Abstract:
BACKGROUND : The incidence of multidrug-resistant tuberculosis (MDR-TB) is increasing and the emergence of
extensively drug-resistant tuberculosis (XDR-TB) is a major challenge. Controlling resistance, reducing transmission
and improving treatment outcomes in MDR/XDR-TB patients is reliant on susceptibility testing. Susceptibility testing
using phenotypic methods is labour intensive and time-consuming. Alternative methods, such as molecular assays
are easier to perform and have a rapid turn-around time. The World Health Organization (WHO) has endorsed the
use of line probe assays (LPAs) for first and second line diagnostic screening of MDR/XDR-TB.
METHODS : We compared the performance of LPAs to BACTEC MGIT 960 system for susceptibility testing of bacterial
resistance to first-line drugs: rifampicin (RIF), isoniazid (INH), ethambutol (EMB), and second-line drugs ofloxacin (OFL)
and kanamycin (KAN). One hundred (100) consecutive non-repeat Mycobacterium tuberculosis cultures, resistant to
either INH or RIF or both, as identified by BACTEC MGIT 960 were tested. All isoniazid resistant cultures (n = 97) and RIF
resistant cultures (n = 90) were processed with Genotype®MTBDRplus and Genotype®MTBDRsl line probe assays (LPAs).
The agar proportion method was employed to further analyze discordant LPAs and the MGIT 960 isolates.
RESULTS : The Genotype ®MTBDRplus (version 2) sensitivity, specificity, PPV and NPV from culture isolates were as follows:
RIF, 100%, 87.9, 58.3% and 100%; INH, 100%, 94.4%, 93.5% and 100%. The sensitivity, specificity PPV and NPV for Genotype
® MTBDRsl (version 1 and 2) from culture isolates were as follows: EMB, 60.0%, 89.2%, 68.2% and 85.3%; OFL, 100%, 91.4%,
56.2% and 100%; KAN, 100%, 97.7%, 60.0% and 100%. Line probe assay showed an excellent agreement (k = 0.93) for INH
susceptibility testing when compared to MGIT 960 system while there was good agreement (k = 0.6–0.7) between both
methods for RIF, OFL, KAN testing and moderate agreement for EMB (k = 0.5). A high RIF mono-resistance (MGIT 960 33/
97 and LPA 43/97) was observed.
CONCLUSION : LPAs are an efficient and reliable rapid molecular DST assay for rapid susceptibility screening of MDR and
XDR-TB. Using LPAs in high MDR/XDR burden countries allows for appropriate and timely treatment, which will reduce
transmission rates, morbidity and improve treatment outcomes in patients.
