Effects of improved water, sanitation, handwashing and nutrition on early childhood IgG immune repertoire development against Shigella and enteroinvasive Escherichia coli (EIEC)
Walas, N.; Kamau, E.; Zhang, M.; Kamath, K.; Reifert, J.; Shon, J.; Ali, S.; Rahman, M. Z.; Shoab, A. K.; Famida, S. L.; Akther, S.; Hossen, M. S.; Mutsuddi, P.; Rahman, M.; Mertens, A. N.; Charles, R.; Leung, D.; Luby, S.; Lin, A.; Arnold, B. F.
Show abstract
We studied effects of a combined water, sanitation, handwashing, and nutritional supplementation (WSH+N) intervention on Shigella/EIEC IgG immune development among Bangladeshi children enrolled in a cluster randomized trial. We used a bacterial display assay to measure IgG-specific binding to Shigella/EIEC Ipa proteins (IpaA, IpaB, IpaC, IpaD, IpaH) from a substudy of 120 children (60 intervention, 60 control) at median ages 3-, 14-, and 28-months. We found that the WSH+N intervention did not impact IgG seroprevalence (56% vs 53%, P=0.6) or IgG epitope repertoire development (P=0.15-0.97), but there were distinct age-based patterns of IgG linear epitopes and motifs charting the development of the immune repertoire. Samples from before age 6-months, reflecting predominantly maternal IgG, had higher epitope breadth and magnitude compared with samples from older ages. A modeling analysis of maternal-child IgG dynamics suggests peak susceptibility occurs between 6 and 9 months of age. With this methodology, we find that intensive, household-based WASH interventions were insufficient to reduce early childhood infection to Shigella/EIEC. Our results motivate complementary interventions, such as vaccines, to prevent Shigella/EIEC infection in the first two years of life.
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