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PROPHYLAXIS OF INFECTIOUS DISEASES IN TRAVELERS

PROPHYLAXIS OF INFECTIOUS DISEASES IN TRAVELERS

Sexually Transmitted Diseases
Precautions in Eating and Drinking
Vaccinations
Prevention of Malaria
Traveler’s Diarrhea
Medical Therapy Abroad
Bibliography

Travelers to foreign lands are at high risk to contract an infectious disease; in fact, 30% to 65% of international voyagers experience a diarrheal or systemic illness during or shortly following their stay abroad. Although the majority of these afflictions are of little consequence medically, a number of infections acquired by travelers can be life-threatening, especially when diagnosis is delayed because physicians may be unfamiliar with the manifestations of imported diseases. Thus, preventive measures are essential to increase the chances of illness-free travel and to reduce the likelihood that a serious disease will be acquired abroad.
Updated recommendations for chemoprophylaxis and immunoprophylaxis are published yearly by the Medical Letter and biannually by the Centers for Disease Control (CDC) in Health Information for International Travel, which can be purchased through the Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402 (202-512-1800). The CDC also maintains automated information services available at 888-232-3228 or on the Internet at http://www.cdc.gov. Finally, many medical centers have travelers’ clinics, and reviews on the subject are regularly published; these contain useful information, including recommendations for medical travel kits, guidelines for insect avoidance, suggestions for preventing sexually transmitted diseases, and special information for travelers who are pregnant, disabled, or have chronic illnesses, including infection with HIV.
The clinician must realize that a number of exotic infections can be acquired within the boundaries of the continental United States, including plague (southwestern states), Rocky Mountain spotted fever (mid-Atlantic and south-central states), and relapsing fever (mountainous areas of the western states). Some infections potentially acquired through travel in the United States can produce catastrophic illnesses in patients with underlying conditions; for example, babeosis (Shelter Island, New York; Nantucket Island, Massachusetts) in a splenectomized person and coccidioidomycosis (southwestern states) in a pregnant woman are potentially lethal diseases. The primary care physician, therefore, should review all travel plans and be prepared to provide specific advice for preventing travel-related illnesses.
Sexually Transmitted Diseases
The advice that the physician offers to patients planning trips abroad should include a discussion of sexually transmitted diseases. Because business travelers or long-term residents of foreign countries often engage in sexual intercourse with native peoples, special attention must be paid to these groups. Sexual activity abroad places the traveler at risk for a variety of diseases, including gonorrhea, syphilis, chancroid, herpes simplex, and, most important, hepatitis B and infection with HIV. Travelers must be advised that abstinence is the only means of completely eliminating the risk for acquiring a sexually transmitted disease and that intercourse with male or female prostitutes must be avoided; the danger of sexual relations with prostitutes is highlighted by the fact that in some areas of the world, more than 50% of these persons are HIV-infected. Although the use of condoms reduces the risk for a sexually transmitted disease, it does not entirely eliminate the possibility of acquiring such an illness. Of note, condoms acquired abroad have a greater failure rate than do those purchased in the United States; thus, travelers who believe that they will need them should purchase an adequate supply before departure. Finally, female barrier contraceptives offer no protection from sexually transmitted diseases.
Precautions in Eating and Drinking
Many of the infections acquired by the international traveler result from the ingestion of food or water contaminated by human feces. As a consequence, most water in less developed countries should be considered unfit for consumption or for use in personal hygiene activities, such as brushing teeth. A variety of treatments are available to render water safe for ingestion. Heating water to 65°C will eliminate all enteric bacterial pathogens, and heating to 100°C will disinfect water entirely. Halogenation with chlorine or iodine, contact inactivation with iodine resins, and filtration with sediment and microbial filters are other methods of generating water fit for consumption; preparations or devices for each of these methods are commercially available. If electricity is available, a small coil or beverage heater can be used to boil water for personal use.
Tap water that is too hot for hand washing is considered partially pasteurized and probably safe for brushing teeth, but it is not necessarily safe for drinking. In any case, hot tap water should be cooled without adding potentially contaminated ice cubes or colder water. Alcoholic beverages (e.g., beer, wine), drinks made with boiling water (e.g., tea, coffee), and carbonated beverages are usually safe to drink. Because of their acidic pH, carbonated beverages are bactericidal for common enteric pathogens, such as Salmonella typhi. Unless the purity of canned or bottled water and beverages can be ensured, the traveler cannot presume that their use will prevent illness; for example, bottled beverages have been implicated as the cause of an epidemic of typhoid fever, and bottled water has been linked to an outbreak of cholera.
