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Prevalence of antibodies to West Nile fever, sandfly fever Sicilian, and sandfly fever Naples viruses in healthy adults in Israel.

BACKGROUND: The arbovirus infections West Nile fever (WNF) and sandfly fever (SFF) are both endemic in the Middle East. Despite the fact that the mosquito and sandfly vectors of these viruses are still found in Israel, SFF has not been reported since 1948, whereas outbreaks of WNF occur periodically. It is suspected that some of the cases of nonspecific febrile illnesses in Israel may in fact be either WNF or SFF. AIM: To determine the extent of past arbovirus infections in subgroups of Israeli soldiers. METHODS: Sera from random samples of three groups of healthy soldiers aged 18-20 (n=273), 21-30 (n=497), and 40-55 years (n=285) were examined for IgG and IgM antibodies to West Nile virus (WNV), sandfly fever Sicilian virus (SFSV), and sandfly fever Naples virus (SFNV), using an ELISA method. RESULTS: The prevalence of antibodies increased with age for all three viruses examined, and ranged from 7.0%, 0, and 2.8%, for WNV, SFSV, AND SFNV, respectively, in soldiers aged 18-20 years, to 41.9%, 23.7%, and 30.8%, in those aged 40-55 years. The percentage of seropositives for IgG who were also IgM positive were 1.0%, 5.9%, and 3.4%, for WNV, SFSV, AND SFNV, respectively. 17.5% of the seropositives for WNV were also positive for SFSV, as compared with 5.7% among the WNV-seronegatives. Among the seropositives for WNV, 23.99% were positive for SFNV, compared with 9.1% of WNV seronegatives. 48.2% of seropositives for SFSV were positive for SFNV, as compared with 8.4% for SFSV-seronegatives. In the age agroup 40-55 years, there were significantly higher prevalence rates in those born in Israel compared with those born abroad. CONCLUSIONS: There is still significant exposure to WNV, SFSV, and SFNV in Israel. Arborviruses are probably responsible for many cases of non-specific febrile illness in this region.

Adolescent↗

Neutralizing antibodies for sandfly fever Naples virus in human sera on the island of Mljet.

Sera from apparently healthy residents of various age from different localities of the Adriatic island of Mljet were tested by the plaque reduction neutralization test (PRNT) for antibodies to sandfly fever Naples virus (SFN). An average of 51.4% of the sera examined was found to have neutralizing antibodies. Reactors to SFN virus were found in all the age groups examined and the antibody prevalence appeared to increase with age. The presence of SFN neutralizing antibodies in all age groups indicates that the virus must have been present endemically and that it is still active on the island of Mljet.

Adolescent↗

[Sandfly fever Naples virus (serotype Toscana) infection with meningeal involvement after a vacation in Italy].

HISTORY AND CLINICAL FINDINGS: A 69-year-old man was admitted to our hospital with severe headache, recurrent episodes of fever and deterioration of general health. He returned from a vacation in Tuscany (Italy) a few days before admission. Physical examination revealed slight nuchal rigidity and an elevated body temperature of 37.8 C but was otherwise unremarkable. INVESTIGATIONS: Differential blood count showed a lymphocytopenia. Other abnormal laboratory findings included an elevated blood sedimentation rate and a slightly increased C-reactive protein value. Abdominal sonography demonstrated a marginally enlarged spleen. DIAGNOSIS, TREATMENT AND CLINICAL COURSE: A lumbar puncture was performed. Cerebrospinal fluid analysis revealed a lymphocytic meningitis. Serological examination of a blood sample showed specific IgM-antibodies against sandfly fever Naples virus (SFNV), subtype Toscana virus (TOSV). After this diagnosis had been made initially instituted intravenous administration of antibiotics and antiviral medication were discontinued. The patient's symptoms improved rapidly under symptomatic treatment. Slight headaches without episodes of fever persisted for a few weeks without residual neurological symptoms. CONCLUSIONS: A history of travel should always be sought in patients with clinical signs for meningitis. Considering the increasing spread and incidence of SFNV and its subtype Toscana in mediterranean countries, such virus should be kept in mind when treating patients who present such symptoms after returning from those countries during the summer season.

Acyclovir↗

Sandfly fever viruses in Italy.

