Cost-benefit ratio of tick-borne encephalitis vaccination of French troops based in Kosovo
[Cost-benefit ratio of tick-borne encephalitis vaccination of French troops based in Kosovo]

Desjeux G,  Lemardeley P,  Colin C,  Pascal B,  Labarere J.

[Article in English]

Hopital d'Instruction des Armees Desgenettes. Service de Medecine des Collectivites, BP 25, 69998 Lyon-Armees.

Background: French military troops based in Kosovo are exposed to Tick-Borne Encephalitis (TBE) biorisk. An efficacious vaccine is available to prevent this disease, burdened by high morbidity and mortality. The epidemiologic features of TBE in Kosovo are unprecise. To help the French Department of Defense to make a decision about immunization against TBE, we performed a cost-benefit analysis. Methods: By a Bayes'analysis decision, we have estimated the net benefits for a three-injection vaccine program versus absence of vaccination, for all French military troops based in Kosovo. Time expectancy was 4 years. Through the review of several medical reports, we have estimated the useful parameters for this study: morbidity incidence rate, mortality rate, sequelae rate, efficacy vaccine and side effects. We have chosen as initial hypothesis a sero-conversion rate of 1,080 per 100,000 men-by-year. Human life was valorized in francs, by calculating the allowance paid by Department of Defense to the family in case of death or for sequelae. Results: Net benefits arised to 2.17 millions of francs. The vaccine program cost was 25.0 millions of francs. 140 cases of encephalitis viruses were saved by vaccination. Nevertheless a sensibility analysis has shown that results are well reliable with TBE incidence rate. Conclusion: The break even point being close to the incidence rate of the initial assumption, the decision to vaccine all French military troops depends at the same time on a better knowledge of the incidence of the disease in Kosovo, but also of the number of potentially avoided cases of tick-borne encephalitis and of the programs of vaccination concerning this disease of the other countries forming the United Nations Organization forces.

Health assessment of U.S. military personnel deployed to Bosnia-Herzegovina for operation joint endeavor.

Sanchez JL Jr,  Craig SC,  Kohlhase K,  Polyak C,  Ludwig SL,  Rumm PD.

[Article in English]

U.S. Army Center for Health Promotion and Preventive Medicine, Aberdeen Proving Ground, MD 21010, USA.

In anticipation of U.S. forces deploying to Bosnia-Herzegovina, plans were established to conduct medical surveillance of all military service members. This surveillance would provide the Department of Defense with an overview of the hospitalization and outpatient morbidity experience of U.S. forces. Standardized collection of medical data from all U.S. camps using 14 diagnostic categories based on International Classification of Diseases, 9th Revision, codes began in March 1996. Special assessments for hantavirus and tick-borne encephalitis (TBE) infection risk were also conducted. The average disease and nonbattle injury rate for U.S. forces was 7.1 per 100 soldiers per week. Injuries accounted for 28% of medical visits, whereas undefined/other visits accounted for 33%. The majority of remaining visits were for respiratory (14%), dermatologic (10%), and gastrointestinal (6%) complaints. There was one confirmed and one suspected case of hemorrhagic fever with renal syndrome; only 0.1% of individuals (2 of 1,913) tested seroconverted to hantavirus during deployment. No cases of TBE were reported, and the overall low seroconversion rate (0.42%, 4 seroconversions among 959 unimmunized personnel) reflected a very low risk of infection with TBE-related viruses. Operation Joint Endeavor and follow-on Operations Joint Guard and Joint Forge have been extremely healthy deployments.

The degree of attenuation of tick-borne encephalitis virus depends on the cumulative effects of point mutations.

Gritsun TS,  Desai A,  Gould EA.

[Article in English]

Institute of Virology and Environmental Microbiology, Mansfield Road, Oxford OX1 3SR, UK.

An infectious clone (pGGVs) of the tick-borne encephalitis complex virus Vasilchenko (Vs) was constructed previously. Virus recovered from pGGVs produced slightly smaller plaques than the Vs parental virus. Sequence analysis demonstrated five nucleotide differences between the original Vs virus and pGGVs; four of these mutations resulted in amino acid substitutions, while the fifth mutation was located in the 3' untranslated region (3'UTR). Two mutations were located in conserved regions and three mutations were located in variable regions of the virus genome. Reverse substitutions from the conserved regions of the genome, R(496)-->H in the envelope (E) gene and C(10884)-->T in the 3'UTR, were introduced both separately and together into the infectious clone and their biological effect on virus phenotype was evaluated. The engineered viruses with R(496) in the E protein produced plaques of smaller size than viruses with H(496) at this position. This mutation also affected the growth and neuroinvasiveness of the virus. In contrast, the consequence of a T(10884)-->C substitution within the 3'UTR was noticeable only in cytotoxicity and neuroinvasiveness tests. However, all virus mutants engineered by modification of the infectious clone, including one with two wild-type mutations, H(496) and T(10884), showed reduced neuroinvasiveness in comparison with the Vs parental virus. Therefore, although the H(496)-->R and T(10884)-->C substitutions clearly reduce virus virulence, the other mutations within the variable regions of the capsid (I(45)-->F) and the NS5 (T(2688)-->A and M(3385)-->I) genes also contribute to the process of attenuation. In terms of developing flavivirus vaccines, the impact of accumulating apparently minor mutations should be assessed in detail.

Tick-borne encephalitis virus NS1 glycoprotein during acute and persistent infection of cells.

Bugrysheva JV,  Matveeva VA,  Dobrikova EY,  Bykovskaya NV,  Korobova SA,  Bakhvalova VN,  Morozova OV.

[Article in English]

Novosibirsk Institute of Bioorganic Chemistry of Siberian Branch of Russian Academy of Sciences, Lavrentyev's Prospect 8, 630090 -90, Novosibirsk, Russia

Tick-borne encephalitis virus (TBEV) was propagated in porcine embryo kidney (PS) cells until 48 h whereas human kidney (RH) cells maintained the virus persistence during at least 2 months. One of possible reasons of flavivirus chronic infection might be abnormal NS1 gene expression. Immunoblotting with monoclonal antibodies (MAbs) revealed the similarity of the intracellular and secreted NS1 nonstructural glycoprotein size and linear antigenic determinants in both the infected cell lines. However, according to the competitive binding of MAbs with the TBEV NS1 extracellular glycoprotein, its contiguous epitopes differed for acute or persistent infection. To map the TBEV NS1 glycoprotein antigenic determinants its recombinant analogues were used. All the studied MAbs could bind with the full-length NS1 recombinant protein. Deletion of the TBEV NS1 gene internal region resulted in defective NS1d1 protein without the region between 269 and 333 a.a. Lack of NS1d1 binding with 20B4 MAb and diminished binding with 22H8 and 17C3 MAbs permitted to map their antigenic determinants within or nearby deleted region, respectively. Interaction of other MAbs with the NS1 and NS1d1 recombinant proteins did not differ, suggesting that their epitopes were located in the region of N-terminal 268 a.a. or C-terminal 19 a.a. of the TBEV NS1 protein. The second NS1d2 truncated protein contained the first N-terminal 33 a.a. of the TBEV NS1 protein and was able to bind with 29G9 MAb. Taken together the data stand for the differences in the N-terminal structure of the TBEV NS1 multimers secreted from the acute and persistent infected cells whereas the intracellular and secreted monomer processing was the same. The modified NS1 protein oligomers in the RH cellular line might slow virus replication and could result in the TBEV persistence.

[No title available]

[No authors listed].

[Article in Russian]

Binding of tick-borne encephalitis (TBE) virus RNA to proteins was studied by 3 methods: gel retardation, RNA-protein cross-linking under UV light, and RNA-protein blotting. Two cellular proteins with molecular weights about 30 and 22 kDa were detected in the nuclear fraction of two cell strains (PS and RH) and in blood mononuclear cells of patients with TBE. Weak interaction between the studied RNA and viral proteins can result from trace amounts of TBE virus proteins in infected cells and by lack of additional binding factors. Bacterial super-products and affinity chromatography for isolation of native glycoproteins were used to increase the amount of viral proteins. Purified E and NS1 proteins did not react with viral RNA, while incubation with recombinant nonstructural TBE virus NS3 protein led to a shift in the mobility of TBE virus RNA in gel in the absence of cross-linking under conditions of UV exposure after addition of heparin. Poor binding of nonstructural TBE virus NS3 protein is based on electrostatic binding. Oligoribonucleotide 14 nucleotide residues long corresponding to 5'-terminal of TBE virus genome did not react with NS3 protein, probably because of its small size or absence of certain sequences.

Risk for human tick-borne encephalitis, borrelioses, and double infection in the pre-ural region of russia.

Korenberg EI,  Gorban LY,  Kovalevskii YV,  Frizen VI,  Karavanov AS.

[Article in English]

Gamaleya Research Institute for Epidemiology and Microbiology, Russian Academy of Medical Sciences, Moscow, Russia.

We assessed the risk for human tick-borne encephalitis (TBE), ixodid tick-borne borrelioses, and double infection from 1994 to 1998 in Perm, which has among the highest rates of reported cases in Russia. We studied 3,473 unfed adult Ixodes persulcatus ticks collected from vegetation in natural foci and 62,816 ticks removed from humans. TBE virus and Borrelia may coexist in ticks.

Distribution and characterization of tick-borne encephalitis viruses from Siberia and far-eastern Asia.

Hayasaka D,  Ivanov L,  Leonova GN,  Goto A,  Yoshii K,  Mizutani T,  Kariwa H,  Takashima I.

[Article in English]

Laboratory of Public Health, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.

In this study, tick-borne encephalitis (TBE) viruses from Siberia and far-eastern Asia were characterized in order to determine virus subtype distribution. TBE viruses were isolated from ticks (Ixodes persulcatus) collected in the far-eastern (Khabarovsk and Vladivostok) and Siberian (Irkutsk) regions of Russia in 1999. Phylogenetic analysis showed that isolates formed distinct clusters of far-eastern and Siberian subtypes. There was also a minor difference in antigenicity between the Irkutsk isolates and other TBE virus strains, as demonstrated by the reactivity of monoclonal antibodies. Amino acid alignments of the E gene showed that the Irkutsk isolates had a single amino acid change at position 234 (Q or H); this amino acid position is considered to be a 'signature' of Siberian subtype TBE viruses. Strains isolated in Irkutsk also exhibited equivalent or somewhat higher virulence in mice compared with far-eastern TBE virus isolates. All viruses isolated in this study (i.e. far-east Asian and Siberian isolates) have 3' non-coding regions (NCRs) of almost the same length, which contrasts with the various sizes of 3'NCRs of other TBE viruses strains reported previously. The data presented in this study show that the 3'NCR is uniform among TBE viruses isolated from Siberia and far-eastern Asia and that the 3'NCR is essential for TBE virus growth in tick and/or rodent host cells.

MeSH Terms:

• 3' Untranslated Regions/genetics
• Amino Acid Sequence
• Animal
• Antibodies, Monoclonal/immunology
• Antibodies, Viral/immunology
• Antigens, Viral/chemistry
• Antigens, Viral/genetics
• Antigens, Viral/immunology
• Asia, Central
• Base Sequence
• Brain/virology
• Encephalitis Viruses, Tick-Borne/*classification
• Encephalitis Viruses, Tick-Borne/genetics
• Encephalitis Viruses, Tick-Borne/*isolation & purification
• Encephalitis Viruses, Tick-Borne/pathogenicity
• Encephalitis, Tick-Borne/*virology
• Fluorescent Antibody Technique, Indirect
• Genes, Viral/genetics
• Human
• Mice
• Molecular Sequence Data
• Phylogeny
• Sequence Alignment
• Serotyping
• Siberia
• Support, Non-U.S. Gov't
• Survival Rate
• Ticks/virology
• Variation (Genetics)/genetics
• Viral Envelope Proteins/chemistry
• Viral Envelope Proteins/genetics
• Viral Envelope Proteins/immunology
• Virulence/genetics

Substances:

• 0 (3' Untranslated Regions)
• 0 (Antibodies, Monoclonal)
• 0 (Antibodies, Viral)
• 0 (Antigens, Viral)
• 0 (Viral Envelope Proteins)
• 145420-18-4 (glycoprotein E, flavivirus)

Secondary Source ID:

• GDB/AB001026
• GENBANK/AB002293
• GENBANK/AB002295
• GENBANK/AB002296
• GENBANK/AB002297
• GENBANK/AB022292
• GENBANK/AB022703
• GENBANK/AB049345
• GENBANK/AB049346
• GENBANK/AB049347
• GENBANK/AB049348
• GENBANK/AB049349
• GENBANK/AB049350
• GENBANK/AB049351
• GENBANK/AB049352
• GENBANK/AB049353
• GENBANK/AB049390
• GENBANK/AB049391
• GENBANK/AB049392
• GENBANK/AB049393
• GENBANK/AB049394
• GENBANK/AB049395
• GENBANK/AB049396
• GENBANK/AB049397
• GENBANK/AB049398
• GENBANK/AB049399
• GENBANK/AB049400
• GENBANK/AB049401

Enzootic transmission of deer tick virus in New England and Wisconsin sites.

Ebel GD,  Campbell EN,  Goethert HK,  Spielman A,  Telford SR 3rd.

[Article in English]

Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

To determine whether rodents that are intensely exposed to the deer tick-transmitted agents of Lyme disease, human granulocytic ehrlichiosis, and human babesiosis are also exposed to deer tick virus (DTV), we assayed serum samples from white-footed mice (Peromyscus leucopus) and meadow voles (Microtus pennsylvanicus) in sites densely infested by deer ticks. To conduct serosurveys, we developed an enzyme-linked immunosorbent assay (ELISA) and Western blot assay by cloning, expressing, and purifying a portion of the DTV envelope glycoprotein (DTV rE) for use as test antigen. Sera from mice and voles trapped in Massachusetts, Rhode Island, and Wisconsin were screened by ELISA for IgG reactive to DTV rE. Samples that were positive or borderline by ELISA were subsequently analyzed by immunoblotting. Samples reactive in both assays were considered to be positive. Three percent of 264 mouse samples collected from sites in Rhode Island, 3.8% of 52 samples from mice trapped in Wisconsin, and 3.9% of 282 samples collected from mice trapped on Nantucket Island, MA were positive. No samples from either Great Island, MA, or voles from any study site were reactive. A reverse transcriptase-polymerase chain reaction yielded molecular evidence of DTV infecting questing adult deer ticks in sites where seroreactive mice were trapped, but not from ticks collected where serologic evidence of virus perpetuation was absent. White-footed mice appear to be exposed to DTV in certain sites where other deer tick-borne agents perpetuate. This virus may be maintained in the same enzootic cycle.

MeSH Terms:

• Animal
• Antigens, Viral/isolation & purification
• Arachnid Vectors/virology
• Blotting, Western
• DNA Primers
• Encephalitis, Tick-Borne/transmission
• Encephalitis, Tick-Borne/*veterinary
• Encephalitis, Tick-Borne/virology
• Enzyme-Linked Immunosorbent Assay
• Female
• Flavivirus/genetics
• Flavivirus/immunology
• Flavivirus/*isolation & purification
• Ixodes/*virology
• Male
• Massachusetts
• Microtinae/*virology
• Peromyscus/*virology
• RNA, Viral/isolation & purification
• Reverse Transcriptase Polymerase Chain Reaction
• Rhode Island
• Rodent Diseases/blood
• Rodent Diseases/transmission
• Rodent Diseases/*virology
• Support, U.S. Gov't, P.H.S.
• Wisconsin

Substances:

• 0 (Antigens, Viral)
• 0 (DNA Primers)
• 0 (RNA, Viral)

Grant Support:

• AI-37993/AI/NIAID
• AI-42402/AI/NIAID
• RO1 AI-39002/AI/NIAID
• T32 AI-07350/AI/NIAID
• T32 AI-07535/AI/NIAID

Adaptation of tick-borne encephalitis virus to BHK-21 cells results in the formation of multiple heparan sulfate binding sites in the envelope protein and attenuation in vivo.

Mandl CW,  Kroschewski H,  Allison SL,  Kofler R,  Holzmann H,  Meixner T,  Heinz FX.

[Article in English]

Institute of Virology, University of Vienna, Vienna, Austria. christian.mandl@univie.ac.at

Propagation of the flavivirus tick-borne encephalitis virus in BHK-21 cells selected for mutations within the large surface glycoprotein E that increased the net positive charge of the protein. In the course of 16 independent experiments, 12 different protein E mutation patterns were identified. These were located in all three of the structural domains and distributed over almost the entire upper and lateral surface of protein E. The mutations resulted in the formation of local patches of predominantly positive surface charge. Recombinant viruses carrying some of these mutations in a defined genetic backbone showed heparan sulfate (HS)-dependent phenotypes, resulting in an increased specific infectivity and binding affinity for BHK-21 cells, small plaque formation in porcine kidney cells, and significant attenuation of neuroinvasiveness in adult mice. Our results corroborate the notion that the selection of attenuated HS binding mutants is a common and frequent phenomenon during the propagation of viruses in cell culture and suggest a major role for HS dependence in flavivirus attenuation. Recognition of this principle may be of practical value for designing attenuated flavivirus strains in the future.

MeSH Terms:

• *Adaptation, Physiological
• Animal
• Binding Sites
• Cell Line
• Disease Models, Animal
• Encephalitis Viruses, Tick-Borne/genetics
• Encephalitis Viruses, Tick-Borne/growth & development
• Encephalitis Viruses, Tick-Borne/metabolism
• Encephalitis Viruses, Tick-Borne/*pathogenicity
• Encephalitis, Tick-Borne/*virology
• Heparitin Sulfate/*metabolism
• Mice
• Models, Molecular
• Mutation
• Plaque Assay
• Viral Envelope Proteins/*genetics
• Viral Envelope Proteins/*metabolism
• Virulence

Substances:

• 0 (Viral Envelope Proteins)
• 145420-18-4 (glycoprotein E, flavivirus)
• 9050-30-0 (Heparitin Sulfate)

Epidemiology of tick-borne encephalitis (TBE) and phylogenetic analysis of TBE viruses in Japan and Far Eastern Russia.

Takashima I,  Hayasaka D,  Goto A,  Kariwa H,  Mizutani T.

[Article in English]

Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. takasima@vetmed.hokudai.ac.jp

In Oshima, the southern part of Hokkaido, a tick-borne encephalitis (TBE) patient was found in 1993; in addition TBE virus was isolated from the blood samples of sentinel dogs, ticks pools, and rodents spleens in 1995 and 1996 by suckling mice. 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. Based on the synonymous substitution rates of these virus E-protein genes, the lineage-divergence times of these TBE virus strains were predicted phylogenetically to be approximately 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. European TBE vaccine was found to be effective in TBE virus, Hokkaido strain. This review provides evidence that the Oshima strains of TBE virus in Hokkaido emerged from the Far Eastern Russia a few hundred years ago, which explains why the virulence of these strains is similar to that of TBE viruses isolated in Russia. Practical application of the vaccine should be considered in Japan.

Publication Types:

• Journal Article
• Review
• Review, Tutorial

MeSH Terms:

• Amino Acid Sequence
• Animal
• Disease Models, Animal
• Dogs
• Encephalitis Viruses, Tick-Borne/*classification
• Encephalitis Viruses, Tick-Borne/genetics
• Encephalitis Viruses, Tick-Borne/pathogenicity
• Encephalitis, Tick-Borne/*epidemiology
• Encephalitis, Tick-Borne/virology
• Human
• Japan/epidemiology
• Mice
• Molecular Sequence Data
• *Phylogeny
• Russia/epidemiology
• Support, Non-U.S. Gov't
• Time Factors
• Viral Envelope Proteins/chemistry
• Viral Envelope Proteins/genetics
• Virulence

Substances:

• 0 (Viral Envelope Proteins)

[Early summer meningoencephalitis in low risk areas].
[Early summer meningoencephalitis in low risk areas]

Woessner R,  Grauer MT,  Falk U,  Gaertner B,  Mueller-Lantzsch N,  Haass A,  Treib J.

[Article in German]

Neurologische Klinik, Universitatskliniken des Saarlandes, Homburg/Saar.

MeSH Terms:

• Animal
• Cross-Sectional Studies
• Encephalitis, Tick-Borne/*epidemiology
• Encephalitis, Tick-Borne/transmission
• Germany/epidemiology
• Human
• Incidence
• Ixodes
• *Population Surveillance
• Risk Assessment

[Tick-borne encephalitis in Norway].
[Tick-borne encephalitis in Norway]

Ormaasen V,  Brantsaeter AB,  Moen EW.

[Article in Norwegian]

Infeksjonsmedisinsk avdeling Medisinsk divisjon Ulleval sykehus 0407 Oslo. vidar.ormaasen@ioks.unio.no

BACKGROUND: Tick-borne encephalitis is caused by a virus that is transmitted to man by tick-bite. The virus is found in central and eastern parts of Europe and also in Sweden. MATERIAL AND METHODS: We report the first two cases of tick-borne encephalitis resulting from transmission of virus in Norway. RESULTS: Both patients had been to the island of Tromoy on the south coast of Norway. The course of the disease was very different in the two patients. One patient had significant neurological dysfunction. The other patient had intense headache, but no motor dysfunction. Both patients had reduced general health and fever, and leukocytosis and increased protein was found in the spinal fluid. The incubation period is most often 1 to 2 weeks. The disease may have a bi-phasic course with initial fever, headache and muscle pain. One week later symptoms of encephalitis follow. Subclinical infection is common, especially in children. One third of patients get permanent sequelae after encephalitis. Diagnosis is made by demonstration of antibodies in serum. Treatment is symptomatic. INTERPRETATION: These two patients indicate that there may be a reservoir of TBE virus in Norway.

MeSH Terms:

• Aged
• Case Report
• Disease Reservoirs
• Encephalitis, Tick-Borne/diagnosis
• Encephalitis, Tick-Borne/epidemiology
• Encephalitis, Tick-Borne/*transmission
• English Abstract
• Human
• Male
• Middle Age
• Norway/epidemiology

Locations of carbohydrate sites on alphavirus glycoproteins show that E1 forms an icosahedral scaffold.

Pletnev SV,  Zhang W,  Mukhopadhyay S,  Fisher BR,  Hernandez R,  Brown DT,  Baker TS,  Rossmann MG,  Kuhn RJ.

Comment in: 

• Cell. 2001 Apr 6;105(1):5-8

[Article in English]

Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.

There are 80 spikes on the surface of Sindbis virus arranged as an icosahedral surface lattice. Each spike consists of three copies of each of the glycoproteins E1 and E2. There are two glycosylation sites on E1 and two on E2. These four sites have been located by removal of the glycosylation recognition motifs using site-specific mutagenesis, followed by cryoelectron microscopy. The positions of these sites have demonstrated that E2 forms the protruding spikes and that E1 must be long and narrow, lying flat on the viral surface, forming an icosahedral scaffold analogous to the arrangement of the E glycoprotein in flaviviruses. This arrangement of E1 leads to both dimeric and trimeric intermolecular contacts, consistent with the observed structural changes that occur on fusion with host cell membranes, suggesting a similar fusion mechanism for alpha- and flaviviruses.

MeSH Terms:

• Alphavirus/*chemistry
• Alphavirus/genetics
• Alphavirus/*ultrastructure
• Amino Acid Motifs/genetics
• Animal
• Binding Sites/genetics
• Carbohydrates/*chemistry
• Cell Line
• Cryoelectron Microscopy
• Encephalitis Viruses, Tick-Borne/chemistry
• Glycosylation
• Hamsters
• Membrane Glycoproteins/chemistry
• Membrane Glycoproteins/genetics
• *Models, Molecular
• Mutagenesis, Site-Directed
• Protein Conformation
• Ross River Virus/chemistry
• Sindbis Virus/chemistry
• Sindbis Virus/ultrastructure
• Support, Non-U.S. Gov't
• Support, U.S. Gov't, Non-P.H.S.
• Support, U.S. Gov't, P.H.S.
• Viral Envelope Proteins/chemistry
• Viral Envelope Proteins/genetics
• Viral Fusion Proteins/*chemistry
• Viral Fusion Proteins/genetics

Substances:

• 0 (Carbohydrates)
• 0 (Membrane Glycoproteins)
• 0 (Viral Envelope Proteins)
• 0 (Viral Fusion Proteins)
• 0 (glycoprotein E1, Sindbis virus)
• 0 (glycoprotein E2, Sindbis virus)

Grant Support:

• AI45976/AI/NIAID
• GM56279/GM/NIGMS

Self-replicative RNA vaccines elicit protection against influenza A virus, respiratory syncytial virus, and a tickborne encephalitis virus.

Fleeton MN,  Chen M,  Berglund P,  Rhodes G,  Parker SE,  Murphy M,  Atkins GJ,  Liljestrom P.

[Article in English]

Microbiology and Tumorbiology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden.

In genetic vaccination, recipients are immunized with antigen-encoding nucleic acid, usually DNA. This study addressed the possibility of using the recombinant alpha virus RNA molecule, which replicates in the cytoplasm of transfected cells, as a novel approach for genetic vaccination. Mice were immunized with recombinant Semliki Forest virus RNA-encoding envelope proteins from one of 3 viruses: influenza A virus, a tickborne flavivirus (louping ill virus), or respiratory syncytial virus (RSV). Serologic analyses showed that antigen-specific antibody responses were elicited. IgG isotyping indicated that predominantly Th1 type immune responses were induced after immunization with RSV F protein-encoding RNA, which is relevant for protection against RSV infection. Challenge infection showed that RNA immunization had elicited significant levels of protection against the 3 model virus diseases.

MeSH Terms:

• Animal
• Encephalitis Viruses, Tick-Borne/genetics
• Encephalitis Viruses, Tick-Borne/*immunology
• Encephalitis, Tick-Borne/prevention & control
• Female
• IgG/biosynthesis
• Immunity, Cellular
• Influenza/prevention & control
• Influenza A Virus/genetics
• Influenza A Virus/*immunology
• Influenza Vaccine/administration & dosage
• Influenza Vaccine/immunology
• Mice
• Mice, Inbred BALB C
• RNA, Viral/*immunology
• Respiratory Syncytial Virus Infections/prevention & control
• Respiratory Syncytial Virus Vaccines/genetics
• Respiratory Syncytial Virus Vaccines/immunology
• Respiratory Syncytial Viruses/genetics
• Respiratory Syncytial Viruses/*immunology
• Semliki Forest Virus/genetics
• Semliki Forest Virus/immunology
• Support, Non-U.S. Gov't
• Th1 Cells
• Transfection
• Vaccines, Synthetic/genetics
• Vaccines, Synthetic/immunology
• *Viral Vaccines/genetics
• *Viral Vaccines/immunology

Substances:

• 0 (IgG)
• 0 (Influenza Vaccine)
• 0 (RNA, Viral)
• 0 (Respiratory Syncytial Virus Vaccines)
• 0 (Vaccines, Synthetic)
• 0 (Viral Vaccines)

Improving the in vitro antigen specific T cell proliferation assay: the use of interferon-alpha to elicit antigen specific stimulation and decrease bystander proliferation.

von Baehr V,  Mayer W,  Liebenthal C,  von Baehr R,  Bieger W,  Volk HD.

[Article in English]

Institute of Medical Immunology, Charite Medical School, Campus Mitte, Humboldt University Berlin, D-10098, Berlin, Germany. baehr@ber.ladr.de

The measurement of the proliferative response of primed T cells to an antigenic stimulus (lymphocyte transformation assay: LTT) is commonly used for determining T cell immune responsiveness. However, the ratio between the spontaneous and the antigen-triggered response (stimulation index) is frequently quite low (<3-5) making the interpretation difficult. We modified the assay by the addition of interferon-alpha and the use of fresh autologous serum instead of human AB pool serum. These measures significantly enhanced the stimulation index following stimulation with tetanus toxoid, Candida albicans and tick-borne encephalitis (TBE) viral antigen in studies of sensitized patients. There was no concomitant increase in false positive results. Kinetic studies showed a reduced nonspecific background proliferation of non-stimulated cultures particularly between days 4 and 6 of culture. Furthermore, the positive effect of interferon-alpha were confirmed in studies of patients with contact allergy to nickel and gold. We conclude that this modified form of proliferation assay significantly increases the signal to noise ratio which can be attained. This may be of particular value when looking at T cell responses in immunocompromised patients or in diagnostic attempts to detect very low frequencies of antigen-specific T cells.

MeSH Terms:

• Adult
• *Antigens/administration & dosage
• Antigens, Fungal/administration & dosage
• Antigens, Viral/administration & dosage
• Candida albicans/immunology
• Encephalitis Viruses, Tick-Borne/immunology
• Female
• Human
• In Vitro
• Interferon Alfa-2a/administration & dosage
• Kinetics
• *Lymphocyte Transformation
• Male
• Middle Age
• T-Lymphocytes/*immunology
• Tetanus Toxoid/administration & dosage

Substances:

• 0 (Antigens)
• 0 (Antigens, Fungal)
• 0 (Antigens, Viral)
• 0 (Tetanus Toxoid)
• 76543-88-9 (Interferon Alfa-2a)

Infectious cDNA clone of attenuated Langat tick-borne flavivirus (strain E5) and a 3' deletion mutant constructed from it exhibit decreased neuroinvasiveness in immunodeficient mice.

Pletnev AG.

[Article in English]

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA. apletnev@niaid.nih.gov

Forty-five years ago a naturally attenuated tick-borne flavivirus, Langat (LGT) strain TP21, was recovered from ticks in Malaysia. Subsequently, it was tested as a live attenuated vaccine for virulent tick-borne encephalitis viruses. In a large clinical trial its attenuation was confirmed but there was evidence of a low level of residual virulence. Thirty-five years ago further attenuation of LGT TP21 was achieved by multiple passages in eggs to yield mutant E5. To study the genetic determinants of the further attenuation exhibited by E5 and to allow us to manipulate the genome of this virus for the purpose of developing a satisfactory live attenuated tick-borne flavivirus vaccine, we recovered infectious E5 virus from a full-length cDNA clone. The recombinant E5 virus (clone 651) recovered from a full-length infectious cDNA clone was more attenuated in immunodeficient mice than that of its biologically derived E5 parent. Increase in attenuation was associated with three amino acid substitutions, two located in the structural protein E and one in nonstructural protein NS4B. Subsequently an even greater degree of attenuation was achieved by creating a viable 320 nucleotide deletion in the 3'-noncoding region of infectious full-length E5 cDNA. This deletion mutant was not cytopathic in simian Vero cells and it replicated to lower titer than its E5-651 parent. In addition, the E5 3' deletion mutant was less neuroinvasive in SCID mice than its E5-651 parent. Significantly, the deletion mutant proved to be 119,750 times less neuroinvasive in SCID mice than its progenitor, LGT strain TP21. Despite its high level of attenuation, the E5 3' deletion mutant remained highly immunogenic and intraperitoneal (ip) inoculation of 10 PFU induced complete protection in Swiss mice against subsequent challenge with 2000 ip LD50 of the wild-type LGT TP21.

MeSH Terms:

• Animal
• Antibodies, Viral/immunology
• Base Sequence
• Brain/pathology
• Brain/*virology
• Cell Line
• Cercopithecus aethiops
• Chick Embryo
• Cloning, Molecular
• Consensus Sequence/genetics
• DNA, Complementary/genetics
• DNA, Recombinant/*genetics
• DNA, Viral/*genetics
• Encephalitis Viruses, Tick-Borne/*genetics
• Encephalitis Viruses, Tick-Borne/immunology
• Encephalitis Viruses, Tick-Borne/isolation & purification
• Encephalitis Viruses, Tick-Borne/*pathogenicity
• Encephalitis, Tick-Borne/immunology
• Encephalitis, Tick-Borne/pathology
• Encephalitis, Tick-Borne/prevention & control
• Encephalitis, Tick-Borne/virology
• Mice
• Mice, SCID
• Neutralization Tests
• Ovum
• Plaque Assay
• Sequence Deletion/*genetics
• Serial Passage
• Survival Rate
• Vaccination
• Vaccines, Attenuated/genetics
• Vaccines, Attenuated/immunology
• Viral Vaccines/genetics
• Viral Vaccines/immunology
• Virulence/genetics

Substances:

• 0 (Antibodies, Viral)
• 0 (DNA, Complementary)
• 0 (DNA, Recombinant)
• 0 (DNA, Viral)
• 0 (Vaccines, Attenuated)
• 0 (Viral Vaccines)

Mutational evidence for an internal fusion peptide in flavivirus envelope protein E.

