Archive for the ‘Lyme’ Category

Borrelia burgdoeri Co-Localizing With Amyloid Markers in Alzheimer’s Disease Brain Tissues

https://content.iospress.com/articles/journal-of-alzheimers-disease/jad215398

Borrelia burgdorferi Co-Localizing with Amyloid Markers in Alzheimer’s Disease Brain Tissues

Accepted Oct. 24, 2021, Published Dec. 5, 2021

LDA-Columbia 2021 Lyme Conference Videos Available for Public Viewing

The Lyme Disease Association Inc. (LDA) has been able to release for the public on LDA’s You Tube Channel, a number of lectures from the LDA-Columbia 21st annual Lyme & Tick-borne Diseases 2021 CME conference.  See lectures by

  • John Aucott
  • Adrian Baranchuk
  • Ed Breitschwerdt
  • Catherine Brissette
  • Marna Ericson
  • Brian Fallon
  • Kim Lewis
  • Ken Liegner
  • Ricardo Maggi

Topics include Lyme & COVID 19; cardiac manifestations of Lyme; Bartonella; Borrelia colonizing dura matter; Suicidal behavior & Lyme; Lyme therapies; Disulfiram treatment for Lyme; PCR detection of Borrelia, Babesia & Bartonella; and Bartonella henselae in malignant melanoma.

NOTE: Some videos are not available due to ongoing research on the topic.

https://www.youtube.com/watch?v=NZV1HL1nwxk&list=PLxRaIwc57w2kisRXk9-UNBirXjc1xx6iY  Go Here for presentations

A Test to Find Many Infections at Once On Horizon

https://www.lymedisease.org/multiplex-test-on-horizon/

LYME SCI: A test to find many infections at once is on the horizon

Dec. 13, 2021

By Lonnie Marcum

What if you had access to a single test that could detect 3 different kinds of vector-borne bacteria all at the same time?  Well, it looks like researchers out of North Carolina State University and Galaxy Labs have done just that.

Research led by Ricardo Maggi, Ed Breitschwerdt, and colleagues has led to the development of a new test utilizing a multiplex droplet digital PCR “BBB ddPCR” that can simultaneously detect the three B’s—Babesia, Bartonella and Borrelia from both the Lyme and relapsing fever complex. (Maggi et al., 2021)

Once this combined test is clinically validated and available for clinical use, it will lead to improved diagnostics for patients with Lyme and other vector-borne diseases.

Humans and animals are greatly affected by tick-borne diseases. Currently, 75% of all vector-borne disease cases reported in the U.S. are caused by ticks. And 82% of the tick-borne cases are due to Lyme disease. (Rosenberg et al., 2018)

“Standard” tests fall short

Despite recent advancements for diagnostic testing for other illnesses, the CDC continues to recommend tests for Lyme and other tick-borne diseases that were designed more than three decades ago—and fall way short of what’s needed.

For example, the CDC-endorsed two-tier test for Lyme disease predates a full understanding of the immune response to Lyme disease. It has several technical limitations, including the inability to differentiate between active infection, past infection, and reinfection. (Branda et al., 2018; Schutzer et al., 2019)

The standard test combination also misses 89% of early infection (false-negatives), cannot detect all strains of disease-causing Borrelia, and suffers from cross-reactivity with other infectious diseases leading to false-positives. (Steere et al., 2008; Cook, Puri, 2016)

“The ability to co-amplify multiple vector-borne pathogens within a single sample with high sensitivity will greatly enhance the efficiency and efficacy of clinical diagnostic testing, particularly of volume-limited or otherwise hard to obtain sample matrices,” the authors state.

New approaches needed

New diagnostic approaches have been effectively applied to diseases such as Zika. And COVID-19, a disease discovered less than two years ago, already has better diagnostic tools available to it than tick-borne infections identified nearly a century ago.

Importantly, serology testing for COVID was deemed unreliable and unsuitable for diagnosis, yet serology remains the diagnostic standard of care for tick-borne diseases. (Serology tests look for antibodies in blood serum.)

All tick-borne diseases face major hurdles that prevent accurate early diagnosis and treatment. Serology as a diagnostic standard of care is problematic for all infections, but is especially problematic for immune-evasive, low-abundance infections.

Microbial testing techniques

Commonly used diagnostic techniques for tick-borne diseases include both direct and indirect detection methods, though some are only used in research studies. Both direct and indirect diagnostic methods are prone to false-negative and false-positive results.

For this reason, many experienced Lyme and tick-borne disease practitioners will recommend a combination of both direct and indirect tests, or a series of tests to confirm a diagnosis.

