Assessing Antimalarial Efficacy in a Time of Change to Artemisinin-Based Combination Therapies: The Role of Médecins Sans Frontières

During the 1990s, high levels of Plasmodium falciparum (Pf) resistance to common antimalarials were reported from malaria-endemic countries, raising questions about the efficacy of chloroquine (CQ), then the mainstay of antimalarial treatment. Drug resistance was considered a prime contributing factor to increased malaria mortality and morbidity across Africa [1,2]. The natural successor to CQ, sulfadoxine-pyrimethamine (SP), had a short therapeutic lifespan [3], and the choice of an effective first-line regimen emerged as a key issue in Pf malaria control. Artemisinin-based combination therapy (ACT), adopted in southeast Asia since the early 1990s, appeared to be the best available option [3]. Summary Points More than 12,000 patients were enrolled in 43 efficacy studies in 18 countries of Asia and Africa between 1996 and 2004, accounting for one fourth of the overall research output in these countries. This has provided extensive evidence on the efficacy of most drug regimens currently in use for uncomplicated malaria, which was often used for treatment policy changes by the concerned countries. The greatest contribution was in conflict-affected countries of sub-Saharan Africa, where studies represent the vast majority of available data and where “traditional” academic research institutions were not or barely represented. The vast majority of the studies were published in peer-reviewed journals, which shows that research performed in difficult settings can be of a high enough standard to ensure publication and to be useful in policy change. This work demonstrates the potential role of non-governmental agencies in collecting the necessary evidence to stimulate and inform policy change in international health. Medecins Sans Frontieres (Doctors Without Borders, or MSF) is a humanitarian medical aid organisation, dedicated to providing assistance to populations who lack access to health care. In the 1990s, antimalarial resistance was emergent in most countries where MSF was operating, but scientific evidence of this resistance was often lacking, and CQ or SP were still recommended by national malaria control programmes. Faced with a lack of data and the reluctance of international technical advisors and donors to review treatment strategies, MSF initiated in vivo studies to document the situation in its programme locations. While the primary aim was optimising treatment strategies for MSF patients, results were often used to formulate national policy change. Studies followed World Health Organization (WHO) recommendations [4,5], were usually conducted in insecure or difficult-to-access sites where data were absent, and were generally supported by MSF's epidemiological unit, Epicentre, in collaboration with national Ministries of Health, WHO, and other partners. Here, we describe the output of MSF's work in antimalarial efficacy assessment during the last decade, and place it within the broader context of studies leading to regimen change from monotherapies to mostly artemisinin-based combinations during a critical decade in malaria control. We also describe challenges and lessons learned whilst carrying out this research and discuss its role within antimalarial policy change.