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STATE-OF-THE-ART CLINICAL ARTICLE
Protection of Travelers
Martin S. Wolfe
From Traveler’s Medical Service, Washington, D.C.
Approximately 15 million Americans travel abroad each
year, and about half of them go to the developing world. Tourists usually visit these areas for a period of weeks, during which
time they may be exposed to diseases that are not present, or
are at best rare, in the United States. Longer-term travelers or
expatriates in the developing world are at an increased and
prolonged risk of becoming ill.
It is necessary for physicians who deal with traveling patients
to be familiar with the potential diseases to which such patients
might be exposed. Advice on immunizations, malaria prophylaxis, prevention and self-treatment of traveler’s diarrhea, and
other preventive measures must be given before travel. In addition, on the traveler’s return, there must be an awareness and
recognition of problems resulting from the trip.
Perhaps the most valuable general resource for information
on preventive measures for travelers is Health Information for
International Travel, published by the U.S. Public Health Service and revised yearly. This and other helpful publications are
listed and annotated in the suggested reading list at the end of
this paper.
Recommended items for a medical kit and information on
their use can be found in Health Hints for the Tropics, published by the American Society of Tropical Medicine and Hygiene.
Immunization
Endemic and Epidemic Diseases
Yellow fever. Since the 1980s, there has been a reemergence
of yellow fever in areas of Africa and South America where this
disease is endemic. In 1996, a Swiss traveler and an American
traveler returned to their countries with yellow fever, which
they contracted near Manaus, Brazil; both died. Neither had
been vaccinated against yellow fever [1]. Yellow fever vaccine
is required both for protection against infection in areas of
endemicity and for entry into these areas and other countries
subsequently visited. This is the only vaccine required for entry
Received 5 March 1997; revised 15 April 1997.
Reprints or correspondence: Dr. Martin S. Wolfe, Traveler’s Medical Service, 2141 K Street, N.W., Washington, DC 20037.
Clinical Infectious Diseases 1997;25:177–86
q 1997 by The University of Chicago. All rights reserved.
1058–4838/97/2502–0001$03.00
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into particular countries (listed in Health Information for International Travel).
Yellow fever vaccine is administered only at designated centers, and the date of immunization and origin and batch of the
vaccine must be recorded on the International Certificate of
Vaccination, which is then valid for 10 years. Children below
the age of 9 months are usually exempted from these requirements, as are persons who are allergic to eggs, pregnant, or
immunosuppressed. Yellow fever vaccine is associated with
mild reactions that occur 5 – 10 days after vaccination in £5%
of recipients.
Cholera. In 1988, the World Health Organization (WHO)
dropped the requirement for cholera vaccine, and the International Certificate of Vaccination no longer has a special section
for cholera. Cholera vaccine is not recommended for most
travelers, even those to cholera-epidemic areas such as South
America, because the currently available, injectable, inactivated vaccine is not very effective in preventing cholera. Travelers should practice appropriate hygiene in handling food and
water to prevent cholera as well as numerous other diseases.
The new oral cholera vaccines are effective and better tolerated and provide high-level protection, at least for several
months. An inactivated whole-cell Vibrio cholerae 01 plus
recombinant B subunit of cholera toxin (WC/rBS) vaccine has
been marketed in Sweden. A second live, oral, single-dose,
genetically engineered vaccine (CVD 103-HgR) is now marketed in a number of European countries [2]. Neither of these
vaccines appears to offer protection against the recently occurring 0139 serogroup of V. cholerae. The WHO has not yet
formulated recommendations on the use of these vaccines in
travelers, and when these vaccines will be available in the
United States is not yet known.
Smallpox. The last reported case of endemic smallpox occurred in 1977. In 1982, the WHO deleted smallpox from the
list of diseases subject to the International Health Regulations.
The risk from smallpox vaccine exceeds the risk of smallpox,
and smallpox vaccination is not indicated for any international
traveler.
Certain other vaccines are recommended for protection
against diseases prevalent in many parts of the world. For
children, routine childhood immunizations should be up-todate before travel is undertaken.
Poliomyelitis. In September 1994, the Pan American Health
Organization certified that wild poliovirus transmission has
been interrupted in the Americas. Wild poliovirus continues to
circulate elsewhere, and until the world is certified as being
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polio free, high levels of coverage by immunization must be
maintained. Polio remains a definite hazard to travelers to polio-affected areas of the developing world. Many travelers have
had the basic series of trivalent oral polio vaccine (OPV) or
enhanced-potency inactivated injectable polio vaccine (IPV)
during childhood. For such persons, a single booster dose of
either vaccine is recommended before travel; the need for further supplementary booster doses has not been established.
Unvaccinated or partially vaccinated travelers should complete a primary vaccination series with the vaccine that is appropriate to their age and previous immunization status. Unvaccinated adult travelers (those ú18 years of age) should
preferably receive IPV, as the risk of vaccine-associated paralysis following OPV is slightly higher for adults than for children.
Tetanus and diphtheria. It is essential for all Americans,
traveling or not, to maintain immunity against these two diseases by getting a booster dose of vaccine at 10-year intervals.
Most travelers will have received the basic series of diphtheriapertussis-tetanus (D-P-T) vaccine during childhood. For boosters, persons ú7 years of age receive a tetanus and diphtheria
toxoid (Td) vaccine that has a smaller amount of diphtheria
toxoid. In recent years there has been an outbreak of diphtheria
in Russia and the new independent states, and travelers to this
region must be protected against this disease [3].
Measles. In the United States, children are routinely vaccinated against measles, usually with the measles-mumps-rubella
(MMR) vaccine, at age 15 months. The risk of contracting
measles is much greater in the developing world than in the
United States, and the age of vaccination should be lowered
to 6 months for younger children traveling to measles endemic
or epidemic areas. A dose of single antigen measles or MMR
vaccine should be given, and these children should then be
revaccinated with an additional dose of MMR vaccine at age
12 – 15 months and at entry into school.
Almost all infants õ6 months of age will be protected by
maternal measles antibody, and no additional means of providing protection against measles is considered necessary for children in this age group. Adults born in the United States before
1957 are considered immune to measles, but persons born after
1957 who travel abroad should be protected against measles.
Those travelers who have not previously received two doses
of measles vaccine and who do not have a history of measles
should receive one dose of measles vaccine unless there is a
contraindication [4].
Typhoid fever. This disease is endemic in much of the developing world, and typhoid vaccine is recommended for travelers
to those areas, where it is difficult to follow good water and
food hygiene practices. The parenteral inactivated vaccine was
formerly the only available vaccine; immunization with this vaccine required a basic series of two doses given 4 weeks apart
and a booster dose given at 3-year intervals for continued protection. This vaccine is only 70% effective and is not well tolerated.
An oral, live-attenuated Ty21a-strain vaccine is available; this
vaccine is administered in capsule form, with one capsule taken
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every other day for 4 days. It is no more protective than the
two-dose parenteral vaccine but is much better tolerated, and a
booster series is required only every 5 years [5].
A parenteral capsular polysaccharide Vi-antigen vaccine
(Typhim Vi, Connaught Laboratories, Swiftwater, PA) has also
been licensed in the United States. A single dose will offer
simpler and similar protection for 2 years, and fewer adverse
reactions have been reported in association with this vaccine
than with the presently available two-dose injectable vaccine.
This vaccine will be of particular value for persons who must
travel immediately and have not previously received a basic
typhoid vaccine series [6].
Meningococcal meningitis. Meningococcal meningitis is endemic throughout the world, but particular areas are recognized
where epidemics due to Neisseria meningitidis serogroup A
and C occur. In the sub-Saharan Sahel region of Africa, epidemics due to these serogroups occur almost yearly in the
winter and early spring months. Epidemics have also occurred
in Nepal, parts of India, Mongolia, Saudi Arabia, and East
and Central Africa [7]. Meningitis is extremely uncommon in
travelers, but immunization with the quadrivalent A/C/Y/W135 vaccine is recommended for all travelers to the above
areas. Saudi Arabia requires proof of immunization for meningococcal meningitis from all visa applicants. Outbreaks of meningococcal meningitis due to N. meningitidis serogroup B also
occur, but there is currently no available vaccine against this
serogroup [8].
Rabies. Relatively few countries can be considered rabies
free (see Health Information for International Travel for listing). A three-dose preexposure vaccination series (1 mL administered intramuscularly over the deltoid muscle) can be recommended for individuals at high risk in rabies-endemic areas
where risk of infection, primarily from dog bites, is a constant
threat. These might include young children, joggers, persons
who work with animals, field-workers, and persons in remote
areas who are distant from facilities where postexposure treatment can be obtained.
Preexposure immunization offers valuable added protection
when exposure to rabies occurs; however, administration of
two postexposure vaccine doses is still required. The need for
human rabies immune globulin, which is often difficult to obtain, is eliminated. Two vaccines, both very expensive, are
currently available: human diploid cell vaccine (HDCV) and
rabies vaccine, adsorbed (RVA) [9]. The need for administering
routine booster doses of vaccine depends on the exposure risk
category noted in Health Information for International Travel.
The benefit from booster doses must be weighed against an
Ç6% occurrence of an immune-complex-like reaction to the
booster doses.
Japanese encephalitis. Rare cases of Japanese encephalitis
(JE) have occurred in resident expatriates and travelers in certain areas of the Far East and Southeast Asia where JE is
endemic. The risk to short-term travelers to urban areas in
these regions is very low. Persons who travel or reside in
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Protection of Travelers
rural agricultural areas of countries where JE is endemic are
at greater risk. A three-dose JE vaccine series is recommended
for persons spending §1 month in areas of endemicity during
the transmission season, especially if travel will include rural
areas, and for certain shorter-term travelers to areas where
epidemics occur and risk is high.
