Patient with severe fever with thrombocytopenia syndrome virus infection and central nervous system disturbance in Dongyang, Zhejiang Province, China, 2017.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever that was first described in China in 2011. We report a patient who died of Severe fever with thrombocytopenia syndrome virus (SFTSV) infection, with a rapidly progressive central nervous system (CNS) disturbance, in Dongyang, Zhejiang Province, China, in 2017. CASE PRESENTATION: A 64-year-old man was admitted to hospital after 4 days of fever. SFTSV was detected 1 day after the patient was admitted to hospital. The patient presented with CNS disturbance and died 4 days after admission. Detailed clinical and epidemiological investigations and laboratory tests were conducted. Reduced platelet, white blood cell, lymphocyte, and neutrophil counts, elevated lactate dehydrogenase, creatine kinase, aspartate aminotransferaseand alanine aminotransferase concentrations, and an increased activated partial thromboplastin time were observed. In a phylogenetic analysis, the isolate clustered close to a strain derived from South Korea. CONCLUSIONS: This is the first case of SFTSV infection with CNS disturbance in Dongyang, Zhejiang Province, China. The surveillance of suspected cases of SFTS is important in SFTSV endemic regions.

The Emergence of Severe Fever with Thrombocytopenia Syndrome Virus.

Severe fever with thrombocytopenia syndrome (SFTS) is a newly recognized hemorrhagic fever disease found throughout Asia with a case fatality rate between 12% and 30%. Since 2009, SFTS has been reported in China throughout 14 Chinese Provinces. In addition, SFTS has been recognized in South Korea and Japan with the first confirmed cases reported in 2012. A similar disease, caused by the closely related Heartland virus, was also reported in the United States in 2009. SFTS is caused by SFTS virus, a novel tick-borne virus in the family Bunyaviridae, genus Phlebovirus. Unlike other mosquito- and sandfly-borne bunyaviruses, SFTS virus has not been extensively studied due to its recent emergence and many unknowns regarding its pathogenesis, life cycle, transmission, and options for therapeutics remains. In this review, we report the most current findings in SFTS virus research.

A Cluster of Symptomatic and Asymptomatic Infections of Severe Fever with Thrombocytopenia Syndrome Caused by Person-to-Person Transmission.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus that was identified to be the etiological pathogen of the emerging infectious disease, severe fever with thrombocytopenia syndrome (SFTS). SFTSV could be transmitted through tick bite. Transmission of SFTSV among humans has also been reported mainly through direct blood contact. In July 2014, a cluster of six suspected SFTS cases occurred in Shandong Province, China. In this cluster, both symptomatic and asymptomatic persons were included. By analyzing the clinical data and results of laboratory tests, and conducting the epidemiological interviews with the cases and their families, risk factors responsible for the transmission were evaluated. The findings suggested that SFTSV transmission among humans may cause asymptomatic infection via personal contact without blood exposure.

Toscana virus encephalitis following a holiday in Sicily.

We report a case of Toscana virus encephalitis. This emerging pathogen is among the three most common causes of meningoencephalitis in Europe during the warm season, yet remains under-recognised. Doctors should consider Toscana virus infection in patients presenting with neurological symptoms who have a relevant exposure history during the summer months.

Clinic-epidemiologic study of human infection by Granada virus, a new phlebovirus within the sandfly fever Naples serocomplex.

Granada virus (GRV), a new phlebovirus within the Naples serocomplex, has been recently described in phlebotomine sandflies from Spain. The presence of anti-GRV immunoglobulin G (IgG) antibodies was investigated by indirect fluorescence assay (IFA) and neutralization test (NT) in 920 serum samples from the Granada population. By IFA, an overall GRV seroprevalence of 15.8% (N = 145) was observed, significantly increasing up to 65 years. NT was positive in 18% of anti-GRV IFA-positive samples. IgG antibodies against Toscana virus (TOSV), a hyperendemic phlebovirus within Granada province, were detected in 40% of anti-GRV-positive cases. Anti-GRV IgM antibodies were detected in 36 (6.6%) of 547 acute-phase serum samples from individuals with febrile illness, exanthema, and/or acute respiratory infection. All positives were anti-TOSV IgM-negative. GRV may infect humans, with most cases being asymptomatic. The codetection of anti-GRV and anti-TOSV IgG antibodies could be attributable to cross-reactivity or exposure to the same transmission vector.

Emergence of Toscana virus in Europe.

Toscana virus (TOSV) is an arthropod-borne virus first identified in 1971 from the sandfly Phlebotomus perniciosus in central Italy. Many case reports in travelers and clinical research and epidemiologic studies conducted around the Mediterranean region have shown that TOSV has a tropism for the central nervous system (CNS) and is a major cause of meningitis and encephalitis in countries in which it circulates. In central Italy, TOSV is the most frequent cause of meningitis from May to October, far exceeding enteroviruses. In other northern Mediterranean countries, TOSV is among the 3 most prevalent viruses associated with meningitis during the warm seasons. Therefore, TOSV must be considered an emerging pathogen. Here, we review the epidemiology of TOSV in Europe and determine questions that should be addressed in future studies. Despite increasing evidence of its major role in medicine as an emerging cause of CNS infections, TOSV remains an unstudied pathogen, and few physicians are aware of its potential to cause CNS infections.

Unusual presentation of life-threatening Toscana virus meningoencephalitis.

This case report describes a brother and a sister with severe meningoencephalitis caused by Toscana virus (TOSv). The clinical presentation was characterized by stiff neck, deep coma, maculopapular rash, diffuse lymphadenopathy, hepatosplenomegaly, renal involvement, tendency to bleeding, and diffuse intravascular coagulation. The boy had epididymo-orchitis. Recovery with neurologic sequelae as hydrocephalus was observed. Microbiological diagnosis was obtained by serological tests and reverse transcriptase-polymerase chain reaction. Sequencing of polymerase chain reaction products from the S and M segments was carried out. TOSv may be a causative agent in severe meningoencephalitis.

Encephalitis without meningitis due to sandfly fever virus serotype toscana.

The role of Toscana (TOS) virus in producing encephalitis without meningitis is uncertain. We studied 2 cases of TOS virus encephalitis without meningitis by means of nested polymerase chain reaction assay and DNA sequencing. Findings confirm that TOS virus may directly cause encephalitis and suggest the usefulness of DNA sequencing in investigating relationships between TOS virus molecular patterns and the spectrum of neurological involvement.

Experimental infection of nonhuman primates with sandfly fever virus.

Due to the lack of an animal model, previous studies of sandfly fever have relied upon human challenge trials. We examined the infectivity and potential pathogenicity of sandfly fever virus in cynomolgus monkeys (Macaca fascicularis). Three different preparations of sandfly fever virus. Sicilian strain, and a placebo were compared by different routes of administration. The most notable postchallenge clinical event was a decrease in lymphocytes in the intramuscularly challenged monkeys. Plaque-reduction neutralization responses peaked earlier in animals challenged intravenously as compared with those in animals challenged intramuscularly. There was no evidence for neurotropism or meningeal inflammation. Sandfly fever virus was infectious for cynomolgus monkeys, but produced no detectable clinical disease that might serve as a marker for animal modeling studies. On the other hand, the preclinical data provide supportive evidence for safe parenteral administration of a Sicilian strain of sandfly fever virus inoculum to humans as a challenge model for sandfly fever disease.