Allison SL,  Schalich J,  Stiasny K,  Mandl CW,  Heinz FX.

[Article in English]

Institute of Virology, University of Vienna, A-1095 Vienna, Austria. steve.allison@univie.ac.au

The envelope protein E of the flavivirus tick-borne encephalitis (TBE) virus promotes cell entry by inducing fusion of the viral membrane with an intracellular membrane after uptake by endocytosis. This protein differs from other well-studied viral and cellular fusion proteins because of its distinct molecular architecture and apparent lack of involvement of coiled coils in the low-pH-induced structural transitions that lead to fusion. A highly conserved loop (the cd loop), which resides at the distal tip of each subunit and is mostly buried in the subunit interface of the native E homodimer at neutral pH, has been hypothesized to function as an internal fusion peptide at low pH, but this has not yet been shown experimentally. It was predicted by examination of the X-ray crystal structure of the TBE virus E protein (F. A. Rey et al., Nature 375:291-298, 1995) that mutations at a specific residue within this loop (Leu 107) would not cause the native structure to be disrupted. We therefore introduced amino acid substitutions at this position and, using recombinant subviral particles, investigated the effects of these changes on fusion and related properties. Replacement of Leu with hydrophilic amino acids strongly impaired (Thr) or abolished (Asp) fusion activity, whereas a Phe mutant still retained a significant degree of fusion activity. Liposome coflotation experiments showed that the fusion-negative Asp mutant did not form a stable interaction with membranes at low pH, although it was still capable of undergoing the structural rearrangements required for fusion. These data support the hypothesis that the cd loop may be directly involved in interactions with target membranes during fusion.

MeSH Terms:

• Animal
• COS Cells
• Cercopithecus aethiops
• Encephalitis Viruses, Tick-Borne/*metabolism
• Gene Expression
• Hydrogen-Ion Concentration
• Leucine/genetics
• Lipid Bilayers/metabolism
• Membrane Fusion/*physiology
• Mutagenesis
• Peptides/chemistry
• Peptides/genetics
• Peptides/*metabolism
• Peptides/physiology
• Protein Structure, Quaternary
• Support, Non-U.S. Gov't
• Viral Envelope Proteins/chemistry
• Viral Envelope Proteins/genetics
• Viral Envelope Proteins/*metabolism
• Viral Envelope Proteins/physiology

Substances:

• 0 (Lipid Bilayers)
• 0 (Peptides)
• 0 (Viral Envelope Proteins)
• 145420-18-4 (glycoprotein E, flavivirus)
• 7005-03-0 (Leucine)

Prevalence of tick-borne encephalitis virus in Ixodes ricinus ticks in Finland.

Han X,  Aho M,  Vene S,  Peltomaa M,  Vaheri A,  Vapalahti O.

[Article in English]

Haartman Institute, University of Helsinki, Finland. Xiuqi.Han@helsinki.fi

Approximately 20 cases of tick-borne encephalitis (TBE) occur annually in Finland. The known endemic areas are situated mainly in the archipelago and coastal regions of Finland, with highest incidence in Aland islands. Ixodes ricinus panels collected in 1996-1997 from two endemic areas were screened for the presence of RNA. Two distinct RT-PCR methods were applied, and were shown to have an approximate detection limit of 10 focus forming doses (FFD)/100 microl. One out of 20 pools (a total of 139 ticks) from Helsinki Isosaari Island and one out of 48 pools (a total of 450 ticks) from Aland were positive with both methods, whereas the remaining pools were negative. The observed overall frequency (0.34%) in ticks in endemic areas of Finland, was similar to the low incidence found by virus isolation in mice in the 1960s (0.5%). Viral RNA was detectable in a diluted sample representing 0.005% of a positive pool of ten nymphs suggesting that the viral RNA load within an infected tick pool was approximately equivalent to 20,000-200,000 FFD. Sequence analysis did not show geographical clustering of the Finnish strains, suggesting an independent emergence of different TBE foci from the south. TBE virus RNA positive ticks were not found in I. ricinus panels consisting of 130 pools (726 ticks) from Helsinki city parks or 41 pools (197 ticks) from Vormsi Island in Estonia. Copyright 2001 Wiley-Liss, Inc.

MeSH Terms:

• Animal
• Base Sequence
• Encephalitis Viruses, Tick-Borne/genetics
• Encephalitis Viruses, Tick-Borne/*isolation & purification
• Encephalitis, Tick-Borne/*epidemiology
• Endemic Diseases
• Finland/epidemiology
• Human
• Ixodes/*virology
• Mice
• Molecular Sequence Data
• Prevalence
• RNA, Viral/analysis
• Reverse Transcriptase Polymerase Chain Reaction
• Sensitivity and Specificity
• Sequence Alignment
• Sequence Analysis/methods
• Support, Non-U.S. Gov't
• Viral Load
• Viral Nonstructural Proteins/genetics
• Virus Replication

Substances:

• 0 (NS5 protein, flavivirus)
• 0 (RNA, Viral)
• 0 (Viral Nonstructural Proteins)

Biophysical characterization and vector-specific antagonist activity of domain III of the tick-borne flavivirus envelope protein.

Bhardwaj S,  Holbrook M,  Shope RE,  Barrett AD,  Watowich SJ.

[Article in English]

Department of Human Biological Chemistry & Genetics and Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA.

The molecular determinants responsible for flavivirus host cell binding and tissue tropism are largely unknown, although domain III of the envelope protein has been implicated in these functions. We examined the solution properties and antagonist activity of Langat virus domain III. Our results suggest that domain III adopts a stably folded structure that can mediate binding of tick-borne flaviviruses but not mosquito-borne flaviviruses to their target cells. Three clusters of phylogenetically conserved residues are identified that may be responsible for the vector-specific antagonist activity of domain III.

MeSH Terms:

• Amino Acid Sequence
• Animal
• Cercopithecus aethiops
• Circular Dichroism
• Conserved Sequence
• Encephalitis Viruses, Tick-Borne/*drug effects
• Encephalitis Viruses, Tick-Borne/metabolism
• Flavivirus/drug effects
• Flavivirus/metabolism
• Models, Molecular
• Molecular Sequence Data
• Peptide Fragments/chemistry
• Peptide Fragments/pharmacology
• Protein Structure, Tertiary
• Receptors, Virus/*antagonists & inhibitors
• Receptors, Virus/metabolism
• Recombinant Fusion Proteins/chemistry
• Recombinant Fusion Proteins/metabolism
• Sequence Alignment
• Substrate Specificity
• Support, Non-U.S. Gov't
• Support, U.S. Gov't, Non-P.H.S.
• Vero Cells
• Viral Envelope Proteins/*chemistry
• Viral Envelope Proteins/metabolism
• Viral Envelope Proteins/*pharmacology

Substances:

• 0 (Peptide Fragments)
• 0 (Receptors, Virus)
• 0 (Recombinant Fusion Proteins)
• 0 (Viral Envelope Proteins)
• 145420-18-4 (glycoprotein E, flavivirus)

Langat virus M protein is structurally homologous to prM.

Holbrook MR,  Wang H,  Barrett AD.

[Article in English]

Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609, USA.

Langat (LGT) virus M protein has been generated in a recombinant system. Antiserum raised against the LGT virus M protein neutralizes tick-borne encephalitis serocomplex flaviviruses but not mosquito-borne flaviviruses, indicating that the M protein is exposed on the surface of virions. The antiserum recognizes intracellular LGT virus prM/M and binds to prM and M in Western blots of whole-cell lysates and purified virus, respectively. These data suggest that the prM and M proteins are structurally similar under native conditions and support the hypothesis that the "pr" portion of prM facilitates proper folding of the M protein for expression on the virion surface.

MeSH Terms:

• Amino Acid Sequence
• Animal
• Antibodies, Viral/immunology
• Antibody Specificity/immunology
• Blotting, Western
• Cercopithecus aethiops
• Cross Reactions/immunology
• Cytoplasm/virology
• Encephalitis Viruses, Tick-Borne/chemistry
• Encephalitis Viruses, Tick-Borne/*immunology
• Flavivirus/immunology
• Immune Sera/immunology
• Molecular Sequence Data
• Neutralization Tests
• Sequence Alignment
• Serology
• Support, Non-U.S. Gov't
• Vero Cells
• Viral Envelope Proteins/*chemistry
• Viral Envelope Proteins/*immunology

Substances:

• 0 (Antibodies, Viral)
• 0 (Immune Sera)
• 0 (Viral Envelope Proteins)
• 0 (prM-M protein)

[Autochthonous cases of tick-borne encephalitis in Rhineland-Palatinate]

Woessner R,  Muhl A,  von Arnim WH,  Treib J.

[Article in German]

Neurologische Klinik, Westpfalz-Klinikum GmbH, Kaiserslautern.

Tick-borne encephalitis (TBE) is a neurotrophic viral disease which is endemic to certain regions. Such areas in Germany include Bavaria, Baden-Wurttemberg, and the Odenwald region in Hessen. So far, it has not been endemic to Rhineland-Palatinate. There, only two single cases of TBE occurred in the years 1992 and 1997, near the town of Idar-Oberstein. We report two new cases of TBE which appeared in 1999 and two current cases from the Idar-Oberstein region which have been verified clinically and serologically. At admission, the patients suffered from headache, muscle pains, and high fever, in one case meningitis was suspected. In all four patients, serology for borrelia was negative in serum and CSF. The described cases indicate that it is possible to acquire TBE in Rhineland-Palatinate, although only two cases have been reported in this area over the previous 10 years. Particularly in regions with a low incidence of TBE, the disease should be taken into consideration as a differential diagnosis. Studies of tick populations in regions with a low incidence can help in evaluating the benefit of possible vaccine recommendations by local public health authorities.

MeSH Terms:

• Adolescence
• Adult
• Case Report
• Diagnosis, Differential
• Encephalitis, Tick-Borne/*diagnosis
• Encephalitis, Tick-Borne/epidemiology
• Endemic Diseases/*prevention & control
• English Abstract
• Female
• Germany/epidemiology
• Human
• Incidence
• Lyme Neuroborreliosis/diagnosis
• Male
• Meningitis/diagnosis
• Middle Age
• Practice Guidelines

[On the problem of pathomorphosis of modern tick-borne encephalitis in Ural]

Erman BA,  Zaitseva LN,  Drozdova LI,  Volkova LI,  Obraztsova RG.

[Article in Russian]

Centre of Laboratory Diagnosis of Mother and Child Diseases, Ekaterinburg.

Pathology study of 32 patients who died of tick-borne encephalitis (TBE) in the Ural Region in 1990s revealed differences with this infection registered in 1940-1950s. Pathological changes in the central nervous system by their severity and location are like those observed in the Far East TBE. Apart from grave alterative changes in the nerve cells of motor nuclei of the spinal cord and brain, three types of pathological changes are observed: productive inflammation, exudative inflammation without pronounced inflammatory reaction. Differences in the organism reactions to the infectious process are explained by differences in the virus virulence and organism immunological status.

MeSH Terms:

• Acute Disease
• Adolescence
• Adult
• Aged
• Brain/pathology
• Brain/virology
• *Encephalitis Viruses, Tick-Borne
• Encephalitis, Tick-Borne/epidemiology
• Encephalitis, Tick-Borne/*pathology
• Encephalitis, Tick-Borne/physiopathology
• English Abstract
• Female
• Human
• Inflammation/pathology
• Male
• Middle Age
• Siberia/epidemiology
• Spinal Cord/pathology
• Spinal Cord/virology

Oligodeoxynucleotides containing CpG motifs induce low levels of TNF-alpha in human B lymphocytes: possible adjuvants for Th1 responses.

Bohle B,  Orel L,  Kraft D,  Ebner C.

[Article in English]

Department of Pathophysiology, Division of Immunopathology, University of Vienna, Vienna, Austria. barbara.bohle@akh-wien.ac.at

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) represent potential adjuvants for specific immunotherapy of type I allergies because they foster Th1-like immune responses. However, previous work has shown that CpG-ODN induce systemically active levels of TNF-alpha in murine macrophages. The goal of the present study was to evaluate the release of TNF-alpha in human cells by a CpG-ODN proven to induce Th1 immune responses in cells from atopic individuals and in mice. CpG-ODN induced TNF-alpha in cells from atopic and healthy individuals. However, the amounts were low, as determined by comparison with commonly used Ags. Intracellular cytokine staining of PBMC revealed that CpG-ODN-induced TNF-alpha derived exclusively from B lymphocytes. TNF-alpha contributed to the CpG-ODN-augmented proliferation and Ig synthesis in PBMC, but was not involved in IFN-gamma synthesis. In conclusion, our findings indicate that certain CpG-ODN induce low amounts of TNF-alpha in human B lymphocytes and may therefore be used to modulate Th2-biased immune responses in allergic patients.

MeSH Terms:

• Adjuvants, Immunologic/*pharmacology
• Antigens, Viral/pharmacology
• B-Lymphocytes/*immunology
• B-Lymphocytes/*metabolism
• Cell Division/immunology
• Cells, Cultured
• Comparative Study
• CpG Islands/*immunology
• Dose-Response Relationship, Immunologic
• Encephalitis Viruses, Tick-Borne/immunology
• Human
• IgG/biosynthesis
• IgM/biosynthesis
• Interferon Type II/biosynthesis
• Leukocytes, Mononuclear/immunology
• Leukocytes, Mononuclear/metabolism
• Monocytes/immunology
• Monocytes/metabolism
• Oligodeoxyribonucleotides/*immunology
• Oligodeoxyribonucleotides/pharmacology
• Support, Non-U.S. Gov't
• Tetanus Toxoid/pharmacology
• Th1 Cells/*immunology
• Th1 Cells/*metabolism
• Tuberculin/pharmacology
• Tumor Necrosis Factor/*biosynthesis
• Tumor Necrosis Factor/physiology
• Viral Vaccines/pharmacology

Substances:

• 0 (Adjuvants, Immunologic)
• 0 (Antigens, Viral)
• 0 (CPG-oligonucleotide)
• 0 (IgG)
• 0 (IgM)
• 0 (Oligodeoxyribonucleotides)
• 0 (Tetanus Toxoid)
• 0 (Tuberculin)
• 0 (Tumor Necrosis Factor)
• 0 (Viral Vaccines)
• 82115-62-6 (Interferon Type II)

[No title available]

[No authors listed].

[Article in Russian]

Territorial Center of State Sanitary and Epidemiological Inspection, Krasnoyarsk, Russia.

For the first time in the Krasnoyarsk region the population Haemaphysalis concinna ticks were found to be infected with the causative agents of three natural focal tick-borne infections--tick-borne encephalitis, tick-borne rickettsiosis and tularemia. The existence of the combined natural focus of these three infections has been confirmed by epidemiological data. Ticks Dermacentor nuttalli also play a similar role in combined foci of tick-borne encephalitis and tick-borne rickettsiosis in these focal territories.

[Expression of the NS1 gene of tick-borne encephalitis virus in gram-negative bacteria from the mouse nasopharynx]

Morozova OV,  Maksimova TG,  Popova RV,  Martsinkevich ON,  Bakhvalova VN.

[Article in Russian]

Bacteria were isolated from the nasopharynx of BALB/c mice and electroporated with pUR290(NS1)2 containing two copies of tick-borne encephalitis virus (TBEV) strain Sofjin NS1 under the control of the lac promoter. The plasmid persisted in transformants for at least ten passages. The NS1 gene expression was detected in Gram-negative enterobacteria via immunoblotting with monoclonal antibodies against TBEV nonstructural glycoprotein NS1. Recombinant NS1 was detected in bacterial cells and in the culture medium. Intranasal immunization with recombinant bacteria activated production of antibodies against NS1 in serum of BALB/c mice. The humoral immune response to NS1 failed to protect immunized mice from a TBEV challenge.

