America's Biggest Cover-Up: 50 More Things Everyone Should Know About The Chronic Fatigue Syndrome Epidemic And Its Link To AIDS
by Neenyah Ostrom
Table of Contents
1. Some CFS Patients May Be "Non-HIV AIDS" Cases
2. A Virus Found In AIDS Patients Is Found In CFS Patients With Brain Lesions And May Be The Primary Attacker Of The Immune System
3. HHV-6 Kills An Important Immune System Cell In AIDS And CFS Patients
4. HHV-6 Seems To Be Causing Lung Disease In Immunosuppressed Individuals
5. A Virus Found Growing In CFS Patients Has Been Linked To Miscarriage
6. HHV-6 Infections Can Be Fatal
7. A New Virus, HHV-7, Has Also Been Found In CFS Patients
8. A Natural Immune System Anti-Viral Pathway Doesn't Work In CFS
9. A Mysterious Organism Called A Mycoplasma May Be Peripherally Involved In CFS
10. Just As In AIDS, Immune System Cells Called Monocytes Do Not Work Properly In CFS Patients
11. As In AIDS, The Immune System Is Both Over-Stimulated And Depressed In CFS
12. One Researcher Thinks That CFS Should Be Called "Lymphokine Overdose Disease"
13. CFS, Like AIDS, May Be Primarily A Tumor Necrosis Factor Disease
14. Zinc Deficiency May Contribute To CFS
15. Magnesium Can Be A Missing Element In CFS
16. There Is A Hormonal Imbalance In CFS Similar To The One In AIDS
17. CFS Patients' "Crimson Crescents" May Be Diagnostic Of The Syndrome
18. CFS Patients May Develop A Cancer Similar To One Found In AIDS
19. Like AIDS Patients, CFS Patients May Be Especially Susceptible To Tuberculosis
20. CFS Patients Have A Brain Defect Similar To That Found In AIDS Dementia
21. There Can Be A Significant Weight Fluctuation In CFS
22. Dizziness Can Be A Severe Problem In CFS
23. As In AIDS, Sinusitis Can Become Chronic In CFS
24. A Recent Rise In Childhood Asthma May Be An Effect Of The CFS Epidemic
25. Endometriosis Seems To Be Common In Women With CFS
26. Pregnancy Can Be A Disaster For A CFS Patient
27. Men With CFS Can Develop Chronic Prostate Infections
28. CFS Can Cause A Particular Type Of Heart Murmur
29. Like AIDS Patients, CFS Patients May Bruise More Easily Than Healthy People
30. CFS Can Lead To Serious Diseases Of The Mouth and Gums
31. CFS Can Cause Perception Problems For Drivers
32. People With CFS Often Have Bizarre Sleep Problems
33. CFS Is Often Characterized By Nausea
34. CFS Patients Can Develop Serious Bladder Problems
35. Fingers Can Become Swollen In CFS
36. CFS Patients Can Develop Skin Rashes And Other Disorders, Especially Acne And Shingles
37. The Hair Can Be Severely Affected By CFS
38. CFS Patients Can Have False Positive Tests For Syphilis
39. In CFS Patients, As In AIDS Patients, The T4 Cells May Be Sequestered In The Lymph Nodes
40. Sunbathing May Make CFS Symptoms Worse
41. As It Progresses, CFS Can Be Measured In "Stages"
42. Some CFS Patients Become Suicidal
43. Health Care Workers May Be At Increased Risk For CFS
44. CFS Can Result In Financial Disaster
45. A Drug Made From Pig Liver Appears To Help Some CFS Patients
46. An Experimental Drug That Appears Promising For CFS And AIDS Is Being Evaluated By The FDA
47. Nothing Is Being Done To Protect The Blood Supply From CFS- Infected Blood
48. CFS Has Spawned A Powerful Patient Movement That Has Become Mired In Denial
49. The Two "Variants" Of HHV-6 Appear To Act Very Differently
50. A Virus That Causes An "Acquired Immune Deficiency Syndrome" In Pigs May Be The Real Cause of CFS And AIDS
Chronic Fatigue Syndrome is not the only illness that is frustrating contemporary medical science. Gloom pervaded the Ninth International AIDS Meeting (held in Berlin in June 1993), as clinicians and researchers acknowledged that little progress was being made in fighting the illness. The drug that has been touted for years by the U.S. government as stopping the progression of AIDS and extending patients' lives, AZT, does neither. In fact, researchers revealed, AZT is so toxic that it may actually hurt AIDS patients more than it helps. And the immune system marker used to evaluate AIDS patients' health (and AZT's action), T4 cell counts, it was admitted in Berlin, has essentially no correlation with patients' health.
Although uneasiness and distress permeated news reports during and following the Berlin meeting, no reporter asked the obvious question: Is it possible that so little progress has been made in combating AIDS because a mistake has been made in the definition of the epidemic?
This book will attempt to answer not only that question, but also other, potentially even more alarming, ones: Is CFS actually part of the AIDS epidemic? Are CFS and AIDS, in fact, the same illness?
Since the Berlin conference, for anyone interested in observing it, evidence linking these two refractory epidemics, AIDS and Chronic Fatigue Syndrome, has continued to accumulate.
Anxiety about the direction of AIDS research had really begun at the previous international AIDS conference, held in Amsterdam in 1992.
The bombshell of 1992's AIDS conference was the announcement that some researchers had identified cases of AIDS without evidence of infection with the "AIDS virus," HIV.
These "non-HIV AIDS cases" had severely depleted T4 (or CD4) cells, like AIDS patients; they also developed life-threatening opportunistic infections.
What wasn't known to most observers was that one of the researchers who had first publicly identified some of the non-HIV AIDS cases, Dr. Sidhur Gupta of the University of California, Irvine, is a Chronic Fatigue Syndrome researcher.
And some of the non-HIV AIDS cases, it was soon revealed, were actually CFS patients.
Shortly after the June 1992 AIDS conference in Amsterdam, Chronic Fatigue Syndrome researcher Dr. Paul Cheney announced that he had 20 CFS patients in his practice who had the same immune system deficiencies as the non-HIV AIDS cases.
The hallmark of the HIV-negative AIDS cases, as defined by the Centers for Disease Control and Prevention, is a depletion of the T4 (or CD4) cells.
Therefore, the CDC decided to call the HIV-negative, AIDS-like disease "ICL" (an abbreviation of the tongue twisting "idiopathic CD4-positive T-lymphocytopenia," which means, simply, an unexplained loss of T4 cells).
Most healthy people have a T4 cell count of approximately 1,000; a T4 cell count below 800 is considered abnormal. In order to be diagnosed with ICL, a person must have a T4 cell count of less than 300.
One of the most puzzling things about the ICL cases to AIDS researchers -- other than the fact that they don't have HIV -- is that most of the patients do not fit into recognized AIDS "risk behavior" categories; that is, they are not gay men, IV drug users, or the sexual partners of people in those risk groups.
How can AIDS exist in the absence of the virus that causes it? None of the AIDS researchers gathered in Amsterdam in June 1992 seemed able to answer that question.
The mystery of what role HIV plays in causing the immune system deterioration and symptoms seen in AIDS deepened in early October 1992 when a British medical journal carried a report about a strain of HIV that does not appear to cause any kind of illness.
An Australian research team wrote to The Lancet to report on five people who had received blood from a man later found to be infected with HIV. However, ten years following the transfusions, the five blood recipients, as well as the original, HIV-positive donor, remained free of AIDS symptoms and were apparently healthy. The Australian researchers concluded that all six people were infected with a non-disease-causing strain, or type, of HIV.
Studies have shown that HIV is spread only through blood products (i.e., in transfusions), or through exchange of bodily fluids, such as during sex. AIDS is considered to be primarily a sexually-transmitted disease, but one that requires many exposures -- some estimates run as high as 500 exposures -- to catch.
CFS appears to be transmitted much more easily; some researchers have guessed that it might be spread by saliva, as when people share eating utensils. Dr. Cheney, in fact, has reported that as many as 40 percent of his CFS patients also have a close associate -- not a sexual partner -- who has an illness similar to CFS.
Dr. Cheney's statistic -- along with the mystery of why AIDS could develop without HIV infection and why HIV infection does not always lead to AIDS -- raises the possibility that a virus or bacteria that spreads more easily than HIV could be attacking people's immune systems.
Dr. Cheney described the immune system damage seen in CFS patients for the Food and Drug Administration in May 1993. Dr. Cheney told the FDA that five of his CFS patients had died during the preceding six months. Two of these patients committed suicide, which is all too common among CFS patients. But three of Dr. Cheney's patients who died, like AIDS patients, succumbed to overwhelming infections that their damaged immune systems just couldn't fight off.
But Dr. Cheney's CFS patients, like the ICL patients, appeared not to be infected with HIV, even though they developed AIDS-like immunodeficiencies and, in some cases, life-threatening opportunistic infections.
One of the AIDS-like immunodeficiencies seen in CFS involves cells in the immune system that are important in fighting infections: natural killer cells. Natural killer cells are the scavengers of the immune system; they attack and kill anything that appears to be foreign, including the body's own cells that are infected with viruses or other disease-causing agents. Because of that activity, natural killer cells are considered to be part of the immune system's front line of defense against both viruses and cancer.
Natural killer cells are also essential in protecting against tuberculosis, but at the same time, they are disabled by the TB germ. If a person's natural killer cells are not working properly, they are at much increased risk for developing active tuberculosis.
In both AIDS and Chronic Fatigue Syndrome patients, natural killer cells are almost completely disabled. One study of CFS patients found that their natural killer cells' functioning was decreased by 86 percent.
In other words, if a healthy person's natural killer cells worked at 100 percent capacity, a CFS patient's natural killer cells are working at only 14 percent.
Of all the conditions in which natural killer cell activity has been studied, only AIDS patients have been found to have natural killer cells as disabled as those of CFS patients.
However, most AIDS researchers have concentrated on studying the immune system cells implicated in the non-HIV AIDS cases, the T4 (or CD4) cells. T4 cells have been thought to be a good indicator of failing or improving health in AIDS patients; when their numbers decreased, patients were thought to be at higher risk of developing serious infections. Conversely, rising numbers of T4 cells were seen as proof that therapies, such as AZT, were improving patients' health.
As a result of this belief that T4 cell numbers correlated well with health status, very few scientists have studied the natural killer cells and how they fit into the puzzle of AIDS.
In early 1993, however, a study was published in the prestigious British medical journal Nature which not only forged several more links between the AIDS and Chronic Fatigue Syndrome epidemics, but also went a long way toward explaining why natural killer cells stop working in both syndromes.
National Cancer Institute researcher Dr. Robert C. Gallo and his colleagues made an astonishing assertion in the Nature study: They reported that a virus found to be actively growing in both AIDS and Chronic Fatigue Syndrome patients, Human Herpes Virus 6 (HHV-6), infects and kills natural killer cells. Moreover, according to the report from the Gallo laboratory, HHV-6 is the only virus known to be able to do that.
This landmark study answered two previously unanswered questions: It explains at least part of what the actively growing (or "replicating") HHV-6 is doing in AIDS and Chronic Fatigue Syndrome patients, and it partly explains why natural killer cells don't work in those patients.
In fact, Dr. Gallo and his co-workers suggested that HHV-6 "may contribute to the immune dysfunctions associated with CFS and AIDS."
Even studies of T4 cells published in early 1993 inadvertently linked the AIDS and Chronic Fatigue Syndrome epidemics.
The government scientist responsible for Chronic Fatigue Syndrome research at the National Institutes of Health, Dr. Stephen Straus, finally admitted in early 1993 -- after 13 years of trying to prove that Chronic Fatigue Syndrome is a type of depression -- that immune system deficiencies are part of the illness. Dr. Straus and his colleagues published data showing that CFS patients, like AIDS patients, experience a drop in the number of T4 cells in their blood.
Dr. Straus proposed a novel mechanism to explain the loss of T4 cells in CFS patients: The T4 cells of CFS patients are not destroyed, as they are in AIDS patients, according to Dr. Straus; the T4 cells are just hiding in the lymph nodes where they cannot be detected by blood tests.
Therefore, according to Dr. Straus, the T4 cell depletion observed in CFS patients is completely different from the T4 cell depletion seen in AIDS patients.
Unfortunately, Dr. Straus was unable to produce any evidence to support this theory (and still has not). Dr. Straus did not suggest, in contradiction to what Dr. Cheney has found, that any of his CFS patients had T4 cell counts so low they could be identified as ICL patients.
Almost simultaneously, Dr. Yvonne Rosenberg, a scientist working at the Henry M. Jackson Foundation Research Laboratory in Rockville, Maryland, announced that her studies had indicated that T4 cells in AIDS patients are not as decimated as they might appear to be. Instead, Rosenberg suggested, at the prestigious Keystone Conference held the last week of March, 1993, that AIDS patients' T4 cells are sequestered in the lymph nodes where they remain unmeasured by blood tests.
Although Dr. Anthony Fauci, the man in charge of AIDS research in the United States, attended the conference and presented the work his research group had performed on the lymph nodes of AIDS patients, neither he nor any other government scientist chose to comment about the parallel finding about T4 cells in the lymph nodes of AIDS and CFS patients.
And, as the Centers for Disease Control and Prevention (CDC) lurches toward finishing its several-year-long surveillance study to estimate how many people in the U.S. have Chronic Fatigue Syndrome, new information on that subject has come from a surprising source. A group of researchers at the New England Medical Center (in Boston) studying Lyme disease discovered that up to 50 percent of people diagnosed with Lyme disease actually have Chronic Fatigue Syndrome.
The Lyme disease researchers set out to answer another question altogether. They were trying to figure out why Lyme disease treatment is unsuccessful in so many cases.
Lyme disease is caused by a bacterium similar to the one that causes syphilis; it is treated with antibiotics. But a large percentage of people diagnosed as having Lyme disease didn't improve when treated with antibiotics, and the Boston researchers were trying to find out why.
They discovered that the patients whose Lyme disease didn't respond to antibiotics didn't have Lyme disease.
Even more surprisingly, they found that almost 50 percent of those wrongly diagnosed with Lyme disease had, instead, a putatively viral illness: Chronic Fatigue Syndrome.
In addition to its importance to people with Lyme disease and their physicians, this study potentially has enormous importance for the CDC surveillance study. The CDC study is examining people diagnosed with CFS, to see how many of them fit the very strict CDC definition. From those numbers, CDC investigators will extrapolate to the rest of the population and attempt to estimate how many Americans have CFS.
But they are not examining people who have been diagnosed with other, more accepted illnesses, like Lyme disease.
As the New England Medical Center study showed, there could be thousands -- or hundreds of thousands -- of people who have Chronic Fatigue Syndrome who have been diagnosed as having some other disease. Those people are quite unlikely to be counted by the CDC.
The CDC's estimate of how many Americans have CFS could, therefore, be terribly wrong unless this type of misdiagnosis is taken into consideration.
And this kind of misdiagnosis is likely to continue until there is a diagnostic test available for CFS.
Many researchers are attempting to create such a test for CFS. One line of research that originally appeared to be promising involved finding a retrovirus, like the virus that supposedly causes AIDS, in CFS patients. Some researchers had believed that finding such a retrovirus, and proving that it causes CFS, would result in a definitive way to diagnose the syndrome, as the HIV antibody test has done for AIDS.
But the "CFS retrovirus" research apparently ran into some roadblocks, and little progress has been made since the single report describing the retrovirus was published in early 1991.
Meanwhile, HIV has come under intensified scrutiny as a disease-causing organism.
Although the controversy over whether HIV causes AIDS -- with or without the help of "co-factors" -- has continued, few attacks on the retrovirus have appeared in the medical literature. In June 1993, however, an Australian research team published a devastating attack on the HIV antibody test, often called the "AIDS test."
The Australian research team, in fact, raised serious questions not only about whether HIV causes AIDS, but even about its existence as a distinct, infectious retrovirus.
Writing in the June 11, 1993, issue of the journal Bio/Technology, Eleni Papadopoulos-Eleopulos and her colleagues examined the HIV antibody test and found that it had many problems.
Eleopulos and her co-workers found that the HIV antibody test is not consistent; that is, the same blood sample tested in several laboratories does not give the same results in every test performed. They suggest that some of the biological molecules that the HIV antibody test is measuring may be just background junk, cell proteins that are contaminating the test.
Even more disturbing, through an extensive study of the HIV literature, Eleopulos and her colleagues raised the question of whether HIV has ever really been isolated as a discrete entity. The answer they reached is that it has not.
