Diagnosis of Lyme Borreliosis

Abstract

A large amount of knowledge has been acquired since the original descriptions of Lyme borreliosis (LB) and of its causative agent, Borrelia burgdorferi sensu stricto. The complexity of the organism and the variations in the clinical manifestations of LB caused by the different B. burgdorferi sensu lato species were not then anticipated. Considerable improvement has been achieved in detection of B. burgdorferi sensu lato by culture, particularly of blood specimens during early stages of disease. Culturing plasma and increasing the volume of material cultured have accomplished this. Further improvements might be obtained if molecular methods are used for detection of growth in culture and if culture methods are automated. Unfortunately, culture is insensitive in extracutaneous manifestations of LB. PCR and culture have high sensitivity on skin samples of patients with EM whose diagnosis is based mostly on clinical recognition of the lesion. PCR on material obtained from extracutaneous sites is in general of low sensitivity, with the exception of synovial fluid. PCR on synovial fluid has shown a sensitivity of up to >90% (when using four different primer sets) in patients with untreated or partially treated Lyme arthritis, making it a helpful confirmatory test in these patients. Currently, the best use of PCR is for confirmation of the clinical diagnosis of suspected Lyme arthritis in patients who are IgG immunoblot positive. PCR should not be used as the sole laboratory modality to support a clinical diagnosis of extracutaneous LB. PCR positivity in seronegative patients suspected of having late manifestations of LB most likely represents a false-positive result. Because of difficulties in direct methods of detection, laboratory tests currently in use are mainly those detecting antibodies to B. burgdorferi sensu lato. Tests used to detect antibodies to B. burgdorferi sensu lato have evolved from the initial formats as more knowledge on the immunodominant antigens has been collected. The recommendation for two-tier testing was an attempt to standardize testing and improve specificity in the United States. First-tier assays using whole-cell sonicates of B. burgdorferi sensu lato need to be standardized in terms of antigen composition and detection threshold of specific immunoglobulin classes. The search for improved serologic tests has stimulated the development of recombinant protein antigens and the synthesis of specific peptides from immunodominant antigens. The use of these materials alone or in combination as the source of antigen in a single-tier immunoassay may someday replace the currently recommended two-tier testing strategy. Evaluation of these assays is currently being done, and there is evidence that certain of these antigens may be broadly cross-reactive with the B. burgdorferi sensu lato species causing LB in Europe

Expression of C-Reactive Protein and Serum Amyloid A in Early to Late Manifestations of Lyme Disease

“…Although we found CRP expression to be elevated in specific stages of active Lyme disease, as well as in antibiotic-refractory Lyme arthritis and PTLDS, the results are suggestive of distinct underlying mechanisms within the different manifestations. Our data indicate that the highest levels of CRP during active Lyme disease correspond to the early stage of infection, when the concentration of spirochetes is greatest in skin and/or blood [20]. The CRP response in early Lyme disease appeared to subside after the dissemination of the organism to extracutaneous sites and its clearance from blood, when a robust IgG response to B. burgdorferi has developed.…”

Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to the C6-peptide in Lyme neuroborreliosis

“…However, pleocytosis may be absent and specific intrathecal antibodies expressed as antiborrelia antibody index (AI) in paired CSF/serum samples may be negative the first few weeks, and in addition, a positive AI may also persist several months and even years despite appropriate antibiotic treatment (5)(6)(7)(8)(9)(10)(11). Therefore, there is a need for additional markers of ongoing LNB.…”

Chronic Lyme Disease: A Review

“…It should be noted however, that B. burgdorferi culture and PCR have low sensitivity in most body fluids from patients with Lyme disease [56,57]. The initial report claiming frequent isolation of B. burgdorferi from patients with post-Lyme disease syndrome using MPM media [58] has not been reproduced by other researchers [49,59,60].…”