Lyme Disease Frontiers: Reconciling Borrelia Biology and Clinical Conundrums

Abstract

Lyme disease is a complex tick-borne zoonosis that poses an escalating public health threat in several parts of the world, despite sophisticated healthcare infrastructure and decades of effort to address the problem. Concepts like the true burden of the illness, from incidence rates to longstanding consequences of infection, and optimal case management, also remain shrouded in controversy. At the heart of this multidisciplinary issue are the causative spirochetal pathogens belonging to the Borrelia Lyme complex. Their unusual physiology and versatile lifestyle have challenged microbiologists, and may also hold the key to unlocking mysteries of the disease. The goal of this review is therefore to integrate established and emerging concepts of Borrelia biology and pathogenesis, and position them in the broader context of biomedical research and clinical practice. We begin by considering the conventions around diagnosing and characterizing Lyme disease that have served as a conceptual framework for the discipline. We then explore virulence from the perspective of both host (genetic and environmental predispositions) and pathogen (serotypes, dissemination, and immune modulation), as well as considering antimicrobial strategies (lab methodology, resistance, persistence, and clinical application), and borrelial adaptations of hypothesized medical significance (phenotypic plasticity or pleomorphy).

Efficacy of Double-Dose Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome (PTLDS) and Associated Co-infections: A Report of Three Cases and Retrospective Chart Review

“…The stationary, persister, and biofilm forms of Borrelia burgdorferi (Bb) have been found to be resistant to standard antibiotic treatments and a cause of persistent inflammation [ 29 , 30 , 31 ]. This phenotypic plasticity of Borrelia and its survival in biofilms may help to explain in part clinical conundrums and persistent symptomatology [ 32 ].…”

Analysis of the concentration of selected serological parameters in patients undergoing antibiotic treatment of Lyme disease and assessment of their potential application in the control of the therapy effectiveness – pilot study

“…may manifest itself as Lyme arthritis or Lyme carditis several months or years after the infection. Clinical symptoms in the nervous system (encephalitis, polyneuropathy) and skin (acrodermatitis chronica atrophicans-ACA, lymphocytoma) may additionally be observed [1,2,3,4]. There is also a form referred to as Post-Treatment Lyme Disease Syndrome (PTLDS), which develops when antibiotic therapy does not bring expected clinical results.…”

“…There are various criteria of diagnosis of PTLDS, e.g. fatigue, extensive musculoskeletal pain, and cognitive difficulties resulting in debilitation of professional, educational, personal, or social activities [1].…”

“…The diagnosis of LD is based on the presence of at least one clinical symptom: EM, Borrelial lymphoma, ACA, or a complex of symptoms related to Lyme carditis, Lyme arthritis, neuroborreliosis [3]. Another element of LD diagnostics, with the exception of early EM skin lesions, involves two-stage serological tests aimed at detection of specific anti-Borreliella antibodies [1,2]. Their absence in patients with suspected Lyme disease usually excludes the diagnosis [3].…”

Pathogenesis of Fungal and Bacterial Microbes

“…This Special Issue also covers the role of microbial pathogenesis with thought-provoking Reviews spanning diverse species of bacterial and fungal pathogens. For example, the complexity of Lyme disease in consideration of the illness burden, incidence rates, consequences of infection, and optimal case management strategies are explored by Bamm et al to highlight the intricate relationship between host and pathogen during this disease [ 9 ]. This extensive Review discusses the juxtaposition between established and emerging concepts in Borrelia (the causative agent of Lyme disease) biology and pathogenesis through coverage of diagnostic challenges and disease classification, diverse components of the host-pathogen interplay that impact disease severity and outcome, as well as the consequences (e.g., resistance) and opportunities (e.g., alternative anti-microbials) with medical intervention.…”