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Researchers Closing in on Definitive Lyme Tests As NIH Amps Up Lyme Efforts

It wasn’t until 1983 that Borrelia burgdorfii, a bacteria carried by the black-legged or deer ticks, was identified as the cause of Lyme disease. That didn’t mean a good diagnostic test has been available – far from it.

None of the currently available tests (PCR, antibodies) are anything near definitive. PCR tests often fail when they simply miss the low numbers of bacteria present. The most commonly used tests, antibody tests, on the other hand, don’t begin to be accurate until a month or more into the disease.

That’s not a good scenario for a person bitten by a tick who needs a quick regimen of antibiotics to ward off the potential joint, connective tissue, heart and nervous system complications that can occur, 20-30% of whom never get the infamous Lyme rash. Public health authorities estimate that as many 300,000 people are exposed to Lyme disease every year – but only 30,000 cases are reported.

Lyme disease

Lyme disease has been a scourge for decades, but doctors still use tests developed in the 1990’s.

The current tests are so problematic that health officials in areas with high rates of Lyme disease often simply provide prophylactic doses of antibiotics to anyone exposed to a tick who comes down with a fever, headache, etc.

Plus people who remain ill after treatment, or who are diagnosed using controversial tests, can be given long term courses of antibiotics long term which carry their own risks. The number one thing that’s wanted and needed in the Lyme world is an effective diagnostic test. The good news is that one may be on the horizon.

The current slate of antibody tests were agreed upon back in 1993 at the Dearborn Conference when our understanding of Lyme disease was in its infancy. Twenty three years later, experts experienced in the clinical and laboratory aspects of Lyme and other infectious diseases met at the Cold Spring Harbor to discuss better Lyme diagnostic tests.

That meeting and discussions afterward laid the basis for a 2019 Viewpoint article in the Journal of Clinical Infectious Diseases with the provocative title, “Direct Diagnostic Tests for Lyme Disease“.

Direct Diagnostic Tests for Lyme Disease

Direct Diagnostic Tests for Lyme Disease Steven E Schutzer Barbara A Body Jeff Boyle Bernard M Branson Raymond J Dattwyler Erol Fikrig Noel J Gerald Maria Gomes-SoleckiMartin Kintrup Michel Ledizet … Show more Clinical Infectious Diseases, Volume 68, Issue 6, 15 March 2019, Pages 1052–1057, https://doi.org/10.1093/cid/ciy614

The Viewpoint effort was lead by Stephen Schutzer – an immunologist and sometime ME/CFS researcher – who in 2011 used an analysis of proteins in the cerebral spinal fluid to distinguish post-treatment Lyme disease from chronic fatigue syndrome (ME/CFS).

The authors got right to the point: the serologic tests presently used, they wrote, “cannot distinguish active infection, past infection, or reinfection”. “Reliable direct-detection methods, on the other hand, now appear achievable”.

It should be noted that the scientific advances allowing such statements to be made provide hope not just for Lyme disease patients but for those with other difficult-to-detect infections. Reliable diagnostic tests have recently been developed quickly for a number of newly emerging diseases such as Middle East respiratory syndrome – coronavirus, Zika infection, and even 2 newly recognized tick-borne borrelia infections (Borrelia mayonii, Borrelia miyamotoi).

B. burgdorfii is a different case, however. Three factors in its makeup (low bacterial load, high antigenic diversity and a wacky genome) have made it particularly difficult to capture.

Antigen Capture

Instead of directly looking for the bacteria itself, it’s possible to look for the antigens (proteins) the bacteria sloughs off into the blood, urine, etc. Past antigen capture efforts have been thrown off by the high antigenic variability found in the Lyme bacteria but new developments in mass spectrometry, and antigen enrichment and stabilization are making antigen capture a real possibility for capturing B. burgdorfii. 

A Better PCR

B burgdorfii

Three aspects of B. burgdorfii make it difficult to find.

B. burgdorfii’s second trick for evading capture – low bacterial loads in the blood – have made it difficult to capture by PCR.  Enter high-throughput sequencing techniques that have been developed to scan larger blood samples. Frequently used to detect exotic infections, the authors asserted these techniques can “be applied successfully to Lyme disease diagnostics”.

They know – because they’ve done them. These tests, which are 200 times more sensitive than normal PCR, may just be the tip of the iceberg, though. Adding other measures to their Lyme test kit allowed the authors to increase the sensitivity of their PCR a jaw-dropping 16,000 fold – enabling them to catch many more cases of Lyme disease than had been previously detected.

Instead of the .5 ml of plasma usually taken, the authors took 1.25 ml of whole blood, used a technique to amplify the bacteria present, and then used multiple primers.

Next Generation Sequencing

B. burgdorfii’s third evasive maneuver – its complex and unusual genome consisting of high levels of circular plasmids – has enabled it to evade capture in the past, but the development of a new technique (“long-read sequencing”) has allowed Pacific Bioscience to uncover hallmark sequences of the bug’s genome that can conceivably be targeted in diagnostic tests.

Serology Not Dead Yet

Serological testing, which relies on assessing the immune response to the bug, has a couple of problems, but doctors are familiar with serological testing and it may be cheaper and easier to use than other techniques. Improved serological testing could clearly provide a boon as well.

Just a week ago, a biomedical engineering group from Columbia published a study using a new serological test which purportedly can diagnose a Lyme infection in just 15 minutes. This test which uses “microfluidics” was much more effective than the standard tests at diagnosing early infections. The test needs to be further refined and tested, but the early results were good.

Effective Lyme Test Now Technically Possible

The advances enabled the authors to assert that “the goal of an active-infection diagnostic test is now technically achievable”. Note the word “technically”. We’re not there yet.

Understanding the full breadth of B. burgdorfii’s genetic diversity, creating better genomic databases, optimizing sample collection procedures and other issues need to be resolved for that to happen. That’s all a matter of funding; i.e. the political will to get the Lyme (and other tick-borne illnesses) under control.

New NIH Emphasis on Lyme Disease 

Finally, in a last bit of good news – the NIH will be ploughing more resources into Lyme research over the next five years.

Lyme disease has differed little from ME/CFS, fibromyalgia and others in its neglect at the NIH, and new NIH emphasis on Lyme was the result of years of advocacy work. In some ways, ME/CFS advocacy is on a parallel track – it’s just a few years behind. A Congressional Lyme Disease Caucus,led by two Lyme champions, and that was officially formed in 2013, paved the way.

Lyme strategic plan

Years of advocacy paid off when the NIH published a strategic plan for Lyme. The NIH is now working on a strategic plan for ME/CFS.

The 2016 21st Century Cures Act mandated the establishment of the Tick-Borne Diseases Working Group the NIH. In 2018, that group produced a report outlining recommendations for research which included increasing funding, improving diagnostics and, more importantly, developing a strategic plan.

That plan was recently published, and when it was, Rep. Chris Smith, one of the leaders of the Lyme Caucus, and a long time advocate for more Lyme research, reported advocacy efforts had paid off:

“After lagging for decades, NIH is all in for researching Lyme and other tick-borne diseases to better diagnose and treat those suffering from this horrific disease. This is great news for patients and Lyme-literate doctors who will now have serious, federal partners working aggressively to improve strategies for the detection, treatment, and one day, prevention of Lyme.”

That plan includes a number of intriguing focii, including determining the cause of an ME/CFS-like disease (post-treatment Lyme disease syndrome), better understanding the only known food allergy that can be induced by an insect bite (alpha gal syndrome), and developing rapid and direct detection diagnostic tests as well as vaccines and immune-based treatments.

Lyme isn’t the only neglected disease benefiting from effective advocacy. The money the HEAL project is pumping into efforts at the NIH to fight the opioid epidemic and create better pain drugs resulted from a public outcry. ME/CFS, with its ramp-up of advocacy efforts, and the NIH’s work on a strategic plan, is hopefully following a similar path as Lyme disease.

See- Did a Pivotal Moment for ME/CFS Just Happen?

Smith is not nearly done with Lyme advocacy. His next trick is a bill (TICK Act (HR 3073) that would create a national strategy to prevent and treat Lyme and similar diseases.

Conclusion

Rapidly decreasing technological costs are helping the search for better diagnostic tests. More work needs to be done, though, to validate a test and bring it to market.

The takeaway message from the Direct Diagnosis paper is that we now have the technology needed to develop a reliable, effective test for Lyme disease. Such a test would identify many people who don’t know they have the disease and stop unneeded treatment in those who don’t have it. It should also help us understand what’s going on in those who have been treated and remain ill (post-treatment Lyme Disease).

The missing element has been the political will to comprehensively tackle the disease and provide the necessary research funding.

