title: Validation of biomarkers for distinguishing Mycobacterium tuberculosis from non-tuberculous mycobacteria using gas chromatography-mass spectrometry and chemometrics.
abstract: Tuberculosis (TB) remains a major international health problem. Rapid differentiation of Mycobacterium tuberculosis complex (MTB) from non-tuberculous mycobacteria (NTM) is critical for decisions regarding patient management and choice of therapeutic regimen. Recently we developed a 20-compound model to distinguish between MTB and NTM. It is based on thermally assisted hydrolysis and methylation gas chromatography-mass spectrometry and partial least square discriminant analysis. Here we report the validation of this model with two independent sample sets, one consisting of 39 MTB and 17 NTM isolates from the Netherlands, the other comprising 103 isolates (91 MTB and 12 NTM) from Stellenbosch, Cape Town, South Africa. All the MTB strains in the 56 Dutch samples were correctly identified and the model had a sensitivity of 100% and a specificity of 94%. For the South African samples the model had a sensitivity of 88% and specificity of 100%. Based on our model, we have developed a new decision-tree that allows the differentiation of MTB from NTM with 100% accuracy. Encouraged by these findings we will proceed with the development of a simple, rapid, affordable, high-throughput test to identify MTB directly in sputum.
authors.affiliation: Analytical Chemistry and Forensic Science, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ngoc A
authors.initials: NA
authors.lastname: Dang
authors.forename: Sjoukje
authors.initials: S
authors.lastname: Kuijper
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Walters
authors.forename: Mareli
authors.initials: M
authors.lastname: Claassens
authors.forename: Dick
authors.initials: D
authors.lastname: van Soolingen
authors.forename: Gabriel
authors.initials: G
authors.lastname: Vivo-Truyols
authors.forename: Hans-Gerd
authors.initials: HG
authors.lastname: Janssen
authors.forename: Arend H J
authors.initials: AH
authors.lastname: Kolk
mesh_terms: D000465:Algorithms; D015415:Biomarkers / Q000378:metabolism*; D016002:Discriminant Analysis; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D006868:Hydrolysis; D016018:Least-Squares Analysis; D008745:Methylation; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D009426:Netherlands; D009170:Nontuberculous Mycobacteria / Q000302:isolation & purification*; D015203:Reproducibility of Results; D013019:South Africa; D013696:Temperature
chemical_list: D015415:Biomarkers