Two serologically distinct agents, the sandfly fever Sicilian and the sandfly fever Naples viruses, were isolated by Sabin from blood samples taken during an Italian epidemic of febrile illness. Since then, several different viruses have been isolated from sandflies and/or humans in both the Old and New World. Toscana virus, a new virus closely antigenically related to sandfly fever Naples virus, was isolated in 1971 from the sandfly Phlebotomus perniciosus in Italy. Extensive studies on the importance of Toscana virus as a human pathogen demonstrated its association with acute neurologic diseases. A serosurvey for the presence of antibodies to sandfly fever Sicilian, sandfly fever Naples and Toscana viruses indicated that, as in other Mediterranean areas, both sandfly fever Sicilian and sandfly fever Naples viral infections decreased or disappeared after the 1940s in countries performing insecticide-spraying malaria eradication campaigns. In contrast, clinical cases of aseptic meningitis or meningoencephalitis caused by Toscana virus are observed annually in Central Italy during the summer. Toscana virus may be present in other Mediterranean countries where sandflies of the genus Phlebotomus are present.

Animals↗

High prevalence rates of antibody to three sandfly fever viruses (Sicilian, Naples, and Toscana) among Cypriots.

Neutralizing antibodies to sandfly fever Naples, sandfly fever Sicilian and Toscana viruses were investigated among 479 sera collected from a normal human population in Cyprus. Antibody prevalence rates of 57%, 32% and 20% were found to Naples, Sicilian and Toscana viruses, respectively. The observed frequency of dual and triple infections was higher than would be expected with a random chance of infection. Antibody prevalence rates were similar for men and women for all three viruses tested, but one of two study sites had significantly higher antibody prevalence to Naples and Sicilian viruses than the other. Individuals with antibodies to both Naples and Toscana viruses had higher antibody levels to Naples virus than those with antibodies to Naples virus only. If the antibody prevalence rates found in this study reflect a history of clinical disease as described in the literature, sandfly fever poses a significant public health problem in Cyprus.

Adolescent↗

Sandfly fever among Swedish tourists.

All clinical and serologically confirmed cases of sandfly fever among Swedish tourists during 1986-1989 were investigated. A total of 37 cases of Sicilian virus sandfly fever and 1 case of Naples virus sandfly fever were recorded from Cyprus. One case of Toscana virus infection was documented from Spain. The clinical and laboratory findings did not differ from those in previous reports, except for elevated aminotransferase levels. A questionnaire, that offered a possibility to estimate the number of cases that had not been reported, was sent to 713 tourists who had visited different hotels in Cyprus and Mallorca in September 1987. Serum samples from 95 of these tourists were tested for sandfly fever virus antibodies. These tests indicated that only some 20% of the real number of sandfly fever infections had been diagnosed. Both clinical cases and cases found by the questionnaire showed a focal distribution with an overrepresentation of certain hotels in Cyprus. The results were reported to the local health officers and possibly due to the measures undertaken hereafter the number of sandfly fever cases diagnosed have decreased.

Adult↗

Serologic survey for selected viral and rickettsial agents of brown bears (Ursus arctos) in Croatia.

Sera from 22 (13 wild and nine captive) European brown bears (Ursus arctos) from Croatia were tested to 18 viral and rickettsial agents. Serologic evidence of exposure was found to the following agents (number positive/number examined): Bhanja virus (3/15), Tahyna virus (3/15), West Nile virus (4/15), Naples sandfly fever virus (1/15), human adenovirus (1/22), influenza A (1/22) and B (1/22) virus, cytomegalovirus (1/22), parainfluenza virus 1 (2/22), Chlamydia psittaci (1/22), Coxiella burnetii (2/22), and canine parvovirus 2 (CPV-2) (7/22). Evidence of exposure to arboviruses was found exclusively among free-living bears. Evidence of exposure to agents usually transmitted directly was predominant among captive bears. Canine parvovirus 2 antibodies were the most frequently found antibodies and the only antibody common to both groups of bears. This may be the first report of antibodies to CPV-2 in bears.

Animals↗

Laboratory infection of the sandfly Phlebotomus papatasi Scopoli (Diptera, Psychodidae) with three Phleboviruses.