  • Direct detection methods directly confirm the presence of a pathogen. Direct methods for tick-borne diseases include: growing the pathogen in culture; microscopic examination of blood or tissue; polymerase chain reaction (PCR) which detects the DNA of one pathogen; quantitative PCR (qPCR) detects the quantity of a pathogen; multiplex PCR detects DNA of more than one pathogen; and fluorescence in situ hybridization (FISH) “maps” the genetic material in cells.
  • Indirect detection  methods detect the host immune system’s response to infection, providing indirect evidence of infection. Indirect  methods are able to determine if there has been recent or prior exposure to a pathogen. These methods, however, cannot confirm if an infection is active, nor whether it has been cleared. The most frequently used indirect serologic tests for tick-borne diseases include ELISA (enzyme-linked immunosorbent assay); IFA (immunofluorenscence antibody test); immunoblots like the Western blot; enzyme-linked immunospot (ELISPOT); and lymphocyte transformation tests (LTTs). (Springer et al., 2021)

Looking for antibodies

Both direct and indirect detection techniques have their strengths and weaknesses. For example, the most common tests for Lyme disease, the ELISA and Western blot, both  look for antibodies generated as the immune system tries to fight the infection.

Immunocompromised patients who do not mount a proper immune response, or those who receive early treatment may not develop detectable antibodies.

In addition, intracellular, low-yield and stealth pathogens like Borrelia and Bartonella are notoriously difficult to find by direct detection techniques like PCR.

The main reason for this is that little DNA from “low abundance” pathogens is found in blood. If there’s not enough DNA in the blood sample, standard PCR  cannot detect it.

Because of this, blood has not been the preferred sample type for detecting Borrelia burgdorferi DNA by PCR. However, PCR has had more success detecting the relapsing fever species of Borrelia, due to the higher levels of spirochetes in the blood. Conventional PCR, however, can be useful for the detection of Borrelia DNA from skin biopsies of Lyme-associated rashes, the fluid or tissue from joints (synovial fluid and synovium.)

The new approach

The research team, led by Dr. Ricardo Maggi and Dr. Ed Breitschwerdt at NCSU and Dr. Jennifer Miller at Galaxy Diagnostics, based their new multiplex droplet digital PCR assay “BBB ddPCR” on a wealth of knowledge they’ve gained from developing better diagnostics for Bartonella.

They recently published a paper explaining how their “BAPGM enrichment” along with the ddPCR improves upon the standard qPCR for Bartonella. (Maggi et al., 2020)

The proprietary BAPGM™ liquid culture increases the number of bacteria in a blood sample, allowing easier detection by PCR. With the “ddPCR, instead of running one PCR on one sample, the extracted DNA gets generated into 10,000-20,000 droplets. We then run a PCR reaction on each droplet,” explains Amanda Elam, PhD. “Bartonella ddPCR alone is incredible, increasing sensitivity about 10 times over standard PCR.”

The new assay, called the “multiplex BBB ddPCR,” detected DNA from 24 species of Babesia, 31 Bartonella species, and 13 Borrelia species (from the Lyme disease, relapsing fever, and cluster of Borrelia associated with reptiles).

The assay also detected two Theileria species (T. equi and T. cervi), as well as Chlamydophila felis DNA from naturally infected animals.

The authors state, “The multiplex BBB ddPCR assay presented herein reliably detected single and co-infections involving vector-borne pathogens from the genera Babesia, Bartonella, Borrelia, and Theilaria, using a variety of animal and human clinical samples, vectors, and experimentally infected tissues and cell-lines.”

Bringing new tests to market takes time

As Amanda Elam, Phd, CEO & Co-founder of Galaxy Labs, explained during this year’s Invisible International conference, the development process for commercializing a new test, from prototype to clinical validation to FDA approval, can take 5-10 years.

Elam says it may be another two years before the multiplex BBB ddPCR test is available to the public. She anticipates the individual ddPCR tests for Bartonella, Babesia and Borrelia will be available sooner.

The researchers state they have future plans to add other vector-borne organisms such as Anaplasma, Ehrlichia, and Rickettsia species to the existing multiplex ddPCR platform. In my opinion, a single assay able to detect multiple species of the most common tick-borne diseases would have profound effects on both animal and human medicine.

