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Delaying Iron Therapy until 28 Days after Antimalarial Treatment Is Associated with Greater Iron Incorporation and
Sarah E Cusick1, Robert O Opoka2, Steven A Abrams3
1Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN; scusick@umn.edu.
Insights
Delaying iron therapy in children with malaria improved iron absorption but did not show a short-term benefit in hematologic recovery. Further research is needed to determine optimal timing for iron supplementation during malaria treatment.
Area of Science:
- Pediatrics
- Tropical Medicine
- Nutritional Science
Background:
- Malaria-induced inflammation can impair iron absorption.
- Concurrent iron therapy with antimalarials may be less effective.
- Delayed iron supplementation might improve iron bioavailability.
Purpose of the Study:
- Compare erythrocyte iron incorporation in children receiving immediate versus delayed iron supplementation.
- Assess the impact of delayed iron therapy on hematologic recovery in pediatric malaria patients.
Main Methods:
- Randomized trial involving 100 children (6-59 months) with malaria and anemia.
- Iron stable isotopes (57Fe and 58Fe) used to track iron incorporation.
- Groups received iron supplementation immediately or 28 days after antimalarial treatment.
Main Results:
- Delayed iron supplementation significantly increased iron incorporation (16.5% vs 7.9%).
- No significant differences in hemoglobin or iron status markers at day 56 between groups.
- Poorer iron status observed in the delayed group at day 28, prior to final assessment.
Conclusions:
- Delaying iron supplementation enhances iron incorporation in children with malaria.
- No clear short-term hematologic benefit was observed from delaying iron therapy.
- Optimal timing for iron supplementation in this context requires further investigation.
Background:
Iron therapy begun concurrently with antimalarial treatment may not be well absorbed because of malaria-induced inflammation. Delaying the start of iron therapy may permit better iron absorption and distribution.
Objective:
We compared erythrocyte iron incorporation in children who started iron supplementation concurrently with antimalarial treatment or 28 d later. We hypothesized that delayed iron supplementation would be associated with greater incorporation and better hematologic recovery.
Methods:
We enrolled 100 children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L who presented to Mulago Hospital, Kampala, into a randomized trial of iron therapy. All children were administered antimalarial treatment. Children with zinc protoporphyrin (ZPP) ≥80 μmol/mol heme were randomly assigned to start iron supplementation concurrently with the antimalarial treatment [immediate iron (I) group] or 28 d later [delayed iron (D) group]. All children were administered iron-stable isotope (57)Fe on day 0 and (58)Fe on day 28. We compared the percentage of iron incorporation at the start of supplementation (I group at day 0 compared with D group at day 28, aim 1) and hematologic recovery at day 56 (aim 2).
Results:
The percentage of iron incorporation (mean ± SE) was greater at day 28 in the D group (16.5% ± 1.7%) than at day 0 in the I group (7.9% ± 0.5%; P < 0.001). On day 56, concentrations of hemoglobin and ZPP and plasma ferritin, soluble transferrin receptor (sTfR), hepcidin, and C-reactive protein did not differ between the groups. On day 28, the hemoglobin (mean ± SD) and plasma iron markers (geometric mean; 95% CI) reflected poorer iron status in the D group than in the I group at this intervening time as follows: hemoglobin (105 ± 15.9 compared with 112 ± 12.4 g/L; P = 0.04), ferritin (39.3 μg/L; 23.5, 65.7 μg/L compared with 79.9 μg/L; 58.3, 110 μg/L; P = 0.02), sTfR (8.9 mg/L; 7.4, 10.7 mg/L compared with 6.7 mg/L; 6.1, 7.5 mg/L; P = 0.01), and hepcidin (13.3 ng/mL; 8.3, 21.2 ng/mL compared with 38.8 ng/mL; 28.3, 53.3 ng/mL; P < 0.001).
Conclusions:
Delaying the start of iron improves incorporation but leads to equivalent hematologic recovery at day 56 in Ugandan children with malaria and anemia. These results do not demonstrate a clear, short-term benefit of delaying iron. This trial was registered at clinicaltrials.gov as NCT01754701.
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