• Daniel Camprubí-Ferrer, José Antonio Oteo, Emmanuel Bottieau, Blaise Genton, Leire Balerdi-Sarasola, Aránzazu Portillo, Ludovico Cobuccio, Steven Van Den Broucke, Sonia Santibáñez, Dániel Cadar, Natalia Rodriguez-Valero, Alex Almuedo-Riera, Carme Subirà, Valérie d'Acremont, Miguel J Martinez, Montserrat Roldán, Jessica Navero-Castillejos, Marjan Van Esbroeck, and Jose Muñoz.
• ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona 08036, Spain.
• J Travel Med. 2023 Feb 18; 30 (1).

BackgroundDiagnosis of undifferentiated non-malaria fevers (NMF) in returning travellers is a great challenge. Currently, there is no consensus about the use of empirical antibiotics in returning travellers with undifferentiated NMF. Although studies in endemic areas showed that a wide range of pathogens implicated in undifferentiated NMF are treatable with doxycycline, the role of doxycycline in returning travellers with fever still has to be explored.MethodsProspective European multicentre cohort study of febrile international travellers (November 2017-November 2019). Immunological and molecular diagnostic techniques for doxycycline responding illnesses (DRI) agents such as Anaplasma phagocytophilum, spotted fever group Rickettsia spp., typhus group Rickettsia spp., Coxiella burnetii, Bartonella spp., Orientia tsutsugamushi, Borrelia miyamotoi, Borrelia recurrentis and Leptospira spp. were systematically performed in all patients with undifferentiated NMF. We estimated the prevalence and predictive factors of DRI in returning travellers with undifferentiated NMF.ResultsAmong 347 travellers with undifferentiated NMF, 106 (30·5%) were finally diagnosed with DRI. Only 57 (53·8%) of the 106 DRI infections were diagnosed by the standard of care. The main causes of DRI were: 55 (51·9%) Rickettsia spp., 16 (15·1%) C. burnetii; 15 (14·2%) Bartonella spp.; 13 (12·3%) Leptospira spp. and 10 (9·5%) A. phagocytophilum. The only predictive factor associated with DRI was presenting an eschar (aOR 39·52, 95%CI 4·85-322·18). Features of dengue such as retro-orbital pain (aOR 0·40, 95%CI 0·21-0·76) and neutropenia (aOR 0·41, 95%CI 0·21-0·79) were negatively associated with DRI.ConclusionsAlthough DRI are responsible for 30% of undifferentiated NMF cases in travellers, those are seldom recognized during the first clinical encounter. Empirical treatment with doxycycline should be considered in returning travellers with undifferentiated fever and negative tests for malaria and dengue, particularly when presenting severe illness, predictive factors for rickettsiosis or no features of dengue.© 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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