Epidemiology and Clinical Features of Imported Dengue Fever in Europe: Sentinel Surveillance Data from TropNetEurop

Travelers have the potential both to acquire and to spread dengue virus infection. The incidence of dengue fever (DF) among European travelers certainly is underestimated, because few centers use standardized diagnostic procedures for febrile patients. In addition, DF is currently not reported in most European public health systems. Surveillance has commenced within the framework of a European Network on Imported Infectious Disease Surveillance (TropNetEurop) to gain information on the quantity and severity of cases of dengue imported into Europe. Descriptions of 294 patients with DF were analyzed for epidemiological information and clinical features. By far the most infections were imported from Asia, which suggests a high risk of DF for travelers to that region. Dengue hemorrhagic fever occurred in 7 patients (2.4%) all of whom recovered. Data reported by member sites of the TropNetEurop can contribute to understanding the epidemiology and clinical characteristics of imported DF. - tinations. The incidence of epidemic and endemic dengue has increased substantially, notably in the Americas, where, since 1977, various epidemics have occurred [14]. It is estimated that the current annual global incidence of dengue infection is 50100 million patients per year [5]. Among the factors that have been implicated in the current increase in the incidence of dengue are international travel, which introduces new strains to different parts of the world; urbanization; overpopulation; crowding; poverty; and a weakened publichealth infrastructure [6]. Structured data on the epidemiology and clinical course of dengue infection in travelers are rare. Although case reports on imported dengue are relatively frequent, they do not allow for an estimation of the risk of illness for travelers. Various case reports regarding dengue infections in international travelers returning from areas of endemicity have been published [2, 4, 713]. In a small number of systematic studies on this topic, serological evidence of recent dengue infection was found in 7%45% of febrile patients after they had returned from areas of endemicity [1417]. A retrospective study of a small cohort of Swiss travelers showed a surprisingly high prevalence of antibodies to dengue virus (8%) among symptomatic patients [18]. These results were supported further by a prospective study of 130 febrile patients who had returned from areas where dengue is endemic, which found a prevalence of 6.9% [16]. In the latter study, 9 of 10 patients who tested positive for dengue had acquired the infection in Southeast Asia. Similar to the sparse data on the true incidence of DF among travelers, little is known about the clinical spectrum of DF and the proportion of subclinical infections in this group. Studies from areas of endemicity suggest that 14%87% of all dengue infections manifest few or atypical symptoms [1921]. Yet the proportion of subclinical dengue infections among travelers is of importance, because it has been suggested that infection with one serotype of dengue virus can predispose for the development of dengue hemorrhagic fever (DHF) and/or dengue shock syndrome on reinfection with another serotype [22]. The lack of surveillance data for imported cases of infectious diseases in Europe prompted the founding in February 1999 of the European Network on Imported Infectious Disease Surveillance (TropNetEurop), which is an electronic network of clinical sites related to imported infectious diseases. The network is designed to effectively detect emerging infections of potential regional, national, or global impact at their point of entry into the European population. Sentinel surveillance reporting is carried out by participating sites by use of a standardized and computerized reporting system. Immediate transmission of anonymous patient and laboratory data to the central database ensures the timely detection of sentinel events. Membership is voluntary and self-selected by participating centers and is monitored by the steering committee of the network. Although the organization of the network does not guarantee that data collected will be representative for Europe, most major referral centers on the continent are represented: there are 37 clinical sites throughout 14 European countries. From the beginning, DF has been one of the major targets for this network. The present article summarizes results from the first years of sentinel surveillance for imported DF. PATIENTS, MATERIALS, AND METHODS Member sites of the imported infectious disease network TropNetEurop treat 51,000 patients per year. During the 3year period from January 1999 through December 2001, 294 patients with DF were reported by 24 sites within the network. The final diagnosis was qualified in every patient by the reporting center, which stated the diagnosis as suspected, probable, or confirmed. For a diagnosis of confirmed dengue, the virus was detected by isolation or immunohistochemical analysis of necropsy tissue specimens or a type-specific plaque-reduction neutralization test revealed at least a 4-fold increase in antibody titers [23]. A variety of test kits were used by the reporting centers, all of which are established and widely used assays. In-house kits were not used. In all serological methods, cross-reactions with other flaviviruses might have interfered with results, with the ELISA method being particularly vulnerable. Yellow fever vaccination, especially, may play a crucial role here, since many travelers to areas where dengue is endemic also receive that vaccine before departure. Cases for which samples were positive for IgM antibody alone were reported as probable dengue infections. Suspected infections had the diagnosis established on clinical grounds only. A standardized, anonymous questionnaire was used for data collection. Reported case patients were sorted according to the following 2 categories: (1) patient classification (immigrant/refugee, foreign visitor, European living in Europe, or European living outside Europe) and (2) reason for travel (tourism, business, immigration, military, research/education, missionary/ volunteer/humanitarian aid, visiting relatives/friends, or other). Travel and case histories were analyzed for clinical and epidemiological features of the infection. Individual data points were stored in a computerized database (Access; Microsoft) and were analyzed by means of SAS (SAS Institute). Patients with a diagnosis of suspected dengue infection were excluded from the present analyses. Analyses with a clinical end point also excluded patients with multiple infections. Of the 309 reported patients with DF during the period evaluated, 294 had no other diagnosis reported; 212 (72.1%) had confirmed cases, according to the definition used by the surveillance network. A further 26 patients (8.8%) were classified as having probable cases, and 25 (8.5%) as having suspected cases. The diagnosis status was unknown for 26 pa (...truncated)