Thursday, May 7, 2009

Reeves shows his true colors



***********************************************

From: Kristin   Loomis [mailto:kristin_loomis@hhv-6foundation.org]
Sent: Wednesday, February 13, 2008 11:54 AM
To:  Reeves,  William C. (CDC/CCID/NCZVED)
Cc: Dharam  Ablashi
Subject:  Mini-conference on "Viruses &  CFS"

Dr.   Reeves,

I am writing to invite you to participate in a  mini-conference  we are
organizing on "Viruses in CFS" on June  22-23rd in Baltimore,  Maryland,
just after the 6th International  Conference on HHV-6 & 7. We  would also be
honored if you would  serve on the advisory committee.

A  draft list of speakers  (incomplete) is as follows-

John  Chia, MD, EV Med Research, Lomita, CA, USA   (enterovirus)
Jose G. Montoya, MD, Stanford University, USA (HHV-6 & EBV)
Andrew Lloyd, MD, UNSW School of Medical Sciences (post viral
fatigue)
Anthony Komaroff, MD, Harvard Medical School, Boston, USA  (infections in
CFS   overview)
Brigitte Huber, PhD, Tufts University, Boston, MA, USA
(retrovirus)
Keizo Tomanga, PhD, DVM, Osaka University, Japan (borna virus)
Nancy Klimas, MD, University of Miami, Florida, USA (immune  markers in
viral  infections vs CFS)
Kazuhiro Kondo, MD, PhD, Jikei University School of Medicine, Tokyo,
Japan    (HHV-6 & 7)
Ron Glaser, PhD, Ohio State University Medical Center, Columbus,  Ohio,  USA
(EBV)
Jonthan Kerr, MD, St. George's, University of London, UK  (parvovirus,
gene   expression)
Dan Peterson, MD, Sierra Internal Medicine, Incline Village, USA  (novel
viruses  – NCI study)
Birgitta Evengard, MD, PhD, Umeå University, Umeå, Sweden (viral    markers)


In addition, we  hope  you will attend at least the third day of the main
conference on  HHV-6 &  7, which will be devoted exclusively to HHV-6 in
CNS  disease. As you may know,  there have been a growing number of papers
implicating HHV-6 in encephalitis,  status epilepticus, mesial temporal
lobe epilepsy and MS.

Jacobson at  the NINDS found HHV-6B is in  two thirds of brain resections
from patients with  mesial temporal lobe  epilepsy and suggests that
smoldering virus can cause  seizures by  altering glutamate transport
. What
is especially interesting:  although  the copy numbers are quite high in the
brain tissue, they are barely   perceptible in the CSF and plasma
. Unless
one has an extremely  sensitive HHV-6  assay, it is not possible to detect
in the spinal  fluid or plasma in spite of  a clearly pathogenic disease
process in  the temporal lobes. Those papers are  attached.
I have  highlighted some of the recent papers on HHV-6 in CNS  disease
below.



HHV-6 & Schizophrenia. HHV-6 has been   implicated  as a trigger in
schizophrenia by a large study done  by Johns  Hopkins  and the US military.
HHV-6, six to 12 months  before diagnosis.    (Niebuhr 2007 attached)

HHV-6 & post-transplant  acute  limbic  encephalitis (PALE). A study at
Harvard has  implicated HHV-6 in   this form of limbic encephalitis. (Seely
2007   attached)

HHV-6 &  rhomboencephalitis. A  paper from  George Washington University
suggests  that HHV-6 is  associated with  condition, characterized by
seizures, ataxia,   encephalopathy and  opsoclonus-myoclonus. HHV-6A was
found in  two of the three  cases.   (Crawford 2007  attached)

HHV-6 & CFS.    Anthony  Komaroff wrote an excellent review on the role of
HHV-6  in CFS.   The studies that used an assay  that can differentiate
between active and  latent disease all found a positive  association.
(Komaroff 2006) Montoya's  paper with pilot data  on treating HHV-6/EBV  low
grade infections in CFS  patients  with Valcyte (Kogelnik  2006).

HHV-6 & Amnesia.  Four  patients with HHV-6  associated anterograde amnesia
after stem cell  transplantation were  reported. Three other  case reports
were published in the  past few  years and amnesia  is also a symptom of the
PALE syndrome described   above.  (Gorniak 2006)

HHV-6B & Epilepsy/ Status  Epilepticus.   A 200 patient multi-center study
found that primary   infection causes  35-40% of SE cases. There will be a
major  paper out  on this soon.

