We did not see an increase in overall bacterial pathogens in the stool in either the PRV or the placebo group. A similar distribution of bacterial pathogens in western Kenya has been shown before, although we did not test for diarrheagenic E. coli [16]. A limitation was that we were not

able to test for other viral pathogens, such as norovirus; therefore, we are unable to definitely rule out replacement disease by other diarrhea-causing viruses in the vaccinated children. While replacement disease with non-vaccine pneumococcal serotypes has been observed after introduction of pneumococcal conjugate vaccines, a similar phenomenon has not been observed with rotavirus Dasatinib vaccines [43]. Replacement disease after rotavirus vaccines is less likely since they demonstrate cross-protection against all rotavirus serotypes [13] and [35]. Moreover, most gastroenteritis-causing pathogens, including rotavirus, do not have an asymptomatic colonization period of the colon prior to causing disease, as most pneumococci do in the nasopharynx. Without a phase of colonization, it seems less likely that reduction learn more of rotavirus disease will lead to replacement disease

by other pathogens. Our study had several limitations. First, the number of RVGE identified by the clinic-based catchment surveillance was lower than expected, which limited the statistical power to detect differences between the treatment groups. This MTMR9 was particularly pertinent during the second year of life when only 5 cases of severe RVGE were identified. The Kenya site specific analysis was done as a post-hoc analysis on a small sample size, thus the efficacy findings have wide confidence intervals and caution should be used in interpreting

the point estimates alone. Second, we used different case definitions for severe gastroenteritis in the clinic-based catchment and the home visit surveillance. The home visit definition (i.e. IMCI) of severity was based on dehydration status, whereas the clinic definition (i.e. Vesikari Clinical Scoring System) included severity and duration of clinical signs in addition to hydration status [11] and [14]. This difference might have led to imprecision in our estimates of the burden of severe RVGE that occurred in the community, where we assumed comparable severity between the home-based and clinic-based definitions. In addition, we were limited in our estimation of the burden of RVGE in the community because we did not test stools for gastroenteritis episodes identified at home. The findings of this study in Kenya reinforce the 2009 WHO recommendation that rotavirus vaccines be introduced in the immunization program of countries with high diarrheal mortality [5].