate of Vaccination or Prophylaxis) for entry.
• This is particularly relevant for travellers moving between different endemic regions where the risk of introducing infection to a previously unaffected area is a specific public health concern.
• The yellow fever vaccine is a live attenuated preparation and carries specific contraindications and precautions.
• These include significant immunosuppression, pregnancy and breastfeeding (where the decision requires individualised risk benefit assessment against the specific travel related exposure risk).
• Age extremes (with specific caution in infants under nine months and adults over sixty given a recognised, though uncommon, association with severe vaccine associated adverse events in these age groups).
• Careful individualised assessment and specialist travel medicine advice are required before administration in these specific populations.
• Mosquito bite avoidance measures form an important adjunctive preventive strategy alongside vaccination, particularly relevant for the small proportion of travellers in whom vaccination is contraindicated or for whom full immunity has not yet developed (generally considered established within ten days of vaccination).
• Outbreak response in affected regions incorporates mass vaccination campaigns, vector control measures, and enhanced surveillance, reflecting the substantial epidemic potential of this disease, particularly within the urban transmission cycle in areas of high population density and inadequate vaccination coverage.