title: Intermittent preventive treatment in infants as a means of malaria control: a randomized, double-blind, placebo-controlled trial in northern Ghana.
abstract: Morbidity and mortality from malaria remain unacceptably high among young children in sub-Saharan Africa. Intermittent preventive treatment in infancy (IPTi) involves the administration of antimalarials alongside routine vaccinations and might be an option in malaria control. In an area of intense, perennial malaria transmission in northern Ghana, 1,200 children received IPTi with sulfadoxine-pyrimethamine or placebo at approximately 3, 9, and 15 months of age. Children were followed up until 24 months of age to assess morbidity and adverse events. During the intervention period (3 to 18 months of age), IPTi reduced the incidences of malaria and severe anemia by 22.5% (95% confidence interval, 12 to 32%) and 23.6% (95% confidence interval, 4 to 39%), respectively, and reduced hospitalizations and episodes of asymptomatic parasitemia by one-third. Protection was pronounced in the first year of life and not discernible in the second. The malaria-protective effect was largely confined to a period of 1 month after sulfadoxine-pyrimethamine treatments. Following the intervention, protection against asymptomatic parasitemia persisted. In contrast, a significant rebound of severe malaria, predominantly severe malarial anemia, occurred among children having received IPTi. Although the treatment was generally well tolerated, one case of moderately severe skin reaction followed sulfadoxine-pyrimethamine treatment. IPTi reduces malaria and anemia in infants in northern Ghana. Extension of IPTi into the second year of life by administering a dose at 15 months of age provided no substantial benefit beyond a 1-month prophylactic effect. Although this simple intervention offers one of the few available malaria-preventive measures for regions where malaria is endemic, the observed rebound of severe malaria advises caution and requires further investigation.
authors.affiliation: Institute of Tropical Medicine and International Health, Charité--University Medicine Berlin, Berlin, Germany. frank.mockenhaupt@charite.de
authors.forename: Frank P
authors.initials: FP
authors.lastname: Mockenhaupt
authors.forename: Klaus
authors.initials: K
authors.lastname: Reither
authors.forename: Philipp
authors.initials: P
authors.lastname: Zanger
authors.forename: Felix
authors.initials: F
authors.lastname: Roepcke
authors.forename: Ina
authors.initials: I
authors.lastname: Danquah
authors.forename: Eiman
authors.initials: E
authors.lastname: Saad
authors.forename: Peter
authors.initials: P
authors.lastname: Ziniel
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Dzisi
authors.forename: Marc
authors.initials: M
authors.lastname: Frempong
authors.forename: Patrick
authors.initials: P
authors.lastname: Agana-Nsiire
authors.forename: Felicia
authors.initials: F
authors.lastname: Amoo-Sakyi
authors.forename: Rowland
authors.initials: R
authors.lastname: Otchwemah
authors.forename: Jakob P
authors.initials: JP
authors.lastname: Cramer
authors.forename: Sylvester D
authors.initials: SD
authors.lastname: Anemana
authors.forename: Ekkehart
authors.initials: E
authors.lastname: Dietz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bienzle
mesh_terms: D000740:Anemia / Q000453:epidemiology / Q000209:etiology; D000962:Antimalarials / Q000627:therapeutic use*; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D005869:Ghana / Q000453:epidemiology; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017053:Infection Control / Q000379:methods*; D008288:Malaria / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D008297:Male; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D013413:Sulfadoxine; D011739:Pyrimethamine