Then there is how this all plays out in fast-paced labs for a technology the CDC study called “complex (and) technically demanding.” Dutch researchers looked at the performance of eight commercial versions of the first tier test and five of the second in 2011; they reported “widely divergent” results depending on which combination was used. In comparison to Lyme tests, antibody testing for HIV infection is a breeze. In 2017, two British researchers calculated the statistical probability of accuracy for each test in a head-to-head comparison. For late-stage Lyme disease—when two-tiered testing supposedly works best—Lyme tests falsely ruled patients negative 17 percent of the time. The HIV test was falsely negative in 0.1 percent of cases. Writing in the International Journal of Medicine in 2017, the researchers noted that was a 170-fold difference.
The Lyme controversy would cease to exist if there was a better test and, moreover, a standard, predictable, and accepted way to culture Borrelia burgdorferi, namely to grow it from a sample of an infected person’s blood. To really know how well the test works, Leeflang told me, you need to measure test performance in people who are known to have Lyme disease and, as important, in people who don’t. “You need a gold standard,” she said. In 2013, a Lyme disease researcher at the University of New Haven in Connecticut, Eva Sapi, introduced a culture test, her results published in the International Journal of Medical Sciences. Sapi’s methodology was challenged in an article by CDC’s Johnson, who has published on, and has patents for, Lyme disease diagnostic technology. The CDC subsequently recommended against use of what I’m told was an imperfect study but a promising technology.
Instead, the agency has for many years upheld use of a diagnostic strategy that is indisputably flawed. “Until we can separate the infected from the uninfected and the cured from the uncured,” wrote Elizabeth Maloney, a physician and author of the International Lyme and Associated Diseases Society guidelines, “arguments over diagnostic and therapeutic approaches will continue.” Dattwyler hopes not. He has been working on a new antibody test that, if approved and marketed, will more accurately diagnose infections. He acknowledged it would not distinguish current from past infection, as with the old test, which is a huge problem in areas where people are repeatedly infected. Beyond this, he volunteered that the test on which he has worked for a dozen years would likely make him some money. “It is going to change,” he said. “It’s going to change because I’m one of the guys leading the charge to change it.”
Catching the Strains
Joanne Drayson, a silver-haired civil servant from Merrow, England, told me her Lyme disease story across a quiet table in East Horsley, Surrey, a village southwest of London. Like others with long-lasting Lyme disease, she was riled over her treatment missteps and determined to change things for those who would follow. This is how a movement is building around the world, one Joanne Drayson at a time. From 2003 to 2007, Drayson had seen eight doctors and been told she suffered a variety of ailments including fibromyalgia, musculoskeletal disease, and myalgic encephalomyelitis, also called chronic fatigue syndrome. Her joint pain and weakness persisted even after twenty months on steroids, which suppress antibody production and may explain why she tested negative for Lyme disease. By happenstance, her real problem became clear when she developed a chest infection and was prescribed amoxicillin. Finally, four years into her search and within twenty-four hours, she felt better, much better.
“Perhaps,” her primary care physician suggested, “you have Lyme disease.” To Drayson, a gardener, grandmother, and soft-spoken pensioner, this was an ironic gift. In a survey, 52 percent of late-stage Lyme disease sufferers in the UK said it took more than two years to get their diagnoses. So did 61 percent of 6,000 such patients in a survey by the US-based research and advocacy group LymeDisease.org. At the time, Drayson knew nothing about Lyme disease. Looking back, she recalled two rounds of tick bites, two rounds of flu-like symptoms, and each time, rashes on her legs. She had even reported the first rash to her doctor, and it was in her records. Finally, at this juncture in 2007, Drayson was delighted to have an answer and to have gotten better on antibiotics. The problem came later, when she needed regular rounds of amoxicillin to manage her symptoms.
