Chapter 119: Health Recommendations for International Travel

According to the United Nations World Tourism Organization, international tourist arrivals grew dramatically from 25 million in 1950 to >1 billion in 2016; limited data suggest that the only areas without the growth of tourism were in Africa. Not only are more people traveling; travelers are seeking more exotic and remote destinations. In addition to tourism travel, travel across borders has increased in other sectors as well—e.g., for visits with friends and relatives (VFRs) in travelers’ places of birth, for immigration, for business, and for missionary and volunteer work. Travel from industrialized to developing regions has been increasing, with Asia and the Pacific and the Middle East the emerging destinations. Figure 119-1 summarizes the monthly incidence of health problems during travel in developing countries. Studies continue to show that 50–75% of short-term travelers to the tropics or subtropics report some health impairment. Most of these health problems are minor: only 5% require medical attention, and <1% require hospitalization. Although infectious agents contribute substantially to morbidity among travelers, these pathogens account for only ~1% of deaths in this population. Cardiovascular disease and injuries are the most frequent causes of death among travelers from the United States, accounting for 49 and 22% of deaths, respectively. Age-specific rates of death due to cardiovascular disease are similar among travelers and non-travelers. In contrast, rates of death due to injury (the majority from motor vehicle, drowning, or aircraft accidents) are several times higher among travelers. Motor vehicle accidents account for >40% of travelers’ deaths that are not due to cardiovascular disease or preexisting illness.

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).

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.

IMMUNIZATIONS FOR TRAVEL

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.

Routine Immunizations

DIPHTHERIA, TETANUS, AND POLIO

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.

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.

MEASLES

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.

INFLUENZA

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.

PNEUMOCOCCAL INFECTION

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.

Required Immunizations

YELLOW FEVER

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).

MENINGOCOCCAL MENINGITIS

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.

Recommended Immunizations

HEPATITIS A AND B

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.

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.

TYPHOID AND PARATYPHOID FEVER

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.

MENINGOCOCCAL MENINGITIS

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.

JAPANESE ENCEPHALITIS

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.

CHOLERA

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.

RABIES

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.

PREVENTION OF MALARIA AND OTHER INSECT-BORNE DISEASES

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.

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).

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.

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.

PREVENTION OF GASTROINTESTINAL ILLNESS

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.

Etiology

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.

Precautions

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.

Self-Treatment

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.

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.

Prophylaxis

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.

Illness after Return

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.

PREVENTION OF OTHER TRAVEL-RELATED PROBLEMS

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.

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.

THE TRAVELER’S MEDICAL KIT

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.

PREGNANCY AND TRAVEL

A woman’s medical history and itinerary, the quality of medical care at her destinations, and her degree of flexibility determine whether travel is wise during pregnancy (See also Chap. 466). According to the American College of Obstetrics and Gynecology, the safest part of pregnancy in which to travel is between 18 and 24 weeks, when there is the least danger of spontaneous abortion or premature labor. Some obstetricians prefer that women stay within a few hundred miles of home after the 28th week of pregnancy in case problems arise. In general, however, healthy women may be advised that it is acceptable to travel.

Relative contraindications to international travel during pregnancy include a history of miscarriage, premature labor, incompetent cervix, or toxemia. General medical problems such as diabetes, heart failure, severe anemia, or a history of thromboembolic disease also should prompt the pregnant woman to postpone her travels. Finally, destinations in which the pregnant woman and her fetus may be at excessive risk (e.g., those in Zika-affected areas, those at high altitudes, those where live-virus vaccines are required, and those where multidrug-resistant malaria is endemic) should be avoided.

Malaria

Malaria during pregnancy carries a significant risk of morbidity and mortality. Levels of parasitemia are highest and failure to clear the parasites after treatment is most frequent among primigravidae. Severe disease, with complications such as cerebral malaria, massive hemolysis, and renal failure, is especially likely in pregnancy. Fetal sequelae include spontaneous abortion, stillbirth, preterm delivery, and congenital infection. Chloroquine and mefloquine are considered to be safe in all trimesters.

