Health_Advice_and_Immunizations_for_Trav.pdf

Review Articles
Primary Care
1716 · June 8, 2000
The New England Journal of Medicine
HEALTH ADVICE AND
IMMUNIZATIONS FOR TRAVELERS
EDWARD T. RYAN, M.D., AND KEVIN C. KAIN, M.D.
From the Tropical and Geographic Medicine Center and the Travelers’
Advice and Immunization Center, Division of Infectious Diseases, Massa-
chusetts General Hospital, and Harvard Medical School, Boston (E.T.R.);
and the Centre for Travel and Tropical Medicine, Division of Infectious
Diseases, Toronto General Hospital and the University of Toronto, Toron-
to (K.C.K.). Address reprint requests to Dr. Ryan at the Division of Infec-
tious Diseases, Jackson 504, Massachusetts General Hospital, 55 Fruit St.,
Boston, MA 02114, or at etryan@partners.org.
©2000, Massachusetts Medical Society.
ACH year, 1 billion passengers travel by air,
and over 50 million people from industrial-
ized countries visit the developing world.1,2
Travelers may be exposed to a variety of pathogens
and risks, and 20 to 70 percent of people report some
health problems while traveling.3,4 Overall, during
international travel, 1 to 5 percent of travelers seek
medical attention, 0.01 to 0.1 percent require emer-
gency medical evacuation, and 1 in 100,000 dies.3
Although infectious diseases cause considerable mor-
bidity among travelers, they account for only 1 to
4 percent of deaths that occur during international
travel.5 Cardiovascular disease is the most frequent
cause of death among all travelers; however, age-spe-
cific rates of mortality from cardiovascular disease are
similar to those of nontravelers. Trauma, especially
from motor vehicle accidents, accounts for 21 to 26
percent of travel-associated deaths, with rates that are
several times higher than those for nontravelers.5,6
This review is intended as an introduction to com-
mon and potentially life-threatening illnesses and in-
juries among travelers and will focus on ways to min-
imize these risks.
RISK ASSESSMENT
To assess the traveler’s risk of illness or injury, the
health care provider must consider both the travel-
er’s medical condition and the details of the planned
journey, including the exact itinerary, the length of
stay in each area, the type of travel (urban vs. rural,
business vs. backpacking), the level of accommodation
(hotels, hostels, homes, or camping), and the expect-
E
ed activities (freshwater exposure, contact with ani-
mals, or sexual activity). Special effort should be made
to identify travelers who are at high risk, including
those traveling off the usual tourist routes, backpack-
ers, long-term travelers, and foreign-born persons
who are returning to visit family and friends, since
such travelers are more likely than others to acquire
a number of serious illnesses.
PERSONAL PRECAUTIONS
AND TRAVEL-RELATED ILLNESSES
Illnesses Associated with Travel
Simple measures can prevent or treat many of the
conditions associated with travel itself, such as mo-
tion sickness, jet lag, barotrauma associated with air
travel, and venothrombosis associated with prolonged
sitting (Table 1).2 During high-altitude commercial
flights, atmospheric pressure in the cabin is equiva-
lent to that at approximately 2500 m above sea level.
At this pressure, the partial pressure of arterial oxy-
gen (PaO2) falls to approximately 65 mm Hg; those
with certain serious cardiopulmonary conditions or
a base-line PaO2 of less than 70 mm Hg may benefit
from supplemental oxygen.2,7
Traveler’s Diarrhea
Diarrhea is the most common illness of travelers.
Ten to 60 percent of travelers to developing nations
have diarrhea; at least 20 percent of affected travelers
are bedridden for part of their trip, and 40 percent
change their itinerary because of diarrhea.8-10 Studies
have identified a causative agent in approximately 50
to 75 percent of affected persons.10 Enterotoxigenic
(and possibly enteroaggregative) Escherichia coli and
species of campylobacter, shigella, and salmonella ac-
count for the majority of identifiable bacterial patho-
gens.10,11 Viral causes are less commonly identified,
and parasitic infections are rare. The average duration
of the untreated illness is approximately four days;
complications may include reactive arthritis, postinfec-
tious enteropathy, and Campylobacter jejuni–associ-
ated Guillain–Barré syndrome.9,10,12,13 Travelers should
be instructed about ways to avoid illnesses transmitted
through food and water and about the importance
of fluid replacement should diarrhea occur. Prophylax-
is is rarely indicated; however, most travelers should
carry an antimotility agent and an antibiotic for
self-treatment of diarrhea (Table 2).8,10,11,14,15 Although
fluoroquinolone antibiotics are generally used for di-
arrhea, fluoroquinolone resistance is increasing in or-
ganisms that cause traveler’s diarrhea, especially C. je-
juni, and the use of fluoroquinolone antibiotics in
children and pregnant women is not approved.16-19
Downloaded from www.nejm.org by KENNETH A. LOCKE on April 15, 2004.
Copyright © 2000 Massachusetts Medical Society. All rights reserved.

