Evaluation of GenoTypeW MTBDRplus for the rapid detection of drug-resistant tuberculosis in Ghana
International Journal of Tuberculosis and Lung Disease
Noguchi Memorial Institute for Medical Research, University of Ghana, P O Box LG 581, Legon, Ghana; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland; National Tuberculosis Control Programme, Ghana Health Service, Accra, Ghana, 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 (GenoTypew 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. RESULT S : 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%. CONCLUS ION: The high sensitivity of MTBDRplus makes it a valuable addition to the conventional TB diagnostic algorithm in Ghana. © 2015 The Union.
isoniazid; rifampicin; ahpC gene; amino acid substitution; antibiotic resistance; Article; bacterial gene; bacterium detection; bacterium isolate; bacterium isolation; codon; cross-sectional study; drug resistant tuberculosis; drug sensitivity; gene amplification; gene expression profiling; Ghana; human; indirect proportion method; inh A; katG gene; MTBDRplus; mutational analysis; oxyR gene; phenotype; polymerase chain reaction; priority journal; promoter region; rpoB gene; single nucleotide polymorphism
097134/Z/11, National Science Foundation; PP00P3-150750, NSF, National Science Foundation