As the number of children traveling with their parents is increasing globally, so are the rates of travel-related infections.1,2 According to the latest report of the United Nation World Tourism Organization, 1135 million persons crossed international borders in 2014,2 of whom 7%–10% were children.1,2 Although tourism is the major reason for travel, with the growing global migration, 33%3 to 49%1 of the traveling children did so to visit friends or relatives, a proportion higher than that in traveling adults.4
Because diarrhea is the most common travel-associated illness,5 this article intends to provide an update on existing knowledge on this topic in children, highlight clinical areas requiring further research and training and conclude with practical recommendations.
Travelers’ diarrhea is usually defined as passage of ≥3 unformed stools/24 hours—often accompanied by nausea/vomiting, abdominal cramps or fever—that develops during or within 14 days of returning from travel to a resource-limited location.5 However, as stooling of healthy young children varies, some authors define travelers’ diarrhea as a ≥2-fold increase in the frequency of unformed stools following overseas travel. Diarrhea affects 10% to 41% of the traveling children; when compared with adults, higher rates were found in children.5Unfortunately, data from a multicenter study showed that ill children returning from international travel were less likely than adults to have had received pretravel medical advice and more likely to require inpatient care.4
SOURCE OF PEDIATRIC DATA
Most previous studies on travelers’ diarrhea have been performed in adults; pediatric studies were generally based on single-center experiences, often with a small patient numbers and sometimes reporting only on hospitalized children. It is encouraging that large, multicenter-based data are recently more often utilized; the major ones are discussed briefly below.
GeoSentinel Surveillance Network
This network of the International Society of Travel Medicine and the Centers for Disease Control and Prevention is based on travel clinics at >50 sites across 6 continents that systematically collect information on ill-returning travelers. Analysis of data from 1840 children returning from 218 global destinations who presented to the clinics during 1997–2007 documented that diarrhea was the most common (28%) travel-associated health problem, usually of acute onset (80%), with bacteria as the cause in 29%.4
Foodborne Disease Active Surveillance Network
This network is operated by the Centers for Disease Control and Prevention and includes 10 clinical sites which report laboratory-confirmed infections, based on the study of 9 pathogens commonly transmitted through food products. Since 2004, data regarding international travel among US residents with enteric infections upon return to the United States have been routinely collected. During 2004–2009, 13% of the 64,039 enteric infections studied were travel-associated, of whom 24.2% were children. The main causative pathogens, in the whole population, were Campylobacter (42%), non-typhoidal Salmonella (32%) and Shigella (13%) spp, resulting in 5 deaths.6
Global Foodborne Infections Network
This World Health Organization-based network was created to build global capacity for detection, control and prevention of foodborne and other enteric infections.7 A recent report on worldwide distribution of foodborne outbreaks highlights the relevance of foodborne diseases, which were associated with 33 million Disability-Adjusted Life Years in 2010; 40% of the disease burden occurred in children under 5 years of age.7
This consortium includes 18 clinics in the United States providing care to international travelers. The consortium provides analysis of travel demographic characteristics, pretravel consultations and travel-related health issues. Although the portion of children among travelers has been studied and the impact of travelers’ diarrhea appreciated, data specifically related to children have not been published.8
The University of Zurich Center for Travel Medicine, a World Health Organization Collaborative Center for Travelers Health and a member of the GeoSentinel Network, records data on travel-associated health problems and specifically focuses on pediatric experience.1 Investigators from the University of Munich Travel Clinic focused on children and adolescents and showed that diarrhea was the most common travel-related illness.3 The Spanish Tropical Medicine Network on Imported Infections showed that 13.5% of the 606 children followed presented with gastrointestinal disorders.9
Travel destination has a major impact on the risk for travelers’ diarrhea (also on the causative pathogens, as discussed below), with highest rates associated with travel to Africa and South Asia.1,3,6 The incidence and severity of travelers’ diarrhea are age-dependent: infants and toddlers have the highest incidence rates, greatest severity and higher likelihood of requiring hospitalization.3,5,6,9 Compared with travel for tourism, to visit friends or relatives children are at higher risk of travelers’ diarrhea, as they are less likely to attend pretravel clinics, have longer periods of visit, often stay in rural areas in resource-poor locations and less frequently adhere to recommended precautions.3–5,9
Travelers’ diarrhea is usually infectious, caused by microbial pathogens endemic at the travel destination.10 Bacteria predominate,3,5,6 including enterotoxigenic Escherichia coli (ETEC; especially in Latin America and Africa), enteroaggregative E. coli (Latin America and Southeast Asia), Campylobacter (Asia), Shigella (Africa and Latin America) and Salmonella spp. Less frequent causative bacteria are Aeromonas, Plesiomonas and Vibrio spp (including Vibrio cholerae). Arcobacter and enterotoxigenic Bacteroides fragillis, which are difficult to detect, are potentially emerging pathogens in travelers’ diarrhea.5 Parasites, especially Giardia lamblia and Entamoeba histolytica, are also important, especially in travelers to Asia.3,4,9 Viruses, especially norovirus, were often not tested for in the past, but are likely important.11 One small study detected norovirus in 4/21 (17%) children returning from the tropics with a recent episode of acute diarrhea.12Norovirus infections can be associated with other pathogens, such as ETEC.13 Because rotavirus remains the most common cause of diarrhea worldwide, it can be travel-related in children under 3 years of age not vaccinated against rotavirus.5
CLINICAL MANIFESTATIONS AND MANAGEMENT
The average time from departure to diarrhea onset in children is 8 days.5 Depending on the causative pathogen, travelers’ diarrhea is often watery, with nausea and abdominal cramps, but can be bloody/mucousy with high fever (clinical picture of dysentery).5 Most cases are self-limited; however, children are more susceptible to dehydration and electrolyte imbalance as a result of fluid losses.5 Invasive bacterial pathogens, mainly Shigella, Salmonella and Campylobacter spp, can cause intestinal perforation and bacteremia.
Correcting fluid and electrolyte losses, preferably by oral rehydration solutions (ORS), is the mainstay of treating travelers’ diarrhea. Frequent small-amount administration is critical in the vomiting child. In the pretravel visit, caregivers should be advised regarding the symptoms and signs of dehydration and the use of ORS. Appropriate ORS or sachets should be included in the routine health pack of all travelers, as they may not be readily available in local pharmacies at the travel destination. Breastfeeding or the child’s regular diet should be resumed within 4–6 hours of correcting dehydration. Antimicrobial therapy is not recommended routinely, but should be considered for children with suspected Shigella or Campylobacter spp and certain E. coli infections. Treatment is also required for Giardia lamblia and Entamoeba histolytica infections. Because the specific etiological diagnosis will rarely be available, some clinical characteristics can suggest that antimicrobials may be beneficial: for example, moderate to severe bloody diarrhea with fever suggests Shigella spp. Azithromycin is the empiric drug of choice for childhood travelers’ diarrhea, as it covers most relevant pathogens, is well-tolerated, is conveniently dosed once daily (a dose of 10 mg/kg/day, maximum 500 mg, for 3 days is typically recommended) and drug resistance is overall uncommon. Rifaximin, a nonabsorbable antimicrobial agent, can be used in children >12 years for noninvasive enteropathogens. Carrying antibiotics for self-treatment, with detailed pretravel instructions, is advisable. A prolonged diarrheal course of more than 1 or 2 weeks with weight loss in a child traveling to a resource-limited region may suggest Giardia lamblia infection; in such cases, tinidazole (single dose) can be highly effective, although other alternatives such as metronidazole or nitazoxanide are suitable alternatives.10
Antimotility agents, such as loperamide, should not be used in patients with fever, patients with bloody diarrhea or in children<3 years, as it can lead to serious adverse events, such as toxic megacolon and central nervous system depression.6 Zinc supplementation is not recommended in the treatment of travelers’ diarrhea in children.
Immunocompromised Traveling Child
With the advances of modern pediatrics—including increased survival of children with primary immunodeficiencies and HIV infection, organ transplantation, and widespread use of biologic and cytotoxic agents—the number of immunocompromised children that travel has increased considerably. Besides the common pathogens, in these children, additional pathogens can cause moderate to severe disease, including Cryptosporidium parvum and Cystoisospora belli.5 These patients may also be at increased risk of complications, such as bacteremia associated with Salmonella or Campylobacter spp.5 These children must have professional pretravel advice, with extra precautions regarding water, food and animal exposure and detailed instructions regarding special medications that should be carried during travel.
With the exception of cholera vaccine—licensed in certain locations for children ≥2 years of age, which may also offer some cross-protection against ETEC—no vaccine to prevent travelers’ diarrhea is available. Rotavirus vaccination is highly desirable for infants younger than 6 months of age. Personal hand hygiene and food and beverage precautions are keys to prevent travelers’ diarrhea (Table 1).
Attending a pretravel clinic to obtain appropriate advice is highly recommended, not only for diarrhea prevention but also to prevent other travel hazards. In young children, adherence to hygiene measures is critical, but obviously more difficult because of their natural curiosity and habit of exploring the environment with their hands and mouth. It is advisable that adults traveling with children carry readily available foods, such as healthy snacks, to avoid the pressure of buying food from street vendors. Most important is safe drinking water (eg, bottled water) when traveling to resource-limited countries. Bathing in swimming pools or lakes of unknown microbiological quality poses a risk for ingestion of contaminated water by children. Routine antibiotic prophylaxis is not recommended.
PEDIATRIC TRAVELERS’ DIARRHEA-RELATED GAPS
As discussed earlier, data focused on travelers’ diarrhea in children are very limited, and as a consequence, specific guidelines for children are generally lacking.4 The Pediatric Interest Group of the International Society of Travel Medicine, created in 2010, performed a survey which shed some light on the gaps concerning pediatric travelers’ diarrhea.14 They found that physicians practicing pediatric travel medicine had diverse professional backgrounds and often lacked formal education in travel medicine. Significant variations in the approach to a variety of clinical scenarios were identified, sometimes with lack of awareness of existing guidelines. The main conclusion was that better strategies to facilitate education and support pediatric-focused research in travel medicine are required to formulate more robust evidence-based guidelines for children.14
CONCLUSIONS AND RECOMMENDATIONS
- In an era of increasing international travel, travelers’ diarrhea is one of the most common illnesses that children and families will encounter.
- Risk factors for travelers’ diarrhea include certain destinations (such as Africa or South Asia), young age, visit friends or relatives and adventure travel.
- During a pretravel medical visit, caregivers should be given information on appropriate precautions regarding hygiene and behavior during travel. Parents should also receive information on acute diarrhea manifestations, symptoms and signs of dehydration and appropriate use of ORS and empiric antibiotic treatment.
- As no vaccine against most forms of travelers’ diarrhea is available (except cholera and rotavirus infection), prevention centers around hygiene and food and water precautions.
- Travelers’ diarrhea is usually self-limited; dehydration and electrolyte disturbances are the most frequent complications.
- The mainstay of treatment is correction of fluid and electrolyte losses, preferably by ORS. Carrying commercial ORS and an antibiotic agent (eg, azithromycin) for self-treatment is advisable
- Antimicrobial use should be limited to moderate to severe bloody diarrhea, severe watery diarrhea in areas where V. cholerae or ETEC are prevalent or for prolonged debilitating diarrhea (preferably after medical consultation, stool culture and parasite examination).
- Pediatric-focused research into travelers’ diarrhea is needed to formulate evidence-based guidelines tailored for children, including immunocompromised children.
- Better strategies are needed to increase the uptake of pretravel clinic visits and improve the training of physicians providing pretravel advice to families.
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