The provision of health advice and the administration of prophylactic measures can help reduce the morbid and, at times, mortal risks of infectious illnesses that may be acquired during international travel. The Centers for Disease Control and Prevention (CDC) publishes Health Information for International Travel, which provides information on required and recommended vaccinations and malaria prophylaxis, as well as general advice.Information may also be obtained from state public health departments, local physicians or clinics catering to travelers, the embassies of individual countries, and Internet-based advisory services. Even the most up-to-date information sources, however, may not be able to provide precise information on specific diseases prevalent in specific locales, because mechanisms for recognizing and reporting diseases are often lacking in developing areas.
Pretravel Evaluation and Immunizations
Medical consultation should be obtained at least 1 month before international travel to allow time for immunizations [see Table 1 ]. A general patient medical history should be obtained to define pertinent underlying medical conditions. For instance, splenectomy predisposes a person to more severe malaria, babesiosis, and infections with encapsulated bacteria, including meningococcal infections. A history of allergies to antimicrobial agents or to other components of vaccines should be determined. Knowledge of the duration and purpose of a trip, as well as of the countries and locales to be visited, can help in estimating the risks of exposure to endemic diseases. In addition, specific groups of travelers—including pregnant women; persons with HIV; persons with chronic diseases such as chronic obstructive pulmonary disease, diabetes mellitus, hypercoagulable states, and cardiovascular disease; and health care workers— may require more time before travel to address their potentially altered needs for immunization and prophylaxis.
Table 1 Guidelines for Immunizations for Travelers
|
Asia |
Eastern Mediterranean, North Africa |
Middle East |
Sub-Saharan Africa |
Pacific Islands |
Caribbean, Mexico, Central and South America |
North America, Europe, Japan, Australia, New Zealand |
|
|
Yellow fever |
X (some countries) |
X (some South American countries) |
|||||
|
Cholera* |
|||||||
|
Polio |
X (some countries |
X (some countries |
|||||
|
Tetanus/diphtheria (booster every 10 yr) |
X |
X |
X |
X |
X |
X |
X |
|
Measles (if born after 1957 and not recipient of 2 doses of vaccine) |
X |
X |
X |
X |
X |
X |
X |
|
Typhoid |
X |
X |
X |
X |
X |
X |
|
|
Rabies (for prolonged visits) |
X |
X |
X |
X |
X |
||
|
Hepatitis A |
X |
X |
X |
X |
X |
X |
|
|
Hepatitis B (especially for prolonged visits) |
X |
X |
X |
X |
X |
X |
|
|
Meningococci |
X (during outbreaks) |
X (during outbreaks) |
X (especially Mecca, during Hajj) |
X (especially in meningococcal "belt" countries) |
X (during outbreaks) |
||
|
Japanese encephalitis |
Xf |
*Only if required by a country. Prolonged visits to some regions.
Figure 1 Yellow fever (gray areas) is endemic in parts of Africa (left) and South America (right). Several countries consider these zones infected areas and require an International Certificate of Vaccination against yellow fever from travelers from these zones.
Required immunization
The only immunization legally required for entrance into specific countries is that for yellow fever.
Yellow Fever
Yellow fever is a mosquito-transmitted viral infection, whose severity may range from an influenzalike illness to potentially fatal hepatitis and hemorrhagic fever. Yellow fever occurs only in equatorial Africa and in areas of tropical South America [see Figure 1].1 Persons older than 6 months visiting countries where yellow fever is known to exist should be immunized. In addition, those traveling outside of urban areas in countries that are in the yellow fever endemic zones but are not officially reporting the infection should be immunized because the disease may be underrecognized. Some countries, especially in Asia, may require yellow fever immunizations for entry, especially for persons who have traveled in potentially endemic countries.1 Yellow fever vaccine, a live virus vaccine grown in chick embryos, is effective.
Although generally safe, yellow fever vaccines are uncommonly associated with encephalitis (referred to as yellow fever vaccine-associated neurotropic disease [YEL-AND]) and a potentially fatal multiorgan system failure (referred to as yellow fever vaccine-associated viscerotropic disease [YEL-AVD]). In the United States, estimated rates of these two complications are four to six cases per million doses for encephalitis and three to five cases per million doses for multiorgan failure.1 However, the risks of illness and death due to yellow fever in an unvacci-nated traveler are greater, estimated to be one per 1,000 and one per 5,000 a month, respectively.1 Thus, for those entering yellow fever endemic areas, yellow fever vaccination is indicated; however, vaccine use should be limited to those who are truly at risk. This is especially true for travelers older than 60 years, because they appear to be at greater risk for developing YEL-AVD.2 For these travelers, vaccine may be indicated only if the risk of potential exposure is high (e.g., when travel in endemic areas outside urban centers is anticipated). A history of thymus disorders appears to be a contraindication for vaccine. In an analysis of 23 vaccinated persons who developed YEL-AVD, four (17%) had a history of thymus disease.2 Travelers with a history of thymus disorders or dysfunction, including myasthenia gravis, thymo-ma, thymectomy, or DiGeorge syndrome, should not receive yellow fever vaccine. If travel to yellow fever-endemic regions cannot be deferred, persons with thymus disorders should be advised to use N,N-diethyl-m-toluamide (DEET) and permeth-rin to reduce mosquito bites [see Insect Repellents and Avoidance, below].2
Initially, a single subcutaneous dose of 0.5 ml is given. A booster dose is required every 10 years. Immunizations, which are recorded on the International Certificate of Vaccination, are available only from designated physicians and centers, an updated listing of which can be found on the Internet at http://www2.ncid.cdc.gov/travel/yellowfever. Yellow fever vaccine, which contains both egg proteins and gelatin, rarely causes anaphylaxis.3 For those persons allergic to egg proteins or gelatin, skin testing with yellow fever vaccine (per directions included on the package insert) may help determine whether vaccine can be given safely.
Because yellow fever vaccine is a live virus vaccine, cautions and potential contraindications to its use apply to those who are pregnant, lactating, or immunocompromised. In these persons, if the sole indication for administration of yellow fever vaccine is to satisfy legal requirements for entry, a physician’s letter documenting the contraindications to vaccination can be provided to the traveler; in addition, advice should be sought from the embassy or consulate of the country or countries to be visited.
Other immunizations
Influenza
Travelers are at increased risk for influenza infection.1 Influenza, like hepatitis A, has become one of the more common infections in travelers that are preventable by vaccine. In temperate countries, influenza is prevalent in the winter months; whereas in the tropics, influenza transmission occurs year-round. For travelers to the Northern Hemisphere, the risk is greatest during December through February; and for travelers to the Southern Hemisphere, the risk is greatest from April through September. Summertime outbreaks of influenza have occurred on cruise ships in the Northern and Southern hemispheres. For travelers to tropical countries, the risk of influenza exists throughout the year.1
Persons at high risk for influenza, including those older than 50 years, should receive influenza vaccine (1) if influenza vaccine was not received during the preceding fall or winter, (2) if travel is planned to the tropics, (3) if travel is planned with large groups of tourists (e.g., on cruise ships), or (4) if travel is planned during seasons in which influenza is prevalent.1,4 In North America, travel-related influenza vaccination should be administered in the spring, if possible, because vaccine may be unavailable in the summer.
Cholera
Cholera is caused by toxigenic Vibrio cholerae groups 01 and 0139. Although the number of cases of cholera seen in the United States has increased in recent years, many of the cases have been the result of the illness being imported into the United States by travelers from other countries; tourists from the United States visiting other countries have only rarely been infected. Cholera is acquired by ingestion of contaminated water, ice, or food, including raw or undercooked fish and shellfish. Travelers in endemic regions should be advised of the precautions to be followed to minimize risks of acquiring cholera and other enteric infections [see Travel-Related Illness, below] and of the importance of rehydration in the treatment of cholera. Dietary precautions include consuming only boiled or treated water, eating thoroughly cooked food, avoiding all fruit not peeled by onself, and avoiding under-cooked or raw fish or shellfish, including seviche.
