In 1997, a Boston University Medical Center physician named Sam Donta wrote a paper that began, “Two hundred seventy-seven patients with chronic Lyme disease were treated with tetracycline for 1 to 11 months (mean, 4 months); the outcomes for these patients were generally good. Overall, 20% of the patients were cured; 70% of the patients’ conditions improved, and treatment failed for 10% of the patients.” Two decades later, doctors like Donta are ostracized in the name of keeping patients safe from overuse of antibiotics. Yet there is little data showing the risk of “adverse events” tied to such treatment is any greater than the accepted risks of many other medications. Reports on the worst outcomes of prolonged antibiotic treatment for Lyme disease, namely serious infection and death, are few and focus almost exclusively on intravenous care. They are also used to instill fear in doctors who consider any kind of longer antibiotic treatment.
A brief report on the death of a thirty-year-old woman from a fungus in an intravenous catheter used to dispense antibiotics has been cited seventy times in the scientific literature. The short case report of the death of a fifty-two-year-old woman has been cited thirty-eight times; after ten weeks on IV treatment, she developed an all-too common infection from Clostridium difficile, which kills 14,000 Americans annually. These footnoted cases are used to bolster blanket dismissals that state, as one did, that long-term antibiotic treatment has “contributed to injury and even deaths of patients.” Such citations rarely say how many deaths. A list of studies posted by the CDC on the risk of prolonged Lyme disease treatment includes just six published papers in twenty-one years; four are single reports of deaths related to intravenous care. A fifth covered gall bladder complications, and a sixth focused on “unorthodox” treatments “marketed” to patients. This is hardly an extensive body of literature.
Antibiotics are not risk-free and should be used only in spare and appropriate measure. In a Lyme treatment trial published in 2003, four of fifty-five patients had severe side effects from antibiotics, including one allergic reaction and three intravenous-line infections. Holly Ahern, a New York microbiologist and scientific advisor to patient advocates, said, frankly, “I am not a fan. They cause collateral damage to our micro-biome.” For one, overuse of the drugs can promote antibiotic resistance in patients to other infections. Yet while the risks of prolonged antibiotics are common to and acceptable for conditions such as acne, urinary tract infection, or tuberculosis, a line has been arbitrarily drawn on Lyme disease. And it is based on medical recommendations that have been raised to the level of dogma.
In the years since intravenous-line infections were reported in the 2003 Lyme trial, and in other trials as well, strides have been made in the safety of intravenous line care. The Journal of Hospital Infections pointed in 2011 to “huge success…in reducing catheter-related bloodstream infection.” But, most significantly, Lyme physicians have seen patients improve in treatment regimens that often involve multiple, usually oral, antibiotics. They generally prescribe them along with drugs to treat other infections delivered by ticks; antimicrobial herbs, and sometimes, antibody-boosting therapy derived from human plasma. “The risks of oral antibiotics are almost negligible with a proper diet and adequate probiotic supplementation,” said a leading Lyme disease physician in New York State, Richard Horowitz, who sees IV antibiotics as helpful in neurological cases but “not viable” in the long term. “The risk however of not properly treating chronic Lyme is a life filled with pain and disabling symptoms.”
Doctors audacious enough to take on long-term Lyme disease know that antibiotics have limited effect and are trying to figure out what works. For thirty years, Horowitz has been on this quest, convinced that prevailing treatment recommendations have led to a “dysfunctional” model of care. He reported significant success in 2016 when he combined antibiotics with, of all things, a sulfa drug used for leprosy, called Dapsone. Horowitz, whose findings were published in Clinical & Experimental Dermatology Research, had picked up on the success of test tube experiments at Johns Hopkins that found the drugs effective at killing spirochetes that had survived initial antibiotic treatment. This was a marriage of laboratory findings and real-world practice to find out what works in intractable cases, a kind of work that is, for Lyme disease, all-too scarce.
