title: Asymptomatic malaria infection affects the interpretation of biomarkers of iron and vitamin A status, even after adjusting for systemic inflammation, but does not affect plasma zinc concentrations among young children in Burkina Faso.
abstract: BACKGROUND
  Biomarkers of iron [plasma ferritin (pF)], vitamin A [retinol binding protein (RBP)], and zinc status [plasma zinc (pZn)] are affected by the acute phase response, independent of micronutrient status.
  
  
  OBJECTIVE
  The objective of these analyses was to assess how asymptomatic malaria infection affects the interpretation of these biomarkers after adjustment for elevated acute phase proteins (APPs).
  
  
  METHODS
  Soluble transferrin receptor (sTfR), pF, RBP, and pZn concentrations were measured among 451 asymptomatic children aged 6-23 mo in Burkina Faso and adjusted for elevated APP (C-reactive protein ≥5 mg/L and/or α-1-acid-glycoprotein ≥1 g/L) based on a 4-group categorical model. Plasma histidine-rich protein II (HRP2) concentrations ≥0.75 μg/L were considered indicative of current or recent malaria parasitemia.
  
  
  RESULTS
  Of the children in the study, 57.4% had at least 1 elevated APP, and 48.5% had elevated HRP2. After adjusting for APP, children with elevated HRP2 had higher pF (23.5 ± 1.5 μg/L vs. 11.1 ± 0.8 μg/L; P < 0.001) and lower RBP (0.79 ± 0.01 μmol/L vs. 0.92 ± 0.01 μmol/L; P < 0.001) than those without, but there were no differences in pZn among those with and without elevated HRP2 (64.9 ± 12.7 μg/dL vs. 64.9 ± 11.1 μg/dL; P = 0.98). Children with elevated HRP2 had higher sTfR than those without (17.6 ± 0.5 mg/L vs. 12.3 ± 0.4 mg/L; P < 0.0001). After adjusting for HRP2, along with APP, the estimated prevalence of iron deficiency (pF < 12 μg/L) increased from 38.7% to 50.6% and vitamin A deficiency (RBP < 0.84 μmol/L) decreased from 33.4% to 27.7%.
  
  
  CONCLUSIONS
  Asymptomatic malaria is associated with indicators of micronutrient status, even after adjusting for APP. Adjusting indicators of iron and vitamin A status based only on APP may inaccurately estimate the prevalence of micronutrient deficiencies in settings with a high prevalence of malaria and inflammation. This trial was registered at clinicaltrials.gov as NCT00944853.
authors.affiliation: Department of Nutrition, University of California, Davis, CA;
authors.forename: K Ryan
authors.initials: KR
authors.lastname: Wessells
authors.affiliation: Department of Nutrition, University of California, Davis, CA;
authors.forename: Sonja Y
authors.initials: SY
authors.lastname: Hess
authors.affiliation: Health Sciences Research Institute, 01 BP 545 Bobo-Dioulasso 01, Burkina Faso.
authors.forename: Zinewendé P
authors.initials: ZP
authors.lastname: Ouédraogo
authors.affiliation: Health Sciences Research Institute, 01 BP 545 Bobo-Dioulasso 01, Burkina Faso.
authors.forename: Noel
authors.initials: N
authors.lastname: Rouamba
authors.affiliation: Health Sciences Research Institute, 01 BP 545 Bobo-Dioulasso 01, Burkina Faso.
authors.forename: Jean-Bosco
authors.initials: JB
authors.lastname: Ouédraogo
authors.affiliation: Department of Nutrition, University of California, Davis, CA; khbrown@ucdavis.edu.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Brown
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000210:Acute-Phase Reaction / Q000097:blood; D000293:Adolescent; D018798:Anemia, Iron-Deficiency / Q000453:epidemiology; D058070:Asymptomatic Diseases / Q000453:epidemiology*; D015415:Biomarkers / Q000097:blood*; D002050:Burkina Faso; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D005260:Female; D005293:Ferritins / Q000097:blood*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D019266:Iron, Dietary / Q000008:administration & dosage; D016014:Linear Models; D008288:Malaria / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D008297:Male; D018977:Micronutrients / Q000097:blood; D009752:Nutritional Status; D009961:Orosomucoid / Q000378:metabolism; D015995:Prevalence; D011506:Proteins / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D012177:Retinol-Binding Proteins / Q000378:metabolism; D014801:Vitamin A / Q000008:administration & dosage / Q000097:blood*; D014802:Vitamin A Deficiency / Q000453:epidemiology; D015032:Zinc / Q000008:administration & dosage / Q000097:blood*; D000099053:Histidine-Rich Glycoprotein
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D006454:Hemoglobins; D019266:Iron, Dietary; D018977:Micronutrients; D009961:Orosomucoid; D011506:Proteins; D012177:Retinol-Binding Proteins; D000099053:Histidine-Rich Glycoprotein; D014801:Vitamin A; D002097:C-Reactive Protein; D005293:Ferritins; D015032:Zinc
keywords: acute phase proteins; asymptomatic malaria; biomarkers; deficiency; ferritin; iron; micronutrient status; retinol binding protein; soluble transferrin receptor; zinc