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Tebibi K, Ben Laamari R, Saied Z, Maghrebi O, Touzi H, Meddeb Z, Ben Sassi S, Triki H, Belghith M, Rezig D. Profile of Cytokines and T Cell Subsets Transcription Factors in Cerebrospinal Fluid of Patients with Viral Encephalitis. Viral Immunol 2024; 37:459-469. [PMID: 39527011 DOI: 10.1089/vim.2024.0058] [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] [Indexed: 11/16/2024] Open
Abstract
This study investigates the demographic, clinical characteristics, virological profiles, and immunological responses of patients with viral encephalitis (VE) compared with a control group. The VE group displayed a wide range of neurological symptoms. Virological analysis revealed the predominance of Herpesviridae family viruses. Immune responses in cerebrospinal fluid (CSF) from patients with VE were examined, highlighting an immunological shift toward T helper 1 (Th1) cells dominance, altered T helper 17 cells/regulatory T cells (Th17/Tregs) balance, and high interleukin-6 expression. These findings provide insights into the complex immunological landscape of VE, highlighting the role of specific cytokines and T cell subsets in its pathogenesis and potentially guiding targeted therapeutic strategies.
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Affiliation(s)
- Khadija Tebibi
- Research Laboratory "Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health", Pasteur Institute of Tunis, Tunis, Tunisia
- Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Rafika Ben Laamari
- Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia
- Laboratory of Transmission, Control, and Immunobiology of Infections, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Zakaria Saied
- Neurological Department of Mongi Ben Hmida Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Olfa Maghrebi
- Laboratory of Transmission, Control, and Immunobiology of Infections, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Henda Touzi
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis, Tunisia
| | - Zina Meddeb
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis, Tunisia
| | - Samia Ben Sassi
- Neurological Department of Mongi Ben Hmida Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Henda Triki
- Research Laboratory "Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health", Pasteur Institute of Tunis, Tunis, Tunisia
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis, Tunisia
| | - Meriam Belghith
- Laboratory of Transmission, Control, and Immunobiology of Infections, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Dorra Rezig
- Research Laboratory "Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health", Pasteur Institute of Tunis, Tunis, Tunisia
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University of Tunis El Manar (UTM), Tunis, Tunisia
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Hoxha I, Trájer AJ, Dvorak V, Halada P, Šupić J, Obwaller AG, Poeppl W, Walochnik J, Alić A, Kniha E. Phlebotomine sand flies (Diptera: Psychodidae) of Bosnia and Herzegovina: distribution, ecology and environmental preferences. Acta Trop 2024; 260:107393. [PMID: 39278523 DOI: 10.1016/j.actatropica.2024.107393] [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: 08/12/2024] [Accepted: 09/07/2024] [Indexed: 09/18/2024]
Abstract
Sand flies (Diptera: Phlebotominae) are the principal vectors for the protozoan parasites Leishmania spp. and for phleboviruses. The sand fly fauna on the Balkan Peninsula, including Bosnia and Herzegovina (BIH), is diverse and the circulation of Leishmania infantum as well as phleboviruses has been proven. However, recent data on the sand fly fauna in BIH are scarce. In this study, we surveyed understudied regions in central and northeastern BIH to update the sand fly distribution and gain insights into the ecological and environmental factors shaping their appearance. CDC light trapping was conducted in 2022 and 2023 and a combination of morphological and molecular methods (cytochrome oxidase I barcoding) was performed for species identifications. We mapped the currently known distribution, modelled climatic suitability patterns and performed environmental analyses by applying machine learning methods. In addition, we analyzed blood meals by host gene sequencing and MALDI-TOF peptide mass mapping and screened for Leishmania spp. DNA and Phlebovirus RNA. Altogether, 591 sand flies of four species were trapped, predominantly Phlebotomus neglectus (97 %), but also Ph. balcanicus, Ph. mascittii, and Ph. papatasi. Records of seven sand fly species known to be endemic were plotted onto distribution maps based on 101 datapoints, identifying Ph. neglectus as the overall predominant species. The environmental analyses of sand fly species indicated variation in altitudinal, thermal, and precipitation conditions across the sand fly-positive sites. Phlebotomus simici, Phlebotomus tobbi, and Sergentomyia minuta are typically found exclusively in Mediterranean and subtropical climate zones, whereas other species typically inhabit continental regions. The Inverse Distance Weighted (IDW) interpolation of sand fly species numbers and Shannon entropy values suggested the southeastern coastal region of BIH as a primary focus for sand fly occurrence. This finding was corroborated by modeled average climatic suitability patterns for sand flies, depicting four distinct meso-regions for sand fly occurrence. The results of the ensemble method highlight the importance of annual precipitation to distinguish between positive and negative sand fly trapping sites in BIH. In total, 55 blood meals of two sand fly species, Ph. neglectus and Ph. balcanicus, were analyzed and five host species identified. Our comprehensive assessment of ecological and environmental preferences of sand flies in BIH may support further entomological surveys and help to better understand and evaluate potential hot spots of disease transmission in the country.
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Affiliation(s)
- Ina Hoxha
- Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria
| | - Attila J Trájer
- University of Pannonia, Sustainability Solutions Research Lab, Veszprém, Hungary
| | - Vít Dvorak
- Department of Parasitology, Faculty of Science, Charles University Prague, Prague, Czech Republic
| | - Petr Halada
- BioCeV, Institute of Microbiology of The Czech Academy of Sciences, Vestec, Czech Republic
| | - Jovana Šupić
- Department of Clinical Sciences of Veterinary Medicine, Faculty of Veterinary Medicine, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Adelheid G Obwaller
- Division of Science, Research and Development, Federal Ministry of Defence, Vienna, Austria
| | - Wolfgang Poeppl
- Department of Dermatology and Tropical Medicine, Military Medical Cluster East, Austrian Armed Forces, Vienna, Austria
| | - Julia Walochnik
- Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria
| | - Amer Alić
- Department of Clinical Sciences of Veterinary Medicine, Faculty of Veterinary Medicine, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
| | - Edwin Kniha
- Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria.
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Keskek Turk Y, Ergunay K, Kohl A, Hughes J, McKimmie CS. Toscana virus - an emerging Mediterranean arbovirus transmitted by sand flies. J Gen Virol 2024; 105:002045. [PMID: 39508743 PMCID: PMC11542635 DOI: 10.1099/jgv.0.002045] [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] [Accepted: 10/15/2024] [Indexed: 11/15/2024] Open
Abstract
Toscana virus (TOSV) is an emerging arthropod-borne virus (arbovirus) of medical importance that is increasing its range across much of the Mediterranean Basin, Europe and the Middle East. Transmitted by Phlebotomus spp. sand flies, it is the most clinically relevant sand fly-borne phlebovirus. Initially isolated in the Tuscany region of Central Italy, it has now been detected in multiple countries that surround this geographical area. Infection of the vertebrate host can cause fever and neurological disease, following the dissemination of the virus to the brain. The prevalence is high in some regions, with a notable percentage of individuals showing seroconversion. TOSV can be a leading cause of acute meningitis and encephalitis (AME) during the summer months. In this comprehensive review, we will focus on several key topics. We discuss how TOSV has spread to establish outbreaks of infection in both humans and animals around the Mediterranean and the wider region. Clinical aspects of TOSV infection in humans are described, along with the best standards in diagnosis. Finally, we focus our discussion on the role of the sand fly vector, describing their biology, vector competency, implications for putative vertebrate reservoirs, the effect of the climate emergency on sand fly distribution and the putative role that sand fly-derived salivary factors may have on modulating host susceptibility to TOSV infection.
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Affiliation(s)
| | - Koray Ergunay
- Walter Reed Biosystematics Unit (WRBU), Smithsonian Institution, Museum Support Center, Suitland, MD, USA
- One Health Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, USA
- Department of Entomology, Smithsonian Institution–National Museum of Natural History (NMNH), Washington, DC, USA
- Department of Medical Microbiology, Virology Unit, Faculty of Medicine, Hacettepe University, Ankara, Türkiye
| | - Alain Kohl
- Centre for Neglected Tropical Diseases, Departments of Tropical Disease Biology and Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK
| | - Joseph Hughes
- MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, Scotland, UK
| | - Clive S. McKimmie
- Skin Research Centre, York Biomedical Research Institute, Hull York Medical School, University of York, York, UK
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Laroche L, Bañuls AL, Charrel R, Fontaine A, Ayhan N, Prudhomme J. Sand flies and Toscana virus: Intra-vector infection dynamics and impact on Phlebotomus perniciosus life-history traits. PLoS Negl Trop Dis 2024; 18:e0012509. [PMID: 39321202 PMCID: PMC11458028 DOI: 10.1371/journal.pntd.0012509] [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: 04/01/2024] [Revised: 10/07/2024] [Accepted: 09/04/2024] [Indexed: 09/27/2024] Open
Abstract
Toscana virus (TOSV) is a leading cause of summer viral meningitis in Southern Europe (Central Italy, south of France, Spain and Portugal) and can cause severe neurological cases. Within the Mediterranean basin, it is transmitted by hematophagous sand flies belonging to the Phlebotomus genus. Despite the identification of the primary TOSV vectors, the viral developmental cycle in vector species remains largely unknown. Limited research has been conducted on transmission dynamics and the vector competence and vectorial capacity of the principal TOSV vector, Phlebotomus perniciosus. In this context, we investigated the intra-vector TOSV infection dynamics in Ph. perniciosus, as well as its impact on the vector life history traits. Female sand flies were experimentally infected with TOSV through an artificial blood meal. Systemic dissemination of the virus was observed approximately three days post-infection, potentially resulting in a short extrinsic incubation period. Moreover, the study revealed a longer hatching time for eggs laid by infected females. This research brought additional experimental insights regarding the vector competence of Ph. perniciosus but also provided the first insight into TOSV developmental cycle and its impact on the vector. These findings prompt further exploration of TOSV transmission dynamics, raise new hypotheses on the virus transmission and highlight the importance of follow-up studies.
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Affiliation(s)
- Lison Laroche
- MIVEGEC, Université de Montpellier – IRD – CNRS, Centre IRD, Montpellier, France
- Department of Life Sciences, Imperial College London, London, United Kingdom
| | - Anne-Laure Bañuls
- MIVEGEC, Université de Montpellier – IRD – CNRS, Centre IRD, Montpellier, France
| | - Rémi Charrel
- Unité des Virus Emergents (UVE: Aix-Marseille Univ, Universita di Corsica, IRD 190, Inserm 1207, IRBA), Marseille, France
| | - Albin Fontaine
- Unité des Virus Emergents (UVE: Aix-Marseille Univ, Universita di Corsica, IRD 190, Inserm 1207, IRBA), Marseille, France
- Unité de virologie, Département Microbiologie et maladies infectieuses, Institut de Recherche Biomédicale des Armées (IRBA), Marseille, France
| | - Nazli Ayhan
- Unité des Virus Emergents (UVE: Aix-Marseille Univ, Universita di Corsica, IRD 190, Inserm 1207, IRBA), Marseille, France
- Centre National de Référence des Arbovirus, Marseille, France
| | - Jorian Prudhomme
- MIVEGEC, Université de Montpellier – IRD – CNRS, Centre IRD, Montpellier, France
- Université de Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Santé Environnement Travail), UMR_S 1085, Rennes, France
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Marsili G, Pallotto C, Fortuna C, Amendola A, Fiorentini C, Esperti S, Blanc P, Suardi LR, Giulietta V, Argentini C. Fifty years after the first identification of Toscana virus in Italy: Genomic characterization of viral isolates within lineage A and aminoacidic markers of evolution. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2024; 122:105601. [PMID: 38830443 DOI: 10.1016/j.meegid.2024.105601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 04/18/2024] [Accepted: 05/03/2024] [Indexed: 06/05/2024]
Abstract
Toscana Virus (TosV) was firstly isolated from phlebotomine in our Institute about fifty years ago. Later, in 1984-1985, TosV infection, although asymptomatic in most cases, was shown to cause disease in humans, mainly fever and meningitis. By means of genetic analysis of part of M segment, we describe 3 new viral isolates obtained directly from cerebrospinal fluid or sera samples of patients diagnosed with TosV infection in July 2020 in Tuscany region. Phylogenesis was used to propose the clustering of TosV lineage A strains in 3 main groups, whereas deep mutational analysis based on 12 amino acid positions, allowed the identification of 9 putative strains. We discuss deep mutational analysis as a method to identify molecular signature of host adaptation and/or pathogenesis.