The line in the sand on Lyme-dispensed antibiotics means patients in the United States and other countries cannot get drugs their doctors might actually want to prescribe. An Austrian woman said she feared that her doctor might refuse her more antibiotics if her name was used in this book because it would potentially identify him. A Canadian man, Patrick Leech, convinced his doctor to grant two months of doxycycline after suffering facial palsy, joint pain, and muscle spasms; the pharmacist called the doctor, and he was denied. Lyme specialty physicians in many states have withstood licensing board investigations that centered on their use of antibiotics, dogging their practices for years, and leading other physicians to steer clear.
Instead of treating and judiciously retreating, doctors misdiagnose and refer patients elsewhere, underestimate the implications of Lyme disease, and avoid patients altogether. This happens especially in later cases, but in early ones too. Doctors have been told that medicine has Lyme disease figured out. “There’s no evidence in North America of persistence of the spirochete after treatment,” the chief author of the Lyme treatment guidelines, Dr. Gary Wormser, told me in an interview in 2012. “We’ve published on it, and we’ve looked. You show me a credible study in the U.S. that shows persistence of the organism after treatment.” There is, indeed, such evidence, some published before I spoke with Wormser, who declined to speak for this book, and a good deal afterward. These studies, which I will discuss in chapters 4 and 7, document lingering spirochetes in antibiotic-treated animals and their survival after being dosed heavily with antibiotics in test tubes. Animal and test-tube studies are accepted means of testing hypotheses in many scientific endeavors—and for spurring further research in humans—but their findings have been rejected for Lyme disease. These published studies, however, demonstrate the significant shades of gray in the black-and-white picture of Lyme disease care as practiced in America. While antibiotics are by no means a cure, and intravenous antibiotics pose risks, there is evidence that additional courses can provide relief for lingering, persistent, intractable Lyme disease. And there are reasons to question the trials and studies that have found otherwise.
“Lonely Battle”
When Barbara Pronk’s email arrived in inboxes, there was a furious scramble to save her. Her website post was taken down. Police were dispatched to the flat by the sea. Colleagues were horrified. One of them read the email in Australia, where she had been transferred, and instantly knew: Barbara, a serious, competent woman, a perfectionist at planning, was already dead. Barbara had indeed planned well. She had bought the medications she took online. She had rented the apartment for the purpose of suicide. She had picked out her coffin.
It matters little that Barbara Pronk, who died alone, may have contracted her illness from the bite of a tick in Florida or in her home country at some other time. The factors that led her own survival to clash with that of a tick are widely shared in many parts of the developed world.
After Barbara’s death, the Dutch Parliament made a commitment to address Lyme disease. Three clinics were planned to treat the disease, though arguments have ensued on what treatments to use and for how long. Research money was made available by Parliament, enabling various experiments. Sheep were employed in forest patches to attract and remove ticks. Deer were fenced from areas to test the effect. Ticks were monitored in the dunes and heather. Climate change was measured. Surveys were done, finding that 31 percent of Lyme patients were infected in their own gardens. Said Willem Takken, the Dutch entomologist, “There is no nature area where you are safe.”
For Barbara, Lyme disease was “a long tough battle, a lonely battle, a hopeless battle, a grueling battle.” In her final note, she called her experience “degrading,
” the disease “not recognized and heavily underestimated.” Barbara’s experience—her maze of skeptical doctors and ineffective treatments, her intolerable pain—led her to believe that suicide was the “number 1” cause of Lyme death. She may, indeed, be right. A New Jersey psychiatrist who had long treated Lyme disease went through his case records in a study of patients with suicidal thoughts and actions. He found many who had attempted or considered suicide after a Lyme diagnosis who had never done so before, and a host of suicide risk factors among Lyme patients: “explosive anger, intrusive images, sudden mood swings, paranoia, dissociative episodes, hallucinations, disinhibition, panic disorder,” and so on. When he calculated the frequency of these observations and applied them to the estimated population of chronically ill Lyme patients, the psychiatrist, Robert Bransfield, concluded there were perhaps 1,200 suicides in the United States each year. His paper, published in 2017 in the journal Neuropsychiatric Disease and Treatment, was the first to explore the association between Lyme disease and suicide and was far from a definitive tally of death. But it raised an important question surrounding a disease that is known to invade the mind, cause depression and cognitive problems and, moreover, send its victims for help in a system that offers little.