Routine immunization is not recommended for travelers.1 In the unlikely event that a locale requires immunization for cholera, immunization would need to be obtained outside the United States in countries in which current cholera vaccine is available. Currently, no country requires proof of cholera immunization as a condition for entry, and the World Health Organization recommends against such a requirement. Some local authorities, however, may require immunization (to determine local requirements, travelers may consult the embassies of the countries to which they will be traveling). The only cholera vaccine licensed for use in the United States is no longer manufactured. In other countries, two cholera vaccines (Dukoral, from Biotec AB, and Mutacol, from Berna) have been licensed for use, but neither of these vaccines is indicated for most travelers.1 Travelers who are at risk for cholera and who expect to travel to areas remote from medical care should take with them packets of oral rehydration salts. Antimicrobial agents often employed for therapy for traveler’s diarrhea, such as ciprofloxacin, are usually very effective in helping terminate cholera infections.5
Poliomyelitis
Travelers to countries in which polio is endemic or in which there is a current epidemic are at risk for the disease and should be immunized. Countries considered to be free of wild poliovirus are all countries in the Western Hemisphere, the Western Pacific Region (which includes China), and the European region.1 Polio transmission continues in some developing countries, including Afghanistan, India, Pakistan, Nigeria, and Niger, although efforts to achieve global eradication of polio are ongoing.
Travelers who were immunized previously should receive one booster dose of polio vaccine. Oral live virus vaccine is no longer recommended for immunizations in the United States.6 The inactivated vaccine is preferred to avoid the small risk of paralytic disease from the oral vaccine. Patients with an altered immune status should receive inactivated vaccine. Children who have not been immunized should receive a full series of immunizations with inactivated polio vaccine. Adults who have not been immunized should receive a series of three doses of en-hanced-potency inactivated vaccine.1 If there is insufficient time before travel for at least three doses of inactivated vaccine to be given at intervals of 1 to 2 months, the following alternatives are recommended1: if less than 1 month is available before travel, a single dose of inactivated vaccine is given; if between 1 and 2 months is available before travel, two doses of inactivated vaccine are administered 4 weeks apart. Travelers who were incompletely immunized previously should receive the remaining required doses of vaccine.
Tetanus and Diphtheria
A tetanus-diphtheria booster should be administered every 10 years [see 7:V Anaerobic Infections].1 Older persons and women are more likely to lack the tetanus and diphtheria antibodies and thus are more likely to require boosters.7,8
Pneumococcal Infections
There are no data on the risk to travelers of acquiring pneu-mococcal infections; however, those at risk, including those older than 65 years [see 7:I Infections Due to Gram-Positive Cocci], are recommended as candidates to receive pneumococcal vaccinations.
Measles
Because of the declining prevalence of measles in the United States, disease imported by immigrants and by returning residents accounts for an increasing proportion of cases in this country. Measles may be acquired during travel in developed countries, including those in Europe and Asia, as well as in less developed countries.1 Most persons who were born before 1957 are immune because of natural exposure and do not require vaccination. Persons who were born after 1956 who either have not been immunized or were immunized before 1980 and who have neither serologic evidence of infection nor a history of physician-diagnosed measles should be immunized with a single subcutaneous dose of measles vaccine before travel. Measles vaccine is contraindicated for both pregnant and immunodeficient patients. HIV-infected patients, unless they are severely immunocompro-mised, should be immunized before travel because measles can be severe and even fatal in persons with HIV infection.1,9
Typhoid
Salmonella typhi infection is prevalent in many areas of Asia, Africa, and Latin America. Typhoid is acquired from contaminated food or water. Although the overall risk of acquiring typhoid during travel remains low (2.3 million cases per million travelers),10 foreign travel accounted for 74% of 1,393 cases of typhoid reported to the CDC between 1994 and 1999.11 The risk was greatest for those traveling to the Indian subcontinent (India, Pakistan, and Bangladesh) and Haiti. Of note, even those traveling for no more than a couple of weeks were at risk of acquiring typhoid. Given the safety of current typhoid vaccines, typhoid vaccination should be considered for short-term travel in high-risk areas, as well as for any travel to areas off the usual tourist itinerary.11
Two typhoid vaccines are available for use in the United States. One typhoid vaccine is an oral vaccine (Vivotif Berna, from Berna) that uses the attenuated Ty21a strain of S. typhi; this vaccine does not cause the local and systemic side effects frequently produced by the older, parenteral vaccine. The oral vaccine is supplied as a packet of four enteric-coated capsules that must be refrigerated. Patients need explicit guidance on refrigerating the vaccine because failure to do so might compromise its efficacy.12 At least 2 weeks before departure, the traveler takes one capsule every other day until all four capsules have been taken. Because mefloquine and antibiotics inhibit the growth in vitro of S. typhi strains, including Ty21a, it is prudent to separate the oral administrations of mefloquine and antibiotics and of Ty21a vaccine by 24 hours.1 It is recommended that a booster dose of Ty21a vaccine, consisting of four capsules taken on alternate days, be given every 5 years to persons who continue to be at risk for exposure to typhoid. The safety of the oral vaccine has not been established for patients with deficient humoral or cell-mediated immunity, and thus, patients with congenital or acquired immunodeficiencies should not receive it. It may be given to children 6 years of age or older.
