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.
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.
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 infections (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.
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
Ashley, E.A.; et al. Spread of Artemisinin Resistance in Plasmodium falciparum Malaria. New England Journal of Medicine (2014) 371 (5) 411-423. [DOI: 10.1056/NEJMoa1314981]
Spread of Artemisinin Resistance in Plasmodium falciparum Malaria