ABSTRACT
Objectives: To evaluate the relationship between plasma zinc concentrations (PZC) and clinical signs of zinc deficiency, and to determine a cut-off for PZC below which individuals would have an increased likelihood of having clinical signs associated with zinc deficiency. Methods: Electronic bibliographic searches were performed to identify literature from experimental zinc depletion studies and case reports of individuals with acrodermatitis enteropathica (AE). Data extracted from relevant literature included demographic characteristics, PZC and the presence or absence of clinical signs likely associated with zinc deficiency. Results: PZC were significantly lower among experimentally depleted individuals with clinical signs than those who remained asymptomatic (zinc depletion studies: (36.0+16.8 vs. 67.9+13.3μg/dL, P<0.034) and among patients with clinical signs of AE before undergoing highdose therapeutic zinc supplementation (35.0 (24.1, 47.4) μg/dL) compared with post-treatment values (108.0 (79.3, 127.0) μg/dL; P<0.01). Among individuals with restricted dietary Zn intake, PZC predicted clinical signs with 88% sensitivity and 75% specificity when using a cutoff of 60μg/dL, and 71% and 92% when applying a cutoff of 40μg/dL. Among individuals with AE, PZC predicted clinical signs with 88% sensitivity and 88% specificity when using a cutoff of 60μg/dL, and 63% and 95% when applying a cutoff of 40μg/dL. Conclusions: These analyses demonstrate a clear relationship between PZC and the presence of clinical signs associated with zinc deficiency among presumably healthy individuals undergoing periods of dietary zinc restriction, as well as individuals with AE pre- and post-treatment, further validating the utility of PZC as a biomarker of severe Zn deficiency.
ABSTRACT
Objectives: To assess how asymptomatic malaria infection affects the interpretation of biomarkers of iron, vitamin A and zinc status after adjustment for elevated acute phase proteins (APP). Methods: Plasma ferritin (pF), transferrin receptor (sTfR), retinol binding protein (RBP) and zinc (pZn) concentrations were measured among 451 asymptomatic children aged 6-23 months in Burkina Faso, and adjusted for elevated APP (C-reactive protein ≥5 mg/L and/or alpha-1-acidglycoprotein ≥1g/L) based on a four-group categorical model, as per Thurnham. Histidine-rich protein II (HRP2) concentrations >0.75 ng/mL were considered indicative of current or recent malaria parasitemia. Results: 57.4% of children had at least one elevated APP, and 48.5% had elevated HRP2. After adjusting for APP, children with elevated HRP2 had higher pF (23.5+1.5 vs. 11.1+0.8 μg/L, P<0.001) and lower RBP (0.79+0.01 vs. 0.92+0.01 μmol/L, P<0.001) vs. those without. Controlling for APP, there were no differences in pZn among those with and without elevated HRP2 (62.9+0.8 vs. 62.9+0.8 μg/dL, P=0.98). sTfR did not differ by APP status when controlling for HRP2, but was increased in children with elevated HRP2 vs. those without (17.6+0.5 vs. 12.3+0.4mg/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<0.84μmol/L) decreased from 33.4% to 27.7%. Conclusions: Current or recent malaria parasitemia affects 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.