Lessons From the US Rotavirus Vaccination Program
Authors: Roger I. Glass, Manish Patel, Umesh Parashar
Journal: JAMA (2011)

EVERY WINTER, CHILDREN, PARENTS, AND CLINICIANS IN the United States have to deal with the annual seasonal outbreak of rotavirus, the most common cause of severe diarrhea in children worldwide. Before the implementation of routine vaccination against rotavirus in 2006, most US children had experienced an episode of rotavirus diarrhea by the age of 5 years, an estimated 400 000, or 1 child in 6, required outpatient treatment and about 55 000 to 70 000 children, or 1 in 50, were hospitalized. The health consequences of this annual event in the United States were unsettling and were estimated to cost more than $1 billion per year. When the first new rotavirus vaccine was licensed in 2006, uncertainty existed about whether parents would agree to have their infants immunized and whether clinicians would actively promote its use. Rotavirus vaccines had been severely stigmatized in 1999 when an earlier vaccine, tetravalent rhesus-human reassortant vaccine (RotaShield, Wyeth Laboratories) was abruptly removed from the market because of its link with intussusception, an uncommon form of intestinal obstruction. To assess whether the next generation of rotavirus vaccines harbored the same complication, the US Food and Drug Administration (FDA) required manufacturers to enroll and follow up more than 60 000 infants in clinical trials. Merck and GlaxoSmithKline set off cautiously to conduct multicenter trials of the pentavalent human-bovine WC3 reassortant rotavirus vaccine (RotaTeq, Merck & Co) and the RIX4144 strain human rotavirus vaccine (Rotarix, GlaxoSmithKline Biologicals), ultimately recruiting more than 70 000 infants each, some of the largest and most costly licensure trials ever conducted. Neither vaccine was associated with intussusception in these trials. Over the past 4 years, uptake of the new vaccines has been remarkable. In the United States, the vaccines are expensive, about $200 for the series, but this hurdle of cost was addressed in part by Centers for Disease Control and Prevention’s (CDC’s) Vaccines for Children Program, a federally funded program that provides vaccines at no cost to those unable to pay. By 2010, nearly 60% of US children aged 19 to 35 months were immunized against rotavirus. Because rotavirus diarrhea affects children in the first 5 years of life, it may soon be possible to evaluate the full benefit of the vaccine. For the past decade, the CDC has monitored rotavirus activity in the United States from laboratories that document weekly the number of fecal specimens from children seeking care for diarrhea and the percentage of these specimens that test positive for rotavirus. In 2008, the effects of the rotavirus immunization program were first noted from this surveillance program when the number of rotavirus detections decreased by 64%; these declines have been sustained through 2010. Reports assessing discharge data from hospitals around the country noted that hospitalizations for acute gastroenteritis declined by 45% during the 2008 winter rotavirus season, averting approximately 50 000 hospitalizations nationwide. An unanticipated finding was that hospital admissions for diarrhea also declined among unvaccinated individuals aged 5 through 24 years, suggesting that the vaccine was having a herd effect, perhaps by preventing rotavirus transmission from a younger immunized cohort. More recently, a series of independent regional studies have documented excellent performance of the vaccine against rotavirus disease and documented an 85% to 90% reduction in hospital discharges and visits to emergency departments. Previously, diarrheal illnesses were reported on 10% to 12% of all hospital discharge records for children younger than 5 years, and surveillance indicated that rotavirus accounted for about 40% to 50% of these events. Consequently, an 85% to 90% reduction in this disease from vaccination should lead to a 4% to 6% reduction in total hospitalizations for children younger than 5 years with the commensurate savings in hospital and indirect costs. The introduction of rotavirus vaccines has not been without challenges. In 2010, the identification of porcine circovirus (PCV) in Rotarix led to a temporary suspension of this vaccine; PCV genetic material was also later identified in RotaTeq. More recently, both Rotarix and RotaTeq have been associated with a low-level but elevated risk of intussusception—about 5to 10-fold lower than that seen