Harvard study identifies symptom clusters in Lyme patients with persistent symptoms after treatment

retrospective study of 270 post-treatment Lyme patients identified the most debilitating neurological symptoms, paving the way for future studies on root causes of disease and better treatments.

The largest study to-date characterizing ongoing symptoms [1] of Lyme patients after antibiotic treatment has been published by a group of investigators at Harvard-affiliated hospitals and Invisible International, a non-profit organization. They also examined the relationship between symptom severity and perceived disability, identifying five of the most debilitating symptom categories — fatigue, cognitive deficits, neuropathy (nerve numbness or weakness in the extremities), migraine headaches, and mood disorders.

The study lays a scientific foundation for future research that will help the growing ranks of post-treatment Lyme patients suffering from lingering symptoms. Lyme disease is the fastest vector-borne illness in the United States, with an estimated 476,000 new cases a year, according to the Centers for Disease Control. Approximately 10 to 36% [2] of those treated with antibiotics go on to experience disabling long-haul symptoms, such as severe fatigue, joint/muscle pain, cognitive problems, and neurologic symptoms.

Patient impairment was assessed through medical chart reviews of 270 individuals who had been treated for Lyme borreliosis through the Dean Center for Tick-Borne Illness at Spaulding Rehabilitation Hospital Boston, a Harvard affiliate, between 2015 and 2018. Symptom and disability data was also collected through scientifically validated questionnaires. Symptom clusters were defined as two or more symptoms occurring together, indicating that they might share the same triggering mechanism. This approach, used in other chronic conditions, such as cancer and inflammatory bowel disease, helps guide researchers in identifying root causes and better treatment strategies.

“This study is an important first step in figuring out why these patients aren’t getting better,” said Dr. Nevena Zubcevik, DO, the first author on the study and the former co-director of the Dean Center for Tick Borne Illness. “Going forward, we’re taking what we’ve learned to set up a multi-institutional clinical data repository that will provide high quality, de-identified tick-borne illness patient data to any interested researcher.”

To expedite the discovery of clinical treatments for patients suffering with chronic tick-borne illness, Dr. Zubcevik is now leading the Tick Bytes Clinical Data Research Platform through Invisible International, in her role as Chief Medical Officer. The resulting open-source data would enable researchers to access prospectively acquired clinical and laboratory data, as well as possible biorepository specimens, on a large group of well-defined pediatric and adult patients with complex Lyme disease. This repository would also collect data on mixed infections and/or environmental/toxic exposures, influences that often worsen the outcomes of these patients. Using this precision-medicine approach, more quality evidence will reach physicians, insurers, and government. This, in turn, will improve diagnostics and treatment options, leading to better outcomes, insurance coverage, and government funding. Invisible is currently raising funds to launch 10 data collection sites at research institutions, community clinics, and hospitals across the nation.

Invisible International, a 501(c)(3) nonprofit organization, is dedicated to reducing the suffering and social marginalization associated with invisible illnesses through innovation, education, and data-driven change projects. Invisible’s core team includes board-certified health-care providers in Infectious Disease, Internal Medicine, Family Medicine, Psychiatry, Pharmacy, Pathology, and Physical Medicine and Rehabilitation, many trained at or are affiliated with top-tier universities such as Harvard, Stanford, MIT, Brown, UC Berkeley, UC San Francisco, the US Air Force Academy, University of Virginia, and University of Pittsburgh.

This study and Invisible International’s Change Platform for Tick-borne Illness were funded by generous donations from Mark and Eileen Lovell. The organization is currently seeking additional support to expand its TickBytes data collection sites. To learn more about how you can help, go to: https://invisible.international/give

You can sign up to receive news and updates at https://invisible.international/mission

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Other related courses: Persistent Lyme diseaseNeurologic complications of Lyme diseaseBorrelia persistence “Bench to Bedside” E-Colloquium

Photo credit: francescoch/iStock

End Notes

[1]

Marques A. Chronic Lyme disease: a review. Infect Dis Clin North Am. 2008;22(2):341-viii. doi:10.1016/j.idc.2007.12.011

Asch ES, Bujak DI, Weiss M, Peterson MG, Weinstein A. Lyme disease: an infectious and postinfectious syndrome. J Rheumatol. 1994 Mar;21(3):454-61. PMID: 8006888. [Retrospective evaluation of 215 Lyme patients who were diagnosed and treated > 1 year prior.  Found/described persistent symptoms in 114 (53%).]

