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Common Cold Tied to Transplant Rejection

Viral genes in heart muscle may affect failure

WEDNESDAY, May 16 (HealthScout) -- A common cold virus apparently can cause organ transplants to fail.

A new study shows that children whose heart transplants show signs of viral attack are about six times more likely to suffer organ rejection than those whose grafts are free of infection.

The study is "potentially a landmark. It is important, novel and could change the outcome for heart transplant patients" as well as other organ recipients, says Dr. Steven E. Lipshultz, chief of pediatric cardiology at the University of Rochester's Children's Hospital at Strong.

The findings appear in the May 17 New England Journal of Medicine.

Viruses are well-known culprits in inflammations of heart muscle and blood vessels. And certain microbes, such as cytomegalovirus, have been linked to organ transplant failure. But the latest work is the first to implicate adenoviruses, which cause colds and other infections, in heart graft rejection.

"I think it's difficult to demonstrate causality, but certainly we've shown a very strong association," says lead study author Dr. Girish Shirali, director of pediatric echocardiography at the Medical University of South Carolina in Charleston.

Shirali did the study while at Loma Linda University in California. He and his colleagues there followed 149 child transplant recipients, ages 1 month to 18 years, from 1994 to 1999, regularly testing samples of their heart muscle for viral genes.

Nearly 50 samples from 34 patients tested positive for viruses. Adenovirus was the most common microbe, three times more common than the next most prevalent species, enterovirus. Parvovirus, cytomegalovirus and other pathogens also cropped up.

Of the 34 infected children, 29, or 85 percent, suffered at least one episode of transplant rejection within three months of a positive biopsy, and nine ultimately had complete graft failure.

"We had kids who were chugging along for four or five years without a problem, and within a few months they have four to five rejections, cardiovascular disease, and then we list them for a re-transplant," Shirali says.

Yet, among the 115 children whose biopsies were negative for virus genes, only 39, or about one-third, had rejection incidents within three months of the testing. Survival rates were 64 percent for the infected children and 96 percent for those whose biopsies were free of a virus, and none of those with negative biopsies lost their transplants.

In all, children whose heart muscles had traces of viral DNA were about 6.5 times more likely to suffer either partial or full rejection, compared with uninfected patients. For adenovirus alone, the risk of graft failure was 4.7 times higher.

Why viral infection would trigger organ rejection is not clear, but the reaction may be related to the patients' already hobbled immune response, Shirali says.

"You start out with children who are immune-suppressed to prevent rejection and, on top of that, we add this viral attack. That might end up somehow modulating the immune response and might change the whole interaction between the host and the graft," he says. Therefore it might be possible to pre-treat transplant patients with viral vaccines, he says.

Study co-author Dr. Jeffrey Towbin, head of heart failure and transplant service at Baylor College of Medicine in Houston, says it's likely that other viruses, besides those the study found, also play a role in graft rejection. "I'm sure that there are other important viruses that we aren't smart enough to have looked for yet," Towbin says.

What To Do

For more about heart transplants, try the Cambridge and Oxford Heart Transplantation Foundation or Johns Hopkins University.

Read other HealthScout articles about transplants.

SOURCES: Interviews with Girish Shirali, M.D., director of pediatric echocardiography, Medical University of South Carolina, Charleston; Jeffrey Towbin, M.D., professor of pediatric cardiology and head, heart failure and transplant service, Baylor College of Medicine, Houston, and Steven E. Lipshultz, M.D., professor of pediatrics and oncology, University of Rochester School of Medicine, chief of pediatric cardiology, Children's Hospital at Strong, Rochester, N.Y.; May 17, 2001 New England Journal of Medicine
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