A prioritised research agenda for DOTS-Plus for multidrug-resistant tuberculosis (MDR-TB).

MULTIDRUG-RESISTANT tuberculosis (MDR-TB) is defined as a form of tuberculosis (TB) due to Mycobacterium tuberculosis that is resistant to at least isoniazid and rifampicin, the two most powerful anti-TB drugs. This form of TB was documented in nearly every country surveyed by the World Health Organization (WHO)/International Union Against Tuberculosis and Lung Disease (IUATLD) Global Drug Resistance Surveillance Project during the period 1994– 2000. Some settings, such as those in the former Soviet Union, show a high proportion of MDR-TB cases among new TB cases.1,2 Other settings show a lower proportion, but have a considerable MDR-TB burden in terms of total number of patients due to the size of the population and the magnitude of TB as a whole.3 The diversity in the epidemiology of MDR-TB poses a challenge for its management in various settings. Drug resistance in bacteria is a natural phenomenon, but selective pressure induced by man-made mechanisms is the primary cause of MDR-TB. Drug resistance in TB (to isoniazid, para-aminosalicylic acid [PAS], streptomycin, and capreomycin) was documented shortly after the advent of these chemotherapeutic agents, and principles to manage such patients were proposed accordingly.4–6 With the implementation of the internationally accepted DOTS† strategy for TB control and its essential component of standardised short-course chemotherapy (SCC), a comprehensive control strategy is available that, when followed properly, prevents the emergence of drug resistance. All currently recommended regimens are based upon the first-line drugs isoniazid, rifampicin, pyrazinamide, ethambutol and streptomycin.7 Unfor-