Central Nervous System Involvement during Infection by Phlebovirus Toscana of Residents in Natural Foci in Central Italy (1977–1988)

Loredana Nicoletti Laboratory of Virology, Istituto Superiore di Sanita, Department of Infectious Diseases, Santa Maria Nuova Hospital, Department of Infectious Diseases, Hospital of Prato, Department of Infectious Diseases, Hospital of Fermo, Department of Neurology, University of Florence, Epidemiological Investigation Unit for Neurotropic Viruses, Rome, Italy

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Paola Verani Laboratory of Virology, Istituto Superiore di Sanita, Department of Infectious Diseases, Santa Maria Nuova Hospital, Department of Infectious Diseases, Hospital of Prato, Department of Infectious Diseases, Hospital of Fermo, Department of Neurology, University of Florence, Epidemiological Investigation Unit for Neurotropic Viruses, Rome, Italy

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Silvana Caciolli Laboratory of Virology, Istituto Superiore di Sanita, Department of Infectious Diseases, Santa Maria Nuova Hospital, Department of Infectious Diseases, Hospital of Prato, Department of Infectious Diseases, Hospital of Fermo, Department of Neurology, University of Florence, Epidemiological Investigation Unit for Neurotropic Viruses, Rome, Italy

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Maria Grazia Ciufolini Laboratory of Virology, Istituto Superiore di Sanita, Department of Infectious Diseases, Santa Maria Nuova Hospital, Department of Infectious Diseases, Hospital of Prato, Department of Infectious Diseases, Hospital of Fermo, Department of Neurology, University of Florence, Epidemiological Investigation Unit for Neurotropic Viruses, Rome, Italy

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Antonella Renzi Laboratory of Virology, Istituto Superiore di Sanita, Department of Infectious Diseases, Santa Maria Nuova Hospital, Department of Infectious Diseases, Hospital of Prato, Department of Infectious Diseases, Hospital of Fermo, Department of Neurology, University of Florence, Epidemiological Investigation Unit for Neurotropic Viruses, Rome, Italy

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Dario Bartolozzi Laboratory of Virology, Istituto Superiore di Sanita, Department of Infectious Diseases, Santa Maria Nuova Hospital, Department of Infectious Diseases, Hospital of Prato, Department of Infectious Diseases, Hospital of Fermo, Department of Neurology, University of Florence, Epidemiological Investigation Unit for Neurotropic Viruses, Rome, Italy

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Pietro Paci Laboratory of Virology, Istituto Superiore di Sanita, Department of Infectious Diseases, Santa Maria Nuova Hospital, Department of Infectious Diseases, Hospital of Prato, Department of Infectious Diseases, Hospital of Fermo, Department of Neurology, University of Florence, Epidemiological Investigation Unit for Neurotropic Viruses, Rome, Italy

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Francesco Leoncini Laboratory of Virology, Istituto Superiore di Sanita, Department of Infectious Diseases, Santa Maria Nuova Hospital, Department of Infectious Diseases, Hospital of Prato, Department of Infectious Diseases, Hospital of Fermo, Department of Neurology, University of Florence, Epidemiological Investigation Unit for Neurotropic Viruses, Rome, Italy

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Paolo Padovani Laboratory of Virology, Istituto Superiore di Sanita, Department of Infectious Diseases, Santa Maria Nuova Hospital, Department of Infectious Diseases, Hospital of Prato, Department of Infectious Diseases, Hospital of Fermo, Department of Neurology, University of Florence, Epidemiological Investigation Unit for Neurotropic Viruses, Rome, Italy

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Ermanno Traini Laboratory of Virology, Istituto Superiore di Sanita, Department of Infectious Diseases, Santa Maria Nuova Hospital, Department of Infectious Diseases, Hospital of Prato, Department of Infectious Diseases, Hospital of Fermo, Department of Neurology, University of Florence, Epidemiological Investigation Unit for Neurotropic Viruses, Rome, Italy

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Marzia Baldereschi Laboratory of Virology, Istituto Superiore di Sanita, Department of Infectious Diseases, Santa Maria Nuova Hospital, Department of Infectious Diseases, Hospital of Prato, Department of Infectious Diseases, Hospital of Fermo, Department of Neurology, University of Florence, Epidemiological Investigation Unit for Neurotropic Viruses, Rome, Italy

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Marco Balducci Laboratory of Virology, Istituto Superiore di Sanita, Department of Infectious Diseases, Santa Maria Nuova Hospital, Department of Infectious Diseases, Hospital of Prato, Department of Infectious Diseases, Hospital of Fermo, Department of Neurology, University of Florence, Epidemiological Investigation Unit for Neurotropic Viruses, Rome, Italy

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Central nervous system (CNS) involvement was detected during infection caused by the sand fly-transmitted Phlebovirus Toscana. One hundred fifty-five cases of Toscana virus-associated meningitis or meningoencephalitis were identified in a survey that lasted ten years, conducted in two regions of central Italy. Diagnosis was performed by different serologic tests. A combination of hemagglutination-inhibition and plaque-reduction neutralization or indirect immunofluorescence for IgM, and enzyme-linked immunosorbent assays for IgM were considered the most suitable tests for the diagnosis of Toscana virus infection. A few strains of Toscana virus were isolated from the cerebrospinal fluid of seropositive patients. Toscana virus-associated CNS disease occurred during the summer, reaching a peak value in August, when the maximum activity of the sand fly vector occurs and virus isolates are obtained in their natural foci.

The results suggest that Toscana virus should be considered as a possible cause of CNS disease in Mediterranean countries where sand flies of the genus Phlebotomus are known to be present.

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