Data show that 1.1 billion persons crossed an international border in 2014, and this number is projected to increase to 1.8 billion persons in 2025.¹ Tourism is increasing in both high- and low-income destinations, and is the first- or second-largest source of revenue in 20 of the 48 least developed countries.²

Only a minority of international travelers—36% in one study—seek pretravel counseling; of those, 60% see a primary care clinician, 10% see a travel subspecialist, and 30% turn to friends and family.³ Although research supports some portions of the pretravel encounter (e.g., malaria prophylaxis, immunizations), the benefit of counseling on other topics (e.g., motor vehicle crashes, safe sex) has not yet been demonstrated.⁴

Although consulting a clinician is beneficial to patients at any time before international travel, pretravel visits should ideally occur at least six weeks before departure to maximize benefit of immunizations and other preventive measures. The pretravel consultation is likely to be particularly useful in those visiting low-income nations.

Table 1 outlines the recommended components of the pretravel consultation,^5,6 and Table 2 provides resources for clinicians who provide pretravel services. Physicians who perform pretravel consultations only occasionally or who have minimal training in travel medicine may want to refer complex cases to a clinician experienced in travel medicine.

Assessment

The assessment should include dates of travel, anticipated itinerary, planned activities, mode of travel, and reason for travel. Additionally, clinicians should inquire about the traveler's acceptance level for health risks and budget for health care expenditures.

A full medical history should be elicited from the traveler, including immunization records, medications, allergies, and medical conditions. Certain conditions, if uncontrolled, may increase health risks in travelers and include congestive heart failure, hypertension, seizures, diabetes mellitus, and mental illness. Clinicians may recommend against particular trips or activities if they exceed the traveler's physical abilities or if there is a specific contraindication. Persons who have had a myocardial infarction or coronary artery bypass within the previous two weeks, or a complicated myocardial infarction within the previous six weeks,⁷ are thought to be at higher risk of cardiovascular events when flying. Prior use of antimalarials and any adverse effects experienced should be recorded. Physicians should ask women about pregnancy status and birth control method, if applicable.

Selected travel hazards and risk reduction strategies are included in Table 3.^8–12

Noninfectious Risks

The most common cause of death in nonelderly international travelers is motor vehicle crashes, which account for 18% to 24% of deaths in all travelers. Deaths from motor vehicle crashes are markedly more common in low-income nations. Other common causes of death in travelers include violence (e.g., homicide, suicide) and drowning.^13,14

Immunization-Preventable Diseases

eTable A summarizes immunizations recommended for international travelers. Live vaccines should be avoided in travelers who are pregnant or immunocompromised.

ROUTINE VACCINES

In general, the diseases on the routine domestic immunization schedule are more common in travelers than are the travel-specific illnesses; hence, travelers should be up to date on the routine vaccines recommended by the Advisory Committee on Immunization Practices. The most common vaccine-preventable illnesses in international travelers are influenza and hepatitis A. The influenza season is between April and September in the southern hemisphere, and it occurs year-round in locations near the equator. Immunization for influenza should be advised when available. Hepatitis A, transmitted by contaminated food and water, is ubiquitous in low-income nations, and the vaccine is appropriate for all travelers older than one year.¹⁵

TRAVEL-SPECIFIC VACCINES

Travel-specific immunizations include those for typhoid fever,¹⁶ yellow fever, Japanese encephalitis, rabies, and cholera. Travelers may be required to show proof of vaccination for yellow fever to enter or return from nations within endemic regions (tropical Africa and tropical South America). Physicians should document yellow fever vaccination on travelers' International Certificate of Vaccination or Prophylaxis (“yellow card,” as approved by the World Health Organization). An example of the vaccine certificate is available at http://www.who.int/ihr/IVC200_06_26.pdf?ua=1. If travelers have a contraindication to the yellow fever immunization, clinicians should write a letter of exemption or complete the waiver section of the vaccine certificate; these are generally accepted at international borders. Travelers to Saudi Arabia for the annual hajj and umrah (Muslim pilgrimage) are required to show proof of immunization for meningococcal meningitis.

Protection Against Insects and Other Arthropods

PERSONAL PROTECTION MEASURES

It is important to stress to travelers that taking antimalarials does not negate the need for personal protection measures (Table 4¹⁷ ), which guard against malaria and numerous other arthropod-borne diseases (e.g., dengue fever, a common illness in most tropical countries).^18,19

Insect repellent should be applied to exposed skin. The most effective insect repellents contain 20% to 50% diethyltoluamide (DEET)^20,21 or 20% picaridin. Other effective insect repellents are oil of lemon eucalyptus (PMD) and IR3535. Insect repellent should not be applied onto or under clothing. Regular reapplication is important.

