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Oct 21 2011

Lyme Disease – Always Learning.

If you’ve ever been camping or hiking or hunting or had an outdoor pet or gone anywhere near a tree or have a TV or know anyone who fits any of these situations, you’ve probably heard of Lyme Disease. I live in Minnesota, land of forests and lakes, big-ass mosquitos and lots and lots of ticks. I think it’s only natural and healthy for me to have an interest in the subject.

Disclaimers: I am not a doctor, nor an infectious disease researcher, nor a specialist on Lyme Disease or post-treatment Lyme disease syndrome (PLDS). I do have experience with serological testing, immunoassays and laboratory science. This blog post was inspired by a press release about antibodies linked to long-term Lyme symptoms. I welcome and appreciate any comments, corrections or conversation that are expressed with respect, and in the case of claims, with references. Also, I hold up the Centers for Disease Control and Prevention (CDC) as the gold standard for dissemination of accurate and reliable public information on infectious disease. If you think that the CDC or “western medicine” is misguided or intentionally evil, or that all American physicians are controlled by the mob (hat tip to an earlier commenter), you should probably stop reading here.

So, with that out of the way! – As a layperson I’m going to provide a quick overview of the disease as it is defined by the CDC, I’ll attempt to summarize the controversy over the cause of long-term symptoms that affect a subset of those infected by Lyme disease - which are called Chronic Lyme Disease by some medical practitioners - and I’ll introduce an article that may provide some insight into the underlying cause of long-term Lyme symptoms.

Here’s the CDC’s intro to Lyme disease:

Lyme disease is caused by the bacterium Borrelia burgdorferi and is transmitted to humans through the bite of infected blacklegged ticks. Typical symptoms include fever, headache, fatigue, and a characteristic skin rash called erythema migrans. If left untreated, infection can spread to joints, the heart, and the nervous system. Lyme disease is diagnosed based on symptoms, physical findings (e.g., rash), and the possibility of exposure to infected ticks; laboratory testing is helpful if used correctly and performed with validated methods. Most cases of Lyme disease can be treated successfully with a few weeks of antibiotics.

Let’s focus on that last sentence: “Most cases of Lyme disease can be treated successfully with a few weeks of antibiotics.” Whatdoyoumean, most cases? Well, we started with the CDC, so let’s see what they have to say about that:

Approximately 10 to 20% of patients treated for Lyme disease with a recommended 2-4 week course of antibiotics will have lingering symptoms of fatigue, pain, or joint and muscle aches1. In some cases, these can last for more than 6 months. Although often called “chronic Lyme disease,” this condition is properly known as “Post-treatment Lyme disease Syndrome” (PTLDS).

Here’s the deal-eo: Antibiotics act on the bacteria that cause Lyme disease. After two-four weeks the bacteria is presumed to be gone from your body. No more bacteria, no more need for antibiotics. But some people don’t feel better after the treatment. Or a patient may never have had a diagnosed case of Lyme disease, but have all of the vague symptoms of Lyme disease (fatigue, depression, etc.) with no evidence of infection. Or they may have a positive serological result (blood test) for B.burgdorferi, but haven’t recently been in a situation where they were likely to pick up a tick.

Some medical practitioners claim that these people who continue to have Lyme Disease symptoms after antibiotic treatment have Chronic Lyme Disease, by which I mean, they believe that a longer-than-advised period of antiobiotic treatment may be neccessary to clear the body of Borrelia. And you ask “Why would they think that? Why wouldn’t we just do a blood test to verify that the patient no longer has Lyme disease?”

That’s an excellent question, and the answer revolves around the fact that it can be tricky to positively diagnose an active infection. From Wikipedia (bolding is mine):

Because of the difficulty in culturing Borrelia bacteria in the laboratory, diagnosis of Lyme disease is typically based on the clinical exam findings and a history of exposure to endemic Lyme areas. The EM rash, which does not occur in all cases, is considered sufficient to establish a diagnosis of Lyme disease even when serologic blood tests are negative. Serological testing can be used to support a clinically suspected case, but is not diagnostic by itself.

See what they did there? Blood tests are available, but they’re not great. They’re not right all of the time. The available tests have a less than encouraging specificity for the disease*, and both the serological tests (which look for antibodies made by your body in response to the bacteria if you’ve been infected) and PCR analysis (which looks for the genetic material of the bacteria which may be present in your blood)  may result in false negatives or false positives.

So you feel like crap, and your doctor can’t tell you what’s wrong with you, and you know that you had Lyme disease a month or a year ago, or maybe you didn’t but it could be Lyme disease because you did go camping earlier in the spring, and so maybe you should take antibiotics until you feel better. Which could be months or years. Here’s the thing about prolonged antibiotic treatment: It doesn’t appear to alleviate post-infection Lyme disease symptoms.

You’ve probably heard about antibiotic resistance, right? If not, go visit our friends at the CDC again and they’ll tell you all about it. Aside from the risk of needlessly using an antibiotic that may make you less able to fight off bacterial infections, you don’t want to be taking a treatment that doesn’t have an effect. That’s a waste of your money and your time and your intelligence.

Unfortunately, doctors don’t have a consistant, proven treatment for long-term Lyme disease symptoms. Initial treatment with antibiotics early after infection will help lower your risk of developing serious late-stage Lyme illnesses, but after that all patients can do is wait for weeks or months or years for the symptoms to resolve themselves. That’s not very reassuring and so some people are willing to try pseudoscientific therapies or to demand prolonged antibiotic treatments.

But we may have uncovered a clue to understanding the cause of what some people claim is “Chronic Lyme Disease”. The study discussed in the article below suggests that the lingering symptoms suffered by someone who has post-treatment Lyme Disease syndrome may not be caused by an active Borrelia infection, but rather that the person may have gone through a prolonged period of infection before getting treatment, which appears to result in an increased and varied response by the immune system and eventually chronic inflammation. Not bugs, but our own immune system running amok after an infection.

The following is taken from an August 5th online publication by the journal, Nature:

Alaedini’s team looked at antibodies made in response to a protein called VlsE, which is found on the surface of Borrelia burgdorferi, the tick-borne bacterium that causes Lyme disease.

The antibodies recognize a snippet of the protein called an epitope, and recruit the immune system to attack the bacterium. The researchers found that post-Lyme sufferers have a greater variety of antibodies to this epitope than patients whose infection cleared up quickly.

This finding suggests that patients with chronic symptoms have experienced a prolonged infection, caused by microbes that have evaded the immune system by varying the epitopes they carry. As a result of these variations, the body makes new antibodies targeting the modified protein. The longer the microbe manages to keep changing, the more diverse its host’s antibodies become.

Some post-Lyme sufferers had varied antibodies against VlsE epitopes despite being diagnosed and treated early, says Alaedini. “That could mean they naturally have a different antibody response to the infection than most people; it could mean they weren’t treated properly; or it’s possible they were reinfected and the second infection was never treated,” he says.

Alaedini suggests that higher levels of antibodies could increase the body’s levels of cytokines, immune-system proteins that can trigger the symptoms experienced by patients with post-Lyme disease syndrome. “Various cytokine profiles have been associated with fatigue, anxiety and depression,” he explains.

If these antibodies are unique to people with chronic Lyme disease, it could lead to a test and treatments for the disorder, Alaedini says. It could also guide treatment of the disease itself. “If patients with an acute infection develop antibodies to these epitopes, perhaps they require a more aggressive course of therapy,” he adds.

If “Chronic Lyme Disease” turns out to be the result of an immune system gone wild, then it will stand to reason that it is not a persistant bacterial infection; we will have a proof for patients that more antibiotics is not the answer.

Thanks for reading.

———————————-

*But there are new assays being developed all the time! For example, a new study was just published in September 15th issue of the journal Clinical Infectious Disease that compared the standard antibody test (two-tiered WCS EIA/Western blot) to a new two-tiered approach (WCS EIA/C6 peptide EIA). Positive predictive value only went from 66% to 70%, but specificity was increased from 48% to 64% AND removes the necessity of having to do a Western blot. It’s not exactly ready to take the place in our laboratories as the new gold standard, but we may be getting closer. Reference: Branda JA, Linskey K, Kim YA, Steer AC, Ferraro MJ. Two-Tiered Antibody Testing for Lyme Disease With Use of 2 Enzyme Immunoassays, a Whole-Cell SonicateDisease. Clin Infect Dis 2011; 53:541-7.

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    Crazy or just the Lyme disease? | ~ Dancing with fireflies ~

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