A new vaccine against a diarrheal disease that kills about 600 children a day worked well in a large trial in Africa and appears to be a practical way to protect millions of children, scientists said on Wednesday.
The new vaccine against rotavirus, the most common cause of death from diarrhea in children under age 5, is made by an Indian company and was tested in Niger by Doctors Without Borders.
The vaccine is expected to be as cheap as or cheaper than current alternatives. More important, it can last for months without refrigeration, which makes it far easier to use in remote villages with no electricity.
It must be approved by the World Health Organization before it can be widely distributed, a process that is underway.
Still, experts hailed the new vaccine as a leap forward.
“This is great news,” said Dr. Paul A. Offit, an infectious disease specialist at the Children’s Hospital of Philadelphia and one of the inventors of another rotavirus vaccine, Rotateq, which was launched in 2006.
“I wish there were 10 companies making rotavirus vaccine,” Dr. Offit said, “because thousands of children are dying of this.”
About 215,000 children under 5 die each year of rotavirus, almost half of them in just four countries: India, Pakistan, Nigeria and the Democratic Republic of Congo, according to the W.H.O.
A major 2013 study sponsored by the Bill and Melinda Gates Foundation found that rotavirus was the leading cause of fatal diarrhea in children under age 2 — and the only major one not caused by bacteria or parasites, which are treatable with antibiotic and antiparasitic drugs.
One of that study’s conclusions was that more rotavirus vaccine should be available. Repeated bouts of diarrhea can rob children of nutrients and leave them permanently stunted.
The new study, published in the New England Journal of Medicine, found that the vaccine, made by the Serum Institute of India, was 67 percent effective in preventing severe episodes of rotavirus-related diarrhea. There were only 31 cases among the 1,780 children who got three doses of the vaccine, while there were 87 among the 1,728 children who got a placebo.
There were no cases of intussusception, a rare but potentially lethal bowel obstruction. In 1999, the first American rotavirus vaccine, Rotashield, was withdrawn from the market because of fears that it triggered intussusception.
More than 300 medical personnel were involved in the trial in Niger, one of the world’s poorest countries. A trained health worker spent 24 hours a day in each of the 132 villages that the 3,500 children in the study live in.
While 67 percent protection is imperfect, it is greater than that provided by Merck’s Rotateq or Rotarix, a vaccine made by GSK, when tested in Africa.
“Would we want a perfect vaccine? Definitely — and I also want a pony,” said Rebecca F. Grais, who directed the trial for Doctors Without Borders. “But a vaccine that prevents two-thirds of the deaths and hospitalizations that rotavirus causes is definitely worth considering.”
“This provides hope in environments where there wasn’t any,” she said, “so our level of enthusiasm is very high.”
Even a moderately effective vaccine — combined with the herd protection that builds up once most children in an area are vaccinated and immune — “can have a huge public health impact,” said Dr. Anita Zaidi, an expert in diarrheal diseases at the Bill and Melinda Gates Foundation, which helped underwrite the initial development and testing of the new vaccine.
Rotavirus vaccines are normally 80 to 90 percent effective in wealthy and middle-income countries. But among previously available vaccines, Rotarix was only 61 percent effective in a trial in Africa, while Rotateq was only 39 percent effective.
Infants in poor countries with open sewers and polluted water have more viruses and bacterial toxins in their intestines, blocking access to the gut cells where the vaccines would normally attach, Dr. Offit explained. And because mothers also get rotavirus, he added, they develop antibodies to it. Their babies get the antibodies in breast milk, and these may neutralize some of the vaccine.
Vaccines also may be less effective in poor countries because they may imperfectly match the circulating rotavirus strains, experts said, or because poor diets cause frequent diarrhea, removing protective gut bacteria.
The new vaccine is known as BRV-PV, and will be called Rotasiil, said Rajeev M. Dhere, the executive director of the Serum Institute.
Forty-two poor or lower-middle-income countries are now using rotavirus vaccine, said Dr. Seth Berkley, the chief executive of Gavi, the Vaccine Alliance, which buys billions of dollars of vaccines for poorer countries.
The market remains huge, especially since Nigeria, the Democratic Republic of Congo and other countries with great needs have yet to start immunizing against rotavirus. How useful Rotasiil will be for them will depend on many factors, Dr. Berkley said.
The vaccine must have W.H.O. approval before Gavi and United Nations agencies can buy it. Then, ideally, the price will drop well below that of existing vaccines. Rotarix costs Gavi $5 for two doses, while Rotateq is $10.50 for three. The initial price for Rotasiil will be about $6 for three doses, but could be lower if large amounts are ordered, Dr. Dhere said. The Serum Institute is ready to make about 60 million doses a year initially.
The fact that the new vaccine can stay unrefrigerated for up to six months at 104 degrees is a big advantage, Dr. Berkley said. Rotateq and Rotarix need refrigeration, and another new vaccine, Rotavac, from Bharat Biotech, another Indian company, must be stored frozen — a great challenge in rural areas with power failures.
But Rotasiil must be reconstituted with liquid, which might be a hindrance, he said. That adds an extra step where mistakes could happen.
Normally, Dr. Berkley said, a national health ministry will buy only one brand for the entire country, since thousands of vaccinators must be retrained each time a protocol changes. The space needed to store three doses of Rotasiil plus diluent could be a problem, he added. But Dr. Grais, who led the Niger trial, noted that at least two vaccines used in Africa, those against measles and cholera, are reconstituted, “so this is nothing out of the ordinary.”
Rotasiil is much easier to store, because refrigerator space is at such a premium in clinics in the developing world, she said. Other rotavirus vaccines take up as much space as all other commonly used refrigerated vaccines combined.
The real prices to poor countries should start low and then rise, Dr. Berkley said. At first, the poorest normally reimburse Gavi as little as 20 cents a dose, then slowly “graduate” and are eventually expected to pay the full Gavi price. As these countries become richer, they inch closer to paying private-market prices.
The goal is to get vaccine companies to expect enough profit that they enter the field, but to foster enough competition to keep prices reasonable.
In any case, getting more rotavirus vaccine into more babies “is really important,” Dr. Berkley said. “As we’ve rolled it out in different countries, I’ve seen whole pediatric wards empty out.”
Source: NY Times