For subjects with multiple episodes, only the first episode was counted. Exact inference was used, and

follow-up time was accounted for in the calculations. The primary analysis of efficacy was based on the per-protocol subject population. For the per-protocol (PP) efficacy analyses, children with laboratory-confirmed wild type rotavirus disease earlier than 14 days post-dose 3 were considered to be non-evaluable. Also, subjects with at least one gastroenteritis episode that could not be classified as RVGE or non-RVGE with certainty due to incomplete data – and with HDAC inhibitor no other episodes classified as RVGE – were considered non-evaluable. Intention-to-treat analyses were also performed. They encompassed all children who received at least one dose of vaccine or placebo, including protocol violators, and with a timeframe starting immediately following

Dose IOX1 1 as the starting point for case evaluation. The 95% confidence intervals (CI) for the rate reduction (incidence in the placebo group minus the incidence in the vaccine group) were derived using the method of Miettinen and Nurminen [13]. Analysis of immunogenicity was also based on a per-protocol strategy; subjects with laboratory confirmed wild type rotavirus disease between vaccine doses were considered non-evaluable. Seroresponse rates and GMTs were calculated with corresponding 95% CIs based on binomial and normal distributions, respectively. A total of 1960 infants were enrolled in the trial at the Mali sites, of whom 979 received PRV and 981 received placebo; 1013 of the infants were males and the median age at the first dose was 48.0 days (Fig. 1). Table 1 indicates that the number and incidence of serious adverse events (SAEs) that occurred within 14 days of ingestion of each dose among subjects in the vaccine versus the placebo group were comparable. Overall, 5 subjects (0.5%) who received PRV and 6 subjects (0.6%) who received placebo reported a SAE; 4 subjects (1 in not the PRV group) dropped out of the

study due to a SAE. Among the subjects who received PRV, none of the SAEs was considered to be vaccine-related. A total of 8 deaths occurred within 14 days following any vaccination during the study; 3 deaths (0.3%) were in PRV recipients and 5 (0.5%) in placebo recipients. The most common SAE for both the PRV and the placebo groups was pneumonia, 0.2% and 0.3%, respectively. Two separate serological assays were utilized to address the immune responses elicited by PRV. Serum anti-rotavirus IgA antibodies were measured by EIA because these are useful for measuring immune responses to vaccine in young infants (IgA antibodies are not transferred transplacentally as IgG antibodies are); both the vaccine and placebo groups had a GMT of 1.6 at baseline (pD1) prior to receiving the first dose of vaccine. Table 2 shows that 82.