Effects of Child and Maternal Histo-Blood Group Antigen Status on Symptomatic and Asymptomatic Enteric Infections in Early Childhood.

Josh M Colston,Julia W Schwarz,Ruthly Francois,Pablo Peñataro Yori,Nora Pisanic,Maribel Paredes Olortegui,Robert Klapheke,Jie Liu,Mondar Maruf Moin Ahmed,Robert L Atmar,Robert E Black,Eric R Houpt,Md Amran Gazi,Esto Mduma,Margaret N Kosek,Benjamin J J Mccormick,Erling Svensen

doi:10.1093/infdis/jiz072

Abstract

BackgroundHisto-blood group antigens (HBGAs) such as fucosyltransferase (FUT)2 and 3 may act as innate host factors that differentially influence susceptibility of individuals and their offspring to pediatric enteric infections.MethodsIn 3 community-based birth cohorts, FUT2 and FUT3 statuses were ascertained for mother-child dyads. Quantitative polymerase chain reaction panels tested 3663 diarrheal and 18 148 asymptomatic stool samples for 29 enteropathogens. Cumulative diarrhea and infection incidence were compared by child (n = 520) and mothers’ (n = 519) HBGA status and hazard ratios (HRs) derived for all-cause diarrhea and specific enteropathogens.ResultsChildren of secretor (FUT2 positive) mothers had a 38% increased adjusted risk of all-cause diarrhea (HR = 1.38; 95% confidence interval (CI), 1.15–1.66) and significantly reduced time to first diarrheal episode. Child FUT2 and FUT3 positivity reduced the risk for all-cause diarrhea by 29% (HR = 0.81; 95% CI, 0.71–0.93) and 27% (HR = 0.83; 95% CI, 0.74–0.92), respectively. Strong associations between HBGAs and pathogen-specific infection and diarrhea were observed, particularly for noroviruses, rotaviruses, enterotoxigenic Escherichia coli, and Campylobacter jejuni/coli.ConclusionsHisto-blood group antigens affect incidence of all-cause diarrhea and enteric infections at magnitudes comparable to many common disease control interventions. Studies measuring impacts of interventions on childhood enteric disease should account for both child and mothers’ HBGA status.

Highlights

Histo-blood group antigens (HBGAs) such as fucosyltransferase (FUT)2 and 3 may act as innate host factors that differentially influence susceptibility of individuals and their offspring to pediatric enteric infections
Child FUT2 and FUT3 positivity reduced the risk for all-cause diarrhea by 29% (HR = 0.81; 95% confidence interval (CI), 0.71–0.93) and 27% (HR = 0.83; 95% CI, 0.74–0.92), respectively
The variability observed in the effectiveness of preventive interventions [4, 5] and in pathogen-specific diarrhea incidence between populations suggests that inherited host factors may differentially influence susceptibility to certain enteric infections [6,7,8,9,10], and a cluster of fucosyltransferase (FUT) genes—primarily the FUT2 and FUT3 genes—have emerged as candidates [11]

Summary

Methods

In 3 community-based birth cohorts, FUT2 and FUT3 statuses were ascertained for mother-child dyads. Multivariate Cox regression models were fitted for all-cause diarrhea and individual pathogens adjusting mothers’ and infants’ FUT2 and FUT3 status for each other and for covariates and stratifying by sample type (diarrheal or surveillance stools). Stratified Cox models were fitted comparing O with A/B/AB blood groups for those sites where such information was available (BGD and PEL) among secretors adjusting for covariates but not FUT statuses. For 3 pathogen strains with reported binding sites for H Type I antigens, hypothesized to be present at greatest concentration in FUT2+/FUT3− individuals—P[4]/P[8] rotavirus, CFA/I+ ETEC, and Campylobacter jejuni/coli—and for all-cause diarrhea, separate Cox models were fitted comparing HRs of Lewis normal to null type among secretor children (see Figure 2). Analyses were carried out using Stata 13.1 [33]

Results

Discussion

Conclusion