HHV-6 & MS. A   group in Spain  with a sensitive PCR  assay has shown
consistently higher rates of  HHV-6A in patients with MS than   in controls.
(Alvarex Lafuente 2006,  2005) They also show a  gene interaction  with
MHC2TA. (Martinez   2007)


At your convenience, we would love  to  get your input on a study we are
doing of monozygotic twins  discordant for  CFS. We are testing these
samples for a number of  viruses as well as 30+  cytokines at Stanford.

Best  regards,

Kristin  Loomis
Executive  Director
HHV-6 Foundation
277 San Ysidro  Road
Santa Barbara,  CA
805-969-1174
805-695-8465 Fax
http://www.hhv-6foundation.org/

***********************************************************

On 2/13/08 3:20 PM, "Reeves, William C.  (CDC/CCID/NCZVED)" <wcr1@CDC.GOV>
wrote:

Thank you very much for your kind invitation  to  participate in the
conference and serve on the advisory committee.   The  HHV-6/7 field is
certainly moving forward unusually rapidly  and you have  gathered together
an unusually talented group of  participants.   Unfortunately, late June is
particularly bad for  me and I am committed  to other activities for all of
the  month.

*********************************************************

From: Dharam  Ablashi [mailto:dharam_ablashi@hhv-6foundation.org]
Sent: Wednesday, February 20, 2008 4:50 PM
To: Reeves,  William C. (CDC/CCID/NCZVED)
Cc: House, Joann (CDC/CCID/NCZVED);  Kristin Loomis
Subject: Re: Mini-conference on "Viruses &  CFS"

Dear Bill,

Thank you for your response to the email from Kristin Loomis. Since  you are
not able to attend, would you be able to send someone from your group  to
represent the CDC  or present new data relating to viral infections in  CFS?
Also, we would still love to have you on the advisory committee and would
like to hear any suggestions you might have on the program.

Although  direct evidence may be lacking in the peripheral blood, the
evidence in  tissues deserves further investigation. We have been in touch
with a number of  investigators who have sent slides from past upper
endoscopies of CFS patients  and found them positive for either HHV-6 or
enterovirus or both, while  negative for EBV
and several other pathogens. In
one case, a CFS patient's  gall bladder also turned up a strong positive for
HHV-6 infection.  We  would be happy to send you photographs if you are
interested. Alternatively,  we could send unstained slides from a few of
these CFS biopsies and the  monoclonal antibodies if you would like to look
at these tissue samples at the  CDC. Or, if you have access to your own
biopsy samples, you could send slides  directly Georgetown at the address
below.

Would the CDC support a  small study to do immunohistochemistry by in-situ
PCR on 10-20 CFS samples and  10-20 controls at Georgetown? If yes we would
be delighted to help organize  this for you. We would appreciate a chance to
discuss this with you and your  team when convenient.

Finally, would you be willing to assist us in  making a request from the CDC
for conference support for this mini-conference?  You have been generous in
providing grants to IACFS conferences in the past,  providing grants of at
least  $25,000.

We  would greatly appreciate your help as the conference will be quite
expensive  to put on due to the expense of travel grants to speakers.

Best  Regards,

Dharam Ablashi
Scientific Director
HHV-6  Foundation


Address to send Slides  for immunohistochemistry for HHV-6, enterovirus,
EBV, lyme, parvovirus,  etc:


Dan Hartmann, PhD
Director of Molecular   Diagnostics
Georgetown Pathology
Georgetown University  Hospital
3900  Reservoir Road, N.W.
Med Dent Building, SW  201
Washington, D.C.  20007
202-784-3614
hartmand@gunet.georgetown.edu

******************************************************

On 2/20/08 3:38 PM, "Reeves, William C. (CDC/CCID/NCZVED)" <wcr1@CDC.GOV>
wrote:


Dr. Ablashi,

It's good to hear from you again and it looks like HHV-6 is taking  off in
ways I bet you never could have imagined when you first began to  describe
it.

My Branch has been reorganized as the Chronic Viral Diseases Branch  and no
longer has responsibility for herpes group virus research at CDC.   I
suggest you contact Dr. D. Scott Schmid and see if he or a member of  his
Branch can represent CDC at the meeting.  He took over responsibility  for
herpes work at CDC after Phil Pellett left.  I see that you have  invited
Dr. Andrew Lloyd from the University of New South Wales.  He was  PI on the
post-infection fatigue studies that CDC funded and collaborated on  and he
can present this work much more elegantly than  I.

