THE JOURNAL OF INFECTIOUS DISEASES. VOL. 137. NO.5. MAY 1978 © 1978 by the University of Chicago. 0022-1899/78/3705-0014$00.75
The Epidemiology of Diarrhea Due to Enterotoxigenic Escherichia coli R. Bradley Sack
From the Department of Medicine, Division of Geographic Medicine, The Johns Hopkins School of Medicineand the Baltimore City Hospitals, Baltimore, Maryland
high frequency (30%-60% within the first three weeks) when traveling in developing countries where these organisms abound. It is not known why, considering the severity of cholera-like disease, travelers' diarrhea is relatively mild. Either host or bacterial factors may be responsible. A portion of the acu te diarrheal diseases of childhood are also caused by enterotoxigenic E. coli. Data collected thus far suggest that this disease, although relatively uncommon in the United States, is also more common in the developing world. Since diarrheal disease is a leading cause of death in children under five years of age, this suggests that enterotoxigenic E. coli is also an important contributing pathogen to this pattern of mortality. The E. coli involved in producing childhood diarrhea seem to be the same as those that produce travelers' diarrhea [2-4]. The incidence of travelers' diarrhea may, therefore, be an index of the extent of enterotoxigenic E. coli diarrhea in any particular geographic environment. Enterotoxigenic E. coli have also been described as agents in hospital nursery outbreaks of diarrheal disease and in outbreaks of waterborne diarrheal illness, such as the recently described outbreak in Crater Lake, Ore. [5].
Clinical Syndromes
The most severe clinical illness caused by enterotoxigenic organisms is a cholera-like syndrome, indistinguishable clinically at the time of admission to the hospital from that caused by Vibrio cholerae; it is associated with a significant, although ill-defined, rate of mortality. The disease can, however, be treated effectively with fluid replacement. This syndrome, which has been described in western countries, is most commonly seen in areas where cholera is endemic. Enterotoxigenic E. coli are the most common cause of travelers' diarrhea (table 1). This disease, although relatively mild, is of great personal and economic importance to the traveler and to the countries visited. It is postulated that travelers from developed countries are relatively nonimmune and, therefore, develop the disease with
Relation of Enterotoxins to Serotypes and Antibiotic Susceptibility
Our studies in Bangladesh, India, the United States, Kenya, and Morocco indicate that enterotoxigenic E. coli are unusually susceptible to antibiotics, particularly those E. coli that produce both LT and ST or LT alone [2, 3, 6, 7]. Such sensitivity is in marked contrast to the usually high degree of multiple antibiotic resistance found in nonenterotoxigenic E. coli isolated from the same patients and from the environment. This finding suggests some basic interac-
Please address requests for reprints to Dr. R. Bradley Sack, Department of Medicine, The Baltimore City Hospitals, 4940 Eastern Avenue, Baltimore, Maryland 21224.
639
Downloaded from http://jid.oxfordjournals.org/ at Sheffield University on September 5, 2015
The following is a brief description of three clinical categories of diarrheal syndromes induced by enterotoxigenic Escherichia coli. Although they occur worldwide, these syndromes are particularly prevalent in the less hygienic areas of the developing world. All of the clinical syndromes may be caused by enterotoxigenic E. coli that produce one, or both, of two enterotoxins: a heat-labile, cholera-like enterotoxin (LT) and a heat-stable, low-molecular-weight, nonantigenic enterotoxin (ST) [1]. The genetic material that controls the production of these enterotoxins is located in the bacterial plasmid and is thus relatively easily transferable. There exist definable relationships in these E. coli among enterotoxin production, antibiotic sensitivities, and serotype.
640
Table 1.
Sack
Etiologic agents in travelers' diarrhea.
Agent Enterotoxigenic Escherichia coli Other pathogens (Shigella, Salmonella, invasive E. coli, rotavirus) Unknown
Incidence (%)
50-70
References 1. Gyles, C. L., So, M., Falkow, S. The enterotoxin plas-
2.
10-20 20-30
3.
4.
5.
6.
7.
8.
