Effects of zinc supplementation as adjunct therapy on the systemic immune responses in shigellosis

Background: Zinc is lost during diarrheal diseases, and zinc deficiency induces intestinal morphology-altering inflammatory responses that zinc supplementation can correct. Objective: We assessed the in vivo effect of zinc supplementation on systemic and mucosal responses in mildly to moderately malnourished (defined as <-1 but >-2 and <-2 but >-3 weight-for-height z scores, respectively, based on the National Center for Health Statistics growth reference) children with shigellosis. Design: A double-blind placebo-controlled trial was conducted in Shigella flexneri-infected children aged 12-59 mo. Daily for 14 d, elemental zinc (20 mg) and multivitamins (vitamins A and D, thiamine, riboflavin, and nicotinamide) plus calcium were given at twice the US recommended dietary allowance to the zinc group (n = 28), and multivitamins plus calcium were given to the control group (n = 28). All subjects received standard antibiotic therapy. Results: There was no significant interaction between zinc supplementation and time, but zinc supplementation showed a significant effect on serum zinc concentrations. With a ≥4-fold increase in serum shigellacidal antibody titers from baseline used as the cutoff, the proportion of children with shigellacidal antibody response was greater in the zinc group than in the control group (P < 0.03). There was a significant (P = 0.02) treatment x time interaction for the proportions of circulating CD20⁺ and CD20⁺CD38⁺ cells, which were higher on day 7 in the zinc group than in the control group (P < 0.007). No effect was seen on histopathologic features or the expression of innate and inflammatory mediators in the rectum. Conclusion: Adjunct therapy with zinc during acute shigellosis significantly improved seroconversion to shigellacidal antibody response and increased the proportions of circulating B lymphocytes and plasma cells.