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

J Pediatr Gastroenterol Nutr. 2017 Jan;64(1):104-108. doi: 10.1097/MPG.0000000000001323.

Abstract

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 coli, and 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.

MeSH terms

  • Biomarkers / blood
  • Body Weight
  • Campylobacter / growth & development
  • Cryptosporidium / growth & development
  • Diarrhea / etiology*
  • Diarrhea / microbiology
  • Diarrhea / parasitology
  • Diarrhea / virology
  • Enteropathogenic Escherichia coli / growth & development
  • Feces / microbiology
  • Feces / parasitology
  • Feces / virology
  • Female
  • Flagellin / immunology*
  • Gastrointestinal Microbiome*
  • Growth Disorders / etiology*
  • Growth Disorders / microbiology
  • Growth Disorders / parasitology
  • Growth Disorders / virology
  • Humans
  • Immunoglobulin A / blood*
  • Infant
  • Infections / complications
  • Intestinal Diseases / complications
  • Intestines* / microbiology
  • Intestines* / parasitology
  • Intestines* / virology
  • Lipopolysaccharides / immunology*
  • Male
  • Nutritional Status
  • Polymerase Chain Reaction
  • Rotavirus / growth & development
  • Shigella / growth & development
  • Tanzania

Substances

  • Biomarkers
  • Immunoglobulin A
  • Lipopolysaccharides
  • Flagellin