In a study of more than 68,000 infants published in the New England Journal of Medicine, the investigational vaccine Rotateq demonstrated that it can safely prevent 98 percent of severe cases of viral diarrhea and vomiting that account for 2 million hospital visits and 500,000 pediatric deaths each year worldwide.
In one of the largest pre-licensure vaccine clinical trials ever conducted worldwide, research championed by an Eastern Virginia Medical School investigator demonstrated that the oral vaccine Rotateq virtually eliminated the most severe cases of rotavirus, a common childhood virus that sometimes becomes deadly.
"This is good news for children everywhere," said principal investigator David O. Matson, M.D., professor of pediatrics at Eastern Virginia Medical School (EVMS) and head of infectious diseases at EVMS' Center for Pediatric Research. "In a matter of hours, vomiting and diarrhea from rotavirus can lead to dehydration, which can result in hospitalization and even be life-threatening."
Rotavirus causes about 70,000 hospital admissions in the United States annually, or about five percent of all pediatric admissions. It also results in 250,000 visits each year to U.S. emergency rooms.
In the developing world, where prompt hospitalization and effective treatment may not be available, rotavirus kills half a million infants a year, about one child each minute. Matson, widely regarded as one of the nation's leading rotavirus researchers, has studied the virus for over two decades.
"Development of a safe and effective rotavirus vaccine has been a worldwide priority since the virus was discovered in the 1970s," Matson said. "It became clear at that time that it was one of the major killers of children, and there was no effective treatment."
Rotavirus is endemic and infections occur in almost all children. The severity of rotavirus infection ranges from no symptoms to dehydrating gastroenteritis that can be fatal.
Efforts to eradicate rotavirus disease were almost derailed in 1999 when another vaccine was pulled from the market because it caused a rare bowel obstruction called intussusception at a rate of one in 10,000 patients. Intussusception takes place when the bowel folds in on itself, causing an intestinal blockage.
Because the bowel obstruction was so rare, and the increased incidence was so small, the only way to evaluate the safety of a new rotavirus vaccine was to launch a clinical trial involving more than 60,000 infants.
In 2000, Merck asked Matson to serve as the U.S. principal investigator in a clinical trial of RotaTeq, a vaccine under development.
RotaTeq targets five major strains of rotavirus, which account for 90 percent of rotavirus disease. The trial involved infants in the United States, Belgium, Costa Rica, Finland, Germany, Guatemala, Italy, Jamaica, Mexico, Sweden and Taiwan.
Infants were randomly assigned to receive three doses of vaccine or placebo, given four to 10 weeks apart. Because of the bowel obstruction associated with the withdrawn vaccine, a primary goal of the study was to determine whether RotaTeq was safe. Overall, 68,038 infants between six and 12 weeks participated, 34,035 in the vaccine group and 34,003 in the placebo group. All were monitored for serious adverse events, including intussusception.
During the study, infants who received the vaccine actually had a lower incidence of intussusception: 12 cases among vaccine recipients and 15 among those who received a placebo. No other significant side effects or complications were reported.
Rotateq also proved to be effective, nearly eliminating serious rotavirus-related gastroenteritis. The vaccine reduced rotavirus-related hospital admissions by 96 percent. In addition, RotaTeq reduced rotavirus-related emergency rooms visits by 94 percent, and doctor's office visits by 86 percent.
"The protective effect is strongest against the most severe disease," Matson said.
RotaTeq is presently under review by the U.S. Food and Drug Administration (FDA). Merck has filed for licensure of RotaTeq in 50 other countries and plans to evaluate the use of RotaTeq in the developing world.
The Merck study appeared in the same issue of the New England Journal of Medicine as a study of a rotavirus vaccine developed by GlaxoSmithKline. An accompanying editorial underscores the need for a rotavirus vaccine.