title: A randomized, placebo-controlled, double-blind trial on sulfadoxine-pyrimethamine alone or combined with artesunate or amodiaquine in uncomplicated malaria.
abstract: The therapeutic efficacy of sulfadoxine-pyrimethamine (SP) alone, SP plus amodiaquine (AQ), and SP plus artesunate (AS) was assessed in a randomized, placebo-controlled, and double-blind trial among 438 children with uncomplicated Plasmodium falciparum malaria in northern Ghana. Clinical and parasitological responses were monitored for 28 days following treatment; 86%, 98% and 97% of SP-, SP + AQ-, and SP + AS-treated patients achieved adequate clinical and parasitological response (ACPR) within 2 weeks, respectively. Parasite clearance was better with SP + AS than with SP or SP + AQ treatment but re-infections were more common. Polymerase chain reaction (PCR)-corrected rates of ACPR at day 28 were 72.2% for SP, 94.1% for SP + AQ (P < 0.0001), and 94.5% for SP + AS (P < 0.0001). Gametocyte prevalence and density 1 week after treatment were highest in children treated with SP, and lowest in patients receiving SP + AS. No severe adverse events attributable to study medication were observed. In northern Ghana, more than one of four children suffered SP treatment failure within 4 weeks. Both SP + AQ and SP + AS are efficacious alternative therapeutic options in this region. Although SP + AS and SP + AQ treatments have virtually identical cure rates, rapid parasite clearance and pronounced gametocidal effects are the advantages of the former, whereas cost and a lower rate of late re-infections are those of the latter.
authors.affiliation: Institute of Tropical Medicine, Charité, Humboldt University, Berlin, Germany. frank.mockenhaupt@charite.de
authors.forename: Frank P
authors.initials: FP
authors.lastname: Mockenhaupt
authors.forename: Stephan
authors.initials: S
authors.lastname: Ehrhardt
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Dzisi
authors.forename: J
authors.initials: J
authors.lastname: Teun Bousema
authors.forename: Nasstasja
authors.initials: N
authors.lastname: Wassilew
authors.forename: Jonas
authors.initials: J
authors.lastname: Schreiber
authors.forename: Sylvester D
authors.initials: SD
authors.lastname: Anemana
authors.forename: Jakob P
authors.initials: JP
authors.lastname: Cramer
authors.forename: Rowland N
authors.initials: RN
authors.lastname: Otchwemah
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.forename: Teunis A
authors.initials: TA
authors.lastname: Eggelte
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bienzle
mesh_terms: D000655:Amodiaquine / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D002675:Child, Preschool; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D010270:Parasite Egg Count / Q000379:methods; D010963:Plasmodium falciparum / Q000235:genetics; D011739:Pyrimethamine / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D012717:Sesquiterpenes; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D011739:Pyrimethamine