8% vs. 1.5%, respectively) [9]. Finally, Doxorubicin datasheet high infection rates of rotavirus evaluated by serological screening (40%) have been documented in Malawian infants

less than 6 Libraries months of age [3]. Although our study was not powered to examine schedule-specific HRV efficacy, an exploratory analysis indicated that vaccine efficacy over 2 consecutive rotavirus seasons was observed to be higher in the HRV_3D than in the HRV_2D groups. Consistently, the point-efficacy estimate of HRV_3D was higher than that of HRV_2D for outcomes of severe RVGE, any severity-RVGE (albeit not significant), and all-cause severe gastroenteritis. In the previously published efficacy data during the first year of life, there was likewise a trend for greater severe RVGE efficacy with 3 doses of vaccine in the South African cohort (81.5% [95% CI: 55.1–93.7] efficacy HRV_3D vs 72.2% [95% CI: 40.1–88.4] efficacy HRV_2D) [3]. An implication of the higher vaccine efficacy observed in the HRV_3D 3-deazaneplanocin A compared to HRV_2D group over 2

consecutive rotavirus seasons in this study indicates the need for protection beyond the first year of life against severe RVGE. The attack rate of severe RVGE during the second rotavirus season (1.2%) was a one-third of the overall attack rate of 3.2% seen over the 2 consecutive rotavirus seasons among the placebo group. Our study was also not designed to explore for differences in vaccine efficacy between the first and second years of life, however, it is worth noting that lower point-estimates

of vaccine efficacy over two next consecutive rotavirus seasons compared to that seen in the first season was observed in the HRV_2D arm, which is the licensed schedule for Rotarix use. Several possibilities exist to explain the lower efficacy observed in the HRV_2D group over two consecutive rotavirus seasons. First, children in the placebo group may have developed protection against severe RVGE through natural exposure to wild-type rotavirus during the first year of life in South Africa. However, exposure of placebo recipients to wild-type rotavirus would also have been expected to occur in other settings such as in clinical trials in Europe and Latin America, where efficacy against S-RVGE persisted in the second year of life, but as noted, the incidence rates in the first year of life in Europe and Latin America were lower [7] and [9]. In addition, vaccine efficacy was 85% over the 2 consecutive rotavirus seasons in the HRV_3D arm in our study. This suggests that protection of the placebo recipients through wild-type infection in the first year of life was unlikely to be the main reason for the lack of efficacy in the HRV_2D arm over the full follow-up period.