Intussusception rates not greater among rotavirus vaccine recipients

Larger cohort studies are needed to rule out a small increased risk, however.

Issue: August 2007

ATLANTA — Ongoing monitoring of rotavirus vaccine recipients is necessary, but the observed rates of intussusception are not greater compared with the general population.

The Vaccine Adverse Event Reporting System (VAERS) received 1,251 reports following vaccination with rotavirus vaccine (RotaTeq, Merck) from March 1, 2006, to June 14, 2007, according to Penina Haber, MPH, of the CDC Immunization Safety Office, Office of the Chief Science Officer. The most common adverse events reported were diarrhea, fever, hematochezia and vomiting.

Haber and Manish Patel, MD, MPH, of the CDC National Center for Immunization and Respiratory Diseases, presented updated safety data on the vaccine at the Meeting of the Advisory Committee on Immunization Practices, held here.

Ongoing studies

From March 2006 to June 14, 2007, about 6.2 million doses of vaccine had been distributed, according to Haber. Five hundred seventy-three of the adverse event reports VAERS received occurred after administration of the RotaTeq vaccine alone, and 609 occurred after the first dose.

VAERS confirmed 117 reports of intussusception; no deaths were reported, according to Haber. Thirty-eight of the reports occurred one to 21 days following vaccination, and 23 of those reports occurred within seven days of vaccination. Age at symptom onset ranged from 9 to 45 weeks, with a mean age of 23 weeks. Forty-six percent of the infants were girls, and gender information was not available on 11% of the children.

Haber discussed unpublished data from Merck’s ongoing post-licensure safety study, which is a prospective, observational, active surveillance designed to monitor intussusception rates and overall safety. The study population included a large, insured population in the United States with an annual birth cohort of about 100,000. Merck plans to include 44,000 vaccinated children in the final study size, according to Haber. The post-licensure study researchers will compare adverse events among participants who received the vaccine with several control groups 30 days after vaccination for each dose. Merck reported 7,196 infants received the vaccine through the third quarter of 2006; no cases of intussusception occurred among vaccine recipients, although three cases occurred in controls. The next review will include about 18,000 vaccine recipients who received vaccine from February 2006 to December 2006, and follow-up will occur through March 31, 2007, according to Haber.

Observed and actual rates

Patel discussed the observed rates of intussusception among the vaccine recipients and the expected rates of intussusception among infants aged 6 to 35 weeks. The researchers calculated the rates by age stratification because the rate of intussusception varies in infants during the first six months.

Based on the assumption that VAERS reported data was 100% complete and 100% of the doses were administered, the total number of expected cases of intussusception during the first 21 days following vaccination would be 99. VAERS received 38 reports, according to Patel. Among infants aged 6 to 14 weeks, 30 cases were expected but only 14 reports were received. VAERS expected 36 reports among infants aged 15 to 23 months but received 14 reports; 33 cases were expected among infants aged 24 to 35 months but there were only 10 reports.

Patel also calculated expected and actual reports received within seven days following vaccination. VAERS expected 33 total cases; they received 23 reports. Using age stratification, they expected 10 cases among infants aged 6 to 14 weeks and received 10 reports. VAERS expected 12 cases among infants aged 15 to 23 weeks and received nine reports, and they expected 11 cases among 24- to 35-week-olds but received four reports, according to Patel.

He also discussed limitations to the data. These calculations were based on the assumption that 100% of the distributed doses were administered, but it is unclear how many were actually administered. In the case of the Rotashield vaccine, which was pulled from the market in 1999 due to increased intussusception risk, 66% of the distributed doses were administered.

Patel noted several factors favoring vaccine uptake, however. Approximately 400,000 doses have been administered each month, and the Vaccines for Children rotavirus vaccine contract, which began in July 2006, purchases vaccine for almost 50% of the children in the United States.

In addition, the number of infants included in these data are small, according to Patel. Continued Vaccine Safety Datalink data and post-licensure data from Merck are important, and a large cohort is needed to exclude the possibility of a smaller risk.

“The observed reporting rates of intussusception do not appear to be greater than what we would expect to occur by chance alone. Nonetheless, these data must be interpreted with the limitations of passive surveillance data in mind. We cannot rule out a small increased risk, and we need ongoing monitoring,” Patel said.

He recommended ongoing monitoring of vaccinees, especially during the first seven days following vaccination. – by Lauren Riley

For more information:

Haber P, Baggs J, Patel M, et al. Summary of RotaTeq vaccine reports to VAERS, 3/1/06-6/14/07. Presented at: Meeting of the Advisory Committee on Immunization Practices; June 27-28, 2007; Atlanta.