Abstract
The discovery of high prevalences of antibiotic resistance in some pathogens, in some parts of the world, has provoked fears of a widespread loss of drug efficacy. Here, we use a mathematical model to investigate the evolution of resistance to four major anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol and streptomycin) in 47 sites around the world. The model provides a new method of estimating the relative risk of treatment failure for patients carrying drug-resistant strains and the proportion of patients who develop resistance after failing treatment. Using estimates of these two quantities together with other published data, we reconstructed the epidemic spread of isoniazid resistance over the past 50 years. The predicted median prevalence of resistance among new cases today was 7.0% (range 0.9-64.3%), close to the 6.3% (range 0-28.1%) observed. Predicted and observed prevalences of resistance to isoniazid plus rifampicin (multidrug-resistant or MDR-TB) after 30 years of combined drug use were also similar, 0.9% (0.1-5.9%) and 1.0% (range 0-14.1%), respectively. With current data, and under prevailing treatment practices, it appears that MDR-TB will remain a localized problem, rather than becoming a global obstacle to tuberculosis control. To substantiate this result, further measurements are needed of the relative fitness of drug-resistant strains.
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Selected References
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- Blower S. M., Small P. M., Hopewell P. C. Control strategies for tuberculosis epidemics: new models for old problems. Science. 1996 Jul 26;273(5274):497–500. doi: 10.1126/science.273.5274.497. [DOI] [PubMed] [Google Scholar]
- Castillo-Chavez C., Feng Z. To treat or not to treat: the case of tuberculosis. J Math Biol. 1997 Jun;35(6):629–656. doi: 10.1007/s002850050069. [DOI] [PubMed] [Google Scholar]
- Dye C., Scheele S., Dolin P., Pathania V., Raviglione M. C. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA. 1999 Aug 18;282(7):677–686. doi: 10.1001/jama.282.7.677. [DOI] [PubMed] [Google Scholar]
- Dye C., Williams B. G. Criteria for the control of drug-resistant tuberculosis. Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8180–8185. doi: 10.1073/pnas.140102797. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Farmer P., Kim J. Y. Community based approaches to the control of multidrug resistant tuberculosis: introducing "DOTS-plus". BMJ. 1998 Sep 5;317(7159):671–674. doi: 10.1136/bmj.317.7159.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
- García-García M. L., Ponce de León A., Jiménez-Corona M. E., Jiménez-Corona A., Palacios-Martínez M., Balandrano-Campos S., Ferreyra-Reyes L., Juárez-Sandino L., Sifuentes-Osornio J., Olivera-Díaz H. Clinical consequences and transmissibility of drug-resistant tuberculosis in southern Mexico. Arch Intern Med. 2000 Mar 13;160(5):630–636. doi: 10.1001/archinte.160.5.630. [DOI] [PubMed] [Google Scholar]
- Glynn J. R., Vynnycky E., Fine P. E. Influence of sampling on estimates of clustering and recent transmission of Mycobacterium tuberculosis derived from DNA fingerprinting techniques. Am J Epidemiol. 1999 Feb 15;149(4):366–371. doi: 10.1093/oxfordjournals.aje.a009822. [DOI] [PubMed] [Google Scholar]
- Heymann S. J., Brewer T. F., Wilson M. E., Fineberg H. V. The need for global action against multidrug-resistant tuberculosis. JAMA. 1999 Jun 9;281(22):2138–2140. doi: 10.1001/jama.281.22.2138. [DOI] [PubMed] [Google Scholar]
- Horsburgh C. R., Jr The global problem of multidrug-resistant tuberculosis: the genie is out of the bottle. JAMA. 2000 May 17;283(19):2575–2576. doi: 10.1001/jama.283.19.2575. [DOI] [PubMed] [Google Scholar]
- Pablos-Méndez A., Raviglione M. C., Laszlo A., Binkin N., Rieder H. L., Bustreo F., Cohn D. L., Lambregts-van Weezenbeek C. S., Kim S. J., Chaulet P. Global surveillance for antituberculosis-drug resistance, 1994-1997. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance. N Engl J Med. 1998 Jun 4;338(23):1641–1649. doi: 10.1056/NEJM199806043382301. [DOI] [PubMed] [Google Scholar]
- van Soolingen D., Borgdorff M. W., de Haas P. E., Sebek M. M., Veen J., Dessens M., Kremer K., van Embden J. D. Molecular epidemiology of tuberculosis in the Netherlands: a nationwide study from 1993 through 1997. J Infect Dis. 1999 Sep;180(3):726–736. doi: 10.1086/314930. [DOI] [PubMed] [Google Scholar]