Raggedy Ann Syndrome: What is the mysterious ailment that knocked the stuffing out of this Nevada resort community and where else is it striking?
Incline Village on the north shore of Lake Tahoe presents itself to the first-time visitor as a high-altitude Carmel-by-the-Sea, a muted symphony of cedar and redwood A-frames, upscale condos, and lakefront mansions tucked among imposing stands of ponderosa pine. For the adult at play, the village offers two Robert Trent Jones golf courses, an in-town ski lodge, the stylish Hyatt Lake Tahoe Hotel and Casino, and an assortment of private beaches and boat docks. It is, by design, a resort community for the well-to-do, dependent for its prosperity on vacationers and rising property values.
Two years ago something happened to Incline Village that was decidedly not part of the area’s master plan. A mysterious illness struck the town. The sufferers felt as though they had come down with mono or the flu – sore throats, swollen lymph glands, aching muscles – only the symptoms wouldn’t go away. For month after month. One woman said the overwhelming fatigue made her feel like Raggedy Ann without the stuffing. Soon many of these people began to display a bewildering array of neurological complications: weakness in the limbs or partial paralysis, black- outs, vivid nightmares, spatial disorientation, memory loss. A patient driving into the business district, which has only three intersections, couldn’t figure out how to get home.
“I was afraid I’d be ostracized or run out of town with a scarlet EBV on my chest.”
Word of the puzzling epidemic was received in Incline Village about as cheerfully as might have been, say, a great white shark attack. “Nobody wanted to hear that you were sick,” says an area resident with the disease. “If they believed you they didn’t want to get near you; and if they didn’t they said you were ruining the economy.’
By the summer of 1986 the illness had a name – chronic Epstein-Barr virus syndrome – and a gathering national reputation. Much to the dismay of local realtors, ABC TV’s newsmagazine 20-20 came to town. Chris Guthrie, a young mother with both the illness and fresh good looks to provide a sympathetic focus for the report, remembers going to the local supermarket at the time. A stranger stopped her in the checkout line to warn her that she was going to ruin business around Lake Tahoe and had no right to appear on network television. “I just felt devastated,” she says. “I was afraid I would be ostracized or run out of town with a scarlet EBV on my chest. But my strongest feeling was, if I could help one person out there who was going through what I had, it would be worth it.”
Patients with chronic Epstein-Barr virus syndrome are great ones for taking their story to the media – with good reason. Until recently the medical profession by and large refused to recognize their complaints. Sufferers were written off as hypochrondriacs, given a tranquilizer, told to sit in a closet or have an affair. Many now feel vindicated because a specific virus has been nominated as the cause of their troubles.
Ironically, however, top researchers in the field are pulling back from the Epstein-Barr terminology even as the media has come to accept and widely disseminate it. More accurately, researchers say, they have identified a widespread “chronic mononucleosis-like illness” in adults that is sometimes accompanied by high levels of antibodies to the Epstein-Barr virus in the blood.
Whether Epstein- Barr is the cause of the syndrome or a symptom of a more basic problem – perhaps a new virus on the loose – has not yet been sorted out.
Indeed, just two things appear certain at this stage. First, like pneumonia in the 19th century or leukemia in the 20th, chronic mono may well turn out to have several different causes. Second, for an illness with virtually no medical standing only a few years ago, quite an astonishingly large number of people suffer from it.
How many? The federal government’s Centers for Disease Control doesn’t know and only recently started planning a surveillance system to find out. “The CDC took the position very adamantly until 1986 that no such disease existed,” says Ted Van Zelst of Minann, Inc., an illinois-based foundation that has championed the cause of chronic mono patients in congressional testimony. The most conservative view is that there are many thousands of sufferers. But based on the north Lake Tahoe epidemic, in which at least 200 of the 20,000 residents became ill, some experts say one percent of the nation may be afflicted – more than 2 million Americans. Reports from physicians in New York, Boston, Atlanta, Denver, Houston, and Los Angeles suggest that a low-level epidemic is quietly surfacing all over the country. Commercial labs describe the growth in demand for the Epstein-Barr blood test with words like “astronomical.”
