What ferocious creature is responsible for over half a million deaths annually among children under five? It isn’t lions, or killer bees, or Rottweilers gone rabid: It’s rotavirus. This villainous pathogen is the most common cause of severe diarrhea among infants and young children worldwide, resulting in hundreds of thousands of childhood deaths in the developing world each and every year.
In 1999, the first rotavirus vaccine licensed for use in the United States was withdrawn from the market after it was reported to result in a 1 in 10,000 risk of intussusception in the ten days following initial vaccination. Since then, two second-generation rotavirus vaccines have come into extensive use worldwide, resulting in a substantial reduction in rotavirus mortality. But what about intussusception risk? And does a complete understanding of the risks and benefits still favor their use?
In this week’s edition of NEJM, a group of investigators from Mexico, Brazil, and the Centers for Disease Control and Prevention in Atlanta seek to answer exactly these questions in a report on post-licensure surveillance of one of the second-generation rotavirus vaccines. At 69 hospitals in Mexico and Brazil, active surveillance was used to identify 615 children with intussusception, matching them with 2048 neighborhood control children of the same age and gender. In Mexico, the risk of intussusception in the week following initial vaccination was increased five-fold using both self-controlled case-series and case-control methods. In Brazil, no such risk was apparent after initial vaccination, although a smaller risk was identified in the days following administration of the second dose of vaccine. The annual incidence of intussusception with the second-generation vaccine was estimated to be less than a fifth of that associated with the first-generation RotashieldTM vaccine. The authors estimate that rotavirus vaccination caused about 96 intussusceptions annually in both countries combined, but prevented 80,000 hospitalizations and 1,300 deaths each year, making a compelling case for continued rotaviral vaccination in developing countries.
In an accompanying editorial, Dr. Harry Greenberg of Stanford University concludes that the benefits of rotaviral vaccination in developing countries far outweighs the risk of intussusception, and that ongoing efforts to vaccinate these children should continue. This conclusion is in keeping with current recommendations of the World Health Organization (WHO). This study may bolster the efforts of the Global Alliance for Vaccines and Immunizations (GAVI), who received US$4.3 billion in donor pledges earlier this week to order to scale-up immunization programs between 2011 and 2015.
“Just like anything else in life, vaccines come with risks and benefits,” says infectious disease specialist and NEJM deputy editor Dr. Lindsey Baden, “This report provides a better estimate of intussusception risk, and helps us understand this risk in the context of the clear benefits that this vaccine provides to children in the developing world.”