Unconventional Approaches to Direct Detection of Borreliosis and Other Tick Borne Illnesses: A Path Forward.

Abstract

The current COVID-19 pandemic has brought to public attention the conceptual difference between a test for COVID-19 derived RNA or proteins indicating the presence of an active infection, versus COVID-19 serology testing indicating pathogen infection. Only the former test for molecules derived from COVID-19 provides reliable evidence of a current active infection. As such, nucleic acid amplification methods, and COVID-19 antigen immunoassays, are used to diagnose SARS-CoV-2 active infection [1] and possible reinfection [2], to assess infection duration [3] and to guide patient management [4]. COVID-19 serology testing is used only for surveillance purposes [5] (not diagnosis of active infection), to guide public health measures [6], and to monitor vaccine response [7]. Thus, we would not use a positive COVID-19 serum antibody test to indicate the presence of an active COVID-19 infection. In striking contrast, no clinically accredited molecular test exists to detect molecules directly derived from Borreliosis. Nevertheless, treatment decisions concerning the diagnosis of acute and persistent Borreliosis are currently made based on Borreliosis serology testing and clinical evaluation of the patient’s medical history and symptoms [8]. Thus, diagnosis and management of Borreliosis is hampered by subjective tools and indirect markers of the disease. Consequently, there is an urgent need to find, and validate, direct molecular markers derived from the pathogen itself. Integrating a direct test for Borreliosis into clinical practice will dramatically raise the level of evidence-based clinical management for this widespread tick-borne disease. In addition to improved objective diagnosis of active Borreliosis, a direct test can provide important clues about the biologic functional state of the pathogen, leading to insights for pathogenesis and new treatment strategies.