title: Etiology of Diarrhea, Nutritional Outcomes, and Novel Intestinal Biomarkers in Tanzanian Infants.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: *Division of Pediatric Gastroenterology, UMass Memorial Children's Medical Center, Worcester †Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston MA ‡Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania §Lucile Packard Children's Hospital at Stanford, Palo Alto, CA ||Departments of Nutrition and Global Health and Population, Harvard School of Public Health ¶Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA #Department of Biology, Georgia State University, Atlanta **Kilimanjaro Clinical Research Institute, Moshi, Tanzania ††Division of Infectious Diseases and International Health, University of Virginia, Charlottesville.
authors.forename: Kerri B
authors.initials: KB
authors.lastname: Gosselin
authors.forename: Said
authors.initials: S
authors.lastname: Aboud
authors.forename: Christine M
authors.initials: CM
authors.lastname: McDonald
authors.forename: Sabrina
authors.initials: S
authors.lastname: Moyo
authors.forename: Nasim
authors.initials: N
authors.lastname: Khavari
authors.forename: Karim
authors.initials: K
authors.lastname: Manji
authors.forename: Rodrick
authors.initials: R
authors.lastname: Kisenge
authors.forename: Wafaie
authors.initials: W
authors.lastname: Fawzi
authors.forename: Mark
authors.initials: M
authors.lastname: Kellogg
authors.forename: Hao Q
authors.initials: HQ
authors.lastname: Tran
authors.forename: Gibson
authors.initials: G
authors.lastname: Kibiki
authors.forename: Jean
authors.initials: J
authors.lastname: Gratz
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Andrew
authors.initials: A
authors.lastname: Gewirtz
authors.forename: Eric
authors.initials: E
authors.lastname: Houpt
authors.forename: Christopher
authors.initials: C
authors.lastname: Duggan
mesh_terms: D015415:Biomarkers / Q000097:blood; D001835:Body Weight; D002167:Campylobacter / Q000254:growth & development; D003458:Cryptosporidium / Q000254:growth & development; D003967:Diarrhea / Q000209:etiology* / Q000382:microbiology / Q000469:parasitology / Q000821:virology; D054308:Enteropathogenic Escherichia coli / Q000254:growth & development; D005243:Feces / Q000382:microbiology / Q000469:parasitology / Q000821:virology; D005260:Female; D005408:Flagellin / Q000276:immunology*; D000069196:Gastrointestinal Microbiome; D006130:Growth Disorders / Q000209:etiology* / Q000382:microbiology / Q000469:parasitology / Q000821:virology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007223:Infant; D007239:Infections / Q000150:complications; D007410:Intestinal Diseases / Q000150:complications; D007422:Intestines / Q000382:microbiology / Q000469:parasitology / Q000821:virology; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D009752:Nutritional Status; D016133:Polymerase Chain Reaction; D012401:Rotavirus / Q000254:growth & development; D012760:Shigella / Q000254:growth & development; D013636:Tanzania
chemical_list: D015415:Biomarkers; D007070:Immunoglobulin A; D008070:Lipopolysaccharides; D005408:Flagellin