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Chen J, Zhang Y, Zhang X, Zhang M, Yin X, Zhang L, Peng C, Fu B, Fang L, Liu W. Epidemiology and Ecology of Usutu Virus Infection and Its Global Risk Distribution. Viruses 2024; 16:1606. [PMID: 39459938 PMCID: PMC11512428 DOI: 10.3390/v16101606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 10/05/2024] [Accepted: 10/09/2024] [Indexed: 10/28/2024] Open
Abstract
Usutu virus (USUV) is an emerging mosquito-transmitted flavivirus with increasing incidence of human infection and geographic expansion, thus posing a potential threat to public health. In this study, we established a comprehensive spatiotemporal database encompassing USUV infections in vectors, animals, and humans worldwide by an extensive literature search. Based on this database, we characterized the geographic distribution and epidemiological features of USUV infections. By employing boosted regression tree (BRT) models, we projected the distributions of three main vectors (Culex pipiens, Aedes albopictus, and Culiseta longiareolata) and three main hosts (Turdus merula, Passer domesticus, and Ardea cinerea) to obtain the mosquito index and bird index. These indices were further incorporated as predictors into the USUV infection models. Through an ensemble learning model, we achieved a decent model performance, with an area under the curve (AUC) of 0.992. The mosquito index contributed significantly, with relative contributions estimated at 25.51%. Our estimations revealed a potential exposure area for USUV spanning 1.80 million km2 globally with approximately 1.04 billion people at risk. This can guide future surveillance efforts for USUV infections, especially for countries located within high-risk areas and those that have not yet conducted surveillance activities.
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Affiliation(s)
- Jiahao Chen
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, 20 Dong-Da Street, Fengtai District, Beijing 100071, China; (J.C.); (X.Z.); (M.Z.); (X.Y.); (L.Z.); (C.P.)
| | - Yuanyuan Zhang
- Department of Disease Control and Prevention, No. 926 Hospital of Joint Logistics Support Force, Kaiyuan 661600, China;
| | - Xiaoai Zhang
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, 20 Dong-Da Street, Fengtai District, Beijing 100071, China; (J.C.); (X.Z.); (M.Z.); (X.Y.); (L.Z.); (C.P.)
| | - Meiqi Zhang
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, 20 Dong-Da Street, Fengtai District, Beijing 100071, China; (J.C.); (X.Z.); (M.Z.); (X.Y.); (L.Z.); (C.P.)
| | - Xiaohong Yin
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, 20 Dong-Da Street, Fengtai District, Beijing 100071, China; (J.C.); (X.Z.); (M.Z.); (X.Y.); (L.Z.); (C.P.)
| | - Lei Zhang
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, 20 Dong-Da Street, Fengtai District, Beijing 100071, China; (J.C.); (X.Z.); (M.Z.); (X.Y.); (L.Z.); (C.P.)
| | - Cong Peng
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, 20 Dong-Da Street, Fengtai District, Beijing 100071, China; (J.C.); (X.Z.); (M.Z.); (X.Y.); (L.Z.); (C.P.)
| | - Bokang Fu
- School of Public Health, Anhui Medical University, Hefei 230022, China;
| | - Liqun Fang
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, 20 Dong-Da Street, Fengtai District, Beijing 100071, China; (J.C.); (X.Z.); (M.Z.); (X.Y.); (L.Z.); (C.P.)
| | - Wei Liu
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, 20 Dong-Da Street, Fengtai District, Beijing 100071, China; (J.C.); (X.Z.); (M.Z.); (X.Y.); (L.Z.); (C.P.)
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Gravemann U, Boelke M, Könenkamp L, Söder L, Maurer M, Ziegler U, Schulze TJ, Seltsam A, Becker SC, Steffen I. West Nile and Usutu viruses are efficiently inactivated in platelet concentrates by UVC light using the THERAFLEX UV-Platelets system. Vox Sang 2024. [PMID: 38699884 DOI: 10.1111/vox.13648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 04/10/2024] [Accepted: 04/17/2024] [Indexed: 05/05/2024]
Abstract
BACKGROUND AND OBJECTIVES West Nile virus (WNV) and Usutu virus (USUV) are mosquito-borne flaviviruses (Flaviviridae) that originated in Africa, have expanded their geographical range during the last decades and caused documented infections in Europe in the last years. Acute WNV and USUV infections have been detected in asymptomatic blood donors by nucleic acid testing. Thus, inactivation of both viral pathogens before blood transfusion is necessary to ensure blood product safety. This study aimed to investigate the efficacy of the THERAFLEX UV-Platelets system to inactivate WNV and USUV in platelet concentrates (PCs). MATERIALS AND METHODS Plasma-reduced PCs were spiked with the virus suspension. Spiked PC samples were taken after spiking (load and hold sample) and after UVC illumination on the Macotronic UV illumination machine with different light doses (0.05, 0.1, 0.15 and 0.2 (standard) J/cm2). Virus loads of WNV and USUV before and after illumination were measured by titration. RESULTS Infectivity assays showed that UVC illumination inactivated WNV and USUV in a dose-dependent manner. At a UVC dose of 0.2 J/cm2, the WNV titre was reduced by a log10 factor of 3.59 ± 0.43 for NY99 (lineage 1) and 4.40 ± 0.29 for strain ED-I-33/18 (lineage 2). USUV titres were reduced at the same UVC dose by a log10 factor of 5.20 ± 0.70. CONCLUSIONS Our results demonstrate that the THERAFLEX UV-Platelets procedure is an effective technology to inactivate WNV and USUV in contaminated PCs.
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Affiliation(s)
- Ute Gravemann
- German Red Cross Blood Service NSTOB, Springe, Germany
| | - Mathias Boelke
- Institute for Parasitology, University of Veterinary Medicine, Hannover, Germany
- Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, Hannover, Germany
| | - Laura Könenkamp
- Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, Hannover, Germany
- Department of Biochemistry, University of Veterinary Medicine, Hannover, Germany
| | - Lars Söder
- Institute of Virology, University of Veterinary Medicine, Hannover, Germany
| | - Maurice Maurer
- Institute for Parasitology, University of Veterinary Medicine, Hannover, Germany
- Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, Hannover, Germany
| | - Ute Ziegler
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald-Island of Riems, Germany
| | - Torsten J Schulze
- German Red Cross Blood Service NSTOB, Springe, Germany
- Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Oldenburg, Oldenburg, Germany
| | - Axel Seltsam
- Bavarian Red Cross Blood Service, Institute Nuremberg, Nuremberg, Germany
| | - Stefanie C Becker
- Institute for Parasitology, University of Veterinary Medicine, Hannover, Germany
- Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, Hannover, Germany
| | - Imke Steffen
- Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, Hannover, Germany
- Department of Biochemistry, University of Veterinary Medicine, Hannover, Germany
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Crivei LA, Vata A, Teodor D, Porea D, Cozma AP, Anita A, Oslobanu LE, Morosan S, Savuta G. An Assessment of West Nile and Usutu Viruses' Seroprevalence in Hospitalized Patients: A Preliminary Study on Flavivirus Exposure in Eastern Romania. Pathogens 2024; 13:133. [PMID: 38392871 PMCID: PMC10892458 DOI: 10.3390/pathogens13020133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 01/12/2024] [Accepted: 01/26/2024] [Indexed: 02/25/2024] Open
Abstract
WNV and USUV are closely related epornitic flaviviruses transmitted by Culex mosquitoes which can cause febrile and neurodegenerative disease in humans. The impact of both viruses on public health has increased in the recent decades. AIM The aim of the study was to evaluate the seroprevalence of WNV and USUV in hospitalized patients from eastern Romania who did not show symptoms corresponding to the case definition. METHODS Human blood samples from the hospitalized patients were collected in 2015 and from April to September 2019 in Iasi County, Romania. The samples were screened by ELISA for anti-WNV IgG, IgM, and anti-USUV IgG antibodies. RESULTS A cumulative seroprevalence of 3.4% was recorded for anti-WNV IgG antibodies and 9.1% for anti-WNV IgM. No sample was positive for anti-USUV antibodies. CONCLUSION The cumulative seroprevalence observed provides support for the consideration of WNV as being endemic in the east of Romania. The absence of anti-USUV antibodies may be related to cross-reactivity and cohort size, thus, USUV should be considered in clinical practice and become an objective for active surveillance in Romania.
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Affiliation(s)
- Luciana Alexandra Crivei
- Regional Center of Advanced Research for Emerging Diseases, Zoonoses and Food Safety, Department of Public Health, Faculty of Veterinary Medicine, Iași University of Life Sciences, 700490 Iași, Romania; (D.P.); (A.A.); (L.E.O.); (G.S.)
| | - Andrei Vata
- “Sf. Parascheva” Infectious Diseases Hospital of Iasi, 700490 Iasi, Romania; (A.V.); (D.T.)
- Department of Infectious Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700490 Iași, Romania
| | - Danut Teodor
- “Sf. Parascheva” Infectious Diseases Hospital of Iasi, 700490 Iasi, Romania; (A.V.); (D.T.)
| | - Daniela Porea
- Regional Center of Advanced Research for Emerging Diseases, Zoonoses and Food Safety, Department of Public Health, Faculty of Veterinary Medicine, Iași University of Life Sciences, 700490 Iași, Romania; (D.P.); (A.A.); (L.E.O.); (G.S.)
- Laboratories and Research Stations Department, Danube Delta National Institute for Research and Development, 820112 Tulcea, Romania
| | - Andreea Paula Cozma
- Faculty of Veterinary Medicine, Iași University of Life Sciences, 700490 Iași, Romania; (A.P.C.); (S.M.)
| | - Adriana Anita
- Regional Center of Advanced Research for Emerging Diseases, Zoonoses and Food Safety, Department of Public Health, Faculty of Veterinary Medicine, Iași University of Life Sciences, 700490 Iași, Romania; (D.P.); (A.A.); (L.E.O.); (G.S.)
- Faculty of Veterinary Medicine, Iași University of Life Sciences, 700490 Iași, Romania; (A.P.C.); (S.M.)
| | - Luanda Elena Oslobanu
- Regional Center of Advanced Research for Emerging Diseases, Zoonoses and Food Safety, Department of Public Health, Faculty of Veterinary Medicine, Iași University of Life Sciences, 700490 Iași, Romania; (D.P.); (A.A.); (L.E.O.); (G.S.)
- Faculty of Veterinary Medicine, Iași University of Life Sciences, 700490 Iași, Romania; (A.P.C.); (S.M.)
| | - Serban Morosan
- Faculty of Veterinary Medicine, Iași University of Life Sciences, 700490 Iași, Romania; (A.P.C.); (S.M.)
- Faculté de Médecine, Sorbonne Université, UMS 28, Inserm, 75013 Paris, France
| | - Gheorghe Savuta
- Regional Center of Advanced Research for Emerging Diseases, Zoonoses and Food Safety, Department of Public Health, Faculty of Veterinary Medicine, Iași University of Life Sciences, 700490 Iași, Romania; (D.P.); (A.A.); (L.E.O.); (G.S.)
- Faculty of Veterinary Medicine, Iași University of Life Sciences, 700490 Iași, Romania; (A.P.C.); (S.M.)
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Blanquer A, Rivas F, Gérardy M, Sarlet M, Moula N, Ziegler U, Groschup MH, Desmecht D, Marichal T, Garigliany M. Evaluation of Non-Vector Transmission of Usutu Virus in Domestic Canaries ( Serinus canaria). Viruses 2024; 16:79. [PMID: 38257779 PMCID: PMC10819963 DOI: 10.3390/v16010079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 12/21/2023] [Accepted: 12/22/2023] [Indexed: 01/24/2024] Open
Abstract
Usutu virus (USUV) is a flavivirus transmitted to avian species through mosquito bites that causes mass mortalities in wild and captive bird populations. However, several cases of positive dead birds have been recorded during the winter, a vector-free period. To explain how USUV "overwinters", the main hypothesis is bird-to-bird transmission, as shown for the closely related West Nile virus. To address this question, we experimentally challenged canaries with intranasal inoculation of USUV, which led to systemic dissemination of the virus, provided the inoculated dose was sufficient (>102 TCID50). We also highlighted the oronasal excretion of infectious viral particles in infected birds. Next, we co-housed infected birds with naive sentinels, to determine whether onward transmission could be reproduced experimentally. We failed to detect such transmission but demonstrated horizontal transmission by transferring sputum from an infected to a naive canary. In addition, we evaluated the cellular tropism of respiratory mucosa to USUV in vitro using a canary tracheal explant and observed only limited evidence of viral replication. Further research is then needed to assess if and how comparable bird-to-bird transmission occurs in the wild.
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Affiliation(s)
- Aude Blanquer
- Fundamental and Applied Research for Animals & Health (FARAH), Laboratory of Pathology, Faculty of Veterinary Medicine, University of Liège, Sart Tilman B43, B-4000 Liège, Belgium; (A.B.); (F.R.); (M.G.); (M.S.); (D.D.)
| | - Felipe Rivas
- Fundamental and Applied Research for Animals & Health (FARAH), Laboratory of Pathology, Faculty of Veterinary Medicine, University of Liège, Sart Tilman B43, B-4000 Liège, Belgium; (A.B.); (F.R.); (M.G.); (M.S.); (D.D.)
| | - Mazarine Gérardy
- Fundamental and Applied Research for Animals & Health (FARAH), Laboratory of Pathology, Faculty of Veterinary Medicine, University of Liège, Sart Tilman B43, B-4000 Liège, Belgium; (A.B.); (F.R.); (M.G.); (M.S.); (D.D.)
| | - Michaël Sarlet
- Fundamental and Applied Research for Animals & Health (FARAH), Laboratory of Pathology, Faculty of Veterinary Medicine, University of Liège, Sart Tilman B43, B-4000 Liège, Belgium; (A.B.); (F.R.); (M.G.); (M.S.); (D.D.)
| | - Nassim Moula
- Animal Resources Veterinary Management Department, Faculty of Veterinary Medicine, GIGA Research (AFT), Sart Tilman B23B, B-4000 Liège, Belgium;
| | - Ute Ziegler
- Friedrich-Loeffler-Institut, Institute for Novel and Emerging Infectious Diseases, Südufer 10, 17493 Greifswald-Insel Riems, Germany; (U.Z.); (M.H.G.)
| | - Martin H. Groschup
- Friedrich-Loeffler-Institut, Institute for Novel and Emerging Infectious Diseases, Südufer 10, 17493 Greifswald-Insel Riems, Germany; (U.Z.); (M.H.G.)
| | - Daniel Desmecht
- Fundamental and Applied Research for Animals & Health (FARAH), Laboratory of Pathology, Faculty of Veterinary Medicine, University of Liège, Sart Tilman B43, B-4000 Liège, Belgium; (A.B.); (F.R.); (M.G.); (M.S.); (D.D.)
| | - Thomas Marichal
- Laboratory of Immunophysiology, GIGA Institute, University of Liège, B-4000 Liège, Belgium;
- Faculty of Veterinary Medicine, University of Liège, Sart Tilman B42, B-4000 Liège, Belgium
| | - Mutien Garigliany
- Fundamental and Applied Research for Animals & Health (FARAH), Laboratory of Pathology, Faculty of Veterinary Medicine, University of Liège, Sart Tilman B43, B-4000 Liège, Belgium; (A.B.); (F.R.); (M.G.); (M.S.); (D.D.)
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Bergmann F, Holicki CM, Michel F, Bock S, Scuda N, Priemer G, Kenklies S, Siempelkamp T, Skuballa J, Sauerwald C, Herms L, Muluneh A, Peters M, Hlinak A, Groschup MH, Sadeghi B, Ziegler U. Reconstruction of the molecular evolution of Usutu virus in Germany: Insights into virus emersion and circulation. PLoS Negl Trop Dis 2023; 17:e0011203. [PMID: 37782665 PMCID: PMC10569574 DOI: 10.1371/journal.pntd.0011203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 10/12/2023] [Accepted: 09/07/2023] [Indexed: 10/04/2023] Open
Abstract
Usutu virus (USUV) is a mosquito-borne flavivirus that is widely distributed in southern and central Europe. The zoonotic virus circulates primarily between birds and mosquitoes, can, however, in rare cases infect other mammals including humans. In the past, USUV has been repeatedly associated with mass mortalities in birds, primarily blackbirds and owls. Birds commonly succumb either due to the peracute nature of the infection or due to severe encephalitis. In Germany, USUV has spread rapidly since its first detection in 2010 in mosquitoes under the presence of susceptible host and vector species. Nonetheless, there is to date limited access to whole genome sequences resulting in the absence of in-depth phylogenetic and phylodynamic analyses. In this study, 118 wild and captive birds were sequenced using a nanopore sequencing platform with prior target enrichment via amplicons. Due to the high abundancy of Europe 3 and Africa 3 in Germany an ample quantity of associated whole genome sequences was generated and the most recent common ancestor could be determined for each lineage. The corresponding clock phylogeny revealed an introduction of USUV Europe 3 and Africa 3 into Germany three years prior to their first isolation in the avifauna in 2011 and 2014, respectively. Based on the clustering and temporal history of the lineages, evidence exists for the genetic evolution of USUV within Germany as well as new introductions thereof into the country.
