Reasons for the lower efficacy are not well understood but several hypotheses include higher levels of maternal antibody, neutralization of the vaccine by breast milk, high level of other infections in the intestines, and malnutrition. To address the question of interference by neutralizing factors in breast milk, a randomized control trial Selumetinib was conducted in which mother-infant pairs were randomized into two groups, where mothers were either encouraged to breastfeed or withhold breastfeeding during the 30 min before and after each dose of Rotarix vaccine [39]. There was no difference in the proportion of infants who seroconverted

in the two groups which is consistent with other recently published studies [40]. Another study examined the effect of an increasing the number of doses on the infants’ immune response to the vaccine. In this study, children were randomized to receive either 3 or 5 doses of Rotarix vaccine [41]. Seroconversion rates in both groups were low and there was no difference in the proportion of infants seroconverting in the 3 and

5 dose arms. Finally, several papers provide insight into the debate surrounding rotavirus vaccine introduction and offer insights into interpreting results from the clinical trials and applying lessons learned from the international experience with rotavirus vaccine introduction. In a synthesis of the debate and of the available evidence for rotavirus vaccines, Panda et al. examine disease burden data, host and environmental I-BET-762 chemical structure factors, vaccine efficacy, immunization program issues, and economic considerations surrounding rotavirus vaccine in India [42]. The authors note that the overall immunization system performance in India needs to be strengthened but scientific, economic, and societal factors suggest that rotavirus vaccine introduction would be a good investment for India. As various point estimates of rotavirus vaccine efficacy for different rotavirus vaccines are now available, Neuzil et al. [43] propose a framework for evaluating

new rotavirus vaccines with a special focus on design characteristics of the clinical trials. This framework identifies co-administration with oral polio vaccines, age at vaccine administration, measure of severe disease and specificity of outcome, and length found of follow-up period as some of the key design effects to review when comparing point estimates from clinical trials. Comparing the Rotavac vaccine to the currently available international vaccine, Neuzil et al. conclude that the point estimate for efficacy of Rotavac compares quite favorably to the point estimate for efficacy from clinical trials of RotaTeq and Rotarix performed in low-income settings. Finally, Rao et al. [44] review global data on licensed rotavirus vaccine performance in terms of impact on disease, strain diversity, safety, and cost-effectiveness to provide a framework for decision-making regarding rotavirus vaccine introduction in India.