After approximately 2 months of onset of illness, they both had anti-Toscana virus IgM and IgG with increased levels (Schultze et al., 2012). P. perniciosus is present in Malta, and recognized as the vector of Leishmania infantum ( Pace et al., 2011). In 1984, sandfly fever was first reported in Cyprus during an outbreak of febrile illness in Swedish soldiers,

serving in the United Nations forces (Niklasson and Eitrem, 1985). Neutralisation tests revealed that Naples, Toscana virus and Sicilian virus were co-circulating and caused acute infections demonstrated through seroconversion. Naples and Sicilian virus strains were isolated (Eitrem et al., 1990). Three years later, 35 of 72 Swedish tourists were found to have antibodies against Sicilian virus after visiting different hotels in Cyprus (Eitrem et al., 1991a). Seroprevalence in Cypriot residents showed high rates of neutralizing antibodies Duvelisib concentration Autophagy Compound high throughput screening (⩾1:80) against Naples (57%), Sicilian

(32%) and Toscana virus (20%) (Eitrem et al., 1991b). In 2002, a sandfly fever epidemic occurred in Greek soldiers stationed close to the capital Nicosia. Fifteen blood samples were RT-PCR positive. Virus isolation was obtained from blood specimens, and genetic analysis showed that this strain was related to but clearly distinct from Sicilian virus. This virus was named Sandfly fever Cyprus virus (Konstantinou et al., 2007 and Papa et al., 2006). In early studies, seroprevalence rates of 22% and 62% were found for Sicilian and Naples virus, respectively (PRNT (80)) in the Mediterranean Region (Tesh et al., 1976). In the Aegean Region, Sicilian and Naples virus neutralizing antibodies were detected in 0.8% and 13.9% sera, respectively among 1074 healthy residents (Serter, 1980). Sandfly fever was first diagnosed in one case of meningitis in a patient returning to Germany (Becker et al., 1997). Sicilian virus was suspected based on ELISA and immunoblot results. According to CDC criteria for the diagnosis of arboviral diseases (2012 Case Definitions: Nationally Notifiable Conditions Infectious Reverse transcriptase and Non-Infectious Case), this case should be

considered as probable, but not confirmed. Moreover, CNS manifestations were reported seldom with Sicilian virus and direct evidence (RT-PCR, virus isolation) remains to be provided. Extensive investigations have been initiated during the last decade, especially in the regions where outbreaks have occurred: in the Mediterranean region in 2008, in the Aegean region in 2004-8), and in Central Anatolia in 2007-8). IgM antibodies to Sicilian virus, Sicilian or Cyprus virus, and Cyprus virus were detected by immunofluorescence assay in 36%, 12%, and 4% of acute patient sera, respectively. The recurrent problem of cross reactivity between these antigenically related viruses is exemplified here. No serological technique other than neutralization is currently capable of resolving this issue.