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.
Highlights
Tuberculosis (TB) remains a major international health threat, with 8.7 million new cases and 1.4 million deaths in 2011 [1]
In the Netherlands all hospitals are required by law to send all mycobacterial isolates, whether Mycobacterium tuberculosis complex (MTB) or non-tuberculous mycobacteria (NTM), to the Dutch Mycobacteria Reference Laboratory at the RIVM for species determination, drug susceptibility testing and strain typing for contact investigations
Chemometric method The partial least square discriminant analysis (PLS-DA) model we developed to classify samples as NTM or MTB is based on the concentration levels of 20 compounds in the THM-GCMS chromatograms [17]
Summary
Tuberculosis (TB) remains a major international health threat, with 8.7 million new cases and 1.4 million deaths in 2011 [1]. An estimated 13% of new TB cases occur in those infected with HIV [1]. The Ziehl-Neelsen test cannot distinguish Mycobacterium tuberculosis complex (MTB) from non-tuberculous mycobacteria (NTM). Rapid culture systems have been developed, for example, the Mycobacteria Growth Indicator Tube (MGIT) method [9] and the Microscopic Observation Drug Susceptibility assay [10]. These tests do not differentiate between MTB and NTM. This distinction, is essential to ensure the correct choice of therapy
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