T2 Magnetic Resonance Assay-Based Direct Detection of Three Lyme Disease-Related Borrelia Species in Whole-Blood Samples

Snyder, Jessica L.; Giese, Heidi; Bandoski-Gralinski, Cheryl; Townsend, Jessica; Jacobson, Beck E.; Shivers, Robert P.; Schotthoefer, Anna M.; Fritsche, Thomas R.; Green, Clayton; Callister, Steven M.; Branda, John A.; Lowery, Thomas J.

doi:10.1128/jcm.00510-17

Cited by 9 publications

(3 citation statements)

References 31 publications

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“…Recently, T2 magnetic resonance assay was evaluated to detect Candida spp. and some bacteria in whole blood (Mylonakis et al, 2015 ; Snyder et al, 2017 ; Peker et al, 2018 ). In the present study, we evaluated the Magicplex TM Sepsis test (MP), comparing it with conventional BC.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Magicplex™ Sepsis Real-Time Test for the Rapid Diagnosis of Bloodstream Infections in Adults

Zboromyrska¹,

Cillóniz

Cobos-Trigueros

et al. 2019

Front. Cell. Infect. Microbiol.

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Sepsis is a serious health condition worldwide, affecting more than 30 million people globally each year. Blood culture (BC) is generally used to diagnose sepsis because of the low quantity of microbes occurring in the blood during such infections. However, ~50% of bloodstream infections (BSI) give negative BC, this figure being higher for sepsis, which delays the start of appropriate antimicrobial therapy. This prospective study evaluated a multiplex real-time polymerase chain reaction, the MagicplexTM Sepsis test (MP), for the detection of pathogens from whole blood, comparing it to routine BC. We analyzed 809 blood samples from 636 adult patients, with 132/809 (16.3%) of the samples positive for one or more relevant microorganism according to BC and/or MP. The sensitivity and specificity of MP were 29 and 95%, respectively, while the level of agreement between BC and MP was 87%. The rate of contaminated samples was higher for BC (10%) than MP (4.8%) (P < 0.001). Patients with only MP-positive samples were more likely to be on antimicrobial treatment (47%) than those with only BC-positive samples (18%) (P = 0.002). In summary, the MP test could be useful in some clinical setting, such as among patients on antibiotic therapy. Nevertheless, a low sensitivity demonstrated impairs its use as a part of a routine diagnostic algorithm.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the Magicplex™ Sepsis Real-Time Test for the Rapid Diagnosis of Bloodstream Infections in Adults

Zboromyrska¹,

Cillóniz

Cobos-Trigueros

et al. 2019

Front. Cell. Infect. Microbiol.

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“…It appears possible to detect B. burgdorferi in the blood with higher sensitivity [27] in early Lyme disease. In addition, there are a variety of PCR-based assays in development that use unconventional signal detection or amplification methods [27,28], with the potential to achieve a limit of detection (LOD) that is substantially lower than with standard PCR methods.…”

Section: Detection Of Dna: Nucleic Acid Amplification Testsmentioning

confidence: 99%

Direct Diagnostic Tests for Lyme Disease

Schutzer

Body²,

Boyle

et al. 2018

Clinical Infectious Diseases

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Borrelia burgdorferi was discovered to be the cause of Lyme disease in 1983, leading to seroassays. The 1994 serodiagnostic testing guidelines predated a full understanding of key B. burgdorferi antigens and have a number of shortcomings. These serologic tests cannot distinguish active infection, past infection, or reinfection. Reliable direct-detection methods for active B. burgdorferi infection have been lacking in the past but are needed and appear achievable. New approaches have effectively been applied to other emerging infections and show promise in direct detection of B. burgdorferi infections.

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“…can often be detected using culture or polymerase chain reaction (PCR) of skin biopsies taken from EM lesions [4], this approach is impractical for routine use. Blood PCR has not been very useful; the sensitivity of whole-blood or plasma PCR in patients with EM is usually in the 30%-50% range [5][6][7][8][9], and blood PCR is seldom positive in patients with later manifestations of LB [10]. Similarly, cerebrospinal fluid PCR is poorly sensitive in patients with Lyme neuroborreliosis [11,12], leaving PCR analysis of joint fluid/synovial tissue from patients with suspected Lyme arthritis as the only clinically useful PCR application.…”

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confidence: 99%

Detection of Borrelia burgdorferi Cell-free DNA in Human Plasma Samples for Improved Diagnosis of Early Lyme Borreliosis

Branda

Lemieux

Blair³

et al. 2020

Clinical Infectious Diseases

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Background Laboratory confirmation of early Lyme borreliosis (LB) is challenging. Serology is insensitive during the first days to weeks of infection, and blood PCR offers similarly poor performance. Here, we demonstrate that detection of Borrelia burgdorferi (B.b.) cell-free DNA (cfDNA) in plasma can improve diagnosis of early LB. Methods B.b. detection in plasma samples using unbiased metagenomic cfDNA sequencing performed by a commercial laboratory (Karius Inc.) was compared with serology and blood PCR in 40 patients with physician-diagnosed EM, 28 of whom were confirmed to have LB by skin biopsy culture (N=18), seroconversion (N=2) or both (N=8). B.b. sequence analysis was performed using investigational detection thresholds, different from Karius’ clinical test. Results B.b.cfDNA was detected in 18/28 patients (64%) with laboratory-confirmed EM. In comparison, sensitivity of acute-phase serology using modified two-tiered testing (MTTT) was 50% (P=0.45); sensitivity of blood PCR was 7% (P=0.0002). Combining B.b.cfDNA detection and MTTT increased diagnostic sensitivity to 86%, significantly higher than either approach alone (P≤0.04). B.b.cfDNA sequences matched precisely with strain-specific sequence generated from the same individual’s cultured B.b. isolate. B.b.cfDNA was not observed at any level in plasma from 684 asymptomatic ambulatory individuals. Among 3000 hospitalized patients tested as part of clinical care, B.b.cfDNA was detected in only two individuals, both of whom had clinical presentations consistent with LB. Conclusions This is the first report of B.b.cfDNA detection in early LB and a demonstration of potential diagnostic utility. The combination of B.b.cfDNA detection and acute-phase MTTT improves clinical sensitivity for diagnosis of early LB.

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T2 Magnetic Resonance Assay-Based Direct Detection of Three Lyme Disease-Related Borrelia Species in Whole-Blood Samples

Cited by 9 publications

References 31 publications

Evaluation of the Magicplex™ Sepsis Real-Time Test for the Rapid Diagnosis of Bloodstream Infections in Adults

Evaluation of the Magicplex™ Sepsis Real-Time Test for the Rapid Diagnosis of Bloodstream Infections in Adults

Direct Diagnostic Tests for Lyme Disease

Detection of Borrelia burgdorferi Cell-free DNA in Human Plasma Samples for Improved Diagnosis of Early Lyme Borreliosis

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