Chapter 64. Pretravel Preparation

A family of five with children of 2, 4, and 6 years of age is planning a trip to Costa Rica. They will visit the jungle for a bird-watching trip. They wonder if they need medications to prevent malaria.

A similar family is planning to visit relatives in Nigeria during the dry season in March. What vaccines and medications do they need?

Clinicians caring for children are frequently asked these questions. Children visiting developing countries are at risk of travel-related illnesses such as malaria and diarrheal diseases. Accidents and injuries may also occur. To help prevent these, clinicians must know how to find the needed information and provide appropriate medical advice. Others may choose to refer the child and family to a travel medicine clinic. For some communities, travel clinics are too distant for routine referrals, thus the clinician is called upon to provide the needed services.

Approximately 1 billion passengers travel by air every year. Of these, over 50 million will visit a developing country.1,2 While children only account for 4% of this group, approximately 25% of travel-related hospitalizations are in children. In one study, 40% of pediatric travelers to the tropics or subtropics experienced traveler's diarrhea.3 As a consequence, close to 20% required bed confinement. In another study, imported febrile illnesses, such as malaria, represented 1% of hospital admissions.4 At one pediatric travel clinic, children frequently traveled to high-risk regions, such as Africa, Latin America, and Southeast Asia.5 Unfortunately many pediatric-age travelers (and/or their parents) do not comply with effective preventive measures.6 Many of these travelers needed prophylaxis against malaria and vaccinations to protect against hepatitis A and typhoid fever.

While there is great comfort in visiting friends and relatives abroad, studies have shown that these travelers are at the highest risk of acquiring an infection. Of travelers visiting developing countries, 25–40% do so to visit friends and relatives (VFRs).7 Only 16% of VFRs who were originally immigrants sought pretravel medical advice. In addition, VFRs were frequently prescribed inappropriate prophylaxis or none at all, had longer stays, and spent time in high-risk areas.8

Traveling for international adoption also poses specific risks for accompanying children. Adopted children may have gastrointestinal parasites and other enteric pathogens; may have scabies; or be a chronic carrier for hepatitis B. They may transmit pertussis or measles to the adopting family. The adopting family needs to be counseled pretravel and receive the necessary vaccines and prophylactic medications.9

Children are traveling for diverse reasons; to study abroad, with parents on international adoption trips, for adventurous exploration, missionary and humanitarian work, to visit family and relatives, and for ecologic projects. While most travel for short periods of time, others may be relocating because of parental work. Not all parents realize the importance of planning ahead to keep their families healthy. Because certain vaccines and medications need to be given days or weeks before travel, and because not all clinicians provide travel advice, appointments with a travel medicine specialist should be made at least 1 month before travel.

To successfully advise families about their travel health needs, it is important to know exactly where and when they are going. Some infections may be acquired only in certain countries or regions within countries. Clinicians planning to counsel travelers need to have up-to-date information on disease activity. Epidemics of meningococcal disease, hepatitis A, SARS, poliomyelitis, and measles have occurred recently. These may force changes in travel plans or immunization needs. Up-to-date country-specific information can be obtained from various sources such as the Travelers’ Health Sections of the Centers for Disease Control and Prevention (www.cdc.gov/health) and the World Health Organization (www.who.int/ith). In addition, the International Association for Medical Assistance to Travelers (www.iamat.org) offers detailed advice to travelers, and Shoreland (www.shoreland.com) offers Travax®, an online subscription service with medical travel information for physicians. While containing useful information, travel books may not have the latest up-to-date information on disease activity.

Because of unfamiliarity with travel medicine, reimbursement issues for travel visits, and lack of specific vaccines, many clinicians refer their patients (and families) to travel medicine clinics. A list of these appears on Web sites of the International Society of Travel Medicine (www.istm.org) and the American Society of Tropical Medicine and Hygiene (www.astmh.org). Unfortunately, some families get inappropriate travel advice from peers, friends, relatives, neighbors, and at times medical providers. Inadequate information may also come from travel brochures or travel agents.

Before travel, a health assessment of the whole family is important. Is anyone taking medications? Are there any allergies? Immunization records need to be reviewed. Is everyone up-to-date? Proper travel advice will result from a careful assessment of travel plans and individual needs. Appropriate measures include provision of vaccines and prophylactic medications, risk-reducing/disease prevention education, and frequently medications for self-treatment.

