Archive for the ‘Lyme’ Category

What Can Chronic Lyme Disease Teach Us About Long COVID?

https://www.lymedisease.org/kinderlehrer-lyme-long-covid/

What can chronic Lyme disease teach us about long COVID?

By Daniel Kinderlehrer, MD

One-third of patients who were sick with COVID-19 have come down with chronic symptoms, now known as long COVID or long hauler syndrome or post-COVID syndrome.1

For the most part, these are people who had mild SARS-CoV-2 infections. And although vaccinations mostly protect patients from serious illness and death, recent data suggests that breakthrough cases of vaccinated people who catch the virus are at the same risk of developing long COVID as the unvaccinated.2 As yet, we don’t have data on the Omicron variant and long COVID.

Distressingly familiar symptoms

The symptoms of long COVID are distressingly familiar to patients who suffer from persistent illness with Lyme disease: severe fatigue, muscle aches and joint pains, impaired cognition (“brain fog”), insomnia, headaches, sleep disorders, cough and shortness of breath, palpitations and lightheadedness.3,4 Many patients have also reported mood issues with anxiety, depression, and even psychosis.3-5

Like the condition we call chronic Lyme, long COVID can be totally disabling, with people exhausted or short of breath after walking across the room. Sometimes these symptoms last a few months, but some folks are still ill for over a year without respite. There are now reported suicides among those who were suffering from long COVID.6

Those of us who are treating patients with chronic tick-borne infections witness these same symptoms every day in our patients. It is likely that these disorders have similar pathogenesis.

In patients with chronic Lyme, the issue is not microbes invading tissue, the way we imagine a strep throat or a wound infection, essentially disrupting cellular hardware.

Chaos in the immune system

Instead, these patients have a software or regulatory problem. Chaos in the immune system leads to immune suppression, autoimmunity and systemic inflammation;7,8 hormonal imbalances lead to fatigue and decreased resistance to infection;9 disorders of the nervous system results in impaired cognition, sleep disorders, and neuropsychiatric symptoms.10

No matter the cause, chronic inflammation has severe consequences. It often results in dysautonomia: disorder in the autonomic nervous system (ANS). In a healthy individual, the ANS employs the sympathetic arm (mostly stimulatory), with the parasympathetic (calming), to keep us well-balanced, in homeostasis.

But when the ANS is inflamed and out of balance, the result is fluctuations in pulse and blood pressure—with palpitations, lightheadedness and passing out. Dysautonomia can also trigger a myriad of other symptoms including shortness of breath, heat and cold intolerance, sweats and anxiety.11

Further downstream effects of systemic inflammation manifest as sensitivity syndromes, particularly to foods and mold. Mast cells are primitive white blood cells that evolved to protect our mucous membranes from invasion. When they become trigger-happy, they discharge histamine and a squadron of other inflammatory mediators called cytokines.

Mast cells

This is called mast cell activation syndrome. MCAS causes an array of symptoms including hives, flushing, itching, swelling, headaches, brain fog and pain syndromes. The cytokines released by MCAS stimulate the vagus nerve (the tenth cranial nerve), which can worsen symptoms of dysautonomia, impair cognition, and trigger neuropsychiatric symptoms, gastrointestinal syndromes, and breathing problems.12

And compounding the felony, the vagus nerve can further trigger mast cells to degranulate and release their inflammatory messengers.13 It’s a self-perpetuating cycle that leads to even more inflammation, disabling symptoms, and disability.

Patients with chronic Lyme frequently have endocrine issues. The most common are dysregulation of the adrenal glands and abnormal thyroid metabolism. Not only will these contribute to fatigue, but also to immune suppression.14,15

Meanwhile, immune suppression can result in activation of previously dormant viral infections like Epstein-Barr virus, which in turn contributes to fatigue, pain and inflammation.16

In addition, chronic inflammation and infection can result in hyperviscosity issues, in which “thick blood” slows circulation, reducing delivery of oxygen and nutrients to cells.17

Finally, chronic inflammation results in oxidative stress, in which highly reactive molecules called free radicals interfere with normal metabolism, like mitochondrial function.18 Mitochondria are the energy producing organelles in each of our cells, and mitochondrial dysfunction can result in debilitating fatigue.

These same issues are present in the unfortunate thousands of people suffering from long COVID.

Similarities between chronic Lyme and long COVID

In its acute stages, SARS-CoV-2 can invade tissues and cause life-threatening organ damage. But in its chronic stage, the pathophysiology appears similar to chronic Lyme—targeting software, not hardware. The result is pandemonium in our regulatory systems, with immune, endocrine, and nervous system dysfunction, and all the downstream issues associated with chronic inflammation.

As with patients with chronic Lyme, those with long COVID suffer from autoimmune inflammation. Antibodies to SARS-CoV-2 cross-react with multiple tissues including the gut, lung, heart and brain.19 There are now reports of SARS-CoV-2 infection resulting in PANS, Pediatric Acute-onset Neuropsychiatric Syndrome—autoimmune inflammation of the brain resulting in severe mood and behavioral symptoms in children and adolescents.20

According to most clinical descriptions of long COVID patients, the majority suffer from severe dysautonomia, with wild fluctuations in pulse and blood pressure.21 In addition, many patients have evidence of adrenal insufficiency and thyroid dysregulation, with elevations in thyroid antibodies and increased reverse T3.22-24

And, consistent with their excess inflammation and hyperreactive state, many long COVID patients have developed food sensitivities and suffer from excessive mast cell activation.25 And no surprise, SARS-CoV-2 infection creates oxidative stress that impairs mitochondrial function.26

SARS-CoV-2 can also result in hyperviscosity syndromes, sometimes severe enough to require anticoagulation.27

Latent viruses re-emerge

As with chronic Lyme, immune dysregulation promoted by SARS-CoV-2 infection can result in reactivation of latent viruses. Researchers in the United States and Turkey found that two-thirds of patients with long COVID had a reactivated Epstein-Barr virus infection compared to only 10% of controls.28

Here is something to think about: How many patients with long COVID actually have chronic Lyme that was activated by the viral insult? This has been reported to me by my colleagues. The two microbes most associated with this activation phenomenon are Bartonella and Mycoplasma, both capable of causing serious autoimmune problems.29,30 And some folks suffering from chronic Lyme have relapsed after getting COVID-19.

