Is Chronic Fatigue Syndrome Triggered By a Virus? If So, Which One(s)?

Chronic fatigue syndrome (CFS)  is an extremely puzzling disease that is reported to affect as high as 2% of the world’s population (Wyller, 2007). Many physicians discount it as a valid diagnosis, or at the very least, as a single, unitary disease. Rather, it is regarded by many of them as being a facet or sequelae of some other disease process. The problem is, no one seems to know with any certainty, which one disease it is, or if many concurrent diseases seem to trigger it (Sanders & Korf, 2009).

CFS Symptoms

The symptomatology usually involves,  more than anything else,  a debilitating lethargy lasting for more than six months.  Sleep disorders, muscle pain, difficulty concentrating on tasks and memory impairment are often seen.

Overwhelmingly, its sufferers are middle-aged women. CFS is often confused with fibromyalgia, rheumatoid arthritis,  and systemic lupus erythematosus, other diseases with similar signs that are also  more common in women than in men.

Clinical depression is so often encountered in CFS patients  that it is not clear to many clinicians if they are not witnessing a case that is primarily a matter of out-of-control depression (or anxiety) with somatic side-effects, rather than vice-versa. In a small, but by no means atypical interview-based study of CFS patients, in this case  Norwegian women aged 25-55,  a number strongly associated its onset with personal dilemmas such as break-ups with boyfriends or conflicts at home  over household  chores or child-rearing (Soderlund & Malterud, 2005).  Some  also expressed a sense of persistent helplessness, indicating that they could not extricate themselves from situations that seemed to trigger the disease, making them feel even more vulnerable to repeated bouts. Almost all patients felt stigmatized as being psychologically,  rather than physically,  ill, and feared being regarded as self-pitying and/or lazy.

Competing Non-Viral Theories of Causation

As with many diseases more common among women than men, an autoimmune basis is often proposed. Elevated levels of markers typical of autoimmune disease inflammation,  such as interleukin-1 are common. Lab work may indicate that T-cell production and function is altered, usually lowered. However,  there are rarely reports of soft or hard tissue involvement that are characteristic of most of the long-lasting autoimmune diseases.

There is also a hormone deficiency, or rather hormone inadequacy theory, of CFS. Cortisol, a natural hormone often produced in response to one’s being physically or mentally challenged by an emotional  situation or difficult task, is thought to be extremely beneficial as part of the body’s coping response. Some studies indicate that CFS patients, on average, have lower amounts of cortisol.  The problems with this hypothesis include the fact that the levels of cortisol are not lower at a statistically significant level, and that injections of cortisol rarely improve CFS symptoms in a sustained manner.

A tendency to low blood pressure or sudden drops in blood pressure, have been reported in some studies of CFS patients, particularly if they are required to stand for longer periods of time. Medications to offset this are under clinical trials, based on those drugs improving the lot of patients with Neurally Mediated Hypotension (NMH), a disease which is better understood than CFS that  nonetheless shares some of the same propensity for one’s feeling faint on standing. It is noteworthy that some CFS patients can be induced into experiencing a rapid drop in blood pressure using tilt tables, in the same manner as NMH patients. Final results are not yet in, but preliminary studies suggest that a small portion of enrolled CFS patients seem to improve with NMH meds, while the majority do not.

There are also reports that silicone breast implants,  hepatitis B vaccinations, and organophosphate insecticides  may trigger CFS (Ortega-Hernandez & Shoenfeld, 2009) , although it is readily apparent that these must be rare cases since most CFS patients have had neither procedure, nor worked in agriculture, and especially few have had both procedures in close temporal proximity while handling substances that are increasingly banned worldwide. Not surprisingly,  implications that vaccinations are involved have been hotly refuted (Zuckerman, 2006).

The Viral Infection Theory

Without doubt, the greatest number of papers dealing with CFS causation involve one or more viruses. These associations of disease with viruses usually come via blood sample analyses or biopsy of tissue, with subsequent detection by some combination of PCR of DNA, gene  sequencing microarrays, tell-tale protein analyses and other markers (Kaushik et al, 2005; Klimas, Koneru & O’Brien, 2007).  Studies typically try to detect the suspect virus within cells, and see if it is being propagated sufficiently to be circulating outside cells in other fluids or tissues, as this could provide a means by which it is transmitted from one person to another.

