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

Enteropathogenic (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 low-income 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 , a negative regulator of the locus of enterocyte effacement, was associated with the absence of diarrhea in aEPEC-positive children; , 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 positivity, negativity, and the presence of the gene-was associated with undernutrition; and spp., norovirus, and enteroaggregative (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 (, , , and genes) and spp., norovirus, and EAEC to be major contributors to diarrhea and undernutrition in children from a low-income Brazilian region.