CHRONIC FATIGUE SYNDROME AMONG PHYSICIANS

[Guest guest]

Towards the end the article states this:

The sequence data on the prototype stealth virus may also bear on Public

Health concerns regarding the wisdom of having used African green monkeys to

produce live poliovirus vaccine.

http://www.ccid.org/articles/physicianscfs.htm

Scheduled to appear in " Medical Crossfire "

Pre-published with permission of Editor

CHRONIC FATIGUE SYNDROME AMONG PHYSICIANS:

A POTENTIAL RESULT OF OCCUPATIONAL

EXPOSURE TO STEALTH VIRUSES

W. , M.D., Ph.D.

Center for Complex Infectious Diseases

Rosemead, CA 91770  

Subtitle: CFS In Physicians

Address for Correspondence:

CCID

3328 s Avenue

Rosemead, CA 91770

Phone: 626-572-7288

Fax: 626-572-9288

E-mail: <A HREF= " mailto:ccidlab@... " >ccidlab@...</A>

Abstract

Four physicians with complex chronic disabling illnesses labeled as chronic

fatigue syndrome (CFS) were shown by culture to be stealth virus infected.

The clinical histories indicate multi-system stealth virus infection with

encephalopathy (MSVIE). The exposure of physicians and other health care

providers to stealth viruses is a potential occupational hazard.

Introduction

Complex arrays of symptoms typify a number of common, chronic, disabling

illnesses. To varying extents many patients report and/or demonstrate: i)

Impaired mental capacities, including loss of short term memory, difficulties

in verbal expression and/or comprehension, attention deficit and lethargy;

ii) altered personality, including a reduced capacity to relate emotionally

to others; iii) mood changes, including depression, anxiety and anger; iv)

sleep disturbance; v) instability of autonomic nervous system regulation of

blood pressure, pulse rate and/or bowel functions; vi)headaches and; vii)

generalized body aches and pains. The medical community is split between

those who view these symptoms as an indication of an underlying organic

disease process, and those who consider the symptoms merely as an extension

of the normal stresses and strains of everyday living (1,2). Clinicians who

advocate organic disease have used various diagnostic terms such as chronic

fatigue syndrome (CFS), fibromyalgia, depression, Gulf war syndrome,

irritable bowel syndrome, attention deficit, multiple chemical sensitivity,

etc.; without clear-cut distinguishing clinical or laboratory criteria. The

use of imprecise clinical labels has helped bolster those who believe that

none of the illnesses constitute serious medicine.

Public Health authorities have also been slow in pursuing a possible

infectious etiology of CFS and related conditions. Reports of community

outbreaks of CFS-like illnesses have typically been discredited as emotional

over-reactions of those affected, fueled by over-zealous, incompetent

physicians (3). With little support from established medicine, patients have

generally had to fend for themselves in explaining their illness to family,

friends and disability insurance carriers.

For several years, I have been culturing atypical cytopathic viruses from CFS

patients (4-6). I coined the term " stealth " because the viruses were

apparently unseen by the cellular immune defenses responsible for triggering

an anti-viral inflammatory response. I postulated that stealth-adaptation

involved the deletion of critical viral genes that coded the major antigens

targeted by T lymphocytes (4). DNA sequencing data obtained on an African

green monkey simian cytomegalovirus (SCMV)-derived stealth virus support this

hypothesis (7).

During the course of studies on stealth-adapted viruses, numerous physicians

have requested personal testing because of their own symptoms. Four

particularly severe cases have been selected to help underscore the apparent

occupational infectivity of stealth viruses.

Methods

Stealth Virus Cultures: Mononuclear cells were isolated from blood collected

in acid-citrate-dextrose (ACD), yellow-topped tubes, using ficoll-paque

(Pharmacia, NJ). The cells were added to MRC-5 fibroblasts and to rhesus

monkey kidney cells (BioWhittaker, MD). The inoculated cultures were observed

for the development over one to several days, of rounded vacuolated cells

that form syncytia (4). The cytopathic effect (CPE) was enhanced by regularly

replacing the medium (X-Vivo-15, BioWhittaker, MD). Confirmation of the CPE

can, if required, be generally obtained by positive immunostaining of the

culture with broadly reactive polyclonal antisera raised against various

human herpesviruses. Immunostaining will generally also occur with the

patient's own plasma and with many normal human sera (4). The CPE is

morphologically distinguishable from that typically caused by human

cytomegolovirus, human herpesvirus-6, adenovirus and enteroviruses.

Additional distinctions from these conventional viruses can be made by using

highly specific monoclonal typing antibodies, and by sequencing of polymerase

chain reaction (PCR) products generated using various primer sets under low

stringency conditions (4,6).

