As 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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  • I’m not sure my previous response transmitted.. your test on Jan. 4th is not at all reliable; blood tests are not a diagnostic tool. You may be infected and need treatment. I am a Support System, advocate & activist. Jane in RI.

  • to Cindy: Your experience is very common, unfortunately; and your question is very valid. Please contact me for “All Things Lyme”.

    • Please help. I have had several blood tests done and they all come back positive for Lyme. I have been on Antibiotics 3 times since April 2018. The pain is just getting worse

  • If I was diagnosed with Lyme disease in April 2018 and just had more blood work on January 4 2019 and it came back with 5 strands positive. Is it possible to a false positive? I am still in a lot of pain.

    • Have you been on the antibiotics for a certain period of time… 21-28 weeks. Doxycycline or something else? If it’s not helping maybe you need to see a LLMD or ND that specializes in Lyme. I’m trying some natural methods on my own first since these doctors are out of pocket typically. If I don’t get better I have the name of an LLMD I’m going to see.

      Right now I’m trying an herbalist to see if I get better with her capsules/tinctures/etc. I’m slowly getting better, but I’ll know more when I stop and if my symptoms are still lingering.

    • I meant 21-28 days not weeks;-) That is the typical CDC recommended guidelines. Was wondering if you did that or a longer course.

  • I to have been dealing with medical issues for 30 years or better. I have had issues no medical doctor can explain what why or how come. I’m sick and tired of being passed off as well as over incessing on having Lyme disease. I have been diagnosed with fibromyalgia, rheumatoid arthritis, PTSD, depression, overstressed, anxiety etc. I have had my immune system bottom out, my red/white blood count levels bottom out. Doctors can’t figure out what is going on with me. I live at the doctor’s/hospital for medical issues, severe pain, dizziness, passed out but know one has a clue what’s ever wrong. They guess, assume or lay blame. I have had so many health issues, irritable bowel syndrome, head aches, joint pain stiffness, bad eye vision, chest pains, no appetite, flu like symptoms, constant colds year round, stomach problems etc. I feel like my body is a bruise when touched I’m so tender. I itch like crazy. I have begged doctors to test bit they ask why I feel I need it. They have run a single test years ago twice but they were negative back then. I have all the symptoms of Lyme. I don’t want to have it but I don’t want to go on living like I am. Any ideas?? Help??

    • Brenda,

      If you have the money to see an LLMD or ND doctor that specializes in Lyme I would try to see one of them. Some LLMD doctors do accept insurance but most of the ones I’ve found do not.

      Sometimes you can find an internist that is Lyme aware and that is a good place to start for lab work to test for other things as well. I started with an internist to navigate and I am trying some natural herbs on my own to see if that works first. If I don’t get better I have the name of an LLMD I am going to see.

      A lot of us are not only dealing with Lyme but other coinfections, food allergies, etc. I’ve had to make a complete lifestyle change.

      It sucks to deal with this disease that a lot of people don’t understand. Best of luck!

    • Do you have an IUD? I know it sounds like a silly question. But worth investigating if you do.

  • If you’ve had Lyme tests come back negative, try the IGeneX lab test. Most people who get negative results for Lyme test positive through this test. Most Lyme literate doctors use this test over the mayo serum test.

    • 100% on using the IGeneX test! Iv had Lyme for over 20 yrs and it wasn’t properly diagnosed or treated until I had a Dr OUT of Network (Functional Dr) run the IgeneX test. It’s really sad how many people are u diagnosed or misdiagnosed and are told they have some other issue and continue on being sick. I can now live a life of freedom and have answers after so many years thanks to this test . Don’t count on the Lyme test at your drs office to show you results ! It is expensive to test the right way for Lyme, but I would pay it all over again to live a happier, healthier life! Find a Dr that will dig for answers for you because most will not do that. I finally found the right Dr after so many yrs and she knew what to test me and how to treat me.

