Afebrile Plasmodium falciparum parasitemia decreases absorption of fortification iron but does not affect systemic iron utilization: a double stable-isotope study in young Beninese women

Abstract

Background: Iron deficiency anemia (IDA) affects many young women in sub-Saharan Africa. Its etiology is multifactorial, but the major cause is low dietary iron bioavailability exacerbated by parasitic infections such as malaria.

Objective: We investigated whether asymptomatic Plasmodium falciparum parasitemia in Beninese women would impair absorption of dietary iron or utilization of circulating iron.

Design: Iron absorption and utilization from an iron-fortified sorghum-based meal were estimated by using oral and intravenous isotope labels in 23 afebrile women with a positive malaria smear (asexual P. falciparum parasitemia; > 500 parasites/μL blood). The women were studied while infected, treated, and then restudied 10 d after treatment. Iron status, hepcidin, and inflammation indexes were measured before and after treatment.

Results: Treatment reduced low-grade inflammation, as reflected by decreases in serum ferritin, C-reactive protein, interleukin-6, interleukin-8, and interleukin-10 (P < 0.05); this was accompanied by a reduction in median serum hepcidin of ≈ 50%, from 2.7 to 1.4 nmol/L (P < 0.005). Treatment decreased serum erythropoietin and growth differentiation factor 15 (P < 0.05). Clearance of parasitemia increased geometric mean dietary iron absorption (from 10.2% to 17.6%; P = 0.008) but did not affect systemic iron utilization (85.0% compared with 83.1%; NS).

Conclusions: Dietary iron absorption is reduced by ≈ 40% in asymptomatic P. falciparum parasitemia, likely because of low-grade inflammation and its modulation of circulating hepcidin. Because asymptomatic parasitemia has a protracted course and is very common in malarial areas, this effect may contribute to IDA and blunt the efficacy of iron supplementation and fortification programs. This trial was registered at clinicaltrials.gov as NCT01108939.

FIGURE 1.

Overview of the study design.

FIGURE 2.

Iron absorption in Beninese women (n = 23) who consumed a sorghum porridge labeled with 3 mg ⁵⁷Fe as NaFeEDTA before (day 1) and after (day 25) malarial treatment. Iron absorption on day 1 was significantly lower than that on day 25 (Wilcoxon's signed-rank test, P = 0.008). The box plots show the median and 25th and 75th percentiles. Whiskers in the plots represent the highest and lowest values. The line graph shows individual iron absorption of the 23 women before and after treatment. fract. abs., fractional absorption.

FIGURE 3.

Erythrocyte iron utilization in Beninese women (n = 23) who received an intravenous dose of 100 μg ⁵⁸Fe-labeled iron citrate before (day 1) and after (day 25) malarial treatment. Iron utilization did not differ significantly between the 2 d (Wilcoxon's signed-rank test, P = 0.107). The box plots show the median and 25th and 75th percentiles. Whiskers in the plots represent the highest and lowest values that are not outliers. Outliers (values that are between 1.5 and 3 times the interquartile range) are represented by circles beyond the whiskers. The line graph shows individual iron utilization of the 23 women before and after treatment.