Pediatric Annals

Preparing Children for Travel to Tropical and Developing Regions

John C Christenson MD

Abstract

Returned travelers may complain of acute or prolonged diarrhea. Causes of acute disease usually are identified through stool cultures and examination for ova and parasites (including antigen assays). The detection of less common parasites such as Cyclospora cayetanensis may require special stains. Giardiasis, tropical sprue, and other parasitic infections also may cause chronic problems in some travelers. Tuberculosis and anemia are observed in returned travelers who have spent extended periods of time abroad. Short-term travelers do not require routine screening for these conditions.

Pediatricians may consult with specialists in infectious diseases and tropical and travel medicine when evaluating pediatric travelers with signs of the previously mentioned problems.

SUMMARY

Visiting a grandparent for a first time, exploring the ruins of an ancient civilization in a distant country, or river rafting through a tropical jungle are all moments that are never forgotten. Illness, visits to the doctor, and disability should not be a part of these experiences. Diseases such as malaria, yellow fever, travelers' diarrhea, and hepatitis A are preventable. Through the use of vaccines, prophylactic medications, and disease-prevention education, clinicians may help ensure their pediatric patients have enjoyable and rewarding travel experiences.

1. Ryan ET, Kairt KC. Health advice and immunizations for travelers. N Engl J Med. 2000;342(23): 1716-1725.

2. Cossar JH. Reid D, Fallon RJ, et al. A cumulative review of studies on travellers, their experience of illness and die implications of these findings. J Infect. 1990;21(l):27-42.

3. Pitzinger B, Steffen R, Tschopp A. Incidence and clinical features of traveler's diarrhea in infants and children. Pediatr Infect Dis J. 1991; 10( 10):7 19-723.

4. Riordan FA, Tarlow MJ. Imported infections in east Birmingham children. Postgrad Med J. 1998;74(867):3r5-37.

5. Christenson JC, Fischer PR, Hale DC, Derrick D. Pediatric travel consultation in an integrated clinic. J Travel Med. 200 1 ;8( 1 ): 1 -5.

6. Pickering LK, ed. Red Book: 2003 Report of the Committee on Infectious Diseases. 26th ed. Evanston, IL: American Academy of Pediatrics: 2004.

7. Fradin MS. Mosquitoes and mosquito repellents: a clinician's guide. Ann Intern Med. 1998;128(ll):931-940.

8. Fradin MS, Day JF. Comparative efficacy of insect repellents against mosquito bites. N Engl J Med. 2002;347(1): 13-18.

9. Albright TA, Binns HJ, Katz BZ. Side effects of and compliance with malaria prophylaxis in children. J Travel Med. 2002;9(6):289-292.

10. Fischer PR, Bialek R. Prevention of malaria in children. Clin Infect Dis. 2002;34(4):493-498.

11. Alghashan AA, Nahata MC. Clinical use of fluoroquinolones in children. Ann Pharmacother. 2000;34(3):347-359.

12. Stauffer WM, Konop RJ, Kamat D. Traveling with infants and young children. Part III: travelers' diarrhea. J Travel Med. 2002; 9(3):141-150.

13. Ryan ET, Wilson ME, Kain KC. Illness after international travel. N Engl J Med. 2002;347(7):505-516.

14. Cossar JH, Reid D, Fallon RJ, et al. A cumulative review of studies on travellers, their experience of illness and the implications of these findings. J Infect. 1990;21(1):27-42.

15. Fatal yellow fever in a traveler returning from Amazonas, Brazil, 2002. MMWR Morb Mortal Wkly Rep. 2002;51(15):324-325.

16. Centers for Disease Control and Prevention (CDC). Fatal respiratory diphmeria in a US traveler to Haiti - Pennsylvania, 2003. MMWR Morb Mortal WkIy Rep. 2004; 52(53): 1285- 1286.

17. Lee N, Hui D, Wu A, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003; 348(20): 1986- 1994.

18. Mayer LW, Reeves MW, Al-Hamdan N, et al. Outbreak of W135 meningococcal disease in 2000: not emergence of a new W 135 strain but clonal expansion within the electophoretic type-37 complex. J Infect Dis. 2002; 185(11): 1596- 1605.

