Journal article
Sources of multidrug resistance in patients with previous isoniazid-resistant tuberculosis identified using whole genome sequencing: A longitudinal cohort study
V Srinivasan, VTN Ha, DN Vinh, PVK Thai, DTM Ha, NH Lan, HT Hai, TM Walker, DDA Thu, SJ Dunstan, GE Thwaites, PM Ashton, M Caws, NTT Thuong
Clinical Infectious Diseases | OXFORD UNIV PRESS INC | Published : 2020
DOI: 10.1093/cid/ciaa254
Abstract
Background. Meta-analysis of patients with isoniazid-resistant tuberculosis (TB) given standard first-line anti-TB treatment indicated an increased risk of multidrug-resistant TB (MDR-TB) emerging (8%), compared to drug-sensitive TB (0.3%). Here we use whole genome sequencing (WGS) to investigate whether treatment of patients with preexisting isoniazid-resistant disease with first-line anti-TB therapy risks selecting for rifampicin resistance, and hence MDR-TB. Methods. Patients with isoniazid-resistant pulmonary TB were recruited and followed up for 24 months. Drug susceptibility testing was performed by microscopic observation drug susceptibility assay, mycobacterial growth indicator tube,..
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Awarded by Agency for Science, Technology and Research
Funding Acknowledgements
This work was supported by the Wellcome Trust (Research Fellowship 081814/Z/06/Z to M. C.); the Wellcome Trust Intermediate Fellowship in Public Health and Tropical Medicine (206724/Z/17/Z to N. T. T. T.); the Wellcome Trust Major Overseas Program (106680/B/14/Z to G. T.) and Wellcome Trust Clinical Research Career Development Fellowship (214560/Z/18/Z to T. M. W.); the Agency for Science, Technology and Research, Biomedical Research Council; and the National Health and Medical Research Council (A*STAR/NHMRC grant APP1056689 to S. J. D.).