Drug-Resistant Tuberculosis--Current Dilemmas, Unanswered Questions, Challenges, and Priority Needs

University College London, Centre for Clinical Microbiology, Division of Infection and Immunity, London, UK.
The Journal of Infectious Diseases (Impact Factor: 6). 04/2012; 205 Suppl 2(suppl 2):S228-40. DOI: 10.1093/infdis/jir858
Source: PubMed


Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the pre-DOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrug-resistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drug-resistant tuberculosis pose a threat to global tuberculosis control. Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for drug susceptibility testing are inadequate in most tuberculosis-endemic countries, especially in Africa; thus diagnosis is missed, routine surveillance is not implemented, and the actual numbers of global drug-resistant tuberculosis cases have yet to be estimated. This exposes an ominous situation and reveals an urgent need for commitment by national programs to health system improvement because the response to MDR tuberculosis requires strong health services in general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate patient management within resource-poor national tuberculosis programs, reducing treatment efficacy and increasing the cost of treatment to the extent that it could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite nearly 20 years of WHO-promoted activity and >12 years of MDR tuberculosis-specific activity, has the country response to the drug-resistant tuberculosis epidemic been so ineffectual? The current dilemmas, unanswered questions, operational issues, challenges, and priority needs for global drug resistance screening and surveillance, improved treatment regimens, and management of outcomes and prevention of DR tuberculosis are discussed.

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    • "To this death toll the burden of economic losses (job losses, social segregation, and supervision of special programs for treatment) add up to make tuberculosis a still undefeated global public health enemy. There are few therapeutic options for tuberculosis treatment and clinical strains resistant to one or several of the anti-tubercular drugs have been described [2]–[4]. In order to improve existing drugs or to develop new ones, an understanding of mycobacterial physiology and pathogenesis mechanisms is urgently needed. "
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