Seasonal intermittent preventive treatment with artesunate and sulfadoxine-pyrimethamine for prevention of malaria in Senegalese children: a randomised, placebo-controlled, double-blind trial.
BACKGROUND
In the Sahel and sub-Sahelian regions of Africa, malaria transmission is highly seasonal. During a short period of high malaria transmission, mortality and morbidity are high in children under age 5 years. We assessed the efficacy of seasonal intermittent preventive treatment-a full dose of antimalarial treatment given at defined times without previous testing for malaria infection.


METHODS
We did a randomised, placebo-controlled, double-blind trial of the effect of intermittent preventive treatment on morbidity from malaria in three health-care centres in Niakhar, a rural area of Senegal. 1136 children aged 2-59 months received either one dose of artesunate plus one dose of sulfadoxine-pyrimethamine or two placebos on three occasions during the malaria transmission season. The primary outcome was a first or single episode of clinical malaria detected through active or passive case detection. Primary analysis was by intention-to-treat. This study is registered with , number NCT00132561.


RESULTS
During 13 weeks of follow-up, the intervention led to an 86% (95% CI 80-90) reduction in the occurrence of clinical episodes of malaria. With passive case detection, protective efficacy against malaria was 86% (77-92), and when detected actively was 86% (78-91). The incidence of malaria in children on active drugs was 308 episodes per 1000 person-years at risk, whereas in those on placebo it was 2250 episodes per 1000 person-years at risk. 13 children were not included in the intention-to-treat analysis, which was restricted to children who received a first dose of antimalarial or placebo. There was an increase in vomiting in children who received the active drugs, but generally the intervention was well tolerated.


CONCLUSIONS
Intermittent preventive treatment could be highly effective for prevention of malaria in children under 5 years of age living in areas of seasonal malaria infection.
Cissé
Badara
B
London School of Hygiene & Tropical Medicine, London, UK. badara.cisse@lshtm.ac.uk
Sokhna
Cheikh
C
Boulanger
Denis
D
Milet
Jacqueline
J
Bâ
El Hadj
el H
Richardson
Keshena
K
Hallett
Rachel
R
Sutherland
Colin
C
Simondon
Kirsten
K
Simondon
François
F
Alexander
Neal
N
Gaye
Oumar
O
Targett
Geoffrey
G
Lines
Jo
J
Greenwood
Brian
B
Trape
Jean-François
JF
D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D001512:Bedding and Linens; D002675:Child, Preschool; D004311:Double-Blind Method; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000517:prevention & control*; D015995:Prevalence; D011739:Pyrimethamine / Q000627:therapeutic use*; D012621:Seasons; D012675:Senegal / Q000453:epidemiology; D012717:Sesquiterpenes / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D012717:Sesquiterpenes; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D011739:Pyrimethamine