Micronutrients, Immunological Parameters, and Dengue Virus Infection in Coastal Ecuador: A Nested Case-Control Study in an Infectious Disease Surveillance Program

Abstract

BACKGROUND: Micronutrients are known to modulate host immunity, and there is limited literature on this association in the context of dengue virus infection (DENV). METHODS: Using a nested case-control design in a surveillance program, we measured the following: anthropometry; nutritional biomarkers including serum ferritin, soluble transferrin receptor, retinol-binding protein (RBP), 25-hydroxy vitamin D, folate, and vitamin B12; and a panel of immune response markers. We then compared these measures across 4 illness categories: healthy control, nonfebrile DENV, other febrile illness (OFI), and apparent DENV using multivariate polytomous logistic regression models. RESULTS: Among 142 participants, serum ferritin (ng/mL) was associated with apparent DENV compared to healthy controls (odds ratio [OR], 2.66; confidence interval [CI], 1.53-4.62; P = .001), and RBP concentrations (µmol/L) were associated with apparent DENV (OR, 0.03; CI, 0.00-0.30; P = .003) and OFI (OR, 0.02; CI, 0.00-0.24; P = .003). In a subset of 71 participants, interleukin-15 levels (median fluorescent intensity) were positively associated with apparent DENV (OR, 1.09; CI, 1.03-1.14; P = .001) and negatively associated with nonfebrile DENV (OR, 0.89; CI, 0.80-0.99; P = .03) compared to healthy controls. CONCLUSIONS: After adjusting for the acute-phase response, serum ferritin and RBP concentrations were associated with apparent DENV and may represent biomarkers of clinical importance in the context of dengue illness.