title: Randomized, double-blind, placebo-controlled trial of monthly versus bimonthly dihydroartemisinin-piperaquine chemoprevention in adults at high risk of malaria.
abstract: Intermittent preventive treatment (IPT) is increasingly used to reduce malaria morbidity and mortality in children and pregnant women. The efficacy of IPT depends on the pharmacokinetic and pharmacodynamic properties of the antimalarial drugs used. Healthy adult male volunteers whose occupation put them at high risk of malaria on the Northwest border of Thailand were randomized to receive a 3-day-treatment dose of dihydroartemisinin-piperaquine monthly (DPm) or every 2 months (DPalt) or an identical placebo with or without fat (6.4 g/dose) over a 9-month period. All volunteers were monitored weekly. One thousand adults were recruited. Dihydroartemisinin-piperaquine was well tolerated. There were 114 episodes of malaria (49 Plasmodium falciparum, 63 P. vivax, and 2 P. ovale). The protective efficacy against all malaria at 36 weeks was 98% (95% confidence interval [CI], 96% to 99%) in the DPm group and 86% (95% CI, 81% to 90%) in the DPalt group (for both, P < 0.0001 compared to the placebo group). As a result, the placebo group also had lower hematocrits during the study (P < 0.0001). Trough plasma piperaquine concentrations were the main determinant of efficacy; no malaria occurred in participants with a trough concentration above 31 ng/ml. Neither plasma piperaquine concentration nor efficacy was influenced by the coadministration of fat. DPm is safe to use and is effective in the prevention of malaria in adult males living in an area where P. vivax and multidrug-resistant P. falciparum malaria are endemic.
authors.affiliation: Shoklo Malaria Research Unit, Mae Sod, Thailand.
authors.forename: Khin Maung
authors.initials: KM
authors.lastname: Lwin
authors.forename: Aung Pyae
authors.initials: AP
authors.lastname: Phyo
authors.forename: Joel
authors.initials: J
authors.lastname: Tarning
authors.forename: Warunee
authors.initials: W
authors.lastname: Hanpithakpong
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ashley
authors.forename: Sue J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Phaikyeong
authors.initials: P
authors.lastname: Cheah
authors.forename: Pratap
authors.initials: P
authors.lastname: Singhasivanon
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Niklas
authors.initials: N
authors.lastname: Lindegårdh
authors.forename: François
authors.initials: F
authors.lastname: Nosten
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D018890:Chemoprevention; D004041:Dietary Fats / Q000008:administration & dosage; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006400:Hematocrit; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology / Q000517:prevention & control*; D016780:Malaria, Vivax / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000502:physiology; D010966:Plasmodium vivax / Q000187:drug effects* / Q000502:physiology; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D012306:Risk; D013785:Thailand; D010879:Piperazines
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004041:Dietary Fats; D010919:Placebos; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines