Human seroprevalence of Toscana virus and Sicilian phlebovirus in the southwest of Portugal.

Toscana virus (TOSV) is emergent in the Mediterranean region and responsible for outbreaks of encephalitis or meningoencephalitis. Sicilian phlebovirus (SFSV) cause epidemics of febrile illness during the summer. The aim of this study was to evaluate the presence of antibodies against TOSV and SFSV in humans in the southwest of Portugal. Neutralizing antibodies to TOSV and SFSV were respectively detected in 5.3% and 4.3% out of 400 human sera tested highlighting the need to increase public health awareness regarding phleboviruses and to include them in the differential diagnosis in patients presenting with fever of short duration and neurological manifestations.

Update in Diagnostics of Toscana Virus Infection in a Hyperendemic Region (Southern Spain).

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.

Seroprevalence of Toscana Virus and Sandfly Fever Sicilian Virus in European Bat Colonies Measured Using a Neutralization Test.

Toscana phlebovirus (TOSV) and Sicilian phlebovirus (SFSV) are endemic in the Mediterranean area where they are transmitted to humans by infected sandflies. Vertebrates of several species have been postulated to act as reservoirs of these viruses, but convincing evidence is still awaited. Among them, bats have been suggested, however documented evidence is lacking. Here we tested a total of 329 bats belonging to eight species collected from twelve localities in southern Spain for the presence of neutralizing antibodies specific to TOSV and SFSV. Positive sera were detected in Schreiber's long-fingered bat (Miniopterus schreibersii), mouse-eared Myotis (Myotis myotis), European free-tailed bat (Tadarida teniotis), and common serotine (Eptesicus serotinus) with the latter showing the highest prevalence rates for SFSV (22.6%) and TOSV (10%). There was no difference between females and males. Results suggest that bats are not likely to play a major role in the natural cycle of these two sandfly-borne phleboviruses. However, large breeding colonies of bats can be used as sentinels for surveillance of the presence of such viruses in a given locality. In addition, capture-recapture studies should be initiated in order to understand better the dynamics of TOSV and SFSV in bat populations.

Two clusters of Toscana virus meningo-encephalitis in Livorno Province and Elba Island, July-September 2018.

BACKGROUND: Toscana virus (TOSV) is an arbovirus transmitted to humans by Phlebotomus spp sandflies. It causes aseptic meningitis and meningoencephalitis with marked seasonality. Here we describe the clinical, microbiological and epidemiological features of two clusters of cases occurred in Tuscany in 2018. METHODS: A confirmed case was defined as the detection of anti-TOSV IgM and IgG in serum sample, in presence of typical clinical manifestations. We consulted hospital records of hospitalized patients to collect clinical information and obtained epidemiological information from the local health authority investigation report. We telephonically interviewed patients using a standard questionnaire for a 6 months follow-up. RESULTS: A total of 12 cases of TOSV meningo-encephalitis with onset between 4th of July and 12th of September accessed health care services in the province of Livorno. Eight cases were males with median age 41,5 and four were not resident in the area. Serological investigations confirmed a recent TOSV infection. Eight cases reported visiting Elba Island and four had a possible occupational-related exposure. CONCLUSIONS: This surge of infection emphasizes the need of information campaigns coupled with adequate surveillance and control interventions against TOSV that, among other arboviruses, is a growing issue of concern in Italy.

Ubiquitin and Not Only Unfolded Domains Drives Toscana Virus Non-Structural NSs Protein Degradation.

The non-structural protein NSs of the Phenuiviridae family members appears to have a role in the host immunity escape. The stability of Toscana virus (TOSV) NSs protein was tested by a cycloheximide (CHX) chase approach on cells transfected with NSs deleted versions fused to a reporter gene. The presence of intrinsically disordered regions (IDRs) both at the C- and N-terminus appeared to affect the protein stability. Indeed, the NSsΔC and NSsΔN proteins were more stable than the wild-type NSs counterpart. Since TOSV NSs exerts its inhibitory function by triggering RIG-I for proteasomal degradation, the interaction of the ubiquitin system and TOSV NSs was further examined. Chase experiments with CHX and the proteasome inhibitor MG-132 demonstrated the involvement of the ubiquitin-proteasome system in controlling NSs protein amount expressed in the cells. The analysis of TOSV NSs by mass spectrometry allowed the direct identification of K104, K109, K154, K180, K244, K294, and K298 residues targeted for ubiquitination. Analysis of NSs K-mutants confirmed the presence and the important role of lysine residues located in the central and the C-terminal parts of the protein in controlling the NSs cellular level. Therefore, we directly demonstrated a new cellular pathway involved in controlling TOSV NSs fate and activity, and this opens the way to new investigations among more pathogenic viruses of the Phenuiviridae family.