What all this means is that chronic mono is bidding fair to become, as Newsweek magazine recently headlined it, “the malaise of the 80s.” A comparison with AIDS is probably inevitable – both maladies attack the immune system, trigger a widevariety of symptoms, and are newly recognized on the epidemiological scene. But the differences are more pronounced. For one thing, AIDS kills; chronic mono, as one patient put it, “just makes you wish you were dead.” For another, the demographics are nearly photographic negatives of one another. Whereas AIDS got its foothold among homosexual men, intravenous drug users, and Haitian immigrants, the chronic Epstein-Barr virus syndrome seemed to show an early appetite for the conventional upper middle class. Two out of three victims are women. Adults in the physical prime of life are more susceptible than any other age group. At the outset, doctors treating the disease actually called it the Yuppie Plague because of its apparent preference for well-educated, ambitious professional people.
Like Sandy Schmidt. Community leader, sports enthusiast, and manager of her husband’s estate planning business in Incline Village, Schmidt had just finished running the San Francisco marathon when the illness caught up with her in July 1985. “At first I thought it was post-race fatigue,” she says. “But it was so exaggerated. I was sleeping 15 hours a day and getting worse. I’d try to stay up, but just couldn’t concentrate or think or work.”
Joyce Reynolds, a bank teller in north Lake Tahoe, contracted the disease more than two years ago. She has become, in her own words, “a total recluse.” Her children no longer visit because they are afraid of catching the bug. Even as simple a thing as going to the movies with her husband can land her in bed for days.
According to a recent poll of chronic Epstein-Barr sufferers, 40 percent have been forced to leave their jobs or schooling. Marriages fall apart. Depression is a common complication. To these stresses add the unsympathetic skepticism of much of the medical community. “Massively overdiagnosed,” “a vogue disease, like hypoglycemia,” and “wastebasket diagnosis” are just some of the professional judgments that have found their way into print.
These days, however, the debate is switching from whether such a syndrome exists to how extensive it is and what causes it. Events at Incline Village helped bring about the change, partly because of some persuasive original research done there and partly because of the sheer melodrama of the situation.
“It was such a setup,” says one scientist who has studied the outbreak, “this beautiful paradise of a tourist resort beset by a lurking evil.”
The struggle for recognition of chronic mono as a new and possibly widespread illness is a story of medicine at the ragged edge of the known and the unknown.
And it all begins with a pair of country doctors convinced that something extraordinary was happening in their practice and stubbornly determined to find some answers – long after prudence dictated looking the other way.
Dan Peterson was the first internal medicine specialist to set up shop in Incline Village following the construction of a new hospital there in the early 1980s. As the practice flourished he was joined by Paul Cheney, a lanky, fair-haired man with a doctorate in physics from Duke, a medical degree from Emory, and all the intellectual intensity such a combination implies. Young, intimidatingly bright, and highly trained, the two were building the power- house practice in town, as other physicians in the area were well aware.
When a few patients with a difficult-to-treat flu began straggling into their offices in the fall of 1984, Peterson and Cheney didn’t think much of it. “We were convinced these people had a viral disease,” Cheney recalls, “so we were very surprised when they didn’t get well, like we kept telling them they would.”
The most obvious diagnosis for patients with swollen lymph glands, aching muscles, sore throat, and disabling fatigue would be acute infectious mononucleosis. But the classic blood test for mono, which measures a clotting reaction, came up negative for almost all the patients. Furthermore, adults rarely get mono; yet here were dozens of people in their 30s all with the symptoms at the same time.
A list of more obscure alternatives was worked up, screened, and systematically discarded, including the possibility that what the doctors were seeing was all in the patients’ heads. “These were people with nothing to gain by being sick,” says Cheney. “Some of them had been coming in for regular checkups for years. We knew them as productive, happy, vigorous adults. All of a sudden they got sick and wouldn’t get well. In some cases they were sweating so much at night their spouses had to get up and change the bed sheets. That’s just not how psychosomatic illness looks.”
Baffled, Peterson and Cheney began searching for clues in the scientific literature. Almost immediately they ran across an intriguing pair of articles in the January 1985 Annals of Internal Medicine. The papers were written by Stephen Straus, head of the medical virology section of the National Institute of Allergy and Infectious Diseases in Washington, D.C., and James F. Jones, now with the National Jewish Center for Immunology and Respiratory Medicine in Denver. They described several dozen patients who had been referred for recurrent or persistent illness characterized by chronic fatigue, fever, headaches, and depression. In both groups the vast majority of patients had elevated levels of antibodies to the Epstein-Barr virus.
Recognizing their patients’ symptoms, Peterson and Cheney ordered the Epstein-Barr blood tests, which had just become available from commercial labs.
Test after test came back showing high levels of antibodies to the virus, some very impressively so. “We thought, ‘Aha! we’ve got a bunch of chronic Epstein-Barr virus patients,’ ” recalls Cheney. But having a name for it didn’t solve the problem. By June their first patients were no better, and as many as 15 new cases a week were being diagnosed. People from the adjoining towns of Truckee and Tahoe City were coming in. Soon a pattern of contagion was evident: a third of one high school faculty, an entire girls’ basketball team, members of the Hyatt casino staff. “We were horrified,” says Cheney. “We felt like we were in a nightmare that wouldn’t end. So I did the only thing I knew how to do: I called the place that’s supposed to figure this kind of thing out.”
The Centers for Disease Control in Atlanta is the federal government’s frontline force against serious public health problems like the AIDS epidemic. Over the years the agency has also had to check out a lot of false alarms. Keeper of the gate of medical probity against the latest fad diagnosis, the CDC was skeptical of the chronic Epstein-Barr virus syndrome from the start – and not without good cause. As any medical student knows, the virus isn’t supposed to cause the pattern of illness the people in Tahoe were experiencing.
Epstein-Barr is a member of the herpes family of viruses, which brings humankind chicken pox, cold sores, genital lesions, shingles, and other ailments. The viruses are tricky. They have a habit of hiding out in the body in a latent state, then popping back on the attack. The patient experiences an unpredictable waxing and waning of symptoms. Even in this elusive company, however, the Epstein-Barr virus stands out as the most eccentric and fascinating herpes of them all.
The key epidemiological fact about the virus is that it shows up everywhere.
Blood samples collected from isolated tribes in the Amazon rain forests have proved free of measles antibodies but positive for Epstein-Barr. The virus is easily passed along in saliva, which explains its ubiquity. Oddly enough, however, the consequences of contracting it vary dramatically from place to place and culture to culture. In the United States and Western Europe, the virus causes infectious mononucleosis, that familiar bane of adolescence and college years. In Africa it is involved with Burkitt’s lymphoma, a fast-growing tumor of the jaw. Burkitt’s, which affects young boys, looks like a grotesque exaggeration of mumps, and without treatment promptly leads to death. In Asia the same virus has been linked to cancer of the nose cavity and roof of the mouth, especially in older men.
The question epidemiologists have long asked is: With the Epstein-Barr virus distributed throughout the world, why does it lead to such distinct, narrowly targeted illnesses in various populations and localities?
Part of the answer lies in the company it keeps – what researchers call its causal co-factors.
Burkitt’s lymphoma, for example, appears in a belt across central Africa marked by low elevation, high rainfall, and warm temperatures – the precise boundaries of mosquito country. The co-factor allowing the virus to trigger Burkitt’s lymphoma seems to be a weakening of the immune system brought on by constant exposure to malaria and yellow fever. The virus’ ally in nose and mouth cancer is less clear-cut, but scientists suspect a diet heavy in salted and smoked fish.
In the case of infectious mononucleosis, the key co-factor is age. In general, a toddler exposed to the Epstein-Barr virus will develop antibodies and never exhibit so much as a sniffle. An older child may have a mild sore throat for a day or two. But a young adult encountering the virus for the first time stands a better than even chance of spending a truly miserable month or so in bed with mono. It seems that the more mature and powerfully developed the immune system, the worse the reaction.
Obviously, if early exposure confers a kind of immunity, conventional ideas about good hygiene don’t hold up. In Barbados, Indonesia, and Mexico, where nearly all children have the Epstein-Barr virus in their blood by age six, infectious mononucleosis is virtually unheard of. But in Sweden, England, and the United States, where parents are fastidious about the exchange of saliva, many infants and young children don’t get exposed; as a result, mono is fairly common among teenagers.
