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Rotaviruses cause life-threatening gastroenteritis in children throughout the world. The burden of disease has resulted in the development of two live, attenuated vaccines that are now licensed in many countries. This review summarizes new data on these vaccines, their effectiveness, and remaining challenges including new data on the rotavirus enterotoxin, a potential antiviral target.Live attenuated rotavirus vaccines are used to protect infants against severe rotavirus-induced gastroenteritis and, RotaTeq, a pentavalent bovine-based vaccine, and, Rotarix, a monovalent human rotavirus, are now currently licensed in many countries. Initial results of the licensed RotaTeq vaccine have been promising in the USA and results of immunogenicity and efficacy in developing countries are expected soon. However, universal vaccine implementation is challenging due to age limitations on administration of these vaccines. Chronic rotavirus infections in immunocompromised children may remain a problem and require the development of new treatments including antiviral drugs. Increasing data on the mechanisms of action of the rotavirus enterotoxin highlight this pleiotropic protein as a good target as well as a unique calcium agonist.Rotavirus is now a commonly occurring vaccine-preventable disease among children in developed countries and hopefully this also will soon be true for developing countries. Future studies will determine whether other methods of prevention, such as nonreplicating vaccines and antiviral drugs, will be needed to treat disease in immunocompromised children.