Downloaded from http://jid.oxfordjournals.org/ at Sheffield University on September 5, 2015
tions, and possible incompatibilities, between R plasmids and enterotoxin plasmids. We have also found that enterotoxin-producing E. coli belong to a large number of serotypes which, for the most part, differ from the classical enteropathogenic serotypes. 0rskov et. al. have identified, however, a few select serotypes that are particularly common among enterotoxigenic strains, regardless of geographic location [8]. These serotypes are 06: H16, 08:H9, 015:Hll, 025:H42, 078:Hll,12, 0128:H7, 0149:HIO, and 0159:H4,34. The interrelationship of serotype and enterotoxin production may have to do with other virulence factors of these organisms. Enterotoxigenic E. coli are of greatest importance in the developing world, where sanitary conditions are often poor. General measures undertaken to contain enteric bacteria should also be adequate to stop these organisms from causing outbreaks of disease.
mids of Escherichia coli. J. Infect. Dis. 130:40-49, 1974. Merson, M. H., Morris, G. K., Sack,D. A., Wells, J. G., Feeley, J. C., Sack, R. B., Creech, W. B., Kapikian, A. Z., Gangarosa, E. J. Travelers' diarrhea in Mexico. A prospective study of physicians and family members attending a congress. N. Eng!. J. Med. 294:1299-1305, 1976. Sack, D. A., Kaminsky, D. C., Sack, R. B., Wamola, I. A., 0rskov, F., 0rskov, I., Slack, R. C. B., Arthur, R. R., Kapikian, A. Z. Enterotoxigenic Escherichia coli diarrhea of travelers: a prospective study of American Peace Corps volunteers. Johns Hopkins Med. J. 141: 63-70,1977. Gorbach, S. L., Kean, B. H., Evans, D. G., Evans, D. J., Jr., Bessudo, D. Travelers' diarrhea and toxigenic Escherichia coli. N. Eng!. J. Med. 292:933-936, 1975. Rosenberg, M. L., Koplan, J. P., Wachsmuth, I. K., Wells, J. G., Gangarosa, E. J., Guerrant, R. L., Sack, D. A. Epidemic diarrhea at Crater Lake from enterotoxigenic Escherichia coli. Ann. Intern. Med. 86:714-718, 1977. Sack, R. B., Hirschhorn, N., Brownlee, I., Cash, R. A., Woodward, W. E., Sack, D. A. Enterotoxigenic Escherichia coli-associated diarrheal disease in Apache children. N. Engl. J. Med. 292:1041-1045,1975. Sack, D. A., McLaughlin, J. C., Sack, R. B., 0rskov, F., 0rskov, I. Enterotoxigenic Escherichia coli isolated from patients at a hospital in Dacca. J. Infect. Dis. 135:275-280,1977. 0rskov, F., 0rskov, I., Evans, D. J., Jr., Sack, R. B., Sack, D. A., Wadstrom, T. Special Escherichia coli serotypes among enterotoxigenic strains from diarrhoea in adults and children. Med. Microbiol. Immunol, 162:73-80, 1976.
The Epidemiology of Diarrhea Due to Enterotoxigenic Escherichia coli R. Bradley Sack
From the Department of Medicine, Division of Geographic Medicine, The Johns Hopkins School of Medicineand the Baltimore City Hospitals, Baltimore, Maryland
high frequency (30%-60% within the first three weeks) when traveling in developing countries where these organisms abound. It is not known why, considering the severity of cholera-like disease, travelers' diarrhea is relatively mild. Either host or bacterial factors may be responsible. A portion of the acu te diarrheal diseases of childhood are also caused by enterotoxigenic E. coli. Data collected thus far suggest that this disease, although relatively uncommon in the United States, is also more common in the developing world. Since diarrheal disease is a leading cause of death in children under five years of age, this suggests that enterotoxigenic E. coli is also an important contributing pathogen to this pattern of mortality. The E. coli involved in producing childhood diarrhea seem to be the same as those that produce travelers' diarrhea [2-4]. The incidence of travelers' diarrhea may, therefore, be an index of the extent of enterotoxigenic E. coli diarrhea in any particular geographic environment. Enterotoxigenic E. coli have also been described as agents in hospital nursery outbreaks of diarrheal disease and in outbreaks of waterborne diarrheal illness, such as the recently described outbreak in Crater Lake, Ore. [5].
Clinical Syndromes
The most severe clinical illness caused by enterotoxigenic organisms is a cholera-like syndrome, indistinguishable clinically at the time of admission to the hospital from that caused by Vibrio cholerae; it is associated with a significant, although ill-defined, rate of mortality. The disease can, however, be treated effectively with fluid replacement. This syndrome, which has been described in western countries, is most commonly seen in areas where cholera is endemic. Enterotoxigenic E. coli are the most common cause of travelers' diarrhea (table 1). This disease, although relatively mild, is of great personal and economic importance to the traveler and to the countries visited. It is postulated that travelers from developed countries are relatively nonimmune and, therefore, develop the disease with
Relation of Enterotoxins to Serotypes and Antibiotic Susceptibility
Our studies in Bangladesh, India, the United States, Kenya, and Morocco indicate that enterotoxigenic E. coli are unusually susceptible to antibiotics, particularly those E. coli that produce both LT and ST or LT alone [2, 3, 6, 7]. Such sensitivity is in marked contrast to the usually high degree of multiple antibiotic resistance found in nonenterotoxigenic E. coli isolated from the same patients and from the environment. This finding suggests some basic interac-
Please address requests for reprints to Dr. R. Bradley Sack, Department of Medicine, The Baltimore City Hospitals, 4940 Eastern Avenue, Baltimore, Maryland 21224.