JE vaccine is associated with moderately frequent local and
mild systemic side effects and uncommonly with more serious
adverse reactions, which are characterized by urticaria, angioedema, itching, and, rarely, respiratory distress. The rate of
serious reactions among American citizens is approximately
two-to-six per 1,000 recipients, and these reactions may be
delayed in onset for £2 weeks [10].
Hepatitis. Hepatitis A is the most common type of hepatitis
contracted by unprotected travelers to areas of endemicity [11].
Two hepatitis A vaccines are now available in the United
States. HAVRIX (SmithKline Beecham, Philadelphia) was approved in 1995 and VAQTA (Merck, Westpoint, PA) became
available in 1996. HAVRIX is marketed in a 1,440-unit formulation for adults and a 720-unit formulation for children 2 – 18
years of age. VAQTA is supplied as a dose of 50 units per
milliliter for adults and as a dose of 25 units per 0.5 milliliters
for children and adolescents 2 – 17 years of age.
Following administration of an initial single dose of either
vaccine, protective immunity can be assumed to be present by
4 weeks. Since protection may not be complete until 4 weeks
after vaccination, persons traveling to a high-risk area õ4
weeks after administration of the initial dose should also receive an injection of immune globulin (0.02 mL/kg) at a different site. A second booster dose of hepatitis A vaccine, given
6 – 12 months after the initial dose, is expected to give longterm protection (possibly for §20 years) [12].
Immune globulin is an alternative protective measure and
can be used in children õ2 years of age. It is very uncommon
for a traveler or long-term resident to develop symptomatic
hepatitis A when the appropriate dose of immune globulin is
taken. Persons undertaking short-term travel (for õ3 months)
will be protected by a single intramuscular dose (0.02 mL/
kg). Persons undertaking travel for longer periods, as well as
residents, should receive an intramuscular dose of 0.06 mL/kg
at 4-month to no more than 6-month intervals.
No transmission of hepatitis B virus, HIV, hepatitis C virus,
or other viruses have been reported in association with the use
of intramuscular immune globulin [12]. However, because of
concern over possible transmission of hepatitis C virus by immune globulin and some other globulin products, the U.S. Food
and Drug Administration (FDA) is requiring manufacturers to
initiate a new inactivation process. During the time needed
to implement the particular inactivation step and obtain FDA
approval, the major manufacturer of immune globulin in the
United States has voluntarily withdrawn this product from the
market, making immune globulin presently very difficult to
obtain. Immune globulin is not protective against hepatitis
types B, C, and E.
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Hepatitis B is more prevalent in the developing world and
is a particular hazard for those travelers who might have contact
with blood or have sexual contact with local residents. When
these types of contacts are likely to occur, a recombinant hepatitis B vaccine series can be administered. Both available vaccines can be given in a standard three-dose series over a 6month period; however, Engerix B (SmithKline Beecham) is
approved for an accelerated course of 3 monthly doses, with
a fourth booster dose given 12 months after the first dose.
Although hepatitis B vaccine is safe and effective, its relatively
high cost and the extended course of doses are major inhibitors
of its wide use in travelers.
Influenza and pneumococcal infection. Persons considered at
high risk of contracting influenza who are traveling to areas of
the world where influenza is epidemic should receive influenza
vaccine. Pneumococcal polysaccharide vaccine is recommended
for the prevention of pneumococcal infection only in persons at
high risk for the infection; such persons would receive it in the
United States as well as while traveling. These two vaccines
can be given simultaneously, with no decrease in effectiveness
or increase in adverse reactions.
Some vaccines are no longer required or available, including
smallpox and typhus vaccines. BCG vaccine is rarely recommended for American travelers, but the worldwide increase in
multidrug-resistant tuberculosis may reawaken interest in this
product. Certain vaccines are indicated only for specific situations or for travel to specific, remote locations.
Plague. The recent outbreak of bubonic and pneumonic
plague in India and the periodic occurrence of limited plague
outbreaks in more remote areas make vaccination against
plague a consideration for certain individuals at high risk for
this disease. These persons include mammologists, ecologists,
and other field-workers who have regular contact with wild
rodents or their fleas in areas where plague is enzootic or
epizootic. The usual traveler to plague-endemic countries is at
low risk of infection. Plague vaccine has a number of drawbacks, including the fact that it became totally unavailable
during the recent outbreak in India. It is not effective against
pneumonic plague; a series of doses and periodic booster doses
are required to maintain immunity; and reactions occur frequently.
It would be better for travelers who are genuinely at risk
for acquiring plague to consider antibiotic prophylaxis with
doxycycline (100 mg b.i.d.) during periods of exposure in areas
where plague is actively epizootic or endemic. However, this
recommendation is extrapolated from experience with tetracycline for the treatment of plague, since the results of controlled
chemoprophylaxis trials have not been reported. Plague vaccine
is manufactured by Greer Laboratories (P.O. Box 800, Lenoir,
NC) [13].
Tick-borne encephalitis. This is a viral infection of the CNS,
which occurs in forested areas of central and eastern Europe
and the former Soviet Union. An effective vaccine may be
obtained in Europe and can be considered for those travelers
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or residents who are at risk of exposure to forested areas of
those countries where the disease is endemic [14].