Case Histories

Case 1: An internist, who is now age 44, was well until 1987. At that time a

nurse accidentally struck her in the hand with the needle of a syringe

containing blood collected from an elderly patient. The patient had developed

a transient acute encephalitis-like illness shortly after receiving a blood

transfusion and subsequently became demented requiring nursing home care. The

physician began developing symptoms within several days of the needle stick.

These included vomiting, stiff neck, vertigo, headache, left eye pain,

photosensitivity, somnolence and periodic fever to 100oC. CT and MRI scans

were read as normal. The acute symptoms peaked at approximately two weeks and

gradually improved. By two months, the patient had regained her usual

alertness and, in spite of continuing vertigo, photophobia and headaches, she

returned to work. Gradually over the ensuing year, she became progressively

more clumsy and even occasionally fell onto patients being examined. She had

difficulty reading because of down-beating nystagmus. A repeat MRI was again

negative. Routine viral cultures on a cerebrospinal fluid (CSF) sample were

negative. Detailed auditory and vestibular testing were consistent with

endolymphatic hydrops with perilymphatic fistula, worse on the left side, and

benign paroxysmal positional nystagmus, worse on the right side. The

physician was unable to continue working. Her overall clinical condition has

further deteriorated over the last ten years. Daily attacks of vertigo,

ataxia, headaches, photophobia; and week-long attacks of severe fatigue; have

prevented her from resuming any type of work. Her short term memory also

became impaired. She has experienced frequent upper respiratory tract

infections, which, based on positive serologies, have been labeled as

Legionnaire's disease, Mycoplasma pneumoniae and Chlamydia pneumoniae. Among

her many illnesses, she has had recurrent bouts of nausea, abdominal pain and

diarrhea; one episode being attributed to C. difficile infection. Her thyroid

had periodically become swollen and painful, with signs of de Quervain's

thyroiditis with thyrotoxicosis associated with thyroid stimulating

immunoglobulin. Resolution has required from 6 months to 2 years of

prednisone therapy. She has had attacks of pancreatitis, interstitial

cystitis, and is allergic to many foods and medications. The C5-C6 cervical

disc has herniated, as has the L4-L5 lumbar disc. She has a reduced blood

volume with orthostatic hypotension.

Additional laboratory testing has included positive PCR for chlanydia and for

mycoplasma, and positive serology for Borna virus. Her blood has shown

cryoglobulins and increased fibrinogen split products with signs of platelet

activation. Both CD4 and CD8 T lymphocyte levels have been reduced. Blood

2-5A' synthetase, RNase-L, alpha interferon and interleukin-10 levels were

raised. Urinary and stool porphyins were elevated. Her urine also showed

excess mercapturic acid, D-glucaric acid, B-alanine, and hydroxyproline. A

stealth virus culture was strongly positive

Brain imaging showed a 4mm herniation of the cerebellar tonsils, mild

cerebral atrophy and discernable subcortical encephalomalacia. Reduced

perfusion and metabolic activities involving the frontal, temporal and

parietal lobes, were shown using SPECT and PET scans, respectively.

Several years ago, the patient acquired a pet dog. The dog has had a

remarkable medical history, including partial complex seizures, elevated

liver enzymes, hypothyroidism, and recurrent prostate, urinary,

gastrointestinal and eye infections. The dog also tested positive for stealth

virus.

Case 2: At 43 years of age, a previously healthy ophthalmologist experienced

acute flu-like symptoms, which included sore throat, swollen cervical lymph

nodes, night sweats, muscle aches and fatigue. The symptoms were gradually

resolving when he began to develop burning parenthesia involving different

regions of his body. These were accompanied by marked muscle weakness.

Palpable nerves were tender. He had to discontinue work for two months. When

he returned, he was still bothered by paresthesia, weakness, insomnia and

fatigue. A further exacerbation occurred eight months later with several days

of confusion and disorientation, followed by apparent reduction in short-term

memory, attention span, and verbal expression and comprehension. Muscle

fasciculation was also noted. He again discontinued work and has remained

disabled for the last 11 years. During this time he has periodically

developed superficial, mucus exudative lesions that involve areas within the

nostrils and on the lips. Cognitive impairments were documented on

neuropsychological testing. Hypoperfusion was seen on SPECT scan and

hypometabolism was seen on PET scan. Abnormal routine laboratory testing has

included slightly elevated liver function tests. Special tests have shown

marked elevations in alpha interferon and in interleukin 1. Material

collected from the exudative lesions has shown herpesviral like-particles on

electron microscopy. Viruses were also seen in a semen preparation and in an

ultracentrifuge pellet from an aceellular CSF sample. Multiple stealth virus

cultures from blood, CSF, lip lesion, and semen, have been consistently

positive on multiple occasions between 1992 and 1998. Case 3: In 1983, a

38-year old medical oncologist was exposed to hematemesis and bloody diarrhea

from an elderly patient with persistent thrombocytopenia, splenomegaly and

progressive cirrhotic liver disease. The patient showed elevated liver

enzymes, but remarkably normal bilirubin until shortly before her death.

