Approximately 21% of Switzerland s 7.7 million. Profile of Travel-Associated Illness in Children, Zürich, Switzerland

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1 158 Profile of Travel-Associated Illness in Children, Zürich, Switzerland Thomas Hunziker, MD, Christoph Berger, MD, Georg Staubli, MD, Alois Tschopp, PhD, Rainer Weber, MD, David Nadal, MD, Christoph Hatz, MD, and Patricia Schlagenhauf, PhD University of Zürich Centre for Travel Medicine, World Health Organisation Collaborating Centre for Travellers Health, University of Zürich, Zürich, Switzerland; Division of Infectious Diseases, University of Zürich Children s Hospital, Zürich, Switzerland; Emergency Department, Division of Infectious Diseases, University of Zürich Children s Hospital, Zürich, Switzerland; Division of Biostatistics, Institute of Social and Preventive Medicine, University of Zürich, Zürich, Switzerland; Division of Infectious Diseases, University Hospital Zürich, Zürich, Switzerland DOI: /j x See the Editorial by Karl Neumann, pp of this issue. Background. The number of families traveling with their children to their country of origin and/or to tropical destinations has increased in Switzerland and includes a changing profile and multinational range of patients. Defining the profile of reported travel-associated illnesses will help to improve the prevention and treatment of such illnesses in children. Methods. This study includes children aged up to 16 years who sought medical advice for a presumed travel-related illness at the emergency room of the University of Zürich Children s Hospital during the period July 2007 to December Results. We analyzed data on 328 children (58.8% male, mean age: 4.62 y) who presented with travel-associated illness. Our analysis included 155 traditional (mainly tourist) travelers, 162 children who were visiting friends and relatives (VFR), and 11 immigrants. Some 11% were hospitalized. No deaths occurred. The main conditions recorded were diarrheal illness (39%), respiratory (28.7%) and febrile/systemic illness (13.4%). With increasing age, the proportion of children with diarrheal disease increased, while the proportion with respiratory illness declined. There were significant associations between geographic area of exposure and the profile of travel-related disease (p < 0.001). Among 36 children with more serious diseases requiring hospitalization, 12 (3.7% overall) presented with potentially serious diseases: malaria (n = 2), Salmonella typhi (n = 3), Salmonella paratyphi (n = 2), meningococcal meningitis (n = 1), tuberculosis (n = 2), visceral leishmania (n = 1), and hepatitis A (n = 1). Eleven of the 12 children presenting with these potentially serious illnesses were VFR or immigrant children. Conclusion. The main diagnoses for ill-returned Zürich children who presented for emergency care were diarrhea, respiratory, and febrile/systemic illness. A broad spectrum of morbidity was seen including meningococcal meningitis, malaria, tuberculosis, typhoid fever, leishmania, and hepatitis A. Diagnoses varied between geographic regions visited, and VFR child travelers constituted a large proportion of sick-returned children presenting for emergency care. Approximately 21% of Switzerland s 7.7 million population are less than 20 years of age, and 22% of Swiss residents are foreign-born. International travel has become increasingly popular worldwide. The number of families traveling with their children to and from tropical destinations has steadily increased over the last years providing potential exposures to tropical diseases. This is a global trend. Travel data of US residents from 2000 reported that 7% (1.9 million) of US international travelers were children. 1 There is little published literature on the Corresponding Author: Patricia Schlagenhauf, PhD, University of Zürich Centre for Travel Medicine, WHO Collaborating Centre for Travelers Health, Institute for Social and Preventive Medicine, University of Zürich, Hirschengraben 84, CH-8001 Zürich, Switzerland. pat@ifspm. uzh.ch incidence and type of illness in Europe-based children who travel. The aims of this study are to characterize the profile of travel-associated illness occurring in children in Zürich, identify risk groups, and use this information as an evidence base to formulate pre-travel health advice. Methods The Zürich Centre of the GeoSentinel surveillance network (GeoSentinel, The Global Surveillance Network of the International Society of Travel Medicine and the Centers for Diseases Control and Prevention; provided clinicianbased pediatric surveillance data for this analysis during an 18-month period. The Zürich site is a composite site of the University Hospital and the University of Zürich Children s Hospital. For the purpose of our study, patients were included if they were younger than 2012 International Society of Travel Medicine, Journal of Travel Medicine 2012; Volume 19 (Issue 3):

