Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 15 March 2002:
Vol. 295. no. 5562, pp. 2042 - 2046
DOI: 10.1126/science.1063814
Prev | Table of Contents | Next

Review

Erasing the World's Slow Stain: Strategies to Beat Multidrug-Resistant Tuberculosis

Christopher Dye,* Brian G. Williams, Marcos A. Espinal, Mario C. Raviglione

Multidrug-resistant tuberculosis (MDR) is perceived as a growing hazard to human health worldwide. Judgments about the true scale of the problem, and strategies for containing it, need to come from a balanced appraisal of the epidemiological evidence. We conclude in this review that MDR is, and will probably remain, a locally severe problem; that epidemics can be prevented by fully exploiting the potential of standard short-course chemotherapy (SCC) based on cheap and safe first-line drugs; and that best-practice SCC may even reduce the incidence of MDR where it has already become endemic. On the basis of the available, imperfect data, we recommend a three-part response to the threat of MDR: widespread implementation of SCC as the cornerstone of good tuberculosis control, improved resistance testing and surveillance, and the careful introduction of second-line drugs after a sound evaluation of cost, effectiveness, and feasibility.

Communicable Diseases, World Health Organization, CH-1211 Geneva 27, Switzerland.
*   To whom correspondence should be addressed. E-mail: dyec{at}who.int

