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

et al. (2008) Scaling up programmatic management of drug-resistant tuberculosis: A prioritized research agenda. PLoS Med 5(7): e150. doi:10.1371/journal.pmed.0050150 Scaling Up Programmatic Management of Drug-Resistant Tuberculosis: A Prioritized Research Agenda Frank G. J. Cobelens 0 1 Einar Heldal 0 1 Michael E. Kimerling 0 1 Carole D. Mitnick 0 1 Laura J. Podewils 0 1 Rajeswari Ramachandran 0 1 Hans L. Rieder 0 1 Karin Weyer 0 1 Matteo Zignol 0 1 on behalf of the Working Group on MDR-TB of the Stop TB Partnership 0 1 0 Frank G. J. Cobelens is with the KNCV Tuberculosis Foundation , The Hague , The Netherlands , and the Center for Infection and Immunity Amsterdam, Academic Medical Centre , Amsterdam , The Netherlands. Einar Heldal is with the Norwegian Association of Heart and Lung Patients , Oslo , Norway. Michael E. Kimerling is with the Gorgas Tuberculosis Initiative, Department of Medicine, University of Alabama at Birmingham , Birmingham , Alabama, United States of America (current affiliation: Drug Resistant TB Program, Bill & Melinda Gates Foundation, Seattle, Washington, United States of America). Carole D. Mitnick is with Harvard Medical School , Boston , Massachusetts, United States of America. Laura J. Podewils is with the Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America. Rajeswari Ramachandran is with the Tuberculosis Research Centre, Indian Council of Medical Research , Chennai, Tamil Nadu , India. Hans L. Rieder is with the International Union against Tuberculosis and Lung Disease , Paris , France. Karin Weyer is with the South African Medical Research Council , Pretoria, Gauteng , South Africa ( current affiliation: Stop TB Department, World Health Organization , Geneva , Switzerland) . Matteo Zignol is with the Stop TB Department, World Health Organization , Geneva , Switzerland 1 Abbreviations: DOTS , directly observed treatment, short-course; DR-TB, drug- resistant tuberculosis; DST, drug susceptibility testing; GLC, Green Light Committee; MDR-TB, multidrug-resistant tuberculosis; PMDT , programmatic management of drug-resistant tuberculosis; TB, tuberculosis; WHO, World Health Organization; XDR-TB , extensively resistant tuberculosis Summary Points - 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 19942007, 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. programmatic management of drug-resistant tuberculosis in resource-limited settings. achievement of this scale-up. resistance testing; clinical trials of simplified and shorter second-line treatment regimens; new and improved strategies for diagnosis of drug-resistant tuberculosis, treatment adherence, and infection control; understanding of the geographic variations in occurrence of drug resistance; and clinical trials of prophylactic treatment of contacts of patients with drug-resistant tuberculosis. Drug-resistant tuberculosis (DR-TB): Disease caused by a strain of M. tuberculosis that is resistant to any anti-tuberculosis drug. Multidrug-resistant tuberculosis (MDR-TB): Disease caused by a strain of M. tuberculosis that is resistant to at least isoniazid and rifampicin [3,4]. Extensively drug-resistant tuberculosis (XDR-TB): Disease caused by a strain of M. tuberculosis that is resistant to isoniazid and rifampicin plus any fluoroquinolone and at least one of the three injectable second-line drugs (amikacin, kanamycin, capreomycin) [6,7]. Concurrently, the Green Light Committee (GLC) was established by the Stop TB Partnership to facilitate access to concessionally priced, quality-assured second-line antituberculosis drugs for MDR-TB management projects that meet the criteria for rational use [9,10]. Evaluation of the first GLC-endorsed pilot projects of MDR-TB management in five resource-limited countries showed treatment success rates of 59%83% [11]. Based on the experiences from the DOTS-Plus pilot projects, the WHO recently issued guidelines for what is now called programmatic management of drugresistant TB (PMDT). Funding for MDR-TB treatment has dramatically increased in the past few years, and is available through governments and donors, including the Global Fund to Fight AIDS, Tuberculosis and Malaria, and UNITAID. Now that the effectiveness and feasibility of MDR-TB management in resource-limited settings has been demonstrated, the emerging global MDR-TB epidemic requires moving beyond the pilot project stage in order to mainstream MDR-TB management into national tuberculosis control programs. Currently, fewer than 2% of all estimated MDR-TB patients receive appropriate treatment [1]. The Global Plan to Stop TB 20062015 urges a dramatic scale-up of MDR-TB treatment as a routine component of TB control; a 2007 addendum calls for the treatment of 1.6 million MDR-TB patients by 20 (...truncated)