Chronic Lyme disease: how one tick bite can ruin your health for ever


BARELY a summer day went by that I didn’t hear someone talking about Lyme disease. In the four years I lived on Long Island in New York, checking for ticks became second nature. After a walk in the woods. After a stroll in the marshy grasses by the beach. After a backyard barbecue.

I remember the first one I found on my clothing: a lone star tick, its distinctive white dot almost shining up at me from the crook of my elbow. I panicked until I found out that lone stars don’t transmit Lyme disease.

The first time I found the kind of tick that does spread the disease burrowing into my leg, I retched, then rushed to the doctor; the second time, I calmly went to the clinic to have it removed and get tested. In time, panic gave way to low-level, background worry.

Maybe I was right to be alarmed. Lyme disease is on the rise around the world. This bacterial infection spread by tick bites can lead to joint pain, fatigue, neurological damage and even temporary facial paralysis. If caught early, it is treatable – in most cases. But some people report symptoms that never go away, even after treatment.

“For some people, Lyme disease symptoms never go away”

This condition is commonly known as chronic Lyme disease. Yet we still don’t know whether Lyme disease, which is maddeningly difficult to diagnose, is the true culprit. What is clear is that a growing group of people are in pain and distress. Helping them means finding an answer to a surprisingly difficult question: does chronic Lyme disease exist? Can a single tick bite really undermine your health for the rest of your life?

It is undisputed that Lyme disease is becoming more common. In the US, around 15,000 cases were reported each year in the late 1990s. Today, it is about 30,000 cases, although recent estimates from the Centers for Disease Control and Prevention suggest that 10 times as many people get the infection. In the UK, there are an estimated 2000 to 3000 new cases every year, but a recent analysis suggests the real figure may be closer to 8000. Elsewhere in Europe, Lyme disease cases have been steadily rising for more than 30 years, and the World Health Organization estimates that now at least 65,000 people in the region get the disease annually.

Lyme disease is nothing new. A bacterium that causes it, Borrelia burgdorferi, can now be found throughout North America as well as in parts of Europe and Asia. It was thought to have originated in North America, until a 2008 study of the bacterium’s genes placed its origins in Europe. But by around 15,000 years ago – long before humans crossed the Bering Strait – it was present in North America, quietly colonising birds, small rodents and deer.

When humans arrived, we slowly reduced the number of predators that kept these host animals’ numbers in check. As their numbers grew, so too did the number of ticks that transmit B. burgdorferi.

We didn’t know about this particular danger until 1977, when Lyme disease was first identified. It was named after a town in Connecticut where a cluster of children developed what seemed to be juvenile arthritis after first getting a mysterious bullseye rash. This “Lyme arthritis” was eventually renamed Lyme disease, and a few years later entomologist Willy Burgdorfer pinned the blame on B. burgdorferi, a spirochete bacterium, so-called because it is shaped like a corkscrew. It causes the vast majority of Lyme disease cases in the US. In Europe, B. burgdorferi is still present, but two other species, Borrelia afzelii and B. garinii, cause most cases of Lyme disease.

The precise mechanisms behind Lyme symptoms aren’t well understood, but we do know that when a tick carrying a type of Borrelia bites you, the bacteria replicate in the tick’s gut and pass through its salivary glands into your bloodstream, a process that can take up to 48 hours. That may sound like a long time not to notice a tick hanging off your body, but most Lyme disease infections are brought on by a bite from a nymph, an immature tick that can be as small as 2 millimetres wide.

Some research indicates that the bacteria then activate enzymes that can cause collagen fibres – like those in tendons or ligaments – to break down, resulting in weakness or arthritis-like symptoms. Pain and tingling, as well as more severe neurological damage, may be caused by the inflammation of tissues or nerves after direct contact with the bacteria, or it could be a result of immune responses to the bacteria.

Detecting B. burgdorferi is difficult. It replicates slowly but moves quickly out of the blood and into body tissues, making direct blood tests less effective. Even when we can find the bacteria, they are nearly impossible to grow in culture, meaning we need highly sensitive tests to identify them in order to confirm an infection. We simply don’t have those, says John Aucott at Johns Hopkins University in Maryland.

