Risk of intussusception following administration of a pentavalent rotavirus vaccine in US infants.

CONTEXT Current rotavirus vaccines were not associated with intussusception in large prelicensure trials. However, recent postlicensure data from international settings suggest the possibility of a low-level elevated risk, primarily in the first week after the first vaccine dose. OBJECTIVE To examine the risk of intussusception following pentavalent rotavirus vaccine (RV5) in US infants. DESIGN, SETTING, AND PATIENTS This cohort study included infants 4 to 34 weeks of age, enrolled in the Vaccine Safety Datalink (VSD) who received RV5 from May 2006-February 2010. We calculated standardized incidence ratios (SIRs), relative risks (RRs), and 95% confidence intervals for the association between intussusception and RV5 by comparing the rates of intussusception in infants who had received RV5 with the rates of intussusception in infants who received other recommended vaccines without concomitant RV5 during the concurrent period and with the expected number of intussusception visits based on background rates assessed prior to US licensure of the RV5 (2001-2005). MAIN OUTCOME MEASURE Intussusception occurring in the 1- to 7-day and 1- to 30-day risk windows following RV5 vaccination. RESULTS During the study period, 786,725 total RV5 doses, which included 309,844 first doses, were administered. We did not observe a statistically significant increased risk of intussusception with RV5 for either comparison group following any dose in either the 1- to 7-day or 1- to 30-day risk window. For the 1- to 30-day window following all RV5 doses, we observed 21 cases of intussusception compared with 20.9 expected cases (SIR, 1.01; 95% CI, 0.62-1.54); following dose 1, we observed 7 cases compared with 5.7 expected cases (SIR, 1.23; 95% CI, 0.5-2.54). For the 1- to 7-day window following all RV5 doses, we observed 4 cases compared with 4.3 expected cases (SIR, 0.92; 95% CI, 0.25-2.36); for dose 1, we observed 1 case compared with 0.8 expected case (SIR, 1.21; 95% CI, 0.03-6.75). The upper 95% CI limit of the SIR (6.75) from the historical comparison translates to an upper limit for the attributable risk of 1 intussusception case per 65,287 RV5 dose-1 recipients. CONCLUSION Among US infants aged 4 to 34 weeks who received RV5, the risk of intussusception was not increased compared with infants who did not receive the rotavirus vaccine.

[1]  W Katherine Yih,et al.  Real-Time Surveillance to Assess Risk of Intussusception and Other Adverse Events After Pentavalent, Bovine-Derived Rotavirus Vaccine , 2010, The Pediatric infectious disease journal.

[2]  Roger I Glass,et al.  Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP). , 2009, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[3]  Robert L Davis,et al.  Real-Time Vaccine Safety Surveillance for the Early Detection of Adverse Events , 2007, Medical care.

[4]  Katherine J. Lee,et al.  Intussusception following rotavirus vaccine administration: post-marketing surveillance in the National Immunization Program in Australia. , 2011, Vaccine.

[5]  J. Ward,et al.  Lack of association between rotavirus infection and intussusception: implications for use of attenuated rotavirus vaccines. , 2002, The Pediatric infectious disease journal.

[6]  Manish M Patel,et al.  Sociodemographic and Dietary Risk Factors for Natural Infant Intussusception in the United States , 2010, Journal of pediatric gastroenterology and nutrition.

[7]  H. Greenberg.  Rotavirus vaccination and intussusception--act two. , 2011, The New England journal of medicine.

[8]  T. Vesikari,et al.  Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. , 2006, The New England journal of medicine.

[9]  F. Destefano,et al.  Predictive Value of ICD-9-CM Codes Used in Vaccine Safety Research , 2008, Methods of Information in Medicine.

[10]  Robert T. Chen,et al.  Population-based study of rotavirus vaccination and intussusception , 2001, The Pediatric infectious disease journal.

[11]  J. Heyse,et al.  Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. , 2006, The New England journal of medicine.

[12]  J. Carlin,et al.  Changing epidemiology of intussusception in Australia , 2005, Journal of paediatrics and child health.

[13]  J. Stockman.  Intussusception Risk and Health Benefits of Rotavirus Vaccination in Mexico and Brazil , 2013 .

[14]  U. Parashar,et al.  Rotavirus vaccination coverage among infants aged 5 months - immunization information system sentinel sites, United States, June 2006-June 2009. , 2010, MMWR. Morbidity and mortality weekly report.

[15]  Manish M Patel,et al.  Assessment of postlicensure safety of rotavirus vaccines, with emphasis on intussusception. , 2009, The Journal of infectious diseases.

[16]  A. Steele,et al.  Co-administration study in South African infants of a live-attenuated oral human rotavirus vaccine (RIX4414) and poliovirus vaccines. , 2010, Vaccine.

[17]  F. Destefano,et al.  Quality of HMO vaccination databases used to monitor childhood vaccine safety. Vaccine Safety DataLink Team. , 1999, American journal of epidemiology.

[18]  J. Bines,et al.  Acute intussusception in infants and children as an adverse event following immunization: case definition and guidelines of data collection, analysis, and presentation. , 2004, Vaccine.

[19]  T. Lieu,et al.  Predictive value of seizure ICD-9 codes for vaccine safety research. , 2009, Vaccine.

[20]  Benjamin Schwartz,et al.  The first rotavirus vaccine and intussusception: epidemiological studies and policy decisions. , 2003, The Journal of infectious diseases.

[21]  J. Stockman,et al.  Safety and Efficacy of a Pentavalent Human-Bovine (WC3) Reassortant Rotavirus Vaccine , 2007 .

[22]  Steven J. Jacobsen,et al.  The Vaccine Safety Datalink: A Model for Monitoring Immunization Safety , 2011, Pediatrics.

[23]  C. Steiner,et al.  Reduction in acute gastroenteritis hospitalizations among US children after introduction of rotavirus vaccine: analysis of hospital discharge data from 18 US states. , 2010, The Journal of infectious diseases.

[24]  Benjamin A Lopman,et al.  Uptake, Impact, and Effectiveness of Rotavirus Vaccination in the United States: Review of the First 3 Years of Postlicensure Data , 2011, The Pediatric infectious disease journal.

[25]  R. Glass,et al.  Inhibitory Effect of Breast Milk on Infectivity of Live Oral Rotavirus Vaccines , 2010, The Pediatric infectious disease journal.

[26]  Manish M Patel,et al.  Decline and Change in Seasonality of US Rotavirus Activity After the Introduction of Rotavirus Vaccine , 2009, Pediatrics.

[27]  A. Elixhauser,et al.  Effect of rotavirus vaccination programme on trends in admission of infants to hospital for intussusception , 2001, The Lancet.

[28]  B. Schwartz,et al.  Intussusception among infants given an oral rotavirus vaccine. , 2001, The New England journal of medicine.

[29]  Manish M Patel,et al.  Sustained Decline in Rotavirus Detections in the United States Following the Introduction of Rotavirus Vaccine in 2006 , 2011, The Pediatric infectious disease journal.

[30]  Manish M Patel,et al.  Oral rotavirus vaccines: how well will they work where they are needed most? , 2009, The Journal of infectious diseases.