title: Intermittent preventive treatment for malaria in Papua New Guinean infants exposed to Plasmodium falciparum and P. vivax: a randomized controlled trial.
abstract: BACKGROUND
  Intermittent preventive treatment in infants (IPTi) has been shown in randomized trials to reduce malaria-related morbidity in African infants living in areas of high Plasmodium falciparum (Pf) transmission. It remains unclear whether IPTi is an appropriate prevention strategy in non-African settings or those co-endemic for P. vivax (Pv).
  
  
  RESULTS
  In this study, 1,121 Papua New Guinean infants were enrolled into a three-arm placebo-controlled randomized trial and assigned to sulfadoxine-pyrimethamine (SP) (25 mg/kg and 1.25 mg/kg) plus amodiaquine (AQ) (10 mg/kg, 3 d, n = 374), SP plus artesunate (AS) (4 mg/kg, 3 d, n = 374), or placebo (n = 373), given at 3, 6, 9 and 12 mo. Both participants and study teams were blinded to treatment allocation. The primary end point was protective efficacy (PE) against all episodes of clinical malaria from 3 to 15 mo of age. Analysis was by modified intention to treat. The PE (compared to placebo) against clinical malaria episodes (caused by all species) was 29% (95% CI, 10-43, p ≤ 0.001) in children receiving SP-AQ and 12% (95% CI, -11 to 30, p = 0.12) in those receiving SP-AS. Efficacy was higher against Pf than Pv. In the SP-AQ group, Pf incidence was 35% (95% CI, 9-54, p = 0.012) and Pv incidence was 23% (95% CI, 0-41, p = 0.048) lower than in the placebo group. IPTi with SP-AS protected only against Pf episodes (PE = 31%, 95% CI, 4-51, p = 0.027), not against Pv episodes (PE = 6%, 95% CI, -24 to 26, p = 0.759). Number of observed adverse events/serious adverse events did not differ between treatment arms (p > 0.55). None of the serious adverse events were thought to be treatment-related, and the vomiting rate was low in both treatment groups (1.4%-2.0%). No rebound in malaria morbidity was observed for 6 mo following the intervention.
  
  
  CONCLUSIONS
  IPTi using a long half-life drug combination is efficacious for the prevention of malaria and anemia in infants living in a region highly endemic for both Pf and Pv.
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Senn
authors.forename: Patricia
authors.initials: P
authors.lastname: Rarau
authors.forename: Danielle I
authors.initials: DI
authors.lastname: Stanisic
authors.forename: Leanne
authors.initials: L
authors.lastname: Robinson
authors.forename: Céline
authors.initials: C
authors.lastname: Barnadas
authors.forename: Doris
authors.initials: D
authors.lastname: Manong
authors.forename: Mary
authors.initials: M
authors.lastname: Salib
authors.forename: Jonah
authors.initials: J
authors.lastname: Iga
authors.forename: Nandao
authors.initials: N
authors.lastname: Tarongka
authors.forename: Serej
authors.initials: S
authors.lastname: Ley
authors.forename: Anna
authors.initials: A
authors.lastname: Rosanas-Urgell
authors.forename: John J
authors.initials: JJ
authors.lastname: Aponte
authors.forename: Peter A
authors.initials: PA
authors.lastname: Zimmerman
authors.forename: James G
authors.initials: JG
authors.lastname: Beeson
authors.forename: Louis
authors.initials: L
authors.lastname: Schofield
authors.forename: Peter
authors.initials: P
authors.lastname: Siba
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rogerson
authors.forename: John C
authors.initials: JC
authors.lastname: Reeder
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
mesh_terms: D000655:Amodiaquine / Q000627:therapeutic use; D000962:Antimalarials / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008288:Malaria / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects / Q000472:pathogenicity*; D010966:Plasmodium vivax / Q000187:drug effects / Q000472:pathogenicity*; D011739:Pyrimethamine / Q000627:therapeutic use; D013413:Sulfadoxine / Q000627:therapeutic use
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine