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 beverages), 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.
Campylocater
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 1). 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.
TABLE 1. Composition
of World Health Organization Oral Rehydration Solution (ORS) for
Diarrheal Illness
|
| Ingredient |
Amount |
|
| Sodium chloride |
3.5 grams/liter |
| Potassium chloride |
1.5 grams/liter |
| Glucose |
20.0 grams/liter |
| Trisodium citrate* |
2.9 grams/liter |
|
| *An earlier formulation
used sodium bicarbonate 2.5 grams/liter had a shorter shelf-life,
but was physiologically equivalent, and may still be produced
in some countries. |
Infants
with Diarrhea
Children aged 0-2 years are at high risk of acquiring traveler's
diarrhea. The greatest risk to the infant with diarrhea is dehydration.
Dehydration is best prevented by use of 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. 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. The dehydrated child will drink ORS
avidly; ORS is given to the child as long as the dehydration persists.
The 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 children receiving semi-solid 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
develops signs of moderate to severe dehydration (Table 2), bloody
diarrhea, fever of greater than 102 o F, or persistent vomiting.
While medical attention is being obtained, the infant should be
offered ORS.
Precautions
in Children and Pregnant Women
Although 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
adjustment of doses of medication. Physicians should be aware
of the risks of tetracyclines to children under 8 years of age.
There are few data available about usage of antidiarrheal drugs
in children. Drugs should be prescribed with caution for pregnant
women and nursing mothers.
TABLE 2. Assessment
of the Dehydration Levels in Infants
| |
Signs |
| Mild |
Moderate |
Severe |
| General Condition |
Thirsty,
restless,
agitated |
Thirsty,
Restless,
irritable |
Withdrawn,
somnolent,
or comatose |
| Pulse |
Normal |
Rapid and weak |
Rapid and weak |
| Anterior fontanelle |
Normal |
Sunken |
Very sunken |
| Eyes |
Normal |
Sunken |
Very sunken |
| Tears |
Present |
Absent |
Absent |
| Urine |
Normal |
Reduced and
concentrated |
None for
several hours |
| Weight loss |
4-5% |
6-9% |
10% or more |
†
Use of tradenames is for identification only and does not imply
endorsement by the Public Health Service or the U.S. Department
of Health and Human Services. 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, Kansas
City, Missouri (telephone:(816)421- 2880).
Reference:
CDC Health Information for International Travel
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