A concise summary of advice frequently given to travelers appears in Table 64–1.

Travel immunizations are categorized as required, recommended, or routine. Routine vaccinations and boosters against measles, mumps, rubella, polioviruses, varicella, pertussis, influenza, and diphtheria should normally be given at appropriate ages. However, sometimes travel plans require that they be administered on an accelerated schedule. If necessary, first doses, doses within a series, and boosters can all be administered early. For example, young infants can receive the first doses of most routine vaccines as early as 6 weeks of age. Infants can receive a measles vaccine as early as 6 months for travel to high-risk areas. The American Academy of Pediatrics Redbook® is an excellent resource for this information.10 Frequently administered travel vaccines appear in Table 64–2.

Currently, only two vaccines generally fall into the required category. Yellow fever vaccination is the only vaccine that requires documentation on an official certificate of vaccination. Countries with endemic and/or epidemic yellow fever may require proof for entry. The vaccine must have been administered at least 10 days before intended entry, and an official stamp must appear on the certificate.11 Only authorized practitioners and clinics are allowed to administer yellow fever vaccine and issue this official certificate. Children younger than 4 months should never receive yellow fever vaccine because of the risk of developing postvaccination encephalitis. Children older than 9 months can be vaccinated safely. For children between the ages of 6 and 9 months, the risk of acquiring the disease must be greater than the potential side effects of the vaccine. Travel to yellow fever endemic regions should be postponed if at all possible for children in these younger age groups.11

The quadrivalent meningococcal vaccine (A, C, Y, W135) is required by Saudi Arabia for all visitors making the Hajj pilgrimage to Mecca and Medina. Polio vaccination has also been required in recent years.

Most other vaccines fall in the recommended category. Since the incidence of hepatitis A is high in the developing world, travelers should receive the safe and highly protective hepatitis A vaccine. Passively transferred maternal antibodies blunt the immune response to hepatitis A vaccination in children younger than 1 year. This is especially so in infants younger than 6 months born from seropositive mothers.12 Passive immunization with gamma globulin can also prevent hepatitis A infection but it is generally reserved for infants younger than 1 year of age.

Typhoid fever results from the consumption of contaminated water or food as well as by intimate contact with documented Salmonella typhi carriers. Vaccination is recommended for even short-term travel to high-risk areas in the Indian Subcontinent, Asia, Africa, and Latin America; and for travelers planning to stay for extended periods of time in most areas of the developing world.13 Injectable and oral vaccine formulations are available. The live-attenuated Ty21a oral vaccine (Vivotif Berna) is recommended for travelers older than 6 years. This formulation has fewer side effects and confers longer protection than the injectable capsular polysaccharide vaccine (Typhium Vi), which can be given to travelers as young as 2 years of age.14

Because of a high incidence of invasive meningococcal disease, travelers to Sub-Saharan Africa are advised to receive the meningococcal vaccine. While this vaccination is generally recommended for children older than 2 years, it can confer protection in younger patients against some serogroups, especially serogroup A.15 The quadrivalent conjugate vaccine is routinely recommended for children and adults at 11–55 years of age. It confers higher antibody titers and longer duration of protection.16

Rabies vaccination is recommended for travelers visiting remote areas of the developing world where access to prompt postexposure administration of rabies immunoglobulin and vaccine is less likely. Travelers, especially children, planning extended stay abroad (usually to rural areas) may need Japanese encephalitis virus or tick-borne encephalitis vaccines.

While no vaccine or toxoid is 100% effective or safe, those described above are generally well tolerated with minimal side effects, such as fever, injection site pain, and redness. In most cases, severe side effects are not observed when appropriately administered. Live vaccines such as measles–mumps–rubella, yellow fever, oral typhoid, and varicella should never be administered to immunocompromised travelers.

The most effective way of preventing malaria and other mosquito-borne diseases such as dengue fever, chikungunya, yellow fever, and Japanese encephalitis virus is to avoid mosquito bites. This is achievable through the proper use of protective clothing (permethrin-treated long-sleeved shirts and blouses and long pants; closed shoes, and hats) and effective insect repellents; avoidance of outdoor activities during peak mosquito biting times, and by sleeping in dwellings with door and window screens or air conditioning; and/or by using permethrin-impregnated bed nets while sleeping. Dark colored clothing, floral fragrances such as those in perfumed soaps, lotions, hair care products, and deodorants may attract mosquitoes. When possible, these should be avoided.

There are many insect repellents on the market, and the choice of which one to use can be confusing to parents. N,N-diethyl-3-methylbenzamide, formerly known as N,N-diethyl-m-toluamide (DEET), is the most effective insect repellent available. Products with ≥30% DEET can be used safely in children, but higher concentrations are not necessary.17 Products containing 20–30% DEET protect an individual for 4–5 hours,18 while products with lower concentrations protect for shorter periods.17 Products with microencapsulated DEET (such as UltraThon®) may provide protection for even longer periods of time. The use of higher concentrations of DEET does not correlate with increased toxicity, but inappropriate use does. While wristbands are popular among some travelers, protection is measured in seconds or minutes. Natural products, such as those containing citronella, confer limited protection and are not recommended for protection in the tropics.

Recently, a new insect repellent, 7–15% picaridin (KBR 3023), was released in the Unites States. In clinical trials, picaridin was found to be as effective as DEET, but at a concentration of 20%.19,20

Because of potential absorption through mucosal membranes, insect repellents containing DEET should not be applied to the faces of young children. In addition, they should not be applied to the hands of young children since they tend to bring them to their mouths. Once the family returns indoors, the insect repellent can be washed off if the area is screened, air conditioned, or they are under bednets.

While malaria-transmitting mosquitoes usually bite between dusk and dawn, other disease-transmitting mosquitoes are diurnal biters, so insect repellents and proper clothing may be needed during the day as well. The application of permethrin to clothing also reduces bites. Permethrin 0.5% on clothing will last an average of 2 weeks. Parents can purchase permethrin at most recreational outdoor stores or via the Internet. Insect repellents and permethrin-impregnated clothing will also minimize bites by ticks, flies, and other insects. Inspection of children's clothing and skin after returning from outdoors is important to minimize tick exposures. Permethrin-impregnated bednets are also protective.

The risk of infection and type of malaria in the developing world varies from country to country. Before providing advice, clinicians should familiarize themselves with the worldwide distribution of chloroquine-susceptible and chloroquine-resistant Plasmodium falciparum and other species. Since resistance is not a problem in Central America, chloroquine can be used there. Most malaria-endemic areas of Africa, Asia, and South America have chloroquine-resistant P. falciparum. For these areas, mefloquine, doxycycline, primaquine, or atovaquone-proguanil are used. Parts of Southeast Asia have strains of P. falciparum that are mefloquine-resistant.

The choice of antimalarial medication is also influenced by duration of travel, cost, and ease of administration. Most travelers prefer not to take medications every day. Others dislike the idea of taking medications for 4 weeks after returning home. Some travelers will only need intermittent protection against malaria since they are traveling in and out of malaria regions. Doxycycline is the cheapest option. While inexpensive, travelers must be aware of the potential for photosensitivity reactions and yeast superinfection.

Certain antimalarial agents cannot be used in certain patient populations. For example, while chloroquine is safe in pregnancy, doxycycline and atovaquone-proguanil should be avoided; but mefloquine can be given safely after the first trimester. Doxycycline is also contraindicated in children under the age of 8 years.

Since suspensions or elixir formulations of these medications are not available in the United States, and are not palatable, the pharmacist needs to compound these in ways that children will find acceptable. Grinding down tablets and dividing them in portions according to body weight is desirable. The contents in a little sachet-envelope or small gel capsule can then be poured onto food or mixed with chocolate syrup. To minimize gastrointestinal discomfort, all antimalarial medications should always be taken with meals. To avoid “pill esophagitis,” medications should be taken while awake, upright, and with sufficient fluids.

To maximize effectiveness, antimalarial prophylaxis medications need to be started before entering an endemic region. Chloroquine needs to be started at least 1 week prior to arrival, mefloquine at least 1–2 weeks. Doxycycline and atovaquone-proguanil can be started 24–48 hours prior.16,21,22 Dosage information appears on Table 64–3.

