title: Rapid screening of MDR-TB using molecular Line Probe Assay is feasible in Uganda.
abstract: BACKGROUND
  About 500 new smear-positive Multidrug-resistant tuberculosis (MDR-TB) cases are estimated to occur per year in Uganda. In 2008 in Kampala, MDR-TB prevalence was reported as 1.0% and 12.3% in new and previously treated TB cases respectively. Line probe assays (LPAs) have been recently approved for use in low income settings and can be used to screen smear-positive sputum specimens for resistance to rifampicin and isoniazid in 1-2 days.
  
  
  METHODS
  We assessed the performance of a commercial line probe assay (Genotype MTBDRplus) for rapid detection of rifampicin and isoniazid resistance directly on smear-positive sputum specimens from 118 previously treated TB patients in a reference laboratory in Kampala, Uganda. Results were compared with MGIT 960 liquid culture and drug susceptibility testing (DST). LPA testing was also performed in parallel in a University laboratory to assess the reproducibility of results.
  
  
  RESULTS
  Overall, 95.8% of smear-positive specimens gave interpretable results within 1-2 days using LPA. Sensitivity, specificity, positive and negative predictive values were 100.0%, 96.1%, 83.3% and 100.0% for detection of rifampicin resistance; 80.8%, 100.0%, 100.0% and 93.0% for detection of isoniazid resistance; and 92.3%, 96.2%, 80.0% and 98.7% for detection of multidrug-resistance compared with conventional results. Reproducibility of LPA results was very high with 98.1% concordance of results between the two laboratories.
  
  
  CONCLUSIONS
  LPA is an appropriate tool for rapid screening for MDR-TB in Uganda and has the potential to substantially reduce the turnaround time of DST results. Careful attention must be paid to training, supervision and adherence to stringent laboratory protocols to ensure high quality results during routine implementation.
authors.affiliation: Foundation for Innovative New Diagnostics, Kampala, Uganda. heidi.albert@finddiagnostics.org
authors.forename: Heidi
authors.initials: H
authors.lastname: Albert
authors.forename: Freddie
authors.initials: F
authors.lastname: Bwanga
authors.forename: Sheena
authors.initials: S
authors.lastname: Mukkada
authors.forename: Barnabas
authors.initials: B
authors.lastname: Nyesiga
authors.forename: Julius Patrick
authors.initials: JP
authors.lastname: Ademun
authors.forename: George
authors.initials: G
authors.lastname: Lukyamuzi
authors.forename: Melles
authors.initials: M
authors.lastname: Haile
authors.forename: Sven
authors.initials: S
authors.lastname: Hoffner
authors.forename: Moses
authors.initials: M
authors.lastname: Joloba
authors.forename: Richard
authors.initials: R
authors.lastname: O'Brien
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000379:methods; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012293:Rifampin / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology; D013997:Time Factors; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis*; D014454:Uganda
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin