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Health maintenance recommendations are based not only on the traveler’s destination but also on assessment of risk, which is determined by such variables as health status, specific itinerary, purpose of travel, season, and lifestyle during travel. Detailed information regarding country-specific risks and recommendations may be obtained from the Centers for Disease Control and Prevention (CDC) publication Health Information for International Travel (available at www.cdc.gov/travel).
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Fitness for travel is an issue of growing concern in view of the increased numbers of elderly and chronically ill individuals journeying to exotic destinations (see “Travel and Special Hosts,” below). Since most commercial aircraft are pressurized to 2500 m (8000 ft) above sea level (corresponding to a Pao2 of ~55 mmHg), individuals with serious cardiopulmonary problems or anemia should be evaluated before travel. In addition, those who have recently had surgery, a myocardial infarction, a cerebrovascular accident, or a deep-vein thrombosis may be at high risk for adverse events during flight. A summary of current recommendations regarding fitness to fly has been published by the Aerospace Medical Association Air Transport Medicine Committee (www.asma.org/publications/medical-publications-for-airline-travel). A pre-travel health assessment is advisable for individuals considering particularly adventurous recreational activities, such as mountain climbing and scuba diving.
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IMMUNIZATIONS FOR TRAVEL
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Immunizations for travel fall into three broad categories: routine (childhood/adult immunizations and boosters that are important regardless of travel), required (immunizations that are mandated by international regulations for entry into certain areas or for border crossings), and recommended (immunizations that are desirable because of travel-related risks). Required and recommended vaccines commonly given to travelers are listed in Table 119-1.
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Routine Immunizations
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DIPHTHERIA, TETANUS, AND POLIO
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Diphtheria (Chap. 145) continues to be a problem worldwide. Large outbreaks have occurred in countries that do not have rigorous vaccination programs or that have reduced their public vaccination programs. Serologic surveys show that tetanus (Chap. 147) antibodies are lacking in many North Americans, especially in women aged >50. With the recent increase in pertussis among adults, the diphtheria–tetanus–acellular pertussis (Tdap) combination is now recommended for adults as a once-only replacement for the 10-year tetanus–diphtheria (Td) booster.
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The risk of polio (Chap. 199) to the international traveler is extremely low despite challenges faced by eradication programs. Wild-type poliovirus has been eradicated from most areas of the world; Nigeria, Afghanistan, and Pakistan are the only countries where polio continues to be endemic. Some countries may actually require travelers who have been in country for >4 weeks to show proof on exiting that they have received polio vaccine within the previous year. (Because this list of countries changes, providers should check the CDC travelers’ health website at www.cdc.gov/travel.) Studies in the United States suggest that 12% of adult travelers are unprotected against at least one poliovirus serogroup. Foreign travel offers an ideal opportunity to have polio immunization updated.
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Measles (rubeola) continues to be a major cause of morbidity and death in the developing world (Chap. 200). Several outbreaks of measles in the United States and Canada have been linked to imported cases, especially from Europe, where large outbreaks have occurred. The group at highest risk consists of persons born after 1956 and vaccinated before 1980, in many of whom primary vaccination failed. The measles–mumps–rubella (MMR) vaccine is typically used; its coverage of rubella also addresses a growing concern in some areas of Eastern Europe and Asia.
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Influenza (Chap. 195)—possibly the most common vaccine-preventable infection in travelers—occurs year-round in the tropics and during the summer months in the Southern Hemisphere (coinciding with the winter months in the Northern Hemisphere). One prospective study showed that influenza developed in 1% of travelers to Southeast Asia per month of stay. Annual vaccination should be considered for all travelers who do not have a contraindication. The speed of global spread of the pandemic H1N1 virus in 2009 illustrated why influenza immunization is so important for travelers.
