Malaria and Age Variably but Critically Control Hepcidin Throughout Childhood in Kenya

Abstract

Both iron deficiency (ID) and malaria are common among African children. Studies show that the iron-regulatory hormone hepcidin is induced by malaria, but few studies have investigated this relationship longitudinally. We measured hepcidin concentrations, markers of iron status, and antibodies to malaria antigens during two cross-sectional surveys within a cohort of 324 Kenyan children ≤ 8 years old who were under intensive surveillance for malaria and other febrile illnesses. Hepcidin concentrations were the highest in the youngest, and female infants, declined rapidly in infancy and more gradually thereafter. Asymptomatic malaria and malaria antibody titres were positively associated with hepcidin concentrations. Recent episodes of febrile malaria were associated with high hepcidin concentrations that fell over time. Hepcidin concentrations were not associated with the subsequent risk of either malaria or other febrile illnesses. Given that iron absorption is impaired by hepcidin, our data suggest that asymptomatic and febrile malaria contribute to the high burden of ID seen in African children. Further, the effectiveness of iron supplementation may be sub-optimal in the presence of asymptomatic malaria. Thus, strategies to prevent and eliminate malaria may have the added benefit of addressing an important cause of ID for African children.

Cord Blood Hepcidin: Cross-Sectional Correlates and Associations with Anemia, Malaria, and Mortality in a Tanzanian Birth Cohort Study

“…These results are consistent with the hypothesis that deleterious effects of increased hepcidin on iron availability for erythropoiesis may be counterbalanced by beneficial effects for pathogen control. 29 Similar to the pediatric studies that have found high concentrations of hepcidin during episodes of malaria parasitemia, [30][31][32][33][34][35] we observed that cord hepcidin levels were elevated for children born during the high-transmission season and to mothers experiencing placental malaria at delivery. This link between placental malaria infection and hepcidin also aligns with a genome-wide expression analysis that found malaria-infected placentas had a 4-fold upregulation of hepcidin RNA.…”

“…43 Building on the hypothetical framework of the Atkinson and others' (2015) study that explored whether healthy child hepcidin concentrations could influence subsequent susceptibility to malaria, we investigated the prospective associations of cord hepcidin with risks of anemia, malaria, and mortality. 35 Unlike the earlier study based on older Kenyan children, 35 we did observe that the cord hepcidin was associated with modestly delayed onset of early malaria infections, findings which resonate with mouse models of hepcidin-mediated malaria protection. 13,44 Nevertheless, higher hepcidin levels were not significantly associated with decreased parasitemia nor severe malaria risk.…”

Prevalence and Predictors of Malaria in Human Immunodeficiency Virus Infected Patients in Beira, Mozambique

“…This evidence is in line with the current literature [ 20 , 21 ]. In fact, correlation between age and level of malaria transmission is well known also among HIV negative patients: IgG levels, tending to increase with the age [ 22 , 23 , 24 ], influence the severity of malaria and immune response.…”

Soluble transferrin receptor level, inflammation markers, malaria, alpha‐thalassemia and selenium status are the major predictors of hemoglobin in children 6–23 months in Malawi

“…Prolonged exclusive breastfeeding, delayed initiation of complementary foods, and initiating complementary feeding with poorly diversified diet could contribute for the lower hemoglobin levels in infants. Further, a study that analyzed hepcidin pattern among young Kenyan children concluded that hepcidin-a negative regulator of iron absorption-declines throughout infancy and reaches the lowest level between 1 and 2 years of age, suggesting iron absorption is higher in the second year of age than during infancy (Atkinson et al, 2015 .004 *…”