Comparison of line probe assay to BACTEC MGIT 960 system for susceptibility testing of first and second-line anti-tuberculosis drugs in a referral laboratory in South Africa
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Authors
Maningi, Nontuthuko Excellent
Malinga, Lesibana Anthony
Antiabong, John Francis
Lekalakala, Ruth M.
Mbelle, Nontombi Marylucy
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central
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.
Description
Keywords
Drug-resistance, Line-probe assay, MGIT 960 system, Multidrug-resistant tuberculosis (MDR-TB), Mycobacterium tuberculosis (MTB), Kanamycin (KAN), Ofloxacin (OFL), Ethambutol (EMB), Rifampicin (RIF), Isoniazid (INH)
Sustainable Development Goals
Citation
Maningi, N.E., Malinga, L.A., Antiabong, J.F. et al. 2017, 'Comparison of line probe assay to BACTEC MGIT 960 system for susceptibility testing of first and second-line anti-tuberculosis drugs in a referral laboratory in South Africa', BMC Infectious Diseases, vol. 17, art. no. 795, pp. 1-8.