Virulence-Related Genes and Coenteropathogens Associated with Clinical Outcomes of Enteropathogenic Escherichia coli Infections in Children from the Brazilian Semiarid Region: a Case-Control Study of Diarrhea

Abstract

Enteropathogenic Escherichia coli (EPEC) is a major cause of diarrhea in children from developing countries and presents high genetic variability. We aimed to characterize the EPEC virulence-related gene (VRG) distribution and copathogens associated with diarrhea and nutrition-related outcomes in children from the lowincome Brazilian semiarid region. A cross-sectional case-control study of diarrhea was conducted in 1,191 children aged 2 to 36 months from the northeast region of Brazil. Stool samples were collected and clinical, epidemiological, and anthropometric data were identified from each child. A broad molecular evaluation of enteropathogens was performed, and EPEC-positive samples were further investigated for 18 VRGs using five multiplex PCRs. EPEC was detected in 28.2% of the study population, with similar proportions among cases and controls. Typical EPEC (tEPEC) infections were more often associated with diarrhea than atypical EPEC (aEPEC) infections, while aEPEC infections presented a higher prevalence. The VRG ler, a negative regulator of the locus of enterocyte effacement, was associated with the absence of diarrhea in aEPEC-positive children; espB, a major component of the type 3 secretion system, was associated with diarrhea in tEPEC-positive children; the presence of procolonization VRGs-the combination of cesT positivity, espP negativity, and the presence of the map gene-was associated with undernutrition; and Campylobacter spp., norovirus, and enteroaggregative E. coli (EAEC) coinfections were associated with increased clinical severity in EPEC-infected children. These data identified tEPEC strains associated with diarrhea and specific VRGs of EPEC (ler, espB, cesT, and map genes) and Campylobacter spp., norovirus, and EAEC to be major contributors to diarrhea and undernutrition in children from a low-income Brazilian region.

Epidemiology of Enteroaggregative, Enteropathogenic, and Shiga Toxin–ProducingEscherichia coliAmong Children Aged <5 Years in 3 Countries in Africa, 2015–2018: Vaccine Impact on Diarrhea in Africa (VIDA) Study

“…Conflicting findings have also been reported concerning the association between MSD and the remaining DEC, aEPEC, EAEC, and STEC. The lack of a relationship that we observed in VIDA corroborates negative findings from recent studies that included Etiology, Risk Factors, and Interaction of Enteric Infections and Malnutrition and the Consequences for Child Health and Development project (MAL-ED) [ 10 ] and others [ 3 , 10 , 25 , 30 ]. Among the 7 sites and 3 age strata in GEMS [ 23 ], EAEC was only associated with endemic MSD in children aged 12–23 months from Bangladesh [ 31–33 ].…”

“…There is evidence to suggest that DEC induce intestinal inflammation that can lead to growth and nutritional faltering even in the absence of diarrheal disease [ 8 , 25 , 44–50 ], particularly during the first 2 years of life. In addition, both tEPEC and EAEC were associated with an increased risk of death in GEMS within 2–3 months after onset of the MSD episode [ 51 ].…”

Association between Pathogenic Variants of Diarrheagenic Escherichia coli and Growth in Children under 5 Years of Age in the Global Enteric Multicenter Study

“…A cross-sectional case-control study involving Brazilian children aged 2–36 months found a stronger link between tEPEC (typical EPEC) infections and clinical severity of diarrhea and undernutrition, compared with the cases of aEPEC (atypical EPEC) infections. 17 On the basis of the presence of the Escherichia coli adherence factor (EAF) plasmid encoding bundle-forming pili (BFP), EPEC can be subgrouped into tEPEC and aEPEC. 18 Typical EPEC is usually linked to incidences of gastroenteritis, even severe diarrhea among infants, whereas aEPEC is associated with a wide array of clinical manifestations, ranging from asymptomatic colonization to prolonged diarrhea, based on different settings.…”