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.
Highlights
The genus Phlebovirus of the Phenuviridae Family has been recently expanded and currently includes 60 viral species officially recognized by the International Committee on Taxonomy of Viruses (ICTV) [1].From a virological point of view, phleboviruses are enveloped viruses characterized by three-segmented, single-stranded, negative-sense RNA with a high rate of point mutations, reassortments, and recombinations that generate new viruses [2]
For 17 (40.5%) patients, a history of travels in endemic areas was reported, whereas 17 (40.5%) patients did not report a history of travel in the previous weeks
The outbreak reported in the Lombardy region in 2013 involved 14 patients out of 19 with no history of travel in endemic areas, suggesting the local acquisition of the infection and a spread of phlebovirus activity in new unexpected areas
Summary
From a virological point of view, phleboviruses are enveloped viruses characterized by three-segmented, single-stranded, negative-sense RNA with a high rate of point mutations, reassortments, and recombinations that generate new viruses [2]. For this reason, several new phleboviruses have been discovered, increasing the species variety [3]. No reservoir host has been definitely identified for phleboviruses, a role of humans as a reservoir has been hypothesized because of a transient viremia in the case of the Toscana virus (TOSV) [4]. TOSV, Sandfly fever Sicilian virus (SFSV), Sandfly Naples virus (SFNV), and Sandfly fever Cyprus virus (SFCV) are SFVs with well-known pathogenic potential for humans. SFSV, SFNV and SFCV are responsible for a self-limited febrile condition, whereas
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