In other words, it’s complicated. Inflammation is widespread and there are imbalances throughout the body. There is no single intervention that can heal those who suffer from long COVID.

Medical detective work needed

Long COVID patients require careful medical detective work that uncovers the underlying imbalances. Interventions include decreasing inflammation; normalizing endocrine function; stabilizing the autonomic nervous system; supporting mitochondrial function; uncovering sensitivity syndromes; addressing mast cell activation syndrome and vagal nerve dysfunction; and treating reactivated infections.

One more thought. It is now clear that some patients with long COVID improve when they are vaccinated.31 This suggests that these folks may still have active infection with the corona virus. We know that SARS-CoV-2 has the capacity to disable and evade the immune response,32 and some patients do not successfully clear the virus over long periods of time.33,34

As we learn more, it may be appropriate to treat persistent SARS-CoV-2 infection in patients with long COVID with anti-viral drugs that are now becoming available. While the Infectious Disease Society of America maintains otherwise, there is a wealth of data and clinical experience that antibiotics are effective in treating patients with chronic Lyme.33

The good news is that we have been largely successful treating our patients with chronic Lyme. Ninety percent of my patients get 80 to 100% better, even after being ill for years. It’s a careful process that involves detective work, trial and error, curiosity and determination. Let’s hope the same is true for those with long COVID.

Dr. Daniel Kinderlehrer is an internal medicine physician in Denver, Colorado, with a practice devoted to treating patients with tick-borne illness. He is the author of  Recovery From Lyme Disease: The Integrative Medicine Guide to the Diagnosis and Treatment of Tick-Borne Illness.

References

  1. Logue JK, Franko NM, McCulloch DJ, et al. Sequelae in Adults at 6 Months After COVID-19 Infection. JAMA Netw Open.2021;4(2):e210830.
  2. https://www.medrxiv.org/content/10.1101/2021.10.26.21265508v1 (Accessed November 9, 2021)
  3. https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-long-term-effects/art-20490351#:~:text=Long%2Dterm%20effects%20COVID,within%20a%20few%20weeks. (Accessed November 30, 2021)
  4. Taquet M, Dercon Q, Luciano S, Geddes JR, Husain M, Harrison PJ. Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19. PLoS Med. 2021;18(9):e1003773. doi:10.1371/journal.pmed.1003773
  5. Varatharaj A, Thomas N, Ellul MA, et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study [published correction appears in Lancet Psychiatry. 2020 Jul 14;:]. Lancet Psychiatry. 2020;7(10):875-882. doi:10.1016/S2215-0366(20)30287-X
  6. Sher L. Post-COVID syndrome and suicide risk. QJM. 2021;114(2):95-98. doi:10.1093/qjmed/hcab007
  7. Singh SK, Girschick HJ. Lyme borreliosis: from infection to autoimmunity. Clin Microbiol Infect. 2004;10(7):598-614. doi:10.1111/j.1469-0691.2004.00895.x
  8. Lochhead RB, Strle K, Arvikar SL, Weis JJ, Steere AC. Lyme arthritis: linking infection, inflammation and autoimmunity. Nat Rev Rheumatol. 2021;17(8):449-461. doi:10.1038/s41584-021-00648-5
  9. Silverman MN, Heim CM, Nater UM, Marques AH, Sternberg EM. Neuroendocrine and immune contributors to fatigue. PM R. 2010;2(5):338-346. doi:10.1016/j.pmrj.2010.04.008
  10. Pegah Touradji, John N Aucott, Ting Yang, Alison W Rebman, Kathleen T Bechtold, Cognitive Decline in Post-treatment Lyme Disease Syndrome, Arch Clin Neuropsychol. 2019;34(4):455–465, https://doi.org/10.1093/arclin/acy051
  11. https://www.ninds.nih.gov/Disorders/All-Disorders/Dysautonomia-Information-Page (Accessed November 30, 2021)
  12. Aken C. Mast cell activation syndromes. J Allergy Clin Immunol. 2017;140:349-55.
  13. Stead RH, Colley EC, Wang B, et al. Vagal influences over mast cells. Auton Neurosci. 2006;125(1-2):53-61. doi:10.1016/j.autneu.2006.01.002
  14. Bancos I, Hazeldine J, Chortis V, et al. Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality. Eur J Endocrinol. 2017;176(4):471-480. doi:10.1530/EJE-16-0969
  15. Schoenfeld PS, Myers JW, Myers L, LaRocque JC. Suppression of cell-mediated immunity in hypothyroidism. South Med J. 1995;88(3):347–349.
  16. Koester TM, Meece JK, Fritsche TR, Frost HM. Infectious Mononucleosis and Lyme Disease as Confounding Diagnoses: A Report of 2 Cases. Clin Med Res. 2018;16(3-4):66-68.
  17. Sloop GD, De Mast Q, Pop G, Weidman JJ, St Cyr JA. The Role of Blood Viscosity in Infectious Diseases. Cureus. 2020;12(2):e7090.
  18. Peacock BN, Gherezghiher TB, Hilario JD, Kellermann GH. New insights into Lyme disease. Redox Biol. 2015;5:66-70.
  19. Taefehshokr N, Taefehshokr S, Hemmat N, Heit, B. Covid-19: perspectives on innate immune evasion.  Immunol.2020;11:580641.
  20. Pavone P, Ceccarelli M, Marino S, Caruso D, Falsaperla R, Berretta M, Rullo EV, Nunnari G. SARS-CoV-2 related paediatric acute-onset neuropsychiatric syndrome. Lancet Child Adolesc Health. 2021 Jun;5(6):e19-e21.
  21. Barizien, N., Le Guen, M., Russel, S. et al.Clinical characterization of dysautonomia in long COVID-19 patients. Sci Rep. 2021;11:14042. https://doi.org/10.1038/s41598-021-93546-5
  22. Akbas MA, Akbas N. Adrenal Insufficiency in the Covid-19 Era. Am J Physiol Endocrinol Metab 320: E784–E785, 2021.
  23. Lui DTW, Lee CH, Chow WS, et al. Long COVID in Patients With Mild to Moderate Disease: Do Thyroid Function and Autoimmunity Play a Role?. Endocr Pract. 2021;27(9):894-902.
  24. Khoo B, Tan T, Clarke SA, et al. Thyroid Function Before, During, and After COVID-19, J Clin Endocrinol Metab. 2021;106(2):e803-e811.
  25. Afrin LB, Weinstock LB, Molderings GJ. Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome. Int J Infect Dis. 2020 Nov;100:327-332.
  26. Wood E, Hall KH, Tate W. Role of mitochondria, oxidative stress and the response to antioxidants in myalgic encephalomyelitis/chronic fatigue syndrome: A possible approach to SARS-CoV-2 ‘long-haulers’?.Chronic Dis Transl Med. 2021;7(1):14-26.
  27. Maier CL, Truong AD, Auld SC, Polly DM, Tanksley CL, Duncan A. COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia?. Lancet. 2020;395(10239):1758-1759.
  28. Gold JE, Okyay RA, Licht WE, Hurley DJ. Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation. Pathogens. 2021;10(6):763.
  29. Kinderlehrer DA. Is Bartonella a Cause of Primary Sclerosing Cholangitis? A Case Study. Gastrointest Disord. 2020;2(1):48-57.
  30. Biberfeld G. Autoimmune reactions associated with Mycoplasma pneumoniae infection. Zentralbl Bakteriol Orig A. 1979;245(1-2):144-149.
  31. https://www.yalemedicine.org/news/vaccines-long-covid (Accessed January 21, 2022)
  32. Taefehshokr N, Taefehshokr S, Hemmat N, Heit, B. Covid-19: perspectives on innate immune evasion.  Immunol.2020;11:580641.
  33. Vibholm LK, Nielsen SSF, Pahus MH, et al. SARS-CoV-2 persistence is associated with antigen-specific CD8 T-cell responses. EBioMedicine. 2021;64:103230.
  34. Sun J, Xiao J, Sun R, et al. Prolonged Persistence of SARS-CoV-2 RNA in Body Fluids. Emerg Infect Dis. 2020;26(8):1834-1838.
  35. Kinderlehrer, D.A. Recovery From Lyme Disease: The Integrative Medicine Guide to Diagnosing and Treating Tick-Borne Illness, Skyhorse Publishing, 2021, p.15-30.

