Journal
CLINICAL INFECTIOUS DISEASES
Volume 73, Issue 1, Pages 43-49Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciaa728
Keywords
iron deficiency; immunity; children; malaria; Africa
Categories
Funding
- Wellcome [107769, 107743, 110255, 202800, 10628, 064693, 079110, 095778]
- KEMRI-Wellcome Trust Research Programme [203077]
- Oxford University Clinical Academic School Transitional Fellowship
- Senior Research Fellowship of the National Health and Medical Research Council of Australia [1077636]
- DELTAS Africa Initiative Sub-Saharan Africa Consortium for Advanced Biostatistics Training (SSACAB) [107754]
- African Academy of Sciences's Alliance for Accelerating Excellence in Science in Africa (AESA)
- New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency)
- UK government
- UK Medical Research Council (MRC)
- UK Department for International Development (DFID) under the MRC/DFID Concordat agreement
- European Union
- DELTAS Africa Initiative [DEL-15-003]
- MRC [MC_UU_00027/5, MR/R010161/1, MC_UP_1204/15] Funding Source: UKRI
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Iron deficiency in children is associated with lower levels of specific antibodies to malaria, potentially leading to impaired acquisition of immunity to the disease. These lower antibody levels persist over time in iron-deficient children.
Background. Iron 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. 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. Results. The 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 (beta) -0.46; 95 confidence interval [CI], -.66, -.25 P < .0001; beta -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 beta -0.34; -0.52, -0.16 for anti-AMA-1 antibodies and beta -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. Conclusions. Reduced 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.
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