scholarly journals Arthritis and Diagnostics in Lyme Disease

2021 ◽  
Vol 6 (1) ◽  
pp. 18
Author(s):  
Javier A. Quintero ◽  
Raluchukwu Attah ◽  
Reena Khianey ◽  
Eugenio Capitle ◽  
Steven E. Schutzer
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Diagnostic Tests ◽  
Laboratory Tests ◽  
Diagnostic Methods ◽  
Lyme Arthritis ◽  
Differential Diagnoses ◽  
Antibody Testing ◽  
Active Infection ◽  
Indirect Measure

The diagnosis of Lyme disease, caused by Borrelia burgdorferi, is clinical but frequently supported by laboratory tests. Lyme arthritis is now less frequently seen than at the time of its discovery. However, it still occurs, and it is important to recognize this, the differential diagnoses, and how laboratory tests can be useful and their limitations. The most frequently used diagnostic tests are antibody based. However, antibody testing still suffers from many drawbacks and is only an indirect measure of exposure. In contrast, evolving direct diagnostic methods can indicate active infection.

scholarly journals Development of a sensitive molecular diagnostic assay for detecting Borrelia burgdorferi DNA from the blood of Lyme disease patients by digital PCR

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0235372
Author(s):  
Srirupa Das ◽  
Denise Hammond-McKibben ◽  
Donna Guralski ◽  
Sandra Lobo ◽  
Paul N. Fiedler
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Digital Pcr ◽  
Diagnostic Methods ◽  
Molecular Diagnostic ◽  
Diagnostic Assay ◽  
Timely Manner ◽  
Blood Samples ◽  
Pcr Technology ◽  
Analytical Processing

Lyme disease patients would greatly benefit from a timely, sensitive, and specific molecular diagnostic test that can detect the causal agent Borrelia burgdorferi at the onset of symptoms. Currently available diagnostic methods recommended by the Centers for Disease Control and Prevention for Lyme disease involve indirect serological tests that rely on the detection of a host-antibody response, which often takes more than three weeks to develop. With this process, many positive cases are not detected within a timely manner, preventing a complete cure. In this study, we have developed a digital polymerase chain reaction (PCR) assay that detects Lyme disease on clinical presentation with a sensitivity two-fold higher than that of the currently available diagnostic methods, using a cohort of patient samples collected from the Lyme disease endemic state of Connecticut, USA, in 2016–2018. Digital PCR technology was chosen as it is more advanced and sensitive than other PCR techniques in detecting rare targets. The analytical detection sensitivity of this diagnostic assay is approximately three genome copies of B. burgdorferi. The paucity of spirochetes in the bloodstream of Lyme disease patients has hindered the clinical adoption of PCR-based diagnostic tests. However, this drawback was overcome by using a comparatively larger sample volume, applying pre-analytical processing to the blood samples, and implementing a pre-amplification step to enrich for B. burgdorferi-specific gene targets before the patient samples are analyzed via digital PCR technology. Pre-analytical processing of blood samples from acute patients revealed that the best sample type for Lyme disease detection is platelet-rich plasma rather than whole blood. If detected in a timely manner, Lyme disease can be completely cured, thus limiting antibiotic overuse and associated morbidities.

scholarly journals Lyme disease: New knowledge regarding its physiopathology, diagnosis, therapy and prevention

2002 ◽  
Vol 55 (5-6) ◽  
pp. 207-212
Author(s):  
Jovan Vukadinov ◽  
Sinisa Sevic ◽  
Grozdana Canak ◽  
Nadezda Madle-Samardzija ◽  
Vesna Turkulov ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Antigenic Variation ◽  
Clinical Symptoms ◽  
Epidemiological Studies ◽  
Lyme Arthritis ◽  
Major Protein ◽  
Selective Treatment ◽  
Multisystem Disease ◽  
New Guidelines

