5 Jun

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.

Adverse Effects

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:

Rash. Urticaria.

Asthma symptoms.

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).

Special Considerations

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.

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