The second typhoid vaccine is a capsular polysaccharide vaccine for parenteral use (Typhim Vi, from Aventis Pasteur ). Primary vaccination consists of one I.M. dose of 0.5 ml; the same dose is administered as a booster every 2 years. The vaccine is well tolerated but, like the oral vaccine, protects only 50% to 80% of recipients.1,13 This vaccine is safe for immunocompromised persons, including HIV-infected patients.1 The only contraindication to its use is a history of serious reactions to the vaccine. It may be given to children 2 years of age and older.
Rabies
Rabies vaccine—either human diploid cell rabies vaccine (HDCV), purified chick embryo cell vaccine (PCEC), or rabies vaccine adsorbed (RVA)—is an inactivated viral preparation. Immunizations with either of the three vaccine preparations consists of three I.M. doses, 1 ml each, administered on days 0, 7, and 21 or 28.1 Preexposure immunization with rabies vaccine is not indicated for most travelers but should be strongly considered for persons who anticipate contact with wild animals or who are living for a month or more where rabies is endemic. Dog rabies is present in most countries of Asia, Africa, and Central and South America and is prevalent in parts of Brazil, Bolivia, Mexico, El Salvador, Guatemala, Colombia, Ecuador, Peru, India, Nepal, the Philippines, Sri Lanka, Thailand, and Vietnam.1 Preexposure immunization does not eliminate the need for postexposure immunization but abbreviates its course and eliminates the need to administer rabies immune globulin. If left untreated, rabies is fatal, and postexposure rabies immune globulin and postexposure vaccine are frequently unavailable in many areas of the world.
Plague
Plague vaccine is no longer commercially available. Vaccination against plague is not indicated for most travelers.1 However, prophylaxis should be considered for travelers to areas in which plague is epidemic or actively epizootic. For adults, tetracycline or doxycycline is appropriate prophylactic therapy; for children younger than 8 years, trimethoprim-sul-famethoxazole is recommended.1
Hepatitis A
Hepatitis A is prevalent in many less-developed countries [see Figure 2] and is the most common infection acquired by travelers that is preventable by vaccine. In visitors to developing countries, even those staying in luxury hotels, the incidence of hepatitis A in unprotected travelers is about 3 per 1,000 travelers per month of stay, and this rate rises to 20 per 1,000 travelers per month for those eating or drinking under poor hygienic conditions.14
Immunization for hepatitis A is recommended for persons who will be traveling or working in countries with intermediate or high endemicity for hepatitis A infection.1 Although hepatitis A previously was prevented solely by the administration of immune globulin, two monovalent inactivated hepatitis A vaccines and a combined hepatitis A and hepatitis B vaccine are now available. The monovalent vaccines, HAVRIX (Glaxo-SmithKline) and VAQTA (Merck), have proved safe and highly effective.15 For adults, two I.M. 1.0 ml doses should be administered in the deltoid muscle at 0 and 6 to 12 months. For persons between 2 and 18 years of age, two doses, 0.5 ml each, should be administered at 0 and 6 to 12 months. VAQTA contains no preservative, whereas HAVRIX contains 2-phe-noxyethanol. The bivalent hepatitis A and hepatitis B vaccine, TWINRIX (GlaxoSmithKline), is likewise safe and effective and is administered to those 18 years of age or older in three I.M. 1.0 ml doses at 0, 1, and 6 months. TWINRIX contains 2-phenoxyethanol.
With the monovalent vaccines, many persons who have been vaccinated will have detectable antibody responses within 2 weeks after the first dose; 94% to 100% of persons treated will have protective levels of antibody by 1 month after the first dose. The second dose of vaccine provides longer-term protection. If the immunization schedule is unduly interrupted, it is not necessary to restart the full regimen; the second dose may simply be administered. A vaccination series started with one brand of vaccine may be completed with the same or the other brand of hepatitis A vaccine. Travelers who receive vaccine less than 2 weeks before travel are at risk for acquiring hepatitis and should also receive immune globulin, given at an injection site different from the one for vaccine.
For travelers who are allergic to vaccine components or who opt not to receive the vaccine, immune globulin should be administered. Administration of immune globulin should begin shortly before departure in a dose of 2.0 ml I.M. for adults (1.0 ml for patients, including children, weighing 23 to 45 kg; 0.5 ml for those weighing less than 23 kg). If the stay is to be longer than 3 months, the adult dose is 5.0 ml (2.5 ml for patients weighing 23 to 45 kg; 1.0 ml for those weighing less than 23 kg). If the duration of stay is prolonged, the latter dosage schedule should be repeated every 4 to 6 months. Immune globulin should be given at least 2 weeks after measles, mumps, or rubella live virus vaccines. Conversely, these vaccines should be given at least 3 months after immune globulin. Immune globulin does not interfere with the immune response to killed virus vaccines or to yellow fever or polio vaccines.
Because immune globulin has been in limited supply and because the hepatitis A vaccines have proved to be highly effective against hepatitis A infection, which is frequent in travelers, immunization with hepatitis A vaccine has become the principal approach for preventing hepatitis A infection in travelers. The hepatitis A vaccines are safe in pregnancy and immunosuppression.
Hepatitis B
The risk to travelers of acquiring hepatitis B is generally low, compared with the risk of acquiring hepatitis A. The risk increases, however, in regions where hepatitis B is highly prevalent [see Figure 3], if there is contact with blood or bodily secretions, if sexual contact with infected persons occurs, or if travel is pro-longed.1 Immunization for hepatitis B, which is recommended for all persons who work in health care fields with potential exposure to human blood, is especially important for medical workers traveling in countries with high or intermediate hepatitis B endemicity. Hepatitis B immunization should be considered for persons residing for more than 6 months in regions where hepatitis B is endemic and for persons with potential contact with blood (including those receiving tattoos or body piercing), potential sexual contact, or potential need for medical or dental procedures.
Two monovalent hepatitis B vaccines are available, both of which include recombinant HBsAg (hepatitis B surface antigen) protein produced in yeast. Except for rare hypersensitivi-ty reactions to vaccine components, including yeast proteins, the two recombinant vaccines are safe and efficacious; there are no other medical contraindications, including pregnancy and immunosuppression, for administration of these vaccines. The two vaccines, Recombivax HB (Merck) and Engerix-B (Glaxo-SmithKline), are administered in three I.M. doses: at 0, 1, and 6 months. Engerix-B may also be given in four doses: at 0, 1, 2, and 12 months. Immunization should start 6 months before travel, but if this schedule is not feasible, some protection is afforded by one or two doses administered before travel. Full protection will be achieved in most cases by completion of the three-dose or four-dose schedule.1 For travelers who will depart before the recommended series can be completed, an accelerated regimen, involving doses given on days 0, 7, and 14, can be administered; the accelerated regimen is not approved by the Food and Drug Administration. Travelers receiving the accelerated course should receive a booster at least 6 months later to provide long-term immunity.1
An additional vaccine for hepatitis B is TWINRIX, a combined hepatitis A and hepatitis B vaccine. Primary immunization with TWINRIX consists of three doses administered at 0, 1, and 6 months. The bivalent vaccine can be used to complete immunization series started with monovalent hepatitis A and B vaccines.
