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Why some people recover quickly and others don’t


Why some people recover from Lyme disease, while others experience months, years or even decades of chronic symptoms has long puzzled doctors. New research offers clues to an immune system marker in the blood that is elevated in people with persistent symptoms of Lyme disease, even after receiving antibiotics.

In the new study, published May 9 in the Center for Disease Control and Prevention’s Emerging Infectious Diseases journal, researchers found that an immune system marker in the blood called interferon-alpha was elevated in people who had been treated for Lyme disease but who had persistent symptoms. .

Interferon-alpha is one of the few key signaling proteins the body makes to tell immune cells to fight off bacteria or viruses. If blood levels are too high, the immune system can overreact, causing pain, swelling and fatigue – symptoms often seen with Lyme disease.

In patients with high levels of interferon-alpha, the immune response to Lyme bacteria can cause chronic inflammation even after the infection clears, said Klemen Strle, assistant research professor of molecular biology and microbiology at the ‘Tufts University and study author new study.

“We think this is a possible driver of persistent symptoms,” Strle said. And since a number of drugs are already approved to reduce interferon-alpha, he suggested the research could mean a possible treatment option for persistent Lyme symptoms.

The study was small, including 79 people diagnosed with Lyme disease, and found only a link between higher levels of interferon alpha and persistent Lyme disease symptoms, not just the immune marker was itself causing the lasting symptoms. A larger clinical trial would be needed to confirm the link.

Male and female adult blacklegged ticks, Ixodes scapularis, on a sesame seed bun to demonstrate relative size.
Male and female adult blacklegged ticks, Ixodes scapularis, on a sesame seed bun to show their relative sizes.CDC

Between 30,000 and 500,000 people each year develop Lyme disease from a tick bite, according to the CDC. For the most part, the infection is mild and easy to treat with antibiotics. About 10% experience symptoms like fatigue and brain fog as well as muscle, joint and nerve pain that persists even after treatment.

The new findings represent a significant shift in understanding of why some people infected with Lyme experience chronic symptoms. Previously, some researchers thought that a specific strain of the spiral-shaped bacterium Borrelia burgdorferi that causes Lyme disease might be the cause. Others have wondered if undetectable low levels of infection persist in the body after treatment. The new research suggests that how the body reacts to the bacteria — not the bug itself — could lead to long-lasting symptoms.

It’s still unclear why some people have high levels of interferon alpha, but Strle said he’s looking into a possible genetic cause.

Although interferon alpha research is still in its early stages, Dr. Roberta DeBiasi, chief of the division of pediatric diseases at Children’s National Hospital in Washington, DC, called it “very well-designed and interesting.”

“It provides a possible therapeutic target that could be studied in clinical trials to treat these patients,” she said.

For people struggling with persistent Lyme symptoms, any biological explanation for the condition called post-treatment Lyme disease syndrome, or PTLDS, is a step forward.

Years of Lyme Symptoms

Rebecca Greenberg isn’t sure when she first contracted Lyme disease, but she has her suspicions. Greenberg, now 26, vividly remembers her mother pinching a small, firm tick on the back of her neck after playing at a playground near Albany, New York, when she was 9. She may have had several tick bites during her stay in the Adirondacks, but she didn’t worry about it until she started feeling sick at age 15.

“I was so tired I was telling my mom I couldn’t wake up to go to school anymore,” said Greenberg, who grew up in upstate New York but now lives down south. from Florida. “My muscles would hurt, my joints would hurt and I would get these migraines.”

Rebecca Greenberg.
Rebecca Greenberg.Courtesy of Rebecca Greenberg

Doctors told Greenberg his symptoms were likely hormonal, and when Greenberg landed in the emergency room unable to move the left side of his body, they prescribed him anti-anxiety medication and suggested he see a neurologist. Those doctors weren’t much help either, Greenberg said. Her symptoms eventually became so severe that she stopped going to school and needed a wheelchair.

It wasn’t until 2011, after Greenberg’s mother posted her daughter’s mystery illness on Facebook, that a pediatrician friend suggested Lyme disease. Antibody tests soon showed Greenberg had been infected with Lyme and two other bacterial infections, babesiosis and bartonella.

