Rotavirus vaccines have emerged as important vaccines in preventing severe childhood diarrhea and, in low-income countries, deaths. As a class of vaccines, they have accelerated the development of surveillance systems to monitor vaccine safety.
Two trials recently published in NEJM evaluated the risk of intussception in young infants in the context of the overall health benefits conferred by the 2 different rotavirus vaccines. The studies, one done by CDC and the other funded through the FDA, were post-marketing studies designed to evaluate the safety of two vaccines licensed in 2006 and in wide-spread use since then. Having such active surveillance shows how things have evolved since the first rotavirus vaccine (RotaShield, Wyeth Lederle) was voluntarily withdrawn from the U.S. market in 1999.
Back then, the first signs of an association between vaccine administration and intussception were detected through the Vaccine Associated Adverse Events Reporting (VAERS), a passive surveillance system that allows physicians or parents to report possible adverse events. Those signals prompted CDC to undertake a study evaluating the VAERS signals using data collected in the Vaccine Data Safety Link and estimated excess risk of intussception at 1 to 2 cases per 10,000 vaccine recipients. The Wyeth vaccine was voluntarily withdrawn from the market.
The question of an association between rotavirus vaccine administration and intussception is a tough one because bowel telescoping in young infants tends to peak during the same months (2, 4, 6) at which vaccines are administered.
As part of the FDA licensure trials, the pentavelent vaccine (RV5, RotaTeq, Merck) and the monovalent vaccine (RV1, Rotarix, GlaxoSmithKline) each had enrolled more than 60,000 children to establish an initial safety data. The two new studies in NEJM extend our understanding of the safety of these vaccines regarding the risk of intussception. The CDC study used the Vaccine Data Safety Link system, finding an insignificantly elevated relative risk of 1.1 for the RV5 vaccine and a significantly elevated relative risk of 9.5 for RV1 vaccine. However, in the FDA-sponsored study, the RV5 vaccine was associated with approximately 1.5 excess cases of intussception per 100,000 first doses and the RV1 assessment was underpowered.
In an accompanying editorial, Drs. Roger Glass and Umesh D. Parashar wrote that the intussception risk of both vaccines was low compared to the health benefits of reduced deaths, hospitalizations and emergency room visited caused by rotavirus infection and diarrhea. Researchers still need to do additional research to determine the mechanism of intussception after vaccination and if some groups of infants face a higher risk.
The development of rotavirus vaccines has driven improvements in the development of vaccine surveillance efforts.