Early or late, from the Antibes to Zaire, nearly everyone is exposed to the Epstein-Barr virus by the age of 30. This viral omnipresence helps explain why the CDC was so leery of the Incline Village report. After all, you can’t have an epidemic of a disease when everyone has already been immunized against it.
Or can you? How the Epstein-Barr virus might pull off such a trick is best explained at the cellular level. The virus infects the B lymphocytes of the immune system, white blood cells formed in the bone marrow that normally manufacture anti- bodies against disease. Once infected by the Epstein-Barr virus, B cells proliferate lustily and become immortalized, as the scientists put it. When the virus transforms a B cell, the immune system responds by producing a legion of activated killer T cells. These are equipped to identify the virus- infected B cells and spit out inflammatory agents to destroy them.
Paradoxically, it is the process of getting well at the microbial level that makes the patient feel horribly sick. During the course of infectious mono, the immune system is literally at war with itself, T cell attacking transformed B cell until the Epstein-Barr invasion is eventually brought under control.
The threat is never wholly eliminated, however. A few transformed B cells harboring the virus – about one in a million – remain present in otherwise healthy individuals. This post-infection condition has been described as a kind of armed truce, with a few virus-infected B cells always trying to multiply and run amok, and the T cells ever vigilant to keep their numbers low. If for any reason the immune system should fail to react to a flare-up of these infected B cells, the results can be deadly serious. For example, transplant patients, who have had their immune systems chemically suppressed in order to prevent rejection of a newly introduced organ, suffer increased numbers of tumors. Some of these are masses of Epstein- Barr – infected B cells that multiply out of control. AIDS patients, whose helper T cells are under attack by the AIDS virus, are similarly vulnerable to B cell cancers.
On the other hand, what happens if the immune system reacts to an uprising of virally infected B cells, but for some reason fails to master it for months or years – if war breaks out but neither side wins? As long as this state of affairs prevails, the patient will feel fatigued, achy, feverish, and depressed, as though he or she had a perpetual case of mono – which is the clinical description of chronic Epstein-Barr virus syndrome.
Under this hypothesis, the virus is envisioned as merely the canary in the coal mine of the body. The fundamental cause of the illness is presumed to be something else, some unknown agent that damages the immune system and prevents it from reining in the Epstein-Barr infection.
It might be a chemical toxin, a known virus or bacterium, geneticpredisposition, or something entirely new. Or it might be nothing at all beyond a case of mass hysteria or confused misdiagnosis by local physicians. It was the latter possibility that CDC epidemiological investigators Gary Holmes and Jon Kaplan were leaning toward when they arrived in the Tahoe basin inSeptember 1985.
Eight months later, in May 1986, their report on the situation appeared in the CDC’s authoritative Morbidity and Mortality Weekly Report, concluding that the data on the alleged epidemic at Incline Village “neither prove nor disprove” the Epstein- Barr virus’ culpability. The report questioned the reliability of the commercial lab test for the virus and pointed out that the test results were equivocal anyway, because some people with high antibody counts are perfectly healthy. Blood analysis of a small subset of patients suggested that such familiar viruses as herpes simplex and cytomegalovirus were equally likely explanations for the symptoms. The report left the impression that nothing out of the ordinary had happened at Lake Tahoe. Physicians were urged not to diagnose patients as having chronic Epstein-Barr virus syndrome until more“definable and treatable” conditions such as anxiety and depression had been ruled out.
To say that the opposing parties in this controversy hold one another in low esteem would be an understatement. “I would not take what he was telling you about patients at face value,” Gary Holmes says of Cheney. “I think that’s true of a lot of physicians, especially private physicians, who get caught up. They think they notice something, then they start seeing it everywhere.”
For his part, Cheney believes that the CDC came to Incline Village with preconceived notions. “I think, personally, that after the publication of the two papers by Straus and Jones and the commercial availability of the Epstein-Barr blood test in 1985, the CDC was bombarded with reports like ours,” he says, “They felt the chronic Epstein-Barr virus diagnosis was being overmade, so they said, well, we’ve got to put a stop to this.”
Nonetheless, it wasn’t long before the news spread that a pair of federal investigators had come into town inquiring about a mysterious disease. A version of the story broke in the local biweekly, the North Lake Tahoe Bonanza, and within a few days Peterson and Cheney were fielding alarmed calls from San Francisco papers asking about an out- break of AIDS at Lake Tahoe.
To clear the air, the two held a press conference at the Hyatt.
An enterprising reporter rang up the other physicians in town for their reaction. Not only had these doctors not seen any evidence of a fatigue syndrome, they found it very unusual that all the cases were showing up in a single practice. The newspaper reports, they said, had caused undue concern among tourists and local residents. “There has to be something wrong with Peterson and Cheney’s diagnosing procedure,” one of them concluded.
In fact, many of the fatigue sufferers had been to other area doctors in the first place. “Peterson and Cheney believed we were sick,” says Irene Baker, one of a group of local teachers with chronic mono. “That’s why they got all these patients.” Publicly the polite skepticism of the CDC and open disavowal of local physicians undermined Peterson’s and Cheney’s credibility. Privately, Cheney admits, there were long periods of self-doubt. “We’d sit down at the end of a day and I’d say, ‘Dan, could we both be deluded at the same time? Are we seeing this in everyone because we’re attuned to it?’ If enough people who know more than you do tell you your diagnosis is garbage, then you start to believe it. The thing that kept pulling us back, though, was our patients.”
Gerald Kennedy, who teaches auto mechanics and drafting, had a nearly flawless 24-year attendance record at Tahoe-Truckee Unified High School. That’s fortunate, because the accumulated sick leave has helped support his family for the last two rocky years. “It’s been a new experience, I’ll tell you,” he says.
“People are skeptical about it. After a while you feel a little better and you start question- ing yourself. That’s when you try doing something – maybe drive out, sit by the lake in a lawn chair and fish for a couple of hours – and pay the penalty for the next week. It’s like riding a roller coaster.”
“Yeah, or a picket fence,” says Baker, who teaches at the same high school.
Following a year of bed rest, Baker can now struggle through a day in the classroom. She has managed this much through sheer perseverance and with the help of a young daughter who has taken over the household chores. “My life right now revolves around work and rest.” She spells it out: “There’s no F-U-N.”
After a year and a half with the illness, Sandy Schmidt began to feel better in November. The longest well period before that was a month. She now feels her old energetic self, and has even begun to run again. “I’m still a little guarded about making blanket statements that it’s gone forever,” she says. There have been too many disappointments for that. But she’s encouraged.
Schmidt, Baker, and Kennedy represent the spectrum of recovery in the Lake Tahoe patients. About a third of the 200 people diagnosed over the last two years or so consider themselves well again. The majority are “cycling” – going through periods of relatively good health followed by relapses. And a final group – 15 to 20 percent of the original – are as sick as ever. The range of symptoms is enormous, everything from prolonged sleeplessness, low-grade fevers, and intense headaches to alcohol intolerance and sensitivity to bright light.
Some patients have taken to wearing portable stereo headphones around their homes to drown out a perpetual ringing in their ears.
In one support group for Tahoe patients, there have been four miscarriages, a case of total paralysis requiring months on mechanical ventilators, and a B cell lymphoma. Most consistently, however, patients complain about a drastic decline in mental acuity – an inability to concentrate, remember names, think. “Of all the things I’ve lost,” a patient fired from her job and divorced by her husband wrote Cheney, “I miss my mind the most.”
Even with their problems, the Tahoe patients are fortunate in one respect: They readily found a pair of doctors who believed their ailments were more than psychosomatic. Widespread skepticism on the part of doctors may explain how the early stereotype of chronic mono sufferers got started. “Well-educated high-achievers would be the people least likely to take no for an answer,” says Anthony Komaroff, a professor of medicine at Harvard University. “But in our experience we’re seeing people from all walks of life: lots of non-Yuppies, blue- collar workers, blacks as well as whites.”
Recently, chronic mono sufferers stopped getting mad at their doctors and started getting even – with their own organization, medical advocates, and lobbying effort. “It’s a grassroots kind of thing,” says Van Zelst of the Minann foundation. “The patients are literally having to slug it out with the medical profession.”
