M.E./CFS and HHV6

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Date: 4 maart 2002

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From: cesar quintero <sezar99q@...>

M.E./CFS and HHV6 = Help M E Special ----------

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HHV6 most Prevalent virus in ME/CFS patients

Dr Ablashi, an international authority in herpes virology

provided further significant evidence of the importance of HHV6

in ME/CFS disease. Along with the leading clinician Dr

and the eminent scientist Prof. Gupta of the University of

California and others additional evidence showed the high rate

of HHV6 infection in patients. This significant prevalence is

consistent with several studies that have shown an association

with HHV6.

HHV6 has been the most identified virus to be associated with

ME/CFS since the first major study of the Tahoe outbreak. In

that extensive study conducted by some of the most respected

names in medicine, there was indication of HHV6 involvement in

70% of patients.

This study (below) also demonstrated significant improvement in

patients that underwent potent antiviral therapy that caused the

elimination of the virus.

This study tells us that antivirals hold great promise for the

treatment of ME. The variability of response also tells us that

an antiviral that is specific for our disease is yet to be

identified and much more work is needed to find the most

effective antiviral for our disease.

HHV6 has not been universally found in all patients yet is the

most consistently identified virus in our disease. Which is also

associated with encephalitis, demyelination, destruction of NK

cells and with the abnormal RnaseL enzyme.

We should realize that M.E. is a complex disease and HHV6 is

an important and dangerous part. And may be activating and

reactivating along with other infections and immune factors:

urgent and massive investigation is needed.

I believe we must demand that the health authorities make

immediate major investment in pursuing the infections and their

treatment. If we don't make these demands then who will ? The

numbers of us with this disease is growing everyday and has

risen by more than 1000% over the last 20 years.

Quintero

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CHRONIC FATIGUE SYNDROME (CFS): HHV-6

REACTIVATION AND CLINICAL MANIFESTATIONS BEFORE,

DURING, AND AFTER ANTIHERPESVIRUS THERAPY

H. Eastman, M. Roman, C. Owen, K. Olsen, K. Steininger, D.

, S. Gupta, J. Whitman, and D. Ablashi

OBJECTIVE: Over the years, many viral agents have been

suspected in the etiology of CFS. Recently, HHV-6, a beta

herpesvirus, has been reported to be involved in the

pathogenesis of CFS. We investigated the active infection of

HHV-6 in CFS patients using (1) short-term culture of peripheral

blood mononuclear cells (PBMCs), (2) IgM and IgG antibody

evaluation in the plasma, and (3) nested PCR on plasma,

cerebral spinal fluid (CSF), and PBMCs. We also characterized

the HHV-6 isolates obtained as being Variant A or B. Seven

CFS patients showing active HHV-6 infection were treated with

three different antiherpesvirus compounds (Foscarnet,

Ganciclovir, Valciclovir) to see if control of HHV-6 infection would

alter the clinical manifestations.

MATERIALS AND METHODS: Specifically, we studied 24 CFS

patients staged according to the severity of the disease. These

patients came from Sierra Internal Medicine, Incline Village, NV,

and the Medical Sciences Division, University of California at

Irvine, Irvine, CA. The immunovirological assays used (i.e., IFA

to detect HHV-6 antigen positive cells or to titer plasma for

antibody) have previously been described (Ablashi et al., J Clin

Virol 16:129, 2000). PBMCs from CFS patients were cultured

(14 days) to detect HHV-6 infection using HHV-6 monoclonal

antibodies. The modified nested PCR protocol used was based

on the method described by Secchiero el al. (J Clin Microbiol

33:2124, 1997). HHV-6 specific primers against the major

capsid protein were used. These primers generate a 258 bp

fragment in the second stage PCR. DNA was isolated from

PBMCs, plasma, and CSF samples using QIAgen columns.

RESULTS: 1. HHV-6 infection was detected in 14/24 (58.3%) of

the CFS patients by the methods described. HHV-6 infection

was detected in the PBMCs in short-term culture as early as

three days, using IFA and HHV-6 early (p41) and late (gpl 16)

monoclonal antibodies. The number of infected PBMCs varied

from patient to patient. 2. IgM antibody to HHV-6 detected by

IFA ranged from 1:20 to >1:160, and the IgG titer ranged from

1:80 to 1:1280. The presence of HHV-6 IgM antibody correlated

well with the presence of HHV-6 in the PBMCs in 85% of the

samples studied. 3. Nested PCR detected HHV-6 DNA in 15%

of the plasmas and 25% of the CSF from the CFS patients. 4.

