Journal article

Sources of Multidrug Resistance in Patients With Previous Isoniazid-Resistant Tuberculosis Identified Using Whole Genome Sequencing: A Longitudinal Cohort Study

Vijay Srinivasan, Vu TN Ha, Dao N Vinh, Phan VK Thai, Dang TM Ha, Nguyen H Lan, Hoang T Hai, Timothy M Walker, Do DA Thu, Sarah J Dunstan, Guy E Thwaites, Philip M Ashton, Maxine Caws, Nguyen TT Thuong

CLINICAL INFECTIOUS DISEASES | OXFORD UNIV PRESS INC | Published : 2020

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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University of Melbourne Researchers

Grants

Awarded by Wellcome Trust


Awarded by Wellcome Trust Intermediate Fellowship in Public Health and Tropical Medicine


Awarded by Wellcome Trust Major Overseas Program


Awarded by Wellcome Trust Clinical Research Career Development Fellowship


Awarded by National Health and Medical Research Council (A*STAR/NHMRC)


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.).