Early diagnosis is critical

Patients who receive early diagnosis and prompt treatment for tick-borne diseases tend to get better. But what about the huge percentage of patients who are not diagnosed quickly? In fact, fewer than 12% of the 14,000+ patients in LymeDisease.org’s patient-led research project, MyLymeData, received a diagnosis within the first month after the tick bite. (Johnson, 2019)

A delayed diagnosis is critical to understanding why so many patients are left with debilitating symptoms after standard treatment for Lyme. (Fallon et al., 2008; Fallon et al., 2012) During the months to years that patients suffer without a diagnosis, the untreated infection spreads throughout the body, embedding itself deeply into connective tissues where standard antibiotics have a hard time reaching. (Cabello et al., 2017; Caskey, Embers, 2015; Embers et al., 2012; Gadila et al., 2021)

One study demonstrated that delaying treatment by as little as 9-19 days is predictive of persistent Lyme symptoms. (Bouquet et al., 2016) During this time, infection can spread to the organs, brain, bone marrow, and heart. (Coughlin et al., 2018; Novak et al., 2019)

Early diagnosis of tick-borne diseases can save lives. Using advanced molecular detection techniques, these researchers have shown how an improved multiplex assay can more rapidly diagnose patients infected with multiple pathogens, speeding the delivery of life saving treatment.

Here’s what we need

We currently need better diagnostic tools for all tick-borne diseases including:

  • Anaplasmosis,
  • Babesiosis (Babesia duncani, Babesia microti),
  • Borrelia miyamotoi disease,
  • Bourbon virus disease,
  • Colorado tick fever,
  • Ehrlichiosis (E. chaffeensis, E. ewingii, E. muris),
  • Heartland virus disease,
  • Lyme disease (Borrelia burgdorferi, B. mayonii)
  • Powassan virus disease,
  • Rocky Mountain spotted fever,
  • Rickettsiosis (R. parkeri, R 364D),
  • S.T.A.R.I. (Southern Tick-Associated Rash Illness)
  • Tick-borne relapsing fever (B. hermsii, B. turicatae, B. parkerii)
  • Tularemia

I’ve written about several other types of advanced diagnostics on the horizon. I look forward to seeing promising tests like these become more widely available.

LymeSci is written by Lonnie Marcum, a Licensed Physical Therapist and mother of a daughter with Lyme. She serves on a subcommittee of the federal Tick-Borne Disease Working Group. Follow her on Twitter: @LonnieRhea  Email her at: lmarcum@lymedisease.org.

References

Bouquet J, et al (2016) Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease. Am Society Micro. DOI: 10.1128/mBio.00100-16

Branda JA., et al. (2018) Advances in Serodiagnostic Testing for Lyme Disease Are at Hand, Clinical Infectious Diseases, Volume 66, Issue 7, 1 April 2018, Pages 1133–1139, https://doi.org/10.1093/cid/cix943

Cabello FC, Godfrey HP, Bugrysheva JV, Newman SA. (2017) Sleeper cells: the stringent response and persistence in the Borreliella (Borrelia) burgdorferi enzootic cycle. Environ Microbiol 19(10):3846-3862, 2017. doi: 10.1111/1462-2920.13897

Caskey JR, Embers ME. (2015) Persister Development by Borrelia burgdorferi populations in vitro. Antimicrob Agents Chemother 59(10):6288-6295, 2015. DOI: 10.1128/AAC.00883-15

Cook, MJ., Puri BK. (2016) Commercial test kits for detection of Lyme borreliosis: a meta-analysis of test accuracy. Int’l J of Gen Med. DOI https://doi.org/10.2147/IJGM.S122313

Coughlin, J.M., Yang, T., Rebman, A.W. et al. (2018) Imaging glial activation in patients with post-treatment Lyme disease symptoms: a pilot study using [11C]DPA-713 PET. J Neuroinflammation 15, 346. https://doi.org/10.1186/s12974-018-1381-4

Embers ME, Barthold SW, Borda JT, Bowers L, Doyle L, Hodzic E, Jacobs MB, Hasenkampf NR, Martin DS, Narasimhan S, Phillippi-Falkenstein KM, Purcell JE, Ratterree MS, Philipp MT. (2012) Persistence of Borrelia burgdorferi in rhesus macaques following antibiotic treatment of disseminated infection. PLoS One 7(1):e29914, 2012. https://doi.org/10.1371/journal.pone.0029914

Fallon BA, Keilp JG, Corbera KM, Petkova E, Britton CB, Dwyer E, Slavov I, Cheng J, Dobkin J, Nelson DR, Sackeim HA. (2008) A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 70(13):992-1003. doi: 10.1212/01.WNL.0000284604.61160.2d. Epub 2007 Oct 10. PMID: 17928580.

Fallon, Brian & Petkova, Eva & Keilp, John & Britton, Carolyn. (2012). A Reappraisal of the U.S. Clinical Trials of Post-Treatment Lyme Disease Syndrome. The open neurology journal. 6. 79-87. 10.2174/1874205X01206010079.

Gadila SKG, Rosoklija G, Dwork AJ, Fallon BA and Embers ME (2021) Detecting Borrelia Spirochetes: A Case Study With Validation Among Autopsy Specimens. Front. Neurol. 12:628045. doi: 10.3389/fneur.2021.628045

Johnson, Lorraine (2019): 2019 Chart Book — MyLymeData Registry. (Phase 1 April 27, 2017. Sample 3,903). figshare. Preprint. https://doi.org/10.6084/m9.figshare.7849244

Maggi R, Breitschwerdt EB, Qurollo B, Miller JC. Development of a Multiplex Droplet Digital PCR Assay for the Detection of Babesia, Bartonella, and Borrelia Species. Pathogens. 2021; 10(11):1462. https://doi.org/10.3390/pathogens10111462

Maggi RG, Richardson T, Breitschwerdt EB, Miller JC. Development and validation of a droplet digital PCR assay for the detection and quantification of Bartonella species within human clinical samples. J Microbiol Methods. 2020 Sep;176:106022. doi: 10.1016/j.mimet.2020.106022. Epub 2020 Aug 11. PMID: 32795640.

Novak P, Felsenstein D, Mao C, Octavien NR, Zubcevik N (2019) Association of small fiber neuropathy and post treatment Lyme disease syndrome. PLoS ONE 14(2): e0212222. https://doi.org/10.1371/journal.pone.0212222

Rosenberg R, Lindsey NP, Fischer M, et al. (2018) Vital Signs: Trends in Reported Vectorborne Disease Cases — United States and Territories, 2004–2016. MMWR Morb Mortal Wkly Rep 2018;67:496–501. DOI: http://dx.doi.org/10.15585/mmwr.mm6717e1

Schutzer, S.E., et al. (2019) Direct Diagnostic Tests for Lyme Disease, Clinical Infectious Diseases. 3/15, 68 (6), 1052–1057. doi: https://doi.org/10.1093/cid/ciy614

Springer, A., Glass, A., Probst, J. et al. Tick-borne zoonoses and commonly used diagnostic methods in human and veterinary medicine. Parasitol Res 120, 4075–4090 (2021). DOI: https://doi.org/10.1007/s00436-020-07033-3

Steere, A. C., McHugh, G., Damle, N., & Sikand, V. K. (2008). Prospective study of serologic tests for lyme disease. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 47(2), 188–195. https://doi.org/10.1086/589242

Lyme Arthritis in Children Can Present Throughout the Year

https://danielcameronmd.com/lyme-arthritis-in-children-can-present-throughout-the-year/

Lyme arthritis in children can present throughout the year

Lyme arthritis in children

Lyme arthritis in children can present throughout the year for those living in areas endemic for Lyme disease, according to a study by Sundheim and colleagues. In their article, “Seasonality of Acute Lyme Disease in Children,” investigators described 690 children with Lyme disease residing in three endemic regions of the United States. [1]

The study’s objective was to “evaluate the seasonality of pediatric Lyme disease in three endemic regions in the United States,” writes Sundheim. Participants had been treated at 8 different medical centers throughout the Northeast and UpperMidwest.

Of the 690 children with Lyme disease, 77 (11.2%) had a single EM lesion, 247 (35.7%) had early disseminated disease, and 366 (53.1%) had arthritis, wrote the authors. “Children with early and early-disseminated Lyme disease most frequently presented in the summer months (June through August).”

The authors acknowledged that results could not be applied to non-endemic areas of the country, as all the participating centers were located in regions endemic for Lyme disease.

The authors did not routinely test for co-infections. “Multiplex polymerase chain reaction panels for tick-borne co-infections have demonstrated that a substantial portion of adults with Lyme disease have co-infections.”

Editor’s comments: Sundheim et al. dismissed 2,490 children (78.3%) as clinical mimics. It would have been helpful if the authors had followed up these children to determine whether any of them might have presented with Lyme disease over time.

The authors did not appear to look for other manifestations of Lyme disease and focused rather on individuals with “early (single EM lesion), early-disseminated (multiple EM lesions, headache, cranial neuropathy, or carditis), or late (arthritis).”

References:
  1. Sundheim KM, Levas MN, Balamuth F, et al. Seasonality of Acute Lyme Disease in Children. Trop Med Infect Dis. Nov 9 2021;6(4)doi:10.3390/tropicalmed6040196

What it Means For a Patient to Be Heard

https://www.globallymealliance.org/blog/what-it-means-for-a-patient-to-be-heard

What it Means for a Patient to Be Heard

Dec. 15, 2021

A friend experiencing unusual fatigue finally went to see a doctor recently. “I was so nervous,” she told me. “I was afraid he wouldn’t believe me.”