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Affiliation(s)
- Giulia Marsili
- Dipartimento di Malattie Infettive, Istituto Superiore di Sanità, Roma, Italy
| | - Carlo Pallotto
- SOC Malattie Infettive 1, Azienda USL Toscana Centro, Bagno a Ripoli, Firenze, Italy; Clinica delle Malattie Infettive, Azienda Ospedaliera Santa Maria della Misericordia, Università di Perugia, Perugia, Italy
| | - Claudia Fortuna
- Dipartimento di Malattie Infettive, Istituto Superiore di Sanità, Roma, Italy
| | - Antonello Amendola
- Dipartimento di Malattie Infettive, Istituto Superiore di Sanità, Roma, Italy
| | | | - Sara Esperti
- SOC Malattie Infettive 1, Azienda USL Toscana Centro, Bagno a Ripoli, Firenze, Italy; Dipartimento di Malattie Infettive, Azienda Ospedaliero-Universitaria di Modena, Policlinico di Modena, Università di Modena e Reggio Emilia, Modena, Italy
| | - Pierluigi Blanc
- SOC Malattie Infettive 1, Azienda USL Toscana Centro, Bagno a Ripoli, Firenze, Italy; SOC Malattie Infettive 2, Azienda USL Toscana Centro, Pistoia, Italy
| | - Lorenzo Roberto Suardi
- SOC Malattie Infettive 1, Azienda USL Toscana Centro, Bagno a Ripoli, Firenze, Italy; UO Malattie Infettive, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Venturi Giulietta
- Dipartimento di Malattie Infettive, Istituto Superiore di Sanità, Roma, Italy
| | - Claudio Argentini
- Dipartimento di Malattie Infettive, Istituto Superiore di Sanità, Roma, Italy.
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Polat C, Ayhan N, Ergünay K, Charrel RN. Comprehensive evaluation of nucleic acid amplification methods widely used for generic detection of sandfly-borne phleboviruses. Microbiol Spectr 2024; 12:e0342823. [PMID: 38456695 PMCID: PMC10986501 DOI: 10.1128/spectrum.03428-23] [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: 09/22/2023] [Accepted: 02/13/2024] [Indexed: 03/09/2024] Open
Abstract
Sandfly-borne phleboviruses (SBPs), which cause sandfly fever, aseptic meningitis, encephalitis, and meningoencephalitis, are emerging pathogens of major public health concern. Virus nucleic acid testing is essential for SBP diagnosis, especially in the early stages of infection, and for the discovery of novel SBPs. The efficacy of utilizing generic primers that target conserved nucleotide sequences for the detection of both known and novel SBPs has not been extensively evaluated. We aimed to compare and evaluate the performance of five generic primer sets, widely used to detect S- and L-segments of arthropod-borne phleboviruses and designed as singleplex (n = 3) and nested (n = 2) formats, including both well-known and recently characterized 15 Old World virus strains. Furthermore, we performed in silico analysis to assess the detection capabilities of these generic primer sets. The initial evaluation of previously published generic primer sets for SBP detection yielded two singleplex primer sets with the potential to be adapted for use in real-time or high-throughput detection settings. Studies are ongoing to develop and further optimize a preliminary assay and test various hosts and vectors to assess their capacity to detect known and novel viruses. IMPORTANCE Virus nucleic acid testing is the primary diagnostic method, particularly in the early stages of illness. Virus-specific or syndromic tests are widely used for this purpose. The use of generic primers has had a considerable impact on the discovery, identification, and detection of Old World sandfly-borne phleboviruses (OWSBP). The study is significant because it is the first to carry out a comparative evaluation of all published OWSBP generic primer sets.
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Affiliation(s)
- Ceylan Polat
- Department of Medical Microbiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
- Unité des Virus Emergents, Aix Marseille University, Marseille, France
| | - Nazli Ayhan
- Unité des Virus Emergents, Aix Marseille University, Marseille, France
- National Reference Center for Arboviruses, National Institute of Health, and Medical Research (Inserm) and French Armed Forces Biomedical Research Institute (IRBA), Marseille, France
| | - Koray Ergünay
- Department of Medical Microbiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
- Walter Reed Biosystematics Unit (WRBU), Smithsonian Institution Museum Support Center, Suitland, Maryland, USA
- One Health Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland, USA
- Department of Entomology, Smithsonian Institution-National Museum of Natural History (NMNH), Washington, DC, USA
| | - Remi N. Charrel
- Unité des Virus Emergents, Aix Marseille University, Marseille, France
- Laboratoire des Infections Virales Aigues et Tropicales, Pole des Maladies Infectieuses, AP-HM Hopitaux Universitaires de Marseille, Marseille, France
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Mori A, Matucci A, Pomari E, Accordini S, Piubelli C, Donini A, Nicolini L, Castilletti C. Urine: A Pitfall for Molecular Detection of Toscana Virus? An Analytical Proof-of-Concept Study. Viruses 2024; 16:98. [PMID: 38257798 PMCID: PMC10821263 DOI: 10.3390/v16010098] [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: 11/21/2023] [Revised: 01/03/2024] [Accepted: 01/05/2024] [Indexed: 01/24/2024] Open
Abstract
Toscana virus (TOSV), a sandfly-borne virus, is an important etiological agent in human acute meningitis and meningoencephalitis in the Mediterranean area during the summer. However, the actual number of TOSV infections is underestimated. Laboratory confirmation is necessary because TOSV infection has overlapping clinical features with other neuro-invasive viral infections. Nowadays, the reference test for direct diagnosis in the acute phase of TOSV infection is the PCR based method for detecting TOSV in cerebrospinal fluid and/or plasma, serum, or blood. Although poorly employed, urine is another helpful biological matrix for TOSV detection. Urine is a matrix rich in PCR inhibitors that affect PCR efficiency; consequently, false negatives could be generated. To investigate the potential effect of urine PCR inhibitors on TOSV detection, we compared undiluted and diluted urine using 10-fold series of spiked TOSV. The results showed a significant improvement in TOSV detection performance in diluted urine (1 TCID50 vs. 1 × 104 TCID50 limit of detection and 101.35% vs. 129.62% efficiency, respectively, in diluted and undiluted urine). In conclusion, our data provide preliminary important insights into the use of diluted urine to limit the impact of the inhibitory effects of urine on the detection of TOSV in RT-PCR-based approaches.
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Affiliation(s)
| | | | - Elena Pomari
- Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, 37024 Verona, Italy; (A.M.); (S.A.); (C.P.); (A.D.); (L.N.)
| | | | | | | | | | - Concetta Castilletti
- Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, 37024 Verona, Italy; (A.M.); (S.A.); (C.P.); (A.D.); (L.N.)
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García-Cervera C, Iftimie SM, Martínez MJ, Vázquez González A, Parra-Pérez S, Revuelta-López-Cordón L, Gil-Toral J, Vileu Vallverdu RM, Martínez Mateo A, López-Azcona AF, Pujol-Bajador I, Ballester-Bastardie F, Castro-Salomó A. Report on the first two confirmed autochthonous cases of West Nile virus encephalitis in Catalonia, Spain. Infect Dis (Lond) 2023; 55:798-802. [PMID: 37471287 DOI: 10.1080/23744235.2023.2236703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 07/06/2023] [Accepted: 07/10/2023] [Indexed: 07/22/2023] Open
Abstract
BACKGROUND West Nile virus (WNV) is a mosquito-borne flavivirus that can cause Central Nervous System infection in humans. Previous autochthonous cases of WNV encephalitis have been described in Spain, but none in Catalonia. MATERIALS AND METHODS We report on the first two autochthonous cases of encephalitis in humans caused by the West Nile virus (WNV) diagnosed in Catalonia (northeastern region of Spain). RESULTS An old married couple presented with clinical and biological signs compatible with viral encephalitis. Acute and convalescent serum samples showed IgM and IgG positivity for WNV. In addition, IgM was also detected in cerebrospinal fluid in the male patient. The serological results were later confirmed by microneutralization assays. CONCLUSIONS WNV infection must be considered in patients presenting with meningoencephalitis with viral CSF characteristics when common pathogens are excluded.
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Affiliation(s)
- Carles García-Cervera
- Internal Medicine Department, Hospital Universitari Sant Joan de Reus, Reus, Tarragona, Spain
- Infectious Diseases Unit, Hospital Universitari Sant Joan de Reus, Reus, Tarragona, Spain
| | - Simona Mihaela Iftimie
- Internal Medicine Department, Hospital Universitari Sant Joan de Reus, Reus, Tarragona, Spain
- Infectious Diseases Unit, Hospital Universitari Sant Joan de Reus, Reus, Tarragona, Spain
- Department of Clinical Medicine, Faculty of Medicine, Universitat Rovira I Virgili, Reus, Tarragona, Spain
| | - Miguel J Martínez
- Department of Clinical Microbiology, CDB, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain; Institute for Global Health (ISGlobal), Barcelona, Spain
| | - Ana Vázquez González
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain; CIBER de Epidemiología y Salud Publica (CIBERESP), Madrid, Spain
| | - Sandra Parra-Pérez
- Internal Medicine Department, Hospital Universitari Sant Joan de Reus, Reus, Tarragona, Spain
- Department of Clinical Medicine, Faculty of Medicine, Universitat Rovira I Virgili, Reus, Tarragona, Spain
| | | | - Joan Gil-Toral
- Internal Medicine Department, Hospital Universitari Sant Joan de Reus, Reus, Tarragona, Spain
| | - Rosa Mercè Vileu Vallverdu
- Camp de Tarragona Epidemiological Surveillance Service, "Servei de Vigilància Epidemiològica al Camp de Tarragona, Subdirecció Regional al Camp de Tarragona I Terres de l'Ebre. Agència de Salut Pública de Catalunya", Catalonia, Spain
| | - Ana Martínez Mateo
- Chief of Public Health Agency of Catalonia, Department of Health, Barcelona, Spain
| | | | - Isabel Pujol-Bajador
- Microbiology Department, Hospital Universitari Sant Joan de Reus, Reus, Tarragona, Spain
- Department of Microbiology, Faculty of Medicine, Universitat Rovira I Virgili, Reus, Tarragona, Spain
| | | | - Antoni Castro-Salomó
- Internal Medicine Department, Hospital Universitari Sant Joan de Reus, Reus, Tarragona, Spain
- Infectious Diseases Unit, Hospital Universitari Sant Joan de Reus, Reus, Tarragona, Spain
- Department of Clinical Medicine, Faculty of Medicine, Universitat Rovira I Virgili, Reus, Tarragona, Spain
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Calzolari M, Russo S, Marzani K, Dalmonte G, Ricchi M, Bonilauri P. Development of a Real-Time PCR Assay for the Detection of the Phlebovirus Fermo Virus. Viruses 2023; 15:2082. [PMID: 37896859 PMCID: PMC10612048 DOI: 10.3390/v15102082] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 10/02/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open
Abstract
Fermo virus is a Phlebovirus that is increasingly reported in sand flies from northern Italy. The natural cycle is not fully understood, but the virus has been detected by direct methods only in sand flies. Although there is serological evidence that it can infect vertebrates, the virus has not been directly detected in animals or humans. Here, we have developed and reported a specific real-time PCR for Fermo virus. The availability of the described method will be useful to characterize the epidemiology of the FERV, ensuring, compared to previously available protocols, a more sensitive detection in insects and the possible detection in vertebrates to evaluate the presence of reservoirs and the pathogenic potential of the virus in humans or animals.
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Affiliation(s)
- Mattia Calzolari
- Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna “B. Ubertini”, 25124 Brescia, Italy; (S.R.); (K.M.); (G.D.); (M.R.); (P.B.)
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Benbetka C, Hachid A, Benallal KE, Khardine FA, Ayhan N, Bouredjoul N, Boulehbal WM, Bellila D, Khaldi A, Charrel R. Epidemiology, Isolation, and Genetic Characterization of Toscana Virus in Algerian Patients Displaying Neurological Infection, 2016-2018. IJID REGIONS 2023; 7:193-198. [PMID: 37123383 PMCID: PMC10131063 DOI: 10.1016/j.ijregi.2023.03.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 03/16/2023] [Accepted: 03/17/2023] [Indexed: 05/02/2023]
Abstract
Purpose The current study reports the results of the diagnosis of neuro-invasive Toscana virus (TOSV) infection in Algeria between 2016 and 2018 and describes the first isolation of TOSV strain from human samples in North Africa. Materiel and methods Cerebrospinal fluid (CSF) and sera samples were obtained from 720 hospitalized patients displaying neurological infection symptoms of unknown etiology, of which 604 were screened for TOSV. The diagnosis was performed by serological and/or RT-PCR tests. In addition, TOSV was isolated in vivo and in vitro from CSF and genetically characterized. Results 23 cases of TOSV neurological infections were detected. Cases were located in 11 Wilayas (administrative provinces), mainly in northern Algeria. In addition, we report the isolation of TOSV strain belonging to lineage A from human samples with its complete coding sequence. Conclusion Even though the number of infections is probably underestimated, TOSV is endemic in Algeria, with several cases of neuro-invasive diseases in humans recorded each year. Therefore, the diagnosis of TOSV should be included in the differential diagnosis of neurological diseases, especially aseptic meningitis, during the period of activity of the phlebotomine vector. Further studies are required to measure precisely the nationwide prevalence of TOSV in Algeria.