The National Chronic Epstein-Barr Virus Syndrome Association in Portland, Oregon, enrolled more than 11,000 members in its first year, and according to president Gidget Faubion, it doesn’t hesitate to mobilize them. When James F. Jones’ funding for research on the disease at Denver’s National Jewish Center was held up by slow moving medical review panels, Faubion’s group sent out an alert. Two thousand members wrote Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, to express their impatience. The money appeared.
As this example illustrates, the chronic mono sufferer’s chosen weapon is the pen. Houston pathologist William Hermann wryly suggests that polygraphia – voluminous letter writing – be recognized as a symptom of the disease. So effective has this campaign been that in its latest funding bill Congress specifically instructed both the CDC and the National Institutes of Health on steps it wants taken with regard to chronic Epstein-Barr virus syndrome – including more research and a surveillance network to report on the incidence.
After the early public relations debacle with the CDC, the rehabilitation of Peterson’s and Cheney’s reputations began when Harvard’s Komaroff agreed to visit Incline Village in February 1986. Komaroff’s team conducted a thorough epidemiological study: They drew blood, interviewed patients, and searched for alternative causes and patterns of spread. At the same time they looked into an outbreak of fatigue in the nearby ranching town of Yerington, Nevada.
Komaroff’s conclusion was unequivocal: Something very real had taken place in both communities. During the interviews he noticed what he came to regard as a signature for the illness – the high proportion of patients who named a definite date of onset, a date that marked the transition in their lives from good health to misery. “You hear that once or twice and say, ‘Gee, that’s strange,’ ” says Komaroff. “But when you hear it 50, 100, 200 times and you add in the sore throats, swollen glands, low-grade fevers – which are hardly a reflection of anxiety – it seems overwhelming to me that this is evidence of organic illness.”
Komaroff’s support helped Cheney establish ties with several other East Coast researchers. The fruits of these collaborations were recapped at a medical conference in Austin, Texas, in November. Cheney reported on a variety of sophisticated lab tests showing that chronic mono sufferers’ immune systems were impaired. Among the most disturbing results were a series of pictures demonstrating brain damage in many of the patients from north Lake Tahoe.
A magnetic resonance imaging scan allows a look at the soft tissues of the body as clearly as an x-ray reveals the bones. The scans from Lake Tahoe show what look like small holes in the brains of 45 of the 80 chronic fatigue patients examined – bright white spots against a gray field. Most of the spots are small and well-defined, not like the larger smudges associated with multiple sclerosis. Some- times their location corresponds closely to the patient’s neurological symptoms. For instance, a young secretary who previously had a clear brain scan discovered one day that she could no longer pick up the phone with her left arm. A subsequent scan turned up lesions in an area of the brain that is responsible for motor control on the left side of the body.
A battery of tests administered by several California neuropsychologists yielded results equally suggestive of physical – not psychosomatic – disease.
Patients were asked to perform simple tasks that measured manual dexterity, long- and short-term memory, and ability to solve visual problems and arrange numbers and letters in proper sequence. A blindfolded patient would be asked to put round, square, or triangular blocks through a board with matching holes using the right hand, then the left.
“What we found were spectacular differences,” Cheney told the Austin conference. A patient able to do the task easily with one hand couldn’t get a single block in with the other. “This kind of discrepancy is not characteristic of any psychological disease.” If Cheney insists on this point, it’s because he and Peterson have had it questioned so often by infectious disease specialists to whom they have referred patients.
From February to April 1986 Cheney called the CDC regularly to report the new findings on the Incline Village patients. None of it was included in the May 1986 article on the syndrome in the Morbidity and Mortality Weekly Report. In fact, Holmes told the Los Angeles Times later that month that the agency planned no further study of the matter. Shortly thereafter the CDC’s public affairs office turned down a request from 20-20 for an on-camera interview on the subject.
But Cheney wouldn’t accept that the case was closed. Because of Incline Village’s new notoriety, he was receiving a steady stream of inquiries from fatigue sufferers around the nation. As an exercise in ad hoc epidemiology, he decided to plot the date the illness struck each of 185 current sufferers who had contacted him from 35 states. The resulting graph describes a flat line from 1953 to 1977 followed by a steeply rising curve.
