High rate of undiagnosed cases of fever among returning travelers from tropical areas tested for malaria: a single-center retrospective study.

BACKGROUND Fever in travelers returning from tropical areas is a challenging clinical problem due to the broad spectrum of potential underlying causes. We aimed to assess the epidemiology of fever in travelers returning from tropical areas and evaluate the proportion of individuals remaining without a diagnosis.

METHODS This was an observational, retrospective, single-center study conducted between January 2018 and December 2024 including febrile travelers who were tested for malaria with onset of symptoms within 30 days of returning to Italy. Epidemiological, clinical, imaging and laboratory data were collected from health records. A multivariable logistic regression model was built to assess factors associated with remaining without a definite diagnosis.

RESULTS Among the 778 returning travelers included in the study, 446/778 (57%) remained undiagnosed. Diagnostic capacity improved over time, with the proportion of definite diagnoses rising from 29.4% in 2018 to 57.8% in 2024. An arboviral infection was identified in 107 individuals (13.6%), with dengue being the most frequent diagnosis (95 cases, 12.2%), followed by malaria (72 cases, 9.3%) and pneumonia (42 cases, 5.4%). When compared to travelers returning from Africa, travelers from the America and the Western Pacific regions showed lower odds of remaining without a definite diagnosis, respectively aOR 0.45 (95% CI 0.28-0.73, p=0.001) and aOR 0.49 (95% CI 0.26-0.95, p=0.034).

CONCLUSIONS Although over half of febrile travelers remained undiagnosed, this proportion declined in recent years, while dengue emerged as the predominant diagnosis in febrile returning travelers.