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s a kid in rural Connecticut in the early 2000s, Kathleen McWilliams was well acquainted with the danger of ticks. After days spent playing outside in the wooded areas around her house, “our home routine was you brushed your teeth, you went to the bathroom, and you did a tick check,” she said.

So when, at age 15, McWilliams suddenly spiked a 104-degree fever, her mom immediately thought Lyme disease, the tick-borne illness caused by the bacterium Borrelia burgdorferi. She requested a Lyme test. While they waited for results, McWilliams’s symptoms morphed into near-constant dizziness and achy joints, two more markers of the disease.

But, after two weeks had passed, they got surprising news: Her Lyme test came back negative.

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Had it been positive, McWilliams’s doctor would have prescribed a high dose of antibiotics that would quickly clear the infection. Without that diagnosis, McWilliams’s symptoms worsened while the doctor ran a second Lyme test at her mother’s insistence. She recalls classes in which she was so dizzy she struggled to stay upright, and soccer games in which her knees and shoulders throbbed.

“I remember feeling pretty frustrated about it, because as somebody who was never sick, it was really hard to be so sick, and not have any answers,” she said.

Two weeks later, their suspicions were confirmed: McWilliams tested positive for Lyme. After a course of antibiotics, the disease and her symptoms disappeared.

Her ordeal is a common one; every year, some 300,000 people in the United States are diagnosed with Lyme disease, according to the Centers for Disease Control and Prevention, and that number is on the rise. Some people wait months or years to get a correct Lyme diagnosis. And their cases highlight a problem: Tests for Lyme in the first month of infection are frequently wrong. When diagnosed and treated early the infection is a simple one to get rid of, but left untreated it can cause a myriad of lingering symptoms, from severe arthritis to short-term memory problems.

Now, a number of research groups are working to improve Lyme tests to catch infections in the early stages. One avenue being studied by the CDC aims to create a Lyme “signature” of small molecules in the blood — an approach that, in early testing, catches a dramatically higher share of early infections.

A tricky diagnosis

Presently there’s only one Food and Drug Administration-approved laboratory test for Lyme disease: a blood test that relies on detecting antibodies, proteins the body’s immune system makes in response to the disease. But while this approach is good at diagnosing the disease at later stages, it can miss the disease early on when antibody levels are low. In the first three weeks after infection, the test only detects Lyme 29 to 40 percent of the time. (The test is 87 percent accurate once Lyme spreads to the neurological system, and 97 percent accurate for patients who develop Lyme arthritis). The CDC cautions that because the test is not likely to be positive until 4 to 6 weeks after infection, doctors who suspect Lyme based on symptoms should prescribe antibiotics even if the test is negative.

In practice, however, this doesn’t always happen. “I have to use clinical judgement quite often in early Lyme,” said Dr. Daniel Cameron, who leads a private practice specializing in Lyme in Mt. Kisco, N.Y., and has been treating Lyme for 30 years. “But there are doctors who are still waiting for that [positive] test, and if they can’t confirm it with a test, they’re reluctant to diagnose Lyme, and they don’t treat.”

He added that some doctors may hesitate to diagnose based on symptoms because they are accustomed to using highly accurate tests for other diseases, or because Lyme symptoms can look like those of multiple other illnesses, such as chronic fatigue or fibromyalgia.

In recent years, concerns about unreliable Lyme testing have even pushed state governments to get involved. In 2013, Virginia passed a Lyme Disease Testing Disclosure Act requiring physicians to inform patients that a negative Lyme test does not necessarily mean they are Lyme-free, and Maryland followed suit in 2016 with a similar law.

“Lyme disease is a serious problem here in the United States and we really need to find solutions to some of the limitations that we have, particularly in diagnosing this infection,” said Claudia Molins, a microbiologist at the CDC. “We want a test that can be used within the first two weeks of infection and that does not rely on antibody production.”

So Molins and her colleagues are focusing on metabolomics — an approach that, rather than testing directly for the immune response to the infection, instead looks for a wide spectrum of collateral damage.

Specifically they’re looking for so-called metabolite biosignatures: the litany of sugars, peptides, lipids, amino acids, fatty acids, and nucleotides normally present in the blood.

Infections like Lyme, the thinking goes, change the levels of these things — and they do so in a predictable, measurable way.

Molins and her team tested that hypothesis by tapping a unique CDC resource — freezers filled with well-characterized blood serum samples. They used serum from 89 early Lyme patients, within the first month of infection, and 50 healthy controls to develop an algorithm to detect Lyme blood signatures.

The researchers then tested that algorithm on a larger sample of serums and found that they could diagnose 88 percent of early Lyme cases, and could differentiate Lyme from other diseases (including mononucleosis and fibromyalgia) 93 percent of the time. The results were published in a 2015 study in Clinical Infectious Diseases.

Microbiologist Elli Theel, who directs the Infectious Diseases Serology Laboratory at Mayo Clinic, calls the 2015 study “incredibly promising.” “The sensitivity they showed just in early Lyme disease patients was very high, the highest I’ve actually seen,” she said.

In an upcoming publication, the researchers also showed that metabolomics can differentiate Lyme from a similar tick-borne disease called southern tick-associated rash illness (STARI). The disease causes similar symptoms as Lyme, including a bullseye rash, and occurs in overlapping geographic regions. Currently there is no laboratory test to diagnose STARI, and little is known about how the disease progresses and how to treat it, something Molins hopes will change with better testing.

Moving to clinics

Now, the researchers are trying to make metabolomics more practical in clinical settings. Their main hurdle is equipment: Laboratories like theirs use a different kind of mass spectrometer than hospitals do, so the team is currently adapting their technique for a mass spectrometry platform already used for diagnosing metabolic birth defects in many hospitals.

“Really it makes sense to try to target a platform that’s already available instead of reinventing the wheel, so to speak,” Molins explained.

They are also working on developing better biosignatures and algorithms for identifying Lyme based on new blood samples they recently collected from clinics affiliated with Colorado State University and New York Medical College. Eventually they will begin real-time testing on patients’ serum samples collected in clinics and mailed to the CDC.

“People are very scared of having Lyme disease, and with reason. And so if you can more accurately tell them if they have this infection or not, I think it’s also [good] for their own ease of mind and understanding what they’re dealing with,” Molins said. “I think we owe it to the patients to give them a proper diagnosis.”

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  • Could you tell me what the best test is for Lyme disease? I have been diagnosed with MS, but suspect I could have Lyme disease. I grew up in R.I., and probably had more than 100 tick bites. My mom used a lighted match to make the tick let go of my skin. Thanks!!!

  • I had persistent fevers, sinus infections and eventually full blown arthritis and it wasn’t until probably 3 years later a PA from a small urgent care clinic in upstate NY put the pieces together and tested me for Lyme. Sure enough, positive. Did a few rounds to finally get a clearance that the bands went down to 2 bands. Doctors in the Bronx never thought to test. In fact, when I got the diagnosis, my primary care doc at Montefiore thought it was a mistake.

  • I have had Lyme disease for about 7 years. It is very hard to find a doctor that specializes in Lyme and knowledgeable enough to treat my condition. It is a very hard disease to deal with and getting the proper treatment makes it even more challenging… I hope things change because people are truly suffering…

  • The statement that antibody tests are more accurate in later stages is wrong. It is true that antibodies can take weeks to develop after the tick bite, but then they start to wane, which is why there isn’t longterm resistance to re-infection. There are also well documented sero-negative cases. Plus, the 2 tier test that the CDC insists on, is based on only one lab strain of the lyme spirochete. There are many strains. There are also other species. This is all well-documented in the medical literature and when it is pointed out to the CDC, they say the two tier test is only for surveillance. But…..most doctors know they can get in trouble without a positive test, and the CDC smears any other kind of test even for clinical purposes. Culture is the gold standard for other diseases, but sorry, CDC says you can’t use in lyme. We need the CDC and NIH to clean house of the people who have been responsible for this public health disaster.

    • I fully agree, CDC guidelines for phycians is lagging and a risk for patients or suffer. I live in a state that most MDs believe Lyme does not exist here, so getting diagnoses is most difficult. Currently class action lawsuit regarding this matter against the CDC.

  • A promising new approach from the same institutions who mismanaged Lyme disease for over 25 years (not just in the US, they dictate Lyme ‘science’ in most of the English speaking world), now that’s funny …

    This is all marketing for new diagnostic tests that are in the pipeline. Tests that were patented by (ex-) CDC/IDSA workers, so they can remain in control over Lyme diagnostics and treatment and profit from it. Much better Lyme diagnostics are already available, but strongly discouraged by the CDC/IDSA cabal. They don’t care about the patients, only about power and money.

  • The problem with the testing, *as CDC is well aware,* is that it was designed to exclude the neurological Lyme cases, and include only the HLA-linked hypersensitivity arthritic knee (with no other symptoms) cases. That was 1994, when their LYMErix OspA “vaccine” trials were underway and they discovered that it’s really not a good idea to inject an immunosuppressive triacyl lipoprotein into people. (See also the NECC fungal meningitis scandal, and who’s going to prison.) Oops! So CDC officers who had interests in intended vector-borne diseases vaccines and test kit royalties literally changed the definition to exclude the cases that messed up their trial data. Now, what’s laughable about the CDC supposedly coming up with a more accurate test is that they surely are using blood that has been qualified by the fraudulent testing scheme to falsely validate their new test method. So the sickest victims, who have a “pseudolymphoma” (Steere, 1988), or “post sepsis immune paralysis” (think B cell AIDS), still will be hung out to die. TruthCures.org

    • Weird that your first instinct after reading the above article was to post a link to a highly biased smear article against Dr. Cameron. Almost seems like you’re part of the troll army the IDSA types use to discredit anyone who diagnoses or treats outside their very rigid and biased guidelines.

      To the readers: There has been a war over the definition, diagnosis and treatment of the chronic form of Lyme disease for over 20 years. The “scientists” affiliated with IDSA, NIH, CDC, etc have used their political power and connections to enforce their belief on others that Lyme is easily diagnosed and easily treated with a short course of antibiotics, and any symptoms remaining after treatment are a phenomenon called ABL (Anything But Lyme) even though the gold standard diagnostic tests are garbage and there’s plenty of peer reviewed science to support chronic Lyme disease being related to persistent infection.

      As part of the IDSA affiliates’ effort to enforce their will, they have waged a campaign to discredit and de-license doctors all across the country as punishment for treating with longer courses of antibiotics. Compliant state medical boards investigate those doctors and come up with whatever trumped up charges they can muster.

      If you’re unlucky enough to get the chronic form of Lyme disease, my condolences because you won’t just be battling an illness, but also medical corruption.

  • The problem with this devastating disease is the constant 35 plus years of inaccurate information. The western blot is and has always been a inadequate test that as stated tests for antibodies to the bacteria. Not all immune systems are the same along with the complicating possibility of co-infections making the test worthless. For the people in parts of the country that supposedly don’t have a risk the patient and the physician never think lyme and thus they are cast into the pile of don’t know what is causing this and they become one of the chronic lyme suffers.

    Must change the idea that this is a isolated problem in the United States. Its an epidemic in this country and other countries. There has been a test for this disease for a long time. Its called a DNA test for the borrelia; however, its costly. As Willy Burgdorferi stated “Dr. Burgdorfer: The controversy in Lyme disease research is a shameful affair. And I say that because the whole thing is politically tainted. Money goes to people who have, for the past 30 years, produced the same thing—nothing.

    • DNA tests don’t need to be expensive, but they often are because DNA Lyme testing is strongly discouraged by the CDC cabal with ridiculous arguments, and the result is that DNA testing for Lyme is a ‘niche’ activity, which always means relatively high prices. And it doesn’t help that most patients have to pay these tests out of pocket as well.

      In Europe you can order Lyme DNA testing for horses or other pets for just $35; these are basically the same tests that could be used for human diagnostics and even those prices are artificially high due to low volume. If DNA testing becomes generally accepted for Lyme disease and labs have much higher testing volume it could be about the same price as a standard Lyme Elisa test (plus some extra charge if you want a DNA sequencing confirmation). Of course CDC/IDSA will fight this tooth and nail, because DNA testing will turn up many unconvenient truths.

  • It sounds like people should have a followup test 2-3 months later to confirm if they are Lyme free. Par procedure for slower developing diseases… good thing it only takes several months, rather than years or decades.

    • Waiting 2-3 months can affect the rest of your life. As with many other diseases, a Lyme diagnosis should be made based on clinical symptoms. Starting antibiotics for 4-6 weeks is a must. Otherwise, the bacteria can invade every part of the body, including bones. (The corkscrew shape literally twists itself in.) Treatment then is expensive and not always successful.

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