Dr John Chia
82% of CFS patients had high levels
of enteroviruses in their digestive systems.
More than 70 different types
of enteroviruses connected with symptoms ME/CFS
Dr Chia is an infectious disease
specialist practicing in Torrance, California, USA and has
published research recently (Chronic fatiguesyndrome associated
with chronic enterovirus infection of the stomach) on the role
of enteroviruses in the aetiolgy of ME/CFS – an area which has
been implicated as one of the causes by a number of
studies. There are more than 70 different types of enteroviruses
that can affect the central nervous system, heart and muscles,
all of which is consistent with the symptoms of ME/CFS. By
analyzing samples of stomach tissue from 165 patients with CFS,
Dr. Chia's team discovered that 82% of these individuals had
high levels of enteroviruses in their digestive systems. Dr
Chia's research may result in the development of antiviral drugs
to treat the debilitating symptoms of ME/CFS..
program. He studied the consequences of parvovirus B19 infection
in ME/CFS and showed that a percentage of infected cases
developed ME/CFS which persisted for several years. He has
reported 88 human genes whose dysregulation is associated with
CFS, and which can be used to derive genomic CFS subtypes which
have marked differences in clinical phenotype and severity.
An Interview With Dr. John
Chia M.D. Enteroviruses and Chronic Fatigue Syndrome Part II:
Persistence, Treatment and the Future by Cort Johnson.
You're an infectious
disease specialist and thus the types of patients you see, I
presume, have an acute onset of ME/CFS that was associated with
an infectious event. Do you have any idea if your findings will
relate to gradual onset patients?
I do not pick the patients who came to see
me. About 20% or more of the patients have so called gradual
onset of CFS without a clear-cut flu-like illness. It is
important to look for prior episodes of fatigue following a
flu-like illness. Several patients became debilitated without an
obvious preceding flu, but already had a prior episode of
fatigue that lasted a few weeks to a few months years earlier.
Many of them had frequent respiratory infection in the previous
year, or "IBS" or functional dyspepsia for years before
developing more fatigue.
Many of them had frequent
respiratory infection in the previous year, or "IBS" or
functional dyspepsia for years before developing more fatigue.
The case I presented at the symposium
illustrated this principle. The patient developed a respiratory
infection in November but did not have abdominal pain and onset
of fatigue until May of the next year. After the colonoscopy
performed in August, the patient developed a severe flare of the
viral infection, including fevers, myalgia, profound fatigue,
abdominal pain, vomiting, and leukopenia, requiring
hospitalization. She had 100,000 copies of viral RNA in the 40
micron section of the terminal ileum biopsy obtained one week
earlier. It is not an accident that the flare happened after the
colonoscopy and biopsy. The infection has been active but at
different sites. One would swallow the infected respiratory
secretions into the GI tract, but the initial GI symptoms will
not manifest since the patient is still fighting the viruses in
the respiratory tract.
Later on, which can be months down the
line, after the immune response subsided, the viruses in the GI
tract will start to grow. These are not necessarily two
different infections. One patient had clearly documented viral
myocarditis following severe bronchitis in December, but did not
develop CFS until June the next year without another infection.
We have seen a number of patients who could have respiratory
symptoms for one week, to follow by severe GI symptoms; the
latter often were attributed to the side-effects of antibiotics.
However, the same cycles would occur even without taking the
antibiotics. Months later, the patient would develop ME/CFS.
Furthermore, a number of patients would
tell me the CFS started in March or April but could not even
remember that they had recurrent bronchitis in the previous
October through December. The GI symptoms could only be 1-2 days
when the patients were traveling, which they thought were
self-limited food poisoning. The interval between the initial
infection and the onset of ME/CFS can be variable, so the
absence of a flu-like illness has to be scrutinized by very
You related several
instances of a patient getting ill with one infection, seeming
to recover and then being unable to recover from the next one.
They seem to have recovered but apparently they really didn't.
Do you have any ideas concerning what's happening between that
first and second infection?
We have noticed that patients often would
have two symptomatic infections before developing ME/CFS; the
two episodes could be occurring within one year or years apart.
In animal models, one can demonstrate that a prior viral
infection can predispose to more severe, subsequent enterovirus
infection. I believe, although this is difficult to prove in
humans, that pre-existing antibody against a prior strain of
virus can bind to, and yet not able to neutralize, the new
viruses, and eventually result in uptake by the monocytes. These
infected monocytes become the "Trojan horses" that would home
into the tissues such as brain, heart and muscles (tropism) and
become macrophages. This process could be associated with
variable inflammatory symptoms. One could not even start to
suspect the "Trojan horses", if the process is clinically silent
A closely spaced infection may predispose
to a more severe, second infection when the immune response has
not shifted back to normal. A shift to the Th2-dominant response
occurred when patients received steroids at the onset of the
respiratory illness associated with asthma, or when they
developed "allergic rashes" after eating shellfish, or severe
neck or back pain. Many of the patients who developed recurrent
respiratory infections, often with asthma or allergic rhinitis,
during childhood are Th2 -polarized in response to the next
infection. If the infective pathogens do not persist in the
body, then nothing more will happen. If the next infection is
capable of persisting in the body, such as EBV, enterovirus,
adenovirus, parvovirus and others, then chronic infection will
An appropriate immune response, manifested
as fevers, nausea, vomiting along with flu-like symptoms in
acute hepatitis B, would usually eradicate the viral infection.
But minimal inflammatory symptoms at the onset of this type of
infection is often followed by chronic persistence of hepatitis
B infection. An appropriate immune response is paramount in
controlling and eradicating the initial infection.
There is no doubt that an
inappropriate immmune response to persisting pathogens is an
integral part of this illness, as in tuberculosis or any other
If I understood this
correctly, when you put biopsy tissues into culture the viruses
didn't grow out unless you unless you blocked the immune
response. Does this mean that viral infections in chronic
fatigue syndrome (ME/CFS) patients persist at least in part
because of a problem with the immune response?
This was the only way we could grow
viruses from human stomach tissues in monkey kidney cells. The
in vitro finding does not necessarily correlate with the in vivo
situation, but "this thinking" led to the experimental
conditions that allowed us to grow the non-cytopathic virus.
There is no doubt that an inappropriate immmune response to
persisting pathogens is an integral part of this illness, as in
tuberculosis or any other disseminated infections.
Do you accept gut biopsies
from patients for testing for enteroviruses? If so, how do they
arrange to have them sent to your office? What is the cost?
Should they send more than one if possible?
The best area to biopsy is the antrum of
the stomach, which is also the best place to look for H. pylori.
We will need 5 unstained slides, on charged slides for
immunochemical staining. The charge is $250 for the staining.
This test is far more sensitive and specific as compared to
serum antibody and serum viral RNA testing. The results of the
comparison will be presented at the next IACFS meeting. See the
attached test request form for more details.
For a test requisition form
to have Dr. Chia analyze whether pathogens are present in
stomach biopsies gathered during an endoscopy.
Is there an effective
treatment for these viruses? Are strong anti-virals needed? Will
immune supportive therapies help? How about therapies designed
to aid the gut such as probiotics?
What is the ultimate drug useful for the
chronic viral infection remains unclear. I believe that
antivirals directed against RNA replication (interferons) will
be useful for this illness. Immune support or modulation may
help but these viruses are capable of controlling our immune
responses to allow their own persistence. Probiotics may help to
change the microbial flora but will not change the viral
infection in the lining of the gut.
Dig Deeper! Interferon's and
Chronic Fatigue Syndrome (ME/CFS) Treatment
It’s been reported that
some antivirals temporarily worked quite well but that your
patients tended to relapse after the therapy has been stopped.
This is an atypical response to anti-virals is it not? What’s
going on here?
The good news
The good news about what we
have shown in our patients is that CFS is a treatable disease
even if they relapsed after treatment.
It is not an atypical response if one
assumes the infection is chronic and persistent. Do any
antivirals for HIV actually cure the disease? One would be
totally surprised if HIV does not rebound (relapse) when one
stops HAART (highly active anti-retroviral therapy) in these
patients, and the same often apply to hepatitis B and C. Do
antiviral drugs cure herpes virus (HSV1 or 2)? Recurrence of
disease is common after treatment for cold sores or genital
herpes but this does not make the antiviral an ineffective
treatment for the disease. The good news about what we have
shown in our patients is that CFS is a treatable disease even if
they relapsed after treatment. With better and more tolerable
treatment, we should be able to control the symptoms and even
put the patient into remission, but a cure may be difficult to
As someone who’s treated
over a thousand chronic fatigue syndrome patients could you
outline what you’ve found to be more effective in treating the
My approach is not different from anybody
else when treating the symptoms.
- Poor sleep: any medications for sleep
but the usual hypnotics do not work well. Most of the
patients need more powerful drugs.