This research caused Eleopulos and her co-workers to conclude that, not only is the HIV antibody test extremely unreliable and perhaps not at all useful, but that it may be a test for something that does not cause AIDS.
This takes us back to the original questions: Is it possible that a mistake has been made in formulating the definition of AIDS? Is Chronic Fatigue Syndrome actually part of the AIDS epidemic?
If this is even a remote possibility, why haven't other books been written about it? Why isn't every health reporter in the country writing about it, every investigative reporter investigating?
The answer, I believe, is pretty simple, and it is a problem that has dogged the AIDS epidemic from the beginning: denial.
From the very beginning of the AIDS epidemic, the syndrome has been characterized as affecting "the other": Haitians (i.e., blacks), gay men, IV drug users, and these groups' sexual partners. These individuals have been contrasted -- and still are -- with the "innocent victims" of the AIDS epidemic: the unknowing wives, and their babies.
AIDS patients, and people who test HIV-positive (whatever that actually turns out to mean), have been so badly treated, so discriminated against, so scapegoated and demonized that it is not surprising that there is an almost reflexive recoiling from the possibility that AIDS is not the narrowly-defined illness that it has been portrayed as being.
People have been murdered for testing HIV-positive; they have been accused of murder; they have been driven to suicide; they have been jailed; they have been denied jobs and health insurance and places to live.
Given all this, denial that AIDS could be even more widespread than government officials admit is not too surprising. What rational person would want to be diagnosed with an illness that could produce such terrible repercussions in every area of life?
Oddly enough, this denial appears to be most fiercely concentrated among medical researchers, and not among the patients themselves.
Chronic Fatigue Syndrome patients, in fact, know they suffer from a profoundly debilitating, life-altering illness that is destroying their immune systems.
Until the denial among medical professionals about the relationship between the AIDS and Chronic Fatigue Syndrome epidemics is overcome, however, it is difficult to imagine how either epidemic can be ended.
A disturbing announcement was made at the July 1992 international AIDS conference held in Amsterdam: Several people with symptoms of AIDS, but who had no evidence of infection with either HIV-1 or HIV-
2 (the viruses generally believed, at the time, to cause AIDS), had been identified by the U.S. Centers for Disease Control. A few weeks later, in early September, Newsweek made an even more shocking announcement: that Chronic Fatigue Syndrome researcher Dr. Paul Cheney had in his practice 20 CFS patients who had the same immune system deficiencies as the non-HIV AIDS cases revealed at the Amsterdam conference.
What wasn't known to most observers was that one of the researchers who had first said publicly that he was aware of such cases, Dr. Sidhur Gupta of the University of California, Irvine, is himself a Chronic Fatigue Syndrome researcher.
The fact that some CFS patients were developing exactly the same immune system problems as AIDS patients, however, raised the questions not only of what was causing that immune system destruction but also of the relationship that exists between the two syndromes.
The hallmark of the HIV-negative AIDS cases, as established by the Centers for Disease Control, is a depletion of a type of immune system cell called T4 (or CD4) cells. The T4 cells of AIDS patients can fall to very low levels and, although recent studies have suggested that there is no real correlation with health status, a decreasing T4 cell count is generally viewed as a sign of worsening disease.
The CDC decided to call the HIV-negative, AIDS-like disease "ICL" (an abbreviation for "idiopathic CD4-positive T-lymphocytopenia," which simply means an unexplained depletion of T4 cells).
Most healthy people have a T4 cell count of approximately 1,000; a T4 cell count below 800 is considered abnormal. In order to be diagnosed with ICL, a person must have a T4 cell count of less than 300.
One of the most puzzling things about the ICL cases to AIDS researchers -- other than the fact that they didn't have HIV -- is that most of the patients do not fit into recognized AIDS "risk behavior" categories; that is, they were not gay men, IV drug users, or the sexual partners of people in those risk groups. These cases may, in fact, be dramatic evidence that federal officials have not told the public the whole truth about the nature and the full scope of the AIDS epidemic.
The mystery of what role HIV actually plays in causing the immune system deterioration and symptoms seen in AIDS deepened in early October 1992. The British medical journal The Lancet reported that five people had received blood from a man later found to be infected with HIV; however, ten years later, the five transfusion recipients as well as the original, HIV-positive blood donor remained free of AIDS symptoms and were apparently healthy. The Australian researchers who reported those cases concluded that these six people were infected with a non-disease-causing strain, or type, of HIV.
The link between the immune system dysfunction seen in AIDS and in CFS was made explicit in early 1993 when government scientists admitted that CFS patients, like AIDS patients, suffer a decline in T4 cells. The government's leading CFS researcher, Dr. Stephen Straus at the National Institute of Allergy and Infectious Diseases, published a research paper in The Journal of Clinical Immunology in which a decrease in the number of T4 cells in CFS patients was documented.
Dr. Straus proposed a novel mechanism to explain the loss of T4 cells in CFS patients: The T4 cells of CFS patients were not depleted, as they were in AIDS patients, according to Dr. Straus; they were just hiding in organ tissues. Unfortunately, Dr. Straus was unable to produce any evidence to support this theory (and still has not done so). Dr. Straus did not suggest that any of his CFS patients had T4 cell counts so low that they could be identified as ICL patients.
Meanwhile, Dr. Cheney, in addition to announcing that some of his CFS patients had low enough T4 cell counts to be considered non-
HIV AIDS cases, reported that as many as 40 percent of his CFS patients also had a close associate with an illness similar to CFS. This information -- along with the mystery of why AIDS could develop without HIV infection and why HIV infection does not always lead to AIDS -- raised the possibility that a virus or bacteria that spreads more easily than HIV could be attacking people's immune systems.
A virus that has been considered for several years a possible cause of Chronic Fatigue Syndrome is Human Herpes Virus 6 (HHV-6). This virus was first discovered in AIDS and cancer patients in the mid-1980s at the National Cancer Institute. It was subsequently found that people with Chronic Fatigue Syndrome, like people with AIDS, can have extremely high levels of antibodies to HHV-6.
As more is learned about HHV-6, its ability to attack the immune system -- and perhaps other parts of the body, like the nervous system -- has been documented in more and more frightening ways. Even more alarmingly, the most recent research on HHV-6 suggests that it, and not HIV, is the primary infection that destroys an important part of the immune system in AIDS.
That part of the immune system is the natural killer (NK) cells. NK cells are crucial to the immune system's front-line defense against both viruses and cancer, because they attack and kill any cells they perceive to be foreign. If the NK cells aren't working properly -- which they aren't, in both AIDS and CFS -- this very important protection is knocked out.
The research team that discovered the existence of HHV-6, working with Dr. Robert C. Gallo at the National Cancer Institute, announced in early April 1993 that HHV-6 is the only virus known to be able to infect and kill NK cells.
Furthermore, Dr. Gallo and his colleagues asserted, HHV-6 infection allows the AIDS virus, HIV, to invade NK cells and kill them.
The question of how many other kinds of cells require HHV-6 to be present before HIV can invade them remains, at this time, unanswered.
HHV-6 is capable of wreaking all kinds of havoc, not all of which is confined to the immune system. In January 1992, a study was published showing that a large percentage of CFS patients who had HHV-6 actively growing in their blood streams also showed evidence of organic brain disease.
When CFS patients from the first detected outbreak of CFS in the U.S. -- which occurred in Incline Village, Nevada, in the mid-1980s -- were studied, brain scans showed that 80 percent of those infected with actively growing HHV-6 had (several years after the initial outbreak) developed brain lesions.
No one knows what the lesions mean or are doing to the patients, or whether HHV-6 is actively growing at the site of the brain damage.
But the Incline Village CFS patients were also found to have NK cells that weren't functioning properly. Now, we know that HHV-6 is, most likely, directly responsible for the dysfunction in the CFS patients' NK cells, but the virus' involvement in causing the brain lesions has yet to be proven conclusively.
The scientists studying the Incline Village patients concluded that there was an infectious agent, capable of being spread from person to person, in the CFS patients: HHV-6.
This very important study of CFS patients not only indicates that CFS is a contagious illness, but also suggests that HHV-6 is its cause.
Human Herpes Virus 6 (HHV-6) was first discovered in people with damaged immune systems who had cancer or AIDS. However, when studies showed that it seemed to infect about 90 percent of the world's population by age three, HHV-6 was generally portrayed by scientists as a fairly harmless virus.
More recent research, however, has thrown the supposition about HHV-6 being harmless into doubt. For one thing, there are two different types of HHV-6; one is isolated from infants, and seems to cause only a mild childhood illness, with fever and rash, called roseola.
The other type of HHV-6, however, is found in very sick adults who have AIDS, cancer, Chronic Fatigue Syndrome, or other immune system abnormalities. And the newest research on this type of HHV-6 suggests that it may be the cause of the immune system deficiencies seen in both AIDS and CFS.
National Cancer Institute researcher Robert Gallo and his co-workers are generally credited with the discovery of HHV-6, and Dr. Gallo and his lab workers have continued to study the virus intensively. (Dr. Gallo's claims to virus discovery have to be taken with a grain of salt, however. He also claimed, for a number of years, to have discovered HIV, the "AIDS virus." After a lengthy investigation and charges of virus-lifting by other scientists, however, Dr. Gallo admitted that he had simply "discovered" a virus that had been sent to him by Pasteur Institute scientist Luc Montagnier and his research group. For having made false claims about discovering the "AIDS virus," Dr. Gallo was judged guilty of scientific misconduct by the National Institutes of Health in December 1992.)
The HHV-6 that Dr. Gallo and his colleagues are studying at the National Cancer Institute is the type that infects adults who have AIDS, cancer, or Chronic Fatigue Syndrome.
In April 1993, Dr. Gallo and his colleagues published an astonishing report in the prestigious British medical journal Nature. They reported that HHV-6 was able to infect and kill the natural killer cells, which are an important part of the immune system, and that it was the only virus ever found to do so.
Natural killer cells are the body's front-line defense against viruses and some kinds of cancer. When natural killer cells encounter a cell that is "foreign" -- either because it is infected with a virus or because it has become cancerous -- they engulf and destroy it. Unlike other types of immune system cells, natural killer cells do not require any type of priming or activating by another part of the immune system; that is why they are considered to be the first line of defense in protecting the body against certain invaders.
In both AIDS and Chronic Fatigue Syndrome patients, the natural killer cells just don't work the way they do in healthy people. One researcher found a natural killer cell activity deficit of 86 percent in the Chronic Fatigue Syndrome patients she studied. AIDS patients have similar deficits in natural killer cell activity. Before Dr. Gallo's study linking HHV-6 and natural killer cell destruction, no one had been able to explain why natural killer cells stopped working in AIDS and CFS patients.
Dr. Gallo and his colleagues, however, not only showed that HHV-6 can infect and kill natural killer cells, but actually suggested that the virus "may play a role in the acquired immunodeficiency syndrome (AIDS) and in the chronic fatigue syndrome, two disorders associated with a defective NK cell activity."
They are also the first researchers to confirm that the immune system abnormalities seen in AIDS and CFS are actually the same.
In fact, in the conclusion of their research report, Dr. Gallo and co-workers stated that their results "elucidate a novel mechanism whereby HHV-6 may contribute to the immune dysfunction associated with CFS and AIDS."
Further studies of HHV-6 in AIDS and CFS patients may provide even more examples of how this virus causes the immune system abnormalities the two syndromes share and may even suggest even more strongly that CFS and AIDS are simply different manifestations of the same illness.
People who receive organ transplants are given drugs that suppress their immune systems so that they do not reject the transplanted organs, thus placing them in a state that is similar to AIDS or CFS. While they are in that immunosuppressed state, they are especially vulnerable to infections, just like CFS and AIDS patients are. Now it appears that an often-fatal lung illness that can occur following bone marrow transplantation may be caused by a virus that infects AIDS and CFS patients, Human Herpesvirus 6 (HHV-6).
If HHV-6 is causing lung disease in bone marrow transplant recipients, that raises the question: Is HHV-6 also causing lung disease in CFS and AIDS patients?
Another extremely serious immunological complication that occurs after bone marrow transplantation, Graft-Versus-Host Disease (GVHD), may also be caused by HHV-6. Both of these findings were published in the New England Journal of Medicine in July 1993.
The lung illness caused by HHV-6 is pneumonitis, which is inflammation of the lung (basically, a type of pneumonia). When lung tissues from patients who'd had bone marrow transplants and subsequently developed pneumonitis of unknown cause were examined by a research group in Seattle, the tissues were found to contain considerable amounts of HHV-6.
That led the researchers to conclude that HHV-6 was probably causing some cases of the often-fatal pneumonitis in bone marrow transplant patients.
This is the first time that HHV-6 has been implicated in causing a lung illness.
Graft-Versus-Host Disease (GVHD) is another potentially life-threatening illness that strikes bone marrow transplant recipients. In GVHD, the donor's healthy T-cells (which are impaired in AIDS and CFS) attack the recipient's tissues; GVHD is a form of organ rejection. The symptoms of GVHD include fever, rash, hepatitis, diarrhea or abdominal pain, vomiting, and weight loss.
Some of the bone marrow transplant patients studied by the Seattle researchers who developed pneumonitis caused by HHV-6 also developed severe GVHD.
Those patients were also found to have very high levels of HHV-6, particularly in their lungs.
That is to say, three conditions occurred together in the patients: high levels of HHV-6, pneumonitis, and severe GVHD.
This led the Seattle researchers to suggest that HHV-6 is the likely cause of both the pneumonitis and the GVHD seen in some bone marrow transplant recipients.
Another report about HHV-6 also appeared in the same issue of the New England Journal of Medicine. This report was from Japan, where researchers had observed a ""mononucleosis-like illness'' they believed to be caused by HHV-6.
The 43-year-old man described by the Japanese research team was admitted to the hospital with a high fever, rash, swollen lymph nodes, a swollen spleen, and inflamed tonsils; he was also suffering from liver dysfunction.
This man, too, had high levels of HHV-6 during his illness, leading the Japanese researchers to conclude that the man's ""mononucleosis-like illness'' had been caused by HHV-6.
Although some researchers have suggested that HHV-6 is a basically harmless virus that infects approximately 90 percent of the world's population by the age of three, new information being published about the virus indicates that some varieties, or strains, are capable of causing profound immune dysfunction and serious illness. These three problems may be just the tip of the iceberg in terms of the damage that HHV-6 is able to inflict on the immune system.
One of the viruses that has been found to be active in both CFS and AIDS patients, Human Herpes Virus 6 (HHV-6), has been linked by Japanese scientists to miscarriage.
HHV-6 is a virus that primarily invades the T-cells of the immune system (though it can also live in other immune system cells). T-cells are critical in regulating immune responses -- both in getting an immune response started, and in shutting it down. When the T-cells don't work because a virus is attacking them, the immune response can be severely affected, as is seen in both CFS and AIDS.
Very recently, HHV-6 has been found to be the only virus that is capable of invading and killing natural killer (NK) cells. NK cells don't work properly in both CFS and AIDS; a deficiency of NK cell activity, in fact, has been cited by numerous researchers to be the most consistent immune system abnormality found in CFS patients. If the NK cell activity of AIDS patients is examined, it, too, is found to be consistently abnormal. HHV-6, which is known to be actively growing in both AIDS and CFS patients, has been identified as the only virus known to be able to infect and kill NK cells. It is reasonable to assume that it is causing the abnormal NK cell activity seen in both sets of patients.
HHV-6 has also been linked, in CFS patients, to the development of brain lesions (areas of dead or damaged brain tissue). A recent study found that CFS patients with a lot of active HHV-6 also had developed brain lesions that are visible on specialized brain scans; patients without active HHV-6 did not have brain lesions.
A Japanese research team from the Nara Medical University studied 30 patients who'd had miscarriages early in pregnancy (at 6-12 weeks). When tissue from the miscarriages was examined, they were found to contain HHV-6 antibodies that were four times higher than those found in pregnant women who did not miscarry. In a report published in the British medical journal The Lancet in November 1992, the Japanese research team suggested that active HHV-6 "may predispose" to miscarriage in pregnant women.
Human Herpes Virus 6, HHV-6, has been presented to the world as rather a Dr. Jekyll-Mr. Hyde kind of a virus: On the one hand, researchers like Dr. Jay Levy at the University of California-San Francisco point out that HHV-6 infects so large a percentage of people world-wide that it must be essentially harmless. On the other hand, some pediatricians have reported that HHV-6 infections have been fatal.
It is possible, given that more than 10 different strains, or types, of HHV-6 have been identified, that different strains of the virus cause different levels of illness, ranging from almost unnoticeable (a "silent" infection) to deadly.
High levels of antibodies to HHV-6 have been found in several groups of very sick patients, including AIDS and CFS patients.
No one knows for sure what damage HHV-6 is doing in those patients. In the laboratory, however, it has been demonstrated that at least some strains of HHV-6 are very efficient killers of immune system cells -- especially T4 (or CD4) and natural killer cells, the two types of cells most affected in both CFS and AIDS.
And HHV-6 has recently been found in more than one-third of a group of Kaposi's sarcoma tumor biopsies, suggesting that it may play a role in causing this unusual cancer seen in AIDS patients.
Recently, the HHV-6 strains have been divided by researchers into two groups, or variants: Variant A, viruses which have been isolated from sick adults (those with CFS, AIDS, or cancer); and Variant B, which has been found in relatively healthy babies.
Most of the fatal HHV-6 infections identified in the medical literature, however, have occurred in very young children. Cases of fatal hepatitis, or liver disease, caused by HHV-6 in children were reported in the medical literature in 1990 and 1991. HHV-6 infection was localized, not surprisingly, primarily in the children's livers.
In summer 1992, however, a group of New York University re searchers reported a fatal, systemic -- that is, spread throughout many different organs and tissues -- HHV-6 infection in a 13-month-old girl.
The child's illness began with a fever and lack of appetite; soon, however, she began to show evidence of hemorrhaging -- uncontrolled bleeding or leaking of blood vessels -- on her face, trunk, arms, legs, and around her lips. This child also developed liver disease. She died from congestive heart failure on the fifth day after being hospitalized.
When an autopsy was performed on the child, HHV-6 infected white blood cells were found in numerous internal organs: heart, lungs, liver, spleen, thymus, kidney, and bladder, as well as in the gastrointestinal tract, salivary glands, bone marrow, lymph nodes, middle ear, peripheral nerves, and skeletal muscle.
Not too surprisingly, the physicians concluded that this disseminated, or very widespread, HHV-6 infection had killed the little girl.
If certain strains of HHV-6 are capable of causing fatal illnesses -- assuming that this is a strain-dependent phenomenon, which it may not be -- it seems that a reasonable next step in HHV-6 research would be to identify the most deadly strains.
A new virus, called Human Herpes Virus 7 (HHV-7), was isolated from a CFS patient in 1992. This virus was found in the National Cancer Institute; it has been studied most intensively in the laboratory of Dr. Robert C. Gallo.
Whenever Dr. Gallo and his colleagues claim to be studying a new virus it should again be noted that he, and certain colleagues, have been under investigation for several years because of allegedly fraudulent claims that the Gallo lab isolated the AIDS virus (HIV) in 1983. In fact, on December 31, 1992, Dr. Gallo and one of his colleagues involved in the isolation of HIV were found by the National Institutes of Health (only one of the regulatory bodies investigating Dr. Gallo and his colleagues) to be guilty of scientific misconduct.
The other virus found actively growing in both AIDS and CFS patients, Human Herpes Virus 6 (HHV-6), was also isolated in the Gallo laboratory in the mid-1980s; Dr. Gallo's account of the discovery of that virus, like his account of the discovery of the AIDS virus, has been challenged by other scientists.
It is not known whether HHV-6 -- which is closely related to HHV-7 -- contributes to causing CFS, or AIDS. It is known that HHV-6 infects and kills not only T4 cells, one of the major cells that is affected in AIDS, but also infects and kills natural killer cells, which are dysfunctional in both AIDS and CFS.
Like HHV-6, HHV-7 is believed to infect T-cells.
And also like HHV-6, HHV-7 is quite similar to cytomegalovirus (CMV), which can cause blindness and other serious illnesses in AIDS patients. However, HHV-7 is different enough from both HHV-6 and CMV to be declared by Dr. Gallo's research team to be an entirely new human virus.
An important question not posed by these investigators is: Where are these "new" viruses, found to be infecting both AIDS and CFS patients, coming from?
The immune system has evolved many different mechanisms to fight invaders: viruses, bacteria, parasites, and anything perceived as "non-self," such as defective or cancerous cells. Some of those mechanisms are incredibly specific, like antibodies; others are pretty general, like natural killer cells. One of the continuing mysteries of the immune system is how all of these mechanisms interact, overlap, and appear to compensate for each other to protect against infectious agents.
One way the immune system protects against viruses is through a biochemical pathway with the name "2'-5'A synthetase/RNase L pathway." This pathway's anti-viral effects are turned on by interferon, one of the chemicals (called cytokines) produced by T-cells and other cells of the immune system.
Although this sounds rather technical -- and it is -- the most important fact about the pathway is very simple: It malfunctions in both CFS and AIDS patients.
Basically, the pathway works like this: When a virus is detected by the immune system, interferon is produced. Interferon stimulates the inactive chemical 2'5'A synthetase; it interacts with other chemicals and produces a biologically active substance called 2'-5'A. "Biologically active" means that the 2'-5'A is capable of acting on other molecules and making them active, too.
And that is what 2'-5'A does; it activates another immune system substance, RNase L. Activated RNase L is then able to stop the invading virus from reproducing itself and spreading the infection.
When this pathway works correctly, interferon production results, through the steps outlined, in stopping viruses from spreading throughout the body. But in CFS patients -- and AIDS patients -- the pathway doesn't work properly.
Dr. Robert Suhadolnik, working at Temple University in Philadelphia, has discovered that CFS patients have too much of both active substances in the pathway, 2'-5'A and RNase L.
As a result, not only viral reproduction, but also much of the cell's own internal activity, is halted. That means that the cells of the immune system are unable to react properly to invaders.
The failure of this pathway is another example of how an overreaction by a portion of the immune system in a person with CFS can actually result in decreased immunity.
The defect in the anti-viral pathway also suggests that CFS patients, like AIDS patients, are vulnerable to opportunistic infections that can make them very sick.
Interestingly, one of the experimental treatments for CFS (and one which has also shown promise in treating AIDS) is Ampligen, a chemical that is structurally similar to interferon. It appears to correct the defect seen in the 2'-5'A Synthetase/RNase L pathway. Studies using Ampligen to treat CFS are currently being reviewed by the Food and Drug Administration.
Another interesting observation made by Dr. Suhadolnik demonstrates how a malfunction in the immune system in CFS can result in either up- or down-regulation. While most CFS patients studied by Dr. Suhadolnik have increased amounts of RNase L, he has also reported that he has seen some CFS patients in whom there is virtually no detectable RNase L -- which is exactly what is found in AIDS patients.
That finding has led some researchers to speculate that a retrovirus -- like HIV, the "AIDS virus" -- may be involved in causing CFS.
This natural anti-viral pathway may provide not only an understanding of what goes wrong in CFS, but also a way to diagnose the syndrome. In July 1992, a research firm in Houston, Texas, announced that the firm had developed a diagnostic test for CFS. The company is Oncore Analytics, Inc., and the test measures the anti-viral pathway. The Oncore test is performed on a blood sample.
The virus that causes CFS has not yet been identified and, in fact, there are still researchers and clinicians who do not believe that a virus -- or any infectious agent -- causes CFS. If the Oncore test, which measures a defect in an anti-viral pathway, is capable of reliably separating CFS patients from healthy people, that would be another piece of evidence suggesting that CFS is caused by a virus.
Mycoplasmas are extremely small bacteria, and are perhaps the smallest self-sufficient organisms that exist. Mycoplasmas can cause human disease -- particularly pneumonia and a type of urinary tract infection -- but have not been considered to be major human pathogens. Since 1986, however, there has been speculation that a newly-discovered type of mycoplasma may be involved as a co-factor in causing AIDS and, perhaps, even CFS.
The new mycoplasma was discovered in AIDS patients by Dr. Shyh-Ching Lo at the Armed Forces Institute of Pathology. The mycoplasma appears to invade many internal organs -- kidneys, spleen, brain, liver -- and causes the organ tissue to die.
While Dr. Lo's suggestion that the mycoplasma might play some role in causing AIDS is controversial, Dr. Luc Montagnier, the Pasteur Institute researcher who discovered HIV, the "AIDS virus," has found the same kind of mycoplasma infecting French AIDS patients. Dr. Montagnier, like Dr. Lo, believes that this mycoplasma may play an important role in causing AIDS.
And Dr. Lo has been able to accomplish with the mycoplasma what no scientist has been able to do using HIV: Dr. Lo has taken mycoplasma from AIDS patients' tissues, injected them into animals, watched the animals die of a wasting illness that resembles AIDS, and then re-isolated the mycoplasma from the animals' tissues.
In other words, Dr. Lo has created a classical animal model for the mycoplasma-caused illness. Such an animal model does not exist for HIV and AIDS; no animal has ever been made to develop an AIDS-like illness after being infected with HIV.
Dr. Lo also found the new mycoplasma in a number of non-AIDS patients -- previously healthy people who died very suddenly following a flu-like illness. These cases prove that this particular mycoplasma can infect people who do not have AIDS.
Fortunately, mycoplasma can be controlled by readily-available antibiotics such as doxycycline or tetracycline. The fact that many CFS patients report that their symptoms improve when they take doxycycline causes Dr. Lo to suspect that the mycoplasma may be involved in causing some cases or symptoms of CFS.
Unfortunately, Dr. Lo's work is still very much in the research stage, and a diagnostic test for the mycoplasma is not readily available. But if a physician suspects a CFS patient may be infected with the mycoplasma, it is safe to treat the patient with an anti-mycoplasma antibiotic, just in case, according to Dr. Lo.
Some CFS patients report considerable improvement in their symptoms when they take antibiotics. "The burning feeling in my spine and head disappear," CFS patient "Ruth" told me, when she takes ciprofloxacin, an antibiotic. She added, "The joint pain -- especially the neck pain -- goes away, and I am able to think clearly when I take ciprofloxacin."
Cells called monocytes are an essential part of the immune system. Monocytes are found in the circulating blood, and they perform a variety of functions: They ingest and kill invaders, they communicate with other immune system cells to indicate when an immune response should be mounted, and they make a number of enzymes that are essential to properly functioning immunity.
Monocytes are the precursor cells to another very important type of immune system cell called macrophages. Macrophages are essentially the mature forms of monocytes; they are found situated in organ tissues (rather than in the blood, like monocytes). Macrophages perform basically the same functions as monocytes.
Like just about every other cell in the immune system, monocytes do not work properly in CFS patients. Some research teams have found that about half of CFS patients have monocytosis, in which too many monocytes are produced. When there is an excess of monocytes, there can be an excess of the lymphokines that the monocytes produce; these lymphokines can make patients feel very sick.
Additionally, a Spanish research team from the University of Navarra, in Pamplona, studied monocyte function in CFS patients and found it to be disturbed in a large percentage of patients. The Spanish researchers examined the delicate fibers on the surfaces of monocytes and macrophages, called "vimentin filaments," that are thought to help the cells move about in the body and to play a role in immune responses.
When the monocytes and macrophages of CFS patients were compared to those of healthy people, the Spanish scientists found a "marked reduction" in the vimentin filaments. Consequently, they found, the monocytes and macrophages of CFS patients are quite dysfunctional.
In fact, 30 of 35 people who fit the U.S. CDC criteria for CFS (six men and 29 women who ranged in age from 19 to 51) had, according to the Spanish research team, "monocyte dysfunction."
The balance maintained between the interacting parts of the immune system appears to be extraordinarily delicate, we are learning as scientists unravel more and more of its mystery. What is becoming clear is that it's possible for one part of the immune system to be over-stimulated at the same time as other parts are depressed.
In CFS, the immune system cells called T-cells are often over-stimulated; this state is called "T-cell activation." Research has shown that, when T-cells are activated, they make immune system chemicals called cytokines; interleukin and interferon are examples of cytokines. When the T-cells make excessive amounts of cytokines, they can actually cause symptoms similar to those seen in CFS.
Fever, swollen glands, sore throat, aching muscles and joints, sleep disturbance, and even psychological symptoms can be caused by excessive amounts of cytokines.
Dr. Paul Cheney, who was one of the first physicians to recognize CFS in the U.S. -- and who has a number of CFS patients who can be designated "non-HIV AIDS cases" because they have very low T4 cell counts -- explains it this way: The sicker his patients feel, the more T4 cells (which are also called CD4 cells) they have. The less sick the patients feel, the lower their CD4 cell counts are.
Dr. Cheney says that the notion of "sick" is used differently with respect to AIDS and CFS patients.
"Sick is a semantic term in the sense that it implies different meaning in CFS than it does in AIDS," Dr. Cheney says. "We have sort of defined AIDS patients as what happens to them, and when bad things happen to them, they have low CD4 counts. CFS patients feel bad all the time, and their CD4 counts are actually high."
Dr. Cheney blames his sickest patients' symptoms on having activated T-cells. "It will make you royally sick" to have activated T-cells, he points out. "And, I'll tell you, the sickest people I have, the people who come in here who are really, really, sick, they'll have CD4 counts of 2,000," which is about twice as high as normal. "And the cytokines that are being expressed, of course, typically cause CD4 cell proliferation" -- so the T-cells, which are already too high, increase even more. This is the type of T-cell malfunction that can occur when the immune system is over-stimulated.
But Dr. Cheney also has CFS patients with very low CD4 cells counts; so low, in fact, that they can be diagnosed as being "non-HIV AIDS," or ICL, cases. Dr. Cheney believes that both sets of patients -- those with high CD4 cell counts and those with low CD4 cell counts -- have CFS. He thinks that the patients with the low T4 cell counts, however, are in "a different state" from other CFS patients.
Dr. Cheney says that his CFS patients who have fewer than 200 CD4 cells -- a level that is considered very dangerous for AIDS patients -- are "not feeling so good." He also points out, however, that those patients who have CD4 counts between 300 and 500 typically don't feel too bad, even though 1000 T4 cells is considered "normal."
"Looking at this group as a whole, the patients with low CD4 counts are relatively less sick -- less symptomatic, I should say," Dr. Cheney says. "Their symptoms aren't as severe. They seem to be more stable. If I had to guess what is happening, I think what is happening is that you are looking at the same disease in two different states."
One of those states is "up-regulated," in which the T-cells are activated and producing large amounts of cytokines; the other is a state of down-regulation, in which even the numbers of immune system cells drop.
Sometimes increased amounts of certain cytokines can cause the depression of some types of immune system cells. One of the cytokines that is elevated in CFS, for instance, is interleukin 1 (abbreviated IL-1). IL-1 has been shown to cause other parts of the immune system -- like natural killer cell activity -- to be suppressed. This is only one example of how an elevation in one part of the immune system can cause the depression of another part.
Dr. William A. Carter is a Professor of Oncology and Hematology at Hahnemann University in Philadelphia. He is also the co-developer of an experimental drug called Ampligen, which has shown promise in treating both Chronic Fatigue Syndrome and AIDS, and is currently under review by the Food and Drug Administration. At a conference held in late 1991, Dr. Carter discussed a clinical trial of Ampligen and explained that he thinks CFS could be called "lymphokine overdose disease."
Lymphokines are substances produced by white blood cells (also called lymphocytes) when the immune system encounters an invader. They include the interferons (alpha-, beta-, and gamma-interferon), the interleukins (there are at least 12 interleukins), tumor necrosis factor, and others. Most lymphokines stimulate cells to do something: either to reproduce themselves (interleukin-2 used to be called "T-cell growth factor," for instance), or to interact with other components of the immune system (gamma-interferon works in this way).
When Dr. Carter made his 1991 presentation at the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy, he was also interviewed by the on-site Conference Journal. The lymphokine that Dr. Carter spoke about in his interview was interleukin-1 (IL-1), the primary action of which is to stimulate cells to produce interleukin-2 (IL-2).
Dr. Carter told the Conference Journal that his research group had determined that more than two-thirds of CFS patients have abnormally high levels of lymphokines; because of that, he suggested that CFS might more appropriately be named "lymphokine overdose disease."
According to Dr. Carter, many of the symptoms of CFS -- such as fatigue, memory loss, and other problems with thinking -- are probably caused by the high levels of lymphokines that patients are making in their own bodies.
CFS patients who have very high levels of IL-1 responded well to Ampligen treatment, Dr. Carter told the Conference Journal. Just as importantly, the patients in Dr. Carter's study who had high levels of IL-1 and who received a placebo (inert, or phony) substance instead of Ampligen got progressively worse.
