Chapter 45: Travel Medicine

Twenty-seven million people from the United States travel internationally per year; one-third of them travel to developing nations. Approximately 50%–70% of travelers become ill during their travel overseas. The number of children traveling with families continues to increase. Children who travel are especially susceptible to infectious diseases, trauma, and other health problems, which vary with the destination. Preparation for travel with children and infants includes consideration of destination-specific risks, underlying medical problems, and administration of both routine and travel-related vaccines. Pretravel counseling should ideally take place at least 1 month prior to travel, given the need to develop an effective immune response from any travel-associated vaccinations. The physician involved in pretravel counseling should focus on the issues listed in Table 45–1.

Travel Plans

Parents and care providers should be advised that travel with children and infants is much more enjoyable when the number of journeys in a single trip is limited, travel time is kept relatively short, and travel delays are anticipated. Planning for delays and other problems should include bringing new or favorite toys or games for distraction and carrying extra food and drink, changes of clothing, and fever medications.

Medical Care During Travel

It is useful to obtain names and addresses of local health care providers at the family’s destination. This is available from travel medicine practitioners or from the membership directory of the International Society of Travel Medicine. The International Association for Medical Assistance to Travelers website (www.iamat.org) is another useful resource with a worldwide directory of providers proficient in English. Travel insurance, which is highly encouraged, should not only cover medical care at the destination but also provide 24-hour helplines with information regarding English-speaking physicians and hospitals, and arrange and pay for evacuation to a medical facility that provides necessary treatment that is not available locally. In emergencies, parents and caretakers should take their children to the largest medical facility in the area, which is more likely to have a pediatric unit and trauma services.

Trauma

Trauma is a common cause of morbidity and mortality in traveling children. Parents should rent larger, safer vehicles, and use car seats whenever possible. However, in many developing countries, car seats are not available, so caretakers may need to travel with their own. Taxis often do not have seatbelts, so it may be necessary to request taxis with seatbelts by calling in advance.

Air Travel

Healthy term infants can travel by commercial pressurized airplane. Children at higher risk during air travel may include premature infants and those with chronic cardiac or pulmonary disease, so appropriate counseling with their specialist is indicated. Many parents request advice regarding sedation of their child during travel. While this is not recommended, the most widely used agent is diphenhydramine. It is advisable to try a test dose prior to travel as idiosyncratic reactions and overdosing can lead to an anticholinergic syndrome or a paradoxical stimulating effect.

Ear Pain

Children and infants often have pain during ascent and descent of commercial airplanes due to changes in middle ear pressure causing retraction or protrusion of the tympanic membrane. Methods that can alleviate or minimize ear pain during these times include chewing, swallowing, nursing, and bottle feeding.

Motion Sickness

Almost 60% of children will experience motion sickness during travel. While older children have symptoms similar to those in adults (such as nausea, epigastric discomfort, headache, general discomfort), children younger than 5 years may have gait abnormalities as the predominant symptom. Nonpharmacologic preventive strategies include eating a light meal at least 3 hours before travel; avoiding dairy products and foods high in calories, protein, and sodium before travel; sitting in the middle of the back seat or in the front seat if age-appropriate; focusing on a stable object or the horizon; avoiding reading or other visual stimuli; eye closure; fresh air; and limiting excessive head movement. Pharmacologic intervention has not been well studied in children, but if necessary, antihistamines such as diphenhydramine are recommended for children younger than 12 years and scopolamine is acceptable for children older than 12 years. These measures, however, are not evidence-based.

High Altitude

Acute mountain sickness is as common in children as in adults, but it may go unrecognized due to its subtle presentation, such as unexplained mental fussiness or change in appetite and sleep patterns. High-altitude pulmonary edema (HAPE) is seen in children traveling to high altitudes; it also occurs in children who live at high altitude, descend for an extended period, and return to altitude. Mild symptoms of altitude sickness can be treated with rest and hydration, or analgesics such as ibuprofen or acetaminophen. High-altitude sickness is milder and resolves much more quickly in children compared to adults, so prophylaxis is usually not required. Acetazolamide has not been studied in children for acute mountain sickness, but it is safe in this age group and has been used for both prophylaxis and treatment. The pediatric dose is 5 mg/kg/day (125 mg maximum) divided twice daily, starting 1 day before ascent, and continued for 2 days at high altitude.

