Abstract
BackgroundIntermittent preventive treatment for malaria in Infants (IPTi) has been shown to give effective and safe protection against malaria. It has been suggested that IPTi might have long-lasting beneficial effects but, in most settings, the protection provided by IPTi appears to be short-lived. Knowledge of the duration of protection given by IPTi would help interpret the results of existing trials and suggest optimal delivery schedules for IPTi. This study investigated how the protective efficacy of IPTi against malaria and anaemia changes over time.Methods and FindingsA secondary analysis of data from a cluster-randomised, placebo-controlled trial of IPTi using sulfadoxine-pyrimethamine (SP) in Ghana was conducted. In this trial IPTi was given to 2485 infants at 3, 4, 9 and 12 months of age; children remained in follow-up until two years of age. Poisson regression with a random effect to adjust for the cluster-randomised design was used to determine protective efficacy of IPTi against clinical malaria and anaemia in defined time strata following administration of IPTi. Analysis of first-or-only clinical malaria episode following the individual IPTi doses showed that some protection against malaria lasted between 4 to 6 weeks. A similar pattern was seen when the incidence of all malaria episodes up to 2 years of age was analysed in relation to the most recent IPT, by pooling the incidence of malaria after the individual IPTi doses. Protective efficacy within four weeks of IPTi was 75.2% (95% CI: 66–82) against malaria, 78.9% (95% CI: 69–86) against high parasite density malaria, and 93.8% (95% CI: 73–99) against anaemia. Protection against these outcomes was short-lived, with evidence of any effect lasting for only 6, 6 and 4 weeks respectively. Protection in children who were parasitaemic when receiving IPTi appeared to be of shorter duration than in uninfected children. There was no evidence of any benefit of IPTi after the immediate period following the IPTi doses.ConclusionsIntermittent preventive treatment provides considerable protection against malaria and anaemia for short periods, even in an area of intense seasonal transmission. Due to the relatively short duration of protection provided by each dose of IPTi, this treatment will be of most benefit when delivered at the time of peak malaria incidence.
Highlights
Intermittent preventive treatment (IPT) is a promising strategy for preventing malaria morbidity in infants and children, in sub-Saharan Africa where the disease burden is highest
Due to the relatively short duration of protection provided by each dose of IPTi, this treatment will be of most benefit when delivered at the time of peak malaria incidence
Primary endpoints in the trial were clinical malaria detected in children attending health centres or the hospital and anaemia in children admitted to the study hospital for any illness; the same endpoints have been used for this analysis
Summary
Intermittent preventive treatment (IPT) is a promising strategy for preventing malaria morbidity in infants and children, in sub-Saharan Africa where the disease burden is highest. Sulfadoxine-pyrimethamine (SP) given to Tanzanian infants alongside routine vaccinations gave high protective efficacy against malaria and anaemia; this protection appeared to be sustained long after the chemoprophylactic period of SP, suggesting that development of protective immunity might have been facilitated by the treatment [1,2,3]. Subsequent studies in infants and children have shown IPT to be an effective preventive measure against malaria, but none of these have shown a sustained benefit beyond the period that might reasonably be attributed to drugs [4,5,6,7,8,9,10,11,12]. Knowledge of the duration of protection given by IPTi would help interpret the results of existing trials and suggest optimal delivery schedules for IPTi. This study investigated how the protective efficacy of IPTi against malaria and anaemia changes over time
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