Visceral leishmaniasis as a leading cause of fever of unknown origin in immunocompetent adults: A prospective, observational, single-center study

Aim: To evaluate the presentation patterns of visceral leishmaniasis (VL) as a cause of fever of unknown origin (FUO) and compare them with other FUO etiologies. Materials and methods: This prospective observational study was conducted at the Clinic for Infectious Diseases and Febrile Conditions in Skopje, Republic of North Macedonia, from 2019 to 2025. We included ninety-four immunocompetent patients, aged 14 or over who met the FUO criteria by Durack and Street and had a definitive etiology subsequently established. Based on the final diagnosis, patients were categorized into those with VL and those with alternative FUO etiologies. Demographic, clinical, and laboratory data from standardized investigations were compared between the groups using appropriate statistical tests. Results: Sixty-six percent of participants were male, and their median age was 49 years (IQR 36-65). Infectious diseases were responsible for 52.1% of all FUO cases, followed by noninfectious inflammatory disorders (20.2%), miscellaneous causes (17%), and malignancies (10.6%). VL was the leading single diagnosis, identified in 17% of the total cohort. Compared with non-VL FUO cases, VL patients more often presented with weight loss, diaphoresis, and splenomegaly (all p<0.001), hepatomegaly (p=0.002), and higher febrile peaks (p=0.026). Hematologic abnormalities were more pronounced in VL, with lower hemoglobin, hematocrit, leukocyte, and platelet counts (all p≤0.006), as well as lower albumin (p=0.029) and higher globulin levels (p=0.001). Conclusion: Visceral leishmaniasis can be an important yet underrecognized cause of FUO in endemic regions. Greater clinical awareness and early diagnostic testing are essential to prevent delays and inappropriate treatment.