Around the time of Barbara Pronk’s death, there were five Lyme disease suicides in the Netherlands. In one, a twenty-seven-year-old man from the central city of Lelystad, Jeroen Link, jumped from a rugged limestone cliff on the English Channel in Normandy, France. Jeroen had been an energetic, trouble-making, endearing youngster. He grew to a blonde and muscular adult who loved playing soccer with his friends despite struggling with Lyme disease since he was fifteen. He too had been told, in the common Dutch expression, that his malady was between his ears. When he told his parents what he intended to do, they were not surprised. “We talked, hugged, cried,” his father, Johan, wrote on Facebook two months before Barbara’s death. “What could I do? I was numb. Ideally I wanted to keep him with me, of course, but I also gave him peace and quiet. No more pain.” Commented one woman in response, “Those of us that are afflicted by this, know exactly where this young man’s mind was.” Jeroen’s suicide, covered in the Dutch press along with the others, was one more reason the Dutch Parliament took up the Lyme disease cause.
“Please imagine, your own partner, son, daughter, father or mother was affected by this monstrous disease,” Barbara implored in her final note. “A healthy person has 1,000 wishes, a sick man only one.” Barbara wasn’t asking for her health. That was gone. She was asking for change.
CHAPTER 3:
An Ancient Bug Revives
* * *
The minuscule, ringlet-shaped organism known as Borrelia burgdorferi, the source of considerable human misery, has seen the world through the ages. Fifteen to twenty million years ago, a baby tick in the Cordillera Septentrional Mountains of the Dominican Republic sipped the blood of some prehistoric animal and was caught in a torrent of sap from a pine tree. The gut of that prehistoric tick, seen under a microscope in the twentieth century, would reveal wiggling corkscrew-shaped Lyme bacteria, preserved in motion like the ash-covered victims of Pompeii. A few million years later, in the Pleistocene Age, the bacterium that would be the driver of Lyme disease was caught under a global sheet of ice, survived a two-million-year sleep, and emerged 12,000 years ago when the ice retreated.
Nestled, like its forebears, in the alimentary canal of hard-bodied ticks, Borrelia burgdorferi and the ticks it inhabited thence began a northward migration saddled on birds or attached to roving vertebrates. Genetic markers tell us these post-Ice Age bugs moved swiftly from the southern United States to the Northeast, then the Midwest, galvanized much as they are today by a warming climate. Across the Atlantic, meantime, the bug was ensconced, among other places, in the Italian Alps. There, a bearded shepherd, nicknamed Ötzi, was shot in the shoulder with an arrow some 5,300 years ago, his forty-five-year-old body entombed in a glacier. A belated postmortem revealed this prehistoric murder victim to be the first known case of Lyme disease. Quite remarkably, he even carried a mushroom-like fungus with antibiotic properties, perhaps to quell the pain, to keep the infection in check.
The children of Lyme, Connecticut, from which the disease took its name, were not B. burgdorferi’s first young victims, as they most certainly were not the last. Some five hundred years before the birth of Christ, the Lyme pathogen lived inside the knees of prehistoric Tchefuncte Indian teenagers in Louisiana, whose buried bones show rheumatoid arthritis-like disfigurement since linked to Borrelia. That particular Lyme disease endemic subsided, scientists speculate, after the hunter-gatherers turned to agriculture, giving ticks less chance to bite. Yet the pathogen remained, infecting the tissue of colonial Americans and prospering amid the abundant forests, meadows, and deer of America and Europe in the 1700s. In 1774, a Rev. Dr. John Walker precisely described what is today believed to be quintessential Lyme disease on an island in Scotland’s Hebrides. “This disease,” he wrote, “arises from a worm lodged under the skin, that penetrates with exquisite pain, the interior parts of the limbs.”
To this point in human history, the fortunes of Borrelia burgdorferi were rising. Then, in the 1800s, things changed. Deer were hunted for meat and fur. Agriculture slowly consumed the forests that sustained the mammals and, by extension, the ticks to which they were literally linked. By 1900, the North American deer population plummeted to almost zero, from perhaps six million in 1500. European stocks dwindled for the same reasons. For centuries, small mammals had harbored and nurtured the spirochete during the first two stages of a tick’s life: as babies, called larvae, and as juveniles, or nymphs. But deer were key to the mature arachnid. The ungulates were the marital bed for the adult arachnids; they were the place where each succeeding generation of Ixodes ticks was made possible. “Deforestation of much of the Northeast during the 18th and 19th centuries resulted in the near total elimination of deer, and presumably also of deer [or blacklegged] ticks,” wrote the first researchers to posit this theory, Alan Barbour and Durland Fish, in 1993. Gone were the deer. Gone were the ticks. Gone was Borrelia burgdorferi. Or at least, that is how the latest chapter in the on-again-off-again life of B. burgdorferi goes—a bug that natural history shows was not to be written off, and certainly not this time.
George Poinar Jr. is an Oregon entomologist and college professor who delicately dissects fossilized resin, huge yellow chunks of it, to unravel secrets on an epochal scale. It was Professor Poinar who found that tick in Dominican amber, its gut awash in what are officially termed “Borrelia-like” cells. (He used a strong microscope to identify the spirochetes; extraction would destroy the specimen.) That, however, wasn’t by a long shot his oldest discovery of pathogen-packed ticks. Encased in another chunk of amber from Myanmar, half a world away and a hundred million years old, he found another set of cells, Rickettsia-like, inside the belly of a very old tick, the hard kind like Ixodes. As with B. burgdorferi, Rickettsia rickettsii emerged around the turn of the twenty-first century as a pathogen to watch. The cause of sometimes-fatal Rocky Mountain spotted fever, its numbers, though small, have soared in the United States since 2000 as ticks move and grow in number. Studying ancient ticks makes Poinar think they and the microbes they carry have aligned themselves over the ages in a compact that somehow works for both, a notion supported by genomic research.
“I feel that ticks were carrying and transmitting Borrelia-like organisms for millions of years,” he told me. “A close association evolved between these two organisms that allowed the successful transfer of pathogens…back and forth from vertebrate [the animal] to vector [the tick] and vice versa. The longer two organisms have been associated with one another, the more finely tuned the association becomes.” Poinar’s research points to the most primitive origins of modern-day ticks and the cargo they haul. For all we know, Borrelia may have been in a tick that hitched a flight on a pterodactyl, so old and resilient is this remarkable, indefatigable, unfathomable organi
sm.
A Bug of Many Talents
The story of how and why Borrelia burgdorferi, and with it Lyme disease, rather suddenly materialized in 1970s in the Northeast state of Connecticut is not simple. Nothing, indeed, is simple about the spirochete’s mechanisms and methods, which are nothing short of a symphonic arrangement involving the guts of ticks; the blood of animals; and all the changes of temperature, viscosity, and chemistry therein. Nature is by definition complex, of course, but this ancient bug stands apart.
Remarkable? Like the tick that carries it, which can sense the breath of a potential meal from fifty feet, this spirochete has special talents. When it passes through the mouth of a tick to the animal or human the tick has bitten, B. burgdorferi stops producing a protein on its surface that helped it adhere to the tick’s digestive tract (so as not to be swallowed whole). By thus “down-regulating,” as it’s called, the bacterium relinquishes a red flag that would otherwise signal its host to kill it. And when it passes into the human bloodstream, which for them is akin to a kayaker on the Colorado River after a raging storm, B. burgdorferi swings on tethers within blood vessels, planting anchors along the way to steady and slow its movement. That’s not all by a mile.
Indefatigable? Millions of years of evolution have blessed B. burgdorferi with a powerful, and hidden, propulsion mechanism. Its flagellum—that tiny mechanism that helps a bacterium swim—is internal, shielded by a membrane that lets it bypass alarm bells normally set off in any self-respecting immune system. This structure allows it, moreover, to swim Olympian-like through fluids that would be the death of many bacteria and to penetrate tough joint capsules, the pericardium around the heart, and meninges that encase the brain, something few bacteria can do. Tara Moriarty, a Borrelia researcher at the University of Toronto, likened it to a fast-moving snake, a “flat wave,” skinny at one end and as comfortable in liquid as in solid. Coiled as spirochetes are, they look under microscopy like so many tiny, whirring drills.
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