Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease

Lahey, Lauren J.; Panas, Michael W.; Mao, Rong; Delanoy, Michelle; Flanagan, John J.; Binder, Steven R.; Rebman, Alison W.; Montoya, José G.; Soloski, Mark J.; Steere, Allen C.; Dattwyler, Raymond J.; Arnaboldi, Paul M.; Robinson, William H.

doi:10.1128/jcm.02111-15

Cited by 36 publications

(40 citation statements)

References 42 publications

(39 reference statements)

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“…On-going work into new immunoassay techniques and combinations of antigen targets that may help inform disease stage will hopefully improve LD diagnostics in the future [60,79,90]. Development of point-of care tests that do not require highly specialized technical skills and subjective interpretation of the results would help address some of the criticisms of immunoblot techniques.…”

Section: Discussionmentioning

confidence: 99%

The Accuracy of Diagnostic Tests for Lyme Disease in Humans, A Systematic Review and Meta-Analysis of North American Research

et al. 2016

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There has been an increasing incidence of Lyme disease (LD) in Canada and the United States corresponding to the expanding range of the Ixodes tick vector and Lyme disease agent (Borrelia burgdorferi sensu stricto). There are many diagnostic tests for LD available in North America, all of which have some performance issues, and physicians are concerned about the appropriate use and interpretation of these tests. The objective of this systematic review is to summarize the North American evidence on the accuracy of diagnostic tests and test regimes at various stages of LD. Included in the review are 48 studies on diagnostic tests used in North America published since 1995. Thirteen studies examined a two-tier serological test protocol vs. clinical diagnosis, 24 studies examined single assays vs. clinical diagnosis, 9 studies examined single immunoblot vs. clinical diagnosis, 7 studies compared culture or PCR direct detection methods vs. clinical diagnosis, 22 studies compared two or more tests with each other and 8 studies compared a two-tiered serological test protocol to another test. Recent studies examining the sensitivity and specificity of various test protocols noted that the Immunetics® C6 B. burgdorferi ELISA™ and the two tier approach have superior specificity compared to proposed replacements, and the CDC recommended western blot algorithm has equivalent or superior specificity over other proposed test algorithms. There is a dramatic increase in test sensitivity with progression of B. burgdorferi infection from early to late LD. Direct detection methods, culture and PCR of tissue or blood samples were not as sensitive or timely compared to serological testing. It was also noted that there are a large number of both commercial (n = 42) and in-house developed tests used by private laboratories which have not been evaluated in the primary literature.

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Section: Discussionmentioning

confidence: 99%

The Accuracy of Diagnostic Tests for Lyme Disease in Humans, A Systematic Review and Meta-Analysis of North American Research

et al. 2016

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“…The common goal of many of these emerging approaches is to directly detect the presence or absence of Borrelia in a sensitive and specific manner. These evolving techniques have begun to uncover a substantial number of cases where there is evidence of active or previous Borrelia infection, alongside negative serology [44][45][46][47][48][49][50]. However, the majority of these approaches are not yet widely adopted in the clinic, but have been useful in research to learn more about the mechanisms of disease at various stages.…”

Section: Diagnostic Challengesmentioning

confidence: 99%

Lyme Disease Frontiers: Reconciling Borrelia Biology and Clinical Conundrums

Bamm

Mainprize

et al. 2019

Pathogens

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Lyme disease is a complex tick-borne zoonosis that poses an escalating public health threat in several parts of the world, despite sophisticated healthcare infrastructure and decades of effort to address the problem. Concepts like the true burden of the illness, from incidence rates to longstanding consequences of infection, and optimal case management, also remain shrouded in controversy. At the heart of this multidisciplinary issue are the causative spirochetal pathogens belonging to the Borrelia Lyme complex. Their unusual physiology and versatile lifestyle have challenged microbiologists, and may also hold the key to unlocking mysteries of the disease. The goal of this review is therefore to integrate established and emerging concepts of Borrelia biology and pathogenesis, and position them in the broader context of biomedical research and clinical practice. We begin by considering the conventions around diagnosing and characterizing Lyme disease that have served as a conceptual framework for the discipline. We then explore virulence from the perspective of both host (genetic and environmental predispositions) and pathogen (serotypes, dissemination, and immune modulation), as well as considering antimicrobial strategies (lab methodology, resistance, persistence, and clinical application), and borrelial adaptations of hypothesized medical significance (phenotypic plasticity or pleomorphy).

