Vitamin A status, inflammation adjustment, and immunologic response in the context of acute febrile illness: A pilot cohort study among pediatric patients.

Vitamin A is necessary for an adequate immune response to infections. Infection also alters vitamin A biomarkers, which interferes with assessment of vitamin A deficiency and thus impairs clinical management. Here we apply multiple strategies to adjust vitamin A biomarkers for inflammation during acute infection and evaluate associations between adjusted vitamin A status and immunologic response markers. We measured biomarkers in pediatric patients presenting with acute febrile illness in Guayaquil, Ecuador at paired acute and convalescent visits. Four adjustment strategies were applied to retinol-binding protein (RBP) concentrations: Thurnham correction factor (TCF), BRINDA regression correction (BRC), CRP-only adjustment factor (CRP), and proof-of-concept for a proposed interleukin 6 regression model (IL-6 RM). Adjusted RBP concentrations were compared between visits using the paired Wilcoxon signed-rank test. Multivariate regression analysis was used to assess associations between adjusted vitamin A status and immunologic response markers. A sample of 57 participants completed the acute visit 1, and 18 of these individuals completed the convalescent visit 2. The IL-6 RM was the only strategy resulting in adjusted RBP concentrations that were not significantly different between paired visits (p = 0.20). Following RBP adjustment, 0.0% of participants were classified as vitamin A deficient (RBP ≤ 0.70 μmol/L) and 14.0% were classified as vitamin A insufficient (RBP ≤ 1.05 μmol/L). Adjusted vitamin A insufficiency was associated with an increase in macrophage inflammatory protein 1-alpha (MIP-1α, p = 0.03) and a pro-inflammatory immune response profile (p = 0.03) during the acute visit. We introduce a strategy for adjusting vitamin A in the context of clinical illness based on IL-6 concentrations that will need to be validated in larger studies. Assessment of vitamin A during infection allows for further understanding of how vitamin A status modulates immunopathology and enables targeted strategies for vitamin A supplementation in the context of infection among children in settings with high burdens of undernutrition and infectious diseases.