Introduction

Yellow fever is a mosquito-borne viral haemorrhagic fever. Symptoms usually develop 3-6 days after an individual has been bitten by an infected mosquito. It produces a spectrum of illness, with approximately one in seven people infected developing a rapidly progressive (or 'toxic phase') illness characterised by hepatitis, renal failure, and haemorrhagic and cardiovascular shock. Of these severely affected cases, approximately half will die. The World Health Organization (WHO) estimates that there are about 200,000 cases globally and 30,000 deaths due to the disease per year despite there having been an effective vaccine available for more than half a decade.^[1]

As there is no specific treatment available, vaccination is the best method of preventing and controlling the disease. The main preventive strategies employed against yellow fever are:

• Giving yellow fever vaccine as part of routine infant immunisation (usually at the same time as measles vaccine) in countries where the disease is endemic.
• The use of mass vaccination campaigns to prevent outbreaks in high-risk areas.
• Control of Aedes aegypti mosquitoes in urban centres.

Yellow fever is endemic in many parts of sub-Saharan Africa and tropical South America, where both sporadic cases and epidemic outbreaks may occur. Yellow fever is rare in travellers to these regions and, since 1996, there have been just six fatal imported cases in European and US travellers. All were in unvaccinated travellers.

Yellow fever vaccination is recommended for travel to all countries in the endemic zones, whether or not an international certificate is required, and especially if rural areas will be visited. (Consult up-to-date country specific advice.)

Available vaccine

This vaccination is not available on the National Health Service and is given by registered Yellow Fever Centres.

• The 17D live attenuated vaccine was developed in 1936 by Max Theiler and his team and became widely available in 1951. It has been one of the most successful antiviral vaccines to date and over 540 million doses have been used worldwide.^[2]
• Wherever high vaccination rates (>80%) have been achieved the incidence of yellow fever has declined. However, whilst the majority of countries with endemic yellow fever do have vaccination programmes, few achieve vaccination coverage of more than half of their population.^[1][3]
• Expansion of travel to these areas has increased demand for the vaccine and every year there are shortages.

Vaccination schedule

• It is administered as a single dose by deep subcutaneous route and provides immunity in 95-100% of travellers. It should be given at least ten days prior to travel to the endemic area to allow sufficient immunity to develop.
• Immunity probably persists for life, but re-vaccination is advised after 10 years for those whose risk of contracting the disease persists.
• The vaccine can only be given at specialist centres.
• Proof of yellow fever vaccination, recorded on an International Certificate of Vaccination, is now the only vaccination certificate that should be required in international travel. Many countries require this of travellers, including those in transit, arriving from infected areas or from countries with infected areas.^[4] Some countries require evidence of vaccination from all entering travellers, even when they have come directly from a non-endemic country. This can be strictly enforced, particularly for people arriving in Asia from Africa or South America. Failure to comply may result in being quarantined for several days. The certificate is valid from the tenth day after primary vaccination and lasts for 10 years. The certificate is also valid immediately after re-immunisation if the re-immunisation occurs within the 10-year period. If vaccination is contra-indicated, dispensation is possible and an exemption certificate of WHO standard should be issued.
• Live vaccines can be given at the same time as inactivated ones. Other live vaccines can be administered at the same time as yellow fever vaccine, but must be given at different sites and in different syringes. If they are not given on the same day, they should be separated by an interval of at least three weeks.
• It is good practice to obtain written or verbal consent, prior to vaccination.
• Patient details, together with date, time, batch number and site of vaccination should be recorded, and an immunisation certificate issued, which is signed by the patient and stamped by the issuing centre.

The following groups of people should be immunised:

• Laboratory workers handling infected material
• Persons aged nine months or older who are travelling to countries that require an International Certificate of Vaccination for entry.
• Persons aged nine months or older who are travelling to or living in infected areas or countries in the yellow fever endemic zone (see maps on www.nathnac.org), even if these countries do not require evidence of immunisation on entry.

Contra-indications and precautions to vaccination^[5]

• Aged 5 months or under (Infants aged 6 to 9 months should only be immunised if the risk of yellow fever during travel is unavoidable; expert opinion should be sought in these situations).
• Anaphylaxis or serious hypersensitivity reactions:
  • It should not be given to those who have had a confirmed anaphylactic reaction or serious hypersensitivity reaction following a previous dose of the same vaccine.
  • Do not give if an individual has had a confirmed anaphylactic reaction to egg.
  • Those who have a thymus disorder.
  • Those who are considered to be immunocompromised due to a congenital condition, disease process or treatment.
• The following are precautions:
  • If an individual is acutely unwell, immunisation should be postponed until they have fully recovered. This is to avoid confusing the differential diagnosis of any acute illness by wrongly attributing any sign or symptoms to the adverse effects of the vaccine.
  • Minor illnesses without fever or systemic upset are not valid reasons to postpone immunisation.
  • People over 60 years of age. The risk for neurologic and viscerotropic adverse events increases with age.
  • Breast-feeding. There is no evidence of harm to the baby from vaccination of the breast-feeding mother ^[6]. While there is a theoretical risk that yellow fever vaccine virus is excreted in breast milk, vaccination should be considered in cases where there is a real risk to the mother from yellow fever disease.
  • Pregnancy. Yellow fever vaccine should not be given because of the theoretical risk of fetal infection from the live virus vaccine. Pregnant women should be advised not to travel to a high-risk area. When travel is unavoidable, the risk from the disease and the theoretical risk from the vaccine have to be assessed on an individual basis. WHO states that the vaccine may be considered after the sixth month of pregnancy and should be administered if the destination risk is high.

Adverse reactions

The most commonly reported symptoms include:

• Headache, myalgia and low-grade fever. These are common - they can occur in 10-30% of those vaccinated.
• Injection site erythema and local soreness which can occur.
• Post-vaccine encephalitis - this is a rare event, more commonly seen in infants.
• Yellow fever vaccine-associated neurotropic disease (YEL-AND). This can occur 4-23 days after the vaccination and typically starts with a fever and headache and then progresses to include one or more of confusion, focal neurological deficits, coma and Guillain-Barré syndrome. Usually patients completely recover from this. It occurs in around four cases per million doses of the vaccine.
• Yellow fever vaccine-associated viscerotropic disease (YEL-AVD). This can occur 2-7 days after the vaccination and typically patients develop fever, malaise, headache and myalgias and then progresses to hepatitis and multi-organ failure, like wild-type yellow fever. It also has similarly high fatality rates. It is extremely rare (three cases per million doses of vaccine).

A safer inactivated yellow fever vaccine is being trialled which could be useful for vaccinating people at higher risk of adverse events from the live vaccine ^[7].