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Go here to read about a Lyme patient’s journey with COVID.

I beg you to do your homework before agreeing to be a lab rat in an ongoing experiment. Lyme/MSIDS patients are disadvantaged as their bodies are already fighting an epic war. Adding an experimental, fast-tracked, gene therapy injection that doesn’t protect you from getting COVID or stop you from transmitting it is questionable at best and unbelievably dangerous at worst. Further, it’s been proven time and time again that natural immunity is far superior to an injection that only works on certain variants, and poorly at that.

And of course, the BIG elephant in the room is that there are effective, cheap, successful treatments for COVID – thereby nullifying the need for a “vaccine”. The reason the EUA for these injections is still in play is due to the censorship and banning of effective treatments, and the horrific conflicts of interest in public health.

Category:

Inflammation, Lyme, Mast Cell Activation Syndrome (MCAS), Psychological Aspects, vaccines, Viruses

Problematic Lyme Testing Shortchanges Patients, Especially Children

https://www.lymedisease.org/greenberg-lyme-testing-problems/

Problematic Lyme testing shortchanges patients, especially children

by Rosalie Greenberg, MD

Many scientists and physicians agree that there are important issues concerning present Lyme disease (LD) testing.

In this post, I will address how the commercial testing cleared by the Food and Drug Administration (FDA) and approved by the Centers for Disease Control and Prevention (CDC) results in under-identification of the number of individuals, especially children, suffering from LD.

Two-tier testing

First, let’s review the recommended testing to confirm exposure to Borrelia burgdorferi (Bb), the bacteria that causes LD. Testing consists of two parts or “tiers.” Results of these two tests depend upon the ability to detect the antibodies that our bodies make when exposed to the Bb bacteria.

The first is an enzyme-linked immunosorbent assay (ELISA). The ELISA is considered a screening test. According to CDC recommendations, if the ELISA result is negative, the search is over and no further testing is needed.

Looking for antibodies

If the result is equivocal or positive, the second part of the test, or second tier called a Western Blot (WB), should be done. The WB looks for the presence of antibodies to certain proteins (each numbered according their different weights) associated with Bb.

These proteins are depicted on special testing strips as lines called bands. The bands are numbered 18, 22, 23-25, 28, 30, 31, 34, 39, 41, 45, 58, 66, 73, 88, and 93, reflecting their weight in units called kilodaltons.

Testing consists of exposing the patient’s serum (blood without the clotting factors or blood cells) to the antigen bands to see if a reaction occurs. A positive band is supposed to represent an antibody response to a protein found on the Lyme spirochete. I say “supposed to” because there is the potential that some of the bands can become positive from other infections.

The initial goal of this two-tiered approach, using the ELISA as an initial screen followed by the more specific WB, was to create a test that was highly sensitive and specific in identifying the studied infection.

By eliminating the unlikely cases during the first part of the testing and then using more specific identifiers in the second part, the test should be very good, or specific, in identifying most real or true cases of LD. This, in a nutshell, is the rationale for using the two-tiered testing.

Lyme suppresses the immune system

The problems with this type of testing are many. One major difficulty in using the ELISA and WB is that the bacterial organism responsible for Lyme disease, Bb, is in itself immunosuppressive.

So how could a test that depends upon the person’s immune response (the production of antibodies) be much good if we know the organism suppresses the immune system? In other words, if what you are measuring (antibodies) can be affected by the cause of the illness itself (Bb), then depending on this test to make the LD diagnosis is questionable.

This major flaw in the recommended testing diminishes the value of the test. Unfortunately, relying on a test that is so subject to error is the weak foundation that has provided support for much of LD research. This testing is additionally problematic in many ways.

The ELISA is a poor screening test

The concept of two-tier testing is not unique to LD and has been used effectively in diagnosing other illnesses such as Acquired Immunodeficiency Syndrome (AIDS).

