0025-7125/92 $0.00 + .20
TRAVEL MEDICINE
TRAVELERS' DIARRHEA Prevention and Treatment Pablo C. Okhuysen, MD, and Charles D. Ericsson, MD
EPIDEMIOLOGY
Travelers' diarrhea has been defined as the occurrence of three or more loose stools each day or any number of loose stools accompanied by abdominal cramping, fever, or vomiting, occurring among travelers from industrialized to developing nations. 83 It affects 20% to 70% of travelers when travel is confined to 2 weeks. 77, 109 Travelers' diarrhea occurs worldwide and varies with the population studied and the region visited. High risk areas are the developing nations of Africa, Asia, and Latin America. Intermediate risk occurs in the Caribbean Islands, Israel, Southern Europe, South Africa, and China. Northern Europe, Japan, Australia, and North America are low risk areas. 109 The newly arrived traveler is at higher risk of developing illness when compared to the expatriate living in the same area. When individuals from high risk areas travel to industrialized nations, they do not experience a statistically significant higher attack rate of diarrhea when compared to local low-risk controls. 18, 101 Also, individuals from high risk areas experience a lower rate of diarrhea when traveling to another high risk developing region as compared with travelers coming to the same area from low risk regions. 52 Panamanian tourists traveling in a group in Mexico 101 had a high incidence of viral diarrhea: This was a closed population traveling together in a bus. The attack rates and pathogens isolated suggests the possibility of an outbreak within the group rather than exogenously acquired travelers' diarrhea. Although all age groups are at risk, incidence is the highest among the very young (40%), presumably owing to increased fecal or oral contamination93 and decreased immunity, and in the 15- to 29-year-age groups (36%), perhaps owing to adventurous travel style and the ingestion of higher volumes of potentially contaminated food. Males and females are affected equally. Compliance with the traditional preventive dietary recommendations of "boil it, From the Department of Internal Medicine, and Center for Infectious Diseases, University of Texas School of Medicine and Public Health at Houston (PCO, CDE); and University Center for Travel Medicine at Herman Hospital (CDE), Houston, Texas MEDICAL CLINICS OF NORTH AMERICA VOLUME 76' NUMBER 6 • NOVEMBER 1992
1357
1358
OKHUYSEN & ERICSSON
cook it, peel it, or forget it" is generally low among travelers, and the frequency of illness despite educational efforts is proportional to the number of dietary indiscretions.72 DIETARY CONSIDERATIONS
Unpeeled fruits, uncooked vegetables (for example, salads), and prepared meals that have been stored at inadequate temperatures or cooked at insufficient temperatures are believed to be the main sources of enteric pathogens for the traveler. To a lesser extent, the ingestion of nonpurified water or ice made from it and perhaps the water used for dental hygiene are additional sources. The location where meals are taken by the travel er is important. A higher incidence of travelers' diarrhea is found when food is purchased from street vendors or restaurants or eaten at the homes of locals than when the traveler prepares his or her own meals. 36 The majority of enteropathogenic agents responsible for travelers' diarrhea are frequently viable despite refrigeration. Organisms in contaminated ice will survive concentrations of alcohol found in drinks mixed with tequila and whisky.20 Enteric pathogens also survive temperatures up to 65°C, which is necessary to kill organisms reliably. Foods at this temperature are too hot to touch. These temperatures are rarely found in tap water sources of hotels in developing countries,2 and they are commonly not reached in rewarmed meals. SUSCEPTIBILITY
During travel to developing regions with heavy bacterial contamination, the gut of the traveler is exposed to organisms to which he or she has no immunity. An analogy can be made to the susceptibility of infants to diarrhea in developing countries. Not surprisingly, similar pathogens can be isolated from individuals with diarrhea in both of these populations. Individuals with a history of gastrectomy are believed to be at increased risk of acquiring infection because a reduction in gastric acidity decreases the inoculum dose for certain enteric pathogens necessary to cause diarrhea 44, 58 and predisposes to typhoid and nontyphi salmonella infections, shigellosis, cholera, and giardiasis.59 Individuals on histamine type-2 blockers have developed severe salmonel10sis. 57 Whether travelers on antacid therapy or short-acting H-2 blockers taken at night are at increased risk for the acquisition of travelers' diarrhea remains unclear. ETIOLOGY
Preformed toxins or other dietary factors should be considered in the proportion of travelers experiencing short-lived illness. The frequency with which pathogens such as Clostridium perfringens and Bacillus?5 cause disease in travelers is uncertain. Infectious organisms are found with higher frequency when stools from illnesses conforming to the above definition are studied. Invasive organisms tend to be more commonly isolated the more severe the presenting disease. Bacteria, parasites, viruses,48 and probably algae4 are responsible for
IRA VELERS' DIARRHEA
1359
travelers' diarrhea (Table 1). Frequently, multiple pathogens are isolated from the same individual. The relative proportion of enteropathogens isolated varies with the population studied, season, and site of travel. 49 The proportion of individuals with travelers' diarrhea in whom a pathogen is not isolated is now approximately 20% in some studies. With the advent of newer diagnostic techniques for determination of Norwalk virus and the use of polymerase chain reaction, this percentage may decrease even further. In general, bacterial pathogens are responsible for the majority of travelers' diarrhea episodes. Organisms commonly isolated are Escherichia coli, Shigella, Salmonella, Campylobacter, Aeromonas, Plesiomonas,69 and occasionally Vibrio sp. Although other species such as Citrobacter and Klebsiella are mentioned in some studies ' (Citrobacter has demonstrated virulence properties like the production of enterotoxins similar to those produced by E. coli47 ) , their role as enteric pathogens has not been well defined. Food-borne diarrhea outbreaks owing to Clostridium perfringens, Shigella, and Salmonella have all been described in travel groups aboard airplanes and cruise ships.l2. 82 Escherichia coli
During the past two decades, the pathogenic potential and mechanisms by which E. coli causes human disease have been elucidated. E. coli causing diarrhea are presently classified by their ability to produce toxins (enterotoxigenic E. coli [ETEC]), binding to enteric cells with specific adherence patterns (enteroadherent E. coli [EAECj), invasiveness (enteroinvasive E. coli [EIEC]), pathogenic serotype (EPEC), or by the production of a hemorrhagic dysentericlike diarrhea (EHEC). The most common pathogen isolated in cases of travelers' diarrhea, ETEC possesses several virulence properties. Fimbrial antigens known as colonization factors are associated with attachment to host receptors in the intestinal mucosa. Once attached, ETEC causes illness through the production of two wellcharacterized plasmid-mediated enterotoxins: heat stable (ST) or heat labile Table 1. AGENTS COMMONLY ISOLATED IN CASES OF TRAVELERS' DIARRHEA Percentages of Travelers' Diarrhea Organism
Asia
Middle East
ETEC* EAEC** ElECt Salmonella Shigella Campylobacter Aeromonas Vibrio non-01 Rotavirus E. histolytica Giardia Unknown
20-34
57
References
3 6-18 2-17 5-41 1 1-16
2-7 4-20 2 6
1 42 1, 31, 90, 118
61
Latin America
Africa
Worldwide
40 5 6.5 7 15 3 2 2 10
TRAVEL MEDICINE
TRAVELERS' DIARRHEA Prevention and Treatment Pablo C. Okhuysen, MD, and Charles D. Ericsson, MD
EPIDEMIOLOGY
Travelers' diarrhea has been defined as the occurrence of three or more loose stools each day or any number of loose stools accompanied by abdominal cramping, fever, or vomiting, occurring among travelers from industrialized to developing nations. 83 It affects 20% to 70% of travelers when travel is confined to 2 weeks. 77, 109 Travelers' diarrhea occurs worldwide and varies with the population studied and the region visited. High risk areas are the developing nations of Africa, Asia, and Latin America. Intermediate risk occurs in the Caribbean Islands, Israel, Southern Europe, South Africa, and China. Northern Europe, Japan, Australia, and North America are low risk areas. 109 The newly arrived traveler is at higher risk of developing illness when compared to the expatriate living in the same area. When individuals from high risk areas travel to industrialized nations, they do not experience a statistically significant higher attack rate of diarrhea when compared to local low-risk controls. 18, 101 Also, individuals from high risk areas experience a lower rate of diarrhea when traveling to another high risk developing region as compared with travelers coming to the same area from low risk regions. 52 Panamanian tourists traveling in a group in Mexico 101 had a high incidence of viral diarrhea: This was a closed population traveling together in a bus. The attack rates and pathogens isolated suggests the possibility of an outbreak within the group rather than exogenously acquired travelers' diarrhea. Although all age groups are at risk, incidence is the highest among the very young (40%), presumably owing to increased fecal or oral contamination93 and decreased immunity, and in the 15- to 29-year-age groups (36%), perhaps owing to adventurous travel style and the ingestion of higher volumes of potentially contaminated food. Males and females are affected equally. Compliance with the traditional preventive dietary recommendations of "boil it, From the Department of Internal Medicine, and Center for Infectious Diseases, University of Texas School of Medicine and Public Health at Houston (PCO, CDE); and University Center for Travel Medicine at Herman Hospital (CDE), Houston, Texas MEDICAL CLINICS OF NORTH AMERICA VOLUME 76' NUMBER 6 • NOVEMBER 1992
1357
1358
OKHUYSEN & ERICSSON
cook it, peel it, or forget it" is generally low among travelers, and the frequency of illness despite educational efforts is proportional to the number of dietary indiscretions.72 DIETARY CONSIDERATIONS
Unpeeled fruits, uncooked vegetables (for example, salads), and prepared meals that have been stored at inadequate temperatures or cooked at insufficient temperatures are believed to be the main sources of enteric pathogens for the traveler. To a lesser extent, the ingestion of nonpurified water or ice made from it and perhaps the water used for dental hygiene are additional sources. The location where meals are taken by the travel er is important. A higher incidence of travelers' diarrhea is found when food is purchased from street vendors or restaurants or eaten at the homes of locals than when the traveler prepares his or her own meals. 36 The majority of enteropathogenic agents responsible for travelers' diarrhea are frequently viable despite refrigeration. Organisms in contaminated ice will survive concentrations of alcohol found in drinks mixed with tequila and whisky.20 Enteric pathogens also survive temperatures up to 65°C, which is necessary to kill organisms reliably. Foods at this temperature are too hot to touch. These temperatures are rarely found in tap water sources of hotels in developing countries,2 and they are commonly not reached in rewarmed meals. SUSCEPTIBILITY
During travel to developing regions with heavy bacterial contamination, the gut of the traveler is exposed to organisms to which he or she has no immunity. An analogy can be made to the susceptibility of infants to diarrhea in developing countries. Not surprisingly, similar pathogens can be isolated from individuals with diarrhea in both of these populations. Individuals with a history of gastrectomy are believed to be at increased risk of acquiring infection because a reduction in gastric acidity decreases the inoculum dose for certain enteric pathogens necessary to cause diarrhea 44, 58 and predisposes to typhoid and nontyphi salmonella infections, shigellosis, cholera, and giardiasis.59 Individuals on histamine type-2 blockers have developed severe salmonel10sis. 57 Whether travelers on antacid therapy or short-acting H-2 blockers taken at night are at increased risk for the acquisition of travelers' diarrhea remains unclear. ETIOLOGY
Preformed toxins or other dietary factors should be considered in the proportion of travelers experiencing short-lived illness. The frequency with which pathogens such as Clostridium perfringens and Bacillus?5 cause disease in travelers is uncertain. Infectious organisms are found with higher frequency when stools from illnesses conforming to the above definition are studied. Invasive organisms tend to be more commonly isolated the more severe the presenting disease. Bacteria, parasites, viruses,48 and probably algae4 are responsible for
IRA VELERS' DIARRHEA
1359
travelers' diarrhea (Table 1). Frequently, multiple pathogens are isolated from the same individual. The relative proportion of enteropathogens isolated varies with the population studied, season, and site of travel. 49 The proportion of individuals with travelers' diarrhea in whom a pathogen is not isolated is now approximately 20% in some studies. With the advent of newer diagnostic techniques for determination of Norwalk virus and the use of polymerase chain reaction, this percentage may decrease even further. In general, bacterial pathogens are responsible for the majority of travelers' diarrhea episodes. Organisms commonly isolated are Escherichia coli, Shigella, Salmonella, Campylobacter, Aeromonas, Plesiomonas,69 and occasionally Vibrio sp. Although other species such as Citrobacter and Klebsiella are mentioned in some studies ' (Citrobacter has demonstrated virulence properties like the production of enterotoxins similar to those produced by E. coli47 ) , their role as enteric pathogens has not been well defined. Food-borne diarrhea outbreaks owing to Clostridium perfringens, Shigella, and Salmonella have all been described in travel groups aboard airplanes and cruise ships.l2. 82 Escherichia coli
During the past two decades, the pathogenic potential and mechanisms by which E. coli causes human disease have been elucidated. E. coli causing diarrhea are presently classified by their ability to produce toxins (enterotoxigenic E. coli [ETEC]), binding to enteric cells with specific adherence patterns (enteroadherent E. coli [EAECj), invasiveness (enteroinvasive E. coli [EIEC]), pathogenic serotype (EPEC), or by the production of a hemorrhagic dysentericlike diarrhea (EHEC). The most common pathogen isolated in cases of travelers' diarrhea, ETEC possesses several virulence properties. Fimbrial antigens known as colonization factors are associated with attachment to host receptors in the intestinal mucosa. Once attached, ETEC causes illness through the production of two wellcharacterized plasmid-mediated enterotoxins: heat stable (ST) or heat labile Table 1. AGENTS COMMONLY ISOLATED IN CASES OF TRAVELERS' DIARRHEA Percentages of Travelers' Diarrhea Organism
Asia
Middle East
ETEC* EAEC** ElECt Salmonella Shigella Campylobacter Aeromonas Vibrio non-01 Rotavirus E. histolytica Giardia Unknown
20-34
57
References
3 6-18 2-17 5-41 1 1-16
2-7 4-20 2 6
1 42 1, 31, 90, 118
61
Latin America
Africa
Worldwide
40 5 6.5 7 15 3 2 2 10
