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The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis.

Identifieur interne : 000137 ( Main/Exploration ); précédent : 000136; suivant : 000138

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis.

Auteurs : Keertan Dheda [Afrique du Sud] ; Tawanda Gumbo [États-Unis] ; Gary Maartens [Afrique du Sud] ; Kelly E. Dooley [États-Unis] ; Ruth Mcnerney [Afrique du Sud] ; Megan Murray [États-Unis] ; Jennifer Furin [États-Unis] ; Edward A. Nardell [États-Unis] ; Leslie London [Afrique du Sud] ; Erica Lessem [États-Unis] ; Grant Theron [Afrique du Sud] ; Paul Van Helden [Afrique du Sud] ; Stefan Niemann [Allemagne] ; Matthias Merker [Allemagne] ; David Dowdy [États-Unis] ; Annelies Van Rie [Belgique] ; Gilman K H. Siu [République populaire de Chine] ; Jotam G. Pasipanodya [États-Unis] ; Camilla Rodrigues [Inde] ; Taane G. Clark [Royaume-Uni] ; Frik A. Sirgel [Afrique du Sud] ; Aliasgar Esmail [Afrique du Sud] ; Hsien-Ho Lin [Taïwan] ; Sachin R. Atre [Inde] ; H Simon Schaaf [Afrique du Sud] ; Kwok Chiu Chang [République populaire de Chine] ; Christoph Lange [Namibie] ; Payam Nahid [États-Unis] ; Zarir F. Udwadia [Inde] ; C Robert Horsburgh [États-Unis] ; Gavin J. Churchyard [Afrique du Sud] ; Dick Menzies [Canada] ; Anneke C. Hesseling [Afrique du Sud] ; Eric Nuermberger [États-Unis] ; Helen Mcilleron [Afrique du Sud] ; Kevin P. Fennelly [États-Unis] ; Eric Goemaere [Afrique du Sud] ; Ernesto Jaramillo [Suisse] ; Marcus Low [Afrique du Sud] ; Carolina Morán Jara [Pérou] ; Nesri Padayatchi [Afrique du Sud] ; Robin M. Warren [Afrique du Sud]

Source :

RBID : pubmed:28344011

Abstract

Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis). This poses several challenges similar to those encountered in the pre-chemotherapy era, including the inability to cure tuberculosis, high mortality, and the need for alternative methods to prevent disease transmission. This phenomenon mirrors the worldwide increase in antimicrobial resistance and the emergence of other MDR pathogens, such as malaria, HIV, and Gram-negative bacteria. MDR and XDR tuberculosis are associated with high morbidity and substantial mortality, are a threat to health-care workers, prohibitively expensive to treat, and are therefore a serious public health problem. In this Commission, we examine several aspects of drug-resistant tuberculosis. The traditional view that acquired resistance to antituberculous drugs is driven by poor compliance and programmatic failure is now being questioned, and 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. These factors have implications for the design of new interventions, drug delivery and dosing mechanisms, and public health policy. We discuss epidemiology and transmission dynamics, including new insights into the fundamental biology of transmission, and we review the utility of newer diagnostic tools, including molecular tests and next-generation whole-genome sequencing, and their potential for clinical effectiveness. Relevant research priorities are highlighted, including optimal medical and surgical management, the role of newer and repurposed drugs (including bedaquiline, delamanid, and linezolid), pharmacokinetic and pharmacodynamic considerations, preventive strategies (such as prophylaxis in MDR and XDR contacts), palliative and patient-orientated care aspects, and medicolegal and ethical issues.

DOI: 10.1016/S2213-2600(17)30079-6
PubMed: 28344011


Affiliations:


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Le document en format XML

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<name sortKey="Murray, Megan" sort="Murray, Megan" uniqKey="Murray M" first="Megan" last="Murray">Megan Murray</name>
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<name sortKey="Dowdy, David" sort="Dowdy, David" uniqKey="Dowdy D" first="David" last="Dowdy">David Dowdy</name>
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<nlm:affiliation>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD</wicri:regionArea>
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<name sortKey="Van Rie, Annelies" sort="Van Rie, Annelies" uniqKey="Van Rie A" first="Annelies" last="Van Rie">Annelies Van Rie</name>
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<nlm:affiliation>University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; International Health Unit, Epidemiology and Social Medicine, Faculty of Medicine, University of Antwerp, Antwerp, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; International Health Unit, Epidemiology and Social Medicine, Faculty of Medicine, University of Antwerp, Antwerp</wicri:regionArea>
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<nlm:affiliation>Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China.</nlm:affiliation>
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<name sortKey="Pasipanodya, Jotam G" sort="Pasipanodya, Jotam G" uniqKey="Pasipanodya J" first="Jotam G" last="Pasipanodya">Jotam G. Pasipanodya</name>
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<nlm:affiliation>Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX</wicri:regionArea>
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<name sortKey="Rodrigues, Camilla" sort="Rodrigues, Camilla" uniqKey="Rodrigues C" first="Camilla" last="Rodrigues">Camilla Rodrigues</name>
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<nlm:affiliation>Department of Microbiology, P.D. Hinduja National Hospital & Medical Research Centre, Mumbai, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Microbiology, P.D. Hinduja National Hospital & Medical Research Centre, Mumbai</wicri:regionArea>
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<name sortKey="Clark, Taane G" sort="Clark, Taane G" uniqKey="Clark T" first="Taane G" last="Clark">Taane G. Clark</name>
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<nlm:affiliation>Faculty of Infectious and Tropical Diseases and Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Faculty of Infectious and Tropical Diseases and Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London</wicri:regionArea>
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<name sortKey="Sirgel, Frik A" sort="Sirgel, Frik A" uniqKey="Sirgel F" first="Frik A" last="Sirgel">Frik A. Sirgel</name>
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<country xml:lang="fr">Afrique du Sud</country>
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<name sortKey="Esmail, Aliasgar" sort="Esmail, Aliasgar" uniqKey="Esmail A" first="Aliasgar" last="Esmail">Aliasgar Esmail</name>
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<nlm:affiliation>Lung Infection and Immunity Unit, Department of Medicine, Division of Pulmonology and UCT Lung Institute, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Lung Infection and Immunity Unit, Department of Medicine, Division of Pulmonology and UCT Lung Institute, University of Cape Town, Groote Schuur Hospital, Cape Town</wicri:regionArea>
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<name sortKey="Lin, Hsien Ho" sort="Lin, Hsien Ho" uniqKey="Lin H" first="Hsien-Ho" last="Lin">Hsien-Ho Lin</name>
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<nlm:affiliation>Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.</nlm:affiliation>
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<wicri:regionArea>Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei</wicri:regionArea>
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<name sortKey="Atre, Sachin R" sort="Atre, Sachin R" uniqKey="Atre S" first="Sachin R" last="Atre">Sachin R. Atre</name>
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<nlm:affiliation>Center for Clinical Global Health Education (CCGHE), Johns Hopkins University, Baltimore, MD, USA; Medical College, Hospital and Research Centre, Pimpri, Pune, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Center for Clinical Global Health Education (CCGHE), Johns Hopkins University, Baltimore, MD, USA; Medical College, Hospital and Research Centre, Pimpri, Pune</wicri:regionArea>
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</affiliation>
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<name sortKey="Schaaf, H Simon" sort="Schaaf, H Simon" uniqKey="Schaaf H" first="H Simon" last="Schaaf">H Simon Schaaf</name>
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<nlm:affiliation>Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town</wicri:regionArea>
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</affiliation>
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<author>
<name sortKey="Chang, Kwok Chiu" sort="Chang, Kwok Chiu" uniqKey="Chang K" first="Kwok Chiu" last="Chang">Kwok Chiu Chang</name>
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<nlm:affiliation>Tuberculosis and Chest Service, Centre for Health Protection, Department of Health, Hong Kong SAR, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Tuberculosis and Chest Service, Centre for Health Protection, Department of Health, Hong Kong SAR</wicri:regionArea>
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<author>
<name sortKey="Lange, Christoph" sort="Lange, Christoph" uniqKey="Lange C" first="Christoph" last="Lange">Christoph Lange</name>
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<nlm:affiliation>Division of Clinical Infectious Diseases, German Center for Infection Research, Research Center Borstel, Borstel, Schleswig-Holstein, Germany; International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany; Department of Medicine, Karolinska Institute, Stockholm, Sweden; Department of Medicine, University of Namibia School of Medicine, Windhoek, Namibia.</nlm:affiliation>
<country xml:lang="fr">Namibie</country>
<wicri:regionArea>Division of Clinical Infectious Diseases, German Center for Infection Research, Research Center Borstel, Borstel, Schleswig-Holstein, Germany; International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany; Department of Medicine, Karolinska Institute, Stockholm, Sweden; Department of Medicine, University of Namibia School of Medicine, Windhoek</wicri:regionArea>
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<name sortKey="Nahid, Payam" sort="Nahid, Payam" uniqKey="Nahid P" first="Payam" last="Nahid">Payam Nahid</name>
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<nlm:affiliation>Division of Pulmonary and Critical Care, San Francisco General Hospital, University of California, San Francisco, CA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Pulmonary and Critical Care, San Francisco General Hospital, University of California, San Francisco, CA</wicri:regionArea>
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<region type="state">Californie</region>
</placeName>
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<author>
<name sortKey="Udwadia, Zarir F" sort="Udwadia, Zarir F" uniqKey="Udwadia Z" first="Zarir F" last="Udwadia">Zarir F. Udwadia</name>
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<nlm:affiliation>Pulmonary Department, Hinduja Hospital & Research Center, Mumbai, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Pulmonary Department, Hinduja Hospital & Research Center, Mumbai</wicri:regionArea>
<wicri:noRegion>Mumbai</wicri:noRegion>
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<author>
<name sortKey="Horsburgh, C Robert" sort="Horsburgh, C Robert" uniqKey="Horsburgh C" first="C Robert" last="Horsburgh">C Robert Horsburgh</name>
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<nlm:affiliation>Schools of Public Health Medicine, Boston University, Boston, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Schools of Public Health Medicine, Boston University, Boston, MA</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
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<author>
<name sortKey="Churchyard, Gavin J" sort="Churchyard, Gavin J" uniqKey="Churchyard G" first="Gavin J" last="Churchyard">Gavin J. Churchyard</name>
<affiliation wicri:level="1">
<nlm:affiliation>Aurum Institute, Johannesburg, South Africa; School of Public Health, University of Witwatersrand, Johannesburg, South Africa; Advancing Treatment and Care for TB/HIV, South African Medical Research Council, Johannesburg, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Aurum Institute, Johannesburg, South Africa; School of Public Health, University of Witwatersrand, Johannesburg, South Africa; Advancing Treatment and Care for TB/HIV, South African Medical Research Council, Johannesburg</wicri:regionArea>
<wicri:noRegion>Johannesburg</wicri:noRegion>
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<author>
<name sortKey="Menzies, Dick" sort="Menzies, Dick" uniqKey="Menzies D" first="Dick" last="Menzies">Dick Menzies</name>
<affiliation wicri:level="4">
<nlm:affiliation>Montreal Chest Institute, McGill University, Montreal, QC, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Montreal Chest Institute, McGill University, Montreal, QC</wicri:regionArea>
<orgName type="university">Université McGill</orgName>
<placeName>
<settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
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<author>
<name sortKey="Hesseling, Anneke C" sort="Hesseling, Anneke C" uniqKey="Hesseling A" first="Anneke C" last="Hesseling">Anneke C. Hesseling</name>
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<wicri:regionArea>Centre for the AIDS Programme of Research in South Africa (CAPRISA), MRC HIV-TB Pathogenesis and Treatment Research Unit, Durban</wicri:regionArea>
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<country xml:lang="fr">Afrique du Sud</country>
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<title xml:lang="en">The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis.</title>
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<name sortKey="Dheda, Keertan" sort="Dheda, Keertan" uniqKey="Dheda K" first="Keertan" last="Dheda">Keertan Dheda</name>
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<nlm:affiliation>Lung Infection and Immunity Unit, Department of Medicine, Division of Pulmonology and UCT Lung Institute, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa. Electronic address: keertan.dheda@uct.ac.za.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Lung Infection and Immunity Unit, Department of Medicine, Division of Pulmonology and UCT Lung Institute, University of Cape Town, Groote Schuur Hospital, Cape Town</wicri:regionArea>