The studies you are proposing sound very interesting.  Again,  since my
group does not work directly with herpesviruses, we cannot  collaborate in
laboratory studies; I suggest you contact Dr. D. Scott Schmid  for possible
collaboration on immunohistochemistry studies.  As you know  Dr. Schmid
worked with Carlos Lopez and Phil Pellett back in the old days of  HHV-6 and
this could be of great interest to him.  Unfortunately, I  cannot provide
funding for studies such as you are proposing at this point in  time due to
severe budget constraints.  However, you may wish to contact  Dr. Suzanne
Vernon newly appointed Scientific Director at the CFIDS  Association of
America.  I understand they are launching a major new  research funding
effort for well designed focused pilot studies such as the  one you
proposed.

Finally, I cannot help with funding for any conferences at this  time.
Again, you may wish to apply to the CFIDS Association of  America.

*************************************************

From: Kristin Loomis [mailto:kristin_loomis@hhv-6foundation.org]
Sent: Thursday, May 01, 2008 4:46 PM
To: Reeves, William C. (CDC/CCID/NCZVED)
Cc: Schmid, Scott (CDC/CCID/NCIRD); Dharam Ablashi; Tony Komaroff
Subject: Conference: Viruses in CFS & Post Viral Fatigue

Dr. Reeves,

Thanks for your email about the conference on Viruses in CFS.

Since you are the leading CFS researcher in the world, we hope that you will
reconsider and find a way to attend (or send a representative) to this this
1.5 day conference that will feature over 20 scientists from 7 countries
discussing post-viral fatigue and the possible role of viruses in CFS. Given
the illustrious list of CFS researchers who will be in attendance, your
absence will be noticed, and your input sorely missed!

The conference is being sponsored by the IACFS/ME and the HHV-6 Foundation
and will be chaired by Tony Komaroff and Andrew Lloyd. This was an expensive
conference for us to sponsor and we are flying in scientists from Australia,
Japan and Germany. The Program Committee would still welcome your
participation as a speaker to give your perspective on the possible role of
viruses in CFS, and directions for future research.

We are confused by your response to Dharam (below), because it appears that it may be impossible structurally for the CDC to study the role of viruses in CFS. You wrote that you do not study herpesviruses because that is done by Dr. Schmid. However Dr. Schmid tells us that he does not study CFS. So if viruses do play a role in a subset of CFS patients (as many scientists suspect), then apparently a role for viruses in CFS could never be uncovered by the CDC because the subject would never be studied given the CDC's current organizational structure. Is this correct?

We are also curious to know if there are issues relating to the CDC
definition of CFS that also prevent you from studying viral etiology? If it
turns out, for example, that various infections could be found for 8-10
subsets of CFS – would you then say that these subsets are "by definition"
not CFS, so there is no reason to study them?  If it is your policy to
exclude viral etiology (or infectious etiology) from your research for
structural reasons or due to the way you have defined CFS, then it would be
important for others to understand this "gap" in CFS research (i.e. that the
CDC will study everything relating to chronic fatigue EXCEPT viral etiology)
if this is indeed the case.

As you know, many virologists suspect that CFS researchers have been looking
in the wrong compartment for evidence of virus in these patients, and that
tissue, not blood, is the best place to look for these cell-associated
viruses that are not found in the plasma.


Is the CDC doing nothing to confirm the potentially hugely important data from Chia that implicates enterovirus in a large subset of CFS patients? FYI- although it is unrelated to HHV-6, our foundation arranged to send a
number of CFS antrum biopsy samples to the pathology department at
Georgetown, where Chia's results were confirmed. (They also find HHV-6 in
those tissue samples by the way, but not EBV.) What about the reports from
China, Germany and Japan that Borna virus might be involved in a subset of
CFS? And parvovirus? Or EBV/retrovirus K-18 associated CFS?

You might be interested to know that a top virologist from Japan will
present evidence at our International Conference on HHV-6 & 7 (just before
the CFS conference) that HHV-6 latency proteins can induce encephalopathy
and psychiatric disease. A Danish group will show evidence that HHV-6
activates the K-18 endogenous retrovirus superantigen.
A group from a top
cardiac center in Germany that present their data which shows that in over
1600 myocarditis biopsies, Parvovirus B-19 and HHV-6 were the two most
common pathogens. They suspect that their cardiac clinic sees only "the tip
of the iceberg" and that there are many subclinical myocarditis patients who
have no cardiac symptoms -- just fatigue that is indistinguishable from
CFS.  Given the Peckerman finding of reduced cardiac output in CFS, we think
this is an intriguing observation.
We hope you agree.

The brochures for both conferences are attached and a partial list of the
CFS speakers is below. We look forward to hearing from you.

Best regards,

Kristin Loomis
HHV-6 Foundation

Partial list of speakers at the Symposium on Viruses in CFS and Post-Viral
Fatigue:


Jose  Montoya, MD, an infectious disease specialist at Stanford will be
announcing the results of his Roche sponsored trial of Valcyte in CFS
patients  with elevated antibodies to HHV-6 and EBV.
Brigitte  Huber, PhD, Tufts will discuss her NIH funded study of how viruses
such as  EBV and HHV-6 can transactivate an endogenous retrovirus, HERV
K-18, which can  in turn induce a superantigen which results in a
dysregulated immune system  and CFS.
Kazuhiro  Kondo, MD, PhD from Jikea University in Tokyo will present his
findings  that HHV-6 latency proteins and their role in CFS and other CNS
diseases.
John  Chia, MD, an infectious disease specialist from California will
present  new data on enterovirus infections in CFS patients and will explain
why  examining stomach biopsy tissue is the best way to find these pathogens
that  rarely circulate much in the peripheral blood.
Anthony  Komaroff, MD, of Harvard Medical School will give an overview on
HHV-6 and  the reasons to suspect viruses in CFS.
Nancy  Klimas, MD, of University of Miami, will talk about immune markers
in  viral infections and compare them to what is found in subsets of CFS
patients.
Birgitta  Evengard, MD, PhD of Sweden, will discuss viral markers in CFS and
present  new data on the indications of viral infection in Swedish twin
pairs  discordant for CFS.
Barbara  Savoldo, MD from Baylor College of Medicine, will compare CFS and
chronic  EBV and present results of their trial of immunotherapy (cytotoxic
T-cell  lymphocyte infusions) for severe chronic EVB patients.
Parvovirus  experts Mariko Seishima, MD from Japan will talk about evidence
of  elevated antibodies to Parvovirus in CFS patients, and Dirk Lassner,
PhD, from Germany and as well the high rate of Parvovirus B-19 in viral
myocarditis in Germany with the possible implications for a subset of CFS
patients.
Marshall  Williams, PhD from Ohio State University will explain how certain
enzymes  produced by EBV and HHV-6 can produce sickness behavior in the
absence of  viral replication.
Borna virus  disease experts Liv Bode, and Keizo Tomonaga will present
evidence that Borna virus may play a role in a subset of CFS patients in
Germany, Japan and China.
Andrew  Lloyd, MD, from Australia will present new insights from his
CDC-funded  study of CFS in post-viral fatigue, and Peter White, MD, from
the UK  will give an overview of past studies that have tried to find
evidence of  continuing infection in post-viral CFS patients.

*****************************************************

On 5/2/08 10:48 AM, "Reeves, William C. (CDC/CCID/NCZVED)" <wcr1@cdc.gov>
wrote:


1) What precisely is the objective of my attendance at the meeting?  What do you want me to do?

2) I do not understand the confusion regarding my response to Dr. Ablashi.
Responsibility for CFS research at CDC has been assigned to my Branch.
Responsibility for laboratory work on herpes group viruses has been assigned
to Dr. Schmid's Branch (in a different Center).  My laboratory team does not
have expertise in herpes group viruses, we do not have reagents appropriate
to working with this group of viruses nor do we have some of the specialized
equipment used to work with this type of virus.  This in no way precludes
CDC studying the role of herpesviruses in CFS.  For example, cervical cancer
is caused by a virus (HPV); my Branch has responsibility for laboratory work
on papillomaviruses at CDC, responsibility for epidemiology of cervical
cancer resides in another center, responsibility for vaccine issues resides
in yet another center, and responsibility for screening in a fourth center.
The various groups in all 4 centers work together on the common problem.
With respect to CFS following acute infection my group has worked with
various investigators at CDC and internationally and in all cases laboratory
work outside the domain of my Branch was the responsibility of our
collaborator.  Dr. Schmid's comment to Dr. Ablashi that he does not study
CFS likely reflects the fact that his work on herpesgroup viruses is driven
by CDC priorities (and resource allocation) in other areas such as STD's
mental retardation, bioterrorism, and vaccine preventable diseases.

