Dr. Chia jolted the small chronic fatigue syndrome (ME/CFS) research world when he published a paper indicating that 80% of his patients had a previously undiagnosed enteroviral infection. This in combination with the results of a small but quite successful antiviral trial by Dr. Jose Montoya of Stanford thrust infections back into the spotlight.
Given this it seemed appropriate to give a brief overview of the ‘Pathogen Question’ in chronic fatigue syndrome (ME/CFS) before Dr. Chia’s interview. Because the interview with Dr. Chia is rather technical at spots a brief summary of Dr. Chia’s work is given below the ‘Pathogen Question’ overview. For those desiring to go straight to the interview see the links below.
The Pathogen Question – A Short Overview by Cort Johnson
There may be no issue in chronic fatigue syndrome (ME/CFS) more complex or confusing than the role pathogens play in this disease. The disease often starts with some sort of infection but standard follow up pathogen tests are usually negative. Pathogen and immune research dominated the research agenda in the 1990s but dropped off greatly as research efforts brought sometimes intriguing but hardly jaw-dropping results; certainly there was little that appeared to be substantial enough to explain a disease as severe as this one. The underwhelming results resulted in a shift in federal funding priorities from the immune system to identifying the multi-systemic abnormalities found in the disease.
Immune Research – If pathogens can’t be found directly, they can often be inferred by tests indicating that an on-going immune response in present. Researchers particularly look for high levels of powerful immune messengers called cytokines which travel through the blood activating the different components of the immune system. Chronic fatigue syndrome (ME/CFS) patients do show signs of immune activation and/or immune abnormalities (unusual RNase L activity, NK cell dysfunction etc.) but the significance of these abnormalities has been unclear to the traditional medical community.
Several of the abnormalities involve segments of the immune system which are relatively ‘new’ to science (RNase L) or which previously have not been deemed particularly important (NK cells). What researchers really wanted to see were blatant problems with T-cells or cytokines. Chronic fatigue syndrome (ME/CFS) cytokine studies have had mixed results, however; except for early in the disease, when many CFS patients are in the throes of infection, ME/CFS patients do not show the startling cytokine up regulation seen in many infectious diseases.
Still, chronic fatigue syndrome (ME/CFS) patients’ symptoms (fatigue, muscle and joint pain, sore throat, swollen lymph nodes) and the immune studies suggest immune activation is occurring. Dr. Chia believes ME/CFS patients’ symptoms are caused by an inflammatory response but that the specific agents of that response – whether they are cytokines, chemokines or others – have not been elucidated. (We will see in an upcoming issue of Phoenix Rising that the Whittemore-Peterson Neuro-immune Institute is attempting to identify a unique immune signature in a subset of ME/CFS patients.). p>
Hidden From View. If pathogens are at the heart of this disease they will be unusual in either their type, or where they are found, or the kind of activity they engage in. Indeed each current theory focusing on pathogens in this disease assumes that they must be hidden in some way. HHV-6A, for instance, is not only difficult to detect but is found in a part of the body – the central nervous system – that is almost impossible to directly access. Dr. Chia suggests that enteroviruses in chronic fatigue syndrome (ME/CFS) could have an unusual structure and/or are located in a part of the body (gastrointestinal system) that pathologists rarely examine.
The question of whether a hidden chronic infection is present in ME/CFS has gained more currency as pathogen detection techniques have improved. Some researchers are looking for and finding more evidence of pathogen activity in ME/CFS and the Whittemore Peterson Neuro-Immune Institute is using highly sophisticated tests in an attempt to document the immune abnormalities present in at least a subset of ME/CFS patients.
Still, how important a role pathogens play in this disease is very much up in the air. Different research groups tend to find abundant evidence of ‘their pathogen’ but not others – an unsettling situation for patients. Studies and anecdotal reports do indicate that antiviral therapies can work very well – at least for a time – in some patients, but there is little talk at present of a cure.
The researchers studying pathogens in ME/CFS are basically on their own; mostly without federal funding, they’ve had to raise the money on their own (Dr. Chia), rely on state and private funding (Dr. Peterson) or get help from drug companies (Dr. Lerner, Dr. Montoya) and other foundations (Dr. Montoya, Dr. Peterson). Will this small group of researchers unlock the key to this disease? Only time will tell.
Dr. John Chia (MD): Enterviruses and Chronic Fatigue Syndrome (ME/CFS)
“There’s no doubt in my mind that this is a treatable disease”
Dr Chia is one of the most articulate proponents of an infectious cause of this disease. He came to chronic fatigue syndrome (ME/CFS) the way many, if not most professionals have, via a personal connection. His son Andrew was 14 when he came down with a mysterious illness. It took a year in the lab for this infectious disease specialist to track down the bug (a Coxsackie virus) and several years before his son fully recovered.
By the time his son recovered, Dr. Chia had taken on chronic fatigue syndrome (ME/CFS) as a cause of his own and he had a new partner – his son. Andrew Chia graduated with honors from UC Irvine in 2005 and is now applying for medical school intending to focus on chronic fatigue syndrome (ME/CFS). Indeed, with Dr. Chia’s wife offering support, studying chronic fatigue syndrome (ME/CFS) has become something of a family affair. At the London conference he laughed, saying “Other families go out to candlelight dinner; we head out to the lab” as he thanked his wife for her help.
The interview with Dr. Chia provides hope tinged with a dose of reality; this is a very complex disease and many questions remain unanswered, but Dr. Chia has created a window into it that has paid dividends and, given sufficient funding, will hopefully pay more in the future. That future, however, still appears to be quite distant.
A Personal Search – Dr. Chia is one of a very small handful of researchers who have displayed an interest in enteroviruses in chronic fatigue syndrome (ME/CFS) and he is the only researcher able to maintain a consistent focus on it over time. Although he’s only recently become well known to the public, he’s been studying the disease for over 15 years.
