Effect of maternal nutrient supplementation on malaria antibody immunity during pregnancy and infancy

Abstract

Malaria in pregnancy accounts for significant morbidities and mortalities among pregnant women and children. Most endemic regions often experience high prevalence of nutrient deficiencies, which further worsen the burden of adverse pregnancy outcomes and poor child growth outcomes. Nutrient deficiencies could also impede the development of naturally acquired immunity to malaria increasing the susceptibility to infection in high risk groups. Therefore supplementing maternal diet with energy rich multiple micronutrient supplements could benefit the pregnant mother and the child by improving pregnancy outcomes and development of immunity against malaria. The hypothesis of this study was that a lipid-based nutrient supplementation (LNS) during pregnancy and lactation improves malaria antibody responses in pregnant mothers and their infants at 6 months of age.

The mothers and their children were enrolled in a longitudinal randomised controlled clinical trial in Malawi. First, antibodies to a range of malaria antigens were determined in maternal plasma samples collected at study entry and at 36 gestation weeks. Antibody levels and the rate of change in antibody levels from enrolment to 36 weeks were comparable across the three nutrient supplementation groups LNS, multiple micronutrient supplement (MMN) and iron and folic acid (IFA). Similarly, malaria antibody levels at 6 months in infants were not affected by the maternal supplementation type. These findings suggest that maternal LNS does not improve antibody levels during pregnancy or malaria antibody acquisition during infancy compared to the MMN and IFA groups.

Secondly, the study investigated if malarial antibodies are predictive of pregnancy outcomes and malaria clinical outcomes. Immunoglobulin G and opsonising antibodies to variant surface antigens (VSA) expressed by placental-binding parasite isolates positively associated with maternal haemoglobin concentration at 36 weeks suggesting these antibodies may have a potential role in protecting pregnant women against malaria-induced anaemia. The analysis was adjusted for the supplementation type. Similarly, in a separate pregnancy cohort from Sudan, women with severe malaria had significantly lower IgG to placental-binding parasite isolates and high levels of pro-inflammatory cytokine secretion compared to uninfected pregnant mothers, demonstrating the importance of pregnancy-associated malaria antibodies in potential protection against maternal outcomes in pregnancy. The main study further reports that antibodies to merozoite and schizont antigens were not associated with most pregnancy outcomes or worsen the outcomes suggesting these antibodies may be presenting as markers of exposure instead.

Finally, the factors determining antibody acquisition at 6 months was investigated while adjusting for maternal nutrient supplementation. Both the season at birth and spatial heterogeneity affected antibody levels. Children born in the rainy season and those who were born in certain study sites reported high antibody levels as a result of differences in transmission intensity between study sites and seasonal variations. In addition, naturally acquired antibody to most malaria antigens at 6 months demonstrated no association with subsequent clinical malaria (from 6-18 months) suggesting these antibodies may be acting as markers of malaria exposure; it should be noted that most antibodies measured at 6 months were frequently very low or undetectable. Further studies investigating the functional antibodies could provide beneficial information regarding the functional role of antibodies at 6 months in infants.

Overall, the current thesis provides valuable information for understanding the relationship between nutrition and malaria immunity, an area of research that is poorly studied in literature. Nutrient supplementation with LNS during pregnancy and lactation did not improve malaria antibody immunity during pregnancy or infancy. Importantly, the study reported that pregnancy associated malaria antibodies may have a potential role in protection against malaria induced anaemia and severe malaria while antibodies to merozoite and schizont antigens act as markers of exposure. Findings from the current study are beneficial for future nutrient supplementation trials and the serology data collected for both pregnant women and children provide important information regarding the differences between biomarkers of protective immunity and markers of exposure. Furthermore, serology at 6 months may provide valuable information for future malaria serosurveillance studies and mapping malaria transmission intensity in study areas.