Enteric Infections

Pregnant travelers must be extremely cautious regarding their food and beverage intake. Dehydration due to TD can lead to inadequate placental blood flow. Infections such as toxoplasmosis, hepatitis E, and listeriosis also can cause serious sequelae in pregnancy.

The mainstay of therapy for TD during pregnancy is rehydration. Loperamide may be used if necessary. For self-treatment, azithromycin may be the best option. Although quinolones are increasingly being used safely during pregnancy and rifaximin is poorly absorbed from the gastrointestinal tract, these drugs are not approved for this indication.

Because of the serious problems encountered when infants are given local foods and beverages, women are strongly encouraged to breast-feed when traveling with a neonate. A nursing mother with TD should not stop breast-feeding but should increase her fluid intake.

Air Travel and High-Altitude Destinations

Commercial air travel is not a risk to the healthy pregnant woman or to the fetus. The higher radiation levels reported at altitudes of >10,500 m (>35,000 ft) should pose no problem for the healthy pregnant traveler. Since each airline has a policy regarding pregnancy and flying, it is best to check with the specific carrier when booking reservations. Domestic air travel is usually permitted until the 36th week, whereas international air travel is generally curtailed after the 32nd week.

There are no known risks for pregnant women who travel to high-altitude destinations and stay for short periods. However, there are likewise no data on the safety of pregnant women at altitudes of >4500 m (15,000 ft). A prominent concern is that most of these destinations are remote.

THE HIV-INFECTED TRAVELER

The HIV-infected traveler is at special risk of serious infections due to a number of pathogens that may be more prevalent at travel destinations than at home (See also Chap. 197). However, the degree of risk depends primarily on the state of the immune system at the time of travel. For persons whose CD4+ T cell counts are normal or >500/μL, data suggest no greater risk during travel than for persons without HIV infection. Individuals with AIDS (CD4+ T cell counts of <200/μL) and others who are symptomatic need special counseling and should visit a travel medicine practitioner before departure, especially when traveling to developing countries.

Several countries deny entry to HIV-positive individuals for prolonged stay, even though these restrictions do not appear to decrease rates of transmission of the virus. In general, HIV testing is required for individuals who wish to stay abroad for >3 months or who intend to work or study abroad. Some countries will accept an HIV serologic test done within 6 months of departure, whereas others will not accept a blood test done at any time in the traveler’s home country. Border officials often have the authority to make inquiries of individuals entering a country and to check the medications they are carrying. If antiretroviral drugs are identified, the person may be barred from entering the country. Information on testing requirements for specific countries is available from consular offices but is subject to frequent change.

Immunizations

All of the HIV-infected traveler’s routine immunizations should be up to date (Chap. 118). The response to immunization may be impaired at CD4+ T cell counts of <200/μL and in some cases at even higher counts. Thus HIV-infected persons should be vaccinated as early as possible to ensure adequate immune responses. For patients receiving antiretroviral therapy, at least 3 months must elapse before regenerated CD4+ T cells can be considered fully functional; therefore, vaccination of these patients should be delayed. However, when the risk of illness is high or the sequelae of illness are serious, immunization is recommended. In certain circumstances, it may be prudent to check the adequacy of the serum antibody response before departure.

Because of the increased risk of infections due to Streptococcus pneumoniae and other bacterial pathogens that cause pneumonia after influenza, the conjugate pneumococcal vaccine (Prevnar 13) followed by the 23-valent polysaccharide vaccine (Pneumovax) as well as influenza vaccine should be administered. The estimated rates of response to influenza vaccine are >80% among persons with asymptomatic HIV infection and <50% among those with AIDS.

In general, live attenuated vaccines are contraindicated for persons with immune dysfunction. Because measles (rubeola) can be a severe or lethal infection in HIV-positive patients, these patients should receive the measles vaccine (or the combination MMR vaccine) unless the CD4+ T cell count is <200/μL. Between 18 and 58% of symptomatic HIV-infected vaccinees develop adequate measles antibody titers, and 50–100% of asymptomatic HIV-infected persons seroconvert.

