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

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.