MeSH Terms:

• Animal
• Antibodies, Viral/biosynthesis
• Cell Line
• Cloning, Molecular
• Encephalitis Viruses, Tick-Borne/*genetics
• English Abstract
• Gram-Negative Bacteria/*genetics
• Mice
• Mice, Inbred BALB C
• Nasal Mucosa/immunology
• Nasal Mucosa/microbiology
• Nasopharynx/*microbiology
• Plasmids
• Recombination, Genetic
• Swine
• Viral Nonstructural Proteins/*genetics
• Viral Vaccines/immunology

Substances:

• 0 (Antibodies, Viral)
• 0 (Plasmids)
• 0 (Viral Nonstructural Proteins)
• 0 (Viral Vaccines)

[Comparative in vitro study of the effectiveness of various immunomodulating substances in tick-borne encephalitis]

Krylova NV,  Leonova GN.

[Article in Russian]

Suppressing effect of tick-borne encephalitis (TBE) virus on expression of lymphocyte subpopulation receptors has been demonstrated in vitro. Effects of 14 immunomodulators on expression of T lymphocyte receptors under the effect of TBE virus have been compared. Anti-TBE immunoglobulin, 4-iodantipyrin, and leukinferon had the highest protective effect after a preventive injection. Thymalin and leukinferon in combination with human leukocytic interferon were the most effective within the treatment protocols. Further studies of sensitivity of immunoregulator cells to immunomodulators is recommended with the aim of adding these drugs to therapy of TBE patients.

MeSH Terms:

• Adjuvants, Immunologic/*pharmacology
• Adjuvants, Immunologic/therapeutic use
• Comparative Study
• Encephalitis, Tick-Borne/drug therapy
• Encephalitis, Tick-Borne/*immunology
• English Abstract
• Human
• In Vitro
• Receptors, Antigen, T-Cell/immunology
• Rosette Formation
• T-Lymphocyte Subsets

Substances:

• 0 (Adjuvants, Immunologic)
• 0 (Receptors, Antigen, T-Cell)

[Protective activity of a bacterial plasmid, bearing the gene for the tick-borne encephalitis virus NS1 nonstructural protein]

Timofeev AV,  Kondrat'eva II,  Karganova GG,  Stephenson J.

[Article in Russian]

Three intramuscular injections (50 micrograms each) with bacterial plasmid pMV45 carrying nonstructural gene of NS1 protein of tick-borne encephalitis (TBE) virus protected 88% Balb/c mice from lethal challenge with the virus. Antibodies to NS1 nonstructural protein were detected in the sera of vaccinated mice after the challenge. Absence of antibodies to E structural protein indicated absence of manifest infectious process in mice vaccinated with plasmid and challenged with a lethal dose of TBE virus.

MeSH Terms:

• Animal
• Antibodies, Viral/blood
• Cercopithecus aethiops
• Encephalitis Viruses, Tick-Borne/*genetics
• English Abstract
• Mice
• Mice, Inbred BALB C
• Plasmids/*administration & dosage
• Vero Cells
• Viral Envelope Proteins/immunology
• Viral Nonstructural Proteins/*genetics
• Viral Nonstructural Proteins/immunology
• Viral Vaccines/*administration & dosage

Substances:

• 0 (Antibodies, Viral)
• 0 (NS1 protein, flavivirus)
• 0 (Plasmids)
• 0 (Viral Envelope Proteins)
• 0 (Viral Nonstructural Proteins)
• 0 (Viral Vaccines)
• 145420-18-4 (glycoprotein E, flavivirus)

[Genetic typing of tick-borne encephalitis virus based on an analysis of the levels of homology of a membrane protein gene fragment]

Zlobin VI,  Demina TV,  Belikov SI,  Butina TV,  Gorin OZ,  Adel'shin RV,  Grachev MA.

[Article in Russian]

All heretofore known genomic structures of tick-borne encephalitis (TBE) virus are analyzed. The authors prove the adequacy of using short fragment of E protein gene for characterization of philogenetic relationships between TBE strains. Three main genotypes of the virus are distinguished, one corresponding to Far Eastern variant, one to West, and the third includes strains belonging to Ural Siberian and Central Siberian and Transbaikal variants. Results of genetic typing by nucleotide sequences are confirmed by analysis of amino acid sequences of E protein fragments, specific marker amino acids in definite positions being determined for each genotype.

MeSH Terms:

• Amino Acid Sequence
• Encephalitis Viruses, Tick-Borne/*genetics
• English Abstract
• Genotype
• Molecular Sequence Data
• Phylogeny
• Sequence Homology, Amino Acid
• Species Specificity
• Viral Envelope Proteins/chemistry
• Viral Envelope Proteins/*genetics

Substances:

• 0 (Viral Envelope Proteins)
• 145420-18-4 (glycoprotein E, flavivirus)

[Analysis of genetic variability of strains of tick-borne encephalitis virus by primary structure of a fragment of the membrane protein E gene]

Zlobin VI,  Demina TV,  Mamaev LV,  Butina TV,  Belikov SI,  Gorin OZ,  Dzhioev IP,  Verkhozina MM,  Kozlova IV,  Voronko IV,  Adel'shin RV,  Grachev MA.

[Article in Russian]

Primary structures of gene fragments of E protein (160 n.b.) have been determined for 29 tick-borne encephalitis (TBE) strains isolated from different parts of a territory. Analysis of homology of nucleotide sequences of these strains and data on 6 TBE strains published by other authors showed that they can be divided into 6 groups (genotypes) by the following gene typing criteria: strain structure within the genotypes differing by no more than 9%, differences between strains of different genotypes are at least 12%. Based on these criteria, the prototype strains of the Far Eastern antigenic variant (Sofyin), Central European antigenic variant (Neudoerfle), and Vergina strain form different genotypes 1, 2, and 6, respectively. East Siberian strain Aina and Ural Siberian strain Lesopark-II belong to the same TBE virus genotype 3; two-thirds of analyzed strains belong to this genotype. Genotype 4 is represented by one strain 178-79, and genotype 5 by strain 886-84, both isolated in East Siberia.

MeSH Terms:

• Base Sequence
• DNA Primers
• Encephalitis, Tick-Borne/*genetics
• English Abstract
• Molecular Sequence Data
• Polymerase Chain Reaction
• RNA, Viral
• Sequence Homology, Nucleic Acid
• Species Specificity
• *Variation (Genetics)
• Viral Envelope Proteins/*genetics

Substances:

• 0 (DNA Primers)
• 0 (RNA, Viral)
• 0 (Viral Envelope Proteins)
• 145420-18-4 (glycoprotein E, flavivirus)

[Specific antigenic preparations as inducers of blood leukocyte respiratory burst in chemiluminescent analysis]

Dorokhina NA,  Savchenko AA,  Chesnokov AB,  Polonskaia ZG,  Ol'khovskii IA,  Shakina NA.

[Article in Russian]

Functional activity of blood leukocytes of normal subjects and patients with herpesvirus infection was studied by the chemiluminescent method in vitro with specific antigenic preparations (tick-borne encephalitis vaccine, ADPT vaccine, and herpetic vaccine). Functional response of blood leukocytes to vaccine preparations is specific and depends on the antigen and metabolic status of cells of recipients. The range of chemiluminescent response of blood leukocytes is wide: no changes in tick-borne encephalitis vaccine, weak response to herpetic vaccine, and pronounced changes in functional activity in response to ADPT vaccine. Testing with different doses of specific inducers helps additionally evaluate the metabolic reserve of blood leukocytes. A pronounced response of leukocytes to specific antigenic preparations in vitro (e.g. to ADPT vaccine) prompts development of methods for predicting the reaction of nonspecific reactivity system to vaccination.

MeSH Terms:

• *Antigens, Viral
• Chemiluminescence
• Diphtheria-Tetanus-Pertussis Vaccine/immunology
• Encephalitis Viruses, Tick-Borne/immunology
• English Abstract
• Herpes Simplex/*blood
• Human
• In Vitro
• Leukocytes/immunology
• Leukocytes/*metabolism
• Neutrophil Activation
• Recurrence
• *Respiratory Burst/immunology
• Simplexvirus/immunology
• Viral Vaccines/immunology

Substances:

• 0 (Antigens, Viral)
• 0 (Diphtheria-Tetanus-Pertussis Vaccine)
• 0 (Viral Vaccines)

Seasonal population dynamics of ixodes ticks and tick-borne encephalitis virus.

Korenberg EI.

[Article in English]

Vector Laboratory, Gamaleya Research Institute for Epidemiology and Microbiology Russian Academy of Medical Sciences. focus@edkor.msk.ru

Seasonality of the epidemic and epizootic processes of tick-borne encephalitis (TBE) depend on the period of activity of ixodid ticks Ixodes persulcatus Schulze and I. ricinus Linnaeus, which are the main reservoirs and vectors of TBE virus, and also on the process of their activation. The period of activity is the period during which the ticks occur in the active state. Activation is the transition into this state of ticks that moulted from the preceding stage and completed post-moulting development. For I. persulcatus, the first adult ticks generally emerge between April 10 and May 9. Under a variety of natural conditions, activation of adult I. persulcatus after wintering lasts for 45-86 days and this period may be even longer in certain areas of the Far East. The period during which one-half of the entire tick population becomes activated (AT50) comprises no more than 10-20 days. In adult I. ricinus ticks the activation period may last even longer than in I. persulcatus. The data on duration of the period of activity and on activation of larval and nymphal stages of both tick species were considered. Ticks exhausting their nutrient reserves and failing to find a host die quickly. The period during which 50% of the entire tick population die under natural conditions is designated LT50. The main types of I. persulcatus and I. ricinus seasonal activity within their species ranges were reviewed. Data on the relationship between TBE virus reproduction in a natural focus and physiological age, pattern of activation, and seasonal changes in age structure of the tick population were analyzed. Seasonal changes in the prevalence of infection among active unfed adult ticks in a natural population are determined by virus content in individual ticks at the moment of their activation and also by the duration of subsequent virus persistence (the rate of virus loss) in ticks. Apparently, the opportunity and frequency of horizontal TBE virus transmission under natural conditions, change during the season of tick activity.

Publication Types:

• Journal Article
• Review
• Review, Tutorial

MeSH Terms:

• Animal
• Asia/epidemiology
• Encephalitis Viruses, Tick-Borne/*physiology
• Encephalitis, Tick-Borne/epidemiology
• Encephalitis, Tick-Borne/transmission
• Europe/epidemiology
• Ixodes/*growth & development
• Ixodes/virology
• Population Dynamics
• Seasons
• Tick Infestations

Alterations in the proliferative response of peripheral lymphocytes in tick-borne encephalitis.

Shilov YI,  Ryzhaenkov VG.

[Article in English]

Institute of Ecology and Genetics of Microorganisms, Ural Division, Russian Academy of Sciences, ul. Pushkina 1-57, Perm, 614000 Russia.

MeSH Terms:

• Acute Disease
• Cells, Cultured
• Encephalitis, Tick-Borne/blood
• Encephalitis, Tick-Borne/classification
• Encephalitis, Tick-Borne/*immunology
• Enzyme-Linked Immunosorbent Assay
• Human
• IgM/blood
• *Lymphocyte Transformation
• Lymphocytes/*immunology
• Phytohemagglutinins
• Reference Values

Substances:

• 0 (IgM)
• 0 (Phytohemagglutinins)
• 0 (phytohemagglutinin-P)

Prevalence of antibodies to tickborne encephalitis and West Nile flaviviruses and the clinical signs of tickborne encephalitis in dogs in the Czech Republic.

Klimes J,  Juricova Z,  Literak I,  Schanilec P,  Trachta e Silva E.

[Article in English]

Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic.

Blood sera from 151 dogs from areas of the Czech Republic endemic for human tickborne encephalitis (TBE) were examined for the presence of antibodies to TBE and West Nile (WN) flaviviruses by the haemagglutination-inhibition test Antibodies to TBE virus at titres equal to or exceeding 40 were found in five dogs. Antibodies to WN virus were detected in only one dog that also had a high antibody titre to TBE, suggesting this was a cross-reaction between the two closely related viruses. Three of the dogs (all rottweilers) with a TBE titre of 320 had clinical signs of meningoencephalitis or encephalitis. They all survived after treatment for the clinical signs. It was proved by seroconversion that the disease was caused by the TBE virus in one of these three dogs, and it seems very likely that the virus was responsible for the disease in the other two.

MeSH Terms:

• Animal
• Antibodies, Viral/*analysis
• Antigens, Protozoan
• Czech Republic
• Dog Diseases/*virology
• Dogs
• Encephalitis Viruses, Tick-Borne/*immunology
• Encephalitis, Tick-Borne/diagnosis
• Encephalitis, Tick-Borne/immunology
• Encephalitis, Tick-Borne/*veterinary
• Female
• Male
• Support, Non-U.S. Gov't
• West Nile Virus/*immunology

Substances:

• 0 (Antibodies, Viral)
• 0 (Antigens, Protozoan)
• 0 (QF116 antigen)

[Incidence of tick-borne encephalitis in the West Bohemia Region 1960-1999--evaluation of vaccination]

Pazdiora P,  Benesova J,  Brejcha O,  Holecek J,  Hruba P,  Kubatova A,  Moravkova I,  Ouradova R,  Spacilova M,  Turkova D,  Vodrazkova Z,  Struncova V.

[Article in Czech]

In 1960-1999 in the West Bohemian region 1216 cases of tick-borne encephalitis were recorded, four were fatal. Since 1992 there was a marked increase in the number of these infections--in 1992-1999 the relative morbidity was 6.7 per 100,000 population per year, the highest specific morbidity shifted to the age group of 55-64 years. In the whole region changes occurred as to the probable transmission of infection. By the end of 1999 in western Bohemia the hygiene service immunized, by at least three doses against tick-borne encephalitis 23,225 subjects, i.e. 2.7% of the population. The negligible vaccination rate did not have so far an impact on the epidemiological characteristics of the infection. In view of the more frequent and clinically more severe affection in elderly subjects it is important to raise the vaccination rate in particular in more advanced age groups.

MeSH Terms:

• Adolescence
• Adult
• Aged
• Child
• Child, Preschool
• Czech Republic/epidemiology
• Encephalitis, Tick-Borne/*epidemiology
• Encephalitis, Tick-Borne/prevention & control
• Female
• Human
• Incidence
• Infant
• Male
• Middle Age
• *Vaccination

[Application of the 3 R]

Schober-Bendixen S.

[Article in English]

Fa. Immuno AG, A-Orth/Donau.

This report describes the various ways in which animal experiments were replaced, reduced or refined by the manufacturer in the quality control of the tick-borne encephalitis (TBE) vaccine over the past fifteen years. The total number of test animals was reduced from 4.278 to 2.011 per vaccine lot. This involves a reduction of 34.005 test animals per year. If a further planned change submitted to the regulatory authorities is approved, the number of animals used will be further reduced to 961 per vaccine lot. This will result in a total saving of 49.755 animals per year. A newly developed TBE vaccine, which will be submitted to the EC regulatory authorities in 1997, will involve even further reductions in the number of test animals required for quality control. Only 531 test animals will be required per lot for this newly developed vaccine i. e. almost 90% reduction compared to the numbers required for the original vaccine. It has been possible to convince the national regulatory authority that only a minimal amount of animal tests are essential for the quality control of this vaccine. This has been made possible by the intensive search for replacement tests and by the high standard of validation of these tests. It will probably not be possible to totally eliminate animal tests for vaccine quality control in the future. However, the vigorous implementation of the 3R"s will certainly lead to a reduction in the number of animals required and the reduction of animal suffering. The aim of this policy must be seen not only as a reduction in the number of animals used, but primarily a reduction in suffering to the lowest possible levels for the animals still required.

Comparison of six different commercial IgG-ELISA kits for the detection of TBEV-antibodies.

Niedrig M,  Vaisviliene D,  Teichmann A,  Klockmann U,  Biel SS.

[Article in English]

Robert Koch-Institut, Nordufer 20, D-I 3353 Berlin, Germany.

BACKGROUND: Tick-borne encephalitis virus (TBEV) is a pathogenic human flavivirus endemic in some parts of Europe and Asia. Commercial enzyme immunoassays (EIA) for the detection of IgG antibodies are often used in TBEV-seroprevalence studies, as well as for the confirmation of a successful vaccination against TBEV. However, the detection of TBEV-specific antibodies can be biased by the cross-reactivity between different flavivirus genera. OBJECTIVES: To compare different EIA test systems for the detection of TBEV-IgG antibodies. STUDY DESIGN: Six commercial EIA kits for the detection of TBEV-specific antibodies are compared, using serum panels (n=139) of subjects with a documented clinical history (109 sera from TBEV infected patients, 30 sera from people vaccinated against TBEV). For the analysis of possible cross-reactivities, 24 sera from yellow fever vaccinated people and 13 sera positive for Dengue virus-specific antibodies were also included. RESULTS: The sensitivity of the different TBEV test systems ranges from 73 to 99%. However, when testing the yellow fever and Dengue virus positive specimens, problems with the flavivirus cross- reactivity become obvious, resulting in specificities between 14 and 81%. CONCLUSIONS: This study shows the necessity of further improvement of the existing TBEV test systems regarding both sensitivity and specificity.

MeSH Terms:

• Antibodies, Viral/*blood
• Comparative Study
• Cross Reactions
• Dengue/immunology
• Encephalitis Viruses, Tick-Borne/*immunology
• Encephalitis, Tick-Borne/*immunology
• Enzyme-Linked Immunosorbent Assay
• Human
• IgG/*blood
• Reagent Kits, Diagnostic
• Sensitivity and Specificity
• Yellow Fever/immunology

Substances:

• 0 (Antibodies, Viral)
• 0 (IgG)
• 0 (Reagent Kits, Diagnostic)

Diagnostic immunoassays for tick-borne encephalitis virus based on recombinant baculovirus protein expression.

Marx F,  Gritsun TS,  Grubeck-Loebenstein B,  Gould EA.

[Article in English]

Department of Microbiology, Medical School, University of Innsbruck, Fritz-Pregl Strasse 3/II, A-6020, Innsbruck, Austria. florentine.marx@uibk.ac.at

The baculovirus expression system that utilizes Autographa californica nuclear polyhedrosis virus was used to express the highly antigenic envelope protein E of a tick-borne encephalitis (TBE) complex virus, as well as a C-terminally truncated form of protein E (Etr). The recombinant proteins were produced with a histidine-tag at their carboxy-terminus. Protein purification by nickel agarose chromatography resulted in high concentrations of pure Etr protein, but only poor yields of E protein. Therefore, Etr was used to develop a sensitive and specific enzyme-linked immunosorbent assay (ELISA), as well as an immunoblot assay to detect TBE virus-specific antibodies in sera from immunized human blood donors. Sera from non-vaccinated blood donors were used as controls. The data show that the recombinant TBE virus-specific Etr protein exhibits the antigenic epitopes and conformation necessary for specific antigen-antibody recognition. Thus, the baculovirus expression system provides a cheap and easy method to generate recombinant viral antigens for TBE virus-specific serodiagnosis.

MeSH Terms:

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Viral/blood
• *Blotting, Western
• Cloning, Molecular
• Encephalitis Viruses, Tick-Borne/immunology
• Encephalitis Viruses, Tick-Borne/*isolation & purification
• Encephalitis, Tick-Borne/*diagnosis
• Encephalitis, Tick-Borne/virology
• *Enzyme-Linked Immunosorbent Assay/methods
• Human
• Middle Age
• Nucleopolyhedrovirus/*genetics
• Peptide Fragments/genetics
• Peptide Fragments/immunology
• Recombinant Proteins/genetics
• Recombinant Proteins/immunology
• Serologic Tests
• Support, Non-U.S. Gov't
• Viral Envelope Proteins/*genetics
• Viral Envelope Proteins/immunology
• Viral Vaccines/administration & dosage

Substances:

• 0 (Antibodies, Viral)
• 0 (Peptide Fragments)
• 0 (Recombinant Proteins)
• 0 (Viral Envelope Proteins)
• 0 (Viral Vaccines)
• 145420-18-4 (glycoprotein E, flavivirus)

[Evaluation of FcR and CR receptor expression in granulocytes and immune complex level in patients with tick-borne encephalitis].

Izycka A,  Jablonska E,  Zajkowska J,  Hermanowska-Szpakowicz T,  Izycki T.

[Article in Polish]

Zakladu Immunopatologii AM w Bialymstoku.

The aim of this study was to estimate expression of FcR and CR membrane receptors of PMN and circulating immune complexes level in serum from infected patients before and after treatment. Before treatment we observed significant decrease of PMN percentage with FcR and CR receptors in comparison to control. After treatment there was increase of PMN percentage with receptors in comparison to values before treatment but it did not reach values of controls. Immune complexes level before treatment was significant higher than controls before treatment and it decreased after treatment but did not reach control level. Depression of phagocytic activity of PMN may be one of the main reasons for spreading viral infection.

Publication Types:

• Clinical Trial
• Controlled Clinical Trial
• Journal Article

MeSH Terms:

• Adult
• Aged
• Antigen-Antibody Complex/*analysis
• Encephalitis, Tick-Borne/*immunology
• Encephalitis, Tick-Borne/therapy
• Female
• Human
• Male
• Middle Age
• Neutrophils/*metabolism
• Phagocytosis
• Receptors, Complement/*analysis
• Receptors, IgG/*analysis

Substances:

• 0 (Antigen-Antibody Complex)
• 0 (Receptors, Complement)
• 0 (Receptors, IgG)

MRI in tick-borne encephalitis.

Alkadhi H,  Kollias SS.

[Article in English]

Institute of Neuroradiology, University Hospital of Zurich, Switzerland.

The tick-borne encephalitis (TBE) virus gives rise to epidemic encephalitis. Mild forms usually manifest as influenza-like episodes or are clinically silent. MRI is usually normal in TBE. We describe severe TBE in a patient who presented with fever and altered mental status after a tick bite and a specific antibody response to TBE. MRI revealed pronounced signal abnormalities in the basal ganglia and thalamus, without contrast enhancement. These findings coincide well with neuropathological studies of severe nerve cell degeneration with inflammatory cell infiltrates, neuronophagia and reactive astrocytosis in the deep grey matter. We review the literature and discuss the relevant differential diagnosis.

Publication Types:

• Journal Article
• Review
• Review, Tutorial

MeSH Terms:

• Brain/*pathology
• Case Report
• Diagnosis, Differential
• Encephalitis, Tick-Borne/*pathology
• Female
• Human
• *Magnetic Resonance Imaging
• Middle Age

[Genetic analysis of tick-borne encephalitis virus strains from West Siberia]

Bakhvalova VN,  Rar VA,  Tkachev SE,  Dobrikova EI,  Morozova OV.

[Article in Russian]

Tick-borne encephalitis (TBE) virus strains were isolated in West Siberia in the forest-steppe region near the Ob river in 1981-1992. Hybridization of genome RNA of 46 TBE strains with [32P]cDNA of TBE Sofyin strain revealed essential differences in the genomes of West-Siberian and Far-Eastern Sofyin strains of TBE virus. Nucleotide sequences of 6 TBE strains (1348-1503 n.) have been determined. A 89-98% homology of Siberian TBE strains has been shown, while the similarity of the respective fragment of E gene for West Siberian and Sofyin strains was no more than 81%. No significant changes in E gene of TBE strains have been detected over a 12-year period.

MeSH Terms:

• Base Sequence
• Encephalitis Viruses, Tick-Borne/*genetics
• Encephalitis, Tick-Borne/*virology
• English Abstract
• *Genome, Viral
• Human
• Molecular Sequence Data
• Siberia

[A medico-geographical assessment of the land area of the Maritime Territory relative to tick-borne encephalitis with some remarks on the structural organization of the foci of said infection]

Bolotin EI.

[Article in Russian]

A division of the Primorskiy Kray into districts in relation to the tick-borne encephalitis was based on three criteria: long-term dynamics of infection, chorological structure of ixodid tick populations and probability of this or that clinical form of infection.

MeSH Terms:

• Animal
• Arachnid Vectors
• Comparative Study
• *Disease Reservoirs/statistics & numerical data
• Encephalitis, Tick-Borne/*epidemiology
• Encephalitis, Tick-Borne/transmission
• Geography
• Human
• Ixodes
• Morbidity/trends
• Probability
• Siberia/epidemiology

Seasonal synchrony: the key to tick-borne encephalitis foci identified by satellite data.

Randolph SE,  Green RM,  Peacey MF,  Rogers DJ.

[Article in English]

Department of Zoology, University of Oxford, UK. sarah.randolph@zoology.ox.ac.uk

A previous analysis of tick infestation patterns on rodents in Slovakia suggested that the key to the focal distribution of western-type tick-borne encephalitis virus (TBEv) in Europe is the geographically variable degree of synchrony in the seasonal activity of larval and nymphal Ixodes ricinus ticks. This prediction is here tested by examining records, from 7 different countries, of the seasonal variation in the abundance of larvae and nymphs feeding on rodents or questing on the vegetation. Larvae consistently started feeding and questing earlier in the year at sites within TBEv foci than elsewhere, so that they appeared in the spring as soon as nymphs were active. Such larval nymphal synchrony is associated with a rapid fall in ground-level temperatures from August to October as revealed by the satellite-derived index of Land Surface Temperature (LST). Likewise, of 1992 pixels sampled on a grid across Europe, the 418 that fell within TBEv foci were characterized by a higher than average rate of autumnal cooling relative to the peak midsummer LST. It is proposed that such a seasonal temperature profile may cause unfed larvae to pass the winter in quiescence, from which they emerge synchronously with nymphs in the spring.

MeSH Terms:

• Animal
• Arachnid Vectors/*physiology
• Encephalitis, Tick-Borne/*epidemiology
• Human
• Ixodes/*physiology
• Rodentia
• *Satellite Communications
• *Seasons
• Support, Non-U.S. Gov't

Myopericarditis associated with central European tick-borne encephalitis.

Duppenthaler A,  Pfammatter JP,  Aebi C.

[Article in English]

Department of Paediatrics, University of Bern, Inselspital, Switzerland.

The case of an 11-year-old child with acute myopericarditis associated with central European tick-borne encephalitis is presented. Cardiac involvement was demonstrated by pericardial effusion, elevated serum concentration of troponin-I and cardiac arrhythmia. Co-infections with enteroviruses, Borrelia burgdorferi or the agent of human granulocytic ehrlichiosis were excluded. Recovery was uneventful. CONCLUSION: Central European tick-borne encephalitis can be complicated by cardiac involvement.

MeSH Terms:

• Arrhythmia/diagnosis
• Case Report
• Child
• Ehrlichiosis/complications
• Electrocardiography
• Encephalitis Viruses, Tick-Borne/*isolation & purification
• Encephalitis, Tick-Borne/*complications
• Female
• Human
• Pericarditis/diagnosis
• Pericarditis/*virology
• Troponin I/blood

Substances:

• 0 (Troponin I)

Trends in flavivirus infections in Japan.

Kurane I,  Takasaki T,  Yamada K.

[Article in English]

National Institute of Infectious Diseases, Tokyo, Japan.

Although Japanese encephalitis has declined as an important cause of illness and death in Japan, infection with other flaviviruses has become a public health concern. Recently, reports of imported dengue cases, as well as isolations of tick-borne encephalitis virus, have increased.

MeSH Terms:

• Dengue/*epidemiology
• Encephalitis, Tick-Borne/*epidemiology
• Human
• Japan/epidemiology

[Meningitis and encephalitis in 1998]

Zabicka J,  Zielinski A.

[Article in Polish]

Zaklad Epidemiologii, Panstwowego Zakladu Higieny, Warszawa.

In 1998--3,024 cases of meningitis and 581 cases of encephalitis were reported. It was 1,436 cases less then in 1997. A significant decrease of enteroviral meningitidis was observed and strains of ECHO30 was not dominant, it was Cox B5. Among bacterial factors the most common was N. meningitidis. 131 sporadic cases of meningitis caused by this bacteria were reported with serotype B dominating (96%). There were 103 cases of bacterial meningitis caused by S. pneumoniae and 101 cases caused by H. influenzae b among those with confirmed diagnosis. There were 208 cases of tick-borne encephalitis, diagnosed mainly in endemic areas of Bialystok and Suwalki voivodeships.

MeSH Terms:

• Adult
• Encephalitis/*epidemiology
• Encephalitis/microbiology
• Encephalitis/mortality
• Female
• Haemophilus Infections/microbiology
• Human
• Male
• Meningitis, Bacterial/*epidemiology
• Meningitis, Bacterial/microbiology
• Meningitis, Bacterial/mortality
• Neisseriaceae Infections/microbiology
• Poland/epidemiology
• Staphylococcal Infections/microbiology
• Tick-Borne Diseases/complications
• Tick-Borne Diseases/parasitology

[Serologic and clinical evidence for endemic occurrences of human granulocytic ehrlichiosis in North-Eastern Switzerland]

Weber R,  Pusterla N,  Loy M,  Leutenegger CM,  Schar G,  Baumann D,  Wolfensberger C,  Lutz H.

[Article in German]

Abteilung Infektionskrankheiten und Spitalhygiene, Departement Innere Medizin, Universitatsspital Zurich. infweb@usz.unizh.ch

BACKGROUND: Tick-borne human granulocytic ehrlichiosis (HGE) has not been diagnosed in Switzerland, although the HGE agent has been identified in ticks and animal reservoirs and human infections have been suspected on the basis of serological surveys. METHODS: We retrospectively tested sera of 48 persons with antibodies to B. burgdorferi and/or tick-borne encephalitis virus for the presence of antibodies to E. phagocytophila (a surrogate marker of the agent of HGE), and reviewed their charts with regard to clinical manifestations possibly associated with a tick-borne infection. We then prospectively examined EDTA blood of 80 patients who presented with fever 7 to 21 days after a tick bite for the presence of the HGE agent (using nested PCR and microscopic examination of blood smears) and anti-E. phagocytophila antibodies. We also collected clinical data. RESULTS: The retrospective study revealed 12 persons (25%) with anti-E. phagocytophila antibody titers > or = 1:80, suggesting coinfection with HGE and either Lyme Borrelia or tick-borne encephalitis virus. Among these, 7 patients presented with clinical manifestations compatible with HGE disease. The prospective investigation identified 8 patients (10%) with anti-E. phagocytophila antibody titers > or = 1:80, and 7 of these presented with signs and symptoms suggesting HGE. The HGE agent, however, was detected neither by PCR nor by microscopic examination. CONCLUSIONS: Serological and clinical data suggest the occurrence of an HGE-like agent as well as of coinfections with HGE and B. burgdorferi or tick-borne encephalitis virus in Switzerland. However, the HGE agent was not identified in persons living in Switzerland.

MeSH Terms:

• Adolescence
• Adult
• Aged
• Animal
• Antibodies, Bacterial/blood
• Antibodies, Viral/blood
• Borrelia burgdorferi/immunology
• Case Report
• Ehrlichia/immunology
• Ehrlichiosis/*epidemiology
• Ehrlichiosis/immunology
• Ehrlichiosis/transmission
• Encephalitis Viruses, Tick-Borne/immunology
• Female
• Human
• Male
• Middle Age
• Retrospective Studies
• Switzerland/epidemiology
• Ticks

Substances:

• 0 (Antibodies, Bacterial)
• 0 (Antibodies, Viral)

[Tick-borne meningoencephalitis in Thurgau Canton: a clinical and epidiomological analysis]

Schwanda M,  Oertli S,  Frauchiger B,  Krause M.

[Article in German]

Medizinische Klinik, Kantonsspital Munsterlingen.

BACKGROUND: Tick-borne meningo-encephalitis (TBE) is caused by a flavivirus species that is transmitted from rodents to humans by Ixodes ticks. The clinical picture of central nervous system involvement varies from febrile headache to lethal encephalitis. To date no specific treatment exists, although protective active immunisation is available. METHODS: We present the clinical and epidemiological data from 73 patients with TBE who acquired the infection in Canton Thurgau in the years 1996-1999. RESULTS: Canton Thurgau is a state in eastern Switzerland with a population of 230,000. Within the last five years the reported cases of TBE have increased more than threefold. The area where infectious tick bites were registered has expanded from the western to the eastern part and now encompasses the entire state. The risk of infection is clearly related to frequent activities in wooded areas, though outdoor activities not in forests also carry a considerable risk. In > 80% of the cases a postviral neurasthenic syndrome develops involving absence from work for two months on average. In the elderly and patients who present with encephalitic symptoms, a worse outcome with persistent neurological symptoms or even death has been observed. CONCLUSION: The increasing incidence of TBE, the expansion of infectious ticks to the east and high morbidity justify active immunisation against TBE on a broad scale in Canton Thurgau.

MeSH Terms:

• Adolescence
• Adult
• Aged
• Aged, 80 and over
• Animal
• Child
• Child, Preschool
• Encephalitis, Tick-Borne/diagnosis
• Encephalitis, Tick-Borne/*epidemiology
• Encephalitis, Tick-Borne/therapy
• Female
• Human
• Incidence
• Male
• Meningoencephalitis/diagnosis
• Meningoencephalitis/*epidemiology
• Meningoencephalitis/therapy
• Middle Age
• Support, Non-U.S. Gov't
• Switzerland/epidemiology
• Ticks

[Epidemiology and progress of early summer meningoencephalitis in Baden-Wurttemberg between 1994 and 1999. A prospective study of 731 patients]

Kaiser R.

[Article in German]

Neurologische Klinik und Poliklinik, Universitat Freiburg.

BACKGROUND AND OBJECTIVE: Tick-borne encephalitis (TBE) may develop into a serious disease leading to invalidism in a considerable proportion of patients. Detailed clinical and epidemiological data about the risks of TBE in Baden-Wurttemberg have been missing. A prospective study was started in 1994 to investigate the areas of risk in this part of Germany and to describe the clinical course and prognosis of TBE. PATIENTS AND METHODS: Doctors at all departments of Internal Medicine, Neurology and Paediatrics, at diagnostic laboratories and the departments of public health were asked to participate in this study. Data were recorded by means of a questionnaire. RESULTS: Between 1994 and 1999, 771 patients with TBE were recorded. Detailed clinical and epidemiological data were available for 731 patients. In 88% of the patients infection took place during leisure time activity, two thirds of infections occurring between June and August. The median incubation period was 8 days with a range of 4-28 days. 71% of the patients reported a prodromal stage with flu-like symptoms. TBE manifested as isolated meningitis in 47%, as meningoencephalitis in 42% and as meningoencephalomyelitis in 11%. With increasing age the number with a serious course of disease also increased. The most frequent symptoms were impairment of consciousness, ataxia and pareses of the limbs. In the children, the course of disease and prognosis was much better than in adults. Of 230 patients who were re-examined between 1 and 5 years after the acute illness 23% suffered from persisting moderate or severe symptoms. The death rate was about 1.4%. CONCLUSION: In Baden-Wurttemberg, tick bites are associated with a high risk of tick-borne encephalitis and severe neurological complications. Therefore, active immunization is recommended for all persons exposing themselves to ticks. Persisting complications after TBE are by far more common than serious complications after active immunization.

MeSH Terms:

• Adolescence
• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Child
• Child, Preschool
• Encephalitis, Tick-Borne/complications
• Encephalitis, Tick-Borne/*epidemiology
• Female
• Germany/epidemiology
• Human
• Infant
• Infant, Newborn
• Male
• Meningoencephalitis/complications
• Meningoencephalitis/*epidemiology
• Middle Age
• Prognosis
• Prospective Studies
• Risk Factors
• Seasons
• Sex Factors
• Support, Non-U.S. Gov't

Tick-borne encephalitis virus strains of Western Siberia.

Bakhvalova VN,  Rar VA,  Tkachev SE,  Matveev VA,  Matveev LE,  Karavanov AS,  Dobrotvorsky AK,  Morozova OV.

[Article in English]

Institute of Systematics and Ecology of Animals of Siberian Branch of Russian Academy of Sciences, Frunze Street 11, 630091 91, Novosibirsk, Russian Federation.

Tick-borne encephalitis virus (TBEV) strains were isolated from ticks in Western Siberia for 12 years. Molecular hybridization of the 46 viral RNA with the TBEV cDNA and oligonucleotide probes revealed differences between the Siberian and Far Eastern strains. A comparison of the viral E gene fragment nucleotide sequence showed 89-98% homology between Siberian TBEV strains, whereas their similarity with strains from other populations was less than 83%. However, the viral E and NS1 glycoprotein antigenic structures appeared to be conservative because of the degenerate genetic code. This was shown by enzyme-linked immunosorbent assay with the corresponding monoclonal antibodies (MAb). The single exception was the MAb 17C3 against nonstructural glycoprotein NS1, which could distinguish Siberian from Far Eastern strains. Moreover, the neurovirulence differed between strains from the two natural populations. Lower neuroinvasiveness of the Siberian strains in comparison with Far Eastern Sofyin strain might be caused by both E and NS1 glycoprotein mutations.

MeSH Terms:

• Animal
• Antibodies, Monoclonal
• Base Sequence
• Encephalitis Viruses, Tick-Borne/genetics
• Encephalitis Viruses, Tick-Borne/*isolation & purification
• Encephalitis Viruses, Tick-Borne/pathogenicity
• Enzyme-Linked Immunosorbent Assay
• Mice
• Molecular Sequence Data
• RNA, Viral/analysis
• Sequence Alignment
• Siberia
• Support, Non-U.S. Gov't
• Viral Envelope Proteins/*genetics
• Viral Envelope Proteins/immunology
• Viral Nonstructural Proteins/*genetics
• Viral Nonstructural Proteins/immunology
• Virulence

Substances:

• 0 (Antibodies, Monoclonal)
• 0 (NS1 protein, flavivirus)
• 0 (RNA, Viral)
• 0 (Viral Envelope Proteins)
• 0 (Viral Nonstructural Proteins)
• 145420-18-4 (glycoprotein E, flavivirus)

Structures and mechanisms in flavivirus fusion.

Heinz FX,  Allison SL.

[Article in English]

Institute of Virology, University of Vienna, Austria.

Publication Types:

• Journal Article
• Review
• Review, Tutorial

MeSH Terms:

• Animal
• Encephalitis Viruses, Tick-Borne/physiology
• Flavivirus/chemistry
• Flavivirus/metabolism
• Flavivirus/*physiology
• Flavivirus Infections/virology
• Human
• Membrane Fusion/*physiology
• Viral Fusion Proteins/*chemistry
• Viral Fusion Proteins/*metabolism

Substances:

• 0 (Viral Fusion Proteins)

Serological investigations of red foxes (Vulpes vulpes L.) for determination of the spread of tick-borne encephalitis in Northrhine-Westphalia.

Wurm R,  Dobler G,  Peters M,  Kiessig ST.

[Article in English]

Staatliches Veterinaruntersuchungsamt, Arnsberg, Germany. WURM@svua-arnsberg.nrw.de

Serum samples from 786 red foxes shot between January 1995 and August 1996 in the southern half of Northrhine-Westphalia, located in western Germany, were tested for the presence of antibodies against tick-borne encephalitis (TBE) virus using the Immunozym FSME IgG All Species-ELISA (Immuno, Heidelberg, Germany) as a screening test: 759 sera were negative, 23 (2.9%) were borderline, and four (0.5%) were positive. Nine of the 27 ELISA reactive sera were confirmed by the TBE Western-Blot (Immuno, Heidelberg, Germany). Furthermore these 27 sera were tested for neutralizing antibodies by means of a plaque reduction neutralization test (PRNT) against TBE and West Nile viruses. Only one single serum was found to have a neutralization titre (+1:800 PRNT80) against TBE virus. All other 26 sera were negative for neutralizing antibodies against TBE or West Nile virus. Since the titre of the single serum is low, it can be interpreted that if TBE virus is present, its prevalence is extremely low. Northrhine-Westphalia is not classified as a TBE-endemic area. Further calculated serological testing of game and virological investigation of collected ticks in the affected area seem to be meaningful and necessary.

MeSH Terms:

• Animal
• Antibodies, Viral/*blood
• Blotting, Western/veterinary
• Encephalitis Viruses, Tick-Borne/*immunology
• Encephalitis, Tick-Borne/epidemiology
• Encephalitis, Tick-Borne/prevention & control
• Encephalitis, Tick-Borne/*veterinary
• Enzyme-Linked Immunosorbent Assay/veterinary
• Foxes/*virology
• Germany/epidemiology
• Seroepidemiologic Studies

Substances:

• 0 (Antibodies, Viral)

Difference in pathogenesis between herpes simplex virus type 1 encephalitis and tick-borne encephalitis demonstrated by means of cerebrospinal fluid markers of glial and neuronal destruction.

Studahl M,  Rosengren L,  Gunther G,  Hagberg L.

[Article in English]

Department of Infectious Diseases, Gothenburg University, Sahlgrenska University Hospital/Ostra, Sweden. marie.studahl@infect.gu.se

We determined the extent of neuronal and glial cell destruction in 13 patients with herpes simplex type 1 (HSV-1) encephalitis, 15 patients with tick-borne encephalitis (TBE), and 20 noninfectious controls by analyzing the cerebrospinal fluid (CSF) concentrations of neurofilament protein (a marker of neurons, mainly axons), neuron-specific enolase (a marker of neurons, mainly somas), glial fibrillary acidic protein, and S-100 protein (markers of astrocytes). In addition, in patients with HSV-1 encephalitis CSF samples were collected serially before 7, 8-14, and 18-49 days and 3-10 months after the onset of neurological symptoms. In the acute stage of HSV-1 encephalitis we found markedly higher CSF levels of the cell damage markers than in patients with TBE. The concentration of cell damage markers in HSV-1 encephalitis decreased within 45 days after acute infection, except for neurofilament protein. The CSF concentrations of neurofilament protein increased during the second week, remained extremely high throughout the next month, and decrease thereafter. The changes in these markers of neuronal and glial destruction demonstrate the neuronal and astroglial cell damage during the first month after HSV-1 encephalitis. In contrast, most patients with TBE had signs only of slight astrogliosis, except for two patients with paresis.

MeSH Terms:

• Adult
• Aged
• Biological Markers/*analysis
• Encephalitis, Herpes Simplex/*physiopathology
• Encephalitis, Tick-Borne/*physiopathology
• Female
• Glial Fibrillary Acidic Protein/*cerebrospinal fluid
• Herpesvirus 1, Human/*pathogenicity
• Human
• Male
• Middle Age
• Nerve Tissue Protein S 100/*cerebrospinal fluid
• Neurofilament Proteins/*cerebrospinal fluid
• Neuroglia/cytology
• Neuroglia/pathology
• Neurons/cytology
• Neurons/pathology
• Phosphopyruvate Hydratase/*cerebrospinal fluid
• Support, Non-U.S. Gov't

Substances:

• 0 (Biological Markers)
• 0 (Glial Fibrillary Acidic Protein)
• 0 (Nerve Tissue Protein S 100)
• 0 (Neurofilament Proteins)
• EC 4.2.1.11 (Phosphopyruvate Hydratase)

[Determination of antibodies after immunization with the FSME-Immun vaccine]

Pazdiora P,  Januska J,  Kubatova A.

[Article in Czech]

Krajska hygienicka stanice, Plzen.

During 1997-1999 607 sera were obtained from subjects immunized with vaccine FSME-Immun. The presence of antibodies was assessed using EIA TBEV-Ig TEST-Line tests, Clinical Diagnostics, Immunozym FSME of Immuno Co. and the virus neutralizing test. Between the results of tests sufficient correlation was not found to allow valid evaluation of the presence of postvaccination antibodies by several methods. When using the Immunozyme FSME test it was found that on the day of administration of the 4th dose of vaccine 15 subjects of 94 had an antibody titre equal to or < 126 VIEU/ml, on the day of administration of the 5th dose this was the case in 5 of 13 immunized subjects. After administration of the 3rd, 4th and 5th dose adequate, i.e. at least three-year immunity, was acquired, depending on age, by 64.1-97.9% of the immunized subjects. As antibody titres higher than 600 VIEU/ml in different age groups were recorded only in 20.0-61.7% of the subjects, the authors do not consider it desirable in subjects immunized with the Austrian vaccine to prolong the time interval between vaccinations beyond three years.

MeSH Terms:

• Adolescence
• Adult
• Aged
• Antibodies, Viral/*analysis
• Child
• Child, Preschool
• Encephalitis Viruses, Tick-Borne/*immunology
• Encephalitis, Tick-Borne/immunology
• Encephalitis, Tick-Borne/*prevention & control
• Human
• Middle Age
• Viral Vaccines/*immunology

Substances:

• 0 (Antibodies, Viral)
• 0 (Viral Vaccines)

The results of tick-bone encephalitis (TBE)-vaccination.

Clement J,  Van Ranst M,  Leirs H.

[Article in English]

Publication Types:

• Letter

MeSH Terms:

• Antibodies, Viral/blood
• Encephalitis Viruses, Tick-Borne/*immunology
• Enzyme-Linked Immunosorbent Assay
• Human
• IgG/blood
• Neutralization Tests
• Vaccination
• Viral Vaccines/*immunology

Substances:

• 0 (Antibodies, Viral)
• 0 (IgG)
• 0 (Viral Vaccines)

Role of small mammals in the persistence of Louping-ill virus: field survey and tick co-feeding studies.

Gilbert L,  Jones LD,  Hudson PJ,  Gould EA,  Reid HW.

[Article in English]

Institute of Biological Sciences, Department of Biological and Molecular Sciences, Stirling University, Stirling, UK. lucy.gilbert@stir.ac.uk

Louping-ill (LI) is a tick-borne viral disease of red grouse, Lagopus lagopus scoticus Lath. (Tetraonidae: Galliformes), and sheep, Ovis aries L. (Bovidae: Artiodactyla), that causes economic loss to upland farms and sporting estates. Unvaccinated sheep, grouse and mountain hares, Lepus timidus L. (Leporidae: Lagomorpha), are known to transmit LI virus, whereas red deer, Cenrus elaphus L. (Cervidae: Artiodactyla), and rabbits, Oryctolagus cuniculus L. (Leporidae: Lagomorpha), do not. However, the role of small mammals is unknown. Here, we determine the role of small mammals, in particular field voles, Microtus agrestis L. (Muridae: Rodentia), in the persistence of LI virus on upland farms and sporting estates in Scotland, using field sampling and non-viraemic transmission trials. Small mammals were not abundant on the upland sites studied, few ticks were found per animal and none of the caught animals tested seropositive to LI virus. Laboratory trials provided no evidence that small mammals (field voles, bank voles, Clethrionomys glareolus L. (Muridae: Rodentia), and wood mice, Apodemus sylvaticus L. (Muridae: Rodentia), can transmit LI virus between cofeeding ticks and, in the field, LI virus was prevalent only in areas with known LI virus competent hosts (grouse, mountain hares or unvaccinated sheep) and absent elsewhere. In contrast to the case of tick-borne encephalitis (TBE) virus in Europe, it is concluded that small mammals seem to be relatively unimportant in LI virus persistence.

MeSH Terms:

• Animal
• Disease Vectors
• Encephalitis Viruses, Tick-Borne/*isolation & purification
• Encephalitis, Tick-Borne/epidemiology
• Encephalitis, Tick-Borne/*veterinary
• Mice
• Rabbits
• Scotland/epidemiology
• Seroepidemiologic Studies
• Sheep
• Sheep Diseases/epidemiology
• Support, Non-U.S. Gov't
• Tick Infestations/*veterinary

Attenuation of tick-borne encephalitis virus by structure-based site-specific mutagenesis of a putative flavivirus receptor binding site.

Mandl CW,  Allison SL,  Holzmann H,  Meixner T,  Heinz FX.

[Article in English]

Institute of Virology, University of Vienna, A-1095 Vienna, Austria. christian.mandl@univie.ac.at

The impact of a specific region of the envelope protein E of tick-borne encephalitis (TBE) virus on the biology of this virus was investigated by a site-directed mutagenesis approach. The four amino acid residues that were analyzed in detail (E308 to E311) are located on the upper-lateral surface of domain III according to the X-ray structure of the TBE virus protein E and are part of an area that is considered to be a potential receptor binding determinant of flaviviruses. Mutants containing single amino acid substitutions, as well as combinations of mutations, were constructed and analyzed for their virulence in mice, growth properties in cultured cells, and genetic stability. The most significant attenuation in mice was achieved by mutagenesis of threonine 310. Combining this mutation with deletion mutations in the 3'-noncoding region yielded mutants that were highly attenuated. The biological effects of mutation Thr 310 to Lys, however, could be reversed to a large degree by a mutation at a neighboring position (Lys 311 to Glu) that arose spontaneously during infection of a mouse. Mutagenesis of the other positions provided evidence for the functional importance of residue 308 (Asp) and its charge interaction with residue 311 (Lys), whereas residue 309 could be altered or even deleted without any notable consequences. Deletion of residue 309 was accompanied by a spontaneous second-site mutation (Phe to Tyr) at position 332, which in the three-dimensional structure of protein E is spatially close to residue 309. The information obtained in this study is relevant for the development of specific attenuated flavivirus strains that may serve as future live vaccines.

MeSH Terms:

• 3' Untranslated Regions
• Animal
• Binding Sites
• Cattle
• Chick Embryo
• Encephalitis Viruses, Tick-Borne/*pathogenicity
• Mice
• Mutagenesis, Site-Directed
• Receptors, Virus/*metabolism
• Structure-Activity Relationship
• Swine
• Viral Envelope Proteins/*chemistry
• Viral Envelope Proteins/physiology

Substances:

• 0 (3' Untranslated Regions)
• 0 (Receptors, Virus)
• 0 (Viral Envelope Proteins)

Ticks and tick-borne disease systems in space and from space.

Randolph SE.

[Article in English]

Analyses within geographical information systems (GISs) indicate that small- and large-scale ranges of hard tick species (Ixodidae) are determined more by climate and vegetation than by host-related factors. Spatial distributions of ticks may therefore be analysed by statistical methods that seek correlations between known tick presence/absence and ground- or remotely-sensed (RS) environmental factors. In this way, local habitats of Amblyomma variegatum in the Caribbean and Ixodes ricinus in Europe have been mapped using Landsat RS imagery, while regional and continental distributions of African and temperate tick species have been predicted using multi-temporal information from the National Oceanic and Atmospheric Administration-Advanced Very High Resolution Radiometer (NOAA-AVHRR) imagery. These studies illustrate ways of maximizing statistical accuracy, whose interpretation is then discussed in a biological framework. Methods such as discriminant analysis are biologically transparent and interpretable, while others, such as logistic regression and tree-based classifications, are less so. Furthermore, the most consistently significant variable for predicting tick distributions, the RS Normalized Difference Vegetation Index (NDVI), has a sound biological basis in that it is related to moisture availability to free-living ticks and correlated with tick mortality rates. The development of biological process-based models for predicting the spatial dynamics of ticks is a top priority, especially as the risk of tick-borne infections is commonly related not simply to the vector's density, but to its seasonal population dynamics. Nevertheless, using statistical pattern-matching, the combination of RS temperature indices and NDVI successfully predicts certain temporal features essential for the transmission of tick-borne encephalitis virus, which translate into a spatial pattern of disease foci on a continental scale.

Publication Types:

• Journal Article
• Review
• Review, Tutorial

MeSH Terms:

• Animal
• Arachnid Vectors
• Climate
• Forecasting/methods
• Geography
• Human
• *Information Systems
• *Satellite Communications
• Support, Non-U.S. Gov't
• Tick Infestations/*epidemiology
• Tick Infestations/parasitology
• Tick-Borne Diseases/*epidemiology
• Tick-Borne Diseases/parasitology
• Ticks/classification
• Ticks/*physiology

[An epizootiological and epidemiological surveillance in combined foci of ixodid tick-borne borreliosis and tick-borne encephalitis]

Nafeev AA,  Merkulov AV.

[Article in Russian]

MeSH Terms:

• Animal
• *Arachnid Vectors
• Borrelia Infections/*epidemiology
• Borrelia Infections/transmission
• Disease Outbreaks
• *Disease Reservoirs
• Encephalitis, Tick-Borne/*epidemiology
• Encephalitis, Tick-Borne/transmission
• Human
• Incidence
• *Ixodes
• Population Surveillance/*methods
• Risk Factors
• Russia/epidemiology
• Tick-Borne Diseases/*epidemiology
• Tick-Borne Diseases/transmission

[The situation of tick-borne encephalitis morbidity in the Maritime Territory]

Borisova ON,  Gorkovenko LE.

[Article in Russian]

MeSH Terms:

• Animal
• Arachnid Vectors
• Child
• Disease Reservoirs/statistics & numerical data
• Encephalitis, Tick-Borne/*epidemiology
• Encephalitis, Tick-Borne/transmission
• Human
• Incidence
• Morbidity/trends
• Mortality/trends
• Siberia/epidemiology
• Ticks

Heterogeneity in the host preference of Japanese encephalitis vectors in Chiang Mai, northern Thailand.

Mwandawiro C,  Boots M,  Tuno N,  Suwonkerd W,  Tsuda Y,  Takagi M.

[Article in English]

Department of Medical Entomology, Institute of Tropical Medicine, Nagasaki, Japan.

Experiments, using the capture-mark-release-recapture technique inside large nets, were carried out in Chiang Mai, northern Thailand, to examine heterogeneity in the host preference of Japanese encephalitis (JE) vectors. A significantly higher proportion of the vector species that were initially attracted to a cow fed when released into a net with a cow than when released into a net containing a pig. However, Culex vishnui individuals that had been attracted to a pig had a higher feeding rate in a net containing a pig rather than a cow. When mosquitoes were given a choice by being released into a net containing both animals, they exhibited a tendency to feed on the host to which they had originally been attracted. This feeding preference was, however, not shown by the offspring of pig-fed individuals. We have therefore shown evidence of physiological/behavioural conditioning in the host preference of JE vectors rather than genetic variability. Our results suggest that effective control of JE might be achieved by increasing the availability of cows (the dead-end hosts of JE virus) to deflect the vectors from pigs (the amplifying host). The behavioural imprinting which we have found would tend to re-inforce the initial tendency of the vectors to bite cows.

MeSH Terms:

• Animal
• Cattle/parasitology
• Culex/*physiology
• Encephalitis Virus, Japanese
• Encephalitis, Tick-Borne/epidemiology
• Encephalitis, Tick-Borne/*parasitology
• Feeding Behavior
• Female
• Host-Parasite Relations
• Human
• Insect Vectors/*physiology
• Swine/parasitology
• Thailand/epidemiology

[Experimental tick-borne encephalitis in golden hamsters treated with specific immunotherapy]

Leonova GN,  Isachkova LM,  Borisevich VG,  Fisenko AI.

[Article in Russian]

Efficiency of various protocols of specific immunoglobulin treatment was evaluated in golden hamsters inoculated with two Far Eastern tick-borne encephalitis (TBE) strains. After a low therapeutic dose (0.1 ml) of immunoglobulin, corresponding to total dose (60 ml) per course, all parameters (survival, immunogenicity, pathomorphology of the brain) deteriorated in animals infected with both strains. A higher dose (0.2 ml) corresponding to total dose of 120 ml notably improved all the studied parameters. The efficiency of specific immunoglobulin depends on the clinical and pathogenetic characteristics of TBE, determined by the properties of TBE strains. The results validate therapy and prevention of TBE by high-titer immunoglobulin in adequate total dose, monitored by blood analyses for TBE antigen and evaluations of the time course of IgM antibodies.

MeSH Terms:

• Animal
• Antibody Formation
• Encephalitis, Tick-Borne/immunology
• Encephalitis, Tick-Borne/*therapy
• Hamsters
• *Immunization, Passive
• Mesocricetus

[7 questions about early summer meningoencephalitis. When is there a risk for residual damage?]

Brandner M.

[Article in German]

Universitatsklinikum Essen, Institut fur Virologie.

Publication Types:

• Letter

MeSH Terms:

• Brain Damage, Chronic/*diagnosis
• Brain Damage, Chronic/mortality
• Cross-Sectional Studies
• Encephalitis, Tick-Borne/*diagnosis
• Encephalitis, Tick-Borne/mortality
• Germany/epidemiology
• Human
• Survival Rate

Gelatin-induced urticaria and anaphylaxis after tick-borne encephalitis vaccine.

Worm M,  Sterry W,  Zuberbier T.

[Article in English]

Publication Types:

• Letter

MeSH Terms:

• Adult
• Anaphylaxis/*etiology
• Case Report
• Encephalitis, Tick-Borne/*prevention & control
• Female
• Gelatin/*adverse effects
• Human
• Polymers/*adverse effects
• Preservatives, Pharmaceutical/*adverse effects
• Urticaria/*etiology
• Vaccination/adverse effects
• Viral Vaccines/*adverse effects

Substances:

• 0 (Hemaccel)
• 0 (Polymers)
• 0 (Preservatives, Pharmaceutical)
• 0 (Viral Vaccines)
• 9000-70-8 (Gelatin)

Swiss Army Survey in Switzerland to determine the prevalence of Francisella tularensis, members of the Ehrlichia phagocytophila genogroup, Borrelia burgdorferi sensu lato, and tick-borne encephalitis virus in ticks.

Wicki R,  Sauter P,  Mettler C,  Natsch A,  Enzler T,  Pusterla N,  Kuhnert P,  Egli G,  Bernasconi M,  Lienhard R,  Lutz H,  Leutenegger CM.

[Article in English]

Swiss Armed Forces Biological Service, Bern, Switzerland.

A total of 6071 Ixodes ricinus ticks were collected on Swiss Army training grounds in five regions of Switzerland. The aim of the survey was to assess the prevalence of ticks infected with the human pathogens Francisella tularensis, members of the Ehrlichia phagocytophila genogroup, Borrelia burgdorferi sensu lato, and the European tick-borne encephalitis virus. TaqMan PCR (PE Biosystems, USA) and TaqMan RT-PCR (PE Biosystems) analyses were performed on DNA and RNA extracted from pools of ten ticks grouped by gender. Here, for the first time, it is shown that ticks may harbor Francisella tularensis in Switzerland, at a rate of 0.12%. Furthermore, 26.54% of the ticks investigated harbored Borrelia burgdorferi sensu lato, 1.18% harbored members of the Ehrlichia phagocytophila genogroup, and 0.32% harbored the European tick-borne encephalitis virus. A new instrumentation was applied in this study to carry out and analyze more than 2300 PCR reactions in only 5 days. Furthermore, the results reveal that people working in outdoor areas, including army personnel on certain training grounds contaminated with ticks containing tick-borne pathogens, are at risk for different tick-borne diseases.

MeSH Terms:

• Animal
• Borrelia burgdorferi/*isolation & purification
• Ehrlichia/*isolation & purification
• Encephalitis Viruses, Tick-Borne/*isolation & purification
• Female
• Francisella tularensis/*isolation & purification
• Human
• Ixodes/growth & development
• Ixodes/*microbiology
• Ixodes/virology
• Male
• Military Personnel
• Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Risk Factors
• Support, Non-U.S. Gov't
• Switzerland/epidemiology
• Tick-Borne Diseases/epidemiology

Characterization of monoclonal antibodies against Hokkaido strain tick-borne encephalitis virus.

Komoro K,  Hayasaka D,  Mizutani T,  Kariwa H,  Takashima I.

[Article in English]

Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.

A tick-borne encephalitis (TBE) patient was found in Hokkaido in 1993, and TBE viruses were isolated from animals and ticks in our previous studies. To develop a diagnostic reagent to identify TBE viruses, monoclonal antibodies (Mabs) were produced against the TBE virus strain Hokkaido (Oshima 5-10). Seven Mabs were obtained which reacted with the envelope protein of the Oshima 5-10 strain. These Mabs were flavivirus genus-specific, TBE virus complex-specific or TBE virus type-specific. The Mabs are applicable for identification of TBE virus strains.

MeSH Terms:

• Animal
• Antibodies, Monoclonal/biosynthesis
• Antibodies, Monoclonal/*immunology
• Antibodies, Viral/biosynthesis
• Antibodies, Viral/*immunology
• Antigens, Viral/immunology
• Antigens, Viral/isolation & purification
• Cell Line
• Encephalitis Viruses, Tick-Borne/*immunology
• Fluorescent Antibody Technique, Indirect
• Hamsters
• Japan
• Mice
• Mice, Inbred BALB C
• Support, Non-U.S. Gov't
• Viral Envelope Proteins/immunology

Substances:

• 0 (Antibodies, Monoclonal)
• 0 (Antibodies, Viral)
• 0 (Antigens, Viral)
• 0 (Viral Envelope Proteins)
• 145420-18-4 (glycoprotein E, flavivirus)

Chimeric Langat/Dengue viruses protect mice from heterologous challenge with the highly virulent strains of tick-borne encephalitis virus.

Pletnev AG,  Karganova GG,  Dzhivanyan TI,  Lashkevich VA,  Bray M.

[Article in English]

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. apletnev@niaid.nih.gov

Langat virus (LGT), a tick-borne flavivirus, is naturally attenuated for humans but it is very virulent in SCID mice. In contrast, viable recombinant chimeras of LGT (preM and E genes) and dengue type 4 virus (all other sequences) recovered in mosquito cell culture were completely attenuated in SCID mice but still capable of providing protection against LGT. To develop the chimeras into vaccine candidates, we adapted them to replicate efficiently in simian Vero cells, a satisfactory substrate for human vaccines. The adapted chimeras remained completely attenuated for SCID mice and, significantly, provided protection in immunocompetent mice against tick-borne encephalitis virus, the most virulent of the tick-borne flaviviruses.

MeSH Terms:

• Adaptation, Physiological
• Animal
• Cercopithecus aethiops
• Dengue Virus/genetics
• Dengue Virus/*immunology
• Encephalitis Viruses, Tick-Borne/genetics
• Encephalitis Viruses, Tick-Borne/*immunology
• Encephalitis Viruses, Tick-Borne/pathogenicity
• Encephalitis, Tick-Borne/immunology
• Encephalitis, Tick-Borne/*prevention & control
• Female
• Genetic Vectors/genetics
• Genetic Vectors/immunology
• Human
• Mice
• Mice, Inbred BALB C
• Mice, SCID
• Support, U.S. Gov't, Non-P.H.S.
• Vaccines, Synthetic/genetics
• Vaccines, Synthetic/*immunology
• Vero Cells
• Viral Envelope Proteins/genetics
• Viral Envelope Proteins/*immunology
• Viral Vaccines/genetics
• Viral Vaccines/*immunology
• Virulence

Substances:

• 0 (Genetic Vectors)
• 0 (Vaccines, Synthetic)
• 0 (Viral Envelope Proteins)
• 0 (Viral Vaccines)
• 0 (prM-M protein)
• 145420-18-4 (glycoprotein E, flavivirus)

[The possible role of alpha 2-macroglobulin in regulating the immune components of the brain in tick-borne encephalitis]

Merzeniuk ZA,  Churliaev IA,  Nikiforova NV,  Kuksinskii VA,  Lykova OF,  Konysheva TV.

[Article in Russian]

Institute for Advanced Medical Training, Novokuznetsk, Russia.

In tick-borne encephalitis certain immunopathological reactions develop in the tissues of the central nervous system; alpha 2-macroglobulin may serve as the marker of the activity of these reactions. The dynamic study of liquor taken from 16 patients with the meningeal and focal forms of tick-borne encephalitis (TBE), 8 patients with severe craniocerebral traumas accompanied by meningitis and 10 patients with osteochondrosis was made. As revealed in this study, in TBE patients the level of alpha 2-macroglobulin increases 3.5-fold and remains stable during the acute period of the disease.

