Rotavirus vaccine effective at preventing disease in Asia, Africa

Zaman K. Lancet. 2010; DOI:10.1016/S0140-6736(10)60755-6.

Armah GE. Lancet. 2010; DOI:10.1016/S0140-6736(10)60889-6.

Nelson EAS. Lancet. 2010; DOI:10.1016/S0140-6736(10)60896-3.

Safety and efficacy data from two clinical trials in Asia and Africa back WHO’s recommendation to implement the pentavalent rotavirus vaccine in developing countries across both continents.

In a randomized, double-blind, placebo-controlled study supported by GAVI and Merck, researchers from the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh, and PATH in Seattle conducted a clinical trial in which infants were randomly assigned to receive either pentavalent rotavirus vaccine (RV5, RotaTeq, Merck) or placebo. The study represents the first clinical efficacy trial of a licensed rotavirus vaccine in developing countries in Asia.

The study population was composed of infants aged 4 to 12 weeks with no signs of gastrointestinal disease, according to the researchers, and vaccine and placebo were administered as one 2 mL-doses at approximately 6, 10 and 14 weeks. Study sites included rural Matlab, Bangladesh, and urban and periurban Nha Trang, Vietnam.

The researchers performed follow-up for about 2 years after receipt of the final dose and ultimately included 991 infants from the RV5 group and 978 from the placebo group in their analysis. During this time, 38 cases of severe gastroenteritis (Vesikari score ≥ 11) occurred among infants who received RV5 compared to 71 among those who received placebo.

These results translated to a vaccine efficacy of 48.3% (95% CI, 22.3-66.1) against severe disease (P=.0005). Serious adverse events, with pneumonia serving as the most common condition, were observed in 2.5% of infants in the vaccine group and 2% among those assigned to receive placebo within 14 days of any dose.

“Our trial shows that a live oral rotavirus vaccine has the potential to halve the incidence of severe rotavirus gastroenteritis in developing populations in Asia,” wrote the researchers. “Alongside efficacy results for this vaccine in Africa, our study supports WHO’s strong recommendation for expansion of rotavirus vaccine use to the poorest nations in Africa and Asia.”

“Our main goal is to prevent the most severe disease that might lead to death in areas where treatment is inaccessible,” said study researcher John C. Victor, PhD, MPH, of PATH in Seattle, in a press release. “Because we saw indications that the vaccine is even more efficacious in preventing the most severe disease children experience, I am very optimistic about the impact that rotavirus vaccines will have on mortality in these settings.”

Success in Africa

A second study, also funded by PATH and Merck, evaluated the effects of RV5 in three sites in Africa — rural areas of Ghana, Kenya and an urban area of Mali. The trial yielded results that were comparable to those found in the Asian trial.

Using a similar study population and structure, researchers from the University of Ghana, Accra, and PATH in Seattle randomly assigned 5,468 infants to receive RV5 or placebo.

Seventy-nine cases of severe rotavirus gastorenteritis per 2,610.6 person-years of follow-up occurred among the 2,733 infants who were administered RV5 when compared with 129 cases per 2,585.9 person-years among the 2,735 receiving placebo, the researchers said, with efficacy reaching 39.3% (95% CI, 19.1-54.7; P=.0003). This clinical trial also demonstrated increased efficacy during the first year of life — more than 64% — and more than 19% in the second year of life.

Data indicated that 1.5% of 2,723 infants from the vaccine group and 1.7% from the placebo group experienced serious adverse events within 14 days of any dose. The most frequently cited problem was gastroenteritis, the researchers said.

“Introduction of rotavirus vaccines for African children along with the imminent introduction of pneumococcal and meningococcal conjugate vaccines in parts of Africa, could instigate a new era of reduction of childhood disease and mortality,” wrote the researchers.

Looking ahead

In an accompanying editorial, E. Anthony S. Nelson, MBCHB, MD, of the Chinese University of Hong Kong, and Roger I. Glass, MD, PhD, of the NIH, note that implementation of the rotavirus vaccine in developing countries faces several challenges.

“The introduction of rotavirus vaccines in national programmes, even in high-income countries, has been slow,” they wrote. “Apart from issues of their lower effectiveness in low-income countries and concerns about vaccine price, there are still some perceptions about adverse effects and intussusception from the earlier vaccine, Rotashield.”

Nelson and Glass also noted that findings indicating evidence of porcine circovirus in the monovalent rotavirus vaccine and RV5 have somewhat tainted public opinion. Other concerns include the controversy surrounding the potential involvement of industry in WHO’s recommendations on vaccination during the 2009 influenza A (H 1N1) pandemic.

However, they remain optimistic. “Some countries that introduced rotavirus vaccines into their national programs early on have already begun to see tremendous benefit,” they wrote.

To forge ahead, Nelson and Glass said the vaccines should be used more widely so more data can be collected on their safety and efficacy and governments should be reassured about cost concerns. Further research on why the vaccine is less effective in developing countries is also important.

“Could simple interventions, such as slightly delaying immunization adding an additional dose of vaccine, or withholding breast milk around the time of vaccine administration, improve the efficacy of the vaccine in these challenging settings?” they wrote. “Finding an answer to these questions could add value to these new vaccines while doing much to improve the health and survival of children.”

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