Travelers need to be alerted regarding potential side effects. Because medications may require discontinuation, alternate prophylaxis should be discussed before travel. A different medication may be needed that may not be available in the destination country. Some travelers are concerned about the potential of neuropsychiatric disturbances with mefloquine. This medication is contraindicated in people with seizure disorders and in those suffering from anxiety and depression. It is also contraindicated in people with cardiac conduction abnormalities. While most side effects such as nausea and upset stomach are minor, less common ones may be more disturbing. Among these are strange vivid dreams, insomnia, dizziness, weakness, anxiety, and agitation. Children generally tolerate antimalarial medications better than adults.23 However, approximately 10% of children experience difficulties with mefloquine such as vivid dreams, diarrhea, vomiting, changes in sleep patterns, headaches, and even hallucinations. About 23% of children taking chloroquine experience nausea, headaches, vomiting or changes in sleep. But, while 5–8% of adults will discontinue these agents because of side effects, only 1% of children will do so. Atovaquone-proguanil (Malarone®) has the least potential for side effects.

Despite taking appropriate antimalarial prophylaxis during travel malaria may still manifest itself weeks to months after returning from an endemic area. Families spending extended periods of time in an endemic area where Plasmodium vivax and Plasmodium ovale are present may need to receive terminal prophylaxis. This is intended to eliminate the hypnozoite stage of the parasite in the liver. This is achieved by taking primaquine for a period of 14 days. A glucose-6-phosphate dehydrogenase level should be checked before administering primaquine because it may cause severe hemolysis in individuals who are glucose-6-phosphate dehydrogenase deficient.

The goal of antimalarial prophylaxis is to rapidly clear infections and reduce mortality and morbidity caused by the malaria parasite. Because no regimen is 100% effective it is important that families be educated about methods of bite prevention and the need to seek care immediately if someone develops a febrile illness during or after a trip to an endemic area. Malaria is discussed further in Chapter 66 (Malaria) and Chapter 65 (Fever in the returned traveler).

Traveler's diarrhea is a common problem among visitors to the developing world. A study by Pitzinger and associates showed a 60% attack rate in children younger than 2 years of age.3 Travelers to Northern Africa, India, and Latin America were the most affected. Approximately 19% of affected travelers were confined to bed, with 15% requiring treatment by a physician and approximately 1% requiring hospitalization.

Approximately 80% of traveler's diarrhea is caused by bacterial pathogens such as enterotoxigenic Escherichia coli, Campylobacter jejuni, nontyphoidal Salmonella, and Shigella. Traveler's diarrhea may also be caused by noroviruses (Norwalklike viruses), rotavirus, and parasites such as Giardia lamblia or Entamoeba histolytica.

Traveler's diarrhea can be prevented by avoiding contaminated food and beverages. Tap water or products prepared with it, such as ice, should be avoided. Travelers should avoid foods that are not boiled, cooked, or peeled. Pasteurized milk products, bottled water (especially carbonated), and sodas are usually safe. Proper hand hygiene before eating is particularly important in children.

If diarrhea occurs, parents need to be prepared to prevent or treat dehydration with oral fluids. Powdered oral rehydration salts can be purchased before the trip but are also available in most countries. Undiluted fruit juices, sport drinks, or soda are not appropriate rehydration solutions. They contain large amounts of sugar, which may worsen the diarrhea. With certain enteric infections, vomiting can be a problem and some younger children may require IV rehydration. However, most children can tolerate small amounts of fluids by mouth. By using a spoon or dropper to give 1–5 mL/min, rehydration can be achieved. Rehydrating a seriously dehydrated child can require 1–1½ ounces of fluid per pound of weight over a 2–4-hour period.