PRIMARY CARE
Volume 342 Number 23 · 1717
*DEET denotes N,N-diethyl-m-toluamide, now called N,N-diethyl-3-methylbenzamide.
TABLE 1. PERSONAL PRECAUTIONS FOR TRAVELERS TO THE DEVELOPING WORLD.
ILLNESS OR EVENT PRECAUTIONS
Traveler’s diarrhea Avoid uncooked food (other than peeled fruits or vegetables), nonbottled beverages, and unpasteurized dairy
products. Eat well-cooked, hot foods. Do not eat food purchased from street vendors. Use bottled water
for drinking, making ice cubes, and brushing teeth. Wash hands with soap and water frequently, especially
before each meal.
Respiratory infections Avoid excessive outdoor activity in areas of heavy air pollution during hot or humid parts of the day. Consider
tuberculin skin testing before and after travel.
Arthropod-borne illnesses (including ma-
laria, dengue, yellow fever, and Japanese
encephalitis)
Minimize exposure of skin.
Use repellents according to manufacturers’ instructions (daytime use for dengue, nighttime use for malaria).
For skin: 10 to 30 percent DEET-based products.*
For clothes: Consider treating with permethrin-based products.
To prevent malaria: minimize outdoor evening and night activity. Consider use of an insecticide-treated mos-
quito net unless bedroom is protected against mosquitoes; consider use of insecticide spray in bedroom
at night.
Regularly check for adherent ticks during rural activities.
Sexually transmitted diseases Abstain from sex or use safe-sex precautions, including condoms in all encounters.
Avoid relations with commercial sex workers.
Accidents, trauma, and injuries Avoid nighttime driving in rural areas. Use seat belts and infant or child car seats if available. Avoid use of
alcohol while driving or engaging in water sports. Use flotation devices or life jackets. Use helmets when
riding bicycles. Avoid politically unstable areas. Avoid use of motorcycles and mopeds and overcrowded
public transportation. Check rooms for exits. Keep a flashlight handy.
Blood-borne infections (including hepati-
tis B, hepatitis C, and human immuno-
deficiency virus)
Avoid skin-perforating procedures (acupuncture, piercing, tattooing, venipuncture) and sharing of razors.
Avoid invasive medical or dental procedures. Avoid contact with blood or blood products. Consider car-
rying a sterile or disposable needle or syringe.
Altitude illness Ascend slowly. Acclimatize for at least 2 to 3 days at 2500 to 3000 m before ascending higher, then allow
approximately 2 days per 1000 m of altitude gained. If symptoms of altitude illness develop, stop ascent;
if symptoms persist or worsen, descend immediately. Avoid excessive physical activity until acclimatized.
Minimize use of alcohol; drink plenty of fluids. Mountain climbers and others traveling at 3500 to 5000 m
may benefit from expert advice.
Bites or envenomations Do not pet or feed animals (especially dogs and monkeys). Avoid direct contact with animals. Consider min-
imizing jogging or bicycling. Check bedding before use. Check shoes before wearing. Use covered foot-
wear except on the beach; consider wearing reef shoes in the water. Avoid touching or handling marine
creatures.
Freshwater- and seawater-related illnesses Avoid swimming or wading in nonchlorinated fresh water, especially if stagnant or slowly flowing. Eating
predatory reef fish (barracuda, jackfish, grouper, snapper) may cause ciguatera poisoning. Scuba divers
should have certification. Follow established timetables for flying after diving.
Heat-, humidity-, and sun-related illnesses Drink plenty of fluids; avoid dehydration; rest frequently. Avoid excessive physical activity. Wear light-colored,
loose-fitting clothing. Wear sunscreen with a sun protection factor (SPF) of 15 to 40; wear hat and sun-
glasses.
Transportation-associated illnesses During flight: To prevent barotrauma, chew or swallow during ascent and descent; for young children, feed
or use pacifier during ascent and descent. To prevent venothrombosis, avoid dehydration, minimize al-
cohol consumption, and move around the cabin during prolonged flights. To prevent motion sickness,
move to center of vehicle; fix eyes on still, distant objects; increase airflow across face. Consider use of
prophylaxis. To prevent jet lag, melatonin and dietary modifications are of unproved benefit. The body
clock normally resets 1 hr per day; engage in activity in sunlight after arrival at destination.
General Consider taking a medical kit containing thermometer, tweezers, bandages, sunscreen, insect repellent, topical
antibiotic, an analgesic such as acetaminophen, an antimotility agent for diarrhea, and other medications
(see Table 2). Consider also taking water purifier or tablets and disposable needle or syringe. Carry all
medicines in prescription bottles. Carry list of medical conditions, allergies, medications, dosages, and
contact numbers. If there is a cardiac problem, carry copy of recent electrocardiogram. When undertaking
high-risk or long-term travel, consider obtaining medical-evacuation insurance.

1718 · June 8, 2000
T
ABLE
2.
P
ROPHYLAXIS
AND
S
ELF
-T
REATMENT
FOR
T
RAVEL
-R
ELATED
I
LLNESSES
.
