TRAVELERS' DIARRHEA
Epidemiology
Travelers' diarrhea (TD) is a syndrome characterized by a twofold or greater increase in
the frequency of unformed bowel movements. Commonly associated symptoms include abdominal
cramps, nausea, bloating, urgency, fever, and malaise. Episodes of TD usually begin
abruptly, occur during travel or soon after returning home, and are generally
self-limited. The most important determinant of risk is the destination of the traveler.
Attack rates in the range of 20 to 50 percent are commonly reported. High-risk
destinations include most of the developing countries of Latin America, Africa, the Middle
East, and Asia. Intermediate risk destinations include most of the Southern European
countries and a few Caribbean islands. Low risk destinations include Canada, Northern
Europe, Australia, New Zealand, the United States and a number of the Caribbean islands.
TD is slightly more common in young adults than in older people. The reasons for this
difference are unclear, but may include a lack of acquired immunity, more adventurous
travel styles, and different eating habits. Attack rates are similar in men and women. The
onset of TD is usually within the first week, but may occur at any time during the visit,
and even after returning home.
TD is acquired through ingestion of fecally contaminated food and/or water. Both cooked
and uncooked foods may be implicated if improperly handled. Especially risky foods include
raw or undercooked meat and seafood, and raw fruits and vegetables. Tap water, ice, and
unpasteurized milk and dairy products may be associated with increased risk of TD; safe
beverages include bottled carbonated beverages (especially flavored beverag-es), beer,
wine, hot coffee or tea, or water boiled or appropriately treated with iodine or chlorine.
The place food is prepared appears to be an important variable; with private homes,
restaurants, and street vendors listed in order of increasing risk.
TD typically results in four to five loose or watery stools per day. The median
duration of diarrhea is 3 to 4 days. Ten percent of the cases persist longer than 1 week,
approximately 2 percent longer than 1 month, and less than 1 percent longer than 3 months.
Persistent diarrhea is thus quite uncommon and may differ considerably from acute TD with
respect to etiology and risk factors. Approximately 15 percent of cases experience
vomiting, and 2 to 10 percent may have diarrhea accompanied by fever or bloody stools, or
both. Travelers may experience more than one attack of TD during a single trip. Rarely is
TD life-threatening.
Etiology
Infectious agents are the primary cause of TD. Travelers from industrialized countries to
developing countries frequently develop a rapid, dramatic change in the type of organisms
in their gastrointestinal tract. These new organisms often include potential enteric
pathogens. Those who develop diarrhea have ingested an inoculum of virulent organisms
sufficiently large to overcome individual defense mechanisms, resulting in symptoms.
Enteric Bacterial Pathogens
Enterotoxigenic Escherichia coli (ETEC) are the most common causative agents of TD in all
countries where surveys have been conducted. ETEC produce a watery diarrhea associated
with cramps and a low-grade or no fever.
Salmonella gastroenteritis is a well-known disease that occurs throughout the
world. In the industrialized nations, this large group of organisms is the most common
cause of outbreaks of food-associated diarrhea. In the developing countries, the
proportion of cases of TD caused by non-typhoidal salmonellae varies but is not high.
Salmonellae also can cause dysentery characterized by bloody mucus-containing small-volume
stools.
Shigellae are well known as the cause of bacillary dysentery. The shigellae are the
cause of TD in from 0 to about 20 percent of travelers to developing countries.
Campylobacter jejuni is a common cause of diarrhea throughout the world, and is
responsible for a small percentage of the reported cases of TD, some with bloody diarrhea.
Additional studies are needed to determine how frequently it causes TD.
Vibrio parahaemolyticus is associated with ingestion of raw or poorly cooked
seafood and has caused TD in passengers on Caribbean cruise ships and in Japanese people
traveling in Asia. How frequently it causes disease in other areas of the world is
unknown.
Other less common bacterial pathogens include E. coli, Yersinia
enterocolitica, Vibrio cholerae O1 O139, and other non-O1, Vibrio fluvialis,
and possibly Aeromonas hydrophila and Plesiomonas shigelloides.
Viral Enteric Pathogens--Rotavirus and Norwalk-like Virus
Along with the newly acquired bacteria, the traveler may also acquire many viruses. In six
studies, for example, 0 to 36 percent of diarrheal illnesses in travelers (median 22
percent) were associated with rotaviruses in the stools. However, a comparable number of
asymptomatic travelers also had rotaviruses, and up to 50 percent of symptomatic persons
with rotavirus infections also had nonviral pathogens. Ten to fifteen percent of travelers
develop serologic evidence of infection with Norwalk-like viruses. The roles of
adenoviruses, astroviruses, coronaviruses, enteroviruses, or other viral agents in causing
TD are even less clear. Although viruses are commonly acquired by travelers, they do not
appear to be frequent causes of TD in adults.
