This may have resulted in accelerated waning of immunity

This may have resulted in accelerated waning of immunity selleckchem in the HRV_2D group, and consequently lack of efficacy over a 2-year period. The immunogenicity of a HRV_2D compared to HRV_3D in settings such as ours, however, needs further validation as our study was not powered to address this. A third further possible reason for decreased efficacy of Rotarix in our setting over 2 consecutive seasons may relate to the possibility of severity of gastroenteritis episodes in which rotavirus is identified during the second year being due to co-infection with other enteric pathogens. In this study,

co-infections were not evaluated. Co-infection with rotavirus and other bacterial and viral enteropathogens has been observed in infants and toddlers in similar settings,

and occurs in about 20% of cases [27] and [28]. As it is not possible to rule out the possibility of co-infection contributing to severe gastroenteritis symptoms rather than rotavirus per se being responsible for the illness severity in our study, this also needs to be evaluated further. The possibility of co-infection contributing to more severe illness in subsequent years is corroborated by the observation that rotavirus infections after the first natural rotavirus infection are significantly less severe than first rotavirus infection [21]. As HRV mimics natural rotavirus infection, theoretically subsequent rotavirus Dinaciclib solubility dmso infection in vaccinees should be less severe.

However, the persistence of protection observed in the HRV_3D group make it unlikely that this is a major reason for the diminished vaccine efficacy over 2 consecutive rotavirus found seasons in the HRV_2D group. These data, together with the exploratory analysis which indicated higher point estimate of sero-conversion rates in the HRV_3D group (66.7%) than HRV_2D group (57.1%), indicate that a 3-dose schedule of Rotarix may have an advantage in providing longer-term protection against severe RVGE and severe all-cause gastroenteritis than a 2-dose schedule. The sero-conversion rates are similar to those observed in an earlier immunogenicity study in South Africa, which also reviewed the 2-dose schedule at 10 and 14 weeks of age and the 3-dose schedule at 6, 10 and 14 weeks of age [18]. Although South Africa has introduced a 2-dose schedule of Rotarix, based on its licensure conditions, the dosing schedule being used includes a dose at 6 and 14 weeks of age, rather than the 10 and 14 weeks of age schedule evaluated in our study. The rationale for this dosing schedule included the aim of conferring protection as early as possible with the first dose of vaccine being at 6 rather than 10 weeks of age and minimizing missing the opportunity of vaccination at the earliest well-baby visit.

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