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 of 20%–50%
are commonly reported. High-risk destinations include most of the
low-income 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 some of the Caribbean islands.
TD is slightly more common in young adults than
in older people. The reasons for this difference are unclear, but
could 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 of
travel but can occur at any time during the visit and even after
returning home.
TD is acquired through ingestion of fecally contaminated
food or water or both. Both cooked and uncooked foods might be implicated
if they have been 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 can be
associated with increased risk of TD. Safe beverages include bottled
carbonated beverages (especially flavored beverages), beer, wine,
hot coffee or tea, or water boiled and 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 3–4 days.
Approximately 10% of cases persist >1 week, approximately 2% longer
than 1 month, and <1% longer than 3 months. Persistent diarrhea
is thus quite uncommon and can differ considerably from acute TD
with respect to etiology and risk factors. Approximately 15% of ill
people have vomiting, and 2%–10% have diarrhea accompanied
by fever or bloody stools or both. Travelers can have more than one
episode of TD during a single trip. Rarely is TD life threatening.
Causes of Travelers' Diarrhea
Infectious agents are the primary cause of TD. Travelers
from industrialized countries to developing countries frequently
experience a rapid, dramatic change in the type of organisms in their
gastrointestinal tract. These new organisms often include potential
enteric pathogens. Travelers with 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
among the most common causative agents of TD in all countries where
surveys have been conducted. ETEC produce a watery diarrhea associated
with cramps; fever may be low-grade or absent.
Salmonella gastroenteritis is a well-known disease
that occurs throughout the world. In industrialized nations, this
large group of organisms is the most common cause of outbreaks of
food-associated diarrhea. In low-income countries, the proportion
of cases of TD caused by nontyphoidal salmonellae varies, but is
not high. Salmonellae also can cause dysentery characterized by small-volume
stools containing bloody mucus.
Shigellae, which are well known as the cause of
bacillary dysentery, are the cause of TD in up to 20% of travelers
to developing countries.
Campylobacter jejuni is a common cause of
diarrhea throughout the world; it is responsible for a small percentage
of 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 travelers in Asia. How frequently
it causes disease in other areas of the world is unknown.
Less common bacterial pathogens include other diarrheogenic E.
coli, Yersinia enterocolitica, Vibrio cholerae O1 and O139,
non-O1 V. cholerae, Vibrio fluvialis, and possibly Aeromonas
hydrophila and Plesiomonas shigelloides.
Viral Enteric Pathogens—Rotaviruses and
Norwalk-Like Virus
The traveler may also acquire many viruses. Studies
have shown that as much as 36% of diarrheal illnesses in travelers
(median 22%) was associated with rotaviruses in the stool. However,
a comparable number of asymptomatic travelers also had rotaviruses,
and up to 50% of symptomatic people with rotavirus infections also
had nonviral pathogens. Approximately 10%–15% of travelers
have 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
travelers commonly acquire viruses, they do not appear to be frequent
causes of TD in adults.
Parasitic Enteric Pathogens
While less commonly implicated as the cause of TD
than bacteria, enteric protozoa are recognized etiologic agents of
TD. In the small number of studies that have included appropriate
testing for these parasites in travelers or expatriates in developing
countries, a variable proportion of TD, from 0% to 12%, has been
attributed to Giardia intestinalis, Entamoeba histolytica, Cryptosporidium
parvum, and Cyclospora cayetanensis. The likelihood of
a parasitic etiology is higher when diarrheal illness is prolonged. E.
histolytica should be considered when the patient has dysentery
or invasive diarrhea (bloody stools); however, E. histolytica infection
can also have mild, nonspecific symptoms. Specific diagnostic testing
is required to identify E. histolytica, C. parvum,
and C. cayetanensis. Dientamoeba fragilis, Isospora
belli, Balantidium coli, and Strongyloides stercoralis can
cause occasional cases of TD. While not common causes of TD, these
parasites should be considered in persistent, unexplained cases,
and the possibility of these agents should be discussed with the
laboratory before requesting evaluation.
Unknown Causes
No data have been published to support noninfectious
causes of TD, such as changes in diet, jet lag, altitude, and fatigue.
Existing evidence indicates that in all but a few instances, such
as drug-induced or preexisting gastrointestinal disorders, an infectious
agent or agents is the cause of diarrhea in travelers. However, even
with the application of the best existing methods for detecting bacteria,
viruses, and parasites, 20%–50% of cases of TD remain without
identified causes.
Prevention
There are four possible approaches to prevention
of TD: 1) instruction regarding food and beverage consumption, 2)
immunization, 3) use of nonantimicrobial medications, and 4) use
of prophylactic antimicrobial drugs. Data indicate that meticulous
attention to food and beverage consumption, as mentioned previously,
can decrease the likelihood of developing TD. Most travelers, however,
encounter difficulty in observing the requisite dietary restrictions
100% of the time.
No available vaccines and none that are expected
to be available in the next 3 years are effective against TD. Several
nonantimicrobial agents have been advocated for prevention of TD.
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 four times a day, or two tablets four times
a day), has decreased the incidence of diarrhea by about 60% in several
placebo-controlled studies. Side effects include temporary blackening
of the tongue and stools; occasional nausea and constipation; and,
rarely, tinnitus. Whether there is risk to the traveler from the
use of such large doses of bismuth subsalicylate for a period of >3
weeks has not been sufficiently evaluated. Bismuth subsalicylate
should be avoided by travelers with aspirin allergy, renal insufficiency,
and gout, and by those who are taking anticoagulants, probenecid,
or methotrexate. In travelers already taking aspirin or related 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 children and adolescents
with chickenpox or influenza because of a potential risk of Reye
syndrome. Bismuth subsalicylate has not been approved for infants
and children <3 years of age. Bismuth subsalicylate appears to
be an effective prophylactic agent for TD but is not recommended
for periods of >3 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, and Intestopan) are not helpful in preventing
TD, can have serious neurologic side effects, and should never be
used for prophylaxis of TD.
Prophylactic Antibiotics for the Prevention of
Travelers' Diarrhea
Controlled studies have indicated that a variety
of antibiotics, including doxycycline, trimethoprim-sulfamethoxazole
(TMP/SMX), trimethoprim alone, and the fluoroquinolone agents ciprofloxacin
and norfloxacin, when taken prophylactically have been 52%–95%
effective in preventing TD in several areas of the developing world.
The effectiveness of these agents, however, depends on the antibiotic
resistance patterns of the pathogenic bacteria in each area of travel,
and such information is seldom available. Resistance to fluoroquinolones
is the least common but this situation is changing as use of these
agents increases worldwide.
Although effective in preventing some bacterial
causes of diarrhea, antibiotics have no effect on the acquisition
of various viral and parasitic diseases. Prophylactic antibiotics
can 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 doxycyline,
fluoroquinolones, 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 (e.g., 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 might be induced by antimicrobial therapy (e.g., antibiotic-associated
colitis, Candida vaginitis, and Salmonella enteritis).
Because of the uncertain risk involved in the widespread administration
of these antimicrobial agents, their prophylactic use is not recommended.
Although it seems reasonable to use prophylactic antibiotics in certain
high-risk groups, such as travelers with immunosuppression or immunodeficiency,
no data 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, CDC does not recommend prophylactic antimicrobial
agents 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 in the following section. Some
travelers might wish to consult with their physicians and might elect
to use prophylactic antimicrobial agents for travel under special
circumstances, once the risks and benefits are clearly understood.
Treatment
Travelers 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 in 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. While the combination
appears to give the stools more consistency, it has not been shown
to decrease cramps and frequency of stools or 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 two 262.5-mg tablets every 30 minutes for eight doses) decreased
the frequency of stools and shortened the duration of illness in
several placebo-controlled studies. Treatment was limited to 48 hours
at most, with no more than eight doses in a 24-hour period. There
is concern about taking large amounts of bismuth and salicylate without
supervision, especially for people who might be intolerant of 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, such as diphenoxylate and loperamide, come in convenient
dosage forms and provide prompt symptomatic but temporary relief
of uncomplicated TD. However, they should not be used by people with
high fever or with blood in the stools. Use of these drugs should
be discontinued if symptoms persist >48 hours. Diphenoxylate and
loperamide should not be used in infants <2 years of age.
Antimicrobial Treatment
Travelers who have 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, might
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. The antibiotic regimen
most likely to be effective is ciprofloxacin (500 mg) taken twice
a day. Other fluoroquinolones, such as norfloxacin, ofloxacin, or
levofloxacin, might be equally effective. Fewer side effects and
less widespread antibiotic resistance have been reported with the
fluoroquinolones than with TMP/SMX. Three days of treatment is recommended,
although less than three days might be sufficient. Nausea
and vomiting without diarrhea should not be treated with antimicrobial
drugs. There is no contraindication to using an antimotility agent
along with an antibiotic for TD, as long as there is no high fever
or blood in the stool.
