Randomized Trial of Piperaquine with Sulfadoxine-Pyrimethamine or Dihydroartemisinin for Malaria Intermittent Preventive Treatment in Children

Badara Cisse,Babacar Faye,Matthew Cairns,Ousmane Ndiaye,Brian Greenwood,Cecile Cames,Paul Milligan,Yue Cheng,Jean Louis Ndiaye,Kirsten Simondon,Aminata Collé Lô,Oumar Gaye,Oumar Faye,Ernest Faye,Maguette Ndiaye,Jean-Francois Trape,James G Beeson

doi:10.1371/journal.pone.0007164

Abstract

BackgroundThe 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.MethodsTreatments 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.Results1893 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/µL, 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.ConclusionsSeasonal 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. Trial RegistrationClinicalTrials.gov NCT00529620

Highlights

The incidence of malaria is declining in many parts of Africa, it remains an important public health problem, especially in poorer rural communities with limited access to health care
Intermittent preventive treatment (IPT) with antimalarial drugs given to all children once a month during the transmission season can provide a high degree of protection against malaria [1]
Seasonal IPT with sulfadoxine-pyrimethamine (SP) and one dose of artesunate resulted in a 90% reduction in incidence of clinical malaria in a trial in Senegal [3]

Summary

Introduction

The incidence of malaria is declining in many parts of Africa, it remains an important public health problem, especially in poorer rural communities with limited access to health care. Intermittent preventive treatment (IPT) with antimalarial drugs given to all children once a month during the transmission season can provide a high degree of protection against malaria [1]. A second trial in Senegal [4] showed that a combination of two non-artemisinin drugs with relatively long half lives (SP and amodiaquine (AQ), the latter given over three days) was more effective than SP with one or three doses of artesunate and more effective than AQ with artesunate, in preventing malaria. 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

Results

Conclusion