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Affiliation(s)
- Chahrazed Benbetka
- Laboratory of Arboviruses and Emerging Viruses, Institut Pasteur of Algeria, 16000, Algiers, Algeria
- Department of Immunology, Béni-Messous Teaching Hospital, University of Algiers, 16000, Algiers, Algeria
- Faculty of Pharmacy, University of Algiers 1, 16000, Algiers, Algeria
- Co-first authors.
| | - Aissam Hachid
- Laboratory of Arboviruses and Emerging Viruses, Institut Pasteur of Algeria, 16000, Algiers, Algeria
- Faculty of Pharmacy, University of Algiers 1, 16000, Algiers, Algeria
- Co-first authors.
| | - Kamal Eddine Benallal
- Laboratory of Parasitic Eco-epidemiology and Population Genetics, Institut Pasteur of Algeria, 16000, Algiers, Algeria
| | - Fayez Ahmed Khardine
- Laboratory of Arboviruses and Emerging Viruses, Institut Pasteur of Algeria, 16000, Algiers, Algeria
| | - Nazli Ayhan
- Unité des Virus Emergents, UVE: Aix Marseille Université, IRD 190, Inserm 1207, AP-HM Hôpitaux Universitaires de Marseille, 13005, Marseille, France
| | - Nesrine Bouredjoul
- Laboratory of Arboviruses and Emerging Viruses, Institut Pasteur of Algeria, 16000, Algiers, Algeria
| | | | - Djamila Bellila
- Faculty of Natural Sciences, University of Algiers 1, 16000, Algiers, Algeria
| | - Aldjia Khaldi
- Laboratory of Arboviruses and Emerging Viruses, Institut Pasteur of Algeria, 16000, Algiers, Algeria
- Faculty of Pharmacy, University of Algiers 1, 16000, Algiers, Algeria
| | - Rémi Charrel
- Unité des Virus Emergents, UVE: Aix Marseille Université, IRD 190, Inserm 1207, AP-HM Hôpitaux Universitaires de Marseille, 13005, Marseille, France
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11
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Laroche L, Ayhan N, Charrel R, Bañuls AL, Prudhomme J. Persistence of Toscana virus in sugar and blood meals of phlebotomine sand flies: epidemiological and experimental consequences. Sci Rep 2023; 13:5608. [PMID: 37019992 PMCID: PMC10076283 DOI: 10.1038/s41598-023-32431-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 03/27/2023] [Indexed: 04/07/2023] Open
Abstract
Many virological studies have tested the persistence of enveloped RNA viruses in various environmental and laboratory conditions and shown their short-term persistence. In this article, we analyzed Toscana virus (TOSV) infectivity, a pathogenic sandfly-borne phlebovirus, in two different conditions: in the sugar meal and blood meal of sand flies. Our results showed that TOSV RNA was detectable up to 15 days in sugar solution at 26 °C and up to 6 h in blood at 37 °C. Moreover, TOSV remains infective for 7 days in sugar solution and for minimum 6 h in rabbit blood. TOSV has shown persistent infectivity/viability under different conditions, which may have important epidemiological consequences. These results strengthen new hypotheses about the TOSV natural cycle, such as the possibility of horizontal transmission between sand flies through infected sugar meal.
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Affiliation(s)
- Lison Laroche
- UMR MIVEGEC, Université de Montpellier - IRD 224 - CNRS 5290, 911 Avenue Agropolis, 34394, Montpellier, France.
| | - Nazli Ayhan
- UVE, Aix Marseille Université - IRD 190 - Inserm 1207 - AP-HM Hôpitaux Universitaires de Marseille, Marseille, France
| | - Rémi Charrel
- UVE, Aix Marseille Université - IRD 190 - Inserm 1207 - AP-HM Hôpitaux Universitaires de Marseille, Marseille, France
| | - Anne-Laure Bañuls
- UMR MIVEGEC, Université de Montpellier - IRD 224 - CNRS 5290, 911 Avenue Agropolis, 34394, Montpellier, France
| | - Jorian Prudhomme
- UMR MIVEGEC, Université de Montpellier - IRD 224 - CNRS 5290, 911 Avenue Agropolis, 34394, Montpellier, France
- INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France
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12
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Balaska S, Calzolari M, Grisendi A, Scremin M, Dottori M, Mavridis K, Bellini R, Vontas J. Monitoring of Insecticide Resistance Mutations and Pathogen Circulation in Sand Flies from Emilia-Romagna, a Leishmaniasis Endemic Region of Northern Italy. Viruses 2023; 15:148. [PMID: 36680189 PMCID: PMC9862798 DOI: 10.3390/v15010148] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/28/2022] [Accepted: 12/29/2022] [Indexed: 01/05/2023] Open
Abstract
The continuously expanding distribution of sand flies, proven vectors of Leishmania and of several phleboviruses, is a growing public health issue in Europe. Especially in Italy, visceral leishmaniasis (VL) is occurring with increasing incidence northward, in previously non-endemic provinces. Around the globe, disease elimination efforts largely focus on sand fly vector insecticidal control, often leading to the development of resistance. In Emilia-Romagna (ER), northern Italy, insecticides are heavily applied for agricultural and mosquito control, but not specifically against sand flies. Here, we investigated the sand fly species composition in certain environmental settings in ER provinces and monitored the presence of pyrethroid resistance mutations and pathogen circulation. Phlebotomus perfiliewi, a dominant vector of Leishmania infantum, was detected almost exclusively in the region. No mutations in the voltage-gated sodium channel gene, e.g., knock-down resistance mutations I1011M, L1014F/S, V1016G, or F1020S, were recorded. Pathogen monitoring revealed that almost 40% of the tested sand fly pools were positive for Leishmania, while the presence of Toscana and Fermo phleboviruses was also observed in much lower frequencies (≤3% positive pools). Regular epidemiological and entomological monitoring, alongside resistance surveillance, is highly recommended to ensure the sustainability and efficiency of vector control interventions.
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Affiliation(s)
- Sofia Balaska
- Institute of Molecular Biology & Biotechnology, Foundation for Research & Technology Hellas, 70013 Heraklion, Greece
- Department of Biology, University of Crete, 70013 Heraklion, Greece
| | - Mattia Calzolari
- Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna (IZSLER) “B. Ubertini”, 25124 Brescia, Italy
| | - Annalisa Grisendi
- Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna (IZSLER) “B. Ubertini”, 25124 Brescia, Italy
| | - Mara Scremin
- Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna (IZSLER) “B. Ubertini”, 25124 Brescia, Italy
| | - Michele Dottori
- Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna (IZSLER) “B. Ubertini”, 25124 Brescia, Italy
| | - Konstantinos Mavridis
- Institute of Molecular Biology & Biotechnology, Foundation for Research & Technology Hellas, 70013 Heraklion, Greece
| | - Romeo Bellini
- Centro Agricoltura Ambiente (CAA) “Giorgio Nicoli”, Via Sant’Agata 835, Crevalcore, 40014 Bologna, Italy
| | - John Vontas
- Institute of Molecular Biology & Biotechnology, Foundation for Research & Technology Hellas, 70013 Heraklion, Greece
- Pesticide Science Lab, Department of Crop Science, Agricultural University of Athens, 11855 Athens, Greece
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Calzolari M, Romeo G, Munari M, Bonilauri P, Taddei R, Sampieri M, Bariselli S, Rugna G, Dottori M. Sand Flies and Pathogens in the Lowlands of Emilia-Romagna (Northern Italy). Viruses 2022; 14:v14102209. [PMID: 36298764 PMCID: PMC9608450 DOI: 10.3390/v14102209] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/23/2022] [Accepted: 10/04/2022] [Indexed: 11/06/2022] Open
Abstract
Cases of sand fly-borne diseases in the Emilia-Romagna region, such as meningitis caused by Toscana virus and human leishmaniasis, are reported annually through dedicated surveillance systems. Sand flies are abundant in the hilly part of the region, while the lowland is unsuitable habitat for sand flies, which are found in lower numbers in this environment with respect to the hilly areas. In this study, we retrieved sand flies collected during entomological surveillance of the West Nile virus (from 2018 to 2021) to assess their abundance and screen them for the presence of pathogens. Over the four-year period, we collected 3022 sand flies, more than half in 2021. The most abundant sand fly species was Phlebotomus (Ph.) perfiliewi, followed by Ph. perniciosus; while more rarely sampled species were Ph. papatasi, Ph. mascittii and Sergentomyia minuta. Sand flies were collected from the end of May to the end of September. The pattern of distribution of the species is characterized by an abundant number of Ph. perfiliewi in the eastern part of the region, which then falls to almost none in the western part of the region, while Ph. perniciosus seems more uniformly distributed throughout. We tested more than 1500 female sand flies in 54 pools to detect phleboviruses and Leishmania species using different PCR protocols. Toscana virus and Leishmania infantum, both human pathogens, were detected in 5 pools and 7 pools, respectively. We also detected Fermo virus, a phlebovirus uncharacterized in terms of relevance to public health, in 4 pools. We recorded different sand fly abundance in different seasons in Emilia-Romagna. During the season more favorable for sand flies, we also detected pathogens transmitted by these insects. This finding implies a health risk linked to sand fly-borne pathogens in the surveyed area in lowland, despite being considered a less suitable habitat for sand flies with respect to the hilly areas.
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14
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Daoudi M, Calzolari M, Boussaa S, Bonilauri P, Torri D, Romeo G, Lelli D, Lavazza A, Hafidi M, Dottori M, Boumezzough A. Identification of Toscana Virus in Natural Population of Sand flies (Diptera: Psychodidae) from Moroccan Leishmaniasis foci. J Infect Public Health 2022; 15:406-411. [DOI: 10.1016/j.jiph.2022.03.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 02/21/2022] [Accepted: 03/13/2022] [Indexed: 10/18/2022] Open
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15
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Sanbonmatsu-Gámez S, Pedrosa-Corral I, Navarro-Marí JM, Pérez-Ruiz M. Update in Diagnostics of Toscana Virus Infection in a Hyperendemic Region (Southern Spain). Viruses 2021; 13:v13081438. [PMID: 34452304 PMCID: PMC8402649 DOI: 10.3390/v13081438] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 07/10/2021] [Accepted: 07/19/2021] [Indexed: 12/23/2022] Open
Abstract
The sandfly fever Toscana virus (TOSV, genus Phlebovirus, family Phenuiviridae) is endemic in Mediterranean countries. In Spain, phylogenetic studies of TOSV strains demonstrated that a genotype, different from the Italian, was circulating. This update reports 107 cases of TOSV neurological infection detected in Andalusia from 1988 to 2020, by viral culture, serology and/or RT-PCR. Most cases were located in Granada province, a hyperendemic region. TOSV neurological infection may be underdiagnosed since few laboratories include this virus in their portfolio. This work presents a reliable automated method, validated for the detection of the main viruses involved in acute meningitis and encephalitis, including the arboviruses TOSV and West Nile virus. This assay solves the need for multiple molecular platforms for different viruses and thus, improves the time to results for these syndromes, which require a rapid and efficient diagnostic approach.
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Affiliation(s)
- Sara Sanbonmatsu-Gámez
- Laboratorio de Referencia de Virus de Andalucía, Servicio de Microbiología, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain; (S.S.-G.); (I.P.-C.); (J.M.N.-M.)
- Instituto de Investigación Biosanitaria ibs.Granada, 18012 Granada, Spain
- Red de Investigación Cooperativa en Enfermedades Tropicales (RICET), 28029 Madrid, Spain
| | - Irene Pedrosa-Corral
- Laboratorio de Referencia de Virus de Andalucía, Servicio de Microbiología, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain; (S.S.-G.); (I.P.-C.); (J.M.N.-M.)
- Instituto de Investigación Biosanitaria ibs.Granada, 18012 Granada, Spain
| | - José María Navarro-Marí
- Laboratorio de Referencia de Virus de Andalucía, Servicio de Microbiología, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain; (S.S.-G.); (I.P.-C.); (J.M.N.-M.)
- Instituto de Investigación Biosanitaria ibs.Granada, 18012 Granada, Spain
- Red de Investigación Cooperativa en Enfermedades Tropicales (RICET), 28029 Madrid, Spain
| | - Mercedes Pérez-Ruiz
- Instituto de Investigación Biosanitaria ibs.Granada, 18012 Granada, Spain
- Red de Investigación Cooperativa en Enfermedades Tropicales (RICET), 28029 Madrid, Spain
- Servicio de Microbiología, Hospital Regional Universitario de Málaga, 29010 Málaga, Spain
- Correspondence:
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16
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Thirion L, Pezzi L, Pedrosa-Corral I, Sanbonmatsu-Gamez S, Lamballerie XD, Falchi A, Perez-Ruiz M, Charrel RN. Evaluation of a Trio Toscana Virus Real-Time RT-PCR Assay Targeting Three Genomic Regions within Nucleoprotein Gene. Pathogens 2021; 10:pathogens10030254. [PMID: 33668339 PMCID: PMC7996202 DOI: 10.3390/pathogens10030254] [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: 10/26/2020] [Revised: 02/01/2021] [Accepted: 02/16/2021] [Indexed: 12/30/2022] Open
Abstract
Toscana virus (TOSV) can cause central nervous system infections in both residents of and travelers to Mediterranean countries. Data mining identified three real-time RT-qPCR assays for detecting TOSV RNA targeting non-overlapping regions in the nucleoprotein gene. Here, they were combined to create a multi-region assay named Trio TOSV RT-qPCR consisting of six primers and three probes. In this study, (i) we evaluated in silico the three RT-qPCR assays available in the literature for TOSV detection, (ii) we combined the three systems to create the Trio TOSV RT-qPCR, (iii) we assessed the specificity and sensitivity of the three monoplex assays versus the Trio TOSV RT-qPCR assay, and (iv) we compared the performance of the Trio TOSV RT-qPCR assay with one of the reference monoplex assays on clinical samples. In conclusion, the Trio TOSV RT-qPCR assay performs equally or better than the three monoplex assays; therefore, it provides a robust assay that can be used for both research and diagnostic purposes.
