Daily preventive zinc supplementation increases the antibody response against pathogenic Escherichia coli in children with zinc insufficiency: a randomised controlled trial

Abstract

Zinc deficiency impairs the antibody-mediated immune response and is common in children from lower-income countries. This study aimed to investigate the impact of different zinc supplementation regimens (7, 10 or 20 mg/day elemental zinc)-therapeutic dispersible zinc tablets (TZ), daily multiple micronutrient powder (MNP), daily preventive zinc tablets (PZ) and placebo powder (control)-and compare between baseline and endline antibody production against pathogenic Escherichia coli in Laotian children (aged 6-23 months). Fifty representative plasma samples of each treatment group were randomly selected from 512 children to determine anti-E. coli IgG antibody levels and avidity. Of the 200 children, 78.5% had zinc deficiency (plasma zinc concentration < 65 µg/dL) and 40% had anaemia before receiving zinc supplementation. aAfter receiving the TZ, MNP or PZ regimen, the plasma anti-E. coli IgG levels were significantly increased compared with baseline; the effect on the antibody level was more pronounced in children with zinc deficiency. Interestingly, there was increased anti-E. coli IgG avidity in the control and PZ groups. This study suggests that PZ might be the optimal zinc supplementation regimen to increase both the quantity and quality of antibody responses in children with zinc deficiency. Clinical trial registration: https://ichgcp.net/clinical-trials-registry/NCT02428647 (NCT02428647, 29/04/2015).

Conflict of interest statement

The spouse of SYH worked for the Bill & Melinda Gates Foundation, which provided part of the financial support. The other authors declare no competing interests.

© 2022. The Author(s).

Figures

Figure 1

Plasma IgG levels in response to pathogenic Escherichia coli of the four intervention groups. (a) Plasma samples from baseline and endline of each intervention group (Control, n = 50; TZ, therapeutic zinc with diarrhoea, n = 48; MNP, zinc-containing micronutrient powder, n = 47; PZ, preventive zinc, n = 50) were used to determine the anti-E. coli IgG levels. The bars represent the median with the interquartile range of each group and each dot represents an individual sample. The P-value was determined with the Kruskal–Wallis test. (b) Changes in the antibody level in each individual. The P-values indicate significant differences between baseline and endline of each intervention group determined by the Wilcoxon matched-pairs signed rank test (**P < 0.01; ***P < 0.001; ns, non-significant). (c) The pie charts show the percentages of children who showed no change or an increase or decrease of at least 10% in antibody levels at endline compared with baseline for each group. (d) Chi-square analysis of the relative risk and P-values of increasing antibody levels for each intervention group compared with the Control group.

Figure 2

Changes in the avidity index of children among the four intervention groups. (a) Plasma samples from baseline and endline of each intervention group (Control, n = 50; TZ, therapeutic zinc with diarrhoea, n = 50; MNP, zinc-containing micronutrient powder, n = 50; PZ, preventive zinc, n = 50) were used to determine the avidity index. Bars represent the median with the interquartile range of each group; each dot represents an individual sample. The P-value was determined with the Kruskal–Wallis test. (b) Changes in the avidity index of each individual. The P-values indicate significant differences between baseline and endline of each intervention group determined by the Wilcoxon matched-pairs signed rank test (**P < 0.01; ***P < 0.001; ns non-significant). (c) The pie charts show the percentages of children who showed no change or an increase or decrease of at least 5% in the avidity index at endline compared with baseline for each group. (d) Chi-square analysis of relative risk and P-values of increasing avidity from each intervention group compared with the Control group.

Figure 3

The plasma IgG level and avidity index of the four intervention groups divided by the baseline zinc status. For each group, the (a) plasma IgG level and (b) avidity index were divided into zinc-sufficient and zinc-deficient sub-groups (C control; TZ therapeutic zinc with diarrhoea; MNP zinc-containing micronutrient powder; PZ preventive zinc). Children who had baseline plasma zinc lower than 65 μg/dL were categorised in the zinc-deficient sub-group. The sample sizes are indicated above each graph. Each dot represents an individual sample. Zn Suf zinc sufficient group; Zn Def zinc deficient group. The P-values indicate significant differences between baseline and endline of each intervention group determined by the Wilcoxon matched-pairs signed rank test. *P < 0.05; **P < 0.01; ***P < 0.001; ns non-significant.