Therapy of uncomplicated falciparum malaria: a randomized trial comparing artesunate plus sulfadoxine-pyrimethamine versus sulfadoxine-pyrimethamine alone in Irian Jaya, Indonesia.
Combining artesunate with existing antimalarial drugs may improve cure rates, delay emergence of resistance, and reduce transmission. We performed a randomized comparative trial to quantify the effect of adding artesunate to sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria in Indonesia. Using a modified 1997 World Health Organization protocol for assessment of therapeutic efficacy of antimalarial drugs, 105 patients (stratified by age/ethnic group) were randomized: 53 received artesunate orally, 4 mg/kg of body weight, a single daily dose for three days, plus sulfadoxine-pyrimethamine orally (1.25 mg of pyrimethamine/kg of body weight), a single dose on day 0, and 52 patients received sulfadoxine-pyrimethamine alone. Six from the combination group were withdrawn from analysis, as were six of the sulfadoxine-pyrimethamine group. Treatment failure rates on day 14 were 0% in the artesunate plus sulfadoxine-pyrimethamine group and 8.7% in the sulfadoxine-pyrimethamine group (P = 0.12). Treatment failure rates on day 28 were 4.4% and 15.2%, respectively (P = 0.16). Relative risk of treatment failure at 28 days was 0.3 (95% confidence interval [CI] = 0.1-1.3). Mean fever clearance time (1.3 versus 1.7 days) and mean parasite clearance time (1.4 versus 2.0 days) were both faster in the artesunate plus sulfadoxine-pyrimethamine group than in the sulfadoxine-pyrimethamine group (P = 0.08 and P < 0.0001, respectively). Only 20 (39.2%) of 51 patients treated with artesunate plus sulfadoxine-pyrimethamine were still parasitemic on day 1 compared with 45 (86.5%) of 52 patients treated with sulfadoxine-pyrimethamine alone (P = 0.000001, relative risk [RR] = 0.4, 95% CI = 0.3-0.6). Gametocyte carriage was lower following artesunate plus sulfadoxine-pyrimethamine than following sulfadoxine-pyrimethamine (RR = 0.5, 95% CI = 0.2-1.0 on day 7 and RR = 0.5, 95% CI = 0.2-1.1 on day 14). Mild diarrhea, rash, and itching resolved without treatment. Combined artesunate plus sulfadoxine-pyrimethamine resulted in more rapid fever and parasiteclearance, was well tolerated, reduced risk of treatment failure, and lowered gametocyte carriage.
Tjitra
E
E
National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia.
Suprianto
S
S
Currie
B J
BJ
Morris
P S
PS
Saunders
J R
JR
Anstey
N M
NM
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D037621:Artemisinins; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005334:Fever; D006801:Humans; D007214:Indonesia; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010270:Parasite Egg Count; D018512:Parasitemia / Q000188:drug therapy / Q000503:physiopathology; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use*; D012306:Risk; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D012717:Sesquiterpenes; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D011739:Pyrimethamine