ME/CFS in the Department of Medicine

What is Infection-Associated Chronic Fatigue Syndrome?

At Stanford, we believe that a subset of cases of Chronic Fatigue Syndrome (CFS) may be related to infection. The nature of the association is still unknown, but we use two possible hypotheses in our research. One hypothesis is that the symptoms of CFS could be triggered by the persistent activity of a pathogen (for example, a bacteria or virus) in the patient. However, the second hypothesis is that the symptoms of CFS may be caused not by the pathogen itself, but rather by the body’s immune response to the pathogen.

Clinical, scientific and epidemiological observations made by several research groups, including our own, have led to the development of these hypotheses. From an epidemiological perspective, it has been known for many years that the onset of CFS is often acute and preceded by a viral or infection-like illness. Work led by Andrew Lloyd in Dubbo, Australia confirmed that the onset of CFS in some patients is marked by acute infection. Lloyd and his research team looked at acute infections of Epstein-Barr virus (glandular fever), Coxiella burnetii (Q fever), or Ross River virus (epidemic polyarthritis) in 253 patients.  They found that six months after the acute infection, 11% of the patients developed CFS.1 This study demonstrates that in Australia, a number of patients developed CFS following an acute infection.

From the basic sciences point of view, it has been observed that many of the infectious agents that may be associated with CFS remain in the body for the patient’s entire life (i.e, there is a latent infection). These infectious agents are usually obligate intracellular pathogens, meaning they can only survive by infecting a host cell. It is thus possible that the acute infection marking the onset of CFS could become chronic and, in this manner, it could be biologically plausible that the infection could be responsible for a chronic illness.

It has also been observed that many infectious pathogens implicated in CFS can affect the central nervous system. Cognitive impairment is a common feature of CFS. It is possible that a chronic infection or inflammation in the brain may result in diminished cognitive capacity in these patients.

John Chia, MD, infectious disease specialist, has reported numerous findings that suggest an association between CFS and infection with enteroviruses.  It has been observed that CFS patients commonly suffer from gastrointestinal complaints, and that between 35-92% of CFS patients have irritable bowel syndrome2. Chia has observed, “80-90% of our 1400 CFS patients have recurring gastrointestinal symptoms of varying severity… compared to only 3/100 controls.”3

In a recent study, Chia’s group found enterovirus VP1 protein in 82% of stomach biopsy samples of CFS patients, which “seems to correlate with the high percentage of CFS patients with GI complaints.” Additionally, “enteroviral protein was detected in the initial stomach biopsy specimens of six patients who developed GI infection before the onset of CFS, and also in biopsy specimens taken years later when the patients had persistent GI symptoms and fatigue.”3
“This finding suggests that enterovirus infection initiated GI symptoms and CFS, and the persistence of the virus years later likely was responsible for the patient’s symptoms.”3 Chia’s clinical observations and research thus suggest a strong association between enteroviral persistence/infection and CFS.

Additionally, A. Martin Lerner, MD, president of the Treatment Center for CFS, has reported in several publications that long-term antiviral treatment of a subgroup of CFS patients identified by different markers for herpesviruses have resulted in significant clinical improvement of their CFS related symptoms.4

In summary, it is plausible that the persistent activity of intracellular pathogens or the immune response against them could lead to the complex and chronic dysfunction observed in patients with CFS. Furthermore, it is possible that if the infectious trigger is appropriately identified, significant clinical benefit can be observed with appropriate long-term antimicrobial therapy.

CITATIONS:

1 Hickie et al.Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study.” BMJ. 2006 Sep 16;333(7568):575. Epub 2006 Sep 1.

2 Frissora CL, Koch KL. “Symptom overlap and comorbidity of irritable bowel syndrome with other conditions.” Curr Gastroenterol Rep. 2005 Aug;7(4):264-71.

3 Chia JK, Chia AY. “Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach.”J Clin Pathol. 2008 Jan;61(1):43-8. Epub 2007 Sep 13.

4 Lerner AM et al. “Subset-directed antiviral treatment of 142 herpesvirus patients with chronic fatigue syndrome.” Virus Adaptation and Treatment May 2010:2 47-57

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