GlobeX Travel Vaccine

Cause
The yellow fever virus, an arbovirus of the Flavivirus genus.

Transmission
Yellow fever in urban and some rural areas is transmitted by the bite of infective Aedes aegypti mosquitoes and by other mosquitoes in the forests of South America. The mosquitoes bite during daylight hours. Transmission can occur at altitudes up to 2300 metres. Yellow fever virus infects humans and monkeys.
In jungle and forest areas, monkeys are the main reservoir of infection, with transmission from monkey to monkey carried out by mosquitoes. The infective mosquitoes may bite humans who enter the forest area, usually causing sporadic cases or small outbreaks.
In urban areas, monkeys are not usually involved and infection is transmitted among humans by mosquitoes. Introduction of infection into densely populated urban areas can lead to large epidemics of yellow fever.
In Africa, an intermediate pattern of transmission is common in humid savannah regions. Mosquitoes infect both monkeys and humans, causing localized outbreaks.

Nature of the disease
Although most of the infections are asymptomatic and not detected, some infections lead to an acute illness characterized by two phases. Initially, there is fever, muscular pain, headache, chills, anorexia, nausea and/or vomiting, often with bradycardia. About 15% of patients progress to a second phase after a few days, with resurgence of fever, development of jaundice, abdominal pain, vomiting and haemorrhagic manifestations; half of these patients die 10–14 days after onset of illness.

Geographical distribution
The yellow fever virus is endemic in some tropical areas of Africa and central and South America. The number of epidemics has increased since the early 1980s. Other countries are considered to be at risk of introduction of yellow fever due to the presence of the vector and suitable primate hosts (including Asia, where yellow fever has never been reported).

Risk for travellers
The normally low risk to travellers increases with travel to jungle areas in endemic countries and in or near cities during urban outbreaks. Areas where yellow fever virus is present far exceed those offi cially reported. The risk of exposure to infection can be reduced by taking measures to prevent mosquito bites (see Chapter 3). It should be noted that the mosquito vectors of yellow fever bite mostly during daylight hours. Although reported cases of human disease are the principal indicator of disease risk, some countries may have no reported cases, either because of a high level of vaccine coverage against yellow fever in the population or because poor surveillance resulted in no cases being reported. However, the risk of yellow fever may still persist as the virus, the vector or the animal reservoir is still present.

Vaccine
The 17D vaccine, which is based on a live, attenuated viral strain, is the only commercially available yellow fever vaccine. It is given as a single subcutaneous (or intramuscular) injection. Yellow fever vaccine is highly effective (approaching 100%), while the disease may be fatal in adults who are not immune. With few exceptions (see below), vaccination is recommended for all travellers to countries or areas where there is a risk of yellow fever transmission (see country list and Annex 1).

Precautions and contraindications
Tolerance of the vaccine is generally excellent – only 2–5% of vaccine recipients have mild reactions, including myalgia and headache. Contraindications include true allergy to egg protein, cellular immunodefi ciency (congenital or acquired, the latter sometimes being only temporary) and symptomatic HIV infection. Many industrialized countries administer yellow fever vaccine to persons with symptomatic HIV infection provided that the CD4 count is at least 200 cells/ mm3. Asymptomatic HIV-positive individuals may have a reduced response to the vaccine. There is a theoretical risk of harm to the fetus if the vaccine is given during pregnancy, but this must be weighed against the risk to the mother of remaining unvaccinated and travelling to a high-risk zone. (However, pregnant women should be advised not to travel to areas where exposure to yellow fever may occur.) Encephalitis has been reported as a rare event following vaccination of infants under 9 months of age; as a result, the vaccine is contraindicated in children aged under 6 months and is not recommended for those aged 6–8 months. There have been recent reports of a small number of serious adverse events (including deaths), of vaccine-associated viscerotropic disease, following immunization with the yellow fever 17DD vaccine. The evidence suggests that the incidence of adverse events may be different in regions where yellow fever is endemic (from 0 to 0.21 per 100 000 doses) and in regions with populations not exposed to the virus (from 0.09 to 0.4 per 100 000 doses). The risk of adverse events may be related to population differences (e.g. previous vaccination or exposure to wild yellow fever virus). This risk appears to be limited to the fi rst immunization. Also recently identifi ed as potential risk factors are a history of thymus disease (e.g. thymoma) and age over 60. Adverse events of vaccine-associated neurotropic disease have been reported (e.g. meningoencephalitis, acute disseminated encephalomyelitis and Guillain-Barré syndrome). The incidence rate reported in travellers from the United States and Europe ranges between 0.19 to 0.8 per 100 000 doses. The risk to unvaccinated individuals who visit countries where there may be yellow fever transmission is far greater than the risk of a vaccine-related adverse event, and it remains important for all travellers at risk to be vaccinated. Nonetheless, great care should be exercised not to prescribe yellow fever vaccination to individuals who are not at risk of exposure to infection, based on an accurate assessment of the travel itinerary. Yellow fever vaccination should be encouraged as a key prevention strategy, but it is important to screen travel itineraries, particularly of older travellers, and carefully evaluate the potential risk of systemic illness after yellow fever vaccination.

Type of vaccine: Live, attenuated
Number of doses: One priming dose of 0.5 ml
Booster: 10-yearly (if re-certification is needed)
Contraindications: Egg allergy; immunodeficiency from medication, disease or symptomatic HIV infection; hypersensitivity to a previous dose; pregnancy (see text above)
Adverse reactions: Rarely, encephalitis or hepatic failure
Before departure: International certificate of vaccination becomes valid 10 days after vaccination
Recommended for: All travellers to areas with risk of yellow fever transmission and wherever mandatory
Special precautions: Not for infants under 9 months of age; restrictions in pregnancy