Checkmate for a Child-Killer? Vaccine Researchers Close in on Rotavirus

Article excerpt

For medical professionals battling one of the worlds deadliest childhood infections, 1998 offered soaring hope. That fall, the first vaccine against human rotavirus--a highly contagious if somewhat obscure diarrhea-causing pathogen--went into pediatric use throughout the United States. The following year brought a shattering disappointment: Reports of a rare but serious side effect caused the manufacturer to suspend the vaccine's production.

In the aftermath of that setback, researchers redoubled their efforts to find a safe way to check the spread of rotavirus. Advanced trials of competing vaccine candidates are now under way, and early results suggest that the medical pieces needed to checkmate rotavirus may soon be in place.

Rotavirus may not be a household term, but it's a universal germ. "All humans are infected by the time they're 5 years old," says virologist H. Fred Clark of the Children's Hospital of Philadelphia. "Everybody gets [infected], regardless of economic status. Ordinary hygienic measures do not prevent the spread of rotavirus"

Infection typically confers lifelong immunity, so the disease almost always appears in young children rather than in adults.

Diagnosis of short-term rotavirus infections is rare. But each year in the United States, rotavirus makes 50,000 or more kids sick enough to require hospitalization, causes 20 to 40 deaths, and racks up costs of about $1 billion.

In poorer countries, rotavirus takes an even greater toll. A worldwide body count of at least 450,000 and up to 800,000 each year puts rotavirus sixth among infectious killers. Among children, only pneumococcus, malaria, and measles are more deadly than rotavirus.

BAD BREAK The unveiling 5 years ago of a vaccine designed by scientists at the National Institutes of Health (NIH) in Bethesda, Md., and produced by Wyeth Laboratories of Marietta, Pa., appeared to be a major breakthrough for global health.

Albert Z. Kapikian and his NIH colleagues fashioned their vaccine from a strain of rotavirus that naturally infects rhesus monkeys. To make the rhesus strain recognizable to the human immune system, the scientists added genes from the four most common human rotavirus strains.

Wyeth-funded studies revealed that giving infants three oral doses of the live, hybrid virus prevented many cases of rotavirus infection and reduced the severity of infections that did occur (SN: 10/25/97 p. 263). The U.S. government approved the vaccine, which Wyeth named RotaShield. Pediatricians in the U.S. administered more than 1 million doses of the Wyeth vaccine between October 1998 and July 1999.

A study of more than 1,000 children in New Orleans who received the vaccine from their pediatricians found that three doses completely prevented rotavirus infections requiring hospitalization, and that one or two doses reduced the risk of hospitalization by more than 60 percent. Rodolfo E. Begue of Louisiana State University in New Orleans and his colleagues reported the findings in the December 2002 American Journal of Epidemiology.

"It was a very exciting time," Kapikian recalls. He and other researchers expected that foreign countries would follow the U.S. lead and that the vaccine might ultimately save more than 1,000 lives per day.

An unforeseen problem, however, soon froze the vaccine's use. Data from a national system for monitoring vaccines' performance suggested that in the 2 weeks after children received the Wyeth vaccine, they had an elevated risk of developing a potentially fatal intestinal blockage called intussusception.

"We were surprised," says Kapikian. "It was very, very disappointing." The finding led the national vaccine committee to with draw its recommendation.

After the United States rejected the vaccine, no other country took it up--although rotavirus currently kills 1 in every 300 infants in the developing world. …