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Affiliation(s)
- Felicitas Bergmann
- Institute of Novel and Emerging Infectious Disease, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
| | - Cora M. Holicki
- Institute of Novel and Emerging Infectious Disease, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
| | - Friederike Michel
- Institute of Novel and Emerging Infectious Disease, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
| | - Sabine Bock
- Berlin-Brandenburg State Laboratory, Frankfurt (Oder), Germany
| | - Nelly Scuda
- Bavarian Health and Food Safety Authority, Erlangen, Germany
| | - Grit Priemer
- State Office of Agriculture, Food Safety and Fisheries Mecklenburg-Vorpommern (LALLF), Rostock, Germany
| | - Susanne Kenklies
- State Office for Consumer Protection Saxony-Anhalt (LAV), Stendal, Germany
| | - Timo Siempelkamp
- Thuringian State Office for Consumer Protection, Bad Langensalza, Germany
| | - Jasmin Skuballa
- State Institute for Chemical and Veterinary Analysis Karlsruhe, Karlsruhe, Germany
| | - Claudia Sauerwald
- Department of Veterinary Medicine, Hessian State Laboratory, Gießen, Germany
| | - Louise Herms
- Lower Saxony State Office for Consumer Protection and Food Safety (LAVES), Hannover, Germany
| | - Aemero Muluneh
- Saxon State Laboratory of Health and Veterinary Affairs, Dresden, Germany
| | - Martin Peters
- Chemical and Veterinary Investigation Office (CVUA), Arnsberg, Germany
| | - Andreas Hlinak
- Berlin-Brandenburg State Laboratory, Frankfurt (Oder), Germany
| | - Martin H. Groschup
- Institute of Novel and Emerging Infectious Disease, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
- German Center of Infection Research (DZIF), Partner site Hamburg-Lübeck-Borstel-Riems, Greifswald-Insel Riems, Germany
| | - Balal Sadeghi
- Institute of Novel and Emerging Infectious Disease, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
| | - Ute Ziegler
- Institute of Novel and Emerging Infectious Disease, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
- German Center of Infection Research (DZIF), Partner site Hamburg-Lübeck-Borstel-Riems, Greifswald-Insel Riems, Germany
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Vilibic-Cavlek T, Janev-Holcer N, Bogdanic M, Ferenc T, Vujica Ferenc M, Krcmar S, Savic V, Stevanovic V, Ilic M, Barbic L. Current Status of Vector-Borne Diseases in Croatia: Challenges and Future Prospects. Life (Basel) 2023; 13:1856. [PMID: 37763260 PMCID: PMC10532474 DOI: 10.3390/life13091856] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/22/2023] [Accepted: 08/29/2023] [Indexed: 09/29/2023] Open
Abstract
Different vector-borne pathogens are present or have (re-)emerged in Croatia. Flaviviruses tick-borne encephalitis (TBEV), West Nile (WNV), and Usutu (USUV) are widely distributed in continental regions, while Toscana virus (TOSV) and sandfly fever viruses are detected at the Croatian littoral. Recently, sporadic clinical cases of Tahyna orthobunyavirus (TAHV) and Bhanja bandavirus infection and seropositive individuals have been reported in continental Croatia. Acute infections and serologic evidence of WNV, TBEV, USUV, and TAHV were also confirmed in sentinel animals and vectors. Autochthonous dengue was reported in 2010 at the Croatian littoral. Lyme borreliosis is the most widely distributed vector-borne bacterial infection. The incidence is very high in northwestern and eastern regions, which correlates with numerous records of Ixodes ricinus ticks. Acute human Anaplasma phagocytophilum infections are reported sporadically, but there are many records of serologic evidence of anaplasmosis in animals. Mediterranean spotted fever (Rickettsia conorii) and murine typhus (Rickettsia typhi) are the main rickettsial infections in Croatia. Human leishmaniasis is notified sporadically, while serologic evidence of leishmaniasis was found in 11.4% of the Croatian population. After the official eradication of malaria in 1964, only imported cases were reported in Croatia. Since vector-borne diseases show a growing trend, continuous monitoring of vectors is required to protect the population from these infections.
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Affiliation(s)
- Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Natasa Janev-Holcer
- Environmental Health Department, Croatian Institute of Public Health, 10000 Zagreb, Croatia
- Department of Social Medicine and Epidemiology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
| | - Maja Bogdanic
- Department of Virology, Croatian Institute of Public Health, 10000 Zagreb, Croatia
| | - Thomas Ferenc
- Department of Diagnostic and Interventional Radiology, Merkur University Hospital, 10000 Zagreb, Croatia
| | - Mateja Vujica Ferenc
- Department of Obstetrics and Gynecology, University Hospital Center Zagreb, 10000 Zagreb, Croatia
| | - Stjepan Krcmar
- Department of Biology, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
| | - Vladimir Savic
- Poultry Center, Croatian Veterinary Institute, 10000 Zagreb, Croatia
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Maja Ilic
- Department of Communicable Disease Epidemiology, Croatian Institute of Public Health, 10000 Zagreb, Croatia
| | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia
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Gupta PC, Satapathy P, Gupta A, Asumah MN, Padhi BK. Usutu virus: a Flavivirus on the rise amid COVID-19 and monkeypox. Int J Surg 2023; 109:614-615. [PMID: 37093099 PMCID: PMC10389476 DOI: 10.1097/js9.0000000000000207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 01/02/2023] [Indexed: 04/09/2023]
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Cavalleri JV, Korbacska‐Kutasi O, Leblond A, Paillot R, Pusterla N, Steinmann E, Tomlinson J. European College of Equine Internal Medicine consensus statement on equine flaviviridae infections in Europe. Vet Med (Auckl) 2022; 36:1858-1871. [DOI: 10.1111/jvim.16581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 10/19/2022] [Indexed: 11/13/2022]
Affiliation(s)
- Jessika‐M. V. Cavalleri
- Clinical Unit of Equine Internal Medicine, Department for Companion Animals and Horses University of Veterinary Medicine Vienna Vienna Austria
| | - Orsolya Korbacska‐Kutasi
- Clinical Unit of Equine Internal Medicine, Department for Companion Animals and Horses University of Veterinary Medicine Vienna Vienna Austria
- Department for Animal Breeding, Nutrition and Laboratory Animal Science University of Veterinary Medicine Budapest Hungary
- Hungarian Academy of Sciences—Szent Istvan University (MTA‐SZIE) Large Animal Clinical Research Group Üllő Dóra major Hungary
| | - Agnès Leblond
- EPIA, UMR 0346, Epidemiologie des maladies animales et zoonotiques, INRAE, VetAgro Sup University of Lyon Marcy l'Etoile France
| | - Romain Paillot
- School of Equine and Veterinary Physiotherapy Writtle University College Chelmsford UK
| | - Nicola Pusterla
- Department of Medicine and Epidemiology, School of Veterinary Medicine University of California Davis California USA
| | - Eike Steinmann
- Department of Molecular and Medical Virology, Faculty of Medicine Ruhr University Bochum Bochum Germany
| | - Joy Tomlinson
- Baker Institute for Animal Health Cornell University College of Veterinary Medicine Ithaca New York USA
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Khare B, Kuhn RJ. The Japanese Encephalitis Antigenic Complex Viruses: From Structure to Immunity. Viruses 2022; 14:2213. [PMID: 36298768 PMCID: PMC9607441 DOI: 10.3390/v14102213] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 09/30/2022] [Accepted: 10/04/2022] [Indexed: 11/09/2022] Open
Abstract
In the last three decades, several flaviviruses of concern that belong to different antigenic groups have expanded geographically. This has resulted in the presence of often more than one virus from a single antigenic group in some areas, while in Europe, Africa and Australia, additionally, multiple viruses belonging to the Japanese encephalitis (JE) serogroup co-circulate. Morphological heterogeneity of flaviviruses dictates antibody recognition and affects virus neutralization, which influences infection control. The latter is further impacted by sequential infections involving diverse flaviviruses co-circulating within a region and their cross-reactivity. The ensuing complex molecular virus-host interplay leads to either cross-protection or disease enhancement; however, the molecular determinants and mechanisms driving these outcomes are unclear. In this review, we provide an overview of the epidemiology of four JE serocomplex viruses, parameters affecting flaviviral heterogeneity and antibody recognition, host immune responses and the current knowledge of the cross-reactivity involving JE serocomplex flaviviruses that leads to differential clinical outcomes, which may inform future preventative and therapeutic interventions.
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Affiliation(s)
- Baldeep Khare
- Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA
| | - Richard J. Kuhn
- Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA
- Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN 47907, USA
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10
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Graninger M, Hubmer S, Riederer F, Kettner S, Hauk M, Auf T, Aberle JH, Stiasny K, Aberle SW, Camp JV. The first case of Usutu virus neuroinvasive disease in Austria, 2021. Open Forum Infect Dis 2022; 9:ofac255. [PMID: 35873290 PMCID: PMC9297159 DOI: 10.1093/ofid/ofac255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 05/13/2022] [Indexed: 11/13/2022] Open
Abstract
Abstract
Usutu virus (USUV) is a mosquito-borne flavivirus closely related to West Nile virus (WNV) that is endemic in many European countries. We report the first case of USUV neuroinvasive disease in Austria and discuss challenges in differentiating USUV from WNV infections in areas where both viruses are endemic.
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Affiliation(s)
| | - Stefan Hubmer
- Department of Neurology, Klinik Hietzing, Vienna, Austria
| | - Franz Riederer
- Department of Neurology, Klinik Hietzing, Vienna, Austria
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Stephan Kettner
- Department for Anesthesiology and Intensive Care, Klinik Hietzing, Vienna, Austria
- Karl Landsteiner Institute for Anesthesiology and Intensive Care Medicine, Vienna, Austria
| | - Martin Hauk
- Department for Anesthesiology and Intensive Care, Klinik Hietzing, Vienna, Austria
| | - Tasnim Auf
- Department for Cardiology, Klinik Floridsdorf, Vienna, Austria
| | - Judith H. Aberle
- Center for Virology, Medical University of Vienna, Vienna, Austria
| | - Karin Stiasny
- Center for Virology, Medical University of Vienna, Vienna, Austria
| | | | - Jeremy V. Camp
- Center for Virology, Medical University of Vienna, Vienna, Austria
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11
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Nagy A, Csonka N, Takács M, Mezei E, Barabás É. West Nile and Usutu virus seroprevalence in Hungary: A nationwide serosurvey among blood donors in 2019. PLoS One 2022; 17:e0266840. [PMID: 35395048 PMCID: PMC8992992 DOI: 10.1371/journal.pone.0266840] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 03/29/2022] [Indexed: 12/28/2022] Open
Abstract
In Hungary, West Nile virus (WNV) has been responsible for 459 laboratory confirmed human cases between 2004 and 2019, while the first human Usutu virus (USUV) infection was confirmed only in 2018. A comprehensive serosurvey was conducted among blood donors to assess the WNV and USUV seroprevalence in 2019, one year after the largest European WNV epidemic. Altogether, 3005 plasma samples were collected and screened for WNV and USUV specific Immunoglobulin G (IgG) antibodies by Enzyme-Linked Immunosorbent Assay (ELISA). All reactive samples were further tested for tick-borne encephalitis virus IgG antibodies by ELISA. Indirect immunofluorescence test and microneutralization assay were used as confirmatory methods. Overall, the WNV seroprevalence was 4.32%, and in five blood donors USUV seropositivity was confirmed. The highest seroprevalence was measured in Central, Eastern and Southern Hungary, while the Western part of the country proved to be less affected. There was a statistically strong association between the WNV seroprevalence of 2019 and the cumulative incidence in the period of 2004 and 2019 calculated for every NUTS 3 region. The last WNV serological screening was performed in 2016 and the prevalence of anti-WNV IgG proved to be 2.19%. One year after the 2018 WNV outbreak, a significant increase in seroprevalence was observed in the Hungarian population and evidence for USUV seropositivity was also obtained. The spatial pattern of seroprevalence can support the identification of high-risk areas raising awareness of the need for increased surveillance, such as screening vector, equine, and avian populations. The communication with general practitioners and other professionals in primary health care services can support the early identification of acute human cases. Education and awareness-raising on the importance of protection against mosquito vectors amongst residents are also important parts of preventive measures.
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Affiliation(s)
- Anna Nagy
- National Reference Laboratory for Viral Zoonoses, Division of Microbiological Reference Laboratories, National Public Health Center, Budapest, Hungary
- * E-mail:
| | - Nikolett Csonka
- National Reference Laboratory for Viral Zoonoses, Division of Microbiological Reference Laboratories, National Public Health Center, Budapest, Hungary
| | - Mária Takács
- National Reference Laboratory for Viral Zoonoses, Division of Microbiological Reference Laboratories, National Public Health Center, Budapest, Hungary
- Institute of Medical Microbiology, Semmelweis University, Budapest, Hungary
| | - Eszter Mezei
- Department of Communicable Diseases Epidemiology and Infection Control, National Public Health Center, Budapest, Hungary
| | - Éva Barabás
- Confirmatory Laboratory, Hungarian National Blood Transfusion Service, Budapest, Hungary
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12
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Wald ME, Sieg M, Schilling E, Binder M, Vahlenkamp TW, Claus C. The Interferon Response Dampens the Usutu Virus Infection-Associated Increase in Glycolysis. Front Cell Infect Microbiol 2022; 12:823181. [PMID: 35186796 PMCID: PMC8855070 DOI: 10.3389/fcimb.2022.823181] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 01/11/2022] [Indexed: 01/05/2023] Open
Abstract
The mosquito-borne Usutu virus (USUV) is a zoonotic flavivirus and an emerging pathogen. So far therapeutical options or vaccines are not available in human and veterinary medicine. The bioenergetic profile based on extracellular flux analysis revealed an USUV infection-associated significant increase in basal and stressed glycolysis on Vero and with a tendency for basal glycolysis on the avian cell line TME-R derived from Eurasian blackbirds. On both cell lines this was accompanied by a significant drop in the metabolic potential of glycolysis. Moreover, glycolysis contributed to production of virus progeny, as inhibition of glycolysis with 2-deoxy-D-glucose reduced virus yield on Vero by one log10 step. Additionally, the increase in glycolysis observed on Vero cells after USUV infection was lost after the addition of exogenous type I interferon (IFN) β. To further explore the contribution of the IFN response pathway to the impact of USUV on cellular metabolism, USUV infection was characterized on human A549 respiratory cells with a knockout of the type I IFN receptor, either solely or together with the receptor of type III IFN. Notably, only the double knockout of types I and III IFN receptor increased permissiveness to USUV and supported viral replication together with an alteration of the glycolytic activity, namely an increase in basal glycolysis to an extent that a further increase after injection of metabolic stressors during extracellular flux analysis was not noted. This study provides evidence for glycolysis as a possible target for therapeutic intervention of USUV replication. Moreover, presented data highlight type I and type III IFN system as a determinant for human host cell permissiveness and for the infection-associated impact on glycolysis.
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Affiliation(s)
- Maria Elisabeth Wald
- Institute of Virology, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany
- Institute of Medical Microbiology and Virology, Medical Faculty, Leipzig University, Leipzig, Germany
| | - Michael Sieg
- Institute of Virology, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany
| | - Erik Schilling
- Institute of Clinical Immunology, Medical Faculty, Leipzig University, Leipzig, Germany
| | - Marco Binder
- Research Group “Dynamics of early viral infection and the innate antiviral response”, Division “Virus-Associated Carcinogenesis”, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | | | - Claudia Claus
- Institute of Medical Microbiology and Virology, Medical Faculty, Leipzig University, Leipzig, Germany
- *Correspondence: Claudia Claus,
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13
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Severe West Nile Virus Neuroinvasive Disease: Clinical Characteristics, Short- and Long-Term Outcomes. Pathogens 2022; 11:pathogens11010052. [PMID: 35056000 PMCID: PMC8779330 DOI: 10.3390/pathogens11010052] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 12/17/2021] [Accepted: 12/30/2021] [Indexed: 11/26/2022] Open
Abstract
West Nile Virus Neuroinvasive Disease (WNV NID) requires prolonged intensive care treatment, resulting in high mortality and early disability. Long-term results are lacking. We have conducted an observational retrospective study with a prospective follow-up of WNV NID patients treated at the Intensive Care Unit (ICU), University Hospital for Infectious Diseases, Zagreb, Croatia, 2013–2018. Short-term outcomes were vital status, length of stay (LOS), modified Rankin Scale (mRS), and disposition at discharge. Long-term outcomes were vital status and mRS at follow-up. Twenty-three patients were identified, 78.3% males, median age 72 (range 33–84) years. Two patients (8.7%) died in the ICU, with no lethal outcomes after ICU discharge. The median ICU LOS was 19 days (range 5–73), and the median hospital LOS was 34 days (range 7–97). At discharge, 15 (65.2%) patients had moderate to severe/mRS 3–5, 6 (26.0%) had slight disability/mRS 2–1, no patients were symptom-free/mRS 0. Ten (47.6%) survivors were discharged to rehabilitation facilities. The median time to follow-up was nine months (range 6–69). At follow-up, seven patients died (30.5%), five (21.7%) had moderate to severe/mRS 3–5, one (4.3%) had slight disability/mRS 2–1, six (26.1%) had no symptoms/mRS 0, and four (17.4%) were lost to follow-up. Briefly, ten (43.5%) survivors improved their functional status, one (4.3%) was unaltered, and one (4.3%) aggravated. In patients with severe WNV NID, intensive treatment in the acute phase followed by inpatient rehabilitation resulted in significant recovery of functional status after several months.
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14
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Macaluso G, Gucciardi F, Guercio A, Blanda V, La Russa F, Torina A, Mira F, Bella SD, Lastra A, Giacchino I, Castronovo C, Vitale G, Purpari G. First neuroinvasive human case of West Nile Disease in Southern Italy: Results of the 'One Health' approach. Vet Med Sci 2021; 7:2463-2472. [PMID: 34505400 PMCID: PMC8604128 DOI: 10.1002/vms3.591] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Background West Nile Disease (WND) is a zoonotic mosquito‐borne infection involving viral pathogens, human and animal hosts, vectors and environment. Cooperation among medical, veterinary and entomological fields has been promoted by the Italian Public Health Authorities, and an integrated West Nile Virus (WNV) Surveillance Plan has been in force in Italy since 2016 to prevent the transmission risk of WND to humans through an early detection of viral circulation by animal and entomological surveillance. This managing model is unique in Europe. Objectives This survey aimed at presenting the ‘One Health’ approach applied in 2016 to the first autochthonous human case of West Nile Neuroinvasive Disease (WNND) in Sicily (Southern Italy). Methods Serological (anti‐WNV IgM and IgG ELISA, anti‐WNV neutralizing antibodies) and molecular tests were conducted on blood, liquor and urine of a 38‐year‐old man with encephalitis and meningitis. Overall, 2704 adult culicides from 160 mosquito catches were morphologically identified. Female mosquitoes were analysed in pools for WNV RNA detection. Serological (anti‐WNV IgM and IgG ELISA) and molecular analyses for WNV were carried out in 11 horses, 271 chickens and two dogs sampled in farms around the man's residence. Results and conclusions WNND was confirmed by serological analysis on patient's liquor and serum. Collected mosquito species included Culex pipiens (93.56%, CI95% 92.64%–94.49%), Aedes albopictus (5.25%, CI95% 4.41%–6.09%), Culex hortensis (0.59%, CI95% 0.30%–0.88%), Culiseta longiareolata (0.55%, CI95% 0.27%–0.83%) and Anopheles maculipennis s.l. (0.04%, CI95% –0.04% to 0.11%). Mosquito pools were negative for WNV RNA. Two dogs (100%) and two horses (18.18%, CI95% –4.61 to 40.97%) resulted positive for anti‐WNV specific antibodies. The ‘One Health’ approach allowed to report the first human neuroinvasive WND in Sicily and to confirm the local circulation of WNV in animals of the same area where the clinical case occurred, defining the autochthonous origin of the infection.
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Affiliation(s)
- Giusi Macaluso
- Istituto Zooprofilattico Sperimentale della Sicilia "A. Mirri", Palermo, Italy
| | - Francesca Gucciardi
- Istituto Zooprofilattico Sperimentale della Sicilia "A. Mirri", Palermo, Italy
| | - Annalisa Guercio
- Istituto Zooprofilattico Sperimentale della Sicilia "A. Mirri", Palermo, Italy
| | - Valeria Blanda
- Istituto Zooprofilattico Sperimentale della Sicilia "A. Mirri", Palermo, Italy
| | - Francesco La Russa
- Istituto Zooprofilattico Sperimentale della Sicilia "A. Mirri", Palermo, Italy
| | - Alessandra Torina
- Istituto Zooprofilattico Sperimentale della Sicilia "A. Mirri", Palermo, Italy
| | - Francesco Mira
- Istituto Zooprofilattico Sperimentale della Sicilia "A. Mirri", Palermo, Italy
| | - Santina Di Bella
- Istituto Zooprofilattico Sperimentale della Sicilia "A. Mirri", Palermo, Italy
| | - Antonio Lastra
- Istituto Zooprofilattico Sperimentale della Sicilia "A. Mirri", Palermo, Italy
| | - Ilenia Giacchino
- Istituto Zooprofilattico Sperimentale della Sicilia "A. Mirri", Palermo, Italy
| | - Calogero Castronovo
- Istituto Zooprofilattico Sperimentale della Sicilia "A. Mirri", Palermo, Italy
| | - Giustina Vitale
- U.O. Dipartimento Diagnostica Specialistica Patologie Diffusive, Regional Reference Center for diseases transmitted by arthropods, Azienda Ospedaliera Universitaria "P. Giaccone", Palermo, Italy
| | - Giuseppa Purpari
- Istituto Zooprofilattico Sperimentale della Sicilia "A. Mirri", Palermo, Italy
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15
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Schmidt V, Cramer K, Böttcher D, Heenemann K, Rückner A, Harzer M, Ziegler U, Vahlenkamp T, Sieg M. Usutu virus infection in aviary birds during the cold season. Avian Pathol 2021; 50:427-435. [PMID: 34351827 DOI: 10.1080/03079457.2021.1962003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
The mosquito-borne flavivirus Usutu virus (USUV) is responsible for countless deaths in both resident populations and birds kept in outdoor aviaries. Since 2001, USUV outbreaks attract increased attention due to the rapid geographical spread of the virus and its close relation to West Nile virus (WNV), an emerging pathogen in humans and animals. Similar to WNV, the USUV enzootic transmission cycle predominantly involves Culex spp. as vectors, whereas birds serve as amplifying reservoir hosts. In Europe, USUV-associated disease outbreaks in birds are nearly exclusively described during late spring and early autumn (early April to late October). Contagiousness of virus particles excreted by infected animals has not yet been proven, so that the role of non-vector-borne transmission, as it is known for the closely related WNV, remains unclear. Here we report the diagnosis of USUV infection in 15 of 24 birds from mortality outbreaks in eight different aviaries located in Germany, that occured during the cold season between late October 2018 and early April 2019. Detection of USUV was performed using standardized molecular biological methods and immunohistochemistry for verification of the infection. USUV infection in a parrot species, a tropical finch and two estrildid finches are reported for the first time. Further research on the occurrence of USUV infection during the cold season is key to understanding the dynamics of viral transmission as well as for a profound health risk assessment for aviary birds as well as humans.
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Affiliation(s)
- Volker Schmidt
- Clinic for Birds and Reptiles, Faculty of Veterinary Medicine, Leipzig University, An den Tierkliniken 17, D-04103 Leipzig, Germany
| | - Kerstin Cramer
- Clinic for Birds and Reptiles, Faculty of Veterinary Medicine, Leipzig University, An den Tierkliniken 17, D-04103 Leipzig, Germany
| | - Denny Böttcher
- Institute of Veterinary Pathology, Faculty of Veterinary Medicine, Leipzig University, An den Tierkliniken 33, D-04103 Leipzig, Germany
| | - Kristin Heenemann
- Institute of Virology, Faculty of Veterinary Medicine, Leipzig University, An den Tierkliniken 29, D-04103 Leipzig, Germany
| | - Antje Rückner
- Institute of Virology, Faculty of Veterinary Medicine, Leipzig University, An den Tierkliniken 29, D-04103 Leipzig, Germany
| | - Maxi Harzer
- Institute of Virology, Faculty of Veterinary Medicine, Leipzig University, An den Tierkliniken 29, D-04103 Leipzig, Germany
| | - Ute Ziegler
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Südufer 10, D-17493 Greifswald-Insel Riems, Germany
| | - Thomas Vahlenkamp
- Institute of Virology, Faculty of Veterinary Medicine, Leipzig University, An den Tierkliniken 29, D-04103 Leipzig, Germany
| | - Michael Sieg
- Institute of Virology, Faculty of Veterinary Medicine, Leipzig University, An den Tierkliniken 29, D-04103 Leipzig, Germany
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16
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Emerging Trends in the West Nile Virus Epidemiology in Croatia in the 'One Health' Context, 2011-2020. Trop Med Infect Dis 2021; 6:tropicalmed6030140. [PMID: 34449731 PMCID: PMC8396195 DOI: 10.3390/tropicalmed6030140] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 07/22/2021] [Accepted: 07/22/2021] [Indexed: 11/28/2022] Open
Abstract
West Nile virus (WNV) is one of the most widely distributed (re-)emerging arboviruses. In Croatia, acute WNV infections as well as seropositivity were detected in humans, horses, birds and poultry. Although serologic evidence of WNV human infections dates back to the 1970s, no clinical cases were reported until 2012. WNV outbreaks, as well as sporadic infections, were continuously recorded in continental Croatian counties from 2012 to 2018. In addition, acute asymptomatic infections (IgM antibodies) in horses have been regularly notified in continental regions since 2012, while seropositive horses (seroprevalence rates 3.7–21.4%) were detected in both continental and coastal regions. Moreover, WNV seropositivity in poultry (1.8–22.9%) was reported from 2013 to 2020. During the largest WNV outbreak in 2018, WNV RNA was detected for the first time in two dead goshawks (Accipiter gentilis) from the same aviary in North-West Croatia, while WNV antibodies were found in one buzzard (Butteo butteo) from the same region. In addition, WNV RNA was detected in a dead blackbird (Turdus merula) at the Croatian littoral. The phylogenetic analysis of 11 strains detected in urine samples of patients with neuroinvasive disease and 1 strain detected in a goshawk showed circulation of WNV lineage 2. Thus far, WNV has not been detected in mosquitoes in Croatia.
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17
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Previous Usutu Virus Exposure Partially Protects Magpies ( Pica pica) against West Nile Virus Disease But Does Not Prevent Horizontal Transmission. Viruses 2021; 13:v13071409. [PMID: 34372622 PMCID: PMC8310384 DOI: 10.3390/v13071409] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 07/10/2021] [Accepted: 07/14/2021] [Indexed: 11/17/2022] Open
Abstract
The mosquito-borne flaviviruses USUV and WNV are known to co-circulate in large parts of Europe. Both are a public health concern, and USUV has been the cause of epizootics in both wild and domestic birds, and neurological cases in humans in Europe. Here, we explore the susceptibility of magpies to experimental USUV infection, and how previous exposure to USUV would affect infection with WNV. None of the magpies exposed to USUV showed clinical signs, viremia, or detectable neutralizing antibodies. After challenge with a neurovirulent WNV strain, neither viremia, viral titer of WNV in vascular feathers, nor neutralizing antibody titers of previously USUV-exposed magpies differed significantly with respect to magpies that had not previously been exposed to USUV. However, 75% (6/8) of the USUV-exposed birds survived, while only 22.2% (2/9) of those not previously exposed to USUV survived. WNV antigen labeling by immunohistochemistry in tissues was less evident and more restricted in magpies exposed to USUV prior to challenge with WNV. Our data indicate that previous exposure to USUV partially protects magpies against a lethal challenge with WNV, while it does not prevent viremia and direct transmission, although the mechanism is unclear. These results are relevant for flavivirus ecology and contention.
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18
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Zelená H, Kleinerová J, Šikutová S, Straková P, Kocourková H, Stebel R, Husa P, Husa P, Tesařová E, Lejdarová H, Šebesta O, Juráš P, Ciupek R, Mrázek J, Rudolf I. First Autochthonous West Nile Lineage 2 and Usutu Virus Infections in Humans, July to October 2018, Czech Republic. Pathogens 2021; 10:pathogens10060651. [PMID: 34073968 PMCID: PMC8225171 DOI: 10.3390/pathogens10060651] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 05/21/2021] [Accepted: 05/21/2021] [Indexed: 11/16/2022] Open
Abstract
We present epidemiological, clinical and laboratory findings of five Czech patients diagnosed with autochthonous mosquito-borne disease—four patients with confirmed West Nile virus (WNV) and one patient with Usutu virus (USUV) infections, from July to October 2018, including one fatal case due to WNV. This is the first documented human outbreak caused by WNV lineage 2 in the Czech Republic and the first record of a neuroinvasive human disease caused by USUV, which illustrates the simultaneous circulation of WNV and USUV in the country.
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Affiliation(s)
- Hana Zelená
- Public Health Institute, Partyzánské nám. 7, 702 00 Ostrava, Czech Republic; (H.Z.); (J.M.)
- Department of Biomedical Sciences, Faculty of Medicine, University of Ostrava, Syllabova 19, 703 00 Ostrava, Czech Republic
| | - Jana Kleinerová
- Department of Infectious Diseases, Hospital Břeclav, U Nemocnice 3066/1, 690 74 Břeclav, Czech Republic;
| | - Silvie Šikutová
- Institute of Vertebrate Biology, The Czech Academy of Sciences, Květná 8, 603 65 Brno, Czech Republic; (S.Š.); (P.S.)
| | - Petra Straková
- Institute of Vertebrate Biology, The Czech Academy of Sciences, Květná 8, 603 65 Brno, Czech Republic; (S.Š.); (P.S.)
- Veterinary Research Institute, Hudcova 70, 621 00 Brno, Czech Republic
| | - Hana Kocourková
- Department of Infectious Diseases, University Hospital Brno, Jihlavská 20, 602 00 Brno, Czech Republic; (H.K.); (R.S.); (P.H.); (P.H.J.)
- Department of Infectious Diseases, Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
| | - Roman Stebel
- Department of Infectious Diseases, University Hospital Brno, Jihlavská 20, 602 00 Brno, Czech Republic; (H.K.); (R.S.); (P.H.); (P.H.J.)
- Department of Infectious Diseases, Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
| | - Petr Husa
- Department of Infectious Diseases, University Hospital Brno, Jihlavská 20, 602 00 Brno, Czech Republic; (H.K.); (R.S.); (P.H.); (P.H.J.)
- Department of Infectious Diseases, Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
| | - Petr Husa
- Department of Infectious Diseases, University Hospital Brno, Jihlavská 20, 602 00 Brno, Czech Republic; (H.K.); (R.S.); (P.H.); (P.H.J.)
- Department of Infectious Diseases, Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
| | - Eva Tesařová
- Department of Health Insurance, University Hospital Brno, Jihlavská 20, 602 00 Brno, Czech Republic;
| | - Hana Lejdarová
- Transfusion and Tissue Department, University Hospital Brno, Jihlavská 20, 602 00 Brno, Czech Republic;
| | - Oldřich Šebesta
- Regional Public Health Authority of the Southern Moravia Region, Jeřábkova 4, 602 00 Brno, Czech Republic; (O.Š.); (P.J.); (R.C.)
| | - Peter Juráš
- Regional Public Health Authority of the Southern Moravia Region, Jeřábkova 4, 602 00 Brno, Czech Republic; (O.Š.); (P.J.); (R.C.)
| | - Renata Ciupek
- Regional Public Health Authority of the Southern Moravia Region, Jeřábkova 4, 602 00 Brno, Czech Republic; (O.Š.); (P.J.); (R.C.)
| | - Jakub Mrázek
- Public Health Institute, Partyzánské nám. 7, 702 00 Ostrava, Czech Republic; (H.Z.); (J.M.)
| | - Ivo Rudolf
- Institute of Vertebrate Biology, The Czech Academy of Sciences, Květná 8, 603 65 Brno, Czech Republic; (S.Š.); (P.S.)
