Grigg MJ

William T

Menon J

Barber BE

Wilkes CS

Rajahram GS

Edstein MD

Auburn S

Price RN

Yeo TW

Anstey NM

2016

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.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2016; 62(11): 1403-1411

https://pubmed.ncbi.nlm.nih.gov/27107287/?otool=iaurydwlib

https://hdl.handle.net/10137/5354

Plasmodium vivax

artesunate-mefloquine

chloroquine

malaria

randomized, controlled trial

Adolescent

Adult

Aged

Antimalarials

Artemisinins

Child

Child, Preschool

Chloroquine

Female

Humans

Infant

Male

Mefloquine

Middle Aged

Treatment Outcome

Young Adult

Drug Resistance

Malaria, Vivax

Plasmodium vivax

Efficacy of Artesunate-mefloquine for Chloroquine-resistant Plasmodium vivax Malaria in Malaysia: An Open-label, Randomized, Controlled Trial.

Journal Article

Randomized Controlled Trial

Publication