The combined 5-country analysis did demonstrate statistically significant efficacy during the second year of life, which

was not observed when the Africa data were analyzed alone (VE = 19.6% [95% CI:–15.7–44.4]) [5], but was demonstrated in Asia (VE = 45.5% [95% CI: 1.2–70.7]). Thus, the combined estimate for efficacy selleck compound during the second year of life was heavily influenced by the markedly more positive findings in Asia, where factors affecting durability of protection may be different, and may not have represented simply a lack of statistical power to observe a substantial effect in Africa. All participating sites attempted to optimize the quality of care at study health centers and educated communities about the use of oral rehydration solutions. Since mortality from rotavirus results from severe dehydration [16] and is most likely to occur among children with limited access to health care or to oral rehydration solutions, DNA Damage inhibitor we did not expect to show reduction in deaths due to confirmed RVGE among vaccinated

children in this study, principally because children with confirmed RVGE had (by definition) accessed health centers and should have been rehydrated according to clinical algorithms used by study physicians. With knowledge that GE of increasing severity is more likely due to rotavirus [16] and an assumption that mortality increases with clinically more severe GE, our findings of increasing vaccine efficacy with escalating Vesikari clinical scores, suggest the likely utility of the vaccine in preventing mortality due to rotavirus. Indeed, mortality

from diarrheal disease in infants decreased >40% in Mexico following introduction of rotavirus immunization there [17]. To date, there are 27 G and 35 P rotavirus genotypes Endonuclease described [17]. Of these, 12 G types (G1–G6, G8–G12, and G20) and 12 P types (P[3]–P[6], P[8]–P[11], P[14], P[19], P[25], and P[28]) have been detected in humans [18]. As more information becomes available, it is clear that patterns of rotavirus genotypes naturally change over time [19]. In addition, some rotavirus genotypes have emerged over time, and in the case of G9 and G8, some genotypes have become highly prevalent in some settings [19], [20] and [21]. During our study, we detected a wide variety of rotavirus genotypes circulating over the two years that the study was conducted. Clinical studies have suggested that the first GE due to rotavirus tends to be most severe, and that subsequent rotavirus infections, usually of a different serotype, tend to be of less severity [15] and [22]. The immunologic mechanisms and effectors responsible for protection against rotavirus after either natural infection or vaccination are incompletely understood [15]. The recognition that multiple human rotavirus genotypes exist has long raised the critical question of whether protective immunity is homotypic (same G or P type) or heterotypic (different G or P type) [20].