Lyme

by Mary Beth Pfeiffer

  The ultimate goal of the vaccine is for a hungry tick to imbibe on blood laced with inoculation-induced antibodies that would interrupt feeding, cause ejection, or best case, kill the tick. The vaccine might also work in other ways depending on the molecules researchers can identify and target. It might, for one, halt pathogen transmission without stopping feeding, which isn’t ideal. In another approach, it might trigger a response to a biting tick—a noticeable itch or irritation—in line with the “acquired resistance” that Stephen Wikel found in his guinea pigs. A would-be human host, normally helpless against something it cannot feel, would then rid itself, like opossums are known to do, of the parasite.

  A research colleague of Kotsyfakis’, Petr Kopácˇek, resides in the small town of Budweis, south of Prague, where he routinely picks ticks from the mane of his Australian shepherd, Andy. He likes the “acquired resistance” approach, because, as he is fond of saying, “Humans have one advantage. We have hands.” As in, if we feel ticks, we can pick them off. He also believes this route may be the speedier, more promising one. Right now, he feels like he is in something of the slow lane, and it’s clear why.

  In his laboratory in the Institute of Parasitology, Kopácˇek works with Ixodes ricinus ticks, the European relative of the predominant North American tick, Ixodes scapularis. While the magic of modern gene sequencing has opened many doors in tick research, the process is nonetheless protracted. First, Kopácˇek lets larval, or baby, ticks feed on both infected and uninfected mice. Then the ticks molt into nymphs, from which Kopácˇek removes the salivary glands. Think surgery on the head of a pin. Then he sequences the RNA in the saliva to see which molecules show up in infected ticks—are “up-regulated”—and which are missing, or switched off, in clean ones. Molecules are thereby identified that may be key to tick survival, the ones that possibly drive successful attachment and feeding.

  Once identified, Kopácˇek uses a process developed by two Nobel Prize-winning biologists called “RNA interference,” or RNAi; it permits scientists to switch off selected genes on the molecule to see how that affects the biting-fixing-eating process—to confirm the molecule’s role. Then the experiment moves toward its ultimate goal: using the protein molecule—in a recombined, purified form—to make a vaccine that is tried first in animals. Will the animals be protected against infection when tick-bitten, or will they get sick? This is a bit like the search for the Holy Grail, an odyssey involving literally several thousand genetic samples that must be tested. “It is still a lot of work before a candidate molecule may became a vaccine,” Kopácˇek said, who frankly admits he is skeptical of the chance of identifying the right molecules in tick spit. Moreover, he doesn’t trust the organism at the center of this. Borrelia has learned to survive in cold-blooded ticks and warm-blooded mammals and to pass effortlessly back and forth, in Kopácˇek’s words, “to create an efficient camouflage” everywhere it goes. “The Borrelia is very clever,” he told me.

  Kopácˇek’s colleague, Kotsyfakis, was similarly reserved about the chances of success, not so much because of the science but because of the support. A victory over Borrelia, and all the other organisms carried by ticks, will require much more than ANTIDotE promises. The EU’s largesse is too small. The US commitment is anemic, and its approach, disorganized. The mission is complex and daunting. “I feel really that this is a neglected disease,” he told me. “In the Czech Republic, we have the encephalitis virus,”—Tick-Borne Encephalitis or TBE—“people die almost immediately. Whenever you try to apply for Lyme disease funding, even in the states, any kind of funding organization, they consider the ticks do nothing because you will not die.”

  Beyond the obstacles of funding and political support, there is another challenge to a vaccine that targets ticks themselves. They must still bite. The Powassan virus, named for the town in Canada where it claimed its first victim, a child, can be passed in as little as fifteen minutes. Could any antitick vaccine work fast enough to muster antibodies in the time a Powassan-laced tick did its dirty work? Does that negate the value of an antitick vaccine? I asked this of Thomas Mather, known at the University of Rhode Island as the “Tick Guy,” who has fought Lyme disease in the field and the laboratory for decades. “There’s always these little one-offs”—rare though Powassan may be—“that sort of spoil the concept,” he told me. But the idea holds promise. In 2014, Mather’s team reported success in sensitizing what he called “humanized” mice to tick saliva, thwarting half of Lyme infections. He foresees a time when that approach might work against other pathogens.

