Rotavirus Vaccination and Intussusception Risk

W. Katherine Yih Ph.D., M.P.H Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Interview with:
W. Katherine Yih Ph.D., M.P.H
Department of Population Medicine
Harvard Medical School and Harvard Pilgrim Health Care Institute  What are the main findings of the study?

Dr. Yih: The main findings are that vaccination with the first dose of RotaTeq is associated with a small increase in the risk of intussusception, which is concentrated in the first week after vaccination.  The estimated risk is about 1.5 excess cases per 100,000 first doses administered.  This risk is fairly small, amounting to roughly 1/10 of the risk seen after the original rotavirus vaccine (called Rotashield) that was used in 1998-1999, before it was withdrawn from the market.

We also found evidence that Rotarix increases the risk of intussusception.  However, the number of infants receiving Rotarix and the number getting intussusception after Rotarix were too small to allow us to estimate the risk after Rotarix with any precision.  Were any of the findings unexpected?

Dr. Yih: The findings of an increased risk of intussusception after rotavirus vaccination were not entirely unexpected, given that studies conducted in other countries had pointed to an increased risk after one or the other of the two vaccines.  However, several studies conducted in the United States had not found an increased risk.  The state of knowledge about the risk of intussusception after rotavirus vaccination in the United States changed in May-June 2013 with a publication by the Vaccine Adverse Event Reporting System (Haber et al., in Pediatrics), which found an increased risk after RotaTeq, and a public presentation by the Vaccine Safety Datalink (VSD) project to the Advisory Committee on Immunization Practices (Weintraub et al., in the New England Journal of Medicine), which found an increased risk after Rotarix.

At this point, our results for both vaccines are broadly compatible with those of other published studies that have been conducted internationally and in the United States.  Although the VSD study did not find a statistically significant increase in the risk of intussusception after RotaTeq, their point estimate of the risk from Dose 1 was elevated and the 95% confidence interval around this estimate overlaps with ours.  Therefore, I do not consider our results to be inconsistent with the VSD results.  What should clinicians and patients take away from your report?

Dr. Yih: Both rotavirus vaccines provide a high level of protection against severe diarrhea from rotavirus infection.  The benefits of rotavirus vaccination in preventing severe diarrhea and hospitalization in several countries, including the United States, have been amply documented in the scientific literature.  After carefully evaluating the results of this study and of other recent studies of the association between rotavirus vaccination and intussusception, the CDC continues to recommend that all U.S. infants (following the age and precaution/contraindication criteria) receive rotavirus vaccine.  This recommendation is based on their assessment that the benefits of vaccination with either of the two rotavirus vaccines outweigh the risks of intussusception.  For instance, it is estimated that routine rotavirus vaccination will prevent more than 53,000 hospitalizations for severe diarrhea in a U.S. birth cohort of 4.3 million infants followed to 5 years of age.  This number of hospitalizations averted is far greater than the projected number of vaccine-associated intussusception cases.

Although the risk of intussusception is low, if, after rotavirus vaccination, a child appears to have severe abdominal pain (indicated by, for example, severe crying, pulling their legs up to their chest, vomiting, or passing blood in their stool), the parent/guardian should promptly seek medical attention and mention the date and other details of the recent rotavirus vaccination.  What recommendations do you have for future research as a result of this study?

Dr. Yih: A formal risk-benefit evaluation would be helpful in order to establish unequivocally that the benefits of vaccination outweigh the risks.  It would also be useful to have a rigorous comparison of the safety of the two vaccines, with adequate statistical power, since if the risk from one is significantly greater than the risk from the other, this would have policy implications.


Intussusception Risk after Rotavirus Vaccination in U.S. Infants

W. Katherine Yih, Ph.D., M.P.H., Tracy A. Lieu, M.D., M.P.H., Martin Kulldorff, Ph.D., David Martin, M.D., M.P.H., Cheryl N. McMahill-Walraven, M.S.W., Ph.D., Richard Platt, M.D., Nandini Selvam, Ph.D., M.P.H., Mano Selvan, Ph.D., Grace M. Lee, M.D., M.P.H., and Michael Nguyen, M.D.

January 14, 2014DOI: 10.1056/NEJMoa1303164