As a patient with several chronic illnesses that took years to diagnose, I knew exactly how my friend felt. Before being accurately diagnosed with chronic active Epstein Barr virus, Lyme disease, babesiosis, ehrlichiosis, and possible bartonella, I’d been passed off by countless medical practitioners who couldn’t figure out the derivation of my nebulous symptoms including bone-crushing exhaustion, migraine headaches, brain fog, insomnia, and hallucinogenic nightmares. I became so used to hearing, “Well, your bloodwork looks normal, so there’s nothing wrong with you” and “You must just be stressed/depressed/run down,” that I began to question my understanding of my own body. I started to think maybe I was just crazy.

Over the years, I continued to seek answers for the increasing physical symptoms I experienced, but began arriving in doctor’s offices not just nervous, like my friend, but defensive. As women, our fear and defensiveness were not unfounded; a study entitled “The Girl Who Cried Pain: A Bias Against Women in the Treatment of Pain” shows that women are more likely to have their pain characterized as “emotional,” “psychogenic,” and “not real.[i] And regardless of gender, a 2019 study in the Journal of Internal Medicine found that the average amount of time it takes a doctor to interrupt a patient is 11 seconds[ii]. Within 11 seconds, a doctor is already placing a patient into a cookie-cutter box, not hearing important details that could help them make an accurate diagnosis.

To her great surprise, my friend had a different experience with her recent doctor visit. “Not only did he listen,” she told me, “but he was compassionate.” After hearing my friend explain that her fatigue was not normal sleepiness, that she was feeling sick all the time and was sick of it, the doctor said, “That sounds awful. I’m so sorry you’re experiencing that. Let’s try to figure out what’s going on.”

Before even getting a diagnosis—and not knowing if she would even get one—my friend got something else she really needed: validation. In order to trust her doctor, she needed to know that he believed her.

I felt the same way when, years after my symptoms began, I went to see a naturopathic physician. Before the appointment, I wrote out my entire medical history, and carried it like a shield against my chest when I entered the office. That doctor read my entire written account. He underlined points. He jotted notes in the margins. He stopped to ask clarifying questions. He made me feel heard before he even really spoke.

The naturopathic physician was only able to figure out a portion of my diagnosis—chronic active Epstein Barr virus—but he still sticks out as one of the best practitioners I saw, because he didn’t write me off. He wanted to work with me to get me back to health, even if he didn’t have all the answers. In fact, when he suspected underlying tick-borne infection when I presented with erythema migrans (EM) rashes on my elbows a year after first seeing him, he admitted that such an infection was out of his wheelhouse, and sent me instead to a Lyme Literate Medical Doctor (LLMD). Rather than put the responsibility on me when he couldn’t solve the problem, this doctor sent me to someone who could. Unlike so many physicians I’d seen before him, his hubris did not cloud his Hippocratic Oath to first do no harm.

Being heard is critical to all patients, especially those with diseases like Lyme that are steeped in controversy and misunderstanding. These patients need first and foremost for their suffering to be acknowledged—and not just by physicians. Many Lyme warriors fight to be believed by family members, friends, and coworkers. Patients don’t need people to be fully Lyme literate, or to have the magic answer. We just need people to try to understand. To listen. To offer compassion. To take our hands and offer to walk with us, even if we’re not sure of the destination.

[i] Hoffmann, Diane E. and Tarzian, Anita J., The Girl Who Cried Pain: A Bias Against Women in the Treatment of Pain (2001). Available at SSRN: https://ssrn.com/abstract=383803 or http://dx.doi.org/10.2139/ssrn.383803

[ii] Singh Ospina, N., Phillips, K.A., Rodriguez-Gutierrez, R. et al. Eliciting the Patient’s Agenda- Secondary Analysis of Recorded Clinical Encounters. J GEN INTERN MED 34, 36–40 (2019). https://doi.org/10.1007/s11606-018-4540-5

Jennifer Crystal

Opinions expressed by contributors are their own. Jennifer Crystal is a writer and educator in Boston. Her work has appeared in local and national publications including Harvard Health Publishing and The Boston Globe. As a GLA columnist for over six years, her work on GLA.org has received mention in publications such as The New Yorker, weatherchannel.com, CQ Researcher, and ProHealth.com. Jennifer is a patient advocate who has dealt with chronic illness, including Lyme and other tick-borne infections. Her memoir about her medical journey is forthcoming. Contact her via email below.

Email: lymewarriorjennifercrystal@gmail.com