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ABSTRACT |
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Many Schistosoma infections diagnosed in nonendemic areas are chronic infections identified in immigrants; however, disease in returning travelers has received increasing attention. Most reports are descriptions of outbreaks from a single source or observational studies from individual institutions.5–19 A recent cross-sectional study reviewed schistosomiasis in 333 travelers and immigrants treated at several medical centers in Europe.20 Although the clinical and epidemiologic features of schistosomiasis in European and non-European travelers were compared, it does not compare these features to those observed in ill travelers without schistosomiasis and about half the patients were born in Schistosoma-endemic areas. In a prospective study of fever in ill returned travelers, the clinical and laboratory features of acute schistosomiasis were compared with those of other causes of febrile illness to identify diagnostic predictors of tropical diseases in ill travelers.21 To date, however, no study has compared returned travelers with schistosomiasis to travelers with other illnesses to identify factors associated with Schistosoma acquisition during travel. We report on the clinical and epidemiologic features of 401 cases of travel-associated schistosomiasis collected over a decade at 27 GeoSentinel sites in 12 countries.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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GeoSentinel Surveillance Network GeoSentinel sites are specialized travel and tropical medicine clinics on six continents staffed by clinicians who are recruited on the basis of demonstrated training, experience, and publication in travel and tropical medicine. They contribute clinician-based information on all ill returned travelers seen, including travel history. Additional detail has been previously published or is available at www.geosentinel.org.22,23 The sites accounting for the majority of patient intake are within academic centers; several smaller volume sites (almost all with current academic affiliation) are in freestanding locations. The intake at sites reflects a mixed population of tertiary care and self-referred patients. Some sites are restricted to outpatients. No site has its entire practice limited to ill travelers.
To be eligible for inclusion in the GeoSentinel database, patients must have crossed an international border within 10 years and be seeking medical advice at a GeoSentinel clinic for a presumed travel-related illness, referred to as "ill returned travelers." This terminology is used to emphasize that travelers seen at GeoSentinel clinics do not necessarily represent all returned-travelers, only those seeking medical advice regardless of symptoms. Anonymous surveillance data are entered into a structured query language (SQL) database at a central data center. Final diagnoses reported by physicians are used to assign diagnostic codes from a standardized list of over 500 etiologic or syndromic diagnoses.22
Study groups All ill returning travelers who reported to a GeoSentinel site from March 1997 through February 2008, and who had completed travel to a Schistosoma-endemic area were eligible for analysis. Persons born in Schistosoma-endemic countries and those traveling for the sole purpose of immigration were excluded.2,24 A case of travel-associated schistosomiasis was defined as a confirmed or probable Schistosoma infection diagnosed by parasitologic or serologic methods.
A sub-analysis exploring the reasons for presenting to a GeoSentinel clinic was also performed using all patients who had completed travel to a Schistosoma-endemic area and were examined for schistosomiasis. Patients with schistosomiasis were compared with patients who were suspected of having schistosomiasis, based on exposure history with or without clinical findings, but were ultimately found not to be infected (referred to as ruled-out for schistosomiasis). Symptomatic patients were excluded from this part of the analysis if the reporting site documented that it was screening the patient for schistosomiasis and believed the patient was symptomatic with another illness (e.g., soft tissue infection).
Diagnoses Final diagnoses included S. mansoni, S. haematobium, S. japonicum, and Schistosoma-unknown human species. The diagnosis of schistosomiasis was made by microscopy or serologic testing. The exact method of diagnosis was not reported, but all sites used the best serologic technique available in their country, including the Falcon assay screening test–enzyme-linked immunosorbent assay (FAST-ELISA) followed by confirmation and speciation with an enzyme-linked immunoelectrotransfer blot, conventional ELISA, indirect fluorescent antibody (IFA), and indirect hemagglutination (IHA) tests.25 Because serologic testing is unable to distinguish between active and past infections, including those that have been successfully treated, only infections believed by the reporting site to be active on the basis of clinical or epidemiologic information were reported. Also, many of the commercially available serologic tests are genus–specific, not species–specific, thus in many cases the Schistosoma species was not known. Furthermore, no distinction was made between acute schistosomiasis (e.g., Katayama fever) and chronic forms of schistosomiasis.
Definition and groupings Traveler type Patients were assigned to one of four groups (traveler type) based on their reason for travel: tourists, business travelers, travel for missionary, volunteer, research or humanitarian aid work (referred to as missionaries and other volunteers), and all others. The other category includes students, military travelers, travelers visiting friends and family, and those whose reason for travel was unknown. It was also reported whether the patient had lived as an expatriate, which was defined as living in an independent residence with the infrastructure used by local residents of the same economic class.
Clinical symptoms and diagnoses Presenting symptoms in 14 general categories were reported.22 More than one presenting symptom could be reported for each traveler.
Travelers sometimes were diagnosed with other illnesses in addition to schistosomiasis; therefore, all additional confirmed or presumptive final diagnoses were examined and were sorted into six categories: gastrointestinal, genitourinary, respiratory, malaria, and two helminth diagnoses groups. All reported Strongyloides stercoralis, Ascaris lumbricoides, and hookworm (Ancylostoma duodenale and Necator americanus) infections, which are known to cause respiratory symptoms during their migration through the lung, were classified into one helminth group. All other reported helminth infections were classified into the second helminth group.
Timing and duration of travel For travel completed within six months before the clinic visit, the duration of travel for the entire most recent trip with likely exposure and time-to-presentation from that trip was calculated in weeks.
For travel completed more than six months before the clinic visit, duration of travel was reported as "30 or more consecutive days" or "fewer than 30 days"; time-to-presentation was recorded as years before the clinic visit (6 months–2 years, 3–4 years, or 
5 years).
Region of exposure Regions were defined as the United Nations Statistics Branch macrogeographic regions and subregions, with the exception of Sudan, which was included in East Africa.26 When a single region of exposure could not be identified, the likely region of exposure was reported as the continent of exposure or as "multiple regions." When country of exposure was not stated by the reporting site, the likely region of exposure was determined by reviewing individual travel itineraries and the geographic distribution of schistosomiasis.2,24
Statistical analysis
Data analysis was performed with Microsoft Access (Seattle, WA, 2000) and SPSS version 16 (Chicago, IL). Statistical significance was determined by 
2 tests. Fisher’s exact test was used if one or more of the expected values were less than five. Age was examined as both a continuous variable and a dichotomous variable (less than 45 years of age, the 75th percentile). We used logistic regression with backwards elimination to evaluate factors potentially associated with a diagnosis of schistosomiasis after travel to Schistosoma-endemic areas, compared with a different diagnosis after travel to the same areas. P values reported from logistic regressions were based on Wald 2 statistics. A two-sided P value of < 0.05 was considered to indicate statistical significance.
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RESULTS |
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Demographic characteristics and type of travel for patients with a diagnosis of schistosomiasis were compared with those without schistosomiasis (Table 1
). Male travelers and travelers < 45 years of age were more likely to be diagnosed with schistosomiasis relative to another illness. When the data were controlled for age and sex, those traveling for missionary or other volunteer work were twice as likely to be diagnosed with schistosomiasis as were tourist and other types of travelers. Business travelers were less likely to be diagnosed with schistosomiasis than were tourists and other types of travelers. Individuals traveling as expatriates, regardless of the type of travel, were twice as likely to be diagnosed with schistosomiasis as those staying for shorter times and staying in hotels. Having a pre-travel consultation was also associated with being diagnosed with schistosomiasis.
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). All seven cases of S. japonicum were acquired in Southeast Asia. Frequently mentioned locations for Schistosoma exposure included Lake Malawi, the Nile and Omo Rivers, and a hotel swimming pond in Tanzania, where 23 patients were exposed.
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). The median duration of travel for this group was 13 weeks (IQR 4–33 weeks). One hundred ten (27%) travelers presented to a GeoSentinel clinic more than 6 months after travel. Time-to-presentation was between 6 months and two years for 73 (18%), three to four years for 16 (4%), and five or more years for 18 (4%). Of those presenting more than 6 months after travel, 23 (21%) stayed 30 or more consecutive days in at least one Schistosoma-endemic country. Altogether 210 (52%) ill returned travelers with schistosomiasis stayed at least 30 days in a Schistosoma-endemic country. The duration of travel could not be determined for 32 (8%) travelers and time-to-presentation for 40 (10%) travelers who had limited travel information or multiple opportunities for exposure.
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). Of the 319 travelers who were asymptomatic at presentation, 41% were diagnosed with schistosomiasis. Gastrointestinal symptoms, fever, genitourinary symptoms, and fatigue were the most commonly reported symptoms. Returned travelers with schistosomiasis were more likely to present with fever than those who were ruled-out for schistosomiasis. Those with S. haematobium and S. mansoni infections presented with more respiratory symptoms than did those ruled-out for schistosomiasis. Moreover, returned travelers with schistosomiasis who were seen within six months of travel more often presented with fever and respiratory symptoms compared with those who presented later (Table 3
).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Expatriates and those traveling as missionaries, volunteers, researchers, and aid workers were more than twice as likely to be diagnosed with schistosomiasis compared with other travelers. Missionaries and other volunteers tend to remain at their destinations for longer periods of time, which may place them at greater risk for acquiring schistosomiasis. They also may be more likely to engage in behaviors that are similar to those of the local populations. Assigning travelers to categories based on purpose of travel and type of traveler allows identification of persons who would benefit from specific preventive education and post travel follow-up. Our findings should encourage sponsoring organizations to more uniformly screen returning missionaries, volunteers, and expatriates.
