title: Drug-resistant tuberculosis--current dilemmas, unanswered questions, challenges, and priority needs.
abstract: 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.
authors.affiliation: University College London, Centre for Clinical Microbiology, Division of Infection and Immunity, London, UK. a.zumla@ucl.ac.uk
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Abubakar
authors.forename: Mario
authors.initials: M
authors.lastname: Raviglione
authors.forename: Michael
authors.initials: M
authors.lastname: Hoelscher
authors.forename: Lucica
authors.initials: L
authors.lastname: Ditiu
authors.forename: Timothy D
authors.initials: TD
authors.lastname: McHugh
authors.forename: S Bertel
authors.initials: SB
authors.lastname: Squire
authors.forename: Helen
authors.initials: H
authors.lastname: Cox
authors.forename: Nathan
authors.initials: N
authors.lastname: Ford
authors.forename: Ruth
authors.initials: R
authors.lastname: McNerney
authors.forename: Ben
authors.initials: B
authors.lastname: Marais
authors.forename: Martin
authors.initials: M
authors.lastname: Grobusch
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lawn
authors.forename: Giovanni-Battista
authors.initials: GB
authors.lastname: Migliori
authors.forename: Peter
authors.initials: P
authors.lastname: Mwaba
authors.forename: Justin
authors.initials: J
authors.lastname: O'Grady
authors.forename: Michel
authors.initials: M
authors.lastname: Pletschette
authors.forename: Andrew
authors.initials: A
authors.lastname: Ramsay
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Chakaya
authors.forename: Marco
authors.initials: M
authors.lastname: Schito
authors.forename: Soumya
authors.initials: S
authors.lastname: Swaminathan
authors.forename: Ziad
authors.initials: Z
authors.lastname: Memish
authors.forename: Markus
authors.initials: M
authors.lastname: Maeurer
authors.forename: Rifat
authors.initials: R
authors.lastname: Atun
mesh_terms: D000328:Adult; D000349:Africa / Q000453:epidemiology; D000995:Antitubercular Agents / Q000494:pharmacology*; D002648:Child; D003140:Communicable Disease Control / Q000379:methods; D023801:Directly Observed Therapy / Q000941:ethics; D004334:Drug Administration Schedule; D024901:Drug Resistance, Multiple, Bacterial; D019353:Endemic Diseases; D014943:Global Health; D006291:Health Policy; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D028701:Patient Rights; D013997:Time Factors; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology* / Q000517:prevention & control*
chemical_list: D000995:Antitubercular Agents