Membrane feeding and intrathoracic inoculation techniques were used to infect Phlebotomus papatasi sandflies with Phlebotomus fever group viruses. Sandflies were orally infected with Pacui virus, and were inoculated with Pacui, Sicilian sandfly fever and Naples sandfly fever viruses. Pacui virus did not multiply in these insects after oral infection, but an 8 X 10(4)-fold increase in virus concentration occurred within four days of intrathoracic inoculation of this virus. The infection rate was 100%. Sicilian sandfly fever virus multiplied in P. papatasi after infection by inoculation, although the yield was lower, a 20-fold increase in the mean virus concentration occurring over eight days. The results for Naples sandfly fever were inconsistent. A 32-fold increase in mean virus concentration was recorded in a small percentage of insects 14 days after inoculation of the virus.

Animals↗

Dimethyl sulfoxide enhancement of phlebotomus fever virus plaque formation.

Dimethyl sulfoxide (DMSO)incorporated into an agar overlay containing DEAE-dextran enhanced plaque formation in Vero cells by Naples sandfly fever virus passaged in mouse brain or Vero cell cultures. No plaques were visible when DMSO was used without the DEAE-dextran, some plaques were rarely visible (less than 0.5mm) when DEAE-dextran was used without the DMSO, and up to 10-fold more plaques were clearly visible (0.5-1.5 mm) when both chemicals were used. The combined enhancing effect of DMSO and DEAE-dextran was also observed with mouse brain passaged, but not Vero passaged Sicilian sandfly fever virus. Other Phlebotomus group viruses produced a bit plaques (3-5 mm) and did not require DMSO for plaque formation, although an increase in plaque clarity was obtained with DMSO for some of them. Plaque reduction neutralization tests were assayed successfully under agar containing DMSO. The alphavirus Sindbis produced slightly larger plaques under agar containing DMSO, but there was no effect on clarity or size of plaques produced by the flavivirus dengue-2.

Arboviruses↗

Viruses transmitted by sandflies in Italy.

Five different phlebotomus-transmitted viruses have been isolated in Italy. Four of them belong to the Bunyaviridae family (genus Phlebovirus). Sandfly fever Sicilian and Sandfly fever Naples viruses were isolated from sick persons during World War II, Toscana and Arbia viruses have been isolated more recently from Phlebotomus perniciosus and P. perfiliewi. Radi virus is the only phlebotomus-transmitted virus isolated in Italy from P. perfiliewi, which belongs to the Rhabdoviridae family (genus Vesiculovirus). The circulation and the natural cycle of these viruses on the basis of seroepidemiological investigations and ecological studies is discussed.

Animals↗

Arboviral causes of non-specific fever and myalgia in a fever hospital patient population in Cairo, Egypt.

Fever and myalgia are non-specific clinical manifestations of illness which commonly occur in patients with arboviral disease. In Egypt, such illness is often mis-diagnosed as "influenza". To determine arboviral aetiology in patients admitted with fever and myalgia, acute and convalescent sera samples were obtained from 55 patients admitted with these clinical manifestations to the Imbaba Fever Hospital, Giza, Egypt, during October and November 1984. Based on viral isolation, and a comparison of acute and convalescent sera, 4 patients (7%) had acute arboviral infections. Haemagglutination inhibition and indirect immunofluorescence tests showed that one had West Nile virus (WNV) infection, 2 had sandfly fever virus-Naples (SFN), and 1 had sandfly fever virus-Sicilian (SFS) infection. SFN was isolated from the acute serum sample of 1 of the 2 patients with SFN infection.

Adolescent↗

The N terminus of Rift Valley fever virus nucleoprotein is essential for dimerization.

Rift Valley fever virus (RVFV) is a Phlebovirus in the Bunyaviridae family. The nucleoprotein N is the most abundant component of the virion; numerous copies of N associate with the viral RNA genome and form pseudohelicoidal ribonucleoproteins (RNPs) circularized by a panhandle structure formed by the base-paired RNA sequences at the 3' and 5' termini. These structures play a central role in transcription and replication. We investigated the intermolecular interactions of the RVFV N protein and found that after chemical cross-linking treatment, the nucleoprotein from purified RNPs migrates mainly as dimers. The N-N interaction was studied using the yeast two-hybrid system, the GST pull-down method, and mutational analysis. We demonstrated that the N terminus from residue 1 to 71, and particularly Tyr 4 and Phe 11, which are conserved among phlebovirus N sequences, are involved in the interaction. The C-terminal region did not seem to be essential for the N-N interaction. Moreover, we showed that N(TOS), the N protein of the related Toscana phlebovirus, interacts with itself and forms heterodimers with N(RVF), suggesting that the dimeric form of N may be a conserved feature in phlebovirus RNPs.