Applying permethrin to clothing markedly increases protection against insect bites.^22,23 Travelers to malaria-endemic regions should sleep under a bed net impregnated with permethrin unless there is air-conditioning. Wearing long sleeves and pants offers additional protection. The vector for malaria is the female Anopheles mosquito, which feeds at dusk, nighttime, and dawn; minimizing time outdoors during these times will reduce risk. IR3535 does not provide adequate protection against Anopheles mosquitoes and should not be used in malaria-endemic areas.

MALARIA PROPHYLAXIS

Travelers to endemic regions should receive malaria prophylaxis.^24,25 The choice of prophylactic medication (Table 5^20,26 ) should be based on whether the patient is going to an area with chloroquine-sensitive or chloroquine-resistant malaria, whether there could be potential adverse effects or interactions with the patient's medical conditions or other medications, the convenience of dosing schedule, and the cost. A summary of countries where malaria is endemic and prophylaxis recommendations from the Centers for Disease Control and Prevention are available at http://www.cdc.gov/malaria/travelers/country_table/a.html. Recommendations from the World Health Organization are available at http://www.who.int/ith/2015-ith-chapter7.pdf?ua=1.

Regions where chloroquine-sensitive malaria is endemic include Mexico and Central America (west of the Panama Canal), and the island of Hispaniola (Haiti and the Dominican Republic). Options for prophylaxis in these regions are chloroquine (Aralen) and hydroxychloroquine (Plaquenil). Potential adverse effects of these medications include blurred vision, headache, nausea, and vomiting. Hydroxychloroquine may be better tolerated than chloroquine. Primaquine may be used for prophylaxis in areas affected primarily by Plasmodium vivax malaria.

The options for travelers to chloroquine-resistant regions (including most of South America, Asia, and Africa) are doxycycline, atovaquone/proguanil (Malarone), and mefloquine; these agents are equally effective. Doxycycline, which is taken daily, is relatively inexpensive. Potential adverse effects include nausea, photosensitivity, vaginal yeast infections, and esophageal ulceration. Atovaquone/proguanil, also a daily medication, is the most expensive option but has the lowest incidence of adverse effects. Mefloquine, taken weekly, is well-tolerated by most patients, but has a U.S. Food and Drug Administration boxed warning because of its neurologic and psychiatric adverse effects. In some areas of Southeast Asia, malaria is resistant to mefloquine, and doxycycline or atovaquone/proguanil should be used. Antimalarials should not be purchased in low-income nations because there is a high risk of counterfeit, adulterated, or expired medications.

ZIKA VIRUS INFECTION

Zika virus infection is primarily transmitted by mosquitoes, but it can also be sexually transmitted. Since May of 2015, this disease has spread to Mexico and essentially every country in Central and South America and the Caribbean. Risk of microcephaly in the newborn if a woman is infected in the first trimester of pregnancy has been estimated at 1% to 13%. Pregnant women should avoid travel to areas with Zika transmission. Men who live in or visit a Zika-endemic area should use a condom or abstain from sex with a pregnant partner for the remainder of the pregnancy.^27,28

Traveler's Diarrhea

Traveler's diarrhea (TD) is by far the most common infection in international travelers, with a rate of 30% to 70% depending on destination and season of travel. The risk is highest in the first two weeks of travel and slowly declines thereafter.²⁹ Taking medications that reduce gastric acidity, including proton pump inhibitors and antacids, significantly increases the risk of TD.¹⁰ Other risk factors include younger age, diabetes, and immunosuppression.

The etiology of TD is bacterial in 80% to 90% of cases; the remainder are caused by viral or protozoan organisms. Bacterial and viral TD usually present as the sudden onset of loose stools, cramping, and nausea. Other manifestations may include abdominal pain, fever, vomiting, and bloody stools. TD caused by protozoan organisms, such as Giardia, tends to have a more insidious onset and a longer duration of symptoms.³⁰

PREVENTION

Traditional advice (e.g., avoiding food from street stands, tap water, raw foods, and ice) has not been shown to reduce the incidence of TD.³¹ Hand washing reduces risk by 30%; alcohol-based hand sanitizer also significantly reduces risk.³²

Prophylactic antibiotics are not routinely recommended. For patients at particularly high risk, taking bismuth subsalicylate (Pepto-Bismol; two tablets four times daily for the duration of the trip) reduces risk by 50% to 65%.^20,33 Possible adverse effects of bismuth subsalicylate include a black tongue and dark stool, and contraindications include aspirin allergy, renal insufficiency, breastfeeding, and concurrent use of anticoagulants. There is insufficient evidence for the use of probiotics to prevent TD.