Clarissou J, Song A, Bernede C, et al. Efficacy of a long-term antibiotic treatment in patients with a chronic Tick Associated Poly-organic Syndrome (TAPOS). Med Mal Infect. 2009;39(2):108-115. doi:10.1016/j.medmal.2008.11.012. [Open-label prospective study of 100 patients after treatment for chronic TAPOS (Tick Associated Poly-Organic Syndrome), evaluating their evolution on prolonged antibiotics.]

Horowitz RI, Freeman PR. Precision Medicine: The Role of the MSIDS Model in Defining, Diagnosing, and Treating Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome and Other Chronic Illness: Part 2. Healthcare. 2018; 6(4):129. https://doi.org/10.3390/healthcare6040129. [Patient symptom survey and retrospective chart review of 200 patients with chronic Lyme/PTLDS.]

[2]

Strle, F., Cimperman, J., Maraspin, V. et al. Azithromycin versus doxycycline for treatment of erythema migrans: Clinical and microbiological findings. Infection 21, 83–88 (1993). https://doi.org/10.1007/BF01710737. [“Minor” symptoms in 15/52 (29%) who received doxycycline and 10/55 (18%) who received azithromycin.]

Dattwyler, R.J.; Luft, B.J.; Kunkel, M.J.; Finkel, M.F.; Wormser, G.P.; Rush, T.J.; Grunwaldt, E.; Agger, W.A.; Franklin, M.; Oswald, D.; et al. Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease. N. Engl. J. Med. 1997, 337, 289–294. [Persistent symptoms at last follow-up visit in 18/68 (26%) Ceftriaxone vs 10/72 (13.9%) doxycycline.]

Aucott JN, Rebman AW, Crowder LA, Kortte KB. Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here?. Qual Life Res. 2013;22(1):75-84. doi:10.1007/s11136-012-0126-6. [Prospective cohort study of 63 patients with EM rash and systemic symptoms treated with doxycycline reported a 36% rate of PTLDS.]

Experts discuss strategies for fighting those Lyme symptoms that won’t go away

Two tick-borne disease experts, a physician and a researcher, discuss the many ways Lyme bacteria evade the immune system and promising new strategies for fighting lingering symptoms.

People with long-haul Lyme disease symptoms are often sidelined by the medical community. In a 2019 survey of 1,900 Lyme patients, 74% reported being treated disrespectfully by a healthcare provider, and 67% said that they postponed or avoided medical treatment due to discrimination, disrespect, or difficulty obtaining care.

Many of these patients develop chronic Lyme because the latest evidence on diagnostics and treatment isn’t reaching busy frontline physicians, who misdiagnose or undertreat. Some health-care providers don’t know that about 30% of Lyme sufferers don’t see the classic Lyme rash. Or that the Lyme screening tests aren’t reliable in the first month after infection. Or that 10 to 20% of the Lyme patients fail to recover after taking the short course of antibiotics recommended by the Infectious Diseases Society of America (IDSA). And, to add insult to injury, there have been no new NIH-funded chronic Lyme treatment trials for more than 20 years — and Lyme sufferers need relief now.

Invisible International aims to fuel meaningful change for patients by accelerating the flow of new medical knowledge to treating physicians through the Bench-to-Bedside E-Colloquium, a monthly series of interactive discussions between world class researchers and boots-on-the-ground clinicians. The objective is to educate the medical and patient communities about promising new research and treatments, and to build bridges between these communities. Each colloquium will be annotated with the latest evidence from peer-reviewed journal articles.

The inaugural E-Colloquium tackles the controversial topic of “Borrelia persistence,” addressing the questions, “How does the Lyme bacterium, Borrelia burgdorferi, survive a recommended dose of antibiotics in the human body, and what treatment strategies can be used to eradicate the surviving organisms?”

The panel features Kenneth Liegner, MD, a distinguished internist who has been diagnosing and treating Lyme disease and related disorders since 1988, and Monica Embers, PhD, associate professor of microbiology and immunology and the director of the vector-borne disease research center at Tulane University School of Medicine. Embers is a leading expert in identifying treatments that can eradicate B. burgdorferi infections in primates, our closest mammalian relatives. The discussion is moderated by Christine Green, MD, a Stanford-trained and board-certified family medicine physician with 30 years of experience treating patients with tick-borne illness.

Invisible International’s Education Platform for Tick-borne Illness is funded by the Montecalvo Family Foundation, and the organization is currently seeking support to expand the E-Colloquium program. This platform currently offers more than 20 free, online Continuing Medical Education (CME) courses on the diagnostics, epidemiology, immunology, symptoms, and treatment of Lyme disease, Bartonellosis, and other tick-borne diseases.

Invisible International, a 501(c)(3) nonprofit organization, is dedicated to reducing the suffering and social marginalization associated with invisible illnesses through innovation, education, and data-driven change projects. Their core team includes board-certified health-care providers in Infectious Disease, Internal Medicine, Family Medicine, Psychiatry, Pharmacy, Pathology, and Physical Medicine and Rehabilitation, many trained at or affiliated with top-tier universities such as Harvard, Stanford, MIT, Brown, UC Berkeley, UC San Francisco, the US Air Force Academy, University of Virginia, and University of Pittsburgh.

You can sign up to receive news and updates at https://invisible.international/mission

Other related courses: Basic principles of diagnostic testingAntibiotic efficacy for treatment of Lyme diseaseThe impact of immune responses on diagnosis and treatment of Lyme disease

Image credit: Happy Photon, iStock

Lyme advocates weigh-in on research priorities at HHS-LymeX workshop

Invisible’s Chief Medical Officer, Dr. Nevena Zubcevik, joins other Lyme patient advocates in setting priorities for the largest public-private research initiative launched since Lyme disease was discovered.

Last October, the Steven & Alexandra Cohen Foundation announced that they would donate $25 million to the LymeX Innovation Accelerator, a research prize competition to develop better tick-borne disease diagnostics. The competition recently entered its next phase, the collection of ideas from disease stakeholders — patient representatives, the government, academic medicine, and industry — to help define the prize guidelines.

To facilitate this process, the U.S. Department of Health and Human Services (HHS) hosted a LymeX Roundtable Webinar on April 28, 2021, which featured presentations and workshops with key stakeholders.

Dr. Nevena Zubcevik, Invisible’s Chief Medical Officer, was the workshop’s first lightning talk speaker, and in her presentation (starting at minute 37:43), she succinctly summarized why these prizes are so desperately needed: Only about 1 percent of the National Institutes of Health’s Lyme disease research budget (2015 thru 2019) went towards exploring better treatments for the nearly 500,000 Americans who get Lyme disease each year. Her emphatic message to the audience — We need more patient-focused solutions to bring relief to the millions suffering from tick-borne diseases today.

Invisible is working to remedy the treatment gap by launching the Tick Bytes Clinical Data Research Platform. This multi-institutional clinical data repository will provide quality de-identified tick-borne illness patient data to researchers. Researchers can then mine this data using advanced biostatistical methods to discover symptom profiles for mixed infections and treatment regimens that work. With this precision medicine approach, more quality evidence will reach physicians, insurers, and government. This, in turn, will improve diagnostics and treatment options, leading to better outcomes, insurance coverage, and government funding. Invisible is currently raising funds to launch 10 data collection sites at research institutions, community clinics, and hospitals across the nation. To learn more about how you can help, go to: https://invisible.international/give

The Cohen’s $25 million prize fund represents a whopping 50-percent boost to the 2021 NIH Lyme-related research budget, and, most importantly, it allocates more funds to urgently needed early diagnostic tools, since in the first three weeks after infection, the standard tests only detect Lyme disease 29 to 40 percent of the time.

