Iron Deficiency Is Associated With Reduced Levels of Plasmodium falciparum-specific Antibodies in African Children.

Alexander J Mentzer,Alison M Elliott,Angela Nalwoga,Caroline K Bundi,Cleopatra K Mugyenyi,Emily L Webb,Francis M Ndungu,Herbert Opi,James G Beeson,Jedida Mwacharo,John Muthii Muriuki,Joseph K Gikunju,Lawrence Lubyayi,Philip Bejon,Reagan M Mogire,Sarah H Atkinson,Thomas N Williams

doi:10.1093/cid/ciaa728

Abstract

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 1794 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, sex, study site, inflammation, and P. falciparum parasitemia (adjusted mean difference on a log-transformed scale (β) −0.46; 95 confidence interval [CI], −.66, −.25 P < .0001; β −0.33; 95 CI, −.50, −.16 P < .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-AMA-1 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.

Highlights

Iron deficiency (ID) and malaria are common causes of ill-health and disability among children living in sub-Saharan Africa
Iron deficiency (ID) is highly prevalent among young children living in sub-Saharan Africa [1], and iron deficiency anemia (IDA) is the leading cause of years lived with disability among African children [2] due to its negative effects on child development [3]
Malaria is a major public health problem causing approximately 405 000 deaths in 2018, of which 85% occurred in sub-Saharan Africa, mainly among young children

Summary

Methods

The study included 1794 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. Crude differences in means of log antibody levels between iron-deficient and iron-replete children were determined using 2-tailed Student t-tests and univariable linear regression models. Multivariable linear regression models were used to estimate the association between ID and malaria antibody levels, pooling data from all cohorts and adjusting for study site, age, sex, inflammation, and P. falciparum parasitemia at the time of antibody measurement. The linear regressions were run on log transformed data; the beta values returned reflect changes on a log scale. To transform these to fold differences that could be applied to the linear scale, we used the formula 10^Beta.

Results

Discussion

Conclusion