But in LD, the first step, the ELISA, is very limited, on average detecting only 56% of cases. It is so very insensitive, it actually misses 44% of cases of people who do have LD. This is in stark contrast to the 99.5% effective rate found when used in testing for AIDS.1

Compounding this insult, the rule that only those whose results are either indeterminate or positive on the initial ELISA test should go on to the second part of the test.

Basically, present recommended use of the ELISA to screen for LD actually eliminates close to half the LD cases from further testing. According to the official guidelines, testing is halted with a negative ELISA and the individual is told that he/she does not have LD.

Clearly, this easily leads to an underdiagnosis of LD infections. Going on to use the WB in those who were indeterminate or positive on the ELISA, results in a 99% specificity (accuracy). But if you’ve already missed half the infected group, then the testing is quite problematic.

The Western Blot has its own issues

The WB looks for the presence of an immune response to Bb proteins, focusing on two types of antibodies: immunoglobulin M (IgM) and immunoglobulin G (IgG).

When a person comes in contact with an infectious agent, the body makes IgM antibodies as its first line of defense. In general, it takes two to four weeks to be at a consistently detectable level, with production peaking at around four weeks and becoming undetectable after six months.

Persistent ongoing detectable IgM levels beyond the one-month period are subject to controversy in their meaning. Some scientists consider these false positives, while others view them as evidence of persistent infection and associated with chronic illness.

The second antibody produced in the body is IgG. It develops over four to eight weeks after exposure to Bb, peaks at approximately six weeks and is gone in less than one year.

IgG antibodies are produced to target specific threats like viruses, bacteria and other potentially harmful microorganisms, and forms the basis of long-term protection against microorganisms.

Difference between IgM and IgG? Not so clear cut

Typically, with infectious illness exposure, the IgM antibody response decreases after a while and one is left only with the IgG response. But this transition is not so clear with exposure to the Lyme bacteria.

In the WB test, the laboratory compares the patient’s blood with blots representing a pattern of numbered bands to those seen in previously well documented CDC LD cases. To be considered a positive WB, the tested blot must show a match by having the required minimum number of reactive bands.

As noted, the bands are numbered by weight, with the following bands previously identified as: 18, 22, 23-25, 28, 30, 31, 34, 39, 41,45, 58, 66, 73, 88, and 93. All of the bands written in black are specific indicators that are seen only in Bb infections.

Three of these bands have been considered highly specific for LD and are given names based on their outer surface proteins (OSP). These bands are known as OSP A (Band 31), OSP B (Band 34) and OSP C (Band 23).

Some doctors believe that a positive result on even only one of these highly specific bands is good evidence of exposure to the Bb bacteria. It’s important to keep in mind that one can be exposed to an infectious agent (e.g. virus, bacteria, fungus, etc.) but not necessarily become ill. Therefore exposure and actual illness are different.

In the listing, the color blue has been used for bands 28, 45, 58, 66 which are considered nonspecific to LD. This means they can appear positive because the person can have other infections, not only LD . Band 41 is somewhat controversial regarding specificity and that is why I colored it green.

A positive WB assay is based on having two of the following three bands 23, 39, 41 being positive to be considered an IgM (Immunoglobulin M) antibody positive test. A positive WB IgG (Immunoglobulin G) antibody test requires the presence of 5 of 10 bands: 18, 23-25, 28, 30, 39, 41, 45, 58, 66, or 93.

“Positive” vs. “false positive”

According to present CDC guidelines, an IgM antibody test can be considered a positive indicator of early exposure to the infection only during the first 30 days after onset of illness.

A positive IgM antibody test is generally considered a marker of an acute (recent onset) illness. The official recommendation is that positive IgM antibody results should be disregarded if the patient has been sick for more than 30 days (i.e. 30 days after the bite.)

After that time, the “gospel” according to the CDC and Infectious Disease Society of America (IDSA) proclaims that a positive IgM antibody test is a false positive. A false positive means that the test is read as positive but isn’t due to LD but caused by another infection or problem.

As noted previously, the typical immunologic progression with infections is a transition from initial production of IgM antibodies to the subsequent production of IgG antibodies. But the situation in LD isn’t typical.

As previously discussed, Bb bacteria are capable of immunosuppression. This means that the organism itself can interfere with the immune system’s response to infections. The normal transition from making IgM antibodies to IgG antibodies can be hindered.

In part, this is because of problems that occur in what’s called germinal centers, the part of the lymphoid tissue where the antibodies are made.2

“The rule” that all IgM antibodies present after 30 days from the initial infection must be considered false positives, effectively serves to dismiss and minimize the number of real cases of LD.

A negative IgM WB test with a positive IgG WB are considered to indicate either late-stage LD or are a residual result left over from a past infection that is no longer present.

The result of this two-tiered testing system is meant to be 99% specific – meaning these are real cases of LD and not false positives.

This present testing approach is so flawed that a statistical analysis by Cook and Puri found that the LD two-tiered testing resulted in 500 times more false-negative (read as non-Bb but really is) outcomes than similar two-tiered tests used in the diagnosis of AIDS.3

Dearborn conference

The 1994 Second National Conference on Serologic Diagnosis of Lyme Disease was held in Dearborn, Michigan. It was attended by representatives of the Association of State and Territorial Public Health Laboratory Directors, CDC, the FDA, the National Institutes of Health (NIH), the Council of State and Territorial Epidemiologists, and the National Committee for Clinical Laboratory Standards.

The goal was to establish a set of nationwide standards for LD testing for the purpose of creating consistency in reporting WB results. Unfortunately, the standards selected at that meeting are still in use. In addition to selecting the two-tier testing, the decision was made to eliminate two of the highly specific bands, 31, and 34, from the required testing.

​These bands were removed because a vaccine against LD using these proteins was in the planning stage. Investigators knew that the use of these two specific proteins in the vaccine could create false positives for these bands in vaccinated individuals. Put another way, because these proteins were to be used in the vaccine, the vaccinated individuals could test positive for these bands but not have LD.

Participants at the Dearborn meeting seemed to doubt the ability of doctors to remember to ask if the individual had already received the vaccine when the person was getting new testing for LD. Could it be that such a simple step, of asking a question, was all that would have been needed to retain these two highly specific bands as possibilities for optimal testing?

