- RV1 —
- monovalent rotavirus vaccine
- RV5 —
- pentavalent rotavirus vaccine
There are 2 US Food and Drug Administration–approved vaccines for the prevention of rotavirus gastroenteritis in infants. Rotarix is a live, oral, monovalent rotavirus vaccine (RV1) administered as a 2-dose series, and RotaTeq is a live, oral, pentavalent rotavirus vaccine (RV5) administered as a 3-dose series. RV1 and RV5 are typically administered along with other routinely recommended vaccines at the 2- and 4-month well-child visits, with the third dose of RV5 administered at the 6-month visit. Because a previously licensed rotavirus vaccine, RotaShield, was associated with an increased risk of intussusception, prelicensure safety studies of >60 000 children for both RV1 and RV5 were conducted to assess for the occurrence of intussusception.1,2 Although these studies showed no increased risk of intussusception, subsequent postmarketing studies have demonstrated small increased risks of intussusception for both vaccines, primarily after first doses and, to a lesser extent, after the second doses.3–8
In this issue of Pediatrics, Tate and colleagues compared the years pre- and postintroduction of rotavirus vaccines in the United States and found no significant difference in intussusception hospitalization rates in children <12 months of age comparing the 2 time periods.9 However, in children 8 to 11 weeks of age, the age range when the majority of the first doses of rotavirus vaccines were given, they found intussusception hospitalization rates to be significantly higher in the postlicensure period compared with the prelicensure period. Tate et al’s observation that an additional 7 to 26 US children aged 8 to 11 weeks may be hospitalized for intussusception annually is not so surprising given the findings from the postmarketing studies. In addition to those hospitalized cases noted by Tate et al, there are likely also a significant number of nonhospitalized cases that either self-reduce or are managed nonsurgically in emergency departments. Thus, on a population-based level, the effect may be somewhat larger than Tate et al noted. Given that ∼4 million children are born in the United States annually, with an individual risk for intussusception of 1 in 20 000 to 1 in 100 000 after rotavirus vaccine, we could expect between 40 to 200 US children could have rotavirus vaccine–related intussusception each year.10
Although the evidence is building that there is an increased risk, albeit uncommon, of intussusception with the receipt of rotavirus vaccine, the benefits of the rotavirus vaccination program have been dramatic. Before the introduction of RV5 and RV1, there were between 55 000 and 70 000 children hospitalized each year in the United States and >400 000 children with outpatient visits due to rotavirus-related disease.11 In the years after introduction of rotavirus vaccines, national rates of rotavirus detection declined by 58% to 90%.12 More important, serious disease due to rotavirus resulting in hospitalization or emergency department visits have been reduced by 90%.13–15 The huge impact of the US rotavirus vaccine program far outweighs the small increased risk of intussusception found in postlicensure studies.
Although the risk of rotavirus vaccine–associated intussusception is low, it is still important that we learn more about the mechanisms through which rotavirus vaccines increase the risk for intussusception. To date, this is still unclear. Possible mechanisms include theories that a gastrointestinal infection may lead to enlargement of the Peyer patches in the terminal ileum, which in turn acts as a lead point for the occurrence of intussusception, and that there are alterations in the motility of the intestine that contribute to the risk of intussusception. However, it is not understood whether the live, attenuated rotavirus vaccines cause this to happen and, if this does occur, why it occurs only in some children. Currently, the Center for Disease Control and Prevention’s Clinical Immunization Safety Assessment Project is undertaking a pilot study to further elucidate mechanisms underlying rotavirus vaccine–induced intussusception by examining anatomic and motility changes in young infants after the first dose of rotavirus vaccine (ClinicalTrials.gov; identifier NCT02542462). By increasing our knowledge about intussusception, we may be able to better understand the intriguing age-related findings in this study where there were no differences in the overall rate of intussusception hospitalizations for children <12 months of age pre- and postlicensure. A possible explanation could be due to a shift in intussusception events for certain susceptible children that is induced by rotavirus vaccine and a lower rate of intussusception in older children due to the prevention of wild-type rotavirus-associated intussusception. It will be important to better understand the role of rotavirus and rotavirus vaccines and intussusception with increased uptake of rotavirus vaccines around the world, especially when diagnosis and management of intussusception will be more challenging in resource-poor countries.
When discussing rotavirus vaccine with parents, pediatricians should acknowledge and discuss any potential risks, including intussusception, noting that the risk is low but can be serious when it occurs. The discussion should be couched in terms that, independent of rotavirus vaccination, intussusception is the most common abdominal emergency in children younger than 2 years of age, and parents should be advised to seek urgent medical care for symptoms and signs where the diagnosis is suspect.16 While acknowledging vaccination risks, it is paramount as pediatricians that we also communicate to parents and families the enormous benefits of rotavirus vaccination in preventing rotavirus disease in the United States.
- Accepted June 20, 2016.
- Address correspondence to Emmanuel B. Walter, MD, MPH, Duke Clinical Vaccine Unit, 2608 Erwin Rd, Suite 210, Durham, NC 27705. E-mail:
Opinions expressed in these commentaries are those of the author and not necessarily those of the American Academy of Pediatrics or its Committees.
FINANCIAL DISCLOSURE: Dr Walter has received funding from GlaxoSmithKline, Merck, Novartis, Novavax, and Pfizer to conduct clinical research studies. He has received support from Novartis as a member of a Data Safety Monitoring Board and from Merck as a consultant. Dr Staat has indicated she has no financial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: Dr Walter has received funding from GlaxoSmithKline, Merck, Novartis, Novavax, and Pfizer to conduct clinical research studies. He has received support from Novartis as a member of a Data Safety Monitoring Board and from Merck as a consultant. Dr Staat has indicated she has no financial relationships relevant to this article to disclose.
COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2016-1082.
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- Copyright © 2016 by the American Academy of Pediatrics