Rotavirus vaccines: an update Penelope H. Dennehy Purpose of review Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and has a major global impact on childhood morbidity and mortality. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease. Recent findings Rotavirus disease prevention efforts suffered a great setback in 1999 with the withdrawal of the RRV-TV vaccine less than a year after its introduction. Several new rotavirus vaccine candidates have now been developed and are undergoing clinical trials. Summary New safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries. Keywords rotavirus, vaccine Curr Opin Pediatr 17:88–92. © 2005 Lippincott Williams & Wilkins. Introduction Rotavirus is the most common cause of severe diarrhea disease in infants and young children worldwide, particu- larly in developing countries where it is estimated to be responsible for 20% of diarrhea deaths and 6% of all diarrhea episodes [1••]. A recent study estimated an an- nual incidence of 418,000 to 520,000 deaths globally be- cause of rotavirus, of which 85% were in low-income countries [2]. Rotavirus is also the cause of a substantial disease burden for children in the United States, accounting for 20 to 40 deaths annually, and approximately 50,000 hospitaliza- tions because of severe diarrhea and dehydration [3]. Rotavirus is responsible for as many as 50% of pediatric admissions to hospitals because of diarrhea and 20 to 25% of cases of pediatric diarrhea in outpatient clinics. During the peak rotavirus season, the virus may be the cause of more than 75% of inpatient pediatric admissions for gastrointestinal illness [4]. Virtually all children be- come infected in the first 3 to 5 years of life, but severe diarrhea and dehydration occur primarily among children 3 to 35 months of age. Vaccination is the only control measure likely to have a significant impact on the inci- dence of severe dehydrating rotavirus disease. Seven ro- tavirus groups (A to G) are described, but only groups A, B, and C infect humans. Group A rotaviruses are the most important from a public health standpoint. Rotavi- ruses contain two structural proteins: VP7, the glycopro- tein (G protein), and VP4, the protease-cleaved protein (P protein). These two proteins define the serotype of the virus and are considered critical to vaccine develop- ment because they are targets for neutralizing antibod- ies, which may provide protection [5]. A typing system has been developed to specify each protein. Until recently, four rotavirus strains (G1,P[8], G3,P[8], G4,P[8], and G2,P[4]) made up 96% of the globally iden- tified strains [6]. However, several recent surveys high- light the emergence of previously rare types, such as serotypes G5, G6, G8, G10, and in particular G9 [5–7]. Different strains predominate in regions throughout the world. The development of successful rotavirus vaccines may require inclusion of all the major P or G types caus- ing disease in a specific region. Natural protection Longitudinal studies have demonstrated that naturally acquired rotavirus infections provide protection against rotavirus disease upon reinfection, and that protection is Division of Pediatric Infectious Diseases, Rhode Island Hospital and Brown Medical School, Providence, Rhode Island, USA Correspondence to Penelope H. Dennehy, MD, Division of Pediatric Infectious Diseases, Rhode Island Hospital, 593 Eddy Street Providence, RI 02903, USA Tel: 401 444 4298; fax: 401 444 5650; e-mail: pdennehy@lifespan.org Current Opinion in Pediatrics 2005, 17:88–92 © 2005 Lippincott Williams & Wilkins 1040-8703 88