Worldwide, rotaviruses account for more than 125 million cases of infantile
gastroenteritis and nearly 1 million deaths per year, mainly in developing countries. Rather than other control measures, vaccination is most likely to have a major impact on rotavirus disease incidence. The peak incidence of rotavirus
diarrhea occurs between 6 and 24 months of age. In developing countries, however, cases are not uncommon among children younger than 6 months. G serotypes 1 to 4 are responsible for most disease, but there are indications that in Brazil that G type 5 is of emerging epidemiological importance. Both homotypic and heterotypic responses are elicited during natural
rotavirus infection, and the immunological response at the intestinal mucosal surface is probably the more consistent predictor of clinical immunity. With the primary objective of protecting children against life-threatening dehydrating
diarrhea, many approaches to
rotavirus vaccine development have been attempted. One
vaccine, the tetravalent rhesus-human reassortant
rotavirus vaccine (
RRV-TV), was given licensing approval in the United States of America, introduced to the market, and later withdrawn. A number of studies have found better efficacy of
RRV-TV in developed countries than in developing ones. Field trials with a 4 x 10(4) plaque-forming units (PFU) preparation of
RRV-TV have been carried out in two countries in Latin America, Brazil and Peru. Those trials yielded protective efficacy rates against all rotavirus
diarrhea ranging from 18% to 35%. Data from a large catchment trial in Venezuela with a higher
RRV-TV dose, of 4 x 10(5) PFU/dose, indicated an efficacy rate of 48% against all rotavirus
diarrhea and 88% against severe rotavirus
diarrhea. It appears that breast-feeding does not compromise the efficacy of
RRV-TV if three doses of the
vaccine are administered. Similarly, possible interference of
oral poliovirus vaccine with the "take" of the
rotavirus vaccine can be overcome by giving three doses of the
rotavirus vaccine or by using a higher-titer formulation of it. Wild enteroviruses, however, may cause primary
rotavirus vaccine failure in developing countries. Studies in Peru with
RRV-TV have shown a trend towards higher
vaccine efficacy rates against "pure" (rotavirus-only) diarrheal episodes. Economic analyses made in the United States indicate that a
vaccine that costs less than US$ 9 per dose would lead to a net savings in medical costs. To date, however, cost-benefit studies have not been done in developing countries. In the future, it is possible that some Latin American countries might adapt their
polio production facilities to the preparation of
rotavirus vaccines for human use. A year after
RRV-TV was licensed for vaccination of infants in the United States, the occurrence of
intussusception as an adverse event led to the
vaccine's withdrawal from the market. The implications of that action, particularly for Latin America, will be addressed in this article, including the need to explore alternative rotavirus candidate
vaccines, particularly through the conduct of parallel clinical trials in both developed and developing countries.