Effectiveness of GenoType MTBDRsl in excluding TB drug resistance in a clinical trial.

OBJECTIVES: To assess the performance of the GenoType MTBDRsl v1, a line-probe assay (LPA), to exclude baseline resistance to fluoroquinolones (FQs) and second-line injectables (SLIs) in the Standard Treatment Regimen of Anti-tuberculosis Drugs for Patients With MDR-TB 1 (STREAM 1) trial.METHODS: Direct sputum MTBDRsl results in the site laboratories were compared to indirect phenotypic drug susceptibility testing (pDST) results in the central laboratory, with DNA sequencing as a reference standard.RESULTS: Of 413 multidrug-resistant TB (MDR-TB) patients tested using MTBDRsl and pDST, 389 (94.2%) were FQ-susceptible and 7 (1.7%) FQ-resistant, while 17 (4.1%) had an inconclusive MTBDRsl result. For SLI, 372 (90.1%) were susceptible, 5 (1.2%) resistant and 36 (8.7%) inconclusive. There were 9 (2.3%) FQ discordant pDST/MTBDRsl results, of which 3 revealed a mutation and 5 (1.3%) SLI discordant pDST/MTBDRsl results, none of which were mutants on sequencing. Among the 17 FQ- and SLI MTBDRsl-inconclusive samples, sequencing showed 1 FQ- and zero SLI-resistant results, similar to frequencies among the conclusive MTBDRsl. The majority of inconclusive MTBDRsl results were associated with low bacillary load samples (acid-fast bacilli smear-negative or scantily positive) compared to conclusive results (P < 0.001).CONCLUSION: MTBDRsl can facilitate the rapid exclusion of FQ and SLI resistances for enrolment in clinical trials.

Spatiotemporal evidence for cross-border spread of MDR-TB along the Trans-Siberian Railway line.

BACKGROUND: Mongolia has the fifth highest incidence of tuberculosis (TB) in the Western Pacific Region, with high rates of multidrug-resistant TB (MDR-TB). OBJECTIVE: To examine the recent spatiotemporal dynamics of MDR-TB in Mongolia. METHODS: All MDR-TB cases diagnosed from 2004 to 2012, identified from the National Tuberculosis Control Programme database, were included in the study. Cases diagnosed from 2006 to 2012 were further examined using spatial scan statistics. RESULTS: Few MDR-TB cases (n = 29) were diagnosed before the programmatic management of MDR-TB was introduced in 2006. During 2006-2012, 1106 MDR-TB cases were detected, at an annualised rate of 5.9 cases per 100 000 population. Most (>80%) cases were identified in the 15-44 year age group; 45% were among those aged 15-29 years. Case notification rates were highest in the capital city, Ulaanbaatar, with an increasing trend over time in all locations. Three MDR-TB hotspots were identified, all in close proximity to the Trans-Siberian Railway line. The majority of the MDR-TB isolates were resistant to all first-line drugs tested. CONCLUSION: Spatiotemporal analysis indicates likely cross-border spread of MDR-TB along the Trans-Siberian Railway line, with subsequent spatial expansion across Mongolia. The frequency of MDR-TB among young patients with pan-resistance to all first-line drugs suggests ongoing MDR-TB transmission within the community.