Vaccines, Blood & Biologics
New Study on the Detection of Murine Leukemia Virus-related Virus Gene Sequences in the Blood of Patients with Chronic Fatigue Syndrome (CFS) and Healthy Blood Donors - Questions and Answers
- Questions about Murine Leukemia Viruses (MLV) and Chronic Fatigue Syndrome (CFS) New Study
- Questions about Other MLV and CFS Studies
- Questions about FDA Policy
What are murine leukemia viruses?
Murine leukemia viruses (MLV) are retroviruses known to cause cancer in certain mice. In 2006, investigators found that a type of MLV, called xenotropic murine leukemia virus-related virus (XMRV), could potentially infect humans. XMRV is one of a number of MLVs that appear to be transmitted to humans.
What is CFS?
Chronic fatigue syndrome (CFS) is a debilitating disorder defined solely by clinical symptoms and the absence of other causes. It’s unknown what causes CFS.
Has MLV or XMRV previously been associated with CFS or other disease?
A previous study, published in the journal [Lombardi et. al. Science October 23, 2009 326: 585], reported finding XMRV in a high percentage of CFS patients and a small percentage of healthy blood donors. However, other studies conducted in the U.S., Netherlands, and UK did not detect evidence of XMRV or other MLV-related viruses in CFS patients.
XMRV was first identified in tissue samples from some prostate cancer patients in 2006. However, one subsequent study failed to find XMRV in prostate cancer tissues, and another study found the virus only rarely in such tissues.
What did the new study evaluate?
Investigators from the Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research, the National Institutes of Health (NIH) Clinical Center, and Harvard Medical School have published a study in the scientific journal Proceedings of the National Academy of Sciences that examines the presence of MLVs in blood collected from two groups -- patients diagnosed with CFS and healthy blood donors.
This study tested blood samples collected from the New England area in the mid-1990s from 37 patients diagnosed with CFS, as well as samples from 44 healthy blood donors collected in the Clinical Center Blood Bank, NIH, between 2003 and 2006. Investigators performed DNA sequencing on each sample that produced positive product for verification of MLV-like gene sequences. Diverse MLV gene sequences, similar to that of the recently discovered XMRV, were identified in samples from 32 of the 37 patients with CFS (86.5%) and 3 of the 44 (6.8%) healthy blood donors that were tested.
Follow-up samples were collected from 8 of the CFS patients in 2010, and 7 of these again tested positive for MLV-like gene sequences.
What did the new study conclude?
This study supports a previous investigation[Lombardi et al. Science October 23, 2009 326: 585]that showed XMRV, a genetic variant of MLV-like viruses, to be present in the blood of people with CFS. The study demonstrates a strong association between a diagnosis of CFS and the presence of MLV-like virus gene sequences in the blood. The study also showed that MLV-like viral gene sequences were detected in a small fraction of healthy blood donors. Although the statistical association with CFS is strong, this study does NOT prove that these retroviruses are the cause of CFS. Further studies are necessary to determine if XMRV or other MLV-related viruses can cause CFS.
Are there studies that support different conclusions?
Some previous studies from the United States (including a study by the Centers for Disease Control and Prevention), the United Kingdom and the Netherlands reported finding no evidence of XMRV or other MLV-related infections in people with CFS. These different findings could be caused by a variety of factors (for example, difference in study populations), and underscore the need for additional studies and standardized methods.
Can MLV or XMRV be transmitted by blood or tissue products?
Additional research is needed to investigate the possibility that these MLV-related viruses and XMRV may be transmitted by blood or human tissue and are capable of causing disease. Investigators at FDA, NIH, CDC and other scientific institutions are in the process of conducting studies to verify the capabilities of the tests used by the different laboratories for the detection of XMRV or MLV-related viruses in blood. These studies are intended to develop and standardize a highly sensitive and specific XMRV test to better study its association with disease, as well as the possibility that XMRV can be transmitted to blood or tissue recipients.
What are the implications for blood donors?
At present, FDA does not have a donor policy specific to XMRV or other MLVs. There is currently no evidence that XMRV or MLVs are transmitted by transfusion in humans or that XMRV or other MLVs cause human disease. FDA regulations require that donors be in good health at the time of donation.
Does FDA agree with the AABB recommendation to discourage donation by people with history of CFS?
FDA does not object to the AABB recommendation. The AABB recommendation is consistent with a long-standing position of the Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) Association of America that individuals with CFS voluntarily should not donate blood.
How are the differences between the CDC and FDA study results being evaluated?
Differences in the results could reflect differences in the patient populations that provided the samples. Alternatively, undefined differences in the method of sample preparation could be contributing to the discordant test results. All of the scientists involved are working collaboratively to design experiments to quickly answer this scientifically puzzling question. An independent investigator at the National Heart, Lung, and Blood Institute (NHLBI) set up a test set of 36 samples, including known positives and presumed negatives. Both the FDA/NIH and CDC labs participated in this test, and the results showed that both labs were able to detect XMRV present at low levels in blinded samples. Additionally, the CDC laboratory provided 82 samples from their published negative study to FDA, who tested the samples blindly. Initial analysis shows that the FDA test results are generally consistent with CDC, with no XMRV-positive results in the CFS samples CDC provided (34 samples were tested, 31 were negative, 3 were indeterminate).
What do these findings mean to CFS patients and clinicians who treat them?
Although this study found MLV-like viral gene sequences in a high percentage of CFS patients, this does not prove that these retroviruses are the cause of CFS or of any other disease. Moreover, other studies have not found evidence of such retroviruses in patients with CFS. Further studies are necessary to determine if XMRV or other MLV-like viruses are reproducibly associated with CFS, and if so whether the virus is a causative agent or a harmless co-traveler. The different findings from various studies reinforce the need for more research--including careful analysis of other cohorts of CFS patients from different geographic regions, studies of larger populations of healthy people, and testing of transmissibility of the agents through blood transfusions in animal models. FDA, NIH, and CDC have and will continue to collaborate with other agencies and groups involved in this research.