The impact of early life exposure to Plasmodium falciparum on the development of naturally acquired immunity to malaria in young Malawian children

Priyanka Barua,James G Beeson,Per Ashorn,Stephen J Rogerson,Kenneth Maleta

doi:10.1186/s12936-019-2647-8

Abstract

BackgroundAntibodies targeting malaria blood-stage antigens are important targets of naturally acquired immunity, and may act as valuable biomarkers of malaria exposure.MethodsSix-hundred and one young Malawian children from a randomized trial of prenatal nutrient supplementation with iron and folic acid or pre- and postnatal multiple micronutrients or lipid-based nutrient supplements were followed up weekly at home and febrile episodes were investigated for malaria from birth to 18 months of age. Antibodies were measured for 601 children against merozoite surface proteins (MSP1 19kD, MSP2), erythrocyte binding antigen 175 (EBA175), reticulocyte binding protein homologue 2 (Rh2A9), schizont extract and variant surface antigens expressed by Plasmodium falciparum-infected erythrocytes (IE) at 18 months of age. The antibody measurement data was related to concurrent malaria infection and to documented episodes of clinical malaria.ResultsAt 18 months of age, antibodies were significantly higher among parasitaemic than aparasitaemic children. Antibody levels against MSP1 19kD, MSP2, schizont extract, and IE variant surface antigens were significantly higher in children who had documented episodes of malaria than in children who did not. Antibody levels did not differ between children with single or multiple malaria episodes before 18 months, nor between children who had malaria before 6 months of age or between 6 and 18 months.ConclusionsAntibodies to merozoite and IE surface antigens increased following infection in early childhood, but neither age at first infection nor number of malaria episodes substantially affected antibody acquisition. These findings have implications for malaria surveillance during early childhood in the context of elimination.Trials registration Clinical Trials Registration: NCT01239693 (Date of registration: 11-10-2010). URL: http://www.ilins.org

Highlights

Antibodies targeting malaria blood-stage antigens are important targets of naturally acquired immunity, and may act as valuable biomarkers of malaria exposure
The nutrient supplements received by their mothers were iron and folic acid (IFA) in 33.6%, multiple micronutrients (MMN) in 33.4%, and 32.9% received lipid based nutrient supplements (LNS)
Antibody levels were measured as optical density (OD) for schizont and merozoite antigens, or as geometric mean fluorescence intensity (MFI) for variant surface antigens (VSA)

Summary

Introduction

Antibodies targeting malaria blood-stage antigens are important targets of naturally acquired immunity, and may act as valuable biomarkers of malaria exposure. Acquired immunity to malaria develops over time with continuous exposure to infection [3]. Blood stage merozoite antigens and variant surface antigens (VSA) expressed on infected erythrocytes (IE) are important targets of this protective immunity. Antibodies to merozoite antigens inhibit invasion of red blood cells (RBCs), prevent intra-erythrocytic growth [4], and promote opsonization for phagocytic clearance [5] and complement fixation [6]. Crucial for the primary interaction between merozoites and RBCs in parasite invasion [12], MSP1 is a major target of opsonizing following natural exposure [13]. The level of IgG against Rh2A9 in children (5–14 years) was associated with lower risk of malaria [19]

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