A descriptive analysis of the routine use of genotype MTBDRsl in a high HIV/TB prevalent region in South Africa.

Abstract

Background. Since the implementation of shortened drug regimens for the management of drug resistant tuberculosis (TB), there is a growing need for rapid detection of resistance to second line antimycobacterial drugs. The GenoType MTBDRsl Version 2 allows for the rapid molecular detection of resistance conferring mutations to fluoroquinolones (FQ) and second line injectable drugs (SLIDs). Although the GenoType MTBDRsl is recommended for use directly on smear positive and smear negative clinical specimens, the feasibility of using this assay routinely within a programmatic setting in high HIV/TB endemic areas requires exploration. Objectives. To assess the feasibility of routinely using the GenoType MTBDRsl in a high HIV/TB prevalent region and to describe the various circulating resistance patterns detected by this test in KwaZulu-Natal. Methods. A retrospective data analysis of all GenoType MTBDRsl results in newly diagnosed rifampicin resistant (RR-TB)/multidrug resistant TB (MDR-TB) specimens was performed. The assays performance on direct testing of smear positive and smear negative specimens was compared. The various mutation patterns for FQ and SLIDs identified by this test was observed. 21 Results. Of 1873 RR-TB/MDR-TB, 37,4% were smear negative and 62,5% was smear positive. In smear negative specimens, the GenoType MTBDRsl showed an inconclusive rate of 61,2%, whilst amongst the smear positive specimens, an inconclusive rate of only 6,6% was observed. The commonest mutation pattern observed for FQ occurred at the gyrA gene at codon 90 (A90V) 61/158(38,6%) followed by the D94G mutation 31/158 (19,6%). Heteroresistance for FQ was observed in the gyrA gene for 6/158 (10,1%) isolates. For SLIDs, the commonest mutation occurred in the rrs region specifically A1401G, 71/108 (65,7%) followed by C1402T at 20/108 (18.5%). Conclusion. The routine use GenoType MTBDRsl Version 2 assay is more feasible in smear positive specimens as compared to smear negative specimens in high HIV/TB settings. To improve future development of the assay, further studies looking at the various resistance patterns are required.