key: cord-0746051-wyk9p7mu authors: Yoshimura, Yukihiro; Miyata, Nobuyuki; Miyajima, Makiko; Sakamoto, Yohei; Amano, Yuichiro; Tachikawa, Natsuo title: Diseases affecting patients returning from abroad: Experience of a travel clinic in Japan from 2004 to 2014 date: 2016-10-22 journal: J Infect Chemother DOI: 10.1016/j.jiac.2016.09.005 sha: dc42a2a4e56107012dd91c3682e43432ad5cee1c doc_id: 746051 cord_uid: wyk9p7mu The number of patients returning from or staying abroad is likely to increase in the future. We performed a retrospective study of patients returning from abroad in our travel clinic in Japan. All patients presenting within 6 months of traveling abroad between 2004 and 2014 were included in the present study. A total of 2374 (mean age, 35 years) patients were seen by doctors specializing in treating infectious diseases. Of these, 918 were females and 87 of them lived abroad. Diagnoses and exposure regions were recorded for all patients. The most frequent region visited before attending our clinic was Southeast Asia (n = 1050, 44%), with a median duration for staying abroad of 8 days. The major purposes for overseas travel were tourism (n = 1302, 55%) and business (n = 684, 29%). Of the 2399 individual diagnoses made, the most frequent were diseases of the gastrointestinal system (n = 1083, 45%), skin and soft tissue (n = 440, 18%), systemic febrile disease without specific systems (419, 18%), and the respiratory system (353, 15%). The relative incidences of specific diseases changed drastically due to significant disease outbreaks, such as pandemic influenza in 2009. Exposure regions remained relatively constant throughout the study period, except for Japan. Vaccine-preventable diseases accounted for 5.3% of all the diseases, and 402 (26%) patients received pre-travel consultation and prophylaxis with vaccines and/or anti-malarial drug. We should make an effort to make more people notice the risk of travel and properly perform prophylaxis. Each year, more than 16 million Japanese residents travel abroad and more than 19 million foreign people visit Japan according to Japan National Tourism Organization. The number of foreign tourists traveling to Japan has been increasing, with more patients visiting clinics in Japan after or during travel. There is a lack of published small case series regarding infectious and non-infectious diseases among patients visiting travel clinics in Japan [1e3]. Our clinic is a member of the global travel-associated disease surveillance network "GeoSentinel," which has recently reported largescale studies on ill travelers [4] . However, most of the data are provided by European and North American clinics, and the report does not reveal the patients and diseases in real settings, such as the travel clinics in Japan. Accordingly, we evaluated the characteristics of patients visiting our travel clinic following recent travel abroad to help improve the clinical practice of Japanese doctors and establish prevention strategies. We performed a retrospective study of patients attending our clinic between 2004 and 2014 who had a history of abroad travels within 6 months of their initial presentation. Our clinic is located in Yokohama, Japan's second most populated city (over 3 million residents), approximately 40 km south of Tokyo. Our hospital is a 650-bed community-based acute care teaching facility, and our clinic is run by 2e4 doctors for infectious disease, with inputs from other specialties, such as dermatology and pediatrics. We obtained data regarding patient demographics, travel histories, reasons for most recent overseas travel, and pre-travel vaccinations using a questionnaire for all patients (pre-travel information was added to the questionnaire in 2006). Regions were classified as East Asia (except Japan), Southeast Asia, South Asia, Oceania, Middle East, Europe, Africa, North America, and Latin America. Reasons for traveling abroad included tourism, business, study, missionary or volunteer work, visiting friends and relatives (VFR), and immigration or residence. VFR is defined as a condition when people visit a foreign country to see friends, family, or relatives; it does not depend on where they were born, how developed the foreign country is or which they migrated or not. In cases where there were multiple reasons, the most important reason was considered. Physicians determined exposure regions according to clinical course, travel history, and infection window periods. Therefore, potential exposure regions included Japan, airplanes, or none (disease not associated with any specific exposure). Diagnoses were made according to clinical, laboratory, and imaging findings, with every effort taken to determine the underlying etiologies. For example, in cases where acute bacterial colitis was suspected but no pathogen was detected, the final diagnosis was recorded as acute colitis of unknown etiology. Diseases were classified according to organ system as systemic febrile (no specific organ), respiratory, gastrointestinal, skin and soft tissue, hepatobiliary, genitourinary, and neurological diseases. When patients attended our clinic in the recovery phase, we used information from clinical correspondence to determine their underlying etiology. Real-time PCR was used to detect the pathogenic gene of diarrheagenic Escherichia coli strains. This study is performed independently of GeoSentinel, which collects information only on travel-associated diseases. This study was approved by our institutional review board. A total of 2374 patients were seen at our clinic during the study period ( Table 1 ). The mean age of patients was 35 ± 14 years, with 918 people female (39%). Of the 2374 included patients, 2251 (95%) were Japanese, 120 (5.1%) were born in foreign countries (2 Japanese) and 87 (3.7%) lived abroad (57 Japanese). The most frequently traveled region before clinic visit was Southeast Asia (n ¼ 1050, 44%), whilst 102 patients (4.3%) had traveled to multiple regions. The median duration of overseas travel was 8 days (0e27480 days). The predominant reasons for overseas travel were tourism (n ¼ 1302, 55%), business (n ¼ 684, 29%), and VFR (n ¼ 209, 9%). The highest number of patients seen per year was in 2007, with the lowest number seen in 2010. The number of patients has increased since 2012 (Table 2 ). Of the 2399 diagnoses made in our clinic, the most frequently affected organ system was the gastrointestinal system, followed by skin and soft tissue, and systemic febrile diseases. Acute and chronic diarrhea were the most frequently observed gastrointestinal diseases, with fewer cases of enteric fever, esophagitis, and gastritis (Table 3 ). Causative agents identified in cases of gastrointestinal disease included Campylobacter spp., Salmonella spp., Shigella spp., and diarrheagenic E. coli, with Giardia intestinalis being the most frequently observed parasitic infection (Table 3 ). Three cases of irritable bowel syndrome and one case of drug-induced (atovaquone/proguanil) diarrhea were also observed. The majority of skin/soft tissue diseases were caused by animal exposure with or without post-exposure prophylaxis against rabies, insects bite, and lymphadenitis ( Table 4 ). The predominant sources of animal exposure were dogs, monkeys, and cats, with squirrels, sheep, lions, donkeys, bats, and boars identified as less frequent sources. Systemic febrile diseases are shown in Table 5 . A total of 81 cases of dengue fever, 76 cases of malaria, 4 cases of measles, 4 cases of chikungunya fever, 4 cases of leptospirosis, and 1 case of murine typhus were diagnosed. Respiratory diseases were predominantly unspecified upper respiratory infections or influenza (Table 6 ). Bronchitis and pneumonia were observed in 34 and 26 cases respectively. Frequent causative agents identified in cases of pneumonia included Haemophilus influenzae, Streptococcus pneumoniae, and Mycoplasma pneumoniae. Cases of genitourinary diseases included 10 cases of urinary tract infection and 2 cases of prostatitis (Table 7) . There was one case of a foreign doctor developing acute pseudomonas prostatitis. Hepatobiliary diseases included hepatitis and biliary infection (Table 8 ). Hepatitis A virus was the most frequent cause of hepatitis. The predominant neurological disease was aseptic meningitis (Table 9 ). The case of rabies developed right shoulder pain, cough, anxiety, and confusion 3 months after a dog bite in the Philippines. He was diagnosed with rabies and provided with intensive care, although eventually died. Data pertaining to infrequent diseases, such as endocrine, bone/ joint, ophthalmological, otological, and other diseases, are shown in Table 10 . There were 2 cases of newly diagnosed HIV infection. Diseases rarely diagnosed in Japan but observed in the present study included rabies, cutaneous leishmaniasis, melioidosis, and murine typhus. The most frequent regions of exposure were Southeast Asia (n ¼ 1014, 43%), South Asia (n ¼ 377, 16%), Africa (n ¼ 259, 11%), East Asia (n ¼ 225, 9.4%), and "unspecified" (n ¼ 106, 4.5%; Table 11 ). Outcomes were generally good in the present study, with only one fatal case of rabies and 220 (9.5%) patients admitted to hospital. Pre-travel vaccination or anti-malarial chemoprophylaxis was performed in 394 (25%) and 13 (0.8%) patients, respectively. Vaccine-preventable diseases were diagnosed in 127 cases, including influenza (81), typhoid fever (17), hepatitis A (7), rubella (6), varicella (5), measles (4), pneumococcal pneumonia (3), tuberculosis (2), mumps (1) and rabies (1). To our knowledge, this is the largest study of patients presenting at a Japanese travel clinic with a history of traveling abroad. A 12year study of infectious diseases in travelers presenting to a Japanese clinic was published although this study was not comprehensive [2] . The majority of studies evaluating travel-associated Although the total number of patients visiting our clinic changed year by year, no correlation was observed between the number of patients leaving and coming to Japan over the years. The highest number of patients was seen in 2007, which may have been influenced by 2 deaths due to rabies in Japan in 2006. The lowest number of patients was seen in 2010, and this may be attributed to the H1N1 influenza pandemic in 2009. Many factors likely underlie the changes in the numbers of patients presenting to our clinic, with public awareness of disease pandemic likely being a major contributor. We included patients living in foreign countries, with their median duration of staying abroad influenced by this. The most frequently involved organ system was the gastrointestinal system over the entire study period, with the majority of cases diagnosed as enterocolitis. The ratio is much more than that of GeoSentinel's report (34%) [4] . The variety and frequency of causative agents identified in the present study were comparable to previous reports, except for strongyloides [4, 7, 8] . Regarding Vibrio cholerae serotype O1/non-O1 infections, no cases were observed after 2007. This finding may be attributable to infectious disease law revision in 2007, by which quarantine stations have not tested Vibrio cholera since then. With regard to parasites, giardia species and Entamoeba histolytica were the most common causative agents, with other helminths, such as, strongyloides, rarely identified. Cases of helminthic infection may be rare due to a relatively short duration of stay and low-risk behavior in foreign countries. Skin and soft tissue diseases are commonly associated with animal exposure. The large number of patients with animal exposure in the present study may be attributed to poor knowledge of the risk of animal bites among the Japanese population. The number of cases with animal exposure was the greatest in 2007 and declined thereafter. This number was likely considerably influenced by 2 cases of Japanese individuals who contracted rabies abroad and died in Japan in 2006. These 2 deaths increased awareness and education regarding rabies among the Japanese population; however, this awareness may have subsequently declined as no cases have since been observed in Japan. Therefore, when people were injured during contact with animals abroad, only a small fraction of them might have attended clinics. Among all sources of animal exposure, monkeys were the second most prominent. The high number of individuals injured by monkeys may be attributed to individuals being less wary of monkey attacks than of dog attacks, particularly in wildlife parks. These findings indicate Japanese travelers should be more cautious when dealing with animals likely to carry rabies. The underlying etiology in cases of systemic febrile disease was not determined in more than half of cases. For example, [11] ; however, the reasons for this low number remain unclear. Upper respiratory infection was the most frequent respiratory diagnosis, followed by influenza. The H1N1 influenza pandemic occurred in 2009, and our clinic also experienced a large number of suspected cases. Although 23 of the 81 cases of influenza observed in the present study were diagnosed in 2009, influenza A/B was diagnosed in every year of the study period. As previous studies have reported year-round circulation of influenza viruses in tropical countries [12] , influenza should be included as a differential diagnosis in all seasons in patients with a history of travel to tropical areas. The causative agent was confirmed in 16 of 23 cases of pneumonia. Four of these 16 cases were atypical pneumonia (M. pneumoniae in 3 cases and Chlamydophila pneumoniae), which has a longer incubation period and predominantly affects younger people compared to the typical pneumonia. Two cases of pulmonary tuberculosis, with longer incubation periods, were also observed. These results corroborate those of a previous report [4, 13] . Regarding diseases that are rarely observed in Japan, we experienced cases of rabies, melioidosis, murine typhus, and cutaneous leishmaniasis. No cases of Ebola virus disease, yellow fever, Zika virus infection, Middle East respiratory syndrome, plague, or anthrax were encountered; however, appropriate preparations should be in place for such lethal and/or highly infectious diseases. Vaccine-preventable diseases, excluding tuberculosis, were observed in 127 (5.3%) cases [14] . The proportion of patients receiving pre-travel consultation with vaccination/anti-malarial chemoprophylaxis was similar to a previous report [3] and was relatively low compared with that in foreign countries, where 20e40% of travelers undergo prophylaxis [4,15e17] . Therefore, greater awareness among Japanese travelers is required regarding travel-associated diseases and the importance of prophylaxis. The limitations of the present study were the inclusion of patients from a single center and uncertainty regarding some diagnoses. First, single-center studies are subject to selection bias. Second, diagnostic laboratory techniques were limited at our facility, with viral culture, PCR, and many serological tests unavailable at our hospital, with these techniques only performed in highly suspected or severe cases. Third, the quality of diagnosis may have varied according to physicians' skill and experience. In conclusion, we report the findings of a longitudinal study of diagnoses in a real-world travel clinic setting in Japan. Gastrointestinal and skin and soft tissue diseases were the most common among patients with a history of overseas travel. Further, the incidence of diseases changed year by year and may have been influenced by specific disease outbreaks. As a low proportion of patients had received vaccination or pre-travel consultation before travel, Japanese travelers should be better informed regarding travel-related health risks. All authors have declared no conflicts of interest. 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