Adwoa Asante-Poku1,2,3, Isaac Darko Otchere1, Emelia Danso1, David Delali Mensah1, Frank Bonsu4, Sebastien Gagneux2,3, Dorothy Yeboah-Manu1. 1. Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. 2. Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland. 3. University of Basel, Basel, Switzerland. 4. National Tuberculosis Control Program, Ghana Health Service.
Abstract
BACKGROUND: Rapid but simple diagnostic tools for the detection of drug-resistant (DR) tuberculosis (TB) have been acknowledged as being important for its effective management and control. OBJECTIVE: To establish a molecular line-probe assay (GenoType MTBDRplus) for detecting DR-TB in Ghana. METHOD: We first screened 113 Mycobacterium tuberculosis isolates using the indirect proportion method and MTBDRplus. The rpoB and katG genes and the promoter regions of oxyR-ahpC and inhA were sequenced to identify mutations in isolates found to be resistant on phenotypic drug susceptibility testing and/or MTBDRplus. We then analysed an additional 412 isolates using only MTBDRplus. RESULTS: Respectively 43 (8.2%) and 8 (1.5%) isolates were resistant to isoniazid (INH) and rifampicin (RMP), while 8 (1.5%) were multidrug-resistant. In resistant isolates, mutations in codon 450 of rpoB and codon 315 of katG, conferring resistance to respectively RMP and INH, dominated. We found two RMP-resistant isolates with a S450L substitution, each harbouring an additional mutation at S388L and Q409R. Using phenotypic testing as gold standard, the MTBDRplus assay showed a sensitivity and specificity in the detection of RMP and INH resistance and multidrug resistance of respectively 100% and 100%, 83.3% and 100%, and 100% and 100%. CONCLUSION: The high sensitivity of MTBDRplus makes it a valuable addition to the conventional TB diagnostic algorithm in Ghana.
BACKGROUND: Rapid but simple diagnostic tools for the detection of drug-resistant (DR) tuberculosis (TB) have been acknowledged as being important for its effective management and control. OBJECTIVE: To establish a molecular line-probe assay (GenoType MTBDRplus) for detecting DR-TB in Ghana. METHOD: We first screened 113 Mycobacterium tuberculosis isolates using the indirect proportion method and MTBDRplus. The rpoB and katG genes and the promoter regions of oxyR-ahpC and inhA were sequenced to identify mutations in isolates found to be resistant on phenotypic drug susceptibility testing and/or MTBDRplus. We then analysed an additional 412 isolates using only MTBDRplus. RESULTS: Respectively 43 (8.2%) and 8 (1.5%) isolates were resistant to isoniazid (INH) and rifampicin (RMP), while 8 (1.5%) were multidrug-resistant. In resistant isolates, mutations in codon 450 of rpoB and codon 315 of katG, conferring resistance to respectively RMP and INH, dominated. We found two RMP-resistant isolates with a S450L substitution, each harbouring an additional mutation at S388L and Q409R. Using phenotypic testing as gold standard, the MTBDRplus assay showed a sensitivity and specificity in the detection of RMP and INH resistance and multidrug resistance of respectively 100% and 100%, 83.3% and 100%, and 100% and 100%. CONCLUSION: The high sensitivity of MTBDRplus makes it a valuable addition to the conventional TB diagnostic algorithm in Ghana.
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