Enteric pathogens, intestinal permeability and nitric oxide production in acute gastroenteritis

Abstract

BACKGROUND: Aboriginal children hospitalized with diarrheal disease in northern Australia have high rates of acidosis, hypokalemia and osmotic diarrhea, as well as abnormal small bowel permeability and elevated nitric oxide (NO) production. METHODS: In a study of 291 diarrheal admissions and 84 controls, we examined the relationship of diarrheal severity outcomes with specific enteric pathogens. NO production was measured by urine nitrate plus nitrite excretion on a low nitrate diet, small bowel permeability by the lactulose:rhamnose ratio on a timed blood specimen and stool pathogens by standard microbiologic investigations and PCR. RESULTS: The addition of diagnostic tests for diarrheagenic Escherichia coli to standard stool microbiologic testing increased the rate of specific diagnoses from 53% to 75%, but with multiple pathogens isolated from 34%. The most frequently isolated pathogens from diarrheal patients were enteroaggregative E. coli (28.9%), rotavirus (26.5%), enteropathogenic E. coli (17.2%), Salmonella spp. (10.7%), Cryptosporidium parvum (7.2%) and Strongyloides stercoralis (7.2%). High geometric mean permeability ratios (95% confidence intervals) occurred with rotavirus (19.6; 15.3 to 25.1), enteroaggregative E. coli (21.2; 15.3 to 29.3) and Cryptosporidium (23.0; 15.1 to 35.1) compared with 9.4 (6.8 to 13.1) for no pathogens. NO production was highest for Cryptosporidium (3.7; 2.3 to 6.1) compared with 0.6 (0.4 to 1.1) for no pathogens. Multiple regression analysis revealed significant associations (P < 0.001) for rotavirus with acidosis and osmotic diarrhea, for Strongyloides with wasting and hypokalemia and for Cryptospoidium with severe and prolonged diarrhea. CONCLUSIONS: Cryptosporidium, Strongyloides, rotavirus and enteroaggregative E. coli are important contributors to the severe manifestations of acute gastroenteritis in Australian Aboriginal children.