For an overview of the devastating impact of poor testing and treatment options on Lyme patients, read the new LymeX publication, “The Health+ Lyme Disease Human-Centered Design.” To join the LymeX online community, go to: https://lymex.crowdicity.com/

Invisible International is a 501(c)(3) nonprofit foundation dedicated to reducing the suffering associated with invisible illnesses and social marginalization through innovation, education, and change projects. To donate or to learn more about our many programs to reduce the impact of tick-borne illness, visit the website: https://invisible.international

How LymeTV is crushing those evil ticks seeking world domination

Tick bites woman. Woman bites back, by launching LymeTV, a media foundation that aims to end the ignorance surrounding tick-borne diseases.

While Adina Bercowicz was applying to graduate school, she began experiencing a variety of mysterious symptoms, including crushing fatigue, joint aches, and frequent mind-blowing headaches. She thought it would go away in a few days, but it didn’t. And for the next two years, she kept visiting doctors, searching for relief from her forever illness. Her symptoms progressed into debilitating chronic pain and a significant cognitive decline, so bad that she couldn’t even recognize her own car.

She had to put her education and life on hold. That is, until a Miami-based physician recognized that Adina’s symptoms were similar to those of her daughter who was suffering with Lyme disease. To explore that possibility, her medical team extracted spinal fluid and a pathologist discovered that it was teeming with Borrelia burgdorferi, the corkscrew-shaped, tick-borne bacterium that causes Lyme disease. It was direct evidence that she had Lyme encephalitis, brain inflammation that can cause memory and concentration issues, headache, mild depression, irritability, fatigue, or excessive daytime sleepiness.

But despite years of treatment, she couldn’t get better, and she ultimately ended up in the intensive care unit to undergo allergy desensitization to ceftriaxone, the best antibiotic for treating her brain infection. Around the same time, it was discovered that the tick or ticks that bit her had also transmitted other pathogens along with Lyme, including the Rocky Mountain spotted fever bacterium, and babesia and anaplasma, two microbes that infect human blood cells.

She was left aghast with the question, why did it take five years to figure this out and get treated? Although her treatment relieved many of her major symptoms, she was left with the permanent damage caused by years of an unchecked infection.

“A tick bite can kill you,” says Adina, to those who think that these diseases are easy to diagnose, treat, and cure.

Adina’s frustration with the medical community’s lack of knowledge about tick-borne diseases inspired her to start LymeTV.org. This foundation aims to educate physicians and the public on the latest tick-borne disease science through TV commercials, a documentary, community events, and prevention resources targeting school-aged children. Yan Zelener, PhD, with degrees from MIT and Columbia University, is LymeTV’s director of science and research and Adina’s husband.

LymeTV’s latest project, the Tick Jedi School Health Program, features a fun, interactive, educational cartoon that teaches kids about tick avoidance, tick checks, and Lyme disease basics. (The animation’s screenwriters have written episodes for Disney Channel and Disney—ABC Television Group, ensuring an age-appropriate learning experience.) Designed for children from five to twelve years old, the program also comes with prevention posters and workbooks that engage kids with fun educational activities.

This project was a top-five winner of the Invisible International 2020 Hackathon, which was focused on creating education and awareness around tick-borne illness. Hackathon funding is helping LymeTV with outreach to schools and summer camps.

Tick-borne illnesses like Lyme disease affect children more than any other age group, yet only about 1 in 10 check for ticks after playing outside. Lyme disease is the fastest growing vector-borne illness in the United States, with an estimated 476,000 new cases a year, according to the Centers for Disease Control. If ticks take a blood meal undetected, they can transmit other dangerous bacteria and viruses to humans and pets, including the Babesia parasite, the Rocky Mountain spotted fever bacterium, and the Powassan virus. Prevention through tick checks and avoidance is the best way to stay safe.

LymeTV is a 501(c)(3) a nonprofit foundation based in Portland, Maine, focused on reducing the incidence of dangerous tick-borne diseases. Learn more about the Tick Jedi program and try out their interactive cartoon here: https://tickjedi.com

Schools, camp, and other organizations can register here for the program’s complete set of educational resources.

Invisible International is a 501(c)(3) nonprofit foundation dedicated to reducing the suffering associated with invisible illnesses and social marginalization through innovation, education, and change projects, such as the Lovell family-sponsored Hackathon that helped fund the Tick Jedi program. To donate or to learn more about our many programs to reduce the impact of tick-borne illness, visit the website: https://invisible.international

Infectious new dance helps kids check for Lyme-infected ticks

A children’s songwriting duo has created a catchy new dance-jingle that makes tick checks fun and easy, potentially reducing the incidence of dangerous tick-borne diseases in kids.

Tick-borne illnesses like Lyme disease affect children more than any other age group, yet only about 1 in 10 check for ticks after playing outside. To encourage kids to do more and better tick checks, comedic songwriters “Louis and Dan and the Invisible Band” created a “viral” song-and-dance routine to help kids remember to check for creepy-crawly ticks in their favorite hiding places.

Sponsors of this project, PA Lyme Resource Network and Invisible International, have also organized an educational campaign around the dance called the #TickCheckChallenge. (This project was developed for the Invisible International 2020 Hackathon, which was focused on creating education and awareness around tick-borne illness.) To help spread the word about the importance of tick checks, they’re encouraging people to record their own TikTok-style interpretations of the dance, then share them on social media, following the instructions at https://palyme.org/tick-check-challenge/

Lyme disease is the fastest growing vector-borne illness in the United States, with an estimated 476,000 new cases a year, according to the Centers for Disease Control. If ticks take a blood meal undetected, they can transmit other dangerous bacteria and viruses to humans and their pets, including the Babesia parasite, Rocky Mountain spotted fever, and the Powassan virus. Initial symptoms are often hard to detect, mimicking those of the flu or Covid-19 — fever, chills, headache, and aches. Prevention through tick checks is the best way to stay safe.

PA Lyme Resource Network is a 501(c)(3) nonprofit foundation with a mission to reduce the suffering of Lyme and tick-borne disease patients via education, prevention, patient support, and advocacy. Their signature “Dare 2B Tick Aware Program” has provided 300+ tick education seminars to date, as well as an informative suite of prevention materials made available to the public.

Invisible International is a 501(c)(3) nonprofit foundation dedicated to reducing the suffering associated with invisible illnesses and social marginalization through innovation, education, and change projects, such as the Lovell family Hackathon that funded the Tick Check Challenge. To donate or to learn more about our many programs to reduce the impact of tick-borne illness, visit the website: https://invisible.international

How to post your videos:

Learn how to create your own video here: https://palyme.org/tick-check-challenge/

Post your video to your social media channels, tagging three friends, and put #TickCheckChallenge on every post so that we can share your efforts to raise awareness.  

To listen to more health-education songs by Louis & Dan and the Invisible Band, go to www.louisdaninvisibleband.com.

Image: kohei_hara @iStock, Video: Chris Flicek

Free online medical education courses on cat scratch disease and Bartonella

Invisible International has released six new courses on Bartonella, the family of stealth bacteria best known for causing cat scratch disease and trench fever. Courses cover disease history, transmission, reservoir hosts, risk factors, disease manifestations, and diagnosis.

In the last few years, there has been a growing body of knowledge on the Bartonella family of bacteria, particularly Bartonella henselae, the causative agent of cat scratch disease. In this course series, a leading expert on Bartonellosis in mammals, Edward Breitschwerdt, DVM, provides a fascinating overview of the latest in clinical manifestations and diagnostic methodologies for detecting these evasive, slow-growing pathogens. His message to both physicians and veterinarians — Bartonella-related diseases are more common than previously known and these stealth organisms may be the culprit behind many illnesses of “unknown etiology.”

In humans, Bartonella henselae is typically transmitted by cat bites or scratches, sometimes by flea bites. Three to 10 days after inoculation, the infected may experience a fever and a lesion at the wound site. Swollen lymph nodes may appear one to two weeks later. Many report headaches, lack of appetite, weight loss, vomiting, and, occasionally, a sore throat. While most cases resolve without treatment, five to 20 percent of the infected exhibit severe symptoms of the disease. Complications can involve the eyes, nervous system, brain, heart, liver, spleen, skin, and musculoskeletal system. A major focus of this course series is to provide physicians veterinarians with new evidence to help them explore Bartonella as a differential diagnosis in their most confounding cases.

Breitschwerdt also presents some interesting evidence on possible Bartonella transmission by ants, spiders, mites, needle sticks, and ticks. Tick-to-human transmission is a controversial topic in infectious disease circles, but after reviewing the latest research (mostly from Europe), Breithschwerdt concludes that it is “highly likely.” He also reminds physicians to ask sick patients about their exposure to animals, since Bartonella often runs in families, infecting both pets and their human companions.

Edward Breitschwerdt, DVM, the course’s author, is a professor of medicine and infectious diseases at the North Carolina State University College of Veterinary Medicine. He is also an adjunct professor of medicine at Duke University Medical Center and a diplomate in the American College of Veterinary Internal Medicine (ACVIM). As a leading expert on bartonellosis, he directs the Intracellular Pathogens Research Laboratory in the Institute for Comparative Medicine and co-directs the Vector Borne Diseases Diagnostic Laboratory at NCSU. These courses are currently in review for CME credit by the American Academy of Family Physicians.

This project is funded by the Montecalvo Platform for Tick-Borne Illness Education, through Invisible International, a 501(c)(3) nonprofit foundation dedicated to reducing the suffering associated with invisible illnesses and social marginalization through innovation, education, and data-driven change projects. You can sign up to receive news and updates at: https://invisible.international/mission

Links to Bartonella courses: History of a hidden pandemic, Vectors and other modes of transmission, Reservoir hosts: Bats, cats, dogs, mice and men, Comparative infectious disease causation, Disease expression and host immunity, and Diagnosis of Bartonella species infections.

Image credit: ehaurylik @iStock

Free online medical education course on early Lyme disease

Three patient case studies guide physicians on how to diagnose and treat early Lyme disease. This online course summarizes the latest research on disease risk, symptoms, and treatment options.

Diagnosing early Lyme disease cases can be notoriously difficult. Initial symptoms mimic those of the flu or Covid-19 — fever, chills, headache, and aches. The recommended antibody testing isn’t reliable in the first month. And many of those infected by a tick never see the tick or the most helpful diagnostic sign — an expanding erythema migrans rash at the bite site.

In the meantime, it’s more important than ever for physicians to keep up with clinically relevant information that will enhance their Lyme disease diagnostic and case management skills. Lyme disease is the fastest vector-borne illness in the United States, with an estimated 476,000 new cases a year, according to the Centers for Disease Control. Approximately 10 to 20% of those treated with antibiotics go on to experience disabling long-haul symptoms, such as severe fatigue, joint/muscle pain, brain fog, and neurologic symptoms. Prompt diagnosis and treatment of early Lyme disease results in better outcomes.

Case studies in early Lyme disease” is an online continuing medical education course that discusses disease risk in geographic regions, Lyme disease rashes, NIH-funded treatment trials, the basics on how Lyme bacteria evade the immune system, and the pros and cons of various patient treatment options. Participants’ diagnostic skills are tested with three real-life patient case studies. This course has been approved for 1.0 CME credit by the American Academy of Family Physicians.

Elizabeth L. Maloney, MD, the course’s author, is a Minnesota family physician focused on tick-borne disease education and policy. She is also the education director of Invisible International; the founder/president of the Partnership for Tick-borne Diseases Education; a former subcommittee member of the HHS Tick-borne Diseases Working group; and a peer reviewer for the Canadian Institutes of Health Research.

This project was funded by the Montecalvo Platform for Tick-Borne Illness Education, through Invisible International, a 501(c)(3) nonprofit foundation dedicated to reducing the suffering associated with invisible illnesses and social marginalization through innovation, education, and data-driven change projects. You can sign up to receive news and updates at https://invisible.international/newsletter

Other related courses: Basic principles of diagnostic testing, 7 years of blood-based Lyme disease testing, Serologic testing in Lyme disease.

Image credit: Tricia Shears 2009, Lyme rash on a 5-yr-old

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