Intussusception rotavirus vaccine-associated

The first rotavirus vaccine was a tetravalent rhesus rotavirus strain. It was licensed in the United States in 1998 and subsequently withdrawn from the market due to an association with intussusception. A pentavalent human-bovine reassortant rotavirus vaccine was approved by the FDA in February 2006. The exact mechanism by which the vaccine produces an immune response is unknown however, this live virus vaccine replicates in the small intestines and induces immunity. 

The epidemiology of hospitalizations and deaths associated with intussusception among US infants has been described (7). Such data could be useful for further clinical trials with newly developed rotavirus vaccines. 

Two second-generation rotavirus vaccine candidates (one composed of five human-animal reassortants, RotaTeq , and the other a monovalent attenuated human rotavirus vaccine, Rotarix ) were in development in 1999, and after 7 years of study, they were licensed by the European Medicines Agency (EMA), the Food and Drug Administration (FDA), and many other licensing authorities. Both vaccines are efficacious and both underwent extensive safety trials in more than 130000 children, in whom there was no association with intussusception. In the years since licensing, there have been substantial reductions in the rates of hospitalization and death from rotavirus in both developed and less-developed countries. As part of post-licensing safety follow-up, the possible effect of the widespread use of rotavirus vaccines on rates of intussusception has been monitored carefully [2V]. 

The risk of intussusception and other adverse events temporally connected with the administration of bovine-derived rotavirus vaccine (RotaTeq, manufactured by Merck) from May 2006 to May 2008 (see also SEDA-33, 662) has been studied in children aged 4-48 weeks [23 ]. Adverse events over the next 30 days were ascertained from in-patient, out-patient, and emergency department files cases of intussusception were validated by reviewing the medical records. The study population received 207621 doses of RotaTeq , of which 42% were first doses. Five children had computerized diagnosis codes for intussusception, and 6.75 cases were expected based on historical rates (RR = 0.74). There was no increased risk of intussusception or any other adverse event. Two of five children with suspected intussusception based on diagnosis codes met the case criteria after review of their medical records. The authors concluded that RotaTeq is not associated with an increased risk of intussusception. 

Further studies have confirmed that there is an increased risk of intussusception associated with the use of rhesus rotavirus tetravalent vaccine (RRV-TV). The association has been assessed in infants in 19 states of the USA (8). Each infant hospitalized with intussusception between 1 November 1998 and 30 June 1999 was matched according to age with four healthy controls who had been born at the same hospital. The authors estimated that one case of intussusception would occur for every 4670-9474 infants immunized. 

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