Campylobacter jejuni virulence genes and immune-inflammatory biomarkers association with growth impairment in children from Northeastern Brazil.

Campylobacter spp. have been associated with anthropometric Z-score decrements, but the role of specific virulence genes associated with these outcomes has not been explored. This study aimed to investigate whether specific Campylobacter jejuni virulence-related gene and immune-inflammatory biomarkers are associated with malnutrition in children from Northeastern Brazil. A case-control study was performed in Fortaleza, Brazil. Children aging 6-24 months were characterized as malnourished (cases) if weight-for-age Z-score (WAZ) = 2 and as nourished (controls) if WAZ ≥ 1. DNA samples were extracted from stools and screened for C. jejuni/coli by real-time PCR. A subsequent C. jejuni-specific PCR was employed and positive samples were evaluated for 18 C. jejuni virulence genes by using four multiplex PCRs. C. jejuni was detected in 9.71% (33/340) of the children's samples, being 63.63% (21/33) from nourished and 37.37% (12/33) from malnourished children. The cadF, iamA, cheW, and sodB genes were the most frequent genes (100%, 90.9%, 87.9%, and 75.8%, respectively), while some others (ceuE, jlpA, pldA, and pVir) showed low rates (all below 6%). Malnourished children were significantly associated with infection with C. jejuni strains lacking cdtB gene (active subunit of cytolethal distending toxin) and harboring flgE gene (flagellar hook protein). These strains were also associated with children presenting increased serum SAA and sCD-14, but decreased IgG anti-LPS. These data reinforce the impact of Campylobacter jejuni infection on children without diarrhea and highlight the contribution of a specific virulence gene profile, cdtB(-)flgE(+) and increased systemic response in malnutrition children.

Prevalence and virulence gene profiling of enteroaggregative Escherichia coli in malnourished and nourished Brazilian children.

The impact of enteroaggregative E. coli (EAEC) infection on childhood malnutrition and inflammation has been suggested, regardless of diarrhea. We investigated whether EAEC and its virulence-related genes (VRGs) are associated with malnutrition in a case-control study. Children aged 6-24 months from Brazil were enrolled as malnourished if weight-for-age Z-score (WAZ) ≤ -2 and nourished if WAZ > -1. Stools were cultured and examined for E. coli. DNA was extracted from fecal isolates and tested for EAEC by polymerase chain reaction (PCR). Positive samples were analyzed by 5 multiplex PCRs to identify 20 EAEC VRGs. Biomarkers of intestinal barrier function and inflammation were measured. The prevalence of EAEC was 39.94%. Samples that presented both aaiC and aatA genes were associated with malnutrition (P = 0.045). A high prevalence of VRGs was observed and the aafC gene was significantly associated with malnourished (P = 0.0101). Strains lacking aar and pic genes were associated with malnutrition (P = 0.018), while the concomitant presence of aar, pic, agg4A, and capU genes was associated with nourished (P = 0.031). These data reinforce the EAEC impact on malnutrition, the importance of aar as negative regulator and the great contribution of AAF/II fimbria for the pathobiology of EAEC.

Determinant Variables, Enteric Pathogen Burden, Gut Function and Immune-related Inflammatory Biomarkers Associated With Childhood Malnutrition: A Prospective Case-Control Study in Northeastern Brazil.

Malnutrition results in serious consequences for growth and cognitive development in children. We studied select child and maternal biologic factors, socioeconomic factors, enteric pathogenic burden and gut function biomarkers in 402 children 6-24 months of age in Northeastern Brazil. In this prospective case-control study, not being fed colostrum [odds ratio (OR): 3.29, 95% confidence interval (CI): 1.73-6.26], maternal age ≥18 years (OR: 1.88, 95% CI: 1.10-3.22) and no electric fan (OR: 2.46, 95% CI: 1.22-4.96) or bicycle (OR: 1.80, 95% CI: 1.10-2.95) in the household were positively associated, and higher birth weight (OR: 0.27, 95% CI: 0.19-0.38), larger head circumference (OR: 0.74, 95% CI: 0.66-0.82) and shortness of breath in the last 2 weeks (OR: 0.49, 95% CI: 0.27-0.90) were negatively associated with malnutrition. Subclinical enteric pathogen infections were common, and enteroaggregative Escherichia coli infections were more prevalent in malnourished children (P = 0.045). Biomarkers such as the lactulose-mannitol test, myeloperoxidase, neopterin and calprotectin were highly elevated in both malnourished and nourished children. Nourished children had a better systemic immune response than the malnourished children, as detected by elevated serum amyloid A-1 and soluble cluster of differentiation protein 14 biomarkers (P < 0.001). Serum amyloid A-1 and soluble cluster of differentiation protein 14 were also associated with better nutritional Z scores. Neonatal, maternal and socioeconomic factors were associated with malnutrition in children. There was a substantial subclinical enteric pathogen burden, particularly with enteroaggregative E. coli, in malnourished children.

Geography, population, demography, socioeconomic, anthropometry, and environmental status in the MAL-ED cohort and case-control study Sites in Fortaleza, Ceará, Brazil.

The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort in the study's Fortaleza, Brazil, catchment area has a population of approximately 82 300 inhabitants. Most of the households (87%) have access to clean water, 98% have electricity, and 69% have access to improved toilet/sanitation. Most childbirths occur at the hospital, and the under-5 mortality rate is 20 per 1000 live births. The MAL-ED case-control study population, identified through the Institute for the Promotion of Nutrition and Human Development (IPREDE), serves 600 000 inhabitants from areas totaling about 42% of the city of Fortaleza. IPREDE receives referrals from throughout the state of Ceará for infant nutrition, and provides services including teaching activities and the training of graduate students and health professionals, while supporting research projects on child nutrition and health. In this article, we describe the geographic, demographic, socioeconomic, anthropometric, and environmental status of the MAL-ED cohort and case-control study populations in Fortaleza, Brazil.