Rotavirus vaccination for prevention of serious acute gastroenteritis and the importance of postlicensure safety monitoring.

With the ability to save millions of lives each year in both the developed and developing nations, vaccination against childhood infectious diseases is a priority area for global health. An essential aspect of the success of any vaccination program is the careful monitoring following implementation to ensure that the benefits of the program outweigh any risks to the recipients or the community. Infant rotavirus vaccination programs are an important example of the collaborative expertise required for effective and timely monitoring and reporting of any adverse events following implementation. Rotavirus vaccines have been instrumental in reducing morbidity from rotavirus infection. Prior to the introduction of rotavirus vaccine, it is estimated that >500 000 rotavirus-related child deaths occurred globally each year [1]. Studies assessing the impact of rotavirus vaccine on incidence of rotavirus hospitalizations have occurred in numerous countries, including Australia and the United States, with dramatic reductions in the incidence of rotavirus hospitalizations (up to 80% reduction) shown following implementation of the rotavirus vaccination programs and suggestions of herd immunity benefits for older, unvaccinated populations [2–6]. The development of vaccines to prevent serious infectious diseases has been a global triumph, but large-scale postlicensure studies are essential to ensure that vaccination programs deliver the anticipated benefits. In response to the overwhelming global burden of rotavirus infections, particularly in children aged <5 years, a live, attenuated tetravalent rotavirus vaccine (RotaShield) was licensed for routine use in infants in 1998, before being withdrawn in 1999 due to concerns about an increased risk of intussusception in vaccine recipients [7]. RotaShield was estimated to cause 10–20 episodes of intussusception per 100 000 doses given to infants, and recommendations for use were subsequently withdrawn, a decision that even today remains controversial. However, with the commitment of vaccine development teams, industry partners, academic researchers, epidemiologists, and public health advocates, two second-generation rotavirus vaccines (RotaTeq [RV5] and Rotarix [RV1]) were developed, and their use has now been implemented as part of a national immunization program in at least 28 countries [8]. Monitoring following introduction of these rotavirus vaccine programs occurs in many countries, partly due to the reported association between RotaShield and intussusception and partly due to a heightened awareness of the importance of implementation of surveillance following introduction of new vaccines. Large-scale clinical trials, each involving >60 000 participants, which were conducted prior to licensing of the current rotavirus vaccines, mainly in Finland and the United States for RV5 and in Latin American countries for RV1, demonstrated no significant increase in intussusception [9–11]. In these trials, a large sample size was required to establish the safety of these vaccines because intussusception is a rare event. Although unable to entirely exclude any increased risk of intussusception, the studies were powered to detect risks of the magnitude determined following the RotaShield vaccine implementation. Because of the possibility of rare but serious adverse events following vaccination, postlicensure surveillance is essential for identifying and monitoring these events. From extensive postlicensure surveillance underway following introduction of RV5 and RV1 vaccines, suggestions of an increased risk of intussusception with the current rotavirus vaccines have come from Mexico and Australia, albeit at a much lower relative risk than identified with the earlier RotaShield vaccine. The Received and accepted 28 February 2012; electronically published 26 April 2012. Correspondence: Michelle Clarke, BAppSci, GDSTC, Department of Paediatrics, Women’s and Children’s Hospital, 72 King William Rd, North Adelaide, SA 5006, Australia ([email protected]). The Journal of Infectious Diseases 2012;206:3–5 © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@ oup.com. DOI: 10.1093/infdis/jis318