Dairy products, including ice cream, should not be consumed because of potentially inadequate pasteurization and refrigeration. Fresh vegetables and fruits, such as lettuce and tomatoes, and food served by street vendors should be avoided. Because the treatment of vegetables with chemicals is either impractical or makes food inedible, boiling is usually necessary to ensure that cysts and pathogenic bacteria are killed. Fruits should be peeled before being eaten. Fish and meat must be cooked well and eaten while hot. Finally, bathing, swimming, and boating in fresh or brackish water must be restricted because of the risk for accidentally ingesting microbial pathogens and because of concern about schistosomiasis, which is endemic to portions of Africa, the Middle East, South America, the Caribbean, the Philippines, and Southeast Asia.
Vaccinations
State and local health departments and the CDC can provide invaluable assistance in supplying up-to-date information on specific vaccine recommendations. In general, because some vaccines require multiple doses, immunization schedules should be established early to ensure optimal protection before the traveler departs. Live-virus vaccines must not be administered to immunocompromised patients, and the decision concerning their use in pregnant women should be individualized; for example, pregnant women who must travel to areas of endemic yellow fever should be vaccinated because the complications of yellow fever are assumed to be more severe than those associated with the vaccine. HIV-infected travelers should not receive the bacille Calmette-Guérin (BCG) vaccine or the live-attenuated polio vaccine, and patients with AIDS should not be given the yellow fever vaccine.
Regardless of destination, travelers should be fully immunized with routine vaccines, including those for diphtheria, tetanus, measles, and perhaps mumps and rubella. In addition, persons traveling to rural areas of the tropics may require updated immunization against polio. The hepatitis A vaccine is now recommended for susceptible travelers planning trips to any location outside the United States, Canada, Western Europe, Japan, Australia, or New Zealand. In general, a serologic response to the hepatitis A vaccine will occur within 2 weeks; if travel will be commencing within a few days and if the destination is in a highly endemic area, the patient can be given the hepatitis A vaccine plus a dose of human immune globulin.
Depending on the destination and the duration and purpose of travel, a number of other vaccinations may be necessary; these include the meningococcal, plague, rabies, and yellow fever vaccines. The oral live-attenuated typhoid vaccine should be offered to persons going to rural tropical regions or other areas where typhoid is endemic, including India, Pakistan, Chile, and Peru. Hepatitis B vaccine is recommended for persons traveling to highly endemic regions (Southeast Asia or sub-Saharan Africa), especially medical personnel and persons likely to have sexual contacts; persons at risk for hepatitis B can be identified by screening for the presence of antibodies to that virus. Cholera vaccine is not routinely recommended; however, some countries require proof of vaccination against cholera (as well as yellow fever) as a condition for entry. Specific information regarding vaccination requirements can be secured from the CDC or the Medical Letter, or through one of the references listed below. Required vaccinations must be recorded and validated by the stamp of an official vaccination center in the document “International Certificate of Vaccination”; public health departments can give the locations of these centers. Finally, smallpox vaccine is no longer required by any country.
Prevention of Malaria
Malaria presents the most serious infectious threat to the international traveler. The number of imported civilian cases of malaria has increased steadily during the past two decades. The problem of imported malaria appears directly attributable to the fact that most travelers are not informed about the possibility of acquiring the disease or about the importance of chemoprophylaxis. Between 25% and 30% of visitors to malarious areas do not seek health information, and many travelers requesting guidelines for prevention from physicians are given incorrect advice. (“Take malaria prophylaxis if you want to.” “Ask when you get down there.”) As a consequence, fewer than 20% of persons traveling to regions of endemic malaria receive appropriate chemoprophylaxis.