  • Hang in there! I also have some of the same symptoms as you. I’ve had stabbing, burning, weird movements all along my guts. Sometimes it migrates to under the ribs. Other times it feels like a fist is shoved under my ribs. It is very painful. I also have terrible palpitations and can hardly get off the couch to take showers. Can’t do the simplest tasks and feel like I’m 80 yrs. old..even thou I’m only 47. Lot of times I get air hunger. Been to many doctors and specialists and I believe they think I’m crazy or having a panic disorder. I know I’m not! You know your own body…so keep researching and you will find a lyme literate or ilad doc. They don’t advertise due to b.s. politics and others don’t believe in chronic lyme disease! I found one and met my doctor today! He’s given me hope and I can’t tell you how grateful I am! I will get my results soon and due to my symptoms, he believes I have the lyme disease even though it was negative that was done in another place. I will pray for you and hope you will get your answer soon! I know it is very scary at times…

  • Hi my name is Mike I have been suffering from debilitating symptoms for over 15 years. Believe all my symptoms are caused from lyme disease. There are no lime literate doctors in my area, need help finding one. My symptoms are severe burning skin pain with itching and rashes, very painful joints, and muscle pain, eye issues,stomach problems, cluster headaches, swollen lymph nodes in armpits, memory problems,severe dizziness, lightheaded along with a alot of other symptoms, been diagnosed with Raynauds Phenomenon, degenerative arthritis, and fibromyalgia. No relief of any of my symptoms, struggling to hang on, as have lost faith in of the medical field. Had lyme test came back negative twice. Don’t know where to turn. Doctors don’t believe me and think I’m crazy, bit know in my heart something is wrong with me. If you can help in any way. I would forever be greatful.
    Best wishes thank you Michael.
    Omaha,Nebraska

    • Hey there Michael, I feel you brother of the same name. Your not crazy first of all, and you know your body better than some doctor who gives a few minutes of their time and bs prescription. Couple things you may try…. first dont give up hope, try to stay positive, keep moving forward, looking/fighting for answers. Quit sugar in All Forms, tough to do, but it’s gonna help your gut, where they say 70% of your immune system resides. Google FM/a it’s a blood test for Fibromyalgia. Not to many doctors know about it, and insurance is beginning to cover it. It’s said to be like 95% accurate. The company behind it, is right now applying to the FDA to do a trial using an old school TB vaccine to try and cure Fibromyalgia. Perhaps this will give you more of direct path to follow? I took the test and was found positive for fibro. As far as lyme goes, that’s a big hazy picture for sure. What’s real and what’s not ? Is basic test accurate or not ? – the expensive test is not covered. Can you get it from more than certain tick bites? Latent infections suddenly cropping up from years ago? What do you actually do about it? Im not to sure anyone really knows? Lastly(?), there is also a website called Hormones Matter. There is an old school doctor on there by the name of Derrick Lonsdale(93 years young). He has a theory about thiamine deficiency(beriberi) as a root cause of chronic disease. It’s an interesting theory and worth a look. I’m not a doctor, just a guy who shares your pain and your name. Good luck Michael- Now Forward….I feel like I’m talking to myself here 😉

    • Mike, your symptoms sound much like mine. I too have had negative Lyme tests (in 2009, IGG test negative with 1 pos. band and positive IGM).
      I was bit by a tick in 2006, had the bullseye rash, but didn’t get treated for Lyme for almost 9 months ( and then only at my insistence). In 2009, I had the blood test. My doctor told me I most likely had Lyme, but not any more ( hence the test results above). Again, I have pretty much all the same symptoms you have. Hard to deal with, but I just go to a lot of different docs for the different problems. Doesn’t seem like anything is getting any better; just progressively worse so far. I did run across an article from Tulane University (Dec. 2017) that was very interesting. Maybe we’ll start seeing more improved studies like this. One of their results showed negative test results when there was a bullseye rash.
      I wish I could be more positive, but maybe there will be something in the future.

    • https://www.lymedisease.org/find-lyme-literate-doctors/

      https://www.ilads.org/patient-care/provider-search/

      If you don’t have a Lyme literate doctor near you there are some doctors online that have a natural protocol you can follow online. I followed Marty Ross MD. There are others like Rawls, etc.

      https://www.treatlyme.net/
      One of his treatments are two tinctures you can purchase online.

      https://www.mindbodygreen.com/wc/dr-william-rawls

      If these types of treatments aren’t for you there is a lot of good information on their sites as well. Best of Luck. I hope this helps 🙂

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