Instead, we keep an eye out for a telltale bullseye rash, or erythema migrans, that 70 to 80 per cent of people get. It usually crops up a few days to a month after a tick bite and can linger for weeks. Spotting this distinctive rash isn’t a foolproof diagnostic method, however. It can be easy to miss – either because it is in a hard-to-see place on your body or has faded before you notice.

It also may not also be visible under hair or on darker skin. A recent study led by researchers at the University of Maryland found that African Americans were ess likely to notice the rash than white people, and were also more likely to have arthritis after contracting Lyme disease. One reason may be that if people don’t see the rash, they are less likely to receive treatment before long-term symptoms set in.

If a rash has been spotted or you suspect Lyme infection, there are several kinds of tests that look for antibodies that the immune system produces to fight the infection. It can take several weeks for the body to produce enough antibodies to show up on these tests. These antibodies can also have similar proteins to those deployed to fight other invaders, leading to false positive results. And antibodies to Lyme disease can linger in the body after an infection has cleared, so these tests cannot determine whether someone has a current infection. All these issues mean that a combination of the two most common tests are only accurate about 40 per cent of the time.

For doctors, it can be a very frustrating situation, especially when it comes to assessing chronic symptoms. Lyme disease should be simple to treat because we have antibiotics that fight the bacteria that cause it. But because many people don’t realise they are infected and tests for Lyme disease are so unreliable, it can be nearly impossible to determine whether someone who seems to have chronic Lyme disease was actually infected with Lyme initially or has another condition altogether.

“A lot of the work we do on a day-to-day basis as a clinician is detective work. And when you cannot find a clear biological marker that justifies what disease the patient has, it’s extremely frustrating. But we often cannot find any evidence that bacteria are still there,” says Marcelo Campos, a primary care physician in Massachusetts and a lecturer at Harvard Medical School.

That fact, and the nebulous definition of chronic Lyme disease, has led some doctors to question whether B. burgdorferi is really to blame. This scepticism has driven a bitter conflict between patient groups fighting for recognition of chronic Lyme disease and a medical establishment baffled by how to diagnose, let alone treat, something with no discernible cause.

This conflict is worsened by the tension over misuse of antibiotics: some activist groups, such as the International Lyme and Associated Diseases Society, advocate long-term antibiotic treatment for people with chronic Lyme disease. This is despite several clinical trials demonstrating that the approach works no better than placebo and comes with significant risks, including contributing to the rise in antibiotic-resistant bacteria.

These so-called Lyme wars are one of the latest chapters in a long history of the medical establishment dismissing hard to define chronic illnesses – such as chronic fatigue syndrome or fibromyalgia – or chalking up symptoms to attention-seeking or misidentified mental health issues.

“There is no doubt that chronic Lyme exists. The question is the cause”

To find out more, Aucott and his colleagues are running studies that enrol people at the time of their skin rash, so it is clear they have recently contracted Lyme disease. These participants have also never been diagnosed with other chronic pain or fatigue conditions. “They get treated with standard antibiotic therapy and most people get better, but about 10 per cent don’t,” he says. “So I don’t know how anyone could say it doesn’t exist.”

He says there is now plenty of evidence to show that chronic Lyme, or what doctors now call post-treatment Lyme disease syndrome, definitely does exist. “[For people with Lyme disease], there’s always a subgroup that has symptoms after therapy. There’s really no doubt that they’re there, the question is the cause. That’s the controversy,” says Aucott.

Because of the overlap in symptoms with some common pain and fatigue conditions, there aren’t reliable figures for how many people report long-term Lyme symptoms. But some estimates suggest that up to 20 per cent of people who get Lyme disease may experience post-treatment symptoms. If that is the case, a recent analysis calculated that, in 2016, there would have been between 69,000 and 1.5 million people in the US with post-treatment Lyme disease. The estimates for 2020 reached as high as 1.9 million cases.