Low Incidence and Mortality from SARS-CoV-2 in Southern Europe. Proposal of a hypothesis for Arthropod borne Herd immunity.

SARS-CoV-2 incidence and mortality in Europe have shown wide variation. Northern Italy in particular the Lombardy region, north-eastern French regions, Switzerland and Belgium were amongst the hardest hit, while the central and southern Italian regions, all the Balkan countries from Slovenia to Greece and the Islands of Malta and Cyprus had much fewer cases and deaths per capita, and deaths per number of cases. Differences in public health measures, and health care delivery, in the author's opinion, can only partly explain the difference. The geographical distribution of Phlebotomus sand-flies and the relative distribution of arthropod borne diseases Leishmaniasis and Phlebovirus infections especially the Sicilian Sandfly fever group corresponds to most areas of low prevalence of SARS-CoV-2. A hypothesis is proposed whereby repeated arthropod or sandfly vector infection of humans by novel viruses of zoonotic origins carrying bat or mammalian RNA/DNA, such as phleboviruses may have resulted in the development of an effective evolutionary immune response to most novel zoonotic viruses such as SARS-CoV-2 by means of survival of the fittest possibly over many generations. This process probably ran in parallel and concurrent with the progressive evolution of novel coronaviruses which spread from one mammalian species to another. Other possible, but less likely mechanisms for the role of sandfly meals within a much shorter time frame may have led to, (i) previous exposure and infection of humans with the SARS-Cov-2 virus itself, or a closely related corona virus in the previous decades, or (ii) exposure of human populations to parts coronavirus protein namely either S or more likely N protein carried mechanically by arthropods, but without clinical disease causing direct immunity or (iii) by causing infection with other arthropod borne viruses which could carry bat DNA/RNA and have similar functional proteins resulting in an immediate cross-reactive immune response rather than by natural selection. The Evidence possibly supporting or disputing this hypothesis is reviewed, however the major problem with the hypothesis is that to date no coronavirus has ever been isolated from arthropods. Such a hypothesis can only be supported by research investigating the possible biological relationship of arthropods and coronaviruses where paradoxically they may be promoting immunity rather than disease.

Epidemiology of Toscana virus in South Tuscany over the years 2011-2019.

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.

Novel Toscana Virus Reverse Genetics System Establishes NSs as an Antagonist of Type I Interferon Responses.

The sand fly-borne Toscana virus (TOSV) is the major cause of human meningoencephalitis in the Mediterranean basin during the summer season. In this work, we have developed a T7 RNA polymerase-driven reverse genetics system to recover infectious particles of a lineage B strain of TOSV. The viral protein pattern and growth properties of the rescued virus (rTOSV) were found to be similar to those of the corresponding wild-type (wt) virus. Using this system, we genetically engineered a TOSV mutant lacking expression of the non-structural protein NSs (rTOSVɸNSs). Unlike rTOSV and the wt virus, rTOSVɸNSs was unable to (i) suppress interferon (IFN)-b messenger RNA induction; and (ii) grow efficiently in cells producing IFN-b. Together, our results highlight the importance of NSs for TOSV in evading the IFN response and provide a comprehensive toolbox to investigate the TOSV life cycle in mammalian and insect host cells, including several novel polyclonal antibodies.

Serologic evidence of widespread Toscana virus infection in Bulgaria.

BACKGROUND: Toscana virus (TOSV) is an emerging sandfly-borne virus that is endemic in Mediterranean countries. METHODS: In order to detect TOSV circulation among the human population of Bulgaria, serum samples from 459 apparently healthy adult individuals, residing in19 out of 28 districts in the country, were tested for the presence of IgG antibodies to TOSV. RESULTS: An overall seroprevalence rate of 24.4% was observed, ranging from 4.4% to 53.5% in the districts. Rates were highest in persons over 60 years of age and residing in the southern districts. CONCLUSION: The results of the first TOSV seroprevalence study in Bulgaria revealed that infection is widespread. Physicians should be aware of the virus circulation during summer and consider the diagnosis in cases of febrile illness, meningitis or meningoencephalitis.

Circulation of Toscana Virus in a Sample Population of Corsica, France.