Vaccination During Pregnancy
Pregnancy and breast-feeding are not contraindications to
the administration of toxoid vaccines, killed or inactivated vaccines, or immune globulin when risk of infection is present.
Live measles-mumps-rubella vaccines and live oral typhoid
vaccine are contraindicated during pregnancy. If inactivated
polio vaccine is not available, pregnant women at risk of exposure to polio should receive oral polio vaccine. Yellow fever
vaccine is contraindicated unless exposure to yellow fever virus
is unavoidable.
Altered Immunocompetence
Killed or inactivated vaccines and immune globulin are not
contraindicated for immunocompromised persons. Oral polio
vaccine should not be given to any immunocompromised person or their household contacts or other close contacts. Except
in highly unusual circumstances, yellow fever vaccine is contraindicated for immunosuppressed persons. Measles-mumpsrubella vaccine is recommended for immunosuppressed individuals for whom it is indicated. For detailed information on
vaccines and other travel health advice for HIV-infected travelers, see [15].
Prevention of Malaria
Malaria is one of the greatest risks to travelers to many parts
of the developing world. When traveling where malaria occurs,
it is essential to take effective antimalarial drug prophylaxis
and to practice mosquito-avoidance measures.
Drug prophylaxis. Falciparum malaria is the most serious
species of malaria; Plasmodium falciparum is widely resistant
to chloroquine and, to a lesser extent, to other available antimalarial drugs. Chloroquine resistance of P. falciparum is absent only in Haiti, the Dominican Republic, Central America,
and parts of the Middle East. In these areas, a weekly 500-mg
dose of chloroquine phosphate (equal to 300 mg base) can be
used. In the United States, generic chloroquine phosphate is
not available, and only oral Aralen phosphate (500-mg salt
tablet; Sanofi Winthrop, New York) can be purchased. Aralen
is much more expensive, the 500-mg strength tablet is difficult
to administer to children, and the pink-coated tablets resemble
candy and have led to lethal overdoses in young children. Other
tablet and liquid formulations of chloroquine are available
abroad. Serious eye damage does not occur with the recommended weekly dose of chloroquine [16]. Chloroquine is considered safe for use during pregnancy.
For protection against chloroquine-resistant P. falciparum
malaria, which is present in most malaria-endemic areas, there
are three available regimens recommended by experts in the
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United States. The most effective regimen for adults is a weekly
250-mg dose of mefloquine (Lariam; Roche Laboratories, Nutley, NJ). There is a rather high degree of mefloquine resistance
among P. falciparum parasites in border areas of Thailand and
in Cambodia and Papua New Guinea, and rare confirmed cases
of resistance in tropical Africa and other malarious areas have
been reported.
Comparative studies have indicated that the adverse effects
of mefloquine are similar in frequency and quality to those
of chloroquine. Reported adverse effects of mefloquine include
insomnia, bad dreams, dizziness, headache, irritability, and gastrointestinal symptoms. More-serious reactions—toxic psychosis and hallucinations—occur in approximately one in 10,000
users [17]. A study of long-term mefloquine use in Peace Corps
volunteers in Africa showed this drug to be well tolerated [18].
However, in a more recent study of travelers from the United
Kingdom, it was reported that 0.7% of these travelers had a
neuropsychiatric adverse event unpleasant enough to temporarily
prevent them from carrying out their day-to-day activities [19].
Contraindications to mefloquine therapy include a history of
psychiatric disorders or epilepsy and abnormalities of the cardiac
conduction system. Mefloquine is not recommended for emergency self-treatment of malaria because of the more frequent
side effects (hallucinations and convulsions) associated with the
high dosages used for treatment of malaria. Mefloquine is safe
for use in pregnant women and young children.
For travelers who cannot tolerate mefloquine or have a condition that contraindicates its use and in those areas where considerable resistance to mefloquine is present, doxycycline, at a
daily dose of 100 mg, can be used by adults [20]. Doxycycline
cannot be used by pregnant women or children õ8 years of age.
Potential adverse effects associated with doxycycline include
photosensitivity, gastrointestinal effects, and moniliasis.
For persons who are unable to use either mefloquine or
doxycycline, a weekly dose of chloroquine phosphate (as
above) plus a 200-mg daily dose of proguanil (Paludrine; Imperial Chemical Industries, Macclesfield, Cheshire, England) are
recommended. Both these drugs are considered safe for use
during pregnancy. Paludrine is not available in the United
States but can be obtained abroad. The combination of chloroquine and proguanil is the least effective of the available
regimens [17]. It is recommended that travelers using this combination carry Fansidar (pyrimethamine-sulfadoxine; Roche)
for emergency self-treatment. Halfan (halofantrine) (Smith
Kline Beecham), which is used only for treatment abroad, was
expected to be of particular value for self-treatment. However,
recent serious cardiac arrhythmias have been reported in association with the use of this drug, which has held up its marketing
in this country and has dampened enthusiasm for its use in
unsupervised self-treatment [21].
All of the regimens must be taken regularly while travelers
are in malarious areas, and these regimens must be taken for
4 weeks after leaving these areas. Amodiaquine (Parke-Davis,
France) and Maloprim (pyrimethamine/dapsone) (Wellcome,
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Protection of Travelers
London) are used abroad, but neither is available in the United
States. Both have been associated with bone marrow toxicity
and are not recommended. Fansidar is no longer recommended
for prophylaxis because of the high incidence of fatal cases of
Stevens-Johnson syndrome associated with the prophylactic
use of the drug.
Chloroquine-resistant P. vivax malaria is present in Indonesia, Papua New Guinea, and parts of Southeast Asia and Latin
America. Primaquine resistance among P. vivax parasites is
also present in these same areas as well as in the Solomon
Islands, and higher doses of the drug may be required to eliminate infection [22]. To prevent potential subsequent relapsing
malaria that is associated with persisting liver forms of
P. vivax and Plasmodium ovale, which are not eliminated by
other antimalarial drugs and can occur for £3 years after travelers have left most malarious areas, therapy with primaquine
should be considered. This treatment is particularly important
for persons who have had intense or prolonged exposure in
malarious areas. Primaquine is taken after the conclusion of
terminal suppressive therapy with one of the above described
regimens. The dose is 15 mg of base, given daily for 14 days
for adults and 0.3 mg of base/kgrd (not to exceed 15 mg) for
young children. Primaquine may cause severe hemolysis in
persons with glucose-6-phosphate dehydrogenase deficiency;
therefore, this condition must be ruled out before primaquine is
used. Pregnancy is a contraindication to the use of primaquine.
Mosquito avoidance measures. Transmission of malaria by
mosquitoes occurs primarily between dusk and dawn. Since
drug prophylaxis is imperfect, measures to reduce contact with
mosquitoes during those hours are an essential adjunct in the
prevention of malaria. These measures include: (1) remaining
in well-screened areas; (2) using mosquito nets, preferably impregnated with permethrin or deltamethrin [23]; (3) wearing
clothes that cover most of the body, although this may be
uncomfortable in a tropical environment; (4) using insect repellents containing deet (diethyltoluamide) (an optimum repellant
is a 35% deet-concentration lotion in a long-acting formulation,
commercially available as Hour Guard (available from Amway
distributors); high concentrations of deet may cause a severe
rash, seizures, and neurological damage in children); (5) using
permethrin (Permanone; Fairfield American, Newark, NJ) insecticide as a repellant spray for clothing and to impregnate
mosquito bed nets; and (6) using pyrethrum-containing flyinginsect spray in living areas.
Even with conscientious use of drug prophylaxis and antimosquito measures, it is still possible to contract malaria. Travelers
who have returned from malarious areas and develop fever §10
days (or up to 3 years) after initial exposure to malaria while
traveling should be promptly evaluated for possible malarial infection. Research is continuing on a malaria vaccine, but such a
vaccine is not expected to be available for some years.
Traveler’s Diarrhea
Up to half of the travelers from industrialized countries who
visit the developing world develop diarrhea, often accompanied
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by low-grade fever, abdominal cramping, or vomiting. The
most common etiology is bacteria; enterotoxigenic Escherichia
coli is by far the leading agent. Other important bacterial agents
are Shigella species, Campylobacter jejuni, and Salmonella
species. Aeromonas species, Plesiomonas shigelloides, and
Vibrio parahaemolyticus are less commonly recognized causes.
Rotavirus and the Norwalk agent are the usual viral etiologies.
Most intestinal parasites have a relatively longer incubation
period than do bacteria and viruses, and the initial symptoms
of parasitic infection usually occur following return from travel.
Cryptosporidiosis and Entamoeba histolytica infection can occasionally cause symptoms within a few days of infection [24].
Prevention. Infection primarily occurs from consuming microbiologically contaminated food and water. Recommended
preventive measures to be practiced by the traveler include:
(1) eating well-cooked foods; (2) avoiding vegetable salads,
unpeeled fruits, and ice cubes; (3) boiling drinking water for
3 minutes, which should effectively kill all organisms in the
water and will compensate for thermal barriers (filth) and
higher elevations; (4) disinfecting water with iodine tablets or
portable iodine resin filters; (5) avoiding dairy products unless
they are known to be hygienically prepared, pasteurized, and
properly refrigerated; (6) avoiding custards, cream pastries,
salads made with mayonnaise, and raw or poorly steamed shellfish, since these are excellent vehicles for the growth and multiplication of pathogenic organisms that cause food poisoning.
Meticulous attention to the food and beverage hygiene measures described above can decrease the likelihood that traveler’s
diarrhea will occur, but this meticulousness is admittedly difficult to accomplish. Other preventive measures include frequent
handwashing and the use of prophylactic Pepto-Bismol (bismuth subsalicylate) and prophylactic antibiotic drugs. There
are no current vaccines against the common agents of traveler’s
diarrhea. The use of Pepto-Bismol in a dosage of two tablets
four times daily for periods of £3 weeks appears to be a safe
and effective means of reducing the occurrence of traveler’s
diarrhea by Ç65% in persons at risk [24]. Persons who are
already taking salicylates should not use prophylactic PeptoBismol.