Medications/First-Aid Kit

A small medical kit is useful when traveling. Included in this kit should be medications for illnesses that the child experiences at home, trip-specific items, and the usual first-aid kit items (Table 45–2). Medications should be purchased prior to travel, as those obtained at some destinations may be of poor quality or contain toxic substances.

Many vaccine-preventable diseases remain prevalent in developing countries, and outbreaks still occur in areas where these diseases are considered rare. The schedule for some vaccines may be accelerated for travel, and some vaccines can be given earlier than the recommended age. Vaccination pertaining to children traveling follows the routine vaccination schedule as outlined in Chapter 10. The recommended intervals balance the high-risk age for disease with infant immunologic responses. The recommended minimum interval between doses is listed in Table 45–3. Barriers to some early immunizations are antibody from the mother interfering with an infant’s ability to mount an antibody response, particularly to live vaccines, and the lack of a T-cell–dependent immune response to certain immunogens in those younger than 2 years. Minor febrile illnesses are not a contraindication to routine or travel vaccines and should not lead to their postponement. Live vaccines should be given together or separated by 30 days or more.

Diphtheria-Tetanus-Acellular Pertussis Vaccine

Immunization is recommended prior to travel to developing countries because of the greater risk of disease from diphtheria, tetanus, and pertussis. Tetanus risk is high in several areas of the developing world where fecal contamination of soil is extensive. Infants should receive their first diphtheria-tetanus-acellular pertussis (DTaP) at 6 weeks of age for an adequate immune response, with a 4-week interval between the subsequent two doses. Adequate protection is achieved after the third dose. The fourth dose may be given 6–12 months after the third dose provided that the child is 12 months of age or older. Tdap is licensed for children at least 11 years of age. Adolescents and adult caretakers, who are prominent vectors in the spread of pertussis to young children, should receive a single Tdap booster. If more than 5 years have elapsed since the last dose, a booster should be considered for children and adolescents to minimize tetanus risk. Tdap is preferred to Td in children older than 11 years if they have not received Tdap previously.

Haemophilus influenzae Type b Vaccine

The indications for vaccination of Haemophilus influenzae type b (Hib) in children traveling are the same as for the US residents. If previously unvaccinated, infants younger than 15 months should receive at least two doses prior to travel. An accelerated schedule can start at a minimum of 6 weeks of age, with a 4-week interval between the first, second, and third doses, and at least 8 weeks between third and fourth doses.

Hepatitis A Vaccine

Hepatitis A is one of the most common vaccine-preventable illnesses globally, and vaccination should be provided prior to travel to developing countries. Hepatitis A is much less common in the developed world, so children from these areas are likely to be susceptible when traveling to high-risk areas. Although two doses of the vaccine are recommended 6–12 months apart, a single dose will provide protection during the trip if given at least 2 weeks prior to departure. The earliest age of administration is 1 year in the United States. If travel will occur within 2 weeks of travel consultation, immune globulin (IG) (0.1 mL/kg IM) can be given simultaneously with hepatitis A vaccine, or for protection of children younger than 1 year traveling for up to 1 month or 0.2 mL/kg if traveling up to 2 months. Additional doses can be given every 2 months (0.2 mL/kg) for ongoing travel in a high-risk setting until 1 year of age, after which time vaccination should be encouraged. IG interferes with measles-mumps-rubella (MMR) and varicella vaccination, so these vaccines should be given 2 weeks prior to immunoglobulin.

Hepatitis B Vaccine

Areas of high endemicity for hepatitis B include most of Asia, the Middle East, Africa, and the Amazon Basin. Unimmunized children are at risk if they receive blood transfusions that have not been screened for HBV surface antigen (HBsAg) or are exposed to unsterilized medical or dental equipment. Children traveling to developing countries should be vaccinated before departure. An accelerated schedule is possible, with the second dose given with a minimum 4-week interval and the third dose given at least 8 weeks after the second dose. The third dose should not be given before 24 weeks of age.