  In the meantime, Mather brings a practical bent to the huge problem of ticks, a chip-away-at-the-edges, we’re-all-in-this-together, better-do-something approach. He believes people should let go of the idea that science is going to solve the problem any time soon. As part of his self-empowerment theme, Mather periodically has folks in the community give him their shoes. He sprays them with permethrin, a synthetic form of an insecticide produced by chrysanthemums, and happily gives them back. His own study showed that folks in permethrin-treated socks and sneakers were seventy-four times less likely to be bitten by ticks. “It’s easy, and it helps,” he said. Call it one bullet in the war on Lyme disease. Mather would gladly take an antitick vaccine, however much it may occasionally miss a quickly transmitted pathogen or two. “It’s not perfect,” he said, “but better than where we are right now.”

  Where are we now? On a mid-April evening in 2017, I ventured onto the path that rings the field across the lane from my home. The breeze was gentle, and the air, warm and inviting. I returned from that walk with my husband, three family dogs, and twenty-five hungry blacklegged ticks. I foreswore future walks, the first time I had done so in thirty-five years. Ticks, nonetheless, have ways. Two weeks later, after a morning shower, there was this itch, at the very top of my inner thigh. Something was stuck in the skin in my groin, so small yet protruding like a tiny upright soldier that I knew instantly. I’d been so careful. I had checked myself. I had banned the Shih tzu from the bed to avoid imported arachnids. Two days before, however, I had taken a walk on a rail trail and picked the dog up afterward. That’s all I could figure.

  I proceeded to pull the thing out, using a fine-tipped tweezer to grab it sideways by its neck. The trick was not to squeeze the contents of the tick’s gut, potentially laden with pathogens, out of it and into me. Then I placed it on a bit of tissue, took a cell phone picture and blew it up. There it was: An engorged nymphal Ixodes scapularis tick, fat and filled with my blood even if it was a mere speck next to the paper clip I’d included for scale. I thought of the many things I’d read and written on what’s in ticks: Borrelia burgdorferi. Babesia, akin to malaria, prominent, growing, and seeping into the blood supply. Anaplasma phagocytophilum, Borrelia miyamotoi, Bartonella henselae. Powassan virus, found in 5 percent of Wisconsin ticks and in 1 to 5 percent in the Hudson Valley. I looked up the odds. In the Netherlands, 2.6 percent of physician-examined tick bites led to Lyme disease, a Dutch study had reported in 2015. But that only counted people who had manifested the erythema migrans rash; in the United States, some 20 to 30 percent of cases do not. And it did not consider those other pathogens carried by what Dr. Kenneth Liegner, an early Lyme pioneer in New York, aptly described to me as “cesspools of infection.”

  Between the time of the walk in the field and the tick in the shower, I called a company in the New York region that helps rid properties of ticks, using a promising technology tested in research underwritten by the Centers for Disease Control. First, the company sprays the backyard’s brushy edges and leaf litter with an insecticide. This is something I’ve not done in forty years as a homeowner but am growing ever-more open to. Then it sets up small CDC-tested feeding stations or “bait boxes.” Here, mice pass through insecticide-coated brushes before the reward of a tasty meal. The chemical thwarts ticks from feeding off, and becoming infected by, the mice. Yards are made tick-free. The estimate to treat my .69 acre was $840; for my son’s one-acre
homestead, $1,200.

  My family is very important to me. But this, clearly, was not the answer, for me or for society at large. At those prices, a relatively infinitesimal number of ticks will be killed off on isolated properties occupied by well-heeled people. And mice, chipmunks, birds, and so forth will eventually bring the ticks right back in.

