Vitamin A status, inflammation, and infection
Background: Populations living in resource-limited regions experience overlapping burdens of malnutrition and infection. It is difficult to accurately assess vitamin A status in the context of inflammation or infection, which impedes research relating to vitamin A status and immunopathology. This research sought to: 1) apply and compare several vitamin A adjustment strategies using a nationally representative nutrition and health survey; 2) apply and compare several vitamin A adjustment methods using a longitudinal cohort of patients with acute febrile illness; and 3) investigate associations between inflammation-adjusted vitamin A status and immunological parameters among cases of acute febrile illness. Methods: Population samples included the ENSANUT-ECU survey and a cohort of patients with acute febrile illness recruited in Guayaquil, Ecuador. Vitamin A adjustment strategies included the Thurnham correction factor (TCF) or internal correction factor (ICF), the BRINDA regression correction (BRC), the C-reactive protein (CRP)-only adjustment factor (CAF), and a newly developed IL-6 regression model (IL-6 RM). Immune function was measured using a multiplex array of 29 markers. Results: In the ENSANUT-ECU survey, proportions of vitamin A deficiency (serum retinol < 0.70 µmol/L) between inflammation status categories were not significantly different after applying the BRC and CAF strategies in children. In the cohort of acute febrile illness, median vitamin A retinol-binding protein (RBP) concentrations differed significantly between paired visits (n = 18) after applying the TCF, BRC, and CAF adjustment strategies, but did not differ after applying the IL-6 RM (p = 0.42). Using the IL-6 RM adjustment, vitamin A insufficiency (RBP ≤ 1.05 µmol/L) was associated with an increase in MIP-1α levels (p = 0.03) and a pro-inflammatory immune response profile (p = 0.02) during the acute visit (n = 58). Conclusions: These findings suggest that in a population-representative survey, BRC and CAF adjustment strategies were comparable to the exclusion method when CRP is the only inflammation marker measured. This research also introduces an IL-6 regression model for adjusting vitamin A status, which allows for interpretation of immune function during acute infection.