One of the most disturbing findings made by Dr. Carter and his research team was that CFS patients with abnormally high levels of IL-1 had "anatomic holes" in their brains that were detected by using brain scans. It was not clear to the research team whether the holes were reversible or permanent.
From this information, Dr. Carter and his colleagues concluded that IL-1 is important in causing the symptoms of CFS, particularly the mental symptoms. Dr. Carter said that increased IL-1 could be used as a "footprint" to help diagnose severe CFS.
Tumor Necrosis Factor, TNF, was one of the first lymphokines to be discovered. Lymphokines -- also called cytokines -- are chemicals that are produced by immune system cells; they help different kinds of cells to communicate with each other in mounting immune responses.
TNF is produced by the immune system cells called macrophages, and was named "Tumor Necrosis Factor" because it was observed to make cancer cells die. TNF is also primarily responsible for causing the extreme weight loss observed in people with cancer and AIDS.
TNF has been found by some researchers to be increased in CFS patients. Other lymphokines -- gamma-interferon, interleukin-2, and interleukin-6, for example -- have also found to be increased in CFS. But some researchers have found these same lymphokines to be decreased in CFS, pointing out once again that a malfunctioning of the immune system can result in contradictory information being gathered.
Whether these cytokines are produced at increased or decreased levels in CFS, it is clear that their normal production is disturbed in these patients. Also, because different lymphokines and various types of immune system cells interact with each other in not-yet-understood ways, it's not clear exactly why CFS patients have abnormal amounts of TNF and other cytokines.
TNF has also been observed to cause HIV to reproduce at higher levels than it normally does. For that reason, Dr. Jay A. Levy, a prominent AIDS researcher in California, has suggested that AIDS is primarily a TNF disease. Dr. Levy has also suggested that, if TNF levels were decreased, a lot of the symptoms and illnesses seen in AIDS patients would disappear.
Interestingly, an experimental drug that has shown promise in treating both AIDS and CFS, Ampligen, has been shown to lower TNF levels, as well as improving symptoms.
Zinc is a trace mineral that is very important in maintaining a healthy immune system. But as many as 85 percent of CFS patients may have a serious zinc deficiency, which is extremely common among AIDS patients as well.
Zinc is perhaps the most important "growth factor" in the human body; any cells that are rapidly reproducing -- such as those involved in healing wounds, immune system cells that are actively fighting infections, and growing fetuses -- require a steady supply of zinc. Zinc deficiency in a pregnant woman can cause very serious birth defects in her child. The most dramatic birth defect caused by zinc is an encephaly, in which a child is born with only part of a brain, or actually no brain at all.
Zinc deficiency can also cause stunted growth (in children), skin lesions, hair loss, and increased susceptibility to infections because of impaired immunity.
A physical sign of zinc deficiency -- which is, according to some researchers, found in a large number of CFS patients -- is white spots on the finger nails, a condition called "leukonychia." Some CFS researchers have reported that a large majority of their CFS patients exhibit the white spots on their fingernails that are indicative of zinc deficiency.
Zinc deficiency may be responsible for another symptom of CFS -- alcohol intolerance. Many CFS patients are unable to tolerate alcohol. Zinc is responsible for helping to form the enzyme that breaks down alcohol, called alcohol dehydrogenase. Too little zinc may lead to insufficient production of alcohol dehydrogenase and, therefore, to alcohol intolerance.
Zinc deficiency, then, may not only contribute to lowered immunity and birth defects among CFS patients and their children, but also to the alcohol intolerance that is often a symptom of the disease.
Magnesium is a trace element that is necessary for the activities of many enzymes; serious deficiency can cause vascular problems, convulsions, tremors, depression, and psychotic behavior. In 1990, a British research team discovered that not only did CFS patients have a deficiency of magnesium in their red blood cells, but that magnesium injections actually helped some symptoms to improve.
In the British study, 35 CFS patients were divided into two groups. One group received a magnesium injection once a week for six weeks; the other group received a placebo injection (in this case, sterile water) once a week for six weeks.
At the end of the study, the patients who were treated with magnesium had much greater improvement in energy, pain, and emotional reactions than the placebo group did.
The British investigators concluded that, while magnesium may not be a cure for CFS, it could prove to be helpful in treating some symptoms of the syndrome.
The U.S. government's leading Chronic Fatigue Syndrome researcher, Dr. Stephen Straus at the National Institute of Allergy and Infectious Diseases, has for several years wasted a great deal of the government's resources by attempting to prove that CFS is a psychiatric illness, similar to depression. In one recent study in which he compared certain hormonal levels in CFS patients to those in people with depression, however, Dr. Straus uncovered a hormonal abnormality that contradicted his own theory.
Dr. Straus, working with researchers at the National Institute of Mental Health and the National Institute of Child Health and Human Development, found that CFS patients have decreased amounts of a hormone called cortisol, which is part of the natural "fight or flight" response.
CFS patients also have decreased amounts of the hormone that instructs the brain to produce cortisol, which is called CRH (which is short for "corticotropin releasing hormone").
Interestingly, cortisol deficiency is also one of the most common hormonal abnormalities seen in AIDS.
Both cortisol and CRH deficiencies can cause lethargy and fatigue. Therefore, Dr. Straus and his colleagues suggested that the CRH and cortisol deficiencies together, or either deficiency alone, could contribute to causing some of the symptoms of CFS.
In the course of this study, however, Dr. Straus inadvertently disproved his hypothesis that CFS is a form of depression. The cortisol and CRH levels found in patients with depression are actually opposite to those found in CFS patients: People with depression have increased amounts of both CRH and cortisol.
Although Dr. Straus's hormone study contributes to our understanding of one system that doesn't work in CFS, it unfortunately doesn't help in finding a treatment or cure. Because of the complex way in which hormonal systems interact, giving CFS patients extra cortisol would signal the body that it isn't necessary to make more cortisol. This could actually worsen the deficiency.
In spite of government documents acknowledging that cortisol treatment of CFS patients could be dangerous, Dr. Straus has proposed a clinical trial to treat CFS patients with compounds like cortisol.
Dr. Straus's possibly dangerous plan to treat CFS patients with steroids like cortisol fails, also, to take into account the fact that the growth of Human Herpes Virus 6 (as well as other viruses) is stimulated by such drugs.
If HHV-6 is causing CFS by growing out of control, cortisol treatment might actually worsen the illness in ways that we don't even understand yet.
A medical bulletin broadcast on the Cable News Network (CNN) in early 1993 reinforced the point that treatment with steroids such as cortisol can have unexpected negative side effects. CNN broadcast a report about a young boy whose asthma was being treated with steroids (like cortisone) when he contracted a mild case of chicken pox.
Chicken pox is caused by a herpes virus called Herpes zoster. Although it is a childhood illness from which most people recover with no deleterious after-effects, this particular young boy actually died from his chicken pox.
The reason he died, according to the CNN report, was because the steroid being used to treat his asthma caused the Herpes zoster virus to grow out of control and kill him.
A Long Island physician who studies CFS, Dr. Burke A. Cunha, has discovered what he calls "crimson crescents" in the throats of CFS patients. The crescents are so distinctive that Dr. Cunha believes that their presence indicates that CFS is present, even if the physician (or the patient) observes no other indication of the syndrome. Even more intriguing, Dr. Cunha has found that the crescents are associated with high levels of Human Herpes Virus 6 (HHV-6), a virus that is found to be actively growing in AIDS and CFS patients.
Dr. Cunha described his finding in a medical journal, and in November 1992, it was the cover story of the Infectious Disease News, a newsletter for primary care physicians. The crescents are described as being "crimson purple," and looking like half of a crescent moon.
Dr. Cunha says the crescents occur in 80 percent of CFS patients.
After he reported his finding in the Annals of Internal Medicine, Dr. Cunha says he received calls from physicians all over the country. They told Dr. Cunha that, once they knew to look for the crescents, they were also finding them in their CFS patients.
Dr. Cunha thinks that many physicians may not have seen the crescents because they occur on both sides of the back of the throat, behind the back molars. Most physicians, Dr. Cunha remarked to Infectious Disease News, don't really look at the sides of the throat.
Dr. Cunha is convinced that the crimson crescents are highly correlated with CFS. "If your patient has crimson crescents, you can now say it is probably chronic fatigue syndrome," Dr. Cunha told Infectious Disease News.
Dr. Cunha also said, however, that he has found the crimson crescents in three to five percent of all patients who complain of sore throat -- which may mean that the number of people who have CFS has been grossly underestimated. The crescents have not been seen in patients with other illnesses that produce sore throats, such as mononucleosois, strep throat, cytomegalovirus infection of the throat, or common viral sore throat.
Dr. Cunha thinks that the crescents may occur in CFS patients because they are caused by the active HHV-6 found in the patients.
"I believe that the virus that causes chronic fatigue comes from young adults or children who give it to adults," Dr. Cunha told Infectious Disease News. "...I don't know why there is a difference, but the children do not have chronic fatigue. HHV-6 is a virus of children, and it may manifest as chronic fatigue in adults."
Dr. Cunha is trying to culture HHV-6 out of the crescents, but he has found that laboratories that perform throat cultures usually do not have the facilities to detect HHV-6, which is a fairly new human virus. To try to find HHV-6, he plans to perform biopsies on the crescents, Dr. Cunha told Infectious Disease News.
Dr. Cunha also pointed out that increased HHV-6 and decreased natural killer cell activity are the two most consistent laboratory findings in CFS. He thinks that the presence of the crimson crescents by themselves, however, are evidence enough that CFS is present.
"If you are a physician out in the middle of nowhere and you can't get HHV-6 titers and you can't get the natural killer cell percentage, then the crimson crescents may be the only way besides history that can suggest the diagnosis" of CFS, Dr. Cunha told Infectious Disease News.
The "crimson crescents" identified in the throats of CFS patients by Long Island physician Burke A. Cunha are, he has pointed out, closely associated with increased antibodies to Human Herpes Virus 6 (HHV-6). Dr. Cunha's description of these crimson-to-purple crescents suggests that they may be manifestations of Kaposi's sarcoma (KS), a type of lesion or tumor seen in AIDS. A finding that strengthens this possibility is that HHV-6 has recently been found in Kaposi's sarcoma tissue. That fact raises several questions: Is HHV-6 the cause of KS? And, given that increased antibodies to HHV-6 are closely associated with the crimson crescents of CFS, are those lesions caused by the virus? And, most importantly, are the "crimson crescents" of CFS actually a form of KS lesion?
Although the conventional wisdom about AIDS says that KS develops only in certain "risk groups," such as gay men, autopsies have shown that greater than 94 percent of all AIDS patients have some form of the tumor-like growths in their internal organs. Experts have agreed that, since KS can occur in many different physical forms internally and externally (on the skin), the possibility exists that the crescents are a type of KS, which also varies in color from red or crimson to deep purple. That possibility should be easy to prove or disprove, once biopsies have been performed on a number of the crimson crescents; however, the research has not yet been performed.
The identity of the crimson crescents may also become mired in a dispute in the scientific community over the nature of KS itself. Some researchers believe KS to be a true cancer, manifest only in typical tumors (such as those observed on the skin). Others believe it is actually an overwhelming inflammatory response, occurring in numerous types of abnormal tissue responses, both in internal organs and on the skin. It does not appear that this dispute among scientists will be resolved any time soon.
Called a "neoplasm" -- which simply means a clump of growing cells -- most researchers agree that KS is not a typical cancer. It can produce lesions and tumors, both internally and on the skin, across a spectrum of different forms; other cancers usually manifest themselves in one particular form, such as breast cancer, for instance, which almost always forms a solid tumor.
In addition, the type of KS seen in AIDS is different from the generally harmless type of KS which was first described around a century ago in older, Mediterranean men.
And although KS in AIDS patients was initially believed to be caused by HIV, the "AIDS virus," numerous cases of AIDS-type KS have now been identified in HIV-negative people.
Speculation has abounded for several years that KS may be caused by a separate, as-yet-unidentified virus, but none has been discovered to date.
In May 1993, however, a research group from the University of Ferrara in Italy reported in the British medical journal The Lancet that they'd found HHV-6 in 35 percent of 20 biopsies of KS tissue. While more work needs to be done to verify this finding, the Italian scientists suggested that HHV-6's "possible contributions" to the development of KS should be investigated; in other words, they suspect that HHV-6 may be the long-sought-after cause of KS.
If the crimson crescents found in CFS patients, which are also associated with HHV-6, are found to be a form of KS, that would make it very difficult for anyone to argue that CFS and AIDS are unrelated diseases.
Tuberculosis is a sometimes-fatal illness that was all but eradicated before the AIDS epidemic began. It is possible for healthy people to become infected with the tuberculosis germ (a bacterium) without becoming sick; this is called a latent infection. But because people with AIDS do not have intact immune systems, they do become sick -- and, at the same time, are contagious to other people -- when they encounter the TB germ.
TB is of particular concern to public health officials because of the way it is spread, which is in saliva droplets that contain bacteria. While prolonged, close contact between people breathing the same air -- like people in jail -- is usually required for TB to spread, it is more casually contagious than almost any other equally serious illness.
And people whose immune systems aren't functioning properly -- like AIDS and CFS patients, as well as cancer patients -- become infected, and sick, with tuberculosis much easier than healthy people.
The natural killer (NK) cells are a front-line defense against other cells infected with TB germs but, in both AIDS and CFS, the NK cells don't work properly.
Ironically, new studies have shown that NK cells do not function properly in people who have TB. Therefore, the very cells that should be protecting the body against the TB infection are made less effective by that infection.
Therefore, a person whose NK cells were not working well in the first place can become very sick, very fast, from TB.
Most people are aware by now that AIDS patients are particularly vulnerable to TB. What isn't commonly known is that CFS patients are also more susceptible to TB than are healthy people, according to the Associate Director of the Centers for Disease Control and Prevention Tuberculosis Division, Dr. Donald E. Kopanoff.
Dr. Kopanoff told Spin magazine in December 1991 that CFS patients, because they are in generally poor health, are at much greater risk for contracting active TB than the rest of the public.
Another part of the immune system that doesn't work properly in CFS patients is the cell-mediated immunity; this is the type of immunity that is controlled primarily by T4 cells. Both CFS and AIDS patients sometimes have severely decreased numbers of T4 cells, which is partially why their cell-mediated immunity doesn't work.
The cell-mediated immunity produces the type of immune response that causes a bump to rise at the site of a skin test for TB (and other diseases, as well). If the cell-mediated immunity is not working properly, no bump is formed at the site of the test, even if the person is infected with TB.
Therefore, when the immune system is not functioning properly, there is no easy and reliable way to distinguish infected from uninfected individuals. The millions of people suffering with CFS all over the world could turn TB into a disaster of enormous proportions, which is another reason patients should demand that the truth be told about this epidemic.
It has been known for some time that CFS patients have abnormal blood flow in their brains; that is, some areas of the brain are not getting as much blood as they should. Very recently, however, studies of patients with AIDS dementia have shown that they, too, have abnormal brain blood flow, raising the question of whether a similar disease process is taking place in both sets of patients.
It has only been possible to measure blood flow in the brain with the development, over the last few years, of very specialized types of brain scan technologies. One type of brain scan that can detect blood flow abnormalities is called SPECT (which stands for "single photon emission computer tomography").
Dr. Ismael Mena has studied CFS patients' brains using SPECT scans at the University of California-Los Angeles, where he is a professor of radiology. Over several years' investigation, Dr. Mena has consistently reported that 71 percent of CFS patients have a diminished flow of blood in their brains.
Dr. Mena has also commented, at scientific conferences, that CFS patients do not have equal blood flow on the two halves of their brains. That is, when the blood flow on the right and left sides (or hemispheres) of the brain were compared in individual CFS patients, the flow in the two halves of the brain can differ by twice as much as they do in healthy people.
This information suggests that some type of organic brain disease may be a component of CFS. While it has long been recognized that AIDS patients can develop very serious mental problems, sometimes labeled "AIDS dementia," only recently have such patients been studied using SPECT scans. The similarity between "AIDS dementia" patients' SPECT scans and those of CFS patients are striking.
SPECT scans in AIDS patients were discussed at the 1992 international AIDS meeting (in Amsterdam) by a research team from the Houston Immunological Institute. Rather shockingly, they found that exactly the same percentage of AIDS patients -- 71 percent -- as CFS patients had abnormalities in brain blood flow. The Houston research team also found that more severe cases of AIDS dementia showed greater abnormalities in brain blood flow, and they suggested that SPECT scans could provide a very important diagnostic tool for physicians treating patients with AIDS.
