Rapid screening of MDR-TB using molecular Line Probe Assay is feasible in Uganda.
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.
Albert
Heidi
H
Foundation for Innovative New Diagnostics, Kampala, Uganda. heidi.albert@finddiagnostics.org
Bwanga
Freddie
F
Mukkada
Sheena
S
Nyesiga
Barnabas
B
Ademun
Julius Patrick
JP
Lukyamuzi
George
G
Haile
Melles
M
Hoffner
Sven
S
Joloba
Moses
M
O'Brien
Richard
R
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
D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin