As we approach Giving Tuesday, a day dedicated to generosity and philanthropy, I urge you to consider the critical work of Invisible International. The shortage of trained providers in this field is worsening, a concern highlighted by the alarming statistics reported by the Centers for Disease Control:
Diseases spread by mosquitoes, ticks, and fleas tripled in the U.S. from 2004 to 2016.
Nine new pathogens spread by these vectors have been discovered since 2004.
Annually, 476,000 Americans are diagnosed with Lyme disease across all 50 states.
Despite these daunting figures, a 2023 study led by Cornell University revealed a stark reality: there is a limited availability of continuing education for life-threatening tick-borne diseases in the United States. (1) Another study revealed that the biggest barrier to patient access to treatment for Lyme disease is lack of physician education. (2)
Invisible International stands at the forefront of addressing this educational gap. We have created 40 CME courses for physicians, impacted over 100 institutions, delivered medical education presentations at 5 conferences, developed 3 clinical guides, and through our educational efforts, we have reached physicians who deliver vector-borne disease awareness to over 1,500,000 patient visits. Our courses, accredited by the Accreditation Council for Continuing Medical Education (ACCME) and reviewed by the American Academy of Family Physicians (AAFP), cover crucial aspects such as prevention, diagnosis, and treatment. These courses are available at no cost online, ensuring accessibility for all who need them.
Our initiative is further strengthened by the support of the Montecalvo Foundation, enabling us to offer these vital resources freely. However, to continue and expand our work, we rely on the generosity of individuals like you. Your donations empower us to educate more healthcare providers, enhance disease awareness, and ultimately save lives.
On this Giving Tuesday, I ask you to join us in this trailblazing mission, ensuring no patient is left behind. Your contribution will directly impact the fight against vector-borne diseases and support healthcare professionals in providing the best possible care to those affected.
On behalf of all of us at Invisible,
Dr. Nev Zubcevik
Chief Medical Officer
Malkowski AC, Smith RP, MacQueen D, Mader EM. Review of Continuing Medical Education in Tick-Borne Disease for Front-Line Providers. PRiMER. 2023;7:497812. Published 2023 Feb 2. (doi:10.22454/PRiMER.2023.497812)
In our new course, “An Introduction to Human Babesiosis,” you’ll learn how to diagnose and treat infections caused by babesia, a malaria-like protozoan parasite that can be transmitted through tick bites, blood transfusions, and organ transplants, or congenitally from mother to fetus. The course is taught by Elizabeth Maloney, MD, the Education Co-director at Invisible, a Minnesota family physician, and the founder/president of Partnership for Tick-borne Diseases Education, a nonprofit providing evidence-based education on tick-borne diseases.
The disease parasite babesia, called babesiosis, lives in red blood cells. It was originally found only in cattle. It crossed over to humans in Croatia in 1956 and in Colorado and Massachusetts in the late 1960s.  Recent studies show that this parasite is more prevalent than previously thought, with Babesia microti being found in 1-in-10 of the ticks in southern New England and up to 15% of ticks in Suffolk County (Long Island), New York. 
When ticks transmit both Lyme disease and babesia simultaneously, patients are sicker and the resulting disease is harder to treat.  Coinfected patients are more likely to have fatigue, headaches, sweats, chills, anorexia, emotional lability, nausea, conjunctivitis, and splenomegaly more frequently than those with Lyme disease alone. The disease can be fatal for patients with damaged or missing spleens.
The course also discusses the global distribution of babesia and a new species of babesia, B. odocoilei, which may be causing unrecognized disease.
“Babesiosis is an emerging infectious disease yet many clinicians have had no or very little training about it. This can lead to missed diagnoses and increased morbidity for patients.” said Dr. Maloney, “unrecognized cases of babesiosis in blood donors have produced transfusion-transmitted cases which carry a significant mortality risk. Informing clinicians about the infection will ultimately improve patient care. The primary goal of this CME offering is for clinicians to include babesiosis in their differential diagnosis, when clinically appropriate.”
The Invisible Education Initiative, funded by the Montecalvo Foundation, provides free, accredited Continuing Medical Education (CME) courses that focus on vector-borne and environmental illness within a One Health framework. These courses are available to clinicians and the public. To donate to this initiative and to learn about Invisible International, please go here http://invisible.international/give.
