ANNUAL REVIEWS
Annu. Rev. Med. 1991. 42:403-10 Copyright © 1991 by Annual Reviews Inc. All rights reserved
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INFECTIOUS DIARRHEA
Annu. Rev. Med. 1991.42:403-410. Downloaded from www.annualreviews.org Access provided by University of California - Davis on 01/29/15. For personal use only.
Mitchell J. Rubinoff, M.D., and Michael Field, M.D. Division of Gastroenterology, Department of Medicine, Columbia University College of Physicians & Surgeons, New York, New York 10032 KEY WORDS:
enteritis, secretion, intestine, enterotoxin, Escherichia coli
ABSTRACT
This review singles out several bacterial and parasitic causes of infectious diarrhea about which there have been interesting recent developments in pathogenesis, diagnosis, or treatment. Diarrheagenic mechanisms and infections by Escherichia coli, Salmonella, Giardia lamblia, Entamoeba histolytica, Cryptosporidia, and Isopora are discussed. INTRODUCTION
Annually more than five million people, 80% of whom are less than one year in age, die from acute infectious diarrhea (1). Although the majority of these deaths occur in the poorer, nonindustrialized nations, diarrheagenic infections are also important causes of illness in more affluent countries, particularly among certain populations such as institutionalized indi viduals, children in day-care centers, travelers to "third world" countries, and patients with the acquired immunodeficiency syndrome (AIDS). In this review we have singled out several bacterial and parasitic causes of infectious diarrhea about which there have been interesting recent developments. DIARRHEAGENIC MECHANISMS
The gastrointestinal tract contributes to host defense against enteric patho gens by both physical and immunologic means (2). Specialized M cells in the epithelium covering lymphoid follicles actively take up bacterial, viral, and protozoal antigens, transferring them to the underlying immunologic 403 0066--4219/9 1/040 1--0403$02.00
Annu. Rev. Med. 1991.42:403-410. Downloaded from www.annualreviews.org Access provided by University of California - Davis on 01/29/15. For personal use only.
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cells (3). Several pathogens-including Vihrio cholera, Campylobacter jejuni, RDEC-I Escherichia coli, Salmonella typhi, Shigella flexneri, and Yersinia enterocolitica-adhere to and interact with intestinal M cells (2). Once enteric pathogens attach to the intestinal mucosa, they can cause diarrhea in one or more of several ways. Some organisms (e.g. V. cholera and toxigenic E. coli) do not invade the intestinal mucosa; they produce toxins that stimulate intestinal fluid and electrolyte secretion (4). Other organisms directly invade and destroy enterocytes. Some enteric pathogens [e.g. Shigella (5)] are both invasive and enterotoxigenic. Some [e.g. entero adherant E. coli (6) and Cryptosporidia (7)] fuse their cell membranes with those of the enterocyte; in the process, one or more cytotoxins are injected directly into the enterocyte. There are two types of bacterial enterotoxins: cytotonic, i.e. causing fluid secretion by activating intracellular enzymes such as adenylate cyclase; and cytotoxic, i.e. causing structural injury (8). V. cholera is the classic example of a cytotonic toxin-secreting organism. Common bacteria that cause diarrhea in the United States include E. coli, which has both cytotoxic and cytotonic strains, Salmonella, which is invasive, Shigella and Cam pylobacter jejuni, which are both invasive and secrete cytotoxins, and Yersinia enterocolitica, which is invasive and also secretes a cytotonic toxin. BACTERIAL DIARRHEAS
The topic of bacterial enteritis has recently been extensively reviewed (9). We briefly discuss here recent findings about diarrheas caused by Escherichia coli and Salmonella. Escherichia coli Five forms of E. coli are now recognized as causing diarrheal disease (6): enterotoxigenic, enteropathogenic, enterohemorrhagic, enteroinvasive, and enteroadherant. Enterotoxigenic E. coli (ETEC) are a common cause of diarrhea among children in underdeveloped countries, Americans traveling abroad, and those living in institutional settings (8). There are two distinct enterotoxins produced by ETEC. The first is a heat-labile toxin of high molecular weight that is immunologically cross-reactive with cholera toxin and that causes secretory diarrhea in a manner identical to cholera toxin. Like cholera toxin, it stimulates enterocyte adenylate cyclase by ADP-ribosylating the alpha-subunit of the GTP-binding protein that stimulates this enzyme (4, 9). Another enterotoxin produced by ETEC is a protein of low molecular
Annu. Rev. Med. 1991.42:403-410. Downloaded from www.annualreviews.org Access provided by University of California - Davis on 01/29/15. For personal use only.
INFECTIOUS DIARRHEA
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weight that is heat-stable and causes intestinal secretion of fluid and elec trolytes by stimulating guanylate cyclase (10, 11). Enterotoxins similar to the heat-stable E. coli toxin are produced by Y. enterocolitica, Klebsiella pneumonia, and Enterobacter (10, 12). On a worldwide basis, ETEC-induced diarrhea is predominantly a dis ease of children under five years of age living in underdeveloped countries. Among the citizens of more affluent, industrialized countries, ETEC related diarrhea is mainly seen in those who have traveled abroad to endemic areas. The disease, except in those who are otherwise debilitated, is self-limited, with loose or watery stools usually beginning two or three days after arrival in the new location. The mainstay of therapy is the correction of fluid and electrolyte losses. Prophylaxis for travelers to endemic areas has been demonstrated with bismuth sub salicylate (13) and with the antibiotics doxycycline and trimethoprim-sulfamethosazole (14). Although antibiotic prophylaxis is usually effective, there is concern that widespread use of antibiotics will result in the emergence of resistant strains (15). Consequently, antibiotic prophylaxis is not recommended for most travelers and especially not for long-term visitors abroad (16). Travelers' diarrhea is effectively treated with trimethoprim-sulfamethoxazole (16) and bismuth subsalicylate (17). Ciprofloxacin, a new fluorinated car boxyquinolone, is also effective against travelers' diarrhea (18) as well as against Shigella, Salmonella, and Campy/obacter diarrheas (19). Enterohemorrhagic E. coli (EHEC) disease is caused by E. coli serotype 0157: H7 (20). In 1982 two outbreaks of hemorrhagic colitis, arising in two different geographic areas, were reported. They were associated with eating undercooked beef hamburgers from a fast-food chain. Since then, several additional outbreaks (21-23) and sporadic cases (23-25) of E. coli 0157: H7 colitis have been described. A population-based prospective study found E. coli 0157: H7 in 0.4% of stool specimens, a recovery rate similar to those of other enteric patho gens such as Shigella, Salmonella, and Campylahacter (26). The very young, the very old, and those with underlying severe debility are more likely to experience significant morbidity, such as the hemolytic uremic syndrome, from EHEC infection (22, 23, 27). The pathogenesis of the hemorrhagic colitis and the hemolytic uremic syndrome is not well understood. Strains of E. coli 0157: H7 produce cytotoxins that share homology and function with Shiga toxin (28). Treat ment is mainly supportive and the illness is usually self-limited, with symptoms lasting from a few days to several weeks. E. coli 0157: H7 is sensitive to most antibiotics in vitro but antibiotics have not been shown to shorten the duration of illness or to diminish the symptoms (21).
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Salmonella
Nontyphoidal Salmonella is the most common cause of bacterial diarrhea reported to the Center for Disease Control. The spectrum of clinical disease caused by Salmonella is quite varied, including fever, nausea, vomiting, diarrhea, and abdominal cramps. Bloody diarrhea can occur, as can bac teremia. Severe infections and deaths can occur in immunocompromised hosts (29). The incidence of Salmonella infections has increased in recent years, outbreaks being traced to contaminated beef, poultry, and milk. Tn 1985 an outbreak of 170,000 cases, including 16,000 culture-proven cases of a multidrug-resistant S. typhimurium, occurred in Chicago and was traced to the ingestion of contaminated pasteurized milk (30). Several outbreaks related to contaminated beef products have been caused by strains that are now resistant to the antibiotic used during livestock pro duction (31). Outbreaks of S. enteritidis in the United States have been traced to contaminated eggs (32). Previously, Salmonella had been shown to contaminate eggs by penetrating through the shell, and infection could be prevented by washing the eggs prior to packaging. However, the recent outbreaks may have been caused by transovarian contamination of eggs (32). Most cases of Salmonella are self-limited, although varied extra intes tinal manifestations do occur. The most common extraintestinal site of infection is atherosclerotic aortic aneurysms (29). Endothelial infections occur in 25% of bacteremic patients over the age of 50 (33). Antibiotics may prolong the duration of the carrier state and should be reserved for infants, the elderly, those with bacteremia, and those who are immu nocompromised (34). PARASITIC DIARRHEAS
Parasitic intestinal infections, now recognized to be common causes of diarrhea, were recently reviewed (35). They are seen in those who have traveled to endemic areas, who live in institutions, or who drink water from contaminated sources. Parasites are common causes of severe diarrhea in patients with AIDS (36, 37). Giardia lamblia Giardia lamblia, a flagellated protozoan, occurs worldwide and can cause varied symptoms. Giardia was found in 15% of the duodenal aspirates of those undergoing upper gastrointestinal endoscopy in a New York City hospital (38). The most common source of infection is the ingestion of water contaminated with animal or human feces containing Giardia cysts.
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Although it was once thought that only campers and skiers drinking stream water were at risk, it is now recognized that many people have been infected by drinking from commercial water sources with inadequate flocculation and filtration systems (39, 40). Some individuals with giardiasis are asymptomatic; others experience various symptoms including diarrhea, bloating, abdominal cramps, flatu lence, anorexia, and steatorrhea. In its extreme form, giardiasis can mimic sprue syndromes, with small intestinal biopsies showing marked villous atrophy (41). Several treatment regimens exist. Quinacrine is the most effective drug, with a 90-95% cure rate, but it has several significant side effects. Thus, metronidazole is often used as a first-line drug despite its slightly lower (85-90%) cure rate. Furazolidine is the drug of choice in children (42). Ameba
The major pathogen among amebic parasites is Entamoeba histolytica. The commensals E. coli, E. nana, E. gingiva/is, and E. hartanni do not cause disease. Intestinal manifestations of E. histolytica infection can range from asymptomatic cyst excretion to fulminant dysentery. Not all strains of E. histolytica are pathogenic. It is estimated that 30% of homosexual males are infected with E. histolytica but only rarely do they experience disease. Stool specimens from these individuals generally do not contain invasive zymodemes (43). Acute amebic colitis must be distinguished from acute inflammatory bowel disease. The principal means of diagnosis is examination of fresh stool. Examination of a single stool sample will detect E. histolytica in only 33 % of infections. Examination of six consecutive specimens increases the diagnostic accuracy to 90% (44). Serologic tests are positive only when there is invasive disease, either colitis or distant abscesses (45). Sporozoans
The sporozoans Cryptosporidium and Isospora have, in recent years, been found to be important causes of diarrhea in the immunocompromised host. Cryptosporidia was long recognized to be a common cause of animal diarrhea. In the immunocompetent host, Cryptosporidia causes a nonbloody, self-limited diarrheal illness (46). In the immunocompromised host, Cryptosporidium can cause severe chronic watery diarrhea (47). The mechanism is not known. No treatment of cryptosporidiosis in patients with AIDS has proven to be effective (35). Isospora belli, unlike Cryptosporidia, does not have an animal host (48). Isospora belli can cause illness in both immunocompetent and immuno compromised hosts (35). While infections in immunocompetent hosts
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are usually self-limited and mild, fulminant dysentery has been reported. In immunocompromised hosts, Isospora belli can cause weight loss and chronic watery diarrhea (48). Patients with AIDS have been successfully treated for Isospora belli with ten days of trimethoprim-sulfamethoxazole;
recurrent infection can be prevented by chronic prophylaxis with either trimethoprim-sulfamethoxazole or sulfadoxine-pyrimethamine (49).
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ACKNOWLEDGMENTS
We thank Drs. D. A. Harrington and D. Taylor (9) and Dr. R. Fedorak (35) for allowing us to read and cite their manuscripts before publication. Literature Cited
I. Synder, J. D., Merson, M. H. 1982. The
magnitude of the global problem of acute diarrheal disease: a review of active surveillance data. Bull. WHO 60: 60513 2. Walker, R. I., Owen, R. L. 1990.Intes tinal barriers to bacteria and their toxins. Annu. Rev. Med. 41: 393-400 3. Karen, D. F. 1989. Mucosal IgA elab oration. Crit. Rev. c/in. Lab. Sci. 27: 159-77 4. Field, M., Rao, M. c., Chang, E. B. 1989.Intestinal electrolyte transport and diarrheal disease. N. Engl. J. Med. 321: 800-6; 879-83 5. Keuseh, G. T., Donohue-Rolfe, A., Jacewizc, M. 1985. Shigella toxin and the pathogenosis of shigellosis. Ciba Found.Symp.112: 193-214 6. Levine, M. M. 1987.Escherichia coli that cause diarrhea: enterotoxigenic, entero pathogenic, enteroinvasive, enterohe morrhagic and enteroadherant. J. Infect. Dis. 155: 377-89 7. Lefkowitch, J. H., Krumholz, S., Feng Chen, K. C., Griffen, P., Despommier, D., Brasitus, T. A. 1984. Crypto sporidiosis of the human small intes tine: A light and electron microscopic study. Hum.Pathol. 15: 746-52 8. Keusch, G. T., Donta, S. T. 1975. Classi fication of enterotoxins on the basis of activity in cell culture. J. Infect. Dis. 131: 58 9. Herrington, D. A., Taylor, D. 1990. Bac terial enteridities in diarrheal diseases. Curro Top. Gastroenterol. In press 10. Rao, M. C. 1988. Bacterial enterotoxins: molecular mechanisms. In Enteric Infec tion, Mechanisms, Manifestations and Management, ed. M. J. G. Farthings, G. T. Keusch, pp. 87-104. London: Chap
