The high burden of severe rotavirus disease in the second year of life documented in the current study emphasises the importance of continued protection, and the potential public health value

that even a modestly efficacious vaccine would bring if incorporated into Malawi’s national immunisation programme. Vaccine efficacy in Malawi was substantially lower than observed in clinical trials of both Rotarix and RotaTeq in upper and middle income countries, where an efficacy of 85–100% against severe rotavirus gastroenteritis had been demonstrated in the first year of life [6], [7] and [8], Selleckchem BLZ945 and where protection is relatively well conserved into the second year of life [29], [30], [31] and [32]. Potential reasons (e.g. maternal antibodies, breastfeeding, concurrent OPV administration, malnutrition, concomitant HIV infection, rotavirus strain diversity, enteric co-infections, “force of

infection”) why the efficacy of live, oral rotavirus vaccines may be lower in developing countries have been discussed previously, but remain incompletely understood [33], [34] and [35]. In our study, all mothers were breastfeeding, and >99% of infants received concomitant OPV [14]. Less than 5% of enrolled infants were HIV infected [14]. The impact of nutritional status Alpelisib datasheet on vaccine efficacy and the role of concurrent infection with other enteric pathogens in this study cohort is currently second being explored. Although there is no reliable, consistent laboratory correlate that predicts clinical protection following rotavirus vaccination [36] and [37], it is known that the serum immune response to rotavirus vaccines decreases by income level of country [33]. The anti-rotavirus IgA seroconversion rate following vaccination in this study, 52.9%, is one of the lowest reported for Rotarix [33]. In this regard, it is worthy of mention that Malawi is a very low income country (Gross National Income per capita of $810 per annum) with an under 5 mortality rate of 100 per 1000 live births (http://www.who.int/gho/countries/mwi.pdf). A particular feature of this study

was the diversity of circulating strains encountered, including genotypes G8, G9 and G12, with only a minority of strains carrying the G1P[8] genotype on which the vaccine is based. Surveillance of rotavirus strains undertaken in Malawi since 1997 has described an extraordinary diversity of rotaviruses [22], and African countries are known to harbour a wide variety of rotavirus strains [38]. The diversity of circulating strains documented during this study, when examined further at the whole genomic level, does not however explain the reduced vaccine efficacy in Malawi [39]. Furthermore, vaccine efficacy was consistent across strain types in both Malawian and South African populations [14] and [40].