TY - JOUR
T1 - Effects of Child and Maternal Histo-Blood Group Antigen Status on Symptomatic and Asymptomatic Enteric Infections in Early Childhood
AU - Colston, Josh M.
AU - Francois, Ruthly
AU - Pisanic, Nora
AU - Peñataro Yori, Pablo
AU - Mccormick, Benjamin J.J.
AU - Olortegui, Maribel Paredes
AU - Gazi, Md Amran
AU - Svensen, Erling
AU - Ahmed, Mondar Maruf Moin
AU - Mduma, Esto
AU - Liu, Jie
AU - Houpt, Eric R.
AU - Klapheke, Robert
AU - Schwarz, Julia W.
AU - Atmar, Robert L.
AU - Black, Robert E.
AU - Kosek, Margaret N.
N1 - Funding Information:
Financial support. This work was funded by the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is carried out as a collaborative project funded by the Bill & Melinda Gates Foundation (BMGF) (BMGF-47075), the Foundation for the National Institutes of Health, and the National Institutes of Health, Fogarty International Center, whereas additional support was obtained from BMGF for the examination of host innate factors on enteric disease risk and enteropathy (Grants OPP1066146 and OPP1152146; to M. N. K.). Additional funding was obtained from teh Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases, Johns Hopkins School of Medicine (to M. N. K) and the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institues of health 1UL1TR001079.
Acknowledgments. We thank the participants, their families, and the study community for their dedicated time and effort to better the understanding the transmission and more enduring impact of enteric infections in early childhood. We also thank the following: Jan Vinje (Centers for Disease Control and Prevention) for critical input and manuscript review; Dr. Leah Jager for consultation regarding the statistical analysis; Dr. Ben Jann (University of Bern, Switzerland) for guidance in generating the figures; Christine Szymanski for insight and encouragement, particularly regarding Campylobacter infection and disease patency; Chris Damman and Anita Zaidi for input on early iterations of the analysis; and Dick Guerrant for final reflections.
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.
PY - 2019/2/15
Y1 - 2019/2/15
N2 - Background: 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. Methods: In 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. Results: Children 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. Conclusions: Histo-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.
AB - Background: 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. Methods: In 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. Results: Children 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. Conclusions: Histo-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.
KW - antibodies, bacterial
KW - bacterial vaccines
KW - colonization factor antigens
KW - controlled human infection model
KW - diarrhea, prevention and control
KW - Escherichia coli infections
KW - fimbriae proteins
KW - immunization, passive
KW - milk proteins, immunology
KW - randomized controlled clinical trial
UR - http://www.scopus.com/inward/record.url?scp=85067494577&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiz072
DO - 10.1093/infdis/jiz072
M3 - Article
C2 - 30768135
AN - SCOPUS:85067494577
VL - 220
SP - 151
EP - 162
JO - The journal of infectious diseases
JF - The journal of infectious diseases
SN - 0022-1899
IS - 1
M1 - jiz072
ER -
