NEWS FEATURE TICK TROUBLE Scientists have no shortage of ideas about how to stop tick-borne illnesses. What is holding them back? BY MELINDA WENNER MOYER n a balmy day in late June, Scott aim to protect people from infection directly. A incidence more quickly than Lyme. In a July Williams waits for a white-footed more radical approach could hamper the ability 2015 position statement, the Entomological mouse (Peromyscus leucopus) to fall of ticks to bite humans or animals, potentially Society of America argued for a national strat- asleep. Williams, a wildlife biologist protecting against dozens of illnesses spread- egy to combat tick-borne diseases. “The recent with the Connecticut Agricultural ing across the United States, Europe, Africa confluence of environmental, ecological, soci- OExperiment Station in New Haven, has just and Asia. ological, and human demographic factors,” it AFLO/NATUREPL.COM transferred the animal from a trap to a plastic That the field needs creative solutions is said, “has created a near ‘perfect storm’ leading bag containing a cotton ball doused in anaes- clear. Many long-recommended interventions, to more ticks in more places throughout North thetic. As soon as the mouse’s breathing slows such as pesticide application or controlling America.” to one breath per second, Williams will take it populations of deer, which are an important out, draw blood, weigh it, put an ear tag on it for host for adult ticks, have had mixed success BACKYARD BATTLEGROUNDS identification and check the animal for ticks, in scientific studies. Even the time-honoured Williams tags, weighs and releases his mouse saving any that are engorged with blood. He protective strategies that most people use are just in time. It has no ticks to bring back to the must work quickly. The mouse will wake up in not evidence-based. “We tell people to wear lab for further analysis, but there will be other about two minutes, and she might be grumpy. repellents, to do tick checks and to shower if opportunities. Members of 32 Connecticut Williams is testing whether vaccinating mice they’ve been in the field, but there’s very little households have volunteered to place traps against Borrelia burgdorferi, the bacterium that data to show that these things reduce human around their properties, and some will also get causes Lyme disease in the United States, can illness,” explains Ben Beard, chief of the CDC’s boxes of mouse treats laden with vaccine. The reduce the proportion of ticks that are infected. bacterial-diseases branch in the division of hope is that, over time, fewer mice and ticks will Health officials are looking on with interest. vector-borne diseases. harbour the bacteria at the sites with the vac- Connecticut has one of the highest rates of Diseases spread by ticks are on the rise cine bait. human Lyme disease in the country, and June around the world, spurred by a combination of The plan is unconventional, because most is peak time for transmission. Borrelia burg- factors, including shifting climates and popula- Lyme-control measures focus on white-tailed dorferi infects an estimated 329,000 people in tion sprawl into rural areas. Reported cases of deer (Odocoileus virginianus), which have the United States each year, according to the Lyme, the most common US tick-borne illness, exploded in number in the United States over US Centers for Disease Control and Preven- have nearly tripled in the country since 1992, the past century as young forests have become tion (CDC) in Atlanta, Georgia. And although although some of the increase could be due to increasingly fragmented by human develop- most people who get prompt treatment recover heightened awareness. Lyme is also a grow- ment and large predators have been all but quickly — Williams has had Lyme three times ing problem in parts of Europe, Mongolia and eradicated. Adult blacklegged ticks (Ixodes — up to one in five develops long-term and China. Yet as bad as it is, there are nastier threats scapularis) typically feed and mate on deer, so potentially life-threatening symptoms, includ- on the rise. In parts of Africa, the Middle East, many scientists have argued that the only way ing heart, vision or memory problems, or Asia and southern Europe, ticks can spread to get rid of Lyme is to get rid of the deer. debilitating joint pain. Crimean–Congo haemorrhagic fever, which is But such efforts have had “an incredibly Williams’s approach is one of several fatal in 40% of cases. And a tick-borne relapsing spotty record”, says Richard Ostfeld, a disease strat­egies being tested in an attempt to thwart fever afflicts as many as 1 in 20 residents in parts ecologist at the Cary Institute of Ecosystem the spread of tick-borne diseases. Some, like the of Senegal. In the United States, ticks spread Studies in