- Fatigue: stimulants such as Ritalin
or Provigil. The effect is quite variable.
- Pain: Ultram or ultracet. Fetanyl
patch seems to work better than the higher potency
- Problems with concentration:
stimulants as above.
- Depression/anxiety: SSRIs and
- Orthostatic intolerance: Midodrine
Midrodrine and Chronic
Fatigue Syndrome (ME/CFS) Treatment
Ritalin and Chronic Fatigue
Syndrome (ME/CFS) Treatment
Pharmaceutical Drugs For
Sleep in Chronic Fatigue Syndrome (ME/CFS)
We’d like to get more
funding to study Chinese herbs, since "Western medicine" is not
going to come through for many years, especially when people are
studying different viruses after 28 years of investigation
Several of your patients
have mentioned that you’re trying oxymatrine. Is it an important
part of your protocol? Are there any other over the counter
immune enhancers you recommend or are exploring?
We have tried a number of Chinese herbs
alone or in combination. The response is variable. Oxymatrine
could boost the immune response, and we will present data at the
next IACFS meeting. We’d like to get more funding to study
Chinese herbs, since "Western medicine" is not going to come
through for many years, especially when people are studying
different viruses after 28 years of investigations. Some of the
OTC (over the counter) immune enhancers have not been too
helpful when tested in a carefully controlled study conducted by
the National Institute of Complementary and Alternative
Medicine. Thymosins from other species are not effective in the
human since these proteins are species-specific.
(After a talk with Dr. Chia's son, Andrew,
a patient of Dr. Chia's reported that Andrew received
substantial benefit from Chinese herbs. The interferon course
helped greatly but he was still plagued with a sore throat and
could not exercise consistently. The Chinese herbs put him over
the top and he is healthy today. She reported that about 50% of
ME/CFS patients receive substantial help from Chinese herbs)
Oxymatrine and ME/CFS
Your attempts to
identify the specific viruses (varicella-zoster, parainfluenza
viruses, adenovirus and respiratory syncytial virus) present
probably failed, as you noted, because of some technical
problems. Is it necessary to identify the specific enteroviral
agent present in order to come up with the right therapy? Where
do you go now in your attempts to identify the pathogens?
The failure to identify these agents by
staining did not mean the testing failed but rather meant these
viruses were not found in stomach by our testing. We have used
multiple antiviral antibodies to see if other agents are in the
stomach. The absence of other viral agents made the enterovirus
even more important in our paper.
The NIH turned its back on
pathogen research in chronic fatigue syndrome (ME/CFS) a couple
of years ago. You, Dr. Montoya and Dr. Lerner, however, have
recently come out with studies suggesting pathogens can play an
important role for at least some chronic fatigue syndrome (ME/CFS)
patients. You attended the Grantsmanship Workshop held by the
Office of Research for Women’s Health (ORWH) last September that
was designed to provide CFS researchers opportunities outside of
the NIH’s CFS research program. How did that go for you? Did you
find any funding opportunities?
I appreciated the opportunity to go to the
Grantsmanship Workshop and met the delightful directors/leaders
of ORWH who are genuinely interested in helping with this
elusive illness. There are funding opportunities for CFS but
there is not yet a clearly designated source of funding where
one can easily get money. The funding will probably take 24
months from the start of the grant writing process, approval
process and then final allocation of money. I hope that some of
the great investigators can get funding quickly for their
EV Med Research is a
privately-funded R&D laboratory whose mission is to define the
most common pathogens responsible for CFS and to develop
effective treatment strategies for this illness.
Do you have funding for
more studies? What’s the next step for you?
I have funding for our studies at this
time. EV Med Research is a privately-funded R&D laboratory whose
mission is to define the most common pathogens responsible for
CFS and to develop effective treatment strategies for this
illness. We will try to define the mechanism of viral
persistence and immune response in the stomach tissues, a place
we can consistently find the viral protein. We have reproducibly
grown the enteroviruses from some of the stomach biopsies with
special techniques. We'd eventually like to look at chemicals
that can stop viral replication. We’d like to define the “viral
form” that persists in the tissue.
Dr. Chia’s Research Foundation, the
Enviromed Foundation, accepts donations. The Enviromed
Foundation is focusing on developing diagnostic tests and
treatment for chronic fatigue syndrome (ME/CFS).
To Overview of the Interview
To Part I of the Interview
A Test Requisition Form
to have Dr. Chia analyze whether pathogens are
present in stomach biopsies gathered during an endoscopy ($250)