inhA promoter mutations: a gateway to extensively drug-resistant tuberculosis in South Africa?
Abstract:SETTING: Western Cape and Eastern Cape Provinces, South Africa.
OBJECTIVE: To assess the potential association between the evolution of extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis and mutations in the inhA promoter or the katG gene.
DESIGN: Analysis of the frequency distribution of isoniazid (INH) resistance conferring mutations in a population sample of drug-resistant isolates of M. tuberculosis.
RESULTS: In the Western Cape and Eastern Cape Provinces, the percentage of isolates exhibiting inhA promoter mutations increased significantly from respectively 48.4% and 62.4% in multidrug-resistant tuberculosis (MDR-TB) isolates to 85.5% and 91.9% in XDR isolates. Data from the Western Cape revealed that significantly more XDR-TB isolates showed mutations in the inhA promoter than in katG (85.5% vs. 60.9%, P < 0.01), while the respective proportions were equal for INH-resistant non-MDR-TB isolates (∼30%).
CONCLUSIONS: inhA promoter mutations are strongly associated with XDR-TB in South Africa. We suggest that this is due to the dual resistance to ethionamide and (low-dose) INH conferred by inhA promoter mutations. The use of molecular probe assays such as the GenoType® MTBDRplus assay, which allows the detection of inhA promoter mutations, could enable treatment regimens to be adjusted depending on the pharmacogenetic properties of the mutations detected.
Document Type: Regular Paper
Affiliations: 1: Biotec Laboratories SA (Pty) Ltd, Cape Town, South Africa 2: National Health Laboratory Service, Greenpoint, Cape Town, South Africa 3: National TB Reference Laboratory, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa 4: Nelson Mandela Bay Municipality, Port Elizabeth, South Africa
Publication date: March 1, 2011
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