Biting back at Lyme disease

Lyme disease, named after the Connecticut town where clusters of children developed a then-mysterious disease in the 1970s, has quietly become one of the Northern Hemisphere’s most stubborn public-health threats. Disease-causing ticks are spreading across North America and Europe, and with them, the bacteria Borrelia that cause the disease. “Tick populations and the associated infection risk are rapidly increasing,” says parasitologist Ondřej Hajdušek of the Czech Academy of Sciences. The numbers back him up: more than 400,000 cases are identified each year in the USA and over 200,000 in Europe1.

Early treatment with antibiotics is effective, but diagnosis often slips through the cracks. Flu-like symptoms blend in with a host of other illnesses, and the telltale expanding bull’s eye rash — first described in 1909 — doesn’t appear in 20–30% of patients. When diagnosis is delayed then neurological, cardiac or arthritic symptoms can follow. The increasing risk of infection and long-term complications is pushing scientists to pursue better prevention tools and more precise therapies.

A growing footprint

In the USA, Lyme disease is primarily transmitted by the black-legged tick (Ixodes scapularis), the species in which researcher Willy Burgdorfer discovered the Borrelia bacteria in 1982. On the West Coast, its cousin I. pacificus has the same role; in Europe, the castor bean tick (I. ricinus) dominates. All belong to the hard-bodied Ixodes genus, and all are adapting to a changing world.

Nowhere is that shift more visible than in the eastern USA, where I. scapularis has surged northward, southward and inland. “Landscape changes, booming deer populations and a warming climate have all contributed,” says Tanner Porter, a research associate at the Translational Genomics Research Institute in Phoenix, Arizona. Surveillance confirms new, thriving tick populations — and rising case numbers.

But tracking this expansion is often tricky2. “Detecting ticks in new places doesn’t always mean they’re newly arrived,” Porter notes, highlighting that it can be an artifact of a lack of previous surveillance. Citizen-science submissions, such as tickMAP, can supplement this surveillance, identifying ticks in counties before formal surveillance does, blurring the line between true spread and improved detection.

In the western USA, the picture appears more static. I. pacificus shows limited range expansion, and scattered reports from places such as Alaska may reflect improved detection rather than shifting ecology. Moreover, western Lyme cases remain a small slice of the national burden.

What is certain is that tick-friendly conditions are changing fast. Climate extremes, shifting wildlife communities and evolving human habits will continue to redefine where ticks thrive — and who finds themselves in their path.

A potentially persistent bite

Even when Lyme infection is caught early and treated with standard antibiotics such as doxycycline, recovery is not guaranteed. John Aucott, an infectious disease physician at Johns Hopkins University who has followed patients for more than two decades, has become a leading voice for those whose symptoms persist.

“There is such a thing as chronic Lyme,” he says, although he prefers the term ‘post-treatment Lyme disease’ (PTLD) for patients who “got antibiotics, but never got better, and definitely had their health forever changed”.

His research estimates that 14% of treated patients develop PTLD — similar in prevalence to long COVID and chronic-fatigue syndrome after Epstein–Barr virus3. Aucott recently worked with a US National Academies panel that recommended grouping these diseases under a single umbrella: infection-associated chronic illnesses. Still, some people in healthcare doubt the veracity of these persistent diseases. “Often, what convinces somebody that chronic Lyme is real is when one of their loved ones, or they themselves get it,” Aucott says.

Patients often describe crushing fatigue, musculoskeletal pain and cognitive fog. The biological origins remain hotly debated. Is it caused by lingering inflammation, remnant bacterial fragments, an autoimmune misfire triggered by infection? “Nobody can agree on what the mechanism of post-treatment Lyme disease is,” Aucott admits.

That uncertainty hasn’t stopped him from pursuing treatments that might relieve symptoms, even before full mechanistic clarity arrives.

Aucott is leading a pilot clinical trial known as T-4, testing whether the antibiotic tetracycline could help people with PTLD. Like doxycycline — today’s frontline Lyme treatment — tetracycline has additional properties that caught his attention.

“They’re anti-inflammatories as well as antibiotics,” he explains. Rheumatologists once used them to treat arthritis; researchers have explored them in animal models of stroke. “It’s more than just an antibiotic,” Aucott says. That dual action enables him to remain “agnostic to the mechanism” — it might help regardless of whether lingering bacteria or misdirected immune responses drive PTLD.

