IDSA News - Nov./Dec. 2010 (Plain Text Version)
In this issue:
Rotavirus Vaccination’s Potential Impact in the Developing World
By Diego Pineda
Despite the global success of vaccination in reducing disease and mortality during the last century, the introduction of new vaccines in low-resource countries has been slow. Kathleen Neuzil, MD, MPH, FIDSA, senior advisor for immunizations at PATH and clinical associate professor at the University of Washington in Seattle, provided an overview of one new vaccine with great potential to reduce mortality in these parts of the world during the Joseph E. Smadel Lecture at the 48th Annual Meeting of IDSA in Vancouver.
According to the World Health Organization (WHO), rotavirus causes 527,000 deaths every year in developing countries. The virus leads to 25 million outpatient visits, 2 million hospitalizations, and an estimated 40 percent of diarrheal hospitalizations worldwide. “Low-resource countries in Asia and Africa carry the greatest rotavirus disease burden,” Dr. Neuzil said.
With the development of two new rotavirus vaccines, Rotateq and Rotarix (licensed in the U.S. in 2006 and 2008, respectively) WHO recommended rotavirus vaccination for the Americas and Europe, but advised more efficacy research be conducted before making a recommendation for Asia and Africa, where the burden of rotavirus is greater, Dr. Neuzil said.
Three large randomized clinical trials including more than 12,000 children in seven countries, conducted between 2005 and 2009, helped provide data to inform WHO’s policy in this area, said Dr. Neuzil, who was involved in a program to design and execute the trials.
They first assessed the efficacy of Rotarix in Malawi and South Africa, co-administered with other vaccines to reflect the “real world” schedule followed in these countries. The researchers did active weekly surveillance for gastroenteritis and severity, seeking infants with at least one episode of severe gastroenteritis between 2 weeks from vaccination until one year of age. The efficacy of the vaccine was 61 percent; for every 100 children vaccinated, 3.9 episodes of the disease were prevented in Malawi, Dr. Neuzil noted.
The other two trials, which assessed Rotateq, included 5,468 children in Ghana, Mali, and Kenya and 2,036 children in Bangladesh and Vietnam. The studies followed the children through two rotavirus seasons. In the African countries, efficacy in the first year was 64.2 percent and 19.6 percent in the second; in Asia, the vaccine showed 51 percent efficacy on the first year and 45 percent in the following year.
On a population level, 60 percent efficacy means 1.7 million lives could be saved between 2010 and 2025, even with conservative estimates of vaccine uptake, Dr. Neuzil said. “That is a lot of lives and lot of morbidity in these countries,” Dr. Neuzil said. Informed by these studies, WHO recommended rotavirus vaccine for infants in all countries in 2009, with a focus on countries with high diarrhea mortality. “This was good news, and the policy change that we were hoping for.”
Subsequent post-marketing studies have continued to illustrate the potential of rotavirus vaccination, including one published in 2010 from Mexico showing that diarrheal deaths after rotavirus vaccine introduction fell by 35 percent. A 2010 study from the United States also showed a significant reduction in hospitalizations due to rotavirus, including infants too young to be vaccinated—again highlighting the greater impact of vaccination at the population level.
Although some post-marketing studies have shown a slight increased risk of intussuception in some regions (but not in others), WHO has estimated that the risk from diarrheal death outweighs the risk of intussuception in developing countries, Dr. Neuzil said.
Vaccine Development Update
During a related symposium on new vaccines, Karen L. Kotloff, MD, from the Center for Vaccine Development at the University of Maryland School of Medicine in Baltimore, reviewed different approaches to develop a group A streptococcus vaccine (GAS). Recent GAS vaccine trials have been successful but were halted due to a lack of commercial interest, Dr. Kotloff said. More data are needed for guidance in correlates of protective immunity, the role of non-type specific antigens in immunity, disease burden, and pilot studies to refine endpoints, she noted.
Other presenters discussed advances in research and trials evaluating vaccines against group B streptococcus, meningococcal vaccines targeting group B disease, and the prospects for a vaccine against Staphylococcus aureus infections. The success of new vaccines will require partnerships between industry, government, and academia to share the risks and benefits of developing these life-saving interventions, said Dr. Kotloff.
Audio and synchronized speaker slides from the 2010 IDSA Annual Meeting are available for purchase online.