I
LLNESS
M
EDICATION
A
DULT
D
OSE
P
EDIATRIC
D
OSE
Malaria*
Prophylaxis
Areas
of
chloroquine
sensitivity†
Chloroquine
phosphate
300
mg
base
(500
mg
salt)
once
per
wk
beginning
1
to
2
wk
before
entering
malarious
area
and
continuing
until
4
wk
after
leaving
5
mg
base/kg
of
body
weight
(8.3
mg
salt/kg),
up
to
adult
dose,
once
per
wk,
as
for
adults
Areas
of
chloroquine
resistance†
Mefloquine
or
228
mg
base
(250
mg
salt)
in
United
States
(250
mg
base
outside
United
States)
once
per
wk
beginning
1
to
2
wk
before
entering
malarious
area
and
continuing
until
4
wk
after
leaving‡
Weight
<15
kg:
5
mg
salt/kg;
15–19
kg:
1
⁄
4
tablet;
20–30
kg:
1
⁄
2
tablet;
31–45
kg:
3
⁄
4
tablet;
>45
kg:
1
tablet
(all
doses
once
per
wk,
as
for
adults)‡
Doxycycline
100
mg
once
per
day
beginning
1
to
2
days
before
entering
malarious
area
and
continuing
until
4
wk
after
leaving§
2
mg/kg
daily,
up
to
adult
dose,
as
for
adults§
Alternatives
Atovaquone/proguanil¶
One
250
mg/100
mg
tablet
per
day
beginning
1
to
2
days
before
entering
malarious
area
and
continuing
until
7
days
after
leaving
Weight
11–20
kg:
62.5
mg/25
mg;
21–30
kg:
125
mg/50
mg;
31–40
kg:
187.5
mg/75
mg;
>40
kg:
250
mg/100
mg
(all
doses
daily,
as
for
adults)
Primaquine¿
30
mg
base
once
per
day
beginning
1
to
2
days
before
entering
malarious
area
and
con-
tinuing
until
7
days
after
leaving
0.5
mg
base/kg
daily,
up
to
adult
dose,
as
for
adults
Chloroquine
phosphate
plus
As
above
As
above
Proguanil**
200
mg
once
per
day
beginning
1
to
2
days
before
entering
malarious
area
and
continuing
until
4
wk
after
leaving
Age
<2
yr:
50
mg;
2–6
yr:
100
mg;
7–10
yr:
150
mg;
>10
yr:
200
mg
(all
doses
daily,
as
for
adults)
Areas
of
mefloquine
resistance†
Doxycycline
As
above
As
above
Although not specifically approved for the treatment
of diarrhea, azithromycin may be a reasonable alter-
native.20,21
Respiratory Infections
After diarrhea, respiratory infection is the most
common illness affecting travelers.3 Persons with un-
derlying cardiopulmonary conditions may be predis-
posed to have severe illness. Immunocompromised
persons and those with marginal cardiopulmonary re-
serve may benefit from carrying an appropriate anti-
biotic for self-treatment. If indicated, influenza and
pneumococcal vaccines should be administered.8,22
Arthropod-Borne Illnesses
Worldwide, approximately 1 in 50 deaths is caused
by an arthropod-borne illness. Malaria and dengue
are the two most common arthropod-borne diseases
of travelers. Most dengue infections in travelers are
mild and self-limited, and dengue often goes undi-
agnosed.23 The mosquitoes that transmit dengue vi-
rus usually bite during the daytime and are urban in-
habitants, whereas the night-biting mosquitoes that
transmit malaria are usually rural. No matter when
or where they travel, persons should limit their ex-
posure to arthropods. A number of insect repellents
are available; products containing DEET (N,N-dieth-
yl-3-methylbenzamide, previously called N,N-diethyl-
m-toluamide) are the most effective and are extreme-
ly safe.24 Travelers should apply products containing
DEET to their exposed skin and, if indicated, apply
products containing permethrin to their clothing and
mosquito nets (Table 1).24
Malaria
Because of the increase in international travel and
in drug-resistant malaria parasites, a growing num-
ber of travelers are at risk of contracting malaria. This
section will briefly review developments in chemo-
prophylaxis against malaria (Table 2). Other impor-
tant details of malaria prevention are available else-
where.8,25-28
As many as 30,000 travelers from industrialized
countries acquire malaria annually.26 Without chemo-
prophylaxis, a traveler’s risk of acquiring malaria is
highest in sub-Saharan Africa and Oceania (more
than 20 percent per month in regions of New Guinea
and approximately 2 percent per month in Africa),
intermediate in South Asia (0.1 to 0.01 percent per
month), and lowest in the Americas and Southeast
Asia (less than 0.01 percent per month).4,29-31 The risk
varies according to the time of travel (high- or low-
transmission season) and the altitude (transmission is
rare above 2000 m). Most travelers to areas where the
risk of malaria is low, such as cities and tourist re-
sorts in Southeast Asia and the Americas, do not re-
quire antimalarial drugs.8,31 Any measure that reduces
exposure to night-biting anopheles mosquitoes will
reduce the risk of acquiring malaria (Table 1).

P
R
I
M
A
RY
C
A
R
E
Vo
l
u
m
e
3
4
2
Nu
m
b
e
r
23
·
1719
*If a traveler is at high risk of contracting malaria, consider using primaquine phosphate (15 mg base; for children, 0.3 mg base per kilogram of body weight, up to adult dose) daily for the last 2 weeks of
chemoprophylaxis to decrease the likelihood of late-onset malaria due to Plasmodium vivax or P. ovale. Persons who are pregnant or deficient in glucose-6-phosphate dehydrogenase should not take primaquine.
Use of primaquine in the last two weeks is not required when the chemoprophylaxis used during exposure was primaquine. Presumptive self-treatment of malaria is not routinely recommended for travelers; travelers
should urgently seek medical attention if fever develops. Expert advice may be beneficial for travelers who will be unable to obtain timely medical care and for those who cannot take optimal prophylaxis.
†Chloroquine-resistant P. falciparum have been reported in all malarious areas except Mexico, Central America west of the Panama Canal, Haiti, the Dominican Republic, and scattered areas of the Middle East.8
Mefloquine-resistant P. falciparum have been reported in the western provinces of Cambodia and in the border regions between Thailand and Myanmar (Burma) and between Thailand and Cambodia.8
‡Mefloquine may be administered weekly for 3 weeks before the malarious area is entered or front-loaded with daily dosing for 3 consecutive days (of the normal weekly dose), then weekly until 4 weeks after
the malarious area has been left. Mefloquine should not be used by persons with psychiatric illness, seizures, or cardiac conduction abnormalities. Mefloquine is not approved for use during pregnancy; however,
its use is probably safe, especially during the second and third trimesters, and limited data suggest that it is safe during the first trimester.8 The pediatric dosage has not been approved by the Food and Drug
Administration, but it has been recommended by the Centers for Disease Control and Prevention.8
§Do not use doxycycline in pregnant women and in children <8 years of age. Doxycycline can cause photosensitivity and vaginal moniliasis and can decrease the efficacy of hormonal contraceptive agents.
Doxycycline should be taken with food and not used simultaneously with antacids or bismuth-containing products.
¶Fixed-combination tablets containing 250 mg of atovaquone and 100 mg of proguanil or 62.5 mg of atovaquone and 25 mg of proguanil may become available in the United States. They should be taken
within 45 minutes after eating.
¿Take primaquine with food. Do not use in pregnant women and persons with glucose-6-phosphate dehydrogenase deficiency.
**Proguanil is not available in the United States. Chloroquine plus proguanil is less effective against malaria than mefloquine or doxycycline in areas where these agents have been studied. Chloroquine plus
proguanil has been used safely in pregnant women.
††Fluid replacement is the primary therapy for traveler’s diarrhea; oral rehydration salts may also be used, especially by children and the elderly. Prophylaxis against traveler’s diarrhea is not routinely recommended.
When it is used, ciprofloxacin (500 mg daily), levofloxacin (500 mg daily), ofloxacin (300 mg daily), or norfloxacin (400 mg daily) can be administered for no more than 3 weeks. An alternative is bismuth
subsalicylate (2 tablets or 2 tablespoons four times a day). Prophylaxis against traveler’s diarrhea could be considered for use in persons with achlorhydria, inflammatory bowel disease, or an immunocompromised
state. Bismuth subsalicylate should not be used in those with salicylate hypersensitivity. Bismuth subsalicylate can cause tinnitus and black discoloration of the tongue and stools.
‡‡Do not use antimotility agents alone if diarrhea is associated with fever or blood in the stool. Some experts would not use any antimotility agent if diarrhea was associated with fever or blood in the stool.
§§Maintain adequate fluid status, especially in infants, small children, and the elderly. Fluoroquinolone antibiotics should not be used in pregnant women and children. Azithromycin (5 to 10 mg per kilogram
once daily) may be an alternative for such persons. Azithromycin may also be an alternative when fluoroquinolone-resistant organisms are present. Newer fluoroquinolones such as gatifloxacin and moxifloxacin are
not approved for the treatment of diarrhea, although they may be effective. Fluoroquinolone antibiotics, especially newer agents (including sparfloxacin), may prolong the corrected QT interval; concurrent use of
such agents with mefloquine and other antimalarial agents that prolong the corrected QT interval has not been studied. Because of unpredictable drug interactions, concurrent use of fluoroquinolones and warfarin,
theophylline, or cyclosporine is best avoided.
¶¶An alternative is a 500-mg sustained-release tablet taken once daily. Acetazolamide may be useful in persons with a history of altitude illness and those ascending rapidly without acclimatization. Acetazolamide
should not be taken by persons allergic to sulfonamides. An alternative is dexamethasone (4 mg every 6 to 12 hours); symptoms may recur when dexamethasone is stopped; dexamethasone should not be used
routinely.
¿¿Limited data are available on the use of acetazolamide in children. Acetazolamide has been used safely in children for other indications at 5 mg per kilogram per day, given in one or two divided daily doses.
Acute traveler’s diarrhea
Self-treatment††
Mild-to-moderate non-
dysenteric diarrhea
Loperamide hydrochloride‡‡
with or without
4 mg, then 2 mg after each loose stool, to a maximum of 16 mg per day Do not use in children <2 yr of age
Antimicrobial agent Single dose of ciprofloxacin (750 mg), levofloxacin (500 mg), or ofloxacin (400 mg)§§ Do not routinely give fluoroquinolone antibiotics§§
Severe or dysenteric
diarrhea
Antimicrobial agent Ciprofloxacin (500 mg) twice daily for 3 days; levofloxacin (500 mg) once daily for 3 days;
norfloxacin (400 mg) twice daily for 3 days; ofloxacin (300 mg) twice daily for 3 days;
or azithromycin (500 mg) once on day 1, then 250 mg daily for 4 additional days; or
azithromycin (1000 mg) once§§
Seek medical attention§§
Altitude illness, mild (acute
mountain sickness)
Prophylaxis Acetazolamide 125–250 mg twice daily, beginning 24–48 hr before ascent and continuing for at least
48 hr after ascent or while at high altitude¶¶
Not routinely recommended¿¿
Downloaded
from
www.nejm.org
by
KENNETH
A.
LOCKE
on
April
15,
2004.
Copyright
©
2000
Massachusetts
Medical
Society.
All
rights
reserved.

1720 · June 8, 2000
The use of antimalarial drugs and their potential
adverse effects must be weighed against the risk of
acquiring malaria. The drug of choice is chloroquine
in areas where chloroquine resistance has not been
described.8,28 Mefloquine is the current drug of choice
for most persons at high risk for malaria who are
traveling in areas where there is chloroquine resist-
ance.8 Although mefloquine is highly efficacious, its
tolerability has been questioned.29,30,32 Severe neuro-
psychiatric reactions (psychosis or convulsions) in re-
sponse to prophylactic doses of mefloquine have been
infrequently reported (in 1 in 10,000 to 1 in 13,000
users). Milder neuropsychological adverse events (anx-
iety, depression, nightmares, sleep disturbances, and
cognitive changes) that are disabling enough to result
in drug discontinuation have been reported in 1 in
140 to 1 in 250 users.25,26,33-35 However, six random-
ized, double-blind trials and seven prospective com-
parative studies failed to find significant differences in
the rates of adverse events or drug discontinuation
between subjects taking mefloquine and those tak-
ing other antimalarial drugs.25,33
Doxycycline is the preferred agent for persons un-
able to take mefloquine and for those traveling to ar-
eas where there is mefloquine resistance — that is, the
western provinces of Cambodia and the border re-
gions between Thailand and Cambodia and between
Thailand and Myanmar (Burma).8 An alternative for
travelers who are unable to take mefloquine or dox-
ycycline is the combination of weekly chloroquine plus
daily proguanil (the product is not available in the
United States). However, chloroquine plus proguanil
is significantly less effective than doxycycline or meflo-
quine in areas where these agents have been studied.30
Although it is not yet approved for this indication in
the United States, trials have demonstrated that pri-
maquine is an effective and well-tolerated chemo-
prophylactic agent.36,37 Primaquine may cause oxidant-
induced hemolytic anemia and methemoglobinemia;
its use is contraindicated in pregnant women and in
persons with glucose-6-phosphate dehydrogenase de-
ficiency. Because of the activity of primaquine against
the liver stages of the malaria parasite, travelers can
discontinue primaquine one week after leaving a ma-
larious area.36-38 Tafenoquine (WR238605), a related
compound, appears to be more active and better tol-
erated than primaquine. Whereas primaquine must be
taken daily, tafenoquine may be effective when taken
as a single loading dose before travel or when taken
weekly during travel. Tafenoquine for malaria preven-
tion is currently being studied in phase 3 trials.39
A fixed-combination tablet of atovaquone and pro-
guanil is highly effective in the prevention of malaria
caused by Plasmodium falciparum and may soon be-
come available in the United States.40 Evidence sug-
gests that this drug combination has activity against
a liver stage of the malaria parasite, allowing travelers
to discontinue it one week after leaving a malarious
area. Halofantrine, artemisinin derivatives, and azith-
romycin should not be used for the prevention of ma-
laria, because of poor absorption, toxicity, unfavor-
able pharmacokinetics, and low efficacy.
Malaria during pregnancy may have severe conse-
quences. If a woman is pregnant or plans to become
pregnant and cannot defer travel to a high-risk area,
appropriate chemoprophylaxis is essential.8,19,25-28 The
use of doxycycline or primaquine is contraindicated
during pregnancy. The use of chloroquine is safe in all
trimesters. Mefloquine may be considered for use
during pregnancy when exposure to chloroquine-
resistant P. falciparum is unavoidable (Table 2).8 Chlor-
oquine plus proguanil is considered safe, but this com-
bination is less effective than mefloquine.8,30
Travelers to malarious areas should be informed
that no measure guarantees complete protection from
malaria. Malaria can be effectively treated early in its
course, but delay may result in a serious or even fatal
outcome. Travelers should seek medical attention im-
mediately if fever develops during or after a visit to
an area where malaria is endemic.
Sexually Transmitted Diseases
Travelers often have a sense of anonymity; they may
feel less inhibited sexually than at home and may place
themselves at greater risk of acquiring sexually trans-
mitted diseases.41 At least 5 percent of short-term
travelers engage in casual sex while abroad, and con-
doms are used in half or fewer of these encounters.42
Long-term workers in foreign countries appear to be
at even greater risk, with up to 50 percent of Euro-
peans who live in sub-Saharan Africa reporting casual
and often unprotected sexual encounters with Afri-
can partners.5,43 The prevalence of infection with the
human immunodeficiency virus among some Euro-
pean overseas workers is 100 to 500 times as high as
among similar populations in Europe.5,43 Travelers
should know the benefits of abstinence or of safe sex-
ual practices, especially the use of condoms, and the
hepatitis B vaccine should be administered if it is in-
dicated.
Altitude Illness
Altitude illness causes substantial morbidity and
occasional deaths among travelers. The incidence and
severity of altitude illness are related to the speed of
ascent, the altitude achieved, the amount of exertion,
and the degree of acclimation. Acute mountain sick-
ness is usually manifested as headache, nausea, light-
headedness, and insomnia; it occurs in more than 25
percent of persons who ascend rapidly to 2500 m or
higher.2,44 High-altitude pulmonary and cerebral ede-
ma are much rarer conditions.2 The risk of altitude
illness may be reduced by graded ascent and the ap-
propriate use of prophylactic medications such as ace-
tazolamide (Tables 1 and 2).2,45 Although effective,
dexamethasone and nifedipine have limited roles in

PRIMARY CARE
preventing altitude illness because of the risk of ad-
verse events.2,45,46 Mountaineers and trekkers travel-
ing above 3500 m should seek expert advice.
Other Illnesses
Travelers are at increased risk for a number of other
illnesses or events, including blood-borne infections;
infections, such as schistosomiasis or leptospirosis, that
are transmitted through exposure to nonchlorinated
fresh water; marine envenomations; motor vehicle ac-
cidents, injuries, and drowning; psychiatric illnesses
and stress; sunburn, heat stroke, and heat exhaustion;
and illnesses such as rabies that are transmitted by an-
imal bites.5,47-49 Travelers should practice simple pre-
cautions that markedly decrease the risk of such ill-
nesses or events (Table 1).
IMMUNIZATIONS
Table 3 summarizes information on immunization
for travelers.
Routine Immunizations
A consultation before travel is an excellent oppor-
tunity to update routine immunizations.50 Travelers
to the developing world should have adequate immu-
nity against measles, mumps, rubella, tetanus, diph-
theria, pertussis, varicella, and Haemophilus influen-
zae type b infection.8 Travelers to Asia and Africa
should also have adequate immunity against poliovi-
rus; the infection has been eliminated from the West-
ern Hemisphere.8,51 If indicated, pneumococcal vac-
cine should be administered.8 Influenza vaccine and
chemotherapeutic agents that are effective against in-
fluenzavirus should be considered for those at high
risk for severe influenza who are traveling to the trop-
ics or with a large tour group at any time of the year
or to the Southern Hemisphere from April through
September.8 Long-term travelers and those whose
activities place them at risk for infections transmitted
by blood or body fluids should be immunized against
hepatitis B (Table 3).8,52
Required Immunizations
Immunization against yellow fever is required by
certain countries for entry, according to World Health
Organization regulations (Table 3).8,28,53 Yellow fever
is a rare but potentially fatal viral infection that is
transmitted by day-biting mosquitoes in areas of Lat-
in America and sub-Saharan Africa. Country-specific
recommendations are available (Table 4).8,28 Vaccina-
tion becomes valid for the purpose of entry 10 days
after primary inoculation, and it must be administered
at an approved World Health Organization Yellow
Fever Vaccinating Center. A list of approved centers
can be obtained from state or national departments
of public health. Persons for whom the vaccine is
contraindicated should be issued a vaccination waiver.
Rarely, other vaccines may be required. Saudi Arabia
requires meningococcal immunization of all pilgrims,
and a number of countries may require vaccination
against cholera (Table 3).
Recommended Immunizations According to Risk
of Infection
Hepatitis A is the most frequent vaccine-prevent-
able, travel-related illness. The risk of infection is ap-
proximately 300 per 100,000 travelers per month in
tourist areas in developing countries, and it is five to
seven times as high for backpackers and those trav-
eling off the usual tourist routes.3,4,54 The hepatitis
A vaccine is indicated for most nonimmune travelers
to the developing world. Four weeks after one dose
of the vaccine, immunity has developed in 95 percent
of persons and persists for at least 6 to 12 months.8,55
Two doses provide long-term immunity. Intramus-
cular immune globulin may be used to provide short-
term protection against hepatitis A infection in per-
sons who require immediate immunity and in children
too young to receive the vaccine.8,55 A combination
vaccine that provides protection against hepatitis A
and B infections may soon become available.56
The incidence of typhoid is approximately 3 to 30
cases per 100,000 travelers to developing countries
per month.3,4 Vaccination should be targeted to trav-
elers at the highest risk: those traveling to South Asia,
North and West Africa, or the more impoverished
areas of Latin America; those traveling beyond the
usual tourist itineraries; long-term travelers (generally
those traveling for more than three to four weeks);
backpackers; and travelers staying with family or
friends in developing nations.8,57 Vaccination should
also be considered for immunocompromised persons
and those with severe atherosclerotic disease, inter-
nal prostheses, or cholelithiasis, since such persons
are most likely to have complicated or prolonged
disease should infection occur.
