Scientists are taking a multi-pronged approach in the battle against Lyme disease, one of the Northern Hemisphere’s most stubborn public-health threats, according to a recent update in the scientific journal, Nature.
Although prompt treatment with standard courses of antibiotics can be effective, many do not receive a diagnosis until the illness has progressed, which can make it harder to treat. Early flu-like symptoms can be difficult to distinguish from a host of other illnesses, and the diagnostic expanding erythema migrans (EM) rash does not always appear. Neurological, cardiac and musculoskeletal symptoms can follow if diagnosis is delayed.
In Europe and the UK, Lyme disease is primarily transmitted by the sheep tick (Ixodes ricinus), while in the United States, the main vectors are the black-legged tick (Ixodes scapularis) and the western black-legged tick (Ixodes pacificus). Changes in climate, wildlife populations, land use, and human behaviour continue to influence where ticks thrive and who is at risk of tick-borne disease. However, reports of ticks in new areas may sometimes reflect improved monitoring rather than true spread.
In the UK, surveillance is largely led by the UKHSA’s Tick Surveillance Scheme (TSS), which collects submissions from the public, clinicians, and vets.
Persistent symptoms
Even after prompt antibiotics, some patients experience ongoing symptoms. Hot debate continues around possible causes including continuing infection, remnant bacterial fragments, persistent inflammation and autoimmune misfires triggered by the initial infection, or a blend.
Research by John Aucott, an experienced Infectious Diseases physician at John Hopkins University, suggests around 14% of treated patients develop ongoing symptoms, a prevalence comparable to long COVID or Chronic Fatigue Syndrome following Epstein-Barr virus infection. The confusion around true causes of ongoing symptoms hasn’t stopped him from pursuing treatments that may help patients before further clarity arrives.
Aucott supports patients who “got antibiotics, but never got better, and definitely had their health forever changed”. He is leading a pilot clinical trial known as T-4 testing whether the antibiotic tetracycline, which also has anti-inflammatory properties, can help people with ongoing symptoms. Tetracyclines were once used by rheumatologists to treat arthritis and have also been studied for the treatment of strokes. Recruitment for the six-month trial is nearly complete, with results expected later this year.
Understanding the bacterium
Some researchers focus on the bacteria directly to better understand how to tackle symptoms. Brandon Jutras, a microbiologist at Northwestern University in Chicago, has found that Borrelia burgdorferi sheds a peptidoglycan cell wall that can persist in tissues long after infection clears. This debris may drive maladaptive immune responses in some patients, potentially contributing to post-treatment symptoms. Treatments that clear cell-wall remnants or block their inflammatory effects could provide new therapeutic options.
Jutras’ team is also exploring the antibiotic piperacillin, which in mice has shown to be highly effective and specific against B. burgdorferi. Currently piperacillin must be injected, but researchers are working on an oral version that could be easier to administer. They are also developing a single preventive injection to wipe out the bacteria immediately after a tick bite, potentially stopping Lyme disease before symptoms even appear.
Tackling ticks
Other approaches target the ticks themselves. Tarsus Pharmaceuticals in California is developing TP-05, an oral drug for humans designed to kill ticks when ingested. High-risk individuals – such as hikers, forestry workers, or residents in tick-dense areas – could take the drug to reduce the chance of a tick surviving long enough to transmit Lyme bacteria. The company positions it as a vaccine alternative, filling a gap where no oral protectives currently exist. A trial assessing TP-05 will continue this year under FDA guidance.
Vaccine development
Vaccine development remains a key focus for prevention. Pfizer and Valneva’s Lyme disease vaccine LB6V (also known as VLA15) is currently in a large phase 3 trial known as VALOR. It targets OspA, a protein expressed by Lyme bacteria inside the tick gut, and covers six major OspA serotypes found in North America and Europe.
When a vaccinated person is bitten, their anti-OspA antibodies enter the tick during its blood meal and block the bacteria from leaving the tick, preventing infection at its source. Approximately 9,400 participants aged five and above, across highly endemic regions, have participated in the study. Results will be shared later this year.
Progress through a combined approach
So it seems as tick populations rise, a combination of strategies is emerging to tackle the increasing threat of Lyme disease. Improved surveillance to track shifting tick ranges, vaccine development to help prevent ill-health, oral prophylactics for high-risk populations, and targeted antibiotics to hit not only the infection but also symptoms caused by a pronounced inflammatory response. While significant challenges remain, the increased attention on Lyme disease research hopefully signals a positive and long-overdue step towards improved prevention and better outcomes for those affected.
Read more in the Nature journal update, Biting back at Lyme disease.