Like Lyme disease, the infection was driven, though certainly not caused, by climate change. It was also supported by small and big mammal hosts like mice and deer. More troubling, however, were many other so-called “reservoirs” of infection and many other methods by which Bartonella was delivered to people—the bite of a tick, sand fly, flea, or louse (indeed, many children do not get through grade school without a brush with head lice)—and, more classically, through the scratch of an infected cat. An epidemic hiding in plain sight, as Breitschwerdt called it, the pathogen was not identified until 1990 and only after it had emerged in an AIDS patient seven years earlier.
By the early 2000s, Lyme disease specialists were finding Bartonella infection, or bartonellosis, in growing numbers of patients. That may not have been surprising, given the widespread prevalence of the pathogen in the environment and the many ways to contract it. A key question remained, however. Was it tick-borne? At least nineteen research studies from 1999 to 2016 had found the pathogen’s DNA in ticks. Rates of ticks infected with Bartonella came in at 18 percent in France; 29 percent in China; 44 percent in Russia; and, in three American states, 35 percent in New Jersey, 13 percent in Indiana, and up to 19 percent in three California studies. Those results certainly pointed to ticks as a potential delivery method of Bartonella.
But tick-borne disease is nothing if not controversial. A 2016 review of the literature, by researchers in Frankfurt, Germany, found multiple studies that showed Bartonella in ticks in California, the Czech Republic, and France, with an average of 15 percent infected in Europe and 40 percent in Finland. The review also found ticks, dogs, and people with dual infections of Bartonella and Lyme disease together, suggesting tick involvement. But in an example of the power of one side of the Lyme divide, the review said the jury was still out, the issue “still controversially discussed.” It referred three times each to two studies, all written in part by Gary Wormser, the lead author on the Infectious Diseases Society of America Lyme disease treatment guidelines. His influence is considerable, his name cited in hundreds of papers. “Clearly,” the Bartonella review concluded, citing Wormser, “Bartonella DNA which was found in several tick species in multiple studies does not prove the presence of viable bacteria.” By then, Ed Breitschwerdt, a veterinarian by training, had seen enough of the Bartonella pathogen to be convinced that tick transmission was likely, even if it wasn’t the only method of delivery.
For Breitschwerdt, the threat of Bartonella is linked to its ubiquitous presence in nature: mice, deer, squirrels, foxes, ground hogs, rabbits, bats, even kangaroos, may harbor the pathogen. Bartonella has been found in red-winged blackbirds in North Carolina, in bottle-nosed dolphins—more often in stranded ones, suggesting debility—and in sea otters in Alaska and California, though not necessarily associated with illness. Most significantly, cats carry it, putting veterinary workers and cat owners at particular risk from scratches or bites from fleas. “Bartonella is as complicated as Lyme disease,” Breitschwerdt said, “and due to the worldwide distribution and numerous vectors”—ticks, fleas, and so on—“may prove to be more important on a global basis.” Many physicians who treat Lyme and other tick-borne diseases agree that Bartonella is a significant threat to human health.
A Cat Bathed, a Baby Lost
In 1998, a man and woman who were raised and married in Long Island, New York, gave birth to twins, a boy and a girl, after years of trying to have children. The father was a carpenter, the mother, a graphic designer. The mother would not know for another decade that the care she extended to a ferocious, feral, flea-infested cat, bathing it twenty years earlier when she was sixteen, would potentially cause her and her family endless heartache and be the stuff of groundbreaking research. The twins, conceived through in-vitro fertilization, survived the caesarean section birth, but the little girl died nine days later. The cause was given as a defect on the left side of the baby’s heart that impeded blood flow, also known as “hypoplastic left heart syndrome.” Long before the births, the couple had suffered many unexplained health problems, including weariness, headaches, urinary and genital pain, atypical forms of pneumonia, and bowel issues. It was after the surviving twin developed a succession of problems—severe colic, night sweats, and hyperactivity—that the woman sought out an unlikely researcher: a veterinarian in North Carolina named Ed Breitschwerdt. She wanted to be tested for Bartonella infection.
