Published On August 24, 2017
THIS SUMMER HAS BROUGHT A SPIKE IN THE NUMBER OF CASES OF LYME DISEASE, which is caused by the bite of a tick carrying the bacterium Borrelia burgdorferi. What comes next isn’t pleasant. Even when the infection has been cleared away with a course of antibiotics, some victims can suffer pain, fatigue and neurocognitive symptoms.
A smaller number of people go on to suffer from antibiotic-refractory Lyme arthritis—a painful inflammation of the joints that long outlasts the infection. And the mechanisms by which B. burgdorferi causes all of these problems are not completely clear, and may not be the same in all patients.
But there have been recent victories against this puzzling disease. In July, the Food and Drug Administration gave fast-track status to a Lyme disease vaccine candidate, VLA15, which was developed by the European company Valneva. The FDA had approved a Lyme vaccine in 1998, but the drug was withdrawn three years later because of poor market performance and concerns about side effects. Valneva has enrolled 180 patients for a small trial of its new vaccine, which is being conducted at two site in the United States and one in Belgium. This vaccine also targets a broader range of strains, including those found in Europe, that the earlier vaccine didn’t affect.
New ways to diagnose Lyme disease are also coming into focus. Blood tests to detect Lyme frequently yield false negative results during the first few weeks after infection. But John Branda, associate director of the Clinical Microbiology Laboratory at Massachusetts General Hospital, and his colleagues published research in August about a test intended to detect Borrelia infection earlier than would any of the methods now commonly used for the diagnosis of Lyme disease. A blood sample is first amplified by polymerase chain reaction (PCR) technology, a routine method that can make the genetic material of a pathogen more easily identifiable. Then the blood undergoes magnetic resonance imaging, which can quickly pick up the Borrelia DNA. The test, known as T2MR, detected Borrelia in blood samples from patients suspected of having Lyme disease that were negative in other tests.
But the most promising advances may be for people who suffer long-term effects of a Lyme infection. After a round of antibiotics, Lyme symptoms soon end for most patients. But for others, joint inflammation can linger well after the final pill.
Allen Steere, an MGH rheumatologist and the researcher who led the team that first identified Lyme disease in the 1970s, is exploring the question of why some people don’t get well after treatment. In patients with antibiotic-refractory Lyme arthritis, there is mounting evidence that Lyme infection triggers an abnormal immune response, which in turn attacks the tissues of the joints, even after B. burgdorferi has been cleared by antibiotics.
Nearly half of those with primarily European Caucasian ancestry carry a particular mutation in the toll-like receptor-1 (TLR-1) gene that can cause excessive inflammation in joints and more frequent antibiotic-refractory arthritis. In 2012, Dr. Klemen Strle and Dr. Steere published a study showing that people with this susceptibility produce a stronger inflammatory response in response to B. burgdorferi.
Now Steere believes that many more severe cases may result when people with that genetic profile encounter a particularly virulent strain of the bacterium. In a 2016 paper in Emerging Infectious Disease, Strle and his colleagues showed that some strains of B. burgdorferi cause a much stronger immune response than others. In the northeastern United States, where most Lyme infections occur, those strains are responsible for 30% to 40% of infections.
When genetic susceptibility and virulent B. burgdorferi strains combine—as they do in as many as 20% of people of Caucasian ancestry who are infected with Lyme disease—ideal conditions are created for an amplified and maladaptive inflammatory response that can attack joint tissues.
The particular immune components of that heightened response are also becoming clearer. Steere published a paper this year about the role of at least four autoantigens—human proteins that can produce a major immune response under certain circumstances—that have a role in persistent joint inflammation in patients with antibiotic-refractory Lyme arthritis. Another paper from his lab looked at Lyme disease patients who produce elevated levels of certain microRNAs—molecules that fine-tune immune responses—which are known to have a role in chronic inflammation, tissue growth and swelling, and impaired wound repair.
The hope, says Steere, is that this growing understanding of Lyme disease may lead to breakthroughs in treatment, and in heading off the worst outcomes. “As someone who saw Lyme disease come into our vocabulary, I’d like to see us advance significantly toward ending it,” he says.
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