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<name sortKey="Gumbo, Tawanda" sort="Gumbo, Tawanda" uniqKey="Gumbo T" first="Tawanda" last="Gumbo">Tawanda Gumbo</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX</wicri:regionArea>
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<nlm:affiliation>Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
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<name sortKey="Dooley, Kelly E" sort="Dooley, Kelly E" uniqKey="Dooley K" first="Kelly E" last="Dooley">Kelly E. Dooley</name>
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<country xml:lang="fr">États-Unis</country>
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<nlm:affiliation>Lung Infection and Immunity Unit, Department of Medicine, Division of Pulmonology and UCT Lung Institute, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Lung Infection and Immunity Unit, Department of Medicine, Division of Pulmonology and UCT Lung Institute, University of Cape Town, Groote Schuur Hospital, Cape Town</wicri:regionArea>
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<name sortKey="Murray, Megan" sort="Murray, Megan" uniqKey="Murray M" first="Megan" last="Murray">Megan Murray</name>
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<nlm:affiliation>Department of Global Health and Social Medicine, Department of Medicine, Harvard Medical School, Boston, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Global Health and Social Medicine, Department of Medicine, Harvard Medical School, Boston, MA</wicri:regionArea>
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<nlm:affiliation>Department of Global Health and Social Medicine, Department of Medicine, Harvard Medical School, Boston, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Global Health and Social Medicine, Department of Medicine, Harvard Medical School, Boston, MA</wicri:regionArea>
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<region type="state">Massachusetts</region>
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<nlm:affiliation>TH Chan School of Public Health, Department of Medicine, Harvard Medical School, Boston, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>TH Chan School of Public Health, Department of Medicine, Harvard Medical School, Boston, MA</wicri:regionArea>
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<nlm:affiliation>School of Public Health and Medicine, University of Cape Town, Cape Town, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>School of Public Health and Medicine, University of Cape Town, Cape Town</wicri:regionArea>
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<name sortKey="Lessem, Erica" sort="Lessem, Erica" uniqKey="Lessem E" first="Erica" last="Lessem">Erica Lessem</name>
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<nlm:affiliation>Treatment Action Group, New York, NY, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Treatment Action Group, New York, NY</wicri:regionArea>
<placeName>
<region type="state">État de New York</region>
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<name sortKey="Theron, Grant" sort="Theron, Grant" uniqKey="Theron G" first="Grant" last="Theron">Grant Theron</name>
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<nlm:affiliation>SA MRC Centre for Tuberculosis Research/DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>SA MRC Centre for Tuberculosis Research/DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg</wicri:regionArea>
<wicri:noRegion>Tygerberg</wicri:noRegion>
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<name sortKey="Van Helden, Paul" sort="Van Helden, Paul" uniqKey="Van Helden P" first="Paul" last="Van Helden">Paul Van Helden</name>
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<nlm:affiliation>SA MRC Centre for Tuberculosis Research/DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>SA MRC Centre for Tuberculosis Research/DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg</wicri:regionArea>
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<name sortKey="Niemann, Stefan" sort="Niemann, Stefan" uniqKey="Niemann S" first="Stefan" last="Niemann">Stefan Niemann</name>
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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Schleswig-Holstein, Germany; German Centre for Infection Research (DZIF), Partner Site Borstel, Borstel, Schleswig-Holstein</wicri:regionArea>
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<wicri:noRegion>Schleswig-Holstein</wicri:noRegion>
<wicri:noRegion>Schleswig-Holstein</wicri:noRegion>
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<name sortKey="Merker, Matthias" sort="Merker, Matthias" uniqKey="Merker M" first="Matthias" last="Merker">Matthias Merker</name>
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<nlm:affiliation>Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Schleswig-Holstein, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Schleswig-Holstein</wicri:regionArea>
<wicri:noRegion>Schleswig-Holstein</wicri:noRegion>
<wicri:noRegion>Schleswig-Holstein</wicri:noRegion>
<wicri:noRegion>Schleswig-Holstein</wicri:noRegion>
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<name sortKey="Dowdy, David" sort="Dowdy, David" uniqKey="Dowdy D" first="David" last="Dowdy">David Dowdy</name>
<affiliation wicri:level="2">
<nlm:affiliation>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
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<name sortKey="Van Rie, Annelies" sort="Van Rie, Annelies" uniqKey="Van Rie A" first="Annelies" last="Van Rie">Annelies Van Rie</name>
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<nlm:affiliation>University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; International Health Unit, Epidemiology and Social Medicine, Faculty of Medicine, University of Antwerp, Antwerp, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; International Health Unit, Epidemiology and Social Medicine, Faculty of Medicine, University of Antwerp, Antwerp</wicri:regionArea>
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<settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
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</affiliation>
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<name sortKey="Siu, Gilman K H" sort="Siu, Gilman K H" uniqKey="Siu G" first="Gilman K H" last="Siu">Gilman K H. Siu</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR</wicri:regionArea>
<wicri:noRegion>Hong Kong SAR</wicri:noRegion>
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<name sortKey="Pasipanodya, Jotam G" sort="Pasipanodya, Jotam G" uniqKey="Pasipanodya J" first="Jotam G" last="Pasipanodya">Jotam G. Pasipanodya</name>
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<nlm:affiliation>Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX</wicri:regionArea>
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<region type="state">Texas</region>
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<name sortKey="Rodrigues, Camilla" sort="Rodrigues, Camilla" uniqKey="Rodrigues C" first="Camilla" last="Rodrigues">Camilla Rodrigues</name>
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<nlm:affiliation>Department of Microbiology, P.D. Hinduja National Hospital & Medical Research Centre, Mumbai, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Microbiology, P.D. Hinduja National Hospital & Medical Research Centre, Mumbai</wicri:regionArea>
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<name sortKey="Clark, Taane G" sort="Clark, Taane G" uniqKey="Clark T" first="Taane G" last="Clark">Taane G. Clark</name>
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<country xml:lang="fr">Royaume-Uni</country>
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<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
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<name sortKey="Sirgel, Frik A" sort="Sirgel, Frik A" uniqKey="Sirgel F" first="Frik A" last="Sirgel">Frik A. Sirgel</name>
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<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>SA MRC Centre for Tuberculosis Research/DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg</wicri:regionArea>
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</affiliation>
</author>
<author>
<name sortKey="Esmail, Aliasgar" sort="Esmail, Aliasgar" uniqKey="Esmail A" first="Aliasgar" last="Esmail">Aliasgar Esmail</name>
<affiliation wicri:level="1">
<nlm:affiliation>Lung Infection and Immunity Unit, Department of Medicine, Division of Pulmonology and UCT Lung Institute, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Lung Infection and Immunity Unit, Department of Medicine, Division of Pulmonology and UCT Lung Institute, University of Cape Town, Groote Schuur Hospital, Cape Town</wicri:regionArea>
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<name sortKey="Lin, Hsien Ho" sort="Lin, Hsien Ho" uniqKey="Lin H" first="Hsien-Ho" last="Lin">Hsien-Ho Lin</name>
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<nlm:affiliation>Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.</nlm:affiliation>
<country xml:lang="fr">Taïwan</country>
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<name sortKey="Atre, Sachin R" sort="Atre, Sachin R" uniqKey="Atre S" first="Sachin R" last="Atre">Sachin R. Atre</name>
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<nlm:affiliation>Center for Clinical Global Health Education (CCGHE), Johns Hopkins University, Baltimore, MD, USA; Medical College, Hospital and Research Centre, Pimpri, Pune, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Center for Clinical Global Health Education (CCGHE), Johns Hopkins University, Baltimore, MD, USA; Medical College, Hospital and Research Centre, Pimpri, Pune</wicri:regionArea>
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<author>
<name sortKey="Schaaf, H Simon" sort="Schaaf, H Simon" uniqKey="Schaaf H" first="H Simon" last="Schaaf">H Simon Schaaf</name>
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<nlm:affiliation>Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town</wicri:regionArea>
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<author>
<name sortKey="Chang, Kwok Chiu" sort="Chang, Kwok Chiu" uniqKey="Chang K" first="Kwok Chiu" last="Chang">Kwok Chiu Chang</name>
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<nlm:affiliation>Tuberculosis and Chest Service, Centre for Health Protection, Department of Health, Hong Kong SAR, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
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<name sortKey="Lange, Christoph" sort="Lange, Christoph" uniqKey="Lange C" first="Christoph" last="Lange">Christoph Lange</name>
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<nlm:affiliation>Division of Clinical Infectious Diseases, German Center for Infection Research, Research Center Borstel, Borstel, Schleswig-Holstein, Germany; International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany; Department of Medicine, Karolinska Institute, Stockholm, Sweden; Department of Medicine, University of Namibia School of Medicine, Windhoek, Namibia.</nlm:affiliation>
<country xml:lang="fr">Namibie</country>
<wicri:regionArea>Division of Clinical Infectious Diseases, German Center for Infection Research, Research Center Borstel, Borstel, Schleswig-Holstein, Germany; International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany; Department of Medicine, Karolinska Institute, Stockholm, Sweden; Department of Medicine, University of Namibia School of Medicine, Windhoek</wicri:regionArea>
<wicri:noRegion>Windhoek</wicri:noRegion>
</affiliation>
</author>
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<name sortKey="Nahid, Payam" sort="Nahid, Payam" uniqKey="Nahid P" first="Payam" last="Nahid">Payam Nahid</name>
<affiliation wicri:level="2">
<nlm:affiliation>Division of Pulmonary and Critical Care, San Francisco General Hospital, University of California, San Francisco, CA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Pulmonary and Critical Care, San Francisco General Hospital, University of California, San Francisco, CA</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Udwadia, Zarir F" sort="Udwadia, Zarir F" uniqKey="Udwadia Z" first="Zarir F" last="Udwadia">Zarir F. Udwadia</name>
<affiliation wicri:level="1">
<nlm:affiliation>Pulmonary Department, Hinduja Hospital & Research Center, Mumbai, India.</nlm:affiliation>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Pulmonary Department, Hinduja Hospital & Research Center, Mumbai</wicri:regionArea>
<wicri:noRegion>Mumbai</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Horsburgh, C Robert" sort="Horsburgh, C Robert" uniqKey="Horsburgh C" first="C Robert" last="Horsburgh">C Robert Horsburgh</name>
<affiliation wicri:level="2">
<nlm:affiliation>Schools of Public Health Medicine, Boston University, Boston, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Schools of Public Health Medicine, Boston University, Boston, MA</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Churchyard, Gavin J" sort="Churchyard, Gavin J" uniqKey="Churchyard G" first="Gavin J" last="Churchyard">Gavin J. Churchyard</name>
<affiliation wicri:level="1">
<nlm:affiliation>Aurum Institute, Johannesburg, South Africa; School of Public Health, University of Witwatersrand, Johannesburg, South Africa; Advancing Treatment and Care for TB/HIV, South African Medical Research Council, Johannesburg, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Aurum Institute, Johannesburg, South Africa; School of Public Health, University of Witwatersrand, Johannesburg, South Africa; Advancing Treatment and Care for TB/HIV, South African Medical Research Council, Johannesburg</wicri:regionArea>
<wicri:noRegion>Johannesburg</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Menzies, Dick" sort="Menzies, Dick" uniqKey="Menzies D" first="Dick" last="Menzies">Dick Menzies</name>
<affiliation wicri:level="4">
<nlm:affiliation>Montreal Chest Institute, McGill University, Montreal, QC, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Montreal Chest Institute, McGill University, Montreal, QC</wicri:regionArea>
<orgName type="university">Université McGill</orgName>
<placeName>
<settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Hesseling, Anneke C" sort="Hesseling, Anneke C" uniqKey="Hesseling A" first="Anneke C" last="Hesseling">Anneke C. Hesseling</name>
<affiliation wicri:level="1">
<nlm:affiliation>Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town</wicri:regionArea>
<wicri:noRegion>Cape Town</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Nuermberger, Eric" sort="Nuermberger, Eric" uniqKey="Nuermberger E" first="Eric" last="Nuermberger">Eric Nuermberger</name>
<affiliation wicri:level="2">
<nlm:affiliation>Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Mcilleron, Helen" sort="Mcilleron, Helen" uniqKey="Mcilleron H" first="Helen" last="Mcilleron">Helen Mcilleron</name>
<affiliation wicri:level="1">
<nlm:affiliation>Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town</wicri:regionArea>
<wicri:noRegion>Cape Town</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Fennelly, Kevin P" sort="Fennelly, Kevin P" uniqKey="Fennelly K" first="Kevin P" last="Fennelly">Kevin P. Fennelly</name>
<affiliation wicri:level="2">
<nlm:affiliation>Pulmonary Clinical Medicine Section, Division of Intramural Research, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Pulmonary Clinical Medicine Section, Division of Intramural Research, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Goemaere, Eric" sort="Goemaere, Eric" uniqKey="Goemaere E" first="Eric" last="Goemaere">Eric Goemaere</name>
<affiliation wicri:level="1">
<nlm:affiliation>MSF South Africa, Cape Town, South Africa; School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>MSF South Africa, Cape Town, South Africa; School of Public Health and Family Medicine, University of Cape Town, Cape Town</wicri:regionArea>
