Efficacy of Artesunate-mefloquine for Chloroquine-resistant Plasmodium vivax Malaria in Malaysia: An Open-label, Randomized, Controlled Trial.
Chloroquine (CQ)-resistant Plasmodium vivax is increasingly reported throughout southeast Asia. The efficacy of CQ and alternative artemisinin combination therapies (ACTs) for vivax malaria in Malaysia is unknown.



A randomized, controlled trial of CQ vs artesunate-mefloquine (AS-MQ) for uncomplicated vivax malaria was conducted in 3 district hospitals in Sabah, Malaysia. Primaquine was administered on day 28. The primary outcome was the cumulative risk of treatment failure by day 28 by Kaplan-Meier analysis.



From 2012 to 2014, 103 adults and children were enrolled. Treatment failure by day 28 was 61.1% (95% confidence interval [CI], 46.8-75.6) after CQ and 0% (95% CI, 0-.08) following AS-MQ (P < .001), of which 8.2% (95% CI, 2.5-9.6) were early treatment failures. All patients with treatment failure had therapeutic plasma CQ concentrations at day 7. Compared with CQ, AS-MQ was associated with faster parasite clearance (normalized clearance slope, 0.311 vs 0.127; P < .001) and fever clearance (mean, 19.0 vs 37.7 hours; P =001) and with lower risk of anemia at day 28 (odds ratio = 3.7; 95% CI, 1.5-9.3; P =005). Gametocytes were present at day 28 in 23.8% (10/42) of patients following CQ vs none with AS-MQ (P < .001). AS-MQ resulted in lower bed occupancy: 4037 vs 6510 days/1000 patients (incidence rate ratio 0.62; 95% CI, .60-.65; P < .001). One patient developed severe anemia not regarded as related to their AS-MQ treatment.



High-grade CQ-resistant P. vivax is prevalent in eastern Malaysia. AS-MQ is an efficacious ACT for all malaria species. Wider CQ-efficacy surveillance is needed in vivax-endemic regions with earlier replacement with ACT when treatment failure is detected.Clinical Trials Registration NCT01708876.
Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.|Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu.
Matthew J
MJ
Grigg
Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu.|Clinical Research Centre, Queen Elizabeth Hospital.|Jesselton Medical Centre.
Timothy
T
William
Clinical Research Centre, Queen Elizabeth Hospital.|Sabah Department of Health, Kota Kinabalu, Malaysia.
Jayaram
J
Menon
Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.|Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu.
Bridget E
BE
Barber
Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.|Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu.
Christopher S
CS
Wilkes
Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu.|Clinical Research Centre, Queen Elizabeth Hospital.|Sabah Department of Health, Kota Kinabalu, Malaysia.
Giri S
GS
Rajahram
Department of Drug Evaluation, Australian Army Malaria Institute, Brisbane, Queensland.
Michael D
MD
Edstein
Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
Sarah
S
Auburn
Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.|Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom.
Ric N
RN
Price
Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.|Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu.|Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
Tsin W
TW
Yeo
Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.|Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu.|Division of Medicine, Royal Darwin Hospital, Darwin, Northern Territory, Australia.
Nicholas M
NM
Anstey
D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007223:Infant; D016780:Malaria, Vivax / Q000188:drug therapy / Q000469:parasitology; D008297:Male; D015767:Mefloquine / Q000627:therapeutic use*; D008875:Middle Aged; D010966:Plasmodium vivax / Q000187:drug effects / Q000472:pathogenicity; D016896:Treatment Outcome; D055815:Young Adult
D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D002738:Chloroquine; D015767:Mefloquine
Plasmodium vivax; artesunate-mefloquine; chloroquine; malaria; randomized, controlled trial