Malaria is an illness caused by Plasmodium species, which is transmitted to humans through the bite of an infected female Anopheles mosquito. The disease is endemic in many areas of the world between 45 degrees north latitude and 45 degrees south latitude; these regions include Haiti, Central America, South America, sub-Saharan Africa, Southeast Asia, and the Middle East. The prevalence of malaria within these regions is not uniform and varies from year to year; annual reports published by the CDC and World Health Organization are indispensable for following changes in the distribution of the disease. Most importantly, detailed and up-to-date information can be obtained 24 hours a day through the CDC (770-488-7788 or 888-232-3228).
All visitors to areas of endemic malaria should receive chemoprophylaxis regardless of length of stay. Chloroquine remains the cornerstone of prophylaxis; adults should take chloroquine phosphate [300 mg base (500 mg salt)] once weekly, beginning 1 week before arrival at the malarious area and continuing during the entire stay and for 4 weeks after departure. Because routine malaria prophylaxis does not eliminate exoerythrocytic parasites, it may not prevent delayed attacks of disease caused by Plasmodium vivax or Plasmodium ovale. Therefore, some authorities recommend that primaquine [15 mg base (23.6 mg salt)] be given daily during the last 2 weeks of the course of chloroquine. Primaquine prophylaxis is controversial; in general, it is recommended primarily for persons (e.g., Peace Corps volunteers) who plan on extended stays in areas where P. vivax or P. ovale is endemic. In any case, primaquine is contraindicated for pregnant women, and because the drug can produce a hemolytic anemia in persons with glucose-6-phosphate dehydrogenase deficiency, candidates for primaquine should be screened for the disorder.
Chloroquine-resistant Plasmodium falciparum is found throughout the world, including countries in South America (Brazil, Colombia, Venezuela), sub-Saharan Africa, Southeast Asia, and Oceania. Because of serious adverse drug reactions and the emergence of resistant strains of malaria, Pyrimethamine sulfadoxine (Fansidar®) is no longer employed as a prophylactic agent. The CDC recommends that mefloquine [Lariam; 228 mg base (250 mg salt)] be taken once weekly, beginning 1 to 2 weeks before arrival and continuing during the stay and for 4 weeks after departure from the endemic area. About 10% of travelers given mefloquine will experience mild neuropsychiatric symptoms, including depression and dizziness, and those symptoms can lead to a discontinuation of the chemoprophylaxis. Unfortunately, mefloquine is not considered safe for use in pregnancy, and doxycycline, which is also effective in preventing infection by chloroquine-resistant P. falciparum, is similarly contraindicated in pregnancy. Of note, in portions of Cambodia, Thailand, and Myanmar (Burma), chloroquine and mefloquine resistance is prevalent, and travelers to those regions should receive doxycycline (100 mg daily) unless contraindicated.
In addition to being given antimalarial drugs, travelers should be informed that malaria-carrying Anopheles mosquitoes are active only during the hours of darkness and that precautions should be taken to minimize contact with the insects; these precautions include using screening or netting in non–air-conditioned sleeping quarters, avoiding outdoors activities from dusk to dawn, wearing long-sleeved shirts and long pants when outside in the evening, and applying repellent [diethyltoluamide (Deet) for skin, permethrin (Permanone) for clothing]. However, such precautions do not obviate the need for chemoprophylaxis. Patients should be advised that chemoprophylaxis is not 100% effective in preventing malaria and that symptoms consistent with malaria (i.e., chills, fever, headache, and malaise) should be promptly reported to a physician.
Traveler’s Diarrhea
Travelers’ diarrhea is the most common malady experienced by international voyagers; it afflicts approximately 20% of all Americans abroad. The risk for traveler’s diarrhea varies considerably by country; in one report, the attack rates among visitors to Mexico, Spain, Israel, France, and the United Kingdom were 38.8%, 25.6%, 15.4%, 12.9%, and 2.5%, respectively. Attack rates for travelers to Africa and South America exceed 30%. Travelers less than 30 years of age and those on package tours appear to be at greater risk. The difficulty of avoiding traveler’s diarrhea is highlighted by epidemics among airline passengers and among clients at luxury hotels in endemic areas.