In the United Kingdom, as elsewhere, doctors risk raising red flags with the authorities if they use too many antibiotics in contravention of accepted guidelines for the treatment of Lyme disease. After being on antibiotics for eight months, Drayson, then fifty-seven, was referred by her primary care doctor to a rheumatologist in London for a consultation. She told the specialist that the antibiotics were helping her and she had less pain than she had had in years. She said she believed the correct diagnosis had at last been found. She told him she had read up on Lyme disease on the Internet, at which point the rheumatologist “wagged his finger” and demurred, Drayson said. The physician followed up with a letter to Drayson’s primary care doctor that sums up the experience of many Lyme patients I have interviewed. “My feeling is that there is no evidence that this patient has been bitten by an Ixodes tick nor has she developed Lyme Borreliosis,” he wrote. Instead, some past infection—he did not specify—had caused chronic fatigue syndrome in Joanne Drayson. Moreover, he wrote, “the patient now has Lyme neurosis due to her reading around the subject.” He recommended that Drayson get off antibiotics, take two prescribed antidepressants, and sign up for cognitive behavioral therapy, a form of psychotherapy that helps people change the potentially negative ways they think. Drayson, the doctor wrote, “of course…was unable to accept” this advice.
For some reason, this esteemed professor of rheumatology felt more comfortable diagnosing Drayson with chronic fatigue syndrome—what the Mayo Clinic describes as “a disorder characterized by extreme fatigue that can’t be explained by any underlying medical condition.” Essentially, he opted for a vague constellation of symptoms rather than an illness, Lyme disease, for which there was at least circumstantial evidence, namely her recorded tick bite, rash, and symptoms. Moreover, he felt better recommending antidepressants, which, though generally safe, come with suicide warnings. He was going by the book, which rejects long-term antibiotic treatment.
In LymeDisease.org’s survey of patients whose Lyme diagnoses had been delayed, “mood disorder” was the most common diagnosis they received, reported by 59 percent. The second and third leading diagnoses were chronic fatigue syndrome, 55 percent, and fibromyalgia, 49 percent. An emergency room physician from the United Kingdom, who I met at a conference in Paris, said he began treating Lyme disease with natural methods as a sideline after seeing many patients who were looking for help. “They’ve been through the mill of the conventional health service,” Andrew Greenland said. They’re told, “it’s in their head.”
As in any disease, some people may think they have Lyme disease but don’t. At the same time, Lyme mimics many diseases to which its symptoms are often attributed. Twelve percent of LymeDisease.org’s survey respondents said they had been diagnosed with multiple sclerosis before being treated for late-state Lyme disease; a Polish study reported in 2000 that multiple sclerosis patients had twice the rate of positive tests for Lyme antibodies than other patients with neurologic diagnoses. Could some MS cases actually be Lyme disease? Similarly, patients at a psychiatric hospital in Prague had twice the rate of Lyme disease antibodies than healthy subjects in the population. “In countries where this infection is endemic,” the Czech researchers wrote in the American Journal of Psychiatry in 2002, “a proportion of psychiatric inpatients may be suffering from neuropathogenic effects of Borrelia burgdorferi.” For such patients, antibiotics might work better than antipsychotic and antidepressant medications. If nothing else, this and research I’ll discuss in chapter 7 suggests doctors should rule out Lyme disease.
In 2016, Kris Kristofferson, the legendary musician, made an announcement. After suffering for years with debilitating memory loss that had been attributed to Alzheimer’s disease, he had been diagnosed with, and successfully treated for, Lyme diseas
e. Joint pain and heart issues resolved; his memory came back.
The failure to recognize Lyme disease, and the tendency to call it something else, goes back again to the tests. Joanne Drayson, like other late-stage patients, did not test positive for Lyme disease though conventional wisdom dictates that, in her late stage of infection, her immune system should have mounted enough antibodies and compiled enough bands to signal a past, if not current, infection. But should she have tested positive, at least using conventional tests? This is where we get into how Lyme disease is viewed—a single, straightforward disease with a reliable test—as opposed to what it often is: a manifestation of one or more tick-borne pathogens that come in many disease-causing species and strains that may or may not be tested for and for which adequate tests may or may not exist. In Scotland, for example, a group of Inverness microbiologists retested archived blood and found more patients were Lyme positive based on markers for local Borrelia strains rather than for the strain targeted by standard two-tiered technology. These were patients who, like Joanne Drayson, had been told they did not have Lyme disease. Then there are the other infections, like babesiosis and bartonellosis, for which doctors often do not test and are not trained to treat. Indeed, science has only scratched the surface on coinfections—does one pathogen mask another’s diagnosis?—and most certainly has not cataloged all the variations of tick-borne disease.
