Abstract
BackgroundIntermittent preventive treatment (IPT) of malaria involves administration of curative doses of antimalarials at specified time points to vulnerable populations in endemic areas, regardless whether a subject is known to be infected. The effect of this new intervention on the development and maintenance of protective immunity needs further understanding. We have investigated how seasonal IPT affects the genetic diversity of Plasmodium falciparum infections and the risk of subsequent clinical malaria.Material and MethodsThe study included 2227 Ghanaian children (3–59 months) who were given sulphadoxine-pyrimethamine (SP) bimonthly, artesunate plus amodiaquine (AS+AQ) monthly or bimonthly, or placebo monthly for six months spanning the malaria transmission season. Blood samples collected at three post-interventional surveys were analysed by genotyping of the polymorphic merozoite surface protein 2 gene. Malaria morbidity and anaemia was monitored during 12 months follow-up.ResultsMonthly IPT with AS+AQ resulted in a marked reduction in number of concurrent clones and only children parasite negative just after the intervention period developed clinical malaria during follow-up. In the placebo group, children without parasites as well as those infected with ≥2 clones had a reduced risk of subsequent malaria. The bimonthly SP or AS+AQ groups had similar number of clones as placebo after intervention; however, diversity and parasite negativity did not predict the risk of malaria. An interaction effect showed that multiclonal infections were only associated with protection in children without intermittent treatment.ConclusionMolecular typing revealed effects of the intervention not detected by ordinary microscopy. Effective seasonal IPT temporarily reduced the prevalence and genetic diversity of P. falciparum infections. The reduced risk of malaria in children with multiclonal infections only seen in untreated children suggests that persistence of antigenically diverse P. falciparum infections is important for the maintenance of protective malaria immunity in high transmission settings.
Highlights
Malaria is one of the most severe infectious diseases
Monthly Intermittent preventive treatment (IPT) with artesunate plus amodiaquine (AS+AQ) resulted in a marked reduction in number of concurrent clones and only children parasite negative just after the intervention period developed clinical malaria during follow-up
The reduced risk of malaria in children with multiclonal infections only seen in untreated children suggests that persistence of antigenically diverse P. falciparum infections is important for the maintenance of protective malaria immunity in high transmission settings
Summary
Malaria is one of the most severe infectious diseases. Despite recent reports of decreasing incidence in some areas, infection by Plasmodium falciparum remains a major threat to health and economic development in Sub-Saharan Africa [1]. Children under five years of age and pregnant women are at highest risk of disease and death Control strategies targeting these groups are, of high priority. A new strategy to control malaria is intermittent preventive treatment (IPT), which involves administration of therapeutic doses of anti-malarial drugs at specified time points regardless whether a subject is known to be infected. Intermittent preventive treatment (IPT) of malaria involves administration of curative doses of antimalarials at specified time points to vulnerable populations in endemic areas, regardless whether a subject is known to be infected. The effect of this new intervention on the development and maintenance of protective immunity needs further understanding. We have investigated how seasonal IPT affects the genetic diversity of Plasmodium falciparum infections and the risk of subsequent clinical malaria
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