Etiology of Acute Diarrhea in Children

By Hal B. Jenson, MD, FAAP, Dean, Western Michigan University School of Medicine, Kalamazoo, Michigan, is Associate Editor for Infectious Disease Alert.

Dr. Jenson reports no financial relationships in this field of study.

Synopsis: Among children less than 5 years of age with acute diarrheal illness, bacterial pathogens were identified in 11% of cases, with the major causes being Salmonella and Shiga toxin-producing Escherichia coli (STEC). Enteroaggregative E. coli (EAEC) was identified in 3.1% of cases and 0.9% of controls.

Source: Denno DM, Shaikh N, Stapp JR, et al: Diarrhea etiology in a pediatric emergency department: A case control study. Clin Infect Dis 2012;55:897-904.

From November 2003 to November 2005, 254 cases of childhood diarrhea and 452 age- and geographically-matched (by zip code) controls were enrolled in a case-control study of the etiology of acute diarrhea among children 10-49 months of age presenting to a pediatric emergency department. Stools were analyzed for Aeromonas, Campylobacter, Escherichia coli O157:H7 (STEC), Pleisiomonas shigelloides, Salmonella, Shigella, Vibrio, and Yersinia by culture; adenoviruses, astroviruses, noroviruses, rotavirus, and Shiga toxin-producing E. coli (STEC) by enzyme immunoassay; Clostridium difficile by cytotoxicity; parasites by microscopy; and enteroaggregative E. coli (EAEC) by PCR. Bacterial cultures of stools were limited to cases only.

One or more diarrheagenic etiologies were identified in stools of 174 cases and 69 controls (adjusted OR, 12.9; 95% CI, 7.9-21.2). Among the 254 cases, there were 29 (11.4%) case stools that contained 30 bacterial pathogens including 13 Salmonella (including 5 Salmonella serovar Typhimurium and 2 Salmonella serovar Heidelberg), 10 STEC (6 O157:H7 and 4 non-O157:H7 serotypes), 5 Campylobacter (including 1 non-C. jejuni) and 2 Shigella sonnei. EAEC were more frequently present in case specimens (3.1%) than control specimens (0.9%) (adjusted OR, 3.9; 95% CI, 1.1-13.7), and their adherence phenotypes were variable. Many viruses were more common among cases than controls including rotavirus (43.3% in cases vs 0.22 in controls), astroviruses (4.3% vs 1.6%), and adenoviruses (3.2% vs 0.9%). Similar rates were found for noroviruses (3.6% in cases vs 3.5% in controls) and C. difficile (5.5% vs 6.2%). Parasites were more common in control stools and isolated from 16 cases total including Cryptosporidia (6), Entamoeba coli (6), Blastocystis hominis (1), Endolimax nana (2), and Giardia lamblia and E. nana (1). A parasite was found in one case stool, which was Cryptosporidia in a 4-year-old girl following travel to Honduras. Dientamoeba fragilis was not found.

Commentary

Definitive determination of the etiology of childhood acute diarrhea is problematic in part because of the overlapping clinical symptoms from a wide variety of microbiologic causes — bacterial, viral, and parasitic. Also, many pathogens are found in equivalent or even higher rates in control stools compared to cases, as in this study for C. difficile, noroviruses, and parasites.

This high rate of rotavirus among cases is as expected, as the study was conducted before widespread use of rotavirus vaccine. The results are remarkable for a higher proportion of bacterial pathogens, especially higher rates of STEC. The O157:H7 serotype predominated (60%) as the cause of acute diarrhea associated with STEC. Similar to other studies of acute diarrhea in children, EAEC was found in a higher proportion of cases than controls, suggesting a broader spectrum of EAEC diarrhea that may present as an acute illness as well as the more characteristic persistent, nonbloody diarrhea. C. difficile was not found to be a cause of acute childhood diarrhea. No cause was identified in almost one-third of cases, though this study focused on established diarrheagenic pathogens.