This trial uses a randomized crossover design to track fatigue and quality-of-life outcomes over 6 months. Recruitment is nearly complete, and he expects to analyze the data in 2026.

Bacterial clues

To prevent chronic illness, some scientists believe that the best strategy is to stop the cascade of damaging inflammation that Lyme bacteria provoke in the body. Brandon Jutras, a microbiologist at Northwestern University’s Feinberg School of Medicine, in Chicago, Illinois, has zeroed in on the bacterium’s cell wall.

“Our basic science approach — if we understand the bacterium we will understand the disease — has allowed us to discover that the peptidoglycan cell wall of B. burgdorferi is a critical determinant of pathogenesis,” Jutras explains. Unusually, the bacterium sheds this cell-wall material as it grows.

Peptidoglycan persists in tissues long after the infection clears4. Jutras believes that these residual pieces may “shape the maladaptive immune response in some, leading to disease”. If correct, treatments that clear cell-wall debris, or block its inflammatory effects, might prevent progression to PTLD.

His team is also exploring the effects of existing antibiotics5. One standout candidate, he says, is piperacillin, which in mice is “highly effective and specific for the Lyme disease agent”. At present, it must be injected, but researchers are working to redesign it as an oral drug. They are also exploring an attention-grabbing idea: a single preventive shot after a tick bite to wipe out the bacteria before symptoms emerge.

Clinical trials will require considerable financial backing. “Both federal and private support are tough to come by these days,” Jutras says. But the potential — a treatment tailored precisely to the pathogen — remains persuasive.

An oral option

The aim of the antibiotics is to disable the microorganism. But what if the best target is the tick itself?

That’s the concept behind TP-05, an oral tick-killing drug being developed by Tarsus Pharmaceuticals in Irvine, California. “TP-05 is the only oral, on-demand therapeutic in development designed to kill ticks before they transmit disease,” says Sesha Neervannan, the company’s chief operating officer. It offers what he calls a “vaccine-alternative” for high-risk groups — forestry workers, hikers and people who live in tick-dense regions.

In a phase 2a “tick-kill” trial, volunteers received TP-05 or placebo, then sterile ticks were placed on their skin. To transmit Lyme bacteria, ticks must usually be attached for 36–48 hours, a window TP-05 aims to slam shut. After 1 day of treatment, tick mortality reached 97% in the high-dose group versus 5% for placebo. A month later, mortality remained nearly as high, and the drug was well tolerated.

“We have clear guidance from the FDA,” Neervannan says, and a phase 2b trial is planned for 2026. With no oral preventives yet available, TP-05 fills a glaring void in Lyme disease protection.

A valorous vaccine

A preventive pill could help those already at risk. But some scientists believe only a vaccine can truly shift the trajectory of Lyme disease. Pfizer is now leading the charge with its investigational vaccine LB6V (also known as VLA15), currently in a large phase 3 trial known as VALOR.

“Lyme disease is the most commonly reported vector-borne illness in Europe and the USA,” says James Groark, global clinical lead for the program being tested at several sites in the USA, Canada and Europe. “There is no vaccine currently available to prevent Lyme disease in humans.”

LB6V targets OspA, a protein expressed by Lyme bacteria while they remain inside the tick gut. The vaccine covers six major OspA serotypes found in North America and Europe, with the intention that it is broadly protective.

The mechanism is striking. “While it’s given to a human, it actually works inside the gut of a tick that bites the host,” Groark explains. When a vaccinated person is bitten, their anti-OspA antibodies enter the tick as part of the blood meal. There, they block the bacteria from escaping the tick and migrating into the human, preventing infection at the source.

The VALOR trial has enrolled roughly 9,400 participants aged five and up across highly endemic regions. Participants receive three doses before their first Lyme season and a booster the following year, with outcomes tracked over two seasons. Pfizer expects to share results after the study concludes in 2026.

A multipronged future

There is no single solution to the Lyme disease crisis. Instead, a suite of interventions might soon emerge: better surveillance to track shifting tick ranges; vaccination to stop infections before they begin; oral prophylactics such as TP-05 to shield high-risk populations; and next-generation antibiotics designed specifically to support those who continue to be affected by PTLD.

With tick populations rising and few regions entirely immune, the urgency to develop better treatments is growing.