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Slow Elimination of Multidrug-Resistant Tuberculosis.
C. Dye and B. G. Williams (2009)
Science Translational Medicine 1, 3ra8
   Abstract »    Full Text »    PDF »
The epidemiological fitness cost of drug resistance in Mycobacterium tuberculosis.
F. Luciani, S. A. Sisson, H. Jiang, A. R. Francis, and M. M. Tanaka (2009)
PNAS 106, 14711-14715
   Abstract »    Full Text »    PDF »
Standardized Regimens and the Emergence of Multidrug-resistant Tuberculosis.
K. C. Chang (2009)
Am. J. Respir. Crit. Care Med. 179, 517-518
   Full Text »    PDF »
Short- versus long-duration antimicrobial treatment for exacerbations of chronic bronchitis: a meta-analysis.
M. E. Falagas, S. G. Avgeri, D. K. Matthaiou, G. Dimopoulos, and I. I. Siempos (2008)
J. Antimicrob. Chemother. 62, 442-450
   Abstract »    Full Text »    PDF »
Impact of enhanced tuberculosis diagnosis in South Africa: A mathematical model of expanded culture and drug susceptibility testing.
D. W. Dowdy, R. E. Chaisson, G. Maartens, E. L. Corbett, and S. E. Dorman (2008)
PNAS 105, 11293-11298
   Abstract »    Full Text »    PDF »
Influence of Multidrug Resistance on Tuberculosis Treatment Outcomes with Standardized Regimens.
A. Mak, A. Thomas, M. del Granado, R. Zaleskis, N. Mouzafarova, and D. Menzies (2008)
Am. J. Respir. Crit. Care Med. 178, 306-312
   Abstract »    Full Text »    PDF »
Initial Drug Resistance and Tuberculosis Treatment Outcomes: Systematic Review and Meta-analysis.
W. Lew, M. Pai, O. Oxlade, D. Martin, and D. Menzies (2008)
Ann Intern Med 149, 123-134
   Abstract »    Full Text »    PDF »
Eliminating human tuberculosis in the twenty-first century.
C. Dye and B. G Williams (2008)
J R Soc Interface 5, 653-662
   Abstract »    Full Text »    PDF »
Mycobacterium tuberculosis strains disrupted in mce3 and mce4 operons are attenuated in mice.
R. H. Senaratne, B. Sidders, P. Sequeira, G. Saunders, K. Dunphy, O. Marjanovic, J. R. Reader, P. Lima, S. Chan, S. Kendall, et al. (2008)
J. Med. Microbiol. 57, 164-170
   Abstract »    Full Text »    PDF »
Competitive release and facilitation of drug-resistant parasites after therapeutic chemotherapy in a rodent malaria model.
A. R. Wargo, S. Huijben, J. C. de Roode, J. Shepherd, and A. F. Read (2007)
PNAS 104, 19914-19919
   Abstract »    Full Text »    PDF »
IL-1 Receptor-Mediated Signal Is an Essential Component of MyD88-Dependent Innate Response to Mycobacterium tuberculosis Infection.
C. M. Fremond, D. Togbe, E. Doz, S. Rose, V. Vasseur, I. Maillet, M. Jacobs, B. Ryffel, and V. F. J. Quesniaux (2007)
J. Immunol. 179, 1178-1189
   Abstract »    Full Text »    PDF »
Drug Resistance in Tuberculosis.
G. J. Ebrahim (2007)
J Trop Pediatr 53, 147-149
   Full Text »    PDF »
Vaccine efficacy of an attenuated but persistent Mycobacterium tuberculosis cysH mutant.
R. H. Senaratne, J. D. Mougous, J. R. Reader, S. J. Williams, T. Zhang, C. R. Bertozzi, and L. W. Riley (2007)
J. Med. Microbiol. 56, 454-458
   Abstract »    Full Text »    PDF »
AccD6, a Member of the Fas II Locus, Is a Functional Carboxyltransferase Subunit of the Acyl-Coenzyme A Carboxylase in Mycobacterium tuberculosis.
J. Daniel, T.-J. Oh, C.-M. Lee, and P. E. Kolattukudy (2007)
J. Bacteriol. 189, 911-917
   Abstract »    Full Text »    PDF »
Molecular Epidemiology of Tuberculosis: Current Insights.
B. Mathema, N. E. Kurepina, P. J. Bifani, and B. N. Kreiswirth (2006)
Clin. Microbiol. Rev. 19, 658-685
   Abstract »    Full Text »    PDF »
The competitive cost of antibiotic resistance in Mycobacterium tuberculosis..
S. Gagneux, C. D. Long, P. M. Small, T. Van, G. K. Schoolnik, and B. J. M. Bohannan (2006)
Science 312, 1944-1946
   Abstract »    Full Text »    PDF »
Methyltransferase Erm(37) Slips on rRNA to Confer Atypical Resistance in Mycobacterium tuberculosis.
C. T. Madsen, L. Jakobsen, K. Buriankova, F. Doucet-Populaire, J.-L. Pernodet, and S. Douthwaite (2005)
J. Biol. Chem. 280, 38942-38947
   Abstract »    Full Text »    PDF »
Detection of Mutations Associated with Isoniazid Resistance in Mycobacterium tuberculosis Isolates from China.
M. Zhang, J. Yue, Y.-p. Yang, H.-m. Zhang, J.-q. Lei, R.-l. Jin, X.-l. Zhang, and H.-h. Wang (2005)
