Abstract
As amply documented in other papers in this volume, there is no doubt that diarrheal diseases are the world’s biggest health problem. They constitute the commonest cause of death among young children in the most populous developing countries (Tables I–III).1,2 Although more difficult to quantify, even greater is the impact of 3 to 12 severe, dehydrating illnesses per year on the physical and mental development of those children who survive. Also alarming is the recent “modernization” trend toward reduced breast-feeding in areas where very poor socioeconomic conditions result in a significant lag in the development of adequate water supply and sanitation facilities. The findings in northeastern Brazil of Nations-Shields suggest that the striking mortality of 15 to 25% in the first 5 years of life will likely increase even further as this trend proceeds (M. Nations-Shields, personal communication, 1981).
The University of Virginia’s Division of Geographic Medicine is supported in part by the Rockefeller Foundation. Much of this work derives from projects supported by the Kellogg Foundation, the Pan American Health Organization, and the World Health Organization.
Chapter PDF
References
Puffer, R. R., and Serrano, C. V. Patterns of Mortality in Childhood. Pan American Sanitary Bureau, Regional Office, World Health Organization, Washington, D.C., 1973.
Gordon, J. E., Chitkara, I. D., and Wyon, J. B. Weanling diarrhea. Am. J. Med. Sci. 245:345, 1963.
Giannella, R. A., Broitman, S. A., and Zamcheck, N. Influence of gastric acidity on bacterial and parasitic enteric infections: A perspective. Ann. Intern. Med. 78:271, 1973.
Bohnhoff, M., Miller, C. P., and Martin, W. R. Resistance of the mouse’s intestinal tract to experimental Salmonella infections. J. Exp. Med. 120:805, 1964.
Mentzing, L. O., and Ringertz, O. Salmonella infection in tourists. 2. Prophylaxis against salmonellosis. Acta Pathol. Microbiol. Scand. 74:405, 1968.
Bartlett, J. G. Antibiotic-associated pseudomembranous colitis. Rev. Infect. Dis. 1:530, 1979.
Formal, S. B., Abrams, G. D., Schneider, H., and Sprinz, H. Experimental Shigella infections VI. Role of the small intestine in an experimental infection in guinea pigs. J. Bacteriol. 85:119, 1963.
Higgens, J. A., Code, C. F., and Orvis, A. L. The influence of motility on the rate of absorption of sodium and water from the small intestine of healthy persons. Gastroenterology 31:708, 1956.
Jones, G. W. The attachment of bacteria to the surfaces of animal cells. In: Microbial Interactions: Receptors and Recognition, Series B, Vol. 3, J. L. Reissig (Ed.), pp. 139–176 Chapman & Hall, London, 1977.
Guerrant, R. L., and Bergman, M. J. Attachment factors among enterotoxigenic Escherichia coli. In: Frontiers of Knowledge in the Diarrheal Diseases, H. D. Janowitz and D. B. Sachar (Eds.). Projects in Health, Montclair, New Jersey, 1979.
Smith, H. W., and Linggood, M. A. Observations on the pathogenic properties of the K88, HLY and ENT plasmids of Escherichia coli with special reference to porcine diarrhea. J. Med. Microbiol. 4:467–485, 1971.
Evans, D. G., and Evans, D. J., Jr. New surface-associated heat-labile colonization factor of enterotoxigenic Escherichia coli isolated from adults with diarrhea. Infect. Immun. 19:727–736, 1978.
Bergman, M. J., Updike, W. S., Wood, S. J., Brown, S. E., III, and Guerrant, R. L. Attachment factors among enterotoxigenic Escherichia coli from patients with acute diarrhea from diverse geographic areas. Infect. Immun. 32:881–888, 1981.
Levine, M. M. and Renneis, M. B. E. coli colonization factor antigen in diarrhea. Lancet ii:534, 1978.
Ulshen, M. H., and Rollo, J. L. Pathogenesis of Escherichia coli gastroenteritis in man— Another mechanism. N. Engl. J. Med. 302:99–101, 1980.
Guerrant, R. L. Yet another pathogenic mechanism for E. coli diarrhea? N. Engl. J. Med 302:113–114, 1980.
Kent, T. H., and Lindenbaum, J. Correlation of jejunal function and morphology in patients with acute and chronic diarrhea in East Pakistan. Gastroenterology 52:972, 1967.
Hirschhorn, N., and Molla, A. Reversible jejunal disaccharidase deficiency in cholera and other acute diarrheal diseases. Johns Hopkins Med. J. 125:291, 1969.
Lifshitz, F., Coello-Ramierz, P., and Gutierrez-Topete, G. Carbohydrate intolerance in infants with diarrhea. J. Pediatr. 79:760, 1971.
Bishop, R. F., Davidson, G. P., Holmes, I. H., and Ruck, B. J. Virus particles in epithelial cells of duodenal mucosa from children with acute nonbacterial gastroenteritis. Lancet ii:1281, 1973.
Agus, S. G., Dolin, R., Wyatt, R. G., Tousimis, A. J., and Northrup, R. S. Acute infectious nonbacterial gastroenteritis: Intestinal histopathology, histologic and enzymatic alterations during illness produced by Norwalk agent in man. Ann. Intern. Med. 79:18, 1973.
Frizzell, R. A., Field, M., and Schultz, S. G. Sodium-coupled chloride transport by epithelial tissues. Am. J. Physiol. 236:F1–F3, 1979.
Field, M., Plotkin, G. R., and Silen, W. Effects of vasopressin, theophylline, and cyclic adenosine monophosphate on short-circuit current across isolated rabbit ileal mucosa. Nature (London) 217:469–471, 1968.
Guerrant, R. L., Chen, L. C., and Sharp, G. W. G. Intestinal adenylcyclase activity in canine cholera: Correlation with fluid accumulation. J. Infect. Dis. 125:377–381, 1972.
Nellans, H. N., Frizzell, R. A., and Schultz, S. G. Coupled sodium-chloride influxes across the brush border of rabbit ileum. Am. J. Physiol. 225:467–475, 1973.
Field, M., Cholera toxin, adenylate cyclase, and the process of active secretion in the small intestine: The pathogenesis of diarrhea in cholera. In: Physiology of Membrane Disorders, T. E. Andreoli, J. F. Hoffman, and D. D. Fanestil (Eds.), pp. 877–899. Plenum, New York, 1978.
Nellans, H. N., Frizzell, R. A., and Schultz, S. G. Effect of acetazolamide on sodium and chloride transport by in vitro rabbit ileum. Am. J. Physiol. 228:1808–1814, 1975.
Klyce, S. D., and Wong, R. K. S. Site and mode of adrenaline action on chloride transport across the rabbit corneal epithelium. J. Physiol. 266:77–799, 1977.
Roggin, G. M., Banwell, J. G., Yardley, J. H., and Hendrix, T. H. Unimpaired response of rabbit jejunum to cholera toxin after selective damage to villus epithelium. Gastroenterology 63:981–989, 1972.
DeJonge, H. R. The response of small intestinal villus and crypt epithelium to cholera toxin in rat and guinea pig. Evidence against a specific role of the crypt cells in choleragen-induced secretion. Biochim. Biophys. Acta 381:128–143, 1975.
Holmgren, J., and Lonnroth, I. Structure and function of enterotoxins and their receptors. In: Cholera and Related Diarrheas, O. Ouchterlony and J. Holmgren (Eds.), 43rd Nobel Symposium. S. Karger, Basel, 1980.
Gill, D. M., and King, C. A. The mechanism of action of cholera toxin in pigeon erythrocyte lysates. J. Biol. Chem. 250:424–432, 1975.
Gill, D. M. Multiple roles of erythrocyte supernatant in the activation of adenylate cyclase by Vibrio cholerae toxin in vitro. J Infect. Dis. 133:S55–S63, 1976.
Hewlett, E. L., Guerrant, R. L., Evans, D. J., Jr., and Greenough, W. G. III. Toxins of Virbro cholerae and Escherichia coli stimulate adenyl cyclase in rat fat cells. Nature 249:371–373, 1974.
Cassel, D., and Selinger, Z. Mechanisms of adenylate cyclase activation by cholera toxin: Inhibition of GTP hydrolysis at the regulatory site. Proc. Natl. Acad. Sci. (U.S.) 74:3307–3311, 1977.
Cassel, D., and Pfeuffer, T. Mechanism of cholera toxin action: Covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system. Proc. Nat. Acad. Sci. (U.S.) 75:2669–2673, 1978.