Among other investigations, the elderly patient was negative for hepatitis A

and B by serology, and strongly positive for anti-EBV viral capsid antigen

(VCA). Within two months of this patient's death, the attending physician

began to experience irritable bowel symptoms with abdominal discomfort and

episodes of diarrhea. He also tested strongly positive for EBV VCA, (titer

1:5,000). His symptoms gradually extended to include diffuse myalgia and

anthralgia, severe and progressive lethargy, and reduced exercise tolerance.

Additionally, the physician began to experience headaches accompanied by

blurring of vision and occasional diplopia, night sweats, periodic

palpitations and insomnia. He became intolerant of bright light, which would

trigger headaches, and was also intolerant of cold night air that would

trigger muscle aches and anthralgia. He also had intermittent bouts of

pharyngitis. The illness continued to progress with increasing generalized

muscle weakness, chest pains, shortness of breath, mild ataxia and tremor. He

was seen by numerous specialists whose aggregate diagnoses included the

following: i) Labile hypertension progressing to fixed hypertension

associated with left ventricular hypertrophy and EKG signs of viral

cardiomyopathy. ii) Hepato-splenomegaly with fluctuating elevated liver

enzymes and steatosis on liver biopsy, now progressing to cirrhosis. iii)

Progressive cerebral atrophy with hypoperfusion and hypometabolism,

manifesting as personality disorder, impaired memory, depression and early

dementia. He has difficulty following conversations and is easily confused.

iv) Endolymphatic hydrops. v) Prolonged episodes of moderate thrombocytopenia

with ecchymosis, telangiectasia and splinter hemorrhages. Plasmacytosis was

seen on bone marrow biopsy with ohgoclonal rearrangements within both B and T

lymphocytes. Megaloblastic anemia, refractory to folic acid and vitamin B12

therapy. vi) Multiple chemical sensitivity and multiple food allergies, which

induce nausea and headaches. vii) Localized psoriasis and; viii) Recent onset

of type II diabetes. He has been on disability since 1984.

Abnormal laboratory tests include elevated levels of alpha interferon,

interleukin 1, tumor necrosis factor and C reactive protein. He has

auto-antibodies to nuclear, nucleolar and cytoplasmic antigens. 1gA and 1gG

levels are below normal, as are qualitative and quantitative NK cell assays.

CD4/CD8 T lymphocyte ratio is elevated. Plasma amino acid levels are reduced,

whereas plasma ammonia is increased. Stealth virus cultures have been

repeatedly positive since 1991.

Case 4: A 55 year old financially successful physician was alerted to a

possible illness when he noticed difficulties switching his concentration

from counting a patient's pulse to watching the clock. He also began to

forget telephone numbers. He had to carefully position himself before getting

up from a stool so as not to stagger and appear drunk. He stopped practicing

medicine when he found himself waiting for another motorist to come to a

traffic light so as to remind him on which color light he could proceed.

Neurological examinations were conducted, but no abnormalities were found.

His colleagues reassured him that it was nothing other than stress. He became

despondent and overweight. His marriage failed and his adult children sided

with their mother in the disposition of various assets. For the next 10

years, the physician lived alone, unable to drive at night because of

disorientation; unable to socialize because of verbal and cognitive problems;

and unable to obtain relief in spite of literary having a pharmacy within his

apartment. A formal neurological examination was arranged in 1994, to help

document his disability for a Public health report. It was essentially

unremarkable except for a 4/5 mild bilateral weakness in hand gripping. The

examining neurologist admitted that he was considering schizophrenia when the

patient began referring to " multiple little men in my brain not listening to

each other. " The disabled physician was provided a trip to Hawaii but only on

four occasions throughout a whole month did he leave his hotel room. His

travelling companion commented on his relentless suffering and inability to

take delight from any of the days' happenings. When not sleeping, he would

struggle with expressing his ideas and would invariably return to the theme

of his illness. Upon his return to California, he answered a mail-order bride

advertisement from the Philippines, where he now resides. Blood and an

otherwise normal CSF sample were strikingly positive in stealth viral

cultures.

