Intradermal Rabies Vaccination

Abstract & Commentary

Synopsis: Children who received intradermal vaccination had lower rabies-neutralizing antibody levels than children intramuscularly immunized.

Source: Sabchareon A, et al. Pediatr Infect Dis J 1998; 17:1001-1007.

Concerned about the high cost of intramuscular rabies vaccine in developing countries, researchers in Thailand compared intradermal (lower volume and, hence, lower cost) and intramuscular use of purified Vero cell rabies vaccine as pre-exposure prophylaxis in children. Three doses of vaccine were given during a 28-day period to each of 190 children, and a booster dose was given a year later. Follow-up data were available from 82% of children one year after the primary series and from 62% of children two years following the booster dose. Children who received intradermal vaccination had lower rabies-neutralizing antibody levels than children intramuscularly immunized. Nonetheless, "adequate" protective titers were achieved in nearly all (94-100% at the different times tested) children whether they received intradermal or intramuscular vaccine. Side effects were generally minor and were similar in each treatment group.

Comment by Philip R. Fischer, MD

Rabies is still a uniformly fatal illness, and there are more than 50,000 human deaths due to rabies each year. Most fatalities occur in children in Asia, South America, and Africa, and exposure to rabid dogs is responsible for more than 99% of human rabies deaths worldwide. Human rabies is almost always associated with an actual bite wound, though other more subtle exposures have been reported. Control of animal rabies depends on vaccination of domestic dogs and elimination of stray dogs. Sadly, however, such control programs require heavy, ongoing expenditures.

Effective rabies vaccines are available. Pre-exposure vaccination provides significant protection and simplifies the post-exposure therapy by obviating the need for rabies immune globulin following exposure to rabies and by decreasing the number of needed post-exposure vaccine doses to two.

There are still, however, several controversial issues in regard to rabies vaccination. Who should be vaccinated? Which vaccine should be used? By which route should vaccine be administered? Cost is a significant factor in determining responses to these questions, and this study from Thailand is, therefore, helpful in identifying a lower cost means of effectively administering rabies vaccine to masses of children at risk of rabies in areas of limited financial resources.

The decision about whether to vaccinate a traveler depends on several individualized factors: age (more risk in children), planned activity (more risk in veterinary workers and spelunkers), destination (most risk in Latin America and Asia, only a few countries risk-free), duration of travel, access during travel to emergent administration of rabies immune globulin, and financial resources (as well as local cost of the pre-exposure vaccine that varies markedly from place to place). Whether immunized before the exposure, additional treatment is necessary following actual or presumed rabies exposure.

Until recently, there were two rabies vaccines available in the United States. Imovax is a human diploid cell rabies vaccine manufactured by Pasteur Merieux Connaught and has forms approved for intradermal and intramuscular use. Rabies Vaccine Adsorbed, produced by SmithKline Beecham, is available for intramuscular use. The FDA recently approved for marketing a new inactivated rabies vaccine (RabAvert, Chiron Corp.) that is grown in primary cultures of chicken fibroblasts. It is the first new vaccine against rabies to be introduced in almost 10 years and has been approved for both pre-exposure prophylaxis and post-exposure vaccination (see TMA Update 1998;8:23-24). A purified Vero cell rabies vaccine from Pasteur Merieux Connaught was used in the Thai study but is not currently available in the United States.

How high an antibody level is "protective" against rabies? The CDC and the WHO consider the lower limit of "protective" to be at different levels. By the higher WHO minimum protective titer, fewer Thai children achieved "adequate" levels, and the intramuscularly treated children were more likely to have "adequate" protection. By the CDC criterion, "protection" was almost always achieved, and there was no difference in efficacy between the two routes of administration. The Thai study provides evidence that the intradermal route will be widely effective and could find generalized use in developing country areas with limited financial resources. It is doubtful, however, that wealthier travelers would choose a route of administration that clearly prompts lower antibody levels that are not uniformly considered to be protective. If cost factors lead travelers to consider the intradermal route of this purified Vero cell rabies vaccine when it becomes available, travel medicine practitioners might, nonetheless, advise intramuscular use in travelers at risk of blunted anti-rabies immune responses (immunosuppressed individuals and individuals who must take chloroquine or similar antimalarials during the course of the rabies vaccination).

Children in the Thai study responded well to a booster dose regardless of their pre-booster antibody titer, and side effects were more common after the booster doses. It could be, as Sabchareon and colleagues point out, that repeated pre-exposure booster doses will not be needed in individuals who can have reasonable access to the two-dose post-exposure vaccination in the event of an animal bite.

This report is useful in leading the way to more affordable rabies prevention in financially challenged areas of the world.