Early epidemiological evidence concluded that four rotavirus strains (P[8]G1, P[4]G2, P[8]G3, and P[8]G4) accounted for nearly 90% of all rotavirus strains circulating globally [21] and [22]. In the past decade, improved laboratory methods, including hybridization assays, oligonucleotide sequencing, and type specific reverse-transcriptase polymerase chain

reaction (RT-PCR) primer kits, have enabled rotavirus surveillance efforts to examine more strains in greater detail, demonstrating far broader Protein Tyrosine Kinase inhibitor strain diversity in developing countries [17], [18], [22] and [23]. Thus, new rotavirus strains are discovered [17], [19], [20], [23] and [24], novel P- and G-combinations are identified [16], [17], [19], [20], [23], [24] and [25], and new emergent reassortant zoonotic strains are reported [26], [27] and [28]. This prolific diversity is observed particularly Sirolimus in the subcontinent where a large number of studies have been conducted. Two commercial rotavirus vaccines are currently available: Rotarix™ (GlaxoSmithKline Biologicals, Belgium), licensed in >100 countries worldwide, and RotaTeq® (Merck & Co., Inc., USA), licensed in approximately 90 countries worldwide. Both these commercial vaccines are pre-qualified by the World Health Organization (WHO) and are recommended for global use in all childhood immunization programs for the prevention of severe rotavirus

disease [13]. In addition, several developing country manufacturers

are developing a new pipeline of rotavirus vaccines [29] and [30]. whatever Three of these candidate vaccines are currently in clinical development in India with different manufacturers, and one has completed Phase 2 immunogenicity studies [31] and [32]. The clinical development of any rotavirus vaccine for use in this region will require an understanding of the epidemiology and strain distribution to facilitate Phase 3 clinical studies and to act as a platform to eventually measure vaccine effectiveness. Ongoing monitoring and review of strain diversity is thus necessary, not only to better understand strain diversity in specific regions, but also for the effective evaluation of vaccine efficacy against a multitude of strains, especially as national immunization policymakers respond to the WHO recommendation for the global use of rotavirus vaccine [13]. This systematic literature review of studies from India, Bangladesh, and Pakistan was conducted to establish a longitudinal description of rotavirus strain diversity and prevalence over three decades in a region that has high rotavirus mortality. Furthermore, the review should be useful for the planning of the Phase 3 studies with the new rotavirus vaccines that are in development by manufacturers in India, and for interpretation of the data that is generated.