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      Recent Progress in Lyme Disease and Remaining Challenges

      review-article
      1 , * , 2 , 3 , 4 , 1 , 5 , 6 , 7 , 8 , 9 , 7 , 1 , 10 , 11 , 12 , 7 , 2 , 13 , 5 , 13 , 14 , 15 , 16 , 16 , 16 , 16 , 16 , 17 , 17 , 18 , 19
      Frontiers in Medicine
      Frontiers Media S.A.
      Lyme disease, pathogenesis, diagnosis, treatment, prevention, field building, PTLD, vaccine

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          Abstract

          Lyme disease (also known as Lyme borreliosis) is the most common vector-borne disease in the United States with an estimated 476,000 cases per year. While historically, the long-term impact of Lyme disease on patients has been controversial, mounting evidence supports the idea that a substantial number of patients experience persistent symptoms following treatment. The research community has largely lacked the necessary funding to properly advance the scientific and clinical understanding of the disease, or to develop and evaluate innovative approaches for prevention, diagnosis, and treatment. Given the many outstanding questions raised into the diagnosis, clinical presentation and treatment of Lyme disease, and the underlying molecular mechanisms that trigger persistent disease, there is an urgent need for more support. This review article summarizes progress over the past 5 years in our understanding of Lyme and tick-borne diseases in the United States and highlights remaining challenges.

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          Most cited references357

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          Pattern recognition receptors and inflammation.

          Infection of cells by microorganisms activates the inflammatory response. The initial sensing of infection is mediated by innate pattern recognition receptors (PRRs), which include Toll-like receptors, RIG-I-like receptors, NOD-like receptors, and C-type lectin receptors. The intracellular signaling cascades triggered by these PRRs lead to transcriptional expression of inflammatory mediators that coordinate the elimination of pathogens and infected cells. However, aberrant activation of this system leads to immunodeficiency, septic shock, or induction of autoimmunity. In this Review, we discuss the role of PRRs, their signaling pathways, and how they control inflammatory responses. 2010 Elsevier Inc. All rights reserved.
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            Persister cells, dormancy and infectious disease.

            Kim Lewis (2007)
            Several well-recognized puzzles in microbiology have remained unsolved for decades. These include latent bacterial infections, unculturable microorganisms, persister cells and biofilm multidrug tolerance. Accumulating evidence suggests that these seemingly disparate phenomena result from the ability of bacteria to enter into a dormant (non-dividing) state. The molecular mechanisms that underlie the formation of dormant persister cells are now being unravelled and are the focus of this Review.
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              Lyme borreliosis.

              Lyme borreliosis (Lyme disease) is caused by spirochaetes of the Borrelia burgdorferi sensu lato species complex, which are transmitted by ticks. The most common clinical manifestation is erythema migrans, which eventually resolves, even without antibiotic treatment. However, the infecting pathogen can spread to other tissues and organs, causing more severe manifestations that can involve a patient's skin, nervous system, joints, or heart. The incidence of this disease is increasing in many countries. Laboratory evidence of infection, mainly serology, is essential for diagnosis, except in the case of typical erythema migrans. Diagnosed cases are usually treated with antibiotics for 2-4 weeks and most patients make an uneventful recovery. No convincing evidence exists to support the use of antibiotics for longer than 4 weeks, or for the persistence of spirochaetes in adequately treated patients. Prevention is mainly accomplished by protecting against tick bites. There is no vaccine available for human beings. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
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                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                18 August 2021
                2021
                : 8
                : 666554
                Affiliations
                [1] 1Icahn School of Medicine at Mount Sinai , New York, NY, United States
                [2] 2Department of Biochemistry, Fralin Life Sciences Institute, Virginia Tech , Blacksburg, VA, United States
                [3] 3Lyme Disease Biobank , Portland, OR, United States
                [4] 4Tulane University Health Sciences , New Orleans, LA, United States
                [5] 5Institute for Systems Biology , Seattle, WA, United States
                [6] 6State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, China
                [7] 7Division of Rheumatology, Department of Medicine, Lyme Disease Research Center, Johns Hopkins University School of Medicine , Baltimore, MD, United States
                [8] 8Cary Institute of Ecosystem Studies , Millbrook, NY, United States
                [9] 9Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center , Richmond, VA, United States
                [10] 10Bard College , Annandale, NY, United States
                [11] 11Department of Biology, Northeastern University , Boston, MA, United States
                [12] 12Yale University School of Medicine , New Haven, CT, United States
                [13] 13Department of Clinical Sciences, Comparative Medicine Institute, College of Veterinary Medicine, North Carolina State University , Raleigh, NC, United States
                [14] 14Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, IN, United States
                [15] 15Steven & Alexandra Cohen Foundation , Stamford, CT, United States
                [16] 16University of California, Los Angeles , Los Angeles, CA, United States
                [17] 17Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine , Baltimore, MD, United States
                [18] 18Center for Immunology and Infectious Diseases and the Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California, Davis , Davis, CA, United States
                [19] 19Columbia University Irving Medical Center , New York, NY, United States
                Author notes

                Edited by: Jean Challacombe, Twist Bioscience, United States

                Reviewed by: John Shearer Lambert, University College Dublin, Ireland; Ryan Oliver Marino Rego, Academy of Sciences of the Czech Republic (ASCR), Czechia

                *Correspondence: Jason R. Bobe jason.bobe@ 123456mssm.edu

                This article was submitted to Infectious Diseases - Surveillance, Prevention and Treatment, a section of the journal Frontiers in Medicine

                †ORCID: Jason R. Bobe orcid.org/0000-0003-1864-8609

                Panga Jaipal Reddy orcid.org/0000-0002-4481-3631

                Article
                10.3389/fmed.2021.666554
                8416313
                34485323
                f0f147aa-3e39-4e57-82b2-5004a7aba0b3
                Copyright © 2021 Bobe, Jutras, Horn, Embers, Bailey, Moritz, Zhang, Soloski, Ostfeld, Marconi, Aucott, Ma'ayan, Keesing, Lewis, Ben Mamoun, Rebman, McClune, Breitschwerdt, Reddy, Maggi, Yang, Nemser, Ozcan, Garner, Di Carlo, Ballard, Joung, Garcia-Romeu, Griffiths, Baumgarth and Fallon.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 February 2021
                : 12 July 2021
                Page count
                Figures: 0, Tables: 2, Equations: 0, References: 344, Pages: 25, Words: 25325
                Categories
                Medicine
                Review

                lyme disease,pathogenesis,diagnosis,treatment,prevention,field building,ptld,vaccine

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