Introduction Lyme disease is a tick-borne disease caused by a spirochete Borrelia burgdorferi, which manifests as a multisystem disease of the skin nervous system, heart and joints. Recently it is the most common vector-borne disease in Yugoslavia. New epidemiological studies New epidemiological studies revealed that ticks can occasionally be infected not only by Borrelia burgdorferi, but also by some other microbes that can cause diseases in humans. Recently discovered the variable major protein-like sequence, antigenic variation of B. burgdorferi B 31 partly explains the ability of this organism to evade an active immune response. A key role in development of clinical symptoms associated with lyme disease belongs to the connection with ability of B. burgdorferi to induce and activate metallopeptidases and fibrinolytic enzymes, leading to extracellular matrix destruction. Diagnosis and treatment Diagnosis of Lyme borreliosis is made on the basis of clinical picture, exposure to ticks in endemic areas and serologic confirmation. It seems that polymerase chain reaction has little role in detection of B. burgdorferi in urine, blood, and spinal fluid samples, but it is most useful in evaluating the effectiveness of antibiotic therapy of Lyme arthritis. Infectious Diseases Society of America had prepared new guidelines for selective treatment of Lyme disease. Vaccination is still the best way of prevention for people living in high-risk areas.

scholarly journals Activation of Natural Killer Cells in Arthritis-Susceptible but Not Arthritis-Resistant Mouse Strains following Borrelia burgdorferi Infection

1998 ◽  
Vol 66 (11) ◽  
pp. 5208-5214 ◽  
Author(s):  
Charles R. Brown ◽  
Steven L. Reiner
Keyword(s):  
Lymph Node ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Nk Cells ◽  
Nk Cell ◽  
Lyme Arthritis ◽  
Mouse Strains ◽  
Target Cells ◽  
Susceptible Mouse ◽  
Resistant Mouse

ABSTRACT Infection of susceptible mouse strains with Borrelia burgdorferi, the agent of Lyme disease, results in the development of arthritis. Components of the innate immune system may be important mediators of this pathology. To investigate the potential role of NK cells in development of experimental Lyme arthritis, we examined their activation in vivo in both resistant and susceptible mouse strains. Following inoculation of B. burgdorferi into the footpad, lymph node NK cells from susceptible C3H/HeJ (C3H) mice produced more gamma interferon than NK cells from resistant DBA/2J mice. Lymph node cells from susceptible C3H and AKR mice also had increased ability to lyse YAC-1 target cells 2 days following infection. Antibody depletion of NK cells from susceptible mice, however, did not alter the development of arthritis following B. burgdorferi challenge. In addition, NK cell depletion had little effect on spirochete burden. Thus, there is a marked activation of NK cells in susceptible mouse strains following infection. Although NK cells are not absolutely required for arthritis, events occurring prior to NK cell activation might be important in mediating pathology in experimental Lyme disease.

scholarly journals Development of a sensitive molecular diagnostic assay for detecting Borrelia burgdorferi DNA from blood of Lyme disease patients by digital PCR

2020 ◽  
Author(s):  
Srirupa Das ◽  
Denise Hammond-McKibben ◽  
Donna Guralski ◽  
Sandra Lobo ◽  
Paul N. Fiedler
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Digital Pcr ◽  
Diagnostic Methods ◽  
Molecular Diagnostic ◽  
Sample Type ◽  
Diagnostic Assay ◽  
Blood Samples ◽  
Pcr Technology ◽  
Analytical Processing