19. CDC. Hepatitis A outbreak associated with green onions at…

Approximately 1 billion passengers travel by air every year. Of these, more than 50 million visit a developing country.1,2 Although children account for only 4% of this group, 25% of travel-related hospitalizations are in children.14 In one study, 40% of pediatric travelers to the tropics or subtropics experienced travelers' diarrhea and, as a consequence, close to 20% required bed confinement.3 In another study, imported febrile illnesses such as malaria represented 1% of hospital admissions.4 Unfortunately, many of these travelers did not comply with effective preventive measures. At a pediatric travel clinic, children frequently were found to be traveling to high-risk regions such as Africa, Latin America, and Southeast Asia.5 Many of these travelers needed prophylaxis against malaria and vaccinations to protect against hepatitis A and typhoid fever. Although the risk of developing certain diseases is low, a recent case of yellow fever in an unvaccinated traveler to Brazil and a case of fatal respiratory diphtheria in a humanitarian worker in Haiti demonstrate that the threat is real and that routine preventive measures are important.15 16 Although there is great comfort in visiting friends and relatives abroad, studies show these travelers are at the highest risk of acquiring an infection.

Children visiting developing countries are at risk of injuries and illnesses, including some that do not occur at home. To help prevent this, pediatricians must know how to find and provide appropriate medical advice, or they may choose to refer the child and family to a travel medicine clinic. For some communities, however, these clinics are too distant for routine referrals and me pediatrician must provide the needed services.

Although it may seem appropriate to ask parents to leave children behind. most children benefit from these travel experiences from emotional, cultural, and social standpoints. Rather than insist children stay home, pediatricians should prepare them in an appropriate manner so they may have a healthy and rewarding travel experience. This article provides basic information to assist pediatricians in helping their patients travel safely.

TRAVEL ASSESSMENT AND ADVICE

Children travel for diverse reasons, including adventurous exploration, ecological projects, schooling, and humanitarian work. Although most children 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 may need to be given days or weeks before travel and because not all pediatricians provide travel advice, appointments generally should be made at least 1 month before travel. Although this may not always happen, any appropriate advice before travel is better than none.

To advise families successfully 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. For example, many urban areas of Central America have no documented malaria transmission, but transmission may be common in rural areas within the same country. Yellow fever may be acquired in eastern Peru or Ecuador but not on the coast. South Africa is free of yellow fever, and malaria only exists in limited regions in the northeast.

Pediatricians planning to counsel travelers must have current information on disease activity. Epidemics of meningococcal disease,18 hepatitis A,19 severe acute respiratory syndrome,17 poliomyelitis,21 and measles20 recently have occurred. These may force changes in travel plans or immunization needs. Country-specific information may be obtained from various sources, such as the Travelers' Health Sections of the Centers for Disease Control and Prevention and the World Health Organization. In addition, the International Association for Medical Assistance to Travellers offers detailed advice, and Shoreland offers Travax, an online subscription service with medical travel information for physicians. Travel books may be less timely than these resources. A list of Web sites providing information on international travel is provided in Table 1.

Table

TABLE 1.Web Sites Relati4 to International Travel Health

TABLE 1.

Web Sites Relati4 to International Travel Health

Because of unfamiliarity with travel medicine, reimbursement issues for travel visits, and lack of specific vaccines, many pediatricians prefer to send their patients to travel medicine clinics. Lists of these appear on Web sites such as the International Society of Travel Medicine and the American Society of Tropical Medicine and Hygiene (Table 1). Although most clinics are found in urban areas, occasionally there may be a knowl-edgeable pediatrician with travel experience in smaller communities. Unfortunately, some families get inappropriate travel advice from peers, friends, relatives, neighbors, and even medical providers. Inadequate information also may come from travel brochures or travel agents.

Pediatric travelers pose specific challenges for some pediatricians. Most medications used as prophylaxis or treatment are not available in pediatric formulations. Although fluoroquinolones frequently are used for the treatment of travelers' diarrhea in adults, some clinicians are reluctant to use them in children. Unfortunately, they instead may elect to use an inferior agent such as trimethoprim-sulfamethoxazole.

Before travel, a health assessment of the whole family often is important.

Immunization records must be reviewed and specific questions should be asked about medication usage and allergies. Many adults and adolescents may need tetanus-diphtheria boosters. Proper travel advice results from careful assessment of travel plans and individual needs. Appropriate measures include provision of vaccines and prophylactic medications, risk-reducing or diseaseprevention education, and, occasionally, medications for self-treatment.

A list of medications frequently prescribed for prevention and treatment of travel-related illnesses is provided in Table 2 (see page 679). General recommendations for travel preparation are provided in the Sidebar (see page 680).

IMMUNIZATIONS

Routine

Travel immunizations are categorized as required, recommended, or routine by public health authorities. Routine vaccinations and boosters against measles, mumps, rubella, polio, varicella, tetanus, and diphtheria normally are given at appropriate ages. However, sometimes travel plans require that they be administered on an accelerated schedule - first doses, doses within a series, and boosters may all be administered early. For example, infants may receive the first doses of most routine vaccines as young as 6 weeks and a measles vaccine at age 6 months for travel to high-risk areas. The American Academy of Pediatrics Red Book6 is an excellent resource for vaccination information.

Required

Yellow fever vaccination is the only vaccine that requires documentation on an official certificate of vaccination, and countries with endemic or epidemic yellow fever require this proof for entry. The vaccine must be given at least 10 days before intended entry, and an official stamp must appear on the certificate. Only authorized practitioners and clinics are allowed to administer yellow fever vaccine and issue an official certificate of vaccination. However, children younger than 4 months should never receive yellow fever vaccine because of the risk of post-vaccination encephalitis. 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 whenever possible for children in this age group; children older than 9 months may be vaccinated safely.

Table

TABLE 2Frequently Prescribed Medications for Travel

TABLE 2

Frequently Prescribed Medications for Travel

The other required vaccine, quadrivalent meningococcal vaccine (A, C, Y, W 135), is required by Saudi Arabia for all visitors making the Hajj pilgrimage to Mecca and Medina.

Recommended

Most other vaccines fall in the recommended category. Because the incidence of hepatitis A is high in the developing world, most travelers to these areas should receive this safe and highly protective vaccine. Although it is licensed in the United States for administration at ages 2 and older, in many countries it is administered to children as young as 1 with acceptable seroconversion rates. Passive immunization with gammaglobulin may also prevent hepatitis A infection but is generally reserved for children younger than 1.

Typhoid fever transmission occurs from consumption of contaminated water or food as well as by intimate contact with documented typhoid fever carriers. Vaccination by either injection or oral formulation is recommended for even short-term travel to high-risk areas in Asia, Africa, Latin America, and the Indian subcontinent, as well as for travelers planning to stay for extended periods in most areas of the developing world. The oral vaccine (Ty21a) is recommended for travelers older than 6 and has fewer side effects and confers longer protection than the injectable (Vi capsular polysaccharide) form, which may be given to patients as young as 2.

Because of a high incidence of meningococcal meningitis, travelers to sub-Saharan Africa are advised to receive meningococcal vaccine. Although this vaccination is generally recommended for children older than 2, it can confer protection in younger patients against some serogroups, especially serogroup A. Additional doses at an older age would be needed to maintain protection. Rabies vaccination is recommended for travelers visiting remote areas of the developing world where access to prompt post-exposure rabies immunoglobulin and vaccine is not likely. Travelers, especia Hy children, planning extended stays abroad (rural areas) may need Japanese encephalitis virus vaccine or tick-borne encephalitis vaccine.

Although no vaccine or toxoid is 100% effective or safe, those described in this article usually are well tolerated or have minimal side effects, such as fever or injection site pain and redness. Severe side effects generally are not observed when appropriately administered. Live vaccines such as the measles, mumps, and rubella, yellow fever, oral typhoid, and varicella vaccines generally should not be given to immunocompromised travelers.

INSECT BITE PROTECTION

Travelers should be counseled that the most effective way of preventing malaria and other mosquito-borne diseases, such as dengue fever, yellow fever, and Japanese encephalitis virus, is to avoid mosquito bites. This may be achieved by wearing long-sleeved clothing and using effective insect repellents. Avoidance of outdoor activities during mosquito seasons and use of window screens or air conditioning, permethrinimpregnated clothing, and bed nets when sleeping are recommended for travelers. Dark colored clothing and floral fragrances, such as those in perfumed soaps, lotions, haircare products and deodorants, may attract mosquitoes. Although 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.

Many insect repellents are available, and choosing between products may be confusing for parents. N,N-diethyl-3methylbenzamide, formerly known as N,N-diethyl-m-toluamide (DEET), is the most effective insect repellent available. Products with 30% or more DEET concentration may be used safely on children, but higher concentrations are not necessary.7 Products containing 20% to 30% DEET protect a person for 4 to 5 hours,8 and products with lower percentages of DEET, such as 4.75% or 6.65%, protect for shorter periods.7 Products with microencapsulated DEET (such as Ultrathon) may provide protection for even longer periods of time.7 High concentrations of DEET do not correlate with increased toxicity but inappropriate use does. Although wristbands are popular among some travelers, protection is measured in seconds or minutes. Natural products such as those containing citronella confer limited protection.

Insect repellents containing DEET should not be applied to the faces of young children because of potential absorption through mucosal membranes. In addition, products should not be applied to the hands of young children because they tend to put them in their mouths. Once the family returns indoors, the insect repellent should be washed off if the indoor area is screened, air conditioned, or they are under bed nets. It is extremely important to emphasize to parents that when visiting tropical areas proper clothing must also be used at night. Long-sleeved shirts, long pants, and closed shoes, in addition to the use of repellents on exposed skin are critical.

The application of permethrin to clothing and permethrin-impregnated bed nets also reduce bites. Permethrin 0.5% on clothing lasts an average of 2 weeks.7 Parents may purchase permethrin at most recreational outdoor stores or via the Internet. Insect repellents and permethrin-impregnated clothing 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 bites.

MALARIA

The risk of infection and type of malaria encountered varies from country to country in the developing world. When providing advice, clinicians should familiarize themselves with this information. Specifically, the presence of chloroquine-susceptible and chloroquine-resistant Plasmodium falciparum should be determined, because this influences the choice of antimalarial medications. Because chloroquine resistance is not a problem in Central America, chloroquine may 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 may be used, but parts of southeast Asia have strains of P falciparum that are now resistant mefloquine.

Some antimalarials cannot be used in certain patients. For example, chloroquine is safe in pregnancy, but doxycycline and atovaquone-proguanil should not be used, and mefloquine should be used with caution in the first trimester of pregnancy.1,22 In addition, doxycycline should not be used in children younger than 8.10 Because these medications are not available in the United States as suspensions or elixirs and are not palatable, pharmacists must compound them in ways children find acceptable. Grinding down tablets and dividing them in portions according to body weight is one option. The tablet powder is stored in a little sachet or small gel capsule and may be poured onto food or mixed with chocolate syrup. To minimize gastrointestinal discomfort, antimalarial medications should always be taken with meals.

Antimalarial prophylaxis medications must be initiated before entering an endemic region. Chloroquine must be started at least 1 week before arrival and mefloquine at least 2 weeks before arrival to allow assessment for side effects. Doxycycline and atovaquone-proguanil may be started 24 to 48 hours before arrival. More detailed information about when to start antimalarial prophylaxis medications can be found elsewhere.32

Because medications may require discontinuation, alternative prophylaxis should be discussed before travel. A different medication may be needed that may not be available in the country. Some travelers are concerned about the potential of neuropsychiatrie disturbances with mefloquine. This medication is contraindicated in people with seizure disorders, psychiatric disorders such as anxiety and depression, or cardiac conduction abnormalities. Potential side effects may be minor, such as nausea and upset stomach, and may include more rare and disturbing complaints such as strange dreams, insomnia, dizziness, weakness, anxiety, and agitation. Children usually tolerate these medications better than adults;9 however, approximately 10% of children experience some difficulties with mefloquine such as vivid dreams, diarrhea, vomiting, changes in sleep, headaches, and hallucinations.9,23 About 23% of children taking chloroquine experience nausea, headaches, vomiting, or changes in sleep.9 Although 5% to 8% of adults discontinue these agents because of side effects, only 1 % of children do so.9

While the choice of antimalarial medications may be straightforward when a family is traveling to a region with chloroquine-susceptible P falciparum or P. vivax, the decision-making process for other Tegions may be a bit more challenging. The choice of antimalarial medication is also influenced by duration of travel, cost, and ease of administration. Some patients do not like taking medicines every day; others may not like the idea of taking medications for 1 mondi after completing a trip. Some travelers may only need intermittent protection against malaria (traveling in and out of malaria regions).