The use of a number of antibiotics has been shown to reduce
the incidence of traveler’s diarrhea, but significant resistance to
tetracycline and trimethoprim-sulfamethoxazole has emerged
worldwide [24]. At present, the fluoroquinolones are very efficacious in preventing traveler’s diarrhea, are not associated
with serious side effects, and are well tolerated. However, several factors, including the usual self-limited nature of traveler’s
diarrhea, the expense, and the lack of effective treatment options for persons who develop diarrhea while receiving fluoroquinolone chemoprophylaxis render prophylaxis with the fluoroquinolones undesirable, since these drugs are currently the
treatment of choice [25].
Treatment. The most important factor in treating traveler’s
diarrhea is the replacement of lost fluids and electrolytes. Such
beverages as tea, broth, carbonated beverages, and fruit juices
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can be consumed to replace lost fluid. Electrolytes can be replaced by consuming salted crackers or a similar source of
sodium chloride. Infants and children may require commercially available rehydration salts in packets, which are diluted
in potable water [24]. For most patients, this is the only treatment required because the diarrheal illness is usually of shortduration and self-limited.
When bowel movements are frequent and abdominal cramps
are severe, antisecretory or antimotility agents may be used.
Pepto-Bismol liquid, taken in a dose of 1 oz every half-hour
for a total of eight doses, is effective because of its antisecretory
activity. Loperamide (Imodium; Janssen Pharmaceutica, Titusville, NJ) and diphenoxylate (Lomotil; G. D. Searle, Chicago)
are commonly used antimotility drugs. Imodium is taken initially in a dose of 4 mg, followed by a 2-mg capsule after each
unformed stool (the total number of capsules should not exceed
eight per day). Lomotil is taken as one tablet every 4 – 6 hours.
As Lomotil contains atropine, dry mouth or urinary retention
is a potential troublesome side effect in the elderly.
Neither of these two antimotility agents is recommended for
children õ2 years of age. A liquid Imodium preparation is
available for children older than 2 years. A number of commonly used products have not conclusively been shown to be
effective in providing symptomatic relief and are not recommended. These include kaolin plus pectin (Kaopectate), which
only gives more consistency to stools; activated charcoal; lactobacillus preparations; and yogurt.
If, after these measures, significant diarrhea continues for
ú3 days or worsens, if blood or mucus is present in the stool,
or if high fever, chills, or severe cramps are present, antibiotic
treatment is indicated. When possible, such treatment should
be administered under the care of a physician. If medical care
is not available and the possibility of this situation has been
discussed with a physician before travel is undertaken, emergency self-treatment is appropriate. There is currently widespread bacterial resistance to most antimicrobials including tetracyclines, trimethoprim-sulfamethoxazole, and ampicillin.
The most effective drugs against all of the usual causative
bacterial agents, including Campylobacter species (for which
trimethoprim-sulfamethoxazole is not useful), are the fluoroquinolones, administered in a 3 – 5 day course. Fluoroquinolone-resistant Campylobacter organisms have recently
emerged, resulting in subsequent relapse of disease. The combination of a fluoroquinolone and loperamide is believed to represent optimal treatment.
General Travel Advice
Flying
Today, long-distance travel is almost always by air, and jet
lag is an expected problem because of disturbances in circadian
rhythm. The average traveler requires Ç1 day to readjust for
every 1 or 2 hours of time change. A variety of techniques
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have recently been developed to prevent jet lag, including a
jet-lag diet, which is started 3 days before travel; attempts to
shift the biological clock to the new time zone by the use of
a bright light head visor and related methods; and the use of
melatonin [26]. A mild sedative may help travelers sleep for
the first nights after arrival in the new time zone.
Motion sickness may be prevented with dimenhydrinate,
meclizine, or a scopolamine disk. Moderation or, better yet,
abstinence from alcohol and excessive and heavy food and
from smoking while flying will result in a more comfortable
trip. Prolonged sitting should be avoided, particularly to prevent venous stasis in the legs and possible formation of pulmonary emboli. If travelers with colds must fly, they should take
nasal decongestants before takeoff and landing.
Acclimatization
Adjustment to high altitudes requires time. It is helpful to
avoid alcoholic beverages, tobacco, excessive food, and, initially, heavy exercise. During time spent at higher altitudes,
increased water intake is necessary. Acetazolamide, at a dose
of 125 mg twice a day, can be taken to prevent altitude sickness.
This dose is as effective as a dose of 250 mg b.i.d., produces
less water loss through urination, and causes fewer side effects.
The drug should be taken on the day of ascent and for the first
2 days at the higher altitude.
Sun and Heat Problems
These are best avoided by limiting prolonged exposure to
the sun and by avoiding overly strenuous exercise. Protection
against strong sunlight can be obtained by applying a broadspectrum sunscreen (that protects against both ultraviolet A
and B) to the skin 30 – 60 minutes before exposure to sunlight.
