Lancet Respir Med. 2014 Apr;2(4):321-338. doi: 10.1016/S2213-2600(14)70031-1. Epub 2014 Mar 24.

Global control of tuberculosis: from extensively drug-resistant to untreatable tuberculosis.

Dheda K1, Gumbo T2, Gandhi NR3, Murray M4, Theron G5, Udwadia Z6, Migliori GB7, Warren R8.

Author information

• 1Lung 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.
• 2Office of Global Health and Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
• 3Departments of Epidemiology, Global Health, and Infectious Diseases, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
• 4Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.
• 5Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
• 6Hinduja Hospital and Research Center, Mumbai, India.
• 7WHO Collaborating Centre for TB and Lung Diseases, Fondazione S Maugeri, Care and Research Institute, Tradate, Italy.
• 8DST/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.

Abstract

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.