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Your search keyword '"Linda Strömqvist Meuzelaar"' showing total 4 results
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4 results on '"Linda Strömqvist Meuzelaar"'

1. A novel blood-based assay for treatment monitoring of tuberculosis

Author

Alexandra J. Zimmer, Samuel G. Schumacher, Erik Södersten, Anna Mantsoki, Romain Wyss, David H. Persing, Sara Banderby, Linda Strömqvist Meuzelaar, Jacqueline Prieto, Devasena Gnanashanmugam, Purvesh Khatri, Stefano Ongarello, Morten Ruhwald, and Claudia M. Denkinger

Subjects
Tuberculosis, Host transcriptional signature, Treatment monitoring, Medicine, Biology (General), QH301-705.5, Science (General), Q1-390
Abstract

Abstract Objectives A novel 3-gene host transcriptional signature (GBP5, DUSP3 and KLF2) has been validated for tuberculosis (TB) treatment monitoring using laboratory-based RNA sequencing platforms. The signature was recently translated by Cepheid into a prototype cartridge-based test that can be run on the GeneXpert instrument. In this study, we prospectively evaluated the change in the expression of the cartridge-based 3-gene signature following treatment initiation among pulmonary TB patients who were microbiologically cured at the end of treatment. Results The 3-gene signature expression level (TB score) changed significantly over time with respect to baseline among 31 pulmonary TB patients. The greatest increase in TB score occurred within the first month of treatment (median fold-increase in TB score: 1.08 [IQR 0.54–1.52]) and plateaued after 4 months of treatment (median TB score: 1.97 [IQR: 1.03–2.33]). The rapid and substantial increase of the TB score in the first month of treatment holds promise for the early identification of patients that respond to TB treatment. The plateau in TB score at 4 months may indicate early clearance of disease and could direct treatment to be shortened. These hypotheses need to be further explored with larger prospective treatment monitoring studies.

Published
2021
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2. Diagnostic Accuracy Study of a Novel Blood-Based Assay for Identification of Tuberculosis in People Living with HIV

Author

Samuel G Schumacher, Devasena Gnanashanmugam, Erik Södersten, Linda Strömqvist Meuzelaar, Jacqueline Prieto, Anna Mantsoki, Purvesh Khatri, David H. Persing, Claudia M. Denkinger, Romain Wyss, Stefano Ongarello, and Sara Banderby

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Tuberculosis, 030106 microbiology, Human immunodeficiency virus (HIV), Host response, Diagnostic accuracy, HIV Infections, medicine.disease_cause, gene signature, Sensitivity and Specificity, Mycobacterium tuberculosis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Cepheid, medicine, diagnostics, host response, Humans, 030212 general & internal medicine, Xpert, Tuberculosis, Pulmonary, rapid tests, biology, human immunodeficiency virus, business.industry, Diagnostic Tests, Routine, Sputum, Mycobacteriology and Aerobic Actinomycetes, Gene signature, biology.organism_classification, medicine.disease, bacterial infections and mycoses, Triage, Confidence interval, 3-gene, nonsputum, tuberculosis, Rifampin, business
Abstract

A nonsputum triage test to rule out tuberculosis (TB) disease is a WHO high-priority diagnostic, and a combinatory score based on a 3-gene host signature has shown promise in discriminating TB from other illnesses. We evaluated the accuracy of an early-prototype cartridge assay (“Xpert MTB Host Response” or Xpert-MTB-HR-Prototype) of this 3-gene signature on biobanked blood samples from people living with HIV (PLHIV) against a comprehensive microbiological reference standard (CMRS) and against Xpert MTB/RIF on the first sputum sample alone., A nonsputum triage test to rule out tuberculosis (TB) disease is a WHO high-priority diagnostic, and a combinatory score based on a 3-gene host signature has shown promise in discriminating TB from other illnesses. We evaluated the accuracy of an early-prototype cartridge assay (“Xpert MTB Host Response” or Xpert-MTB-HR-Prototype) of this 3-gene signature on biobanked blood samples from people living with HIV (PLHIV) against a comprehensive microbiological reference standard (CMRS) and against Xpert MTB/RIF on the first sputum sample alone. We depict results based on performance targets set by the WHO in comparison with a laboratory-based C-reactive protein (CRP) assay. Of 201 patients included, 67 were culture positive for Mycobacterium tuberculosis. The areas under the concentration-time curve (AUCs) for Xpert-MTB-HR-Prototype were 0.89 (confidence interval [CI], 0.83 to 0.94) against the CMRS and 0.94 (CI, 0.89 to 0.98) against Xpert MTB/RIF. Considering Xpert-MTB-HR-Prototype as a triage test (at the nearest upper value of sensitivity to 90%), specificities were 55.8% (CI, 47.2 to 64.1%) compared to the CMRS and 85.9% (CI, 79.3 to 90.7%) compared to Xpert MTB/RIF as confirmatory tests. Considering Xpert-MTB-HR-Prototype as a stand-alone diagnostic test, at a specificity near 95%, the test achieved a sensitivity of 65.7% (CI, 53.7 to 75.9%), while the CRP assay achieved a sensitivity of only 13.6% (CI, 7.3 to 23.4%). In this first accuracy study of a prototype blood-based host marker assay, we show the possible value of the assay for triage and diagnosis in PLHIV.

Published
2021

3. Diagnostic accuracy study of a novel blood-based assay# for identification of TB in people living with HIV

Author

Purvesh Khatri, Anna Mantsoki, Claudia M. Denkinger, Linda Strömqvist Meuzelaar, David H. Persing, Sara Banderby, Devasena Gnanashanmugam, Jacqueline Prieto, Samuel G Schumacher, Erik Södersten, Romain Wyss, and Stefano Ongarello

Subjects
medicine.medical_specialty, biology, business.industry, Human immunodeficiency virus (HIV), Diagnostic test, Diagnostic accuracy, biology.organism_classification, medicine.disease_cause, Active tuberculosis, Triage, Mycobacterium tuberculosis, Internal medicine, medicine, Sputum, medicine.symptom, business, Reference standards
Abstract

A non-sputum triage test to rule out TB disease is a WHO high-priority diagnostic and a combinatory score based on a 3-gene host-signature has shown promise in discriminating TB from other illnesses. We evaluated the accuracy of an early-prototype cartridge-assay (“Xpert MTB Host Response”, or Xpert-MTB-HR-Prototype) of this 3-gene signature on bio-banked blood-samples from PLHIV against a comprehensive microbiological reference standard (CMRS) and against Xpert® MTB/RIF on first sputum alone. We depict results based on performance targets set by WHO in comparison with a laboratory-based CRP assay. Of 201 patients included, 67 were culture-positive for Mycobacterium tuberculosis. AUC for the Xpert-MTB-HR-Prototype was 0·89 (CI 0·83-0·94) against the CMRS and 0·94 (CI 0·89-0·98) against Xpert MTB/RIF. Considering Xpert-MTB-HR-Prototype as a triage test (at nearest upper value of sensitivity to 90%), specificity was 55·8% (CI 47·2-64·1) compared to the CMRS and 85·9% (CI 79·3-90·7) compared to Xpert MTB/RIF as confirmatory tests. Considering Xpert-MTB-HR-Prototype as a stand-alone diagnostic test, at a specificity near 95%, the test achieved a sensitivity of 65·7% (CI 53·7-75·9) while CRP achieved a sensitivity of only 13·6% (CI 7·3-23·4). In this first accuracy study of a prototype blood-based host-marker assay, we show the possible value of the assay for triage and diagnosis in PLHIV.One Sentence SummaryThis is an accuracy study of a blood-based host-marker assay demonstrating its potential in triage and diagnosis of active tuberculosis (TB) in people living with HIV (PLHIV).

Published
2020

4. MegaPlex PCR: a strategy for multiplex amplification

Author

Guido Kopal, J Paul Pasche, Anthony J. Brookes, Owen Lancaster, and Linda Strömqvist Meuzelaar

Subjects
Cell Biology, Computational biology, Biology, Bioinformatics, Polymerase Chain Reaction, Biochemistry, DNA sequencing, Humans, Multiplex, Primer (molecular biology), Molecular Biology, Genotyping, DNA Primers, Biotechnology
Abstract

'MegaPlex PCR' is a robust technology for highly multiplexed amplification of specific DNA sequences. It uses target-specific pairs of PCR primers that are physically separated by surface immobilization. Initial surface-based amplification cycles are then coupled to efficient solution-phase PCR using one common primer pair. We demonstrate this method by co-amplifying and genotyping 75 unselected human single-nucleotide polymorphism (SNP) loci.

Published
2007

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