3) There are no issues relating to the international definition of CFS that
prevent us from studying viral etiology.  If you peruse CFS publications on
the CDC CFS website you will see that we have conducted substantial work in
this area.  Dr. Lloyd who is co-chairing your meeting represents our most
recent collaborator (we are still publishing data from the study we
conducted together).  We have helped Dr. Montoya's group with
instrumentation for monitoring disability and symptoms and recently helped
them to validate scoring from their treatment study.  We collaborated with
Birgitta Evengaard (who I believe will attend the meeting) many years ago to
evaluate the contribution of Bornavirus infection to CFS.  Post-infection
fatigue is an important component of CFS.

*************************************************

------ Forwarded Message
From: Kristin Loomis <kristin_loomis@hhv-6foundation.org>
Date: Tue, 06 May 2008 13:57:31 -0700

Subject: Re: Conference: Viruses in CFS & Post Viral Fatigue

Dr. Reeves,

Thank you for your reply. You asked what we would like you to do at the conference. If you would like to give a presentation relating to viruses, we would love to include it. However, our real objective in seeking your
participation is to encourage you to listen to the presentations and engage in an exchange with the virologists and clinicians who have found what they believe to be compelling evidence that one or more viruses are involved in the etiology of various subsets of CFS.

We will have over twenty presentations from investigators who have studied
viral etiology, with participants flying in from Australia, the UK, Germany,
Sweden, Japan and China  -- so a trip to Baltimore would be very efficient
means to meet them all at once. Also, Stanford's Jose Montoya will be making
an important announcement about the results of his Roche sponsored trial of
Valcyte treatment for CFS patients with apparent viral reactivation. There
will be other significant research presented. For example, a top virologist
from Japan, Kazuhiro Kondo, will present new evidence that an HHV-6 latency
protein induces encephalopathy. A respected retrovirus expert from Denmark
will present evidence that HHV-6 activates endogenous K18 retrovirus
superantigen. The conference is co-sponsored by the IACFS/ME and supported
by the CFIDS Association of America as well as many of the regional CFS
groups.

Since you are such a prominent CFS researcher, and since so many around the
world look to the CDC for guidance, your presence would speak volumes to
this group because it would suggest that you have an interest in their work.
Most of these investigators feel that establishment  medicine is
indifferent, if not dismissive, of their efforts to uncover an infectious
etiology in various CFS subsets. Although I understand you have a busy June,
your absence will inevitably leave the impression with these investigators
(whether true or not) that you don't believe their work is important.
Given
your long service to the field, you could  be helpful to them, just by
sharing your knowledge and contacts. Also, the meeting could be a valuable
time for setting up collaborations for future study. I have summarized at
the end of this email,  a list of specific ideas you might want to explore.

Stanford. The conference would be a great opportunity for you to  get to
know Dr. Montoya and make arrangements to invite him to the CDC or visit
Stanford to learn more. It was a huge accomplishment to interest a major
drug company in backing a trial of an antiviral for a segment of the CFS
population.  If his trial is successful, it will generate enormous interest
in antiviral therapy and alter the research agenda in CFS, so wouldn't it
make sense for you to carve out some time with him?
Although Jose Montoya
appreciates the fact that you answered his question on the surveys, your
input could be valuable to him especially if (as we expect) the trial is
rolled out on a grander scale in the next phase. It would be really helpful
to him to have a significant block of your time to discuss the study in
detail.

Post-Viral Fatigue. The Dubbo study was enormously valuable and we applaud
your effort to study post viral fatigue. Do we think it answered the
question of whether infections remain active in post-viral fatigue? No, but
it was very revealing nonetheless. As we have mentioned to Dr. Lloyd, we
hope he will use his valuable sera to look for EBV early antigen antibodies
(the assay considered by experts to be the best measure of reactivated
virus) and for DNA in the serum using an ultrasensitive PCR. Finally, we
hope he will look for co-infections. Suppose, for example, that the the
acute infection triggers a reactivation of a common virus – such  as HHV-6
or coxsackie B3 -- in the brain tissue?

