Do you recommend the yellow fever vaccine to young children, given past reports of serious adverse events?

It is a ‘gray zone’ for infants aged 6 to 8 months.

The vaccine manufacturer and the FDA approve the yellow fever vaccine for use in children aged 9 months and older, who should be given vaccine if traveling to an area at risk for yellow fever transmission. The vaccine is absolutely contraindicated for use in infants aged younger than 6 months because of the increased risk of post-vaccinal encephalitis. There is, however, a gray zone for children aged 6 to 8 months. ACIP and WHO recognize that there are situations where infants aged 6 to 8 months may need to be immunized because of unavoidable exposure to a high-risk environment for yellow fever virus exposure, such as a travel to or residence in a setting of endemic or epidemic yellow fever.

It is difficult to quantify what is a potentially high-risk exposure, especially relative to the risk of post-vaccinal encephalitis, and so this involves a good measure of judgment. The CDC recommends that practitioners who are considering administering yellow fever vaccine to an infant aged 6 to 8 months consult their state health department or CDC for guidance. CDC can be contacted by calling 800-CDC-INFO.

The decision not to immunize out of fear of post–vaccinal encephalitis is not without risks; an unimmunized person travelling to an endemic area is at a definite, yet hard to quantify, risk of acquiring yellow fever. Nine cases of yellow fever have been reported in unvaccinated Western travelers who traveled to West Africa or South America between 1970 and 2002; eight of them died. This emphasizes how serious and potentially life threatening it is to contract yellow fever, especially for a nonresident. In such a situation where either option of vaccination or non-vaccination has risks, physicians may want to counsel parents that the safest option is a third one, which is to not travel with their less than 9-month-old infant to a yellow fever endemic area, or at least to consider postponing travel, until the infant is at least 9 months old, when the risk of post-vaccine encephalitis is much reduced.

Post–vaccinal encephalitis was much more common in the early years of yellow fever vaccine use, until standardized manufacturing procedures involving use of a seed lot system were adopted in the 1940s. The incidence of encephalitis decreased significantly but still occurred in infants under 6 months of age. Since the 1960s, the vaccine has not been used in infants younger than 6 months, and in the United States the only cases of encephalitis have been in people in their teens and older, with one exception.

Analysis of cases of yellow fever vaccine-associated encephalitis reported to VAERS since the 1990s demonstrate an overall reporting rate of approximately eight cases per 1 million doses of vaccine administered, with no apparent increased risk in children 9 months and older. In fact, the group with the highest risk appears to be in people aged 60 years and older.

Children are also potentially at risk for another serious adverse reaction to yellow fever vaccine, viscerotropic disease, which is similar to wild type yellow fever. This is rare, occurring in approximately four patients per 1 million doses of vaccine administered, but it does have a high case-fatality rate of approximately 50%. Analysis of VAERS reports in the United States suggests that the risk for viscerotropic disease also is greater for patients aged 60 years and older, but has never been reported in a child in the United States.

A practitioner can only order or administer the vaccine if they work in a clinic possessing a registered yellow fever stamp, which can only be issued (in the civilian sector) by their state health department. All travelers to yellow fever endemic areas should practice good mosquito bite precautions. This information, including country-specific vaccination requirements and recommendations, can all be found on the CDC website: http://wwwn.cdc.gov/travel.

Mark Gershman, MD, Yellow Fever Medical Officer, Geographic Medicine and Health Promotion Branch, Division of Global Migration and Quarantine, CDC

Weigh risks, benefits of vaccine.

The issue with all vaccines is whether the risk of the vaccine is greater than the risk of the disease, and the same is true for the yellow fever vaccine (YEL-VAX).

Yellow fever is a dangerous disease with up to 50% mortality in people from non-endemic areas. However, the risk of a traveler acquiring the disease is limited to specific geographic areas, and the risk within those areas varies. For example, if a child is going to live or travel in West Africa, there is no question that the risk for disease is high enough to be worth the potential side effects from YEL-VAX.

The exception is for children younger than 6 months. The current formulation of YEL-VAX has been around since the 1930s and was initially given to all ages. Several cases of encephalitis occurred in very young infants, so it is now recommended to defer vaccination until 9 months of age, although it can be considered as early as 6 months of age if the child is going into a very high risk area.

The issue is a public health concern with the potential spread of yellow fever, and the administration of the vaccine is regulated via the WHO through national health programs.

To avoid the importation of yellow fever by a traveler incubating the disease, many countries require that travelers be immunized against yellow fever and that immunization must be performed at a registered yellow fever vaccination site. Hence proof of yellow fever vaccination may be required for travel to certain countries; however, this requirement is for the protection of the destination country, not the traveler, who may in fact have very low risk of acquiring the disease.

A demonstrative situation would be a traveler going on a cruise around the coast of South America, stopping at popular local ports. The risk that a traveler would acquire yellow fever in either urban Lima (Peru) or in Rio de Janiero (Brazil) is very small, although both countries have areas of endemicity. However, the country of Brazil requires evidence of immunization for any traveler from a country with endemic areas for yellow fever, even if he or she has not been in an area of known transmission, to prevent the possibility of establishing disease in an urban setting such as Rio de Janiero. In this situation, one would strongly consider whether the risk of the vaccine outweighs the likely benefit to the individual traveler.

For children beyond the age of 9 months, the incidence of side effects from the yellow fever vaccine is not high. Recent concerns have focused on the recognition of higher rates of adverse events in older people rather than in children. As YEL-VAX is a live vaccine, it should always be avoided in individuals of any age who are immune compromised.

However, for otherwise healthy children who are going to an area with a risk of yellow fever transmission, I would definitely recommend vaccination with YEL-VAX.

Susan Mclellan, MD, MPH, Associate Professor of Medicine and Tropical Medicine at Tulane University School of Medicine, LA