AbstractLyme disease patients would benefit greatly from a timely, sensitive and specific molecular diagnostic test that can detect the causal agent, Borrelia burgdorferi, at the onset of symptoms. Currently available diagnostic methods recommended by the Centers for Disease Control and Prevention for Lyme disease, involve indirect serological tests that rely on the detection of a host-antibody response which often takes more than three weeks to develop. This results in non-detection of many genuine cases on a timely basis, preventing complete cure. In this study we have developed a digital PCR (polymerase chain reaction) assay that detects Lyme disease on clinical presentation at twice the sensitivity of the currently available diagnostic methods, using a cohort of patient samples collected from the Lyme disease endemic state of Connecticut, USA in 2016-2018. Digital PCR technology was chosen as it is more advanced and sensitive than other PCR techniques in detecting rare targets and the lower limit of detection of this diagnostic assay was found to be three genome copies of B. burgdorferi. The paucity of spirochetes in the bloodstream of Lyme disease patients that hinders the clinical adoption of PCR-based diagnostic tests, was overcome by using a comparatively larger sample volume, pre-analytical processing of blood samples and a pre-amplification step to enrich for B. burgdorferi-specific gene targets before using the digital PCR technology to analyze patient samples. Pre-analytical processing of blood samples from acute patients revealed that the best sample type for Lyme disease detection is platelet-rich plasma and not whole blood. If detected on time, Lyme disease can be cured completely limiting the overuse of antibiotics and associated morbidities.

scholarly journals Misdiagnosis of Late-Onset Lyme Arthritis by Inappropriate Use of Borrelia burgdorferi Immunoblot Testing with Synovial Fluid

2012 ◽  
Vol 19 (11) ◽  
pp. 1806-1809 ◽  
Author(s):  
Sam S. Barclay ◽  
Michael T. Melia ◽  
Paul G. Auwaerter
Keyword(s):  
Lyme Disease ◽  
Synovial Fluid ◽  
Borrelia Burgdorferi ◽  
Late Onset ◽  
Medical Center ◽  
Academic Medical Center ◽  
Primary Objective ◽  
Lyme Arthritis ◽  
Serum Samples ◽  
Content Type

ABSTRACTThe primary objective of this study was to determine whether patients with putative late-onset Lyme arthritis based upon synovial fluidBorrelia burgdorferiIgM and IgG immunoblot testing offered by commercial laboratories satisfied conventional criteria for the diagnosis of Lyme arthritis. Secondary objectives included assessing the prior duration and responsiveness of associated antibiotic therapy. We conducted a retrospective analysis of 11 patients referred to an academic medical center infectious disease clinic during the years 2007 to 2009 with a diagnosis of Lyme disease based upon previously obtained synovial fluidB. burgdorferiimmunoblot testing. Ten of the 11 (91%) patients with a diagnosis of late-onset Lyme arthritis based upon interpretation of synovial fluidB. burgdorferiimmunoblot testing were seronegative and did not satisfy published criteria for the diagnosis of late-onset Lyme arthritis. None of the 10 patients had a clinical response to previously received antibiotics despite an average course of 72 days. Diagnosis of Lyme arthritis should not be based on synovial fluidB. burgdorferiimmunoblot testing. This unvalidated test does not appear useful for the diagnosis of Lyme disease, and this study reinforces the longstanding recommendation to useB. burgdorferiimmunoblot testing only on serum samples and not other body fluids. Erroneous interpretations of “positive” synovial fluid immunoblots may lead to inappropriate antibiotic courses and delays in diagnosis of other joint diseases.

scholarly journals ELISA-Based Measurement of Antibody Responses and PCR-Based Detection Profiles Can Distinguish between Active Infection and Early Clearance ofBorrelia burgdorferi

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
John J. Lazarus ◽  
Akisha L. McCarter ◽  
Kari Neifer-Sadhwani ◽  
R. Mark Wooten
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Intradermal Injection ◽  
Antibody Responses ◽  
Productive Infection ◽  
Active Infection ◽  
Bacterial Dna ◽  
Large Numbers ◽  
Live Bacteria ◽  
Established Infection

Borrelia burgdorferiis a spirochetal bacterium that causes Lyme disease. These studies address whether current research methods using either ELISA to detect seroconversion toB. burgdorferiantigens or PCR quantification of bacterial DNA within tissues can accurately distinguish between a productive infection versus aB. burgdorferiexposure that is rapidly cleared by the innate responses. Mice receiving even minimal doses of liveB. burgdorferiproduced significantly moreB. burgdorferi-specific IgM and IgG than groups receiving large inocula of heat-killed bacteria. Additionally, sera from mice injected with varied doses of killedB. burgdorferirecognized unique borrelial antigens compared to mice infected with liveB. burgdorferi. Intradermal injection of killedB. burgdorferiresulted in rapid DNA clearance from skin, whereas DNA was consistently detected in skin inoculated with viableB. burgdorferi. These data indicate that both ELISA-based serological analyses and PCR-based methods of assessingB. burgdorferiinfection clearly distinguish between an established infection with live bacteria and exposure to large numbers of bacteria that are promptly cleared by the innate responses.