Sandfly-borne phleboviruses pathogenic to humans, such as Toscana virus (TOSV) and Sandfly Fever Sicilian virus (SFSV), are endemic in the Mediterranean region. In France, several autochthonous cases of TOSV infection have been described, causing either meningitis or encephalitis. The aim of the present study was to investigate the seroprevalence of TOSV and SFSV antibodies in a healthy population from Corsica. In this cross-sectional study, participants were enrolled (i) from a medical staff at the University of Corsica and (ii) from general practitioners of the Corsican Sentinelles Network. The seroprevalence study was based on a virus microneutralization assay. A total of 240 sera were tested. Altogether, 54 sera (22.5%) were confirmed positive for TOSV antibodies, whereas none were positive for SFSV (0/240). The residential district of participants was significantly associated with TOSV seropositivity (p value = 0.005). The rate of the seropositivity against TOSV in our study suggests that the Corsican population is well exposed to the TOSV. These results encourage the implementation of a systematic surveillance system including entomological, microbiological, and medical aspects for the collection of better information on the diseases that are associated with phleboviruses in Corsica and beyond in the regions where these viruses are present.

Meningitis and epididymitis caused by Toscana virus infection imported to Switzerland diagnosed by metagenomic sequencing: a case report.

BACKGROUND: We report a rare case of Toscana virus infection imported into Switzerland in a 23-year old man who travelled to Imperia (Italy) 10 days before onset of symptoms. Symptoms included both meningitis and as well epididymitis. This is only the fourth case of Toscana virus reported in Switzerland. CASE PRESENTATION: The patient presented with lymphocytic meningitis and scrotal pain due to epididymitis. Meningitis was initially treated with ceftriaxone. Herpes simplex, tick-borne encephalitis, enterovirus, measles, mumps, rubella and Treponema pallidum were excluded with specific polymerase chain reaction (PCR) or serology. In support of routine diagnostic PCR and serology assays, unbiased viral metagenomic sequencing was performed of cerebrospinal fluid and serum. Toscana virus infection was identified in cerebrospinal fluid and the full coding sequence could be obtained. Specific PCR in cerebrospinal fluid and blood and serology with Immunoglobulin (Ig) M and IgG against Toscana virus confirmed our diagnosis. Neurological symptoms recovered spontaneously after 5 days. CONCLUSIONS: This case of Toscana virus infection highlights the benefits of unbiased metagenomic sequencing to support routine diagnostics in rare or unexpected viral infections. With increasing travel histories of patients, physicians should be aware of imported Toscana virus as the agent for viral meningitis and meningoencephalitis.

Serum cytokine and chemokine changes during Toscana virus meningitis.

Toscana virus is an important arbovirus causing meningitis and meningoencephalitis in countries around the Mediterranean Sea. While the clinical syndrome and laboratory diagnostic procedures have been well described, less is known about the immune response in Toscana virus meningitis and a possible use of cytokine and chemokine changes for the clinical follow-up of patients. We here characterized serum cytokine and chemokine profiles from 37 patients during the acute and convalescent phase of the infection. Only few serum cytokine/chemokine changes were detected during Toscana virus meningitis. Markedly increased concentrations of IP-10, interferon-α, IL-22, and eotaxin were found in the acute phase. Levels of interferon-α, IL-22, and eotaxin remained elevated in the convalescent phase, but decreased concentrations of GM-CSF were detected.

Guillain-Barré-like axonal polyneuropathy associated with Toscana virus infection: A case report.

RATIONALE: Numerous cases of post-infectious Guillain-Barré syndrome (GBS) have been reported in the literature. Toscana virus (TOSV) is an arthropod-borne emerging pathogen in the Mediterranean area. PATIENT CONCERNS: A 40-year-old male patient was admitted to hospital for acute facial weakness, associated to numbness paraesthesias at lower and upper limbs. The neurological examination revealed facial diplegia and reduced tendon reflexes. The nerve conduction studies documented an acute motor and sensory axonal neuropathy (AMSAN); the lumbar puncture detected albuminocytologic dissociation. Serology for human immunodeficiency virus (HIV), Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), mumps, and Borrelia was negative, as was cerebrospinal fluid (CSF) polymerase chain reaction assay for Herpes virus, Borrelia, Mycoplasma pneumoniae, Cryptococcus, and Mycobacterium tubercolosis. Positivity for TOSV IgG antibodies was found on both CSF and serum; the patient remembered being recently exposed to mosquitoes. DIAGNOSES: The AMSAN subtype of GBS, subsequent to a TOSV infection, was diagnosed. INTERVENTIONS: The patient was treated with plasma-exchange with complete clinical recovery, but a relapse occurred 9 months later, when the nerve conduction studies confirmed the presence of an AMSAN, which benefited from oral steroids. OUTCOMES: A good clinical recovery was achieved after treatments. LESSONS: This is the first case, to the best of our knowledge, of a TOSV infection associated to a peripheral neuropathy mimicking a GBS syndrome, both clinically and electrophysiologically. The clinical spectrum of TOSV neurological complications seems to be wider than previously known: this should be taken into account by the scientific community and public health institutions.

Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis.

The presence of the endogenous Leishmania RNA virus 1 (LRV1) replicating stably within some parasite species has been associated with the development of more severe forms of leishmaniasis and relapses after drug treatment in humans. Here, we show that the disease-exacerbatory role of LRV1 relies on type I IFN (type I IFNs) production by macrophages and signaling in vivo. Moreover, infecting mice with the LRV1-cured Leishmania guyanensis (LgyLRV1- ) strain of parasites followed by type I IFN treatment increased lesion size and parasite burden, quantitatively reproducing the LRV1-bearing (LgyLRV1+ ) infection phenotype. This finding suggested the possibility that exogenous viral infections could likewise increase pathogenicity, which was tested by coinfecting mice with L. guyanensis and lymphocytic choriomeningitis virus (LCMV), or the sand fly-transmitted arbovirus Toscana virus (TOSV). The type I IFN antiviral response increased the pathology of L. guyanensis infection, accompanied by down-regulation of the IFN-γ receptor normally required for antileishmanial control. Further, LCMV coinfection of IFN-γ-deficient mice promoted parasite dissemination to secondary sites, reproducing the LgyLRV1+ metastatic phenotype. Remarkably, LCMV coinfection of mice that had healed from L. guyanensis infection induced reactivation of disease pathology, overriding the protective adaptive immune response. Our findings establish that type I IFN-dependent responses, arising from endogenous viral elements (dsRNA/LRV1), or exogenous coinfection with IFN-inducing viruses, are able to synergize with New World Leishmania parasites in both primary and relapse infections. Thus, viral infections likely represent a significant risk factor along with parasite and host factors, thereby contributing to the pathological spectrum of human leishmaniasis.

Serological association between Leishmania infantum and sand fly fever Sicilian (but not Toscana) virus in sheltered dogs from southern Portugal.

BACKGROUND: Phlebotomine sand fly-borne diseases such as leishmanioses and phleboviruses are emerging threats to animal and public health. Canine leishmaniosis caused by Leishmania infantum is an endemic zoonosis in Portugal. Antibodies to Toscana virus (TOSV) and sand fly fever Sicilian virus (SFSV) were also reported in dogs from the south of the country. The aim of this work was to evaluate a possible association between exposure to L. infantum, TOSV and SFSV in sheltered dogs from the south of Portugal. RESULTS: Seventy-six (13.1%) out of 581 dogs were seropositive for L. infantum, 327 (56.3%) for SFSV and 36 (6.2%) for TOSV. Six dogs were co-exposed with L. infantum and TOSV, 51 with L. infantum and SFSV and 25 with TOSV and SFSV. One dog had antibodies to the three pathogens. Leishmania infantum seroprevalence was significantly higher in pure breed dogs than in mongrels and in dogs with clinical signs while SFSV positivity was significantly higher in males, in pure and cross-breed dogs than in mongrels and in those not treated with insecticides. Seroprevalence for both viruses was significantly higher in dogs over than 7 years-old than in those aged 1-7. A significant association was observed between the presence of antibodies to L. infantum and SFSV. CONCLUSIONS: The presence of antibodies to several phlebotomine sand fly-borne pathogens in dogs, reinforces the need to implement efficient prophylactic measures to prevent infection among vertebrate hosts including humans. The results also indicate that dogs are good sentinels for assessing human exposure to TOSV and SFSV. Further studies must be performed to elucidate the role of dogs in the dynamics of transmission and if they can play a role as amplifying or reservoir hosts in the natural cycle of these viruses. Public and animal health impacts of these phleboviruses in Portugal should be addressed via serological and virological studies on both phlebotomine sand flies and vertebrate hosts, especially on humans.

Characterization of antibody response in neuroinvasive infection caused by Toscana virus.

