title: Active surveillance for intussusception in a phase III efficacy trial of an oral monovalent rotavirus vaccine in India.
abstract: BACKGROUND
  Post licensure studies have identified an increased risk of intussusception following vaccination with currently licensed rotavirus vaccines, raising safety concerns generic to all rotavirus vaccines. We describe the surveillance for intussusception in a phase III clinical trial with an oral monovalent rotavirus vaccine developed from the neonatal 116E strain.
  
  
  METHODS
  Using broad screening criteria and active surveillance, the incidence of intussusception between 6 weeks and 2 years of age was measured in 4532 children who received three doses of vaccine and 2267 children who received a placebo in the clinical trial. Possible intussusceptions were evaluated with a screening ultrasonogram. An independent intussusception case adjudication committee reviewed all intussusceptions and graded them on Brighton Collaboration criteria for diagnostic certainty.
  
  
  RESULTS
  We identified twenty-three intussusceptions on ultrasound from 1361 evaluated sentinel events. Eleven were of level 1 diagnostic certainty as determined by the independent intussusception case adjudication committee. None required surgical intervention, and the earliest identified intussusception was at 36 days following the third dose in a placebo recipient. Among vaccine recipients the first event of intussusception occurred 112 days after the third dose. The incidence of ultrasound-diagnosed intussusception was 200/100,000 child-years (95% CI, 120, 320) among those receiving the vaccine and 141/100,000 child-years (95% CI, 50, 310) among those receiving the placebo. The incidence rate of confirmed intussusception among vaccine recipients was 94/100,000 child-years (95% CI, 41, 185) and 71/100,000 child-years (95% CI, 15, 206) among those receiving the placebo.
  
  
  CONCLUSIONS
  In this licensure study, 23 cases of intussusception were identified through an active surveillance system, but there was no temporal association with rotavirus vaccination. The use of active surveillance with broad criteria intended for ensuring safety of children participating in a trial, identified several transient intussusceptions that were of doubtful clinical significance.
authors.affiliation: Christian Medical College, Vellore, India. Electronic address: jacob@cmcsph.org.
authors.forename: Jacob
authors.initials: J
authors.lastname: John
authors.affiliation: KEM Hospital Research Centre, Pune, India.
authors.forename: Anand
authors.initials: A
authors.lastname: Kawade
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Temsunaro
authors.initials: T
authors.lastname: Rongsen-Chandola
authors.affiliation: KEM Hospital Research Centre, Pune, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Bavdekar
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Nita
authors.initials: N
authors.lastname: Bhandari
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Sunita
authors.initials: S
authors.lastname: Taneja
authors.affiliation: PATH, India.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Antony
authors.affiliation: All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Veereshwar
authors.initials: V
authors.lastname: Bhatnagar
authors.affiliation: All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Arun
authors.initials: A
authors.lastname: Gupta
authors.affiliation: All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Madhulika
authors.initials: M
authors.lastname: Kabra
authors.affiliation: Christian Medical College, Vellore, India.
authors.forename: Gagandeep
authors.initials: G
authors.lastname: Kang
mesh_terms: D002675:Child, Preschool; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D007443:Intussusception / Q000453:epidemiology*; D011358:Product Surveillance, Postmarketing; D022243:Rotavirus Vaccines / Q000009:adverse effects*; D014611:Vaccination / Q000009:adverse effects*
chemical_list: D022243:Rotavirus Vaccines
keywords: Children; India; Intussusception; Rotavirus vaccine; Vaccine safety