Evaluation of a sequential enzyme immunoassay testing algorithm for Lyme disease demonstrates lack of test independence but high diagnostic specificity

Wormser, Gary P.; Molins, Claudia R.; Levin, Andrew; Lipsett, Susan C.; Nigrovic, Lise E.; Schriefer, Martin E.; Branda, John A.

doi:10.1016/j.diagmicrobio.2018.02.006

Cited by 10 publications

(6 citation statements)

References 14 publications

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“…Lyme immunoblots are known for having lower sensitivity than most first-tier immunoassays and are generally regarded as labor-intensive and prone to subjectivity or reproducibility issues. These limitations and issues have intensified the search for modified testing methods over the years (14)(15)(16)(17)(18)(19)(20). As an alternative modality, pairing the new BioPlex assay with one of the other first-tier assays consistently preserved most of the high sensitivity of the first-tier assay while retaining a high level of specificity expected of the STT method (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Early sensitivity is clinically important since the diagnosis and treatment of LB in its initial stages is associated with better clinical outcomes (1,3,13). In recent years, modified two-tier (MTT) algorithms have been investigated, with two sequential EIA designs in particular offering better sensitivity in addition to other advantages over the STT algorithm (14)(15)(16)(17)(18)(19)(20). More recently, the U.S. Food and Drug Administration (FDA) has cleared for the first time a two EIA alternative from Zeus Scientific (21).…”

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confidence: 99%

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A Fully Automated Multiplex Assay for Diagnosis of Lyme Disease with High Specificity and Improved Early Sensitivity

et al. 2020

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Lyme borreliosis is a tick-borne disease caused by the Borrelia burgdorferi sensu lato complex. Bio-Rad Laboratories has developed a fully automated multiplex bead-based assay for the detection of IgM and IgG antibodies to B. burgdorferi. The BioPlex 2200 Lyme Total assay exhibits an improved rate of seropositivity in patients with early Lyme infection. Asymptomatic subjects from endemic and nonendemic origins demonstrated a seroreactivity rate of approximately 4% that was similar to other commercial assays evaluated in this study. Coupled to this result was the observation that the Lyme Total assay retained a high first-tier specificity of 96% while demonstrating a relatively high sensitivity of 91% among a well-characterized CDC Premarketing Lyme serum panel. The Lyme Total assay also performs well under a modified two-tier algorithm (sensitivity, 84.4 to 88.9%; specificity, 98.4 to 99.5%). Furthermore, the new assay is able to readily detect early Lyme infection in patient samples from outside North America.

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Section: Discussionmentioning

confidence: 99%

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A Fully Automated Multiplex Assay for Diagnosis of Lyme Disease with High Specificity and Improved Early Sensitivity

et al. 2020

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“…The need for the algorithm to be highly specific is the reason that two EIAs are necessary. While the WCS EIA and C6 EIA are not completely independent tests (30), the use of two assays increases the specificity compared to that of either test alone.…”

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Revisiting the Lyme Disease Serodiagnostic Algorithm: the Momentum Gathers

Marques

2018

J Clin Microbiol

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Lyme disease is a tick-borne illness caused by () , and it is the most common vector-borne disease in the United States, with an estimated incidence of 300,000 cases per year. The currently recommended approach for laboratory support of the diagnosis of Lyme disease is a standard two-tiered (STT) algorithm comprised of an enzyme-linked immunoassay (EIA) or immunofluorescence assay (IFA), followed by Western blotting (WB). The STT algorithm has low sensitivity in early infection, and there are drawbacks associated with the WB use in practice. Modified two-tiered (MTT) algorithms have been shown to improve the sensitivity of the testing in early disease while maintaining high specificity. In this issue of the, A. Pegalajar-Jurado et al. (J Clin Microbiol 56:e01943-17, 2018, https://doi.org/10.1128/JCM.01943-17) report the results of their evaluation of the Liaison VlsE CLIA, the Captia IgG/IgM EIA, and the C6 (Lyme) EIA as MTT algorithms compared with results with the STT algorithm using the same tests as the first-tier test and the ViraStripe IgM and IgG WBs as the second-tier test. The results showed that all MTT algorithms had higher sensitivities than STT algorithms and were highly specific. These results showed that MTT approaches are a valid alternative to the currently recommended STT algorithm for serodiagnosis of Lyme disease, opening the door for the development of rapid diagnostics and point-of-care testing that can provide diagnostic information during the initial patient visit.

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“…In contrast, patients with solitary EM or early-disseminated Lyme disease typically have an immature, developing antibody response (12,13), and reactivity may be demonstrable using one test but not another. Although WCS EIA and the C6 EIA are not completely independent tests (14), these two EIAs react to different sets of antibodies, limiting the overlap of their false-positive distributions (4). The high specificity of the C6 EIA (3, 14-17) might allow this test to replace the immunoblot, without a loss in overall specificity.…”

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confidence: 99%

Evaluation of the Modified Two-Tiered Testing Method for Diagnosis of Lyme Disease in Children

2019

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Conventional two-tiered testing (CTTT) for Lyme disease includes a first-tier enzyme immunoassay (EIA) followed by a supplemental immunoblot, and modified two-tiered testing (MTTT) relies on two different sequential EIAs without the inclusion of an immunoblot. MTTT has shown promising results as an alternative strategy for the diagnosis of Lyme disease in adults but has not yet been evaluated in children. We performed a cross-sectional study of children and adolescents ≤21 years of age undergoing clinical investigation for suspected Lyme disease. Serum specimens were analyzed with both a whole-cell sonicate (WCS) and a C6 EIA, with a supplemental immunoblot if either EIA was positive or equivocal. We compared CTTT (WCS EIA followed by supplemental immunoblot) to MTTT (WCS EIA followed by C6 EIA) using McNemar’s test to evaluate for agreement beyond chance alone. We then used a kappa statistic to measure level of the agreement between testing strategies. We included 1,066 serum specimens, of which 156 (14.6%) had a positive CTTT and 165 (15.5%) had a positive MTTT. There were no significant differences between MTTT and CTTT (P = 0.16). Although the overall agreement between MTTT and CTTT was high (kappa, 0.88; 95% confidence interval, 0.84 to 0.92), 33 children had discordant test results. In a cohort of children and adolescents undergoing investigation for suspected Lyme disease, CTTT and MTTT results agreed in most cases. Since immunoblots are time-consuming, laborious, and challenging to interpret, MTTT provides a promising alternate Lyme disease testing strategy for children.

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Evaluation of a sequential enzyme immunoassay testing algorithm for Lyme disease demonstrates lack of test independence but high diagnostic specificity

Cited by 10 publications

References 14 publications

A Fully Automated Multiplex Assay for Diagnosis of Lyme Disease with High Specificity and Improved Early Sensitivity

A Fully Automated Multiplex Assay for Diagnosis of Lyme Disease with High Specificity and Improved Early Sensitivity

Revisiting the Lyme Disease Serodiagnostic Algorithm: the Momentum Gathers

Evaluation of the Modified Two-Tiered Testing Method for Diagnosis of Lyme Disease in Children

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