Advising patients about international travel

Primary Care: Health Advice and Immunizations for Travelers
NEJM - June 8, 2000 -- Vol. 342, No. 23
Edward T. Ryan, Kevin C. Kain

See also Travel Med (1)

This review is intended as an introduction to common and potentially life-threatening illnesses and injuries among travelers and will focus on ways to minimize these risks. (Table 1) , (Table 2) , (Table 3) , (Table 4)

Risk Assessment - must consider both

the traveler'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 expected activities (freshwater exposure, contact with animals, or sexual activity).

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 motion sickness, jet lag, barotrauma associated with air travel, and venothrombosis associated with prolonged sitting (Table 1).

During high-altitude commercial flights, atmospheric pressure in the cabin is equivalent to that at approximately 2500 m above sea level. At this pressure, the partial pressure of arterial oxygen (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.

Traveler's Diarrhea

Diarrhea is the most common illness of travelers. Enterotoxigenic (and possibly enteroaggregative) Escherichia coli and species of campylobacter, shigella, and salmonella account for the majority of identifiable bacterial pathogens. 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, postinfectious enteropathy, and Campylobacter jejuni-associated Guillain-Barre syndrome.

Travelers should be instructed about ways to avoid illnesses transmitted through food and water and about the importance of fluid replacement should diarrhea occur.

Prophylaxis is rarely indicated; however, most travelers should carry an antimotility agent and an antibiotic for self-treatment of diarrhea (Table 2). Although fluoroquinolone antibiotics are generally used for diarrhea, fluoroquinolone resistance is increasing in organisms that cause traveler's diarrhea, especially C. jejuni, and the use of fluoroquinolone antibiotics in children and pregnant women is not approved. Although not specifically approved for the treatment of diarrhea, azithromycin may be a reasonable alternative.

Respiratory Infections

Immunocompromised persons and those with marginal cardiopulmonary reserve may benefit from carrying an appropriate antibiotic for self-treatment. If indicated, influenza and pneumococcal vaccines should be administered.

Arthropod-Borne Illnesses

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 undiagnosed. The mosquitoes that transmit dengue virus usually bite during the daytime and are urban inhabitants, whereas the night-biting mosquitoes that transmit malaria are usually rural. No matter when or where they travel, persons should limit their exposure to arthropods.

A number of insect repellents are available; products containing DEET (N,N-diethyl-3-methylbenzamide, previously called N,N-diethyl-m-toluamide) are the most effective and are extremely safe. 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).

Malaria

This section will briefly review developments in chemoprophylaxis against malaria (Table 2). Other important details of malaria prevention are available elsewhere.

Without chemoprophylaxis, 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). 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 resorts in Southeast Asia and the Americas, do not require antimalarial drugs.

Any measure that reduces exposure to night-biting anopheles mosquitoes will reduce the risk of acquiring malaria (Table 1).

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. Mefloquine is the current drug of choice for most persons at high risk for malaria who are traveling in areas where there is chloroquine resistance. Severe neuropsychiatric reactions (psychosis or convulsions) in response to prophylactic doses of mefloquine have been infrequently reported (in 1 in 10,000 to 1 in 13,000 users). Milder neuropsychological adverse events (anxiety, 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.

Doxycycline is the preferred agent for persons unable to take mefloquine and for those traveling to areas where there is mefloquine resistance-that is, the western provinces of Cambodia and the border regions between Thailand and Cambodia and between Thailand and Myanmar (Burma). An alternative for travelers who are unable to take mefloquine or doxycycline 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 mefloquine in areas where these agents have been studied.

Although it is not yet approved for this indication in the United States, trials have demonstrated that primaquine is an effective and well-tolerated chemoprophylactic agent. Primaquine may cause oxidant-induced hemolytic anemia and methemoglobinemia; its use is contraindicated in pregnant women and in persons with glucose-6-phosphate dehydrogenase deficiency. Because of the activity of primaquine against the liver stages of the malaria parasite, travelers can discontinue primaquine one week after leaving a malarious area.

Tafenoquine (WR238605), a related compound, appears to be more active and better tolerated 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 prevention is currently being studied in phase 3 trials.

A fixed-combination tablet of atovaquone and proguanil is highly effective in the prevention of malaria caused by Plasmodium falciparum and may soon become available in the United States. Evidence suggests 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 azithromycin should not be used for the prevention of malaria, because of poor absorption, toxicity, unfavorable pharmacokinetics, and low efficacy.

Malaria during pregnancy may have severe consequences. If a woman is pregnant or plans to become pregnant and cannot defer travel to a high-risk area, appropriate chemoprophylaxis is essential. 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). Chloroquine plus proguanil is considered safe, but this combination is less effective than mefloquine.