Abnormal SPECT scan results have not yet been firmly associated with any of the mental abnormalities -- short-term memory loss, for instance, or difficulty concentrating -- observed in CFS patients. But as this still-new technique becomes more refined, it may well help unlock some of the mysteries of the mind associated with not only CFS, but also AIDS.
People who have CFS sometimes experience a dramatic weight loss or gain. Many women CFS patients I've spoken to have gained a significant amount of weight since becoming ill. This may be due to lack of exercise, or possibly even to the as-yet-not-understood hormonal problems associated with CFS.
Another possible explanation for CFS patients' weight gain is that organic changes occur in the brain. The central nervous system, directed by the brain, governs metabolism -- how fast calories, and stored fat, are burned. Changes in the brain waves, sugar metabolism, oxygen flow, and even in the physical appearance of the brain have been documented in CFS patients. It is possible that virus-induced changes in the brains of CFS patients also affect their metabolism, and thereby result in weight gain.
Significant weight loss, however, can also be a component of CFS. One patient I interviewed, a young man named Al, lost 55 pounds in just one year. His weight loss was so precipitous and unexpected, Al told me, that his doctor concluded that he must have either cancer or AIDS.
In AIDS, weight loss is often caused by an overproduction of tumor necrosis factor (TNF). If CFS, like AIDS, turns out to include a major disruption in the production of TNF, that may explain why patients lose weight at certain stages of the illness.
The fluctuation in weight experienced by CFS patients, however, is yet another example of how major systems are dysfunctional -- sometimes overactive, sometimes underactive -- in the syndrome.
Nearly all CFS patients have problems with balance and equilibrium, either occasionally or constantly. It is not known what causes these or other nervous system problems in CFS, or how to cure them.
One patient I interviewed, Al, told me that his dizziness was so pronounced, at times, that the sidewalk he was walking on appeared to be tilting up to meet him.
When this happened he would fall down, and be unable to get up or walk until the dizziness passed.
Balance can be tested very simply by any physician, and CFS re searcher Dr. Paul Cheney performs this test on his patients: The patient stands, feet together, arms at the sides, and closes his or her eyes.
"Then," Dr. Cheney told me, "they fall over." This type of imbalance is very common among his CFS patients, Dr. Cheney says.
AIDS patients can suffer very similar balance disturbances and dizziness, and even have seizures (which CFS patients can also experience). Headache, memory loss, confusion, and weakness of the limbs are other neurological problems that can develop in both CFS and AIDS.
Whatever the exact cause of the balance problems in CFS, it is clear that the central nervous system is very seriously affected by this syndrome.
Infected or inflamed sinus passages, or sinusitis, can become a chronic ailment in CFS patients, as it can in AIDS patients. Like many other aspects of CFS, no formal studies have determined what percentage of CFS patients develop chronic sinusitis. California researcher Dr. Carol Jessop has noted, however, that 40 percent of her CFS patients develop recurrent sinusitis, with bronchitis -- an inflammation of the air passage in the lungs -- developing in 30 percent.
Since as many as 90 percent of CFS patients report having some type of allergy problems, it is perhaps not too surprising that many would also develop chronic sinus problems.
Sinusitis can, in fact, be one of the first signs that CFS is developing.
Sinusitis is also often a major problem for AIDS patients. As the immune system becomes increasingly more depressed, it is less able to destroy the bacteria and other organisms that are inhaled with every breath of air. Pneumocystis carinii infection, which usually occurs in the lungs and causes pneumonia (commonly called PCP), can also occur in the sinuses. There is also the possibility that the sinus pain experienced by AIDS patients can be due to Kaposi's sarcoma, or lymphoma, or another kind of tumor.
After a steady decline over several years in deaths caused by childhood asthma, the number rose again sharply in the early 1990s. In March 1991, in fact, the National Institute of Allergy and Infectious Diseases funded a National Cooperative Inner-City Asthma Study to attempt to prevent the soaring number of asthma deaths.
In early 1992, a study published in the New England Journal of Medicine noted that Americans spent about $6.2 billion on asthma-related health care in 1990.
Is the CFS epidemic responsible for at least part of the rise in asthma, particularly childhood asthma, in the U.S.?
Asthma is caused by a temporary blockage of the airways in the lungs; the airways typically are blocked by an inflammatory response of some type (such as an allergic response) that can cause swelling in the airway, or by accumulation of excess mucous.
Dr. David Bell studied an outbreak of CFS in Lyndonville, New York, in which a number of children developed the syndrome. He found that more than half of the 74 children involved in the outbreak had allergies and/or asthma before developing CFS.
CFS, however, made these children's allergies/asthma worse, according to Dr. Bell. Half of those who had allergies/asthma before they developed CFS told Dr. Bell that their symptoms clearly worsened after they contracted CFS.
Five percent of the children involved in the outbreak who had never had allergies or asthma developed symptoms after being stricken with CFS.
No one knows why asthma and asthma-related deaths among children are rising. But, given that allergies and other inflammatory responses are so common among CFS patients (in both children and adults), the possibility that the CFS epidemic may be contributing to the rise should be investigated.
Endometriosis, a painful condition in which the tissue lining the inside of the uterus (the endometrium) migrates outside the uterus, appears to occur in much higher rates in women with CFS than it does in otherwise healthy women.
The endometrial tissue can migrate to any location in the body once endometriosis begins, but it is often found on the surfaces of organs and structures nearest the cervix, or entrance to the uterus: the bowel, bladder, fallopian tubes, ovaries, the uterine surface, and on the surfaces of the supporting tissues.
The most common symptoms of endometriosis are pain during menstruation (often a dull, persistent pain that seems to be located in the lower back), irregular or heavy menstrual bleeding, pain during sexual intercourse, and infertility.
The cause or causes of endometriosis are unknown.
A Long Island physician who has a large number of CFS patients in his practice, Dr. Perry Orens, believes that there is definitely an increased rate of endometriosis among women CFS patients. Dr. Orens believes that there is an as-yet-unidentified hormonal component in CFS that is causing the increased incidence of endometriosis. This hormonal component of the disease, Dr. Orens also believes, may explain why more women than men have or appear to have -- or at least are diagnosed with -- CFS.
Other researchers have reported that as many as 30 percent of female CFS patients have endometriosis.
The effect of pregnancy on CFS patients varies widely, as do many other aspects of the illness. Some physicians report that their pregnant patients feel much better than they did before they became pregnant; others report serious problems during or following pregnancy, for both mother and child. Since CFS patients are not routinely staged -- that is, there are no accepted guidelines to measure the length or severity of their illness -- these discrepancies may reflect what happens to women who become pregnant in different stages of CFS.
Dr. Paul Cheney, for instance, reports that he has seen some pregnant patients whose symptoms improve dramatically. Dr. Cheney suggests that this might be because of the action of the placenta, the umbilical cord that connects mother and fetus. Not only nutrients, but also blood, with all of its immune system components (like cells, lymphokines, antibodies, etc.), flow through the placenta. Dr. Cheney points out that one action of the placenta is to down-regulate the mother's immunity, so that the mother's immune system does not identify the fetus as something "foreign" that should be destroyed.
On the other hand, some researchers have found that certain problems associated with pregnancy -- like morning sickness -- and fertility can be worsened in CFS patients. California researcher Dr. Carol Jessop has found, too, that the incidence of miscarriage was somewhat higher than normal among her CFS patients.
The most disturbing information about CFS and pregnancy, however, comes from Canadian researcher Dr. Byron Hyde. At a research conference in 1991, Dr. Hyde discussed some women patients who did not have CFS until after they became pregnant. These patients gave birth to babies who died shortly after they were born, because they had what Dr. Hyde described at a research conference as "major, major birth defects" -- such as being born with serious heart defects, or without brains (which is called "anencephaly").
Dr. Hyde has urged that these very serious effects on pregnancy should be studied far more intensively than they have been to date.
Because the majority of patients first diagnosed with CFS were women, little attention has been paid to the problems that are unique to men with the disease. But one such problem is prostatitis, an infection and swelling of the prostate gland, which is instrumental in the production of semen (the fluid containing sperm). This symptom may parallel the recurrent urinary infections and reproductive/endocrinological problems (like premenstrual tension and endometriosis) that many women with CFS suffer.
Dr. Carol Jessop, who studies CFS in San Francisco, says that prostatitis, along with sinusitis, is the most common recurring infection she has observed in men with CFS.
It is not clear what is causing the prostatitis seen in men with CFS, but there are indications that it may be in some way infectious, or caused by an infectious agent. A CFS patient I interviewed, "Susan," told me that, after she developed CFS, her boyfriend developed a prostate infection that did not respond to standard treatment. Not only did Susan's boyfriend develop a refractory prostatitis, but so did a number of his male friends with whom he spent a lot of time, according to Susan.
Because CFS patients' natural killer cells -- which protect against both viral infections and some kinds of cancers -- do not work properly, it is possible that men with CFS are also more prone to developing prostate cancer, as well as prostatitis. Like many aspects of CFS, however, this possibility has not been the subject of a formal study.
A relatively high percentage of CFS patients develop of type of heart murmur called "mitral valve prolapse." Like many other aspects of CFS, this phenomenon has not undergone rigorous study; anecdotally, however, many patients and physicians have noted the prevalence of mitral valve prolapse among CFS patients.
This kind of heart murmur occurs when one of the valves in the heart (the mitral valve, which is on the left side of the heart) collapses to a certain degree (which varies from person to person). In minor cases, mitral valve prolapse can cause little more than a distinctive clicking sound heard when listening through a stethoscope. But in severe cases, mitral valve prolapse can cause chest pain, fatigue, heart arrhythmias -- typically, causing the heart to beat too fast -- or even sudden death.
It is not known why heart problems develop in some CFS patients, and many U.S. researchers doubt that they are connected to CFS. But Dr. Byron Hyde, who studies CFS in Toronto, commented at a 1991 research conference that the heart problems associated with CFS are "major." Dr. Hyde also pointed out that no one in North America is studying this potentially life-threatening aspect of the disease, a statement which is still true today.
Heart failure, however, is a fairly common cause of death in AIDS, and the heart can be affected by a number of problems encountered by AIDS patients. For instance, Kaposi's sarcoma has been found in heart tissue, as well as the tissue that covers the heart. KS has also been found in the aorta, and on the arteries that feed the heart itself.
Additionally, for unknown reasons, heart tissue may simply die in AIDS, a condition called "acute myocardial necrosis" that is fatal.
Viruses can attack the heart, especially the tissue around the outside of the heart muscle, and cause a condition called "endocarditis." It would be useful to determine if viruses that are active in both CFS and AIDS patients -- especially HHV-6 -- are capable of causing some of the heart problems found in both syndromes.
Bruises are caused by the collection of blood under the skin, usually resulting from some kind of trauma that causes superficial blood vessels to break. There is variability in how easily people bruise, of course, just as there is in how easily they sunburn. But when a person begins to bruise much more easily than he or she ever has before, it can be the sign of a serious immunological disease, like some forms of cancer (such as leukemia), CFS, or AIDS.
CFS patients sometimes find that they bruise more easily after they become sick. One reason for that can be the development of a condition called "thrombocytopenia," which is a blood clotting disorder. One reason that some CFS patients may develop thrombocytopenia and easy bruising is because they have decreased numbers of the blood cells most directly responsible for causing blood clots, called platelets.
Thrombocytopenia was recognized very early as an indication that AIDS might be present. In a 1984 physicians' handbook, AIDS: A Basic Guide For Clinicians (published by the W.B. Saunders Company), thrombocytopenia is listed along with fever, weight loss, fatigue, and swollen lymph glands as an indication to physicians that a patient might have AIDS.
A clue about why AIDS and CFS patients might develop thrombocytopenia emerged in mid-
1993, when Japanese researchers reported in the Pediatric Infectious Disease Journal that an infant with a severe HHV-6 infection had also developed thrombocytopenia. The Japanese researchers noted that HHV-6 is known to interfere with the differentiation of bone marrow cells, like those that develop into platelets. They suggested that the possibility that HHV-6 is directly responsible for causing thrombocytopenia in some cases, by infecting bone marrow cells and stopping them from developing into mature platelets, should be further investigated.
In another twist to the CFS story, some researchers hypothesize that CFS can be communicated between patients and their pets. It also appears that CFS patients' sick pets can develop clotting disorders reminiscent of thrombocytopenia.
In the Spring 1992 issue of the CFIDS Chronicle, which was entirely devoted to patients' letters and stories, a woman patient wrote about the illness and death of her dog, who suddenly became "strangely ill."
"Soon afterward, he began to suffer from nosebleeds, which in 1984 had been the prelude to the onset of my CFIDS," the patient wrote. The dog's condition continued to decline: He developed ulcers first in his mouth and around his eyes, then over his whole body, and "he grew unsteady on his feet, became dazed and disoriented," the patient wrote. The dog's laboratory tests showed "immune dysfunction, possibly due to a viral agent," according to this patient, who became convinced that her dog died from a bleeding disorder associated with CFS.
The fact that HHV-6 was isolated from a sick dog (which eventually died) belonging to a CFS patient suggests that this virus could be causing bleeding disorders in more than one species.
The soft tissues inside the mouth, particularly the gums, are quick to reflect ill-health. One reason for this is that the gums contain many blood vessels along which viruses and bacteria can travel. Gum disease, when it occurs in the absence of an obvious explanation (such as inadequate oral hygiene), can signal the presence of immunodeficiency, like that seen in CFS and AIDS.
One of the signs of impaired immunity that appears in both AIDS and CFS is oral thrush, which is an overgrowth of a common yeast, Candida albicans. Thrush is an "indicator" illness in AIDS; that means, if a person considered to be at "high risk" suddenly has thrush for no discernible reason, physicians usually consider the diagnosis of AIDS.
Oral thrush can also occur in CFS patients; in fact, Dr. Paul Cheney has said that oral thrush is "not uncommon" among CFS patients. To date, no formal study has determined exactly what percentage of CFS patients develop thrush.
Another condition that can signal immunodeficiency is a gum disease called gingivitis, a bacterial infection that causes gums to swell, turn red, and bleed (especially when the teeth are brushed). Some CFS patients can actually gauge the severity of their illness by the condition of their gums.
In 1991, the journal PAACNOTES, which is published by the Physicians Association for AIDS Care (based in Chicago), warned that the type of gingivitis developed by AIDS patients (called "ulcerative") is often unresponsive to typical treatment.
Additionally, the periodontal disease seen in AIDS patients -- which affects the jaw bone and can cause teeth to fall out -- can result in loss of 90 percent of the affected bone in as little as 12 weeks, according to PAACNOTES. The journal pointed out that, while some communities report that these gum diseases occur in a very small percentage of AIDS patients (as low as 10 percent), in other communities, they occur in more than 90 percent of AIDS patients.
In mid-1992, a research group at the University of California, San Francisco, reported at the international AIDS meeting held in Amsterdam that oral thrush is associated with AIDS progression and may be used to determine how rapidly a person's health may be failing -- an observation that may hold true for CFS patients, as well.
The nervous system symptoms experienced by CFS patients can be the most frightening: dizziness (also called vertigo) and visual problems such as blurred or double vision, as well as inaccurate depth perception, are extremely common. Transient, or temporary, blindness can occur in CFS. Like AIDS patients, CFS patients can develop "floaters" that obscure the vision and can be very distracting. These symptoms that impair vision may be the most hazardous to the health of CFS patients -- especially if they drive.
Patients have told me that they've sometimes become so confused while driving that they've had to pull over to the side of the road and rest before continuing. While it's not known for sure, it's possible that whatever is causing the visual and perceptual problems in CFS patients is also causing the mental confusion they sometimes experience.
For instance, researchers have found that CFS patients have real problems in processing information; they are unable to put pieces of information together properly. That can result in memory loss, as well as difficulty in judging both position and movement. For example, patients have told me that sometimes they feel so dizzy, they seem to themselves to be walking at an angle to the ground -- they really cannot tell whether they are standing upright or leaning at a slant.
For unknown reasons, the color vision of CFS patients can become quite disturbed. Also, they may lose their ability to see well at night, called "night vision." This can be especially dangerous for CFS patients who go out alone or who drive cars at night.
These perceptual problems may make even climbing stairs or taking an escalator, as well as crossing streets or actually driving a car, exceptionally dangerous for CFS patients while they are experiencing them.
And, of course, all these symptoms, as well as the general visual disturbances reported by patients, worsen with increased fatigue.