Guerrant, R. L., Brunton, L. L., Schnaitman, T. C., Rebhun, L. I., and Gilman, A. G. Cyclic adenosine monophosphate and alteration of Chinese hamster ovary cell morphology: A rapid, sensitive in vitro assay for the enterotoxins of Vibrio cholerae and Escherichia coli. Infect. Immun. 10:320–327, 1974.
Guerrant, R. L., and Brunton, L. L. Characterization of the Chinese hamster ovary cell assay for the enterotoxins of Vibrio cholerae and Escherichia coli and for antitoxin: Differential inhibition by gangliosides, specific antisera, and toxoid. J. Infect. Dis. 135:720–728, 1977.
Donta, S. T., and King, M. Induction of steroidogenesis in tissue culture by cholera enterotoxin. Nature (New Biol.) 243:246–247, 1973.
Donta, S. T., Moon, H. W., and Whipp, S. C. Detection of heat-labile Escherichia coli enterotoxin with the use of adrenal cells in tissue culture. Science 183:334–335, 1974.
DeJonge, H. R. Cyclic nucleotide-dependent phosphorylation of intestinal epithelium proteins. Nature 262:590–593, 1976.
Leitch, G. H., and Amer, M. S. Lanthanum inhibition of V. cholerae and E. coli enterotoxin-induced enterosorption and its effects on intestinal mucosa cyclic adenosine 3′, 5′-monophosphate levels. Infect. Immun. 11:1038–1044, 1975.
Holmgren, J., Sange, S., and Lonnroth, I. Reversal of cyclic AMP-mediated intestinal secretion in mice by chlorpromazine. Gastroenterology 75:1103–1108, 1978.
Bolton, J. E., and Field, M. Ca Ionophore-stimulated ion secretion in rabbit ileal mucosa; Relation to actions of cyclic 3′, 5′-AMP and carbamylcholine. J. Membr. Biol. 35:159–173, 1977.
Donowitz, M., Asarkof, N., and Pike, G. Calcium dependence of serotonin-induced changes in rabbit ileal electrolyte transport. J. Clin. Invest. 66:341–353, 1980.
Sack, D. A., Merson, M. M., Wells, J. C., Sack, R. B., and Morris, G. K. Diarrhea associated with heat-stable enterotoxin-producing strains of Escherichia coli. Lancet ii:239–244, 1975.
Ryder, R. W., Wachsmuth, I. K., Buxton, A. E., Evans, D. G., DuPont, H. L., Mason, E., and Barrett, F. F. Infantile diarrhea produced by heat-stable enterotoxigenic Escherichia coli. N. Engl. J. Med. 295:849–853, 1976.
Hughes, J. M., Rouse, J. D., Barada, F. A., and Guerrant, R. L. Etiology of summer diarrhea among the Navajo. Am. J. Trop. Med. Hyg. 29:613–619, 1980.
Guerrant, R. L., Rouse, J. D., and Hughes, J. M. Turista among the Yale Glee Club in Latin America: Studies of enterotoxigenic bacteria, E. coli serotypes and rotaviruses. Am. J. Trop. Med. Hyg. 29:895–900, 1980.
Staples, D. J., Asher, S. E., and Giannella, R. A. Purification and characterization of heat-stable enterotoxin produced by a strain of E. coli pathogenic for man. J. Biol. Chem. 255:4716–4721, 1980.
Alderete, J. G., and Robertson, D. C. Purification and chemical characterization of the heat-stable enterotoxin produced by porcine strains of enterotoxigenic Escherichia coli. Infect. Immun. 19:1021–1030, 1978.
Pierce, N. F. Differential inhibitory effects of cholera toxoids and gangliosides on the enterotoxins of Vibrio cholerae and Escherichia coli. J. Exp. Med. 137:1009–1023, 1973.
Guerrant, R. L., Hughes, J. M., Chang, B., Robertson, D. C., and Murad, F. Activation of rat and rabbit intestinal guanylate cyclase by the heat-stable enterotoxin of Escherichia coli: Studies of tissue specificity, potential receptors and intermediates. J. Infect. Dis. 142:220–228, 1980.
Burgess, M. N., Bywater, R. J., Cowley, C. M., Mullan, N. A., and Newsome, P. M. Biological evaluation of a methanol-soluble, heat-stable Escherichia coli enterotoxin in infant mice, pigs, rabbits, and calves. Infect. Immun. 21:526–530, 1978.
Guerrant, R. L., Ganguly, U., Casper, A. G. T., Moore, E. J., Pierce, N. J., and Carpenter, C. C. J. Effect of Escherichia coli on fluid transport across canine small bowel: Mechanism and time course with enterotoxin and whole bacterial cells. J. Clin. Invest. 52:1707–1714, 1973.
Hughes, J. M., Murad, F., Chang, B., and Guerrant, R. L. Role of cyclic GMP in the action of heat-stable enterotoxin of Escherichia coli. Nature 271:755–756, 1978.
Field, M., Graf, L. G., Jr., Laird, W. F., and Smith, P. L. Heat-stable enterotoxin of Escherichia coli: In vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine. Proc. Nat. Acad. Sci. (U.S.) 75:2800–2804, 1978.
Hughes, J. M., Murad, F., and Guerrant, R. L. Studies to elucidate the mechanism of action of heat-stable enterotoxin of Escherichia coli. Clin. Res. 26:524A, 1978.
Rao, M. C., Guandalini, S., Laird, W. J., Smith, P. L., and Field, M. Heat-stable enterotoxins: Mechanism of action (Proceedings of the Fifteenth Joint Conference of the U.S.-Japan Cooperative Medical Science Program of Cholera), NIAID, NIH, Bethesda, Maryland, 1979, NIH Publ. No. 80:2003, 1980.
Kimura, H., and Murad, F. Subcellular localization of guanylate cyclase—Minireview. Life Sci. 17:837–743, 1975.
Ong, S-H., Whitley, T. H., Stowe, N. W., and Steiner, A. L. Immunohistochemical localization of 3′:5′-cyclic AMP and 3′:5′-cyclic GMP. Proc. Nat. Acad. Sci. (U.S.) 72:2022–2026, 1975.
Dejonge, H. R. The localization of guanylate cyclase in rat small intestinal epithelium. FEBS Lett. 53:237–242, 1975.
Greenberg, R. N., Guerrant, R. L., Chang, B., Robertson, D. C., and Murad, F. Inhibition of E. coli heat-stable enterotoxin (ST) by quinacrine. Biochem. Pharmacol. 31:2005–2009, 1982.
Greenberg, R. N., Murad, F., Chang, B., Robertson, D. C., and Guerrant, R. L. Inhibition of Escherichia coli heat-stable enterotoxin by indomethacin and chlorpromazine. Infect. Immun. 29:908–913, 1980.
Greenberg, R. N., Murad, F., and Guerrant, R. L. Lanthanum chloride inhibition of secretory response to Escherichia coli heat-stable enterotoxin Infect. Immun. 35:483–488, 1982.
Blacklow, N. R., Dolin, R., Fedson, D. S., DuPont, H., Northrup, R. S., Hornick, R. B., and Chanock, R. M. Acute infectious nonbacterial gastroenteritis: Etiology and pathogenesis. Ann. Intern. Med. 76:993–1008, 1972.
Meeroff, J. C., Schreiber, D. S., Trier, J. S., and Blacklow, N. R. Abnormal gastric motor function in viral gastroenteritis. Ann. Intern Med. 92:370–373, 1980.
Schreiber, D. S., Blacklow, N. R., and Trier, J. S. The mucosal lesion of the proximal small intestine in acute infectious nonbacterial gastroenteritis. N. Engl. J. Med. 288:1318–1323, 1973.
Levy, A. G., Widerlite, L., Schwartz, C. J., Dolin, R., Blacklow, N. R., Gardner, J. D., Kimberg, D. V., and Trier, J. S. Jejunal adenylate cyclase activity in human subjects during viral gastroenteritis. Gastroenterology 70:321–325, 1976.
Kapikian, A. Z., Kim, H. W., Wyatt, R. G., Cline, W. L., Arrobio, J. O., Brandt, C. D., Rodriguez, W. J., Sack, D. A., Chanock, R. M., and Parrott, R. H. Human reovirus-like agent as the major pathogen associated with “winter” gastroenteritis in hospitalized infants and young children. N. Engl. J. Med. 294:965, 1976.
Black, R. W., Merson, M. H., Huq, I., Alim, A. R. M. A., and Yunus, M. D. Incidence and severity of rotavirus and Escherichia coli diarrhea in rural Bangladesh: Implications for vaccine development, Lancet i:141–143, 1981.
Wenman, W. M., Hinde, D., Feltham, S., and Gurwith, M. Rotavirus infection in adults: Results of a prospective family study. N. Engl. J. Med. 301:303–306, 1979.