man & Hall
II. Rao, M. C. 1985. Toxins which activate
guanylate cyclase: Heat stable enter otoxins. Ciba Found. Symp. 112: 74-93 12. Gianella, R. A. 1981. Pathogenesis of acute bacterial diarrheal disorders. Annu.Rev. Med. 32: 341 57 13. DuPont, H. L., Ericsson, C. D., Johnson, P. c., Bitsura, J. A. M., DuPont, M. W., de la Caback, F. J. 1997. Prevention of traveler's diarrhea by the tablet form of bismuth sub sialicyclate. J. Am. Med. Assoc. 257: 1347-50 14. DuPont, H. L., Ericsson, C. D., Johnson, P. c., Cabada, F. J. 1986.Anti microbial agents in the prevention of tra veler's diarrhea. Rev. Infect. Dis. 8: 5167-71 15. Murray, B. E., Rensimer, E. R., DuPont, H. L. 1982. Emergence of high level trimethoprim resistance in fecal Escherichia coli during oral admin istration of trimethoprim or tri methoprim-sulfamethoxazole. N. Engl. J. Med. 306: 130--3 5 16. DuPont, H. L., Reves, R. R., Galinso, E., Sullivan, P. S., Wood, L. V., Mendi ola, J. G. 1982. Treatment of travelers' diarrhea with trimethoprim-sulfameth oxazole and with trimethoprim alone. N. Engl. J. Med. 307: 841-44 17. Steffen, R., Mathewson, J. J., Ericsson, C. D., DuPont, H. L., Helminger, A. et al. 1988. Travelers' diarrhea in West Africa and Mexico: Fecal transport sys tems and liquid bismuth subsalicylate for self-therapy. J. Infect. Dis. 157: 1008-13 18. Ericsson, C. D., Johnson, P. c., DuPont, H. L., Morgan, D. R., Bitsura, J. A. M., de la Cabada, P. J. 1987. Ciprofloxacin or trimethoprim(sulfamethoxasole as initial therapy for travelers' diarrhea: A pla-
Annu. Rev. Med. 1991.42:403-410. Downloaded from www.annualreviews.org Access provided by University of California - Davis on 01/29/15. For personal use only.
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cebo-controlled trial. Ann. Intern. Med. 106: 216--2 0 19. Pichler, H. E. T., Diridl, G., Stickler, K., Wolf, D. 1987. Clinical efficiacy of ciprofloxacin compared with placebo in bacterial diarrhea. Am. J. Med. 82 (Supp!. 4A) : 329-32 20. Riley, L. W., Remis, R. S., Helgerson, S. D., McGee, H. B., Wells, J. G. ct al. 1983. Hemorrhogic collitis associated with a rare Escherichia coli serotype. N. Engl.J. Med. 308: 681-85 21. Carter, A. 0., Borczyk, A. A., Carlson, J. A. K., Harvey, B., Hockin, J. C et al. 1987. A severe outbreak of Escherichia coli 0157: H7-associated hemorrhagic colitis in a nursing home. N. Engl. J. Med. 317: 1496--1500 22. Griffin, P. M., Ostroff, S. M., Tauxe, R. V., Greene, K. D., Wells, J. G. et al. 1988. Illnesses associated with Escher ichia coli 0157-H7 infections: A broad clinical spectrum. Ann. Intern. Med.109:
705-12
23. Ryan, C. A., Tauxe, R. V., Hasek, G. W., Wells, J. G., McFadden, H. W. 1986. Escherichia coli 0157: H7 diarrhea in a nursing home: clinical, epidemiological and pathological findings. J. Infect. Dis. 154: 631-38 24. Pai, C H., Gordon, R., Sims, H. V., Bryan, L. E. 1984. Sporadic cases of hemorrhagic colitis associated with Escherichia coli 0157: H7. Ann. Intern. Med.101: 738-42 25. Remis, R. S., MacDonald, K. L., Riley, L. W., Puhr, N. D., Wells, J. G. et al. 1984. Sporadic cases of hemorrhagic col itis associated with Escherichia coli 0157 : H7. Ann. Intern. Med. 101: 62426 26. MacDonald, K. L., O'Leary, M. J., Cohen, M. L., Nurria, P., Wells, J. G. et al. 1988. Escherichia coli 0157: H7, an emerging gastrointestinal pathogen: results of a one-year, prospective, popu lation-based study. 1. Am. Med. Assoc. 259: 3567-70 27. Spika, J. S., Parsona, J. E., Nordenberg, D., Wells, J. G., Gunn, R. A. et al. 1986. Hemolytic uremia syndrome and diar rhea associated with Escherichia coli 0157 : H7 in a day care center. 1. Pediatr. 109: 287-91 28. Strockbine, N. A., Marques, L. R. M., Neuland, J. W., Smith, H. W., Holmes, R. K., O'Brien, A. D. 1986. Two toxin converting phages from Escherichia coli 0157 : H7 strain 933 encode anti genically distinct toxins with similar bio logic activities. Infect. Immun. 53: 13540 29. Cohen, J. I., Bartlett, J. A., Corey, G.
