The Prolonged Efficacy of a Rotavirus Vaccine

ABSTRACT & COMMENTARY

Synopsis: Vaccination against rotavirus gastroenteritis with three doses of live reassortant rotavirus vaccine was protective against severe rotavirus disease into the third year of life in Finnish children. This vaccine was approved by the FDA on August 31, 1998.

Source: Joensuu J, et al. Prolonged efficacy of rhesus-human reassortant rotavirus vaccine. Pediatr Infect Dis 1998;17: 427-429.

Joensuu and associates studied the efficacy of the rhesus-human reassortant rotavirus tetravalent (RRV-TV) vaccine in the third rotavirus epidemic season of a child's life. Prior trials of RRV-TV vaccine in the United States have concentrated only on the first two rotavirus seasons of the child's life.

In 1993 through 1997, 2273 infants were randomized and received between 2 and 7 months of age three oral doses of vaccine or placebo. All visits by enrolled patients to the clinic or admission to the hospital were recorded. In the third rotavirus epidemic season, five children who received placebo and zero vaccinated children sought medical care for rotavirus gastroenteritis. Therefore, the vaccine had an efficacy of 100% for the prevention of hospital outpatient clinical visits and hospitalization. However, the numbers were small and the confidence intervals for efficacy were wide (95%; CI, 17%-100%).

COMMENT BY LOUIS M. BELL, MD, FAAP

Human rotaviruses are the most common cause of severe dehydrating diarrhea in children worldwide. Rotavirus infection in children is a major cause mortality in developing countries, resulting in an estimated 870,000 deaths each year. In the United States, rotavirus gastroenteritis accounts for 3% of all hospitalizations of children younger than 5 years old (55,000-70,000 hospitalizations per year). Severe disease can be seen in the first three years of life.

Rotaviruses are double stranded RNA viruses with a segmented genome of 11 segments. In the United States, four strains are commonly isolated as defined by the structural glycoprotein (or G protein) and referred to as G1 through G4.

While there are several vaccines in development, the tetravalent rhesus rotavirus-based vaccine (RV-TV) produced by Wyeth-Lederle (RotaShield) is the first to apply for licensure with the FDA. In December 1997, an advisory panel to the FDA recommended that licensure be approved; and on August 31, 1998 the FDA gave final approval.

The vaccine is called a "reassortant" because it combines rhesus rotavirus genes with a single human rotavirus gene that expresses the G protein. It is "tetravalent" because the vaccine combines four different reassortant rotaviruses that cover the human serotypes 1, 2, and 4 with a rhesus strain similar to human serotype 3 into one live oral vaccine, the major serotypes causing disease in the United States.

The RV-TV vaccine is given at 1, 4, and 6 months of age and is not affected by breast-feeding or concurrent use of oral polio vaccine. Of note, vaccine administration is associated with fever (> 38°C) after the first dose in 21% of 2 month olds (placebo 6%) and temperatures higher than 39°C in 2% (placebo 1%).

Universal use of the vaccine has the potential to prevent approximately 70% of the estimated 500,000- 750,000 yearly physician visits and up to 100% of the estimated 55,000 annual hospitalizations for rotavirus gastroenteritis in the United States. The cost of three doses of vaccine for a complete series will be about $150 plus the cost of administration. If this should be recommended for universal use by the AAP and CDC, I can foresee a tremendous battle with health insurance companies concerning reimbursement. It will be interesting to see the recommendations of the Red Book Committee in the coming year if this vaccine is approved by the FDA. (Dr. Bell is Associate Professor of Pediatrics (Infectious Diseases), University of Pennsylvania School of Medicine, Philadelphia, PA.)