Geneva and Seattle - Data from an unprecedented clinical study examining rotavirus vaccines in developing countries of Asia and a new study from Africa, published today in The Lancet, contribute to a growing body of evidence of the safety, efficacy, and lifesaving potential of vaccines preventing severe rotavirus diarrhea.
According to the most recent World Health Organization (WHO) estimates, rotavirus caused more than 500,000 child deaths worldwide in 2004. In Asia and Africa, where more than 85 percent of rotavirus-related deaths occur, prevention through vaccination would have a substantial impact on diarrhea and child mortality.
Reducing child mortality
"Rotavirus vaccination will be needed as part of a package of strategies to improve child survival and to achieve Millennium Development Goal 4," said Anthony Nelson, professor of pediatrics, Chinese University of Hong Kong, and Roger Glass, director of the Fogarty International Center, US National Institutes of Health, in a commentary accompanying the findings. "Some countries that introduced rotavirus vaccines into their national programs early on have already begun to see tremendous benefit."
The clinical studies conducted in Asia and Africa examined Merck & Co., Inc.'s rotavirus vaccine RotaTeq® -one of two available orally administered rotavirus vaccines.
"In the first trials among impoverished populations of Asia, we have demonstrated that rotavirus vaccines slashed the incidence of severe rotavirus diarrhea by half during the first year of life when children are at greatest risk," said Dr. K. Zaman, senior scientist and epidemiologist, International Centre for Diarrhoeal Disease Research in Bangladesh (ICDDR, B) and lead author of the Asian study. "In communities where urgent care is out of reach, vaccination is the best way to prevent deaths from rotavirus."
Highly effective vaccine
More than 2,000 infants in Bangladesh and Vietnam enrolled in the study to evaluate vaccine efficacy in low-income, high-burden settings of Asia. It was the first study in the region to examine rotavirus vaccine efficacy beyond the first year of life.
The vaccine was shown to maintain efficacy-48.3 percent against severe disease-through nearly two years of follow up. Though this efficacy is lower than that demonstrated in developed-country trials, the findings suggest tens of thousands of lives could be saved each year in this region alone given the high burden of diarrhea mortality, if the vaccines are widely used.
"These findings support the World Health Organization's recommendation for expanding use of rotavirus vaccines into the poorest nations in Asia and Africa, where they can be of most benefit," said Dr. Jean-Marie Okwo-Bele, director, Immunization, Vaccines and Biologicals, WHO. "Such vaccines have the potential to re-energize diarrhea control programs around the globe and make major strides towards stopping one of the leading killers of children."
In 2009, WHO reviewed the data, along with other studies conducted in developed and developing country settings, and recommended that every country include rotavirus vaccines in its national immunization program. In countries where diarrhea causes more than 10% of death among children under five years of age, the introduction of the vaccines is strongly recommended.
"The evidence is clear-immunization against rotavirus is one of the best ways to protect millions of children from severe, and often fatal, diarrhea," said Dr. Tachi Yamada, president, Global Health Program, Bill & Melinda Gates Foundation. "Funders and political leaders must now ensure we can deliver these vaccines to the children who need them most."
An African clinical study conducted in Ghana, Kenya, and Mali, also published in this issue of The Lancet, further demonstrated significant protection from rotavirus vaccination in sub-Saharan Africa. This study supplements and supports findings published earlier this year from the first-ever clinical study of rotavirus vaccines in Africa.
"These studies add further evidence that rotavirus vaccines are powerful weapons in saving the lives of the world's most vulnerable children. Yet because of insufficient funding, these vaccines are only included in the routine immunization programs in a handful of the world's poorest countries," said Dr. Julian Lob-Levyt, chief executive officer of the GAVI Alliance, which is campaigning to raise funds to reach its target of supporting the introduction of rotavirus vaccines in at least 44 low-income countries by 2015.
"It is in the lowest-income countries, where access to healthcare is most limited and the disease burden heaviest, that these vaccines are most desperately needed."
Expanding evidence base
Where rotavirus vaccines have been introduced-both in developed and developing countries-studies show major reductions in rotavirus hospitalizations and deaths. Recent findings from Mexico indicate that following vaccine introduction in 2006, diarrhea-related deaths dropped during the 2009 rotavirus season by more than 65 percent among children aged two years and younger.
In Nicaragua, the first developing country to introduce rotavirus vaccine, the vaccine prevented 60 percent of severe cases and cut hospital admissions and emergency room visits in half. More broadly, researchers also are finding that vaccination may indirectly benefit unvaccinated children by limiting the number of circulating infections, suggesting a herd immunity effect, in which the potential impact of vaccination extends beyond that predicted by efficacy studies.
This expanding evidence base emphasizes the important role rotavirus vaccines can fulfill within an integrated set of interventions critical to preventing and treating the many causes of diarrheal disease. Proven, complementary interventions to address the other causes of diarrhea include access to clean, safe water, improved hygiene, sanitation, oral rehydration solution, breastfeeding, vitamin A, and zinc supplementation. As part of its recommendation, WHO encouraged delivery of rotavirus vaccines within a comprehensive approach that utilizes all the tools available against diarrheal disease.
The clinical studies were coordinated and co-funded through a partnership between vaccine manufacturer Merck and the Rotavirus Vaccine Program-a collaboration between PATH, WHO, and the United States Centers for Disease Control and Prevention, funded by the GAVI Alliance.
"WHO called for these studies to determine how rotavirus vaccines would perform in the places with the greatest need today," said Dr. Kathleen Neuzil, senior clinical advisor for Vaccines, PATH. "Oral vaccines are known to perform differently in different settings, and the latest findings reinforce that rotavirus vaccines can have a major public health impact in developing countries in Africa and Asia-much larger than we saw in the United States and Europe. The disease burden is just that much greater."
The GAVI Alliance has undertaken a major campaign urging donors to provide sufficient funds to support rotavirus vaccine introduction. It will hold a funding meeting on October 6, following the September summit in New York on progress toward achieving the Millennium Development Goals. GAVI will underline that achieving Millennium Development Goal 4 will be impossible without widespread immunization against rotavirus and pneumococcal disease.
To request a copy of the study articles, please contact Tony Kirby at Tony.Kirby@Lancet.com.