That appears to be changing as well. Years of advocacy paid off with the recent production of a strategic plan to comprehensively fight Lyme disease. The NIH’s new emphasis should further advance the development of better diagnostic tests and, hopefully create new treatment possibilities. With ME/CFS on a similar path with it’s own strategic plan being developed, it’ll be illuminating to see how much Lyme disease funding shoots up over the next couple of years.

More on Lyme Disease From Simmaron

Post Treatment Lyme Disease Unmasked? Immune Hole in the Illness Identified

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16 Comments

  • Issie

    October 22, 2019 at 6:58 pm - Reply

    Having Post Lyme Disease and also other fungus connected to mosquitoes (similar to malaria, but actually a fungus that forms biofilms and tumors), this has been a long struggle to find solutions. I’m of recent on a new herb recommend by my Functional doc. I wrote about it on this thread. Its Lomatium along with rotating some enzymes. Seeing some positive responses.

    https://www.healthrising.org/forums/threads/potential-linking-fm-mast-cells-sleep-deprivation-food-intolerance-exercise-intolerance-and-me.6217/

  • Tom

    October 22, 2019 at 8:46 pm - Reply

    The first thing that needs to be acknowledged is a definition of Lyme. One of the thorny debates that has raged for decades is what strains and species of Borrelia were going to be detected by a test. It only makes sense that ANY strain or species that and person might have developed an infection SHOULD in incorporated into an effort like this. For many years the use of Borrelia Burgdorferi strain B31 was used as the basis for the 2 tiered test. That was improved but the “huddling” around strains mostly common on the East Coast of the US seemed just plain wrong.

    Any test that claims to be a definitive test must include all reasonable species and strains. Otherwise people with Lyme will be told they don’t have it and the reason will be that the test didn’t include it.

    A Lyme disease definitive should detect ALL species including the European afzelli and garinii, the US andersonii, americana , bissettii, caroliniensis, lonestari, mayonii, miyamotoi and any other that cause a Lyme or Lyme-like infection.

    Not defining what species they are trying to detect right from the beginning will make this another debacle. I hope they get it right. You would think that the definition would be written right up front.

    • Cort Johnson

      October 23, 2019 at 12:13 am - Reply

      Thanks Tom for clarifying that so well. The Viewpoint does mention Borrelia’s astonishing genetic diversity – which I was not aware of. The researchers are certainly cognizant of the need to identify all the strains. The big question that remains seems to be whether the funding will be available to properly do that. Hopefully the new NIH focus will help with that.

      It’s amazing to me that we’re using an inadequate test developed in the 1990’s to diagnose this important infection.

  • Nancy B.

    October 22, 2019 at 11:01 pm - Reply

    It is exciting news that researchers are zeroing in on better tests for Lyme’s–although exactly when the average patient will be able to access these tests will probably be far in the future–or perhaps less available because of cost.

    Regardless of that, one thing that wasn’t addressed in your article is the still raging controversy of how to treat Lyme’s–especially lingering Lyme’s. I couldn’t find the article which gives a dramatic picture of the conflicting viewpoints (and is very political because the doctor’s consulted for the CDC Lyme’s clinical pathway didn’t agree that chronic Lyme’s necessitated long term antibiotic treatment–and so on. I did find this discussion that I thought I’d share, which at least gives a hint of the difference of opinions; https://www.contagionlive.com/news/diagnosis-and-treatment-of-chronic-lyme-disease-a-complex-issue

    Relating it back to our group, I do wonder how many of us will actually be able to trace our troubles back to previously undiagnosed Lyme’s. Not everybody develops the ‘bullseye’ and nymph ticks, which can be very virulent carriers, can be next to impossible to be seen they are so small. See the ‘dot’ at the bottom of the question mark at the end of this sentence? That is the size of the smallest nymphs!

    • Cort Johnson

      October 23, 2019 at 12:16 am - Reply

      I got the sense that commercializing and developing the genomic databases, etc. was the major issue. This is where I think the NIH has to step in – do the steps needed for a company to profitably commercialize the test.

      I gathered, hopefully correctly, that the researchers do believe a definitive test will be able to determine if the bug is still there in Post-Lyme Treatment Syndrome.

  • Issie

    October 23, 2019 at 12:17 am - Reply

    And when it goes undiagnosed for so long there is much more likelihood of having Post Lyme Syndrome, which is also controversial. But, those of us with it know it’s real. Thankfully, I had docs that believed that not everything was being tested and if symptoms fit, than assume it to be. Addressing with antibiotics was not effective that late in the process. But herbs were and an herb with enzymes is seeming to help the Post Lyme symptoms too.

