The use of Rotarix can be resumed and the use of RotaTeq continued because there is no evidence that the porcine virus detected in both rotavirus vaccines poses a safety risk to humans, according to the Food and Drug Administration.

The FDA based its decision on laboratory results from the manufacturers of the two rotavirus vaccines and from FDA laboratories, on a scientific literature review, and on input from scientific and public health experts, according to a statement issued by the agency on May 14. In addition, the agency does not believe a medical follow-up is needed for children who have been vaccinated with these vaccines.

Those experts include the FDA's Vaccines and Related Biological Products Advisory Committee, which met a week before the agency announcement to discuss the recent identification of porcine circovirus (PCV) type 1 DNA in GlaxoSmithKline's rotavirus vaccine, Rotarix, which resulted in the FDA's recommendation to temporarily suspend the use of Rotarix on March 22. At the recent meeting, the FDA announced that PCV has also been detected in Merck & Co.'s rotavirus vaccine, RotaTeq.

In addition, the panel agreed that the benefits of the two rotavirus vaccines greatly outweighed the theoretical risk that the detection of PCV in the vaccines could cause human infection, but recommended more study of this potential risk.

Panelists generally agreed that they were encouraged by the available data that did not indicate that PCV detected in the vaccines caused human infection, but noted that this had not yet been proved. Among the panel's recommendations for further studies were serology studies of children with cystic fibrosis on long-term pancreatic enzyme supplementation to check for evidence of antibodies to PCV. (Pancreatic enzyme supplements are derived from the pancreas of pigs, where PCV is detected.)

When the temporary suspension of Rotarix use was announced in March, the FDA said that PCV1 DNA had not been found in RotaTeq, but recommended that Merck conduct tests. At the meeting, Dr. Norman Baylor, the director of the FDA's Office of Vaccines Research and Review, told the panel that at the May meeting, Merck had informed the agency that fragments of DNA from PCV type 1 and type 2 have been identified in the vaccine in preliminary studies. But no recommendation to suspend the use of this vaccine was made at that time.

PCV is common among pigs but is not known to cause disease in humans. There is currently no evidence that PCV in rotavirus vaccines licensed in the United States pose a human safety risk, according to Dr. Baylor. In a statement issued late on May 6, Merck said that the levels of PCV DNA detected in RotaTeq were “very low,” and that “there is no evidence at this time that DNA from PCV causes any disease in humans.”

At the meeting, GSK presented results of studies conducted since PCV DNA was detected in Rotarix, which has not provided any evidence that PCV1 in Rotarix causes infections in humans, according to the presenters. The company tested stool and blood samples taken from vaccine recipients in four Rotarix clinical trials conducted in Africa, Asia, Latin America, and Europe, which included three studies of healthy infants and one of HIV-positive infants. Overall, PCV1 DNA was detected in the stool of four infants, on the third day after vaccination, which the company said was suggestive of “transient passage” of the PCV DNA through the GI tract, but none of these infants or any other infants in the trials had evidence of antibodies to PCV1 in blood samples that had been taken after they received the last vaccine dose, according to GSK.

The FDA and the companies are continuing to conduct studies.

“We have data to suggest this virus is probably not pathogenic in humans,” said panelist Dr. Jos Romero, chief, pediatric infectious diseases, Arkansas Children's Hospital, Little Rock. “Whether it can infect humans still remains a question, but it looks like it doesn't cause disease,” added Dr. Romero, who, like other panelists, said that more studies are definitely needed. He and others agreed that this should include more research on PCV2.

PCV2 has been identified as a causal agent of a lethal wasting disease in pigs.

Panelist Dr. Harry Greenberg, the Joseph D. Grant Professor of Medicine and Microbiology and Immunology, Stanford (Calif.) University, said that the vaccine risks “would have to be immense” to outweigh the benefits. But he added that more studies are needed to determine that PCV does not cause human infections and recommended more studies of vaccinees, including serial testing of stool specimens for evidence of viral replication. (He disclosed that he was involved in the development of the first rotavirus vaccine and is a strong proponent of rotavirus vaccination, but has no personal financial relationship to the manufacturers.)

The panel's consumer representative, Vicky Debold, director of patient safety at the National Vaccine Information Center, Vienna, Va., said that the available evidence was “colored by a great deal of uncertainty.”

More information for clinicians is available at www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm205548.htm

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