In asymptomatic HIV-infected individuals, CD4+ T cell counts of 200–499/μL (moderate immune suppression) are considered a precaution for yellow fever vaccination; since there is no contraindication, yellow fever vaccine may be considered when these persons travel to endemic areas. Studies of these individuals, along with asymptomatic persons whose CD4+ T cell count is >500/μL, found no serious adverse events, although their immunologic response may be decreased. If the CD4+ T cell count is <200/μL, an alternative itinerary that poses no risk of exposure to yellow fever is recommended. If the traveler is passing through or traveling to an area where the vaccine is required but the disease risk is low, a physician’s waiver should be issued. Although the WHO indicates that a single dose of yellow fever vaccine provides lifetime protection, the CDC recommends boosters every 10 years for HIV-infected individuals.

A transient increase in HIV viremia (lasting days to weeks) has been demonstrated in HIV-infected individuals after immunization against influenza, pneumococcal infection, and tetanus (Chap. 197). At this point, however, no evidence indicates that this transient increase is detrimental.

Gastrointestinal Illness

Decreased levels of gastric acid, abnormal gastrointestinal mucosal immunity, other complications of HIV infection, and medications taken by HIV-infected patients make TD especially problematic in these individuals. TD is likely to occur more frequently, to be more severe, to be accompanied by bacteremia, and to be more difficult to treat. Cryptosporidium, Isospora belli, and Microsporidium infections, although uncommon, are associated with increased morbidity and mortality rates in patients with AIDS.

The HIV-infected traveler must be careful to consume only appropriately prepared foods and beverages, and some may benefit from antibiotic prophylaxis for TD. Sulfonamides (as used to prevent pneumocystosis) are ineffective because of widespread resistance.

Other Travel-Related Infections

Data are lacking on the severity of many vector-borne diseases in HIV-infected individuals. Malaria is especially severe in asplenic persons and in those with AIDS. The HIV load doubles during malaria, with subsidence in ~8–9 weeks; the significance of this increase in viral load is unknown.

Visceral leishmaniasis (Chap. 221) has been reported in numerous HIV-infected travelers. Diagnosis may be difficult, given that splenomegaly and hyperglobulinemia are often lacking and serologic results are frequently negative. Sandfly bites may be prevented by evening use of insect repellents.

Certain respiratory illnesses, such as histoplasmosis and coccidioidomycosis, cause greater morbidity and mortality among patients with AIDS. Although tuberculosis is common among HIV-infected persons (especially in developing countries), its acquisition by the short-term HIV-infected traveler has not been reported as a major problem. From a prospective study, it is estimated that, for travelers not engaged in health care, the risk of tuberculosis infection is ~3% per year of travel.

Medications

Adverse events due to medications and drug interactions are common and raise complex issues for HIV-infected persons. Rates of cutaneous reaction (e.g., increased cutaneous sensitivity to sulfonamides) are unusually high among patients with AIDS. Doxycycline appears to have no clinically significant interactions with either the protease inhibitors or the non-nucleoside reverse transcriptase inhibitors (NNRTIs). Zidovudine levels may be increased with atovaquone. The drug combination atovaquone/proguanil may interact with antiretroviral protease inhibitors such as ritonavir, darunavir, atazanavir, indinavir, and lopinavir as well as the NNRTIs nevirapine, etravirine, and efavirenz. In spite of potential interactions, atovaquone/proguanil is well tolerated and remains the choice for most HIV-infected travelers.

Concomitant administration of the antimalarial drug mefloquine and antiretroviral protease inhibitors such as ritonavir, lopinavir, darunavir, and atazanavir may result in increased levels of mefloquine, with an increased risk of QT prolongation. Similarly, ritonavir may increase chloroquine levels. On the other hand, serum levels of mefloquine may be lowered with the use of efavirenz, nevirapine, or etravirine. Because of the increase in antiretroviral agents and the lack of accumulated data on their interactions with antimalarial agents, decisions about malaria chemoprophylaxis continue to be difficult; with a short duration of travel, an interaction may be inconsequential. With regard to malaria treatment, a hypothetical concern is that the antimalarial drugs lumefantrine (combined with artemether in Coartem) and halofantrine (no longer recommended due to toxicity) may interact with HIV protease inhibitors and NNRTIs since drugs in the latter two categories are known to be potent inhibitors of cytochrome P450. In keeping current with antiretroviral drug interactions, a website from the University of Liverpool (www.hiv-druginteractions.org) is helpful.

CHRONIC ILLNESS, DISABILITY, AND TRAVEL

Chronic health problems need not prevent travel, but special measures can make the journey safer and more comfortable.

Heart Disease

Cardiovascular events are the main cause of deaths among travelers and of in-flight emergencies on commercial aircraft. Extra supplies of all medications should be kept in carry-on luggage, along with a copy of a recent electrocardiogram and the name and telephone number of the traveler’s physician at home. Pacemakers are not affected by airport security devices, although electronic telephone checks of pacemaker function cannot be transmitted by international satellites. Travelers with electronic defibrillators should carry a note to that effect and ask for hand screening. A traveler may benefit from supplemental oxygen; since oxygen delivery systems are not standard, supplementary oxygen should be ordered by the traveler’s physician well before flight time. Travelers may benefit from aisle seating and should walk, perform stretching and flexing exercises, consider wearing support hose, and remain hydrated during the flight to prevent venous thrombosis and pulmonary embolism.

Chronic Lung Disease

Chronic obstructive pulmonary disease is one of the most common diagnoses in patients who require emergency-department evaluation for symptoms occurring during airline flights. The best predictor of the development of in-flight problems is the sea-level PaO₂. A PaO₂ of at least 72 mmHg corresponds to an in-flight arterial PaO₂ of ~55 mmHg when the cabin is pressurized to 2500 m (8000 ft). If the traveler’s baseline PaO₂ is <72 mmHg, the provision of supplemental oxygen should be considered. Contraindications to flight include active bronchospasm, lower respiratory infection, lower-limb deep-vein phlebitis, pulmonary hypertension, and recent thoracic surgery (within the preceding 3 weeks) or pneumothorax. Decreased outdoor activity at the destination should be considered if air pollution is excessive.

Diabetes Mellitus

Alterations in glucose control and changes in insulin requirements are common problems among patients with diabetes who travel. Changes in time zones, in the amount and timing of food intake, and in physical activity demand vigilant assessment of metabolic control. Because of the risk of foot ulcers, travelers should wear closed footwear that has been proven to be comfortable. The traveler with diabetes should pack medication (including a bottle of regular insulin for emergencies), insulin syringes and needles, equipment and supplies for glucose monitoring, and snacks in carry-on luggage. Insulin is stable for ~3 months at room temperature but should be kept as cool as possible. The name and telephone number of the home physician and a card and bracelet listing the patient’s medical problems and the type and dose of insulin used should accompany the traveler. In order to facilitate international border crossings, travelers should carry a physician’s letter authorizing the carriage of needles and syringes. In traveling eastward (e.g., from the United States to Europe), the patient may need to decrease the morning insulin dose on arrival. The blood glucose can then be checked during the day to determine whether additional insulin is required. For flights westward, with lengthening of the day, an additional dose of regular insulin may be required.

Other Special Groups

Other groups for whom special travel measures are encouraged include patients undergoing dialysis, those with transplants, and those with other disabilities. Up to 13% of travelers have some disability, but few advocacy groups and tour companies dedicate themselves to this growing population. Medication interactions are a source of serious concern for these travelers, and appropriate medical information should be carried, along with the home physician’s name and telephone number. Some travelers taking glucocorticoids carry stress doses in case they become ill. Immunization of these immunocompromised travelers may result in less than adequate protection. Thus the traveler and the physician must carefully consider which destinations are appropriate.