Hildebrandt A, Zintl A, Montero E, Hunfeld KP, Gray J. Human Babesiosis in Europe. Pathogens. 2021 Sep 9;10(9):1165. doi: 10.3390/pathogens10091165. PMID: 34578196; PMCID: PMC8468516. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468516/
From the Desk of Dr. Nev Zubcevik A letter to our supporters from Dr. Nev Zubcevik, Chief Medical Officer, on a new clinical tool that will help doctors better understand & care for patients with neurological Lyme disease. Dear community members and supporters,
As a physical medicine and rehabilitation physician, my primary focus is on identifying the root cause of my patients’ illnesses. Only by addressing the underlying cause can we effectively rehabilitate our patient’s injuries. Throughout my years of practice, I have witnessed the devastating impact of untreated or under-treated Lyme disease infection on patients’ nervous systems. This destructive effect severely impairs their cognitive abilities, physical functioning, and overall quality of life. Our team at Invisible International has developed a clinical guide to assist clinicians in the recognition of neurological Lyme disease symptoms and subsequent diagnostic, testing, and treatment strategies to help diagnose and treat patients faster. We are grateful to donors like you who help fuel our work to pave the way for making sure every physician is a Lyme+ knowledgeable physician. To partner with us in developing and disseminating our education to physicians, please consider a tax-deductible donation today.
Lyme patients are at an increased risk of suicide
My deepest concern as a physician is that Lyme patients are extremely vulnerable as a population. Research has shown that Lyme patients face a heightened risk of suicide, primarily because their neurological injury remains largely invisible, causing immense suffering (Fallon et al., 2021). Understanding the clear mechanism of injury caused by the Lyme bacterium is crucial in explaining this invisible damage. By raising awareness among physicians and healthcare professionals about this mechanism, we can approach these patients with a clearer path to diagnosis and treatment.
Our study shows damage to the nervous system
In 2019, our team at Harvard conducted research and published the study “Association of Small Fiber Neuropathy and Post Treatment Lyme Disease Syndrome,” where we investigated the potential link between small fiber neuropathy (SFN) and post-treatment Lyme disease syndrome (PTLDS). Our findings provided both a biomarker of injury and a testing protocol that other physicians can use to objectify their patients’ neurological injury caused by Lyme disease.
In the study, we explored ten participants with a history of PTLDS, and through skin biopsies, we discovered evidence of SFN in all cases. Specifically, nine participants displayed sensory SFN with abnormal epidermal nerve fiber density, and seven individuals exhibited severe SFN. We observed autonomic dysfunction in all PTLDS participants. Additionally, our study revealed reduced cerebral blood flow in all PTLDS patients, suggesting cerebral hypoperfusion.
Our findings suggest that SFN and related dysautonomia may serve as objective markers for PTLDS. The assessment of small fiber density and autonomic dysfunction using skin biopsies and reflex testing could be valuable in therapeutic trials and offer physicians a clearer understanding of PTLDS and its associated symptoms, including cognitive impairment and brain fog.
The mechanisms like direct cytotoxicity by the spirochete, neurotoxic mediators during host-pathogen interactions, and triggered autoimmune reactions are likely to be involved in the pathogenesis of this neuronal injury.
The mechanism of neuronal injury in Lyme is clear
The article “The Pathogenesis of Lyme Neuroborreliosis: From Infection to Inflammation” by Rupprecht et al. (2008) is a crucial source of information that sheds light on the intricate mechanism of neuronal injury in Lyme disease. Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, can lead to neurological manifestations, including painful meningoradiculitis and cranial or peripheral neuritis. Understanding the pathogenesis of this condition is essential for effective management and treatment.
The infection process begins with the spirochetes entering the tick’s salivary glands during feeding and subsequently invading the host’s skin, leading to a local infection called erythema migrans. During the second stage of Lyme disease, the spirochetes can spread to various organs, including the central nervous system (CNS), resulting in neurological complications.
The spirochetes employ various strategies to evade the host’s immune system. They downregulate immunogenic surface proteins, such as OspA and OspC, to minimize their recognition by immune cells. Additionally, they express complement-neutralizing proteins and induce anti-inflammatory cytokines to suppress the host’s immune response. These mechanisms enable the spirochetes to establish infection and persist in the host.
Once the spirochetes enter the CNS, they encounter local immune cells, leading to the production of proinflammatory cytokines and chemokines. The chemokine CXCL13 plays a pivotal role in attracting B-lymphocytes into the cerebrospinal fluid (CSF), resulting in the production of borrelia-specific antibodies. This immune response, however, can also contribute to the neuronal injury.
The neurological dysfunction observed in Lyme neuroborreliosis may result from multiple factors. The spirochetes can directly adhere to neural and glial cells, causing cytotoxicity and inflammation in the surrounding tissues. Furthermore, they induce the release of neurotoxic substances, such as nitric oxide and quinolonic acid, exacerbating the damage. Additionally, the immune response may lead to an autoimmune reaction, with antibodies targeting neural antigens due to molecular mimicry, further contributing to inflammation and demyelination.
The demyelination process is particularly significant as it can disrupt nerve function and result in various neurological symptoms. Damage to the myelin sheath, the protective covering of nerve fibers, can lead to muscle weakness, numbness, tingling, and coordination difficulties.
What we are doing and how you can help
The mechanisms discussed, including immune evasion, inflammation, and demyelination, contribute to the complex clinical picture of this condition. Understanding these processes is crucial for developing targeted therapies to mitigate nerve injury and promote recovery in patients with Lyme neuroborreliosis. We must do better to educate the medical system about this mechanism of injury. With this information, the stigma will disappear, and the patients will be listened to and treated properly. Insurance companies will follow this by covering treatments.
Education leads to meaningful and lasting change. And we are paving the way.
Just in the last 6 months, we have educated physicians via the Montecalvo Education Platform for Vector-Borne Illness to impact over 750,000 patient visits. Our virtual courses have been viewed over 14,000 times. This work is only possible with your support: we rely on gifts from donors like you to make sure no Lyme patient is left behind. Your donations help us expand programming, send our team to conferences, and help us develop educational guides. Please consider making your tax-deductible donation today.
From all of us here at Invisible, With gratitude,
Nevena Zubcevik, DO Chief Medical Officer Invisible International
Fallon BA, Madsen T, Erlangsen A, Benros ME. Lyme Borreliosis and Associations With Mental Disorders and Suicidal Behavior: A Nationwide Danish Cohort Study. Am J Psychiatry. 2021 Oct 1;178(10):921-931. doi: 10.1176/appi.ajp.2021.20091347. Epub 2021 Jul 28. PMID: 34315282.
Novak P, Felsenstein D, Mao C, Octavien NR, Zubcevik N. Association of small fiber neuropathy and post treatment Lyme disease syndrome. PLoS One. 2019 Feb 12;14(2):e0212222. doi: 10.1371/journal.pone.0212222. PMID: 30753241; PMCID: PMC6372188.
Rupprecht TA, Koedel U, Fingerle V, Pfister HW. The Pathogenesis of Lyme Neuroborreliosis: From Infection to Inflammation. Mol Med. 2008 Nov-Dec;14(11-12):205-12. doi: 10.2119/2007-00091.Rupprecht. PMID: 18787810; PMCID: PMC2270991.
The groundbreaking study on Lyme and mental health from Columbia University shines a light on an utterly shocking statistic: People suffering from Lyme borreliosis have “a two-fold higher risk of dying by suicide than those without Lyme disease.”
As a clinician who has been treating Lyme patients for years, I see many reasons for this preventable loss of life. The biggest factor, in my opinion, is that these sufferers feel abandoned and stigmatized by the medical system and society at large. Lyme disease has no reliable test, no vaccine, and no effective treatments in the chronic stages of the disease. Yet physicians and family members often tell them that their very real disease is “all in their heads.” They feel invisible.
To respond to this urgent need, Invisible International is planning two important projects. The first is the Tick Bytes Clinical Data Research Platform, a nationwide clinical data repository that will provide quality tick-borne illness patient data to researchers to facilitate the development of better symptomologies, diagnostic approaches, and treatment protocols. We are currently working to fund 10 data-collection sites in hot spots across the country.
The second is a no cost mental health counseling and group support service for tick-borne illness patients. Led by psychiatrists and clinicians with expertise in Lyme disease, we will create a robust training and education platform for mental health providers. This platform will be tailored for different age groups and for caregivers of patients with tick-borne illness.
Please consider helping us fund these two trailblazing initiatives. Contact us via email or by visiting our giving webpage at https://invisible.international/give
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.
Invisible International, Inc. is a MA nonprofit corporation operating through a fiscal sponsorship with Players Philanthropy Fund, a Maryland charitable trust recognized by IRS as a tax-exempt public charity under Section 501(c)(3) of the Internal Revenue Code (Federal Tax ID: 27-6601178). Contributions to Invisible International are tax-deductible to the fullest extent of the law.