Sexually Transmitted Diseases

At least 5 percent of short-term travelers engage in casual sex while abroad, and condoms are used in half or fewer of these encounters. Long-term workers in foreign countries appear to be at even greater risk, with up to 50 percent of Europeans who live in sub-Saharan Africa reporting casual and often unprotected sexual encounters with African partners. The prevalence of infection with the human immunodeficiency virus among some European overseas workers is 100 to 500 times as high as among similar populations in Europe. Travelers should know the benefits of abstinence or of safe sexual practices, especially the use of condoms, and the hepatitis B vaccine should be administered if it is indicated.

Altitude Illness

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 sickness is usually manifested as headache, nausea, lightheadedness, and insomnia; it occurs in more than 25 percent of persons who ascend rapidly to 2500 m or higher. High-altitude pulmonary and cerebral edema are much rarer conditions. The risk of altitude illness may be reduced by graded ascent and the appropriate use of prophylactic medications such as acetazolamide (Table 1 and Table 2). Although effective, dexamethasone and nifedipine have limited roles in preventing altitude illness because of the risk of adverse events. Mountaineers and trekkers traveling 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 accidents, injuries, and drowning; psychiatric illnesses and stress; sunburn, heat stroke, and heat exhaustion; and illnesses such as rabies that are transmitted by animal bites. Travelers should practice simple precautions that markedly decrease the risk of such illnesses or events (Table 1).

Immunizations

Table 3 summarizes information on immunization for travelers.

Routine Immunizations

Travelers to the developing world should have adequate immunity against measles, mumps, rubella, tetanus, diphtheria, pertussis, varicella, and Haemophilus influenzae type b infection. Travelers to Asia and Africa should also have adequate immunity against poliovirus; the infection has been eliminated from the Western Hemisphere. If indicated, pneumococcal vaccine should be administered. Influenza vaccine and chemotherapeutic agents that are effective against influenzavirus should be considered for those at high risk for severe influenza who are traveling to the tropics or with a large tour group at any time of the year or to the Southern Hemisphere from April through September. 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).

Required Immunizations

Immunization against yellow fever is required by certain countries for entry, according to World Health Organization regulations (Table 3). Yellow fever is a rare but potentially fatal viral infection that is transmitted by day-biting mosquitoes in areas of Latin America and sub-Saharan Africa. Country-specific recommendations are available (Table 4). Vaccination 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-preventable, travel-related illness. The risk of infection is approximately 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 traveling off the usual tourist routes. 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. Two doses provide long-term immunity. Intramuscular immune globulin may be used to provide short-term protection against hepatitis A infection in persons who require immediate immunity and in children too young to receive the vaccine. A combination vaccine that provides protection against hepatitis A and B infections may soon become available.

The incidence of typhoid is approximately 3 to 30 cases per 100,000 travelers to developing countries per month. Vaccination should be targeted to travelers 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. Vaccination should also be considered for immunocompromised persons and those with severe atherosclerotic disease, internal 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 travelers to developing countries (0.2 reported cases per 100,000 travelers per month). Although a number of cholera vaccines are available worldwide, only a poorly tolerated, minimally effective cholera vaccine is available in the United States. Travelers rarely need vaccination against cholera.

The risk of an animal bite may exceed 1 to 2 percent per year for travelers to developing countries. Optimal postexposure prophylaxis against rabies (including rabies immune globulin and tissue-culture-derived vaccines) is often unavailable in many developing countries.Vaccination against rabies before travel should be considered for long-term travelers to the developing world, those who will have unavoidable 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.

Travelers to an area where there is an ongoing outbreak of meningococcal disease caused by Neisseria meningitidis serogroup A, C, Y, or W-135 and those traveling to the "meningitis belt" of sub-Saharan Africa (stretching from Senegal to Ethiopia) between December and June should consider receiving the quadrivalent meningococcal vaccine.

Japanese encephalitis is a viral infection transmitted 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 targeted 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-Guerin vaccine continues 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 reside 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 complicated. (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 northern Europe, Russia, and the Far East may be at very low risk of acquiring tick-borne encephalitis. (50,67) Travelers should not routinely be vaccinated against these illnesses

(Table 3).

From the Tropical and Geographic Medicine Center and the Travelers' Advice and Immunization Center, Division of Infectious Diseases, Massachusetts 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, Toronto (K.C.K.). Address reprint requests to Dr. Ryan at the Division of Infectious Diseases, Jackson 504, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114, or at etryan@partners.org.

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