Because of the high attack rates and substantial disability associated with this illness, strategies have been devised to prevent it. Dietary discretion and restraint appear to be of little value. On the other hand, in controlled studies, a number of antimicrobial regimens have been found to be effective in preventing traveler’s diarrhea, including ciprofloxacin (500 mg daily), norfloxacin (400 mg daily), ofloxacin (300 mg daily), and levofloxacin (500 mg daily). Voyagers who discontinue prophylactic antimicrobials before leaving an endemic region place themselves at risk to suffer a diarrheal illness. Large doses of bismuth subsalicylate (Pepto-Bismol; 60 mL or two tablets taken four times daily for the duration of exposure) also significantly reduce the likelihood of experiencing traveler’s diarrhea; of note, bismuth subsalicylate is less effective than the fluoroquinolones or other antibiotics. Nevertheless, little enthusiasm for these prophylactic regimens exists. A major concern is that the widespread use of antimicrobials will encourage the emergence of drug-resistant pathogens. Further, antimicrobials are not innocuous drugs, and the use of the fluoroquinolones is precluded in pregnant women and children. Although bismuth subsalicylate is generally safe, the logistics of transporting the medicine and taking the necessary dose are formidable for the traveler seeking relaxation. Thus, the role of prophylactic regimens remains controversial. Some experts recommend prophylactic antimicrobials for selected travelers: athletes; military personnel; persons with a diminished gastric acid barrier to infection secondary to factors such as use of antacids or histamine2 blockers; and patients with a significant underlying medical disorder, such as AIDS, diabetes mellitus, chronic renal disease, or congestive heart failure. The prophylactic regimen should be initiated 1 day before departure and continued for 2 days after returning.
Traveler’s diarrhea usually appears early in the course of a stay abroad, typically within the first week. Clinically, the patient experiences the abrupt onset of diarrhea, which consists of four to five watery bowel movements daily and is associated with low-grade fever, malaise, anorexia, nausea, vomiting, and abdominal cramps. Without therapy, the disorder typically resolves within 2 to 4 days; however, the course may be protracted. Enterotoxigenic Escherichia coli is isolated from more than 50% of patients with traveler’s diarrhea; thus, it is the organism most frequently associated with the illness. Other pathogens include invasive E. coli, Campylobacter species, Shigella species, Salmonella species, Vibrio species, Giardia lamblia, Entamoeba histolytica, and rotavirus. In addition, Aeromonas hydrophila and Plesiomonas shigelloides have been identified as causes of a protracted diarrheal illness in travelers.
The cornerstone of therapy for traveler’s diarrhea is adequate hydration, preferably with oral solutions such as fruit juices that contain sugar (glucose or sucrose) and electrolytes. The antimotility agent loperamide (Imodium) can be helpful in controlling symptoms in patients with mild-to-moderate diarrhea. Because of the absence of data on clinical efficacy and because of high rates of side effects, anticholinergic drugs are not recommended.
In general, antimicrobials are required only for diarrhea caused by specific pathogens, such as Shigella. However, controlled studies have demonstrated that the initiation of antimicrobials at the onset of symptoms can reduce abdominal discomfort and decrease the number of unformed stools in patients with traveler’s diarrhea. Thus, loperamide (loading dose of 4 mg followed by 2 mg after each loose bowel movement, to a maximum of 16 mg/d) plus a single dose of ciprofloxacin (750 mg), levofloxacin (500 mg), or ofloxacin (400 mg) will produce a reduction in the severity of symptoms in most patients within 24 hours.
If the diarrheal illness is associated with high fever, substantial constitutional symptoms, or bloody stools, the patient should be instructed to take ciprofloxacin (500 mg twice daily), levofloxacin (500 mg once daily), ofloxacin (300 mg twice dialy), or norfloxacin (400 mg twice daily) for 3 to 5 days; the use of loperamide in the patient with dysentery remains controversial, but many experts support its use to control cramps and fluid loss. Finally, bismuth subsalicylate can also be used to treat traveler’s diarrhea, although the compound is less effective than loperamide and other therapies; because of widespread resistance, trimethoprimsulfamethoxazole is no longer utilized as a prophylactic or therapeutic agent for travel-associated diarrhea. In sum, self-initiated therapy appears to be an attractive alternative to prophylaxis, and most experts recommend it. Gastrointestinal symptoms that persist or progress require a medical evaluation.