Millbrook, New York, who has been mouse vaccine, interrupt the pathogen’s ecologi- at least 16 illnesses, including anaplasmosis, studying tick-borne diseases for decades. cal circuitry by targeting the wild animals that babesiosis, ehrlichiosis and Rocky Mountain When Sam Telford, an epidemiologist at Tufts pass along and amplify the disease. Others, spotted fever, all “serious, life-threatening infec- University in North Grafton, Massachusetts, such as efforts to revive a human Lyme vaccine, tions”, Beard says. And many are increasing in and his colleagues cut the deer population on 406 | NATURE | VOL 524 | 27 AUGUST 2015 © 2015 Macmillan Publishers Limited. All rights reserved FEATURE NEWS The body of an adult Great Island in Cape around their gardens. Or, she says, local LYMErix, manufactured by UK-based pharma­ ixodid tick expands Cod by 50% in the early govern­ments could disperse the bait in parks ceutical company SmithKline Beecham (now as it feeds. 1980s, they saw no drop or forests, much as they do with bait-based Glaxo­SmithKline), was approved by the US in tick numbers — the rabies vaccines for raccoons and coyotes. “The Food and Drug Administration in 1998. It number of tick larvae on the island actually rodents seem to love them,” Williams says of reduced the risk of Lyme caused by US strains increased1. Ostfeld argues that you do not need the vaccine-laced treats. One of his colleagues of Borrelia by 76% in clinical trials4. But it faced many deer to maintain a large tick population. calls them “Fritos for mice”. problems from the start. First, it garnered When deer numbers drop, ticks can either lukewarm support from health officials in the crowd in on the remaining deer or find other United States and was recommended only for hosts. Only when almost all of the deer on Great people aged 15 to 70 in regions where Lyme is Island had been eliminated did tick populations endemic. Then, some recipients complained plummet. But, says Telford, “it is a nightmare “WE’VE DISRUPTED of auto­immune-related side effects such as trying to get the deer population down that arthritis and filed lawsuits against SmithKline low”. And anywhere that is not an island, keep- Beecham. The company voluntarily shelved ing populations down is practically impossible. THE BALANCE OF LYMErix in 2002. Plotkin maintains that this was a mistake. “The vaccine was safe,” he says. DANGER MOUSE Now, a new and potentially improved Ostfeld and others contend that mice are a vaccine has completed safety trials5. Developed major driver for both the tick problem and the NATURE.” by researchers at Stony Brook University and disease problem. Mice, like deer, flourish in Brookhaven National Laboratory in New York, fragmented woodlands — in part because pred- Other scientists argue for more a direct and licensed to Baxter Innovations in Vienna, ators such as foxes and opossums get displaced. means of protecting people against Lyme, the vaccine is similar to LYMErix in that it tar- Ticks then thrive on the rodents, which are poor ideally with a human vaccine. When vaccine gets OspA, but it does not contain the protein groomers. Studies suggest that larval ticks have researcher Stanley Plotkin’s son was 35, he fell segment that some scientists and consumers a 50% chance of surviving when they feed on ill with Lyme disease. As often happens with the feared could cause an auto­immune reaction. mice, but only a 3.5% chance on opossums2. infection, a doctor missed the diagnosis and the It also contains several variants of OspA, so it And mice are typically where ticks pick up young man went untreated for months. Bacte- protects against many Borrelia species known B. burgdorferi. Most mice in Lyme-endemic ria invaded his heart and he collapsed one day to cause Lyme in humans, including those that areas get infected with the bacterium at a young while walking his dog. Plotkin, now an emeri- affect people in Europe. age and, for reasons that are not completely tus professor at the University of Pennsylvania Nevertheless, the vaccine’s future is uncertain: clear, they are particularly good at transmitting in Philadelphia, says that when paramedics in 2014, Pfizer bought the rights to sell many it to ticks. Almost all young ticks that feed on arrived, his son’s heart rate was dangerously of Baxter’s vaccine products, but not the Lyme white-footed mice become infected, compared low. He has since recovered, but the experience candidate. Baxter is now in talks with Great with a mere 1% of ticks that feed on deer. Inter- “further convinced me, if I needed any con- Plains Biotechnology of Roca, Nebraska, which rupting the tick–mouse infection cycle, says vincing”, Plotkin says, “that the lack of a Lyme- has expressed interest in purchasing and devel- Ostfeld, could make ticks a lot less dangerous.