Discordance of the Repeat GeneXpert MTB/RIF Test for Rifampicin Resistance Detection Among Patients Initiating MDR-TB Treatment in Uganda

Abstract

Background The Global Laboratory Initiative (GLI) guidelines recommend to repeat GeneXpertMTB/RIF (XpertMTB/RIF) in patients with a low-pretest probability of rifampicin-resistance (RR). Design/Methods In a cross-sectional study using results of sputum specimens collected from participants screened for the STREAM 2 trial. We recruited all patients with XpertMTB/RIF RR-TB detected who were referred for RR/MDR-TB treatment initiation at Mulago National Referral Hospital, Kampala, between September 2017 and October 2019. At baseline, smear microscopy, repeat XpertMTB/RIF, Xpert Ultra and MTBDRplus assays were done on sputum specimens. Culture-based drug-susceptibility testing (DST) were done on discordant specimens. We analysed the prevalence and factors associated with discordance between initial and repeat XpertMTB/RIF RR and false XpertMTB/RIF RR. False XpertMTB/RIF RR was defined as no RR detected by any of Xpert Ultra, LPA or culture DST (reference comparator). Results A total of 126/130 patients had repeat XpertMTB/RIF results of which, 97 (77.0%) had M. tuberculosis detected of whom, 81 (83.5%) had RR detected, and 1 (1.0%) had RR indeterminate. The prevalence of discordant XpertMTB/RIF RR was 15/96 (15.6%) whereas false XpertMTB/RIF RR prevalence was 10/96 (10.4%). Low bacillary load sputum specimens were more likely to have discordant XpertMTB/RIF RR and false XpertMTB/RIF RR results, aOR (p-value: 95%CI), 0.04 (0.01; 0.00-0.37) and 0.02 (0.01; 0.01-0.35) respectively. Conclusion Our findings show a high false-positive rifampicin resistance rate in low TB burden patients, which calls for repeat testing in order to prevent unnecessary prescription of anti MDR-TB therapy.

Exploring Diagnostic Methods for Drug-Resistant Tuberculosis: A Comprehensive Overview

“…The most commonly used molecular tests were Hain MTBDRplus, MTBDRsl and the GenXpert systems. Regarding the GenXpert, its performance is less optimal when the assay is performed in paucibacillary samples and low RIF-resistance settings, see for example [28,29,36], where the authors reported false-positive results. In those conditions, it is recommended to repeat the Xpert testing in case of a first positive result.…”

“…The authors found that 15/96 (15.6%) isolates had a discordant RR result between the initial and repeated XpertMTB/RIF testing and that 10/96 (10.4%) isolates were falsepositive RR isolates. A low bacillary load on the initial sputum was four times more likely to produce discordant RR results upon repeating the XpertMTB/RIF test [28].…”