It's a difficult quest: The first rotavirus vaccine was pulled off the market in 1999 after a life-threatening side effect struck some U.S. babies, making American parents cautious about testing new, hopefully safer, versions. But doctors in developing countries, where rotavirus hits hardest, are telling public health experts they're desperate for protection.
"This is a disease that's democratic. Every kid in the world gets it. Every kid in the world could benefit from a vaccine that's safe and effective," says Dr. Roger Glass of the Centers for Disease Control and Prevention.
Drug giants Merck & Co. and GlaxoSmithKline now are testing two rotavirus vaccine candidates in a total of 12 countries; Merck's testing includes U.S. babies. In addition, the CDC is working with scientists in India on their own version.
Rotavirus, an intestinal infection, is the leading cause of severe diarrhea in young children. It can rapidly kill, as the sickest children become dehydrated from 10 to 20 episodes of diarrhea in a single day.
Each year, 3 million U.S. children, mostly babies and preschoolers, get rotavirus. Good medical care here means few deaths, roughly 40 a year, but 65,000 are hospitalized. Rotavirus costs the nation more than $1 billion annually in medical bills and parents' lost productivity.
The death toll is much worse in developing countries -- about one child in every 250 dies of rotavirus, Glass says. "They're so dehydrated they wither up like a flower, their eyes sink," he recalls of his days treating rotavirus in Bangladesh.
The last attempt at a vaccine ended in 1999, when American Home Products pulled its RotaShield off the market after a year of sales left 20 U.S. infants with a lifethreatening bowel obstruction. It was a very rare side effect, hitting one in 10,000 vaccine recipients, but deemed too great for Americans because so few babies here die of rotavirus. Many developing countries complained that RotaShield could have saved at least 100 of their children's lives for every case of bowel obstruction.
Now scientists are developing vaccines they hope will prove safer. Each is made from a live strain of rotavirus, but not the monkey strain used in RotaShield -- the theory, still unproven, is that that may be a key safety difference.
Merck's version is a mix of cow and human strains, the types thought to cause most of the world's rotavirus illnesses. Merck says in early studies, babies had none of the fever and very little of the viral spread in the intestines that often accompanied RotaShield -- promising safety signs. Now final Phase 3 testing has begun here and in Finland, Belgium, Germany, Puerto Rico and Jamaica, aiming to enroll at least 60,000 babies, hopefully enough to rule out the side effect.
Merck won't say how many have been vaccinated so far, but "enrollment has not been as enthusiastic as for RotaShield" because U.S. parents and pediatricians remember the frightening bowel problem, says Dr. David Matson of Eastern Virginia Medical School in Norfolk, Va., a lead investigator.
Glaxo's version is a single human-only strain culled from an American baby who never had symptoms, suggesting the immune system is spurred enough by this mild infection to protect. Glaxo notes the human strain has never been linked to bowel obstruction, but studies must prove that safety.
Glaxo now is completing Phase 2 trials in Singapore, Mexico, Brazil and Venezuela, and plans final testing in tens of thousands of babies mostly in Latin America, because it hopes to sell first in developing countries.
The CDC culled yet another strain from babies in India who never became seriously ill, and is working with an Indian biotechnology company to test a resulting vaccine there.
The competition should speed a vaccine to market and eventually force down prices, crucial if developing countries are to benefit, says CDC's Glass.