• Daniel Camprubí-Ferrer, Ludovico Cobuccio, Steven Van Den Broucke, Blaise Genton, Emmanuel Bottieau, Valérie d'Acremont, Natalia Rodriguez-Valero, Alex Almuedo-Riera, Leire Balerdi-Sarasola, Carme Subirà, Marc Fernandez-Pardos, Miguel J Martinez, Jessica Navero-Castillejos, Isabel Vera, Jara Llenas-Garcia, Camilla Rothe, Dániel Cadar, Marjan Van Esbroeck, Nikki Foque, and Jose Muñoz.
• ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
• J Travel Med. 2022 Mar 21; 29 (2).

BackgroundEtiological diagnosis of febrile illnesses in returning travelers is a great challenge, particularly when presenting with no focal symptoms [acute undifferentiated febrile illnesses (AUFI)], but is crucial to guide clinical decisions and public health policies. In this study, we describe the frequencies and predictors of the main causes of fever in travelers.MethodsProspective European multicenter cohort study of febrile international travelers (November 2017-November 2019). A predefined diagnostic algorithm was used ensuring a systematic evaluation of all participants. After ruling out malaria, PCRs and serologies for dengue, chikungunya and Zika viruses were performed in all patients presenting with AUFI ≤ 14 days after return. Clinical suspicion guided further microbiological investigations.ResultsAmong 765 enrolled participants, 310/765 (40.5%) had a clear source of infection (mainly traveler's diarrhea or respiratory infections), and 455/765 (59.5%) were categorized as AUFI. AUFI presented longer duration of fever (p < 0.001), higher hospitalization (p < 0.001) and ICU admission rates (p < 0.001). Among travelers with AUFI, 132/455 (29.0%) had viral infections, including 108 arboviruses, 96/455 (21.1%) malaria and 82/455 (18.0%) bacterial infections. The majority of arboviral cases (80/108, 74.1%) was diagnosed between May and November. Dengue was the most frequent arbovirosis (92/108, 85.2%). After 1 month of follow-up, 136/455 (29.9%) patients with AUFI remained undiagnosed using standard diagnostic methods. No relevant differences in laboratory presentation were observed between undiagnosed and bacterial AUFI.ConclusionsOver 40% of returning travelers with AUFI were diagnosed with malaria or dengue, infections that can be easily diagnosed by rapid diagnostic tests. Arboviruses were the most common cause of AUFI (above malaria) and most cases were diagnosed during Aedes spp. high season. This is particularly relevant for those areas at risk of introduction of these pathogens. Empirical antibiotic regimens including doxycycline or azithromycin should be considered in patients with AUFI, after ruling out malaria and arboviruses.© The Author(s) 2022. Published by Oxford University Press on behalf of International Society of Travel Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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