LYMErix

In 1998, the FDA approved a Lyme vaccine, LYMErix™, which absolutely did have the potential to make these two very specific bands become positive in vaccinated individuals. Although for a variety of reasons that are complicated and will not be addressed here, by February 26, 2002, SmithKline Beecham withdrew the vaccine from the market.

What was accomplished by removing these two highly specific bands? It’s important to keep in mind that these bands were so significant that they were used to make the vaccine. Eliminating them from the diagnostic testing detracted from the WB test’s diagnostic sensitivity.

Band 31 is also special because it is not seen until at least months after initial infection. Its presence could potentially serve as an indication of an ongoing infection (chronic rather than acute infection at time of testing.)

In addition, bands 31 and 34 have been associated with the presence of neuropsychiatric illness in LD, which could have a crucial impact in the approach to treatment in similarly affected patients. Eliminating these bands removed potentially critical information.

Continuing to omit these bands from the tests defies logic.

Dr. Paul Fawcett and colleagues reported results of an important study at a Rheumatology Symposia Conference in Texas in 1995. The research was designed to look at the effect of eliminating the two specific bands from the WB criteria.4

The authors compared the diagnostic utility of applying the older criteria (including bands 31 and 34) vs. the newer WB criteria (as decided at the Dearborn meeting) to 66 child patients with known histories of a tick bite, an erythema migrans rash and symptoms of the illness.

Inclusion of bands 31 and 34 resulted in the identification of 100% of the youth as positive for LD. Using the newer criteria where OSP A and OSP B were omitted resulted in only 31% of the youth being identified as positive for LD.

Grossly inadequate

From their analysis, the investigators concluded:

“The proposed Western Blot Reporting Criteria are grossly inadequate, because it excluded 69% of the infected children.”

Basically by eliminating these bands from the WB, kids became discriminated against and undercounted in the statistics.

It’s unconscionable that these bands were never put back nor to my knowledge has there been significant discussion to reinstate them. This leaves doctors in the position of missing more people who really have LD.

There is more to consider in how the official change in testing criteria has shortchanged children, adolescents and even adults. Common sense dictates that testing for bands 31 and 34 in anyone born after 2002 (when the vaccine was taken off the market) would result in higher sensitivity and specificity. The more bands available for identifying the illness, the more likely you’ll identify positive individuals. Why would any medical professional argue against this?

The omission of bands 31 and 34 presents yet another problem for kids. Evidence in the medical literature indicates that positivity for these bands is associated with the presence of neuropsychiatric issues such as autism. Wouldn’t one want to include in the testing, markers that might alert one to these issues, especially in children?

Continuing to omit these bands for more than two decades has only served to deny the real number of people who have in the past, and perhaps still continue, to suffer from LD. By removing these two bands, we may be removing years of optimum health, as well as impairing social and cognitive development for some children for their lifetime.

Current two-tiered testing is indirect

Since the bacteria is difficult to isolate, much of the current testing is designed to look for reactions indicating that the bacteria is present, further complicating the diagnostic process.

Let me explain. Present approved testing looks for the presence of and intensity level of an individual’s immune response to the LD bacterial proteins. Testing would be much less controversial if the organism could be directly cultured or identification of the bacterial DNA occurred. Most scientists would agree that the indirect approach of looking at antibody response with an illness that can cause immunosuppression is inherently fraught with problems and limitations.

Interestingly, at present some research laboratories are focused on developing better and more direct methods of testing for Bb. This is sorely needed. Consider that in 2020, the National Institute of Health allotted only 13% ($5.3 million) of its total LD budget to advance diagnostic Lyme testing.5

Given that testing is the foundation of much research on the diagnosis and treatment, and present recommendations are problematic, 13% is a small amount. It is disturbing to realize that 30% of this allotted money went toward more antibody testing research (i.e. more indirect testing). This only serves to perpetuate the present problem of using an indirect method to identify an immunosuppressive bacterium.

Current tests only identify a few species of Bb

There are multiple strains or types of Borrelia bacteria that can cause Lyme as well as other diseases (e.g. Borrelia miyamotoi causes tick-borne relapsing fever.) Most labs use the strain B 31 for LD testing. IGeneX laboratory uses two strains: B 31 and Bb 297. The more strains used as possibilities, the increased likelihood of getting a positive test result.

This is part of why IGeneX gets more positive testing for LD than bigger labs like Quest and Labcorp. How many types of Borrelia that cause illness are we missing because of the limitations of our tests?

As you can see, there are multiple problems inherent in the recommended testing. It is crucial to acknowledge that the present faulty testing, which serves as the foundation for many studies, creates bias in all the research that is dependent upon it.

This major flaw has affected and colored too many aspects of our knowledge about LD. The present system of testing results in a significant underestimation of the number of individuals who suffer from LD. Our people, and especially our children, deserve much better from American medicine.

Dr. Rosalie Greenberg is a Board-Certified Adult, Child and Adolescent Psychiatrist, known for her expertise in the diagnosis and management of complex psychiatric problems in children, and pediatric psychopharmacology. Her website is rosaliegreenbergmd.com.

References

1 Stricker RB and Johnson L. Lyme disease diagnosis and treatment: lessons from the AIDS epidemic. Minerva Med 2010 Dec;101(6):419-25. PMID: 21196901.

2 Hasley CJ, Eisner RA, Barthold SW and Baumgarth N. Delays and Diversions Mark the Development of B Cell Responses to Borrelia burgdorferi Infection. J Immunol June 1, 2012, 188 (11) 5612-5622;

3 https://doi.org/10.4049/jimmunol.1103735. Cook MJ and Puri BK. Application of Bayesian decision-making to laboratory testing for Lyme disease and comparison with testing for HIV. Int J Gen Med. 2017; 10: 113–123. Published online 2017 Apr 10. doi: 10.2147/IJGM.S131909 PMCID: PMC5391870.

4 Paul Fawcett et al. Rheumatology Symposia Abstract # 1254. 1995 Rheumatology Conference in Texas.

5 https://www.documentcloud.org/projects/nih-lyme-research-funding-2

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“Setting arbitrary level of antibodies to diagnose a disease that has not been amenable to Koch’s postulates seems open to question.  By the same token, ignoring antibody results unless they meet arbitrary levels seems suspect.  The vast majority of patients in this series showed some WB antibody exposure, but many did not meet the arbitrary limits set….in our present state of knowledge, the diagnosis of chronic Lyme disease is a clinical one.  Many of the patients in this series have suffered serious ‘hurts’ when they have been told that they could not have LD because their WB did not meet arbitrary limits.”   ~ Dr. Burton Waisbren

Category:

Lyme, Testing

Points of View: Lyme Disease & Patients

https://danielcameronmd.com/points-of-view-lyme-disease-patients-and-physicians/

Points of view: Lyme disease patients and physicians

frustration in lyme disease patient as he talks to doctor

Raffetin and colleagues explore the perceptions and experiences of Lyme disease patients in an article entitled “Perceptions, Representations, and Experiences of Patients Presenting Nonspecific Symptoms in the Context of Suspected Lyme Borreliosis.” [1]

By

The authors looked at the perceptions, representations, and experiences of patients who had Lyme disease with nonspecific symptoms and no objective manifestations of the disease. This small study included 12 patients with confirmed and non-confirmed Lyme disease or unexplained symptoms.

“Our study highlights that some physicians may also experience a lack of knowledge and information about [Lyme Borreliosis], increasing the difficulty to answer the patient’s needs,” wrote Raffetin et al. 1

The investigators described several themes from their interviews with patients, along with patient statements expressing their frustrations.

Painful Experience with the Disease, Leading to Confusion and Fear

  • “Nothing could bring me relief …, the pain was almost unbearable.”
  • “Always tired, tired … tired, tired.”

Incomprehension, Fear, and Doubt when Faced with the Lack of Explanation for the Symptoms

  • “We kept doing the analyses, we didn’t understand.”
  • “The patients expressed a feeling of fear of unpredictable flare-ups, of not being cured, etc.”
  • “I was afraid of not knowing how I would end up.”

Long and Difficult Treatment Path, Experienced as an Obstacle Course

Fight against the Medical World

  • “My GP, I am reluctant to ask him, he doesn’t want to believe me.”
  • “They don’t listen, … they look at everything medical, and as long as the tests are negative, they say that you have nothing.”
  • “The absence of consensus on recommendations at the time of the study has reinforced the feeling of abandonment by the scientific community.”

Disease Taking a Serious Toll on the Patient’s Health

Multiple and Negative Repercussions, Experienced as an Injustice

  • “At the professional level, the patients reported absences linked to multiple medical consultations, repeated leave from work, etc.”
  • “Activities were impacted by the unpredictability of the symptoms, leading to the feeling of being overwhelmed by the disease.”
  • “The patients described either a lack of understanding from their relatives, or unconditional support, sometimes with the family adapting to their condition.”

Frustration expressed by doctors

The authors also described the frustration among doctors treating Lyme disease patients. “According to a survey, one-third of general practitioners experience difficulty when faced with the ‘insistent’ demands of ‘hyper-informed’ patients.”

“The major challenge for the doctor is to determine on one hand the limits of his own knowledge and his capacity to answer the patient, and on the other hand the quality of the patient’s information sources.”

Some of the problems lie in the lack of education. “The patients highlighted the poor training of physicians regarding persistent symptoms, as has also been shown in several studies on somatic symptom disorders.”

“These results are consistent with the views of the [general practitioners] interviewed in a study by Lisowski et al., 87% of whom said they were uncomfortable following up with patients who had symptoms after a full course of antibiotics due to having failed to provide codified management.”

The authors emphasized the need for a “coordinated care pathway and careful listening and recognition.” They also suggested that specialized reference centers might help meet these expectations.

Related Articles:
Lyme disease myths lead to frustrations for doctors
References:
  1. Raffetin A, Barquin A, Nguala S, et al. Perceptions, Representations, and Experiences of Patients Presenting Nonspecific Symptoms in the Context of Suspected Lyme Borreliosis. Microorganisms. Jul 15 2021;9(7)doi:10.3390/microorganisms9071515

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Category:

Lyme, research

What We Know & Don’t Know About Lyme Disease

https://www.frontiersin.org/articles/10.3389/fpubh.2021.819541

MINI REVIEW article

Front. Public Health, 21 January 2022 | https://doi.org/10.3389/fpubh.2021.819541

What We Know and Don’t Know About Lyme Disease

Sam T. Donta*

Consultant, Infectious Diseases, Falmouth Hospital, Falmouth, MA, United States

We know the cause of Lyme disease. We know that the bacteria can be found in the initial rash, and occasionally in the blood in the subsequent 2–3 months, but after then, its subsequent location is unknown. Whereas diagnosis and treatment of early Lyme disease is generally straightforward, the etiology of relapsing or persisting symptoms is yet to be defined, and presents clinical challenges. There are no current tests to determine if the infection is still present or absent, thus complicating diagnosis and treatment. Presented here are approaches to the diagnosis and treatment of persisting Lyme disease, based on available published information, and the experience of the author.

Introduction

It has been more than 40 years since the discovery of the causative agent of Lyme disease. Much has been learned, but several key questions remain:

  1. how do we know if the infection has been eradicated
  2. can it become dormant
  3. can it reactivate in patients with persistent symptoms, are these due to continuing infection or to non-infectious sequelae, and 4-are there treatments that can resolve the infection

Pathogenesis

We know that Lyme disease is caused by the bacterium Borrelia burgdorferi, transmitted by the bite of an Ixodes tick. We know that the bacteria may be isolated from the typical erythema migrans rash, and can be occasionally recovered from the circulating blood in the subsequent 2–3 months (1). After that time, it has not been possible to consistently isolate the bacteria from any body fluids or tissues.

So, where are they? Under the skin, as demonstrated in studies with macaque primates (2), and similarly in preliminary studies in humans (3)? Intracellularly, as is the case of most, if not all pathogens that can become latent, then recur? Or both? Hence, the central question at the heart of the controversy surrounding the diagnosis and treatment of Lyme disease; i.e., whether persisting or relapsing symptoms are due to continuing infection or due to post-infectious phenomena.

Accumulating evidence regarding the persistence of biologically active, albeit non-replicating bacteria derives from several studies in various animal models. Hodzic et al. demonstrated that B. burgdorferi can persist in mice following antibiotic treatment but were non-cultivatable (4). Casselli et al. demonstrated that B. burgdorferi can colonize the dura mater in mice, are biologically active, and induce host gene inflammatory responses (5). Embers et al. demonstrated post-antibiotic treatment persistence in a non-human primate naturally tick infected model (6) and recovery of the spirochete by xenodiagnosis (2). Similarly, there was recovery of non-cultivatable B. burgdorferi by xenodiagnosis in a few human patients who had had an erythema migrans rash and had had prior antibiotic treatment (3). These results, plus observations by us and others that retreatment of patients with recurring or persisting symptoms following initial antibiotic treatment using specific antibiotic regimens (7), lend strong support to the hypothesis that it is persistent infection by B. burgdorferi that is the likely cause of persisting symptomatology. In contrast, attribution of post-infectious symptoms to some post-infectious phenomena has only been speculative without any supporting evidence.

Diagnostic Issues

Currently, in the absence of any currently available means to directly detect the bacteria or its products, the diagnosis is dependent on the clinical history and any associated manifestations, along with the results of serologic studies. A major clinical problem is, that with the exception of patients with Lyme arthritis, most patients with continuing symptoms have no objective signs for Lyme disease, making the diagnosis dependent on the clinical picture that overlaps with that of chronic fatigue syndrome and fibromyalgia. Making it more difficult is the fact that many such patients do not have robust serologic responses to the causative organisms (8). And, despite claims that once one is treated with 4 weeks of antibiotics, one no longer has Lyme disease, or, if Lyme test results revert to negative, it means one no longer has Lyme disease, these claims being unsupportable in the absence of any means to prove the bacteria’s absence (9).

It also appears illogical, when patients have persisting or relapsing symptoms identical to those at the initial presentation, to opine that the infection is no longer present and that the remaining symptoms are post-Lyme disease of yet to be defined cause. It would seem more logical to assume that the infection has not been eradicated. It may be that ongoing symptoms are due to post-infectious factors, e.g., autoimmunity without provocation from persistent infection, but that has yet to be demonstrated as an obvious cause of the ongoing clinical picture. It seems much more likely that the cause of symptoms are due to some bacterial product, be it an exotoxin or endotoxin, similar to that that is at the root of most, if not all other bacterial infections, accompanied with host-responses to that virulence product or products, including inflammatory and autoimmune responses (10).

Serologic Issues

A similar lack of logic is present in analyzing the results of Lyme Western blot reactions, specifically IgM responses. How logical is it to use positive IgM responses to support the diagnosis of early Lyme disease, but deem that those same responses in patients with ongoing or relapsing symptoms are false-positive responses? Is it not more logical to assume that continued IgM reactivity, in the presence of ongoing symptoms, might be an indicator of unresolved infection in the absence of any available test to determine the continuing presence or absence of the causative organisms? In support of that conjecture, the results of several studies in various animal models, indicate that the causative borrelia are able to modulate humoral antibody responses such that the normal conversion of IgM to IgG antibody responses is abrogated (11).

Treatment Issues

As if confirming the diagnosis isn’t sufficiently difficult, the treatment of relapsing or persisting symptoms has presented its own challenges. There are many antibiotics that are active in vitro against the Lyme bacteria, but have not been clinically very effective. In early Lyme disease, treatment with doxycycline, amoxicillin, or cefuroxime over a period of a few weeks is generally effective. It is in patients with relapsing or persisting symptoms, including those previously treated, inadequately treated, or untreated, that the question arises as to whether any further antibiotic treatment is effective. The answer appears to be yes, if one looks at the pharmacology of specific antibiotics.

Doxycycline appears to have limited efficacy in patients with persisting or relapsing symptoms, especially in patients with symptoms present for greater than a few months. Doxycycline is highly protein-bound in the circulation, and it is unlikely that sufficient antibiotic can diffuse into tissues and cells to affect the borrelia. In contrast, tetracycline, which is not highly protein bound, appears to be clinically effective (10). Our observational results in several thousands of patients since our initial publication attests to both the greater efficacy of tetracycline vs. doxycycline in terms of both dosing and duration of treatment (12).

Beta-lactam antibiotics, including intravenous ceftriaxone, appear to be of limited clinical efficacy, perhaps because (a) that class of antibiotic has its effects on multiplying organisms, and there is no evidence that the Lyme borrelia are multiplying in persistent or relapsing disease, and (b) they are incapable of intracellular penetration. These antibiotics may offer temporary symptom relief, which might be due to their effects on glutamate accumulation during neurotransmission (13), without resolving the underlying infection.

Of particular interest are the effects of macrolide antibiotics (e.g., erythromycin, clarithromycin, azithromycin) on Lyme disease. They are highly active in vitro, and are capable of intracellular penetration, but appear to be of limited clinical value in patients with persistent symptoms. In analyzing the possible reasons, if the borrelia reside intracellularly in an acidic endosome, as is the case for numerous other microbes capable of intracellular persistence, macrolide antibiotics are not very active at an acidic pH. The use of a lysosomotropic agent (e.g., hydroxychloroquine, amantadine) to alkalinize the acidic endosome appears to result in clinical efficacy (14).

There have been two clinical trials using differing antibiotic regimens over a 3 month period of time in patients with persisting symptoms of Lyme disease. In the first trial, patients were given a month of ceftriaxone followed by 2 months of doxycycline vs. placebo treatment, and positive PCR reactivity to Borrelia burgdorferi was an exclusionary criterim for this study (15). In the other trial, patients with persisting symptoms were given an initial week of IV ceftriaxone, then randomized to being given the combination of clarithromycin and hydroxychloroquine vs. placebo for 3 months (16). In neither trial was there any reported greater improvement between the antibiotic treatment arms and placebo arms. The results of these studies have been reviewed with several reservations being expressed about study design, the instruments used to measure changes in symptoms, and interpretation of the results (17). In the former trial, neither ceftriaxone nor doxycycline were given for 3 months, and the assumption that both antibiotics are of equal efficacy is not supportable according to differing mechanisms of action. In the case of ceftriaxone, its antibiotic activity is based on its interference with replicating organisms, and given that there is no evidence to indicate that, once B. burgdorferi has established itself, there is any multiplication of note, it would not be expected to be effective in patients with persistent symptoms. And in the author’s observational experience, even the use of ceftriaxone over periods of time up to 6 months or more was without much if any benefit, with any possible benefit in a few patients due to ceftriaxone’s interference with the glutamate receptor system. In the case of doxycycline, whether a longer duration of treatment or increased dosing would have been effective remains unanswered. Observations by numerous clinicians suggest that higher doses of doxycycline, i.e., 300–400 mg/day might be more effective than the commonly used dosing of 200 mg/day.

