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 thorough questioning.
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 occur.
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 disseminated infections.
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.
Dig Deeper!
For a test requisition form to have Dr. Chia analyze whether pathogens
are present in stomach biopsies gathered during an endoscopy.
Treatment
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 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 achieve.
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
following symptoms:
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 narcotics.
- Problems with concentration: stimulants as above.
- Depression/anxiety: SSRIs and anxiolytics.
- Orthostatic intolerance: Midodrine
Dig Deeper!
Midrodrine and Chronic Fatigue Syndrome (ME/CFS) Treatment
Dig Deeper! Ritalin and
Chronic Fatigue Syndrome (ME/CFS) Treatment
Dig Deeper!
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)
Dig Deeper! Oxymatrine and
ME/CFS
The Future
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 projects.
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)