Escherichia coli is the predominant nonpathogenic facultative flora of the human intestine. Some E. coli strains, however, have developed the ability to cause disease of the gastrointestinal, urinary, or central nervous system in even the most robust human hosts. Diarrheagenic strains of E. coli can be divided into at least six different categories with corresponding distinct pathogenic schemes. Taken together, these organisms probably represent the most common cause of pediatric diarrhea worldwide. Several distinct clinical syndromes accompany infection with diarrheagenic E. coli categories, including traveler’s diarrhea (enterotoxigenic E. coli), hemorrhagic colitis and hemolytic-uremic syndrome (enterohemorrhagic E. coli), persistent diarrhea (enteroaggregative E. coli), and watery diarrhea of infants (enteropathogenic E. coli). This review discusses the current level of understanding of the pathogenesis of the diarrheagenic E. coli strains and describes how their pathogenic schemes underlie the clinical manifestations, diagnostic approach, and epidemiologic investigation of these important pathogens.

Diarrheagenic Escherichia coli

Few microorganisms are as versatile as Escherichia coli. An important member of the normal intestinal microflora of humans and other mammals, E. coli has also been widely exploited as a cloning host in recombinant DNA technology. But E. coli is more than just a laboratory workhorse or harmless intestinal inhabitant; it can also be a highly versatile, and frequently deadly, pathogen. Several different E. coli strains cause diverse intestinal and extraintestinal diseases by means of virulence factors that affect a wide range of cellular processes.

Pathogenic Escherichia coli

Current estimates of the global burden of disease for diarrhoea are reported and compared with previous estimates made using data collected in 1954-79 and 1980-89. A structured literature review was used to identify studies that characterized morbidity rates by prospective surveillance of stable populations and studies that characterized mortality attributable to diarrhoea through active surveillance. For children under 5 years of age in developing areas and countries, there was a median of 3.2 episodes of diarrhoea per child-year. This indicated little change from previously described incidences. Estimates of mortality revealed that 4.9 children per 1000 per year in these areas and countries died as a result of diarrhoeal illness in the first 5 years of life, a decline from the previous estimates of 13.6 and 5.6 per 1000 per year. The decrease was most pronounced in children aged under 1 year. Despite improving trends in mortality rates, diarrhoea accounted for a median of 21% of all deaths of children aged under 5 years in these areas and countries, being responsible for 2.5 million deaths per year. There has not been a concurrent decrease in morbidity rates attributable to diarrhoea. As population growth is focused in the poorest areas, the total morbidity component of the disease burden is greater than previously.

/pdf/the-global-burden-of-diarrhoeal-disease-as-estimated-from-3cofeyowch.pdf

The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000

ETEC is an underrecognized but extremely important cause of diarrhea in the developing world where there is inadequate clean water and poor sanitation. It is the most frequent bacterial cause of diarrhea in children and adults living in these areas and also the most common cause of traveler's diarrhea. ETEC diarrhea is most frequently seen in children, suggesting that a protective immune response occurs with age. The pathogenesis of ETEC-induced diarrhea is similar to that of cholera and includes the production of enterotoxins and colonization factors. The clinical symptoms of ETEC infection can range from mild diarrhea to a severe cholera-like syndrome. The effective treatment of ETEC diarrhea by rehydration is similar to treatment for cholera, but antibiotics are not used routinely for treatment except in traveler's diarrhea. The frequency and characterization of ETEC on a worldwide scale are inadequate because of the difficulty in recognizing the organisms; no simple diagnostic tests are presently available. Protection strategies, as for other enteric infections, include improvements in hygiene and development of effective vaccines. Increases in antimicrobial resistance will dictate the drugs used for the treatment of traveler's diarrhea. Efforts need to be made to improve our understanding of the worldwide importance of ETEC.

https://cmr.asm.org/content/cmr/18/3/465.full.pdf

Enterotoxigenic escherichia coli in developing countries: epidemiology, microbiology, clinical features, treatment, and prevention

Synergism of nutrition, infection, and immunity: an overview.

A longitudinal study of diarrhea was carried out from May 1988 to April 1989 by household surveillance of 705 children less than 5 years old in rural Bangladesh. Stool samples were examined for enteric pathogens at the beginning of each diarrheal episode. For persistent episodes, stool examination was repeated on days 15-17 of the illness. For each case of persistent diarrhea, stool samples from age-matched acute diarrheal and healthy controls were examined. Compared with healthy controls, cases of diarrhea were associated with Shigella species (P = .07) and rotavirus (P less than .05). Diffusely adherent Escherichia coli (P less than .05) and cryptosporidia (P = .07) were the only enteropathogens associated with persistent diarrhea in comparison with acute diarrhea. No more than 15% of children had the same class of pathogen identified from stool on both days 1-3 and days 15-17, indicating that persistent infection was uncommon. However, a different enteropathogen was frequently found on days 15-17, suggesting that sequential infection may be a cause of persistent diarrhea.

Enteropathogens Associated with Acute and Persistent Diarrhea in Bangladeshi Children <5 Years of Age

A community-based longitudinal study of acute and persistent diarrhoea in 705 children less than five years old was carried out for a year in a rural area of Bangladesh. Diarrhoea morbidity data were collected from each study child every fourth day by home visit. Clinical features of diarrhoeal episodes and diarrhoeal management information were documented. The overall diarrhoeal incidence rate in the study children was 4.6 episodes per child per year. The incidence of persistent diarrhoea was 34/100 child-years. Persistent diarrhoea was positively associated with young age and more severe illness, characterized by the presence of clinical dehydration or blood in the stool in the first week. Use of ORT in the first week was positively associated and use of an antibiotic was negatively associated with the occurrence of persistent diarrhoea. Reduced breast-feeding and consumption of cow's milk at some time during the episode were also positively associated with persistence. This would suggest that appropriate fluid and dietary management for all episodes should be the goal. Children with more severe initial illness characterized by the presence of blood in the stool or clinical dehydration should have more careful follow-up to identify persistent episodes and adverse nutritional effects. Breastfeeding should be continued during acute diarrhoea, but the role of ORT, antibiotics and cow's milk deserves further investigation.

A. K. Siddique

Papers

Enteropathogens Associated with Acute and Persistent Diarrhea in Bangladeshi Children <5 Years of Age

Epidemiological and clinical characteristics of acute and persistent diarrhoea in rural Bangladeshi children

Cell-mediated immune deficiency and malnutrition are independent risk factors for persistent diarrhea in Bangladeshi children