Guidance for programmatic management of latent tuberculosis infection in the European Union/European Economic Area.

Management of latent tuberculosis infection is crucial to end TB in low-incidence setting

ERS/ECDC Statement: European Union standards for tuberculosis care, 2017 update

European Respiratory Society TF-2016-1

Predicting Extensively Drug-Resistant Mycobacterium tuberculosis Phenotypes with Genetic Mutations

Molecular diagnostic methods based on the detection of mutations conferring drug resistance are promising technologies for rapidly detecting multidrug-/extensively drug-resistant tuberculosis (M/XDR TB), but large studies of mutations as markers of resistance are rare. The Global Consortium for Drug-Resistant TB Diagnostics analyzed 417 Mycobacterium tuberculosis isolates from multinational sites with a high prevalence of drug resistance to determine the sensitivities and specificities of mutations associated with M/XDR TB to inform the development of rapid diagnostic methods. We collected M/XDR TB isolates from regions of high TB burden in India, Moldova, the Philippines, and South Africa. The isolates underwent standardized phenotypic drug susceptibility testing (DST) to isoniazid (INH), rifampin (RIF), moxifloxacin (MOX), ofloxacin (OFX), amikacin (AMK), kanamycin (KAN), and capreomycin (CAP) using MGIT 960 and WHO-recommended critical concentrations. Eight genes (katG, inhA, rpoB, gyrA, gyrB, rrs, eis, and tlyA) were sequenced using Sanger sequencing. Three hundred seventy isolates were INH(r), 356 were RIF(r), 292 were MOX(r)/OFX(r), 230 were AMK(r), 219 were CAP(r), and 286 were KAN(r). Four single nucleotide polymorphisms (SNPs) in katG/inhA had a combined sensitivity of 96% and specificities of 97 to 100% for the detection of INH(r). Eleven SNPs in rpoB had a combined sensitivity of 98% for RIF(r). Eight SNPs in gyrA codons 88 to 94 had sensitivities of 90% for MOX(r)/OFX(r). The rrs 1401/1484 SNPs had 89 to 90% sensitivity for detecting AMK(r)/CAP(r) but 71% sensitivity for KAN(r). Adding eis promoter SNPs increased the sensitivity to 93% for detecting AMK(r) and to 91% for detecting KAN(r). Approximately 30 SNPs in six genes predicted clinically relevant XDR-TB phenotypes with 90 to 98% sensitivity and almost 100% specificity