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Induction of severe disease in hamsters by two sandfly fever group viruses, Punta toro and Gabek Forest (Phlebovirus, Bunyaviridae), similar to that caused by Rift Valley fever virus.

Adult golden hamsters inoculated subcutaneously with either of two sandfly fever group viruses, Punta Toro and Gabek Forest (Phlebovirus, Bunyaviridae), developed a fulminating fatal illness characterized by hepatic and splenic necrosis and interstitial pneumonitis. Most animals died within three days after infection; this was accompanied by high levels of viremia. Necropsy and histopathologic examination of the infected animals revealed pathologic changes involving multiple organs that resembled those described in Rift Valley fever. These two hamster-phlebovirus systems may serve as alternative animal models for Rift Valley fever and should be useful in studying the pathogenesis of severe phlebovirus infection and for testing potential therapeutic agents.

Animals↗

Studies on the epidemiology of sandfly fever in Iran. II. The prevalence of human and animal infection with five phlebotomus fever virus serotypes in Isfahan province.

Human and animal sera from an endemic area of sandfly fever in Iran were tested by plaque reduction neutralization method against five different Phlebotomus fever virus serotypes (Naples, Sicilian, Karimabad, Salehabad, and I-47). The overall prevalence of Naples, Sicilian, and Karimabad virus antibodies among the human population was 17%, 25%, and 66%, respectively. All sera were negative against Salehabad and I-47 viruses. Age-specific antibody rates suggested that Sicilian and Karimabad viruses were endemic in the study area but that Naples virus activity was sporadic. These observations were confirmed by isolations of Sicilian and Karimabad viruses from sandflies collected in the study area. Among the animal sera tested, evidence of Phlebotomus fever virus infection was detected only in gerbils. Of 38 Rhombomys opimus tested, 34% had neutralizing antibodies against Sicilian virus and 32% against Karimabad. These results indicate that gerbils are infected with these two viruses and possibly might serve as reservoirs or amplifying hosts. The serologic studies also suggest that the ecology of Sicilian and Karimabad viruses involves chiefly sandflies, gerbils, and man, an epidemiologic pattern previously demonstrated for cutaneous leishmaniasis in the same region of Iran.

Adolescent↗

Serosurvey and laboratory diagnosis of imported sandfly fever virus, serotype Toscana, infection in Germany.

Of eight acute infections in German tourists caused by sandfly fever virus, serotype Toscana (TOS), and diagnosed clinically and serologically, seven were acquired during visits to Tuscany, Italy, and one to Coimbra, Portugal. An indirect immunofluorescence assay (IFA) using infected cells, and a newly developed enzyme-immunoassay (EIA) using crude virus antigen prepared from infected Vero-E6 cells was used to detect anti-TOS IgM and IgG. In a seroepidemiological survey of 859 health care workers and medical students, anti-TOS IgG was detected in 1.0% by IFA, and in 0.7% by EIA. In 2034 German patients hospitalized for various diseases, 1.6% were positive for anti-TOS IgG by IFA, and 0.8% by EIA. Anti-TOS IgG was detected in 43 samples of commercial immunoglobulins at titres of 10-1000 by EIA. Although the seroprevalence of antibodies to TOS is low in Germany, TOS infection should be considered in patients returning from endemic areas who complain of fever, and headaches, and have symptoms of meningitis.

Adult↗

The S RNA segment of Sandfly Fever Sicilian virus: evidence for an ambisense genome.

The complete nucleotide sequence of the S RNA segment of Sandfly Fever Sicilian (SFS) virus (Phlebovirus, Bunyaviridae) was determined from overlapping cDNA clones and by primer extension. The RNA is 1746 nucleotides in length and has two large open reading frames (ORF), one of which (24.8 kDa) is viral-complementary in sense, and the other (30.4 kDa) is in the viral sense. This ambisense genome arrangement has been seen in another member of the Phlebovirus genus, Punta Toro (PT) virus (T. Ihara, H. Akashi, and D. H. L. Bishop, 1984, Virology 136, 293-306), but not in representatives of either the Bunyavirus or Hantavirus genera of the Bunyaviridae. Comparison of the predicted amino acid sequences for SFS virus with the recognized products of PT S RNA (T. Ihara, Y. Matsuura, and D. H. L. Bishop, 1985, Virology 147, 317-325; H. A. Overton, T. Ihara, and D. H. L. Bishop, 1987, Virology 157, 338-350) indicated that the 24.8-kDa ORF encodes the nucleoprotein (N) of SFS virus, and the 30.4-kDa ORF codes for a nonstructural protein (NSs). Subgenomic messenger RNAs, from which these two proteins are presumably translated, were detected in virus-infected cells.

Amino Acid Sequence↗

[Data on a study of a natural focus of sandfly fever in Sevastopol during 1945-1988].