TREATMENT

The primary supportive treatment for TD is rehydration. However, in general, TD is not dehydrating, except for in persons who are very young or old or who have chronic illnesses. If dehydration occurs, travelers can rehydrate with most fluids, including water, juice, soda pop, or tea.

Loperamide (Imodium) is a safe and effective antimotility agent that can be used with or without antibiotics. It should be avoided in persons with warning signs, such as blood in the stool or fever, and in children younger than six years. Diphenoxylate is an alternative antimotility agent.

Without treatment, TD usually lasts three to seven days. A short course of antibiotics usually shortens symptom duration to six to 24 hours.^34,35 Fluoroquinolones are effective for self-treatment of TD in Africa and Latin America. One regimen is ciprofloxacin taken as one 500-mg tablet followed by a second 500-mg tablet 12 hours later. However, a macrolide, such as azithromycin (Zithromax; 500 mg daily for one to three days or one 1,000-mg tablet [higher incidence of nausea]) is more effective in South and Southeast Asia because of the high prevalence of TD caused by fluoroquinolone-resistant Campylobacter. Given the recent warning by the U.S. Food and Drug Administration regarding adverse effects of fluoroquinolones,³⁶ clinicians may consider prescribing a macrolide for self treatment of TD regardless of destination. Rifaximin (Xifaxan), an antibiotic with minimal systemic absorption, can be used as a preventive medication (200 mg once or twice daily) or as treatment (200 mg three times daily for three days). It is not approved by the U.S. Food and Drug Administration for TD prophylaxis.

Because TD is usually self-limited, and antibiotics have potential adverse effects, a course of carry-along antibiotics should be prescribed for the patient to use only if needed. To reduce the risk of creating drug-resistant bacteria, antibiotics should be taken only for severe diarrhea.³⁷

Travelers with TD who develop syncope, dehydration, or symptoms lasting more than one week should seek medical care. Studies show that 3% to 17% of TD cases may result in chronic postinfectious irritable bowel syndrome; the risk increases with multiple bouts of TD.^38,39

Emergency Medical Evacuation Insurance

Emergent medical evacuation from a low-income nation can cost $50,000 to $75,000 or more. Emergency medical evacuation insurance is particularly important for older travelers, for those with chronic medical conditions, and for those engaged in high-risk activities, such as high-altitude climbing. Travelers can visit https://www.squaremouth.com/ to compare travel insurance options, including medical and emergency evacuation insurance.

Travelers with Chronic Medical Conditions

Persons with most medical conditions can travel without restriction, but additional advance preparation may be necessary. Medical conditions should be stable before travel, and patients requiring frequent medical interventions should postpone travel to low-income nations.

Travelers who have chronic medical conditions should carry a list of their medications and physician contact information. Medications should be transported in carry-on, not checked, luggage and remain in the labeled containers in which they were dispensed from the pharmacy. Travelers who have diabetes should accept somewhat higher than usual glucose values during travel days to avoid hypoglycemia. Those requiring oxygen should contact the airline several weeks in advance to arrange for oxygen during flights. The Federal Aviation Administration does not allow passengers to carry their own oxygen tanks; battery-powered portable oxygen concentrators approved by the Department of Transportation may be used. Travelers who have a significant history of cardiac events should travel with a recent electrocardiogram.

Pregnant Women

Most airlines allow pregnant women to fly until 36 weeks of gestation. Pregnant women should not scuba dive because of the potential risk of decompression sickness in the fetus and fetal malformations.⁴⁰

Data Sources: We searched PubMed, the Cochrane Database of Systematic Reviews, Essential Evidence Plus, AHRQ Evidence Reports, and BMJ Clinical Evidence. Key words: travel medicine, immunizations, malaria prophylaxis, traveler's diarrhea, motor vehicle injuries, pretravel consultation. Search dates: May and September 2015, and June 2016.

note: This review updates previous articles by Bazemore and Huntington,²⁶ Lo Re and Guzman,⁴¹ and Dick.⁴²