Scaling Up Programmatic Management of Drug-Resistant Tuberculosis: A Prioritized Research Agenda

Background Tuberculosis (TB) remains a significant global health problem, responsible for an estimated 1.7 million deaths per year worldwide [1]. Resistance to anti-tuberculosis drugs is an important threat to tuberculosis control. The risk of treatment failure and death with standard short-course chemotherapy is highest with resistance to both isoniazid and rifampicin (multidrug-resistant tuberculosis, or MDRTB; see Glossary) [2]. Drug-resistant tuberculosis is “humanmade”: it results from treatment with inadequate drugs or drug regimens, improper case management, and preventable transmission. Its presence generally reflects weak tuberculosis control in the past or present. Between 1994–2007, resistance to any first-line drugs among new tuberculosis cases was reported from 127 settings included in the Global Project on Anti-Tuberculosis Drug Resistance Surveillance, with a median prevalence of 17% [3]. The total number of MDRTB cases estimated to have occurred worldwide in 2006 was 489,139, or 4.8% of all TB cases. [3]. MDR-TB treatment using currently available second-line drugs may cure only 65%–75% of patients [4]. These drugs are more expensive, less potent, and less well tolerated than first-line drugs [4]. Inadequate treatment with second-line drugs may result in extensively drug-resistant tuberculosis (XDR-TB; see Glossary) [5,6]. XDR-TB is associated with high fatality, especially in patients who are co-infected with HIV [5,7]. In affluent countries, treatment with second-line drugs is generally limited to centers with specialized services. Such services are unavailable in many countries, and a programmatic approach is needed to provide treatment to large numbers of MDR-TB patients. In 1999, the World Health Organization (WHO) and partner agencies launched DOTS-Plus, a complementary DOTS-based strategy with provisions for treating MDR-TB based on the five tenets of the DOTS (directly observed treatment, short-course) strategy: sustained political commitment; a rational case-finding strategy; use of secondline drugs under appropriate case management conditions; an uninterrupted supply of quality-assured drugs; and standardized recording and reporting [8]. DOTS-plus pilot projects were started to obtain an evidence base for this strategy. Scaling Up Programmatic Management of Drug-Resistant Tuberculosis: A Prioritized Research Agenda