The parameters of public health utility of vaccination we focused on were efficacy against all-cause severe GE, as well as efficacy against specific rotavirus serotypes, including those not included in the pentavalent formulation. We were also able to more broadly assess indicators of vaccine safety. The point estimate of efficacy against very severe RVGE through the first year of life (67.1%) and the lower bound of the 95% confidence interval (37%) provide

more precision on the potential benefit of routine use of PRV in these settings than was available from the continent-specific AZD4547 clinical trial analyses. Furthermore, the efficacy against very severe (Vesikari score ≥15) all-cause GE of 35.9% during the first year of life suggests that a majority of very severe all-cause GE was caused by rotavirus and that a substantial proportion of potentially lethal illness can be prevented with

this vaccine. A key limitation for broadly interpreting MAPK inhibitor this estimate of efficacy against all GE is that it was likely influenced by timing of vaccination and follow-up period during the first year of life; in areas where rotavirus rates are seasonally affected, the estimate would be artificially elevated if the follow-up (post-dose 3) period oversampled the high season for rotavirus and tended to exclude the low season. In addition, completeness of surveillance and “case capture” varied somewhat from country to country; in Mali during the first year of post-immunization follow-up, it became

clear that many participants with gastroenteritis were not coming to the clinic, but sought care with traditional healers [14]. During the second year of the study, participants were more Ribonucleotide reductase actively encouraged to seek care at study clinics, and traditional healers were encouraged to refer patients to a study clinic. The relative completeness of case-ascertainment within each site may have influenced the overall calculations of efficacy. The point estimates for efficacy are similar to those for efficacy of 2- or 3-doses of the monovalent live-attenuated human rotavirus vaccine (Rotarix®, GlaxoSmithKline Biologicals, Rixensart, Belgium) [6]; however, acknowledging significant differences in study design, including the use of OPV and broad subject inclusion criteria, efficacy is lower than observed during trials in developed countries and developing countries in Latin America [7], [8] and [15]. Immunogenicity of PRV in Africa and Asia was also markedly lower than that observed in other regions [4], [5] and [15]; the causes of these differences will likely be the subject of intensive research and discussion in coming years.