Histologic-blood group antigens (HBGAs) may affect the incidence of all-cause diarrhea and enteric infections in young children, according to study results published in the Journal of Infectious Diseases.

Despite improvements in oral rehydration therapy, water and sanitation, and rotavirus vaccine, diarrheal diseases continue to be a major cause of illness and premature death, and are currently responsible for mortality in approximately 500,000 children a year with modest morbidity decreases. The efficacy of preventative interventions and in pathogen-specific diarrhea incidence has shown variability between populations, which may suggest that inherited host factors may differentially influence susceptibility to certain enteric infections. Previous research has identified the fucosyltransferase (FUT) genes, primarily FUT2 and FUT3, as possible candidates for this influence.

Therefore, this analysis report quantified and modelled associations between infant and maternal secretor (FUT2) status and Lewis (FUT3) type and episodes of infection with the 5 enteric viruses and 5 enteric bacteria that are most strongly associated with diarrhea (adenovirus, astrovirus, norovirus, rotavirus, sapovirus, and Campylobacter; enteroaggregative Escherichia coli, enteropathogenic E coli (typical and atypical); heat-labile and heat-stable enterotoxigenic E coli (LT‑ETEC and ST-ETEC, respectively); and Shigella.

Data was collected from 3 community-based birth cohorts in which FUT2 and FUT3 statuses were collected for mother-child dyads (520 children and 519 mothers). A total of 3633 diarrheal stool samples and 18,148 asymptomatic stool samples were tested via polymerase chain reaction for 29 enteropathogens. Cumulative diarrhea and infection incidence were compared by child and mothers’ histo-blood group antigens status.

Results showed that children of mothers who were FUT2-postitive (secretors) had a 38% increased risk for all‑cause diarrhea after adjustment (hazard ratio [HR] 1.28) and also had a significantly reduced time to first diarrheal episode. However, when children had FUT2- and FUT3-positivity, their risk for all-cause diarrhea was reduced by 29% (HR 0.81) and 27% (HR 0.83), respectively. Further, results showed strong associations between pathogen-specific infection and diarrhea and HBGAs.

These strong associations were particularly noted in cases of infections with noroviruses, rotaviruses, enterotoxigenic E coli, Campylobacter jejuni and C coli. The only pathogen-specific association with maternal secretor positive status was observed in LT-ETEC, with children of secretors showing a 27% reduced risk for diarrhea as a result of LT-ETEC infection when compared with children of non-secretors (HR, 0.63). In the multivariate model, maternal secretors were not associated with all-cause diarrhea risk; however, it was associated with a 34% increased risk for astrovirus (HR, 1.34), but not astrovirus diarrhea. In rotavirus and norovirus infections, associations were only observed in conjunction with the child’s FUT status, not the mother’s. The most increased risk occurred in secretor children infected with GII.4 norovirus (HR 10.45) compared with non-secretor children. Children of Lewis mothers showed a 42% increased risk for rotavirus diarrhea.

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Overall, the study authors concluded that, “More detailed characterization of the pathogen- and strain‑specific effects of [Histo blood group antigens] on enteric infection can inform the development of precision public health and improve the success of regionalized and targeted interventions.”

Reference

Colston JM, Francois R, Pisanic N, et al. Effects of child and maternal histo blood group antigen status on symptomatic and asymptomatic enteric infections in early childhood [published online February 15, 2019]. J Infect Dis. doi:10.1093/infdis/jiz072/5320520