Brian Fallon, MD
This is both a disturbing and an exciting time in the world of Lyme disease.
Disturbing because the medical and public health communities have failed to stem the steady increase in the number of cases of Lyme disease over the last 2 decades; indeed, the CDC now estimates that there are over 300,000 new cases of Lyme disease diagnosed each year in the United States and the geographic spread of cases has expanded dramatically.
Exciting because advances in medical technology are leading to breakthroughs in how we understand this disease.
On the diagnostic front, proteomic and metabolomic studies have identifed novel biologic markers that enhance the sensitivity to identify new cases of Lyme disease.
The holy grail of diagnostics however is a test that can tell whether or not a patient still has active infection. This test has eluded investigators for decades. There are promising new research results however that suggest that tests based on cellular assays (using T-cells or macrophages and challenge with Borrelia antigens) are able to not only detect infection in early disease with a higher degree of sensitivity than current tests but these cellular assays (unlike current antibody-based assays) also become negative after the infection has been treated with antibiotics. These cellular based assays - if the larger studies confirm the initial preliminary findings - may then become the gold standard for diagnosis and serve as a powerful new tool to guide treatment planning.
Investigators are now using mass spectrometry-based technologies, developed in response to biowarfare research, to rapidly screen fluids from the bodies of ticks or humans for previously unidentified pathogens - pathogens in ticks, for example, other than Borrelia burgdorferi, that may be causing human disease. This has lead to "chips" that can detect dozens - even hundreds - of pathogens using just one sample of blood.
Biomarkers predicting disease course
Genomic studies have begun to identify different strains of Borrelia, some of which may be more virulent, and others which may target different organ systems. Immunologic studies are now identifying different host immune responses to a spirochetal infection. These responses may be genetically driven, and predispose certain individuals to develop chronic disease, and others to rapidly eradicate the initial infection.
Prospective studies and treatment studies in humans have identified tentative biomarkers that may serve to guide treatment selection. These immunologic and neuroimaging biomarkers, if confirmed by additional prospective research, will provide clinicians with new tools to distinguish those patients who are most likely to benefit from further antibiotics from those patients who would require other non-antibiotic treatment approaches
Imaging studies in animals using immunoflourescent spirochetes now enable direct real-time visualization of the spirochete’s course through the body. Human neuroimaging studies enable the identification of circuits of the brain particularly affected among patients with chronic symptoms.
Treatment studies in animal models have definitively shown that the Borrelial spirochete is capable of persisting in the animal host – even after aggressive antibiotic therapy. And now microbiologic studies in the lab have shown that some Lyme spirochetes "persist" despite the standard antibiotic therapy. These novel research studies are identifying new antimicrobials that when used in different combinations can be quite powerful in eliminating these Lyme spirochete persisters in the lab setting. Similarly other researchers are identifying pulse dosing as an effective strategy to eliminate persisters in vitro. These however are "in vitro" studies and the next step is to test these strategies in the animal models.
We have two new treatment studies at Columbia - both are for patients with chronic symptoms after Lyme disease. For more information, check our "New Research Studies" at the following link: Current/Recent Research Studies.
The pace of medical discovery has been accelerated by funding from the National Institutes of Health and by the generous support of private donors – individuals and non-profit charitable organizations. Without the support of private donors, the novel, pioneering pilot work that might lead to larger NIH-funded grants would never get started. About 8 years ago, two organizations (Lyme Research Alliance and the Lyme Disease Association) committed themselves to provide the cornerstone funds to establish a major new research Center at one of the world’s foremost medical research institutions - Columbia University. This multi-disciplinary Research Center, formally opened in 2007, is the first in the United States to focus research specifically on the problem of chronic Lyme disease. It brings together experts in neurology, infectious disease, immunology, genetics, neuroimaging, microbiology, neuropsychiatry, pathology, rheumatology, and public health.
As the number of typical and atypical cases of Lyme disease increases in the United States, so does the number of patients who go on to develop chronic persistent symptoms. Lives are being profoundly altered by the bite of a single tick. Our Center’s mission is to identify better diagnostic tests, safer and more effective treatments, and clear biomarkers that will guide treatment selection. The vast intellectual and biotechnological resources at the Columbia University Medical Center will continue to be tapped to achieve our goals, but our researchers will need new funding to initiate new studies. We encourage you to read the content on our website, send in suggestions for change, participate in a research study, and if able, send a contribution to support Lyme research.
Brian Fallon, MD
Director, Lyme and Tick-borne Diseases Research Center