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  lüll Diagnosis of lyme borreliosis Aguero-Rosenfeld ME; Wang G; Schwartz I; Wormser GPClin Microbiol Rev  2005[Jul]; 18 (3): 484-509A 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.|*Borrelia burgdorferi/genetics/immunology/isolation & purification[MESH]|*Clinical Laboratory Techniques[MESH]|Antibodies, Bacterial/blood[MESH]|Bacteriological Techniques[MESH]|Culture Media[MESH]|Humans[MESH]|Immunologic Tests[MESH]|Lyme Disease/*diagnosis/microbiology[MESH]|Polymerase Chain Reaction[MESH] |