Sandfly [correction of Mosquito-borne] fever in Sevastopol was of a marked season character (June-September), with maximum cases registered in August. The morbidity curve corresponded to the sandfly [correction of mosquito] number curve, lagging behind it because of the incubation period. Since 1947 DDT and hexachlorane, having a lasting effect (40-50 days), have been widely used for sandfly [correction of mosquito] control. This was accompanied by intensive improvement of the living conditions in the city, regular sanitation and deratization. As a result of the above measures sandfly [correction of mosquito-borne] fever has not been registered in the city since 1954. The number of sandflies [correction of mosquitoes] reduced drastically, their species composition has changed: in 1959 sandflies [correction of mosquitoes] were found in 5.4% of the houses examined and in 1988, in 0.16% of houses. Since 1958 only 2 (Phlebotomus papatasii Scop and Ph. major Ann.) out of the former 7 species have been caught. Each species strives for self-preservation. Therefore, epidemiological survey of the former foci and sandfly-control [correction of antimosquito] measures are to be performed annually not to permit recovery of sandfly [correction of mosquito] population and repeated epidemics of sandfly [correction of mosquito-borne] fever.

Animals↗

ELISA for detection of IgM and IgG antibodies to sandfly fever Sicilian virus.

An enzyme-linked immunosorbent assay (ELISA) was developed to detect specific human immunoglobulin G and M antibodies to sandfly fever Sicilian (SFS) virus. Acute and early convalescent serum pairs with greater than or equal to 7 days between the 2 specimens were available from 20 patients and all showed significant optical density (OD) increase and significant titre rise (greater than or equal to 4-fold) by IgG ELISA. However, negative or borderline-positive sera were found as late as 11 days after onset of symptoms when tested by IgG ELISA. Specific IgM antibodies were detected during the first week of symptoms, and maximum OD values were obtained during the first 4 weeks after onset of disease. The IgM OD values declined over the following 3-9 months. All sera collected later than 14 months post-onset were negative by IgM ELISA. The combination of early antibody response and the need to test only one serum specimen gives IgM ELISA an advantage over IgG ELISA in patients diagnosis. The IgG ELISA was also evaluated as a seroepidemiological tool and compared to a plaque reduction neutralization test (PRNT) using sera from a normal Cypriot population. Of 183 sera tested, 34 (19%) were positive in plaque reduction neutralization tests (PRNT) and 113 (62%) by IgG ELISA. A number of PRNT-negative sera were strongly positive by IgG ELISA and also by indirect immunofluorescence test, which may suggest the presence of a virus related to SFS in Cyprus which has not yet been isolated.

Acute Disease↗

Studies on the epidemiology of sandfly fever in Iran. I. Virus isolates obtained from Phlebotomus.

A total of 62 virus isolates was obtained from 12,485 male and female sandflies (predominately Phlebotomus papatasi) collected in a village in central Iran during the summer of 1975. The overall virus isolation rate from female sandflies was 1 per 177 insects processed. Of the 62 virus strains obtained, 49 were identified as Sicilian virus, 11 as Karimabad, and 2 as a new member of the vesicular stomatitis serogroup. One isolate each of Sicilian and Karimabad virus was made from pools of male sandflies. The three virus types were active in the sandfly population simultaneously. Sicilian virus isolation rates showed little variation during the study period, suggesting continuous virus activity during the sandfly season. The implications of these findings for the epidemiology of sandfly fever are discussed.

Animals↗

Effects of sandfly fever on isometric muscular strength, endurance, and recovery.

The isometric muscular strength and endurance of 10 male volunteers were measured four times per day for 15 consecutive days. Eight experimental subjects were inoculated with sandfly fever virus and two double-blind controls were given sterile saline on the seventh day. The muscular performances of the control subjects remained essentially constant throughout. Decrements in muscular strength and endurance occurred with the experimentals during the brief period of illness three or four days after inoculation, then performances improved towards baseline levels.

Journal Article↗

Nested RT-PCR for detection of sandfly fever virus, serotype Toscana, in clinical specimens, with confirmation by nucleotide sequence analysis.

A single tube, reverse transcriptase/polymerase chain reaction (RT-PCR) was developed and evaluated for detecting a 400-bp product of the small RNA of sandfly fever virus, serotype Toscana (TOS). For more sensitive detection of genomic TOS RNA, a nested PCR amplifying a 243-bp cDNA within the RT-PCR product was established. Nucleotide sequence analysis of first- and second-round PCR products using the dideoxy cycle sequencing technique confirmed a previously published sequence of the TOS reference strain (ISS. Phl.3). By nested PCR, genomic TOS RNA was amplified from two consecutive sera taken 3 and 7 weeks after the onset of illness in one patient, and from CSF of a second patient obtained at the onset of meningitis. Authenticity of amplified PCR products was confirmed by nucleotide sequence analysis, revealing a sequence identical to the TOS reference strain. RT-PCR and nested PCR are useful for laboratory diagnosis and studies of the molecular epidemiology of TOS infection.

Animals↗

Serological studies on the epidemiology of sandfly fever in the Old World.

