Journal ArticleDOI
The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis
Keertan Dheda,Tawanda Gumbo,Gary Maartens,Kelly E. Dooley,Ruth McNerney,Megan Murray,Jennifer Furin,Edward A. Nardell,Leslie London,Erica Lessem,Grant Theron,Paul D. van Helden,Stefan Niemann,Matthias Merker,David W. Dowdy,Annelies Van Rie,Annelies Van Rie,Gilman Kit Hang Siu,Jotam G. Pasipanodya,Camilla Rodrigues,Taane G. Clark,F. A. Sirgel,Aliasgar Esmail,Hsien-Ho Lin,Sachin R Atre,H. Simon Schaaf,Kwok Chiu Chang,Christoph Lange,Payam Nahid,Zarir F Udwadia,C. Robert Horsburgh,Gavin J. Churchyard,Gavin J. Churchyard,Dick Menzies,Anneke C. Hesseling,Eric L. Nuermberger,Helen McIlleron,Kevin P. Fennelly,Eric Goemaere,Ernesto Jaramillo,Marcus Low,Carolina Morán Jara,Nesri Padayatchi,Robin M. Warren +43 more
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TLDR
Several lines of evidence suggest that alternative mechanisms-including pharmacokinetic variability, induction of efflux pumps that transport the drug out of cells, and suboptimal drug penetration into tuberculosis lesions-are likely crucial to the pathogenesis of drug-resistant tuberculosis.About:
This article is published in The Lancet Respiratory Medicine.The article was published on 2017-04-01. It has received 461 citations till now. The article focuses on the topics: Bedaquiline & Delamanid.read more
Citations
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Journal ArticleDOI
Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection.
Paul K. Drain,Kristina L. Bajema,David W. Dowdy,Keertan Dheda,Kogieleum Naidoo,Samuel G Schumacher,Shuyi Ma,Shuyi Ma,Erin W. Meermeier,David M. Lewinsohn,David R. Sherman,David R. Sherman +11 more
TL;DR: Current understanding of the pathogenesis, immunology, clinical epidemiology, diagnosis, treatment, and prevention of both incipient and subclinical TB, two emerging clinical states of an ancient bacterium are reviewed.
Journal ArticleDOI
A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis
Paolo Miotto,Belay Tessema,Elisa Tagliani,Leonid Chindelevitch,Angela M. Starks,Claudia Emerson,Debra Hanna,Peter S. Kim,Richard Liwski,Matteo Zignol,Christopher Gilpin,Stefan Niemann,Claudia M. Denkinger,Joy Fleming,Robin M. Warren,Derrick W. Crook,Derrick W. Crook,James E. Posey,Sebastien Gagneux,Sebastien Gagneux,Sven Hoffner,Sven Hoffner,Camilla Rodrigues,Iñaki Comas,David M. Engelthaler,Megan Murray,David Alland,Leen Rigouts,Christoph Lange,Keertan Dheda,Rumina Hasan,Uma Devi Ranganathan,Ruth McNerney,Matthew Ezewudo,Daniela Maria Cirillo,Marco Schito,Claudio U. Köser,Timothy C. Rodwell,Timothy C. Rodwell +38 more
TL;DR: This study provides a standardised and comprehensive approach for the interpretation of mutations as predictors of M. tuberculosis drug- resistant phenotypes and has implications for the clinical interpretation of molecular diagnostics and next-generation sequencing as well as efficient individualised therapy for patients with drug-resistant tuberculosis.
Journal ArticleDOI
Phase 2b Controlled Trial of M72/AS01E Vaccine to Prevent Tuberculosis
Olivier Van Der Meeren,Mark Hatherill,Videlis Nduba,Robert J. Wilkinson,Monde Muyoyeta,Elana van Brakel,Helen Ayles,German Henostroza,Friedrich Thienemann,Thomas J. Scriba,Andreas H. Diacon,Gretta L Blatner,Marie-Ange Demoitié,Michele Tameris,Mookho Malahleha,James C Innes,Elizabeth Hellstrom,Neil A. Martinson,Tina Singh,Elaine J Akite,Aisha Khatoon Azam,Anne Bollaerts,Ann M. Ginsberg,Thomas G. Evans,Paul Gillard,Dereck Tait +25 more
TL;DR: M72/AS01E provided 54.0% protection for M. tuberculosis–infected adults against active pulmonary tuberculosis disease, without evident safety concerns, in a phase 2b trial in Kenya, South Africa, and Zambia.
