Rotavirus vaccination and the risk of intussusception

28 August 2013

The TGA, working in collaboration with state health authorities, has completed an investigation into the association between the use of the rotavirus vaccines Rotarix (GSK) and RotaTeq (Merck/CSL) and the occurrence of a rare form of bowel obstruction known as intussusception (IS). IS is a condition caused by the telescoping of one segment of the bowel into another.

Interim results of the investigation were published on the TGA website in February 2011.

The finalisation of the investigation has resulted in additional information on the risk of IS following administration of rotavirus vaccine being added to the Product Information (PI) of the two products available in Australia, Rotarix and RotaTeq.

The final study, undertaken by Professor John Carlin and Dr Katherine Lee, extended the interim study to include data from six jurisdictions (NSW, Victoria, Western Australia, South Australia, Queensland and the Northern Territory) for a three-year period from July 2007 to June 2010.1 Cases of IS in children between 1 and 12 months of age were identified from hospital admissions data in each jurisdiction and, in some states, additional cases were identified through the Paediatric Active Enhanced Disease Surveillance (PAEDS) System. Case validation was through a review of clinical case notes by suitably qualified doctors or nurses in each jurisdiction. Vaccination status for each case was obtained from the Australian Childhood Immunisation Register (ACIR).

The association between rotavirus vaccination and the risk of IS was examined using a self-controlled cases series (SCCS) method and was confirmed with a matched case-control analysis using matched controls from the ACIR.

The SCCS method of analysis was developed by Farrington to investigate associations between vaccination and potential adverse events.2 It compares the frequency with which the outcome (IS) occurred in periods of time following vaccination (exposure) relative to the occurrence of IS outside these times (unexposed time) in the same child. The analysis adjusted for the known effect of age on the incidence of IS.

There were 306 cases of IS suitable for analysis, of which 260 were recorded to have received rotavirus vaccination. Cases were clinically verified as meeting the Brighton Collaboration Level 1 criteria for IS.

Using the SCCS method, there was clear evidence of an elevated risk of IS following the first dose of both rotavirus vaccines. Rotarix had a relative incidence (relative risk) of 6.8 (95% confidence interval [CI] 2.4 to 19.0, p<0.001) and 3.5 (95% CI 1.3 to 8.9, p=0.01) for periods of 1 to 7 and 8-21 days respectively; for RotaTeq the relative incidence was 9.9 (95% CI 3.7 to 26.4, p<0.001) and 6.3 (95% CI 2.8 to 14.4, p<0.001) for the same time periods.

There was also some elevated risk of IS 1-7 days following the second dose of both vaccines. The relative incidence for Rotarix was 2.8 (95% CI 1.1 to 7.3, p=0.03) and for RotaTeq it was 2.8 (95% CI 1.2 to 6.8, p=0.02). There was no evidence of increased risk of IS following a third dose of RotaTeq.

The increased risk of IS following rotavirus vaccination, is estimated as approximately 6 additional cases of IS among every 100,000 infants vaccinated, or 14 additional cases per year in Australia.

Both sponsors of rotavirus vaccines have added new safety information to the post-marketing adverse event sections of their PI.

At this stage, it is uncertain whether rotavirus vaccine administration affects the overall incidence of IS. While there appears to be an increased relative risk of IS, the condition remains rare and this risk is outweighed by the benefits of rotavirus vaccination in preventing rotavirus infections.

Prior to the introduction of rotavirus vaccine, there were an estimated 10,000 hospitalisations annually in Australian children under 5 years due to rotavirus gastroenteritis. Since the introduction of Rotarix and RotaTeq on to the National Immunisation Program (NIP) in July 2007 emergency department visits for acute gastroenteritis in young children have declined and hospitalisations for rotavirus gastroenteritis in the under 5 year age group have been reduced by over 70%.3,4 Based on the established benefits of rotavirus vaccination and the rare occurrence of IS, both the World Health Organization (WHO) and the Australian Technical Advisory Group on Immunisation (ATAGI) have recommended the continued use of rotavirus vaccine for infants.

It is, however, important that health professionals advise parents of the risk of IS and inform them of the signs of the condition and the importance of seeking early medical attention if they suspect the child has IS.

For further information see the Immunise Australia website.

Further information from ATAGI can be found in the Australian Immunisation Handbook.

References

  1. Carlin BJ, Macartney K, Lee KJ et al. Intussusception risk and disease prevention associated with rotavirus vaccines in Australia's national immunisation program. In press.
  2. Whittaker HJ, Farrington CP, Spiessens B, Musonda P. Tutorial in biostatistics: the self-controlled case series method. Statistics in Medicine 2006;(25):1768-97
  3. Macartney KK, Porwal M, Dalton D, Cripps T et al. Decline in rotavirus hospitalisations following introduction of Australia's national rotavirus immunisation programme. J Paediatr Child Health 2011; 2011;47(5):266-70.
  4. Lambert SB, Faux CE, Hall L, Birrell FA et al. Early evidence for direct and indirect effects of the infant rotavirus vaccine program in Queensland. Med J Aust 2009; 191: 157-160.