409
R. 1987. Extra-intestinal manifestations of Salmonella infections. Medicine 66: 349-87 30. Ryan, C A., Nickels, M. K., Hargrett Bean, N. T., Potter, M. E., Endo, T. et al. 1987. Massive outbreak of anti microbial-resistant salmonella traced to pasteurized milk. J. Am. Med. Assoc. 258: 3269-74 31. Holmberg, S. D., Osterholm, M. T., Senger, K. A., Cohen, M. L. 1984. Drug resistant Salmonella from animals fed antimicrobials. N. Engl. J. Med. 311: 617-22 32. St. Louis, M. E., Morse, D. L., Potter, M. E., DeMelf, T. M., Guzewich, J. J. et a!. 1988. The emergence of grade A eggs as a major source of Salmonella enteritidis infections: New implications for the control of salmonellosis. J. Am. Med. Assoc.259: 2103-7 33. Cohen, P. S., O'Brien, T. F., Schoen baum, S. C, Medeiros, A. A. 1978. The risk of endothelial infection in adults with Salmonella bacteremia. Ann.Intern. Med.89:931-32 34. Guerrant, R. 1987. Salmonella infec tions. In Harrison's Principles ofInternal Medicine, ed. E. Braunwald, pp. 592-99. New York: McGraw Hil!. 11th ed. 35. Fedorak, R. 1990. Parasitic diarrhoea in diarrheal diseases. Curro Top. Gastro enteral.In press 36. Smith, P. D., Lune, C, Gill, V. J., Man ischewitz, J. F., Quinnan, G. V. et a!. 1988. Intestinal infections in patients with the acquired immunodeficiency syndrome (AIDS). Ann. Intern. Med. 108: 328-33 37. Anthony, M. A., Brandt, L. J., Klein, R. S. and Bernstein, L. H. 1988. Infectious diarrhea in patients with AIDS. Dig. Dis. Sci.33: 1141-46 38. Carr, M. F. Jr., Ma, J., Green, P. H. R. 1988. Giardia lamblia in patients under going endoscopy: Lack of evidence for a role in nonulcer dyspepsia. Gastro enterology 95: 972-74 39. Hopkins, R. S. et al. 1985. Water-borne disease in Colorado. Three years sur veillance and 18 outbreaks. Am. J. Publ. Health 75: 25 4-57 40. Dykes, A. C, Juranek, D. D., Larenz, R. A., Sinclair, S., Jakubowski, W., Davies, R. 1980. Municipal waterborne giar diasis: An epidemiologic investigation. Ann. Intern. Med. 92: 165-70 41. Hartong, W. A., Gourley, W. K., Arvan itakis, C 1979.Giardiasis: Clinical spec trum and functional-structural abnor malities of the small intestinal mucosa. Gastroenterology 77 : 61--69 42. Wolfe, M. S. 1982. The treatment of
4 lO 43.
44.
Annu. Rev. Med. 1991.42:403-410. Downloaded from www.annualreviews.org Access provided by University of California - Davis on 01/29/15. For personal use only.
45.
46.
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intestinal protozoan infections. Med. Clin. North Am.66: 707-20 Allason-10nes, E., Mindel, A., Sar geaunt, P., Williams, P. 1986. Enta moeba histolytica as a commensal intes tinal parasite in homosexual men. N. Engl.J.Med.315-56 Sawitz, W. G., Faust, E. C. 1942. The probability of detecting intestinal proto zoan by successive stool examinations. Am.J. Trop. Med.22: 131-36 Walsh, J. A. 1986. Problems in recog nition and diagnosis of amebiasis: Esti mation of the global magnitude of mor bidity and mortality. Rev. Infect. Dis. 8: 228-38 Wolfson, J. S., Riehlen, J. M., Waldron, M. A. 1985.Cryptosporidiosis in immu-
nocompctcnt patients. N. Engl. J. Med. 312: 1278-82 47. Soave, R., Armstrong, D. 1986. Cryp tosporidium and crytosporidiosis. Rev. Infect. Dis. 8: 1012-23 48. De Hovitz, J. A., Pape, 1. W., Bouncy, M. 1986. Clinical manifestations and therapy of Isospora belli infection in pati ents with the acquired immune deficiency syndrome. N. Engl. J. Med. 315: 87-90 49. Pape, J. W., Verdier, R. I., Johnson, W. D. 1r. 1989. Treatment and prophylaxis of Isospora belli infection in patients with the acquired immunodeficiency syndrome. N. Engl. J. Med. 320: 104447
Annu. Rev. Med. 1991. 42:403-10 Copyright © 1991 by Annual Reviews Inc. All rights reserved
Further
Quick links to online content
INFECTIOUS DIARRHEA
Annu. Rev. Med. 1991.42:403-410. Downloaded from www.annualreviews.org Access provided by University of California - Davis on 01/29/15. For personal use only.
