No other conflicts of interest are declared. “
“Diarrhoea remains one of the leading causes of mortality in infants and young children and results in over 1.34 million deaths in this age group every year [1]. Rotaviruses are responsible for almost 40% of all Enzalutamide chemical structure serious diarrhoeal episodes in infants and young children under 5 years of age requiring a health care

visit and are considered the single leading cause of diarrhoea deaths worldwide. Rotavirus is estimated to cause about 114 million episodes of diarrhoea, 25 million clinic visits, 2.4 million hospital admissions and more than 450,000 deaths per year globally [2], with more than 90% of these deaths occurring in the low income countries of South Asia and Sub-Saharan Africa [2] and [3]. Most African infants (>75%) have their first serious infection before their first birthday [4]. Studies have shown that the first natural rotavirus infection is the most severe and provides some protection against subsequent severe rotavirus gastroenteritis (RVGE) [5], [6] and [7]. Oral live attenuated rotavirus vaccines have been ERK inhibitor developed in an attempt to duplicate the protection induced by natural rotavirus infection by stimulating intestinal IgA antibodies and other forms of local immunity. However, the multitude of clinical trials with

various live attenuated, orally administered rotavirus vaccines has not demonstrated a viable immune correlate of protection

[8] and [9]. Nevertheless, the serum IgA immune response to these vaccines is considered the best “surrogate” marker of protection available, and is evaluated with all rotavirus vaccines. Serum neutralizing antibody (SNA) is also considered important but neither measure has been shown to consistently correlate with clinical efficacy [8] and [9]. Two new live oral rotavirus vaccines have now been developed and shown to be safe and efficacious against severe RVGE why in developed populations and in Latin America [5], [10], [11], [12] and [13]. In all these studies with both rotavirus vaccine candidates, robust IgA immune responses were observed in various populations ranging from 85 to 95% [10], [11], [12] and [13]. In 2005, following a review of available efficacy data from trials in European and Latin American countries and considering the past history of diminished performance of live oral vaccines in protecting the poorest children in developing countries, WHO requested the evaluation of these vaccines in Asia and Africa to generate immunogenicity and efficacy data in these populations [14]. In response to this mandate, the PATH Rotavirus Vaccine Program and Merck & Co. Inc.