Journal ArticleDOI
Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies
Simon Tiberi,Nelita du Plessis,Gerhard Walzl,Michael J. Vjecha,Martin Rao,Francine Ntoumi,Sayoki Mfinanga,Nathan Kapata,Peter Mwaba,Timothy D. McHugh,Giuseppe Ippolito,Giovanni Battista Migliori,Markus Maeurer,Alimuddin Zumla +13 more
TL;DR: The developmental pipeline and landscape of new and repurposed tuberculosis drugs, treatment regimens, and host-directed therapies (HDTs) for drug-sensitive and drug-resistant tuberculosis are reviewed and a range of HDTs and immune-based treatments are under investigation as adjunctive therapy.
Journal ArticleDOI
Evolution of drug resistance in Mycobacterium tuberculosis: a review on the molecular determinants of resistance and implications for personalized care
Navisha Dookie,Santhuri Rambaran,Nesri Padayatchi,Nesri Padayatchi,Sharana Mahomed,Kogieleum Naidoo,Kogieleum Naidoo +6 more
TL;DR: Advances in sequencing technology will help devise better molecular diagnostics for more effective DR-TB management enabling personalized treatment, and will facilitate the development of new drugs aimed at improving outcomes of patients with this disease.
References
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Journal ArticleDOI
The antimicrobial effect of colistin methanesulfonate on Mycobacterium tuberculosis in vitro
TL;DR: Ulastructure analysis suggests that the disruption of the outer polysaccharide layer of MTB by CMS may lead to enhanced uptake of INH, and may provide insight for further investigations of CMS against MTB.
Journal ArticleDOI
Drug-resistant tuberculosis clinical trials: proposed core research definitions in adults.
Jennifer Furin,Emilie Alirol,Elizabeth Allen,Katherine Fielding,Corinne Merle,Ibrahim Abubakar,Janet Andersen,Geraint Davies,Keertan Dheda,Andreas H. Diacon,Kelly E. Dooley,G. Dravnice,Kathleen D. Eisenach,Daniel Everitt,D. Ferstenberg,A. Goolam-Mahomed,Martin P. Grobusch,Rajeev Gupta,Elizabeth P. Harausz,Mark Harrington,C. R. Horsburgh,Christian Lienhardt,David F. McNeeley,Carole D. Mitnick,Sharon Nachman,Payam Nahid,Andrew J. Nunn,Patrick P. J. Phillips,Carly A. Rodriguez,S. Shah,Charles D. Wells,B. Thomas-Nyang'wa,P. du Cros +32 more
TL;DR: A core set of efficacy and safety definitions as well as other important considerations in DR-TB clinical trials work are presented to ensure there is comparability in clinical trials on multidrug-resistant TB.
Journal ArticleDOI
New Susceptibility Breakpoints and the Regional Variability of MIC Distribution in Mycobacterium tuberculosis Isolates
TL;DR: The data from South Africa, together with recent clinical evidence that the new breakpoints proposed are actually supported by clinical findings in the case of rifampin, mean that there no longer can be any excuses to keep the standard M. tuberculosis susceptibility breakpoints.
Journal Article
Integrating pharmacokinetics, pharmacodynamics and pharmacogenomics to predict outcomes in antibacterial therapy.
TL;DR: Evidence is presented to demonstrate that in addition to drug exposures, host genetic polymorphisms may lead to gene products that modulate microbial response to antibiotic exposure, and these data can be integrated in Monte Carlo simulations, such that antibiotic doses with the highest probability of killing the pathogen and the least probability of causing dose-related toxicity can be predicted.
Journal ArticleDOI
Molecular and phenotypic characterisation of Mycobacterium tuberculosis resistant to anti-tuberculosis drugs.
Belén Rocío Imperiale,Martín José Zumárraga,A. B. Di Giulio,Ángel Adrián Cataldi,Nora Morcillo +4 more
TL;DR: Several isolates showed an association between high INH(R) levels and katG mutation; others from the Haarlem family were prone to becoming MDR-TB and continue to circulate in the community.
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