Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice.
Bottom Line: Quantification of specific precursor → fragment transitions of approximately 2000 individual mycolic acids (MAs) resulted in high analytical sensitivity and specificity.Furthermore, we quantified MA species in lung tissue of TB-infected mice and demonstrated effective clearance of MA levels following curative rifampicin treatment.Thus, our results demonstrate for the first time the feasibility and clinical relevance of direct detection of mycobacterial lipids as biomarkers of TB infection.
Affiliation: Yong Loo Lin School of Medicine, Department of Biochemistry, National University of Singapore, Singapore. email@example.comShow MeSH
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Mentions: Using a blinded format, we conducted a retrospective, multicenter, case–control study of 70 patients with pulmonary TB with varying disease burdens and 40 non-TB controls (individuals with clinical symptoms of TB who were diagnosed as non-TB by culture). For both groups, the HIV status and bacterial burden were known (Fig 2A; for details, see demographic information in Table S2 of Supporting information). Strikingly, robust α-, keto- and methoxy-MA signals were detected in as little as 200 µl of sputum from TB patients (Fig 2B). This was too small of a sample volume for detecting MAs with alternative methods (Shui et al, 2007). Further, the concentration of major MAs detected in sputum obtained from TB-infected individuals was significantly (∼100 times) higher than in samples from non-TB controls (Fig 2C, see also discussion for false positives and negatives). As shown in Fig 2E, we classified 66 out of the 70 TB patients correctly as TB positive (‘true positive’) and 37 out of the 40 non-TB controls correctly as non-TB (‘true negative’). Three were falsely classified as TP positive (‘false positive’) and four were falsely classified as non-TB (‘false negative’). Using these data, we calculated a statistical sensitivity of 94% and a specificity of 93% (sensitivity: number of true positives divided by the sum of true positives and false negatives; specificity: number of true negatives divided by the sum of true negatives and false positives) and even slightly better values for the HIV positive individuals alone (Fig 2F).
Affiliation: Yong Loo Lin School of Medicine, Department of Biochemistry, National University of Singapore, Singapore. firstname.lastname@example.org