  At an animal preserve near where I live, helmeted guineafowl roam between pens of goats and sheep, darting, pecking, and, rather unpleasantly, voicing calls described as “buck wheat” for the hens and “chee chee” for the cocks. The birds can also be seen on a few local lawns and at a nearby horse farm, part of what a 2006 paper in BioScience called their “cult status” as a natural tick remedy. We need environmentally friendly tick solutions, to be sure. The problem is the birds only eat adult ticks and mainly in lawns, researchers have found. That leaves many smaller nymph ticks, particularly in brushy areas, and they are the ones responsible for most cases of Lyme disease. Research is more promising on natural, plant-based, tick-control substances like nootkatone, an oil from Alaska red cedar wood; rosemary oil, and 2-undecanone, a compound in, among other things, wild tomato plants. The CDC gives these substances tacit endorsement by posting favorable research on its website. But consumers must muddle through complex science to figure out what to choose. They need guidance. They need a clear path. They need protection.

  Superbot: Let Ingenuity Loose

  In the mid 1990s, Holly Gaff was a mathematician at Old Dominion University, in Norfolk, Virginia, who wanted to quantify the statistical risk of tick-borne disease. The problem was she had little data with which to work. Following the literal path before her, Gaff began collecting ticks, helping catalog about 100,000 ticks from which to learn. To mathematically model risk, you need to know how many ticks are out there and what is in them.

  By 2014, Gaff had delved so far into the woods that she had become a biologist who had at least some of her answers on tick-borne risk. That’s when she authored a paper in the journal Ticks and Tick-Borne Diseases that contained these unsettling sentences: “Ticks transmit a greater variety of pathogenic, disease-causing agents than any other blood-sucking arthropod,” it began, somewhat ominously. “Despite more than a century of efforts, control of ticks and tick-borne diseases remains a daunting challenge throughout the world.” Indeed. So far, the challenge of a vaccine had been unmet. The baited boxes for mice, described above, were effective but spotty and costly. Deer were fenced, culled, and killed, to little long-term effect. Feeding stations had even been tried at which deer thrust their heads between sets of vertical rollers in pursuit of a bite of corn and, like mice, were doused with an acaricide. After a five-year test, officials in Fairfax County, Virginia, concluded they did not want to set up diners for deer. Although tick populations declined somewhat, the deer congregated, trampled undergrowth, and, more disturbingly, grew in density. Other studies on the method were at turns promising and disappointing.

  If Holly Gaff has her way, little electronic robots may one day troll parks, the edges of ballfields, or wherever people congregate outdoors, all in the service of killing ticks. Her robot is a four-wheeled kind of Superbot, replete with a cape soaked in a chemical that in the case of her experiment was permethrin. The robot even breathed, expelling carbon dioxide in the way that humans do and that makes ticks perk up and extend their forelegs in pursuit of a host. Superbot, or what Gaff calls TickBot, was set loose on three woodland trails in Virginia, its white corduroy cape dragging slowly behind. The results were impressive. Wherever TickBot went, rumbling slightly as an added attractant, the population of lone star ticks was reduced to zero within an hour and stayed at or near there for a full day. Unlike bait boxes and feeding stations, the effect was immediate and thorough. “An hour afterwards, we could sit on the ground in the field site there and not get a tick on us,” Gaff told me. “That was crazy. Lone stars will chase you down.” For this, she thanks a friend at Virginia Military Institute who got Lyme disease and thought to put a remote-controlled car to novel use.

  There are, of course, problems with this approach. The ticks came back after a day. TickBot requires a guide wire to define its course, what Gaff called “a little breadcrumb trail for the robot,” similar to invisible fencing used to contain dogs. The device needs its batteries charged and to be overseen, lest it be hijacked from a public park, for example. It also isn’t known if it will work on the blacklegged ticks in the eastern US, or Ixodes anywhere, that carry Lyme disease. But as with bait boxes and tick-repelling oils, TickBot has potential. Gaff had moved to phase two when I spoke with her, testing it in a child care center and in a neighborhood while substituting a piece of dry ice for piped-in CO2. The ice achieves the same result—making the tick think it’s a mammal. “It’s a living, breathing, moving machine now,” Gaff said. And it obliterates lone star ticks.

