D Papaventsis1, N Casali2, I Kontsevaya2, F Drobniewski2, D M Cirillo3, V Nikolayevskyy4. 1. National Reference Laboratory for Mycobacteria, Sotiria Chest Diseases Hospital, Athens, Greece. 2. Department of Medicine, Imperial College London, London, UK. 3. Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy. 4. Department of Medicine, Imperial College London, London, UK; PHE National Mycobacterium Reference Laboratory, London, UK. Electronic address: vlad.nikolayevskyy@phe.gov.uk.
Abstract
OBJECTIVES: We conducted a systematic review to determine the diagnostic accuracy of whole genome sequencing (WGS) of Mycobacterium tuberculosis for the detection of resistance to first- and second-line anti-tuberculosis (TB) drugs. METHODS: The study was conducted according to the criteria of the Preferred Reporting Items for Systematic Reviews group. A total of 20 publications were included. The sensitivity, specificity, positive-predictive value and negative-predictive value of WGS using phenotypic drug susceptibility testing methods as a reference standard were determined. RESULTS: Anti-TB agents tested included all first-line drugs, a variety of reserve drugs, as well as new drugs. Polymorphisms in a total of 53 genes were tested for associations with drug resistance. Pooled sensitivity and specificity values for detection of resistance to selected first-line drugs were 0.98 (95% CI 0.93-0.98) and 0.98 (95% CI 0.98-1.00) for rifampicin and 0.97 (95% CI 0.94-0.99) and 0.93 (95% CI 0.91-0.96) for isoniazid, respectively. Due to high heterogeneity in study designs, lack of data, knowledge of resistance mechanisms and clarity on exclusion of phylogenetic markers, there was a significant variation in analytical performance of WGS for the remaining first-line, reserved drugs and new drugs. CONCLUSIONS: Whole genome sequencing could be considered a promising alternative to existing phenotypic and molecular drug susceptibility testing methods for rifampicin and isoniazid pending standardization of analytical pipelines. To ensure clinical relevance of WGS for detection of M. tuberculosis complex drug resistance, future studies should include information on clinical outcomes. Crown
OBJECTIVES: We conducted a systematic review to determine the diagnostic accuracy of whole genome sequencing (WGS) of Mycobacterium tuberculosis for the detection of resistance to first- and second-line anti-tuberculosis (TB) drugs. METHODS: The study was conducted according to the criteria of the Preferred Reporting Items for Systematic Reviews group. A total of 20 publications were included. The sensitivity, specificity, positive-predictive value and negative-predictive value of WGS using phenotypic drug susceptibility testing methods as a reference standard were determined. RESULTS: Anti-TB agents tested included all first-line drugs, a variety of reserve drugs, as well as new drugs. Polymorphisms in a total of 53 genes were tested for associations with drug resistance. Pooled sensitivity and specificity values for detection of resistance to selected first-line drugs were 0.98 (95% CI 0.93-0.98) and 0.98 (95% CI 0.98-1.00) for rifampicin and 0.97 (95% CI 0.94-0.99) and 0.93 (95% CI 0.91-0.96) for isoniazid, respectively. Due to high heterogeneity in study designs, lack of data, knowledge of resistance mechanisms and clarity on exclusion of phylogenetic markers, there was a significant variation in analytical performance of WGS for the remaining first-line, reserved drugs and new drugs. CONCLUSIONS: Whole genome sequencing could be considered a promising alternative to existing phenotypic and molecular drug susceptibility testing methods for rifampicin and isoniazid pending standardization of analytical pipelines. To ensure clinical relevance of WGS for detection of M. tuberculosis complex drug resistance, future studies should include information on clinical outcomes. Crown
Authors: Gregory L Armstrong; Duncan R MacCannell; Jill Taylor; Heather A Carleton; Elizabeth B Neuhaus; Richard S Bradbury; James E Posey; Marta Gwinn Journal: N Engl J Med Date: 2019-12-26 Impact factor: 91.245
Authors: Jody Phelan; Denise M O'Sullivan; Diana Machado; Jorge Ramos; Alexandra S Whale; Justin O'Grady; Keertan Dheda; Susana Campino; Ruth McNerney; Miguel Viveiros; Jim F Huggett; Taane G Clark Journal: Genome Med Date: 2016-12-22 Impact factor: 11.117
Authors: Alberto Oliveira; Leticia C Oliveira; Flavia Aburjaile; Leandro Benevides; Sandeep Tiwari; Syed B Jamal; Arthur Silva; Henrique C P Figueiredo; Preetam Ghosh; Ricardo W Portela; Vasco A De Carvalho Azevedo; Alice R Wattam Journal: Front Microbiol Date: 2017-10-12 Impact factor: 5.640