Today, more elderly or chronically ill individuals travel, and more of these individuals journey to remote locations and enjoy adventurous activities. Illness or injury abroad is not uncommon and is best considered before the journey. Persons who develop health problems abroad may incur enormous out-of-pocket expenses. Thus prospective travelers should consider purchasing supplemental travel health insurance and should check with their health insurance company regarding whether they have coverage for illness or injury overseas. Unfortunately, many insurance companies will not cover preexisting illness if it is the reason for trip cancellation or illness abroad. Most countries do not accept routine health insurance from other countries unless there is a special traveler supplement. In most circumstances, travelers are asked to pay in cash for services rendered on an emergency basis, whether in a physician’s office, in an emergency or urgent care center, or even in a hospital. There are several types of travel insurance. It is wise to purchase trip cancellation insurance, especially, for example, if the traveler has an underlying chronic illness and may need to cancel a trip due to an exacerbation of disease. Travel health insurance will cover expenses in the event that medical care abroad is needed. Evacuation insurance will cover medical evacuation, usually to a medical center in another location where it is deemed that the care is similar to that available in the traveler’s home country. The cost of medical evacuation can easily exceed $100,000 U.S. There are a number of travel insurance providers, and it is very important to read the fine print carefully and to determine exactly what each company provides, thereby ensuring an appropriate fit for the individual’s particular circumstances. The U.S. Department of State website lists travel health insurance companies and provides information about whom to contact in an emergency through STEP (the Smart Traveler Enrollment Program: https://travel.state.gov/content/passports/en/go/health/doctors.html).

Travel for the purpose of obtaining health care abroad has received a great deal of attention in the medical literature and the media. Although the data are difficult to confirm, it has been estimated that at least 750,000 Americans travel each year for medical purposes. According to the Department of Commerce website, the numbers of such travelers have doubled recently, and some experts predict massive increases. Lower cost is usually cited as the motivation for this type of tourism, and an entire industry has flourished as a result of this phenomenon. However, the quality of facilities, assistance services, and care is neither uniform nor regulated; thus, in most instances, responsibility for assessing the suitability of an individual program or facility lies solely with the traveler. Persons considering this option must recognize that they are almost always at a disadvantage when being treated in a foreign country, particularly if there are complications. Concerns to be addressed include the quality of the health care facility and its staff; language and cultural differences that may impede accurate interpretation of both verbal and nonverbal communication; religious and ethical differences that may be encountered over issues such as efforts to preserve life and limb or the provision of care for the terminally ill; lack of familiarity with the local medical system; limited access of the care provider to the patient’s medical history; the use of unfamiliar drugs and medicines; the relative difficulty of arranging follow-up care back in the United States; and the possibility that such follow-up care may be fraught with problems should there be complications. If serious issues arise, legal recourse may be difficult or impossible. Patients planning to travel abroad to obtain health care, particularly when surgery is involved, should be immunized for hepatitis B and should consider having baseline hepatitis C and HIV tests preoperatively. Prevalence rates of hepatitis B and C and HIV infection vary considerably around the world and are generally higher in developing regions than in the United States and Western Europe. The latest information available on the safety of the blood supply outside the United States is the WHO’s Global Database on Blood Safety based on data from 2011 (www.who.int/topics/blood_safety/en). Persons researching the accreditation status of overseas facilities should note that, although these facilities may be part of a chain, they are surveyed and accredited individually. Accreditation resources include (1) the Joint Commission International (www.jointcommissioninternational.org), (2) the Australian Council for Healthcare Standards International (www.achs.org.au/achs-international/), and (3) Accreditation Canada International (www.internationalaccreditation.ca). The American Medical Association also offers guidelines for medical tourism (www.medretreat.com/templates/UserFiles/Documents/Whitepapers/AMAGuidelines.pdf).

The most common medical problems encountered by travelers after their return home are diarrhea, fever, respiratory illnesses, and skin diseases (Fig. 119-2). Frequently ignored problems are fatigue and emotional stress, especially in long-stay travelers. The approach to diagnosis requires some knowledge of geographic medicine, in particular the epidemiology and clinical presentation of infectious disorders. A geographic history should focus on the traveler’s exact itinerary, including dates of arrival and departure; exposure history (food indiscretions, drinking-water sources, freshwater contact, sexual activity, animal contact, insect bites); location and style of travel (urban vs rural, first-class hotel accommodation vs. camping); immunization history; and use of antimalarial chemosuppression. Recently, some travelers who have been hospitalized abroad have been shown on return to be colonized with multidrug-resistant bacteria such as Enterobacteriaceae producing ESBLs and bacteria producing NDM-1 (New Delhi metallo-β-lactamase 1); these bacteria may be transmitted to family members and other contacts, especially within the health care system.