The problem with viral theories, as in the overall case of CFS causation, is which viruses? No fewer than thirty distinct types have been implicated, with many of them not being structurally related or descended from one another in some obvious way.

The Epstein Barr virus, EBV, associated in the economically developed world with mononucleosis, and in the less developed world with rare cancers like Burkitt’s lymphoma,  seemed the most likely suspect for the 1980s and 1990s. But it is losing prominence as a most-likely-causation to a variety of other viruses, including a broad assortment of other herpes and  parvoviruses in the 2000s (see, for example,  Komaroff, 2006; Grind, 2008; Li et al, 2009; Sejvar et al, 2008; Shapiro, 2009). One of the reasons for EBV’s downfall is that the increased testing for  viruses of many sorts in a wide variety of clinical and research settings disclosed that  as high as 95% of  those subjects tested  had EBV, with the vast majority being asymptomatic for CFS.

XMRV

The late 2000s  saw a flurry of papers implicating gastrointestinal viruses (see, for example  Chia & Chia, 2008; Fremont et al, 2009), but the most intriguing new candidate is Xenotropic Murine Leukemia Related Virus (XMRV).  As its name suggests it was originally found in mice with blood disorders, but it is much more strongly associated in humans with biopsies from prostate cancer patients.

XMRV  was seriously implicated in a study done at the National Cancer Institute, published last October in Science (Lombardi et al, 2009; nicely summarized and put into context by Coffin & Stoye, 2009) in which 67% of 101 patients with CFS had the virus, while in  a matching number of asymptomatic controls  the virus was present in only 4%.  What was particularly intriguing was that not only was the virus readily detectable in cells and tissues, but also in cell-free cultures, indicating a higher potential for person-to-person infectivity.

But as is the case with so many studies of CFS causation, particularly theories of viral causation or triggering, there are conflicting studies, including the most recent (Erlwein et al, 2010), in which there was a complete absence of the virus in 186 known CFS patients living in the UK.  Erlwein et al  do not suggest that this disproves that XMRV causes CFS in Americans, just apparently not in Brits, although the authors note that XMRV is rarely if ever found in prostate cancer biopsies  from any European patients.

This final theory, that different viruses cause essentially the same disease in different continents, does not appear to help the cause of a strictly medical (as opposed to a psychological mood disorder ) causation for CFS, nor does the fact that a virus strongly associated with prostate cancer could be a causative agent make much sense given that ¾ of the patients with CFS have no prostate gland as they are women.  

Nonetheless, the general notion of some sort of viral triggering seems to destigmatize the disease, and is likely to be the wellspring for most ongoing research in the coming year.

Tony Stankus, FSLA, tstankus@uark.edu, Life Sciences Librarian, Science Coordinator, & Professor

University of Arkansas Libraries MULN 223 E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

Voice: 479-575-4031

Fax: 479-575-4592

Chia, J. K. S., and A. Y. Chia. 2008. Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. Journal of Clinical Pathology 61, (1) (01): 43-8.

Coffin, John M. & Jonathan P. Stoye. 2009. A new virus for old diseases? Science 326: 530-531.

Devanur, L. D., and J. R. Kerr. 2006. Chronic fatigue syndrome.  Journal of Clinical Virology 37, (3) (11): 139-50.

Erlwein, Otto, Steve Kaye, Myra O. McClure, Jonathan Weber, Gillian Wills, David Collier, Simon Wesseley & Anthony Cleare. 2010. Failure to detect novel retrovirus XMRV in chronic fatigue syndrome. PLoS ONE 5, (1), e8519.

Frémont, Marc, Kristine Metzger, Hamada Rady, Jan Hulstaert, and Kenny De Meirleir. 2009. Detection of herpesviruses and parvovirus B19 in gastric and intestinal mucosa of chronic fatigue syndrome patients. In Vivo  23, (2) (2009): 209-13.

Grinde, Bjørn. 2008. Is chronic fatigue syndrome caused by a rare brain infection of a common, normally benign virus? Medical Hypotheses 71, (2) (08): 270-4.

Hickie, Ian, Tracey Davenport, Denis Wakefield, Ute Vollmer-Conna, Barbara Cameron, Suzanne D. Vernon, William C. Reeves, and Andrew Lloyd. 2006. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: Prospective cohort study. BMJ 333, (7568) (09/16): 575.

