title: Efficacy and safety of intermittent preventive treatment in schoolchildren with sulfadoxine/pyrimethamine (SP) and SP plus piperaquine in Democratic Republic of the Congo: a randomised controlled trial.
abstract: In endemic areas, malaria and its adverse effects in schoolchildren may be prevented by intermittent preventive treatment (IPTsc). However, the most appropriate drug regimen for IPTsc remains to be identified. A randomised controlled trial was conducted in Kinshasa, DRC. Enrolled schoolchildren were assigned to a passive control arm (n = 212), sulfadoxine/pyrimethamine (SP) (n = 202) or SP plus piperaquine (SP/PQ) (n = 202). The primary endpoint was haemoglobin (Hb) change. Secondary endpoints were anaemia, parasitaemia prevalence and clinical malaria incidence. Data were analysed by modified intention-to-treat (mITT) and per-protocol. A linear mixed mode was used due to repeated measurements. Of 616 enrolled children, 410 (66.6%) were eligible for mITT analysis. The control arm was used as reference. After 12 months, the Hb level increased by 0.20 g/dL (95% CI -0.61 to 0.47; P = 0.168) and 0.39 g/dL (0.12-0.66; P <0.01) in the SP and SP/PQ arms, respectively. SP treatment reduced anaemia, malaria parasitaemia and clinical malaria by 10% (0-20%; P = 0.06), 19% (2-33%; P = 0.042) and 25% (-32 to 57%; P = 0.37), respectively. The corresponding values for SP/PQ were 28% (19-37%; P <0.001), 40% (26-52%; P <0.001) and 58% (17-79%; P <0.01). No deaths or severe adverse events (SAEs) were observed. SP/PQ offered substantial protection against anaemia, malaria parasitaemia and clinical malaria and showed no SAEs. SP/PQ, a combination of two long-acting non-artemisinin-based antimalarials, may be a valuable option for IPTsc in Africa.
authors.affiliation: Tropical Medicine Department, University of Kinshasa, Kinshasa, Congo; Epidemiology for Global Health Institute, University of Antwerp, Antwerp, Belgium. Electronic address: matangilaj@yahoo.fr.
authors.forename: Junior R
authors.initials: JR
authors.lastname: Matangila
authors.affiliation: Epidemiology for Global Health Institute, University of Antwerp, Antwerp, Belgium.
authors.forename: Joachim Y
authors.initials: JY
authors.lastname: Doua
authors.affiliation: Tropical Medicine Department, University of Kinshasa, Kinshasa, Congo.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mitashi
authors.affiliation: Epidemiology for Global Health Institute, University of Antwerp, Antwerp, Belgium.
authors.forename: Raquel Inocêncio
authors.initials: RI
authors.lastname: da Luz
authors.affiliation: Tropical Medicine Department, University of Kinshasa, Kinshasa, Congo.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lutumba
authors.affiliation: Epidemiology for Global Health Institute, University of Antwerp, Antwerp, Belgium.
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Van Geertruyden
mesh_terms: D000293:Adolescent; D000740:Anemia / Q000453:epidemiology / Q000517:prevention & control; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects*; D018890:Chemoprevention / Q000009:adverse effects / Q000379:methods; D002648:Child; D002675:Child, Preschool; D015023:Democratic Republic of the Congo / Q000453:epidemiology; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008288:Malaria / Q000453:epidemiology / Q000517:prevention & control*; D008297:Male; D018512:Parasitemia / Q000453:epidemiology / Q000517:prevention & control; D011739:Pyrimethamine / Q000008:administration & dosage* / Q000009:adverse effects*; D011804:Quinolines / Q000008:administration & dosage* / Q000009:adverse effects*; D012574:Schools; D013334:Students; D013413:Sulfadoxine / Q000008:administration & dosage* / Q000009:adverse effects*; D016896:Treatment Outcome; D010879:Piperazines
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D006454:Hemoglobins; D011739:Pyrimethamine; D011804:Quinolines; D013413:Sulfadoxine; C001205:fanasil, pyrimethamine drug combination; C034759:piperaquine; D010879:Piperazines
keywords: Intermittent preventive treatment; Kinshasa; Malaria; Piperaquine; Schoolchildren; Sulfadoxine/pyrimethamine