Isolation of tick-borne encephalitis virus from wild rodents and a seroepizootiologic survey in Hokkaido, Japan.
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To determine the vertebrate host of tick-borne encephalitis (TBE) virus in the southern part of Hokkaido, Japan, virus isolation was performed using spleens from small mammals captured in the area. Two virus strains were isolated, one strain from Apodemus speciosus and another from Clethrionomys rufocanus. Virus isolates were inoculated onto baby hamster kidney cell monolayers and antigen slides were prepared for an indirect immunofluorescent antibody assay. Two isolates were identified as TBE viruses by monoclonal antibody reactions. To specify the TBE-endemic area in Hokkaido, rodent, horse, and dog sera collected from 1992 to 1997 were tested for neutralization antibody against TBE virus previously isolated from a dog. The positive cases were distributed in four districts in the southern part of Hokkaido. (+info)
Evaluation of tick-borne encephalitis DNA vaccines in monkeys.
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Tick-borne encephalitis is usually caused by infection with one of two flaviviruses: Russian spring summer encephalitis virus (RSSEV) or Central European encephalitis virus (CEEV). We previously demonstrated that gene gun inoculation of mice with naked DNA vaccines expressing the prM and E genes of these viruses resulted in long-lived homologous and heterologous protective immunity (Schmaljohn et al., 1997). To further evaluate these vaccines, we inoculated rhesus macaques by gene gun with the RSSEV or CEEV vaccines or with both DNA vaccines and compared resulting antibody titers with those obtained by vaccination with a commercial, formalin-inactivated vaccine administered at the human dose. Vaccinations were given at days 0, 30, and 70. All of the vaccines elicited antibodies detected by ELISA and by plaque-reduction neutralization tests. The neutralizing antibody responses persisted for at least 15 weeks after the final vaccination. Because monkeys are not uniformly susceptible to tick-borne encephalitis, the protective properties of the vaccines were assessed by passive transfer of monkey sera to mice and subsequent challenge of the mice with RSSEV or CEEV. One hour after transfer, mice that received 50 microl of sera from monkeys vaccinated with both DNA vaccines had circulating neutralizing antibody levels <20-80. All of these mice were protected from challenge with RSSEV or CEEV. Mice that received 10 microl of sera from monkeys vaccinated with the individual DNA vaccines, both DNA vaccines, or a commercial vaccine were partially to completely protected from RSSEV or CEEV challenge. These data suggest that DNA vaccines may offer protective immunity to primates similar to that obtained with a commercial inactivated-virus vaccine. (+info)
The clinical and epidemiological profile of tick-borne encephalitis in southern Germany 1994-98: a prospective study of 656 patients.
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Seven hundred and nine patients fell ill in southern Germany (Baden-Wurttemberg) after infection with the tick-borne encephalitis (TBE) virus between 1994 and 1998. Detailed clinical and epidemiological data on TBE were available for 656 patients. A biphasic course of the disease occurred in 485 patients (74%). TBE presented as meningitis in 320 patients (49%), as meningoencephalitis in 270 (41%) and as meningoencephalomyelitis in 66 (10%). Eight of the patients (1.2%) died from TBE. Four hundred and forty-five patients (68%) had noticed a tick bite and the first symptoms occurred, on average, 7 days later. The most frequent neurological symptoms were impairment of consciousness (31%), ataxia (18%) and paresis of the extremities (15%) and cranial nerves (11%). Laboratory investigations revealed leucocytosis in the peripheral blood in 224 out of 392 patients (74%), elevation of the erythrocyte sedimentation rate in 223 out of 245 (91%), increased C-reactive protein in 127 out of 155 (82%), pleocytosis in the CSF of all patients tested, damage of the blood-CSF barrier in 255 out of 322 (79%), abnormalities in EEG in 165 out of 214 (77%) and abnormalities in MRI in 18 out of 102 (18%). In general, adolescents up to 14 years of age had a more favourable course of the disease than adults. Of 230 patients who were re-examined at a later time, 53 (23%) had moderate or severe sequelae. Patients with sequelae presented more frequently (P < 0.001) with impaired consciousness (Glasgow Coma Scale < 7), ataxia, pareses of the extremities or cranial nerves, a need for assisted ventilation, abnormal findings in MRI, pleocytosis > 300 cells/microl and impairment of the blood-CSF barrier (total protein > 600 mg/l). In view of the severity of the illness and the high frequency of sequelae, active immunization against TBE is recommended for all subjects living in and travelling to areas of risk. Prevention of TBE by post-exposure prophylaxis with hyperimmunoglobulins is less effective and therefore should be performed only when absolutely necessary. (+info)
Phylogenetic and virulence analysis of tick-borne encephalitis viruses from Japan and far-Eastern Russia.