Parasitic Enteric Pathogens
The few studies that have included an examination for parasites reveal that 0 to 6 percent
of persons with travelers’ diarrhea have Giardia lamblia and 0 to 6 percent have
Entamoeba histolytica. Cryptosporidium has recently been recognized in sporadic cases of
TD.
Dientamoeba fragilis, Isospora belli, Balantidium coli, Cyclospora
(previously known as cyanobacterium-like bodies), or Strongyloides stercoralis may
cause occasional cases of TD. While not major causes of acute TD, these parasites should
be sought in persisting, unexplained cases.
Unknown Causes
No data have been presented to support noninfectious causes of TD such as changes in diet,
jet lag, altitude, and fatigue. Current evidence indicates that in all but a few
instances, e.g., drug-induced or preexisting gastrointestinal disorders, an infectious
agent or agents cause diarrhea in tourists. However, even with the application of the best
current methods for detecting bacteria, viruses, and parasites, 20 to 50 percent of cases
of TD remain without recognized etiologies.
Prevention
There are four possible approaches to prevention of TD. They include instruction regarding
food and beverage consumption, immunization, use of nonantimicrobial med-ications, and
prophylactic antimicrobial drugs.
Data indicate that meticulous attention to food and beverage consumption, as mentioned
above, can decrease the likelihood of developing TD. Most travelers, however, encounter
difficulty in observing the requisite dietary restrictions.
No available vaccines and none that are expected to be available in the next 5 years
are effective against TD.
Several nonantimicrobial agents have been advocated for prevention of TD. Available
controlled studies indicate that prophylactic use of difenoxine, the active metabolite of
diphenoxylate (Lomotil†), actually increases the incidence of TD in addition to
producing other undesirable side effects. Antiperistaltic agents e.g., Lomotil† and
Imodium† are not effective in preventing TD. No data support the prophylactic use of
activated charcoal.
Bismuth subsalicylate, taken as the active ingredient of Pepto-Bismol† (2 oz. 4
times daily, or 2 tablets 4 times daily), has decreased the incidence of diarrhea by about
60 percent in several placebo-controlled studies. Side effects include temporary
blackening of tongue and stools, occasional nausea and constipation, and rarely, tinnitus.
Available data are not extensive enough to exclude a risk to the traveler from the use of
such large doses of bismuth subsalicylate for a period of more than three weeks. Bismuth
subsalicylate should be avoided by persons with aspirin-allergy, renal insufficiency,
gout, and by those who are taking anticoagulants, probenecid, or methotrexate. In patients
already taking salicylates for arthritis, large concurrent doses of bismuth subsalicylate
can produce toxic serum concentrations of salicylate. Caution should be used in giving
bismuth subsalicylate to adolescents and children with chicken pox or flu because of a
potential risk of Reye's syndrome. Bismuth subsalicylate has not been approved for
children under three years old. Bismuth subsalicylate appears to be an effective
prophylactic agent for TD, but is not recommended for prophylaxis of TD for periods of
more than three weeks. Further studies of the efficacy and side effects of lower dose
regimens are needed.
Controlled data are available on the prophylactic value of several other
nonantimicrobial drugs. Enterovioform† and related halogenated hydroxyquinoline
derivatives e.g., clioquinol, iodoquinol, Mexaform†, Intestopan†, and others,
are not helpful in preventing TD, may have serious neurological side effects, and should
never be used for prophylaxis of TD.
Controlled studies have indicated that a variety of antibiotics, including doxycycline,
trimethoprim/sulfamethoxazole (TMP/SMX), trimethoprim alone, and the fluoroquinolo-ne
agents ciprofloxacin and norfloxacin, when taken prophylactically have been 52-95%
effective in preventing traveler's diarrhea in several areas of the developing world. The
effectiveness of these agents, however, depends upon the antibiotic resistance patterns of
the pathogenic bacteria in each area of travel, and such information is seldom available.
Resistance to the fluoroquinolones is the least common, but this may change as the use of
these agents increases worldwide.
While effective in preventing some bacterial causes of diarrhea, antibiotics have no
effect on the acquisition of various viral and parasitic diseases. Prophylactic
antibiotics may give travelers a false sense of security about the risk associated with
consuming certain local foods and beverages.