  • Anonymous

    October 23, 2019 at 1:10 am - Reply

    It’s an intentional stall. Some estimates over 70% of the population in endemic areas is infected, although not all are symptomatic.

  • Nancy B.

    October 23, 2019 at 1:16 am - Reply

    Issie, since you and I both have EDS, on my EDS forum there are many who think they MAY have (late stage) Lyme’s as well, because the symptoms can be so similar. As we are discussing, the current tests are not all that accurate. I think it also informative that there are so many sub-types of the Borrelia virus which makes detection all the more difficult.

    Lyme’s gets all the attention, but there are a whole host of other types of infective agents carried by ticks (and other vectors), like for instance Taxoplasmosis. Having 7 cats I am all too aware of this. As a matter of fact, before I got married in California, the State required a test to see if one is a carrier before they issue the license. I was indeed a carrier but because I wasn’t planning on immediately having children, I was only given a notice to get treatment.

    That was decades ago and I’m sure I have been re-exposed time and time again. Most people are not severely affected, but I’m sure there are plenty of infections that are, either by late effects or the unfortunate vulnerability of certain individuals, flying under the doctor’s radar.

    I’m quite convinced that it will be eventually be found that there are many infectives ‘hibernating’ within the body where the length of time between initial infection and much later symptoms has hidden the real connection. If that wasn’t clear, I mean that certain illnesses can appear to take their course and the person is ‘healed’, but in reality the illness can hide–quietly, undetected–waiting for a vulnerability to reemerge. Or perhaps having had a certain illness, it can tip the genetics to make a person more vulnerable to another kind of malady–such as a cancer.

    Sorry for the bummer of an idea… ;-(
    But I think the new testing will help… 😉

  • sped

    October 23, 2019 at 1:40 am - Reply

    There is a story that Lyme may have been developed as a bioweapon. Here is a concise article for those who don’t have time to read the book “Bitten” by Kris Newby. https://pacificsun.com/bugging-out/

  • Issie

    October 23, 2019 at 2:14 am - Reply

    @Nancy, I’m sure there are some of us “sensitive ones”, who have things that are undetected. One of my former doc discovered a fungus in the blood and organs that he feels came from mosquitoes. He knows it forms biofilm around it and can form tumors. It has been found in plaque from heart by pass, prostate cancer, brain tumor and now a biopsy from my thyroid tumor. We are finding enzymes to be helpful. But he is now in research looking for something more to help us. He no longer sees patients. I do believe there are things we are fighting that have not been found yet. But when they do become discovered, trying to find something to do for them…..becomes a huge problem. At least having detection, gives us a WHY.

  • Eric S

    October 23, 2019 at 4:52 pm - Reply

    Hey Cort…Do you think they will try to do any exercise tests on people with Lyme disease in the near future?…I would think that it could help find out, by the process of elimination, if it’s really ME/CFS, or something else that requires further checking…

    • Cort Johnson

      October 23, 2019 at 5:05 pm - Reply

      I think it would be fascinating. I think Avindra Nath may have Lyme cohort in his NIH ME/CFS Intramural study but I’m sure if he’s using Lyme or Post Lyme or Lyme patients who have recovered.

    • Cort Johnson

      October 23, 2019 at 5:05 pm - Reply

      I think it would be fascinating. I think Avindra Nath may have Lyme cohort in his study but I’m sure if he’s using Lyme or Post Lyme or Lyme patients who have recovered.

  • David R

    October 28, 2019 at 1:47 am - Reply

    The NIH study has a cohort of Lyme patients who have recovered (the other two being ME/CFS less than 3 years, and Healthy control). https://www.nih.gov/mecfs/nih-me-cfs-clinical-study

    • Cort Johnson

      November 5, 2019 at 5:47 pm - Reply

      Thanks David for that!

  • Camilla Cracchiolo

    October 29, 2019 at 12:29 pm - Reply

    Have you been following the research on “persister Lyme”? Apparently some Lyme bacteria survive antibiotic treatment by forming a biofilm to keep it out. A paper published on National Library of Medicine shows one doc trying to get past this with multiple antibiotics together and trying to find new antibiotics. It may be that we’ll need a new drug to clear up these cases.