His first efforts – looking for traces of enteroviral infection (RNA) in the blood – were hardly promising, with early tests being positive in only about 5-10% of patients on the first pass. Many researchers might have left it there but, wary about closing the door on pathogens too quickly after his son’s experience, Dr. Chia took another look.
Multiple tests suggested that up to 30% of the patients carried the pathogen. Importantly, while the percentage of positives in chronic fatigue syndrome (ME/CFS) patients increased as Dr. Chia repeated his tests, the percentage of positive controls remained low. As he’s refined the testing process, the percentage of positive test results has increased; he now picks up the infection in about 30% of patients on the first pass.
A New Focus – Still, he felt the reliance on blood as a testing medium was questionable. Enteroviruses generally enter the body through the nose and move to the lungs, or enter through the mouth and move to the gut. Could the low blood levels be misrepresenting a more extensive infection in the gut? The high rate of gastrointestinal symptoms in his patients prompted him to take a look and what he found was somewhat shocking; multiple tests indicated that fully 80% of his patients (but only 20% of controls) had evidence of enteroviral infection in the gut. He now believes the stomach is the primary source of enteroviral infection with the viruses disseminating into the other organs from there.
There were more surprises; instead of killing the cells, the viruses appeared to be living inside them. (These kinds of smoldering infections are particularly difficult to detect in blood tests because they don’t produce lots of ‘loose’ viruses (virions) that travel through the blood.) The inflammation he found was also ‘mild’. This suggested that a localized inflammatory process centered on the infected cell was not likely the source of his patients’ symptoms. Indeed, it is unclear exactly how the enteroviruses cause the symptoms of ME/CFS.
Extensive research suggested that enteroviral infections were the major problem in his patients. At the London Conference he reported that of 200 patients about 9% had chlamydiae pneumoniae, 3% had Epstein-Barr virus, 1% had other viruses (cytomegalovirus, HHV-6, varicella-zoster, parvovirus), 22% didn’t have any known pathogens, and a whopping 55% had a chronic enterovirus infection. Many of these infections (chlamydiae pneumoniae, Epstein-Barr virus, parvovirus, etc.) are treatable, but enteroviruses present special problems.
Treatment. Dr. Chia gathered a good deal of evidence indicating that rates of enteroviral infection were significantly increased in his patients. But were they significant? Were they causing his patients symptoms? Enteroviuses are, after all, amongst the most ubiquitous of pathogens with virtually everyone having been infected by one at one time or the other. Were they causing ME/CFS or were they simply another opportunistic infection that happened to set up shop in his patients?
It was his success in the treatment arena that convinced Dr. Chia he had found a major cause of this disease. As with his diagnostic work, Dr. Chia’s learning curve in the treatment arena was steep. His son Andrew’s case provides a case in point. Andrew had a Coxsackie (enterovirus) infection. Early attempts to use ribavarin resulted in reduced titers and improved health, but were followed by a quick relapse. Ribavarin plus interferon seemed to result in a complete return to health, but after Andrew pushed too hard on a vacation he relapsed badly and his antibody titers shot up (320) and stayed that way for 3-4 years.
- Dig Deeper! For a test requisition form to have Dr. Chia analyze whether pathogens are present in stomach biopsies gathered during an endoscopy ($250)
Now Dr Chia often combines interferon-y (IFN-y) and interferon-delta (IFN-d), two very strong and very expensive ($5,000/month) drugs, to treat many patients with enteroviral infections (Dr. Chia gives the patient the option of going on a full dose for a month or ½ dose for 2-3 months). Because insurance companies consider the protocol experimental, patients are on the hook for the full bill. Side effects can be intense with some patients becoming bedridden in the early stages of the treatment but success rates have been high; according to his talk at the London conference about 50% of his patients with documented enteroviral infections are ‘significantly improved’ by the treatment.
Update – Dr. Chia has phased out interferon use in his patients in favor of a product called Equilibriant which contains Oxymatrine.
- Dig Deeper! Interferon’s and chronic fatigue syndrome (ME/CFS)
- Dig Deeper! Oxymatrine and chronic fatigue syndrome
Relapse rates, however, are also quite high, with most patients enjoying 9-12 months of greatly improved health followed by a relapse. Interestingly many of the worst off patients have received the greatest benefits. Dr. Chia reported that the best responders tend to have really severe muscle pain and that this pain often clears up completely in the first two weeks of IFN-y/IFN-b treatment.
Effectiveness. How effective is Dr. Chia in treating this disease? According to a lecture given at the 2008 London Conference about 15% of his patients appear to have non-enteroviral infections that are treatable. Fifty-five percent have enteroviruses and about a quarter of his patients are simply mysteries – they have no known pathogen. About half of the enteroviral patients respond well to the interferon treatments. This suggests that Dr. Chia is able to ‘significantly improve’ the health of about 40-45% of the patients he sees.
The Future – Dr. Chia has continued to expand his findings. Through EV Med Research, a privately funded R&D laboratory dedicated to defining the pathogens responsible in ME/CFS and developing treatment strategies, Dr. Chia is focused on determining how the enteroviruses maintain themselves in the stomachs of CFS patients and has been able to use special techniques to grow them in the lab – an important step that will allow him to test treatment options. Unfortunately, thus far the drug companies have shown little interest.
Recognizing that many patients can’t afford the double IFN treatment protocol Dr. Chia is examining Chinese herbs to see if they can help to bolster the immune response and reports that some of them work in some patients and not in others. There are no quick answers to the enteroviral problem; Dr. Chia estimates it will take 7-10 years to develop an effective drug to combat them. With no drug companies hammering on his door, one wonders if even that is an optimistic projection.