Influenza Vaccine

Children are at high risk of respiratory infection during travel. The influenza vaccine is recommended for travel during the influenza season, which is between September and March in the Northern Hemisphere, and between April and August in the Southern Hemisphere, and year round in the tropics. The vaccine available in the United States may not protect against new strains circulating in the Southern Hemisphere. Influenza vaccine is recommended for children at least 6 months of age; those younger than 9 years will need two doses of vaccine administered at least 4 weeks apart if they have received zero or one dose in prior seasons. The current vaccines are the trivalent or quadrivalent inactivated vaccine (IIV) given intramuscularly and the quadrivalent live attenuated vaccine (LAIV) given intranasally. It is preferable to be vaccinated at least 2 weeks prior to departure. The annual seasonal influenza vaccine may not be routinely available in the United States from the late spring to early fall, when it may be needed for travelers but may be available at some travel clinics. Revaccination is not recommended for those who will be traveling during April through September and were vaccinated the preceding fall.

Measles-Mumps-Rubella Vaccine

Measles remains endemic in many parts of the world, including Europe, Africa, and Asia, and outbreaks continue to occur worldwide. Susceptible travelers represent an important cause of outbreaks imported into the United States. Children as young as 6 months traveling outside the United States are recommended to receive the vaccine at least 2 weeks before departure, but any doses given prior to 12 months do not count toward an adequate two-dose series, as maternal antibodies may interfere with the immune response. These infants will still require one dose of measles-mumps-rubella (MMR) at 12–15 months of age and a second dose at 4–6 years of age. The second dose aims to protect those individuals (~ 5%) who did not respond the first time. If an accelerated schedule is required, two doses must be separated by a minimum of 4 weeks.

Meningococcal Vaccine

The highest risk for meningococcal disease is for travelers to the meningitis belt of Africa, (sub-Saharan region) especially during the dry season, and travelers on the Hajj or Umrah pilgrimage to Mecca. Notably, meningococcal disease is decreasing in this region due to vaccination against type A. Vaccination is recommended for those who live or travel to these areas with high rates of meningitis for children 2 months of age and older. The vaccine must be given at least 10 days before international travel. For children younger than 9 months, MenACWY-CRM should be used, and for those 9 months of age and older, either MenACWY or MenACWY-D can be used. Vaccination commencing at 2–6 months of age requires a four-dose series; children aged 7–23 months require a two-dose series at least 8 weeks apart, and those 2–55 years of age require one dose. The duration of protection is 3 years in children and 5 years in adults, and boosters are indicated for ongoing exposure and at-risk hosts.

Hib-MenCY-TT is approved for vaccination of children aged 6 weeks to 9 months. A combined Hib and Neisseria meningitidis serogroup C conjugate vaccine is licensed for infants younger than 6 weeks. These two vaccines should not be used for children traveling to the meningitis belt or the Hajj, as serogroup A is the predominant organism in these regions.

A previously vaccinated infant reaching the age of 9 months and traveling to endemic areas should be revaccinated with MCV4. MPSV4 should be used for persons older than 56 years. Meningococcal vaccination is required by the Saudi Arabian government for pilgrims undertaking the Hajj or Umrah pilgrimage to Mecca and Medina, because of pilgrimage-related international outbreaks of N meningitidis A in 1987 and W-135 in 2000 and 2001. Further information concerning geographic areas recommended for meningococcal vaccination can be obtained from http://www.cdc.gov/travel.

Pneumococcal Vaccine

The indications for vaccination against Streptococcus pneumoniae in children traveling are the same as for routine vaccination. The 13-valent pneumococcal conjugate vaccine (PCV 13) is recommended for children aged 5 years or younger. For children aged 5 years or younger who have completed the PCV 7 series, a single additional dose of PCV 13 is recommended. The minimal interval is 4 weeks between the first three doses and 8 weeks between the third and fourth doses. In addition, the pneumococcal polysaccharide (PPSV23) is recommended for children and adults aged 2 years or older who have certain underlying medical conditions and for all adults aged 65 years or older.

Polio Vaccine

Transmission of wild-type polio still occurs in regions of Asia and Africa, and endemic transmission continues in Afghanistan and Pakistan; vaccine-derived polio is transmitted in other regions. Adequate immunization with inactivated polio vaccine (IPV) should be completed prior to travel to developing countries. The minimum age of administration is 6 weeks of age for IPV. The recommended interval between each dose is 4 weeks. One additional lifetime dose (a fifth dose) of the IPV should be given to caretakers who are traveling to areas with recent circulating polio.

Rotavirus Vaccine

Rotavirus is the most common cause of severe gastroenteritis in infants and young children worldwide, and vaccination with the complete series is recommended prior to travel if age-appropriate. The minimum and maximum age for the first dose is 4 weeks and 14 weeks, 6 days, respectively. There are insufficient data on the safety of older infants. The minimum interval between doses is 4 weeks.

Japanese Encephalitis Vaccine

Japanese encephalitis (JE) is caused by a flavivirus transmitted by the night-biting Culex mosquito. The risk of contracting severe JE is low, especially for travelers who will have a brief stay in an endemic area, as the infection rate in Culex mosquitoes is 3% or lower, and only 1 in 200 infections with JE leads to neuroinvasive disease. The symptoms of JE include seizures, paralysis, coma, and mental status changes; residual neurologic damage occurs in 50% of those with clinical disease (see Chapter 40). The case fatality rate is 30% in those with severe disease. Most symptomatic cases occur in children younger than 10 years and in the elderly. The areas at risk are within Asia, Eastern Russia, some areas of the Western Pacific, and the Torres Strait Islands of Australia. The peak season is between April and October, during and just after the rainy season. The JE vaccine licensed and available for use in the United States is Ixiaro, an inactivated Vero cell culture–derived vaccine. It was approved in May 2013 for use in children aged 2 months and older. The primary series is two doses administered 28 days apart. Each dose is 0.5 mL for adults and children aged 3 years and older, and 0.25 mL for children aged 2 months to 2 years. The JE vaccine is recommended for travelers who plan to spend at least 1 month in endemic areas during the JE transmission season. Vaccine should also be considered in the following scenarios: (1) short-term travelers to nonurban areas who will participate in outdoor activities; (2) travelers to an area with an ongoing JE outbreak; and (3) travelers to endemic areas who are uncertain of specific destinations, activities, or duration of travel.

Rabies Vaccine

Rabies is found worldwide and contracted through the bite or saliva-contaminated scratch of infected animals. Canine rabies is highly endemic in parts of Africa, Asia, and Central and South America (RabNet—www.who.int/rabies/rabnet/en/—provides country-specific animal and human data), where 40% of rabies occurs in children younger than 14 years. This increased risk is because children are attracted to animals, are more likely to be bitten, and may not report minor encounters with animals. Most cases of rabies in travelers occur through the bite of an infected dog, cat, or monkey (particularly those that live near temples in parts of Asia). Bats, mongooses, and foxes are other animals that can transmit disease.

Rabies vaccine is available for pre- and postexposure prophylaxis. It is recommended for travelers to areas in which rabies is endemic and for those who will have occupational or recreational exposure (such as cavers), especially if access to medical care will be limited when traveling. The risk of a bite from a potentially rabid animal is up to 2% for travelers to the developing world. The three types of inactivated virus vaccine available are administered prior to exposure in three doses at days 0, 7, and 21 or 28. Vaccination prior to exposure may not be completely protective; further doses are required if a high-risk bite occurs. The minimum age of administration is 1 year, and duration of protection is 2 years. Malaria chemoprophylaxis with mefloquine or chloroquine should begin 1 month after completing the rabies vaccine series to avoid interference with the immune response.

It is important to counsel travelers about animal avoidance, thorough cleansing of a bite wound with irrigation for at least 5 minutes. In the event of a bite in a nonvaccinated individual, rabies immunoglobulin and four doses of vaccine at days 0, 3, 7, and 14 are required, ideally within 24–48 hours after contact. In a fully vaccinated child exposed to rabies, two booster doses should be given on days 0 and 3 of exposure, and rabies immunoglobulin is not required.

Yellow Fever Vaccine

Yellow fever is a flavivirus transmitted by mosquitoes, found in urban and rural areas in sub-Saharan Africa and equatorial South America. Of those infected with the virus, 15% have moderate to severe infection. The licensed 17D strain live attenuated vaccine is highly effective. It must be administered 10 days before travel to an endemic region to allow for the development of protective antibodies. It is required by many countries for reentry after travel to an endemic area, and receipt of the vaccine should be documented in the International Certificate of Vaccination that became available in December 2007 (wwwnc.cdc.gov/travel/yellowbook provides an updated list of countries in which yellow fever vaccination is recommended). For this reason, it is administered only at certified clinics. The vaccine is given subcutaneously, and a single dose confers lifelong immunity. As of July 1, 2016, a completed International Certificate of Vaccination or Prophylaxis is valid for the entire lifetime of the vaccines, and countries cannot require proof of revaccination as a condition of entry, even if the last vaccination was more than 10 years prior. The recommended minimum age of administration is 9 months, and vaccine should not be administered to at-risk infants younger than 6 months, because of the increased risk of encephalitis (0.5–4 per 1000 vaccines). The risk of severe vaccine-related disease is also higher in adult caretakers older than 60 years. The decision to immunize infants who are 6–8 months of age must balance the infant’s risk for exposure with the risk for vaccine-associated encephalitis. The vaccine is contraindicated in individuals with egg allergy or immunosuppression (including human immunodeficiency syndrome [HIV] with CD4 T-lymphocyte counts < 200 cells/mm³ or a history of thymus disorder or thymectomy). A letter of medical exemption may be required for these travelers. In addition to age limitations, precautions to vaccination include asymptomatic HIV infection and CD4 T-lymphocyte count of 200–499 cells/mm³, pregnancy, and breast-feeding. Adverse effects include encephalitis (15 per million doses for those aged > 60 years) and multisystem disease (5 per million doses in older people). There is currently a shortage of US-manufactured yellow fever vaccine. A comparable alternative vaccine manufactured in France is available to certain travel clinics under an investigational new drug program. A list of clinics supplying yellow fever vaccine is available at the CDC’s Traveler’s Health Website (https://wwwnc.cdc.gov/travel/page/search-for-stamaril-clinics).

Cholera Vaccine

Cholera is an acute, watery diarrheal illness caused by Vibrio cholerae (O1 or O139 serogroups). Global pandemics continue to occur in developing countries. In 2016, the oral cholera vaccine was recommended for travelers 18 years or older to cholera-affected areas. The only cholera vaccine available in the United States is the CVD 103-HgR (Vaxchora), which is a live vaccine against serogroup O1. The vaccine is not indicated for use in children.

Typhoid Vaccine

The risk of typhoid fever in travelers is 1–10:100,000, depending on the destination. Areas at risk include South Asia, West and North Africa, South America, and Latin America. Travelers to the Indian subcontinent are at greatest risk. The vaccine is recommended for long-term travelers to an endemic area, those traveling off standard tourist routes, immunocompromised travelers, those of south Indian ancestry, and patients with cholelithiasis. There are two vaccines available: a capsular polysaccharide (ViCPS) and a live attenuated (Ty21a) vaccine. The ViCPS is given intramuscularly 2 weeks prior to travel. The minimum age of administration for this vaccine is 2 years; efficacy is 75% over 2 years. Fever, headache, and severe local pain and swelling are reported with the ViCPS more frequently than with other vaccines. The Ty21a is an oral vaccine in capsule form given every other day for four doses. The schedule needs to be completed more than 1 week prior to travel to be effective. The capsules should be refrigerated but not frozen and should not be taken with liquids warmer than 37°C. It is licensed for children older than 6 years; efficacy is 80% over 5 years. It is contraindicated in immunodeficient populations. Doses should be delayed for more than 72 hours after receipt of antibiotics, as they interfere with growth of the vaccine strain bacteria. Mefloquine, chloroquine, and prophylactic doses of atovaquone-proguanil can be given concurrently with the typhoid vaccine.

Tuberculosis

Tuberculosis risk is increased for travelers, especially when visiting Africa, Asia, Latin America, and the former Soviet Union. The risk is higher in long-term travelers to countries with a high incidence of tuberculosis and is highest among health care workers. Bacillus Calmette-Guérin (BCG) vaccination is given soon after birth in many countries, but not in the United States. It protects against miliary and meningeal tuberculosis, but not against pulmonary disease, with efficacy only established in children younger than 1 year. It may be considered in children younger than 5 years who will be in a high-risk area for a prolonged period and have a negative test for tuberculosis (tuberculin skin test [TST] or interferon-γ release assay [IGRA]). It should not be given to immunosuppressed individuals. BCG is not widely available in the United States but may be administered in the destination country. A preferred alternative is that travelers to high-prevalence areas have a test for tuberculosis prior to travel and 3 months after return. It should be noted that live virus vaccines can create an anergic state, in which tuberculosis testing can be falsely negative. Therefore, testing should be performed on the same day as any live vaccine administration or at least 28 days later.

Diarrhea is one of the most common illnesses in travelers to the developing world. Children are at highest risk, usually having more severe and prolonged illness than adults. Traveler’s diarrhea is defined in adults as three or more loose stools in a 24-hour period, plus either fever, nausea, vomiting, or abdominal cramping. There is no strict definition in child travelers, as the pattern, consistency, and frequency of stools vary during childhood. A useful definition for traveling children is a change in normal stool pattern, with an increase in frequency (at least three stools per 24 hours) and a decrease in consistency to an unformed state. Most illnesses resolve over a 3- to 5-day period and occur in the first 2 weeks of travel. Enterotoxigenic Escherichia coli (ETEC) is the most common cause, accounting for up to one-third of cases. Other pathogens implicated are listed in Table 45–4. Counseling prior to travel includes education and caution with food handling and food and water consumption and provision for self-treatment in the event of illness.

Prevention

Travelers should seek restaurants with a good safety reputation; eat hot, thoroughly cooked food; eat fruits and vegetables that can be peeled; and avoid tap water. They should also avoid ice cubes, fruit juices, fresh salads, unpasteurized dairy products, cold sauces and toppings, open buffets, undercooked foods, and food or beverages from street vendors. They should check the integrity of caps before buying bottled water to avoid bottles filled with tap water. It is also useful to remind travelers about hand washing after using the toilet and before eating. Families can consider using alcohol-containing hand sanitizers as an alternative to soap and water when access is limited during travel. Pasteurized or boiled milk is considered safe provided that it is stored at the appropriate temperature. It may be necessary to bring powdered milk to mix it with safe drinking water if the quality of milk is questionable. While these measures seem logical and should be recommended, there is little evidence that they prevent traveler’s diarrhea, either in adults or in children.

Chemoprophylaxis & Treatment

The principles of treatment include adequate hydration and a short course of antibiotics when warranted; medical attention should be sought for severe or prolonged disease.

For mild disease, hydration may be all that is necessary, without any diet restriction. This can be achieved with oral rehydration therapy to supplement a regular diet. Packets of dry rehydration powder to be mixed with water are available from pharmacies, either prior to travel or at the destination. If this is not available, parents can be instructed on how to make oral rehydration solution (Table 45–5) or to use a sports drink such as Gatorade as a suitable alternative in older children and toddlers. The breast-fed infant should continue to breast-feed, in addition to receiving oral rehydration therapy.

The vomiting child is at greater risk of dehydration, so aggressive rehydration is crucial. Parents should be reassured that some fluid will be absorbed even if vomiting is ongoing. This is best achieved with small amounts of fluid, given often to prevent further vomiting.

The antimotility agent loperamide, which is often used in adults to minimize symptom duration, is not advised for children because of the risk of adverse events such as toxic megacolon, ileus, extrapyramidal signs, hallucinations, and coma. Bismuth subsalicylate decreases the number of unformed stools in adults. Its routine use is not recommended in pediatrics, as aspirin is contraindicated in children younger than 18 years because of the risk of Reye syndrome, and dosing of bismuth has not been established for children.

For children with signs and symptoms of bacterial gastroenteritis, such as fever or blood in the stool, empiric antibiotic therapy should be considered. The drug of choice in children is azithromycin (10 mg/kg orally once a day for 3 days). It is available in a powdered form that can be reconstituted and stored without refrigeration. It is an ideal choice because of the growing resistance of many gastroenteritis-causing bacteria to ciprofloxacin. There are no pediatric trials of empiric azithromycin, so the dosing recommendations are based on pharmacokinetic data and studies involving the treatment of diarrhea in Africa and Thailand. Ciprofloxacin is currently not recommended for treatment of traveler’s diarrhea in children, though it is used for treatment in adults.