Statistically speaking, the results are not significant, since the data was not collected in a random fashion. Nevertheless, Cheney has ventured a tentative interpretation. The flat line, he says, is consistent with chronic mono as viewed by early investigators like Jones and Straus: a rare, isolated disease long present in the human population. The rising curve, on the other hand, may reflect the appearance of a new infectious agent. It’s a bold speculation, and there are alternative explanations for the curve. For example, if the disease lasts no more than a few years in most cases, people stricken recently should always outnumber current sufferers who got the disease five or ten years ago.
But Cheney favors the new virus thesis, partly, he admits, because he is privy to inside information.
What may prove to be the turning point in this medical mystery unfolded at the
National Cancer Institute’s Laboratory of Tumor Cell Biology last fall. It was there that Robert Gallo and his co-workers announced they had identified a novel herpes virus, christened HBLV (for human B lymphotrophic virus), in six patients suffering from a variety of lymph cancers and blood disorders.
Because the herpes viruses wreak a lot of havoc, the discovery posed a series of pressing questions: Is this virus a new player on the scene, or just a newly discovered one? How is it transmitted and how contagious is it? What illnesses might it cause? Before long Cheney had the federal scientists interested in Incline Village. He summarizes the situation neatly: “They had a virus looking for a disease, and we had a disease looking for a virus.”
The involvement of human B lymphotrophic virus in the Incline Village epidemic is far from proven, but there are grounds for suspicion. For one thing, as its name implies, the new virus seeks out and attacks the same niche in the body as the Epstein-Barr virus – the B cells of the immune system. This suggests that it is ideally situated to function as a co-factor, perhaps by upsetting the balance of power between the immune system and the la- tent Epstein-Barr infection present in all of us.
So much for theory. The proof of this pudding will be in the blood. By the end of 1986, Gallo’s lab had tested 700 blood samples from around the world in an effort to find out the range of their viral . discovery. The test is painstakingly slow and not completely accurate; nevertheless, the results so far are provocative. They suggest that HBLV is markedly less widespread than the Epstein-Barr virus; that HBLV may be much more prevalent in parts of central andmeastern Africa – regions where Burkitt’s lymphoma is common – than in the United States; and that within the United States it is distributed very unevenly.
Taken together, these provisional findings point in a consistent direction: HBLV is indeed a relatively new arrival in this country, and like the AIDS virus it probably came here from Africa. As for the blood samples at Incline Village, published but unauthorized reports say 60 percent of the chronic mono patients there have tested positive for HBLV, as opposed to 30 percent of the general population in north Lake Tahoe. Gallo prefers not to traffic in numbers yet. Like some other researchers in the field, he is cautious because he suspects chronic mono will turn out to have more than one cause. But he will say this:
“My feeling is that HBLV is a very hot candidate to be involved in a portion of what is now being called chronic Epstein-Barr virus syndrome.”
Pressure from Congress and the discovery of the new herpes virus have changed the CDC’s lukewarm institutional interest in the chronic mono syndrome. Last fall, CDC investigators did a telephone survey of internal medicine specialists in Nevada and Georgia to determine how many were seeing long-lasting monolike cases. The investigators wanted to find out if the glut of local publicity over the Incline Village outbreak had skewed the perceptions of Nevada physicians.
The results were virtually identical: Forty percent of doctors contacted in both states reported treating at least one patient meeting the CDC’s chronic mono description. “That’s a pretty frightening number,” says Holmes. “It’s certainly enough to make you feel justified in doing a lot more study.”
Nonetheless, Holmes is the only person at the CDC working on the issue on a regular basis. “On any given day, it’s second or third on my list,” he says.
Like Jones and Straus, he believes that the Incline Village outbreak and what the media is calling chronic Epstein-Barr virus syndrome is not a new phenomenon. “There have been syndromes almost identical to this reported in the literature going back to the 1930s,” he says.
The list of examples is impressive: at Los Angeles County Hospital in 1934; in Akureyri, Iceland, in 1948; and at Royal Free Hospital in England in 1955, to cite just a few. The names have changed (epidemic neuromyasthenia, vegetative neuritis, benign myalgic encephalomyelitis), but some of the symptoms – and especially the protracted course of recovery – remain remarkably constant. As has a tendency to disbelieve: All these outbreaks have been described in medical journals as examples of mass hysteria.
