Global control of tuberculosis: from extensively drug-resistant to untreatable tuberculosis.
Extensively drug-resistant tuberculosis is a burgeoning global health crisis mainly affecting economically active young adults, and has high mortality irrespective of HIV status. In some countries such as South Africa, drug-resistant tuberculosis represents less than 3% of all cases but consumes more than a third of the total national budget for tuberculosis, which is unsustainable and threatens to destabilise national tuberculosis programmes. However, concern about drug-resistant tuberculosis has been eclipsed by that of totally and extremely drug-resistant tuberculosis--ie, resistance to all or nearly all conventional first-line and second-line antituberculosis drugs. In this Review, we discuss the epidemiology, pathogenesis, diagnosis, management, implications for health-care workers, and ethical and medicolegal aspects of extensively drug-resistant tuberculosis and other resistant strains. Finally, we discuss the emerging problem of functionally untreatable tuberculosis, and the issues and challenges that it poses to public health and clinical practice. The emergence and growth of highly resistant strains of tuberculosis make the development of new drugs and rapid diagnostics for tuberculosis--and increased funding to strengthen global control efforts, research, and advocacy--even more pressing.
Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa; Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa. Electronic address: keertan.dheda@uct.ac.za.
Keertan
K
Dheda
Office of Global Health and Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Tawanda
T
Gumbo
Departments of Epidemiology, Global Health, and Infectious Diseases, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Neel R
NR
Gandhi
Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.
Megan
M
Murray
Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Grant
G
Theron
Hinduja Hospital and Research Center, Mumbai, India.
Zarir
Z
Udwadia
WHO Collaborating Centre for TB and Lung Diseases, Fondazione S Maugeri, Care and Research Institute, Tradate, Italy.
G B
GB
Migliori
DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Robin
R
Warren
D054908:Extensively Drug-Resistant Tuberculosis / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy; D014943:Global Health; D006801:Humans; D017758:Infectious Disease Transmission, Patient-to-Professional / Q000517:prevention & control; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy