Comparison of five diagnostic modalities for direct detection of Borrelia burgdorferi in patients with early Lyme disease

Liveris, Dionysios; Schwartz, Ira; McKenna, Donna; Nowakowski, John; Nadelman, Robert B.; DeMarco, Joseph P.; Iyer, Radha; Bittker, Susan; Cooper, Denise R.; Holmgren, Diane; Wormser, Gary P.

doi:10.1016/j.diagmicrobio.2012.03.026

Cited by 60 publications

(61 citation statements)

References 11 publications

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“…This could lead to an underestimate of the sensitivity of serologic testing among patients with EM. On the other hand, it is clear that B. burgdorferi cannot be cultured from EM skin lesions in all patients [28]. Among other potential variables, skin biopsy culture may be negative when the spirochetal burden is relatively low [29].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Modified 2-Tiered Serodiagnostic Testing Algorithms for Early Lyme Disease

Branda¹,

Strle

Nigrovic

et al. 2017

Clinical Infectious Diseases

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Background. The conventional 2-tiered serologic testing protocol for Lyme disease (LD), an enzyme immunoassay (EIA) followed by immunoglobulin M and immunoglobulin G Western blots, performs well in late-stage LD but is insensitive in patients with erythema migrans (EM), the most common manifestation of the illness. Western blots are also complex, difficult to interpret, and relatively expensive. In an effort to improve test performance and simplify testing in early LD, we evaluated several modified 2-tiered testing (MTTT) protocols, which use 2 assays designed as first-tier tests sequentially, without the need of Western blots.Methods. The MTTT protocols included (1) a whole-cell sonicate (WCS) EIA followed by a C6 EIA; (2) a WCS EIA followed by a VlsE chemiluminescence immunoassay (CLIA); and (3) a variable major protein-like sequence, expressed (VlsE) CLIA followed by a C6 EIA. Sensitivity was determined using serum from 55 patients with erythema migrans; specificity was determined using serum from 50 patients with other illnesses and 1227 healthy subjects.Results. Sensitivity of the various MTTT protocols in patients with acute erythema migrans ranged from 36% (95% confidence interval [CI], 25%-50%) to 54% (95% CI, 42%-67%), compared with 25% (95% CI, 16%-38%) using the conventional protocol (P = .003-0.3). Among control subjects, the 3 MTTT protocols were similarly specific (99.3%-99.5%) compared with conventional 2-tiered testing (99.5% specificity; P = .6-1.0).Conclusions. Although there were minor differences in sensitivity and specificity among MTTT protocols, each provides comparable or greater sensitivity in acute EM, and similar specificity compared with conventional 2-tiered testing, obviating the need for Western blots.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Modified 2-Tiered Serodiagnostic Testing Algorithms for Early Lyme Disease

Branda¹,

Strle

Nigrovic

et al. 2017

Clinical Infectious Diseases

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“…Samples from patients with early localized (only an EM) and early disseminated (Lyme carditis or Lyme neuroborreliosis) Lyme disease were tested by culture and PCR when possible. Culture and PCR were performed according to published methods (8)(9)(10)(11). Additionally, joint fluid from patients with late disseminated Lyme arthritis was tested by PCR using the published methods of Li et al (12).…”

Section: Methodsmentioning

confidence: 99%

Collection and Characterization of Samples for Establishment of a Serum Repository for Lyme Disease Diagnostic Test Development and Evaluation

et al. 2014

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Serological assays and a two-tiered test algorithm are recommended for laboratory confirmation of Lyme disease. In the United States, the sensitivity of two-tiered testing using commercially available serology-based assays is dependent on the stage of infection and ranges from 30% in the early localized disease stage to near 100% in late-stage disease. Other variables, including subjectivity in reading Western blots, compliance with two-tiered recommendations, use of different first-and second-tier test combinations, and use of different test samples, all contribute to variation in two-tiered test performance. The availability and use of sample sets from well-characterized Lyme disease patients and controls are needed to better assess the performance of existing tests and for development of improved assays. To address this need, the Centers for Disease Control and Prevention and the National Institutes of Health prospectively collected sera from patients at all stages of Lyme disease, as well as healthy donors and patients with look-alike diseases. Patients and healthy controls were recruited using strict inclusion and exclusion criteria. Samples from all included patients were retrospectively characterized by two-tiered testing. The results from two-tiered testing corroborated the need for novel and improved diagnostics, particularly for laboratory diagnosis of earlier stages of infection. Furthermore, the two-tiered results provide a baseline with samples from well-characterized patients that can be used in comparing the sensitivity and specificity of novel diagnostics. Panels of sera and accompanying clinical and laboratory testing results are now available to Lyme disease serological test users and researchers developing novel tests.

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“…Within days to weeks, B. burgdorferi may disseminate from the site of skin inoculation through the blood or tissues and spread systemically to other areas of the skin (called disseminated EM), as well as the musculoskeletal, cardiac, and neurologic systems. More than 50% of patients with EM are found to have positive PCR or blood culture results at this stage (7,8).…”

mentioning

confidence: 99%

CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study

Aucott

Soloski

Crowder³

et al. 2016

Clin Vaccine Immunol

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d Approximately 10% to 20% of patients optimally treated for early Lyme disease develop persistent symptoms of unknown pathophysiology termed posttreatment Lyme disease syndrome (PTLDS). The objective of this study was to investigate associations between PTLDS and immune mediator levels during acute illness and at several time points following treatment. Seventy-six participants with physician-documented erythema migrans and 26 healthy controls with no history of Lyme disease were enrolled. Sixty-four cytokines, chemokines, and inflammatory markers were measured at each visit for a total of 6 visits over 1 year. An operationalized definition of PTLDS incorporating symptoms and functional impact was applied at 6 months and 1 year following treatment completion, and clinical outcome groups were defined as the return-to-health, symptoms-only, and PTLDS groups. Significance analysis of microarrays identified 7 of the 64 immune mediators to be differentially regulated by group. Generalized logit regressions controlling for potential confounders identified posttreatment levels of the T-cell chemokine CCL19 to be independently associated with clinical outcome group. Receiver operating characteristic analysis identified a CCL19 cutoff of >111.67 pg/ml at 1 month following treatment completion to be 82% sensitive and 83% specific for later PTLDS. We speculate that persistently elevated CCL19 levels among participants with PTLDS may reflect ongoing, immune-driven reactions at sites distal to secondary lymphoid tissue. Our findings suggest the relevance of CCL19 both during acute infection and as an immunologic risk factor for PTLDS during the posttreatment phase. Identification of a potential biomarker predictor for PTLDS provides the opportunity to better understand its pathophysiology and to develop early interventions in the context of appropriate and specific clinical information.

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Comparison of five diagnostic modalities for direct detection of Borrelia burgdorferi in patients with early Lyme disease

Cited by 60 publications

References 11 publications

Evaluation of Modified 2-Tiered Serodiagnostic Testing Algorithms for Early Lyme Disease

Evaluation of Modified 2-Tiered Serodiagnostic Testing Algorithms for Early Lyme Disease

Collection and Characterization of Samples for Establishment of a Serum Repository for Lyme Disease Diagnostic Test Development and Evaluation

CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study

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