Randomized trial of piperaquine with sulfadoxine-pyrimethamine or dihydroartemisinin for malaria intermittent preventive treatment in children.
BACKGROUND
The long terminal half life of piperaquine makes it suitable for intermittent preventive treatment for malaria but no studies of its use for prevention have been done in Africa. We did a cluster randomized trial to determine whether piperaquine in combination with either dihydroartemisin (DHA) or sulfadoxine-pyrimethamine (SP) is as effective, and better tolerated, than SP plus amodiaquine (AQ), when used for intermittent preventive treatment in children delivered by community health workers in a rural area of Senegal.


METHODS
Treatments were delivered to children 3-59 months of age in their homes once per month during the transmission season by community health workers. 33 health workers, each covering about 60 children, were randomized to deliver either SP+AQ, DHA+PQ or SP+PQ. Primary endpoints were the incidence of attacks of clinical malaria, and the incidence of adverse events.


RESULTS
1893 children were enrolled. Coverage of monthly rounds and compliance with daily doses was similar in all groups; 90% of children received at least 2 monthly doses. Piperaquine combinations were better tolerated than SP+AQ with a significantly lower risk of common, mild adverse events. 103 episodes of clinical malaria were recorded during the course of the trial. 68 children had malaria with parasitaemia >3000/microL, 29/671 (4.3%) in the SP+AQ group, compared with 22/604 (3.6%) in the DHA+PQ group (risk difference 0.47%, 95%CI -2.3%,+3.3%), and 17/618 (2.8%) in the SP+PQ group (risk difference 1.2%, 95%CI -1.3%,+3.6%). Prevalences of parasitaemia and the proportion of children carrying Pfdhfr and Pfdhps mutations associated with resistance to SP were very low in all groups at the end of the transmission season.


CONCLUSIONS
Seasonal IPT with SP+PQ in children is highly effective and well tolerated; the combination of two long-acting drugs is likely to impede the emergence of resistant parasites.


BACKGROUND
ClinicalTrials.gov NCT00529620.
Cisse
Badara
B
Department of Parasitology and Mycology, Universite Cheikh Anta Diop, Dakar, Senegal.
Cairns
Matthew
M
Faye
Ernest
E
NDiaye
Ousmane
O
Faye
Babacar
B
Cames
Cecile
C
Cheng
Yue
Y
NDiaye
Maguette
M
Lô
Aminata Collé
AC
Simondon
Kirsten
K
Trape
Jean-Francois
JF
Faye
Oumar
O
NDiaye
Jean Louis
JL
Gaye
Oumar
O
Greenwood
Brian
B
Milligan
Paul
P
D000962:Antimalarials / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage*; D002675:Child, Preschool; D016000:Cluster Analysis; D004338:Drug Combinations; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D008288:Malaria / Q000517:prevention & control*; D008297:Male; D011739:Pyrimethamine / Q000008:administration & dosage*; D011804:Quinolines / Q000008:administration & dosage*; D012424:Rural Population; D012675:Senegal; D013413:Sulfadoxine / Q000008:administration & dosage*; D016896:Treatment Outcome; D010879:Piperazines
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D011739:Pyrimethamine; D011804:Quinolines; D013413:Sulfadoxine; C001205:fanasil, pyrimethamine drug combination; C039060:artenimol; C034759:piperaquine; D010879:Piperazines