Trimethoprim-sulfamethoxazole (TMP-SMX) has been used to treat traveler’s diarrhea in children but is no longer recommended because of increasing antibiotic resistance. Rifaximin, a nonabsorbable derivative of rifamycin, is effective in treating ETEC and other noninvasive enteropathogens. Since it is not absorbed, high concentrations are achieved in the intestinal lumen and it has a good safety profile. It is licensed for patients 12 years and older at a treatment dose of 200 mg three times a day for 3 days.

The use of prophylactic antibiotics in children is not recommended because of the risk of adverse events to prevent a disease of limited morbidity, as well as the potential for emergence of antibiotic resistance. Rifaximin, based on adult studies, is a useful chemoprophylactic agent, but it is expensive and requires further study in pediatrics. Probiotics are of unproven benefit for the prevention of traveler’s diarrhea, with a recent meta-analysis of five randomized controlled trials showing no benefit.

Malaria is the most common preventable infectious cause of death among travelers, and a common cause of fever in the returned traveler (See Also Chapter 43). Children comprise 20% of imported cases of malaria. It is largely a preventable disease in travelers through personal protective measures and chemoprophylaxis. However, no method is 100% protective. The risk of acquiring malaria varies with the season, climate, altitude, number of mosquito bites, and destination, with the highest risk in Oceania, Africa, the Indian subcontinent, and the Amazon.

Prevention of Mosquito Bites

Malaria is transmitted via the night-biting Anopheles mosquitoes. Mosquito bites are avoided by staying in well-screened and air-conditioned rooms from dusk until dawn, wearing clothing covering arms and legs, and avoiding scented soaps, shampoos, and perfumes. Mosquito nets are highly effective and can be used over beds, cribs, playpens, car seats, and strollers. Repellants containing 30% or less DEET are also recommended, as this concentration confers 5–8 hours of protection. When used appropriately, DEET is safe for infants and children older than 2 months. It should not be applied to children’s hands, mouth, or near the eyes, and is best washed off upon returning indoors. There have been case reports of seizures and toxic encephalopathy with use of DEET, but these cases occurred with misapplication. Icaridin (also known as picaridin) is an alternative to DEET available in many countries. A concentration of 20% icaridin is as effective as DEET-containing products. It lacks the corrosiveness and greasy texture of DEET and is advised as safe for children by the American Academy of Pediatrics. However, because it is relatively new, it lacks the safety profile of DEET, especially for children. PMD is a plant-based repellant derived from lemon eucalyptus, and at a 30% concentration is equally effective as DEET. It may be used on children older than 6 months. It is considered safe if directions are followed and has been advocated for use by the Centers for Disease Control and Prevention. Clothing and bed nets may be sprayed with insecticides such as permethrin, which confers protection for 2–6 weeks, even with regular washing. Further studies are needed to establish its safety profile in children. The combination of DEET every 8–12 hours and permethrin on clothing is over 99% effective in preventing mosquito bites.

Chemoprophylaxis

Prophylactic medications suppress malaria by killing asexual blood stages of the parasite before they cause disease, so protective levels of medication must be present in the blood before developing parasites are released from the liver. Therefore, it is necessary to start prophylaxis before the first possible exposure and to continue it for a sufficient period after return to a safe area.

The choice of antimalarial depends on the age of the child, resistance patterns, restrictions on the agent of choice, the child’s ability to swallow tablets, the frequency of dosing, cost, availability of medication, and access to a compounding pharmacy for adequate dispensing of medication. For most children, once-weekly mefloquine is preferable and approved for children of any age. Atovaquone/proguanil is available in pediatric dosing, although only in tablet formulation. It is currently approved in most countries for children weighing greater than 5 kg. Doxycycline is another alternative but should be used only in children 8 years or older because of the risk of teeth staining. Chloroquine is the drug of choice in areas of chloroquine sensitivity (Mexico, Hispaniola, Central America, west and north of the Panama Canal, and parts of North Africa, the Middle East, and China). Pediatric and adult dosing, side effects, and other information about malaria chemoprophylaxis are in Table 45–6.

Antimalarial medications (with the exception of atovaquone/proguanil) are bitter, so it may be necessary to grind the medication into a very sweet food, such as chocolate syrup or sweetened condensed milk. Infants may need to have their medication prepared by a compounding pharmacy, where the appropriate dose can be placed in a gelatin capsule, which can then be opened by the caregiver and mixed into food or liquid.

