Abstract

.Enteroaggregative Escherichia coli (EAEC) cause acute and persistent diarrhea, mostly in children worldwide. Outbreaks of diarrhea caused by EAEC have been described, including a large outbreak caused by a Shiga toxin expressing strain. This study investigated the association of EAEC virulence factors with diarrhea in children less than 5 years. We characterized 428 EAEC strains isolated from stool samples obtained from moderate-to-severe diarrhea cases (157) and healthy controls (217) children aged 0–59 months recruited over 3 years as part of the Global Enteric Multicenter Study (GEMS) in The Gambia. Four sets of multiplex polymerase chain reaction were applied to detect 21 EAEC-virulence genes from confirmed EAEC strains that target pCVD432 (aatA) and AAIC (aaiC). In addition, Kirby-Bauer disc diffusion antimicrobial susceptibility testing was performed on 88 EAEC strains following Clinical Laboratory Standard Institute guidelines. We observed that the plasmid-encoded enterotoxin [odds ratio (OR): 6.9, 95% confidence interval (CI): 2.06–29.20, P < 0.001], aggregative adherence fimbriae/I fimbriae (aggA) [OR: 2.2, 95% CI: 1.16–4.29, P = 0.008], and hexosyltransferase (capU) [OR: 1.9, 95% CI 1.02–3.51, P = 0.028] were associated with moderate-to-severe diarrhea among children < 12 months old but not in the older age strata (> 12 months). Our data suggest that some EAEC-virulent factors have age-specific associations with moderate-to-severe diarrhea in infants. Furthermore, our study showed that 85% and 72% of EAEC strains tested were resistant to sulphamethoxazole-trimethoprim and ampicillin, respectively. Sulphamethoxazole-trimethoprim and ampicillin are among the first-line antibiotics used for the treatment of diarrhea in The Gambia.

Highlights

  • Enteroaggregative Escherichia coli (EAEC) is an important causative agent of both acute and persistent diarrhea among adults and children worldwide[1] and it has been among the most common E. coli pathotypes causing diarrhea among children less than 5 years of age in some developing countries.[2]

  • We observed that the plasmid-encoded enterotoxin [odds ratio (OR): 6.9, 95% confidence interval (CI): 2.06–29.20, P < 0.001], aggregative adherence fimbriae/I fimbriae [OR: 2.2, 95% CI: 1.16–4.29, P = 0.008], and hexosyltransferase [OR: 1.9, 95% CI 1.02–3.51, P = 0.028] were associated with moderate-to-severe diarrhea among children < 12 months old but not in the older age strata (> 12 months)

  • Prevalence of aggregative adherence fimbriae (AAF)/I encoded by aggregative adherence fimbriae/I fimbriae (aggA) gene was slightly higher in cases than controls (29.9% versus 22.9%) (OR: 1.4, 95% CI: 0.89–2.29, P = 0.106) (Table 2)

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Summary

Introduction

Enteroaggregative Escherichia coli (EAEC) is an important causative agent of both acute and persistent diarrhea among adults and children worldwide[1] and it has been among the most common E. coli pathotypes causing diarrhea among children less than 5 years of age in some developing countries.[2]. The pathogenesis of EAEC diarrhea is thought to comprise colonization of the intestinal mucosa, followed by elaboration of enterotoxins and cytotoxins and the release of proinflamatory cytokines from infected epithelial cells,[13,14] induced by the EAEC adherence factors called aggregative adherence fimbriae (AAF). EAEC strains characteristically enhance mucus secretion from the mucosa, potentially trapping the bacterium in a bacterium-mucus biofilm.[1] A distinctive feature of EAEC is its ability to elicit characteristic stacked brick-liked aggregative adherence to HEp-2 or HeLa cells, a test that remains the gold standard to identify this patho-

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