- Correspondence: ; Tel.: +420-519-352-961; Fax: +420-519-352-387
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19
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Screening of Mosquitoes for West Nile Virus and Usutu Virus in Croatia, 2015-2020. Trop Med Infect Dis 2021; 6:tropicalmed6020045. [PMID: 33918386 PMCID: PMC8167590 DOI: 10.3390/tropicalmed6020045] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/29/2021] [Accepted: 04/01/2021] [Indexed: 01/20/2023] Open
Abstract
In the period from 2015 to 2020, an entomological survey for the presence of West Nile virus (WNV) and Usutu virus (USUV) in mosquitoes was performed in northwestern Croatia. A total of 20,363 mosquitoes were sampled in the City of Zagreb and Međimurje county, grouped in 899 pools and tested by real-time RT-PCR for WNV and USUV RNA. All pools were negative for WNV while one pool each from 2016 (Aedes albopictus), 2017 (Culex pipiens complex), 2018 (Cx. pipiens complex), and 2019 (Cx. pipiens complex), respectively, was positive for USUV. The 2018 and 2019 positive pools shared 99.31% nucleotide homology within the USUV NS5 gene and both clustered within USUV Europe 2 lineage. The next-generation sequencing of one mosquito pool (Cx. pipiens complex) collected in 2018 in Zagreb confirmed the presence of USUV and revealed several dsDNA and ssRNA viruses of insect, bacterial and mammalian origin.
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20
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Fall G, Diallo D, Soumaila H, Ndiaye EH, Lagare A, Sadio BD, Ndione MHD, Wiley M, Dia M, Diop M, Ba A, Sidikou F, Ngoy BB, Faye O, Testa J, Loucoubar C, Sall AA, Diallo M, Faye O. First Detection of the West Nile Virus Koutango Lineage in Sandflies in Niger. Pathogens 2021; 10:257. [PMID: 33668365 PMCID: PMC7996184 DOI: 10.3390/pathogens10030257] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 02/18/2021] [Accepted: 02/19/2021] [Indexed: 11/23/2022] Open
Abstract
West Nile virus (WNV), belonging to the Flaviviridae family, causes a mosquito-borne disease and shows great genetic diversity, with at least eight different lineages. The Koutango lineage of WNV (WN-KOUTV), mostly associated with ticks and rodents in the wild, is exclusively present in Africa and shows evidence of infection in humans and high virulence in mice. In 2016, in a context of Rift Valley fever (RVF) outbreak in Niger, mosquitoes, biting midges and sandflies were collected for arbovirus isolation using cell culture, immunofluorescence and RT-PCR assays. Whole genome sequencing and in vivo replication studies using mice were later conducted on positive samples. The WN-KOUTV strain was detected in a sandfly pool. The sequence analyses and replication studies confirmed that this strain belonged to the WN-KOUTV lineage and caused 100% mortality of mice. Further studies should be done to assess what genetic traits of WN-KOUTV influence this very high virulence in mice. In addition, given the risk of WN-KOUTV to infect humans, the possibility of multiple vectors as well as birds as reservoirs of WNV, to spread the virus beyond Africa, and the increasing threats of flavivirus infections in the world, it is important to understand the potential of WN-KOUTV to emerge.
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Affiliation(s)
- Gamou Fall
- Pole of Virology, WHO Collaborating Center For Arbovirus and Haemorrhagic Fever Virus, Institut Pasteur, Dakar BP 220, Senegal; (B.D.S.); (M.H.D.N.); (M.D.); (A.B.); (O.F.); (A.A.S.); (O.F.)
| | - Diawo Diallo
- Pole of Zoology, Medical Entomology Unit, Institut Pasteur, Dakar BP 220, Senegal; (D.D.); (E.H.N.); (M.D.)
| | - Hadiza Soumaila
- Programme National de Lutte contre le Paludisme, Ministère de la Santé Publique du Niger, Niamey BP 623, Niger;
- PMI Vector Link Project, Niamey BP 11051, Niger
| | - El Hadji Ndiaye
- Pole of Zoology, Medical Entomology Unit, Institut Pasteur, Dakar BP 220, Senegal; (D.D.); (E.H.N.); (M.D.)
| | - Adamou Lagare
- Centre de Recherche Médicale et Sanitaire, Niamey BP 10887, Niger; (A.L.); (F.S.); (J.T.)
| | - Bacary Djilocalisse Sadio
- Pole of Virology, WHO Collaborating Center For Arbovirus and Haemorrhagic Fever Virus, Institut Pasteur, Dakar BP 220, Senegal; (B.D.S.); (M.H.D.N.); (M.D.); (A.B.); (O.F.); (A.A.S.); (O.F.)
| | - Marie Henriette Dior Ndione
- Pole of Virology, WHO Collaborating Center For Arbovirus and Haemorrhagic Fever Virus, Institut Pasteur, Dakar BP 220, Senegal; (B.D.S.); (M.H.D.N.); (M.D.); (A.B.); (O.F.); (A.A.S.); (O.F.)
| | - Michael Wiley
- United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702-5011, USA;
- Department of Environmental, Agricultural, and Occupational Health, University of Nebraska, Omaha, NE 68198-4355, USA
| | - Moussa Dia
- Pole of Virology, WHO Collaborating Center For Arbovirus and Haemorrhagic Fever Virus, Institut Pasteur, Dakar BP 220, Senegal; (B.D.S.); (M.H.D.N.); (M.D.); (A.B.); (O.F.); (A.A.S.); (O.F.)
| | - Mamadou Diop
- Biostatistic, Biomathematics and Modelling Group, Institut Pasteur, Dakar BP 220, Senegal; (M.D.); (C.L.)
| | - Arame Ba
- Pole of Virology, WHO Collaborating Center For Arbovirus and Haemorrhagic Fever Virus, Institut Pasteur, Dakar BP 220, Senegal; (B.D.S.); (M.H.D.N.); (M.D.); (A.B.); (O.F.); (A.A.S.); (O.F.)
| | - Fati Sidikou
- Centre de Recherche Médicale et Sanitaire, Niamey BP 10887, Niger; (A.L.); (F.S.); (J.T.)
| | | | - Oumar Faye
- Pole of Virology, WHO Collaborating Center For Arbovirus and Haemorrhagic Fever Virus, Institut Pasteur, Dakar BP 220, Senegal; (B.D.S.); (M.H.D.N.); (M.D.); (A.B.); (O.F.); (A.A.S.); (O.F.)
| | - Jean Testa
- Centre de Recherche Médicale et Sanitaire, Niamey BP 10887, Niger; (A.L.); (F.S.); (J.T.)
| | - Cheikh Loucoubar
- Biostatistic, Biomathematics and Modelling Group, Institut Pasteur, Dakar BP 220, Senegal; (M.D.); (C.L.)
| | - Amadou Alpha Sall
- Pole of Virology, WHO Collaborating Center For Arbovirus and Haemorrhagic Fever Virus, Institut Pasteur, Dakar BP 220, Senegal; (B.D.S.); (M.H.D.N.); (M.D.); (A.B.); (O.F.); (A.A.S.); (O.F.)
| | - Mawlouth Diallo
- Pole of Zoology, Medical Entomology Unit, Institut Pasteur, Dakar BP 220, Senegal; (D.D.); (E.H.N.); (M.D.)
| | - Ousmane Faye
- Pole of Virology, WHO Collaborating Center For Arbovirus and Haemorrhagic Fever Virus, Institut Pasteur, Dakar BP 220, Senegal; (B.D.S.); (M.H.D.N.); (M.D.); (A.B.); (O.F.); (A.A.S.); (O.F.)
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21
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Antiviral Cytokine Response in Neuroinvasive and Non-Neuroinvasive West Nile Virus Infection. Viruses 2021; 13:v13020342. [PMID: 33671821 PMCID: PMC7927094 DOI: 10.3390/v13020342] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 02/14/2021] [Accepted: 02/19/2021] [Indexed: 12/27/2022] Open
Abstract
Data on the immune response to West Nile virus (WNV) are limited. We analyzed the antiviral cytokine response in serum and cerebrospinal fluid (CSF) samples of patients with WNV fever and WNV neuroinvasive disease using a multiplex bead-based assay for the simultaneous quantification of 13 human cytokines. The panel included cytokines associated with innate and early pro-inflammatory immune responses (TNF-α/IL-6), Th1 (IL-2/IFN-γ), Th2 (IL-4/IL-5/IL-9/IL-13), Th17 immune response (IL-17A/IL-17F/IL-21/IL-22) and the key anti-inflammatory cytokine IL-10. Elevated levels of IFN-γ were detected in 71.7% of CSF and 22.7% of serum samples (p = 0.003). Expression of IL-2/IL-4/TNF-α and Th1 17 cytokines (IL-17A/IL-17F/IL-21) was detected in the serum but not in the CSF (except one positive CSF sample for IL-17F/IL-4). While IL-6 levels were markedly higher in the CSF compared to serum (CSF median 2036.71, IQR 213.82–6190.50; serum median 24.48, IQR 11.93–49.81; p < 0.001), no difference in the IL-13/IL-9/IL-10/IFN-γ/IL-22 levels in serum/CSF was found. In conclusion, increased concentrations of the key cytokines associated with innate and early acute phase responses (IL-6) and Th1 type immune responses (IFN-γ) were found in the CNS of patients with WNV infection. In contrast, expression of the key T-cell growth factor IL-2, Th17 cytokines, a Th2 cytokine IL-4 and the proinflammatory cytokine TNF-α appear to be concentrated mainly in the periphery.
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22
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Relevance of oxidative stress in inhibition of eIF2 alpha phosphorylation and stress granules formation during Usutu virus infection. PLoS Negl Trop Dis 2021; 15:e0009072. [PMID: 33493202 PMCID: PMC7861526 DOI: 10.1371/journal.pntd.0009072] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 02/04/2021] [Accepted: 12/14/2020] [Indexed: 12/12/2022] Open
Abstract
Usutu virus (USUV) is an African mosquito-borne flavivirus closely related to West Nile, Japanese encephalitis, Zika, and dengue viruses. USUV emerged in 1996 in Europe, where quickly spread across the continent causing a considerable number of bird deaths and varied neurological disorders in humans, including encephalitis, meningoencephalitis, or facial paralysis, thus warning about USUV as a potential health threat. USUV replication takes place on the endoplasmic reticulum (ER) of infected cells, inducing ER stress and resulting in the activation of stress-related cellular pathways collectively known as the integrated stress response (ISR). The alpha subunit of the eukaryotic initiation factor eIF2 (eIF2α), the core factor in this pathway, is phosphorylated by stress activated kinases: protein kinase R (PKR), PKR-like endoplasmic reticulum kinase (PERK), heme-regulated inhibitor kinase (HRI), and general control non-repressed 2 kinase (GCN2). Its phosphorylation results, among others, in the downstream inhibition of translation with accumulation of discrete foci in the cytoplasm termed stress granules (SGs). Our results indicated that USUV infection evades cellular stress response impairing eIF2α phosphorylation and SGs assembly induced by treatment with the HRI activator ArsNa. This protective effect was related with oxidative stress responses in USUV-infected cells. Overall, these results provide new insights into the complex connections between the stress response and flavivirus infection in order to maintain an adequate cellular environment for viral replication. Usutu virus (USUV) infection impairs eIF2α phosphorylation and SGs assembly, in an oxidative stress related manner, as a mechanism to evade cellular stress response. Our results provide new insights into the complex connections between the stress response and USUV infection to maintain a better cellular environment for viral replication.
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Vilibic-Cavlek T, Barbic L, Mrzljak A, Brnic D, Klobucar A, Ilic M, Janev-Holcer N, Bogdanic M, Jemersic L, Stevanovic V, Tabain I, Krcmar S, Vucelja M, Prpic J, Boljfetic M, Jelicic P, Madic J, Ferencak I, Savic V. Emerging and Neglected Viruses of Zoonotic Importance in Croatia. Pathogens 2021; 10:73. [PMID: 33467617 PMCID: PMC7829938 DOI: 10.3390/pathogens10010073] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 01/08/2021] [Accepted: 01/11/2021] [Indexed: 02/07/2023] Open
Abstract
Several arboviruses have emerged in Croatia in recent years. Tick-borne encephalitis is endemic in continental counties; however, new natural micro-foci have been detected. Two autochthonous dengue cases were reported in 2010. West Nile virus emerged in 2012, followed by emergence of Usutu virus in 2013. Although high seroprevalence rates of Toscana virus have been detected among residents of Croatian littoral, the virus remains neglected, with only a few clinical cases of neuroinvasive infections reported. Lymphocytic choriomeningitis virus is a neglected neuroinvasive rodent-borne virus. So far, there are no reports on human clinical cases; however, the seroprevalence studies indicate the virus presence in the Croatian mainland. Puumala and Dobrava hantaviruses are widely distributing rodent-borne viruses with sporadic and epidemic occurrence. Hepatitis E virus is an emerging food-borne virus in Croatia. After the emergence in 2012, cases were regularly recorded. Seropositivity varies greatly by region and population group. Rotaviruses represent a significant healthcare burden since rotavirus vaccination is not included in the Croatian national immunization program. Additionally, rotaviruses are widely distributed in the Croatian ecosystem. A novel coronavirus, SARS-CoV-2, emerged in February 2020 and spread rapidly throughout the country. This review focuses on emerging and neglected viruses of zoonotic importance detected in Croatia.
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Affiliation(s)
- Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health, 10000 Zagreb, Croatia; (M.B.); (I.T.); (I.F.)
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia;
| | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.B.); (V.S.); (J.M.)
| | - Anna Mrzljak
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia;
- Department of Medicine, Merkur University Hospital, 10000 Zagreb, Croatia
| | - Dragan Brnic
- Department of Virology, Croatian Veterinary Institute, 10000 Zagreb, Croatia; (D.B.); (L.J.); (J.P.)
| | - Ana Klobucar
- Department of Epidemiology, Andrija Stampar Institute of Public Health, 10000 Zagreb, Croatia;
| | - Maja Ilic
- Department of Epidemiology, Croatian Institute of Public Health, 10000 Zagreb, Croatia;
| | - Natasa Janev-Holcer
- Environmental Health Department, Croatian Institute of Public Health, 10000 Zagreb, Croatia; (N.J.-H.); (P.J.)
| | - Maja Bogdanic
- Department of Virology, Croatian Institute of Public Health, 10000 Zagreb, Croatia; (M.B.); (I.T.); (I.F.)
| | - Lorena Jemersic
- Department of Virology, Croatian Veterinary Institute, 10000 Zagreb, Croatia; (D.B.); (L.J.); (J.P.)
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.B.); (V.S.); (J.M.)
| | - Irena Tabain
- Department of Virology, Croatian Institute of Public Health, 10000 Zagreb, Croatia; (M.B.); (I.T.); (I.F.)
| | - Stjepan Krcmar
- Department of Biology, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia;
| | - Marko Vucelja
- Faculty of Forestry, University of Zagreb, 10000 Zagreb, Croatia; (M.V.); (M.B.)
| | - Jelena Prpic
- Department of Virology, Croatian Veterinary Institute, 10000 Zagreb, Croatia; (D.B.); (L.J.); (J.P.)
| | - Marko Boljfetic
- Faculty of Forestry, University of Zagreb, 10000 Zagreb, Croatia; (M.V.); (M.B.)
| | - Pavle Jelicic
- Environmental Health Department, Croatian Institute of Public Health, 10000 Zagreb, Croatia; (N.J.-H.); (P.J.)
| | - Josip Madic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.B.); (V.S.); (J.M.)
| | - Ivana Ferencak
- Department of Virology, Croatian Institute of Public Health, 10000 Zagreb, Croatia; (M.B.); (I.T.); (I.F.)
| | - Vladimir Savic
- Poultry Center, Croatian Veterinary Institute, 10000 Zagreb, Croatia;
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24
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Janssen N, Graovac N, Vignjević G, Bogojević MS, Turić N, Klobučar A, Kavran M, Petrić D, Ćupina AI, Fischer S, Werner D, Kampen H, Merdić E. Rapid spread and population genetics of Aedes japonicus japonicus (Diptera: Culicidae) in southeastern Europe (Croatia, Bosnia and Herzegovina, Serbia). PLoS One 2020; 15:e0241235. [PMID: 33119650 PMCID: PMC7595422 DOI: 10.1371/journal.pone.0241235] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Accepted: 10/11/2020] [Indexed: 12/01/2022] Open
Abstract
The Asian bush mosquito, Aedes japonicus japonicus (Theobald, 1901), a potential vector of several pathogens, has recently established in North America and Central Europe. In 2013, it was found on the Slovenian-Croatian border, and during the following years, it emerged in more and more counties of northwestern Croatia. Surveillance of Ae. j. japonicus and other invasive mosquito species was subsequently extended both spatially and temporally in Croatia and neighbouring Bosnia and Herzegovina and Serbia. Mosquito collections were conducted in 2017 and 2018, based on adult trapping through dry ice-baited CDC traps and BG-Lure-baited BG-Sentinel traps, larval sampling through dippers and nets, and ovitrapping. Aedes j. japonicus specimens from collected samples were subjected to population genetic analysis by comparing microsatellite signatures and nad4 DNA sequences between sampled locations and with data previously obtained from more western European distribution areas. Aedes j. japonicus immature stages were found at 19 sites in Croatia, two sites in Bosnia and Herzegovina and one site in Serbia. In Croatia, four new counties were found colonised, two in the east and two in the south of the previously known distribution area. A spread of 250 km could thus be documented within five years. The findings in Bosnia and Herzegovina and Serbia represent the first records of Ae. j. japonicus in these countries. Genetic analysis suggests at least two introduction events into the surveyed area. Among the locations analysed, Orahovica can be considered a genetic border. The individuals collected west of this point were found to be similar to samples previously collected in the border regions of Southeast Germany/Austria and Austria/Slovenia, while the specimens from more eastern Croatian localities, together with those from Bosnia and Herzegovina and Serbia, were genetically different and could not be assigned to a probable origin. Thus, introduction from Central Europe, possibly by vehicular traffic, into the study area is likely, but other origins, transportation routes and modes of entry appear to contribute. Further dispersal of Ae. j. japonicus to other parts of southeastern Europe is anticipated.
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Affiliation(s)
- Nele Janssen
- Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald–Insel Riems, Germany
| | - Nataša Graovac
- Department of Biology, Josip Juraj Strossmayer University, Osijek, Croatia
| | - Goran Vignjević
- Department of Biology, Josip Juraj Strossmayer University, Osijek, Croatia
| | | | - Nataša Turić
- Department of Biology, Josip Juraj Strossmayer University, Osijek, Croatia
| | - Ana Klobučar
- Andrija Stampar Teaching Institute of Public Health, Zagreb, Croatia
| | - Mihaela Kavran
- Laboratory for Medical and Veterinary Entomology, Faculty of Agriculture, University of Novi Sad, Novi Sad, Serbia
| | - Dušan Petrić
- Laboratory for Medical and Veterinary Entomology, Faculty of Agriculture, University of Novi Sad, Novi Sad, Serbia
| | - Aleksandra Ignjatović Ćupina
- Laboratory for Medical and Veterinary Entomology, Faculty of Agriculture, University of Novi Sad, Novi Sad, Serbia
| | - Susanne Fischer
- Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald–Insel Riems, Germany
| | - Doreen Werner
- Leibniz-Centre for Agricultural Landscape Research, Muencheberg, Germany
| | - Helge Kampen
- Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald–Insel Riems, Germany
| | - Enrih Merdić
- Department of Biology, Josip Juraj Strossmayer University, Osijek, Croatia
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Clinical, Virological, and Immunological Findings in Patients with Toscana Neuroinvasive Disease in Croatia: Report of Three Cases. Trop Med Infect Dis 2020; 5:tropicalmed5030144. [PMID: 32937866 PMCID: PMC7557803 DOI: 10.3390/tropicalmed5030144] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 09/03/2020] [Accepted: 09/08/2020] [Indexed: 01/14/2023] Open
Abstract
Toscana virus (TOSV) is an arthropod-borne virus, transmitted to humans by phlebotomine sandflies. Although the majority of infections are asymptomatic, neuroinvasive disease may occur. We report three cases of neuroinvasive TOSV infection detected in Croatia. Two patients aged 21 and 54 years presented with meningitis, while a 22-year old patient presented with meningoencephalitis and right-sided brachial plexitis. Cerebrospinal fluid (CSF), serum, and urine samples were collected and tested for neuroinvasive arboviruses: tick-borne encephalitis, West Nile, Usutu, TOSV, Tahyna, and Bhanja virus. In addition, CSF and serum samples were tested for the anti-viral cytokine response. High titers of TOSV IgM (1000–3200) and IgG (3200−10,000) antibodies in serum samples confirmed TOSV infection. Antibodies to other phleboviruses (sandfly fever Sicilian/Naples/Cyprus virus) were negative. CSF samples showed high concentrations of interleukin 6 (IL-6; range 162.32−2683.90 pg/mL), interferon gamma (IFN-γ; range 110.12−1568.07 pg/mL), and IL-10 (range 28.08−858.91 pg/mL), while significantly lower cytokine production was observed in serum. Two patients recovered fully. The patient with a brachial plexitis improved significantly at discharge. The presented cases highlight the need of increasing awareness of a TOSV as a possible cause of aseptic meningitis/meningoencephalitis during summer months. Association of TOSV and brachial plexitis with long-term sequelae detected in one patient indicates the possibility of more severe disease, even in young patients.
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26
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Santini M, Zupetic I, Viskovic K, Krznaric J, Kutlesa M, Krajinovic V, Polak VL, Savic V, Tabain I, Barbic L, Bogdanic M, Stevanovic V, Mrzljak A, Vilibic-Cavlek T. Cauda equina arachnoiditis - a rare manifestation of West Nile virus neuroinvasive disease: A case report. World J Clin Cases 2020; 8:3797-3803. [PMID: 32953855 PMCID: PMC7479571 DOI: 10.12998/wjcc.v8.i17.3797] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 05/10/2020] [Accepted: 08/14/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Data regarding the neuroradiology features of the West Nile virus neuroinvasive disease (WNV NID) is rather scarce. To contribute to the knowledge of the WNV NID, we present a patient with a combination of encephalitis and acute flaccid paresis, with cauda equina arachnoiditis as the main magnetic resonance (MR) finding. CASE SUMMARY A 72-year-old female patient was admitted due to fever, headache and gait instability. During the first several days she developed somnolence, aphasia, urinary incontinence, constipation, and asymmetric lower extremities weakness. Cerebrospinal fluid analysis indicated encephalitis. Native brain computed tomography and MR were unremarkable, while spinal MR demonstrated cauda equina enhancement without cord lesions. Virology testing revealed WNV IgM and IgG antibodies in serum and cerebrospinal fluid, which confirmed acute WNV NID. The treatment was supportive. After two months only a slight improvement was noticed but cognitive impairment, loss of sphincter control and asymmetric inferior extremities weakness remained. The patient died after a month on chronic rehabilitation. CONCLUSION Cauda equina arachnoiditis is a rare, but possible neuroradiological feature in acute flaccid paresis form of WNV NID.
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Affiliation(s)
- Marija Santini
- Department for Intensive Care Medicine and Neuroinfectology, University Hospital for Infectious Diseases “Dr Fran Mihaljevic”, Zagreb 10000, Croatia
| | - Ivana Zupetic
- Department of Radiology, University Clinical Hospital Center, Clinic for Traumatology, Zagreb 10000, Croatia
| | - Klaudija Viskovic
- Department of Radiology and Ultrasound, University Hospital for Infectious Diseases “Dr Fran Mihaljevic”, Zagreb 10000, Croatia
| | - Juraj Krznaric
- Department for Intensive Care Medicine and Neuroinfectology, University Hospital for Infectious Diseases “Dr Fran Mihaljevic”, Zagreb 10000, Croatia
| | - Marko Kutlesa
- Department for Intensive Care Medicine and Neuroinfectology, University Hospital for Infectious Diseases “Dr Fran Mihaljevic”, Zagreb 10000, Croatia
| | - Vladimir Krajinovic
- Department for Intensive Care Medicine and Neuroinfectology, University Hospital for Infectious Diseases “Dr Fran Mihaljevic”, Zagreb 10000, Croatia
| | - Vlatka Lovrakovic Polak
- Department of Infectious Diseases, General County Hospital Karlovac, Karlovac 47000, Croatia
| | - Vladimir Savic
- Department of Poultry Center, Laboratory for Virology and Serology, Croatian Veterinary Institute, Zagreb 10000, Croatia
| | - Irena Tabain
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Maja Bogdanic
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Anna Mrzljak
- Department of Medicine, University Hospital Merkur, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
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27
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Bakhshi H, Beck C, Lecollinet S, Monier M, Mousson L, Zakeri S, Raz A, Arzamani K, Nourani L, Dinparast-Djadid N, Failloux AB. Serological evidence of West Nile virus infection among birds and horses in some geographical locations of Iran. Vet Med Sci 2020; 7:204-209. [PMID: 32858762 PMCID: PMC7840194 DOI: 10.1002/vms3.342] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 06/25/2020] [Accepted: 08/05/2020] [Indexed: 12/31/2022] Open
Abstract
Recent expansion of arboviruses such as West Nile (WNV), Usutu (USUV), and tick‐borne encephalitis (TBEV) over their natural range of distribution needs strengthening their surveillance. As common viral vertebrate hosts, birds and horses deserve special attention with routine serological surveillance. Here, we estimated the seroprevalence of WNV, USUV and TBEV in 160 migrating/resident birds and 60 horses sampled in Mazandaran, Golestan, North Khorasan, Kordestan provinces and Golestan province of Iran respectively. ELISA results showed that of 220 collected samples, 32 samples (14.54%), including 22 birds and 10 horses, were positive. Microsphere immunoassay results showed that 16.7% (10/60) of horse blood samples collected in Golestan province were seropositive against WNV (7; 11.7%), Flavivirus (2; 3.3%) and seropositive for USUV or WNV (1; 1.7%). Furthermore, micro virus neutralization tests revealed that four of seven ELISA‐positive bird blood samples were seropositive against WNV: two Egyptian vultures, and one long‐legged buzzard collected in Golestan province as well as a golden eagle collected in North Khorasan province. No evidence of seropositivity with TBEV was observed in collected samples. We showed that WNV, responsible for neuroinvasive infection in vertebrates, is circulating among birds and horses in Iran, recommending a sustained surveillance of viral infections in animals, and anticipating future infections in humans.
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Affiliation(s)
- Hasan Bakhshi
- Malaria and Vector Research Group, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Cécile Beck
- EURL on Equine Diseases, ANSES, Animal Health Laboratory, UMR 1161 Virology, ANSES, INRAE, ENVA, Maisons-Alfort, France
| | - Sylvie Lecollinet
- EURL on Equine Diseases, ANSES, Animal Health Laboratory, UMR 1161 Virology, ANSES, INRAE, ENVA, Maisons-Alfort, France
| | - Maëlle Monier
- EURL on Equine Diseases, ANSES, Animal Health Laboratory, UMR 1161 Virology, ANSES, INRAE, ENVA, Maisons-Alfort, France
| | - Laurence Mousson
- Department of virology, Arboviruses and Insect Vectors, Institut Pasteur, Paris, France
| | - Sedigheh Zakeri
- Malaria and Vector Research Group, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Abbasali Raz
- Malaria and Vector Research Group, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Kourosh Arzamani
- Vector-borne Diseases Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Leila Nourani
- Malaria and Vector Research Group, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Navid Dinparast-Djadid
- Malaria and Vector Research Group, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Anna-Bella Failloux
- Department of virology, Arboviruses and Insect Vectors, Institut Pasteur, Paris, France
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Vilibic-Cavlek T, Petrovic T, Savic V, Barbic L, Tabain I, Stevanovic V, Klobucar A, Mrzljak A, Ilic M, Bogdanic M, Benvin I, Santini M, Capak K, Monaco F, Listes E, Savini G. Epidemiology of Usutu Virus: The European Scenario. Pathogens 2020; 9:699. [PMID: 32858963 PMCID: PMC7560012 DOI: 10.3390/pathogens9090699] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Revised: 08/22/2020] [Accepted: 08/24/2020] [Indexed: 02/07/2023] Open
Abstract
Usutu virus (USUV) is an emerging arbovirus isolated in 1959 (Usutu River, Swaziland). Previously restricted to sub-Saharan Africa, the virus was introduced in Europe in 1996. While the USUV has received little attention in Africa, the virus emergence has prompted numerous studies with robust epidemiological surveillance programs in Europe. The natural transmission cycle of USUV involves mosquitoes (vectors) and birds (amplifying hosts) with humans and other mammals considered incidental ("dead-end") hosts. In Africa, the virus was isolated in mosquitoes, rodents and birds and serologically detected in horses and dogs. In Europe, USUV was detected in bats, whereas antibodies were found in different animal species (horses, dogs, squirrels, wild boar, deer and lizards). While bird mortalities were not reported in Africa, in Europe USUV was shown to be highly pathogenic for several bird species, especially blackbirds (Turdus merula) and great gray owls (Strix nebulosa). Furthermore, neurotropism of USUV for humans was reported for the first time in both immunocompromised and immunocompetent patients. Epizootics and genetic diversity of USUV in different bird species as well as detection of the virus in mosquitoes suggest repeated USUV introductions into Europe with endemization in some countries. The zoonotic potential of USUV has been reported in a growing number of human cases. Clinical cases of neuroinvasive disease and USUV fever, as well as seroconversion in blood donors were reported in Europe since 2009. While most USUV strains detected in humans, birds and mosquitoes belong to European USUV lineages, several reports indicate the presence of African lineages as well. Since spreading trends of USUV are likely to continue, continuous multidisciplinary interventions ("One Health" concept) should be conducted for monitoring and prevention of this emerging arboviral infection.
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Affiliation(s)
- Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health, 10000 Zagreb, Croatia; (I.T.); (M.B.)
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia;
| | - Tamas Petrovic
- Department for Virology, Scientific Veterinary Institute, 21000 Novi Sad, Serbia;
| | - Vladimir Savic
- Poultry Center, Croatian Veterinary Institute, 10000 Zagreb, Croatia;
| | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.B.); (V.S.); (I.B.)
| | - Irena Tabain
- Department of Virology, Croatian Institute of Public Health, 10000 Zagreb, Croatia; (I.T.); (M.B.)
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.B.); (V.S.); (I.B.)
| | - Ana Klobucar
- Department of Epidemiology, Andrija Stampar Teaching Institute of Public Health, 10000 Zagreb, Croatia;
| | - Anna Mrzljak
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia;
- Department of Medicine, Merkur University Hospital, 10000 Zagreb, Croatia
| | - Maja Ilic
- Department of Epidemiology, Croatian Institute of Public Health, 10000 Zagreb, Croatia;
| | - Maja Bogdanic
- Department of Virology, Croatian Institute of Public Health, 10000 Zagreb, Croatia; (I.T.); (M.B.)
| | - Iva Benvin
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.B.); (V.S.); (I.B.)
| | - Marija Santini
- Department for Intensive Care Medicine and Neuroinfectology, University Hospital for Infectious Diseases “Dr Fran Mihaljevic”, 10000 Zagreb, Croatia;
| | - Krunoslav Capak
- Environmental Health Department, Croatian Institute of Public Health, 10000 Zagreb, Croatia;
| | - Federica Monaco
- OIE Reference Center for West Nile Disease, Istituto Zooprofilattico Sperimentale “G. Caporale”, 64100 Teramo, Italy; (F.M.); (G.S.)
| | - Eddy Listes
- Laboratory for Diagnostics, Croatian Veterinary Institute, Regional Institute Split, 21000 Split, Croatia;
| | - Giovanni Savini
- OIE Reference Center for West Nile Disease, Istituto Zooprofilattico Sperimentale “G. Caporale”, 64100 Teramo, Italy; (F.M.); (G.S.)
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Nagy A, Mezei E, Nagy O, Bakonyi T, Csonka N, Kaposi M, Koroknai A, Szomor K, Rigó Z, Molnár Z, Dánielisz Á, Takács M. Extraordinary increase in West Nile virus cases and first confirmed human Usutu virus infection in Hungary, 2018. ACTA ACUST UNITED AC 2020; 24. [PMID: 31311619 PMCID: PMC6636212 DOI: 10.2807/1560-7917.es.2019.24.28.1900038] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BackgroundDuring the 2018 WNV transmission season, similarly to other endemic areas in Europe, a large number of human West Nile virus (WNV) infections were reported in Hungary.AimsWe summarise the epidemiological and laboratory findings of the 2018 transmission season and expand experiences in flavivirus differential diagnostics.MethodsEvery patient with clinical suspicion of acute WNV infection was in parallel tested for WNV, tick-borne encephalitis virus and Usutu virus (USUV) by serological methods. Sera, whole blood and urine samples were also tested for the presence of viral nucleic acid.ResultsUntil the end of December 2018, 215 locally acquired and 10 imported human WNV infections were notified in Hungary. All reported cases were symptomatic; most of them exhibited neurological symptoms. In a large proportion of tested individuals, whole blood was the most appropriate sample type for viral nucleic acid detection, but because whole blood samples were not always available, testing of urine samples also extended diagnostic possibilities. In addition, the first human USUV infection was confirmed in 2018 in a patient with aseptic meningitis. Serological cross-reactions with WNV in different serological assays were experienced, but subsequent molecular biological testing and sequence analysis identified Europe lineage 2 USUV infection.ConclusionCareful interpretation and simultaneous application of different laboratory methods are necessary to avoid misdiagnosis of human USUV cases. Expansion of the laboratory-confirmed case definition criteria for detection of viral RNA in any clinical specimens to include urine samples could increase diagnostic sensitivity.
