The Global Health Impact of Rotavirus Vaccines

Rotavirus causes 25 million outpatient visits annually, and a further 2 million hospitalizations. Worse, it is associated with more than 500,000 deaths every year. Data suggest that vaccinating against this pathogen in low-resource countries would have a significant health impact.

During the Joseph E. Smadel lecture at the 48th annual meeting of the Infectious Diseases Society of America in Vancouver, Kathleen M Neuzil, MD, MPH, FIDSA, PATH, University of Washington School of Medicine, reviewed her experiences as part of the implementation of two rotavirus vaccines in real-world settings in Africa and Asia. Her presentation, “The Global Impact of Vaccines,” presented data from three randomized clinical trials that were done between 2005 and 2009 and which involved 12,000 children at numerous sites in South Africa, Malawi, Kenya, Ghana, Mali, Bangladesh, and Vietnam.

The studies used two vaccines: GlaxoSmithKline's Rotarix, a human monovalent G1 P[8] vaccine that was delivered orally in three doses in two separate treatment arms, and Merck's RotaTeq, a bovine pentavalent vaccine active against G1,G2,G3,G4,P[8] and P[7] that was delivered orally over three doses. Both vaccines were given in the EPI vaccine schedule and in conjunction with oral polio vaccine, which is known to affect the efficacy of the rotavirus vaccines. HIV positive infants were included in the study, and breastfeeding was allowed.

The primary outcome in all three studies was one episode of severe rotavirus gastroenteritis (GE) during the period from two weeks after the last dose until one year of age. The pooled data for the two vaccine dose arms showed a 1.9% incidence of severe rotavirus GE, compared with a 4.9% incidence in the placebo arm, for an overall efficacy of 61.2%. "An important second outcome for this study was the efficacy by country, in terms of the number of rotovirus GE episodes prevented," Neuzil said. "Another interesting finding was the number of rotovirus strains we saw. However, there was no difference in efficacy between the serotypes that were the basis of the vaccine and the strains seen in the study population."

Another study enrolled 5,468 infants in Ghana, Mali, and Kenya, and 2,036 infants in Bangladesh and Vietnam. It began in March 2007, with follow-up ending in March 2009, following the children through a second rotavirus season. Similar to the efficacy seen with Rotarix, the Rota Teq vaccine demonstrated 64.2% efficacy at one year in the African study. Efficacy at year 2 was 19.6%, with overall efficacy for the total follow-up period of 39.3%. In Asia, efficacy at year 1 was 51.0% and 45.5% at year 2, with an overall efficacy of 48.3%.

"When we put these data together, we see some similarity," Neuzil said. "The question that I would frequently get, however, is ‘How do we interpret these data — given that efficacy is around 50%?’ The answer comes from looking at the mortality and morbidity prevented. Using very conservative estimates for roll-out and uptake of vaccine, with 60% efficacy, they save 1.7 million lives annually," Neuzil said.

In summary, Neuzil cited a panel of experts sponsored by the WHO, who were asked to evaluate the implications of using the vaccines given their moderate efficacy in these settings. They wrote that "even vaccines with lesser efficacy in developing countries, compared with industrialized countries, would still lead to substantial public health benefits and would be cost-effective in saving lives in Africa and Asia."