The risk of intussusception following monovalent rotavirus vaccination in England: A self-controlled case-series evaluation.

OBJECTIVE To investigate the risk of intussusception after monovalent rotavirus vaccine (RV1) given to infants aged 2 and 3 months in England. METHODS Hospital Episode Statistics (HES) were used to identify infants aged 48-183 days admitted between 11/03/2013 and 31/10/2014 with intussusception. Diagnosis was confirmed from medical records and HES procedure codes. Vaccination status was obtained from general practitioners. The risk of admission within 1-7 and 8-21 days of vaccination was analysed using the self-controlled case-series (SCCS) method with age effect adjustment by including historical data before RVI introduction in July 2013. RESULTS A total of 119 cases were identified during the study period and intussusception confirmed in 95 of whom 39 were vaccinated 1-21 days before onset. An increased relative incidence (RI) in this period was found, 4.53 (95% confidence interval 2.34-8.58) and 2.60 (1.43-4.81) respectively after the 1st and 2nd doses with an attributable risk of 1.91 and 1.49 per 100,000 doses respectively. The peak risk was 1-7 days after the first dose, RI 13.81 (6.44-28.32), with an estimated 93% of the 15 cases being vaccine-attributable. Mean interval between onset and admission, and clinical features were similar between vaccine-associated and background cases. Despite intussusception being a contraindication to rotavirus vaccination, 10 infants received a further dose; none had a recurrence. The RIs in a meta-analysis combing our results with Australia, Mexico, Brazil and Singapore using RV1, a 2, 4 month schedule and SCCS gave pooled RI estimates of 2.35 (1.45-3.8) and 1.77 (1.29-2.43) in the 21 day period after the 1st and 2nd doses, respectively. The earlier age at the 2nd dose in England did not affect the risk. CONCLUSION We estimate that the RVI programme causes around 21 intussusception admissions annually in England but, since it prevents around 25,000 gastro-intestinal infection admissions, its benefit/risk profile remains strongly positive.

[1]  M. Jit,et al.  Evaluating the potential risks and benefits of infant rotavirus vaccination in England. , 2014, Vaccine.

[2]  C. Atchison,et al.  Rapid Declines in Age Group-Specific Rotavirus Infection and Acute Gastroenteritis Among Vaccinated and Unvaccinated Individuals Within 1 Year of Rotavirus Vaccine Introduction in England and Wales. , 2016, The Journal of infectious diseases.

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

[4]  Katherine J. Lee,et al.  Intussusception risk and disease prevention associated with rotavirus vaccines in Australia's National Immunization Program. , 2013, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  T. Tapiainen,et al.  Evaluation of the Brighton Collaboration case definition of acute intussusception during active surveillance. , 2006, Vaccine.

[6]  M. Cortina-Borja,et al.  National hospital data for intussusception: Data linkage and retrospective analysis to assess quality and use in vaccine safety surveillance. , 2016, Vaccine.

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

[8]  W Katherine Yih,et al.  Intussusception risk after rotavirus vaccination in U.S. infants. , 2014, The New England journal of medicine.

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

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

[11]  E. Miller,et al.  Does oral polio vaccine cause intussusception in infants? Evidence from a sequence of three self-controlled cases series studies in the united kingdom , 2004, European Journal of Epidemiology.

[12]  R. Lynn,et al.  Prospective surveillance study of the management of intussusception in UK and Irish infants , 2012, The British journal of surgery.

[13]  Heather J Whitaker,et al.  The methodology of self-controlled case series studies , 2009, Statistical methods in medical research.

[14]  T. Breuer,et al.  Postmarketing Surveillance of Intussusception Following Mass Introduction of the Attenuated Human Rotavirus Vaccine in Mexico , 2012, The Pediatric infectious disease journal.

[15]  E. Belongia,et al.  Risk of intussusception after monovalent rotavirus vaccination. , 2014, The New England journal of medicine.

[16]  B. Arnould,et al.  The impact of childhood acute rotavirus gastroenteritis on the parents’ quality of life: prospective observational study in European primary care medical practices , 2012, BMC Pediatrics.

[17]  C. Yung,et al.  Intussusception and Monovalent Rotavirus Vaccination in Singapore: Self-Controlled Case Series and Risk-Benefit Study. , 2015, The Journal of pediatrics.

[18]  M. Jit,et al.  Evaluating rotavirus vaccination in England and Wales. Part I. Estimating the burden of disease. , 2007, Vaccine.

[19]  H. Marshall,et al.  Rotavirus vaccination for prevention of serious acute gastroenteritis and the importance of postlicensure safety monitoring. , 2012, The Journal of infectious diseases.

[20]  Mark A. Miller,et al.  Global Illness and Deaths Caused by Rotavirus Disease in Children , 2003, Emerging infectious diseases.

[21]  Heather J Whitaker,et al.  Case series analysis for censored, perturbed, or curtailed post-event exposures. , 2008, Biostatistics.