By the time Breitschwerdt enrolled the family in a North Carolina State University study in 2009, this much was clear: Bartonella had been found in the embryos and offspring of infected white-footed mice and cotton rats, a clear suggestion it could be passed in utero in people. Infected mice also had higher rates of fetal death and low birth weight. Infected cats had trouble maintaining pregnancies. The hormones of pregnancy had even been suspected of promoting the growth of the bacterium in mice, cats, and cows. The couple’s loss and ongoing trauma were both a tragedy and an opportunity. Breitschwerdt could explore the implications of this bacterium for people. When he tested tissue from a cervical biopsy the woman had undergone in 1991, the scientist found Bartonella. When he tested liver and brain tissue from the baby who had died days after her birth, Breitschwerdt found Bartonella. The father was infected with the same Bartonella strain as the mother. Bartonella infection was also found in their surviving son.
Ten years after their baby had died, after a decade of problems with their surviving child and other failed fertility treatments, the couple at last had an explanation, thanks to Bertschweidt’s research. The cause of their grief was not an inherited defect or the mere product of chance. It was not of unknown etiology, or cause. Very likely, a small bacterium floating in the environment, delivered by the claw of a cat or the bite of a flea or from some other insect—few of us will escape exposure to Bartonella though we may remain asymptomatic—was why this family had suffered so much. Yet no doctor had been able to tell them this until they turned to a veterinarian in North Carolina.
In April of 2011, after publication of that case, Breitschwerdt received an email from a veterinarian he had known as a vet school professor years before: “15 years ago, my cardiologist told me I was in an ‘elite group’ of individuals as pertaining to cardiovascular fitness,” the message began. “Last week, we discovered I need a mitral, aortic and tricuspid valve replacement.” The vet suffered endocarditis, a heart infection. Like the Long Island woman, he suspected it might be related to Bartonella. The veterinarian’s death at sixty-seven, and the death of another veterinarian at sixty-three, led to an article by Breitschwerdt in 2015, entitled “Did Bartonella henselae contribute to the deaths of two veterinarians?”
Three years after the vet’s death, Breitschwerdt would find that 28 percent of 114 veterinarians and their technicians were infected with Bartonella. He studied these and other high-risk people who had serious neurological and other problems, finding Bartonella in two veterinarians; a golf coach who had lived on a farm; a horse farmer; and a young woman who had been severely scratched by a cat and suffered disorientation, motor problems, and seizures. He found it in a fourteen-year-old boy who, after a tick bite, developed migraine headaches so severe he was hospitalized. In Israel, 3 percent of long-term Bartonella sufferers had “often severe and disabling” joint disease, one study found; a study of twenty-two endocarditis victims from four countries, six of whom died, found nine infected with known Bartonella species, thirteen with strains not yet identified.
As with Lyme disease, Bartonella testing is imperfect. Standard antibody tests are notoriously inexact—less than 50 percent of infected patients will correctly test positive early in the disease, even fewer later—and these look for just two species of the bug, of perhaps a dozen so far identified. “Bartonella serology is a mess,” said Breitschwerdt, who has founded a lab to test for the pathogen, “and yes, it is a major diagnostic problem.” That is one reason bartonellosis has failed to be recognized, to reach the “tipping point” Ed Breitschwerdt believes is long overdue.
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One of Many
If Bartonella alone can lead to infant death, long-term neurological problems, psychiatric problems, fatal heart infections, seizures, and brain inflammation, consider what it might do when paired with any of a number of other infections that ticks carry. Then consider the diagnostic challenges of identifying, let alone treating, them. The patient advocacy group Lymedisease.org published the results of a survey in 2014 of 3,000 patients who had late-stage cases of Lyme disease. Among them, more than half had been diagnosed with Lyme and at least one other infection, and nearly a third had two or more. The survey only included patients diagnosed on the basis of the early Lyme disease rash or CDC-accepted laboratory tests. The list of infections was telling—a veritable menu of pathogens passed from ticks to people: 32 percent reported a coinfection with babesiosis, which causes a malaria-like illness; 28 percent had bartonellosis; and 15 percent reported ehrlichiosis. Also prevalent: Rocky Mountain spotted fever, 6 percent; anaplasmosis, 5 percent; and tularemia, 1 percent. (In addition, 15 percent had been diagnosed with mycoplasma, an infection that may or may not be tick-borne—there is scientific dispute—but that unquestionably seizes on compromised immune systems.) Recall the survey of 110 Canadian patients who had been diagnosed with Lyme disease; 36 percent said they were also diagnosed with babesiosis; 33 percent with bartonellosis. Three or more infections were reported by sixteen respondents. These nonrandom patient surveys surely overrepresent the general prevalence of coinfection and report illnesses for which diagnostic tests are sometimes uncertain. They are nonetheless indicative of illness in the sickest segment of Lyme patients, which is considerable.