<wicri:noRegion>Cape Town</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Jaramillo, Ernesto" sort="Jaramillo, Ernesto" uniqKey="Jaramillo E" first="Ernesto" last="Jaramillo">Ernesto Jaramillo</name>
<affiliation wicri:level="1">
<nlm:affiliation>World Health Organization, Geneva, Switzerland.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>World Health Organization, Geneva</wicri:regionArea>
<wicri:noRegion>Geneva</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Low, Marcus" sort="Low, Marcus" uniqKey="Low M" first="Marcus" last="Low">Marcus Low</name>
<affiliation wicri:level="1">
<nlm:affiliation>Treatment Action Campaign, Johannesburg, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Treatment Action Campaign, Johannesburg</wicri:regionArea>
<wicri:noRegion>Johannesburg</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Jara, Carolina Moran" sort="Jara, Carolina Moran" uniqKey="Jara C" first="Carolina Morán" last="Jara">Carolina Morán Jara</name>
<affiliation wicri:level="1">
<nlm:affiliation>Socios en Salud, Lima, Peru.</nlm:affiliation>
<country xml:lang="fr">Pérou</country>
<wicri:regionArea>Socios en Salud, Lima</wicri:regionArea>
<wicri:noRegion>Lima</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Padayatchi, Nesri" sort="Padayatchi, Nesri" uniqKey="Padayatchi N" first="Nesri" last="Padayatchi">Nesri Padayatchi</name>
<affiliation wicri:level="1">
<nlm:affiliation>Centre for the AIDS Programme of Research in South Africa (CAPRISA), MRC HIV-TB Pathogenesis and Treatment Research Unit, Durban, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Centre for the AIDS Programme of Research in South Africa (CAPRISA), MRC HIV-TB Pathogenesis and Treatment Research Unit, Durban</wicri:regionArea>
<wicri:noRegion>Durban</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Warren, Robin M" sort="Warren, Robin M" uniqKey="Warren R" first="Robin M" last="Warren">Robin M. Warren</name>
<affiliation wicri:level="1">
<nlm:affiliation>SA MRC Centre for Tuberculosis Research/DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg, South Africa.</nlm:affiliation>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>SA MRC Centre for Tuberculosis Research/DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg</wicri:regionArea>
<wicri:noRegion>Tygerberg</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j">The Lancet. Respiratory medicine</title>
<idno type="eISSN">2213-2619</idno>
<imprint>
<date when="2017" type="published">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis). This poses several challenges similar to those encountered in the pre-chemotherapy era, including the inability to cure tuberculosis, high mortality, and the need for alternative methods to prevent disease transmission. This phenomenon mirrors the worldwide increase in antimicrobial resistance and the emergence of other MDR pathogens, such as malaria, HIV, and Gram-negative bacteria. MDR and XDR tuberculosis are associated with high morbidity and substantial mortality, are a threat to health-care workers, prohibitively expensive to treat, and are therefore a serious public health problem. In this Commission, we examine several aspects of drug-resistant tuberculosis. The traditional view that acquired resistance to antituberculous drugs is driven by poor compliance and programmatic failure is now being questioned, and 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. These factors have implications for the design of new interventions, drug delivery and dosing mechanisms, and public health policy. We discuss epidemiology and transmission dynamics, including new insights into the fundamental biology of transmission, and we review the utility of newer diagnostic tools, including molecular tests and next-generation whole-genome sequencing, and their potential for clinical effectiveness. Relevant research priorities are highlighted, including optimal medical and surgical management, the role of newer and repurposed drugs (including bedaquiline, delamanid, and linezolid), pharmacokinetic and pharmacodynamic considerations, preventive strategies (such as prophylaxis in MDR and XDR contacts), palliative and patient-orientated care aspects, and medicolegal and ethical issues.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Afrique du Sud</li>
<li>Allemagne</li>
<li>Belgique</li>
<li>Canada</li>
<li>Inde</li>
<li>Namibie</li>
<li>Pérou</li>
<li>Royaume-Uni</li>
<li>République populaire de Chine</li>
<li>Suisse</li>
<li>Taïwan</li>
<li>États-Unis</li>
</country>
<region>
<li>Angleterre</li>
<li>Californie</li>
<li>Caroline du Nord</li>
<li>Grand Londres</li>
<li>Maryland</li>
<li>Massachusetts</li>
<li>Québec</li>
<li>Texas</li>
<li>État de New York</li>
</region>
<settlement>
<li>Chapel Hill (Caroline du Nord)</li>
<li>Londres</li>
<li>Montréal</li>
</settlement>
<orgName>
<li>Université McGill</li>
<li>Université de Caroline du Nord à Chapel Hill</li>
</orgName>
</list>
<tree>
<country name="Afrique du Sud">
<noRegion>
<name sortKey="Dheda, Keertan" sort="Dheda, Keertan" uniqKey="Dheda K" first="Keertan" last="Dheda">Keertan Dheda</name>
</noRegion>
<name sortKey="Churchyard, Gavin J" sort="Churchyard, Gavin J" uniqKey="Churchyard G" first="Gavin J" last="Churchyard">Gavin J. Churchyard</name>
<name sortKey="Esmail, Aliasgar" sort="Esmail, Aliasgar" uniqKey="Esmail A" first="Aliasgar" last="Esmail">Aliasgar Esmail</name>
<name sortKey="Goemaere, Eric" sort="Goemaere, Eric" uniqKey="Goemaere E" first="Eric" last="Goemaere">Eric Goemaere</name>
