Hematogenous dissemination in early Lyme disease

Wormser, Gary P.

doi:10.1007/s00508-006-0688-9

Cited by 64 publications

(42 citation statements)

References 28 publications

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“…A recent study of patients with EM showed a greater recovery of B. burgdorferi sensu stricto from blood of symptomatic patients; nevertheless, the majority of symptomatic patients had negative blood cultures (371), raising doubts about the reliability of the assumption that the presence of symptoms indicates dissemination.…”

Section: Laboratory Diagnosismentioning

confidence: 97%

Diagnosis of Lyme Borreliosis

et al. 2005

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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

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Section: Laboratory Diagnosismentioning

confidence: 97%

Diagnosis of Lyme Borreliosis

et al. 2005

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“…With the genetic disruption or absence of these adhesins, spirochetes may be unable to travel by conventional routes or access important microenvironmental niches and thus manifest their altered dissemination phenotype. Although the extracellular matrix (ECM) is important in B. burgdorferi dissemination, as evidenced by direct dissemination through connective tissue (26,27,28,29), spirochetes utilize alternate means to disseminate as well, including bacteremia (19,29,30,31). In addition, a relatively unexplored means of dissemination is through lymphatics, as draining lymph nodes are often culture positive sooner than any other tissues proximal to the inoculation site (20,25,32).…”

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confidence: 99%

The Early Dissemination Defect Attributed to Disruption of Decorin-Binding Proteins Is Abolished in Chronic Murine Lyme Borreliosis

et al. 2013

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The laboratory mouse model of Lyme disease has revealed that Borrelia burgdorferi differentially expresses numerous outer surface proteins that influence different stages of infection (tick-borne transmission, tissue colonization, dissemination, persistence, and tick acquisition). Deletion of two such outer surface proteins, decorin-binding proteins A and B (DbpA/B), has been documented to decrease infectivity, impede early dissemination, and, possibly, prevent persistence. In this study, DbpA/B-deficient spirochetes were confirmed to exhibit an early dissemination defect in immunocompetent, but not immunodeficient, mice, and the defect was found to resolve with chronicity. Development of disease (arthritis and carditis) was attenuated only in the early stage of infection with DbpA/B-deficient spirochetes in both types of mice. Persistence of the DbpA/B-deficient spirochetes occurred in both immunocompetent and immunodeficient mice in a manner indistinguishable from that of wild-type spirochetes. Dissemination through the lymphatic system was evaluated as an underlying mechanism for the early dissemination defect. At 12 h, 3 days, 7 days, and 14 days postinoculation, DbpA/B-deficient spirochetes were significantly less prevalent and in lower numbers in lymph nodes than wild-type spirochetes. However, in immunodeficient mice, deficiency of DbpA/B did not significantly decrease the prevalence or spirochete numbers in lymph nodes. Complementation of DbpA/B restored a wild-type phenotype. Thus, the results indicated that deficiency of DbpA/B allows the acquired immune response to restrict early dissemination of spirochetes, which appears to be at least partially mediated through the lymphatic system.

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“…In Danish Ixodes ricinus three different genospecies were simultaneously present in at least 40% of the ticks (32). Borrelia sensu stricto was found in blood plasma from nearly half of the erythema migrans of American patients when large volumes of blood plasma were used as source of spirochete cultivation (33). Lyme borreliosis, with incidence that has increased in northern countries, becomes chronic and variable.…”

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confidence: 99%