Even now, she still suffers from fatigue and nerve pain. The most debilitating symptoms of her Lyme disease were the psychiatric effects, including severe anxiety, depression and hallucinations, she said.

“I’m basically still putting bandages on all my symptoms,” she said. “A tick turned my life upside down.”

Why diagnosing Lyme is so difficult

As the geographic spread of Lyme ticks intensifies, there is an urgent need for more accurate tests that can detect the infection in its early stages, researchers and health officials agree.

“There is no doubt that the prevalence of Lyme disease and other tick-borne infectious agents is increasing,” Strle said.

The Environmental Protection Agency warns that disease-carrying ticks are more active in warmer temperatures, and climate change will likely mean the insects will increasingly survive the winter and spread to areas beyond the north east, northern California and northern parts of the Midwest.

Learn about Lyme and other tick-borne diseases

Screening for Lyme disease is complicated, especially for doctors unfamiliar with the process, DeBiasi said.

“This leads to many people with Lyme being overlooked or people with symptoms being told they have Lyme when in fact they don’t,” she said. “Combine that with bad information on the internet, and you end up with a lot of confusion.”

Part of the problem is that once the bacteria is passed from a tick to a human, it spreads rapidly through the body at levels that may be too low for a test to detect.

It quickly becomes a detection problem,” explained Brandon Jutras, an associate professor in the biochemistry department at Virginia Tech.

Serological tests, which look for antibodies in the blood, are the best available method for diagnosing Lyme, experts say. However, antibody tests indicate that the immune system has mounted an attack on a virus or bacteria, but cannot determine if there is an active infection. They only work when the immune system generates enough antibodies, which can take six weeks or more after a first tick bite.

The CDC recommends using a combination of antibody tests to diagnose Lyme, including an immunoassay antibody test like ELISA followed by an immunoblot antibody test like the Western blot test.

Doctors and health officials recognize the need for more reliable Lyme disease tests that can detect infection at an early stage.

“We need to do better,” said Jutras, who is working with a team at Virginia Tech to develop a rapid Lyme test that could identify the actual infection at the first sign of a tick bite.

“What we really want is a test that says, ‘Does a person still have the Borelli spirochete? [Lyme bacteria]and do we need to treat it with antibiotics? said Dr. Brian Fallon, director of the Lyme and Tick-Borne Diseases Research Center at Columbia University.

“Chronic Lyme” controversy

Because testing is inadequate, there is no way to link long-lasting symptoms to the original Lyme infection. Many doctors avoid a diagnosis of chronic Lyme since the term implies a persistent infection.

“There’s no way to tell that a Lyme diagnosis from, say, six years ago has anything to do with the symptoms happening now,” DeBiasi said. “Symptoms like musculoskeletal pain, fatigue, difficulty thinking and depression are non-specific. There are many, many possible reasons for these symptoms other than Lyme. »

Fallon of Columbia University prefers the term “long Lyme”.

“‘Chronic’ is a reasonable term if it refers to chronic symptoms,” Fallon said. “The problem is when someone thinks they have an ongoing chronic infection and need more antibiotic treatment.”

DeBiasis insists that the symptoms people experience are real, even though PTLDS experiences are the exception.

As a pediatrician, she has seen panicked parents seek out unproven therapies after finding a tick on their child. In a recent study published in the journal Pediatric Research, DeBiasi and colleagues found that 75% of children with Lyme disease got better within six months of taking antibiotics, while 9% had symptoms affecting their functioning after six months.

“If you give them a little more time, they seem to recover completely,” DeBiasi said.

With the exception of Pfizer and Valneva, which are testing a Lyme disease vaccine in clinical trials, the drug development industry has, for the most part, not focused its energies or dollars on Lyme. . Federal research grants are also lacking, Jutras said.

“Many private foundations have taken over when it comes to research funding for Lyme, but at the federal level, it may be time to revisit some of the priorities when it comes to allocating research funds.”

Joanna Swanson

Joanna Swanson is Europe correspondent at the Thomson Reuters Foundation based in Brussels covering politics, culture, business, climate change, society, economies and inclusive tech. With specific focus in breaking news, she has covered some of the world's most significant stories.