Kaushik, N., D. Fear, S. C. M. Richards, C. R. McDermott, E. F. Nuwaysir, P. Kellam, T. J. Harrison, et al. 2005. Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome. Journal of Clinical Pathology 58, (8) (08): 826-32.

Klimas, Nancy G., and Anne O'Brien Koneru. 2007. Chronic fatigue syndrome: Inflammation, immune function, and neuroendocrine interactions. Current Rheumatology Reports 9, (6) (12): 482-7.

Komaroff, Anthony L. 2006. Is human herpesvirus-6 a trigger for chronic fatigue syndrome? Journal of Clinical Virology 37 Suppl 1, (12): S39-46.

Lerner, A. M., Safedin H. Beqaj, Robert G. Deeter, and James T. Fitzgerald. 2007. Valacyclovir treatment in Epstein-Barr virus subset chronic fatigue syndrome: Thirty-six months follow-up. In Vivo (Athens, Greece) 21, (5) (2007): 707-13.

Li, Haijing, Shufang Meng, Susan M. Levine, Charles W. Stratton, and Yi-Wei Tang. 2009. Sensitive, qualitative detection of human herpesvirus-6 and simultaneous differentiation of variants A and B. Journal of Clinical Virology 46, (1) (09): 20-3.

Lombardi, Vincent C., Francis W. Ruscetti, Jaydip Das Gupta, Max A. Pfost, Kathryn S. Hagen, Daniel L. Peterson, Sandra K. Ruscetti, et al. 2009. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science (New York, N.Y.) 326, (5952) (10/23): 585-9.

Ortega-Hernandez, Oscar, and Yehuda Shoenfeld. 2009. Infection, vaccination, and autoantibodies in chronic fatigue syndrome, cause or coincidence? Annals of the New York Academy of Sciences 1173, (09): 600-9.

Puri, B. K. 2007. Long-chain polyunsaturated fatty acids and the pathophysiology of myalgic encephalomyelitis (chronic fatigue syndrome). Journal of Clinical Pathology 60, (2) (02): 122-4.

Sanders, Patricia, and Jakob Korf. 2008. Neuroaetiology of chronic fatigue syndrome: An overview. The World Journal of Biological Psychiatry: The Official Journal of the World Federation of Societies of Biological Psychiatry 9, (3): 165-71.

Sejvar, James J., Aaron T. Curns, Leonie Welburg, James F. Jones, Louisa M. Lundgren, Lucile Capuron, John Pape, William C. Reeves, and Grant L. Campbel. 2008. Neurocognitive and functional outcomes in persons recovering from West Nile virus illness. Journal of Neuropsychology 2, (09): 477-99.

Shapiro, Judith S. 2009. Does varicella-zoster virus infection of the peripheral ganglia cause chronic fatigue syndrome? Medical Hypotheses 73, (5) (11): 728-34.

Soderlund, Atle, and Kirsti Malterud. 2005. Why did I get chronic fatigue syndrome? A qualitative interview study of causal attributions in women patients. Scandinavian Journal of Primary Health Care 23, (4) (12): 242-7.

Wyller, Vegard Bruun. 2007. The chronic fatigue syndrome--an update. Acta Neurologica Scandinavica.Supplementum 187, : 7-14.

Zuckerman, Jane N. 2006. Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines. Journal of Medical Virology 78, (2) (02): 169-77.

Comments

[Generic Viagra]

The complexity that diabetes brings to all relationships is unquestionable. That it brings it to our marriages and partnerships poses deeper challenges. The guilt I feel for example, for burdening my husband with my limitations, my fatigue after a night of lows, my frustration with the world after a week of highs. None of that is his fault yet I'd be lying if I said that it doesn't slop over onto him at times.

[Keith]

I have come across many references to cfs in relation to systemic yeast infections. Is this seen as serious alternative to a virus by much of the medical profession?

[dental health care]

Recommend surgery for those people who do not like how they look and can change its look and live a better life ...

[Anna CNA]

Thanks for this informative blog. Here you explain about Chronic Fatigue Syndrome Triggered By a Virus? If So, Which One(s)?. It's good job. Keep sharing.

Thanks for this share.