Definitional exclusion. Here is why we asked whether you have decided to
exclude further studies of virus due to the CDC definition:

1. You state on the CDC web site that tests for EBV, enteroviruses,
retroviruses, HHV-6 etc.  have "no demonstrated value" for CFS patients
"other than to rule out an exclusionary condition".
2. Other than the post viral fatigue syndrome (which is not technically
considered CFS) you have published no studies on viral etiology in CFS
since  the 2000.


Therefore, we thought it was a logical question to ask if you have decided
that reactivated viruses or other infections might all be considered off
limits for future study since they could be construed to be "exclusionary
conditions". We are relieved to  learn that you would not define your work
to the study of CFS so narrowly as to exclude the study of infections.

CDC responsibility for HHV-6 and EBV as it relates to CFS.  We are still
confused as we assumed you were the "point man" for all aspects of CFS at
the CDC. Suppose we find the perfect assay that can pick up HHV-6 chronic
infection and want to propose that you test some of your stored samples with
the new assay or send samples out to an expert HHV-6 lab. Are you saying we
should contact about this, not you? Dr. Schmid would presumably be happy to
work on an in-house assay to test for  these viruses if your group allocated
funding for a project, but this would have to be at your direction and
initiative – no?

Reagents. You mentioned that you have no reagents. We have a repository of
reagents for HHV-6 and HHV-7 and have helped Yale and Stanford's pathology
department set up the immunohistochemistry assay at their institutions. They
are both currently looking at HHV-6 in myocarditis and brain tissue samples
at our suggestion. We would be happy to assist you with supplying these
antibodies to the relevant branch at the CDC if you have an interest in
examining tissues.

I hope you don't mind this outpouring . We know that you work hard and are
trying to do the job as you feel it should be done.

Please let me know if I can answer any more questions on the conference.
Dharam and I hope to see you in Baltimore, June 22nd -23rd.

Thank you for your time. A list of ideas to explore at the conference
follows!

Best,

Kristin Loomis
President & Executive Director
HHV-6 Foundation

IDEAS ON POTENTIAL COLLABORATIONS TO DISCUSS AT THE CONFERENCE:
ENTEROVIRUS.

John Chia has made a serious contribution to the debate about CFS with his
startling observation that 80% of the stomach antrum biopsies from CFS
patients test positive for enterovirus proteins (compared to 20% of
controls) and that 37% of these patients had RNA detected. Enterovirus
expert Steve Tracy at University of Nebraska and expert pathologist Dan
Hartmann of Georgetown University have confirmed that they too find RNA and
positive IHC results in samples from Chia's patients
. Chia has done a
remarkable job with this original research as a solo practitioner, but could
really use guidance from you to find a collaborator to confirm or refute
these findings—at the CDC or elsewhere. Perhaps you could meet and make
plans to invite him to meet with your colleagues in the Polio and
Picornavirus Branch at the CDC to get ideas on investigators who might take
an interest in carrying the research further?

PARVOVIRUS/MYOCARDITIS/CFS CONNECTION. One of the most intriguing new ideas
to come along in CFS is the idea that subsets of these patients actually
have subacute, chronic viral myocarditis.
In the US, cardiologists stopped
doing myocardial biopsies 25 years ago on the theory that there was nothing
one could find that was treatable. In Germany, however, cardiologists
continued to do biopsies and treat viral myocarditis aggressively. Three top
German cardiology groups have recently reported that Parvovirus B-19 is the
most common pathogen in myocarditis, followed by HHV-6. Two of the three
groups Germany groups will be at the conference. We would love to set up a
meeting so you can hear this directly from them. Most of these patients have
very few symptoms (except fatigue) until the disease has progressed to a
late stage. Martin Lerner, in the US has also been suggesting the same
process EBV/CMV myocarditis in CFS for over ten years, but has not had the
"smoking gun" biopsy/ immunohistochemistry data to prove it.

ULTRASENSITIVE SERUM/CSF PCR. Several experts in diagnostic assays are
convinced that the only way to find this viruses like HHV-6 and EBV in the
serum or spinal fluid of subacute cases is to start with a large volume of
material and  an concentrate the virus by high speed centrifuge or magnetic
beads. Vanderbilt uses magnetic beads. San Rafaele Institute uses high-speed
centrifuge. Viracor is also concentrating and are coming out with an
ultrasensitive assay that can find 25 copies per ml, is they start with a
minimum volume of 5-6 mls. All of these groups will be in attendance at the
conference and would be delighted to discuss their assays.

BRAIN SECTION IMMUNOHISTOCHEMISTRY/IN SITU PCR. Dan Hartmann, a pathologist
at Georgetown has an interest in looking at brain sections by
immunohistochemistry and in situ hybridization. We would be delighted to
underwrite such as study but could use your help in finding suitable samples
stored on paraffin block. Hartmann will be at the conference as well as
several other expert pathologists.

BORNA VIRUS. We have no idea if Borna disease virus plays a role, but
scientists from Japan, Germany and China have all found elevated antibodies
to BVD in patients compared controls. As with the other viruses associated
with CFS, it is very difficult to find in the peripheral blood. One of the
speakers at our conference, from the Robert Koch Institute, claims to have
an assay that is more sensitive than the serological assays. They have
isolated Borna virus from a CFS patient of Tony Komaroff (to be reported at
the meeting) and suggest that antiviral treatment with Amantadine can bring
relief. There is a huge credibility problem because this virus is so
difficult to detect. You could help them by collaborating to supply blinded
samples an analyzing the results. We could set up meetings for you with all
three of these international scientists.  (Only two are listed on the
brochure, but a neurologist from  Beijing University in China has just asked
to present their Borna/CFS data as well; they published data on elevated
Borna virus  antibodies in CFS patients two years ago.)

HHV-6. Roche believes that the virus can be found in both the brain tissue
and cardiac tissue, even though direct evidence cannot be found  in the
plasma, and they invested over a million dollars in a clinical trial. Dharam
could introduce you to potential collaborators with state of the art assays
such as:

·     Special ultra-sensitive assays for Q PCR for examining CSF or sera
·     Antigenemia using the HHV-6 early antigen
·     ELISPOT to look for interferon gamma response to HHV-6 specific
proteins
·     immunohistochemistry using HHV-6  early, late and latent monoclonal
antibodies
·     antibody capture using electrochemiluminescence

These investigators would all be delighted to test blinded samples from you
and collaborate on future studies.You have not looked at HHV-6 since the
small study of 26 CFS patients done in 1999, using assays, which experts
would now agree (with the benefit of current knowledge) were probably
inappropriate. A qualitative PCR on whole blood cannot differentiate between
active and latent infection, virus isolation is nearly impossible in cases
of chronic (as opposed to acute); the viral load is too low. Several groups
using serological assays showed that IgG and IgM to the early antigen
protein demonstrated significant differences between patients and controls
in both MS and CFS patient populations. (Jacobson 2000, Ablashi 2000,
Patnaik 1995).  Perhaps it is time for a fresh look?
EBV.  Ron Glaser and Marshall Williams have produced intriguing data on
HHV-7 DUTPase that can induce sickness behavior in mice in the absence of
viral replication. They have identified a similar enzyme for CFS. They need
an independent group to validate their findings and would be delighted to
collaborate.  Ron Glaser has announced that he will stop studying CFS
because there is no funding or interest in his work. An interest from the
CDC in helping him validate his work might help persuade him to reconsider.
The first step of course, would be for you to sit down with him learn more
about these significant findings. Marshall Glaser will be at the conference
and would be delighted to speak with you. Also, Jonathan Kerr has found that
various CFS related genes have previously been shown to be up-regulated in
EBV, including the BRLF1 and EB12 genes. The EB12 gene is upregulated 200
fold in EBV infected cells, and was differentially expressed in five of
Kerr's seven subsets. There will be a number of EBV experts at the
conference who might be able to add perspective on this finding.

KSL 5/6/2008
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* * *
Reeves asks:
What precisely is the objective of my attendance at the meeting?  What do you want me to do?

What we, as patients, want you to do, Bill, is the one thing that you absolutely don't want to do: listen to research findings that will prove your stress theory is wrong.  We are not over-stressed, emotional basket cases, we have viral damage.
 
After the patients ripped you a new one at the CDC meeting last week, this is the time to fish or cut bait.  Either do what is beneficial to the patients or get the hell out of "CFS" research that doesn't benefit those of us with ME/CFS, and turn the department over someone who puts patients' health above his own ego-driven need to be right, even to the extent of re-defining CFS so that the patients for whom the definition was written now no longer meet the criteria for their own disease!
 
 
 
 

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