title: Comparison of iron status 28 d after provision of antimalarial treatment with iron therapy compared with antimalarial treatment alone in Ugandan children with severe malaria.
abstract: BACKGROUND
  The provision of iron with antimalarial treatment is the standard of care for concurrent iron deficiency and malaria. However, iron that is given during a malaria episode may not be well absorbed or used, particularly in children with severe malaria and profound inflammation.
  
  
  OBJECTIVE
  We aimed to 1) determine baseline values of iron and inflammatory markers in children with severe malarial anemia (SMA), children with cerebral malaria (CM), and community children (CC) and 2) compare markers in iron-deficient children in each group who received 28 d of iron supplementation during antimalarial treatment with those in children who did not receive iron during treatment..
  
  
  METHODS
  Seventy-nine children with CM, 77 children with SMA, and 83 CC who presented to Mulago Hospital, Kampala, Uganda, were enrolled in a 28-d iron-therapy study. Children with malaria received antimalarial treatment. All children with CM or SMA, as well as 35 CC, had zinc protoporphyrin (ZPP) concentrations ≥80 μmol/mol heme and were randomly assigned to receive a 28-d course of iron or no iron. We compared iron markers at day 0 among study groups (CM, SMA, and CC groups) and at day 28 between children in each group who were randomly assigned to receive iron or to not receive iron.
  
  
  RESULTS
  At day 0, children with CM and SMA had greater values of C-reactive protein, ferritin, and hepcidin than those of CC. At day 28, interactions between study and treatment group were NS. Children in the no-iron compared with iron groups had similar mean values for hemoglobin (115 compared with 113 g/L, respectively; P = 0.73) and ZPP (124 compared with 124 μmol/mol heme, respectively; P = 0.96) but had lower median ferritin [101.0 μg/L (95% CI: 84.2, 121.0 μg/L) compared with 152.9 μg/L (128.8, 181.6 μg/L), respectively; P ≤ 0.001] and hepcidin [45.8 ng/mL (36.8, 56.9 ng/mL) compared with 83.1 ng/mL (67.6, 102.2 ng/mL), respectively; P < 0.011].
  
  
  CONCLUSIONS
  Severe inflammation is a characterization of children with CM and SMA. The withholding of iron from children with severe malaria is associated with lower ferritin and hepcidin at day 28 but not a lower hemoglobin concentration. This trial was registered at clinicaltrials.gov as NCT01093989.
authors: Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN; and scusick@umn.edu.
authors: Sarah E
authors: http://orcid.org/0000-0002-0592-1867
authors: SE
authors: Cusick
authors: Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda.
authors: Robert O
authors: RO
authors: Opoka
authors: Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda.
authors: Andrew S
authors: AS
authors: Ssemata
authors: Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN; and.
authors: Michael K
authors: MK
authors: Georgieff
authors: Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN; and.
authors: Chandy C
authors: http://orcid.org/0000-0002-1634-1411
authors: CC
authors: John
mesh_terms: D000740:Anemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000962:Antimalarials / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002675:Child, Preschool; D019587:Dietary Supplements; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005293:Ferritins / Q000097:blood; D006454:Hemoglobins / Q000378:metabolism; D064451:Hepcidins / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000209:etiology; D019266:Iron, Dietary / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D008288:Malaria / Q000097:blood / Q000150:complications / Q000188:drug therapy; D016779:Malaria, Cerebral / Q000097:blood / Q000188:drug therapy; D008297:Male; D009752:Nutritional Status; D011524:Protoporphyrins / Q000097:blood; D012720:Severity of Illness Index; D014454:Uganda
chemical_list: D000962:Antimalarials; D015415:Biomarkers; D006454:Hemoglobins; D064451:Hepcidins; D019266:Iron, Dietary; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D002097:C-Reactive Protein; D005293:Ferritins
keywords: hepcidin; inflammation; iron; malaria; timing of iron supplementation