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

J Nutr. 2014 Dec;144(12):2050-8. doi: 10.3945/jn.114.200345. Epub 2014 Oct 1.

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.

Keywords: acute phase proteins; asymptomatic malaria; biomarkers; deficiency; ferritin; iron; micronutrient status; retinol binding protein; soluble transferrin receptor; zinc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / metabolism
  • Acute-Phase Reaction / blood
  • Adolescent
  • Anemia, Iron-Deficiency / epidemiology
  • Asymptomatic Diseases / epidemiology*
  • Biomarkers / blood*
  • Burkina Faso
  • C-Reactive Protein / metabolism
  • Child
  • Cross-Sectional Studies
  • Dietary Supplements
  • Female
  • Ferritins / blood*
  • Hemoglobins / metabolism
  • Humans
  • Iron, Dietary / administration & dosage
  • Linear Models
  • Malaria / blood
  • Malaria / diagnosis
  • Malaria / epidemiology*
  • Male
  • Micronutrients / blood
  • Nutritional Status
  • Orosomucoid / metabolism
  • Prevalence
  • Proteins / metabolism
  • Randomized Controlled Trials as Topic
  • Retinol-Binding Proteins / metabolism
  • Vitamin A / administration & dosage
  • Vitamin A / blood*
  • Vitamin A Deficiency / epidemiology
  • Zinc / administration & dosage
  • Zinc / blood*

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • Hemoglobins
  • Iron, Dietary
  • Micronutrients
  • Orosomucoid
  • Proteins
  • Retinol-Binding Proteins
  • histidine-rich proteins
  • Vitamin A
  • C-Reactive Protein
  • Ferritins
  • Zinc

Associated data

  • ClinicalTrials.gov/NCT00944853