Yellow fever

Yellow fever is a vaccine preventable virus, which circulates between infected monkeys or humans and day-biting mosquitoes (National Travel Health Network and Centre, 2022). It is endemic in tropical areas of Africa and Central and South America, and the island of Trinidad in the Caribbean (World Health Organisation (WHO), 2019).

Yellow fever spreads to humans via mosquito bites (US Centers for Disease Control and Prevention, 2022). Infection with yellow (the ‘yellow’ refers to the jaundice that affects some infected people) fever virus can result in a mild illness or cause an acute viral haemorrhagic disease that can be fatal (WHO, 2019).

Travellers from non-endemic regions, such as Europe, are at risk if they travel to countries where it is endemic.

To prevent international spread of yellow fever, under the World Health Assembly International Health Regulations, for entry purposes, countries may require proof of yellow fever vaccination (as a public health

Yellow fever is found in some parts of the tropical and sub-tropical regions of Africa and South and Central America, and the Caribbean Island of Trinidad. It has never been reported in Asia, despite the presence of the mosquito that can carry the virus (United Kingdom Health Security Agency, 2020).

Large epidemics of yellow fever have occurred when infected people have introduced the virus into heavily populated areas with high numbers of mosquitoes and where most people have little or no immunity as a result of a lack of vaccinations (WHO, 2019). 

There are three transmission cycles:

• Sylvatic (jungle) cycle: maintained within monkey or non-human primate populations in jungle or rain forests, with some spread to people in close contact with the forest.
• Intermediate (savannah) cycle: maintained by people, monkeys (and other non-human primates) in rural villages, where increased human transmission leads to small outbreaks.
• Urban cycle: maintained in high-density

Most people infected with yellow fever virus will either have no symptoms or very mild symptoms and will completely recover.

For people who develop symptoms, the time from infection until illness is typically 3–6 days. Symptoms include:

• sudden onset of fever
• chills
• severe headache
• back pain
• general body aches
• nausea and/or vomiting
• fatigue and weakness

Most people who develop symptoms improve within 1 week. For some people who recover, weakness and fatigue may last several months (US Centers for Disease Prevention and Control, 2022).

A small number (15–25%) of people enter a second, more toxic phase within 24 hours of recovering from their initial symptoms. A high fever returns and several body systems are affected, usually the liver and kidneys. In this phase, people are likely to develop jaundice (yellowing of skin and eyes), dark urine and abdominal pain with vomiting. An acute haemorrhagic fever can occur, with bleeding from the mouth, eyes, ears and stomach, and deterioration of major organ function. Half of these people die within 7–10 days (National Travel Health Network and Centre, 2022; WHO, 2023).

Yellow fever virus is an arbovirus of the family Flaviviridae, genus Flavivirus. It is a single-stranded, positive-sense group IV RNA virus spread by Aedes mosquitoes (mainly Aedes aegypti) in Africa and Aedes and Haemagogus mosquitoes in the Americas (Messer, 2022).

Yellow fever is difficult to diagnose, especially during the early stages. More severe cases can be confused with malaria, viral hepatitis, other haemorrhagic fevers, infection with other flaviviruses (like dengue haemorrhagic fever), leptospirosis and poisoning (WHO, 2023).

Initial diagnosis is based on travel history, clinical features and exposure details (Gershman and Staples, 2020). Polymerase chain reaction (PCR) testing in blood and urine can sometimes detect the virus in early stages of the disease. In later stages, testing to identify antibodies is needed (IgM) (WHO, 2023).

If a UK clinician suspects yellow fever in a returned traveller, an urgent referral to an infectious disease or tropical disease clinical team is required. The UK Health Security Agency has a specialist centre for health professionals called the Rare and Imported Pathogens Laboratory that provides advice and diagnosis of a wide range of unusual viral and bacterial infections, including yellow fever (National Travel Health Network

There is no specific treatment for yellow fever (Gershman and Staples, 2020). However, good and early supportive care in hospitals may improve survival rate and specific care to treat dehydration, liver and kidney failure and fever can help improve outcomes. Associated bacterial infections can be treated with antibiotics, but there is currently no anti-viral drug available to treat yellow fever (WHO, 2019).

While all travellers visiting yellow fever risk areas should practice meticulous mosquito bite avoidance (National Travel Health Network and Centre, 2023), vaccination is the most important way to prevent yellow fever (WHO, 2019).

A safe and effective yellow fever vaccine has been available for more than 80 years. This is a live, weakened form of the virus given as a single injection and a single dose provides lifelong protection for most people (US Centers for Disease Control and Prevention, 2022).

The vaccine provides effective immunity within 10 days for 80–100% of people vaccinated, and within 30 days for more than 99% of people vaccinated (WHO, 2019). 

Vaccination is recommended for anyone over the age of 9 months who is at risk of yellow fever infection (National Travel Health Network and Centre, 2022).

However, serious adverse events, including fatal adverse reactions to yellow fever vaccine have been reported (Commission on Human Medicines, 2019; National Travel

Resources

National Travel Health Network and Centre: Yellow fever pre-vaccination checklist https://travelhealthpro.org.uk/factsheet/87/yellow-fever-pre-vaccination-checklist (accessed 15 February 2023)

National Travel Health Network and Centre: Yellow fever vaccine associated neurotropic disease (YEL-AND) and yellow fever vaccine associated viscerotropic disease (YEL-AVD) https://nathnacyfzone.org.uk/factsheet/58/yel-and-and-yel-avd (accessed 15 February 2023)

Pan American Health Organisation: Yellow fever https://www.paho.org/en/topics/yellow-fever (accessed 15 February 2023)

Public Health England, Medicines and Healthcare products Regulatory Agency, NaTHNaC and Health Protection Scotland joint letter: Yellow fever vaccine: stronger precautions in people with weakened immunity and those aged 60 years or older https://travelhealthpro.org.uk/media_lib/mlib-uploads/full/2019-11-21-yellow-fever-vaccine-precautions-letter.pdf (accessed 15 February 2023)

World Health Organisation: Yellow fever Q&A https://www.who.int/news-room/questions-and-answers/item/yellow-fever (accessed 15 February 2023)

United Kingdom Health Security Agency: Yellow fever: guidance, data and analysis https://www.gov.uk/guidance/yellow-fever-guidance-data-and-analysis (accessed 15 February 2023)

United Kingdom Health Security Agency Imported fever service -Clinical advisory and specialist diagnostic service for medical professionals managing travellers who've returned to the UK with fever: https://www.gov.uk/guidance/imported-fever-service-ifs (accessed 15 February 2023)

National Travel Health Network and Centre’s Yellow fever vaccine: contraindications and precautions reminder for more information