Ranging from a mild annoyance to a devastating dehydrating illness, acute diarrheal disease is a leading cause of illness globally, with an estimated 4.6 billion episodes worldwide per year. Diarrheal disease ranks second only to lower respiratory infection as the most common infectious cause of death worldwide. Among children <5 years old, diarrheal disease is a particularly important cause of death. Every year nearly 2 million children in this age group die of diarrheal disease; the majority of these young children are impoverished and live in resource-poor areas. By contributing to malnutrition and thereby reducing resistance to other infectious agents, diarrheal disease is also an indirect factor in a far greater burden of disease.
The wide range of clinical manifestations of acute gastrointestinal illnesses is matched by the wide variety of infectious agents involved, including viruses, bacteria, and parasitic pathogens (Table 128–1). This chapter discusses factors that enable gastrointestinal pathogens to cause disease, reviews host defense mechanisms, and delineates an approach to the evaluation and treatment of patients presenting with acute diarrhea. Individual organisms causing acute gastrointestinal illnesses are discussed in detail in subsequent chapters.
Table 128–1 Gastrointestinal Pathogens Causing Acute Diarrhea
| Save Table
Table 128–1 Gastrointestinal Pathogens Causing Acute Diarrhea
|Mechanism||Location||Illness||Stool Findings||Examples of Pathogens Involved|
|Noninflammatory (enterotoxin)||Proximal small bowel||Watery diarrhea||No fecal leukocytes; mild or no increase in fecal lactoferrin||Vibrio cholerae, enterotoxigenic Escherichia coli (LT and/or ST), enteroaggregative E. coli, Clostridium perfringens, Bacillus cereus, Staphylococcus aureus, Aeromonas hydrophila, Plesiomonas shigelloides, rotavirus, norovirus, enteric adenoviruses, Giardia lamblia, Cryptosporidium spp., Cyclospora spp., microsporidia|
|Inflammatory (invasion or cytotoxin)||Colon or distal small bowel||Dysentery or inflammatory diarrhea||Fecal polymorphonuclear leukocytes; substantial increase in fecal lactoferrin||Shigella spp., Salmonella spp., Campylobacter jejuni, enterohemorrhagic E. coli, enteroinvasive E. coli, Yersinia enterocolitica, Listeria monocytogenes, Vibrio parahaemolyticus, Clostridium difficile, A. hydrophila, P. shigelloides, Entamoeba histolytica, Klebsiella oxytoca|
|Penetrating||Distal small bowel||Enteric fever||Fecal mononuclear leukocytes||Salmonella typhi, Y. enterocolitica|
Enteric pathogens have developed a variety of tactics to overcome host defenses. Understanding the virulence factors employed by these organisms is important in the diagnosis and treatment of clinical disease.
The number of microorganisms that must be ingested to cause disease varies considerably from species to species. For Shigella, enterohemorrhagic Escherichia coli, Giardia lamblia, or Entamoeba, as few as 10–100 bacteria or cysts can produce infection, while 105−108Vibrio cholerae organisms must be ingested orally to cause disease. The infective dose of Salmonella varies widely, depending on the species, host, and food vehicle. The ability of organisms to overcome host defenses has important implications for transmission; Shigella, enterohemorrhagic E. coli, Entamoeba, and Giardia can spread by person-to-person contact, whereas under some circumstances Salmonella may have to grow in food for several hours before reaching an effective infectious dose.
Many organisms must adhere to the gastrointestinal mucosa as an initial step in the pathogenic process; thus, organisms that can compete with the normal bowel flora and colonize the mucosa have an important advantage in causing disease. Specific cell-surface proteins involved in attachment of bacteria to intestinal cells are important virulence determinants. V. cholerae, for example, adheres to the brush border of small-intestinal enterocytes via specific surface adhesins, including the toxin-coregulated pilus and other accessory colonization factors. Enterotoxigenic E. coli, which causes watery diarrhea, produces an adherence protein called colonization factor antigen that is necessary for colonization of the upper small intestine by the organism prior to the production of enterotoxin. Enteropathogenic E. coli, an agent of diarrhea in young children, and enterohemorrhagic E. coli, which causes hemorrhagic colitis and the hemolytic-uremic syndrome, produce virulence determinants that allow these organisms to attach to and efface the brush border of the intestinal epithelium.
The production of one or more exotoxins is important in the pathogenesis of numerous enteric organisms. Such toxins include enterotoxins, which cause watery diarrhea by acting directly on secretory mechanisms in the intestinal mucosa; cytotoxins, which cause destruction of mucosal cells and associated inflammatory diarrhea; and neurotoxins, which act directly on the central or peripheral nervous system.
The prototypical enterotoxin is cholera toxin, a heterodimeric protein composed of one A and five B subunits. The A subunit contains the enzymatic activity of the toxin, while the B subunit pentamer binds holotoxin to the enterocyte surface receptor, the ganglioside GM1. After the binding of holotoxin, a fragment of the A subunit is translocated across the eukaryotic cell membrane into the cytoplasm, where it catalyzes the ADP-ribosylation of a GTP-binding protein and causes persistent activation of adenylate cyclase. The end result is an increase of cyclic AMP in the intestinal mucosa, which increases Cl− secretion and decreases Na+ absorption, leading to a loss of fluid and the production of diarrhea.
Enterotoxigenic strains of E. coli may produce a protein called heat-labile enterotoxin (LT) that is similar to cholera toxin and causes secretory diarrhea by the same mechanism. Alternatively, enterotoxigenic strains of E. coli may produce heat-stable enterotoxin (ST), one form of which causes diarrhea by activation of guanylate cyclase and elevation of intracellular cyclic GMP. Some enterotoxigenic strains of E. coli produce both LT and ST.
Bacterial cytotoxins, in contrast, destroy intestinal mucosal cells and produce the syndrome of dysentery, with bloody stools containing inflammatory cells. Enteric pathogens that produce such cytotoxins include Shigella dysenteriae type 1, Vibrio parahaemolyticus, and Clostridium difficile. S. dysenteriae type 1 and Shiga toxin–producing strains of E. coli produce potent cytotoxins and have been associated with outbreaks of hemorrhagic colitis and hemolytic-uremic syndrome.
Neurotoxins are usually produced by bacteria outside the host and therefore cause symptoms soon after ingestion. Included are the staphylococcal and Bacillus cereus toxins, which act on the central nervous system to produce vomiting.
Dysentery may result not only from the production of cytotoxins but also from bacterial invasion and destruction ...