By Sean Henahan, Access Excellence

CHICAGO - A new vaccine can prevent more than 80 percent of the most severe diarrheal illnesses in children caused by rotaviruses, suggests a large clinical trial

"Rotaviruses, first detected 21 years ago, are the single most important recognized cause of severe diarrhea among infants and children younger than 2 years the world over," says Robert Chanock, M.D., chief of the NIAID Laboratory of Infectious Diseases (LID). "Our goal with this vaccine is to prevent the most severe rotaviral diarrhea, which leads to dehydration and death."

Researchers compared a placebo to two new vaccines developed at the NIAID in a large placebo controlled trial involving more than 1,000 infants at 23 medical centers. One of the vaccine candidates used four clinically important strains of human rotavirus (RRV-TV), while a second candidate used only one of these strains, serotype 1 (RRV-S1).

The infants sere randomly assigned to receive three doses of vaccine or placebo. Following inoculation, both candidate vaccines protected against disease caused by serotype 1 human rotavirus, reported lead researcher David I. Bernstein, M.D., of the J.N. Gamble Institute of Medical Research in Cincinnati, Ohio.

However, only the RRV-TV vaccine protected against disease caused by the other rotavirus strains during the second year after immunization. The researchers are not yet certain whether this finding represents a safeguard against a specific rotavirus strain or a difference in how long protection lasts.

The RRV-TV vaccine protected against 57 percent of all cases of rotaviral diarrhea. When ranked by severity of illness, the RRV-TV's effectiveness ranged from 49 percent protection for less serious cases to 82 percent for the most severe cases. Overall, the RRV-TV vaccine protected against 92 percent of the diarrheal episodes lasting more than three days, and reduced by 78 percent the cases requiring medical visits, the researchers reported.

In comparison, the RRV-S1 vaccine's effectiveness against diarrhea ranged from 40 percent protection against all rotaviral diarrheas, 31 percent for less serious cases and 73 percent for the most severe cases. However, the RRV-S1 vaccine only prevented 36 percent of diarrheal episodes lasting more than three days. The vaccine reduced medical visits by 67 percent.

The severity of illness was rated by evaluating several clinical factors including: dehydration, fever, medical intervention, duration of diarrhea and vomiting, and the number of stools passed and vomiting episodes during 24 hours.

The vaccine was created by substituting a gene from a human rotavirus strain for one in a weakened rotavirus that infects rhesus monkeys. That gene has instructions to make a protein on the virus' surface, VP7, where the immune system can easily recognize it and then tailor-make antibodies to fight that viral strain.

When making the RRV-TV vaccine, the NIAID researchers used this substitution strategy to create weakened forms of three of the four clinically important human rotaviruses. The fourth human strain was represented by a weakened, but unaltered rhesus rotavirus, which has a similar surface protein.

Rotavirus infects 90 percent of humans by age 3 years, regardless of hygiene standards. Even in areas where cholera is common, he notes, rotavirus causes severe illness more frequently in children younger than 2 years. Adults get rotavirus infections as well, but because of their previous rotavirus infections, most people do not become sick or have only mild illnesses.

An effective vaccine would prevent annually more than 1 million cases of severe rotaviral diarrhea in U.S. children younger than 5 years of age. In so doing, it would prevent 65,000 hospitalizations, notes Albert Z. Kapikian, M.D., assistant chief of LID. In developing nations each year, moderate to severe rotaviral diarrhea affects 18 million infants and children, killing more than 870,000.

For further details on this study, see" JAMA, 4/19/95, V.273, No.15, Bernstein et al.