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Affiliation(s)
- Laurence Thirion
- Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207-IHU Méditerranée Infection), 13005 Marseille, France; (L.T.); (L.P.); (X.D.L.)
| | - Laura Pezzi
- Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207-IHU Méditerranée Infection), 13005 Marseille, France; (L.T.); (L.P.); (X.D.L.)
- UR7310, Laboratoire de Virologie, Université de Corse-Inserm, 20250 Corte, France;
| | - Irene Pedrosa-Corral
- Servicio de Microbiología, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria ibs.Granada, 18014 Granada, Spain; (I.P.-C.); (S.S.-G.); (M.P.-R.)
| | - Sara Sanbonmatsu-Gamez
- Servicio de Microbiología, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria ibs.Granada, 18014 Granada, Spain; (I.P.-C.); (S.S.-G.); (M.P.-R.)
| | - Xavier De Lamballerie
- Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207-IHU Méditerranée Infection), 13005 Marseille, France; (L.T.); (L.P.); (X.D.L.)
| | - Alessandra Falchi
- UR7310, Laboratoire de Virologie, Université de Corse-Inserm, 20250 Corte, France;
| | - Mercedes Perez-Ruiz
- Servicio de Microbiología, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria ibs.Granada, 18014 Granada, Spain; (I.P.-C.); (S.S.-G.); (M.P.-R.)
| | - Remi N. Charrel
- Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207-IHU Méditerranée Infection), 13005 Marseille, France; (L.T.); (L.P.); (X.D.L.)
- Correspondence:
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Percivalle E, Cassaniti I, Calzolari M, Lelli D, Baldanti F. Thirteen Years of Phleboviruses Circulation in Lombardy, a Northern Italy Region. Viruses 2021; 13:v13020209. [PMID: 33573092 PMCID: PMC7911539 DOI: 10.3390/v13020209] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 01/27/2021] [Accepted: 01/27/2021] [Indexed: 01/01/2023] Open
Abstract
Phleboviruses transmitted by phlebotomine sandflies are endemic in the Mediterranean basin. Toscana phlebovirus (TOSV), Sicilian phlebovirus (SFSV), and Naples phlebovirus (SFNV) are responsible of summer fever, with well-known pathogenic potential for humans ranging from asymptomatic to mild fever, in addition to neuro-invasive infections during summer. Although TOSV, in particular, is a significant and well-known human pathogen, SFVs remain neglected, with many gaps in the relevant knowledge. Sero-epidemiological studies and case reports recently showed a geographical wider distribution than previously considered, although the real incidence of phleboviruses infections in the Mediterranean area is still unknown. Here we retrospectively evaluated the circulation of phleboviruses during summer seasons between 2007 and 2019 in 649 patients showing neurological symptoms using both molecular and serological approaches. We found that 42/649 (6.5%) subjects experienced phlebovirus infection and only 10/42 cases were detected by molecular assays, whereas the other 32/42 were identified using serological approaches, including neutralization assays. During the 2013 summer, an outbreak in the Lombardy region is described because the prevalence of phlebovirus infection reached 37.2% (19/51 subjects). Interestingly, only 5/19 (26.5%) reported traveling in endemic areas. Of note, no cross-neutralization was observed between different strains tested, showing the possibility to be reinfected by newly discovered phlebovirus strains. In conclusion, phlebovirus infections are still inadequately considered by physicians and are generally underestimated. However, based on our results, sandfly fever viruses should be routinely included in diagnostic panels during summer period, including in Northern Italy.
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Affiliation(s)
- Elena Percivalle
- Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (E.P.); (I.C.)
| | - Irene Cassaniti
- Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (E.P.); (I.C.)
- Department of Clinical Surgical Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
| | - Mattia Calzolari
- Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna B. Ubertini, 25100 Brescia, Italy; (M.C.); (D.L.)
| | - Davide Lelli
- Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna B. Ubertini, 25100 Brescia, Italy; (M.C.); (D.L.)
| | - Fausto Baldanti
- Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (E.P.); (I.C.)
- Department of Clinical Surgical Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
- Correspondence: or
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Reusken C, Baronti C, Mögling R, Papa A, Leitmeyer K, Charrel RN. Toscana, West Nile, Usutu and tick-borne encephalitis viruses: external quality assessment for molecular detection of emerging neurotropic viruses in Europe, 2017. ACTA ACUST UNITED AC 2020; 24. [PMID: 31847946 PMCID: PMC6918591 DOI: 10.2807/1560-7917.es.2019.24.50.1900051] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BackgroundNeurotropic arboviruses are increasingly recognised as causative agents of neurological disease in Europe but underdiagnosis is still suspected. Capability for accurate diagnosis is a prerequisite for adequate clinical and public health response.AimTo improve diagnostic capability in EVD-LabNet laboratories, we organised an external quality assessment (EQA) focusing on molecular detection of Toscana (TOSV), Usutu (USUV), West Nile (WNV) and tick-borne encephalitis viruses (TBEV).MethodsSixty-nine laboratories were invited. The EQA panel included two WNV RNA-positive samples (lineages 1 and 2), two TOSV RNA-positive samples (lineages A and B), one TBEV RNA-positive sample (Western subtype), one USUV RNA-positive sample and four negative samples. The EQA focused on overall capability rather than sensitivity of the used techniques. Only detection of one, clinically relevant, concentration per virus species and lineage was assessed.ResultsThe final EQA analysis included 51 laboratories from 35 countries; 44 of these laboratories were from 28 of 31 countries in the European Union/European Economic Area (EU/EEA). USUV diagnostic capability was lowest (28 laboratories in 18 countries), WNV detection capacity was highest (48 laboratories in 32 countries). Twenty-five laboratories were able to test the whole EQA panel, of which only 11 provided completely correct results. The highest scores were observed for WNV and TOSV (92%), followed by TBEV (86%) and USUV (75%).ConclusionWe observed wide variety in extraction methods and RT-PCR tests, showing a profound absence of standardisation across European laboratories. Overall, the results were not satisfactory; capacity and capability need to be improved in 40 laboratories.
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Affiliation(s)
- Chantal Reusken
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.,Department of Viroscience, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Cecile Baronti
- Unite des Virus Emergents (UVE: Aix Marseille Univ, IRD 190, INSERM 1207, IHU Mediterranee Infection), Marseille, France
| | - Ramona Mögling
- Department of Viroscience, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Anna Papa
- Department of Microbiology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Katrin Leitmeyer
- European Centre for Disease Prevention and Control (ECDC), Solna, Sweden
| | - Remi N Charrel
- Unite des Virus Emergents (UVE: Aix Marseille Univ, IRD 190, INSERM 1207, IHU Mediterranee Infection), Marseille, France
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Epidemiology of Toscana virus in South Tuscany over the years 2011-2019. J Clin Virol 2020; 128:104452. [PMID: 32474372 DOI: 10.1016/j.jcv.2020.104452] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 05/15/2020] [Accepted: 05/17/2020] [Indexed: 11/20/2022]
Abstract
BACKGROUND Toscana virus (TOSV) is a Phlebovirus transmitted to humans by phlebotomines and represent an etiological agent of acute aseptic meningitis (AAM) in countries where the virus is endemic, including Italy. Incidence of TOSV infections is closely associated with the geographical distribution of the phlebotomine vectors which in turn is affected by climate changes that determine survival and spread. As a result, TOSV infections show a seasonal trend with a peak of incidence in summer months. OBJECTIVES To measure the prevalence of TOSV infections in AAM patients in central Italy and evaluate the climate changes in phlebotomine vectors ecology and virus propagation. STUDY DESIGN One thousand and seventy-three cerebrospinal fluid samples (CSFs), collected from patients with suspected viral meningitis, were collected over nine years (2011-2019) during the May to October period and tested for viruses most commonly associated with AAM. Serum samples addressed to the Microbiology and Virology Unit of "S. Maria delle Scotte" Hospital for confirmation acute TOSV infection (n = 324) were tested for TOSV-specific IgM and IgG. RESULTS Among the CSF samples, 1.3% were positive for Enteroviruses; 0.9% for Varicella zoster virus, 1.9% for Herpes simplex virus type-1/2 and 4.6% for TOSV. Serum IgM analyses disclosed TOSV-specific IgM in 27.1% of sera suggesting the predominant involvement of TOSV in neuroinvasive infections. CONCLUSIONS This data confirms the predominant role of TOSV as causative agent of AAM during the summer time in endemic countries. Moreover, climate changes affecting phlebotomine vectors persistence, reproduction and activity could be involved in the cyclic nature of TOSV infection reported during the last nine years.
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An update on Toscana virus distribution, genetics, medical and diagnostic aspects. Clin Microbiol Infect 2020; 26:1017-1023. [PMID: 31904562 DOI: 10.1016/j.cmi.2019.12.015] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 12/18/2019] [Accepted: 12/22/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND Toscana virus is an arbovirus transmitted by sand flies within the Mediterranean area where it can cause febrile illness and neuroinvasive infections during the seasonal circulation period of the vector. Although it is an important cause of meningitis and encephalitis, it remains a neglected virus with limited published data, as demonstrated by <250 peer-reviewed articles since the 1970s. OBJECTIVE The last review article on Toscana virus was published in 2012. The aim was to compile peer-reviewed articles to provide an updated review highlighting recent findings to complement previous review articles. SOURCES PubMed database was searched using the 'Toscana virus' keyword from 2010 to present. A total of 152 articles were retrieved and identified studies were assessed for novel information on virus genetics, and geographic and medical aspects compared with existing knowledge reported in previous review articles. CONTENT Studies addressing medical, veterinary and entomological aspects have provided evidence that Toscana virus is present in North Africa, in the Balkan Peninsula, and in most of the Mediterranean islands. Besides the two previously recognized genetic lineages, a novel evolutionary lineage has been identified in the Balkan Peninsula. Co-circulation of two genetic lineages has been demonstrated in France, in Turkey and in Croatia. In addition to meningitis and meningo-encephalitis, which have been reported for 40 years, various neuroinvasive forms have been recently reported such as Guillain-Barré syndrome, hydrocephalus, myositis, fasciitis, polymyeloradiculopathy, deafness and facial paralysis. IMPLICATION Because it is endemic in countries bordering the Mediterranean, physicians should include Toscana virus in the differential diagnosis of patients presenting with febrile illness and/or neurological manifestations.
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Endy TP. Viral Febrile Illnesses and Emerging Pathogens. HUNTER'S TROPICAL MEDICINE AND EMERGING INFECTIOUS DISEASES 2020. [PMCID: PMC7151808 DOI: 10.1016/b978-0-323-55512-8.00036-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Emerging or emerged diseases and viral pathogens are responsible historically and currently for large epidemics, global pandemics, and significant morbidity and mortality. Our civilization will continue to face the emergence of new pathogens and viruses: viruses will continue to evolve and adapt to new environments at a high rate; our population continues to grow through birth rate, land development, and migration; climate change will continue to increase the vector burden and spread and change the migratory pattern of animals; and our societal mobility will continue to increase through rapid transportation. The clinical evaluation of the febrile patient with a potential emerging viral pathogen involves documenting the likelihood for an infection by a detailed travel history, calculation of an incubation time by exposure, and an understanding of the disease progression though the clinical illness, which drives the differential diagnosis and the type of diagnostics ordered. Ultimately, the proper identification and diagnosis of a patient with a viral febrile illness due to an emerging pathogen will elicit the appropriate precautions to protect health care providers and communities, deliver appropriate therapeutic interventions, and initiate a targeted public health response.
The majority of emerging diseases are caused by viruses, with many that are transmitted by insect vectors or are zoonotic. RNA viruses in particular have high mutation rates and can evolve rapidly in new and changing environments. This, in combination with societal factors, climate change, and rapid travel, has increased the number of epidemics from emerging pathogens in the last several decades. Understanding the travel history, incubation time of potential viruses, and the clinical presentation by illness day is essential in making the right diagnosis and identifying the infecting virus.
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Pérez-Ruiz M, Pedrosa-Corral I, Sanbonmatsu-Gámez S, Gómez-Camarasa C, Navarro-Marí JM. Analytical validation of viral CNS Flow Chip kit for detection of acute meningitis and encephalitis. J Virol Methods 2018; 259:54-59. [PMID: 29902492 DOI: 10.1016/j.jviromet.2018.06.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Revised: 03/17/2018] [Accepted: 06/10/2018] [Indexed: 01/14/2023]
Abstract
A new molecular assay (Viral CNS Flow Chip kit, Master Diagnóstica, Spain) has been developed for the detection of eight viruses causing acute meningitis and encephalitis, i.e. herpes simplex viruses 1-2, varicella zoster virus, human enterovirus, human parechovirus, Toscana virus, human cytomegalovirus and Epstein Barr virus. The new assay is a multiplex one-step RT-PCR followed by automatic flow-through hybridization, colorimetric detection and image analysis. The limit of detection was 50 copies/reaction, and 10 copies/reaction for human enterovirus and the other seven viruses, respectively. The analytical validation was performed with nucleic acids extracted from 268 cerebrospinal fluid samples and the results were compared with routine molecular assays. An excellent coefficient of agreement was observed between V-CNS and routine assays [kappa index: 0.948 (95%CI: 0.928-0.968)]. The overall sensitivity and specificity was 95.9% (95%CI: 91.2-98.3%) and 99.9% (95%CI: 99.6-100%), respectively. Viral CNS Flow Chip kit is an efficient multiplex platform for the detection of the main viruses involved in acute meningitis and encephalitis. The inclusion of a TOSV genome target may improve the laboratory diagnosis of viral neurological infections in endemic areas.
