Deaths from rodent virus raise need for tracking system

Physicians should be alert to unusual infections from transplantation

Providence, RI After the deaths of seven people from a virus transmitted through organ donation in the past two years, authorities are recommending that a tracking system be put in place to monitor patients following transplantation, and until then, physicians should be more vigilant in looking for signs of infection transmitted through transplantation.

The cases and subsequent recommendations are outlined in the current issue of the New England Journal of Medicine.

The recommendations stem from two separate incidents in which lymphocytic choriomeningitis virus (LCMV), carried by household rodents, was transmitted through organ donation. In one incident in 2003, four patients in Wisconsin died after seemingly contracting LCMV from the same donor. In 2005, three of four patients who received organs from a common donor died at hospitals in Rhode Island and Massachusetts from LCMV. The fourth recipient survived following treatment. Patients in both incidents died between nine days and 2 months after transplantation.

"The only way we discovered this virus is because we had two kidney recipients in the same hospital who were rapidly deteriorating. There currently is no rapid way to find out how other transplant patients are doing. Physicians should be able to quickly get an update on other organ recipients so they can make a real-time diagnosis," says lead author Staci A. Fischer, MD, a physician in infectious diseases for transplant services at Rhode Island Hospital, who first alerted authorities to a potential virus when two kidney transplant patients became gravely ill.

The authors also point out that screening procedures did not detect the virus in the two organ donors, even when tests were performed after transplantation, and that the strains of the virus were different in the two incidents, requiring more sophisticated testing. Donor screenings detect certain transmitted illnesses such as syphilis, HIV, and hepatitis B and C. But there is no screening test available for LCMV. Using information on recent rodent exposure during screening may further exclude healthy donors from an already limited organ donor pool, the paper says. However, it may be helpful to include a question at the time of screening about recent exposures not to exclude donors, but to provide relevant information to physicians in case of complications.

"We need to have more sensitive tests for donors," says Fischer, who is also an assistant professor of medicine at Brown Medical School. "Since those tests aren't yet available, clinicians have to be particularly alert for unusual clusters of symptoms in the first few weeks following transplantation. Such symptoms could indicate the possibility of an infection transmitted by an organ donor."

Francis Delmonico, MD, medical director of the New England Organ Bank, says, "Because the transmission of LCMV through transplants is extremely rare, ownership of household pets such as gerbils or hamsters is not a reason to preclude the life-saving gift of organ donation. However, in cases where the disease transmission by an organ transplant is suspected, tests must be performed to determine whether LCMV has been transmitted to the recipients, whether or not the donor had a household pet."

In December 2003, four recipients of organs from a common donor developed unexplained illnesses and died. They ranged in age from 40 to 56 and received a kidney, liver or lung. The patients developed fever, liver damage, severe damage to the lung, rash, brain infection and meningitis. Because three of the patients were at one hospital, it was suspected that the patients developed infection from a common source, so the Wisconsin Department of Health was notified. Autopsies revealed that all four patients had LCMV. But the donor, a 51-year-old man who died from head trauma, had no trace of the virus. Nor did interviews with the donor's family reveal any exposure to rodents.

In April 2005, kidneys, a liver and lung were transplanted from one donor into four patients ranging in age from 41 to 54, located in Rhode Island and Massachusetts. In Rhode Island, both kidney recipients became ill with similar symptoms including fever, diarrhea and pain in the area of the kidney. A review of the hospital's transplant records revealed that the kidney recipients shared a common donor, a 45-year-old woman who died of a brain hemorrhage. The donor had met screening criteria for organ donation, and had no evidence of infection.

The New England Organ Bank, which coordinated the transplants, was contacted, along with physicians at the hospitals in Massachusetts that had received the other organs. Three patients died in Massachusetts and Rhode Island. The patients had developed lethargy, diarrhea, liver damage, rash and fever; one had lung damage and one had seizures. Out of concern that an infection had been transmitted through transplantation, the Rhode Island Department of Health, Massachusetts Department of Public Health and Centers for Disease Control and Prevention (CDC) were notified. Tissues were submitted to the CDC for testing, and a newly developed, more sensitive diagnostic test showed that the transplant recipients had LCMV. The surviving patient was given the antibiotic ribavirin, and immunosuppressant drugs were reduced to help his body fight the infection. The patient is now doing well, Fischer says.

An investigation revealed that a pet hamster had been purchased three weeks before organ donation and was being kept in the donor's home. Though the donor had no evidence of LCMV, testing of hamster tissues detected the virus.

In April 2005, the Organ Procurement and Transplantation Network (OPTN), operated by the United Network for Organ Sharing, broadened its policies to include reporting of suspected donor-transmitted medical conditions to the organ procurement organization (OPO). The OPO is then responsible for investigating and communicating with the transplant centers caring for other recipients from the donor and the involved tissue and eye banks. These organizations, such as the New England Organ Bank, evaluate potential donors and coordinate the distribution of organs within the region and across the country.

LCMV has been recognized since the 1960s. It is transmitted through direct contact with rodents or from airborne droplets from rodent urine or feces. There have been no cases of transmission from one person to another. The infection typically causes mild flu-like symptoms in healthy adults or can cause no symptoms. In recognized cases of LCMV, the mortality rate is less than 1 percent. There are few data on outcomes in transplant patients, who may be more susceptible to the virus because their immune systems are suppressed.

"This virus, unlike a lot of others, has treatment options," Fischer says. "If you are able to identify the virus in time, you could save somebody's life."

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Other authors on the paper are from: Medical College of Wisconsin, Milwaukee; Division of Viral and Rickettsial Diseases, and Division of Healthcare Quality Promotion, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta; Massachusetts General Hospital and Harvard Medical School, Boston; Brigham and Women's Hospital and Harvard Medical School, Boston; Rhode Island Department of Health; Massachusetts Department of Health; Wisconsin Department of Health and Family Services; and the New England Organ Bank.

Founded in 1863, Rhode Island Hospital (www.rhodeislandhospital.org) is a private, not-for-profit hospital and is the largest teaching hospital of Brown Medical School. A major trauma center for southeastern New England, the hospital is dedicated to being on the cutting edge of medicine and research. Rhode Island Hospital ranks 13th among independent hospitals who receive funding from the National Institutes of Health, with research awards of more than $27 million annually. Many of its physicians are recognized as leaders in their respective fields of oncology, cardiology, orthopedics and minimally invasive surgery. The hospital's pediatrics wing, Hasbro Children's Hospital, has pioneered numerous procedures and is at the forefront of fetal surgery, orthopedics and pediatric neurosurgery.


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