OBJECTIVES: Among sandfly-borne pathogens, Toscana virus (TOSV) is a prominent cause of summer meningitis in Mediterranean Europe. Here, we assessed the kinetics of anti-TOSV antibodies over time in 41 patients diagnosed with TOSV meningitis or meningoencephalitis in northeastern Italy. METHODS: Acute and follow-up serum samples were collected up to 20 months after diagnosis of TOSV infection and tested for the presence of specific antibody using immunoenzymatic and indirect immunofluorescence assays. In addition, maturation of anti-TOSV IgG over time was evaluated as well as production of neutralizing antibodies. RESULTS: Specific IgM and IgG response was present at diagnosis in 100% of patients; TOSV-specific IgM and IgG were detected in patients' sera up to 6 and 20 months after diagnosis, respectively. The avidity index (AI) increased over the first month after infection in 100% of patients and most cases exceeded 60% by Day 30 post infection. The AI subsequently plateaued then declined at 20 months after diagnosis. Finally, neutralization assay to TOSV was performed in 217 sera collected from 41 patients; 69.6% of tested samples resulted in reactive and moderate levels of neutralizing antibodies observed during all phases of infection despite high titres of total anti-TOSV IgG. CONCLUSIONS: Specific antibody response develops rapidly and is long-lasting for neuroinvasive TOSV infection. Serodiagnosis of neuroinvasive TOSV requires simultaneous detection of specific IgM and IgG. Moderate levels of neutralizing antibodies were maintained over the study period, while the protective role of antibodies lacking neutralizing activity is unclear and requires further evaluation.

Seroprevalence study of Toscana virus and viruses belonging to the Sandfly fever Naples antigenic complex in central and southern Italy.

Sandfly fever viruses are transmitted by the bite of phlebotomine sandflies; serotypes sandfly fever Naples virus, sandfly fever Sicilian virus and sandfly fever Cyprus virus cause febrile illness, whereas Toscana virus (TOSV) may cause neuroinvasive infections. Although TOSV is an important cause of aseptic meningitis in central and southern Italy, in many cases the infection is asymptomatic, leading to underestimation of the actual spread of the virus. This serosurvey aimed to assess the seroprevalence of TOSV in a random population in Siena (Tuscany, central Italy) in 2003-2004 and 2013-2014 and Bari (Apulia, southern Italy) in 2004 and 2015. 2132 serum samples were tested for the presence of anti-TOSV/SFNV IgG by means of ELISA and IFA commercial tests. Seroprevalence rates were compared in the two cities and over a ten-year period in the same city. Seroprevalence results in the Siena population (22.95% in 2003-2004 vs 26.75% in 2013-2014) confirmed the endemic circulation of TOSV and closely related viruses in central Italy, without major changes over the last decade, while no significant prevalence was observed in Bari (2.90% in 2004 vs 1.85% in 2015).

Seroprevalence of sandfly fever virus infection in military personnel on the western border of Iran.

Military troops deployed to endemic areas are at risk of contracting sandfly fever, an arthropod-borne viral infection. Although typically a self-limited disease, sandfly fever can cause significant morbidity and loss of function among soldiers. We conducted this study to determine the extent of past SFV infection in a group of healthy Iranian military personnel in Ilam province on the western border of Iran. A total of 201 serum samples were tested by indirect immunofluorescence assay (IFA) to detect four common sandfly fever virus serotypes. Demographic data were also collected. Overall, 37 samples (18.4%) were positive for specific IgG antibodies to sandfly viruses. Sandfly fever Sicilian virus (SFSV) and sandfly fever Naples virus (SFNV) were the most common serotypes. A positive test was inversely related to nativity (P<0.01) but was not associated with age (P=0.163), duration of presence in the border region (P=0.08) or employment status (P=0.179). Our findings indicate that past SFV infection is common among military personnel in the western border region of Iran, a Leishmania-endemic region. Therefore, it should be considered in the differential diagnosis of troops presenting with acute febrile illness in similar settings.

Neutralization-based seroprevalence of Toscana virus and sandfly fever Sicilian virus in dogs and cats from Portugal.

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.

Seroprevalence of Toscana virus in dogs from Corsica, France.

BACKGROUND: Toscana virus (TOSV) is an arbovirus belonging to the Bunyaviridae, a family of negative-stranded, enveloped RNA viruses. The virus can be transmitted to humans through the bite of an infected female sand fly of the genus Phlebotomus. Infections are usually asymptomatic but the virus is known to cause aseptic meningitis and/or meningo-encephalitis in the Mediterranean countries. Dogs are good sentinels for detection of viral circulation and are more easily accessible than wild animals. FINDINGS: In 2013 and 2014, we collected sera from 231 adult dogs living in 26 counties in two departments in Corsica, a French island in the Mediterranean. The virus microneutralization-based seroprevalence assay revealed a seropositivity of 3.9 % dogs on the eastern coast of Corsica. CONCLUSIONS: Our study confirms the circulation of TOSV in Corsica. Accordingly, in geographical areas where dogs possess TOSV neutralizing antibodies, direct and indirect TOSV diagnosis should be implemented in patients presenting with febrile illnesses and central nervous system infections such as meningitis and encephalitis.