2 Profile of Travel-Associated Illness in Children years and had sought medical advice for a presumed travel-related illness at the Emergency Room of the University of Zürich Children s Hospital, Switzerland, between July 2007 and December Final diagnoses were assigned by a physician. Data were collected according to a standardized, anonymous questionnaire and entered into a Structured Query Language database. The questionnaire comprises demographic data (age, sex, country of birth, country of residence, current citizenship), travel history in the last 5 years, or outpatient status, major clinical complaint (more than one per patient is possible), reason for most recent travel, and patient classification. Final diagnoses were assigned a diagnostic code from a standardized list of >500 diagnoses, which were also categorized into 21 broad syndrome groups. Definitions Patient diagnoses were defined as follows: diarrhea included gastroenteritis, acute diarrhea of parasitic, viral, bacterial or unknown origin, and chronic diarrhea of unknown origin; dermatologic ; febrile/systemic illness ; other gastrointestinal and genitourinary included abdominal pain, hepatitis, pyelonephritis, appendicitis, and urinary tract infection; injury and musculoskeletal included trauma, fracture, arthritis, nonspecific symptoms or findings, and vertigo; ophthalmologic ; oral and dental ; and respiratory included upper and lower respiratory infections, otitis, bronchitis, and asthma. Due to small case numbers, a simplified regional classification was used: Asia (North East Asia, South Central Asia, South East Asia), South and Central America (Central America, South America), North America, Australia/New Zealand, Caribbean, Eastern Europe, Western Europe, Middle East, North Africa, sub-saharan Africa. Children were divided into three age-groups with approximately equal numbers of cases: infant between 1 and 23 months of age, preschool child from 2 to 5 years of age, and child and adolescent from 6 to 16 years of age. Statistics The software program Statistics Package for the Social Sciences (SPSS) version 17 was used for descriptive statistical analysis. Statistical significance variables were achieved by using chi-square test. Results In the period between July 2007 and December 2008, a total of 40,486 emergency consultations were documented atthe University ofzürich Children s Hospital. We analyzed 328 children included in the GeoSentinel database. The age range was 0 to 16 years with a mean age of 4.62; 58.8% were male and 89% were outpatients. Two thirds of s (total 11% s) Table 1 Demographic characteristics of ill travelers presenting during and after travel at the University of Zürich Children s Hospital Total: 328 (100%) Male: 193 (58.8%) Female: 135 (41.2%) Mean age (y) Age 0 to <2 y 103 (31.4%) 61 (31.6%) 42 (31.1%) Age 2 to 5 y 113 (34.5%) 62 (32.1%) 51 (37.8%) Age 6 to 16 y 112 (34.1%) 70 (36.31%) 42 (31.1%) Reason for travel VFR 162 (49.4%) 98 (50.8%) 64 (47.4%) Tourism 155 (47.3%) 89 (46.1%) 66 (48.9%) Immigration 11 (3.4%) 6 (3.1%) 5 (3.7%) Clinical setting Seen after travel 273 (83.2%) 162 (83.9%) 111 (82.8%) Seen during travel 44 (13.4%) 25 (13.0%) 19 (8.1%) Immigration travel only 11 (3.4%) 6 (3.1%) 5 (3.7%) Patient type Inpatient 36 (11%) 25 (13.0%) 11 (8.1%) Outpatient 292 (89%) 168 (87.0%) 124 (91.9%) Citizenship Switzerland 142 (43.3%) 85 (44.0%) 57 (42.2%) Western Europe 41 (12.5%) 23 (11.9%) 18 (13.3%) Eastern Europe 89 (27.1%) 57 (29.5%) 32 (23.7%) Asia + Middle East 34 (10.4%) 17 (8.8%) 17 (12.6%) Other 22 (6.7%) 11 (5.7%) 11 (8.1%) VFR, visiting friends and relatives. were male. The patients presented during the calendar year with peak numbers following school vacation periods. The basic demographic pattern is shown in Table 1. Our analysis included 155 tourist travelers, 162 visiting friends and relatives (VFR) travelers, and 11 children who were traveling for the purpose of immigration. Table 2 shows the disease spectrum by gender and age-groups. Leading diagnosis groups were diarrhea (39%), respiratory (28.7%), and febrile/systemic illness (13.4%). With increasing age, the proportion of children with diarrheal disease increased, while the proportion with respiratory illness declined (Table 2). There were significant associations between geographic area of exposure and the profile of travel-related disease (p < 0.001) (Table 3). Among travelers returning from Western Balkan Countries and North Africa, diarrhea was the leading diagnosis. In Asia and America (South, Central, and North), respiratory illness is the most frequent diagnosis, and in sub-saharan Africa, febrile/systemic illness was most frequently reported (Table 3). Only a few patients presented with potential serious diseases: two patients with the diagnosis of malaria (both acquired in the sub-saharan region), three patients with Salmonella typhi diagnosis (1 Middle East and 2 Asia), and two with Salmonella paratyphi diagnosis (2 Middle East). Also, a patient from the sub-saharan zone was diagnosed with meningococcal meningitis. Two cases of tuberculosis, one visceral leishmania and one hepatitis A completed the spectrum of exotic diseases. All of these children were hospitalized (Table 4) representing one

3 160 Hunziker et al. Table 2 Travel-related diagnoses in ill children presenting to the emergency room at the University of Zürich Children s Hospital stratified by age, sex, and reason for travel Male: 193 (58.8%) Female: 135 (41.2%) Tourism: 155 (47.3%) VFR: 162 (49.4%) Age 0 to <2 y: 103 (31.4%) Age 2 to 5 y: 113 (34.5%) Age 6 to 16 y: 112 (34.1%) Diarrhea 128 (39%) 77 (39.9%) 51 (37.8%) 61 (39.4%) 66 (40.7%) 34 (33.0%) 44 (38.9%) 50 (44.6%) Febrile/systemic illness (11.4%) 22 (16.3%) 20 (12.9%) 23 (14.2%) 15 (14.6%) 14 (12.4%) 15 (13.4%) (13.4%) Respiratory 94 (28.7%) 54 (28.0%) 40 (29.6%) 43 (27.7%) 44 (27.2%) 41 (39.8%) 31 (27.4%) 22 (19.6%) Dermatologic 27 (8.2%) 14 (7.3%) 13 (9.6%) 13 (8.4%) 12 (7.4%) 4 (3.9%) 14 (12.4%) 9 (8.0%) Other gastrointestinal and 10 (5.2%) 6 (4.4%) 9 (5.8%) 7 (4.3%) 3 (2.9%) 4 (3.5%) 9 (8.0%) genitourinary 16 (4.9%) Oral and dental 10 (3.0%) 8 (4.1%) 2 (1.5%) 4 (2.6%) 6 (3.7%) 4 (3.9%) 4 (3.5%) 2 (1.8%) Injury and musculoskeletal 6 5 (2.6%) 1 (0.7%) 4 (2.6%) 2 (1.2%) 0 (0%) 1 (0.9%) 5 (4.5%) (1.8%) Ophthalmologic 3 (0.9%) 3 (1.6%) 0 (0%) 1 (0.6%) 2 (1.2%) 2 (1.9%) 1 (0.9%) 0 (0%) This table shows a change in illness pattern by age with an increase in diarrheal illness and a decline in respiratory illness by age. Table 3 Regions and diagnoses with highest number of cases Diarrhea (%) Respiratory (%) Febrile/systemic illness (%) Other (%) Total Western Europe Eastern Europe Asia North Africa Sub-Saharan Africa Latin America Other third of ill-returned hospitalized children. Nine of 12 children presenting with potential serious diseases were VFR, 2 of them were immigrants, and 1 tourist traveler. Thus, the overall frequency of more severe, potentially life-threatening diseases among this population of illreturned children was 5.5% among those VFR, 18% among immigrants, and 0.6% among tourist travelers. Discussion This study shows that returned children, who are sick enough to go to the emergency room, present with a broad spectrum of travel-associated morbidities, mainly diarrheal illness (39%), respiratory (28.7%), and febrile/systemic illness (13.4%). Some 12 (3.6%) of children presenting with travel-associated illness have potential serious diseases requiring hospitalization. Eleven of the 12 children presenting with serious illness were VFR or immigrant children. Our study has certain limitations; patients included in the study do not necessarily represent the whole population of Zürich. Many ill-returned children will visit pediatricians or general practitioners, and some children will present in the emergency room due to an inadequate access to the primary health care system. Furthermore, the number of travelers returning in good health is also unknown. Therefore, incidence rates or relative risks cannot be estimated. Similarly, patients with mild or self-limiting disease are more likely to see a general practitioner. On the other hand, Zürich Table 4 Potentially serious diagnoses with sex, age, travel reason, and exposure country Meningitis, meningococcal Male age 4, Immigration from Chad Salmonella typhi Female age 3, Bangladesh Salmonella typhi Male age 6, Iraq Salmonella typhi Female age 5, Immigration from Manila Salmonella paratyphi Female age 1, Tourism in Salmonella paratyphi Male age 11, Malaria Plasmodium falciparum Male age 1, Ghana Malaria P falciparum Male age 2, Ghana Leishmania, visceral Female age 1, Portugal Tuberculosis Male age 2, Kosovo Tuberculosis Female age 6, Hepatitis A Male age 13, Kosovo VFR, visiting friends and relatives. is a large city with a mixed sociocultural population, andmanyofthesepatientsmayprefertogotoamore anonymous University Children s Hospital, particularly if they do not have a regular general practitioner. 2

4 Profile of Travel-Associated Illness in Children 161 Only 0.8% (328 of 40,486) of all emergency consultations had a travel-related reason. Nevertheless, the travel history is essential in ascertaining the possible cause of disease and in the selection of the appropriate diagnosis. Recently, a global analysis of ill-returned children showed that diarrhea is the leading diagnosis in returned children, and our study confirms this finding. 1 The fore-mentioned global analysis, however, shows significant dermatological proportional morbidity that was not observed in the Zürich collective. Our analysis is thus particularly valuable for physicians and pediatricians in the Central European setting. Another report shows no significant difference in the incidence of morbid episodes between children and adults, except for fever which is diagnosed more frequently in children. 3 The study confirms that many of the diagnosed illnesses post travel are commonplace and of short duration. Travelers diarrhea affects over 50% of travelers and can disrupt holidays. 4 The most frequent bacterial pathogens of travelers diarrhea are Escherichia coli, Campylobacter, Shigella, andsalmonella. 3 6 As diarrhea was the most frequent illness in children in this study, this theme is important for inclusion in the pre-travel consultation. Parents should be prepared to treat mild diarrhea with oral rehydration and additionally loperamide for older children. 7,8 In this study, two malaria cases were found, both from Ghana in VFR travelers. As a priority, malaria should be ruled out in children with febrile illness returning from malaria endemic areas. The pre-travel advice is an ideal opportunity to provide concise malaria prevention guidelines and chemoprophylaxis for children. 9 Mosquito bite protection is an essential component of malaria prevention, and N, N-diethyl- 3-methybenzamide (DEET) repellents can be used for infants aged >2 months. 10 Generally, pediatric malaria case numbers are increasing as more children travel and the profile of migration is changing In the study from Stäger et al., 14 returning to the country of origin to visit friends and relatives was a significant risk factor for the acquisition of malaria. A recent analysis suggests that it is cost-effective to subsidize malaria chemoprophylaxis for low-income travelers visiting high-risk malaria endemic areas, and this may encourage use of malaria prophylaxis in VFR travelers. 15 School-, sport-, and community-based strategies to reach VFR children need to be evaluated. 16 A relation between the place of exposure and the spectrum of disease can help in diagnostic approaches and empiric therapies. 17,18 Nontravel medicine practitioners should be reminded to ask the question did you travel recently? when taking a history. Depending on the travel destination, travelers may be exposed to a number of infectious diseases; exposure depends on the presence of infectious agents in the respective area. The risk of becoming infected will vary according to the purpose of the trip, the itinerary within the area, the standards of accommodation, hygiene, and sanitation, as well as the behavior of the traveler and the reason for travel whether it is for tourism, VFR travel, or for immigration. 19 VFR travelers are exposed to an increased risk of travel-related health problems General practitioners should be aware of possibly serious travelrelated disease in VFR risk groups in their community. Africa is associated with malaria, while Asia including is associated with typhoid fever. Two cases of tuberculosis in VFR children were acquired in and Kosovo. Conclusions Physicians attending to returned ill children need to be aware of and to diagnose a complete range of diseases from commonplace to serious. Parents can be provided with a simple range of pediatric medications and instructions on how to treat self-limiting conditions. The pre-travel consultation is an opportunity to provide concise preventive advice for pediatric travelers. The country of origin of settled migrants has an important role to play in the diagnosis profile. VFR children will present with potentially more serious illnesses such as typhoid fever, hepatitis A, and malaria. Acknowledgment We thank the members of the secretariat especially Mrs Lopez from the University of Zürich Children s Hospital, Division of Infectious Diseases. Declaration of Interests P. S. has received research grants and consultancy fees from F. Hoffmann La Roche, speaker s honorary from GSK, and is an advisory board member of sigma tau. The other authors state that they have no conflicts of interest to declare. Authors Contributions Statement All authors have seen and approved the final version of the paper. T. H. was involved in the concept, design, analysis, and writing/revising the paper. He is the guarantor. C. B. was involved with the concept and revision of the paper and gave major input and critical feedback. G. S. was key in capturing data on children presenting with travel-related illness. A. T. provided significant statistical input. G. S., A. T., R. W., D. N., and C. H. critically revised the paper. P. S. was involved in the concept, design, analysis, and writing/revising the paper and she is the project supervisor. References 1. Hagmann S, Neugebauer R, Schwartz E, et al. Illness in children after international travel: analysis from the

5 162 Hunziker et al. GeoSentinel Surveillance Network. Pediatrics 2010; 125: e1072 e Fenner L, Weber R, Steffen R, Schlagenhauf P. Imported infectious disease and purpose of travel, Switzerland. Emerg Infect Dis 2007; 13: Newman-Klee C, D Acremont V, Newman CJ, et al. Incidence and types of illness when traveling to the tropics: a prospective controlled study of children and their parents. Am J Trop Med Hyg 2007; 77: Steffen R, Tornieporth N, Clemens SA, et al. Epidemiology of travelers diarrhea: details of a global survey. J Travel Med 2004; 11: Stauffer W, Christenson JC, Fischer PR. Preparing children for international travel. Travel Med Infect Dis 2008; 6: Pitzinger B, Steffen R, Tschopp A. Incidence and clinical features of traveler s diarrhea in infants and children. Pediatr Infect Dis J 1991; 10: Cézard J, Bellaiche M, Viala J, Hugot J. [Medication in infectious acute diarrhea in children]. Arch Pediatr 2007; 14(Suppl 3):S169 S Birkenfeld G. [Treating travelers diarrhea. When should medication be given?]. Internist (Berl) 2007; 48: Swales C, Chiodini P, Bannister B; HPAACoMPiU Travellers. New guidelines on malaria prevention: a summary. J Infect 2007; 54: Schlagenhauf P, Adamcova M, Regep L, et al. Position of mefloquine as a 21st century malaria chemoprophylaxis. Malar J 2010; 9: Castéla F, Legros F, Lagardère B. [Imported malaria in children in France]. Arch Pediatr 2003; 10: Minodier P, Retornaz K, Kone-Paut I, et al. [Pediatric malaria imported in France]. Arch Pediatr 2001; 8(Suppl 2):266s 268s. 13. Brabin B, Ganley Y. Imported malaria in children in the UK. Arch Dis Child 1997; 77: Stäger K, Legros F, Krause G, et al. Imported malaria in children in industrialized countries, Emerg Infect Dis 2009; 15: Widmer LL, Blank PR, Van Herck K, et al. Costeffectiveness analysis of malaria chemoprophylaxis for travellers to west-africa. BMC Infect Dis 2010; Hagmann S, Schlagenhauf P. Prevention of imported pediatric malaria: travel medicine misses the bull s eye. J Travel Med 2011; 18: Freedman DO, Weld LH, Kozarsky PE, et al. Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J Med 2006; 354: Rack J, Wichmann O, Kamara B, et al. Risk and spectrum of diseases in travelers to popular tourist destinations. J Travel Med 2005; 12: Leroy H, Arvieux C, Biziragusenyuka J, et al. A retrospective study of 230 consecutive patients hospitalized for presumed travel-related illness ( ). Eur J Clin Microbiol Infect Dis 2008; 27: Leder K, Tong S, Weld L, et al. Illness in travelers visiting friends and relatives: a review of the GeoSentinel Surveillance Network. Clin Infect Dis 2006; 43: Bacaner N, Stauffer B, Boulware D, et al. Travel medicine considerations for North American immigrants visiting friends and relatives. JAMA 2004; 291: Angell S, Cetron M. Health disparities among travelers visiting friends and relatives abroad. Ann Intern Med 2005; 142:67 72.

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