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We have previously reported that tick-borne encephalitis (TBE) is endemic in a specific area of Hokkaido, Japan. In Oshima, the southern part of Hokkaido, TBE virus was isolated from sentinel dogs, ticks and rodents in 1995 and 1996. To identify when these TBE viruses emerged in Hokkaido, the times of divergence of TBE virus strains isolated in Oshima and far-eastern Russia were estimated. TBE virus was isolated in Khabarovsk in 1998 and the nucleotide sequences of viral envelope protein genes of isolates from Oshima and Khabarovsk were compared. From the synonymous substitution rate of these virus strains, the lineage divergence time of these TBE virus strains was predicted phylogenetically to be about 260-430 years ago. Furthermore, the virulence of TBE virus isolates from Oshima and Khabarovsk were compared in a mouse model. The results showed that the isolates possessed very similar virulence in mice. This report provides evidence that the Oshima strains of TBE virus in Hokkaido emerged from far-eastern Russia a few hundred years ago and this explains why these strains possess virulence similar to the TBE viruses isolated in Russia. (+info)
Impact of climatic change on the northern latitude limit and population density of the disease-transmitting European tick Ixodes ricinus.
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We examined whether a reported northward expansion of the geographic distribution limit of the disease-transmitting tick Ixodes ricinus and an increased tick density between the early 1980s and mid-1990s in Sweden was related to climatic changes. The annual number of days with minimum temperatures above vital bioclimatic thresholds for the tick's life-cycle dynamics were related to tick density in both the early 1980s and the mid-1990s in 20 districts in central and northern Sweden. The winters were markedly milder in all of the study areas in the 1990s as compared to the 1980s. Our results indicate that the reported northern shift in the distribution limit of ticks is related to fewer days during the winter seasons with low minimum temperatures, i.e., below -12 degrees C. At high latitudes, low winter temperatures had the clearest impact on tick distribution. Further south, a combination of mild winters (fewer days with minimum temperatures below -7 degrees C) and extended spring and autumn seasons (more days with minimum temperatures from 5 to 8 degrees C) was related to increases in tick density. We conclude that the relatively mild climate of the 1990s in Sweden is probably one of the primary reasons for the observed increase of density and geographic range of I. ricinus ticks. (+info)
An accelerated schedule for tick-borne encephalitis vaccine: the American Military experience in Bosnia.
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Tick-borne encephalitis (TBE) is a viral illness endemic to the Balkan region. United States military forces were deployed to Bosnia in early 1996 as part of Operation Joint Endeavor, a U.S.-led multinational peace-keeping operation. To counteract the TBE threat, an inactivated, parenteral vaccine (FSME-Immun Inject; Immuno AG, Vienna, Austria) was offered to soldiers at high risk on a volunteer basis in an accelerated, 3-dose schedule (0, 7, and 28 days). Passive adverse reaction surveillance was conducted on 3,981 vaccinated personnel. Paired sera from a randomly selected group of 1,913 deployed personnel (954 who received vaccine and 959 who were unvaccinated) were tested for antibodies to TBE by an ELISA. Three-dose recipients demonstrated an 80% seroconversion rate (4-fold or greater increase in anti-TBE titers). By comparison, the TBE infection rate in the unvaccinated cohort was found to be only 0.42% (4 of 959). Only 0.18% of vaccinees reported self-limited symptoms. An accelerated immunization schedule appears to be an acceptable option for military personnel or travelers on short-term notice to TBE-endemic areas. (+info)
Recombinant Semliki Forest virus particles expressing louping ill virus antigens induce a better protective response than plasmid-based DNA vaccines or an inactivated whole particle vaccine.
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Louping ill virus (LIV) infection of mice was used as a model to evaluate the protective efficacy of Semliki Forest virus (SFV)-based vaccines in comparison to a standard DNA vaccine and a commercial chemically inactivated vaccine. The recombinant SFV-based vaccines consisted of suicidal particles and a naked layered DNA/RNA construct. The nucleic acid vaccines expressed the spike precursor prME and the nonstructural protein 1 (NS1) antigens of LIV. Three LIV strains of graded virulence for mice were used for challenge. One of these was a naturally occurring antibody escape variant. All vaccines tested induced humoral immunity but gave varying levels of protection against lethal challenge. Only recombinant SFV particles administered twice gave full protection against neuronal degeneration and encephalitis induced by two of the three challenge strains, and partial protection against the highly virulent strain, whereas the other vaccines tested gave lower levels of partial protection. (+info)
Infectious cDNA clones of Langat tick-borne flavivirus that differ from their parent in peripheral neurovirulence.
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Tick-borne flavivirus strain Langat TP21 (LGT TP21) recovered from ticks, is naturally attenuated for humans but retains demonstrable neurovirulence and peripheral virulence ("neuroinvasiveness") for mice. Previously a mutant, strain E5, less virulent for mice was derived from LGT TP21. Multiple attempts to prepare a full-length infectious TP21 cDNA from cDNA fragments cloned in E. coli were uniformly unsuccessful. A more informative sequence than that obtained from these cloned cDNA fragments and similar E5 cDNA fragments was derived from RT-PCR fragments that had not been cloned in E. coli. Comparison of the RT-PCR consensus sequence of TP21 and E5 identified only seven amino acid differences that might be responsible for the observed difference in virulence of these strains for mice. Eleven independent infectious cDNA clones of TP21 were recovered using two overlapping long RT-PCR fragments. Importantly, low-titered virus used to prepare cDNA as template for PCR was harvested early in the growth cycle to minimize the frequency of deletion mutants that accumulated late in infection. The four analyzed rescued clones exhibited clone-specific minimal divergence from the consensus sequence but this limited variation was associated with diminished peripheral virulence for immunocompetent mice. Manipulation of these clones should facilitate elucidation of LGT virulence. (+info)