Etiology of Diarrhea, Nutritional Outcomes, and Novel Intestinal Biomarkers in Tanzanian Infants

Gosselin, Kerri B.; Aboud, Said; McDonald, Christine M. Moyo, Sabrina; Khavari, Nasim; Manji, Karim; Kisenge, Rodrick; Fawzi, Wafaie; Kellogg, Mark; Tran, Hao Q.; Kibiki, Gibson; Gratz, Jean; Liu, Jie; Gewirtz, Andrew; Houpt, Eric; Duggan, Christopher
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Objective: Diarrheal diseases are a leading cause of morbidity and mortality worldwide, but the etiology of diarrhea and its relation to nutritional outcomes in resource-limited settings is poorly defined. We sought to determine the etiology of community-acquired diarrhea in Tanzanian infants and to assess the association with anthropometrics and novel intestinal biomarkers.

Methods: A convenience sample of infants in a trial of zinc and/or multivitamin supplementation in Tanzania was selected. Subjects were enrolled at age 6 weeks and studied for 18 months. Stool samples were obtained from children with acute diarrhea. A novel, polymerase chain reaction-based TaqMan array was used to screen stool for 15 enteropathogens. A subset of subjects had serum gastrointestinal biomarkers measured.

Results: One hundred twenty-three subjects with diarrhea were enrolled. The mean ± SD age at stool sample collection was 12.4 ± 3.9 months. Thirty-five enteropathogens were identified in 34 (27.6%) subjects: 11 rotavirus, 9 Cryptosporidium spp, 7 Shigella spp, 3 Campylobacter jejuni/coli, 3 heat stable-enterotoxigenic Escherichia coliand 2 enteropathogenic E coli. Subjects with any identified enteropathogen had significantly lower weight-for-length z scores (−0.55 ± 1.10 vs 0.03 ± 1.30, P = 0.03) at the final clinic visit than those without an identified pathogen. Fifty of the 123 subjects (40.7%) had serum analyzed for antibodies to lipopolysaccharide (LPS) and flagellin. Subjects with any identified enteropathogen had lower immunoglobulin (IgA) antibodies to LPS (0.75 ± 0.27 vs 1.13 ± 0.77, P = 0.01) and flagellin (0.52 ± 0.16 vs 0.73 ± 0.47, P = 0.02) than those without an identified pathogen.

Conclusions: This quantitative polymerase chain reaction method may allow identification of enteropathogens that place children at higher risk for suboptimal growth. IgA anti-LPS and flagellin antibodies hold promise as emerging intestinal biomarkers.