Sunscreen should be reapplied every 1 – 3 hours after swimming
or sweating, and sunscreens with a sun protection factor of 15
or greater offer a longer period of protection. Ultraviolet radiation can insidiously cause ocular damage, and wearing sunglasses is the best way to prevent this problem. The risk of
heatstroke and sunstroke can be decreased by drinking extra
fluids and adding salt to food; rapid cooling is the mainstay of
treatment.
Prevention of Specific Diseases
Schistosomiasis and infection due to other waterborne organisms. Schistosomiasis can be contracted only in fresh water,
not in the ocean or in chlorinated swimming pools. Even a
single exposure to fresh water in areas of Africa, Latin America,
and the Middle East, where schistosomiasis is endemic, can
lead to infection. Recently, severe and unusual manifestations
of Schistosoma haematobium infection contracted in Lake Malawi in Central Africa have been recognized in the United
States and Europe.
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Protection of Travelers
Attractive ocean beaches, particularly in urban areas, may be
highly polluted. Corals, jellyfish, and other biting and stinging
aquatic creatures are another hazard to bathers.
Sleeping sickness. African trypanosomiasis, or sleeping sickness, is a potential hazard, particularly in the game parks of
East, Central, and South Africa, where wild animals are the
reservoir and the tsetse fly is the vector. Only a handful of
cases have occurred in travelers from the United States. Drug
prophylaxis is not recommended, but the risk of tsetse fly bites
can be decreased by wearing long shirts and trousers and by
using insect repellants.
Bites of snakes and other venomous creatures. Snakes are
usually nocturnal and will generally bite during the day only
if they are attacked or surprised. Boots with long trousers
tucked into them should be worn in areas where poisonous
snakes are present. For travel to remote areas, a snake-bite kit
containing antivenom against local snakes or scorpions should
be taken along. Personal protection measures, similar to those
described with respect to malaria mosquito vectors, are recommended for insects. Travelers with histories of anaphylactic
reactions to the bites of venomous insects should carry an
anaphylactic kit (Ana-Kit [Bayer, West Haven, CT] or EpiPen [Center Laboratories, Port Washington, NY]) and wear an
allergy bracelet.
Skin diseases. Many preexisting skin conditions may be aggravated by humid and hot tropical climates. Skin and clothes
must be kept dry and clean to avoid chafing and prickly heat.
Scabies and lice are best prevented by careful washing of the
body and clothes.
Fungus infection is perhaps the most common skin disorder
in travelers. A topical antifungal lotion should be carried by any
traveler prone to these infections. Athlete’s foot is especially
troublesome in the moist tropics, and regular use of foot powder
and dry socks help prevent it.
Fly-larva infection of the skin (cutaneous myiasis) occurs in
Latin America. In tropical Africa, the tumbu fly deposits eggs
on unironed clothes that are dried outdoors. Larvae hatch in a
few days and then penetrate the skin when it comes in contact
with the clothes, causing a tender boil-like lesion. This infection
can be prevented by ironing clothes dried outdoors.
Travelers to tropical areas should not walk barefoot because
the skin can be invaded by sand fleas, a condition known as
tungiasis. Hookworms and Strongyloides may also penetrate bare
skin, particularly the feet. Hookworms in dogs and cats can
cause creeping eruption on exposed areas of the skin that come
in contact with sandy soil containing the infective larvae.
Return from Travel
Evaluation by a physician usually is not necessary for
persons who remain healthy during and after short-term
travel. Travelers who have undertaken longer-term travel,
as well as residents of areas where the diseases discussed
herein are endemic, should undergo a checkup even if they
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are asymptomatic. Such a checkup should include a physical
examination, complete blood count, chemistry profile, tuberculin skin test, and stool examinations for ova and parasites.
If exposure has occurred, serological screening should be
performed for such infections as HIV infection and schistosomiasis. Both travelers and their physicians must always
consider previous travel in the evaluation of symptoms that
appear months or, rarely, years after they return home.
Symptoms to be concerned about include fever, chills,
sweats, fatigue, anorexia, persistent nausea or diarrhea,
cramps, excessive gas, and weight loss. Differential diagnosis, diagnostic methods, and treatment for symptomatic returnees are fully described in the texts by DuPont, Jong, and
Wolfe (‘‘Travel Medicine’’) in the suggested reading list
that follows.
References
1. World Health Organization. Yellow fever in a traveller. Wkly Epidemiol
Rec 1996; 71:342 – 3.
2. World Health Organization. Cholera in 1994: part II. Wkly Epidemiol Rec
1995; 70:209 – 11.
3. Centers for Disease Control. Diphtheria acquired by U.S. citizens in the
Russian Federation and Ukraine — 1994. MMWR Morb Mortal Wkly
Rep 1995; 44:237 – 44.