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Affiliation(s)
- Anna Nagy
- These authors contributed equally to this work.,National Reference Laboratory for Viral Zoonoses; National Public Health Center, Budapest, Hungary
| | - Eszter Mezei
- Department of Communicable Diseases Epidemiology and Infection Control; National Public Health Center, Budapest, Hungary.,These authors contributed equally to this work
| | - Orsolya Nagy
- Institute of Medical Microbiology, Semmelweis University, Budapest, Hungary.,National Reference Laboratory for Viral Zoonoses; National Public Health Center, Budapest, Hungary
| | - Tamás Bakonyi
- Viral Zoonoses, Emerging and Vector-borne Infections Group, Institute of Virology, University of Veterinary Medicine, Vienna, Austria.,Department of Microbiology and Infectious Diseases, University of Veterinary Medicine, Budapest, Hungary
| | - Nikolett Csonka
- National Reference Laboratory for Viral Zoonoses; National Public Health Center, Budapest, Hungary
| | - Magdolna Kaposi
- National Reference Laboratory for Viral Zoonoses; National Public Health Center, Budapest, Hungary
| | - Anita Koroknai
- National Reference Laboratory for Viral Zoonoses; National Public Health Center, Budapest, Hungary
| | - Katalin Szomor
- National Reference Laboratory for Viral Exanthematous Diseases; National Public Health Center, Budapest, Hungary
| | - Zita Rigó
- National Reference Laboratory for Viral Exanthematous Diseases; National Public Health Center, Budapest, Hungary
| | - Zsuzsanna Molnár
- Department of Communicable Diseases Epidemiology and Infection Control; National Public Health Center, Budapest, Hungary
| | - Ágnes Dánielisz
- Department of Communicable Diseases Epidemiology and Infection Control; National Public Health Center, Budapest, Hungary
| | - Mária Takács
- Institute of Medical Microbiology, Semmelweis University, Budapest, Hungary.,National Reference Laboratory for Viral Zoonoses; National Public Health Center, Budapest, Hungary
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30
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Carletti F, Colavita F, Rovida F, Percivalle E, Baldanti F, Ricci I, De Liberato C, Rosone F, Messina F, Lalle E, Bordi L, Vairo F, Capobianchi MR, Ippolito G, Cappiello G, Spanò A, Meschi S, Castilletti C. Expanding Usutu virus circulation in Italy: detection in the Lazio region, central Italy, 2017 to 2018. ACTA ACUST UNITED AC 2020; 24. [PMID: 30670139 PMCID: PMC6344840 DOI: 10.2807/1560-7917.es.2019.24.3.1800649] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Blood donation screening for West Nile virus (WNV) was mandatory in the Lazio region in 2017 and 2018 (June-November) according to the national surveillance plan. In these years, all five donations reactive in WNV nucleic acid amplification tests harboured instead Usutu virus (USUV). Clade ‘Europe 2’ was identified in four blood donations and a 2018 mosquito pool. The cocirculation of WNV and USUV in Lazio warrants increased laboratory support and awareness of possible virus misidentification.
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Affiliation(s)
- Fabrizio Carletti
- Laboratory of Virology, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy
| | - Francesca Colavita
- Laboratory of Virology, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy
| | - Francesca Rovida
- Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Elena Percivalle
- Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Fausto Baldanti
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Italy.,Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Ida Ricci
- Istituto Zooprofilattico Sperimentale delle regioni Lazio e Toscana, Rome, Italy
| | - Claudio De Liberato
- Istituto Zooprofilattico Sperimentale delle regioni Lazio e Toscana, Rome, Italy
| | - Francesca Rosone
- Istituto Zooprofilattico Sperimentale delle regioni Lazio e Toscana, Rome, Italy
| | - Francesco Messina
- Laboratory of Virology, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy
| | - Eleonora Lalle
- Laboratory of Virology, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy
| | - Licia Bordi
- Laboratory of Virology, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy
| | - Francesco Vairo
- Regional Service for Surveillance and Control of Infectious Diseases (SERESMI)-Lazio Region, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy
| | - Maria Rosaria Capobianchi
- Laboratory of Virology, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy
| | - Giuseppe Ippolito
- Scientific Direction, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy
| | | | - Alberto Spanò
- Unit of Microbiology, Sandro Pertini Hospital, Rome, Italy
| | - Silvia Meschi
- Laboratory of Virology, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy
| | - Concetta Castilletti
- Laboratory of Virology, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy
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Mrzljak A, Novak R, Pandak N, Tabain I, Franusic L, Barbic L, Bogdanic M, Savic V, Mikulic D, Pavicic-Saric J, Stevanovic V, Vilibic-Cavlek T. Emerging and neglected zoonoses in transplant population. World J Transplant 2020; 10:47-63. [PMID: 32257849 PMCID: PMC7109593 DOI: 10.5500/wjt.v10.i3.47] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 03/15/2020] [Accepted: 03/22/2020] [Indexed: 02/06/2023] Open
Abstract
Zoonoses represent a problem of rising importance in the transplant population. A close relationship and changes between human, animal and environmental health ("One Health" concept) significantly influence the transmission and distribution of zoonotic diseases. The aim of this manuscript is to perform a narrative review of the published literature on emerging and neglected zoonoses in the transplant population. Many reports on donor-derived or naturally acquired (re-)emerging arboviral infections such as dengue, chikungunya, West Nile, tick-borne encephalitis and Zika virus infection have demonstrated atypical or more complicated clinical course in immunocompromised hosts. Hepatitis E virus has emerged as a serious problem after solid organ transplantation (SOT), leading to diverse extrahepatic manifestations and chronic hepatitis with unfavorable outcomes. Some neglected pathogens such as lymphocytic choriomeningitis virus can cause severe infection with multi-organ failure and high mortality. In addition, ehrlichiosis may be more severe with higher case-fatality rates in SOT recipients. Some unusual or severe presentations of borreliosis, anaplasmosis and rickettsioses were also reported among transplant patients. Moreover, toxoplasmosis as infectious complication is a well-recognized zoonosis in this population. Although rabies transmission through SOT transplantation has rarely been reported, it has become a notable problem in some countries. Since the spreading trends of zoonoses are likely to continue, the awareness, recognition and treatment of zoonotic infections among transplant professionals should be imperative.
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Affiliation(s)
- Anna Mrzljak
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Rafaela Novak
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Nenad Pandak
- Depatment of Medicine, The Royal Hospital Muscat, Muscat 111, Oman
| | - Irena Tabain
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | | | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Maja Bogdanic
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | - Vladimir Savic
- Poultry Center, Croatian Veterinary Institute, Zagreb 10000, Croatia
| | - Danko Mikulic
- Department of Abdominal and Transplant Surgery, Merkur University Hospital, Zagreb 10000, Croatia
| | - Jadranka Pavicic-Saric
- Department of Anesthesiology and Intensive Medicine, Merkur University Hospital, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health; School of Medicine, University of Zagreb, Zagreb 10000, Croatia
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Caracciolo I, Mora-Cardenas E, Aloise C, Carletti T, Segat L, Burali MS, Chiarvesio A, Totis V, Avšič–Županc T, Mastrangelo E, Manfroni G, D’Agaro P, Marcello A. Comprehensive response to Usutu virus following first isolation in blood donors in the Friuli Venezia Giulia region of Italy: Development of recombinant NS1-based serology and sensitivity to antiviral drugs. PLoS Negl Trop Dis 2020; 14:e0008156. [PMID: 32226028 PMCID: PMC7145266 DOI: 10.1371/journal.pntd.0008156] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 04/09/2020] [Accepted: 02/19/2020] [Indexed: 01/25/2023] Open
Abstract
Surveillance of Usutu virus is crucial to prevent future outbreaks both in Europe and in other countries currently naïve to the infection, such as the Americas. This goal remains difficult to achieve, notably because of the lack of large-scale cohort studies and the absence of commercially available diagnostic reagents for USUV. This work started with the first identification of USUV in a blood donor in the Friuli Venezia Giulia (FVG) Region in Northern-Eastern Italy, which is endemic for West Nile virus. Considering that only one IgG ELISA is commercially available, but none for IgM, a novel NS1 antigen based IgG/M ELISA has been developed. This assay tested successfully for the detection of Usutu virus in blood donors with the identification of a second case of transmission and high levels of exposure. Furthermore, two pan-flavivirus antiviral drugs, that we previously characterized to be inhibitors of other flavivirus infectivity, were successfully tested for inhibition of Usutu virus with inhibitory concentrations in the low micromolar range. To conclude, this work identifies North-Eastern Italy as endemic for Usutu virus with implications for the screening of transfusion blood. A novel NS1-based ELISA test has been implemented for the detection of IgM/G that will be of importance as a tool for the diagnosis and surveillance of Usutu virus infection. Finally, Usutu virus is shown to be sensitive to a class of promising pan-flavivirus drugs. Tropical viruses transmitted by ticks or mosquitoes are becoming a health threat in areas of the world that were previously naïve to these infections. Usutu virus is a mosquito-borne virus that is circulating in Europe causing massive outbreaks in birds. Transmission to humans is documented, with some reports of severe neurological disease. However, the real size of transmission to humans suffers from lack of data due to insufficient surveillance. The first confirmed case of human USUV infection in an asymptomatic blood donor from North-Eastern Italy is hereby demonstrated by molecular assays and virus isolation. Specific Usutu virus serology has also been developed taking advantage of the NS1 viral antigen, which is tested on a number of blood donors demonstrating a high level of Usutu positivity. These findings confirm the human transmission in the region and offer a novel tool for specific Usutu virus surveillance. Finally, two drugs that were previously shown to have a wide spectrum of activity towards members of this family of viruses are shown to inhibit also Usutu virus, opening the way to a novel class antivirals.
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Affiliation(s)
- Ilaria Caracciolo
- Regional Reference Centre for Arbovirus Infections, Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
| | - Erick Mora-Cardenas
- Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, Trieste, Italy
| | - Chiara Aloise
- Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, Trieste, Italy
| | - Tea Carletti
- Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, Trieste, Italy
| | - Ludovica Segat
- Regional Reference Centre for Arbovirus Infections, Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
- Azienda Sanitaria Universitaria Integrata di Trieste, UCO Igiene e Sanità Pubblica, Trieste, Italy
| | - Maria Sole Burali
- Dipartimento di Scienze Farmaceutiche, Università degli Studi di Perugia, Perugia, Italy
| | - Alexsia Chiarvesio
- Centro Unico Regionale Produzione Emocomponenti C.U.R.P.E. P.O. Palmanova A.A.S.2 Bassa Friulana Isontina, Palmanova, Italy
| | - Vivianna Totis
- Centro Unico Regionale Produzione Emocomponenti C.U.R.P.E. P.O. Palmanova A.A.S.2 Bassa Friulana Isontina, Palmanova, Italy
| | - Tatjana Avšič–Županc
- Laboratory of Diagnostics of Zoonoses and WHO Centre, Institute of Microbiology and Immunology, University of Ljubljana, Ljubljana, Slovenia
| | | | - Giuseppe Manfroni
- Dipartimento di Scienze Farmaceutiche, Università degli Studi di Perugia, Perugia, Italy
| | - Pierlanfranco D’Agaro
- Regional Reference Centre for Arbovirus Infections, Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
- Azienda Sanitaria Universitaria Integrata di Trieste, UCO Igiene e Sanità Pubblica, Trieste, Italy
- * E-mail: (PD); (AM)
| | - Alessandro Marcello
- Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, Trieste, Italy
- * E-mail: (PD); (AM)
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Benzarti E, Sarlet M, Franssen M, Desmecht D, Schmidt-Chanasit J, Garigliany MM. New Insights into the Susceptibility of Immunocompetent Mice to Usutu Virus. Viruses 2020; 12:E189. [PMID: 32046265 PMCID: PMC7077335 DOI: 10.3390/v12020189] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 01/29/2020] [Accepted: 02/05/2020] [Indexed: 01/08/2023] Open
Abstract
Usutu virus (USUV) is a mosquito-borne flavivirus that shares many similarities with the closely related West Nile virus (WNV) in terms of ecology and clinical manifestations. Initially distributed in Africa, USUV emerged in Italy in 1996 and managed to co-circulate with WNV in many European countries in a similar mosquito-bird life cycle. The rapid geographic spread of USUV, the seasonal mass mortalities it causes in the European avifauna, and the increasing number of infections with neurological disease both in healthy and immunocompromised humans has stimulated interest in infection studies to delineate USUV pathogenesis. Here, we assessed the pathogenicity of two USUV isolates from a recent Belgian outbreak in immunocompetent mice. The intradermal injection of USUV gave rise to disorientation and paraplegia and was associated with neuronal death in the brain and spinal cord in a single mouse. Intranasal inoculation of USUV could also establish the infection; viral RNA was detected in the brain 15 days post-infection. Overall, this pilot study probes the suitability of this murine model for the study of USUV neuroinvasiveness and the possibility of direct transmission in mammals.
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Affiliation(s)
- Emna Benzarti
- Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Sart Tilman B43, B-4000 Liège, Belgium; (E.B.); (M.S.); (M.F.); (D.D.)
| | - Michaël Sarlet
- Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Sart Tilman B43, B-4000 Liège, Belgium; (E.B.); (M.S.); (M.F.); (D.D.)
| | - Mathieu Franssen
- Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Sart Tilman B43, B-4000 Liège, Belgium; (E.B.); (M.S.); (M.F.); (D.D.)
| | - Daniel Desmecht
- Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Sart Tilman B43, B-4000 Liège, Belgium; (E.B.); (M.S.); (M.F.); (D.D.)
| | - Jonas Schmidt-Chanasit
- Bernhard Nocht Institute for Tropical Medicine, WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research, 20359 Hamburg, Germany;
- Faculty of Mathematics, Informatics and Natural Sciences, University of Hamburg, 20354 Hamburg, Germany
| | - Mutien-Marie Garigliany
- Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Sart Tilman B43, B-4000 Liège, Belgium; (E.B.); (M.S.); (M.F.); (D.D.)
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34
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Experimental Usutu Virus Infection in Domestic Canaries Serinus canaria. Viruses 2020; 12:v12020164. [PMID: 32023880 PMCID: PMC7077186 DOI: 10.3390/v12020164] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Accepted: 01/27/2020] [Indexed: 02/06/2023] Open
Abstract
Usutu virus (USUV) is a neurotropic flavivirus closely related to West Nile virus (WNV). Its enzootic cycle mainly involves mosquitoes and birds. Human infection can occur with occasional, but sometimes severe, neurological complications. Since its emergence and spread in Europe over the last two decades, USUV has been linked to significant avian outbreaks, especially among Passeriformes, including European blackbirds (Turdus merula). Strikingly, no in vivo avian model exists so far to study this arbovirus. The domestic canary (Serinus canaria) is a passerine, which is considered as a highly susceptible model of infection by WNV. Here, we experimentally challenged domestic canaries with two different doses of USUV. All inoculated birds presented detectable amounts of viral RNA in the blood and RNA shedding via feathers and droppings during the early stages of the infection, as determined by RT-qPCR. Mortality occurred in both infected groups (1/5 and 2/5, respectively) and was not necessarily correlated to a pure neurological disease. Subsequent analyses of samples from dead birds showed histopathological changes and virus tropism mimicking those reported in naturally infected birds. A robust seroconversion followed the infection in almost all the surviving canaries. Altogether, these results demonstrate that domestic canaries constitute an interesting experimental model for the study of USUV pathogenesis and transmission.
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35
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Vilibic-Cavlek T, Savic V, Petrovic T, Toplak I, Barbic L, Petric D, Tabain I, Hrnjakovic-Cvjetkovic I, Bogdanic M, Klobucar A, Mrzljak A, Stevanovic V, Dinjar-Kujundzic P, Radmanic L, Monaco F, Listes E, Savini G. Emerging Trends in the Epidemiology of West Nile and Usutu Virus Infections in Southern Europe. Front Vet Sci 2019; 6:437. [PMID: 31867347 PMCID: PMC6908483 DOI: 10.3389/fvets.2019.00437] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Accepted: 11/19/2019] [Indexed: 02/05/2023] Open
Abstract
The epidemiology of West Nile (WNV) and Usutu virus (USUV) has changed dramatically over the past two decades. Since 1999, there have been regular reports of WNV outbreaks and the virus has expanded its area of circulation in many Southern European countries. After emerging in Italy in 1996, USUV has spread to other countries causing mortality in several bird species. In 2009, USUV seroconversion in horses was reported in Italy. Co-circulation of both viruses was detected in humans, horses and birds. The main vector of WNV and USUV in Europe is Culex pipiens, however, both viruses were found in native Culex mosquito species (Cx. modestus, Cx. perexiguus). Experimental competence to transmit the WNV was also proven for native and invasive mosquitoes of Aedes and Culex genera (Ae. albopictus, Ae. detritus, Cx. torrentium). Recently, Ae. albopictus and Ae. japonicus naturally-infected with USUV were reported. While neuroinvasive human WNV infections are well-documented, USUV infections are sporadically detected. However, there is increasing evidence of a role of USUV in human disease. Seroepidemiological studies showed that USUV circulation is more common than WNV in some endemic regions. Recent data showed that WNV strains detected in humans, horses, birds, and mosquitoes mainly belong to lineage 2. In addition to European USUV lineages, some reports indicate the presence of African USUV lineages as well. The trends in WNV/USUV range and vector expansion are likely to continue in future years. This mini-review provides an update on the epidemiology of WNV and USUV infections in Southern Europe within a multidisciplinary "One Health" context.