<name sortKey="Hesseling, Anneke C" sort="Hesseling, Anneke C" uniqKey="Hesseling A" first="Anneke C" last="Hesseling">Anneke C. Hesseling</name>
<name sortKey="London, Leslie" sort="London, Leslie" uniqKey="London L" first="Leslie" last="London">Leslie London</name>
<name sortKey="Low, Marcus" sort="Low, Marcus" uniqKey="Low M" first="Marcus" last="Low">Marcus Low</name>
<name sortKey="Maartens, Gary" sort="Maartens, Gary" uniqKey="Maartens G" first="Gary" last="Maartens">Gary Maartens</name>
<name sortKey="Mcilleron, Helen" sort="Mcilleron, Helen" uniqKey="Mcilleron H" first="Helen" last="Mcilleron">Helen Mcilleron</name>
<name sortKey="Mcnerney, Ruth" sort="Mcnerney, Ruth" uniqKey="Mcnerney R" first="Ruth" last="Mcnerney">Ruth Mcnerney</name>
<name sortKey="Padayatchi, Nesri" sort="Padayatchi, Nesri" uniqKey="Padayatchi N" first="Nesri" last="Padayatchi">Nesri Padayatchi</name>
<name sortKey="Schaaf, H Simon" sort="Schaaf, H Simon" uniqKey="Schaaf H" first="H Simon" last="Schaaf">H Simon Schaaf</name>
<name sortKey="Sirgel, Frik A" sort="Sirgel, Frik A" uniqKey="Sirgel F" first="Frik A" last="Sirgel">Frik A. Sirgel</name>
<name sortKey="Theron, Grant" sort="Theron, Grant" uniqKey="Theron G" first="Grant" last="Theron">Grant Theron</name>
<name sortKey="Van Helden, Paul" sort="Van Helden, Paul" uniqKey="Van Helden P" first="Paul" last="Van Helden">Paul Van Helden</name>
<name sortKey="Warren, Robin M" sort="Warren, Robin M" uniqKey="Warren R" first="Robin M" last="Warren">Robin M. Warren</name>
</country>
<country name="États-Unis">
<region name="Texas">
<name sortKey="Gumbo, Tawanda" sort="Gumbo, Tawanda" uniqKey="Gumbo T" first="Tawanda" last="Gumbo">Tawanda Gumbo</name>
</region>
<name sortKey="Dooley, Kelly E" sort="Dooley, Kelly E" uniqKey="Dooley K" first="Kelly E" last="Dooley">Kelly E. Dooley</name>
<name sortKey="Dowdy, David" sort="Dowdy, David" uniqKey="Dowdy D" first="David" last="Dowdy">David Dowdy</name>
<name sortKey="Fennelly, Kevin P" sort="Fennelly, Kevin P" uniqKey="Fennelly K" first="Kevin P" last="Fennelly">Kevin P. Fennelly</name>
<name sortKey="Furin, Jennifer" sort="Furin, Jennifer" uniqKey="Furin J" first="Jennifer" last="Furin">Jennifer Furin</name>
<name sortKey="Horsburgh, C Robert" sort="Horsburgh, C Robert" uniqKey="Horsburgh C" first="C Robert" last="Horsburgh">C Robert Horsburgh</name>
<name sortKey="Lessem, Erica" sort="Lessem, Erica" uniqKey="Lessem E" first="Erica" last="Lessem">Erica Lessem</name>
<name sortKey="Murray, Megan" sort="Murray, Megan" uniqKey="Murray M" first="Megan" last="Murray">Megan Murray</name>
<name sortKey="Nahid, Payam" sort="Nahid, Payam" uniqKey="Nahid P" first="Payam" last="Nahid">Payam Nahid</name>
<name sortKey="Nardell, Edward A" sort="Nardell, Edward A" uniqKey="Nardell E" first="Edward A" last="Nardell">Edward A. Nardell</name>
<name sortKey="Nuermberger, Eric" sort="Nuermberger, Eric" uniqKey="Nuermberger E" first="Eric" last="Nuermberger">Eric Nuermberger</name>
<name sortKey="Pasipanodya, Jotam G" sort="Pasipanodya, Jotam G" uniqKey="Pasipanodya J" first="Jotam G" last="Pasipanodya">Jotam G. Pasipanodya</name>
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<name sortKey="Van Rie, Annelies" sort="Van Rie, Annelies" uniqKey="Van Rie A" first="Annelies" last="Van Rie">Annelies Van Rie</name>
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<name sortKey="Siu, Gilman K H" sort="Siu, Gilman K H" uniqKey="Siu G" first="Gilman K H" last="Siu">Gilman K H. Siu</name>
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<name sortKey="Chang, Kwok Chiu" sort="Chang, Kwok Chiu" uniqKey="Chang K" first="Kwok Chiu" last="Chang">Kwok Chiu Chang</name>
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<country name="Inde">
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<name sortKey="Rodrigues, Camilla" sort="Rodrigues, Camilla" uniqKey="Rodrigues C" first="Camilla" last="Rodrigues">Camilla Rodrigues</name>
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<name sortKey="Udwadia, Zarir F" sort="Udwadia, Zarir F" uniqKey="Udwadia Z" first="Zarir F" last="Udwadia">Zarir F. Udwadia</name>
</country>
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<region name="Angleterre">
<name sortKey="Clark, Taane G" sort="Clark, Taane G" uniqKey="Clark T" first="Taane G" last="Clark">Taane G. Clark</name>
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<noRegion>
<name sortKey="Lin, Hsien Ho" sort="Lin, Hsien Ho" uniqKey="Lin H" first="Hsien-Ho" last="Lin">Hsien-Ho Lin</name>
</noRegion>
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<noRegion>
<name sortKey="Lange, Christoph" sort="Lange, Christoph" uniqKey="Lange C" first="Christoph" last="Lange">Christoph Lange</name>
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<country name="Canada">
<region name="Québec">
<name sortKey="Menzies, Dick" sort="Menzies, Dick" uniqKey="Menzies D" first="Dick" last="Menzies">Dick Menzies</name>
</region>
</country>
<country name="Suisse">
<noRegion>
<name sortKey="Jaramillo, Ernesto" sort="Jaramillo, Ernesto" uniqKey="Jaramillo E" first="Ernesto" last="Jaramillo">Ernesto Jaramillo</name>
</noRegion>
</country>
<country name="Pérou">
<noRegion>
<name sortKey="Jara, Carolina Moran" sort="Jara, Carolina Moran" uniqKey="Jara C" first="Carolina Morán" last="Jara">Carolina Morán Jara</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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