Approximately 70% of the HHV-6 isolates from CFS patients

were Variant A. 5. Out of the seven patients treated with antiviral

compounds, the patient treated with Foscarnet clinically

improved, and no HHV-6 infection was detectable. Of the four

patients treated with Ganciclovir, only one showed slight clinical

improvement. However, HHV-6 infection could be detected in

the PBMCs of this patient. Of the two patients treated with

Valciclovir, one improved clinically with no HHV-6 infection

detectable. The second patient remained HHV-6 negative

without any clinical improvement.

CONCLUSION:

1.) The data presented, although preliminary, show that the

majority of CFS patients studied have HHV-6 infection.

2.) It was surprising to find CFS patients exhibiting HHV-6 DNA

in the CSF or plasma as well as in HCBMCs infected with CSF

from these patients. These data suggest the presence of

cell-free infectious virus in the CSF. In CFS, it is possible that

HHV-6 is invading the central nervous system and may

participate in the neurological manifestations associated with

this disease.

3.) Seventy percent of the HHV-6 isolates from CFS patients

were classified as Variant A, which is more neuro-tropic.

4.) Potent antiviral agents, such as Foscarnet and Valciclovir,

are useful in suppressing HHV-6, thereby resulting in improved

patient condition. However, longitudinal studies of more patients

with CFS using newer antiviral agents which are less toxic are

required to determine what specific role HHV-6 infection plays

in the pathogenesis of this disease. AACFS - 5th International

Research Conference, at Seattle, Washington 2001

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Just a few of the Important research reports on ME/CFS and

HHV6; see:

A chronic illness characterized by fatigue, neurologic and

immunologic disorders, and active human herpesvirus type 6

infection.

Buchwald D, Cheney P, D, Henry B, Wormsley S,

Geiger A, Ablashi D, Salahuddin S, Saxinger C, Biddle R,

Kikinis R, Jolesz F, Folks T, Balachandran N, J, Gallo R,

Komaroff A,: Boston, Ma. USA

Ann Intern Med 1992 Jan 15;116(2):103-13

Symptoms, signs and laboratory findings in patients with chronic

fatigue syndrome.

Kuratsune H, Yamaguti K, Hattori H, Tazawa H, Takahashi M,

Yamanishi K, Kitani T., Osaka University. Japan

Nippon Rinsho 1992 Nov;50(11):2665-72

Infection of natural killer cells by human herpesvirus 6.

Lusso P, Malnati M, Garzino-Demo A, Crowley R, Long E, Gallo

R.

National Institutes of Health, Bethesda, land 20892.

Nature 1993 Apr 1;362(6419):458-62

Chronic fatigue syndrome: immune dysfunction, role of

pathogens and toxic agents and neurological and cardial

changes.

Hilgers A, J , Dusseldorf, Germany

Wien Med Wochenschr 1994;144(16):399-406

Prevalence of IgM antibodies to human herpesvirus 6 early

antigen (p41/38) in patients with chronic fatigue syndrome.

Patnaik M, Komaroff A , Conley E, Ojo-Amaize E, J;

Specialty Laboratories, Inc.: California, USA.

J Infect Dis 1995 Nov; 172(5):1364-7

Persistent active HHV-6 infections in patients with CFS.

Knox K, Brewer J and Carrigan D,

Fourth Internationsal AACFS Conference. Boston, MA. October,

1998.

Frequent HHV-6 reactivation in multiple sclerosis (MS) and

chronic fatigue syndrome (CFS) patients.

Ablashi D, Eastman H, Owen C, Roman M, Friedman J,

Zabriskie J, D, Pearson G, Whitman J. town

University, Washington, DC, USA.

J Clin Virol 2000 May;16(3):179-91

Evidence of Active HHV-6 Infection and Its Correlation with

RNase L Low Molecular Weight Protein (37 KDa) in CFS

Patients.

D. Ablashi, M. Roman, C. Owen, S. Gupta, C. Herst, D.

, S. Levine, R. , P. , W. Philip, and J.

Whitman; Advanced Biotechnologies Inc, Columbia, MD, USA:

University of California, Irvine, CA, USA: R.E.D. Laboratories,

Belgium: Sierra Internal Med, Incline Village, NV, USA : CFS

Clinic, New York, NY, USA: CBI, Richmond, VA, USA: Vigen

Laboratories, Wilmette, IL, USA

Third International M.E./CFS Research Conference Sydney

Australia, Dec. 2001

Selective Reactivation of Human Herpesvirus 6 Variant A,

Occurs in Critically Ill Immunocompetent Hosts.

Razonable R, Fanning C, Brown R, Espy M, Rivero A, J,

Kremers W, T, Paya C. Mayo Clinic Rochester,

Minnesota

The Journal of Infectious Diseases 2002;185:110-113