J. Clin. Microbiol. 43, 5477-5482
   Abstract »    Full Text »    PDF »
Identification of tailoring genes involved in the modification of the polyketide backbone of rifamycin B by Amycolatopsis mediterranei S699.
J. Xu, E. Wan, C.-J. Kim, H. G. Floss, and T. Mahmud (2005)
Microbiology 151, 2515-2528
   Abstract »    Full Text »    PDF »
Molecular Mechanisms by Which rRNA Mutations Confer Resistance to Clindamycin.
J. Poehlsgaard, P. Pfister, E. C. Bottger, and S. Douthwaite (2005)
Antimicrob. Agents Chemother. 49, 1553-1555
   Abstract »    Full Text »    PDF »
Rates of drug resistance and risk factor analysis in civilian and prison patients with tuberculosis in Samara Region, Russia.
M Ruddy, Y Balabanova, C Graham, I Fedorin, N Malomanova, E Elisarova, S Kuznetznov, G Gusarova, S Zakharova, A Melentyev, et al. (2005)
Thorax 60, 130-135
   Abstract »    Full Text »    PDF »
Reduced Local Growth and Spread but Preserved Pathogenicity of a {Delta}purC Mycobacterium tuberculosis Auxotrophic Mutant in Gamma Interferon Receptor-Deficient Mice after Aerosol Infection.
N. Brown, M. Jacobs, S. K. Parida, T. Botha, A. Santos, L. Fick, B. Gicquel, M. Jackson, V. Quesniaux, and B. Ryffel (2005)
Infect. Immun. 73, 666-670
   Abstract »    Full Text »    PDF »
Transmission of tuberculosis in a high incidence urban community in South Africa.
S. Verver, R. M Warren, Z. Munch, E. Vynnycky, P. D van Helden, M. Richardson, G. D van der Spuy, D. A Enarson, M. W Borgdorff, M. A Behr, et al. (2004)
Int. J. Epidemiol. 33, 351-357
   Abstract »    Full Text »    PDF »
The Prodrug Activator EtaA from Mycobacterium tuberculosis Is a Baeyer-Villiger Monooxygenase.
M. W. Fraaije, N. M. Kamerbeek, A. J. Heidekamp, R. Fortin, and D. B. Janssen (2004)
J. Biol. Chem. 279, 3354-3360
   Abstract »    Full Text »    PDF »
Facilitated Drug Influx by an Energy-uncoupled Secondary Multidrug Transporter.
P. Mazurkiewicz, G. J. Poelarends, A. J. M. Driessen, and W. N. Konings (2004)
J. Biol. Chem. 279, 103-108
   Abstract »    Full Text »    PDF »
Molecular Basis of Intrinsic Macrolide Resistance in the Mycobacterium tuberculosis Complex.
K. Buriankova, F. Doucet-Populaire, O. Dorson, A. Gondran, J.-C. Ghnassia, J. Weiser, and J.-L. Pernodet (2004)
Antimicrob. Agents Chemother. 48, 143-150
   Abstract »    Full Text »    PDF »
Unique Mechanism of Action of the Thiourea Drug Isoxyl on Mycobacterium tuberculosis.
B. Phetsuksiri, M. Jackson, H. Scherman, M. McNeil, G. S. Besra, A. R. Baulard, R. A. Slayden, A. E. DeBarber, C. E. Barry III, M. S. Baird, et al. (2003)
J. Biol. Chem. 278, 53123-53130
   Abstract »    Full Text »    PDF »
Immune Control of Tuberculosis by IFN-{gamma}-Inducible LRG-47.
J. D. MacMicking, G. A. Taylor, and J. D. McKinney (2003)
Science 302, 654-659
   Abstract »    Full Text »    PDF »
Continued Low Rates of Transmission of Mycobacterium tuberculosis in Norway.
U. R. Dahle, P. Sandven, E. Heldal, and D. A. Caugant (2003)
J. Clin. Microbiol. 41, 2968-2973
   Abstract »    Full Text »    PDF »
Mutations in the rpoB Gene of Multidrug-Resistant Mycobacterium tuberculosis Isolates from China.
J. Yue, W. Shi, J. Xie, Y. Li, E. Zeng, and H. Wang (2003)
J. Clin. Microbiol. 41, 2209-2212
   Abstract »    Full Text »    PDF »
Factors Contributing to the Occurrence of Emerging Infectious Diseases.
F. R. Lashley (2003)
Biol Res Nurs 4, 258-267
   Abstract »    PDF »
Impact of DOTS compared with DOTS-plus on multidrug resistant tuberculosis and tuberculosis deaths: decision analysis.
T. R Sterling, H. P Lehmann, and T. R Frieden (2003)
BMJ 326, 574
   Abstract »    Full Text »    PDF »
Cutting Edge: Mycobacterium tuberculosis Blocks Ca2+ Signaling and Phagosome Maturation in Human Macrophages Via Specific Inhibition of Sphingosine Kinase.
Z. A. Malik, C. R. Thompson, S. Hashimi, B. Porter, S. S. Iyer, and D. J. Kusner (2003)
J. Immunol. 170, 2811-2815
   Abstract »    Full Text »    PDF »
Community-Based Therapy for Multidrug-Resistant Tuberculosis in Lima, Peru.
C. Mitnick, J. Bayona, E. Palacios, S. Shin, J. Furin, F. Alcantara, E. Sanchez, M. Sarria, M. Becerra, M. C. S. Fawzi, et al. (2003)
N. Engl. J. Med. 348, 119-128
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)