4. Hill DR, Pearson RD. Measles prophylaxis for international travel [editorial]. Ann Intern Med 1989; 111:699 – 701.
5. Bennish ML. Immunization against Salmonella typhi. Infect Dis Clin Pract
1995; 4:114 – 22.
6. Wolfe MS. Typhim Vi: a new typhoid vaccine. Infect Dis Clin Pract 1995;
4:186 – 8.
7. World Health Organization. Meningococcal meningitis. Wkly Epidemiol
Rec 1995; 70:105 – 7.
8. Wolfe MS. Meningococcal meningitis vaccine for travelers. Infect Dis
Clin Pract 1992; 1:409 – 10.
9. Centers for Disease Control. Rabies prevention—United States, 1991: recommendations of the Advisory Committee on Immunization Practices
(ACIP). MMWR Morb Mortal Wkly Rep 1991;40(RR-3):1–19.
10. Centers for Disease Control. Inactivated Japanese encephalitis virus vaccine.
Recommendations of the Advisory Committee on Immunization Practices
(ACIP). MMWR Morb Mortal Wkly Rep 1993;42(RR-1):1–15.
11. Wolfe MS. Hepatitis A and the American traveler. J Infect Dis 1995;
171(suppl 1):S29 – 32.
12. Centers for Disease Control and Prevention. Prevention of hepatitis A
through active or passive immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb
Mortal Wkly Rep 1996; 45(RR-15):1 – 30.
13. Centers for Disease Control and Prevention. Prevention of plague: recommendations of the Advisory Committee on Immunization Practices
(ACIP). MMWR Morb Mortal Wkly Rep 1996;45(RR-14):1 –15.
14. Tsai TF. Arboviral infections — general considerations for prevention, diagnosis, and treatment in travelers. Seminars in Pediatric Infectious
Disease 1992; 3:62 – 9.
15. Wilson ME, von Reyn CF, Fineberg HV. Infections in HIV-infected travelers: risks and prevention. Ann Intern Med 1991; 114:582 – 92.
16. Appleton B, Wolfe MS, Mishtowt GI. Chloroquine as a malarial suppressive: absence of visual effects. Mil Med 1973; 138:225 – 6.
17. Steffen R, Fuchs E, Schildknecht J, et al. Mefloquine compared with other
malaria chemoprophylactic regimens in tourists visiting East Africa.
Lancet 1993; 341:1299 – 303.
18. Lobel HO, Miani M, Eng T, Bernard KW, Hightower AW, Campbell CC.
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19.
20.
21.
22.
23.
24.
25.
26.
Wolfe
Long-term malaria prophylaxis with weekly mefloquine. Lancet 1993;
341:848 – 51.
Barrett PJ, Emmins PD, Clarke PD, Bradley DJ. Comparison of adverse
events associated with use of mefloquine and combination of chloroquine and proguanil as antimalarial prophylaxis: postal and telephone
survey of travellers. BMJ 1996; 313:525 – 8.
Shanks GD. Malaria chemoprophylaxis for the long-term traveler in Southeast Asia. Journal of Travel Medicine 1994; 1:181 – 3.
Matson PA, Luby SP, Redd SC, Rolka HR, Meriwether RA. Cardiac
effects of standard-dose halofantrine therapy. Am J Trop Med Hyg
1996; 54:229 – 31.
Kain KC. Chemotherapy and prevention of drug-resistant malaria. Wilderness and Environmental Medicine 1995; 6:307 – 24.
Drawing the curtain on malaria [editorial]. Lancet 1991; 337:1515 – 6.
Ericsson CD, DuPont HL. Travelers’ diarrhea: approaches to prevention
and treatment. Clin Infect Dis 1993; 16:616 – 26.
Taylor DN. Quinolones as chemoprophylactic agents for travelers’ diarrhea. Journal of Travel Medicine 1994; 1:119 – 21.
Brzazinski A. Melatonin in humans. New Engl J Med 1997; 336:186 – 95.
Additional Suggested Reading
Bia FJ, ed. Travel medicine advisor. Atlanta: American Health Consultants,
1991.
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Centers for Disease Control and Prevention. Health information for international travel, 1996 – 1997. Atlanta: Centers for Disease Control and
Prevention, 1997.
DuPont HL, Steffen R. Textbook of travel medicine. Hamilton, Ontario,
Canada: B. C. Decker, 1997.
Jong EC, McMullen RC, eds. The travel and tropical medicine manual. 2nd
ed. Philadelphia: W. B. Saunders, 1995.
Wolfe MS, ed. Travel medicine. Med Clin North Am 1992; 76:1261 – 1535.
Wolfe MS, ed. Health hints for the tropics. 11th ed. Northbrook, IL: American Society of Tropical Medicine and Hygiene, 1993.
The ‘‘Conflict-of-Interest Policy’’ of the Office of Continuing Medical Education, UCLA School of Medicine,
requires that faculty participating in a CME activity disclose to the audience any relationship with a pharmaceutical or equipment company which might pose a potential, apparent, or real conflict of interest with regard to
their contribution to the program. The author reports no
conflict of interest.
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