Vitamin A modifies the intestinal chemokine and cytokine responses to norovirus infection in Mexican children.

Vitamin A supplementation is associated with divergent clinical norovirus (NoV) outcomes in Mexican children. Fecal cytokine concentrations following NoV genogroup infections among 127 Mexican children 5-15 mo old enrolled in a randomized, double-blind, placebo-controlled, vitamin A supplementation trial were determined to clarify the role the gut immune response plays in these associations. Stools collected from supplemented children [20,000 IU retinol (3.3 IU = 1 µg retinol) for children < 12 mo of age; 45,000 iu for children ≥ 12 mo] or children in the placebo group were screened for NoV genogroups I (GI) and II (GII). Monocyte chemoattractant protein-1 (MCP-1), TNFα, IL-5, IL-6, IL-8, IL-4, IFNγ, and IL-10 fecal concentrations were also determined. Differences in cytokine levels between the 2 groups following GI and GII infections were determined using ordered logistic regression models. MCP-1 and IL-8 levels were greater among GI- and GII-infected children, respectively, compared with uninfected children, whereas IL-5 levels were greater following both genogroup infections. MCP-1, IL-8, and IL-6 fecal levels were reduced among supplemented children with GII-associated diarrhea compared with the placebo group. Vitamin A-supplemented, GII-infected children had reduced MCP-1 and TNFα levels compared with GII-infected children in the placebo group (P-interaction = 0.02 and 0.03, respectively). Supplemented children with GI-associated diarrhea had higher TNFα and IL-4 levels compared with children in the placebo group with diarrhea (P-interaction = 0.02 and 0.02, respectively). The divergent effects of supplementation on NoV outcomes may result from the different effects vitamin A has on the genogroup-specific immune responses.

Vitamin A supplementation has divergent effects on norovirus infections and clinical symptoms among Mexican children.

BACKGROUND: The effect of vitamin A supplementation on viral gastrointestinal infections among young children living in developing countries remains unclear. METHODS: The effect of vitamin A supplementation on norovirus (NoV) infection among 127 Mexican children 5-15 months of age was studied in a randomized, placebo-controlled trial during June-August 1998. Stool samples collected every 2 weeks and after diarrheal episodes were screened for NoV and characterized at the genogroup level (GI and GII). RESULTS: Of the stool samples collected, 29.9% were positive for NoV, and NoV GI and NoV GII were found in 55.4% and 46.4% of the positive samples, respectively. Vitamin A supplementation reduced the prevalence of NoV GII infections (rate ratio [RR], 0.60 [95% confidence interval {CI}, 0.20-0.82]), increased the length of both NoV GI and GII shedding, and decreased the prevalence of NoV-associated diarrhea (RR, 0.51 [95% CI, 0.26-0.97]). CONCLUSIONS: These findings suggest that NoV is an important cause of pediatric diarrhea in this study population and that vitamin A supplementation has divergent effects on specific outcomes of NoV infection.