Abstract
Rotavirus is the leading cause of diarrheal death among children < 5 years old worldwide, estimated to have caused ~ 215,000 deaths in 2013. Prior to rotavirus vaccine implementation, > 65% of children had at least one rotavirus diarrhea illness by 5 years of age and rotavirus accounted for > 40% of all-cause diarrhea hospitalizations globally. Two live, oral rotavirus vaccines have been implemented nationally in > 100 countries since 2006 and their use has substantially reduced the burden of severe diarrheal illness in all settings. Vaccine efficacy and effectiveness estimates suggest there is a gradient in vaccine performance between low child-mortality countries (> 90%) and medium and high child-mortality countries (57-75%). Additionally, an increased risk of intussusception (~ 1-6 per 100,000 vaccinated infants) following vaccination has been documented in some countries, but this is outweighed by the large benefits of vaccination. Two additional live, oral rotavirus vaccines were recently licensed and these have improved on some programmatic limitations of earlier vaccines, such as heat stability, cost, and cold-chain footprint. Non-replicating rotavirus vaccines that are parenterally administered are in clinical testing, and these have the potential to reduce the performance differential and safety concerns associated with live oral rotavirus vaccines.