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PNEUMOCOCCAL INFECTION
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Regardless of travel, pneumococcal vaccine (Chap. 141) should be administered routinely to all persons aged >65 and to persons between the ages of 2 and 64 who are at high risk of serious infection, including those with diabetes mellitus; those with chronic heart, lung, or kidney disease; those who have been splenectomized or are immunocompromised; and those who have sickle cell disease.
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Required Immunizations
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Documentation of vaccination against yellow fever (Chap. 204) may be required or recommended as a condition for entry into or passage through countries of sub-Saharan Africa and equatorial South America, where the disease is endemic or epidemic, or (according to the International Health Regulations [IHR]) for entry into countries at risk of having the infection introduced. In 2014, the World Health Organization (WHO) adopted a recommendation to remove the 10-year booster-dose requirement from the IHR as of June 2016. Thus one dose of yellow fever vaccine and a completed International Certificate of Vaccination or Prophylaxis should be valid for the lifetime of the vaccinee. Some countries have already adopted this change, as noted on the CDC’s website under the yellow fever vaccine requirements on each country’s destination page. However, it is uncertain when and whether all countries with yellow fever vaccination requirements will adopt this change. Some countries may still require a booster after 10 years, and a booster may be recommended for other travelers as well. This vaccine is given only by state-authorized yellow fever centers, and its administration must be documented on an official International Certificate of Vaccination or Prophylaxis. A registry of U.S. clinics that provide the vaccine is available from the CDC (www.cdc.gov/travel). Data suggest that fewer than 50% of travelers entering areas endemic for yellow fever are immunized, and lack of coverage is a serious problem. Severe adverse events associated with this vaccine have increased in incidence. First-time vaccine recipients may present with a syndrome characterized as either neurotropic (1 case per 125,000 doses) or viscerotropic (overall, 1 case per 250,000 doses; among persons 60–69 years of age, 1 case per 100,000 doses; and among persons ≥70 years of age, 1 case per 40,000 doses). Immunosuppression and thymic disease increase the risk of these adverse events (https://www.cdc.gov/vaccines/hcp/vis/vis-statements/yf.pdf).
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MENINGOCOCCAL MENINGITIS
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Protection against meningitis is required for entry into Saudi Arabia during the Hajj (Chap. 150). Hajj visas cannot be issued without proof of meningococcal vaccination. All adults and children >2 years of age must have received a single dose of quadrivalent A/C/Y/W-135 vaccine and must show proof of vaccination on a valid International Certificate of Vaccination or Prophylaxis.
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Recommended Immunizations
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Hepatitis A (Chap. 332) is one of the most common vaccine-preventable infections of travelers. Older data demonstrated a risk six times greater for travelers who stray from the usual tourist routes. The mortality rate for hepatitis A increases with age, reaching almost 2% among individuals aged >50. Of the four hepatitis A vaccines currently available in North America (two in the United States), all are interchangeable and have an efficacy of >95%. Hepatitis A vaccine is currently given to all children in the United States. Since the most frequently identified risk factor for hepatitis A in the United States is international travel, and since morbidity and mortality risk increase with age, it seems appropriate that all adults be immune prior to travel.
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Long-stay overseas workers appear to be at considerable risk for hepatitis B infection (Chap. 332), although even short-term travelers can acquire this infection if they indulge in behaviors that place them at risk. The recommendation that all travelers be immunized against hepatitis B before departure is supported by two studies showing that 17% of the assessed travelers who received health care abroad had some type of injection; according to the WHO, nonsterile equipment is used for up to 75% of all injections given in parts of the developing world. A 3-week accelerated schedule of the combined hepatitis A and B vaccine has been approved in the United States. Although no data are available on the specific risk of infection with hepatitis B virus among U.S. travelers, ~240 million people in the world have chronic infection. All children and adolescents in the United States are immunized against this illness. Hepatitis B vaccination should be considered for all travelers.
