title: Criteria for the control of drug-resistant tuberculosis.
abstract: Antibiotic resistance is a growing impediment to the control of infectious diseases worldwide, tuberculosis (TB) being among them. TB kills two million people each year and foci of multidrug-resistant TB (MDR-TB) have been identified in Eastern Europe, Africa, Asia, and Latin America. A critical question for health policy is whether standardized short-course chemotherapy for TB, based on cheap first-line drugs, can prevent and reverse the spread of drug resistance. Here we use mathematical modeling, in conjunction with treatment results from six countries, to show that best-practice short-course chemotherapy is highly likely to bring strains resistant to either of the two key drugs isoniazid and rifampicin under control and to prevent the emergence of MDR-TB. However, it is not certain to contain MDR-TB once it has emerged, partly because cure rates are too low. We estimate that approximately 70% of prevalent, infectious MDR-TB cases should be detected and treated each year, and at least 80% of these cases should be cured, in order to prevent outbreaks of MDR-TB. Poor control programs should aim to increase case detection and cure rates together for three reasons: (i) these variables act synergistically; (ii) when either is low, the other cannot succeed alone; and (iii) the second-line drugs needed to raise MDR-TB cure rates are few and extremely costly. We discuss the implications of these results for World Health Organization policy on the management of antibiotic resistance.
authors.affiliation: Communicable Disease Control, Prevention and Eradication, World Health Organization, CH-1211 Geneva 27, Switzerland. dyec@who.ch
authors.forename: C
authors.initials: C
authors.lastname: Dye
authors.forename: B G
authors.initials: BG
authors.lastname: Williams
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D008962:Models, Theoretical; D017410:Practice Guidelines as Topic; D012293:Rifampin / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000517:prevention & control; D014944:World Health Organization
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin