Clinical Characteristics, Laboratory Parameters, and Molecular Epidemiology of Neuroinvasive Flavivirus Infections in a Hotspot Region of Eastern Croatia

Neuroinvasive flaviviruses such as tick-borne encephalitis virus (TBEV) and West Nile virus (WNV) are widely distributed in continental Croatian regions. We analyzed clinical characteristics, laboratory parameters, and molecular epidemiology of neuroinvasive flavivirus infections in eastern Croatia....

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Main Authors: Dario Sabadi, Kristian Bodulić, Vladimir Savić, Nika Vlahović Vlašić, Maja Bogdanić, Ljiljana Perić, Irena Tabain, Dubravka Lišnjić, Mario Duvnjak, Snježana Židovec-Lepej, Barbara Grubišić, Ilija Rubil, Ljubo Barbić, Luka Švitek, Vladimir Stevanović, Petra Smajić, Bernarda Berišić, Mihaela Zlosa, Ivana Rončević, Tatjana Vilibić-Čavlek
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Pathogens
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Online Access:https://www.mdpi.com/2076-0817/14/1/69
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author Dario Sabadi
Kristian Bodulić
Vladimir Savić
Nika Vlahović Vlašić
Maja Bogdanić
Ljiljana Perić
Irena Tabain
Dubravka Lišnjić
Mario Duvnjak
Snježana Židovec-Lepej
Barbara Grubišić
Ilija Rubil
Ljubo Barbić
Luka Švitek
Vladimir Stevanović
Petra Smajić
Bernarda Berišić
Mihaela Zlosa
Ivana Rončević
Tatjana Vilibić-Čavlek
author_facet Dario Sabadi
Kristian Bodulić
Vladimir Savić
Nika Vlahović Vlašić
Maja Bogdanić
Ljiljana Perić
Irena Tabain
Dubravka Lišnjić
Mario Duvnjak
Snježana Židovec-Lepej
Barbara Grubišić
Ilija Rubil
Ljubo Barbić
Luka Švitek
Vladimir Stevanović
Petra Smajić
Bernarda Berišić
Mihaela Zlosa
Ivana Rončević
Tatjana Vilibić-Čavlek
author_sort Dario Sabadi
collection DOAJ
description Neuroinvasive flaviviruses such as tick-borne encephalitis virus (TBEV) and West Nile virus (WNV) are widely distributed in continental Croatian regions. We analyzed clinical characteristics, laboratory parameters, and molecular epidemiology of neuroinvasive flavivirus infections in eastern Croatia. A total of 43 patients with confirmed flavivirus infection hospitalized from 2017 to 2023 were included in the study. Reverse-transcription polymerase chain reaction (RT-qPCR) was used to detect flavivirus RNA in clinical samples (cerebrospinal fluid; CSF, urine). ELISA was used for IgM and IgG antibody detection in serum and CSF with confirmation of cross-reactive samples by virus neutralization test. WNV was detected more frequently (74.4%) than TBEV (25.6%). A statistically significant age difference was found between WNV patients (median 65 years) and TBEV patients (median 36 years). Comorbidities were more frequently detected in WNV patients (hypertension 56.3 vs. 18.2%; diabetes 31.3 vs. 0%). Meningitis was the most common clinical presentation in both TBE and WNV neuroinvasive disease (WNND; 63.6 and 59.4%, respectively). In addition, some rare clinical presentations of WNND were also detected (cerebellitis, polyradiculoneuritis). No significant differences in the frequency of clinical symptoms were observed between WNV and TBEV-infected patients (fever 93.7 vs. 100%; malaise 78.1 vs. 100%; headache 75.0 vs. 100%; nausea 50.0 vs. 63.6%; vomiting 34.4 vs. 54.6%). Comparative analysis of total and differential leukocyte blood count showed similar results. However, CSF pleocytosis was higher in TBE patients, with a significant difference in the neutrophil and lymphocyte count (WNND median 48.5% and 51.5%; TBE median 10.0 and 90.0%, respectively). The length of hospital stay was 12 days for WNND and 9 days for TBE. Phylogenetic analysis of detected WNV strains revealed the presence of WNV lineage 2 in eastern Croatia.