Since most cases of traveler's diarrhea are caused by bacteria, antimicrobial therapy can be used to reduce the duration and severity (Table 64–4). Fluoroquinolones, such as ciprofloxacin and levofloxacin are commonly recommended for use in adults. However not all clinicians are comfortable using these in children. Much has been published in the literature about the risks of arthropathies and tendinopathies with fluoroquinolones but a review of existing data has shown the agents to be effective and safely tolerated by children.24 An equally effective agent is azithromycin. This antimicrobial agent is now considered by many to be the preferred agent for children.25 In Thailand where fluoroquinolone-resistant Campylobacter is a common cause of traveler's diarrhea, azithromycin is clearly useful. Trimethoprim-sulfamethoxazole is no longer recommended because of widespread resistance.26

While antidiarrheal medications, such as loperamide and bismuth subsalicylate, are frequently used by adults, loperamide should not be used in young children because of the risk of paralytic ileus, severe vomiting, and drowsiness. However, bismuth subsalicylate has been shown to be safe and efficacious when used in children. Concern over the use of salicylate-containing antidiarrheal drugs and Reye syndrome does exist, but up to this moment there is no clear evidence to support the association.

In the developed world, empiric antibiotics are generally not prescribed for children with diarrhea. The association of antibiotic use, hemolytic uremic syndrome (HUS) and diarrhea caused by enterohemorrhagic E. coli is well known. Fortunately, effective treatment of enteric infections in the developing world has not led to an increase in HUS. HUS-associated enterohemorrhagic E. coli strains are rare outside developed countries. It is still wise to counsel parents that if a child develops bloody diarrhea, fever and abdominal pain, prompt medical evaluation is necessary.

Probiotics, such as Lactobacillus GG, have been used to treat antibiotic-associated and rotavirus-associated diarrhea with some success. However, there is insufficient data at this time to support their routine use in the prevention or treatment of traveler's diarrhea.

A newly approved nonabsorbable semisynthetic derivative of rifampin, rifaximin, has been shown to be effective in treating traveler's diarrhea. Unfortunately, rifaximin is not recommended for the treatment of invasive intestinal bacterial pathogens such as Shigella, Salmonella, or Campylobacter.27,28 While routinely it is not recommended, chemoprophylaxis has been shown to reduce the occurrence of traveler's diarrhea and possibly postinfectious irritable bowel syndrome.28 Studies in children are still lacking.

Acute respiratory tract infections such as those caused by influenza virus are common among travelers, especially those traveling within the Northern Hemisphere during the period of December through February; and those visiting friends or relatives, and staying longer than 30 days.29 Infections by parainfluenza virus, adenovirus, human metapneumovirus, coronaviruses, and rhinoviruses have also been documented.30

Young infants are frequently flown around the world to visit family. For years, many have expressed concerns over young infants suffering from inflight hypoxia and sudden infant death syndrome during long flights. There is no clear evidence to support this concern. While pretravel fitness-to-fly assessments appear reasonable for young expremature infants with history of lung disease; healthy-term infants appear physiologically capable for travel.31,32

Fever, skin conditions, and diarrhea are among the most common problems afflicting returned travelers.33 A brief discussion of these and when it is necessary to seek medical attention should be discussed before travel. An initial evaluation for these problems require a complete assessment of travel history, countries and regions visited, duration of travel, activities while in country, vaccination history, use of prophylactic and therapeutic medications, and compliance with preventive measures. In returned travelers from the tropics, determining an incubation period greatly influences diagnostic and therapeutic considerations. An onset of fever >3 weeks after return generally eliminates dengue fever, yellow fever, and rickettsias as potential etiologic causes. Common skin problems of pediatric travelers are scabies, fungal dermatosis, and parasitic infections. Among the latter, cutaneous larva migrans or creeping eruption, a pruritic serpentiginous skin condition commonly caused by the larval migration of Ancylostoma braziliense; and myiasis, resulting from the tissue invasion of the fly larvae, are frequently reported.

Returned travelers may complain of acute or prolonged diarrhea. Causes of acute disease are usually identified through stool cultures and examination for ova and parasites (plus antigen assays). The detection of less common parasites as Cyclospora cayetanensis may require special stains. Giardiasis, tropical sprue, and other parasitic infections may cause chronic problems in some travelers.

Tuberculosis and anemia are usually observed only in returned travelers who have spent extended periods of time abroad. Short-term travelers do not require routine screening. Clinicians can consult with specialists in infectious diseases, and tropical and travel medicine when evaluating pediatric travelers with the above problems. Fever in the returned traveler is discussed further in Chapter 65.