Cholera is an extremely rare infection among trav-
elers to developing countries (0.2 reported cases per
100,000 travelers per month). Although a number of
cholera vaccines are available worldwide, only a poor-
ly tolerated, minimally effective cholera vaccine is
available in the United States.8,58,59 Travelers rarely
need vaccination against cholera.8,59
The risk of an animal bite may exceed 1 to 2 per-
cent per year for travelers to developing countries.4
Optimal postexposure prophylaxis against rabies (in-
cluding rabies immune globulin and tissue-culture–
derived vaccines) is often unavailable in many devel-
oping countries.60 Vaccination against rabies before
travel should be considered for long-term travelers to
the developing world, those who will have unavoid-
able direct contact with animals, those who may be
unable to receive timely postexposure prophylaxis, and
those (such as young children) who may be unable
to report possible exposure.8,61,62
Travelers to an area where there is an ongoing out-

1722 · June 8, 2000
*Travelers to the developing world should be immune to measles, mumps, rubella, tetanus, diphtheria, pertussis, varicella, and Haemophilus influenzae
type b infection.8 Those traveling to Asia or Africa should also be immune to poliovirus. Accelerated schedules for routine immunizations are available.8 If
indicated, influenza and pneumococcal vaccines should be administered.
†The time of the first dose is indicated by 0.
‡Generally, the use of live attenuated vaccines in pregnant women and immunocompromised persons should be avoided. Women should not become
pregnant for 3 months after yellow fever vaccination.
§Yellow fever vaccine should never be used in a child <4 months of age; use in children 4 to <9 months of age should be determined by experts, with
the risk of yellow fever infection weighed against the risk of vaccine-induced encephalitis.
¶A combination hepatitis A and B vaccine may soon be available in the United States; it is given in three doses at 0, 1, and 6 months.
¿In some countries, the vaccine is administered to children »1 year of age.
**Doses can also be given at 0, 1, 2, and 12 months. Other accelerated schedules are available but are associated with decreased immunogenicity. A two-
dose regimen of a full adult dose of Recombivax HB (Merck, West Point, Pa.) given at 0 and at 4 to 6 months is also approved for use in children and
adolescents 11 to 15 years of age.
††The vaccine is often poorly tolerated.
‡‡Documentation of vaccination against cholera may occasionally be required for entry into or travel within certain countries.
§§This vaccine is not available in the United States but is available in Europe, Russia, Latin America, and Canada.
¶¶The vaccines are administered intramuscularly (in the deltoid). Alternatively, HDCV may be given intradermally before exposure. Intradermal HDCV
vaccine series should be completed »7 days before chloroquine or mefloquine is begun. Never give RVA or PCEC intradermally. Never give any rabies
vaccine intradermally for post-exposure prophylaxis.
¿¿Saudi Arabia requires all pilgrims to have documentation of meningococcal vaccination at least 10 days and less than 3 years before arrival.
***Serogroup A meningococcal vaccine is safe and can be immunogenic in children »3 months of age. Although the vaccine is safe, responses to other
serogroup components of the vaccine are poor or unknown in children «2 years of age. For children younger than 18 months who are at high risk of
disease, two doses 3 months apart may be given. Boosters are administered at 2 to 3 years when the vaccine is administered to children <4 years of age.
†††Immunization is not routinely administered.
‡‡‡Accelerated series are being evaluated.
§§§An accelerated series is available with doses at 0, 7, and 21 days and a fourth dose at 12 to 18 months.
