Potential Risk to U.S. Blood
Supply Being Investigated
An infectious virus linked to two diseases is drawing the attention of public-health officials, who are investigating the potential threat to the nation's blood supply.
It isn't clear if the virus, known as XMRV, poses a danger, and public-health officials say there isn't evidence of spreading infection. But because of concern over the potential for widespread infection and preliminary evidence that XMRV is transmitted similarly to HIV, officials are quickly trying to determine if action is needed to protect the blood supply.
XMRV was discovered in 2006 when it was found in tumor samples from men with a rare form of familial prostate cancer. Research has also linked the virus to chronic fatigue syndrome and found it in measurable levels in the blood of healthy people. But the evidence isn't conclusive, as several other studies failed to find XMRV in the blood of people with chronic fatigue syndrome, and it isn't known how prevalent the virus is or whether it causes disease.
"These are early days trying to understand the public health significance of XMRV," said Jay Epstein, director of the Office of Blood Research and Review at the Food and Drug Administration.
Efforts are under way to find effective tests for the virus and determine its prevalence, led by a working group funded by the National Institutes of Health and including federal agencies such as the FDA and the Centers for Disease Control and Prevention. Blood banks, academic institutions and at least one advocacy group are also involved.
The focus on XMRV is part of a growing effort to better monitor emerging infections—disorders that have either increased in humans in recent decades or are deemed a potential threat. Currently there are 12 tests used to block infectious agents from entering the blood supply, such as HIV or hepatitis C, and more screens are under study, including those for dengue, human variant Creutzfeldt-Jakob disease and agents that cause malaria. There is no FDA-licensed lab test for XMRV, and officials say they are still setting standards for diagnosing it.
Public-health officials increasingly recognize that even infections not typically found in the U.S. can quickly come here because of global travel. Many viruses also have long incubation periods, making it harder to recognize that the virus was transmitted by a blood transfusion. In an October 2009 report, a federal advisory committee on blood safety and availability concluded that biovigilance in the U.S. is a "patchwork of activities, not a cohesive national program."
The incidence of infectious diseases being transmitted through transfusions is small, typically only a handful each year, according to the American Red Cross and data reported to the FDA. About 16 million units of whole blood and red blood cells were donated in the U.S. in 2006, the latest data available, according to the 2007 National Blood Collection and Utilization Report. The American Red Cross, which collects almost half of blood donations in the U.S., estimated that about 10,000 donors a year turn out to be infected with pathogens that officials screen for. Nearly half are hepatitis C virus.
Michael P. Busch, who runs the Blood Systems Research Institute in San Francisco and is a member of the XMRV working group, notes that everyone harbors benign viral infections. These viruses are transmitted in every blood transfusion, but aren't known to cause diseases in recipients, says Dr. Busch. Even if XMRV is found to be present in large numbers of blood donors, Dr. Busch notes, it is still necessary to determine if XMRV causes diseases.
The working group was established after a paper was published in October in the journal Science, where researchers reported finding the virus in a majority of 101 patients with chronic fatigue syndrome. The study's co-authors at the Whittemore Peterson Institute for Neuro-Immune Disease, the National Cancer Institute and the Cleveland Clinic,also found the virus in nearly 4% of 218 healthy people used as controls in the study.
Extrapolating from those numbers, public-health officials estimated that up to 10 million people in the U.S. and hundreds of millions of people globally could be infected with XMRV, or xenotropic murine leukemia virus-related virus.
The apparent link to CFS, which affects an estimated 17 million people world-wide, and has no specific treatments, has been closely followed by the patient advocacy community. The Whittemore Peterson institute, established by the family of a chronic fatigue patient, has started collecting blood from CFS patients who got their diagnosis following a blood transfusion and plan to launch their own study of the issue, says Annette Whittemore, founder and president of the institute.
The CFIDS Association of America, an advocacy group for chronic fatigue syndrome, set up a bank to collect biospecimens to be used in potential studies about CFS, including XMRV-related ones. Researchers at Emory University and the University of Utah published a study last week showing that XMRV may be treatable with drugs that treat HIV.
The AABB, an association of facilities that collect virtually all of the U.S. blood supply, has also set up an XMRV task force, although the virus doesn't appear on a list of infectious agents evaluated by a special AABB transfusion-risk committee, as concerns came out after the latest list was put together.
Labs in Europe reported earlier this year that they haven't been able to replicate the XMRV findings in patients with chronic fatigue syndrome or prostate cancer. And public-health experts say a key issue in sorting out the disparate findings is to reach agreement on tests that are sensitive and reliable in identifying XMRV in the blood.
The federal working group's project has three phases. First, labs at six participants—including the FDA, the National Cancer Institute, the CDC, and the Whittemore Peterson lab—are using a panel of blood samples to try to establish which of the labs' tests are sensitive and reliable enough to find XMRV in the blood. Results are expected in a few weeks.
In the second phase, also launched, a panel of around 350 different blood samples developed by Dr. Busch's team will be sent to four different labs. Some of the samples are from chronic fatigue patients known to have XMRV. Others from healthy donors have been spiked with the virus or have tested negative. All the samples are blinded, and the study will see whether the different labs can agree on XMRV positive status for chronic fatigue patients.
A third phase may be launched later, using frozen specimens in federal repositories dating to the 1970s. These repositories link donors to recipients and will allow researchers to see if XMRV was transferred in transfusions and help determine prevalence in the past as well as today, as well as geographical clusters or associations with age and gender.
"There is a balance to what we are doing," says Simone A. Glynn, branch chief of transfusion medicine and cellular therapies at the National Heart, Lung and Blood Institute and chairperson of the XMRV working group. "You do not want to transfuse an infectious agent that causes problems. But you do not want to take blood out of the system that is not causing any problems."