DIARRHEA

See “Prevention of Gastrointestinal Illness,” above.

FEVER

Fever in a traveler who has returned from a malarious area should be considered a medical emergency because death from Plasmodium falciparum malaria can follow an illness of only several days’ duration. Although “fever from the tropics” does not always have a tropical cause, malaria should be the first diagnosis considered. The risk of P. falciparum malaria is highest among travelers returning from Africa or Oceania and among those who become symptomatic within the first 2 months after return. Other important causes of fever after travel include dengue, chikungunya, Zika, viral hepatitis (A and E), typhoid and paratyphoid fever, bacterial enteritis, rickettsial infections (including tick typhus, scrub typhus, and Q fever), and—in rare instances—leptospirosis, acute HIV infection, and amebic liver abscess. Studies published by GeoSentinel (an emerging infectious disease surveillance group established by the CDC and the International Society of Travel Medicine) have informed providers about specific illness and syndrome risks in ill returned travelers (Fig. 119-2). Outbreaks of dengue, previously considered to be very rare in Africa, have been documented recently across central Africa. However, in at least 25% of cases, no etiology of fever in a returning traveler can be found, and the fever resolves spontaneously. Clinicians should keep in mind that no present-day antimalarial agent guarantees protection from malaria and that some immunizations (notably, that against typhoid fever) are only partially protective.

When no specific diagnosis is forthcoming, the following investigations, where applicable, are suggested: complete blood count, liver function tests, thick/thin blood films or rapid diagnostic testing for malaria (repeated several times if necessary), urinalysis, urine and blood cultures (repeated once), rapid influenza diagnostic testing, chest x-ray, and collection of an acute-phase serum sample to be held for subsequent examination along with a paired convalescent-phase serum sample.

SKIN DISEASES

Pyodermas, sunburn, insect bites, skin ulcers, and cutaneous larva migrans are the most common skin conditions affecting travelers after their return home. In individuals with persistent skin ulcers, a diagnosis of cutaneous leishmaniasis, mycobacterial infection, or fungal infection should be considered. Careful, complete inspection of the skin is important in detecting the rickettsial eschar in a febrile patient or the central breathing hole in a “boil” due to myiasis.

EMERGING INFECTIOUS DISEASES

In recent years, travel and commerce have fostered the worldwide spread of chikungunya, Zika, influenza caused by novel serotypes, severe acute respiratory syndrome (SARS), and (earlier) HIV infection and the reemergence of cholera as a global health threat. For travelers, some of these issues, along with others, remain a concern. Dengue continues to pose serious health threats in Latin America and Southeast Asia; schistosomiasis is being described in previously unaffected lakes in Africa; and antibiotic-resistant strains of sexually transmitted and enteric pathogens are emerging at an alarming rate.

The growth of global travel and migration now demand that the clinician become as familiar as possible with travel medicine. Practitioners may choose either to refer their patients to a travel clinic before departure or to acquire knowledge that enables them to provide pre-travel counseling and to prescribe appropriate vaccinations and chemoprophylaxis. It is equally important for physicians seeing ill returned travelers to be familiar with common post-travel syndromes and diseases, particularly those that may have been acquired in the developing world, and to identify other physicians who can assist with complex post-travel illnesses. The CDC publishes a biennial text, Health Information for International Travel (accessed through their website at www.cdc.gov/travel), that provides pre-travel health recommendations. The International Society of Travel Medicine (www.istm.org) publishes a list of travel clinics, and the American Society of Tropical Medicine and Hygiene (www.astmh.org) publishes a list of clinical tropical medicine specialists.

As Nobel Laureate Dr. Joshua Lederberg pointed out, “The microbe that felled one child in a distant continent yesterday can reach yours today and seed a global pandemic tomorrow.” The vigilant clinician understands that the importance of a thorough travel history cannot be overemphasized.