“That the numbers were so high was an eye-opener,” says Alison DeLong at Brown University in Rhode Island, who worked on the study. She and her colleagues believe the increasing rates of post-treatment Lyme disease syndrome may not be restricted to the US, especially in light of climate change (see “Ticks in a warming world”).

These people may be forever changed after a tick bite. “Normally if you have an acute infection, everything gets better in a few weeks. This illness, if you get this, you never feel good again. There’s something profoundly altered in the physiology of this unfortunate subset [of people] that develops post-treatment Lyme disease syndrome,” says Aucott.

There are several hypotheses as to what that could be. Aucott and his team have found that changes in the body’s immune response brought on by altered gene regulation patterns are seen in people who have had Lyme disease. This supports the idea that the infection triggers an autoimmune response, in which the body turns against its own healthy cells. This wouldn’t require the presence of living bacteria, which would explain the experience of ongoing fatigue and pain after antibiotic treatment.

Another possibility is that antibiotics don’t kill all the bacteria and instead leave behind some damaged organisms. In animal studies, these zombie bacteria grow slowly, cause more severe arthritis symptoms and resist standard antibiotic treatment. Here, though, there is some hope: last year, a study led by Ying Zhang at Johns Hopkins University found that a cocktail of three antibiotics cleared these persistent bacteria from mice.

There is a third possibility that is a bit of both of these: the amber theory. “The bacteria are dead and killed, but may leave behind protein and cellular fragments as if preserved in amber,” says Aucott. These fragments may cause inflammation that results in joint pain and stiffness. “But it’s a little hard for me to imagine these not being cleared away by the body’s immune system for years,” he says.

It could also be that there are no bacteria left at all, but that the illness alters neural networks, rewiring how a person perceives pain and fatigue. The repetition of pain over several months or years may change a person’s attention to, or even anticipation of, pain, creating a kind of feedback loop. “It’s a neural pathway realignment that becomes self-perpetuating. And you see that in people with fibromyalgia,” says Aucott.

Or it may be simpler than any of that. Post-treatment Lyme disease syndrome could be an entirely different condition caused by another bacteria passed on by ticks, says Campos. Just last year, a new tick-borne illness was identified in Mongolia after a farmer with a history of tick bites went to her local hospital complaining of fever and headaches. She tested negative for known tick-borne diseases, but when researchers analysed her blood and that of 86 others in the region with similar symptoms, they identified a new condition, naming it Alongshan virus after her hometown.

“We know ticks carry many bacteria and co-infection is quite common,” says Campos. “But if you don’t know what you’re looking for, how do you test for it?”

Efforts are under way to create more reliable diagnostic tests, but for now, the best defence is to avoid tick bites (see “Tick check”). Soon, though, we may have a vaccine for Lyme disease. There was one, Lymerix, on the market briefly in the late 1990s, but it was caught up in anti-vaccine sentiment on the rise at the time. Despite a US Food and Drug Administration study confirming it was safe, Lymerix was voluntarily pulled by the manufacturer, wary of an endless string of lawsuits.

A new vaccine on the way should be effective against the six types of Borrelia that cause most Lyme disease in the US and Europe. “We are developing these vaccines for people living in the northern hemisphere on both sides of the Atlantic,” says Thomas Lingelbach, president of the French biotech company Valneva, which is running human trials of the vaccine. Depending on the type of bacteria, between 70 and 90 per cent of people in the trials develop antibodies, he says. The vaccine should be available in 2023.

The trick won’t just be making sure that the vaccine works, though. It is also fighting anti-vaccine sentiment and building enough trust to get people to take it, says Lingelbach.

Knowing a vaccine is on the near horizon may help ease the worry of those living in areas where Lyme disease is rife. But it won’t help people who already have chronic Lyme.

Acknowledging the reality of post-treatment Lyme disease syndrome is a crucial first step towards solving the mystery of what causes it, and developing treatments. But there is a long way to go before we can offer these people the relief that they seek., 3 June 2020