title: Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trials.
abstract: BACKGROUND
  Intermittent preventive treatment (IPT) is a promising strategy for malaria control in infants. We undertook a pooled analysis of the safety and efficacy of IPT in infants (IPTi) with sulfadoxine-pyrimethamine in Africa.
  
  
  METHODS
  We pooled data from six double-blind, randomised, placebo-controlled trials (undertaken one each in Tanzania, Mozambique, and Gabon, and three in Ghana) that assessed the efficacy of IPTi with sulfadoxine-pyrimethamine. In all trials, IPTi or placebo was given to infants at the time of routine vaccinations delivered by WHO's Expanded Program on Immunization. Data from the trials for incidence of clinical malaria, risk of anaemia (packed-cell volume <25% or haemoglobin <80 g/L), and incidence of hospital admissions and adverse events in infants up to 12 months of age were reanalysed by use of standard outcome definitions and time periods. Analysis was by modified intention to treat, including all infants who received at least one dose of IPTi or placebo.
  
  
  RESULTS
  The six trials provided data for 7930 infants (IPTi, n=3958; placebo, n=3972). IPTi had a protective efficacy of 30.3% (95% CI 19.8-39.4, p<0.0001) against clinical malaria, 21.3% (8.2-32.5, p=0.002) against the risk of anaemia, 38.1% (12.5-56.2, p=0.007) against hospital admissions associated with malaria parasitaemia, and 22.9% (10.0-34.0, p=0.001) against all-cause hospital admissions. There were 56 deaths in the IPTi group compared with 53 in the placebo group (rate ratio 1.05, 95% CI 0.72-1.54, p=0.79). One death, judged as possibly related to IPTi because it occurred 19 days after a treatment dose, was subsequently attributed to probable sepsis. Four of 676 non-fatal hospital admissions in the IPTi group were deemed related to study treatment compared with five of 860 in the placebo group. None of three serious dermatological adverse events in the IPTi group were judged related to study treatment compared with one of 13 in the placebo group.
  
  
  CONCLUSIONS
  IPTi with sulfadoxine-pyrimethamine was safe and efficacious across a range of malaria transmission settings, suggesting that this intervention is a useful contribution to malaria control.
  
  
  BACKGROUND
  Bill & Melinda Gates Foundation.
authors.affiliation: Barcelona Centre for International Health Research, Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors.forename: John J
authors.initials: JJ
authors.lastname: Aponte
authors.forename: David
authors.initials: D
authors.lastname: Schellenberg
authors.forename: Andrea
authors.initials: A
authors.lastname: Egan
authors.forename: Alasdair
authors.initials: A
authors.lastname: Breckenridge
authors.forename: Ilona
authors.initials: I
authors.lastname: Carneiro
authors.forename: Julia
authors.initials: J
authors.lastname: Critchley
authors.forename: Ina
authors.initials: I
authors.lastname: Danquah
authors.forename: Alexander
authors.initials: A
authors.lastname: Dodoo
authors.forename: Robin
authors.initials: R
authors.lastname: Kobbe
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lell
authors.forename: Jürgen
authors.initials: J
authors.lastname: May
authors.forename: Zul
authors.initials: Z
authors.lastname: Premji
authors.forename: Sergi
authors.initials: S
authors.lastname: Sanz
authors.forename: Esperanza
authors.initials: E
authors.lastname: Sevene
authors.forename: Rachida
authors.initials: R
authors.lastname: Soulaymani-Becheikh
authors.forename: Peter
authors.initials: P
authors.lastname: Winstanley
authors.forename: Samuel
authors.initials: S
authors.lastname: Adjei
authors.forename: Sylvester
authors.initials: S
authors.lastname: Anemana
authors.forename: Daniel
authors.initials: D
authors.lastname: Chandramohan
authors.forename: Saadou
authors.initials: S
authors.lastname: Issifou
authors.forename: Frank
authors.initials: F
authors.lastname: Mockenhaupt
authors.forename: Seth
authors.initials: S
authors.lastname: Owusu-Agyei
authors.forename: Brian
authors.initials: B
authors.lastname: Greenwood
authors.forename: Martin P
authors.initials: MP
authors.lastname: Grobusch
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Eusebio
authors.initials: E
authors.lastname: Macete
authors.forename: Hassan
authors.initials: H
authors.lastname: Mshinda
authors.forename: Robert D
authors.initials: RD
authors.lastname: Newman
authors.forename: Laurence
authors.initials: L
authors.lastname: Slutsker
authors.forename: Marcel
authors.initials: M
authors.lastname: Tanner
authors.forename: Pedro
authors.initials: P
authors.lastname: Alonso
authors.forename: Clara
authors.initials: C
authors.lastname: Menendez
mesh_terms: D000349:Africa / Q000453:epidemiology; D000740:Anemia / Q000453:epidemiology; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005500:Follow-Up Studies; D006801:Humans; D007115:Immunization Schedule; D015994:Incidence; D007223:Infant; D007226:Infant Mortality; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000517:prevention & control*; D010343:Patient Admission / Q000706:statistics & numerical data; D011739:Pyrimethamine / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D012107:Research Design; D012307:Risk Factors; D012449:Safety; D013413:Sulfadoxine / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine