Abstract
BackgroundIntermittent preventive treatment in infants (IPTi) is a new malaria control tool. However, it is uncertain whether IPTi works mainly through chemoprophylaxis or treatment of existing infections. Understanding the mechanism is essential for development of replacements for sulfadoxine-pyrimethamine (SP) where it is no longer effective. This study investigated how protection against malaria given by SP, chlorproguanil-dapsone (CD) and mefloquine (MQ), varied with time since administration of IPTi.Methods and FindingsA secondary analysis of data from a randomised, placebo-controlled trial in an area of high antifolate resistance in Tanzania was conducted. IPTi using SP, CD, MQ or placebo was given to 1280 infants at 2, 3 and 9 months of age. Poisson regression with random effects to adjust for potential clustering of malaria episodes within children was used to calculate incidence rate ratios for clinical malaria in defined time strata following IPTi. The short-acting antimalarial CD gave no protection against clinical malaria, whereas long-acting MQ gave two months of substantial protection (protective efficacy (PE) 73.1% (95% CI: 23.9, 90.5) and 73.3% (95% CI: 0, 92.9) in the first and second month respectively). SP gave some protection in the first month after treatment (PE 64.5% (95% CI: 10.6, 85.9)) although it did not reduce the incidence of malaria up to 12 months of age. There was no evidence of either long-term protection or increased risk of malaria for any of the regimens.ConclusionPost-treatment chemoprophylaxis appears to be the main mechanism by which IPTi protects children against malaria. Long-acting antimalarials are therefore likely to be the most effective drugs for IPTi, but as monotherapies could be vulnerable to development of drug resistance. Due to concerns about tolerability, the mefloquine formulation used in this study is not suitable for IPTi. Further investigation of combinations of long-acting antimalarials for IPTi is needed.Trial RegistrationClinicaltrials.gov NCT00158574
Highlights
Intermittent preventive treatment in infants (IPTi) is a new control strategy for reducing the malaria burden in endemic countries of sub-Saharan Africa where transmission of malaria is high and malaria is an important cause of mortality and morbidity in infants
Due to concerns about tolerability, the mefloquine formulation used in this study is not suitable for IPTi
There is sufficient evidence that three courses of sulfadoxine-pyrimethamine (SP) IPTi has a protective efficacy of 20–30% against clinical malaria in the first year of life; SP-IPTi may be adopted as a policy in some African countries [1,2]
Summary
Intermittent preventive treatment in infants (IPTi) is a new control strategy for reducing the malaria burden in endemic countries of sub-Saharan Africa where transmission of malaria is high and malaria is an important cause of mortality and morbidity in infants. Some uncertainty about the precise mode of action of IPTi remains, in particular, the relative importance of clearing existing parasitaemia compared to post-treatment prophylaxis against new infections is not certain, and may vary in different epidemiological settings [12]. Two studies of the duration of protection against malaria after IPTi using SP have suggested that post-treatment prophylaxis may be the main protective mechanism [13,14], but this is not yet certain, and it is unclear whether this will be the case for IPTi regimens other than SP. Intermittent preventive treatment in infants (IPTi) is a new malaria control tool. It is uncertain whether IPTi works mainly through chemoprophylaxis or treatment of existing infections. This study investigated how protection against malaria given by SP, chlorproguanil-dapsone (CD) and mefloquine (MQ), varied with time since administration of IPTi
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