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.

advertisement

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.”

Leave a Comment

Please enter your name.
Please enter a comment.

  • Blood tests CAN DEFINITELY miss a positive result for Lyme and co-infections. You should follow up with private testing. ARMIN Labs in Germany are excellent, and extremely reliable. There are also quite a few in the US. When diagnosing Lyme, symptoms, plus blood tests should be considered. Newly infected individuals might not show a positive blood test for many months.

  • Does a blood test for Lyme disease always detect the disease or can it still be missed? We think our daughter may have Lyme disease but her blood test came back negative . We are perplexed as to what else her symptoms could be from , she has had numerous tests and her last blood test was for Lyme .

    • Blood tests for Lyme come back negative often and can’t be relied on. You need to get your daughter an IGENEX (out of Palo Alto, CA) test which is out of pocket, but will show any antibodies. You can order the test on your own and have a Lyme literate Dr interpret it or have a Dr order it and interpret it. I found a functional Dr Out of network that finally helped me after 15 years of mysterious issues. Also, coinfections need to be tested for properly if there is a positive Lyme diagnosis. Testing is a big part of the problem unfortunately and many don’t know about IGENEX or STONYBROOK testing!

  • I sympathize with you. It’s a terrible disease and the fact that Physicians refuse to acknowledge that there is a Pandemic going on, people will continue to suffer needlessly. Most of them are just plain lazy and don’t want to spend the time studying the disease and the co-infections. When faced with a patient who is extremely Lyme literate, they feel insulted. After all, who are we to tell them how to do their job!!! And right there is the rub. They refuse to spend their own time researching, and get angry when faced with us, Lyme patients, who can run circles around them regarding knowledge of Lyme and what treatment is needed. So we get none!! It’s just bloody wrong on all levels.

    • The medical community are scared beyond belief regarding the Pandemic of Lyme and the co-infections that accompany Lyme. Hundreds die each year because of this disease and they are running scared. It’s been around for a very long time, and individuals diagnosed years ago with some other disease, who have since passed away, are scaring the physicians who made those diagnoses back then. It opens the door for many wrongful diagnosis lawsuits. It’s such a convoluted mess, and involves much more than sick people. Everyone is now trying to cover their back !!!

  • I was tested for lymes disease after having burning swelling and shooting pains in both knees ( had TKR in both knees last 6mos) they were fine for months. Big toe sore, red and swollen too..did not see tick bite anywhere..but only one titer came back positive..md will not treat…

  • I had 3 bullseye 3 different times and I can’t even find it in my medical records what a joke my joints hurt so bad must be in my head lol

    • Strange you should say that right now, but I’ve recently discovered that things in my medical file have been kept from me!! I’ve discovered that 15 years ago after a mammogram, there was a lump found in my right breast. They decided it looked okay and decided to leave it alone, but monitor it. NO ONE told me about this for 15 years and I found out by accident. It apparently hasn’t grown at all, so they’ve not bothered to test it at all. They’ve deliberately kept this information from me so I “wouldn’t worry!” OMG, how dare they. I also discovered that ten years ago when I was at the hospital with an extreme headache that I’d actually suffered a STROKE!!! The effects of the stroke had a small impact on my short term memory. They didn’t even explain that to me, but let me think I was experiencing severe migraines!! My God, I’m beginning to wonder if I’m living in a concentration camp. I have no idea what else has been withheld from me because I have to request to see my file 30 days beforehand. Who knows what they remove before I see my file? Writing to the College of Physicians is of little use. Tried that and got the run-around. They all protect each other.

  • Hello, my daughter Brittany who is only 33 yrs old & has 5 kids. She has lost her job & her husband has to work 60 hrs plus to pay all the bills. She has gone to so many Drs that I cannot even tell you how many. About 3 was ago she just got a pace maker put in. About 3 yrs ago she found a tick in her head & did not find it till The next day. She has to use a can or walker to get around. She cannot do anything that she used to do. My grandkids are suffering for she cannot be the mom that she used to be. I lost my daughter who cannot even get out of bed some days. As I am typing this tears are running down my face. We so much are looking for a answer. Please can you help us. Thank you Jodie Davis her mom

    • She definitely needs to be tested for Lyme and all the coinfections through the Igenex test out of Palo Alto, Ca or Stonybrook out of NY. After 15 years I finally found answers through this test but with a Lyme literate Dr here in the San Francisco area! There are answers out there and your daughter should not have to live like that not knowing what’s going on. She needs the RIGHT dr and that Dr needs to be able to interpret the tests and treat accordingly .

    • Also, her diet first of all needs to be completely in check. Removing all dairy, gluten, soy , alcohol, refined sugars for MONTHS and usually forever. This is a place to start, but certainly not the whole picture. I take many supplements, herbs and didn’t do any antibiotics bc they rarely work on old infections. Lowering inflammation is huge and taking stress off the immune system anyway she can.

    • Also, her diet first of all needs to be completely in check. Removing all dairy, gluten, alcohol, refined sugars for MONTHS and usually forever. This is a place to start, but certainly not the whole picture. I take many supplements, herbs and didn’t do any antibiotics bc they rarely work on old infections. Lowering inflammation is huge and taking stress off the immune system anyway she can.

  • Who is Jane Barrows? Please tell me how to get help. I have tremors to the right side of my body and tingling/jittery feeling throughout my body x 3 mths. Has a reactive test result for lyme disease but Dr states “don’t worry about it that it’s only antibodies”. I am worried and my symptoms are worsening daily. I have seen many doctors, did many tests, all normal results therefore cannot be treated for anything. Help.

    • To Dolly…….I may be able to help you find treatment. Email me at . Where are you located? jb

    • Don’t worry about it? I can’t tell you how mad that makes me! It took me 15 years to find answers and that’s just because my symptoms got bad enough. Even then, I was turned away from 5 Kaiser Drs with no answers last year. I then found a Lyme literate Dr that ran the right tests and has helped me tremendously . The IGENEX test is what I took, but the RIGHT dr is KEY!

    • hi my name is margaretmege and I have been sick for years think it started with tick bite but I also have 2 mutated genes MTHFR so that doesn’t help any i was just sick for 3 weeks couldn’t even get out of the chair dr said I had a virus but no one else in my house got sick now I’m feeling better but my knees hurt so bad so I’m going to start with the diet no sugar no dairy no gluten no preservatives what is left to eat in America grass fruit vegetables I’ll try that no broccoli or corn I guess ty for advice sure wish they could find a way to rid our bodies of those spirally bastards

    • Yes! I thought I had MS and was tested a few times for it over the years, u til I found the right Dr out of network that tested me through the IGENEX test and found Lyme. Finding the RIGHT dr is key, but it’s just all so expensive and kind of a nightmare to treat. Diet needs to be excellent first off. No dairy, gluten, soy, alcohol, refined sugars for months ! I take many supplements , herbs and have had huge improvements in a year. I didn’t do any antibiotics bc they don’t usually work long term if it’s not a recent infection .

Sign up for our Daily Recap newsletter

A roundup of STAT’s top stories of the day in science and medicine

Privacy Policy