Just about every physician who cares for CFS patients mentions sleep disorder as one of the most important symptoms to control. Since fatigue can be overwhelming to CFS patients, sleep is critical to restoring what energy they possess. However, although they may sleep far more than they did before becoming sick, CFS patients often report that they wake up feeling just as tired as they did before sleeping.
Dr. Paul Cheney has characterized sleep as the single most important symptom to treat in CFS. Not only is sleep disorder one of the easiest problems to correct in CFS, according to Dr. Cheney, but he has found that CFS patients will not respond well to other treatments if they are not getting adequate sleep.
One possibile explanation for the unrefreshing sleep reported by CFS patients is that they have less dreaming, or REM, sleep time than healthy people.
REM sleep can be disrupted by many things. Nighttime twitching (seizures or ""fasiculations,'' abrupt movements of arms and legs) can interrupt REM sleep. So can pain upon movement, which many CFS patients experience at night.
CFS patients often have a body temperature that is slightly lower than that of healthy people and as a result, have colder extremities. If fingers and toes become too cold during sleep, they can become painful, and that pain can wake the patient.
Other kinds of pain -- like night time headache pain -- can wake the patient. So can frequent urination, which CFS patients -- particularly those prone to bladder infections -- tend to develop.
Breathing problems -- like sleep apnea, in which the person stops breathing for a short period of time -- can contribute to CFS patients' sleep dysfunction.
Nightmares can also disturb CFS patients' sleep. Although it is unknown what causes nightmares, and their significance in CFS is also unknown, many CFS patients report that their dreams have become more intense and more violent and disturbing since they became ill. Children with CFS have reported especially vivid nightmares.
Some researchers have suggested that the disturbed sleep patterns observed in CFS patients may be due to some abnormality in brain chemistry.
Dr. Byron M. Hyde, a physician who studies CFS in Ottawa, Canada, has suggested that major sleep disturbance may be one of the very first symptoms of CFS to develop.
The sleep patterns of CFS patients have also been studied extensively by another Canadian physician, Dr. Harvey Moldofsky, the director of the University of Toronto Sleep Disorders Clinic.
There are bizarre occurrences that can disrupt CFS patients' sleep, such as sudden, flashing lights in the eyes, which can also appear when the patient is awake, or increasingly vivid and disturbing nightmares. No one knows what these strange symptoms mean, what they are caused by, or if they really have anything to do with CFS.
Another reason that the sleep of CFS patients is disturbed is that they can suffer from night sweats, like AIDS patients. One study found that as many as 40 percent of CFS patients experience night sweats.
It is suspected that a person's quality of sleep may correlate with immune function, i.e. that poor quality of sleep may lead to impaired immune functioning. How disturbed sleep and immune dysfunction may be interacting in CFS is currently being studied by Canadian researchers. This research could also have important implications for those studying AIDS and other immune system disorders.
People with CFS have a variety of gastrointestinal problems: bloating, pain, constipation, and diarrhea. Often these symptoms are treated with an anti-ulcer drug named Tagamet, which has two primary actions: It blocks the action of histamine (a naturally-produced substance that governs the production of stomach acid, as well as some allergic reactions), and it stimulates natural killer cell activity. The fact that Tagamet can improve some CFS patients' symptoms rather dramatically has suggested to some observers that histamine may be very important in CFS.
But another gastrointestinal symptom suffered by CFS patients that has not received much attention is nausea. It appears, however, to be pretty common among CFS patients. Nausea can result from any number of causes, and no one knows what is causing it in CFS patients. It may be a side-effect of some kinds of neurological symptoms, such as dizziness but, to date, has not been studied in any systematic fashion.
One study found that 50-60 percent of CFS patients report nausea as a symptom. The same study commented that CFS can begin as something that resembles a "stomach flu," with nausea, fever, diarrhea, muscle aches, and fatigue.
Dr. Carol Jessop is a physician in San Francisco who has seen more than 1,000 CFS patients. At a CFS conference, Dr. Jessop commented that, among the patients she has seen, nausea appears to increase as patients are sick for longer periods of time. Dr. Jessop did not know how to explain this finding, but suggested that nausea be included as one of the criteria used to define and diagnose CFS.
Like AIDS patients, CFS patients can develop yeast infections in their mouths and throats, called "thrush." That localized overgrowth of a type of yeast that lives normally in people's gastrointestinal systems, called Candida albicans, can spread from the mouth into the rest of the gastrointestinal system in CFS patients, as it does in AIDS patients, if the immune system is depressed severely enough to allow the overgrowth to occur.
A serious bladder disease called "interstitial cystitis" appears to develop fairly frequently in CFS. Cystitis is an acute, bacterial bladder infection; the lining of the bladder becomes inflamed and scarred, resulting in diminished bladder capacity. Its symptoms include blood in the urine, as well as frequent urination with burning and pain.
Interstitial cystitis is extremely difficult to treat; the inner lining of the bladder can become extremely inflamed, even raw and scarred. The antibiotic treatments that cure most bladder infections generally do not work on interstitial cystitis.
Part of the problem is that the cause or causes of interstitial cystitis are not known. Auto-immune disease, allergies, stress, and chronic bacterial or viral infections are among the suspected culprits.
A few patients can experience a lessening of the symptoms of cystitis when treated with a blood-thinning chemical, heparin. It is not understood why this drug, most often used to prevent blood clots, has this effect.
CFS patients can develop a whole range of urinary tract problems, from inflammation to tender abdominal muscles to incontinence and, in male patients, chronic prostatitis and even sexual dysfunction.
While most of these conditions are treatable, the reasons why they develop remain mostly mysterious. They are probably due to CFS patients' immune systems being unable to fight off infection by common bacteria.
Antibiotic treatment can sometimes worsen CFS patients' bladder problems, resulting in yeast infections, similar to those that AIDS patients can develop.
One of the reasons that some doctors have trouble taking CFS seriously is because it appears to have a number of very strange symptoms; it is easy for physicians to dismiss a wide range of symptoms as being manifestations of psychiatric, rather than physical, illness.
One of those odd symptoms seen in CFS is finger swelling; finger swelling, however, has gained the
legitimacy of inclusion in the medical literature. A study of the 1984 Incline Village, Nevada, CFS outbreak that was published in a 1991 issue of Reviews of Infectious Diseases reported that finger swelling was observed in 30-40 percent of the patients studied. No explanation for this symptom was suggested by these investigators.
If inflammation and allergy are important aspects of the disease process of CFS, as it appears they might be, the finger swelling might be found to have a very simple explanation. Different kinds of allergies can cause localized swelling -- from contact allergies like poison ivy to food or drug allergies -- and the location of the allergic response doesn't always seem to make sense.
Fingers can swell so much that, not only do fingertips become smooth and sometimes shiny, the fingerprints can also disappear. This is a phenomenon that has been documented most closely by Dr. Paul Cheney, who has all of his patients go to the local police station to be fingerprinted.
There can be significant swelling of face, hands, and feet in CFS, much like that which is seen in lupus. Unfortunately, unlike lupus patients, CFS patients' swelling does not respond well if at all to steroid treatment.
One of the still-unexplained manifestations of CFS is the appearance of skin rashes. Rashes can have several causes; for example, they can be caused by allergic reactions, either by something that comes in contact with the skin (like poison ivy), or by something taken internally (like medicine or a food to which a person is allergic).
Rashes can be caused by infectious agents. The measles virus causes a very distinctive rash, as do Lyme disease and scarlet fever (both of which are caused by bacteria).
Rashes can also have emotional or psychological causes, because of the interaction between mind and body. Even anxiety can cause hives and other kinds of rashes.
No one knows what causes CFS patients to develop rashes, but they occur in about half of adult patients, commonly on the face and upper body.
For some unknown reason, rashes occur even more often in children with CFS than they do in adults. Dr. David Bell, who studied a group of children involved in a CFS outbreak in upstate New York, found that 80 percent of the children developed rashes.
Patients have described many different kinds of rashes to me. One reason that rashes might be so common in CFS is that allergies are worsened; people who had allergies before they developed CFS often find that their allergies are much more severe after they come down with CFS.
One reason for that might be the involvement of a naturally-produced chemical called histamine in CFS. Histamine, which is also increased in AIDS, controls certain kinds of allergic reactions as well as the production of stomach acid.
In addition to causing allergic reactions, histamine is also thought to bind to immune system cells and produce a substance that results in the suppression of the immune system.
So histamine production is another area which demonstrates how the immune system can be both up-regulated and down-regulated at the same time. While too much histamine can produce an allergic reaction -- which is an over-reaction of the immune system -- it can also cause the suppression of the immune system.
Another result of this general malfunctioning of the immune system is that unexpected bacterial and viral infections can appear. Acne, which can result from a bacterial infection, and the re-emergence of herpes virus infections -- like cold sores or shingles -- are examples of the kinds of infections that can occur when the immune system is depressed. AIDS patients, of course, develop the same kinds of bacterial and viral infections because of the down-regulation of their immune systems.
Numerous CFS researchers have reported that their adult patients can develop acne -- even patients who've never had skin problems before they became sick with CFS. Dr. Paul Cheney cautions that this type of acne, and other skin infections, may require more aggressive treatment in CFS patients than they would in healthy people for the treatment to be successful.
Herpes viruses live in harmony with people, generally speaking; once we become infected, the herpes viruses usually stay dormant, kept in check by an intact immune system. But when the immune system is damaged, as it is in CFS, herpes viruses can become reactivated and cause various kinds of skin (and other) problems.
One herpes virus that most people are infected with is herpes simplex, the virus that causes common cold sores. CFS patients sometimes have recurrent cold sores, which signal that the herpes simplex virus is no longer being controlled by their immune systems.
Another herpes virus, herpes zoster, causes chicken pox in children; later in life, it can become reactivated to cause shingles, a very painful skin condition in adults.
Both types of herpes virus reactivations -- cold sores (or other skin lesions caused by herpes simplex) and shingles -- can occur in adult CFS patients because of the "down-regulation" of their immune systems.
In children with CFS, chicken pox -- the childhood disease caused by the herpes zoster virus -- can be particularly troubling. Dr. David Bell has found that, among children with CFS whom he has studied, more than 80 percent had already had chicken pox before they contracted CFS. After developing CFS, however, about 12 percent of those children who'd never had chicken pox got the disease, and about 12 percent had it twice. Dr. Bell even found that one of those 74 children had chicken pox three times after developing CFS, and another had chicken pox five separate times after coming down with CFS.
An experimental treatment for CFS, Kutapressin -- which is an extract of pig liver -- has been found to be useful in treating herpes zoster-caused shingles. If Kutapressin stops the reactivation of herpes viruses, that may be why CFS patients' symptoms appear to improve when they are treated with the drug.
Hair loss can be caused by either severe or chronic illness, particularly when a high fever is present. Since as many as 60 to 90 percent of CFS patients have been reported to run fevers, perhaps it is not surprising that some find that their hair is thinning_or even falling out altogether.
Dr. Paul Cheney has reported that his CFS patients "usually" have brittle, thinning hair. CFS patients' hair sometimes also develops a reddish tint, Dr. Cheney says.
California CFS researcher Dr. Jay Goldstein has found that diffuse, or spotty, hair loss is one of the most common skin-related abnormalities in his patients. He suggests that this hair loss may be caused by hormonal imbalances, which can be treated with medications, usually steroids. In an article Dr. Goldstein wrote in the September 1992 CFIDS Chronicle, however, he pointed out that, "Some of my patients have had to buy wigs."
CFS patient "Nancy" told me that, when she was very sick with CFS, her hair became so thin that her hairdresser suggested that Nancy have her thyroid tested. Thinning hair can be indicative of severe thyroid deficiency, which CFS patients can develop.
"My hair was falling out in clumps," Nancy told me. "At its worst point, I looked like an AIDS or cancer patient who was undergoing chemotherapy. I had barely enough hair to cover my scalp in parts."
Like AIDS patients, CFS patients can test positive on an antibody test for syphilis -- even if they do not have the illness.
Why is that? Some researchers have suggested that CFS patients are experiencing what is called an "antibody storm," in which many different kinds of antibodies are being created by a disturbed, over-active immune system.
In a very detailed study of the immune systems of CFS patients, Miami University researcher Dr. Nancy Klimas also found that CFS patients can have false positive tests for syphilis.
Dr. Klimas and her colleagues suggested that the B-cells, the immune system cells which make antibodies, are extremely dysfunctional in CFS. This research team also suggested that the B-cell malfunction taking place in CFS might result in the lowered natural killer cell activity that has also been observed, since another function of B-cells is to stimulate natural killer cells.
False positive syphilis tests are so common among AIDS patients that, for a while, it was thought that syphilis might be intimately involved in causing AIDS. Although AIDS patients can progress to the neurological form of syphilis much more rapidly than otherwise healthy people do -- in a matter of months, as opposed to 30 or 40 years -- syphilis is no longer considered to be a candidate for causing the symptoms of AIDS.
One of the hallmarks of AIDS throughout the epidemic has been a decreasing T4, or CD4, cell count. In early 1993, research published by government scientists demonstrated that, like AIDS patients, CFS patients' T4 cell counts are substantially decreased.
Most healthy people have T4 cell counts of about 1000. In AIDS, T4 cell counts can fall precipitously; below 200, an AIDS patient is considered to be in danger of developing a potentially life-threatening opportunistic infection.
Dr. Stephen Straus, who is in charge of CFS research at the National Institute of Allergy and Infectious Diseases (part of the National Institutes of Health), directed the study of CFS patients' T4 cells.
Dr. Straus and his colleagues found that CFS patients had "significantly decreased" numbers of a subtype of T4 cells.
In a government press release, however, Dr. Straus emphasized that the loss of T4 cells in CFS patients was completely different from the loss of T4 cells in AIDS patients.
"This decrease does not indicate the CD4 T-cells [T4 cells] are being destroyed, such as happens in AIDS," Straus commented in the press release, "but that more CD4 T-cells appear to change location, shifting from the blood into the tissues. These tissue-based cells escape detection by research blood tests."
A careful reading of Dr. Straus and colleagues' actual research report, however, reveals that this assertion -- that the T4 cells have changed location from the blood into the tissues -- is based on absolutely no data whatsoever. It is just a guess. All that Dr. Straus and his co-workers actually showed was a significant decrease in T4 cells in CFS patients.
Not long after Dr. Straus's research report was published, a report in Science magazine suggested that AIDS patients' T4 cell counts were not really so low as they appeared to be because AIDS patients' T4 cells were also hiding in the lymph nodes.
No one in the lay press appeared to notice these parallel explanations of what was happening to the T4 cells of AIDS and CFS patients.
Dr. Straus's finding about the T4 cells of CFS patients is particularly important because he has attempted, for several years, to prove that CFS is a psychiatric disorder. Discovering this "abnormality of immune regulation" in CFS patients, as he and his coworkers called it in their research report published in the Journal of Clinical Immunology, did not discourage Dr. Straus from pursuing his hypothesis about CFS being a psychological disease. He and his colleagues suggested that, "The [immunologic] abnormalities may be secondary to an underlying neuropsychiatric disorder which affects immune function indirectly...."
Other studies documenting the immune system abnormalities found in CFS patients_like non-functional natural killer cells, for instance_suggest that CFS is primarily an immunological, not a psychological, illness.
It is being increasingly recognized that exposure to sunlight isn't as good for people as we once thought it was. As scientists document the damage that pollution has done to the ozone layer that surrounds the earth and protects all living things from the sun's harmful radiation, people are being warned that unprotected sunbathing not only increases their chances of developing wrinkles and skin cancer, but may also damage their immune systems.
It is not known for sure how sunlight damages the immune system, but it may be through a process similar to the way skin is hurt by the sun's rays. The ultraviolet light that makes up part of the sun's radiation is known to be able to damage skin cells' DNA, the genetic material that resides in every type of cell. It's possible that immune system cells are damaged that way by the sun, as well.
It's also possible that Vitamin D, a vitamin that people make in their bodies after exposure to sunlight, contributes to the worsening of CFS patients' symptoms. It's been suggested that vitamin D may not be processed properly by CFS patients, and that the resulting chemical imbalance may make their symptoms worse.
In any event, most doctors who treat CFS patients caution them to stay out of the sun.
Dr. Charles W. Lapp, who works with Dr. Paul Cheney in Charlotte, North Carolina, advises his patients to avoid sunbathing.
In a "Self-Care Manual" that Drs. Cheney and Lapp wrote for their patients in 1991, they also advise patients to avoid the sun. They caution that exposure to sunshine "may reactivate herpes group viruses or provoke skin reactions."
