Utility of second generation line probe assay (Hain MTBDRplus) directly on 2-month sputa specimens to monitor tuberculosis treatment response

The utility of line probe assay (Genotype MTBDRplus) performed directly on 2-month sputa to monitor tuberculosis treatment response is unknown. We assessed if direct testing of 2-month sputa with MTBDRplus can predict 2-month culture conversion and long-term treatment outcome. Xpert® MTB/RIF-confirmed rifampicin-susceptible tuberculosis cases were recruited at tuberculosis diagnosis and followed up at 2 and 5-6 months. MTBDRplus was performed directly on 2-month sputa and on all positive culture isolates at 2 and 5-6 months. We also investigated the association of a positive direct MTBDRplus at 2 months with subsequent unsuccessful tuberculosis treatment outcome (failure/death during treatment or subsequent disease recurrence). 279 cases (62% HIV-1 co-infected) were recruited. Direct MTBDRplus at 2 months had a sensitivity of 78%(95%CI 65-87) and specificity of 80%(95%CI 74-84) to predict culture positivity at 2 months with a high negative predictive value of 93%(95%CI 89-96). Inconclusive genotypic susceptibility for both rifampicin and isoniazid were seen in 26% of MTDDRplus tests performed directly on sputum. When compared to a reference of MTBDRplus performed on positive cultures, the false positive resistance rate for direct testing of MTBDRplus on sputa was 4% for rifampicin and 2% for isoniazid. Whilst a positive 2-month smear was not significantly associated with an unsuccessful treatment outcome, (aOR 2.69, 95% CI 0.88-8.21), a positive direct MTBDRplus at 2 months was associated with an unsuccessful outcome (aOR 2.87, 95%CI 1.11-7.42). There is moderate utility of direct 2-month MTBDRplus to predict culture conversion at 2 months and also to predict an unfavorable outcome