Sue Faber of Burlington, Ontario, knows the pitfalls of testing. She suffered for years, beginning in 2001, with migrating body pain, fatigue, a chronic cough, and cognitive problems so concerning that she resigned as an emergency room nurse, fearing she didn’t have what it took anymore. Seven or eight specialists later, Faber’s primary care doctor was stumped. “Sue, we’ve tested you for everything,” she said. Nonetheless, the physician said she would try again and, this time, added a Lyme test. Faber flunked: positive on the first tier, negative on the second. Faber did her own research and came to believe her symptoms and progression aligned all-too neatly with Lyme disease. What ensued was an odyssey, shared by many patients, of phone calls, faxes, fights for repeat tests, rejected requests for antibiotics, and costly trips to the United States for care. An alternative test that showed her to be Lyme positive was dismissed. “She was adamant that I didn’t have Lyme,” she said of her doctor.
In the end, Faber, then thirty-nine years old and on disability, prevailed in a hollow victory. In January of 2016 came these words from an infectious disease physician who ran Faber’s final hard-fought test: “Your Euro Lyme is positive.” She did indeed have Lyme disease, but she carried a species that did not show up on the standard North American test. Faber had traveled extensively in Europe as a young adult; she wasn’t the first Canadian to test for a European species. In 2007, a twelve-year-old girl was hospitalized in Toronto with back pain and facial palsy that strongly suggested Lyme disease. After a savvy doctor did a bit of laboratory sleuthing, the girl was found to have picked up a European Lyme species during travel to France, according to a case report in the medical literature. The paper warned doctors: Look for European Lyme bugs, which specifically must be requested when ordering tests.
Soon after her diagnosis, Sue Faber’s story took a perplexing twist. Her middle daughter also tested positive for the European species. But, unlike her mother, she had never been to Europe, raising questions science has yet to answer. Was she infected in Canada with a recently settled European bug? Or, as some researchers and physicians think possible, was the infection passed in utero? Of note, in 2006, a European Lyme disease strain turned up on the Newfoundland coast in a colony of nesting seabirds, typical of a phenomenon playing out around the world. Migrating birds are cargo holds for ticks, as will been seen in chapter 10.
Canada is a new frontier in tick-borne disease, as disease-ridden ticks ride a wave of climate change that is projected to take them 150 to 300 miles farther north by 2050. In just four years through 2013, cases in Canada grew twelvefold, with patient groups mushrooming side-by-side with ticks. When the government’s plan of action was released in 2017, the fruit of the Ottawa conference I mentioned earlier, patients found it so weak and unresponsive that a petition to scotch it drew 20,000 signatures in a week. This kind of response, like the bull’s-eye rashes on children’s thighs, is symptomatic of a burgeoning problem, one that government and medicine, on both sides of the border, have yet to address.
In 2012, four Canadian scientists assessed the nation’s Lyme toll in an article in Open Neurology Journal entitled “Evolving Perspectives on Lyme Borreliosis in Canada.” In it, the researchers considered questions that seem almost naïve by publishing standards for Lyme disease science. Didn’t they know, I thought as I read the article, that those issues were long ago dismissed and not open to debate in the United States? Yet they remain at the heart of how to manage and contain a worldwide epidemic. The scientists questioned whether US-designed two-tiered testing worked for Canada, which has some genetically different variants of Borrelia burgdorferi. That diversity, a 2011 article in Applied and Environmental Microbiology stated, “has consequences for the performance of serological diagnostic tests and disease severity.” In other words, cases could be missed. The scientists also challenged the way that endemic areas were being strictly defined, which would also cause cases to go unrecognized, untreated, and uncounted. They pointed to signs of impending danger. Dogs, as sentinels, were turning up across the country with Borrelia in their bloodstream. Growing numbers of infected ticks and tick species were being found other than those officially recognized.
In 1992, the paper recounted, two Canadian physicians had noted an increase in Lyme disease referrals at a clinic in Vancouver, British Columbia. At that point, the only area of the country known to be endemic for the disease was in Long Point, Ontario, some 2,400 miles away. The doctors studied sixty-five cases and concluded that just two patients likely had Lyme disease, with both illnesses contracted in travel outside the province. The other sixty-three patients, the doctors wrote, had skin diseases, rheumatological and neurological issues, psychiatric illnesses, fibromyalgia, chronic fatigue syndrome, and so on. The physicians’ article in 1993 mirrored a wave of studies, referred to in chapter 4, on alleged overdiagnosis of Lyme disease in what the Canadian doctors said was an “area of nonendemicity”—namely where there were no infected ticks or people. It would be just one more year, in 1994, before the Lyme disease pathogen was reported in British Columbia and another year, 1995, before eighteen areas of the province were declared endemic. Today, Lyme advocacy groups there, as elsewhere in Canada, are still fighting for recognition. “Canadian statistics for Lyme disease are very misleading and, to me, totally unreliable,” said John D. Scott, perhaps the nation’s leading tick researcher. “Public health [officials] do their damnedest to discount and dismiss the problem.”
To Janet Sperling, an author on the critique of her country’s response to Lyme disease, Canada isn’t asking the basic questions. It is merely following the lead and dogma of American medicine. Debate is stifled. Divergent opinions—those expressed at the Ottawa conference but missing from the proposal that grew out of it—are ignored. “The new action plan for Lyme disease,” she told me, “is neither new nor an action plan.”
Patients the Tests Leave Behind
When Brian Fallon embarked on a clinical trial of antibiotic retreatment for Lyme disease patients who remained ill, he struggled to find suitable candidates to study, even in a country with then perhaps 200,000 cases a year. Fallon, director of the Lyme and Tick-borne Diseases Research Center at Columbia University Medical Center in New York City, had to review the case files of 3,368 Lyme disease patients before his study, published in 2008, enrolled just thirty-seven—roughly one of every hundred reviewed. Significantly, more than half of patients were rejected because they didn’t register true positives in two-tiered testing even though they had already been diagnosed with the disease. To be sure, only provable cases should be included in important research. But the fi
gures demonstrate the elusive nature of finding certifiable Lyme disease with standard tests. Jill Auerbach, a long-term patient from New York, was rejected for the study, scoring different numbers of bands—same blood draw, same lab—that combined would have been enough to signal infection.
Indeed, the most famous Lyme disease treatment trial, published in 2001 in the New England Journal of Medicine, included fifty-one patients who similarly flunked the Lyme disease test. For the study, they were counted as having had Lyme disease because they had had the distinctive rash. But, despite persisting symptoms, they stubbornly refused to test positive. They were, in medical parlance, “seronegative.”
Sixteen years since that seronegative study charted the future of Lyme disease care, Christian Perronne is still rankled. An infectious disease physician practicing just outside of Paris, Perronne rejects the French medical guidelines for treatment of Lyme disease, which, he says ruefully, were “exactly copied” from those in the United States. The guidelines sharply limit antibiotic courses based on the New England Journal study, which ruled retreatment was ineffective and risky. Perronne is particularly galled by a huge incongruity. The crafters of Lyme disease guidelines contend that Lyme disease tests work and should be relied on to make diagnoses. But when it came to conducting the seminal study on treatment, fifty-one patients were included for whom the tests failed—something Lyme doctors say regularly occurs. “They’d kill me for that,” Perronne told me in a call from his office at the University of Versailles Saint-Quentin. In it, he described a twenty-year battle to help a patient population that nobody wanted in a medical milieu that believed Lyme disease was “benign” and the test for it “perfect.”
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