In the trial utilizing the combination of clarithromycin and hydroxychloroquine, based on our initial published report, the trial was contaminated by the use of ceftriaxone in all patients prior to randomization to the active or placebo groups. Of greater importance is the failure to consider both the duration of prior symptomatology and the duration of treatment itself. As indicated in our published observations (12, 14), patients with persistent or relapsing symptoms for less than a year appeared to be cured, ie no recurring symptoms for greater than a year, by a treatment course of 3–6 months. In patients with persisting symptoms for >2 or more years, however, treatment success required a treatment duration of 6 or more months, and up to 18 months in patients with persisting symptoms for >5 or more years. Another likely flaw in that trial was not controlling for the use of adjunctive vitamin C. Supplemental vitamin C can be a strong acidifying agent, counteracting the effects of hydroxychloroquine (7, 14), and thus possibly accounting for some of the trial’s failure to show any benefit of this treatment.

Future Directions

The key remaining questions are whether there can be found a better, more direct detection test to indicate the presence or absence of active B. burgdorferi, and whether additional controlled treatment trials using longer durations of treatment with the tetracycline or clarithromycin/hydroxychloroquine regimen, or regimens utilizing different antibiotics or combination of certain antibiotics that might prove effective. The results of recent in vitro and early animal model experiments by Zhang (18) and by Lewis (19) might hold promise of other potentially effective approaches to the management of patients with persistent symptoms of Lyme disease.

Of additional likely importance is the potential role of antibiotic tolerance as a mechanism of persistence and “resistance” of B.burgdoferi to treatment in patients with persisting symptoms. Recent results of experiments with other bacterial organisms that can persist demonstrate the likely role of antibiotic-tolerance as the mechanism by which they persist (20). This mechanism apparently relies on a ribonuclease produced by the organisms. If our preliminary results with BB0755, an annotated ribonuclease, that demonstrated cytotoxic activity with tissue-cultured cells of neural origin (21), is due to its ribonuclease activity, then this possibility might offer an explanation to B.burgdorferi’s antibiotic tolerance.

There are additional questions that a better understanding of the pathophysiology of Lyme disease might lead to better approaches to the diagnosis and treatment of Lyme disease, especially in its persistent form. These include the possible role of antibiotic-tolerant persisters.

Author Contributions

The author confirms being the sole contributor of this work and has approved it for publication.

Conflict of Interest

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

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Keywords: Lyme disease, Lyme diagnosis, Lyme pathogenesis, Lyme treatment, Lyme serology

Citation: Donta ST (2022) What We Know and Don’t Know About Lyme Disease. Front. Public Health 9:819541. doi: 10.3389/fpubh.2021.819541

Received: 21 November 2021; Accepted: 20 December 2021;
Published: 21 January 2022.

Edited by:  Christian Perronne, Assistance Publique Hopitaux De Paris, France

Reviewed by:  Robert Carroll Bransfield, Rutgers, The State University of New Jersey, United States

Copyright © 2022 Donta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Category:

Lyme, research, Testing, Treatment

Neuropathogenicity of Non-Viable Borrelia burgdorferi Ex Vivo

https://www.nature.com/articles/s41598-021-03837

Neuropathogenicity of non-viable Borrelia burgdorferi ex vivo

Geetha Parthasarathy & Shiva Kumar Goud Gadila

Scientific Reports volume 12, Article number: 688 (2022) Cite this article

Abstract

Even after appropriate treatment, a proportion of Lyme disease patients suffer from a constellation of symptoms, collectively called Post-Treatment Lyme Disease Syndrome (PTLDS). Brain PET scan of patients with PTLDS have demonstrated likely glial activation indicating persistent neuroinflammatory processes.

It is possible that unresolved bacterial remnants can continue to cause neuroinflammation.

In previous studies, we have shown that non-viable Borrelia burgdorferi can induce neuroinflammation and apoptosis in an oligodendrocyte cell line.

In this follow-up study, we analyze the effect of sonicated remnants of B. burgdorferi on primary rhesus frontal cortex (FC) and dorsal root ganglion (DRG) explants. Five FC and three DRG tissue fragments from rhesus macaques were exposed to sonicated B. burgdorferi and analyzed for 26 inflammatory mediators. Live bacteria and medium alone served as positive and negative control, respectively. Tissues were also analyzed for cell types mediating inflammation and overall apoptotic changes.

Non-viable B. burgdorferi induced significant levels of several inflammatory mediators in both FC and DRG, similar to live bacteria. However, the levels induced by non-viable B. burgdorferi was often (several fold) higher than those induced by live ones, especially for IL-6, CXCL8 and CCL2. This effect was also more profound in the FC than in the DRG. Although the levels often differed, both live and dead fragments induced the same mediators, with significant overlap between FC and DRG. In the FC, immunohistochemical staining for several inflammatory mediators showed the presence of multiple mediators in astrocytes, followed by microglia and oligodendrocytes, in response to bacterial remnants. Staining was also seen in endothelial cells. In the DRG, chemokine/cytokine staining was predominantly seen in S100 positive (glial) cells. B. burgdorferi remnants also induced significant levels of apoptosis in both the FC and DRG. Apoptosis was confined to S100 + cells in the DRG while distinct neuronal apoptosis was also detected in most FC tissues in response to sonicated bacteria.

Non-viable B. burgdorferi can continue to be neuropathogenic to both CNS and PNS tissues with effects likely more profound in the former. Persistence of remnant-induced neuroinflammatory processes can lead to long term health consequences.

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**Comment**

An important work for sure which shows even non-viable pathogen remnants cause health problems in patients.  The fact remains; however, that unresolved infections CAN ALSO cause major health problems in patients, yet is not politically correct and therefore researched by those espousing with the current accepted narrative.

Category:

Inflammation, Lyme, research