Tallett, S., MacKenzie, C., Middleton, P., Kerzner, B., and Hamilton, R. Clinical, laboratory, and epidemiological features of a viral gastroenteritis in infants and children. Pediatrics 60:217–222, 1977.
Sack, D. A., Chowdhury, A. M. A. K., Eusof, A., Ali, M. A., Merson, M. H., Islam, S., Black, R. E., and Brown, K. H. Oral hydration in rotavirus diarrhea: A double-blind comparison of sucrose with glucose electrolyte solution. Lancet ii:280–283, 1978.
Torres-Pinedo, R., Lavastida, M., Rivera, C. L., Rodriguez, H., and Ortiz, A., Studies on infant diarrhea. I. A comparison of the effects of milk feeding and intravenous therapy upon the composition and volume of the stool and urine. J. Clin. Invest. 45:469–479, 1966.
Middleton, P. J., Szymanski, M. T., Abbott, G. D., Bortolussi, R., and Hamilton, J. R. Orbivirus acute gastroenteritis of infancy. Lancet i:1241–1244, 1974.
Davidson, G. P., Goller, I., Bishop, R. F., Townely, R. R. W., Holmes, P. H., and Ruck, B. J. Immunofluorescence in duodenal mucosa of children with acute enteritis due to a new virus. J. Clin. Pathol. 28:263–266, 1975.
Davidson, G. P., and Barnes, G. L. Structural and functional abnormalities of the small intestine in infants and young children with rotavirus enteritis. Acta Paediatr. Scand. 68:181–186, 1979.
Mebus, C. A., Wyatt, R. G., Sharpee, R. L., Sereno, M. M., Kalica, A. P., Zapikian, A. Z., and Twiehaus, M. J. Diarrhea in gnotobiotic calves caused by the reovirus-like agent of human infantile gastroenteritis. Infect. Immun. 14:471–474, 1976.
Holmes, I. H., Rodger, S. M., Schnagl, R. D., Ruck, B. J., Gust, I. D., Bishop, R. F., and Barnes, G. L. Is lactase the receptor and uncoating enzyme for infantile enteritis (ROTA) viruses? Lancet i:1387, 1976.
Schoub, B. D., Jenkins, T., and Robins-Browne, R. M. Rotavirus infection in high-incidence lactase-deficiency population. Lancet i:328, 1978.
Hamilton, J. R., Gall, D. G., Butler, D. G., and Middleton, P. J. Viral gastroenteritis: Recent progress, remaining problems. Ciba Founda. Symp. 42:209, 1976.
Kerzner, B., Kelly, M. H., Gall, D. G., Butler, D. G., and Hamilton, J. R. Transmissible gastroenteritis: Sodium transport and the intestinal epithelium during the course of viral enteritis. Gastroenterology 72:457–461, 1977.
Gall, D. G., Chapman, D., Kelly, M., and Hamilton, J. R. Na+ transport in jejunal crypt cells. Gastroenterology 72:452–456, 1977.
Shepherd, R. W., Butler, D. G., Cutz, E., Gall, D. G., and Hamilton, J. R. The mucosal lesion in viral enteritis: Extent and dynamics of the epithelial response to virus invasion in transmissible gastroenteritis of piglets. Gastroenterology 76:770–777, 1979.
Davidson, G. P., Gall, D. G., Petric, M., Butler, D. G., and Hamilton, J. R. Human rotavirus enteritis induced in conventional piglets: Intestinal structure and transport. J. Clin. Invest. 60:1402–1409, 1977.
Kapikian, A. Z., Wyatt, R. G., Greenberg, H. B., Kalica, A. R., Wha, K. H., Brandt, C. D., Rodriguez, W. J., Parrott, R. H., and Chanock, R. M. Approaches to immunization of infants and young children against gastroenteritis due to rotaviruses. Rev. Infect. Dis. 2:459, 1980.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1983 The United Nations University
About this chapter
Cite this chapter
Guerrant, R.L. (1983). Pathophysiology of the Enterotoxic and Viral Diarrheas. In: Chen, L.C., Scrimshaw, N.S. (eds) Diarrhea and Malnutrition. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-9284-6_2
Download citation
DOI: https://doi.org/10.1007/978-1-4615-9284-6_2
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4615-9286-0
Online ISBN: 978-1-4615-9284-6
eBook Packages: Springer Book Archive