As for HBLV’s role as a possible new pathogen, Holmes is curious about the possibility but stymied. The CDC has been unable to obtain samples of the virus from Gallo’s lab. “We’ve tried repeatedly but we’ve been rebuffed,” Holmes says.
“We have been kept completely in the dark on it.” For the time being the CDC’s main effort is to help formulate a definition for the syndrome that researchers in the field can agree on.
One key issue is duration. Some researchers say the illness can strike and abate within six months; others insist that it’s not chronic mono unless it lasts two years. Another issue concerns how much weight, if any, to assign to the Epstein-Barr blood test as opposed to physical symptoms. Once it has a clear definition, the CDC plans to set up surveillance networks in four or five states by this fall.
The Epstein-Barr virus lobbying group is not concerned that the discovery of HBLV may have left it plumping for the wrong virus. “We don’t care if they label it CEBV, HBLV, or XYZ,” says Faubion. “All we know is, we’ve got a lot of suffering people with identical symptoms. There’s a national epidemic of immune system dysfunction and viral disorders in progress which until recently the CDC has been more interested in covering up than doing something about.”
The organization is working to gain enough recognition for the fatigue syndrome so that victims can readily qualify for disability benefits. Until now relatively few have qualified, and then only after going through a long, slow process. In the mean- time, medicine can offer little in the way of a remedy.
The antiviral drug acyclovir and injections of immune globulin have been tried, with mixed results. “There are people who claim to have therapies and charge a lot of money for them,” says Straus, who has done studies on patients in treatment. “But there’s not one that works very well.”
That leaves the chronic mono sufferers hoping for a cure and learning to live with the limits of the disease. At Lake Tahoe, after being unable to conceive for a long time, Chris Guthrie is now about to deliver her second child. “I’m very excited,” she says. “I felt my life had been on hold for several years.”
Guthrie is bothered by partial loss of strength in her right arm and is easily tired. She says that blood tests show she has high levels of antibodies to the new HBLV virus. And since she cut back her medication to protect her developing baby, she has had a constant strep throat that makes her voice scratchy and hoarse. But perspectives change over time. “If that’s the worst that happens,” she says, smiling, “that’s nothing.”
Paul Cheney has learned that medical prophets have a tough audience in their hometowns. After he presented his slide lecture at an Incline Village Chamber of Commerce luncheon last July – complete with the results of lab work, psychometric tests, and brain scans – a member of the audience remarked on his way out, “Sounds like a bunch of hypochondriacs to me.” The rumor in town was that Peterson and Cheney were waxing fat off the profits from the specialty lab work they were ordering, when quite the opposite was true; they subsidized the costs with tens of thousands of dollars out of their own pockets. Cheney’s children had some verbal barbs thrown their way at school. “Maybe we violated some law of nature that says one does not do research projects on viruses in resort communities,” Cheney observes. In January he accepted an offer to practice with the Nalle Clinic in North Carolina and left town. The move has reinforced his belief that the chronic mono illness is a national phenomenon: In his first six weeks he diagnosed nine cases of the syndrome.
But his thoughts drift back to the Tahoe patients. Lying awake in the early morning hours, Cheney wonders if HBLV will turn out to be a “big trick,” another canary in the coal mine like the Epstein-Barr virus, disguising yet another agent or pathway of the disease. “Although,” he adds, “I keep telling Tony Komaroff, nature cannot be that sadistic.”
Perhaps the main lesson of Incline Village is that, if not sadistic, nature is certainly resourceful. A few years ago Americans may have believed that the days of contagious disease were numbered. Small pox. Polio. Tuberculosis. One by one, medical technology could be counted on to eliminate the remaining scourges from the face of the Earth – or at least from sanitized and well-regulated industrial societies such as our own. The surprise appearance of the deadly AIDS epidemic shattered that complacent view. The discovery of HBLV underlines the lesson. We are part of a natural world, where evolutionary change – sometimes swift and sharp – goes on apace. Incline Village got the brunt of the publicity; the nation got the disease.
Writer: William Boly, Hippocrates Magazine – July/August 1987
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