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TYPHOID AND PARATYPHOID FEVER
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Most cases of typhoid fever in North America are due to travel, with ~300 cases seen per year in the United States. The attack rate for typhoid fever (Chap. 160) is 1 case per 30,000 travelers per month of travel to the developing world. In the United States, >80% of reports of typhoid fever and >90% of reports of paratyphoid fever caused by Salmonella Paratyphi A are in travelers to southern Asia. One group at particular risk are immigrants and their families who have returned to their homelands for VFRs. Between 1999 and 2006 in the United States, 66% of imported cases of S. typhi infection involved the latter group. Unfortunately, data show that both S. typhi and S. paratyphi A have become increasingly resistant to fluoroquinolone antibiotics (especially strains acquired on the Indian subcontinent). Both of the available vaccines—one oral (live) and the other injectable (polysaccharide)—have efficacy rates of ~70% but are not protective against Paratyphi disease. In some countries, a combined hepatitis A/typhoid vaccine is available.
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MENINGOCOCCAL MENINGITIS
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Although the risk of meningococcal disease among travelers has not been quantified, it is likely to be higher among travelers who live with poor indigenous populations in overcrowded conditions (Chap. 150). Because of its enhanced ability to prevent nasal carriage (compared with the older polysaccharide vaccine), a quadrivalent conjugate vaccine is the product of choice (regardless of age) for immunization of persons traveling to sub-Saharan Africa during the dry season or to areas of the world where there are epidemics. The vaccine, which protects against serogroups A, C, Y, and W-135, has an efficacy rate of >90%. Except in rare outbreak situations, there is no role for meningococcal serogroup B immunization of travelers.
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JAPANESE ENCEPHALITIS
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The risk of Japanese encephalitis (Chap. 204), an infection transmitted by night-biting mosquitoes in rural Asia and Southeast Asia, can be as high as ~1 case per 5000 travelers per month of stay in an endemic area. Most infections are asymptomatic; however, among the very small proportion of infected persons who become ill, death and severe neurologic sequelae are common. Most symptomatic infections in recent years have occurred in tourists to Southeast Asia, of whom one-third had traveled for <1 month in an endemic area. The vaccine efficacy rate is >90%, and vaccination is recommended by the CDC for persons staying >1 month in rural endemic areas or for shorter periods if their activities in these areas (e.g., camping, bicycling, hiking) will increase exposure risk. Recent studies suggest that the vaccine schedule (off-label) may be accelerated to 2 doses within 1 week for last-minute travelers.
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The risk of cholera (Chap. 163) is extremely low, with ~1 case per 500,000 journeys to endemic areas. A live oral cholera vaccine was recently approved in the United States by the U.S. Food and Drug Administration (FDA). Its use should be considered for aid and health care workers in refugee camps or in disaster-stricken/war-torn areas.
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Domestic animals, primarily dogs, are the major transmitters of rabies in developing countries (Chap. 203). Several studies have shown that the risk of rabies posed by a dog bite in an endemic area translates into 1–3.6 cases per 1000 travelers per month of stay. Countries where canine rabies is highly endemic include Mexico, the Philippines, Sri Lanka, India, Thailand, China, and Vietnam. The two vaccines available in the United States provide >90% protection. Rabies vaccine is recommended for long-stay travelers, particularly children (who tend to play with animals and may not report bites), and for persons who may be occupationally exposed to rabies in endemic areas; however, in a large-scale study, almost 50% of potential exposures occurred within the first month of travel. Even after receipt of a preexposure rabies vaccine series, two postexposure doses are required; rabies immune globulin (which is often unavailable in developing countries) is not necessary.
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PREVENTION OF MALARIA AND OTHER INSECT-BORNE DISEASES
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It is estimated that >30,000 American and European travelers develop malaria each year (Chap. 219). The risk to travelers is highest in Oceania and sub-Saharan Africa (estimated at 1:5 and 1:50 per month of stay, respectively, among persons not using chemoprophylaxis); intermediate in malarious areas on the Indian subcontinent and in Southeast Asia (1:250–1:1000 per month); and low in South and Central America (1:2500–1:10,000 per month). Malaria surveillance in the United States from 2012 to 2013 showed a 2% increase in cases, and annual increases have been reported since the early 1970s. Of the more than 1700 cases reported in 2014, 66% were due to Plasmodium falciparum; of cases in which a purpose of travel was reported, 58% were associated with VFRs. Patients traveling for VFRs are at the highest risk of acquiring malaria and may die of the disease if their immunity has waned after living outside an endemic area. There were five deaths due to malaria in the United States in 2014. Only 8% of those infected had adhered to CDC guidelines for chemoprophylaxis. With the worldwide increase in chloroquine- and multidrug-resistant falciparum malaria, decisions about chemoprophylaxis have become more difficult. Table 119-2 lists the currently recommended drugs of choice for prophylaxis of malaria, by destination.
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Several studies indicate that fewer than 50% of travelers adhere to basic recommendations for malaria prevention. Keys to the prevention of malaria include both personal protection measures against mosquito bites (especially between dusk and dawn) and malaria chemoprophylaxis. The former measures entail the use of DEET or picaridin-containing insect repellents, permethrin-impregnated bed nets and clothing, screened sleeping accommodations, and protective clothing. Thus, in regions where infections such as malaria are transmitted, protective products are recommended, even for children and infants. In general, higher concentrations of any active ingredient provide a longer duration of protection. However, studies suggest that concentrations of DEET above ~50% do not offer a marked increase in protection time against mosquitoes. The CDC also recommends oil of lemon eucalyptus (PMD, para-menthane-3,8-diol) and IR3535 (3-[N-butyl-N-acetyl]-aminopropionic acid, ethyl ester). Personal protection measures also help prevent other insect-transmitted illnesses, such as dengue, chikungunya, and Zika (Chap. 204).
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Over the past decade, the incidence of dengue has increased considerably, particularly in the Caribbean region, Latin America, Southeast Asia, and Africa. Chikungunya, another mosquito-borne infection that clinically resembles dengue but primarily causes symptoms and signs of arthralgia and arthritis (at times chronic and destructive) has particularly affected the Caribbean in the last few years. Zika virus has also emerged in the past 2 years. Although only 20% of those who are infected have symptoms, Zika virus has been associated with severe complications (microcephaly and other neurologic and organ-system problems) in newborns of women who become infected during pregnancy. In addition, Guillain-Barré syndrome has been associated with Zika virus. Many questions linger with respect to this illness, its complications, and its transmission, especially its sexual transmission.
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The CDC travelers’ health website must be checked prior to travel in order to assess the risk of all these mosquito-borne diseases at specific destinations. Pregnant women should not travel to Zika-affected areas. Dengue, chikungunya, and Zika viruses are transmitted by an urban-dwelling mosquito that may be found indoors and that bites during daylight, primarily at dawn and dusk. Mosquito avoidance measures are crucial for all travelers to regions where these vector-borne diseases are transmitted.
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PREVENTION OF GASTROINTESTINAL ILLNESS
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Diarrhea, the leading cause of illness in travelers (Chap. 128), is usually a short-lived, self-limited condition. However, 40% of affected individuals need to alter their scheduled activities, and another 20% are confined to bed. The most important determinant of risk is the destination. Incidence rates per 2-week stay have been reported to be 10–40%, with the highest rates in parts of Africa and southern Asia. Infants and young adults are at particularly high risk for gastrointestinal illness and for complications such as dehydration. Recent reviews suggest that there is little correlation between dietary indiscretions and the occurrence of travelers’ diarrhea (TD). Earlier studies of U.S. students in Mexico showed that eating meals in restaurants and cafeterias or consuming food from street vendors was associated with increased risk. For further discussion, see “Precautions,” below.
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The most frequently identified pathogens causing TD are enterotoxigenic Escherichia coli (ETEC) and enteroaggregative E. coli (EAEC) (Chap. 156), although in some parts of the world (notably northern Africa and Southeast Asia) Campylobacter infections (Chap. 162) appear to predominate (See also Table 128-3). Other common causative organisms include Salmonella (Chap. 160), Shigella (Chap. 161), rotavirus (Chap. 198), and norovirus (Chap. 198). The latter virus has caused numerous outbreaks on cruise ships and is an increasingly recognized cause of TD, causing up to 30% of such cases in some studies. Except for giardiasis (Chap. 224), parasitic infections are uncommon causes of TD in short-term travelers. A growing problem for travelers is the development of antibiotic resistance among many bacterial pathogens and the movement of such pathogens worldwide. In centers that have molecular diagnostics capacity, other organisms are being identified in stools of patients with acute and chronic TD, although difficulties are encountered in their significance. The greater availability of these new modes for detection of pathogens in stool samples will reveal more about other and perhaps new pathogens responsible for TD.
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Some experts think that it is not only what travelers eat but also where they eat that puts them at risk of illness. Food sold by street vendors can carry a high risk, and restaurant hygiene can be a major problem over which the traveler has no control. In addition to discretion in choosing the source of food and water, general precautions include eating foods piping hot; avoiding foods that are raw or poorly cooked; and drinking only boiled or commercially bottled beverages, particularly those that are carbonated. Heating kills diarrhea-causing organisms, whereas freezing does not; therefore, ice cubes made from unpurified water should be avoided. In spite of these recommendations, the literature has repeatedly documented dietary indiscretions by 98% of travelers within the first 72 h after arrival at their destination. The maxim “Boil it, cook it, peel it, or forget it!” is easy to remember but apparently difficult to follow. Using hand sanitizer regularly has been shown to reduce TD.
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As TD often occurs despite rigorous food and water precautions, travelers may want to carry medications for self-treatment (See also Table 128-5). An antibiotic is useful in reducing the frequency of bowel movements and the duration of illness in moderate to severe diarrhea. The standard regimen is a 3-day course of a quinolone taken twice daily (or, in the case of some formulations, once daily) or, alternatively, a short regimen of azithromycin. However, studies have shown that one double dose of a quinolone or one dose of azithromycin may be equally effective. For diarrhea acquired in areas such as southern and Southeast Asia, where Campylobacter and other infections may be quinolone-resistant, azithromycin is the antibiotic of choice. Rifaximin, a poorly absorbed rifampin derivative, is highly effective against noninvasive bacterial pathogens such as ETEC and EAEC. The current approach to self-treatment of moderate to severe TD for the typical short-term traveler is to carry three once-daily doses of an antibiotic and to use as many doses as necessary to resolve the illness. If neither high fever nor blood in the stool accompanies diarrhea, loperamide may be taken alone or in combination with an antibiotic; studies have shown that the combination is better than the antibiotic alone and does not prolong illness.
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Because of the growing problem of antimicrobial resistance worldwide, there is an effort to remind travelers that mild to moderate diarrhea may be managed with loperamide alone. For diarrhea that interferes with activity, adding an antibiotic is reasonable. However, the downside of antibiotic use is the change in the gut microbiota leading to carriage with extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae that can persist for many months after return (50% for 1 month and 10% for 1 year). In one study, 28–80% of returned travelers carried these organisms after antibiotic self-treatment.
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Bismuth subsalicylate remains a good option for the prophylaxis of TD but is only ~60% effective. For certain high-risk individuals (e.g., athletes, persons with a repeated history of TD, and persons with chronic diseases), a daily dose of a quinolone, azithromycin, or rifaximin during travel of <1 month’s duration is 75–90% efficacious in preventing TD. A recommendation for the use of probiotics or prebiotics is premature; not enough information is available about the efficacy of using agents containing different organisms, the ideal number of organisms per dose, and the lack of product standardization. Further research on the gut microbiome will further elucidate this area. In Europe and Canada, an oral subunit cholera vaccine (Dukoral) that cross-protects against ETEC has been shown to provide 30–50% protection against TD. However, given the epidemiology of ETEC-induced TD, it is expected that only ~10% of travelers will benefit from this vaccine.