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Affiliation(s)
- Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health, Zagreb, Croatia
- School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Vladimir Savic
- Poultry Center, Croatian Veterinary Institute, Zagreb, Croatia
| | - Tamas Petrovic
- Department for Virology, Scientific Veterinary Institute, Novi Sad, Serbia
| | - Ivan Toplak
- Veterinary Faculty, University of Ljubljana, Ljubljana, Slovenia
| | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases With Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
| | - Dusan Petric
- Laboratory for Medical and Veterinary Entomology, Faculty of Agriculture, University of Novi Sad, Novi Sad, Serbia
| | - Irena Tabain
- Department of Virology, Croatian Institute of Public Health, Zagreb, Croatia
| | - Ivana Hrnjakovic-Cvjetkovic
- Center for Microbiology, Institute of Public Health Vojvodina, Novi Sad, Serbia
- Medical Faculty, University of Novi Sad, Novi Sad, Serbia
| | - Maja Bogdanic
- Department of Virology, Croatian Institute of Public Health, Zagreb, Croatia
| | - Ana Klobucar
- Division of Disinfection, Disinfestation and Pest Control, Andrija Stampar Teaching Institute of Public Health, Zagreb, Croatia
| | - Anna Mrzljak
- School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Medicine, Merkur University Hospital, Zagreb, Croatia
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases With Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
| | | | - Luka Radmanic
- Department of Microbiology and Infectious Diseases With Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
| | - Federica Monaco
- OIE Reference Center for West Nile Disease, Istituto Zooprofilattico Sperimentale “G. Caporale”, Teramo, Italy
| | - Eddy Listes
- Laboratory for Diagnostics, Croatian Veterinary Institute, Regional Institute Split, Split, Croatia
| | - Giovanni Savini
- OIE Reference Center for West Nile Disease, Istituto Zooprofilattico Sperimentale “G. Caporale”, Teramo, Italy
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Benzarti E, Sarlet M, Franssen M, Cadar D, Schmidt-Chanasit J, Rivas JF, Linden A, Desmecht D, Garigliany M. Usutu Virus Epizootic in Belgium in 2017 and 2018: Evidence of Virus Endemization and Ongoing Introduction Events. Vector Borne Zoonotic Dis 2019; 20:43-50. [PMID: 31479400 DOI: 10.1089/vbz.2019.2469] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Wildlife surveillance allowed the monitoring of the zoonotic mosquito-borne Usutu virus (USUV) in birds and bats (Pipistrellus pipistrellus) in southern Belgium in 2017 and 2018. USUV-RNA was detected in 69 birds (of 253) from 15 species, among which 7 species had not previously been reported to be susceptible to the infection. Similarly, 2 bats (of 10) were detected positive by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). USUV-associated lesions were mainly found in Eurasian Blackbirds (Turdus merula), in which USUV antigens were demonstrated by immunohistochemistry in the brain, heart, liver, kidney, intestine, and lung. Partial nonstructural protein 5 gene-based phylogenetic analysis showed several identical or closely related strains from 2016, 2017, and 2018 clustering together within Europe 3 or Africa 3 lineages. Further, one USUV strain detected in a common chaffinch (Fringilla coelebs) manifested a close genetic relationship with the European 1 strains circulating in Hungary and Austria. Our data provide evidence of USUV endemization in southern Belgium in local birds and bats, extension of the host range of the virus and ongoing virus introduction from abroad, likely by migratory birds. Our results highlight the need for vigilance in the forthcoming years toward new virus-associated outbreaks in birds and possible human infections in Belgium.
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Affiliation(s)
- Emna Benzarti
- Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
| | - Michaël Sarlet
- Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
| | - Mathieu Franssen
- Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
| | - Daniel Cadar
- Bernhard Nocht Institute for Tropical Medicine, WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research, Hamburg, Germany
| | - Jonas Schmidt-Chanasit
- Bernhard Nocht Institute for Tropical Medicine, WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research, Hamburg, Germany.,Faculty of Mathematics, Informatics and Natural Sciences, University of Hamburg, Hamburg, Germany
| | - Jose Felipe Rivas
- Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
| | - Annick Linden
- Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
| | - Daniel Desmecht
- Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
| | - Mutien Garigliany
- Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
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37
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Usutu Virus: An Arbovirus on the Rise. Viruses 2019; 11:v11070640. [PMID: 31336826 PMCID: PMC6669749 DOI: 10.3390/v11070640] [Citation(s) in RCA: 75] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 07/08/2019] [Accepted: 07/09/2019] [Indexed: 12/23/2022] Open
Abstract
The Usutu virus (USUV) is a flavivirus that is drawing increasing attention because of its potential for emergence. First isolated in Africa, it was introduced into Europe where it caused significant outbreaks in birds, such as in Austria in 2001. Since then, its geographical distribution has rapidly expanded, with increased circulation, especially in the last few years. Similar to West Nile virus (WNV), the USUV enzootic transmission cycle involves Culex mosquitoes as vectors, and birds as amplifying reservoir hosts, with humans and other mammals likely being dead-end hosts. A similarity in the ecology of these two viruses, which co-circulate in several European countries, highlights USUV’s potential to become an important human pathogen. While USUV has had a severe impact on the blackbird population, the number of human cases remains low, with most infections being asymptomatic. However, some rare cases of neurological disease have been described, both in healthy and immuno-compromised patients. Here, we will discuss the transmission dynamics and the current state of USUV circulation in Europe.
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38
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West Nile Virus and Usutu Virus Co-Circulation in Europe: Epidemiology and Implications. Microorganisms 2019; 7:microorganisms7070184. [PMID: 31248051 PMCID: PMC6680635 DOI: 10.3390/microorganisms7070184] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 06/20/2019] [Accepted: 06/25/2019] [Indexed: 01/01/2023] Open
Abstract
West Nile virus (WNV) and Usutu virus (USUV) are neurotropic mosquito-borne flaviviruses that may infect humans. Although WNV is much more widespread and plays a much larger role in human health, the two viruses are characterized by similar envelope antigens, clinical manifestations, and present overlapping in terms of geographic range of transmission, host, and vector species. This review highlights some of the most relevant aspects of WNV and USUV human infections in Europe, and the possible implications of their co-circulation.
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Konjevoda S, Dzelalija B, Canovic S, Pastar Z, Savic V, Tabain I, Barbic L, Peric L, Sabadi D, Stevanovic V, Vilibic-Cavlek T. West Nile virus retinitis in a patient with neuroinvasive disease. Rev Soc Bras Med Trop 2019; 52:e20190065. [PMID: 31166490 DOI: 10.1590/0037-8682-0065-2019] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 04/16/2019] [Indexed: 11/22/2022] Open
Affiliation(s)
- Suzana Konjevoda
- Department of Ophthalmology, General Hospital Zadar, Zadar, Croatia.,Department of Health, University of Zadar, Zadar, Croatia
| | - Boris Dzelalija
- Department of Infectious Diseases, General Hospital Zadar, Zadar, Croatia
| | - Samir Canovic
- Department of Ophthalmology, General Hospital Zadar, Zadar, Croatia
| | - Zrinjka Pastar
- Department of Health, University of Zadar, Zadar, Croatia
| | - Vladimir Savic
- Poultry Center, Croatian Veterinary Institute, Zagreb, Croatia
| | - Irena Tabain
- Department of Virology, Croatian Institute of Public Health, Zagreb, Croatia
| | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
| | - Ljiljana Peric
- Department of Infectious Diseases, Clinical Hospital Center Osijek, Osijek, Croatia.,Medical Faculty, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Dario Sabadi
- Department of Infectious Diseases, Clinical Hospital Center Osijek, Osijek, Croatia.,Medical Faculty, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
| | - Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health, Zagreb, Croatia.,School of Medicine, University of Zagreb, Zagreb, Croatia
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40
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Vilibic-Cavlek T, Savic V, Sabadi D, Peric L, Barbic L, Klobucar A, Miklausic B, Tabain I, Santini M, Vucelja M, Dvorski E, Butigan T, Kolaric-Sviben G, Potocnik-Hunjadi T, Balenovic M, Bogdanic M, Andric Z, Stevanovic V, Capak K, Balicevic M, Listes E, Savini G. Prevalence and molecular epidemiology of West Nile and Usutu virus infections in Croatia in the 'One health' context, 2018. Transbound Emerg Dis 2019; 66:1946-1957. [PMID: 31067011 DOI: 10.1111/tbed.13225] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 04/19/2019] [Accepted: 05/03/2019] [Indexed: 12/14/2022]
Abstract
In 2018, Croatia reported the largest outbreak of West Nile virus (WNV) infections as well as the re-occurrence of human Usutu virus (USUV) infections. For the first time, fatal WNV and USUV infections were detected in wild birds. We analysed epidemiological characteristics and molecular epidemiology of WNV and USUV infections detected during 2018 transmission season. From April to November, 178 patients with neuroinvasive disease and 68 patients with febrile disease were tested for WNV and USUV. Viral RNA was detected in cerebrospinal fluid (CSF) and urine samples using a real-time RT-PCR. Positive samples were tested by nested RT-PCR and nucleotide sequencing. IgM/IgG antibodies were detected in serum/CSF samples using ELISA with confirmation of cross-reactive samples by virus neutralization test (VNT). WNV neuroinvasive disease was confirmed in 54 and WNV fever in seven patients from 10 continental Croatian counties. Areas affected in 2018 were those in which cases occurred in previous seasons, while in three areas human cases were reported for the first time. Phylogenetic analysis of six strains from patients residing in different geographic areas showed circulation of WNV lineage 2. In three patients, neuroinvasive USUV infection was confirmed by RT-PCR or VNT. Sequence analysis of one detected strain revealed USUV Europe 2 lineage. During the same period, a total of 2,574 horse and 1,069 poultry serum samples were tested for WNV antibodies using ELISA. Acute asymptomatic WNV infection (IgM antibodies) was documented in 20/0.7% horses. WNV IgG antibodies were found in 307/11.9% horses and in 125/12.7% poultry. WNV RNA was detected in two goshawks and USUV RNA was detected in one blackbird from north-western Croatia. In the Zagreb area, 3,670 female mosquitoes were collected. One Culex pipiens pool collected in July tested positive for USUV RNA. Our results highlight the importance of continuous multidisciplinary 'One health' surveillance of these emerging arboviruses.
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Affiliation(s)
- Tatjana Vilibic-Cavlek
- Croatian Institute of Public Health, Zagreb, Croatia.,School of Medicine, University of Zagreb, Zagreb, Croatia
| | | | - Dario Sabadi
- Clinical Hospital Center Osijek, Osijek, Croatia.,Medical Faculty, Josip Juraj Stossmayer University of Osijek, Osijek, Croatia
| | - Ljiljana Peric
- Clinical Hospital Center Osijek, Osijek, Croatia.,Medical Faculty, Josip Juraj Stossmayer University of Osijek, Osijek, Croatia
| | - Ljubo Barbic
- Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
| | - Ana Klobucar
- Andrija Stampar Teaching Institute of Public Health, Zagreb, Croatia
| | - Bozana Miklausic
- University Hospital for Infectious Diseases "Dr Fran Mihaljevic", Zagreb, Croatia
| | - Irena Tabain
- Croatian Institute of Public Health, Zagreb, Croatia
| | - Marija Santini
- School of Medicine, University of Zagreb, Zagreb, Croatia.,University Hospital for Infectious Diseases "Dr Fran Mihaljevic", Zagreb, Croatia
| | - Marko Vucelja
- Faculty of Forestry, University of Zagreb, Zagreb, Croatia
| | | | | | | | | | | | - Maja Bogdanic
- Croatian Institute of Public Health, Zagreb, Croatia
| | | | | | | | | | - Eddy Listes
- Croatian Veterinary Institute, Regional Institute Split, Split, Croatia
| | - Giovanni Savini
- OIE Reference Center for West Nile Disease, Istituto Zooprofilattico Sperimentale "G. Caporale", Teramo, Italy
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Usutu Virus Isolated from Rodents in Senegal. Viruses 2019; 11:v11020181. [PMID: 30795524 PMCID: PMC6409855 DOI: 10.3390/v11020181] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Revised: 01/19/2019] [Accepted: 01/21/2019] [Indexed: 01/23/2023] Open
Abstract
Usutu virus (USUV) is a Culex-associated mosquito-borne flavivirus of the Flaviviridae family. Since its discovery in 1959, the virus has been isolated from birds, arthropods and humans in Europe and Africa. An increasing number of Usutu virus infections in humans with neurological presentations have been reported. Recently, the virus has been detected in bats and horses, which deviates from the currently proposed enzootic cycle of USUV involving several different avian and mosquito species. Despite this increasing number of viral detections in different mammalian hosts, the existence of a non-avian reservoir remains unresolved. In Kedougou, a tropical region in the southeast corner of Senegal, Usutu virus was detected, isolated and sequenced from five asymptomatic small mammals: Two different rodent species and a single species of shrew. Additional molecular characterization and in vivo growth dynamics showed that these rodents/shrew-derived viruses are closely related to the reference strain (accession number: AF013412) and are as pathogenic as other characterized strains associated with neurological invasions in human. This is the first evidence of Usutu virus isolation from rodents or shrews. Our findings emphasize the need to consider a closer monitoring of terrestrial small mammals in future active surveillance, public health, and epidemiological efforts in response to USUV in both Africa and Europe.
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Segura Guerrero NA, Sharma S, Neyts J, Kaptein SJF. Favipiravir inhibits in vitro Usutu virus replication and delays disease progression in an infection model in mice. Antiviral Res 2018; 160:137-142. [PMID: 30385306 DOI: 10.1016/j.antiviral.2018.10.026] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 10/26/2018] [Accepted: 10/28/2018] [Indexed: 01/29/2023]
Abstract
Usutu virus (USUV) is an emerging flavivirus that causes Usutu disease mainly in birds, but infection of mammals such as rodents, bats and horses has also been demonstrated. In addition, human cases (both in immunocompromised and -competent individuals) were also reported. Large outbreaks with other flaviviruses, such as West Nile virus and Zika virus, indicate that one should be vigilant for yet other outbreaks. To allow the identification of inhibitors of USUV replication, we established in vitro antiviral assays, which were validated using a small selection of known flavivirus inhibitors, including the broad-spectrum viral RNA polymerase inhibitor favipiravir (T-705). Next, an USUV infection model in AG129 (IFN-α/β and IFN-γ receptor knockout) mice was established. AG129 mice proved highly susceptible to USUV; an inoculum as low as 102 PFU (1.3 × 105 TCID50) resulted in the development of symptoms as early as 3 days post infection with viral RNA being detectable in various tissues. Treatment of mice with favipiravir (150 mg/kg/dose, BID, oral gavage) significantly reduced viral load in blood and tissues and significantly delayed virus-induced disease. This USUV mouse model is thus amenable for assessing the potential in vivo efficacy of (novel) USUV/flavivirus inhibitors.