At times, malaria may manifest itself weeks to months after returning from an endemic area. Families spending extended periods of time in an endemic area where P. vivax and P. ovale are present may need terminal prophylaxis. This is intended to eliminate the hypnozoite stage of the parasite in the liver and can be achieved with primaquine for a period of 14 days. However, a glucose6-phosphate dehydrogenase level should be checked before administering primaquine because it can cause severe hemolysis in people who are G-6-PD deficient.10 A more detailed review by Fischer and Bialek10 discusses many of these important issues.

The goal of antimalarial prophylaxis is to clear infections rapidly and reduce mortality and morbidity, especially from P. falciparum. Because no regimen is 100% effective, however, it is important that families be educated about bite prevention and the need to seek care immediately if someone develops a febrile illness during or after a trip to a malaria-endemic area.

TRAVELERS' DIARRHEA

Travelers' diarrhea is common among visitors to developing countries. A study by Pitzinger and colleagues3 showed a 60% attack rate in children younger than 2. Travelers to northern Africa, India, and Latin America were the most affected. Approximately 19% of affected travelers were confined to bed, 15% required treatment by a physician, and 1% required hospitalization.

Approximately 80% of travelers' diarrhea is caused by bacterial pathogens such as enterotoxigenic Escherichia coli. Campylobacter jejuni, nontyphoidal Salmonellae, or Shigella. It may also be caused by noroviruses (Norwalk-like viruses), rotavirus, and parasites such as Giardia lamblia or Entamoeba histolytica. Travelers' diarrhea may be prevented by avoiding tap water or products prepared with it, including ice, as well as 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 must 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 because they contain large amounts of sugar, which may worsen diarrhea. With some enteric infections, vomiting may be a problem and some children may require intravenous rehydration. However, most children can tolerate small amounts of fluids by mouth; rehydration may be achieved using a spoon or dropper to give 1 to 5 mL of fluids per minute. Rehydrating a seriously dehydrated child may require 1 to 1 .5 oz of fluid per pound of weight during a 2- to 4-hour period.

Since most cases of travelers' diarrhea are caused by bacteria, antimicrobial therapy may be used to reduce the duration and severity. Fluoroquinolones such as ciprofloxacin and levofloxacin are commonly recommended for use in adults but not all pediatricians 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.11 An equally effective agent is azithromycin, and many now consider this to be the preferred agent for children.12 In countries such as Thailand, where fluoroquinolone-resistant Campylobacter is common, azithromycin is useful; trimethoprimsulfamethoxazole is no longer recommended because of widespread resistance.24,25 While ciprofloxacin and azithromycin commonly are prescribed for the treatement of travelers' diarrhea in children, these agents have not been approved for this indication by the Food and Drug Administration.

While antidiarrheal medications such as loperamide and bismuth subsalicylate commonly are used in adults, loperamide should not be used in young children because of the risk of paralytic ileus, severe vomiting, and drowsiness.26 Bismuth subsalicylate, however, has been shown to be safe and efficacious in children.27,28 Although some have concern regarding the use of salicylate-containing drugs and the development of Reye syndrome, no reported cases document this association with bismuth subsalicylate

In the developed world, empiric antibiotics generally are not prescribed for children with diarrhea. The association of antibiotic use with 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, and HUS-associated enterohemorrhagic E. coli strains are rare outside developed countries. However, parents should be counseled that children with bloody diarrhea, fever, and abdominal pain require immediate medical evaluation.

Probiotics such as Lactobacillus GG have been used to prevent antibioticassociated and rotavirus-associated diarrhea with some success.29,30 However, there are insufficient data to support their routine use in the prevention or treatment of travelers' diarrhea. A newly approved nonabsorbable antibiotic, rifaximin, has been shown to be effective in treating diarrhea and may prove useful for this specific condition.31

ILLNESS AFTER TRAVEL

Fever, skin conditions, and diarrhea are among the most common problems afflicting returned travelers.13 An initial evaluation for these problems requires a complete assessment of travel history, countries and regions visited, duration of travel, activities while abroad, vaccination history, use of prophylactic and therapeutic medications, and compliance with preventive measures. In returned travelers from the tropics, detennining an incubation period greatly influences diagnostic and therapeutic considerations. Onset of fever more than 3 weeks after return generally eliminates dengue fever, yellow fever, and rickettsiae as potential etiologic causes. Common skin problems of pediatric travelers are scabies, fungal dermatosis, and parasitic infections; frequently reported problems among the latter include cutaneous larva migrans or creeping eruption, a pruritic serpentiginous skin condition commonly caused by the larval migration of Ancylostoma braziliense, and myiasis, which results from the tissue invasion of fly larvae.

Returned travelers may complain of acute or prolonged diarrhea. Causes of acute disease usually are identified through stool cultures and examination for ova and parasites (including antigen assays). The detection of less common parasites such as Cyclospora cayetanensis may require special stains. Giardiasis, tropical sprue, and other parasitic infections also may cause chronic problems in some travelers. Tuberculosis and anemia are observed in returned travelers who have spent extended periods of time abroad. Short-term travelers do not require routine screening for these conditions.

Pediatricians may consult with specialists in infectious diseases and tropical and travel medicine when evaluating pediatric travelers with signs of the previously mentioned problems.

SUMMARY

Visiting a grandparent for a first time, exploring the ruins of an ancient civilization in a distant country, or river rafting through a tropical jungle are all moments that are never forgotten. Illness, visits to the doctor, and disability should not be a part of these experiences. Diseases such as malaria, yellow fever, travelers' diarrhea, and hepatitis A are preventable. Through the use of vaccines, prophylactic medications, and disease-prevention education, clinicians may help ensure their pediatric patients have enjoyable and rewarding travel experiences.

REFERENCES

1. Ryan ET, Kairt KC. Health advice and immunizations for travelers. N Engl J Med. 2000;342(23): 1716-1725.

2. Cossar JH. Reid D, Fallon RJ, et al. A cumulative review of studies on travellers, their experience of illness and die implications of these findings. J Infect. 1990;21(l):27-42.

3. Pitzinger B, Steffen R, Tschopp A. Incidence and clinical features of traveler's diarrhea in infants and children. Pediatr Infect Dis J. 1991; 10( 10):7 19-723.

4. Riordan FA, Tarlow MJ. Imported infections in east Birmingham children. Postgrad Med J. 1998;74(867):3r5-37.

5. Christenson JC, Fischer PR, Hale DC, Derrick D. Pediatric travel consultation in an integrated clinic. J Travel Med. 200 1 ;8( 1 ): 1 -5.

6. Pickering LK, ed. Red Book: 2003 Report of the Committee on Infectious Diseases. 26th ed. Evanston, IL: American Academy of Pediatrics: 2004.

7. Fradin MS. Mosquitoes and mosquito repellents: a clinician's guide. Ann Intern Med. 1998;128(ll):931-940.

8. Fradin MS, Day JF. Comparative efficacy of insect repellents against mosquito bites. N Engl J Med. 2002;347(1): 13-18.

9. Albright TA, Binns HJ, Katz BZ. Side effects of and compliance with malaria prophylaxis in children. J Travel Med. 2002;9(6):289-292.

10. Fischer PR, Bialek R. Prevention of malaria in children. Clin Infect Dis. 2002;34(4):493-498.

11. Alghashan AA, Nahata MC. Clinical use of fluoroquinolones in children. Ann Pharmacother. 2000;34(3):347-359.

12. Stauffer WM, Konop RJ, Kamat D. Traveling with infants and young children. Part III: travelers' diarrhea. J Travel Med. 2002; 9(3):141-150.