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Affiliation(s)
- Mercedes Pérez-Ruiz
- Servicio de Microbiología, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria de Granada, Avda. Fuerzas Armadas, 2, Granada, 18014, Spain.
| | - Irene Pedrosa-Corral
- Servicio de Microbiología, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria de Granada, Avda. Fuerzas Armadas, 2, Granada, 18014, Spain
| | - Sara Sanbonmatsu-Gámez
- Servicio de Microbiología, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria de Granada, Avda. Fuerzas Armadas, 2, Granada, 18014, Spain
| | - Cristina Gómez-Camarasa
- Servicio de Microbiología, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria de Granada, Avda. Fuerzas Armadas, 2, Granada, 18014, Spain
| | - José María Navarro-Marí
- Servicio de Microbiología, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria de Granada, Avda. Fuerzas Armadas, 2, Granada, 18014, Spain
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Calzolari M, Chiapponi C, Bellini R, Bonilauri P, Lelli D, Moreno A, Barbieri I, Pongolini S, Lavazza A, Dottori M. Isolation of three novel reassortant phleboviruses, Ponticelli I, II, III, and of Toscana virus from field-collected sand flies in Italy. Parasit Vectors 2018; 11:84. [PMID: 29409533 PMCID: PMC5802049 DOI: 10.1186/s13071-018-2668-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Accepted: 01/23/2018] [Indexed: 02/07/2023] Open
Abstract
Background Different phleboviruses are important pathogens for humans; most of these viruses are transmitted by sand flies. An increasing number of new phleboviruses have been reported over the past decade, especially in Mediterranean countries, mainly via their detection in sand flies. Results At least five different phleboviruses co-circulated in sand flies that were collected in three sites in Emilia-Romagna (Italy) in the summer of 2013. The well-known Toscana virus (TOSV) was isolated; three new, closely related phleboviruses differing in their M segments and tentatively named Ponticelli I, Ponticelli II and Ponticelli III virus, respectively, were isolated; a fifth putative phlebovirus, related to the sand fly fever Naples phlebovirus species, was also detected. The co-circulation, in a restricted area, of three viruses characterized by different M segments, likely resulted from reassortment events. According to the phylogenetic analysis of complete genome sequences, the TOSV belongs to clade A, together with other Italian isolates, while the Ponticelli viruses fall within the Salehabad phlebovirus species. Conclusions Results highlight an unexpected diversity of phleboviruses that co-circulate in the same area, suggesting that interactions likely occur amongst them, that can present challenges for their correct identification. The co-circulation of different phleboviruses appears to be common, and the bionomics of sand fly populations seem to play a relevant role. Such a complex situation emphasizes the need for detailed investigations of the biology of these viruses to better characterize their pathogenic potential for mammals, including humans. Electronic supplementary material The online version of this article (10.1186/s13071-018-2668-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Mattia Calzolari
- Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia-Romagna "Bruno Ubertini", Brescia, Italy.
| | - Chiara Chiapponi
- Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia-Romagna "Bruno Ubertini", Brescia, Italy
| | - Romeo Bellini
- Centro Agricoltura Ambiente "Giorgio Nicoli", Crevalcore, Bologna, Italy
| | - Paolo Bonilauri
- Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia-Romagna "Bruno Ubertini", Brescia, Italy
| | - Davide Lelli
- Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia-Romagna "Bruno Ubertini", Brescia, Italy
| | - Ana Moreno
- Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia-Romagna "Bruno Ubertini", Brescia, Italy
| | - Ilaria Barbieri
- Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia-Romagna "Bruno Ubertini", Brescia, Italy
| | - Stefano Pongolini
- Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia-Romagna "Bruno Ubertini", Brescia, Italy
| | - Antonio Lavazza
- Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia-Romagna "Bruno Ubertini", Brescia, Italy
| | - Michele Dottori
- Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia-Romagna "Bruno Ubertini", Brescia, Italy
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Ayhan N, Alten B, Ivovic V, Martinkovic F, Kasap OE, Ozbel Y, de Lamballerie X, Charrel RN. Cocirculation of Two Lineages of Toscana Virus in Croatia. Front Public Health 2017; 5:336. [PMID: 29312917 PMCID: PMC5732939 DOI: 10.3389/fpubh.2017.00336] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Accepted: 11/27/2017] [Indexed: 01/02/2023] Open
Affiliation(s)
- Nazli Ayhan
- UMR Emergence des Pathologies Virales (EPV), Aix-Marseille Université, IRD 190, INSERM 1207, École des Hautes Etudes en Santé Publique (EHESP), Marseille, France.,IHU Méditerranée Infection, Assistance Publique Hôpitaux de Marseille, Marseille, France
| | - Bulent Alten
- VERG Labs, Ecology Division, Faculty of Science, Department of Biology, Hacettepe University, Ankara, Turkey
| | - Vladimir Ivovic
- Faculty of Mathematics, Natural Sciences and Information Technologies (FAMNIT), University of Primorska, Koper, Slovenia
| | - Franjo Martinkovic
- Faculty of Veterinary Medicine, Department of Parasitology and Parasitic Diseases with Clinics, University of Zagreb, Zagreb, Croatia
| | - Ozge E Kasap
- VERG Labs, Ecology Division, Faculty of Science, Department of Biology, Hacettepe University, Ankara, Turkey
| | - Yusuf Ozbel
- Medical Faculty, Department of Parasitology, Ege University, Bornova, Turkey
| | - Xavier de Lamballerie
- UMR Emergence des Pathologies Virales (EPV), Aix-Marseille Université, IRD 190, INSERM 1207, École des Hautes Etudes en Santé Publique (EHESP), Marseille, France.,IHU Méditerranée Infection, Assistance Publique Hôpitaux de Marseille, Marseille, France
| | - Remi N Charrel
- UMR Emergence des Pathologies Virales (EPV), Aix-Marseille Université, IRD 190, INSERM 1207, École des Hautes Etudes en Santé Publique (EHESP), Marseille, France.,IHU Méditerranée Infection, Assistance Publique Hôpitaux de Marseille, Marseille, France
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Alwassouf S, Maia C, Ayhan N, Coimbra M, Cristovao JM, Richet H, Bichaud L, Campino L, Charrel RN. Neutralization-based seroprevalence of Toscana virus and sandfly fever Sicilian virus in dogs and cats from Portugal. J Gen Virol 2016; 97:2816-2823. [PMID: 27589865 DOI: 10.1099/jgv.0.000592] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Sandfly-borne phleboviruses are endemic in the Mediterranean basin. However, levels of exposure of human and animal populations are inadequately researched. Toscana virus (TOSV) is present in Portugal where it causes human infection and disease; in contrast there are few data for sandfly fever Sicilian virus (SFSV) which has neither been isolated nor detected by molecular tests and for which there are only limited serological data. The sera collected from 1160 dogs and 189 cats in southern Portugal were tested for the presence of neutralizing antibodies against TOSV and SFSV, two viruses recognized as distinct serocomplexes in the Mediterranean region. Our data showed (i) seropositivity to TOSV and SFSV in dogs at a rate of 6.8 and 50.8 %, respectively, and (ii) that 3.7 % of cats were seropositive for TOSV. TOSV findings are in line with previous results obtained with less stringent serological assays. Our results for SFSV in dogs clearly indicate that the virus is circulating widely and that humans may be exposed to infection via the dogs. Although the presence of SFSV was suggested by haemagglutination inhibition in 4/1690 human sera in 1974, this is the first time, as far as we know, that SFSV has been shown to circulate so widely in dogs in Portugal. Future studies should be directed at isolating strains of SFSV in Portugal from dogs, humans and sandflies collected in high prevalence regions. As dogs appear to be good sentinels for SFSV, their role as a possible reservoir in the natural cycle should also be considered.
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Affiliation(s)
- Sulaf Alwassouf
- UMR 'Emergence des Pathologies Virales' (EPV: Aix-Marseille University-IRD 190-Inserm 1207-EHESP), Marseille, France.,Fondation IHU Méditerranée Infection, APHM Public Hospitals of Marseille, Marseille, France
| | - Carla Maia
- Global Health and Tropical Medicine, GHMT, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Lisbon, Portugal.,Faculdade de Medicina Veterinária, Universidade Lusófona de Humanidades e Tecnologias, Lisbon, Portugal
| | - Nazli Ayhan
- UMR 'Emergence des Pathologies Virales' (EPV: Aix-Marseille University-IRD 190-Inserm 1207-EHESP), Marseille, France.,Fondation IHU Méditerranée Infection, APHM Public Hospitals of Marseille, Marseille, France
| | | | - Jose Manuel Cristovao
- Global Health and Tropical Medicine, GHMT, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Lisbon, Portugal
| | - Herve Richet
- UMR 'Emergence des Pathologies Virales' (EPV: Aix-Marseille University-IRD 190-Inserm 1207-EHESP), Marseille, France.,Fondation IHU Méditerranée Infection, APHM Public Hospitals of Marseille, Marseille, France
| | - Laurence Bichaud
- UMR 'Emergence des Pathologies Virales' (EPV: Aix-Marseille University-IRD 190-Inserm 1207-EHESP), Marseille, France.,Fondation IHU Méditerranée Infection, APHM Public Hospitals of Marseille, Marseille, France.,Department of Parasitology, Faculty of Science, Charles University, Prague 2 128 44, Czech Republic
| | - Lenea Campino
- Global Health and Tropical Medicine, GHMT, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Lisbon, Portugal.,Department of Biomedical Sciences and Medicine, Universidade do Algarve, Faro, Portugal
| | - Remi N Charrel
- UMR 'Emergence des Pathologies Virales' (EPV: Aix-Marseille University-IRD 190-Inserm 1207-EHESP), Marseille, France.,Fondation IHU Méditerranée Infection, APHM Public Hospitals of Marseille, Marseille, France
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Remoli ME, Bongiorno G, Fortuna C, Marchi A, Bianchi R, Khoury C, Ciufolini MG, Gramiccia M. Experimental evaluation of sand fly collection and storage methods for the isolation and molecular detection of Phlebotomus-borne viruses. Parasit Vectors 2015; 8:576. [PMID: 26552444 PMCID: PMC4640371 DOI: 10.1186/s13071-015-1192-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Accepted: 10/31/2015] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Several viruses have been recently isolated from Mediterranean phlebotomine sand flies; some are known to cause human disease while some are new to science. To monitor the Phlebotomus-borne viruses spreading, field studies are in progress using different sand fly collection and storage methods. Two main sampling techniques consist of CDC light traps, an attraction method allowing collection of live insects in which the virus is presumed to be fairly preserved, and sticky traps, an interception method suitable to collect dead specimens in high numbers, with a risk for virus viability or integrity. Sand flies storage requires a "deep cold chain" or specimen preservation in ethanol. In the present study the influence of sand fly collection and storage methods on viral isolation and RNA detection performances was evaluated experimentally. METHODS Specimens of laboratory-reared Phlebotomus perniciosus were artificially fed with blood containing Toscana virus (family Bunyaviridae, genus Phlebovirus). Various collection and storage conditions of blood-fed females were evaluated to mimic field procedures using single and pool samples. Isolation on VERO cell cultures, quantitative Real time-Retro-transcriptase (RT)-PCR and Nested-RT-PCR were performed according to techniques commonly used in surveillance studies. RESULTS Live engorged sand flies stored immediately at -80 °C were the most suitable sample for phlebovirus identification by both virus isolation and RNA detection. The viral isolation rate remained very high (26/28) for single dead engorged females frozen after 1 day, while it was moderate (10/30) for specimens collected by sticky traps maintained up to 3 days at room temperature and then stored frozen without ethanol. Opposed to viral isolation, molecular RNA detection kept very high on dead sand flies collected by sticky traps when left at room temperature up to 6 days post blood meal and then stored frozen in presence (88/95) or absence (87/88) of ethanol. Data were confirmed using sand fly pools. CONCLUSIONS While the collection and storage methods investigated had not much impact on the ability to detect viral RNA by molecular methods, they affected the capacity to recover viable viruses. Consequently, sand fly collection and handling procedures should be established in advance depending on the goal of the surveillance studies.
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Affiliation(s)
- Maria Elena Remoli
- Department of Infectious Parasitic and Immune-Mediated Diseases, Unit of Viral diseases and attenuated vaccine, Istituto Superiore di Sanità, Rome, Italy.
| | - Gioia Bongiorno
- Department of Infectious, Parasitic and Immune-Mediated Diseases, Unit of Vector-borne Diseases and International Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
| | - Claudia Fortuna
- Department of Infectious Parasitic and Immune-Mediated Diseases, Unit of Viral diseases and attenuated vaccine, Istituto Superiore di Sanità, Rome, Italy.
| | - Antonella Marchi
- Department of Infectious Parasitic and Immune-Mediated Diseases, Unit of Viral diseases and attenuated vaccine, Istituto Superiore di Sanità, Rome, Italy.
| | - Riccardo Bianchi
- Department of Infectious, Parasitic and Immune-Mediated Diseases, Unit of Vector-borne Diseases and International Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
| | - Cristina Khoury
- Department of Infectious, Parasitic and Immune-Mediated Diseases, Unit of Vector-borne Diseases and International Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
| | - Maria Grazia Ciufolini
- Department of Infectious Parasitic and Immune-Mediated Diseases, Unit of Viral diseases and attenuated vaccine, Istituto Superiore di Sanità, Rome, Italy.
| | - Marina Gramiccia
- Department of Infectious, Parasitic and Immune-Mediated Diseases, Unit of Vector-borne Diseases and International Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
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Schirmer L, Wölfel S, Georgi E, Ploner M, Bauer B, Hemmer B. Extensive Recruitment of Plasma Blasts to the Cerebrospinal Fluid in Toscana Virus Encephalitis. Open Forum Infect Dis 2015; 2:ofv124. [PMID: 26393235 PMCID: PMC4569839 DOI: 10.1093/ofid/ofv124] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Accepted: 08/17/2015] [Indexed: 01/09/2023] Open
Abstract
An unexpectedly extensive recruitment of B cells and plasma blasts to the cerebrospinal fluid (CSF) in a patient with Toscana virus (TOSV) encephalitis is described. Acute infection by TOSV was demonstrated by serological methods and by detection of TOSV-specific nucleic acid in the CSF by real-time polymerase chain reaction and sequencing.
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Affiliation(s)
- Lucas Schirmer
- Department of Neurology , Klinikum Rechts der Isar, Technische Universität München
| | | | - Enrico Georgi
- Microbial Genomics and Bioinformatics , Bundeswehr Institute of Microbiology, German Center for Infection Research (DZIF)
| | - Markus Ploner
- Department of Neurology , Klinikum Rechts der Isar, Technische Universität München
| | - Barbara Bauer
- Institute of Virology, Technische Universität München and Helmholtz Zentrum München, German Center for Infection Research (DZIF)
| | - Bernhard Hemmer
- Department of Neurology , Klinikum Rechts der Isar, Technische Universität München ; Munich Cluster for Systems Neurology (SyNergy) , Munich , Germany
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Magurano F, Baggieri M, Gattuso G, Fortuna C, Remoli ME, Vaccari G, Zaccaria G, Marchi A, Bucci P, Benedetti E, Fiorentini C, Nicoletti L. Toscana virus genome stability: data from a meningoencephalitis case in Mantua, Italy. Vector Borne Zoonotic Dis 2015; 14:866-9. [PMID: 25514123 DOI: 10.1089/vbz.2014.1668] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
In July of 2013, samples from a patient with a neurological syndrome were collected from Mantua hospital and sent to the National Reference Laboratory for Arboviruses (National Institute of Health, Rome). On the basis of the symptoms, serological and molecular assays were performed to diagnose either West Nile virus (WNV) or Toscana virus (TOSV) infection. Molecular and serological tests confirmed TOSV infection. Virus isolation was obtained from cerebrospinal fluid. A full genome sequence was determined from this TOSV strain with next-generation sequencing using Ion Torrent technology. Nucleotide and amino acidic sequences grouped phylogenetically with lineage TOSV A and showed a low genome variability.
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Affiliation(s)
- Fabio Magurano
- 1 Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità , Rome, Italy
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A rapid and specific real time RT-PCR assay for diagnosis of Toscana virus infection. J Clin Virol 2015; 66:107-11. [PMID: 25866349 DOI: 10.1016/j.jcv.2015.03.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2014] [Revised: 02/26/2015] [Accepted: 03/06/2015] [Indexed: 11/22/2022]
Abstract
BACKGROUND To scan a virus (TOSV) belongs to the Phlebovirus genus within the Bunyaviridae family. TOSV is an arbovirus transmitted by sandflies. In Mediterranean countries, TOSV is one of the major viral pathogens involved in aseptic meningitis and meningoencephalitis. OBJECTIVES Development and assessment of a new sensitive and specific real-time RT-PCR assay for TOSV diagnosis. STUDY DESIGN TOSV-specific primers and probe targeting the S-segment of the genome were designed, based on recent TOSV sequences available in public databases. Sensitivity was assessed using 10-fold serial dilutions of a RNA transcript and serial dilutions of TOSV strains isolated from infected human beings. Specificity was determined by testing RNA extracts from closely related Phleboviruses. The assay was then used for TOSV infection diagnosis in 971 clinical samples and for TOSV detection in 2000 sandflies. RESULTS The real-time RT-PCR assay exhibited a sensitivity of under 257 copies per reaction for the RNA transcripts and 0.0056 and 0.014 TCID50 of Italian and Spanish TOSV genotypes per reaction, respectively. No other close Phleboviruses were detected. TOSV was identified in 17 clinical samples and in 3 sandflies. CONCLUSIONS The assay described is a rapid, robust and reliable real-time RT-PCR test for accurate diagnosis of human TOSV infection as well as for the surveillance of TOSV in vector populations.
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Calzolari M, Angelini P, Finarelli AC, Cagarelli R, Bellini R, Albieri A, Bonilauri P, Cavrini F, Tamba M, Dottori M, Gaibani P, Natalini S, Maioli G, Pinna M, Mattivi A, Sambri V, Pierro A, Landini MP, Rossini G, Squintani G, Cinotti S, Varani S, Vocale C, Bedeschi E. Human and entomological surveillance of Toscana virus in the Emilia-Romagna region, Italy, 2010 to 2012. Euro Surveill 2014; 19:20978. [DOI: 10.2807/1560-7917.es2014.19.48.20978] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
Toscana virus (TOSV), transmitted by phlebotomine sandflies, is recognised as one of the most important causes of viral meningitis in summer in Mediterranean countries. A surveillance plan based on both human and entomological surveys was started in 2010 in the Emilia-Romagna region, Italy. Clinical samples from patients with neurological manifestations were collected during 2010 to 2012. The surveillance protocol was improved during these years, allowing the detection of 65 human infections. Most of these infections were recorded in hilly areas, where sandflies reach the highest density. Entomological sampling around the homes of the patients resulted in a low number of captured sandflies, while later sampling in a hilly area with high number of human cases (n=21) resulted in a larger number of captured sandflies. Using this approach, 25,653 sandflies were sampled, of which there were 21,157 females, which were sorted into 287 pools. TOSV RNA was detected by real-time PCR in 33 of the pools. The results highlighted the role of Phlebotomus perfiliewi as the main vector of TOSV and a potential link between vector density and virus circulation. This integrated system shows that an interdisciplinary approach improves the sensitiveness and effectiveness of health surveillance.
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Affiliation(s)
- M Calzolari
- Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia-Romagna, Brescia, Italy
| | - P Angelini
- Public Health Service, Emilia-Romagna Region, Bologna, Italy
| | - A C Finarelli
- Public Health Service, Emilia-Romagna Region, Bologna, Italy
| | - R Cagarelli
- Public Health Service, Emilia-Romagna Region, Bologna, Italy
| | - R Bellini
- Centro Agricoltura Ambiente ‘G Nicoli’, Crevalcore, Italy
| | - A Albieri
- Centro Agricoltura Ambiente ‘G Nicoli’, Crevalcore, Italy
| | - P Bonilauri
- Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia-Romagna, Brescia, Italy
| | - F Cavrini
- Unit of Clinical Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St. Orsola-Malpighi University Hospital, Bologna, Italy
| | - M Tamba
- Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia-Romagna, Brescia, Italy
| | - M Dottori
- Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia-Romagna, Brescia, Italy
| | - P Gaibani
- Unit of Clinical Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St. Orsola-Malpighi University Hospital, Bologna, Italy
| | - S Natalini
- Veterinary and Food Hygiene Service, Emilia-Romagna Region, Bologna, Italy
| | - G Maioli
- Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia-Romagna, Brescia, Italy
| | - M Pinna
- Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia-Romagna, Brescia, Italy
| | - A Mattivi
- Public Health Service, Emilia-Romagna Region, Bologna, Italy
| | - V Sambri
- Unit of Microbiology, Greater Romagna Area Hub Laboratory, Pievesestina, Italy
| | - A Pierro
- Unit of Clinical Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St. Orsola-Malpighi University Hospital, Bologna, Italy
| | - M P Landini
- Unit of Clinical Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St. Orsola-Malpighi University Hospital, Bologna, Italy
| | - G Rossini
- Unit of Clinical Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St. Orsola-Malpighi University Hospital, Bologna, Italy
| | - G Squintani
- Veterinary and Food Hygiene Service, Emilia-Romagna Region, Bologna, Italy
| | - S Cinotti
- Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia-Romagna, Brescia, Italy
| | - S Varani
- Unit of Clinical Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St. Orsola-Malpighi University Hospital, Bologna, Italy
| | - C Vocale
- Unit of Clinical Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St. Orsola-Malpighi University Hospital, Bologna, Italy
| | - E Bedeschi
- Public Health Service, Emilia-Romagna Region, Bologna, Italy
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Toscana virus meningitis case in Switzerland: an example of the ezVIR bioinformatics pipeline utility for the identification of emerging viruses. Clin Microbiol Infect 2014; 21:387.e1-4. [PMID: 25658528 DOI: 10.1016/j.cmi.2014.11.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2014] [Revised: 09/18/2014] [Accepted: 11/05/2014] [Indexed: 02/06/2023]
Abstract
Toscana virus (TOSV) represents a frequent cause of viral meningitis in the Mediterranean Basin that remains neglected in neighbouring countries. We report a documented TOSV meningitis case in a traveller returning from Tuscany to Switzerland. While routine serological and PCR assays could not discriminate between TOSV and Sandfly fever Naples virus infection, a high-throughput sequencing performed directly on the cerebrospinal fluid specimen and analysed with the ezVIR pipeline provided an unequivocal viral diagnostic. TOSV could be unequivocally considered as the aetiological agent, proving the potential of ezVIR to improve standard diagnostics in cases of infection with uncommon or emerging viruses.
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32
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Pierro A, Landini MP, Gaibani P, Rossini G, Vocale C, Finarelli AC, Cagarelli R, Sambri V, Varani S. A model of laboratory surveillance for neuro-arbovirosis applied during 2012 in the Emilia-Romagna region, Italy. Clin Microbiol Infect 2013; 20:672-7. [PMID: 24329773 DOI: 10.1111/1469-0691.12436] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2013] [Revised: 10/03/2013] [Accepted: 10/21/2013] [Indexed: 11/30/2022]
Abstract
Arboviruses with neuroinvasive potential are gaining more attention due to the increased number of cases of autochthonous and imported infections in the human host. Diagnosis of infection caused by these viruses in patients with central nervous system (CNS) diseases is still underestimated and these infections represent an emerging threat to public health. We describe a model suitable for the laboratory surveillance of neuro-arbovirosis that was applied in the Emilia-Romagna region, north-eastern Italy, during the 2012 summer season. One hundred and twenty cases of suspected neuroinvasive infection were tested for arboviral agents on the basis of clinical and laboratory signs and epidemiological data. The most common virus detected was Toscana virus (TOSV): anti-TOSV specific antibodies or viral components were detected in 28.3% of the cases; 79.4% of the TOSV cases were in the acute phase of infection. No cases resulted in acute phase for West Nile (WNV), Usutu (USUV), Chikungunya (CHIKV) or Dengue (DENV) virus infection. Conversely, two patients with a history of staying in a tick-borne encephalitis virus (TBEV) endemic area showed a probable TBEV infection. These results emphasize the importance of a complete and 'ready to act' laboratory diagnostic system to be implemented within the larger frame of a regional integrated surveillance system.
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Affiliation(s)
- A Pierro
- Unit of Clinical Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St Orsola-Malpighi University Hospital, Bologna, Italy
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Dupouey J, Bichaud L, Ninove L, Zandotti C, Thirion-Perrier L, de Lamballerie X, Charrel RN. Toscana virus infections: a case series from France. J Infect 2013; 68:290-5. [PMID: 24247068 DOI: 10.1016/j.jinf.2013.11.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2013] [Revised: 10/22/2013] [Accepted: 11/01/2013] [Indexed: 12/18/2022]
Abstract
Toscana virus (TOSV) is a neglected sandfly-borne pathogen in Mediterranean countries. Although discovered four decades ago, articles that describe the clinical aspects are scarce and consist mostly of case reports, with few series of cases. We studied retrospectively symptomatic TOSV infections in patients hospitalized in Marseille (France) from 2004 to 2011. Seventeen patients were classified as probable or confirmed cases. Fourteen cases (82%) occurred between June and September, and 3 cases in March, April and November. Two cases were potentially imported from Croatia and Tuscany. All patients presented with fever and neurological signs were observed such as aseptic meningitis (n = 6), muscular symptoms (n = 3), or encephalitis (n = 4). The outcome was always favorable. At the acute stage, anti TOSV IgM were observed in 14/17 patients, neutralization tests were positive for 3/8 patients, and RT-PCR confirmed TOSV infections in 5/8 CSF specimens.