Discussion

In spite of the obvious differences, complexities and severity of the

illnesses experienced by these four physicians, they are all currently

diagnosed as having CFS. In current medical practice, this term embraces a

broad range of illnesses without defined boundaries at either the mild or

severe extremes. It lumps seriously ill patients, such as those described in

this paper, with the so called " worried well " who are accused of over

utilizing medical services (8). For sick patients, the CFS label is not

infrequently applied to individuals with variably recurring multi-system

illnesses with an overlay of neuropsychiatric symptomatology. A CFS diagnosis

will often limit the medical quest to determine the actual causes of the many

and varied symptoms experienced by the patient. Being physicians, the

patients described in this paper, have had access to more extensive

laboratory and ancillary testing than do most CFS patients. In particular,

they sought and tested positive for stealth viral infections.

Stealth viruses refer to a molecularly heterogeneous grouping of atypically

structured viruses that induce a vacuolating cytopathic effect (CPE) in

culture, yet seemingly are unable to evoke an anti-viral inflammatory

response in vivo (4-7). Sequence studies on an African green monkey simian

cytomegalovirus-derived stealth virus are consistent with the deletion of

genes coding for the major targets for anti-CMV cytotoxic T lymphocytes (CTL)

mediated immunity (6). More impressively, portions of this virus have gained

many additional sequences of both cellular (9) and bacterial origins (10).

The SCMV and captured cellular and bacterial sequences have undergo

considerable mutations, yielding a diverse range of molecular and antigenic

components. Stealth adaptation can presumably occur with other cytopathic

viruses of human and animal origin. The lack of an accompanying inflammatory

reaction and poor growth in routine viral cultures have helped these viruses

go unnoticed by clinical investigators.

The molecular and antigenic diversity of stealth viruses can help explain the

sometimes baffling results of PCR and serological based assays obtained in

CFS patients. In Case 1, for example, positive results were obtained in tests

for Borna virus, Legionella, chlamydia and mycoplasma. Although it is

conceivable that the patient had all of these infections, it is more likely

that the results reflect molecular and antigenic cross-reactivity. The

presence of stealth viruses, especially their capacity to assimilate genes of

bacterial origins, poses a caveat on the interpretation of many currently

used PCR and serological based tests.

While the encephalopathic manifestations tend to dominate the clinical

features of most CFS patients, as is amply revealed in the case histories,

many other organ systems are affected. The detection of various abnormalities

often reflects the extent to which laboratory and ancillary diagnostic

services are employed. The sensitivity and specificity for CFS of many of the

various tests are not established. Given the vagueness of the clinical

diagnosis, it would not be surprising if major discrepancies occurred. The

diversity of laboratory results is, however, quite consistent with an overall

diagnosis of multi-system stealth virus infection with encephalopathy

(MSVIE). This term can embrace the widespread illnesses, including signs of

autoimmunity, allergy and metabolic failures, that were especially apparent

in cases 1 and 3.

The four physicians have experienced many of the problems faced by CFS

patients. The social toil has included loss of income with considerable

medical expenses incurred in the performance of laboratory tests and

ancillary investigations. Two of the patients were divorced largely due to

personality changes and loss of empathy with their spouses. One physician

lived apart from his wife for several years in fear of transmitting his

infection. Electron microscopy and stealth virus testing of semen was a

hopeful gesture that they might still be able to conceive a healthy child.

The diagnosis of CFS was used in the denial of the first physician's appeal

for Worker's Compensation, even though her initial illness clearly followed a

needle stick injury. Another physician felt pressured to reach a settlement

with his long term disability carrier who had decided to terminate his

benefits.

One of the physicians visited NIH investigators, and met with CDC officials

trying to alert them to his illness without success. Patient 4 was formally

reported to a County Health Department in 1994, again with no response. The

reluctance of Public Health authorities to deal with chronic disabling

illnesses may be partially explained by an inadequacy of conventional

epidemiological tools when applied to complex and varied infectious diseases.

The sequence data on the prototype stealth virus may also bear on Public

Health concerns regarding the wisdom of having used African green monkeys to

produce live poliovirus vaccine.

Although only four cases are presented, many more physicians have sought

stealth virus testing. Several other physicians have begun anti-viral therapy

with ganciclovir with self-reported benefit. Courageous clinicians have

continued to treat CFS patients, but with a greater respect for the potential

contagiousness of the illnesses they are encountering.

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three large state office buildings, California, 1993: was there an outbreak?

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WJ, Zeng LC, Ahmed K, Roy M. Cytomegalovirus-related sequences in an

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fatigue syndrome. Am J Path. 1994;145:441-452.

WJ. Severe stealth virus encephalopathy following chronic fatigue

syndrome-like illness: Clinical and histopathological features. Pathobiology

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WJ. Stealth adaptation of an African green monkey simian

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10. WJ. Bacteria related sequences in a simian cytomegalovirus-derived

stealth virus