9–17.6%) of infants in HRV group (N = 10) and 6% (95% CI: 2.2–12.6%) of infants in the placebo group (N = 6). None of the six rotavirus gastroenteritis stool samples from the placebo recipients BI2536 contained

the HRV G1P[8] vaccine strain whereas in the HRV group, G1P[8] vaccine strain was isolated from one gastroenteritis stool sample. Thus, only one possible case of “vaccine associated” gastroenteritis was observed. Tests to detect pathogens other than rotavirus in the gastroenteritis stool samples were not performed. Therefore, all cause gastroenteritis with G1P[8] vaccine strain shedding was classified as rotavirus gastroenteritis. SAEs were reported in 11 infants (five in HRV and six in placebo groups), with bronchiolitis and gastroenteritis being the most common SAEs. No fatal SAEs, vaccine-related SAEs or intussusception Dolutegravir ic50 were reported in this study. It is important to study the safety of horizontal transmission of the human live-attenuated rotavirus vaccine virus from the vaccinated infants to the infants who received placebo because of the possibility

of conferring indirect protection or the theoretical concern of the ability of these live viruses to mutate and revert to their virulent form. Possible transmission of the HRV vaccine strain to placebo recipients have been observed in earlier clinical trials in infants (5–17 weeks of age at Dose 1) when vaccinated following a 0, 1–2 month schedule. In these studies, HRV vaccine strain was isolated from a total of five placebo recipients and possible transmission may have occurred in the unvaccinated infants [6] and [15]. In the present study, twins living in the same house were chosen because these conditions were conducive to analyze the true transmission TCL rate between the pairs of twins. A total of 15 cases (18.8%) of transmission were observed in the twins that received placebo based on the detection of HRV vaccine strain antigen from at least one of their stool samples

collected. Of these, there were chances that five of the cases were not “true transmission” because in these transmission cases the vaccine virus was isolated from the placebo recipient either before or at the same time as the antigen excreted in the stool samples of the corresponding twin receiving the HRV vaccine (Table 1). The potential explanation for the detection of vaccine virus in the placebo recipients before or at the same time as the vaccine recipients are—firstly, the possible mishandling or contamination of the stool samples, secondly, ELISA test used was not sufficiently sensitive to detect low concentrations of the viral antigen and thirdly, there could have been a short shedding period after vaccine administration (e.g. 1-day, shedding between stool sample collected).