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Affiliation(s)
- J Dupouey
- UMR_D 190 "Emergence des Pathologies Virales", Aix Marseille Univ, IRD French Institute of Research for Development, EHESP French School of Public Health, 13005 Marseille, France; IHU Mediterranee Infection, APHM Public Hospitals of Marseille, 13005 Marseille, France
| | - L Bichaud
- UMR_D 190 "Emergence des Pathologies Virales", Aix Marseille Univ, IRD French Institute of Research for Development, EHESP French School of Public Health, 13005 Marseille, France; IHU Mediterranee Infection, APHM Public Hospitals of Marseille, 13005 Marseille, France
| | - L Ninove
- UMR_D 190 "Emergence des Pathologies Virales", Aix Marseille Univ, IRD French Institute of Research for Development, EHESP French School of Public Health, 13005 Marseille, France; IHU Mediterranee Infection, APHM Public Hospitals of Marseille, 13005 Marseille, France
| | - C Zandotti
- UMR_D 190 "Emergence des Pathologies Virales", Aix Marseille Univ, IRD French Institute of Research for Development, EHESP French School of Public Health, 13005 Marseille, France; IHU Mediterranee Infection, APHM Public Hospitals of Marseille, 13005 Marseille, France
| | - L Thirion-Perrier
- UMR_D 190 "Emergence des Pathologies Virales", Aix Marseille Univ, IRD French Institute of Research for Development, EHESP French School of Public Health, 13005 Marseille, France; IHU Mediterranee Infection, APHM Public Hospitals of Marseille, 13005 Marseille, France
| | - X de Lamballerie
- UMR_D 190 "Emergence des Pathologies Virales", Aix Marseille Univ, IRD French Institute of Research for Development, EHESP French School of Public Health, 13005 Marseille, France; IHU Mediterranee Infection, APHM Public Hospitals of Marseille, 13005 Marseille, France
| | - R N Charrel
- UMR_D 190 "Emergence des Pathologies Virales", Aix Marseille Univ, IRD French Institute of Research for Development, EHESP French School of Public Health, 13005 Marseille, France; IHU Mediterranee Infection, APHM Public Hospitals of Marseille, 13005 Marseille, France.
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[Microbiological diagnosis of emerging arboviral and rodent borne diseases]. Enferm Infecc Microbiol Clin 2013; 33:197-205. [PMID: 24139129 DOI: 10.1016/j.eimc.2013.07.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2013] [Accepted: 07/10/2013] [Indexed: 11/22/2022]
Abstract
Vector borne viruses (VBV) include viruses transmitted by arthropods, rodents and other animals. In Spain the three main autochthonous VBVs causing human diseases are: Toscana, West Nile and Lymphocytic Choriomeningitis viruses. There are also other imported viruses that are potential threats to our public health, due to the presence of competent transmission vectors (dengue and chikungunya viruses in areas infested with Aedes albopictus), or due to the potential person-to-person transmission (Lassa and other viruses causing haemorrhagic fever). The Spanish Society for Infectious Diseases and Clinical Microbiology has responded to the emergence of VBVs by publishing a special issue of Microbiological Proceedings focused on the diagnosis of those emerging vector borne viruses of major concern in our country.
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Nougairede A, Bichaud L, Thiberville SD, Ninove L, Zandotti C, de Lamballerie X, Brouqui P, Charrel RN. Isolation of Toscana Virus from the Cerebrospinal Fluid of a Man with Meningitis in Marseille, France, 2010. Vector Borne Zoonotic Dis 2013; 13:685-8. [DOI: 10.1089/vbz.2013.1316] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Affiliation(s)
- Antoine Nougairede
- UMR_D 190 “Emergence des Pathologies Virales,” Aix Marseille University, IRD French Institute of Research for Development, EHESP French School of Public Health, Marseille, France
- Virology laboratory, IHU Mediterranee Infection, APHM Public Hospitals of Marseille, Marseille, France
| | - Laurence Bichaud
- UMR_D 190 “Emergence des Pathologies Virales,” Aix Marseille University, IRD French Institute of Research for Development, EHESP French School of Public Health, Marseille, France
| | - Simon-Djamel Thiberville
- UMR_D 190 “Emergence des Pathologies Virales,” Aix Marseille University, IRD French Institute of Research for Development, EHESP French School of Public Health, Marseille, France
- Service de Maladies Infectieuses et Tropicales, IHU Méditerranée Infection, Assistance Publique–Hôpitaux de Marseille, Marseille, France
| | - Laetitia Ninove
- UMR_D 190 “Emergence des Pathologies Virales,” Aix Marseille University, IRD French Institute of Research for Development, EHESP French School of Public Health, Marseille, France
- Virology laboratory, IHU Mediterranee Infection, APHM Public Hospitals of Marseille, Marseille, France
| | - Christine Zandotti
- Virology laboratory, IHU Mediterranee Infection, APHM Public Hospitals of Marseille, Marseille, France
| | - Xavier de Lamballerie
- UMR_D 190 “Emergence des Pathologies Virales,” Aix Marseille University, IRD French Institute of Research for Development, EHESP French School of Public Health, Marseille, France
- Virology laboratory, IHU Mediterranee Infection, APHM Public Hospitals of Marseille, Marseille, France
| | - Philippe Brouqui
- Service de Maladies Infectieuses et Tropicales, IHU Méditerranée Infection, Assistance Publique–Hôpitaux de Marseille, Marseille, France
| | - Remi N. Charrel
- UMR_D 190 “Emergence des Pathologies Virales,” Aix Marseille University, IRD French Institute of Research for Development, EHESP French School of Public Health, Marseille, France
- Virology laboratory, IHU Mediterranee Infection, APHM Public Hospitals of Marseille, Marseille, France
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Peyrefitte CN, Grandadam M, Bessaud M, Andry PE, Fouque F, Caro V, Diancourt L, Schuffenecker I, Pagès F, Tolou H, Zeller H, Depaquit J. Diversity of Phlebotomus perniciosus in Provence, Southeastern France: Detection of Two Putative New Phlebovirus Sequences. Vector Borne Zoonotic Dis 2013; 13:630-6. [DOI: 10.1089/vbz.2012.1169] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
| | - Marc Grandadam
- Institut de Recherche Biomédicale des Armées antenne de Marseille, Marseille, France
| | - Maël Bessaud
- UMR190 “Emergence des Pathologies Virales," Aix-Marseille University–IRD French Institute of Research for Development–EHESP French School of Public Health, Marseille, France
| | - Pierre-Emmanuel Andry
- Université de Reims Champagne-Ardenne, ANSES, EA4688 “Transmission vectorielle et épidémiosurveillance de maladies parasitaires (VECPAR),” Reims, France
| | | | | | | | | | - Frédéric Pagès
- Institut de Recherche Biomédicale des Armées antenne de Marseille, Marseille, France
| | - Hugues Tolou
- Institut de Recherche Biomédicale des Armées, Brétigny sur Orge, France
| | | | - Jérôme Depaquit
- Université de Reims Champagne-Ardenne, ANSES, EA4688 “Transmission vectorielle et épidémiosurveillance de maladies parasitaires (VECPAR),” Reims, France
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Pérez-Ruiz M, Navarro-Marí JM, Sánchez-Seco MP, Gegúndez MI, Palacios G, Savji N, Lipkin WI, Fedele G, de Ory-Manchón F. Lymphocytic choriomeningitis virus-associated meningitis, southern Spain. Emerg Infect Dis 2013; 18:855-8. [PMID: 22515986 PMCID: PMC3358079 DOI: 10.3201/eid1805.111646] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Lymphocytic choriomeningitis virus (LCMV) was detected in 2 patients with acute meningitis in southern Spain within a 3-year period. Although the prevalence of LCMV infection was low (2 [1.3%] of 159 meningitis patients), it represents 2.9% of all pathogens detected. LCMV is a noteworthy agent of neurologic illness in immunocompetent persons.
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de Ory F, Avellón A, Echevarría JE, Sánchez-Seco MP, Trallero G, Cabrerizo M, Casas I, Pozo F, Fedele G, Vicente D, Pena MJ, Moreno A, Niubo J, Rabella N, Rubio G, Pérez-Ruiz M, Rodríguez-Iglesias M, Gimeno C, Eiros JM, Melón S, Blasco M, López-Miragaya I, Varela E, Martinez-Sapiña A, Rodríguez G, Marcos MÁ, Gegúndez MI, Cilla G, Gabilondo I, Navarro JM, Torres J, Aznar C, Castellanos A, Guisasola ME, Negredo AI, Tenorio A, Vázquez-Morón S. Viral infections of the central nervous system in Spain: a prospective study. J Med Virol 2012; 85:554-62. [PMID: 23239485 DOI: 10.1002/jmv.23470] [Citation(s) in RCA: 118] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/12/2012] [Indexed: 11/10/2022]
Abstract
The aim of the study was to determine the incidence of viruses causing aseptic meningitis, meningoencephalitis, and encephalitis in Spain. This was a prospective study, in collaboration with 17 Spanish hospitals, including 581 cases (CSF from all and sera from 280): meningitis (340), meningoencephalitis (91), encephalitis (76), febrile syndrome (7), other neurological disorders (32), and 35 cases without clinical information. CSF were assayed by PCR for enterovirus (EV), herpesvirus (herpes simplex [HSV], varicella-zoster [VZV], cytomegalovirus [CMV], Epstein-Barr [EBV], and human herpes virus-6 [HHV-6]), mumps (MV), Toscana virus (TOSV), adenovirus (HAdV), lymphocytic choriomeningitis virus (LCMV), West Nile virus (WNV), and rabies. Serology was undertaken when methodology was available. Amongst meningitis cases, 57.1% were characterized; EV was the most frequent (76.8%), followed by VZV (10.3%) and HSV (3.1%; HSV-1: 1.6%; HSV-2: 1.0%, HSV non-typed: 0.5%). Cases due to CMV, EBV, HHV-6, MV, TOSV, HAdV, and LCMV were also detected. For meningoencephalitis, 40.7% of cases were diagnosed, HSV-1 (43.2%) and VZV (27.0%) being the most frequent agents, while cases associated with HSV-2, EV, CMV, MV, and LCMV were also detected. For encephalitis, 27.6% of cases were caused by HSV-1 (71.4%), VZV (19.1%), or EV (9.5%). Other positive neurological syndromes included cerebellitis (EV and HAdV), seizures (HSV), demyelinating disease (HSV-1 and HHV-6), myelopathy (VZV), and polyradiculoneuritis (HSV). No rabies or WNV cases were identified. EVs are the most frequent cause of meningitis, as is HSV for meningoencephalitis and encephalitis. A significant number of cases (42.9% meningitis, 59.3% meningoencephalitis, 72.4% encephalitis) still have no etiological diagnosis.
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Affiliation(s)
- F de Ory
- National Centre for Microbiology, Majadahonda, Spain.
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Charrel RN, Bichaud L, de Lamballerie X. Emergence of Toscana virus in the mediterranean area. World J Virol 2012; 1:135-41. [PMID: 24175218 PMCID: PMC3782275 DOI: 10.5501/wjv.v1.i5.135] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2012] [Revised: 09/18/2012] [Accepted: 10/10/2012] [Indexed: 02/05/2023] Open
Abstract
Toscana virus (TOSV) is an arthropod-borne virus, identified in 1971, from Phlebotomus perniciosus and Phlebotomus perfiliewi in central Italy. TOSV belongs to the Phlebovirus genus within the Bunyaviridae family. As other bunyaviruses, the genome of TOSV consists of 3 segments (S for small, M for Medium, and L for Large) respectively encoding non structural and capsid proteins, envelope structural proteins, and the viral RNA-dependant RNA-polymerase. It is transmitted by sand flies. Therefore its distribution is dictated by that of the arthropod vectors, and virus circulation peaks during summertime when sandfly populations are active. Here, we reviewed the epidemiology of TOSV in the old world. First evidence of its pathogenicity for humans, specifically its propensity to cause central nervous system (CNS) infections such as meningitis and encephalitis, was reported in central Italy. After 2000, it was recognized that TOSV had a much larger geographic distribution than initially believed, and was present in most of the Western European countries located on the northern border of the Mediterranean Sea (Portugal, Spain, France, Greece, Croatia) as well as eastern countries such as Cyprus and Turkey. In the countries where TOSV is present, it is among the three most prevalent viruses in meningitis during the warm seasons, together with enteroviruses and herpesviruses. Up to now, epidemiological data concerning Northern Africa and other countries located south of the Mediterranean are scarce. TOSV must be considered an emerging pathogen. Despite the important role played by TOSV in CNS infections, it remains a neglected agent and is rarely considered by physicians in diagnostic algorithms of CNS infections and febrile illness during the warm season, probably because of the lack of information.
