Iron deficiency is associated with reduced levels of Plasmodium falciparum-specific antibodies in African children.
Bundi CK., Nalwoga A., Lubyayi L., Muriuki JM., Mogire RM., Opi H., Mentzer AJ., Mugyenyi CK., Mwacharo J., Webb EL., Bejon P., Williams TN., Gikunju JK., Beeson JG., Elliott AM., Ndungu FM., Atkinson SH.
BackgroundIron deficiency (ID) and malaria are common causes of ill-health and disability among children living in sub-Saharan Africa. Although iron is critical for the acquisition of humoral immunity, little is known about the effects of ID on antibody responses to Plasmodium falciparum malaria.MethodsThe study included 1,794 Kenyan and Ugandan children aged 0-7 years. We measured biomarkers of iron and inflammation, and antibodies to P falciparum antigens including apical merozoite antigen 1 (anti-AMA-1) and merozoite surface antigen 1 (anti-MSP-1) in cross-sectional and longitudinal studies.ResultsThe overall prevalence of ID was 31%. ID was associated with lower anti-AMA-1 and anti-MSP-1 antibody levels in pooled analyses adjusted for age, gender, study site, inflammation and P falciparum parasitemia (adjusted mean difference on a log-transformed scale (β) -0.46; 95 CI -0.66, -0.25 P <0.0001; β -0.33; 95 CI -0.50, -0.16 P <0.0001, respectively). Additional covariates for malaria exposure index, previous malaria episodes, and time since last malaria episode, were available for individual cohorts. Meta-analysis was used to allow for these adjustments giving β -0.34; -0.52, -0.16 for anti-AMA-1 antibodies and β -0.26; -0.41, -0.11 for anti-MSP-1 antibodies. Low transferrin saturation was similarly associated with reduced anti-AMA1 antibody levels. Lower AMA-1 and MSP-1 specific antibody levels persisted over time in iron-deficient children.ConclusionsReduced levels of P. falciparum-specific antibodies in iron-deficient children might reflect impaired acquisition of immunity to malaria and/or reduced malaria exposure. Strategies to prevent and treat ID may influence antibody responses to malaria for children living in sub-Saharan Africa.