The Epidemiology, Pathogenesis, Transmission, Diagnosis, and Management of Multidrug-Resistant, Extensively Drug-Resistant, and Incurable Tuberculosis

Hdl Handle:
http://hdl.handle.net/10144/618877
Title:
The Epidemiology, Pathogenesis, Transmission, Diagnosis, and Management of Multidrug-Resistant, Extensively Drug-Resistant, and Incurable Tuberculosis
Authors:
Dheda, K; Gumbo, T; Maartens, G; Dooley, KE; McNerney, R; Murray, M; Furin, J; Nardell, EA; London, L; Lessem, E; Theron, G; van Helden, P; Niemann, S; Merker, M; Dowdy, D; Van Rie, A; Siu, GKH; Pasipanodya, JG; Rodrigues, C; Clark, TG; Sirgel, FA; Esmail, A; Lin, HH; Atre, SR; Schaaf, HS; Chang, KC; Lange, C; Nahid, P; Udwadia, ZF; Horsburgh, CR; Churchyard, GJ; Menzies, D; Hesseling, AC; Nuermberger, E; McIlleron, H; Fennelly, KP; Goemaere, E; Jaramillo, E; Low, M; Jara, CM; Padayatchi, N; Warren, RM
Journal:
The Lancet. Respiratory Medicine
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.
Publisher:
Elsevier. We regret that this article is behind a paywall.
Issue Date:
15-Mar-2017
URI:
http://hdl.handle.net/10144/618877
DOI:
10.1016/S2213-2600(17)30079-6
PubMed ID:
28344011
Submitted date:
2017-03-29
Language:
en
ISSN:
2213-2619
Appears in Collections:
TB

Full metadata record

DC FieldValue Language
dc.contributor.authorDheda, Ken
dc.contributor.authorGumbo, Ten
dc.contributor.authorMaartens, Gen
dc.contributor.authorDooley, KEen
dc.contributor.authorMcNerney, Ren
dc.contributor.authorMurray, Men
dc.contributor.authorFurin, Jen
dc.contributor.authorNardell, EAen
dc.contributor.authorLondon, Len
dc.contributor.authorLessem, Een
dc.contributor.authorTheron, Gen
dc.contributor.authorvan Helden, Pen
dc.contributor.authorNiemann, Sen
dc.contributor.authorMerker, Men
dc.contributor.authorDowdy, Den
dc.contributor.authorVan Rie, Aen
dc.contributor.authorSiu, GKHen
dc.contributor.authorPasipanodya, JGen
dc.contributor.authorRodrigues, Cen
dc.contributor.authorClark, TGen
dc.contributor.authorSirgel, FAen
dc.contributor.authorEsmail, Aen
dc.contributor.authorLin, HHen
dc.contributor.authorAtre, SRen
dc.contributor.authorSchaaf, HSen
dc.contributor.authorChang, KCen
dc.contributor.authorLange, Cen
dc.contributor.authorNahid, Pen
dc.contributor.authorUdwadia, ZFen
dc.contributor.authorHorsburgh, CRen
dc.contributor.authorChurchyard, GJen
dc.contributor.authorMenzies, Den
dc.contributor.authorHesseling, ACen
dc.contributor.authorNuermberger, Een
dc.contributor.authorMcIlleron, Hen
dc.contributor.authorFennelly, KPen
dc.contributor.authorGoemaere, Een
dc.contributor.authorJaramillo, Een
dc.contributor.authorLow, Men
dc.contributor.authorJara, CMen
dc.contributor.authorPadayatchi, Nen
dc.contributor.authorWarren, RMen
dc.date.accessioned2017-03-30T13:40:08Z-
dc.date.available2017-03-30T13:40:08Z-
dc.date.issued2017-03-15-
dc.date.submitted2017-03-29-
dc.identifier.citationThe Epidemiology, Pathogenesis, Transmission, Diagnosis, and Management of Multidrug-Resistant, Extensively Drug-Resistant, and Incurable Tuberculosis. 2017 Lancet Respir Meden
dc.identifier.issn2213-2619-
dc.identifier.pmid28344011-
dc.identifier.doi10.1016/S2213-2600(17)30079-6-
dc.identifier.urihttp://hdl.handle.net/10144/618877-
dc.description.abstractGlobal 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.en
dc.language.isoenen
dc.publisherElsevier. We regret that this article is behind a paywall.en
dc.titleThe Epidemiology, Pathogenesis, Transmission, Diagnosis, and Management of Multidrug-Resistant, Extensively Drug-Resistant, and Incurable Tuberculosisen
dc.identifier.journalThe Lancet. Respiratory Medicineen

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