Mitchell J. Rubinoff, M.D., and Michael Field, M.D. Division of Gastroenterology, Department of Medicine, Columbia University College of Physicians & Surgeons, New York, New York 10032 KEY WORDS:
enteritis, secretion, intestine, enterotoxin, Escherichia coli
ABSTRACT
This review singles out several bacterial and parasitic causes of infectious diarrhea about which there have been interesting recent developments in pathogenesis, diagnosis, or treatment. Diarrheagenic mechanisms and infections by Escherichia coli, Salmonella, Giardia lamblia, Entamoeba histolytica, Cryptosporidia, and Isopora are discussed. INTRODUCTION
Annually more than five million people, 80% of whom are less than one year in age, die from acute infectious diarrhea (1). Although the majority of these deaths occur in the poorer, nonindustrialized nations, diarrheagenic infections are also important causes of illness in more affluent countries, particularly among certain populations such as institutionalized indi viduals, children in day-care centers, travelers to "third world" countries, and patients with the acquired immunodeficiency syndrome (AIDS). In this review we have singled out several bacterial and parasitic causes of infectious diarrhea about which there have been interesting recent developments. DIARRHEAGENIC MECHANISMS
The gastrointestinal tract contributes to host defense against enteric patho gens by both physical and immunologic means (2). Specialized M cells in the epithelium covering lymphoid follicles actively take up bacterial, viral, and protozoal antigens, transferring them to the underlying immunologic 403 0066--4219/9 1/040 1--0403$02.00
Annu. Rev. Med. 1991.42:403-410. Downloaded from www.annualreviews.org Access provided by University of California - Davis on 01/29/15. For personal use only.
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RUBINOFF & FIELD
cells (3). Several pathogens-including Vihrio cholera, Campylobacter jejuni, RDEC-I Escherichia coli, Salmonella typhi, Shigella flexneri, and Yersinia enterocolitica-adhere to and interact with intestinal M cells (2). Once enteric pathogens attach to the intestinal mucosa, they can cause diarrhea in one or more of several ways. Some organisms (e.g. V. cholera and toxigenic E. coli) do not invade the intestinal mucosa; they produce toxins that stimulate intestinal fluid and electrolyte secretion (4). Other organisms directly invade and destroy enterocytes. Some enteric pathogens [e.g. Shigella (5)] are both invasive and enterotoxigenic. Some [e.g. entero adherant E. coli (6) and Cryptosporidia (7)] fuse their cell membranes with those of the enterocyte; in the process, one or more cytotoxins are injected directly into the enterocyte. There are two types of bacterial enterotoxins: cytotonic, i.e. causing fluid secretion by activating intracellular enzymes such as adenylate cyclase; and cytotoxic, i.e. causing structural injury (8). V. cholera is the classic example of a cytotonic toxin-secreting organism. Common bacteria that cause diarrhea in the United States include E. coli, which has both cytotoxic and cytotonic strains, Salmonella, which is invasive, Shigella and Cam pylobacter jejuni, which are both invasive and secrete cytotoxins, and Yersinia enterocolitica, which is invasive and also secretes a cytotonic toxin. BACTERIAL DIARRHEAS
The topic of bacterial enteritis has recently been extensively reviewed (9). We briefly discuss here recent findings about diarrheas caused by Escherichia coli and Salmonella. Escherichia coli Five forms of E. coli are now recognized as causing diarrheal disease (6): enterotoxigenic, enteropathogenic, enterohemorrhagic, enteroinvasive, and enteroadherant. Enterotoxigenic E. coli (ETEC) are a common cause of diarrhea among children in underdeveloped countries, Americans traveling abroad, and those living in institutional settings (8). There are two distinct enterotoxins produced by ETEC. The first is a heat-labile toxin of high molecular weight that is immunologically cross-reactive with cholera toxin and that causes secretory diarrhea in a manner identical to cholera toxin. Like cholera toxin, it stimulates enterocyte adenylate cyclase by ADP-ribosylating the alpha-subunit of the GTP-binding protein that stimulates this enzyme (4, 9). Another enterotoxin produced by ETEC is a protein of low molecular
Annu. Rev. Med. 1991.42:403-410. Downloaded from www.annualreviews.org Access provided by University of California - Davis on 01/29/15. For personal use only.
