title: Artemisinin-naphthoquine combination therapy for uncomplicated pediatric malaria: a tolerability, safety, and preliminary efficacy study.
abstract: Artemisinin-naphthoquine (ART-NQ) is a fixed-dose coformulated antimalarial therapy recommended as a single-dose treatment and marketed in Papua New Guinea among other tropical countries. We conducted a tolerability, safety, and efficacy study of ART-NQ for Papua New Guinean children aged 5 to 12 years with uncomplicated malaria, comparing single-dose ART-NQ (15 and 6 mg/kg of body weight) given with water (group 1; n = 15), single-dose ART-NQ (22 and 9 mg/kg) given with milk (group 2; n = 17), or two daily doses of 22 and 9 mg/kg given with water (group 3; n = 16). Of the 48 children (45 with Plasmodium falciparum malaria, 2 with Plasmodium vivax malaria, and 1 with mixed-species malaria), 2 in group 2 did not attend all follow-up assessments. All regimens were well tolerated, with no serious adverse events. There were no clinically significant changes in pulse, blood pressure, rate-corrected electrocardiographic QT, routine biochemistry/hematology, or hearing after treatment. Fever clearance was prompt. Mean 50% parasite clearance times were 4, 4, and 5 h for groups 1, 2, and 3, respectively. One group 1 patient had PCR-confirmed P. falciparum recrudescence at day 23; four had PCR-confirmed P. falciparum reinfections on day 28 or 42; and three had P. vivax infections detected on day 42. The only recurrent parasitemia in groups 2 and 3 occurred in a group 2 child who developed a P. vivax infection on day 42. Day 14 gametocyte positivity levels were 20%, 27%, and 9% in groups 1, 2, and 3, respectively. The lower single ART-NQ dose was associated with relatively frequent recurrence of parasitemia, but the prolonged gametocytemia in all three groups has implications for the transmission of malaria.
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: John
authors.initials: J
authors.lastname: Benjamin
authors.forename: Brioni
authors.initials: B
authors.lastname: Moore
authors.forename: Sook Ting
authors.initials: ST
authors.lastname: Lee
authors.forename: Michèle
authors.initials: M
authors.lastname: Senn
authors.forename: Susan
authors.initials: S
authors.lastname: Griffin
authors.forename: Dulci
authors.initials: D
authors.lastname: Lautu
authors.forename: Sam
authors.initials: S
authors.lastname: Salman
authors.forename: Peter
authors.initials: P
authors.lastname: Siba
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.forename: Timothy M E
authors.initials: TM
authors.lastname: Davis
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure; D002648:Child; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006309:Hearing; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D009285:Naphthoquinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010219:Papua New Guinea; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D009285:Naphthoquinones; C543979:artemisinin-naphthoquine combination