Having a pre-travel consultation was associated with being diagnosed with schistosomiasis. One possible explanation for this finding is that sponsoring organizations require their employees or volunteers to have a pre-travel consultation, particularly in preparation for prolonged travel, and that people who receive pre-travel health advice are more likely to seek care when they return. Those who presented within six months were more likely to have had a pre-travel encounter, regardless of type of travel.
The effectiveness of the pre-travel consultation may wane over time, as travelers interact with other travelers who may have received different pre-travel health advice or who have never encountered other foreigners seriously ill with schistosomiasis. In a study on the utility of history, examination, and laboratory testing in screening returned travelers for parasitic infections, written and verbal pre-travel briefing did not influence the rate of Schistosoma seropositivity in travelers who stayed three months or longer.27 In 1998, 26% of U.S. Peace Corps Volunteers serving in Tanzania, who had received standard in-country training, were found to be infected with schistosomiasis at the end of their 27 months tour.28 After introduction of an intensive schistosomiasis education campaign, which consisted of additional emphasis on schistosomiasis in pre- and mid-service training sessions and in twice-yearly newsletters and increased one-on-one counseling during routine contact for other reasons, the seroprevalence of schistosomiasis dropped to 5–7% in 1999–2001. In general, avoidance of freshwater in endemic areas, or only using water that has been chlorinated, heated, or left to sit for 48–72 hours, is critical to preventing infection.24
As seen in our study and others, a large proportion of travelers with schistosomiasis are asymptomatic at diagnosis (33% in our study), and when symptoms are present, gastrointestinal symptoms, fever, genitourinary symptoms, and fatigue are most commonly reported.11,16,17,20,27 Because we only used cases that were confirmed by microscopy or serology, we were unable to distinguish between acute schistosomiasis and more chronic forms of schistosomiasis; microscopy and serologic testing are often negative during acute schistosomiasis and may take several weeks to become positive.4–9,17,18 In our study, however, fever and respiratory symptoms, which are common during acute schistosomiasis,10,15,17,18,29–31 were more often reported in travelers who presented within six months; whereas genitourinary symptoms were more often reported in those who presented later. Respiratory complaints are increasingly recognized as an important part of acute schistosomiasis.17,18,29–31 Although first described after infection with S. japonicum, acute schistosomiasis can be seen also after infection with S. mansoni and S. haematobium.4–8,17,29–31 We show that symptoms consistent with acute schistosomiasis are seen in a high proportion of those with S. haematobium and S. mansoni infections, supporting the notion that acute schistosomiasis can occur in all nonimmune travelers, regardless of infecting Schistosoma species. Furthermore, in a recent study of returned Israeli travelers with schistosomiasis, ~25% of asymptomatic travelers went on to develop symptoms of chronic schistosomiasis; therefore, screening for and treating schistosomiasis in all travelers with potential exposure, even if asymptomatic, should be encouraged.17
The limitations of this analysis include those applicable to other published studies that used the GeoSentinel database. The findings can only be generalized to travelers seen in tropical or travel medicine clinics after travel. GeoSentinel sites are specialized travel and tropical medicine clinics recruited on the basis of demonstrated training, experience, and publication in travel and tropical medicine. They contribute clinician-based surveillance data recorded as part of normal patient care. There are no standard protocols dictating the work-up of patients; however, GeoSentinel clinicians would be expected to have tested methodically for schistosomiasis when indicated by exposure history. Some cases may have been missed, as some Schistosoma infections that were ruled out may not have been reported and patients with other illnesses were not necessarily tested for schistosomiasis if the patient or payor declined testing. Although the GeoSentinel database is a comprehensive sample of illnesses acquired by ill returned travelers presenting in 19 countries with exposure in over 230 countries, biases for certain behavior-related diagnoses likely exist because of the geographic distribution and proportionate contribution of the individual sites.
Because GeoSentinel sites do not report the method used for diagnosis, it is unknown what proportion of schistosomiasis cases were diagnosed by direct egg detection or by serology. Only those with suspicion of current infection and/or disease would have been tested in the GeoSentinel setting. Previously treated patients can still have disease. Previously treated infections still provide the information needed for the present analysis in terms of place of exposure, duration of travel, and type of travel.