Amino Acid Sequence↗

Antigenic and biological characterization of Toscana virus, a new Phlebotomus fever group virus isolated in Italy.

Toscana (TOS) virus, a new member of the Phlebotomus fever serogroup of arboviruses, was isolated from sandflies collected in Italy. It was shown to be closely related to Sandfly fever Naples (SFN) virus. The antigenic relationships between the two viruses were analysed in the complement fixation (CF), plaque reduction neutralization (PRN) and indirect fluorescent antibody (IFA) tests. TOS virus multiplied to high titres with a cytopathic effect (CPE) in several vertebrate cell cultures (e.g. Vero, BHK-21, etc.), whereas it failed to replicate in mosquito cell cultures. Plaque formation by TOS virus in Vero cells was not affected by incorporating dimethyl sulphoxide in the overlay, which is known to enhance plaque formation by SFN virus. Some biological characteristics in cell cultures and in mice of a mouse-adapted and a cell-adapted TOS virus strain were studied. After 4-6 passages in the two different systems, changes in plaque size, in the amount of autointerfering activity and of virulence for mice were observed.

Animals↗

Seroprevalence study of Tick-borne encephalitis, Borrelia burgdorferi, Dengue and Toscana virus in Turin Province.

Tick borne encephalitis virus (TBEV) is present in some European countries and it is transmitted by a tick bite. Ixodes ricinus is the main vector of the infection in Italy, where fortunately clinical neurological manifestations, typical of the more serious phase of the disease, are very rarely observed. This behaviour is different from other endemic Euroasiatic areas where numerous cases of encephalitis are described. However TBE transmission has not been widely investigated in Italy and available epidemiological data have been obtained only by studies performed in Central and Northern Regions of the country. In addition seroepidemiological researches were made prevalently on subjects at high risk of tick bite, such as hunters or forest guards from Trentin and Central Italy. No precise information about TBE virus diffusion was available in the Piedmont before our investigations. We found that hunters and wild boar breeders seem to be particularly exposed to the risk of TBE virus infection in Turin Province and in particular in the Susa valley, although no neurological involvement was observed in our population. In particular a seroprevalence of about 5% was detected by the use of purified antigens ELISA test, amongst the subjects at high risk of tick bite. Moreover low risk individuals showed a seroprevalence of below 2%. In addition a parallel seroepidemiological study was performed in Turin Province for Borrelia burgdorferi, the aetiological agent of Lyme disease, also transmitted by tick bite (e.g. Ixodes ricinus), for Dengue and Toscana (TOS) arboviruses, respectively transmitted by Aedes mosquitoes and phlebotomes. Data reported here demonstrate only a sporadic presence in our population of antibodies against Borrelia and Dengue infection. Moreover using an ELISA test performed with viral purified nucleoprotein, we reported a total percentage of about 3% of subjects positive for TOSV.

Animals↗

Serological survey of Toscana virus infections in a high-risk population in Italy.

Toscana virus is the most important agent responsible for meningitis in central Italy. We report a serosurveillance study, using an immunoenzymatic assay, of 360 serum samples harvested from a high-risk population occupationally exposed to Toscana virus in two regions of Italy, Tuscany and Piedmont. The results indicates a seroprevalence of Toscana virus of 77.2% in the forestry workers, particularly in the Tuscany region. This fact is strictly correlated with the ecological niches specific for the survival of Toscana virus arthropod vector.

Arboviruses↗

Acute meningitis owing to phlebotomus fever Toscana virus imported to France.

Acute lymphocytic meningitis, seen in France in summer, is often due to enteroviruses. Arboviruses as West Nile and tick-borne encephalitis do exist in Europe, but other viruses are rarely considered in patients unless they have had recent tropical travel. Toscana virus infection, which is endemic, especially in Italy,1-3 has been documented in some European travelers returning from Italy,4-6 but surprisingly was not documented in France until recently.7 We report a case of meningitis caused by Toscana virus imported to France.

Acute Disease↗