TABLE 3. IMMUNIZATIONS TO PREVENT TRAVEL-RELATED ILLNESSES.*
ILLNESS VACCINE AGE DOSAGE SCHEDULE FOR NONIMMUNE PERSONS† BOOSTER
Yellow fever Live attenuated 17D viral-strain vaccine‡ »9 mo§ 1 dose 10 yr
Hepatitis A¶ Hepatitis A vaccine »2 yr¿ 2 doses at 0 and at 6–18 mo, depending on
vaccine
»10 yr
Immune globulin All ages 1 dose 3 mo if 0.02 ml/kg; 5 mo
if 0.06 ml/kg
Hepatitis B¶ Recombinant hepatitis B surface antigen
vaccine
All ages 3 doses, usually at 0, 1, and 6 mo** Not routine
Typhoid Parenteral heat- and phenol-inactivated
vaccine††
»6 mo 2 doses »4 wk apart or (less effective) 3 doses
1 wk apart
3 yr
Oral live attenuated Salmonella typhi-
murium strain Ty21a vaccine‡
»6 yr 4 oral doses given every other day (outside the
United States, 3 doses often given)
5 yr
Parenteral Vi capsular polysaccharide ty-
phoid vaccine
»2 yr 1 dose 2 yr
Cholera‡‡ Parenteral phenol-inactivated vaccine†† »6 mo 2 doses »1–4 wk apart 6 mo
Oral killed whole-cell recombinant B
subunit vaccine (WC-rBS)§§
»2 yr >6 yr of age: 2 doses separated by 7–42 days
2–6 yr of age: 3 doses separated by 7–42 days
>6 yr of age: 2 yr
2–6 yr of age: 6 mo
Oral live attenuated Vibrio cholerae strain
CVD-103 HgR vaccine‡§§
»2 yr 1 dose 6 mo
Rabies Cell-culture–derived vaccines¶¶ All ages Preexposure, 3 doses at 0, 7, and 21 or 28
days
»6–36 mo, depending
on risk category or re-
sults of serologic tests
Human diploid-cell vaccine (HDCV)
Rabies vaccine adsorbed (RVA)
Purified chick-embryo cell culture
vaccine (PCEC)
Meningococcal
disease¿¿
Meningococcal quadrivalent (A/C/Y/
W-135) polysaccharide vaccine
»2 yr*** 1 dose »3–5 yr
Japanese enceph-
alitis
Inactivated mouse-brain–derived vaccine »1 yr 3 doses at 0, 7, and 14 or 30 days »3 yr
Tuberculosis Bacille Calmette–Guérin vaccine‡†† All ages 1 dose No
Lyme disease††† Borrelia burgdorferi OspA vaccine 15–70 yr 3 doses at 0, 1, and 12 mo‡‡‡ Not established; maybe
yearly
Tick-borne en-
cephalitis†††
Inactivated whole-virus vaccines§§ Variesaccording
to vaccine
3 doses, usually at 0, 1–3 mo, and 9–12 mo;
varies according to vaccine§§§
»3 yr

PRIMARY CARE
break of meningococcal disease caused by Neisseria
meningitidis serogroup A, C, Y, or W-135 and those
traveling to the “meningitis belt” of sub-Saharan Af-
rica (stretching from Senegal to Ethiopia) between
December and June should consider receiving the
quadrivalent meningococcal vaccine.8,63
Japanese encephalitis is a viral infection transmit-
ted by mosquitoes in rural areas of Asia. A three-
dose vaccine is available, but hypersensitivity reactions
occur in up to 0.6 percent of vaccine recipients. These
reactions may be severe and may occur up to two
weeks after vaccination.8,64 Vaccination should be tar-
geted to those planning prolonged visits (usually of
more than four weeks), or shorter periods during
which exposure will be intense, to areas of rural Asia
where the disease is endemic, especially during the
peak transmission season in each area.8
The risk of tuberculosis in the routine traveler is
low.8 Tuberculin skin testing should be performed
before and after prolonged or high-risk travel. The
efficacy of the bacille Calmette–Guérin vaccine con-
tinues to be debated. Administration of the vaccine
may be considered for those at high risk of acquiring
severe tuberculosis, such as young infants who will re-
side for a long time in an area where tuberculosis is
prevalent; those at high risk of acquiring multidrug-
resistant tuberculosis; and those for whom the
treatment of tuberculosis would be extremely com-
plicated.65
Travelers to certain rural areas of the United States
may be at very low risk of acquiring Lyme disease.66
Similarly, travelers to rural areas of eastern and north-
ern Europe, Russia, and the Far East may be at very
low risk of acquiring tick-borne encephalitis.50,67 Trav-
elers should not routinely be vaccinated against these
illnesses (Table 3).
CONCLUSIONS
Travel medicine has become a specialized field.
Practitioners who provide consultation to travelers
should have current knowledge of the global epide-
miology of infectious diseases and should provide up-
to-date recommendations. The advice of a specialist
in travel and tropical medicine may be of special ben-
efit for those planning high-risk or adventure travel,
immunocompromised persons, those with severe or
multiple medical conditions, those who will live
abroad for a long time, those who will travel off the
usual tourist routes in the developing world, preg-
nant women, and persons traveling with young chil-
dren.7,8,17-19 Such specialists may also be helpful in
the care of returned travelers who are ill.
Supported in part by grants from the National Institute of Allergy and
Infectious Diseases, National Institutes of Health (AI/K0801332, to Dr.
Ryan), and the Medical Research Council of Canada (MT-13721, to Dr.
Kain); and by a Career Scientist Award from the Ontario Ministry of
Health (to Dr. Kain).
We are indebted to Stephen B. Calderwood, M.D., Martin S.
Cetron, M.D., David C. Hooper, M.D., Jay S. Keystone, M.D., and
Robert Steffen, M.D., for helpful information and thoughtful review
of the manuscript.
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PRIMARY CARE
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