13. Ryan ET, Wilson ME, Kain KC. Illness after international travel. N Engl J Med. 2002;347(7):505-516.

14. Cossar JH, Reid D, Fallon RJ, et al. A cumulative review of studies on travellers, their experience of illness and the implications of these findings. J Infect. 1990;21(1):27-42.

15. Fatal yellow fever in a traveler returning from Amazonas, Brazil, 2002. MMWR Morb Mortal Wkly Rep. 2002;51(15):324-325.

16. Centers for Disease Control and Prevention (CDC). Fatal respiratory diphmeria in a US traveler to Haiti - Pennsylvania, 2003. MMWR Morb Mortal WkIy Rep. 2004; 52(53): 1285- 1286.

17. Lee N, Hui D, Wu A, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003; 348(20): 1986- 1994.

18. Mayer LW, Reeves MW, Al-Hamdan N, et al. Outbreak of W135 meningococcal disease in 2000: not emergence of a new W 135 strain but clonal expansion within the electophoretic type-37 complex. J Infect Dis. 2002; 185(11): 1596- 1605.

19. CDC. Hepatitis A outbreak associated with green onions at a restaurant - Monaca, Pennsylvania, 2003. MMWR Morb Mortal WkIy Rep. 2003;52(47):1 155-1 157.

20. CDC. Update: measles among children adopted from China. MMWR Morb Mortal WkIy Rep. 2004;53(21):459.

21. CDC. Wild poliovirus importations - West and Central Africa, January 2003-March 2004. MMWR Morb Mortal WkIy Rep. 200;53(20:433-435.

22. Arguin PM, Navin AW, Kozarsky PE, Cetron MS, eds. Health Information for International Travel 2003-2004. Atlanta, GA: CDC; 2003:99-1 16.

23. Petersen E, Ronne T, Ronn A, Bygbjerg I, Larsen SO. Reported side effects to chloroquine, chloroquine plus proguanil, and mefloquine as chemoprophylaxis against malaria in Danish travelers. J Travel Med. 2000;7(2):79-84.

24. Hoge CW, Gambel JM, Srijan A, Pitarangsi C, Echeverría P. Trends in antibiotic resistance among diarrheal pathogens isolated in Thailand over 15 years. Clin infect Dis. 1998;26(2):341-345.

25. Kuschner RA, Trofa AF, Thomas RJ, et al. Use of azithromycin for the treatment of Campylobacter enteritis in travelers to Thailand, an area where ciprofloxacin resistance is prevalent. Clin Infect Dis. 1995;21(3):536-541.

26. Mótala C, Hill ID, Mann MD, Bowie MD. Effect of loperamide on stool output and duration of acute infectious diarrhea in infants. J Pediatr. 1990;117(3):467-471.

27. Soriano-Brucher H, Avendano P, O'Ryan M, et al. Bismuth subsalicylate in the treatment of acute diarrhea in children: a clinical study. Pediatrics. 1991 ;87( 1 ): 1 8-27.

28. Figueroa-Quintanilla D, Salazar-Lindo E, Sack RB, et al. A controlled trial of bismuth subsalicylate in infants with acute watery diarrheal disease. N Engl J Med. 1993;328(23): 1653-1658.

29. Vanderhoof JA, Whitney DB, Antonson DL, et al. Lactobacillus GG in the prevention of antibiotic-associated diarrhea in children. J Pediatr. 1999;135(5):564-568.

30. Isolauri E, Juntunen M, Rautanen T, SiIlanaukee P, Koivula T. A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children. Pediatrics. l991;88(l):90-97.

31. DuPont HL, Jiang ZD, Ericsson CD, et al. Rifaximin versus ciprofloxacin for the treatment of traveler's diarrhea: a randomized, double-blind clinical trial. Clin Infect Dis. 2007;33(11):1807-1815.

32. Information for Health Care Providers: Prescription Drugs for Malaria. CDC Web site. National Center for Infectious Diseases Travelers Health. Available at: http://www. cdc.gov/travel/malariadrugs2.htm. Accessed September 8, 2004.

TABLE 1.

Web Sites Relati4 to International Travel Health

TABLE 2

Frequently Prescribed Medications for Travel

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