Justification: international post-licensure studies of rotavirus vaccines have identified an increased risk of intussusception in children following their administration. The first vaccine against rotavirus ever developed (Rotashield® [RRV-TV]) was withdrawn from use in 1999 after its association with intussusception was confirmed.1 Evidence has also surfaced that the second-generation rotavirus vaccines that are currently available (Rotateq® [RV5] and Rotarix® [RV1]), recommended for routine vaccination by the World Health Organization (WHO), carry a small increased risk, although temporary, of developing intussusception.2,3
Validity or scientific rigour: the review was based on a clearly defined clinical question, the methodology used for the selection and evaluation of individual studies was appropriate and well described. The results and conclusions are free from potential biases related to conflicts of interest. However, the duration of followup after vaccination and criteria used to define intussusception varied between studies.
Clinical relevance: the pooled data of cohort studies found a higher risk of intussusception in the first 7 days following administration of the first dose, and after completion of the RV vaccine series. The data from case-control studies also found an increased risk of intussusception after the first dose and the full series.
However, in this systematic review, the studies that included the withdrawn vaccine (RRV-TV) reported a greater RR (22.70; 95 CI: 14.8 to 35.7) and weighed more in the final results than the data from studies that only included the RV1 and RV5 vaccines. The review also excluded a study that may have influenced the final results because it only included the adverse events reported to the Vaccine Adverse Events Reporting System (VAERS), which estimated that under a worst-case scenario, the excess risk would be of 1.36 cases of intussusceptions per 100 000 doses of RV5.4 This would amount to 55 additional cases of intussusception per year in the United States, to be weighed against a reduction of approximately 40 000 admissions for diarrhoea achieved through vaccination.
Both vaccines, RV1 and RV5, are effective in the first two years of life. RV1 reduced severe cases of diarrhoea caused by rotavirus by more than 80% in countries with a low mortality and by 40% to 57% in countries with high mortality. With the introduction of RV5, severe cases of diarrhoea from all causes dropped by 73% and 96% in countries with a low mortality and 15% in countries with a high mortality. The Cochrane review by Soares-Weiser reported that 58 cases of intussusception had been detected in 97 246 children after vaccination with RV1, and 34 cases in 81 459 children after vaccination with RV5.2 However, other studies have not found significant differences between children given RV1 or RV5 compared to placebo in the incidence of severe adverse events in general and intussusception in particular.2,3
Applicability to clinical practice: the most recently licensed vaccines against rotavirus (RV1 and RV5) are an effective tool for preventing diarrhoea caused by rotavirus, especially in the first year of life. There is an increased risk of intussusception after the first dose of which patients need to be informed, but it is considerably smaller than the risk associated with the original RRV-TV vaccine, which seems to tip the risk-benefit balance in favour of vaccination.5