New Study Shifts Thinking About Risk Of Rare Bowel Blockage Linked To Rotavirus Vaccine

Lone Simonsen, Ph.D., an epidemiologist with the National Institute of Allergy and Infectious Diseases (NIAID), and her colleagues found an overall decrease in hospitalizations for intussusception among infants less than 1 year old from October 1998 to July 1999, when the vaccine was available, relative to previous comparable time periods going back as far as 1993. They derived their data by examining hospital discharge records from 10 states - home to more than one-fourth of the 3.8 million babies born in the United States each year - in which an estimated 300,000 infants had received the vaccine.

Rotaviruses are the most common cause of severe dehydration and diarrhea in infants and young children, causing some 500,000 physician visits, 50,000 hospitalizations and 20 deaths in the United States each year. In developing countries, rotavirus diarrhea is a leading cause of infant mortality, killing 600,000 to 800,000 infants and young children annually.

After extensive clinical trials proved its safety and efficacy, the first vaccine against severe rotavirus diarrhea, developed by NIAID scientists, was licensed in the United States in August 1998. Two months later, public health officials added the oral Rotashield vaccine to the recommended immunization schedule for healthy infants. The vaccine was to be given in a three-dose series at 2, 4 and 6 months of age. Some 1.5 million doses of vaccine were administered to about 1 million U.S. infants. Hopes were high that it was only a matter of time before the vaccine would reach developing countries, where the need for it is so pressing. But in July 1999, after reports of 15 cases of intussusception among vaccinated children, Rotashield's manufacturer, Wyeth Laboratories, pulled the vaccine off the market. A few months later, U.S. public health officials removed it from the list of recommended vaccines. Though currently licensed by the Food and Drug Administration (FDA), Rotashield is not now available.

Intussusception, diagnosed most often in infancy and childhood, strikes about 2,000 infants (1 in every 1,900) in the United States in the first year of life. Its incidence begins to rise at about 2 to 3 months of life, peaks at 4 to 9 months, and then gradually declines at around 18 months. The condition often resolves by itself, but the blockage can require surgery. In the United States, intussusception is rarely fatal.

After the first reports of intussusception linked to Rotashield vaccination, the Centers for Disease Control and Prevention (CDC) conducted a series of studies to examine the evidence for a temporal association between the two. From those data, CDC initially projected there would be one extra case of intussusception for each 2,500 to 5,000 infants who received the vaccine. Based on this projection, vaccine use was halted. More recently, after further analysis of the data, the CDC has revised the risk magnitude downward by approximately half.

In contrast, the Lancet article reports finding a 4 to 10 percent decline in hospitalizations for intussusception among infants less than 1 year of age during the period of Rotashield use when compared with analogous time periods when the vaccine was not yet available.

The earlier CDC studies, explains Dr. Simonsen, extrapolated from data on the temporal association in the post-vaccination weeks to project the probable total magnitude of risk increase during infancy in the population. "Our study," she says, "looked at what actually occurred during the period of Rotashield use. We directly estimated the overall magnitude of the risk." Although the CDC studies found a strong association between Rotashield vaccination and intussusception in the weeks right after vaccination, the current study suggests that the temporal association did not translate into an overall change in the risk of intussusception hospitalizations during the first year of life.