Artesunate–mefloquine versus chloroquine for treatment of uncomplicated Plasmodium knowlesi malaria in Malaysia (ACT KNOW): an open-label, randomised controlled trial

• Published in: The Lancet infectious diseases 2016-02, Vol.16 (2), p.180-188
• Main Authors: Grigg, Matthew J, Dr, William, Timothy, FRCP, Menon, Jayaram, FRCP, Dhanaraj, Prabakaran, MBBS, Barber, Bridget E, FRACP, Wilkes, Christopher S, MBBS, von Seidlein, Lorenz, MD, Rajahram, Giri S, MRCP, Pasay, Cielo, PhD, McCarthy, James S, Prof, Price, Ric N, Prof, Anstey, Nicholas M, Prof, Yeo, Tsin W, PhD
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Antimalarials - therapeutic use; Artemisinins - therapeutic use; Child; Child, Preschool; Chloroquine - therapeutic use; Drug Therapy, Combination; Drugs; Female; Fever; Hematology; Hospitals; Humans; Infectious Disease; Infectious diseases; Malaria; Malaria - drug therapy; Malaysia; Male; Medical research; Mefloquine - therapeutic use; Middle Aged; Parasites; Plasmodium; Plasmodium knowlesi; Plasmodium knowlesi - drug effects; Studies; Substance abuse treatment; Vector-borne diseases; Young Adult
• ISSN: 1473-3099; 1474-4457
• DOI: 10.1016/S1473-3099(15)00415-6

Summary Background The zoonotic parasite Plasmodium knowlesi has become the most common cause of human malaria in Malaysia and is present throughout much of southeast Asia. No randomised controlled trials have been done to identify the optimum treatment for this emerging infection. We aimed to compare artesunate–mefloquine with chloroquine to define the optimum treatment for uncomplicated P knowlesi malaria in adults and children. Methods We did this open-label, randomised controlled trial at three district hospitals in Sabah, Malaysia. Patients aged 1 year or older with uncomplicated P knowlesi malaria were randomly assigned, via computer-generated block randomisation (block sizes of 20), to receive oral artesunate–mefloquine (target dose 12 mg/kg artesunate and 25 mg/kg mefloquine) or chloroquine (target dose 25 mg/kg). Research nursing staff were aware of group allocation, but allocation was concealed from the microscopists responsible for determination of the primary endpoint, and study participants were not aware of drug allocation. The primary endpoint was parasite clearance at 24 h. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov , number NCT01708876. Findings Between Oct 16, 2012, and Dec 13, 2014, we randomly assigned 252 patients to receive either artesunate–mefloquine (n=127) or chloroquine (n=125); 226 (90%) patients comprised the modified intention-to-treat population. 24 h after treatment, we recorded parasite clearance in 97 (84% [95% CI 76–91]) of 115 patients in the artesunate–mefloquine group versus 61 (55% [45–64]) of 111 patients in the chloroquine group (difference in proportion 29% [95% CI 18·0–40·8]; p