This is due to the greater incidence of intussusception in the first year of life in Japan (185 per 100,000 people/year [95% CI: 133250])40than in the US (30-50 per 100,000 people/year)71or Australia (71 per 100,000 people/year [95% CI: 5297]).72 == CONCLUSION == A live-attenuated, orally-administered, monovalent rotavirus vaccine, Rotarix, has been launched on the Japanese market. G2P[4] strains. While postlicensure studies detected a small and finite risk of intussusception associated with the administration of Rotarix, the authors conclude that Rotarix is safe to administer to infants between 6-12 weeks of age for the first dose and by 24 weeks of age for the second dose. However, the authors strongly discourage the delayed administration of the first dose between 13-20 weeks of age, which is allowed without NR4A1 any warning. Given the high incidence of naturally-occurring intussusception in Japan (185 cases per 100,000 children/year among children less than 1 year of age), this should prevent pediatricians and parents from having ill-perceptions of Rotarix being associated with an increased number of temporally-associated intussusception, and fully appreciate the benefit of the rotavirus vaccine. Keywords:diarrhea, heterotypic immunity, immunization, intussusception, Japan, Rotarix, rotavirus == INTRODUCTION == Acute diarrhea is the leading cause of childhood morbidity and mortality worldwide, accounting for approximately 15% of deaths occurring in children less than 5 years of age.1Rotavirus has been recognized as the single most important etiological agent of severe diarrhea2causing an estimated 453,000 deaths annually.3Thus, after reviewing the recent efficacy data generated by studies on Rotarix (GlaxoSmithKline Biologicals, Rixensart, Belgium) in African countries, the Strategic Advisory Group of Experts of the World Health Organization (WHO) in 2009 2009 recommended incorporation of rotavirus vaccines into the national immunization programs of all countries, with an emphasis in those regions where mortality rates in children less than 5 years of age are 10%.46Two major rotavirus vaccines that were prequalified by the WHO are the monovalent, human rotavirusbased vaccine, Rotarix,7and the pentavalent, bovine-human re-assortant vaccine, RotaTeq (Merck & Co, Inc., NJ, USA).8These rotavirus vaccines are licensed in more than 120 countries, but it was not until 2011 that the Ministry of Health, Labor, and Welfare in Japan approved the rotavirus vaccine (Rotarix) for use in infants to prevent rotavirus gastroenteritis. In this review the authors briefly describe two important issues to understand the rotavirus vaccine: the nature DRAK2-IN-1 of protective immunity after natural rotavirus infection and the burden of rotavirus diarrhea in Japan. The authors then concisely summarize the product profile of Rotarix that is most relevant in practice. Finally, the authors address two key issues for practitioners and parents: the efficacy of Rotarix against fully heterotypic strains and the safety of Rotarix with respect to intussusception. == ROTAVIRUS AND ITS SEROTYPES == Rotavirus, taxonomically a species (Rotavirus A) within genusRotavirus, familyReoviridae, is a nonenveloped RNA virus with icosahedral symmetry.9The outer surface of the virion consists of viral spikes (made up of the VP4 trimers) and the outercapsid proteins (made up of the VP7 trimers).9Both VP4 and VP7 independently serve as a neutralization antigen, and define the protease-sensitive protein (P) type and the glycoprotein (G) type, respectively.2,9While serotype should, by definition, be determined by serologic assays, molecular assays have replaced serologic assays in the determination of G and P types of a rotavirus in clinical specimens; hence, referred to as DRAK2-IN-1 the genotype.9While there is an exact match DRAK2-IN-1 between G serotype and G genotype, different numbering systems were adopted to designate P serotype and P genotype, with P genotype being designated within squared brackets. Thus, the P serotype of RIX4414, the vaccine strain in Rotarix, is P1A, whereas its P genotype is P[8]. There are 27 G genotypes and 35 P genotypes described to DRAK2-IN-1 date,10but the G and P type combinations detected in human rotaviruses are mostly limited to G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8].11,12However, previously rare G12 strains appear to have emerged across the globe1315and G8 strains, with either P[6] or P[4], account for a significant proportion of human rotavirus strains in Africa.16,17Such genetic diversity appears to be generated by frequent reassortment of the genome segments and interspecies transmission of rotaviruses between humans and animals.1821 == PROTECTIVE IMMUNITY AFTER NATURAL INFECTION AND THE GUIDING PRINCIPLE OF ROTAVIRUS VACCINES == Complete protection against moderate-to-severe rotavirus-associated diarrhea, but not against mild diarrhea or infection itself, is obtained after asymptomatic infection in the neonatal period22or after two infections with rotavirus, regardless of whether the infections are symptomatic or asymptomatic.23In a cohort study in Mexico,23the adjusted efficacy in protecting against subsequent.