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“…Most recently, multiplex assays for the detection of infection in dogs (29) and in humans (30) have shown strong potential for this diagnostic platform. Specifically, a combination of 10 antigens was used to test serum antibodies from Lyme disease patients at different phases (30). This test showed improved sensitivity over the two-tier test (87.5% versus 67.5%) in the early phase but was not compared to the C6 test or tested against samples from patients with multiple look-alike diseases for specificity.…”

Section: Discussionmentioning

confidence: 99%

Five-Antigen Fluorescent Bead-Based Assay for Diagnosis of Lyme Disease

Embers

Hasenkampf

Barnes

et al. 2016

Clin Vaccine Immunol

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The systematically difficult task of diagnosing Lyme disease can be simplified by sensitive and specific laboratory tests. The currently recommended two-tier test for serology is highly specific but falls short in sensitivity, especially in the early acute phase. We previously examined serially collected serum samples from Borrelia burgdorferi-infected rhesus macaques and defined a combination of antigens that could be utilized for detection of infection at all phases of disease in humans. The five B. burgdorferi antigens, consisting of OspC, OspA, DbpA, OppA2, and the C6 peptide, were combined into a fluorescent cytometric beadbased assay for the detection of B. burgdorferi antigen-specific IgG antibodies. Samples from Lyme disease patients and controls were used to determine the diagnostic value of this assay. Using this sample set, we found that our five-antigen multiplex IgG assay exhibited higher sensitivity (79.5%) than the enzyme immunoassay (EIA) (76.1%), the two-tier test (61.4%), and the C6 peptide enzyme-linked immunosorbent assay (ELISA) (77.2%) while maintaining specificity over 90%. When detection of IgM was added to the bead-based assay, the sensitivity improved to 91%, but at a cost of reduced specificity (78%). These results indicate that the rational combination of antigens in our multiplex assay may offer an improved serodiagnostic test for Lyme disease. With an estimated 300,000 new cases each year, Lyme disease is the most common vector-borne disease in North America (http://www.cdc.gov/lyme/stats/humanCases.html) (1). The burden of this disease in many parts of Europe is also staggering (1, 2). Treatment with antibiotics is generally effective, even more so when employed soon after infection (3). Therefore, early and reliable laboratory diagnosis is critical for effective cure of Lyme disease patients.Patient serum antibodies specific for Borrelia burgdorferi antigens are detected with currently recommended laboratory tests for Lyme disease. While the detection of antigen may be preferred for early diagnosis, this is encumbered by the absence of detectable spirochetes or spirochetal antigen in the bloodstream once the organism has disseminated. Thus, the use of antigen detection from a blood or skin biopsy specimen has not demonstrated favorable sensitivity (4). The two most commonly used tests for diagnosis of Lyme disease in North America are (i) the two-tier test that includes an enzyme-linked immunosorbent assay (ELISA) and confirmatory Western blotting and (ii) the C6 test, where antibodies to a specific peptide within a conserved region of VlsE, the B. burgdorferi antigen, are detected (5-8). Both the twotier and C6 tests exhibit high specificity and are most sensitive for patients in the disseminated phases of disease (5, 8-10). In addition, the C6 test has been evaluated as an indicator of treatment outcome in the United States (11, 12), with a Ն4-fold decline in antibody titer (up to 6 months after treatment) in a majority of patients. The Western blot procedure is technically dema...

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Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease

Cited by 36 publications

References 42 publications

The Accuracy of Diagnostic Tests for Lyme Disease in Humans, A Systematic Review and Meta-Analysis of North American Research

The Accuracy of Diagnostic Tests for Lyme Disease in Humans, A Systematic Review and Meta-Analysis of North American Research

Lyme Disease Frontiers: Reconciling Borrelia Biology and Clinical Conundrums

Five-Antigen Fluorescent Bead-Based Assay for Diagnosis of Lyme Disease

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