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Friday July 13 1:22 PM ET

Yellow Fever Vaccine Safety Questioned

By Keith Mulvihill

NEW YORK (Reuters Health) - Three newly published reports show that in a handful of cases, people receiving the yellow fever vaccine have died shortly after being immunized. However, experts say that the risks associated with yellow fever are much greater than the risk of suffering a fatal reaction to the vaccine, which appears to be a very rare event.

Yellow fever is a mosquito-borne ailment that results in a high fever, a yellowing of the skin due to liver damage (jaundice) and bleeding from the gums, the intestines and the kidneys. The disease is most commonly found in tropical and subtropical regions of Africa and South America, and is fatal in approximately 20% to 50% of victims--with the elderly often at a greater risk of death.

The three studies published in the July 14th issue of the British journal, The Lancet, report on deaths associated with the yellow fever vaccine in three countries--three deaths in the US, two deaths in Brazil and one death in Australia. However, experts caution that yellow fever is a potentially life-threatening ailment and the benefits of the vaccine outweigh the risks in the vast majority of people who are at risk of contracting the illness.

``The bottom line is that the outcomes that were reported in The Lancet are very rare events,'' said Dr. Martin S. Cetron, co-author of one of the studies, who conducts research at the Centers for Disease Control and Prevention (news - web sites) (CDC) in Atlanta, Georgia. ``The vaccine has been used for over 60 years and has been safe and effective not only to people living in endemic areas but to travelers to those regions (where yellow fever is common) as well,'' he told Reuters Health.

The yellow fever vaccine contains a virus that is a weakened version of live, wild-type yellow fever and has been given in an estimated 400 million doses worldwide since its development in the 1930s.

In the first report, Dr. Pedro. Vasconcelos, of the WHO Collaborating Centre for Reference and Research on Arbovirus in Brazil, and colleagues note that a 5-year-old girl and a 22-year-old woman each died within a week of being vaccinated for yellow fever.

In the second report, lead author Dr. Michael Martin of the CDC and colleagues report on the deaths of three Americans--all over the age of 63. A fourth patient who became very ill 9 days after receiving a yellow fever vaccine recovered. In the last report, a letter to The Lancet, Dr. Raymond C. Chan of the South Western Area Pathology Service in Sydney, Australia, and colleagues detail the death of a 56-year-old man who died within 2 weeks of receiving the yellow fever vaccine.

The patients in Brazil and Australia had symptoms similar to those seen in patients with yellow fever, while the US patients had some yellow fever symptoms, in addition to multiple systemic problems, involving the liver, kidney, lungs and brain. The researchers could find no specific link between the cases, such as a certain lot of vaccine or patient characteristic.

``We could not find a common link that would suggest defects in the vaccine,'' Cetron told Reuters Health.

Instead Cetron suggests that there may have been some as yet unknown factor about the individuals who received the vaccine that caused the adverse reaction.

While the exact frequency of adverse events for those receiving the yellow fever vaccine is not known, Cetron stressed that, between 1990 and 1998, a period where 1.6 million doses of the yellow fever vaccine were given out to Americans, only these four cases were documented.

The US researchers conclude that the vaccine should continue to be used, but that ``care should be taken in recommending yellow fever vaccine for older people; for travellers, itineraries should be scrutinized and vaccine should be provided only to those travelling to areas reporting yellow fever activity or areas in the yellow fever endemic zone.''

``Despite the severity of these reactions, overall the findings indicate that no change in practice regarding yellow fever vaccination is needed for endemic or epidemic areas,'' Dr. Philippe Marianneau of the Pasteur Institute in Lyon, France and colleagues write in an accompanying commentary.

``There are no obvious correlations between the cases in these three reports,'' they add.

``The use of (the yellow fever vaccine) remains highly advisable'' for people living in or traveling to regions where yellow fever exists, Marianneau and colleagues conclude.

SOURCE: The Lancet 2001;358:84-85, 91-97, 98-104, 121-122.

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