Another reason for CFS patients to avoid the sun is that many find that their eyes have become extremely sensitive to bright light, a condition that is called "photophobia." Drs. Cheney and Lapp advise their CFS patients to wear sunglasses to protect their eyes from the sun.
One of the problems researchers encounter in studying CFS is that, like AIDS, there is no good indication of when a patient actually becomes infected with the disease-causing agent; therefore, it is difficult to assess the progression, or "natural history," of the syndrome.
A Long Island physician, Dr. Perry Orens, has devised a set of criteria by which to "stage" CFS, in terms of the progression of illness.
Dr. Orens's criteria range from what he has called Class I, in which the patient meets the CDC criteria (50 percent reduction in activities lasting at least six months), to Class IV, in which patients are completely disabled and bedridden.
The system used to classify AIDS patients' disease in stages, called the Walter Reed Classification System (developed at the Walter Reed Army Hospital), is no more specific than Dr. Orens's CFS stages.
In Walter Reed Stages 0 through 2, the patient is essentially healthy; antibodies for HIV and chronically swollen lymph nodes are the only symptoms noted.
In Walter Reed Stage 3, T4 cell counts drop to below 400; in Stage 4, there is a partial failure of the ability to respond to skin tests (i.e., cell mediated immunity begins to fail, as it does in CFS patients). In Stage 5, there is a complete failure of cell-mediated immunity (called "anergy," which is also seen in CFS patients) andor the development of thrush, a yeast infection of the mouth. (CFS patients, of course, can also develop thrush.)
In Stage 6 -- the stage at which patients are said to have AIDS -- opportunistic infections occur.
CFS patients can also develop "opportunistic infections." In his February 1993 testimony to a Food and Drug Administration Scientific Advisory Committee, Dr. Paul Cheney pointed out that of his five CFS patients who'd died during the preceding six months, three died as a result of overwhelming opportunistic infections.
At the very least, it seems that many CFS patients could be classified as being permanently or semi-permanently in Stage 4 of AIDS.
Many CFS patients become severely depressed after they have been sick for a period of time. This is not too surprising: Many patients lose their jobs -- and therefore their livelihoods -- their homes, and often, the relationships most important to them, with family, friends, and spouses.
The inability -- or unwillingness -- of the medical establishment to deal with CFS as a very serious, indeed overwhelming, illness contributes to the depression experienced by CFS patients. Authors Barbara Brooks and Nancy Smith address this problem in some depth in their book, CFIDS: An "Owner's Manual" (BBNS Publishing, Silver Springs, MD).
"When a bad case of the CFIDS blues really has you down, suicide begins to look good by comparison," Brooks and Smith write. "...Suicide, a negative thought for normal people, becomes a positive picture for the CFIDS-depressed person. When your future is so bleak and hopeless, it is no wonder you lapse into such thoughts....Unfortunately, your sense of self-blame may often be reinforced by society in general...."
Brooks and Smith also relate that, "As we spoke to support group leaders around the country, the one thing that struck us was their report of an increasing number of calls they were receiving from suicidal patients. The numbers of patients who are losing everything -- their jobs, their homes, their cars, and their health insurance -- is on the rise. Employers seem to be showing no compassion, and these patients are being dumped. They are truly falling through the cracks of the social system...."
Dr. William A. Carter, a co-inventor of the experimental AIDS and CFS treatment Ampligen and a professor of oncology and hematology at Hahnemann University (Philadelphia), was interviewed at the September 1991 31st Interscience Conference on Antimicrobial Agents and Chemotherapy (held in Chicago). In that interview, which was published in the Conference Journal, Dr. Carter talked about how desperate CFS patients become.
"The effects of this disease are devastating," Dr. Carter said. "It has enormous repercussions. It causes families to go into bankruptcy. We have talked to very few families where the husband or wife still had a viable marriage because it destroys marriages. And it puts a huge burden on the medical system. The incidence of suicide is apparently quite high as the patients become progressively debilitated."
Dr. Paul Cheney, one of the physicians who discovered the first outbreak of CFS in Nevada in 1984, delivered testimony before the Food and Drug Administration Scientific Advisory Committee in February 1993. Dr. Cheney told the FDA, "We are frequently depositioned for disability and other types of litigation. Many cases involve divorce as we witness the disintegration of the family unit....The medical-legal aspects of our practice steadily grow as this disease eats at the fabric of our communities."
The Centers for Disease Control and Prevention (CDC) received so many calls from doctors, nurses, and other health care workers stating that they had developed CFS that a study of CFS in that ""risk group'' was planned for 1991-1992, as documents received under the Freedom of Information Act show.
That study of the incidence of CFS among health care workers, however, was never carried out.
The explanation of the study, which was included in financial projections for the CDC's Fiscal Year 1991 and 1992 New Collections (part of the Department of Health and Human Services budget) states, in part:
"CDC has received a significant number of calls and letters from physicians, nurses, and other health care providers reporting that they, and in many cases, other members of their families, are suffering from chronic fatigue syndrome. CDC plans to conduct a nationwide study of chronic fatigue syndrome in health care providers to determine the prevalence of the illness, its characteristics, and associated exposure factors...."
The CFIDS Chronicle has documented -- probably by accident -- a large number of cases of physicians, nurses, and other health professionals who have developed CFS, many of whom have written articles for the patient advocacy journal.
A Canadian medical researcher described, in the CFIDS Chronicle, how his life had changed since he became ill with CFS. He wrote that it was hard to remember that he used to race against the clock, writing grant applications to fund his research, or to save the lives of the babies he cared for. This doctor mourned the loss of weeks and months that had turned into more than a year of idleness.
A former nurse also wrote to the CFIDS Chronicle, describing how unhappy it made her that she, who used to care for other people, now could not even take care of herself.
I have interviewed a surprising number of physicians who have CFS and, in most instances, they have reported being just as badly treated by their own profession as other CFS patients. Physicians who develop CFS are shocked, I have found, that their colleagues do not take their illness seriously. Like other CFS patients, physician-patients often find that they have to consult numerous doctors before they find someone who is knowledgeable about CFS.
Like teachers and airline personnel, health care professionals may be at greater risk for contracting CFS simply because they have close contact with large numbers of people.
Until the infectious agent that causes CFS is positively identified, however, no one can really explain why health care workers are more at risk for contracting CFS.
If a person becomes so ill that he or she cannot work, financial difficulties usually follow. Unfortunately, even people who believed, before they got sick, that they had built a financial safety net find that it can be snatched from underneath them. And some financial safety nets -- like health insurance -- don't always catch CFS patients.
CFS patients, like AIDS and cancer patients, are also especially vulnerable to medical fraud, which can quickly erode a person's, or a family's, life savings. And, because insurance companies can choose pretty freely what they will and won't pay for, it isn't even possible to use that yardstick to determine whether a treatment or medication is new and promising or is simply a scam.
Dr. Jay Goldstein has written extensively about the problems that his patients have encountered in trying to get their insurance companies to pay for CFS tests and treatments. One of the most common reasons for non-payment, according to Dr. Goldstein, is that the insurance company decides that a treatment is not medically necessary.
Insurance companies can also refuse to pay for treatments or tests that they consider to be experimental. Any treatment that has not received Food and Drug Administration (FDA) approval for treating a certain illness can be ruled to be experimental by insurance companies. Currently, there is not a single CFS treatment that has received FDA-approval.
Dr. Goldstein has also pointed out that it is often downright impossible for a CFS patient to fight his or her insurance company; it is an expensive, time- and energy-consuming process. Unfortunately, many CFS patients just forego treatments and tests rather than try to fight their insurance companies.
There is an especially tragic case of a CFS patient being abandoned by her insurance company that was described in articles in both the New York Times and New York Newsday in 1992. The patient, who had been a brain researcher before becoming disabled by CFS, was simply told one day by her insurance company that the benefits she had been receiving -- such as round-the-clock nursing care -- were no longer going to be provided. This patient's life had been saved twice by her 24-hour-a-day nurse, according to newspaper reports; once when she developed a blood clot in one of her lungs, and a second time when she unexpectedly began hemorrhaging.
Why did the insurance company cut off this patient's benefits? The company denied that it was because of the amount of money her care was costing but, since the patient had developed CFS, according to newspaper accounts, her insurance company had paid more than one million dollars for her care.
In testimony presented to the Food and Drug Administration's Scientific Advisory Committee on February 18, 1993, Dr. Paul Cheney said, "From an economic standpoint, this disease is a disaster."
"Eighty percent of the cases evaluated at my clinic are unable to work or attend school," Dr. Cheney told the FDA. "The average length of illness at the time of presentation is 3.8 years. Ninety percent have become ill since 1980. The yearly case production, if plotted, is exponential. Most are already on or will shortly be on some sort of disability plan, public or private."
In addition to becoming disabled -- which has a huge societal cost, not only in terms of direct payments to the disabled person, but also in terms of person-years of work and taxable income lost -- Dr. Cheney told the FDA that his patients had spent an average of $15,000 on medical care before coming to his clinic.
Kutapressin is a drug made from porcine (pig) liver that has been used, apparently with no bad side effects, to treat herpes infections (such as shingles) since the 1940s. When CFS was first identified in the early 1980s, it was thought to be caused by one of the herpes viruses, the Epstein-Barr virus (EBV), and so a group of researchers in Texas decided to test Kutapressin's effects on CFS patients.
It is not known how Kutapressin works, but researchers theorize that it may affect the production of lymphokines like interleukin-2; an overproduction of lymphokines can cause not only perturbations of the immune system, but also symptoms similar to those seen in CFS.
In the informal Texas study, 270 CFS patients were treated with at least ten injections of Kutapressin.
Patients' response to Kutapressin appeared to be at least partially dose-related; 96 percent of the patients who received more than 40 injections had notable or marked improvement in their symptoms. Of the patients who received 11-40 injections of Kutapressin, 71 percent reported the same level of improvement.
There was only one bad reaction to Kutapressin injection out of more than 8000 injections of the drug, according to the Texas researchers; this patient complained that some symptoms worsened, and the drug was stopped.
At the current time, there are tentative plans to test the efficacy of Kutapressin in treating AIDS, as well as plans for formal tests of Kutapressin in CFS patients.
In February 1993, the Food and Drug Administration's Anti-Viral Drug Advisory Committee met to consider the merits of an experimental drug, Ampligen, that appears to have promise for treating CFS (and, in earlier trials, AIDS). So far, no drug has been approved for the treatment of CFS by the FDA.
Ampligen appears to correct a defect in a very important natural anti-viral pathway. When this pathway isn't working properly, viruses aren't attacked by the body's natural defenses. In CFS patients, as in AIDS patients, this anti-viral pathway is defective; furthermore, Ampligen appears to correct the defect in both sets of patients.
At the February meeting at the FDA, Kim Kenney of the CFIDS Association of America (in Charlotte, NC), told the FDA that approving a drug to treat CFS is extremely important to patients, many of whom are desperate to get better. She told the FDA that "the reactions of our constituents range from impatience to desperation, depending on the severity of their condition. Impatient to get back to work, to enjoy their families again. And for some, desperation to reverse the severely debilitating effects of CFIDS, including dementia, unrelenting muscle and joint pain, severe encephalitis, not to mention the problems that accompany a severely impaired immune system."
Dr. Daniel Peterson, one of the two physicians who identified the original outbreak of CFS in Incline Village, Nevada, in 1984, told the FDA committee that "a significant number" of his patients who fell ill in 1984 "never recovered." Dr. Peterson also said that, over the last eight years, 20 percent of the patients he'd examined had become completely disabled. Dr. Peterson also cautioned that the CDC's "crude incidence" of four per 100,000 "most certainly vastly underestimates the true incidence of the disease."
Dr. Peterson told the FDA that, although Ampligen "appears to have great potential in this disease process, it has been bogged down in a corporate and bureaucratic quagmire, and yet the disability and anguish of the patients and treating physicians remains unaddressed."
Jerry Crum, the CFIDS Association's co-chair of its Public Policy Advisory Committee, also spoke at the February meeting with the FDA. Mr. Crum described his illness, which began in 1985, for the committee:
"What I remember during three years of progressive deterioration were seizures on an average of two to three per week and becoming severely demented. My short-term memory was seriously impaired. When I went for walks in my neighborhood, I couldn't find my way home. My IQ dropped from 130 to 85. I will never, ever forget what it feels like to have an IQ of 85. I was not "stupid." What I had was an indefinite sense of the world around me....If I concentrated very hard, I could follow conversations....I slept 14 or more hours per day and nothing alleviated the ever-present muscle pain I suffered from. I was bleeding from my colon. A lumbar puncture performed by Dr. Peterson confirmed severe encephalitis...."
Ampligen, however, allowed Mr. Crum to live a more normal life. His seizures became infrequent, his IQ increased almost to its pre-illness level, and he became capable of performing his job, which involved complex mathematics, again. "The muscle aches diminished, and I required only ten hours of sleep per night with a nap during the day," Mr. Crum told the FDA. He credits Ampligen with allowing him to "regain a measure of quality to my life, which I thought I would never experience again."
Perhaps most compellingly, however, Mr. Crum described for the FDA what happened to him when he stopped taking Ampligen because, as he said, "Receiving I.V. infusions three times per week is not pleasant." But, within six weeks of discontinuing Ampligen therapy, he once again began having seizures and his IQ again plummeted.
"In short, I regressed to the same seriously ill condition I was in prior to receiving Ampligen," Mr. Crum told the FDA Committee.
Similar testimony from other patients, or their families if they were too impaired to deliver or prepare testimony themselves, was also presented to the FDA committee.
The FDA, however, has yet to grant approval to Ampligen or any other drug to treat CFS.
Is it possible to become infected with CFS through a blood transfusion? Numerous patients have told me that they first became ill after receiving a blood transfusion; and although the Center for Disease Control and Prevention (CDC) has cautioned CFS patients not to give blood, there is no official mechanism in place to screen CFS patients out of the blood-giving population.
A CFS patient who was concerned about the blood supply sent me a copy of a letter written by the person then in charge of CFS research at the CDC, Dr. William Reeves. In the letter, Dr. Reeves cautions the CFS patient not to give blood.
The CDC has no official policy concerning blood donation by CFS patients, Dr. Reeves wrote. "However, since ongoing research indicates an infectious agent may be involved in some cases of CFS, it would seem prudent to refrain from donating blood until this issue is resolved....You should inform officials at the blood collection center that you have CFS; the blood bank may have specific regulations concerning CFS or similar diseases."
The Food and Drug Administration (FDA), the agency responsible for regulating blood collection in the U.S., has no specific questions regarding CFS in its guidelines.
Because the FDA does not specifically prohibit blood donation by CFS patients, the American Red Cross has concluded that it is safe to accept blood from CFS patients. I was told by a representative of the American Red Cross in Washington, DC, that blood donations were accepted from CFS patients as long as their illness was "inactive." There is no agreed-upon definition for "inactive" CFS, however.
While physicians and researchers agree that it is entirely possible that CFS can be contracted from blood transfusions, at the current time, there are no mechanisms in place to protect the public from this occurrence.
That may change at least in part because of a blood banking scandal in France. In the early 1980s, a decision was made by French government officials to delay testing blood and blood products for HIV until a French-made test was available, even though a test developed in the U.S. was available to French blood banks. As a result, a large percentage of French hemophiliacs developed AIDS because they had been transfused with contaminated blood products. In 1993, however, those responsible for making the decision to delay testing -- including more than one former, high government official -- went on trial; some of those involved were sentenced to spend time in jail.
Chronic Fatigue Syndrome patients have created a patient movement the size of which probably has never been equaled in the United States. Patients banded together initially out of self-protection: The media, physicians, their families -- it seemed like everyone -- were telling them that they had psychiatric problems. As the theory that CFS is a psychoneurotic disorder was disproved -- although there are still a few adherents to this outdated theory -- CFS patients organized to achieve political power. A great deal has been achieved by local, as well as national, CFS patient groups in terms of getting CFS moved up on the national health agenda as a problem to be taken seriously.
But while the CFS patient movement has argued that CFS is a neurological and immunological illness, they have not acknowledged the syndrome's connection to AIDS.
This denial on the part of CFS patient advocates is probably a response to the discrimination suffered by AIDS patients. A diagnosis of AIDS can cause a person to lose his or her apartment, job, and important relationships. Routine health care can become very difficult to obtain for AIDS patients. Discrimination against AIDS patients is, in fact, rampant.
