Age of exposure and immunity to malaria in infants

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The development of naturally acquired immunity (NAI) against Plasmodium falciparum (P.falciparum) malaria is poorly understood. Previous studies of continuous and intermittent chemoprophylaxis in infants have provided evidence that the age of first exposure to P.falciparum during infancy may be important in determining the development of NAI, as measured by incidence of clinical malaria during the second year of life. These studies suggest that exposure to P. falciparum prior to 5 months of age does not result in the development of NAI, while exposure to P. falciparum after 5 months of age leads to development of NAI. The overall objective is to evaluate the effect of exposure to P. falciparum erythrocytic stage antigens during different periods of infancy on the development of NAI. In order to explore the effect of age in the build-up of NAI we have designed a 3-arm randomized double-blind placebo-controlled trial in an endemic area of southern Mozambique in which we selectively control exposure to P. falciparum at different periods during infancy (2-5 months, 5-10 months or none) with monthly chemoprophylaxis with Sulphadoxine- Pyrimethamine + Artesunate. Infants will be enrolled at birth from HIV-negative women and allocated to one of three cohorts of 98 children each. Participants will be followed up by active and passive case detection and cross-sectional surveys until 24 months of age. The risk of clinical malaria and anaemia during the second year of life will be compared between cohorts, as well as its correlation with the type and quality of immune responses (antibodies to several P. falciparum antigens, cytokines), oxidative stress markers and host genetic factors. These results should shed light on the determinants of the development of anti-P. falciparum responses early in life and the potential constraints to early life immunisation.