Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach.
BACKGROUND AND AIMS:
The aetiology for chronic fatigue syndrome (CFS) remains elusive although enteroviruses have been
implicated as one of the causes by a number of studies. Since most CFS patients have persistent or
intermittent gastrointestinal (GI) symptoms, the presence of viral capsid protein 1 (VP1),
enterovirus (EV) RNA and culturable virus in the stomach biopsy specimens of patients with CFS was
METHODS: 165 consecutive patients with CFS underwent upper GI endoscopies and antrum biopsies.
Immunoperoxidase staining was performed using EV-specific monoclonal antibody (mAb) or a control mAb
specific for cytomegalovirus (CMV). RT-PCR ELISA was performed on RNA extracted from paraffin sections
or samples preserved in RNA later. Biopsies from normal stomach and other gastric diseases served as
controls. 75 samples were cultured for EV.
RESULTS: 135/165 (82%) biopsies stained positive for VP1 within parietal cells, whereas
7/34 (20%) of the controls stained positive (p< or =0.001). CMV mAb failed to stain any of the biopsy
specimens. Biopsies taken from six patients at the onset of the CFS/abdominal symptoms, and 2-8 years later
showed positive staining in the paired specimens. EV RNA was detected in 9/24 (37%) paraffin-embedded biopsy
samples; 1/21 controls had detectable EV RNA (p<0.01); 1/3 patients had detectable EV RNA from two samples
taken 4 years apart; 5 patient samples showed transient growth of non-cytopathic enteroviruses.
CONCLUSION: Enterovirus VP1, RNA and non-cytopathic viruses were detected in the
stomach biopsy specimens of CFS patients with chronic abdominal complaints. A significant subset of
CFS patients may have a chronic, disseminated, non-cytolytic form of enteroviral infection, which
could be diagnosed by stomach biopsy.
The role of enterovirus in chronic fatigue syndrome.
Two and a half decades after coining of the term chronic fatigue syndrome (CFS), the diagnosis of this
illness is still symptom based and the aetiology remains elusive. Enteroviruses are well known causes of
acute respiratory and gastrointestinal infections, with tropism for the central nervous system, muscles,
and heart. Initial reports of chronic enteroviral infections causing debilitating symptoms in patients
with CFS were met with skeptism, and had been largely forgotten for the past decade. Observations from
in vitro experiments and from animal models clearly established a state of chronic persistence through
the formation of double stranded RNA, similar to findings reported in muscle biopsies of patients with
CFS. Recent evidence not only confirmed the earlier studies, but also clarified the pathogenic role of
viral RNA through antiviral treatment. This review summarises the available experimental and clinical
evidence that supports the role of enterovirus in chronic fatigue syndrome.
Diverse etiologies for chronic fatigue syndrome