Medical Therapy Abroad
Travelers who require medical attention while abroad can contact travel agents, a U.S. or British embassy, or a U.S. military base for assistance in locating physicians and hospitals. Over-the-counter remedies and local medications should be avoided because they may contain multiple antimicrobials or potentially toxic compounds. Persons who plan to travel for extended periods or who are likely to need medical assistance because of advanced age or debilitating illness should be advised to join the International Association for Medical Assistance to Travelers (716-754-4883), a nonprofit organization that can provide a directory of hospitals and competent, English-speaking physicians in foreign countries. Finally, travelers should be warned that although most infections acquired abroad become manifest within a few weeks after return to the United States, some illnesses (e.g., malaria) may not produce symptoms for several months. (A.L.E.)
Bibliography
Advice for travelers. Med Lett 1998;40:47.
A concise summary with specific recommendations on traveler’s diarrhea, immunizations, and malaria prophylaxis.
DuPont HL, et al. Five versus 3 days of ofloxacin for traveler’s diarrhea: a placebo-controlled study. Antimicrob Agents Chemother 1992;36:87.
This double-blind study of 232 students who experienced diarrhea while visiting Mexico and were given a placebo or ofloxacin (300 mg twice daily) for 3 or 5 days demonstrated that the 3-day regimen was comparable with the 5-day course in producing clinical and microbiologic cures.
Ericsson CD. Traveller’s diarrhea. Epidemiology, prevention and treatment. Infect Dis Clin North Am 1998;12:285.
A comprehensive review.
Insect repellents. Med Lett 1989;31:45.
A review of the safety and effectiveness of skin and clothing repellents likely to be used by travelers.
Johnson PC, et al. Comparison of loperamide with bismuth subsalicylate for the treatment of acute traveler’s diarrhea. JAMA 1986;255:757.
In this study of 219 college students in Latin America, the investigators found that loperamide (a 4-mg initial dose followed by 2 mg for every loose stool, to a maximum of 16 mg/d) was as effective as bismuth subsalicylate in treating acute, nondysenteric traveler’s diarrhea.
Jong EC. Immunizations for international travel. Infect Dis Clin North Am 1998;12:249.
The author provides detailed information concerning indications for and administration and efficacy of all vaccines potentially required for the traveler to foreign lands.
Kemper CA, et al. Travels with HIV: the compliance and health of HIV-infected adults who travel. Int J STD AIDS 1997;8:44.
In this retrospective study of 89 HIV-infected patients, the authors found that 45% traveled within the United States and 20%, abroad; more than 40% of the HIV-infected voyagers became ill either during or following their travels.
Mileno MD, Bia FJ. The compromised traveler. Infect Dis Clin North Am 1998;12:369.
The authors provide a detailed review of the special precautions necessary for HIV-infected, asplenic, diabetic, organ transplant, and other immunocompromised voyagers.
Petruccelli BP, et al. Treatment of traveler’s diarrhea with ciprofloxacin and loperamide. J Infect Dis 1992;165:557.
In this study, 142 military personnel with traveler’s diarrhea were given a single dose of ciprofloxacin (750 mg) with a placebo, or a single dose of ciprofloxacin (750 mg) with loperamide, or a 3-day course of ciprofloxacin (500 mg twice daily) plus loperamide. No significant differences in overall outcomes were noted, although patients randomized to the 3-day ciprofloxacin plus loperamide regimen had fewer liquid bowel movements.
Sakmar TP. The traveler’s medical kit. Infect Dis Clin North Am 1992;6:355.
The author provides detailed recommendations concerning items to be taken abroad to prevent or treat illness.
Samuel BU, Barry M. The pregnant traveler. Infect Dis Clin North Am 1998;12:325.
The authors discusses a number of issues pertinent to the pregnant traveler and the fetus, including the risks of immunizations and malaria prophylaxis and the safety of commonly used antiinfective agents.
Taylor DN, et al. Treatment of traveler’s diarrhea: ciprofloxacin plus loperamide compared with ciprofloxacin alone. Ann Intern Med 1991;114:731.
In this double-blind, randomized study, 104 military personnel with traveler’s diarrhea were given ciprofloxacin (500 mg twice daily for 3 days) plus either a placebo or loperamide (a 4-mg first dose, then 2 mg for every loose stool, up to a maximum of 16 mg/d). Treatment with ciprofloxacin plus loperamide resulted in a more rapid resolution of symptoms; however, at 48 hours, 90% of the subjects in both groups had improved or fully recovered.

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