Abstract
BackgroundIntermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) for the prevention of malaria has shown promising results in six trials. However, resistance to SP is rising and alternative drug combinations need to be evaluated to better understand the role of treatment versus prophylactic effects.MethodsBetween March 2004 and March 2008, in an area of western Kenya with year round malaria transmission with high seasonal intensity and high usage of insecticide-treated nets, we conducted a randomized, double-blind placebo-controlled trial with SP plus 3 days of artesunate (SP-AS3), 3 days of amodiaquine-artesunate (AQ3-AS3), or 3 days of short-acting chlorproguanil-dapsone (CD3) administered at routine expanded programme of immunization visits (10 weeks, 14 weeks and 9 months).Principal Findings1,365 subjects were included in the analysis. The incidence of first or only episode of clinical malaria during the first year of life (primary endpoint) was 0.98 episodes/person-year in the placebo group, 0.74 in the SP-AS3 group, 0.76 in the AQ3-AS3 group, and 0.82 in the CD3 group. The protective efficacy (PE) and 95% confidence intervals against the primary endpoint were: 25.7% (6.3, 41.1); 25.9% (6.8, 41.0); and 16.3% (−5.2, 33.5) in the SP-AS3, AQ3-AS3, and CD3 groups, respectively. The PEs for moderate-to-severe anaemia were: 27.5% (−6.9, 50.8); 23.1% (−11.9, 47.2); and 11.4% (−28.6, 39.0). The duration of the protective effect remained significant for up to 5 to 8 weeks for SP-AS3 and AQ3-AS3. There was no evidence for a sustained beneficial or rebound effect in the second year of life. All regimens were well tolerated.ConclusionsThese results support the view that IPTi with long-acting regimens provide protection against clinical malaria for up to 8 weeks even in the presence of high ITN coverage, and that the prophylactic rather than the treatment effect of IPTi appears central to its protective efficacy.Trial RegistrationClinicalTrials.gov NCT00111163
Highlights
It is estimated that approximately 100 million children aged,5 years in Africa live in areas where malaria transmission occurs; each year .800,000 die from the direct effects of malaria [1,2]
These results support the view that IPTi with long-acting regimens provide protection against clinical malaria for up to 8 weeks even in the presence of high insecticide-treated nets (ITNs) coverage, and that the prophylactic rather than the treatment effect of IPTi appears central to its protective efficacy
In 2001, Schellenberg and colleagues in Tanzania demonstrated that intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) administered at routine Expanded Program of Immunization (EPI) visits with iron supplementation from 2–6 months of age reduced the incidence of clinical malaria and severe anaemia by 59% and 50% respectively in the first year of life [7]
Summary
It is estimated that approximately 100 million children aged ,5 years in Africa live in areas where malaria transmission occurs; each year .800,000 die from the direct effects of malaria [1,2]. In 2001, Schellenberg and colleagues in Tanzania demonstrated that intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) administered at routine Expanded Program of Immunization (EPI) visits with iron supplementation from 2–6 months of age reduced the incidence of clinical malaria and severe anaemia by 59% (95% CI: 41, 72; p,0.0001) and 50% (95% CI: 8, 73; p = 0.023) respectively in the first year of life [7]. The mechanism by which IPTi works is not well understood: it is unknown whether the intermittent clearance of existing malaria infections (treatment effect) or the post-treatment prophylactic effect of long-acting drugs is more important [18]. Resistance to SP is rising and alternative drug combinations need to be evaluated to better understand the role of treatment versus prophylactic effects
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