Medical Research

Explained: How researchers are trying to eradicate Lyme disease

Published : October 16, 2021 12:34 IST

Borrelia burgdorferi bacteria can trigger chronic diseases — but a remedy may be in sight. Photo: Callista Images/imago images

Treatment options for Lyme disease are still limited. Now, researchers are pursuing a new approach.

Lyme disease may eventually be a thing of the past, says Kim Lewis, professor of biology and director of the Antimicrobial Discovery Center at Northeastern University in the U.S. city of Boston. The reason for this optimism is the rediscovery of a chemical that is deadly to the bacterium causing the tick-borne illness but harmless to animals. But more on that in a moment.

Lyme disease is caused by a bacterium called Borrelia burgdorferi, which lurks in small rodents such as rats or mice, as well as in deer. They do not show symptoms of the disease. Ticks serve as vectors, meaning they become infected when they feed on blood from these animals and transfer the bacteria to new hosts —such as humans.

Signs of infection

If a person becomes infected with Lyme disease after a tick bite, it can present in a variety of different symptoms. One of the most common signs is the typical circular skin inflammation that forms around the tick bite and spreads in a ring shape. In people with darker complexions, the rash can look like a bruise. This so-called migratory redness (erythema migrans) occurs in 80 to 90 out of 100 infected persons.

However, Lyme disease can also manifest itself in other ways. For example, within the first few weeks after the tick bite, flu-like symptoms such as fatigue, joint pain, muscle pain, a raised temperature or night sweats may indicate an illness. Irregular heartbeat, lower back pain or nerve pain may also occur.

Don't let ticks get to you

It is not yet possible to prevent Lyme disease. Tick bites should be avoided from the outset — also in view of the fact that the insects can transmit other diseases as well, such as tick-borne encephalitis (TBE), for example. This means that anyone who is out and about in meadows or forests should wear clothing that is as long as possible, especially on the legs. Putting on long socks also makes life a little more difficult for the little parasitic arachnids, especially if they are pulled up over the bottom of the pant legs.

Ticks are more visible on light-colored clothing. Anti-tick sprays keep ticks away, at least for a limited time, but not all products are equally reliable. After returning home from an outing in the wild, you should thoroughly check for ticks. If you find one, you should remove it immediately (here is a detailed description of how to do so correctly). The sooner, the better!

How is Lyme disease treated?

In the early stages, Lyme disease is treatable with antibiotics such as doxycycline. However, such medications can disrupt the gut microbiome, leading to symptoms such as diarrhea. At worst, the antibiotic could promote the development of antibiotic resistance. However, if Lyme disease is not treated, it becomes chronic and keeps coming back.

In the U.S. and Canada, there used to be a vaccination against Lyme disease, called LYMErix. In 1998, it was approved by the U.S. national public health agency CDC for high-risk patients, but in 2002, GlaxoSmithKline discontinued the vaccine, saying it was selling poorly. So, at present, people can be vaccinated only against the viral tick-borne disease TBE. In veterinary medicine, however, Lyme disease vaccinations are still available today — for dogs, for example. They need to be refreshed every year.

Very recently, in September 2021, there was news about another possible vaccine against Lyme disease for humans: The two pharmaceutical companies Valneva and Pfizer published positive Phase 2 results, including a booster response, for the vaccine candidate VLA15. "Lyme disease represents a high unmet medical need which impacts the lives of millions of people in the Northern Hemisphere. We are excited by these additional Phase 2 results, which we believe take us a step closer to making a major contribution against this severe disease, subject to regulatory approval," Valneva's chief medical officer, Juan Carlos Jaramillo, said in a press statement.

A targeted Lyme disease treatment

But back to the optimism mentioned at the start of this article: During a recent study, a team under Kim Lewis at Northeastern University found that a compound called hygromycin A is completely harmless to animals and has little effect on most bacteria — except so-called spirochete bacteria, named for their spiral shape. For those, it is deadly. And Borrelia burgdorferi, the pathogen that causes Lyme disease, belongs to just this group.

Hygromycin A is an antimicrobial agent found in soil. The substance was originally discovered in 1953. At the time, however, scientists dismissed it as ineffective, probably because it seemed too weak to fight normal pathogens. But Lewis considers it exceptionally effective against spirochetes.

Lewis' team discovered the efficacy of hygromycin A while screening microorganisms in soil for antimicrobial compounds. "We set out to find such a compound that would selectively kill Borreliella burgdorferi [the alternative name given by some researchers to the pathogen causing Lyme disease: Ed.], placing a bet, if you will, that Mother Nature had bothered to evolve a compound to selectively take out spirochetes that live in the soils," Lewis says.

And indeed, Mother Nature has done exactly that. The team tested hygromycin A to treat Lyme disease in a mouse model and found that, as Lewis puts it, "it clears it very nicely." After five days of treatment with hygromycin A, the infection was cured, as it was in the control group, which had received the antibiotic ceftriaxone. The advantage: Hygromycin A acts very specifically against Borrelia burgdorferi, whereas ceftriaxone acts against many different bacteria, which in turn carries the risk of triggering antibiotic resistance.

The researchers have already licensed the compound to Flightpath, a biotech company specializing in Lyme disease, to conduct development studies and advance production of this treatment.

Eradication of Lyme disease?

"I hope that it will continue moving forward in development and will become the first therapeutic to treat Lyme disease," Lewis says. "It will be very important to see whether treating with hygromycin A will diminish the probability of developing chronic Lyme." But the plans go even further: Lewis' team has also shown that feeding hygromycin-laced bait to mice can eliminate Borrelia burgdorferi infections. Theoretically at least, putting out such bait could eradicate Lyme disease from entire areas or even entire countries.

This idea is not entirely new: A field trial with doxycycline baits was successful. But widespread use of this drug for that purpose is undesirable because it could lead to many microbes developing antibiotic resistance. In the case of hygromycin, however, Lewis' studies indicate that it is extremely difficult for Borrelia burgdorferi to develop a resistance.

The first field trial against Borrelia burgdorferi is scheduled to start next summer. And Lewis' team is also investigating whether hygromycin A can treat other diseases caused by spirochetes, such as syphilis, which is caused by the bacterium Treponema pallidum.