title: Evaluation of GenoType MTBDRplus for the rapid detection of drug-resistant tuberculosis in Ghana.
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.
  
  
  METHODS
  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%.
  
  
  CONCLUSIONS
  The high sensitivity of MTBDRplus makes it a valuable addition to the conventional TB diagnostic algorithm in Ghana.
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.|Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Adwoa
authors.initials: A
authors.lastname: Asante-Poku
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
authors.forename: Isaac Darko
authors.initials: ID
authors.lastname: Otchere
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
authors.forename: Emelia
authors.initials: E
authors.lastname: Danso
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
authors.forename: David Delali
authors.initials: DD
authors.lastname: Mensah
authors.affiliation: National Tuberculosis Control Program, Ghana Health Service.
authors.forename: Frank
authors.initials: F
authors.lastname: Bonsu
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Yeboah-Manu
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D024901:Drug Resistance, Multiple, Bacterial; D005869:Ghana; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D025202:Molecular Diagnostic Techniques / Q000379:methods; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification*; D010641:Phenotype; D012293:Rifampin / Q000494:pharmacology; D012680:Sensitivity and Specificity; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin