Risk Factors for Enterotoxigenic Bacteroides fragilis Infection and Association with Environmental Enteric Dysfunction and Linear Growth in Children: Results from the MAL-ED Study.

Mustafa Mahfuz,Tahmeed Ahmed,Parag Palit,Sharika Nuzhat,Rina Das,Abu Syed Golam Faruque,Towfida Jahan Siddiqua,Md Ahshanul Haque,Shaila Sharmeen Khan

doi:10.4269/ajtmh.21-0780

Abstract

ABSTRACT.Despite reports of enterotoxigenic Bacteroides fragilis (ETBF) isolation from asymptomatic children, no reports exist regarding the possible association of ETBF with long-term complications such as development of environmental enteric dysfunction (EED) and subsequent linear growth faltering in childhood. We aimed to establish a potential association between the burden of asymptomatic ETBF infection and EED and linear growth at 24 months of age using the data collected from 1,715 children enrolled in the multi-country birth cohort study, known as the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health study. Using Poisson regression models, we evaluated the site-specific incidence rate and, subsequently, identified the risk factors and assessed the association between the burden of ETBF infection and EED score and linear growth at 24 months of age. The overall incidence rate of ETBF infections per 100 child-months across all study sites was 10.6%, with the highest and lowest incidence of ETBF infections being reported in Tanzania (19.6%) and Peru (3.6%), respectively. Female gender, longer duration of breastfeeding, and improved water access, sanitation, and hygiene practices, such as improved drinking water source, improved sanitation, and improved floor material in households, along with enhanced maternal education and less crowding in the households were found to be protective against incidences of ETBF infection. The burden of ETBF infections was found to have significant associations with EED and linear growth faltering at 24 months of age across all the study sites. Our findings warrant regular clinical monitoring to reduce the burden of ETBF infections and diminish the burden of enteropathy and linear growth faltering in childhood.

Highlights

Childhood malnutrition accounts for approximately 45% of the cases of “under-five” mortality and has been reported to be associated strongly with a number of acute illnesses and severe damage to several physiological activities, including restricted mental growth and development in later life, cardiovascular and chronic respiratory illnesses, and compromised host immunity.[1,2] Stunting or linear growth faltering is the most prevalent form of childhood malnutrition and affects an estimated 149 million children worldwide.[3,4] The first 2 years of life are a critical window for long-term growth and development, and stunting has been reported to exhibit extremely serious and adverse consequences in children younger 2 years of age.[5]
We investigated the occurrence of the bft gene of enterotoxigenic Bacteroides fragilis (ETBF), and positive cases were analyzed further for co-infection for the presence of distinct other co-pathogens—namely, Campylobacter sp., enterotoxigenic Escherichia coli (ETEC), enteroaggregative E. coli (EAEC), typical enteropathogenic E. coli, Shigella/enteroinvasive E. coli, Cryptosporidium spp. and Giardia spp., as described previously.[41]
A total of 1,715 participants were enrolled across the eight different study sites, and a total of 34,622 monthly nondiarrheal stool samples were collected from the study participants throughout the entire study period, starting from their enrollment after birth

Summary

Introduction

Childhood malnutrition accounts for approximately 45% of the cases of “under-five” mortality and has been reported to be associated strongly with a number of acute illnesses and severe damage to several physiological activities, including restricted mental growth and development in later life, cardiovascular and chronic respiratory illnesses, and compromised host immunity.[1,2] Stunting or linear growth faltering (length-for-age z-score [LAZ] , 2 points of the WHO growth standard) is the most prevalent form of childhood malnutrition and affects an estimated 149 million children worldwide.[3,4] The first 2 years of life are a critical window for long-term growth and development, and stunting has been reported to exhibit extremely serious and adverse consequences in children younger 2 years of age.[5]. Chronic exposure to enteropathogens leading to persistent immune activation, increased intestinal permeability, and enteric inflammation are hallmarks of EED.[8,9] Small

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