High-dose rotavirus vaccine protects kids.

Few microbes span the globe like rotavirus, which causes diarrhea. Virtually everyone in the world, rich or poor, has had a bout with this virus by age 5. Although rotavirus is largely controlled in the United States, causing fewer than 100 deaths each year, the dehydration it produces kills 873,000 children annually in poor countries.

A rotavirus vaccine exists, but it hasn't been approved for general use. The vaccine proved effective in a 1996 U.S. study, but two subsequent studies, in Peru and Brazil, indicated that it gave infants only marginal protection.

Now, a trial in Venezuela using doses 10 times stronger than those in the earlier tests has yielded the first large-scale positive results in a developing country

Employing a form of the vaccine that targets the four main strains of rotavirus, researchers gave the new doses orally to 1,112 infants at ages 2, 3, and 4 months. A control group of 1,095 other babies received an inactive substance. Neither researchers nor parents knew which infants got the vaccine.

For 19 months, whenever the babies became too ill to be treated at home. their parents took them to a hospital near Caracas. These visits revealed that unvaccinated babies were four times as prone to dehydration due to rotavirus as treated infants and more than three times as likely to be hospitalized because of it. Moreover, unvaccinated babies accounted for three times as many cases of rotavirus-induced diarrhea that lasted more than 4 days, and they ran eight times the risk of getting the most severe cases of diarrhea, researchers report in the Oct. 23 New England Journal of Medicine.

The vaccine's only side effect was a brief, mild fever in some of the children.

"Every child should receive this vaccine in the United States and in developing countries," says study coauthor Albert Z. Kapikian, a physician and virologist at the National institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Md. Kapikian and his colleagues have been perfecting the vaccine since 1980; rotavirus was discovered in 1973. After several preliminary trials to arrive at the proper dosage, NIAID and Venezuelan researchers collected the recent data.

The vaccine used in Venezuela derives from a rhesus monkey rotavirus. Putting a modern spin on the work of English physician Edward Jenner, who used cowpox virus 200 years ago to vaccinate people against smallpox, Kapikian and his colleagues at NIAID employed a weakened rotavirus strain that infects these monkeys.

For one strain of human rotavirus, the weakened form of the monkey virus itself offered protection. To guard against the other three strains, the scientists let the monkey virus exchange a gene with each of the target human rotaviruses. This gene encodes a cell surface protein recognizable to the human immune system, which then makes antibodies to fight the virus.

Researchers were surprised that some unvaccinated children showed traces of the viral mix used in the vaccine, indicating that the harmless viruses had spread in the community

In December, a committee of scientists will recommend whether the Food and Drug Administration should approve the rotavirus vaccine for general use in the United States.

Some people are already convinced of its value. "I don't see any impediment [to approval] at this point," says Margaret B. Rennels of the University of Maryland School of Medicine in Baltimore. "Prevention is always better than treatment."

In the United States, rotavirus causes 500,000 visits to the doctor and 55,000 hospitalizations of children each year, says Jon R. Gentsch of the federal Centers for Disease Control and Prevention in Atlanta.