INFECTIOUS DIARRHEA
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weight that is heat-stable and causes intestinal secretion of fluid and elec trolytes by stimulating guanylate cyclase (10, 11). Enterotoxins similar to the heat-stable E. coli toxin are produced by Y. enterocolitica, Klebsiella pneumonia, and Enterobacter (10, 12). On a worldwide basis, ETEC-induced diarrhea is predominantly a dis ease of children under five years of age living in underdeveloped countries. Among the citizens of more affluent, industrialized countries, ETEC related diarrhea is mainly seen in those who have traveled abroad to endemic areas. The disease, except in those who are otherwise debilitated, is self-limited, with loose or watery stools usually beginning two or three days after arrival in the new location. The mainstay of therapy is the correction of fluid and electrolyte losses. Prophylaxis for travelers to endemic areas has been demonstrated with bismuth sub salicylate (13) and with the antibiotics doxycycline and trimethoprim-sulfamethosazole (14). Although antibiotic prophylaxis is usually effective, there is concern that widespread use of antibiotics will result in the emergence of resistant strains (15). Consequently, antibiotic prophylaxis is not recommended for most travelers and especially not for long-term visitors abroad (16). Travelers' diarrhea is effectively treated with trimethoprim-sulfamethoxazole (16) and bismuth subsalicylate (17). Ciprofloxacin, a new fluorinated car boxyquinolone, is also effective against travelers' diarrhea (18) as well as against Shigella, Salmonella, and Campy/obacter diarrheas (19). Enterohemorrhagic E. coli (EHEC) disease is caused by E. coli serotype 0157: H7 (20). In 1982 two outbreaks of hemorrhagic colitis, arising in two different geographic areas, were reported. They were associated with eating undercooked beef hamburgers from a fast-food chain. Since then, several additional outbreaks (21-23) and sporadic cases (23-25) of E. coli 0157: H7 colitis have been described. A population-based prospective study found E. coli 0157: H7 in 0.4% of stool specimens, a recovery rate similar to those of other enteric patho gens such as Shigella, Salmonella, and Campylahacter (26). The very young, the very old, and those with underlying severe debility are more likely to experience significant morbidity, such as the hemolytic uremic syndrome, from EHEC infection (22, 23, 27). The pathogenesis of the hemorrhagic colitis and the hemolytic uremic syndrome is not well understood. Strains of E. coli 0157: H7 produce cytotoxins that share homology and function with Shiga toxin (28). Treat ment is mainly supportive and the illness is usually self-limited, with symptoms lasting from a few days to several weeks. E. coli 0157: H7 is sensitive to most antibiotics in vitro but antibiotics have not been shown to shorten the duration of illness or to diminish the symptoms (21).
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Salmonella
Nontyphoidal Salmonella is the most common cause of bacterial diarrhea reported to the Center for Disease Control. The spectrum of clinical disease caused by Salmonella is quite varied, including fever, nausea, vomiting, diarrhea, and abdominal cramps. Bloody diarrhea can occur, as can bac teremia. Severe infections and deaths can occur in immunocompromised hosts (29). The incidence of Salmonella infections has increased in recent years, outbreaks being traced to contaminated beef, poultry, and milk. Tn 1985 an outbreak of 170,000 cases, including 16,000 culture-proven cases of a multidrug-resistant S. typhimurium, occurred in Chicago and was traced to the ingestion of contaminated pasteurized milk (30). Several outbreaks related to contaminated beef products have been caused by strains that are now resistant to the antibiotic used during livestock pro duction (31). Outbreaks of S. enteritidis in the United States have been traced to contaminated eggs (32). Previously, Salmonella had been shown to contaminate eggs by penetrating through the shell, and infection could be prevented by washing the eggs prior to packaging. However, the recent outbreaks may have been caused by transovarian contamination of eggs (32). Most cases of Salmonella are self-limited, although varied extra intes tinal manifestations do occur. The most common extraintestinal site of infection is atherosclerotic aortic aneurysms (29). Endothelial infections occur in 25% of bacteremic patients over the age of 50 (33). Antibiotics may prolong the duration of the carrier state and should be reserved for infants, the elderly, those with bacteremia, and those who are immu nocompromised (34). PARASITIC DIARRHEAS
Parasitic intestinal infections, now recognized to be common causes of diarrhea, were recently reviewed (35). They are seen in those who have traveled to endemic areas, who live in institutions, or who drink water from contaminated sources. Parasites are common causes of severe diarrhea in patients with AIDS (36, 37). Giardia lamblia Giardia lamblia, a flagellated protozoan, occurs worldwide and can cause varied symptoms. Giardia was found in 15% of the duodenal aspirates of those undergoing upper gastrointestinal endoscopy in a New York City hospital (38). The most common source of infection is the ingestion of water contaminated with animal or human feces containing Giardia cysts.
