Effect of mixed mycobacterium tuberculosis infection on the performance of rapid molecular diagnostic test among patients initiating MDR-TB treatment at Mulago National TB treatment

Abstract

Introduction: Performance of rapid molecular diagnostic test in detecting drug resistant Mycobacterium tuberculosis (MTB) is key in controlling the infection and treatment response of TB. Presence of mixed MTB infection could contribute to the ineffective performance of these rapid molecular diagnostic tests. A cross sectional study nested in the Standardized Treatment Regimen of Anti-Tuberculosis Drugs for patients with MDR-TB (STREAM) clinical trial was carried out to evaluate the effect of mix MTB infection on the performance of Line Probe Assay (LPA) and GeneXpert assays among patients initiating MDR-TB treatment at Mulago National TB treatment Unit. Methods: A total of 120 MTB smear positive sediments were genotyped to determine the presence of mix MTB infection using a standard 24-locus Mycobacterial Interspersed Repetitive Unit–Variable Number Tandem-Repeat (MIRU-VNTR). The LPA and GeneXpert tests were already done from the same sediments in the mother study. Agar proportional drug susceptibility test was performed on all discordant test results including those that showed indeterminate results using LPA or GeneXpert tests. Results: Out of the 120 MTB smear positive sediments genotyped, 35% (42/120) were able to be classified (at least 20/24 MIRU-VNTR loci were amplified). The overall prevalence of mixed MTB infection was 11.9% (5/42). It varied among males 11.1% (n=3) and females 13.3% (n=2) and was highest among middle aged adults 21.1% (n=4). Lineage 4 had the highest frequency of isolates with mix MTB infection. Having mix MTB infection increased the odds of affecting GeneXpert test results (OR 7.556, 95% CI 0.88-64.44). Having HIV (P=0.04) independently predicted presence of mixed MTB infection. Conclusions: Presence of mixed MTB infection may affect the performance of GeneXpert test but not for LPA rapid test. Hence LPA is highly recommended for screening TB among suspected MDR-TB patients.