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Although extremely common, acute TD is usually self-limited or amenable to antibiotic therapy. Persistent bowel problems after the traveler returns home have a less well-defined etiology and usually require medical attention from a specialist. Infectious agents (e.g., Giardia lamblia, Cyclospora cayetanensis, Entamoeba histolytica) appear to be responsible for only a small proportion of cases with persistent bowel symptoms. One of the most common diagnoses in persistent diarrhea after travel is postinfectious irritable bowel syndrome. In as many as 4–13% of cases, symptoms may last months or years. When no infectious etiology can be identified, a trial of metronidazole therapy for presumed giardiasis (or small-intestinal bowel overgrowth), a strict lactose-free diet for a short period, or a trial of high-dose hydrophilic mucilloid may relieve symptoms. Because management of postinfectious irritable bowel syndrome can be quite complicated, these patients should be referred to a specialist.
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PREVENTION OF OTHER TRAVEL-RELATED PROBLEMS
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Travelers are at high risk for sexually transmitted diseases (Chap. 131). Surveys have shown that large numbers of travelers engage in casual sex, and condoms are not used consistently. Increasing numbers of travelers are being diagnosed with illnesses such as schistosomiasis (Chap. 229), Zika (Chap. 204), dengue (Chap. 204), chikungunya (Chap. 204), and tick-borne rickettsial disease (Chap. 182). Travelers are cautioned to avoid bathing, swimming, or wading in freshwater lakes, streams, or rivers in parts of northeastern South America, parts of the Caribbean, Africa, and Southeast Asia. Travelers should avoid walking barefoot because of the risk of hookworm and Strongyloides infections (Chap. 227) and snakebites (Chap. 451). Insect repellents are important for prevention not only of malaria but also of other vector-borne diseases.
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Prevention of travel-associated injury depends mostly on common-sense precautions. Riding on motorcycles (especially without helmets) and in overcrowded public vehicles is not recommended; in developing countries, individuals should never travel by road in rural areas after dark. Of persons who die during travel, fewer than 1% die of infection, whereas 40% die in motor vehicle accidents. Excessive alcohol use has been a significant factor in motor vehicle accidents, drownings, assaults, and injuries. During travel, situational awareness is important; wearing culturally appropriate clothing, avoiding flashy jewelry, and protecting one’s money and passport are safety essentials.
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THE TRAVELER’S MEDICAL KIT
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A traveler’s medical kit is strongly advisable. The contents may vary widely, depending on the itinerary, duration of stay, style of travel, and local medical facilities. While many medications are available abroad (often over the counter), directions for their use may be nonexistent or in a foreign language, or a product may be outdated or counterfeit. Recent studies of antimalarial products in sub-Saharan Africa and Southeast Asia showed that 30–50% were counterfeit or contained inadequate amounts of active drug. The sale and marketing of such medications are a growing industry that is expected to expand. In the medical kit, the short-term traveler should consider carrying an analgesic; an antidiarrheal agent and an antibiotic for self-treatment of TD; antihistamines; a laxative; oral rehydration salts; a sunscreen with broad-spectrum protection (UVA and UVB, with the latter at a level of at least 30 SPF); a DEET- or picaridin-containing insect repellent; an insecticide for clothing (permethrin); and, if necessary, an antimalarial drug. To these medications, the long-stay traveler might add a broad-spectrum general-purpose antibiotic (levofloxacin or azithromycin), an antibacterial eye and skin ointment, and a topical antifungal cream. The appropriate use of all antimicrobial agents should be reviewed prior to travel. Regardless of the duration of travel, a first-aid kit containing such items as scissors, tweezers, and bandages should be considered.