Spread of Artemisinin Resistance in Plasmodium falciparum Malaria
By E. Ashley, M. Dhorda, R. Fairhurst, C. Amaratunga, P. Lim, Seila Suon, Sokunthea Sreng, Jennifer M. Anderson, Sivanna Mao, Baramey Sam and 73 more. New England Journal of Medicine, 2014
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BACKGROUND Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies. METHODS Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined. RESULTS The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand–Cambodia border. Slowly clearing in fections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the “propeller” region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days. CONCLUSIONS Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. (Funded by the U.K. Department of International Development and others; ClinicalTrials.gov number, NCT01350856.)
Subfields: Cell Biology, Public Health, Environmental and Occupational Health
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Citations in the corpus
- Uncovering the essential genome of the human malaria parasite Plasmodium falciparum by saturation mutagenesis (2018, neutral): “Recently, there have been substantial reductions in disease intensity, in part through concerted recent use of artemisinin-combination therapies, but these gains are now threatened by emerging artemisininbased combination therapy (ACT) treatment failures spreading across South East Asia (1, 2).”
- Malaria: Biology and Disease. (2016, positive): “…Cambodia of decreasing sensitivity of P. falciparum to artemisinin derivatives where patients had significantly longer developed further into decreasing clinical efficacy (Ashley et al., 2014a; Guerin et al., 2009; Slater et al., 2016) and potential partner drug resistance (Menard et al., 2015).”