Multiply-infected people should be no surprise, given reports of multiply infected ticks from virtually every country with Borrelia-laced arachnids. In some places, the rates are alarming. In 2016, 45 percent of Ixodes ticks from the French countryside were reported with at least one infection, and nearly half of those had two. In the Netherlands the same year, a third of Borrelia-infected ticks “carried another pathogen from a different genus,” researchers reported in PLOS Tropical Diseases. In 2017, 67 percent of adult ticks in Suffolk County, New York, were positive for the Lyme pathogen, and 45 percent were found to have more than one infection overall. Of perhaps greater concern, a 2014 study suggested that two dangerous pathogens might fare better inside a tick than one. Nymphal ticks, the ones most apt to infect humans, were 83 percent more likely to carry both the Lyme disease and Babesia pathogens than chance alone would predict, researchers writing in PLoS One reported. The finding hints at some kind of mutually beneficial relationship between the pathogens, or with the small mammals that carry them, that isn’t good news for people. Humans infected with both Lyme disease and babesiosis, which is caused by Babesia, “appear to have more intense, prolonged symptoms than those with LD alone,” wrote researchers for the CDC’s Epidemic Intelligence Service in 2006.
But while the literature is rich with reports of ticks carting multiple pathogens, there is a huge problem for the unlucky multitudes who actually contract them. These are the most difficult cases, presenting with infections unfamiliar to many practitioners and for which treatments are unstudied and regimens unclear. In the Netherlands, these patients cross over to Germany or Belgium. From Canada, they come into New York. In England, patients told me of flying to California or Washington, DC, to see physicians willing to treat them. In Australia, 800 patients sent their blood samples to a laboratory accredited in Germany for analysis. Five tick-borne pathogens were detected besides Borrelia: Chlamydia pneumoniae, in 116 patients; Ehrlichia, 63; Rickettsia, 13; Bartonella, 27; and Babesia, 7. Many Australian patients report they cannot get care for these diseases in their country, in part because these test findings are dismissed.
This is where the tragedy of unchecked Lyme disease and its often-related coinfections meets the reality of a system unable to deal with either, let alone both. In Lymedisease.org’s survey of late-stage patients, half saw seven doctors, waited ten years for a Lyme diagnosis, and traveled more than fifty miles for treatment. It isn’t just that doctors do not know what to do in complicated cases, although they don’t. The bigger problem is they have been told there is no problem at all.
Consider a 2014 article in the American Journal of Medicine that reviewed the evidence on tick-borne coinfections. Beyond challenging bartonellosis as a tick-borne disease, Gary Wormser, the treatment guidelines author, and Paul Lantos, of Duke University, dismissed the contention that multiple tick infections can cause lasting problems. In this qualified, carefully sculpted sentence, they concluded: “The medical literature does not support the diagnosis of chronic, atypical tick-borne co-infections in patients with chronic, nonspecific illnesses.” Translation: If the studies haven’t looked at it, if we can’t find it through imperfect tests, if doctors do not know to test for it, and if your symptoms are all over the place, you don’t have it. To be sure, the literature is spare on how to diagnose and treat tick-borne coinfections. Indeed, coinfections were not tested for or considered in the four treatment trials of long-suffering Lyme patients that have dictated short-course antibiotic treatment for nearly a generation. These small, incomplete, and flawed studies have been used, in article after article, to reject the reality of persisting Lyme disease just as a lack of evidence is used to dismiss long-standing coinfections.
Lorraine Johnson, the executive director of Lymedisease.org, is a lawyer with a master’s degree in business and about forty peer-reviewed publications. Her survey results appeared in the open-access journal PeerJ, which has about half the all-important “impact factor” of the journal in which the Lantos-Wormser paper was published. She is nonetheless undeterred.
Johnson compares her approach to the Framingham Heart Study, which found a new way, starting in 1948, to look at a major cause of death in the United States. Researchers enrolled thousands of patients, studied their lifestyles, took detailed case histories, and tracked them over decades. Ultimately, the study drew significant conclusions on the causes of the American epidemic of cardiovascular disease. In that tradition, Johnson’s surveys of advanced Lyme disease patients, which like Framingham are ongoing, have found more than 40 percent of late-stage patients suffering severe fatigue and sleep disturbance; nearly 40 percent with severe joint and muscle pain; and about 30 percent reporting severe cognitive impairment, depression, and other pain.
To be sure, Lymedisease.org’s patient survey isn’t the whole story; it is what Johnson called “observation trials.” These involve, she said, “real clinical patients in a clinical setting receiving treatments that real treating doctors prescribe.” Her PeerJ paper admitted the limitations of self-reported data from a motivated population, just as traditional Lyme studies have reported potential biases. But she and her colleagues did a key thing that the science of the static, prevailing, traditional dogma has not: They listened to and considered what patients said.
The Unknown and Undiscovered
In October of 2001, the Dutchess County Department of Health issued a warning to physicians and laboratory directors in the small, green county of New York, which is located about a ninety-minute drive from the northern reaches of Manhattan. “Public Health Bulletin,” it said: “BABESIOSIS.” Two residents of the bucolic county, bordered by the Hudson River on the west and the state of Connecticut on the east, had shown symptoms of what the alert called a “potentially severe and sometimes fatal disease.”
Babesiosis is in the same protozoan family of diseases as malaria and is characterized by drenching night sweats, chills, body pain, fatigue, and anemia. Like Lyme disease, the illness is caused by the bite of an infected blacklegged tick, sometimes sickening its unsuspecting victims with the double whammy of both diseases at once, an experience victims would not wish on their worst enemy. For decades before the bulletin was issued, babesiosis had been considered a coastal problem, with the first US case emerging in 1969 on Nantucket Island off the coast of Cape Cod, Massachusetts. It became so com
mon there that it was called “Nantucket fever.” Connecticut had seen its first case in 1988 in the southeastern part of the state. In New York around then, intermittent cases were largely limited to Suffolk County on the eastern half of Long Island, which juts into the Atlantic Ocean for a hundred miles from the edge of New York City to its tip at Montauk Point.
The bulletin, welcome though it was, was not news to Dr. Richard Horowitz, an internist who, since 1990, had specialized in complicated tick-borne cases in a practice in Hyde Park, New York, famous as the Hudson River home of President Franklin Delano Roosevelt. It wasn’t long before Horowitz, a blue-eyed Buddhist whose life-mission was tick-disease care and cure, began to suspect there was more than Lyme disease invading the inland idylls of the Hudson Valley. So did his patient Jill Auerbach, the antitick crusader I wrote about in chapter 1, who had already suffered a crushing bout of Lyme disease. Then she was bitten again in 1994 and infected with this novel, debilitating parasite that was not supposed to have been anywhere near her backyard garden in Poughkeepsie.
This is the reality of tick-borne disease in a growth era. Government and medicine does not move nearly as fast as shrews, mice, and deer. While ticks feast and multiply on mammals, while they nimbly move widely on birds, while they flourish in milder winters and stay active in months when snow used to fall, the natural response of government is to resist suggestions that something has changed. Jill Auerbach had sought medical care and been told she had lupus, landing at last in Horowitz’s office. No, he said, those vicious sweats and the crippling fatigue were caused by a new kid on the block, up and coming and dangerous, a tick-borne pathogen called Babesia microti.
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