The diagnosis of febrile illnesses in returning travelers is a great challenge, particularly in those with acute undifferentiated febrile illness (AUFI) characterized by no focal symptoms.

In a prospective European multicenter study of international travelers (2017–2019), Camprubí- Ferrer et al. described the frequencies and predictors of the main causes of fever in travelers. More than 40% of participants with AUFI at centers in Spain, Belgium and Switzerland had malaria or dengue, infections that can be easily diagnosed with rapid diagnostic tests.

After ruling out for malaria, participants with AUFI within two weeks of returning from travel were tested for the presence of dengue, chikungunya and Zika viruses. Of 765 enrolled participants, 60% had AUFI; of these, 29% were viral infections, 21% malaria and 18% bacterial infections. Among the arboviral cases, 85% were dengue and 74% were diagnosed between May and November. After one month, 30% of patients with AUFI remained undiagnosed using standard diagnostic methods.

In conclusion, arboviruses were the most common cause of AUFI after malaria, with most cases diagnosed during the high season for Aedes spp. This study supports the use of empirical antibiotic treatment (e.g., doxycycline or azithromycin) for patients with AUFI, once malaria and arboviruses have been ruled out. https://doi.org/10.1093/jtm/taac002

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