The benefits of widespread prophylactic use of doxycycline, quinolones, TMP/SMX or TMP
alone in several million travelers must be weighed against the potential drawbacks. The
known risks include allergic and other side effects (such as common skin rashes,
photosensitivity of the skin, blood disorders, Stevens-Johnson syndrome and staining of
the teeth in children) as well as other infections that may be induced by antimicrobial
therapy (such as antibiotic-associated colitis, Candida vaginitis, and Salmonella
enteri-tis). Because of the uncertain risk of widespread administration of these
antimicrobial agents, their prophylactic use is not recommended. While it seems reasonable
to use prophylactic antibiotics in certain high risk groups, such as travelers with
immunosup-pression or immunodeficiency, there are no data which directly support this
practice. There is little evidence that other disease entities are worsened sufficiently
by an episode of TD to risk the rare undesirable side effects of prophylactic
antimicrobial drugs. Therefore, prophylactic antimicrobial agents are not recommended
for travelers. Instead, available data support the recommendation that travelers be
instructed in sensible dietary practices as a prophylactic measure. This recommendation is
justified by the excellent results of early treatment of TD as outlined below. Some
travelers may wish to consult with their physician and may elect to use prophylactic
antimicrobial agents for travel under special circumstances, once the risks and benefits
are clearly understood.
Treatment
Individuals with TD have two major complaints for which they desire relief--abdominal
cramps and diarrhea. Many agents have been proposed to control these symptoms, but few
have been demonstrated to be effective by rigorous clinical trials.
Nonspecific Agents
A variety of "adsorbents" have been used in treating diarrhea. For example,
activated charcoal has been found to be ineffective in the treatment of diarrhea. Kaolin
and pectin have been widely used for diarrhea. The combination appears to give the stools
more consistency but has not been shown to decrease cramps and frequency of stools nor to
shorten the course of infectious diarrhea.
Lactobacillus preparations and yogurt have also been advocated, but no evidence
supports use of these treatments for TD.
Bismuth subsalicylate preparation (1 oz of liquid or 2 262.5 mg tablets every 30
minutes for eight doses) decreased the rate of stooling and shortened the duration of
illness in several placebo-controlled studies. Treatment was limited to 48 hours at most,
with, no more than 8 doses in a 24-hour period. There is concern about taking, without
supervision, large amounts of bismuth and salicylate, especially in individuals who may be
intolerant to salicylates, who have renal insufficiency, or who take salicylates for other
reasons.
Antimotility Agents
Antimotility agents are widely used in treating diarrhea of all types. Natural opiates
(paregoric, tincture of opium, and codeine) have long been used to control diarrhea and
cramps. Synthetic agents, diphenoxylate and loperamide, come in convenient dosage forms
and provide prompt symptomatic but temporary relief of uncomplicated TD. However, they
should not be used in patients with high fever or with blood in the stool. These drugs
should be discontinued if symptoms persist beyond 48 hours. Diphenoxylate and loperamide
should not be used in children under the age of 2.
Antimicrobial Treatment
Travelers who develop diarrhea with three or more loose stools in an 8-hour period,
especially if associated with nausea, vomiting, abdominal cramps, fever, or blood in the
stools, may benefit from antimicrobial treatment. A typical 3- to 5-day illness can often
be shortened to 1 to 1 1/2 days by effective antimicrobial agents. The effectiveness of
antibiotic therapy will depend on the etiologic agent and its antibiotic sensitivity.
Antibiotic regimens most likely to be effective are TMP/SMX (160 mg TMP and 800 mg SMX) or
ciprofloxacin (500 mg) taken twice daily. Other fluoroquinolones such as norfloxacin and
ofloxacin may be equally effective as ciprofloxacin. Fewer side effects and less
widespread resistance has been reported with the fluoroquinolones than with TMP/SMX. Three
days of treatment is recommended, although 2 days or fewer may be sufficient. Nausea and
vomiting without diarrhea should not be treated with antimi-crobial drugs.
Travelers should consult a physician, rather than attempt self-medication, if the
diarrhea is severe or does not resolve within several days; if there is blood and/or mucus
in the stool; if fever occurs with shaking chills; or if there is dehydration with
persistent diarrhea.
Oral fluids
Most cases of diarrhea are self-limited and require only simple replacement of fluids and
salts lost in diarrheal stools. This is best achieved by use of an oral rehydration
solution such as World Health Organization Oral Rehydration Salts (ORS) solution (Table
26). This solution is appropriate for treating as well as preventing dehydration. ORS
packets are available at stores or pharmacies in almost all developing countries. ORS is
prepared by adding one packet to boiled or treated water. Packet instructions should be
checked carefully to ensure that the salts are added to the correct volume of water. ORS
solution should be consumed or discarded within 12 hours if held at room temperature, or
24 hours if held refrigerated.
Iced drinks and noncarbonated bottled fluids made from water of uncertain quality
should be avoided. Dairy products aggravate diarrhea in some people and should be avoided.
