Pathogens Associated With Linear Growth Faltering in Children With Diarrhea and Impact of Antibiotic Treatment: The Global Enteric Multicenter Study

• Type of Material: Article
• Authors: Dilruba Nasrin, University of Maryland; William C Blackwelder, University of Maryland; Halvor Sommerfelt, University of Bergen; Yukun Wu, University of Maryland; Tamer H Farag, University of Maryland; Sandra Panchalingam, University of Maryland; Kousick Biswas, Cooperat Studies Program Coordinating Ctr; Debasish Saha, London School of Hygiene & Tropical Medicine; Jahangir M Hossain, London School of Hygiene & Tropical Medicine; Samba O Sow, Centre pour le Développement des Vaccins; Robert FB Reiman, Kenya Office of the US Centers for Disease Control and Prevention; Dipika Sur, National Institute of Cholera and Enteric Diseases; Abu SG Faruque, International Centre for Diarrhoeal Disease Research; Anita KM Zaidi, Aga Khan University; Doh Sanogo, Centre pour le Développement des Vaccins; Boubou Tamboura, Centre pour le Développement des Vaccins; Uma Onwuchekwa, Centre pour le Développement des Vaccins; Byomkesh Manna, National Institute of Cholera and Enteric Diseases; Thandavarayan Ramamurthy, National Institute of Cholera and Enteric Diseases; Suman Kanungo, National Institute of Cholera and Enteric Diseases; Richard Omore, Kenya Med Res Inst Ctr Global Hlth Res KEMRI CGHR; John B Ochieng, Kenya Med Res Inst Ctr Global Hlth Res KEMRI CGHR; Joseph O Oundo, Kenya Med Res Inst Ctr Global Hlth Res KEMRI CGHR; Sumon K Das, International Centre for Diarrhoeal Disease Research, Mohakhali; Shahnawaz Ahmed, International Centre for Diarrhoeal Disease Research, Mohakhali; Shahida Qureshi, Aga Khan University; Farheen Quadri, Aga Khan University; Richard A Adegbola, London School of Hygiene & Tropical Medicine; Martin Antonio, London School of Hygiene & Tropical Medicine; Inacio Mandomando, Centro de Investigação em Saúde de Manhiça (CISM); Tacilta Nhampossa, Centro de Investigação em Saúde de Manhiça (CISM); Quique Bassat, Centro de Investigação em Saúde de Manhiça (CISM); Anna Roose, University of Maryland; Ciara E O'Reilly, US Centers for Disease Control and Prevention, Atlanta; Eric Mintz, Emory University; Usha Ramakrishnan, Emory University; Helen Powell, University of Maryland; Yuanyuan Liang, University of Maryland; James P Nataro, University of Maryland; Myron M Levine, University of Maryland; Karen L Kotloff, University of Maryland
• Language: English
• Date: 2021-12-20
• Publisher: OXFORD UNIV PRESS INC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/infdis/jiab434
• Title of Journal or Parent Work: JOURNAL OF INFECTIOUS DISEASES
• Volume: 224
• Issue: SUPPL 7
• Start Page: S848
• End Page: S855
• Grant/Funding Information: This work was supported by the Bill & Melinda Gates Foundation.
• Keywords: Infectious Diseases; GEMS; pathogens; DISEASE; Microbiology; INFECTION; COMMUNITY; DEVELOPING-COUNTRIES; antibiotics; YOUNG-CHILDREN; stunting; ENTEROTOXIGENIC ESCHERICHIA-COLI; BURDEN; growth faltering; INFANTS; Life Sciences & Biomedicine; Immunology; Science & Technology; children; Diarrhea
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Public Health; Health Sciences, Epidemiology

Abstract

BACKGROUND: The association between childhood diarrheal disease and linear growth faltering in developing countries is well described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment. METHODS: The Global Enteric Multicenter Study enrolled children with moderate to severe diarrhea (MSD) seeking healthcare at 7 sites in sub-Saharan Africa and South Asia. At enrollment, we collected stool samples to identify enteropathogens. Length/height was measured at enrollment and follow-up, approximately 60 days later, to calculate change in height-for-age z scores (ΔHAZ). The association of pathogens with ΔHAZ was tested using linear mixed effects regression models. RESULTS: Among 8077 MSD cases analyzed, the proportion with stunting (HAZ below -1) increased from 59% at enrollment to 65% at follow-up (P < .0001). Pathogens significantly associated with linear growth decline included Cryptosporidium (P < .001), typical enteropathogenic Escherichia coli (P = .01), and untreated Shigella (P = .009) among infants (aged 0-11 months) and enterotoxigenic E. coli encoding heat-stable toxin (P < .001) and Cryptosporidium (P = .03) among toddlers (aged 12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (P = .02). CONCLUSIONS: Linear growth faltering among children aged 0-23 months with MSD is associated with specific pathogens and can be mitigated with targeted treatment strategies, as demonstrated for Shigella.