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When Lyme Lingers

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To untie the Gordian knot that is Lyme, begin with diagnosis. The most common test is often negative during the first several weeks of infection. That’s because it’s designed to detect the antibodies the body generates to battle the bacteria, and those antibodies don’t initially show up in sufficient quantities to produce a positive test result, says Ben Beard, coordinator of the CDC’s national programs on Lyme disease, plague and tularemia. A patient who notices a bull’s-eye rash might test negative, even if she does have Lyme.

Next, factor in the possibility of co-infection. Scientists have identified at least four other disease-causing pathogens in the ticks that carry Lyme. It’s possible that these bacteria behave differently in combination and may cause more severe early infections. Add to that the vast array of possible hosts—people who are young or old, who are healthy or have compromised immune systems—and the resulting symptoms are quite variable and can range from mild to severe.

The bacterium at the root of Lyme disease, Borrelia burgdorferi, is an organism with a remarkable ability to mask its presence so that it won’t be attacked by the human immune system, says Monica Embers, an assistant professor in the Division of Bacteriology and Parasitology at the Tulane University Health Sciences Center. The bacterium may, for example, bind with human proteins on its surface, thus appearing to be made up of human cells. The bacterium also can mask itself when presented with an immune response; as soon as the host starts to attack, it changes its expression—its genetic appearance—to thwart the assault. “It keeps doing this throughout the infection,” Embers says, “so the immune system can’t keep up.”

Embers, using a monkey model, recently led an intriguing study into Lyme bacteria in which uninfected ticks were fed on an infected monkey, then analyzed to determine whether they had become infected. The research was a follow-up to work at University of California, Davis showing that the DNA of the Borrelia spirochetes sometimes persisted in mice after antibiotic treatment. In the study by Embers’ team, published in the journal PLOS ONE in 2012, three rhesus macaques were infected with the Lyme spirochete and treated with a course of oral doxycycline four months later. Then the researchers let laboratory-raised, Lyme-free ticks feed on the primates and they found a few spirochetes in ticks removed from two of the three animals. But it’s not clear whether those organisms were capable of infecting a new host.

Then, in February, researchers at the National Institutes of Health and Tufts University published a human study in which they allowed lab-raised ticks to feed on a positive control patient and 10 previously infected patients who now had post-Lyme disease symptoms. Only two ticks, one removed from the control patient and the other from a post-Lyme patient, subsequently tested positive for Borrelia burgdorferi DNA, but not for active spirochetes. In their conclusions, the authors warned that this work doesn’t prove that live spirochetes persist despite antibiotic treatment.

Meanwhile, Steere and his team are working to find out why patients may have persistent arthritis after antibiotic therapy appears to have eradicated the spirochetal bacterium from the affected joint. Steere’s team recently published a study on a strain of Borrelia burgdorferi found in the Northeast that induces more extreme inflammation than is caused by any other strain, especially in people with a certain genetic predisposition. About half of the Caucasian test subjects possessed a gene mutation that, when confronted with this strain of Lyme, set off an overwrought inflammatory reaction that was most intense in joints. In studies by other researchers, only 8% of African-Americans and no one of Asian descent had this mutated gene.

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1. “Lyme Disease,” by Eugene Shapiro, The New England Journal of Medicine, May 2014. This paper walks readers through the diagnostic and prescriptive steps Shapiro takes in caring for a pregnant 32-year-old woman with a skin rash who had been bitten by a tick.

2. “Lyme Disease,” by Allen C. Steere, The New England Journal of Medicine, July 2001. This seminal review cited many times in medical literature covers how the spirochete is transmitted and goes about its business, as well as the various physical manifestations of its presence in a human host.

3. “Lyme borreliosis,” by Allen C. Steere, Harrison’s Principles of Internal Medicine, 18th Edition, Chapter 173, pp. 1401–1406. Harrison’s Principles is the most widely read book of its kind. Steere’s contribution covers guidelines for diagnosis and treatment and other essential information.

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