639
Downloaded from http://jid.oxfordjournals.org/ at Sheffield University on September 5, 2015
The following is a brief description of three clinical categories of diarrheal syndromes induced by enterotoxigenic Escherichia coli. Although they occur worldwide, these syndromes are particularly prevalent in the less hygienic areas of the developing world. All of the clinical syndromes may be caused by enterotoxigenic E. coli that produce one, or both, of two enterotoxins: a heat-labile, cholera-like enterotoxin (LT) and a heat-stable, low-molecular-weight, nonantigenic enterotoxin (ST) [1]. The genetic material that controls the production of these enterotoxins is located in the bacterial plasmid and is thus relatively easily transferable. There exist definable relationships in these E. coli among enterotoxin production, antibiotic sensitivities, and serotype.
640
Table 1.
Sack
Etiologic agents in travelers' diarrhea.
Agent Enterotoxigenic Escherichia coli Other pathogens (Shigella, Salmonella, invasive E. coli, rotavirus) Unknown
Incidence (%)
50-70
References 1. Gyles, C. L., So, M., Falkow, S. The enterotoxin plas-
2.
10-20 20-30
3.
4.
5.
6.
7.
8.
Downloaded from http://jid.oxfordjournals.org/ at Sheffield University on September 5, 2015
tions, and possible incompatibilities, between R plasmids and enterotoxin plasmids. We have also found that enterotoxin-producing E. coli belong to a large number of serotypes which, for the most part, differ from the classical enteropathogenic serotypes. 0rskov et. al. have identified, however, a few select serotypes that are particularly common among enterotoxigenic strains, regardless of geographic location [8]. These serotypes are 06: H16, 08:H9, 015:Hll, 025:H42, 078:Hll,12, 0128:H7, 0149:HIO, and 0159:H4,34. The interrelationship of serotype and enterotoxin production may have to do with other virulence factors of these organisms. Enterotoxigenic E. coli are of greatest importance in the developing world, where sanitary conditions are often poor. General measures undertaken to contain enteric bacteria should also be adequate to stop these organisms from causing outbreaks of disease.
mids of Escherichia coli. J. Infect. Dis. 130:40-49, 1974. Merson, M. H., Morris, G. K., Sack,D. A., Wells, J. G., Feeley, J. C., Sack, R. B., Creech, W. B., Kapikian, A. Z., Gangarosa, E. J. Travelers' diarrhea in Mexico. A prospective study of physicians and family members attending a congress. N. Eng!. J. Med. 294:1299-1305, 1976. Sack, D. A., Kaminsky, D. C., Sack, R. B., Wamola, I. A., 0rskov, F., 0rskov, I., Slack, R. C. B., Arthur, R. R., Kapikian, A. Z. Enterotoxigenic Escherichia coli diarrhea of travelers: a prospective study of American Peace Corps volunteers. Johns Hopkins Med. J. 141: 63-70,1977. Gorbach, S. L., Kean, B. H., Evans, D. G., Evans, D. J., Jr., Bessudo, D. Travelers' diarrhea and toxigenic Escherichia coli. N. Eng!. J. Med. 292:933-936, 1975. Rosenberg, M. L., Koplan, J. P., Wachsmuth, I. K., Wells, J. G., Gangarosa, E. J., Guerrant, R. L., Sack, D. A. Epidemic diarrhea at Crater Lake from enterotoxigenic Escherichia coli. Ann. Intern. Med. 86:714-718, 1977. Sack, R. B., Hirschhorn, N., Brownlee, I., Cash, R. A., Woodward, W. E., Sack, D. A. Enterotoxigenic Escherichia coli-associated diarrheal disease in Apache children. N. Engl. J. Med. 292:1041-1045,1975. Sack, D. A., McLaughlin, J. C., Sack, R. B., 0rskov, F., 0rskov, I. Enterotoxigenic Escherichia coli isolated from patients at a hospital in Dacca. J. Infect. Dis. 135:275-280,1977. 0rskov, F., 0rskov, I., Evans, D. J., Jr., Sack, R. B., Sack, D. A., Wadstrom, T. Special Escherichia coli serotypes among enterotoxigenic strains from diarrhoea in adults and children. Med. Microbiol. Immunol, 162:73-80, 1976.