Selected human sera from 59 different localities in Africa, the Mediterranean littoral, eastern Europe and Asia were examined by plaque reduction neutralization test against eight sandfly (Phlebotomus) fever virus serotypes (Sicilian, Naples, Arumowot, SudAn 754-61, Karimabad, Salehabad, Gordil and Saint Floris) known to occur in the Old World. Results of these studies provide new information on the geographic distribution and prevalence of human infection with each of the viruses. Specific neutralizing antibodies were detected against all of the agents except Salehabad. Naples and Sicilian antibodies were encountered most frequently and had the widest geographic range; moreover they were found only in areas where Phlebotomus papatasi occurs. Age-specific antibody rates for several of the viruses are presented. These data and the epidemiology of sandfly fever are discussed.

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↗

Serological studies on sandfly fevers in the Republic of Bangladesh.

Blood samples from 160 inhabitants of the Republic of Bangladesh were studied by haemagglutination inhibition (HI), indirect HI, and radial haemolysis in gel tests. The sera were found to contain antibodies to the arborviruses of Sicilian (6.25%) and Naples (1.25%) sandfly fevers and to the Karimabad virus (11.25%) which are transmitted by Phlebotomus papatasi. Antibodies to the Karimabad virus were found among the Bangladesh population for the first time.

Antibodies, Viral↗

Effect of glucose infusion on the concentration of individual serum free amino acids during sandfly fever in man.

After an intravenous glucose load in man, total serum amino acid concentrations are rapidly depressed and remain below baseline values for at least 2 to 3 hr after serum glucose and insulin have returned to preload concentrations. Despite the presence of basal hypoaminoacidemia, a decreased glucose disappearance rate, and hyperinsulinemia in volunteers who were ill with sandfly fever, an intravenous glucose load resulted in a further depression of serum amino acids which was equal to or slightly greater than that observed in the same individuals before exposure to the virus. Although the infectious process may have some effect on insulin-stimulated hepatic disposal of a glucose load, it does not appear to influence the ability on insulin to decrease the rate of release of certain amino acids from skeletal muscle.

Adult↗

Effect of insecticide spraying for malaria control on the incidence of sandfly fever in Athens, Greece.

Sera from 637 Athens residents of various age groups were examined by plaque reduction neutralization test for antibodies against Naples and Sicilian Phlebotomus fever viruses. A marked change in the prevalence of antibodies to both agents was observed in persons born after 1946, when residual insecticide spraying for malaria control was initiated in Greece. The prevalence of Naples and Sicilian neutralizing antibodies among residents greater than or equal to 30 years of age was 36% and 13%, respectively. In contrast, only 4% of persons less than or equal to 29 years of age had Naples antibodies and all were negative to Sicilian. These serologic data confirm previous clinical observations that sandfly fever becam uncommon in Athens after initiation of the insecticide spraying program. Presumedly the spraying program was effective in reducing the Phlebotomus population to levels where virus transmission was minimal. New information on the specificity and duration of Phlebotomus fever neutralizing antibodies is also presented.

Adolescent↗

[A natural focus of sandfly fever in the Republic of Afghanistan].

The serological study of persons contacting dengue-like fever in 1987 in Afghanistan (in Rukha, Parwān Province) revealed that in 74% of cases an increase in the titers of antibodies to Sicilian and Neapolitan sandfly [correction of mosquito-borne] fever viruses was registered. Considering that such diseases appeared here for a number of years and were linked in time with the activity of sandflies [correction of mosquitoes] of the species Phlebotomus papatasii, the suggestion was made on the existence of a stable natural focus of sandfly [correction of mosquito-borne] fevers in the region of Rukha.

Afghanistan↗

Studies on the epidemiology of sandfly fever in Iran. III. Host-feeding patterns of Phlebotomus papatasi in an endemic area of the disease.

Blood meals from 575 Phlebotomus papatasi collected in an Iranian village were identified by precipitin test. The majority of sandfly feedings (57.5%) were on birds, mainly chickens and pigeons. The remaining 42.5% were on mammals (humans, cows, mules, sheep, and goats) or were non-reactive. Calculation of forage ratios of each host species indicated that chickens, equines, and bovines were the preferred hosts of P. papatasi in the village. Results of this study demonstrate that P. papatasi has a much wider natural host range than indicated previously and suggest that this species is an opporunistic feeder and is not strongly anthropophilic. Observations on the diurnal activity of P. papatasi are also presented.

Animals↗

Sandfly fever virus outbreak in Cyprus.

A major outbreak of febrile syndrome occurred during 2002 among the Greek Army forces in Cyprus. Serological and molecular investigations revealed that the causative agent was a Sicilian-like phlebovirus. A virus strain was isolated from a blood sample taken on the first day of the disease. Phylogenetic analysis of partial L RNA segment sequences revealed that the strain from Cyprus differed from sandfly Sicilian virus by 6.7% at the nucleotide level.

Adult↗