Individuals who return to their home country are at the highest risk of travel-related infectious diseases. Sixty percent of malaria cases and over 75% of typhoid cases occur in these travelers, and VFR children are at highest risk of hepatitis A. The reasons for this include the following:

• Longer stays and increased likelihood of pregnancy or young age in the traveler

• Travel to remote rural areas

• Intimate contact with the local population

• Decreased likelihood of seeking (or following) pretravel advice because of familiarity with their home country

• Assumed immunity to infections

• Sociocultural barriers—for example, language barriers, belief systems of illness, prohibitive cost of vaccines and medications if lower socioeconomic status

• Eating and sleeping in local households, where hygiene may be suboptimal

• Use of high-risk forms of transportation

Thus, certain issues need to be emphasized when discussing travel for VFRs. Given the risk of waterborne infections, visiting families should boil water and milk if other safe drinking water is expensive; consume only piping hot foods and beverages; and follow proper hand-washing techniques at all times. Vaccination recommendations and malaria prophylaxis are of greater importance in VFRs, who have greater opportunities to contract vaccine-preventable diseases, such as typhoid, rabies, yellow fever, and meningococcal infection. VFRs have a higher risk of exposure to people with tuberculosis, so tuberculosis testing is recommended approximately 3 months after return from travel.

Adolescent travelers might partake in high-risk activities while traveling, putting them at risk of human immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs) (See Also Chapter 41). The adolescent traveler should be counseled about the risks of STDs, safe sexual practices, and in particular, the importance of barrier contraception. Bringing a supply of latex condoms may be appropriate along with instruction on their proper use. They should be advised that HIV and STDs can also be contracted via oral sex and in nonsexual activities such as intravenous drug use, receiving tattoos, piercings, pedicures, and dental care while traveling. There may be a risk of HIV and other virus transmission through injections and blood transfusion, as many developing countries do not have adequate blood banking and transfusion protocols. In fact, 10%–20% of countries have inadequate screening.

Antiretroviral therapy is recommended if there is exposure to a known HIV-positive contact, and may be considered if the source is unknown but may be difficult to access in most countries (see Chapter 41).

More than one-half of travelers to the developing world experience a health-related travel problem during their trip; 8% require medical attention on return. The majority will develop common medical problems, such as upper respiratory tract infections, pneumonia, urinary tract infections, and otitis media, with the remainder developing travel-related infections. The most common travel-related diseases are malaria (21%), acute traveler’s diarrhea (15%), dengue fever (6%), and typhoid/enteric fever (2%). Children who travel with caretakers visiting friends and relatives are at greatest risk. New pathogens and the changing epidemiology of some infectious diseases pose new risks to travelers—such as Ebola, avian influenza, multidrug-resistant TB, chikungunya virus, zika, and leishmaniasis.

Symptomatic returning travelers should be urgently and thoroughly evaluated for travel-related illness to prevent serious life-threatening disease and transmission to close contacts. The initial evaluation should include questions directed toward the travel itinerary, with dates of arrival and departure, specific activities, rural versus urban location, and accommodations. Specific information should be obtained regarding freshwater contact (eg, schistosomiasis, leptospirosis in some areas), sexual contacts, animal exposures, activities or hobbies, ill person contacts, and sources of food and water. A complete medication and vaccination history should be sought. Despite malaria chemoprophylaxis and protection against mosquitoes, no regimen is 100% protective. A thorough physical examination should include dermatologic examination, eye examination for scleral icterus, conjunctival injection or petechiae, and evaluation for hepatosplenomegaly or lymphadenopathy. Routine laboratory evaluation includes a complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum chemistry, liver enzyme profile, and urinalysis. The laboratory evaluation should also focus on diseases that are life threatening, with thick and thin smears for malaria (ideally three that are 12 hours apart), and blood cultures for typhoid fever. Specific testing should be done as directed by findings on history, physical examination, and preliminary laboratory test findings (Table 45–7). It may be necessary to seek the opinion of individuals with experience in international travel medicine, if available.

Fever is the most common complaint in a child who becomes ill after international travel. The most common travel-related infectious causes of fever are summarized in Table 45–8. A more detailed description of the symptoms, signs, diagnosis, and treatment of these diseases that can occur in the returning traveler is presented in Chapters 40, 41, 42, 43.

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