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Affiliation(s)
- Nidya A Segura Guerrero
- KU Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium; Universidad Pedagógica y Tecnológica de Colombia, Tunja, Colombia
| | - Sapna Sharma
- KU Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium
| | - Johan Neyts
- KU Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
| | - Suzanne J F Kaptein
- KU Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium
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43
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Vilibic-Cavlek T, Kristofic B, Savic V, Kolaric B, Barbic L, Tabain I, Peric L, Sabadi D, Miklausic B, Potocnik-Hunjadi T, Zember S, Stevanovic V, Listes E, Savini G. Diagnostic significance of immunoglobulin G avidity in symptomatic and asymptomatic West Nile virus infection. Rev Soc Bras Med Trop 2018; 51:591-595. [PMID: 30304263 DOI: 10.1590/0037-8682-0482-2017] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 07/18/2018] [Indexed: 12/30/2022] Open
Abstract
INTRODUCTION West Nile virus (WNV) immunoglobulin M (IgM) antibodies have been shown to persist for up to 500 days in certain patients. To evaluate the usefulness of immunoglobulin G (IgG) avidity assessment in the diagnosis of WNV infection, we analyzed 54 WNV IgM- and/or IgG-positive serum samples from 39 patients with neuroinvasive disease and 15 asymptomatic cases tested during a seroprevalence investigation. METHODS Serological tests (WNV IgM/IgG antibody detection, IgG avidity) were performed using commercially available enzyme-linked immunosorbent assays. RESULTS WNV IgM antibodies were detected in 47 (87%) samples. Acute/recent WNV infection was confirmed based on low/borderline avidity index (AI) in 44 IgM-positive samples (93.6%). In three IgM-positive samples (6.4%), high IgG AIs were detected, thus indicating persisting IgM antibodies from previous infections. All IgM-negative samples showed high AIs. Patients with WNV neuroinvasive disease tested within 30 days showed low AIs. In six patients tested 34-50 days after disease onset, AI was borderline (42%-60%), suggesting earlier WNV IgG maturation. Samples with the highest IgM values were associated with the lowest AIs (Spearman's rho coefficient -0.767, p < 0.001). CONCLUSIONS Our results indicate that IgG avidity differentiates current/recent WNV infection from persistent IgM seropositivity from the previous WNV transmission season both in patients with WNV neuroinvasive disease and in asymptomatic persons. A strong negative correlation between IgM antibody levels and AI indicates that in cases with very high IgM levels, determination of IgG avidity may not be necessary. As many patients showed rapid avidity maturation, low IgG avidity is indicative of WNV infection within the previous month.
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Affiliation(s)
- Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health, Zagreb, Croatia.,School of Medicine University of Zagreb, Zagreb, Croatia
| | - Branimir Kristofic
- Department of Gynecology and Obstetrics, County Hospital Cakovec, Cakovec, Croatia
| | - Vladimir Savic
- Poultry Centre, Croatian Veterinary Institute, Zagreb, Croatia
| | - Branko Kolaric
- Department of Epidemiology, Andrija Stampar Teaching Institute of Public Health, Zagreb, Croatia.,School of Medicine University of Rijeka, Rijeka, Croatia
| | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
| | - Irena Tabain
- Department of Virology, Croatian Institute of Public Health, Zagreb, Croatia
| | - Ljiljana Peric
- Department of Infectious Diseases, Clinical Hospital Centre Osijek, Osijek,Croatia.,Medical Faculty, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Dario Sabadi
- Department of Infectious Diseases, Clinical Hospital Centre Osijek, Osijek,Croatia.,Medical Faculty, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Bozana Miklausic
- Department of Infectious Diseases, General Hospital "Dr Josip Bencevic", Slavonski Brod, Croatia
| | | | - Sanja Zember
- Department of Infectious Diseases, General Hospital Varazdin, Varazdin, Croatia
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
| | - Eddy Listes
- Croatian Veterinary Institute, Regional Institute Split, Split, Croatia
| | - Giovanni Savini
- OIE Reference Centre for West Nile Disease, Istituto Zooprofilattico Sperimentale "G. Caporale", Teramo, Italy
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Cheng Y, Tjaden NB, Jaeschke A, Lühken R, Ziegler U, Thomas SM, Beierkuhnlein C. Evaluating the risk for Usutu virus circulation in Europe: comparison of environmental niche models and epidemiological models. Int J Health Geogr 2018; 17:35. [PMID: 30314528 PMCID: PMC6186058 DOI: 10.1186/s12942-018-0155-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 10/08/2018] [Indexed: 12/16/2022] Open
Abstract
Background Usutu virus (USUV) is a mosquito-borne flavivirus, reported in many countries of Africa and Europe, with an increasing spatial distribution and host range. Recent outbreaks leading to regional declines of European common blackbird (Turdus merula) populations and a rising number of human cases emphasize the need for increased awareness and spatial risk assessment. Methods Modelling approaches in ecology and epidemiology differ substantially in their algorithms, potentially resulting in diverging model outputs. Therefore, we implemented a parallel approach incorporating two commonly applied modelling techniques: (1) Maxent, a correlation-based environmental niche model and (2) a mechanistic epidemiological susceptible-exposed-infected-removed (SEIR) model. Across Europe, surveillance data of USUV-positive birds from 2003 to 2016 was acquired to train the environmental niche model and to serve as test cases for the SEIR model. The SEIR model is mainly driven by daily mean temperature and calculates the basic reproduction number R0. The environmental niche model was run with long-term bio-climatic variables derived from the same source in order to estimate climatic suitability. Results Large areas across Europe are currently suitable for USUV transmission. Both models show patterns of high risk for USUV in parts of France, in the Pannonian Basin as well as northern Italy. The environmental niche model depicts the current situation better, but with USUV still being in an invasive stage there is a chance for under-estimation of risk. Areas where transmission occurred are mostly predicted correctly by the SEIR model, but it mostly fails to resolve the temporal dynamics of USUV events. High R0 values predicted by the SEIR model in areas without evidence for real-life transmission suggest that it may tend towards over-estimation of risk. Conclusions The results from our parallel-model approach highlight that relying on a single model for assessing vector-borne disease risk may lead to incomplete conclusions. Utilizing different modelling approaches is thus crucial for risk-assessment of under-studied emerging pathogens like USUV. Electronic supplementary material The online version of this article (10.1186/s12942-018-0155-7) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yanchao Cheng
- Department of Biogeography, University of Bayreuth, Universitätsstr. 30, 95447, Bayreuth, Germany.
| | - Nils Benjamin Tjaden
- Department of Biogeography, University of Bayreuth, Universitätsstr. 30, 95447, Bayreuth, Germany
| | - Anja Jaeschke
- Department of Biogeography, University of Bayreuth, Universitätsstr. 30, 95447, Bayreuth, Germany
| | - Renke Lühken
- Bernhard Nocht Institute for Tropical Medicine, World Health Organization Collaborating Centre for Arbovirus and Hemorrhagic Fever Reference and Research, Hamburg, Germany
| | - Ute Ziegler
- Friedrich-Loeffler-Institut, Institute of Novel and Emerging Infectious Diseases, Südufer 10, 17493, Greifswald - Insel Riems, Germany
| | | | - Carl Beierkuhnlein
- Department of Biogeography, University of Bayreuth, Universitätsstr. 30, 95447, Bayreuth, Germany.,BayCEER, Bayreuth Center for Ecology and Environmental Research, Bayreuth, Germany
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45
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Extinction of Zika Virus and Usutu Virus by Lethal Mutagenesis Reveals Different Patterns of Sensitivity to Three Mutagenic Drugs. Antimicrob Agents Chemother 2018; 62:AAC.00380-18. [PMID: 29914957 PMCID: PMC6125542 DOI: 10.1128/aac.00380-18] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 06/12/2018] [Indexed: 01/02/2023] Open
Abstract
Flaviviruses constitute an increasing source of public health concern, with growing numbers of pathogens causing disease and geographic spread to temperate climates. Despite a large body of evidence supporting mutagenesis as a conceivable antiviral strategy, there are currently no data on the sensitivity to increased mutagenesis for Zika virus (ZIKV) and Usutu virus (USUV), two emerging flaviviral threats. Flaviviruses constitute an increasing source of public health concern, with growing numbers of pathogens causing disease and geographic spread to temperate climates. Despite a large body of evidence supporting mutagenesis as a conceivable antiviral strategy, there are currently no data on the sensitivity to increased mutagenesis for Zika virus (ZIKV) and Usutu virus (USUV), two emerging flaviviral threats. In this study, we demonstrate that both viruses are sensitive to three ribonucleosides, favipiravir, ribavirin, and 5-fluorouracil, that have shown mutagenic activity against other RNA viruses while remaining unaffected by a mutagenic deoxyribonucleoside. Serial cell culture passages of ZIKV in the presence of these compounds resulted in the rapid extinction of infectivity, suggesting elevated sensitivity to mutagenesis. USUV extinction was achieved when a 10-fold dilution was applied between every passage, but not in experiments involving undiluted virus, indicating an overall lower susceptibility than ZIKV. Although the two viruses are inhibited by the same three drugs, ZIKV is relatively more susceptive to serial passage in the presence of purine analogues (favipiravir and ribavirin), while USUV replication is suppressed more efficiently by 5-fluorouracil. These differences in sensitivity typically correlate with the increases in the mutation frequencies observed in each nucleoside treatment. These results are relevant to the development of efficient therapies based on lethal mutagenesis and support the rational selection of different mutagenic nucleosides for each pathogen. We will discuss the implications of these results to the fidelity of flavivirus replication and the design of antiviral therapies based on lethal mutagenesis.
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46
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Lühken R, Jöst H, Cadar D, Thomas SM, Bosch S, Tannich E, Becker N, Ziegler U, Lachmann L, Schmidt-Chanasit J. Distribution of Usutu Virus in Germany and Its Effect on Breeding Bird Populations. Emerg Infect Dis 2018; 23:1994-2001. [PMID: 29148399 PMCID: PMC5708248 DOI: 10.3201/eid2312.171257] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Usutu virus (USUV) is an emerging mosquitoborne flavivirus with an increasing number of reports from several countries in Europe, where USUV infection has caused high avian mortality rates. However, 20 years after the first observed outbreak of USUV in Europe, there is still no reliable assessment of the large-scale impact of USUV outbreaks on bird populations. In this study, we identified the areas suitable for USUV circulation in Germany and analyzed the effects of USUV on breeding bird populations. We calculated the USUV-associated additional decline of common blackbird (Turdus merula) populations as 15.7% inside USUV-suitable areas but found no significant effect for the other 14 common bird species investigated. Our results show that the emergence of USUV is a further threat for birds in Europe and that the large-scale impact on population levels, at least for common blackbirds, must be considered.
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The field is moving on: new diagnostic and therapeutic tools presented at the 28th ECCMID 2018. Infection 2018; 46:289-291. [DOI: 10.1007/s15010-018-1142-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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First genetic characterization of Usutu virus from Culex pipiens mosquitoes Serbia, 2014. INFECTION GENETICS AND EVOLUTION 2018; 63:58-61. [PMID: 29778766 DOI: 10.1016/j.meegid.2018.05.012] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 04/11/2018] [Accepted: 05/16/2018] [Indexed: 02/05/2023]
Abstract
Since its first appearance in Europe, Usutu virus (USUV) diverged to several different genetic lineages. The virus was reported to date from multiple countries across Europe (Hungary, Italy, Switzerland, Spain, Germany, Czech Republic and Belgium). Considering the more frequently published impact of the virus on humans it is crucial to investigate locally circulating genetic variants and trace its evolution. We retrospectively analyzed mosquito samples from Serbia Vojvodina region, collected during 2014. In this study we report the results of the screening of 23,753 female mosquitoes (753 pools) for USUV-specific nucleic-acid. Out of the 753 pools sampled, the presence of USUV RNA was confirmed in 3 pools of Culex pipiens mosquitoes, collected in August. Based on their partial NS5 sequence, all strains were identical, therefore we adjusted one representative strain for complete genome sequencing. Based on phylogenetic analysis the Serbian USUV sequences were most closely related to the virus that emerged in Austria in 2001, in Hungary in 2005 and was circulating until 2015 in Hungary. This data presents a wider geographic distribution of this genetic variant and provides the first genetic data from this region.
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Eiden M, Gil P, Ziegler U, Rakotoarivony I, Marie A, Frances B, L'Ambert G, Simonin Y, Foulongne V, Groschup MH, Gutierrez S, Eloit M. Emergence of two Usutu virus lineages in Culex pipiens mosquitoes in the Camargue, France, 2015. INFECTION GENETICS AND EVOLUTION 2018; 61:151-154. [PMID: 29592838 DOI: 10.1016/j.meegid.2018.03.020] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Revised: 03/01/2018] [Accepted: 03/22/2018] [Indexed: 11/29/2022]
Abstract
Usutu virus (USUV) was detected in 11 Culex pipiens mosquito pools collected in 2015 in Camargue (France) using quantitative real-time RT-PCR assays. Phylogenetic analysis of recovered virus sequences identified USUV lineages Africa 2 and Africa 3, demonstrating the simultaneous occurrence of different strains within the mosquito population. This is the first report on USUV in mosquitoes from France that concurrently accompanied the emergence of Usutu virus in blackbirds and a human case in France during 2015/2016.
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Affiliation(s)
- Martin Eiden
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald, Insel Riems, Germany
| | - Patricia Gil
- CIRAD, UMR ASTRE, F-34398 Montpellier, France; ASTRE, Université de Montpellier, CIRAD, INRA, Montpellier, France
| | - Ute Ziegler
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald, Insel Riems, Germany
| | - Ignace Rakotoarivony
- CIRAD, UMR ASTRE, F-34398 Montpellier, France; ASTRE, Université de Montpellier, CIRAD, INRA, Montpellier, France
| | - Albane Marie
- EID Mediterranée, 165 Avenue Paul Rimbaud, 34184 Montpellier, France
| | - Benoit Frances
- EID Mediterranée, 165 Avenue Paul Rimbaud, 34184 Montpellier, France
| | - Grégory L'Ambert
- EID Mediterranée, 165 Avenue Paul Rimbaud, 34184 Montpellier, France
| | - Yannick Simonin
- Pathogenesis and Control of Chronic Infections, Université de Montpellier, INSERM, EFS, Montpellier, France
| | - Vincent Foulongne
- Pathogenesis and Control of Chronic Infections, Université de Montpellier, INSERM, EFS, Montpellier, France
| | - Martin H Groschup
- Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald, Insel Riems, Germany
| | - Serafin Gutierrez
- CIRAD, UMR ASTRE, F-34398 Montpellier, France; ASTRE, Université de Montpellier, CIRAD, INRA, Montpellier, France.
| | - Marc Eloit
- Institut Pasteur, Biology of Infection Unit, Inserm U1117, Pathogen Discovery Laboratory, Paris, France
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Reusken CB, Ieven M, Sigfrid L, Eckerle I, Koopmans M. Laboratory preparedness and response with a focus on arboviruses in Europe. Clin Microbiol Infect 2017; 24:221-228. [PMID: 29274465 DOI: 10.1016/j.cmi.2017.12.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2017] [Revised: 12/08/2017] [Accepted: 12/12/2017] [Indexed: 12/29/2022]
Abstract
BACKGROUND The global health burden of arboviruses is continuously rising, which results in increasing pressure on local and (inter)national laboratory infrastructures. Timely and accurate diagnosis of cases is one of the main pillars for public health and clinical responses to an arbovirus emergence. AIMS AND SOURCES This narrative review aims to summarize recent advances and to identify needs in laboratory preparedness and response activities, with a focus on viruses transmitted by arthropods in Europe. The review is based on evidence extracted from PubMed searches, Public Health and clinical laboratory experiences from the authors and the authors' opinions substantiated by peer-reviewed scientific literature. CONTENT We illustrate the importance of inter-epidemic laboratory preparedness activities to ensure adequate Public Health and clinical responses. We describe the status of arbovirus endemicity and emergence in Europe thereby highlighting the need for preparedness for these viruses. We discuss the components and pitfalls of an adequate laboratory preparedness and response and the broader context of the current landscape of international research, clinical and laboratory preparedness networks. The complexity of arbovirus laboratory preparedness and response is described. IMPLICATIONS Outbreak preparedness plans need to look beyond national reference laboratories, to include first-line responding onsite hospital laboratories and plans for strengthening of such local capacity and capability as required depending on the nature of the outbreak. In particular, the diagnosis of arbovirus infections is complicated by the existence of geographic overlap of circulation of numerous arboviruses, the overlap in clinical manifestation between many arboviruses and other aetiologies and the existence of cross-reactivity between related arboviruses in serology testing. Inter-epidemic preparedness activities need strong national and international networks addressing these issues. However, the current mushrooming of European preparedness networks requires governance to bring the European preparedness and response to a next level.
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Affiliation(s)
- C B Reusken
- Department of Viroscience, WHO Collaborating Center for Arboviruses and Viral Haemorrhagic Fever Reference and Research, Erasmus University Medical Centre, Rotterdam, the Netherlands.
| | - M Ieven
- Department of Medical Microbiology, Antwerp University Hospital, Antwerp, Belgium; Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium
| | - L Sigfrid
- Centre for Tropical Medicine and Global Health, Nuffield Dept. of Medicine, University of Oxford, Oxford, UK
| | - I Eckerle
- Institut für Virologie. Universitätsklinikum Bonn, Bonn, Germany
| | - M Koopmans
- Department of Viroscience, WHO Collaborating Center for Arboviruses and Viral Haemorrhagic Fever Reference and Research, Erasmus University Medical Centre, Rotterdam, the Netherlands
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