Title : Inflammation-adjusted vitamin A deficiency is associated with higher Schistosoma japonicum infection intensity among children and adolescents in the Philippines
Abstract:
Background: Children with intestinal schistosomiasis are at risk for undernutrition, anemia, linear growth stunting, and impaired cognitive development. Vitamin A deficiency impairs immune function against parasitic pathogens. In rodents, dietary-induced vitamin A deficiency causes higher schistosome worm and egg burden, higher mortality, and a reduced immune response compared to replete vitamin A status. In humans, applying an inflammation-adjustment strategy to vitamin A blood biomarker measures is necessary to estimate vitamin A status during periods of infection or inflammation. To our knowledge, this is the first study to examine relationships between inflammation-adjusted vitamin A status and human schistosomiasis burden.
Methods: This is a secondary analysis using stored sera collected from a cohort of children and adolescents with Schistosoma japonicum infection from Leyte, The Philippines who were followed for 18 months. The original study, conducted from 2002-2003, measured S. japonicum infection intensity by eggs per gram of stool (EPG) using the Kato-Katz method, measured C-reactive protein (CRP) in blood sera, and collected demographic information of age, sex, and socio-economic status (SES). The current analysis added ELISA measures of vitamin A retinol-binding protein (RBP) and alpha-1-acid glycoprotein (AGP) from stored sera collected at baseline. The Thurnham Correction Factor (TCF) inflammation-adjustment method was applied to measures of RBP using co-circulating measures of CRP and AGP to estimate vitamin A status. A sample of N=40 participants was randomly selected based on S. japonicum EPG distribution. Statistical analyses, including multivariate linear regression, was conducted using SAS Studio 3.8 (SAS Institute Inc., Cary, NC).
Results: There were 39 participants with S. japonicum infection included for analysis. The median age was 13.4 years (9.9-16.3 IQR) and 61.5% were male. The median infection intensity at the baseline visit was 83.3 EPG (23.3-206.7 IQR), and the proportions of infection intensity categories were 53.8% light (1-99 EPG), 35.9% moderate (100-399 EPG), and 10.3% heavy (≥400 EPG). After applying the TCF correction to RBP values, 14 participants (35.9%) were categorized as vitamin A deficient (RBP < 0.7 µmol/L). Using a multivariate regression model adjusting for age, sex, and SES, vitamin A deficiency was associated with higher S. japonicum infection intensity (EPG) compared to those with replete vitamin A at the baseline visit (p=0.0172). Baseline vitamin A status was not found to be associated with S. japonicum infection intensity (EPG) at subsequent visits (1, 3, 6, 9, 12, 15, or 18 months after baseline).
Conclusions: After adjusting for inflammation, more than one third (35.9%) of the sample was vitamin A deficient. We report an association between vitamin A deficiency and increased schistosomiasis egg burden at the baseline visit. These results agree with findings reported from animal studies and represent an important discovery for our understanding of nutritional modulation of infection, specific to schistosomiasis. There is often an overlapping geographical burden of micronutrient deficiencies and neglected tropical diseases. In combination with preventive chemotherapy for schistosomiasis, nutritional interventions improving vitamin A status may lead to reduced morbidity for children and adolescents living in endemic areas.
