Reaction to Yellow Fever Vaccine Linked to Several Recent Deaths

 

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WESTPORT, CT (Reuters Health) Jul 12 - The 17DD and 17D-204 yellow fever vaccines have been associated with six deaths in Brazil, the US and Australia, according to three reports in July 14^th issue of The Lancet.

“Yellow fever vaccine has been around for more than 60 years and we never suspected that one of its side effects could be an illness very similar if not identical to wild-type yellow fever,” Dr. Thomas P. Monath, from Acambis Inc., Cambridge, Massachusetts, told Reuters Health.

“This is a new clinical syndrome,” he added. “But I don’t think this is really a new problem; it is a newly recognized problem. We would like to know precisely what the risk is, but I don’t think we can ever accurately know.”

Dr. Monath and colleagues describe the cases of two deaths associated with 17DD yellow fever vaccine in Brazil. The first case involved a 5-year-old white girl who began to show symptoms of fever, headache, malaise, and vomiting 3 days after being vaccinated for yellow fever and measles, mumps and rubella. Five days after becoming ill, she died.

The second case was a 22-year-old black woman who developed symptoms including sore throat and fever 4 days after receiving yellow fever vaccine and died 6 days later.

“This is a very rare host-determined genetic susceptibility to yellow fever,” Dr. Monath said. “It does not seem to be related to any change in the vaccine manufacture or mutations of the host. Regulatory agencies and manufacturers are going to have to revise the package inserts to include mention of this rare side effect.”

These cases two “bounced around the medical system without a diagnosis for a long time,” Dr. Monath said. “Physicians need to instruct patients who receive this vaccine [that] if they get a fever or feel seriously unwell in the first week after vaccination, they need to get medical attention.”

In the second report, Dr. Martin S. Cetron, from the US Centers for Disease Control and Prevention, Atlanta, and colleagues identified four cases of severe illness that developed within days of yellow fever vaccination. Three of the cases date from 1998 and one case dates from 1996. In all these cases, the patients were over the age of 63 years.

All the patients developed symptoms that included fever, myalgia, headache and confusion. Three of these patients died, the researchers report.

In these six cases, the temporal association between vaccination and the development of illness, serologic and histologic findings, isolation of variant vaccine virus and the absence of any other explanation, collectively suggest a causal relationship between the yellow fever vaccine and severe illness.

However, in an interview with Reuters Health, Dr. Cetron cautioned that “in no way should the cases reported this week lead to a discontinuation of the use of the vaccine either in endemic areas, epidemic areas or by travelers to those areas.” The risk of going into an area with known yellow fever unprotected by vaccine is still far greater that the risk of having a vaccine-related adverse event, he stressed.

Both Drs. Monath and Cetron believe that the yellow fever vaccine is both underused and overused. “It is underutilized in the sense that not everyone who goes to the endemic areas is getting immunized and not everyone who lives there is immunized.” Conversely, there are people who travel to places where there is no risk of exposure who receive the vaccine unnecessarily, Dr.  Monath said.

Dr. Cetron stressed that physicians should be sure before giving the vaccine that the patient is actually going to an area of yellow fever risk. “One or perhaps two of the US cases reported a travel destination that was a nonrisk area,” he added.

In the third report, Dr. Raymond C. Chan, of the South Western Area Pathology Service, Sydney, Australia, and colleagues describe a recent case of a 56-year-old man who developed symptoms 3 days after receiving a single dose of the yellow fever vaccine.

The patient died 7 days later. Analysis of serum and tissue samples revealed that “this patient died from yellow fever due to infection with live yellow fever vaccine strain 17D-204.”

Dr. Chan and his colleagues believe that in light of this case and the other reported cases, “re-evaluation of the safety of these vaccines and their indications is required.”

In a journal commentary, Dr. Vincent Deubel, and colleagues from the Institut Pasteur, Lyon, France, also believe that “the use of 17D vaccination remains highly advisable for people living in or traveling to endemic and epidemic zones. However, these three reports raise relevant questions about the mechanisms of attenuation of yellow-fever virus that should be urgently investigated.”

Lancet 2001;358:84-85,91-104,121-122.

 

 

 

 

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