Post-Licensing Study Shows No Elevated Intussusception Risk With Rotavac Vaccine

By Gene Emery

November 12, 2020

NEW YORK (Reuters Health) - The India-produced oral rotavirus vaccine Rotavac does not increase the risk of intussusception for infants, according to a new active-surveillance study at 27 Indian hospitals.

Intussusception has been a concern since the condition was seen in 1998 among recipients of the first rotavirus vaccine, Wyeth-Lederle's RotaShield. It was subsequently pulled from the market, researchers explain in The New England Journal of Medicine.

Second-generation vaccines also sparked concerns in postmarketing surveillance in some countries with one to six excess cases per 100,000 vaccinated children for GlaxoSmithKilne's Rotarix and Merck's RotaTeq.

Nonetheless, the World Health Organization has continued to recommend such vaccinations - there are currently four products on the market - because the benefit of avoiding deaths due to diarrhea outweighs the risks.

"There has been a reluctance to use the rotavirus vaccines because of the perceived risk and also because intussusception in low- and middle-income countries has been projected as having a very high fatality rate," said senior author Dr. Gagandeep Kang of The Wellcome Trust Research Laboratory at Christian Medical College in Vellore, India.

"We hope that this study will reassure policymakers and the public, because we have shown in a large study that Rotavac is safe and the case fatality rate for intussusception in India was 1%, much lower than projected for this common pediatric emergency, which occurs in the absence of rotavirus vaccination as well," she told Reuters Health by email.

Bharat Biotech International makes the three-dose oral Rotavac vaccine tested in the new study. Licensed in 2014, it prevents 56% of cases of severe rotavirus gastroenteritis.

The team looked at 970 confirmed cases of intussusception and found that vaccination did not influence the risk of developing a telescoping intestine, regardless of whether the researchers did a self-controlled case-series analysis or a smaller matched case-control analysis.

The number of doses a child received did not influence the risk.

The Kang team found that after the first dose, two children developed intussusception in one to seven days and two got it within eight to 21 days.

After the second dose, four developed it within one to seven days and 15 developed it between eight and 21 days.

After the third dose, 15 children experienced intussusception within one to seven days and 22 developed symptoms between eight and 21 days.

None of the rates were higher than the background risk.

All of the infants included in the study were younger than 366 days when their intussusception symptoms first appeared. They were followed until around age 18 months.

The children used for the control group in the case-control analysis had been admitted to the hospital with an illness that did not involve the gastrointestinal tract.

Dr. Kang said the key lessons from the paper are, "That vaccine safety should be monitored in immunization programs. That vaccine safety studies can be done well in low- and middle-income countries. That rotavirus vaccines have benefits that far outweigh the risks and the vaccines should be used in all countries."

The risks seem to vary by country. Although Rotarix, for example, has been found not to increase intussusception in seven African countries, "it is associated with a small increase in risk of intussusception in the Americas, Europe and Australia," she said.

"If Rotavac is evaluated in other locations where rotavirus-vaccination-associated risk has been documented, it is feasible that there may be a small risk. We will not have complete answers on potential risk for each product if we do not look for them."

The study was funded by the Bill and Melinda Gates Foundation and others.

SOURCE: The New England Journal of Medicine, online November 11, 2020.