scholarly journals Serum Reactivity against Borrelia burgdorferi OspA in Patients with Rheumatoid Arthritis

2007 ◽  
Vol 14 (11) ◽  
pp. 1437-1441 ◽  
Author(s):  
Yu-Fan Hsieh ◽  
Han-Wen Liu ◽  
Tsai-Ching Hsu ◽  
James C.-C. Wei ◽  
Chien-Ming Shih ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Healthy Subjects ◽  
Disease Activity Score ◽  
Protein A ◽  
Surface Protein ◽  
Lyme Arthritis ◽  
Serum Concentrations ◽  
Outer Surface Protein A

ABSTRACT Lyme arthritis and rheumatoid arthritis share common clinical features and synovial histology. It is unclear whether they also share similar pathogenesis. Previous studies have shown that the severity and duration of Lyme arthritis correlate directly with serum concentrations of antibody against outer surface protein A (OspA) of the causative pathogen Borrelia burgdorferi. We tested the sera of 68 subjects with rheumatoid arthritis, 147 subjects with other autoimmune diseases, and 44 healthy subjects who had never had Lyme disease, as well as sera of 16 patients who had Lyme disease, for reactivity against the B. burgdorferi OspA protein. The sera of about a quarter of the rheumatoid arthritis patients and a 10th of the autoimmune disease and Lyme disease patients reacted against OspA antigen. Of 50 rheumatoid arthritis patients who could be evaluated for disease severity, a 28-joint count disease activity score of >2.6 was noted for 11 of 15 (73%) patients whose sera reacted against OspA antigen and 13 of 35 (37%; P < 0.05) whose sera were nonreactive. Serum reactivity against OspA antigen is associated with the pathogenesis of rheumatoid arthritis.

scholarly journals Detection of Immune Complexes Is Not Independent of Detection of Antibodies in Lyme Disease Patients and Does Not Confirm Active Infection with Borrelia burgdorferi

2005 ◽  
Vol 12 (9) ◽  
pp. 1036-1040 ◽  
Author(s):  
Adriana R. Marques ◽  
Ronald L. Hornung ◽  
Len Dally ◽  
Mario T. Philipp
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Rhesus Macaques ◽  
Protein A ◽  
Surface Protein ◽  
Laboratory Diagnosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Active Infection ◽  
Serum Samples ◽  
Outer Surface Protein A

ABSTRACT The Borrelia burgdorferi-specific immune complex (IC) test, which uses polyethylene glycol (PEG) precipitation to isolate ICs from serum, has been used as a research test in the laboratory diagnosis of early Lyme disease (LD) and has been proposed as a marker of active infection. We examined whether B. burgdorferi-specific antibodies were present within PEG-precipitated ICs (PEG-ICs) in patients with LD, posttreatment Lyme disease syndrome, and controls, including individuals who received the outer surface protein A (OspA) vaccine. Using a B. burgdorferi whole-cell enzyme-linked immunosorbent assay (ELISA), we obtained positive PEG-IC results not only in patients with a history of LD, but also in individuals vaccinated with OspA vaccine. The frequency of positive PEG-IC ELISAs in OspA vaccinees was significantly higher with ELISA-reactive than with ELISA-negative unprocessed serum samples (P = 0.001), demonstrating dependency between the tests. Similar results were found using samples from rhesus macaques infected with B. burgdorferi, uninfected macaques vaccinated with OspA, and controls. Therefore, testing for the presence of antibodies against B. burgdorferi in PEG-IC preparations is not more likely to reflect active infection than testing in unprocessed serum and should not be used in individuals who received the OspA vaccine.

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