Yellow fever is considered to be the original viral hemorrhagic fever. Although most individuals experience only mild illness, approximately 15% of infected persons develop serious dis- ease, with hepatorenal dysfunction, myocardial injury, and hemorrhage (203). 20–80% of serious infections end in death. There is no antiviral therapy speciﬁcally targeted to yellow fever (204).
The incidence of yellow fever has been increasing dra- matically in the past two decades (205). Between 1985–1996, 23,543 cases and 6421 deaths were reported to the World Health Organization, although many more cases are believed to go unreported (203). An outbreak in Guinea in 2000 involved 688 cases with 225 deaths. A massive vaccination program was hampered by insufﬁcient stocks, leading UNICEF to stockpile 2 million doses of 17D vaccine to be used in response to outbreaks (206). Yellow fever is found in tropical South America and sub-Saharan Africa. Two clinically identical forms of yellow fever exist (urban and jungle) and both are spread by Aedes aegypti. The urban form is transmitted from human to human by the A. aegypti mosquitoes. In areas that control A. aegypti, yellow fever has disappeared (204). The jungle form is transmitted among nonhuman primates by var- ious mosquitoes, and humans are incidentally infected. How- ever, the rarity of infections may be an artifact of poor reporting of cases in the past.
The live attenuated yellow fever vaccine was ﬁrst devel- oped 1936, and is produced by growth of the 17D virus strain in chick embryos. It is the only vaccine strain for yellow fever and serious events occur at less than 1 in 1 million. It is so low that it is not feasible, at this time, to develop a new vaccine (207).
Seroconversion rates with the vaccine are 95–98% in both adults and children. Vaccinations consist of a single subcuta- neous injection of 0.5 ml of vaccine. Immunity has been docu- mented for at least 30–35 years and is thought to be lifelong (205). Regardless, a certiﬁcate of yellow fever immunization for international travel to certain countries is only valid for 10 years, requiring revaccination thereafter. Immunization for yellow fever is indicated for anyone ³9 months of age living or traveling in endemic areas (tropical South America or sub- Saharan Africa) (208). Vaccination may also be required for entry into particular countries, and current information is available from health departments.
Despite recent reports of incidents resembling classic yellow fever after vaccination, the yellow fever vaccine is considered to be extremely safe with few side effects (207). Those persons who develop some side effects (2–5%) usually recover in 5–10 days, and immediate hypersensitivity reactions occur at a rate of approximately 1 in 1 million doses (209).
As with all vaccinations, some adverse events are reported. Improved surveillance since the 1990s has brought some previously unreported problems to light. The most recent is the description of 20 incidents that resemble classic yellow fever. It is not known if some of the vaccine recipients had recent prior exposure to wild yellow fever virus before receiving the vaccine. However, the cases occurred in produc- tion lots of virus from three different manufacturers. Rever- sion virulence among several different manufacturers seems unlikely. There may be an idiosyncratic host susceptibility that permits virulence-associated mutations during a pro- longed viremic phase (207). Advanced age may also be a risk factor, but those persons having a repeat vaccination are less likely to have a severe reaction (207,210).
General side effects lasting 5–10 days:
Low-grade fevers. Mild headaches. Myalgia.
Hypersensitivity (immediate reactions) is often associated with egg allergy or the gelatin stabilizer used in the vaccine:
Vaccine-associated neurotrophic disease. World- wide vaccinations (200 million) have resulted in 22 cas- es of encephalitis with laboratory analysis of the presence of the vaccine virus (211).
Vaccine-associated viscerotropic disease (VAVD).
May be associated with 10 cases and ranges from mod- erate illness with focal organ dysfunction to severe dis- ease with overt multiple organ system failure and death (204).
Children. The majority of encephalitis cases were re- ported in children <4 months of age. Recommendations are that children not be vaccinated until they are >9 months of age.
Pregnant women. Vaccination for yellow fever should not occur in pregnant women (207).
Immunocompromised. Immunization should be with- held from immunosuppressed individuals.
Asymptomatic HIV infection. In the United States, asymptomatic infection with HIV is not considered a contraindication (209). In the United Kingdom, HIV is a contradiction (207).
Better surveillance and documentation of yellow fever symptoms resulting from yellow fever vaccine is needed. Addi- tional tests to monitor organ function for viscerotropic compli- cations should be considered. Reactions to the vaccine need to be characterized to determine which ones are vaccine-mediated or which ones resulted from individual risk factors (allergies, immunosuppression, etc.). Behavioral research into why trav- elers to areas of concentrated yellow fever cases are not prop- erly vaccinated prior to traveling may help decrease the number of travelers’ cases of yellow fever.