More information is needed about the effectiveness of pre-travel education on disease prevention in long-term travelers, particularly those traveling for missionary or other volunteer service. Even after the introduction of an intensive schistosomiasis education program, emphasizing the importance of freshwater avoidance, only 26% of Peace Corps Volunteers did not swim in freshwater for their entire tour.28 Even a history of no freshwater exposure, however, is not sensitive enough to rule out infection in potentially exposed travelers; 4.8% of returning travelers were found to be infected with Schistosoma species despite reporting no freshwater contact.27 Prevention messages, especially for those traveling for an extended period of time, should include the possibility of asymptomatic infection and the need for screening on return home, regardless of symptoms.
Received November 14, 2007. Accepted for publication July 17, 2008.
Acknowledgments: In addition to the authors, members of the Geo-Sentinel Surveillance Network who contributed data (in descending order) are: Louis Loutan and François Chappuis, University of Geneva, Geneva, Switzerland; Graham Brown, Joseph Torresi, and Karin Leder, Royal Melbourne Hospital, Melbourne, Australia; Jay S. Keystone and Kevin C. Kain, University of Toronto, Toronto, Canada; Gerd-Dieter Burchard, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany; Marc Shaw, Worldwise Travellers Health and Vaccination Centre, Auckland, New Zealand; Vanessa Field, InterHealth, London, United Kingdom; Carlos Franco-Paredes, Emory University, Atlanta, Georgia; Thomas B. Nutman and Amy D. Klion, National Institutes of Health, Bethesda, Maryland; Christina M. Coyle and Murray Wittner, Albert Einstein School of Medicine, Bronx, New York; Lin H. Chen and Mary E. Wilson, Mount Auburn Hospital, Harvard University, Cambridge, Massachusetts; DeVon C. Hale and Stefanie S. Gelman, University of Utah, Salt Lake City, Utah; Philippe Parola, Fabrice Simon, and Jean Delmont, Hôpital Nord, Marseille, France; Giampiero Carosi and Francesco Castelli, University of Brescia, Brescia, Italy; N. Jean Haulman, David Roesel, and Elaine C. Jong, University of Washington, Seattle, Washington; Mogens Jensenius, Ullevål University Hospital, Oslo, Norway; R. Bradley Sack and Robin McKenzie, Johns Hopkins University, Baltimore, Maryland, (Dec. 1997 to Aug. 2007 only); Effrossyni Gkrania-Klotsas, Addenbrooke’s Hospital, Cambridge, United Kingdom; Michael D. Libman and J. Dick Maclean, McGill University, Montreal, Canada; William M. Stauffer and Patricia F. Walker, University of Minnesota, Minneapolis, Minnesota; Bradley A. Connor, Cornell University, New York, New York; Carmelo Licitra and Antonio Crespo, Orlando Regional Health Center, Orlando, Florida; Prativa Pandey, CIWEC Clinic Travel Medicine Center, Kathmandu, Nepal; Elizabeth D. Barnett, Boston University, Boston, Massachusetts; and Alejandra Gurtman, Mount Sinai Medical Center, New York City, New York (Oct. 2002 to Aug. 2005 only).
Financial support: GeoSentinel, the Global Surveillance Network of the International Society of Travel Medicine, is supported by Cooperative Agreement U50/CI000359 from the Centers for Disease Control and Prevention.
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. None of the authors had any conflicts of interest.
* Address correspondence to Deborah J. Nicolls, Division of Infectious Diseases, Emory University, 550 Peachtree Street NE, Suite 7000, Atlanta, GA 30303. E-mail: djn7{at}columbia.edu 
DJN and LHW contributed equally to this paper.
Authors’ addresses: Deborah J. Nicolls, Division of Infectious Diseases, Emory University, 550 Peachtree Street NE, Suite 7000, Atlanta, GA 30303, Tel: 404-849-4831, Fax: 404-686-4508, E-mail: djn7{at}columbia.edu. Leisa H. Weld, Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, GA 30333. Eli Schwartz, Center of Geographic Medicine, Sheba Medical Center, 52621 Tel Hashomer, Israel, Tel: +972 (3) 530-5000; Fax: +972 (3) 530-2011. Christie Reed, Division of Global AIDS, MS E-04, Centers for Disease Control and Prevention, Atlanta, GA 30333, Tel: 404-639-4212, Fax: 404-639-8114. Frank von Sonnenburg, Department of Infectious Diseases and Tropical Medicine, University of Munich, Leopoldstr. 5, 80802 Munich, Germany, Tel: +49 (89) 398844; Fax: +49 (89) 336112. David O. Freedman, University of Alabama at Birmingham, Birmingham, AL. Phyllis E. Kozarsky, Division of Infectious Diseases, Emory University, 550 Peachtree Street NE, Suite 7000, Atlanta, GA 30303, Tel: 404-686-6173, Fax: 404-686-4508.
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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