Travelers should be advised to consult a physician
rather than attempt self-medication if the diarrhea is severe or
does not resolve within several days; if there is blood or mucus,
or both, in the stools; 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 the fluids and salts lost in diarrheal
stools. Fluid replacement is best achieved by use of an oral rehydration
solution such as World Health Organization oral rehydration salts
(ORS) solution (Table 4–2). This solution
is appropriate for treating as well as preventing dehydration. Travelers
should be advised that 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 kept refrigerated.
Travelers should be advised to avoid iced drinks
and noncarbonated bottled fluids made from water of uncertain quality.
Dairy products aggravate diarrhea in some people, and travelers with
diarrhea should be advised to avoid them.
Table 4–2.
Composition of World Health Organization (WHO) Oral Rehydration
Solution for diarrheal illness
Sodium chloride |
3.5 g/L |
Potassium chloride |
1.5 G/L |
Glucose |
20.0 g/L |
Trisodium citrate* |
2.9 g/L |
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Infants with Diarrhea
Infants 2 years of age or younger are at high risk
for acquiring TD. The greatest risk to the infant with diarrhea is
dehydration (Table 4–3). Travelers
should be advised that dehydration is best prevented by use of the
WHO ORS solution in addition to the infant's usual food. 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.
Travelers should be advised to check packet instructions 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 kept refrigerated. A dehydrated
child will drink ORS avidly; travelers should be advised to give
it to the child as long as the dehydration persists. An infant who
vomits the ORS will usually keep it down if it is offered by spoon
in frequent small sips. Breast-fed infants should continue nursing
on demand. For bottle-fed infants, full-strength, lactose-free or
lactose-reduced formulas should be administered. Older infants and
children receiving semisolid or solid foods should continue to receive
their usual diet during the illness. Recommended foods include starches,
cereals, yogurt, fruits, and vegetables. Immediate medical attention
is required for the infant with diarrhea who has signs of moderate
to severe dehydration (Table 4–3),
bloody diarrhea, >30° C (>102° F) fever, or persistent
vomiting. While medical attention is being obtained, the infant should
be offered ORS.
More information is available from CDC in a publication
entitled “The
Management of Acute Diarrhea in Children: Oral Rehydration, Maintenance,
and Nutritional Therapy” (MMWR No. RR-16, October 16, 1992).
ORS packets are available in the United States from Jianas Brothers
Packaging Company, 2533 Southwest Boulevard, Kansas City, Missouri
64108 (1-816-421-2880).
In addition, Cera Products, 8265 I Patuxent Range
Road, Jessup, Maryland 20794 (1-410-997-2334 or 1-888-CERALYTE),
markets a cereal- rather than glucose-based product, Ceralyte, in
several flavors.
Table 4–3.
Assessment of dehydration levels in infants
|
General
condition |
Thirsty,
restless, agitated |
Thirsty,
restless, irritable |
Withdrawn,
somnolent, or comatose; rapid deep breathing |
Pulse |
Normal |
Rapid,
weak |
Rapid,
weak |
Anterior
fontanelle |
Normal |
Sunken |
Very
sunken |
Eyes |
Normal |
Sunken |
Very
sunken |
Tears |
Present |
Absent |
Absent |
Mucous
membranes |
Slightly
dry |
Dry |
Dry |
Skin
turgor |
Normal |
Decreased |
Decreased,
with tenting |
Urine |
Normal |
Reduced,
concentrated |
None
for several hours |
Weight
loss |
4%–5% |
6%–9% |
>10% |
|
|
Precautions for Children and Pregnant Women
Although infants and children do not make up a large
proportion of travelers to high-risk areas, some children do accompany
their families. Teenagers should follow the advice given to adults,
with possible adjustments of doses of medication. Physicians should
be aware of the risks of tetracyclines for infants and children <8
years of age. Few data are available about the use of antidiarrheal
drugs in infants and children. Drugs should be prescribed with caution
for pregnant women and nursing mothers.
— Caryn
Bern, Barbara Herwaldt, Phyllis Kozarsky, Stephen Luby, James Maguire
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