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Although it was once thought that only campers and skiers drinking stream water were at risk, it is now recognized that many people have been infected by drinking from commercial water sources with inadequate flocculation and filtration systems (39, 40). Some individuals with giardiasis are asymptomatic; others experience various symptoms including diarrhea, bloating, abdominal cramps, flatu lence, anorexia, and steatorrhea. In its extreme form, giardiasis can mimic sprue syndromes, with small intestinal biopsies showing marked villous atrophy (41). Several treatment regimens exist. Quinacrine is the most effective drug, with a 90-95% cure rate, but it has several significant side effects. Thus, metronidazole is often used as a first-line drug despite its slightly lower (85-90%) cure rate. Furazolidine is the drug of choice in children (42). Ameba
The major pathogen among amebic parasites is Entamoeba histolytica. The commensals E. coli, E. nana, E. gingiva/is, and E. hartanni do not cause disease. Intestinal manifestations of E. histolytica infection can range from asymptomatic cyst excretion to fulminant dysentery. Not all strains of E. histolytica are pathogenic. It is estimated that 30% of homosexual males are infected with E. histolytica but only rarely do they experience disease. Stool specimens from these individuals generally do not contain invasive zymodemes (43). Acute amebic colitis must be distinguished from acute inflammatory bowel disease. The principal means of diagnosis is examination of fresh stool. Examination of a single stool sample will detect E. histolytica in only 33 % of infections. Examination of six consecutive specimens increases the diagnostic accuracy to 90% (44). Serologic tests are positive only when there is invasive disease, either colitis or distant abscesses (45). Sporozoans
The sporozoans Cryptosporidium and Isospora have, in recent years, been found to be important causes of diarrhea in the immunocompromised host. Cryptosporidia was long recognized to be a common cause of animal diarrhea. In the immunocompetent host, Cryptosporidia causes a nonbloody, self-limited diarrheal illness (46). In the immunocompromised host, Cryptosporidium can cause severe chronic watery diarrhea (47). The mechanism is not known. No treatment of cryptosporidiosis in patients with AIDS has proven to be effective (35). Isospora belli, unlike Cryptosporidia, does not have an animal host (48). Isospora belli can cause illness in both immunocompetent and immuno compromised hosts (35). While infections in immunocompetent hosts
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are usually self-limited and mild, fulminant dysentery has been reported. In immunocompromised hosts, Isospora belli can cause weight loss and chronic watery diarrhea (48). Patients with AIDS have been successfully treated for Isospora belli with ten days of trimethoprim-sulfamethoxazole;
recurrent infection can be prevented by chronic prophylaxis with either trimethoprim-sulfamethoxazole or sulfadoxine-pyrimethamine (49).
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ACKNOWLEDGMENTS
We thank Drs. D. A. Harrington and D. Taylor (9) and Dr. R. Fedorak (35) for allowing us to read and cite their manuscripts before publication. Literature Cited
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intestinal protozoan infections. Med. Clin. North Am.66: 707-20 Allason-10nes, E., Mindel, A., Sar geaunt, P., Williams, P. 1986. Enta moeba histolytica as a commensal intes tinal parasite in homosexual men. N. Engl.J.Med.315-56 Sawitz, W. G., Faust, E. C. 1942. The probability of detecting intestinal proto zoan by successive stool examinations. Am.J. Trop. Med.22: 131-36 Walsh, J. A. 1986. Problems in recog nition and diagnosis of amebiasis: Esti mation of the global magnitude of mor bidity and mortality. Rev. Infect. Dis. 8: 228-38 Wolfson, J. S., Riehlen, J. M., Waldron, M. A. 1985.Cryptosporidiosis in immu-
nocompctcnt patients. N. Engl. J. Med. 312: 1278-82 47. Soave, R., Armstrong, D. 1986. Cryp tosporidium and crytosporidiosis. Rev. Infect. Dis. 8: 1012-23 48. De Hovitz, J. A., Pape, 1. W., Bouncy, M. 1986. Clinical manifestations and therapy of Isospora belli infection in pati ents with the acquired immune deficiency syndrome. N. Engl. J. Med. 315: 87-90 49. Pape, J. W., Verdier, R. I., Johnson, W. D. 1r. 1989. Treatment and prophylaxis of Isospora belli infection in patients with the acquired immunodeficiency syndrome. N. Engl. J. Med. 320: 104447