  Around the time I spoke with Gaff, New York was experiencing a particularly bad tick season, the result of a bumper crop of acorns two years earlier that had led to more tick-infested mice a year later, and, this year, to many more ticks. We can thank a changing climate for the calamity of large-tree seeds that set this event in motion. This trend had landed a tick in my groin, my best efforts notwithstanding. When I passed fields full of ball-playing youngsters at the local elementary school, I virtually closed my eyes in fear. There they were, playing on a grassy expanse bordered by a thin strip of woods and a fringe of weeds, the places ticks like best. A pre-sweep with Holly Gaff’s robot, I thought, might just help protect those children, if only funding to test it were as prolific as the ticks.

  But at this school, where parents eagerly watched their offspring from the sidelines, there wasn’t a single sign that warned of ticks in the place where it might do the most good. The grounds were sprayed with a natural tick-deterrent, but only after reports of ticks already on children, which is more than many schools do. The district’s overseer of facilities was sympathetic. “I find ticks on my children all of the time,” Michael Shore told me, “and it scares the heck out of me.” But signs might alarm parents, he said, and routine spraying would be “cost prohibitive.”

  Had my small town in upstate New York had one or two cases of West Nile or Zika virus, which most times, like Lyme, are mild, manageable illnesses, there would have been warning signs, fumigation, and public panic. Yet Lyme disease can be as vicious as those mosquito-borne diseases and is far more common. People living in endemic areas will most likely be exposed to Borrelia burgdorferi at some point in their lives, whether they know they were tick-bitten or not.

  Consider a study of blood donors in Sweden, published in 2017. When compared with younger groups, men sixty to seventy years old had the highest rates of antibodies to the Lyme spirochete, an indicator of either past or current exposure. Fifty-two percent were positive. The longer you live, it can be concluded, the greater the chance of a brush with Lyme disease. Many people are infected more than once. Yet so far, the war against Lyme disease has largely been waged through proclamation—May is Lyme Disease Awareness Month—and by press release. People have been told to tuck their socks into their pants, which I’ve observed few do, and check themselves for ticks. Put clothes in a dryer, after gardening or hiking, to kill arachnids. Spray clothing and shoes with permethrin. Use repellents. Clearly, these things have not stemmed a growing wave of infection from a rising tide of ticks. That’s not a reason to give up on these measures. It’s a call for governments at all levels to step up, from nudging citizens to ward off tick encounters to funding broader antitick research.

  Job Hazard

  In the Netherlands, Lyme disease has been considered an occupational risk since a judge ruled in 2009 that a police officer had had substantial on-the-job exposure to ticks before contracting debilitating Lyme disease. A study ensued on how to manage the risk, concluding in 2013 that workers wearing pants impregnated with permethrin had significantly fewer tick bites than those in untreated clothing. A study at the University of Rhode Island, sim
ilarly, found the chemical created a “hot-foot” effect that caused agitated ticks to bolt from a treated sleeve or pant leg. The chemical is officially classified a “weak carcinogen” by the US Environmental Protection Agency, however, which raised concerns among Dutch workers. In the end, employers were told to provide protective, though not necessarily treated, clothing. In short: Do something.

  Permethrin-impregnated clothing has long been used to ward off malaria, scrub typus, leischmaniasis, and Lyme disease among American military personnel, for whom service in tick- and insect-infested areas is often a greater risk than combat. In 1994, a panel of the National Research Council studied the effects of eighteen-hour-per-day exposure to the clothing for ten years and found service members “unlikely to experience adverse health effects.” Tom Mather, the Rhode Island “Tick Guy,” has concluded the chemical is safe for humans and dogs, though perhaps not bees and fish. In making the risk-benefit calculation of exposure to ticks or to a common, approved insecticide, consider the turn taken in the life of a young Dutch woman who knows the occupational hazards of Lyme disease.

  In 2015, Maaike Boere was twenty-two-years old, employed as a social worker, living on her own, and saving money for a wedding. Then she was bitten by a tick on an outdoor field trip with the disabled people she oversaw. She got a round rash but wrote it off as ringworm. She wasn’t treated for another year, when she got very sick. Along the way, this heretofore active young woman with many friends and a bright future was told by several doctors to get over it, she wasn’t really sick, she needed physical therapy, she had a mental problem. This is the template of many an infuriating Lyme story. One doctor finally believed her, but it was too late. Two three-month rounds of antibiotics—generous to be sure—did not resolve her serious neurological issues.