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Affiliation(s)
- Remi N Charrel
- Remi N Charrel, Laurence Bichaud, Xavier de Lamballerie, Aix Marseille University, IRD French Institute of Research for Development, EHESP French School of Public Health, UMR_D 190 "Emergence des Pathologies Virales", 13005 Marseille, France
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Comparison of a new prototype immunochromatographic assay and a commercial enzyme-linked immunosorbent assay for the detection of serum antibodies against Toscana virus. J Virol Methods 2012; 187:182-4. [PMID: 23022418 DOI: 10.1016/j.jviromet.2012.09.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2012] [Revised: 09/12/2012] [Accepted: 09/17/2012] [Indexed: 11/23/2022]
Abstract
Toscana virus (TOSV) is an arthropod-borne virus, transmitted to humans by Phlebotomus spp. Sandflies, which causes neurological diseases such as aseptic meningitis and meningoencephalitis. The commercial enzyme-linked immunosorbent assay (ELISA) is used widely to detect anti-TOSV IgG and IgM antibodies and to allow for rapid diagnosis of infection (Diesse Diagnostica Senese, Siena, Italy). Recently, an immunochromatographic assay (ICA) was developed for human anti-TOSV IgG or IgM detection by InBios International (Seattle, WA, USA). A comparison of the two diagnostic assays was performed on one hundred serum samples collected from patients hospitalized with suspected TOSV meningitis. Both assays were in excellent agreement, for both IgG and IgM detection. For IgM, 64/65 ELISA positive samples were positive by ICA. One serum, positive for specific IgM by ELISA but negative by ICA, was confirmed by direct diagnosis, with TOSV RNA detection in the patient's cerebrospinal fluid by PCR. For IgG, 64 samples were positive by ICA out of 71 ELISA positive samples. The discordant sera were positive by immunofluorescence and neutralization tests. Three out of these seven samples were also positive by IgM ICA. The sensitivity of these new assays compared to ELISA, which is used routinely, was 98.5% for IgM and 90.1% for IgG, while specificity was 100% in both cases. This data shows that ICA could be a reliable alternative test for serological diagnosis of TOSV infection in humans.
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Punda-Polić V, Mohar B, Duh D, Bradarić N, Korva M, Fajs L, Saksida A, Avšič-Županc T. Evidence of an autochthonous Toscana virus strain in Croatia. J Clin Virol 2012; 55:4-7. [DOI: 10.1016/j.jcv.2012.06.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2012] [Revised: 05/21/2012] [Accepted: 06/08/2012] [Indexed: 10/28/2022]
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Vocale C, Bartoletti M, Rossini G, Macini P, Pascucci MG, Mori F, Tampieri A, Lenzi T, Pavoni M, Giorgi C, Gaibani P, Cavrini F, Pierro AM, Landini MP, Viale P, Sambri V. Toscana Virus Infections in Northern Italy: Laboratory and Clinical Evaluation. Vector Borne Zoonotic Dis 2012; 12:526-9. [DOI: 10.1089/vbz.2011.0781] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Affiliation(s)
- Caterina Vocale
- Department of Haematology and Oncology “L. and A. Seragnoli,” Section of Microbiology, St. Orsola University Hospital, University of Bologna, Bologna, Italy
| | - Michele Bartoletti
- Department of Internal Medicine, Geriatrics and Nephrology, Section of Infectious Disease, St. Orsola University Hospital, University of Bologna, Bologna, Italy
| | - Giada Rossini
- Department of Haematology and Oncology “L. and A. Seragnoli,” Section of Microbiology, St. Orsola University Hospital, University of Bologna, Bologna, Italy
| | | | | | - Fernanda Mori
- Unit of Infectious Diseases, Ospedale degli Infermi, Rimini, Italy
| | - Andrea Tampieri
- Emergency Department, Ospedale Civile S M della Scaletta, Imola, Italy
| | - Tiziano Lenzi
- Emergency Department, Ospedale Civile S M della Scaletta, Imola, Italy
| | | | - Claudia Giorgi
- Unit of Neurologic Disease, Ospedale di Fidenza–S. Secondo, Italy
| | - Paolo Gaibani
- Department of Haematology and Oncology “L. and A. Seragnoli,” Section of Microbiology, St. Orsola University Hospital, University of Bologna, Bologna, Italy
| | - Francesca Cavrini
- Department of Haematology and Oncology “L. and A. Seragnoli,” Section of Microbiology, St. Orsola University Hospital, University of Bologna, Bologna, Italy
| | - Anna Maria Pierro
- Department of Haematology and Oncology “L. and A. Seragnoli,” Section of Microbiology, St. Orsola University Hospital, University of Bologna, Bologna, Italy
| | - Maria Paola Landini
- Department of Haematology and Oncology “L. and A. Seragnoli,” Section of Microbiology, St. Orsola University Hospital, University of Bologna, Bologna, Italy
| | - Pierluigi Viale
- Department of Internal Medicine, Geriatrics and Nephrology, Section of Infectious Disease, St. Orsola University Hospital, University of Bologna, Bologna, Italy
| | - Vittorio Sambri
- Department of Haematology and Oncology “L. and A. Seragnoli,” Section of Microbiology, St. Orsola University Hospital, University of Bologna, Bologna, Italy
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43
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Meningitis por virus Toscana en inmigrante argentino. Enferm Infecc Microbiol Clin 2012; 30:272-3. [DOI: 10.1016/j.eimc.2011.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2011] [Revised: 11/27/2011] [Accepted: 12/04/2011] [Indexed: 11/20/2022]
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Cusi MG, Savellini GG. Diagnostic tools for Toscana virus infection. Expert Rev Anti Infect Ther 2012; 9:799-805. [PMID: 21810052 DOI: 10.1586/eri.11.54] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Toscana virus (TOSV; Phlebovirus, Bunyaviridae) is an important etiological agent of acute meningitis and meningoencephalitis in Mediterranean countries. Laboratory diagnosis has been carried out in serological studies using ELISA, immunofluorescence and/or neutralization tests that are not influenced by the virus viability; however, in the acute phase of the infection, nucleic acid amplification techniques are the methods of choice to diagnose viral meningitis from cerebrospinal fluid samples. Molecular methods are rapid and sensitive and, unlike traditional methods, such as virus isolation by cell culture, they are not influenced by the viability of the virus in the clinical specimen; however, the RNA integrity is crucial for the success of these methods. Real-time PCR is the most important molecular method used in laboratories worldwide, since it is less time-consuming and it reduces the risk of contamination. Therefore, a sensitive real-time PCR has been developed for diagnosis of suspected cases of TOSV infection either autochthonous and/or imported, since a new lineage of TOSV, divergent from the Italian prototype, has recently been reported in Spain.
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Affiliation(s)
- Maria Grazia Cusi
- Department of Biotechology, University of Siena, Policlinico 'S. Maria delle Scotte', V.le Bracci 1, 53100 Siena, Italy.
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Ninove L, Nougairede A, Gazin C, Thirion L, Delogu I, Zandotti C, Charrel RN, De Lamballerie X. RNA and DNA bacteriophages as molecular diagnosis controls in clinical virology: a comprehensive study of more than 45,000 routine PCR tests. PLoS One 2011; 6:e16142. [PMID: 21347398 PMCID: PMC3036576 DOI: 10.1371/journal.pone.0016142] [Citation(s) in RCA: 108] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2010] [Accepted: 12/06/2010] [Indexed: 01/09/2023] Open
Abstract
Real-time PCR techniques are now commonly used for the detection of viral genomes in various human specimens and require for validation both external and internal controls (ECs and ICs). In particular, ICs added to clinical samples are necessary to monitor the extraction, reverse transcription, and amplification steps in order to detect false-negative results resulting from PCR-inhibition or errors in the technical procedure. Here, we performed a large scale evaluation of the use of bacteriophages as ICs in routine molecular diagnosis. This allowed to propose simple standardized procedures (i) to design specific ECs for both DNA and RNA viruses and (ii) to use T4 (DNA) or MS2 (RNA) phages as ICs in routine diagnosis. Various technical formats for using phages as ICs were optimised and validated. Subsequently, T4 and MS2 ICs were evaluated in routine real-time PCR or RT-PCR virological diagnostic tests, using a series of 8,950 clinical samples (representing 36 distinct specimen types) sent to our laboratory for the detection of a variety of DNA and RNA viruses. The frequency of inefficient detection of ICs was analyzed according to the nature of the sample. Inhibitors of enzymatic reactions were detected at high frequency in specific sample types such as heparinized blood and bone marrow (>70%), broncho-alveolar liquid (41%) and stools (36%). The use of T4 and MS2 phages as ICs proved to be cost-effective, flexible and adaptable to various technical procedures of real-time PCR detection in virology. It represents a valuable strategy for enhancing the quality of routine molecular diagnosis in laboratories that use in-house designed diagnostic systems, which can conveniently be associated to the use of specific synthetic ECs. The high rate of inhibitors observed in a variety of specimen types should stimulate the elaboration of improved technical protocols for the extraction and amplification of nucleic acids.
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Affiliation(s)
- Laetitia Ninove
- UMR190, Université de la Méditerranée and Institut de Recherche pour le Développement, Marseille, France.
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Navarro-Marí JM, Palop-Borrás B, Pérez-Ruiz M, Sanbonmatsu-Gámez S. Serosurvey study of Toscana virus in domestic animals, Granada, Spain. Vector Borne Zoonotic Dis 2010; 11:583-7. [PMID: 20925529 DOI: 10.1089/vbz.2010.0065] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
Toscana virus (TOSV) is transmitted by infected sandflies. In Mediterranean countries, TOSV is one of the major viral pathogens involved in aseptic meningitis and meningoencephalitis in humans. It remains unclear if there are animal reservoirs able to maintain the virus through the cold months of the year, when the vector is not circulating. From May to October of 2006 and 2007, we conducted a serosurvey study on domestic animals from Granada province (southern Spain). TOSV was investigated in 1186 serum samples from horses, goats, pigs, cats, dogs, sheep, and cows by serology (indirect fluorescence assay), viral culture, and RT-polymerase chain reaction. Specific anti-TOSV antibodies were detected in 429 (36.2%) serum samples. The highest seropositivity rates were observed in cats (59.6%) and dogs (48.3%). These results suggest that an important percentage of the domestic animals have been infected by TOSV. Significantly different seroprevalence rates were detected in goats among distinct geographical areas. All viral cultures were negative. TOSV was detected by RT-polymerase chain reaction in only one serum sample from a goat. Thus, the studied animals do not seem to act as reservoirs for TOSV; otherwise, they could be amplifying hosts for the virus.
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Gori Savellini G, Weber F, Terrosi C, Habjan M, Martorelli B, Cusi MG. Toscana virus induces interferon although its NSs protein reveals antagonistic activity. J Gen Virol 2010; 92:71-9. [PMID: 20861320 DOI: 10.1099/vir.0.025999-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Toscana virus (TOSV) is a phlebotomus-transmitted virus that belongs to the family Bunyaviridae and causes widespread infections in humans; about 30 % of these cases result in aseptic meningitis. In the present study, it was shown that TOSV is an inducer of beta interferon (IFN-β), although its non-structural protein (NSs) could inhibit the induction of IFN-β if expressed in a heterologous context. A recombinant Rift Valley fever virus expressing the TOSV NSs could suppress IFN-β expression in infected cells. Moreover, in cells expressing NSs protein from a cDNA plasmid, IFN-β transcripts were not inducible by poly(I : C). Unlike other members of the family Bunyaviridae, TOSV appears to express an NSs protein that is a weak antagonist of IFN induction. Characterization of the interaction of TOSV with the IFN system will help our understanding of virus-host cell interactions and may explain why the pathogenesis of this disease is mostly mild in humans.
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Affiliation(s)
- Gianni Gori Savellini
- Department of Molecular Biology, Microbiology Section, University of Siena, 53100 Siena, Italy
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Delassus GS, Cho H, Hoang S, Eliceiri GL. Many new down- and up-regulatory signaling pathways, from known cancer progression suppressors to matrix metalloproteinases, differ widely in cells of various cancers. J Cell Physiol 2010; 224:549-58. [PMID: 20432456 DOI: 10.1002/jcp.22157] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Previously we detected new signaling pathways, some downregulatory and others upregulatory, from seven known suppressors of cancer progression to the expression of eight cancer-promoting matrix metalloproteinases (MMPs) in breast cancer cells. The goals of the present study were to test whether the preceding observations occur only in breast cancer cells and, if not, whether the same downregulatory and upregulatory signaling pathways are active in cells of other human cancers, focusing on activator protein-2alpha, E-cadherin, fibulin1D, interleukin 4, p16(INK4alpha), p53, PTEN, and RKIP, and on MMP1, MMP2, MMP7, MMP13, MMP14, MMP16, MMP19, and MMP25. To this end, in the present study we tested the effects of raising the cellular levels of wild-type copies of these known suppressors of cancer progression on the expression of these MMPs. This study yielded several unexpected results. We have detected 53 new signaling pathways in cells of prostate, brain, lung, ovarian and breast human cancers, with an abundance of signaling pathways as high as approximately 40% of the cancer progression regulator/MMP pairs tested in cells of prostate and breast cancers. Cells of various cancers differed widely and sequence-specifically in the identity of their signaling pathways, so that almost 90% of the pathways were different in cells from one cancer to another. In each of 18 out of 51 signaling pathways, a known suppressor of cancer progression stimulated, rather than inhibited, the expression of a cancer-promoting MMP. Ten signaling pathways were upregulatory in cells of some cancers and downregulatory in cells of other cancers.
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Affiliation(s)
- Gregory S Delassus
- Department of Pathology, Saint Louis University School of Medicine, St. Louis, Missouri 63104-1004, USA
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Sanbonmatsu-Gámez S, Pérez-Ruiz M, Palop-Borrás B, Navarro-Marí JM. Unusual manifestation of toscana virus infection, Spain. Emerg Infect Dis 2009; 15:347-8. [PMID: 19193294 PMCID: PMC2657633 DOI: 10.3201/eid1502.081001] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
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