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spelling doaj-art-ed6567b85cc7404d8c9f30a39249af2c2025-01-24T13:44:47ZengMDPI AGPathogens2076-08172025-01-011416910.3390/pathogens14010069Clinical Characteristics, Laboratory Parameters, and Molecular Epidemiology of Neuroinvasive Flavivirus Infections in a Hotspot Region of Eastern CroatiaDario Sabadi0Kristian Bodulić1Vladimir Savić2Nika Vlahović Vlašić3Maja Bogdanić4Ljiljana Perić5Irena Tabain6Dubravka Lišnjić7Mario Duvnjak8Snježana Židovec-Lepej9Barbara Grubišić10Ilija Rubil11Ljubo Barbić12Luka Švitek13Vladimir Stevanović14Petra Smajić15Bernarda Berišić16Mihaela Zlosa17Ivana Rončević18Tatjana Vilibić-Čavlek19Clinic for Infectious Diseases, University Hospital Centre Osijek, 31000 Osijek, CroatiaResearch Department, University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, 10000 Zagreb, CroatiaPoultry Center, Croatian Veterinary Institute, 10000 Zagreb, CroatiaClinic for Infectious Diseases, University Hospital Centre Osijek, 31000 Osijek, CroatiaDepartment of Virology, Croatian Institute of Public Health, 10000 Zagreb, CroatiaDepartment of Infectology and Dermatovenerology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, CroatiaDepartment of Virology, Croatian Institute of Public Health, 10000 Zagreb, CroatiaDepartment of Infectology and Dermatovenerology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, CroatiaClinic for Infectious Diseases, University Hospital Centre Osijek, 31000 Osijek, CroatiaDepartment of Immunological and Molecular Diagnostics, University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, 10000 Zagreb, CroatiaClinic for Infectious Diseases, University Hospital Centre Osijek, 31000 Osijek, CroatiaClinic for Infectious Diseases, University Hospital Centre Osijek, 31000 Osijek, CroatiaDepartment of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, CroatiaClinic for Infectious Diseases, University Hospital Centre Osijek, 31000 Osijek, CroatiaDepartment of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, CroatiaClinic for Infectious Diseases, University Hospital Centre Osijek, 31000 Osijek, CroatiaClinic for Infectious Diseases, University Hospital Centre Osijek, 31000 Osijek, CroatiaClinic for Infectious Diseases, University Hospital Centre Osijek, 31000 Osijek, CroatiaPoultry Center, Croatian Veterinary Institute, 10000 Zagreb, CroatiaDepartment of Virology, Croatian Institute of Public Health, 10000 Zagreb, CroatiaNeuroinvasive flaviviruses such as tick-borne encephalitis virus (TBEV) and West Nile virus (WNV) are widely distributed in continental Croatian regions. We analyzed clinical characteristics, laboratory parameters, and molecular epidemiology of neuroinvasive flavivirus infections in eastern Croatia. A total of 43 patients with confirmed flavivirus infection hospitalized from 2017 to 2023 were included in the study. Reverse-transcription polymerase chain reaction (RT-qPCR) was used to detect flavivirus RNA in clinical samples (cerebrospinal fluid; CSF, urine). ELISA was used for IgM and IgG antibody detection in serum and CSF with confirmation of cross-reactive samples by virus neutralization test. WNV was detected more frequently (74.4%) than TBEV (25.6%). A statistically significant age difference was found between WNV patients (median 65 years) and TBEV patients (median 36 years). Comorbidities were more frequently detected in WNV patients (hypertension 56.3 vs. 18.2%; diabetes 31.3 vs. 0%). Meningitis was the most common clinical presentation in both TBE and WNV neuroinvasive disease (WNND; 63.6 and 59.4%, respectively). In addition, some rare clinical presentations of WNND were also detected (cerebellitis, polyradiculoneuritis). No significant differences in the frequency of clinical symptoms were observed between WNV and TBEV-infected patients (fever 93.7 vs. 100%; malaise 78.1 vs. 100%; headache 75.0 vs. 100%; nausea 50.0 vs. 63.6%; vomiting 34.4 vs. 54.6%). Comparative analysis of total and differential leukocyte blood count showed similar results. However, CSF pleocytosis was higher in TBE patients, with a significant difference in the neutrophil and lymphocyte count (WNND median 48.5% and 51.5%; TBE median 10.0 and 90.0%, respectively). The length of hospital stay was 12 days for WNND and 9 days for TBE. Phylogenetic analysis of detected WNV strains revealed the presence of WNV lineage 2 in eastern Croatia.https://www.mdpi.com/2076-0817/14/1/69tick-borne encephalitisWest Nile virusneuroinvasive diseaseclinical characteristicslaboratory parametersCroatia
spellingShingle Dario Sabadi
Kristian Bodulić
Vladimir Savić
Nika Vlahović Vlašić
Maja Bogdanić
Ljiljana Perić
Irena Tabain
Dubravka Lišnjić
Mario Duvnjak
Snježana Židovec-Lepej
Barbara Grubišić
Ilija Rubil
Ljubo Barbić
Luka Švitek
Vladimir Stevanović
Petra Smajić
Bernarda Berišić
Mihaela Zlosa
Ivana Rončević
Tatjana Vilibić-Čavlek
Clinical Characteristics, Laboratory Parameters, and Molecular Epidemiology of Neuroinvasive Flavivirus Infections in a Hotspot Region of Eastern Croatia
Pathogens
tick-borne encephalitis
West Nile virus
neuroinvasive disease
clinical characteristics
laboratory parameters
Croatia
title Clinical Characteristics, Laboratory Parameters, and Molecular Epidemiology of Neuroinvasive Flavivirus Infections in a Hotspot Region of Eastern Croatia
title_full Clinical Characteristics, Laboratory Parameters, and Molecular Epidemiology of Neuroinvasive Flavivirus Infections in a Hotspot Region of Eastern Croatia
title_fullStr Clinical Characteristics, Laboratory Parameters, and Molecular Epidemiology of Neuroinvasive Flavivirus Infections in a Hotspot Region of Eastern Croatia
title_full_unstemmed Clinical Characteristics, Laboratory Parameters, and Molecular Epidemiology of Neuroinvasive Flavivirus Infections in a Hotspot Region of Eastern Croatia
title_short Clinical Characteristics, Laboratory Parameters, and Molecular Epidemiology of Neuroinvasive Flavivirus Infections in a Hotspot Region of Eastern Croatia
title_sort clinical characteristics laboratory parameters and molecular epidemiology of neuroinvasive flavivirus infections in a hotspot region of eastern croatia
topic tick-borne encephalitis
West Nile virus
neuroinvasive disease
clinical characteristics
laboratory parameters
Croatia
url https://www.mdpi.com/2076-0817/14/1/69
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