Diagnosis and treatment of acute or persistent diarrhea

Abstract

Studies of microbial pathogens and the toxins they produce are important for determining the mechanisms by which they cause disease and spread throughout a population. Some bacteria produce secretory enterotoxins (such as cholera toxin or the heat-labile or stable enterotoxins produced by Escherichia coli) that invade cells directly. Others invade cells or produce cytotoxins (such as those produced by Shigella, enteroinvasive E coli, or Clostridium difficile) that damage cells or trigger host responses that cause small or large bowel diseases (such as enteroaggregative or enteropathogenic E coli or Salmonella). Viruses (such as noroviruses and rotaviruses) and protozoa (such as Cryptosporidium, Giardia, or Entamoeba histolytica) disrupt cell functions and cause short- or long-term disease. Much epidemiologic data about these pathogens have been collected from community- and hospital-acquired settings, as well as from patients with traveler's or persistent diarrhea. These studies have led to practical approaches for prevention, diagnosis, and treatment.

Sean W. Pawlowski

Cirle Alcantara Warren

Richard Guerrant

Figure 1

Normal intestinal physiology and alteration by pathogens and their toxins. The average oral intake for an adult is 1.5 L fluid/day. Combined with salivary, gastric, biliary, and pancreatic secretions 7 L fluid enter the upper small bowel each day, most of which is absorbed by the time it reaches the distal small bowel. However, this small bowel fluid is mixed with a remarkable bidirectional flux of water and electrolytes in the upper small bowel that probably exceeds 50 L isotonic fluid each day, to aid in the absorption of digested dietary intake.. This striking bidirectional electrolyte transport is driven by an active, adenosine triphosphate (ATP)–dependent active sodium (Na) absorption pump located on the basolateral membranes of both intestinal crypt and villus tip cells (middle). Because the chloride (Cl⁻) channel is located on the luminal surface of the crypt cells, this Na pump mediates secretion of Cl⁻ (along with Na and water) from the crypts and neutral NaCl absorption in the differentiated villus tip cells. Thus, a relatively slight shift in this large bidirectional flux can readily overload the colonic absorptive capacity, which rarely exceeds 2–3 L/day. Like cholera toxin (CT), E coli heat-labile toxin (LT) opens Cl⁻ channels, leading to secretory watery diarrhea or traveler's diarrhea. The E coli heat-stable toxin (ST) activates guanylate cyclase to increase intracellular cyclic guanosine monophosphate (cGMP) levels, inhibiting NaCl absorption and leading to secretory diarrhea. Selective damage of absorptive villus tips, which occurs in viral, protozoal, and other villus-damaging or inflammatory processes, leaves unbalanced secretory crypts that are not offset by healthy villus tip absorption, also leading to watery diarrhea. Small bowel pathogens are presented in the right panels: those that produce secretory enterotoxins are in the red box, those that selectively disrupt absorptive villus tips are in the green box, and ileocolonic pathogens are in the tan box.

Figure 2

Diagnosis, treatment, and causes of diarrheal diseases. For patients with diarrheal illnesses, it is important to first adequately assess the patient and determine the level of dehydration (panel 1). Important factors include duration of illness; alertness, skin turgor, mucous membrane dryness, sunken eyes or fontanelles, and postural hypotension all indicate moderate or severe hypovolemia and dehydration; signs of inflammation include fever, bloody stool, and tenesmus. In cases of dehydration (panel 2), patients can be rehydrated by oral administration of fluids that contain glucose, sugar or starch, and electrolytes; and patients can be given bismuth subsalicylate or loperamide if their diarrhea is not bloody (panel 2). If patients are unconscious or vomiting, fluids should be replaced intravenously. Pediatric patients can be given an oral rehydration solution made of sodium chloride, sodium bicarbonate, potassium chloride, and glucose or glucose polymer (such as sucrose) in water. Or, table salt and sugar can be added to orange juice, and bananas can be added to provide potassium. There are a number of epidemiologic and clinical clues that can be used to identify the infectious agent (panel 3). Epidemiologic factors that should be considered include the food that patients have eaten (raw, undercooked meats, raw seafood), antibiotics taken (especially for C difficile infection), sexual practices (men who have sex with men might have proctitis or colitis with sexually transmitted pathogens), and recent travel (indicate bacterial pathogens such as enterotoxigenic E coli, Salmonella, Shigella, and Campylobacter; persistent diarrhea can be caused by protozoans such as Giardia or Cryptosporidium). Outbreaks of viral-related (norovirus or rotavirus) disease or those caused by organisms with relatively low-infectious inocula that are spread by fecal oral contact, such as Shigella, Giardia, and Cryptosporidium, are most commonly observed in day care settings. Other epidemiologic clues include immunoglobulin A deficiency, which predisposes to giardiasis, and immunosuppression (particularly in patients with AIDS), which can lead to protozoal infections, Mycobacterium avium complex, and intestinal cytomegalovirus infections. Clinical features can also be used to identify the infectious agent. Bloody diarrhea is associated with Shiga toxin-producing E coli, Shigella and E histolytica infections; abdominal pain with Yersinia and some C difficile infections; dysentery with Shigella or Campylobacter infection; wasting with Giardia or Cryptosporidium infection; and fecal inflammation with Shigella, Campylobacter, Salmonella, and some E coli and C difficile infections.

Figure 3

An algorithm for severe, bloody, inflammatory, or outbreak-related infectious diarrhea. In addition to the management of fluid and electrolyte imbalances, nonsecretory or outbreak-related diarrhea may need further workup for definitive causative diagnoses and pathogen-directed therapy. Depending on the epidemiologic setting involved and likely causes, specific diagnostic tests are suggested as discussed in the text. Specific bacteria such as Campylobacter, Shigella, or C difficile and protozoa such as Cryptosporidium, Giardia, or Cyclospora may require specific antibacterial or antiparasitic agents, respectively. Empiric antimicrobial therapy, while awaiting laboratory test results, is usually appropriate for these pathogens. However, antibacterial treatment may worsen diarrhea secondary to EHEC (eg, E coli 0157:H7), which usually presents with noninflammatory, bloody diarrhea.