Oddly, patients who are not involved with the CFS movement in any formal way are much more likely to acknowledge the overwhelming similarities between CFS and AIDS.
It may be that, for "official" patient groups, admitting that CFS is closely related, if not identical, to AIDS is just too frightening.
While such denial is natural and understandable, it should not be allowed to prevent an objective investigation of the possible link between CFS and AIDS. That connection may help solve both puzzles at the same time.
There are many strains of HHV-6 -- that is, viruses that are enough alike to be considered HHV-6, but which differ from each other in small ways. Those strains are further classified as being in a larger grouping, called a "variant." The two variants of HHV-6 appear to have very different disease-causing properties. While this is rather technical information, it may have important implications for understanding both Chronic Fatigue Syndrome and AIDS.
The easiest way to visualize different virus strains is to imagine that a virus is like a string of different-colored beads. If you have three strings of beads that have exactly the same color sequence except for one bead, those strings would be analogous to strains of a virus.
There are many different strains of HHV-6, and more appear to be discovered all the time. Those strains, like the imaginary strings of beads, differ from each other only very slightly.
But as more has been learned about HHV-6, it has become clear that the virus strains differ from each other in ways that allow them to be divided into two groups, called "Variant A" and "Variant B" HHV-6.
These two variants appear to be able to cause very different kinds of illness, and may resolve the apparent paradox that HHV-6 infects about 90 percent of the world population as an apparently harmless, asymptomatic infection, yet can also be associated with catastrophic immune system diseases like AIDS, cancer, and Chronic Fatigue Syndrome.
Recent research has shown that Variant B HHV-6 is the type that infects infants and children, usually by age three, and is associated with a mild illness with fever and rash called roseola.
Variant A HHV-6, however, is the type that is found in very sick adults with AIDS and CFS. Variant A HHV-6 appears to be able to attack the immune system, and infect and kill very important cells. Cells that HHV-6 is known to be able to infect include the cell considered to be the primary target of HIV, the T4 cells, and other very important immune system cells, natural killer cells.
Because HHV-6 can infect the same cells as HIV -- and both viruses have been found cohabitating in the same cell -- some researchers have suggested that HHV-6 may be a "co-factor" in causing AIDS.
Now, however, it is known that HHV-6 is the only virus capable of infecting and killing natural killer cells, the immune system's front-line defense against viruses and some kinds of cancers.
So, along with HHV-6's ability to infect T4 cells, it is becoming clear that HHV-6 is capable of inflicting a considerable amount of damage on the immune system.
Although some scientists consider HHV-6 to be a "co-factor," along with HIV, in causing AIDS, it might be more prudent to determine how much HHV-6 can damage the immune system all by itself.
Is HHV-6 the real AIDS virus?
It may seem silly to look at a pig illness to identify the cause of CFS, but it really isn't. Pigs and humans pass viruses back and forth all the time; in fact, flu viruses change from year to year because they pass from people to pigs and back again and in so doing, mutate, or change, considerably.
There is an illness of pigs, African Swine Fever, that an expert in the field has called "an acquired immune deficiency syndrome of pigs," because it produces symptoms that are so similar to those of AIDS. African Swine Fever is caused by a virus, African Swine Fever Virus (ASFV).
Like AIDS, there is no treatment for African Swine Fever, and no vaccine to prevent ASFV infection. When African Swine Fever is suspected in a herd of pigs, the entire herd is slaughtered to prevent the spread of the very contagious, deadly virus. Because of the vast economic implications such slaughters of pig herds would have on U.S. agriculture, it is against the law to study ASFV on mainland U.S.A. The only place where the virus can be studied, by law, is the Plum Island Animal Disease Center on Plum Island, off the shore of Long Island, New York.
Similarities between the symptoms of ASF and AIDS -- as well as the fact that Haiti, one of the areas in which AIDS appeared earliest, had recently had an ASFV epidemic -- caught the attention of a young scientist in 1983. Dr. Jane Teas, who was working as a researcher at Harvard, began collaborating with Boston University scientist Dr. John Beldekas to try to figure out if ASFV could be causing AIDS.
In 1986, Drs. Teas and Beldekas published a report in the British medical journal The Lancet showing that they had found evidence of ASFV infection in AIDS patients. But after that, the trail was stopped cold, when a group of scientists gathered by the U.S. Department of Agriculture at Cold Spring Harbor Laboratory (on Long Island) issued a memorandum that no further research should be performed to test the ASFV hypothesis. Usually, when a line of research proves not to be fruitful, scientists naturally stop pursuing it; it was, however, unprecedented for a group of scientists gathered by the government to declare that a line of research should no longer be pursued. That is, however, exactly what the scientists gathered by the USDA at the Cold Spring Harbor Laboratory did.
Shortly thereafter, however, two research groups to whom Dr. Teas and Dr. Beldekas had provided information and scientific materials announced almost simultaneous discoveries of a "new" human virus, found in AIDS patients: HHV-6.
HHV-6 and ASFV are very similar viruses; they are the same size, and they infect and kill the same kinds of cells. They both cause bleeding problems (they are "hemorrhagic" viruses), and both attack the immune system, allowing secondary (or "opportunistic") infections to become fatal. They both cause neurological disease. Both viruses mutate (change) easily.
Furthermore, both HHV-6 and ASFV are characterized by having many strains, or types, of virus. ASFV, it has been known for dec ades, can cause a whole range of illness, from extremely acute (in which 100 percent of infected animals die within days) to chronic (in which animals develop immune system and neurological symptoms, but generally survive).
HHV-6, also, has many strains that can cause different levels of disease, from an illness with mild fever and rash, to a fatal, hemorrhagic disease in which the patient rapidly bleeds to death. HHV-6 can cause a collapse of the immune system, and is associated with many kinds of neurological phenomena, including the development of brain lesions. Like ASFV, HHV-6 is found in people with acute illness -- that is, AIDS -- and chronic illness, CFS.
Where did this new human virus come from?
Is it a zoonosis, an animal virus that has mutated and become capable of infecting humans?
When Dr. Teas and Dr. Beldekas were trying to determine if ASFV could be involved in causing AIDS, a major objection to the theory was that pigs in the U.S. were not sick. If a pig virus were causing AIDS, some experts argued, then shouldn't the pigs be sick?
There is, in fact, a world-
wide epidemic among domesticated pigs that bears a great resemblance to African Swine Fever; it has been called "Mystery Swine Disease." Although a "new" virus (called "Lelystadt virus" for the city in which it was isolated) is thought to be causing "Mystery Swine Disease," the new virus has not yet been compared to all the strains of the old virus, ASFV.
Lelystad virus also has not been compared to the new human virus, HHV-6.
One reason that there has been very little progress in fighting both AIDS and CFS may be because HHV-6 is actually the virus that is causing most, if not all, of the damage to the immune system in both syndromes.
If HHV-6 is causing the immune system damage in AIDS and CFS and if HHV-6 is really a strain of ASFV, there is the very real possibility that some scientists have deliberately misled the public.
If government scientists are afraid to admit what HHV-6 really is and how widespread the immunological damage it causes is, then the problem of ending the CFS epidemic may be as political as it is scientific.
Presentations made at a conference jointly sponsored by the National Institute of Allergy and Infectious Diseases and the University of Pittsburgh, "Considerations in the Design of Studies of Chronic Fatigue Syndrome" (held September 15-16, 1988, in Pittsburgh), are collected in Reviews of Infectious Diseases, Volume 13, Supplement 1, January-
February 1991, University of Chicago Press. Another valuable resource is the CFIDS Chronicle, published by the CFIDS Association in Charlotte, North Carolina.
Other selected reports in the medicalscientific literature that provide the scientific basis for statements made in this volume include:
Akashi, Keichi et al.; "Brief Report: Severe Infectious Mononucleosis-Like Syndrome and Primary Human Herpesvirus 6 Infection in an Adult"; New England Journal of Medicine, July 15, 1993.
Asano, Yoshizo et al.; "Fatal Fulminate Hepatitis in an Infant With Human Herpesvirus-6 Infection"; The Lancet, April 7, 1990.
Barnes, Deborah; "Mystery Disease at Lake Tahoe Challenges Virologists and Clinicians"; Science 234:541, 1986.
Becker, Yechiel, Editor; African Swine Fever, Martinus Nijhoff Publishing (Boston/Dordrecht/Lancaster), 1987.
Beldekas, John, Jane Teas, and James R. Hebert; "African Swine Fever Virus and AIDS"; The Lancet, March 8, 1986.
Berneman, Zwi N. et al.; "Human Herpesvirus 7 is a T-Lymphotropic Virus and Is Related to, but Significantly Different From, Human Herpesvirus 6 and Human Cytomegalovirus"; Proceedings of the National Academy of Sciences USA, 89:10552, November 1992.
Bovenzi, Pasqualina et al.; "Human Herpesvirus 6 (Variant A) in Kaposi's Sarcoma"; The Lancet 341:1288, May 15, 1993.
Buchwald, Dedra et al.; "A Chronic Postinfectious Fatigue Syndrome Associated With Benign Lymphoproliferation, B-Cell Proliferation, and Active Replication of Human Herpesvirus-6"; Journal of Clinical Immunology 10(6):335, 1990.
Buchwald, Dedra et al.; "A Chronic Illness Characterized by Fatigue, Neurologic and Immunologic Disorders, and Active Human Herpesvirus Type 6 Infection"; Annals of Internal Medicine 116(2):103, January 15, 1992.
Caliguri, M. et al.; "Phenotype and Functional Deficiency of Natural Killer Cells in Patients With Chronic Fatigue Syndrome"; Journal of Immunology 139:3306, 1986.
Carter, William et al.; "Clinical, Immunological, and Virological Effects of Ampligen, a Mismatched Double-Stranded RNA, in Patients With AIDS or AIDS-Related Complex"; The Lancet, p. 1228, 1987.
Carter, W.; Interview in "Experimental Drug Held Effective for Chronic Fatigue, Immune Dysfunction"; American Society for Microbiology Conference Journal, September 29-October 2, 1991.
Cohen, Jon; "Keystone's Blunt Message: "It's the Virus, Stupid" ";Science 260:292, April 16, 1993.
Cone, Richard W. et al.; "Human Herpesvirus 6 in Lung Tissue From Patients With Pneumonitis After Bone Marrow Transplantation"; New England Journal of Medicine, July 15, 1993.
Cunha, Burke A.; "Crimson Crescents -- A Possible Association With the Chronic Fatigue Syndrome"; Annals of Internal Medicine 116:4347, February 15, 1992.
DeFreitas, Elaine et al.; "Retroviral Sequences Related to Human T-Lymphotropic Virus Type II in Patients With Chronic Fatigue Immune Dysfunction Syndrome"; Proceedings of the National Academy of Sciences USA 88:2922, 1991.
Demitrack, Mark A., Janet K. Dale, Stephen E. Straus et al.; "Evidence for the Impaired Activation of the Hypothalamic-Pituitary-Adrenal Axis in Patients With Chronic Fatigue Syndrome"; Journal of Clinical Endocrinology and Metabolism, December 1991.
Dewhurst, S., K. McIntyre, K. Schnabel, and C.B. Hall; "Human Herpesvirus-6 (HHV-6) Variant B Accounts for the Majority of Symptomatic Primary HHV-6 Infections in a Population of U.S. Infants"; Journal of Clinical Microbiology, February 1993.
Downing, R.G. et al.; "Isolation of Human Lymphotropic Herpesviruses From Uganda"; The Lancet, January 29, 1987.
Eleopulos, Eleni Papadopulos, Valendar F. Turner, and John M. Papdimitriou; "Is a Positive Western Blot Proof of HIV Infection?"; Bio/Technology 11:696, June 1993.
Frenkel, Niza et al.; "Isolation of New Herpesvirus From Human CD4-Positive T Cells"; Proceedings of the National Academy of Sciences USA 87:748, January 1990.
Grufferman, S. et al.; "Epidemiologic Investigation of an Outbreak of Chronic Fatigue-Immune Dysfunction Syndrome in a Defined Population"; American Journal of Epidemiology 128(4), 1988.
Gupta, S. and B. Vayavegula; "A Comprehensive Immunological Analysis in Chronic Fatigue Syndrome"; Scandanavian Journal of Immunology 33:319, 1991.
Holmes, Gary P. et al.; "Chronic Fatigue Syndrome: A Working Case Definition"; Annals of Internal Medicine 108:387, 1988.
Huang, Li-Min et al.; "Human Herpesvirus-6 Associated With Fatal Haemophagocytic Syndrome"; The Lancet, July 7, 1990.
Hyde, Byron Marshall, Editor; The Clinical and Scientific Basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Nightingale Research Foundation, Ottawa, Ontario, Canada, 1992.
Klimas, Nancy G., Fernando R. Salvato, Robert Morgan, and Mary Ann Fletcher; "Immunologic Abnormalities in Chronic Fatigue Syndrome"; Journal of Clinical Microbiology 28(6):1403, June 1990.
Learmont, J. et al.; "Long-term Symptomless HIV-1 Infection in Recipients of Blood Products From a Single Donor"; The Lancet 340:863, 1992.
Levy, Jay A. et al.; "Frequent Isolation of HHV-6 From Saliva and High Seroprevalence of the Virus in the Population"; The Lancet, May 5, 1990.
Lo, Shyh-Ching et al.; "Association of the Virus-Like Infectious Agent Originally Reported in Patients With AIDS With Acute Fatal Disease in Previously Healthy Non-AIDS Patients"; Journal of Tropical Medicine and Hygiene 41:364, 1989.
Lusso, P. et al.; "Induction of CD4 and Susceptibility to HIV-1 Infection in Human CD8-Positive T Lymphocytes by Human Herpesvirus 6"; Nature 349:533, February 7, 1991.
Lusso, P. et al.; "Productive Infection of CD4-Positive and CD8-Positive Mature Human T Cell Populations and Clones by Human Herpesvirus 6"; Journal of Immunology 147(2):685, July 15, 1991.
Lusso, Paolo, Mauro S. Mainati, Alfredo Garzino-Demo, Richard W. Crowley, Eric O. Long, and Robert C. Gallo; "Infection of Natural Killer Cells by Human Herpesvirus 6"; Nature 862:459, April 1, 1993.
Murdoch, J. Campbell; "Cell Mediated Immunity in Patients With Myalgic Encephalomyelitis Syndrome"; New Zealand Medical Journal, p. 511, August 10, 1988.
Prezioso, Paula J. et al.; "Fatal Disseminated Infection With Human Herpesvirus-6"; Journal of Pediatrics 120:921, June 1992.
Prieto, J. et al.; "Naloxone-Reversible Monocyte Dysfunction in Patients With Chronic Fatigue Syndrome"; Scandanavian Journal of Immunology, vol. 30, 1989.
Pruksananonda, Prasong et al.; "Primary Human Herpesvirus 6 Infection in Young Children"; New England Journal of Medicine 326(22):1445, May 28, 1992.
Restrepo, L.M., I.F. Barrera, and L.F. Garcia; "Natural Killer Cell Activity in Patients With Pulmonary Tuberculosis and in Healthy Controls"; Tubercle 71:95, 1990.
Schneider, Keith; "U.S. to Test for Tie Between AIDS and Swine Fever"; New York Times, July 17, 1986.
Steere, Allen C. et al.; "The Overdiagnosis of Lyme Disease"; Journal of the American Medical Association 269(14):1812, April 14, 1993.
Straus, Stephen E. et al.; "Lymphocyte Phenotype and Function in the Chronic Fatigue Syndrome"; Journal of Clinical Immunology 13(1):30, 1993.
Straus, Stephen E. et al.; "Allergy and the Chronic Fatigue Syndrome"; Journal of Allergy and Clinical Immunology 81:791, May 1988.
Straus, Stephen E.; "The Chronic Mononucleosis Syndrome"; Journal of Infectious Diseases 157:405, 1988.
Teas, Jane, John Beldekas, and James Hebert; "African Swine Fever Virus and AIDS"; The Lancet, March 8, 1986.
Teas, Jane; "Could AIDS Agent Be a New Variant of African Swine Fever Virus?"; The Lancet, April 23, 1983.
Wrzos, Helena et al.; "Human Herpesvirus 6 in Monocytes of Transplant Patients"; The Lancet, February 24, 1990.
Wyatt, Linda S., William J. Rodriguez, N. Balachandran, and Niza Frenkel; "Human Herpesvirus 7: Antigenic Properties and Prevalence in Children and Adults"; Journal of Virology, p. 6260, November 1991.
Copyright 1993 by TNM, Inc.