MeSH Terms:

• Acute Disease
• Biological Markers/cerebrospinal fluid
• Brain/*immunology
• Comparative Study
• Craniocerebral Trauma/cerebrospinal fluid
• Craniocerebral Trauma/complications
• Craniocerebral Trauma/immunology
• Encephalitis, Tick-Borne/cerebrospinal fluid
• Encephalitis, Tick-Borne/*immunology
• Human
• Meningitis/cerebrospinal fluid
• Meningitis/etiology
• Meningitis/immunology
• Meningoencephalitis/cerebrospinal fluid
• Meningoencephalitis/etiology
• Meningoencephalitis/immunology
• Osteochondritis/cerebrospinal fluid
• Osteochondritis/immunology
• Spondylitis/cerebrospinal fluid
• Spondylitis/immunology
• alpha-Macroglobulins/cerebrospinal fluid
• alpha-Macroglobulins/*immunology

Substances:

• 0 (Biological Markers)
• 0 (alpha-Macroglobulins)

Natural foci of some viral zoonoses in Croatia.

Turkovic B,  Brudnjak Z.

[Article in English]

Croatian National Institute of Public Health, Zagreb, Croatia.

Results of several-year investigations into the epidemiology and virology of viral zoonoses with natural foci occurring in Croatia, with special reference to tick-borne encephalitis (TBE) and hemorrhagic fever with renal syndrome (HFRS), are presented. The etiologic diagnosis of these diseases was made on the basis of virus isolation from patient blood and/or findings of specific antibodies in the serum. Several TBE and Bhanja virus strains were isolated from different species of ticks, and Calovo virus from mosquitoes, while the presence of Hantaan virus antigen was determined in the lungs of certain micromammalian species, the virus natural reservoirs, by direct immunofluorescence. For the largest HFRS outbreak in Croatia to date, which occurred in 1995 during the war, a detailed description is provided. The role of the geographic aspect is indicated, because an air corridor used by migratory birds which temporarily alight in some areas for a brief stop, whereby they may introduce viruses from other parts of the world, passes just above the territory of Croatia.

MeSH Terms:

• Animal
• Bunyamwera Group Viruses/isolation & purification
• Croatia
• Culicidae/virology
• *Disease Outbreaks
• *Disease Reservoirs
• Encephalitis Viruses, Tick-Borne/*isolation & purification
• Encephalitis, Tick-Borne/*epidemiology
• Hantaan Virus/*isolation & purification
• Hemorrhagic Fever with Renal Syndrome/*epidemiology
• Human
• Rodentia/*virology
• Ticks/virology

[Late sequelae of early summer meningoencephalitis]

Lammli B,  Muller A,  Ballmer PE.

[Article in German]

Medizinische Klinik, Kantonsspital Winterthur.

The incidence of tick-borne encephalitis varies widely in different geographic regions due to local difference in the rate of infected vectors (Ixodes ricinus) transmitting tick-borne encephalitis virus. In the Cantonal Hospital Winterthur a large number of cases are hospitalised due to endemic areas with infected ticks nearby. From 1976 until 1996 132 patients with tick-borne encephalitis were hospitalised (an average of 7 patients per year), compared with 535 cases (41 per year) in the whole of Switzerland during a similar period (1984-1992). While previously tick-borne encephalitis was considered to be a harmless illness with complete recovery, a postencephalitic syndrome after tick-borne encephalitis has recently been reported. Since the prevalence of sequelae differs in these publications, the aim of this study was to investigate sequelae in a Swiss population which had suffered from tick-borne encephalitis. We retrospectively analysed the patients with tick-borne encephalitis hospitalised in the years 1987-1996, to determine the clinical and functional outcome. A few weeks after discharge from hospital, 73% patients still had complaints, and one year later 56%. 32 patients were observed over 5 years and 31% still had some disability. After tick-borne encephalitis 10% of patients did not recover the same quality of life as before. The symptoms most frequently reported were fatigue, concentration deficits and impairment of memory. Objective neurological deficits were rare. Our results correspond well with experience in other countries and demonstrate the substantial morbidity of tick-borne encephalitis. We recommend therefore vaccination against tick-borne encephalitis, an effective measure with a low complication rate.

MeSH Terms:

• Adolescence
• Adult
• Aged
• Aged, 80 and over
• Animal
• Cognition Disorders/diagnosis
• Encephalitis, Tick-Borne/*diagnosis
• Encephalitis, Tick-Borne/prevention & control
• Encephalitis, Tick-Borne/transmission
• Female
• Follow-Up Studies
• Human
• Ixodes/virology
• Male
• Middle Age
• *Neurologic Examination
• *Quality of Life
• Retrospective Studies
• Switzerland

[Tick-borne encephalitis]

Shapira I,  Berger SA.

[Article in Hebrew]

MeSH Terms:

• *Encephalitis, Tick-Borne/epidemiology
• *Encephalitis, Tick-Borne/prevention & control
• Europe/epidemiology
• Human

[Epidemiologic-clinical aspects of tick borne borreliosis in the Szczecin Province]

Niscigorska J.

[Article in Polish]

Katedry i Kliniki Chorob Zakaznych, Pomorskiej Akademii Medycznej w Szczecinie.

The aim of the study was to assess if Szczecin voivodeship is an area of endemic borreliosis, assess the risk due to B. burgdorferi infection in habitants and evaluate clinical manifestations of borreliosis. The study was conducted in 1993-1995, material comprised 299 persons (211 men and 88 women) aged from 3 to 78 years, divided into two groups. Group I consisted of foresters working in four forestry districts, occupationally exposed to tick bite. Group II was completed of Szczecin voivodeship habitants, sporadically exposed to tick bite. Control group consisted of 30 healthy persons without exposure to tick bite. Research programme of study comprised epidemiologic data, clinical examination, evaluation of serum anti-B.b antibodies in all persons and assessment of some infectious parameters (red cells sedimentation--RCS, leukocytosis and C-Reactive Protein--CRP) during borreliosis. High prevalence of borreliosis was noted in both groups. Risk of borreliosis was similar in four forestry districts (Tab. 1). The hazard of infection was not restricted to forest areas only but was present in some parts of Szczecin and its suburbs (parks and gardens). Infection by B.b. was observed in both males and females in all age groups. Risk of B.b infection increased accordingly to duration of exposure but in some examined persons after single tick bite the disease developed (Tab. 2). Some of infected persons do not demonstrate clinical symptoms of borreliosis (Tab. 3). In most cases the disease was diagnosed in early stage of infection (Tab. 4). During infection different organs and systems were involved (Tab. 5). In clinical study skin was the most often affected organ followed by nervous system and joints (Tab. 5, 7). Clinical manifestations comprised erythema migrans chronicum, radiculitis, arthritis, meningitis, encephalitis and uveitis (Tab. 6). Serological study revealed the presence of serum anti-B.b antibodies in 47.6% of examined persons with occupational risk involving tick bite, and 32.7% persons of sporadic risk with negative serology of borreliosis in control group (Tab. 8). The parameters of acute inflammatory phase (RCS, CRP, leukocytosis) are of limited value in diagnosis of borreliosis.

MeSH Terms:

• Adolescence
• Adult
• Aged
• Animal
• Bites and Stings/*epidemiology
• Borrelia burgdorferi
• Case-Control Studies
• Child
• Child, Preschool
• Comorbidity
• Female
• Forestry/statistics & numerical data
• Human
• Incidence
• Infant
• Lyme Disease/diagnosis
• Lyme Disease/*epidemiology
• Male
• Middle Age
• Occupational Diseases/*epidemiology
• Poland/epidemiology
• Risk Factors
• *Ticks

Poliomyelitic-like illness in central European encephalitis.

Schellinger PD,  Schmutzhard E,  Fiebach JB,  Pfausler B,  Maier H,  Schwab S.

[Article in English]

Department of Neurology, University of Heidelberg, Germany. Peter_Schellinger@med.uni-heidelberg.de

Central European encephalitis (CEE) may be accompanied by myeloradiculitic symptoms in up to 5% of patients. The authors report six patients with a myelitic form of CEE mimicking acute poliomyelitis with bulbar and arm predominance and a poor prognosis. Three patients died. Of the survivors, only one can perform most activities of daily living, but still needs assisted ventilation at night. Autopsy in one patient showed severe cervicothoracic inflammation with changes almost exclusively in anterior horn cells and roots, as typically seen in poliomyelitis.

MeSH Terms:

• Adult
• Aged
• Brain/pathology
• Case Report
• Diagnosis, Differential
• Encephalitis, Tick-Borne/*diagnosis
• Encephalitis, Tick-Borne/pathology
• Fatal Outcome
• Female
• Human
• Male
• Motor Neuron Disease/diagnosis
• Motor Neuron Disease/pathology
• Myelitis/*diagnosis
• Myelitis/pathology
• Neurologic Examination
• Neurons/pathology
• Poliomyelitis/*diagnosis
• Poliomyelitis/pathology
• Prognosis
• Quadriplegia/diagnosis
• Quadriplegia/pathology
• Radiculopathy/*diagnosis
• Radiculopathy/pathology
• Respiratory Insufficiency/diagnosis
• Respiratory Insufficiency/pathology
• Spinal Cord/pathology

Powassan encephalitis: a case report with neuropathology and literature review.

Gholam BI,  Puksa S,  Provias JP.

Comment in: 

• CMAJ. 1999 Nov 30;161(11):1416-7

[Article in English]

Department of Medicine, McMaster University, Hamilton, Ont. gholam@globalserve.net

Publication Types:

• Journal Article
• Review
• Review of Reported Cases

MeSH Terms:

• Brain/*pathology
• Case Report
• Encephalitis, Tick-Borne/*diagnosis
• Encephalitis, Tick-Borne/pathology
• Human
• Male
• Middle Age

Powassan encephalitis.

Ralph ED.

Comment on: 

• CMAJ. 1999 Nov 30;161(11):1419-22

[Article in English]

Publication Types:

• Comment
• Editorial

MeSH Terms:

• Canada/epidemiology
• *Encephalitis, Tick-Borne/epidemiology
• *Encephalitis, Tick-Borne/therapy
• *Encephalitis, Tick-Borne/transmission
• Human

[The history of uncovering the feeding route of infection by the tick-borne encephalitis virus]

Shapoval AN.

[Article in Russian]

Publication Types:

• Historical Article
• Journal Article

MeSH Terms:

• Animal
• Arachnid Vectors/virology
• Encephalitis Viruses, Tick-Borne/*pathogenicity
• Encephalitis, Tick-Borne/*history
• Encephalitis, Tick-Borne/transmission
• *Food Microbiology
• History of Medicine, 20th Cent.
• Human
• Ixodes/virology
• Research/history
• Russia

[Prevention of early summer meningoencephalitis. When should you vaccinate?. Interview by Dr. Beate Schumacher.]

Fiedler M.

[Article in German]

Publication Types:

• Interview

MeSH Terms:

• Adolescence
• Adult
• Child
• Child, Preschool
• Cross-Sectional Studies
• Encephalitis Viruses/*immunology
• Encephalitis, Tick-Borne/epidemiology
• Encephalitis, Tick-Borne/*prevention & control
• Germany
• Human
• Infant
• Viral Vaccines/*administration & dosage

Substances:

• 0 (Viral Vaccines)

Germany halts tick-borne encephalitis vaccination.

Weber W.

[Article in English]

Publication Types:

• News

MeSH Terms:

• Child, Preschool
• Encephalitis, Tick-Borne/*prevention & control
• Fever/*etiology
• Germany
• Human
• Infant
• Infant, Newborn
• Risk Assessment
• Seizures, Febrile/*etiology
• Vaccination/*adverse effects
• Viral Vaccines/*adverse effects

Substances:

• 0 (Viral Vaccines)

Experimental infection of monkeys with Langat virus II. Turnover of circulating virus, 1967.

Nathanson N,  Harrington B.

Comment in: 

• Rev Med Virol. 2000 Jul-Aug;10(4):205-6

[Article in English]

Publication Types:

• Biography
• Classical Article
• Historical Article
• Journal Article

MeSH Terms:

• Animal
• Cebidae
• Encephalitis Viruses, Tick-Borne/*physiology
• Encephalitis, Tick-Borne/*history
• Encephalitis, Tick-Borne/virology
• History of Medicine, 20th Cent.
• Macaca fascicularis
• *Viral Load
• Viremia/virology
• Virus Replication

Personal Name As Subject:

• Nathanson N
• Harrington B

Is an isolated initial phase of a tick-borne encephalitis a common event?

Lotric-Furlan S,  Avsic-Zupanc T,  Strle F.

Comment on: 

• Clin Infect Dis. 1999 Apr;28(4):882-90

[Article in English]

Publication Types:

• Comment
• Letter

MeSH Terms:

• Adolescence
• Adult
• Antibodies, Viral/*blood
• Encephalitis Viruses, Tick-Borne/*immunology
• Encephalitis, Tick-Borne/*physiopathology
• Encephalitis, Tick-Borne/virology
• Fever
• Human
• Leukopenia
• Thrombocytopenia

Substances:

• 0 (Antibodies, Viral)

[A cultured concentrated inactivated vaccine against tick-borne encephalitis studied during the immunization of children and adolescents]

Pavlova LI,  Gorbunov MA,  Vorob'eva MS,  Karavanov AS,  Grachev VP,  Ladyshenskaia IP,  Rasshchepkina MN,  Mel'nikova LN,  Lebedeva TM,  Mel'nikov NA,  Gusmanova AG,  Deviatkov MI,  Rozanova EV,  Mukachev MA.

[Article in Russian]

Tarasevich State Research Institute for Standardization and Control of Medical Biological Preparations, Moscow, Russia.

The word deals with the results obtained in the study of the reactogenicity and immunological activity of concentrated and inactivated tissue-culture tick-borne encephalitis vaccine, manufactured by the Chumakov Institute of Poliomyelitis and Viral Encephalitides, in the immunization of children and adolescents. The vaccine proved to be moderately reactogenic and exhibited pronounced immunological activity. In 91.5% of the immunized children the fourfold increase of the antibody level was observed. On the basis of the data obtained in this study the tick-borne encephalitis vaccine was recommended for use in medical practice for the prophylaxis of tick-borne encephalitis among children and adolescents.

Publication Types:

• Clinical Trial
• Journal Article
• Randomized Controlled Trial

MeSH Terms:

• Adolescence
• Analysis of Variance
• Antibodies, Viral/blood
• Austria
• Child
• Comparative Study
• Encephalitis Viruses, Tick-Borne/*immunology
• Encephalitis, Tick-Borne/*prevention & control
• Human
• Immunization/*methods
• Immunization/statistics & numerical data
• Immunization, Secondary/methods
• Immunization, Secondary/statistics & numerical data
• Russia
• Time Factors
• Vaccines, Inactivated/adverse effects
• Vaccines, Inactivated/immunology
• Viral Vaccines/adverse effects
• Viral Vaccines/*immunology

Substances:

• 0 (Antibodies, Viral)
• 0 (Vaccines, Inactivated)
• 0 (Viral Vaccines)

[Clinical characteristics of tick-borne encephalitis complicated by Lyme borreliosis]

Amosov ML,  Lesniak OM,  Obraztsova RG,  Mel'nikov VG,  Bardina TG,  Andreeva EA.

[Article in Russian]

Clinical characteristics of mixed tick borne encephalitis (TBE) + Lyme borrelliosis (LB) infection and monoinfections are compared. Eighty-five patients with TBE + LB mixed infection serologically verified by EIA and 87 with isolated TBE, who fell ill in 1996, were examined. Among patients with mixed infection, cases with blurred TBE predominated; severe forms (meningeal and focal) were almost two times less incident than in TBE monoinfection. Typical clinical symptoms of LB were observed in 63.5% patients, while in the rest 36.5% LB manifested only by circulation of antibodies to B. burgdorferi. Comparative analysis of patients with mixed TBE + LB infection and TBE monoinfection confirmed a more benign course of TBE during the acute period in patients with mixed infection. Mixed infection should be ruled out or confirmed by thorough clinical examinations with obligatory detection of antibodies to agents of both diseases.

MeSH Terms:

• Adolescence
• Adult
• Aged
• Comparative Study
• Encephalitis, Tick-Borne/complications
• Encephalitis, Tick-Borne/*pathology
• Female
• Human
• Immunoenzyme Techniques
• Lyme Disease/complications
• Lyme Disease/*pathology
• Male
• Middle Age

A model for the hepatitis C virus envelope glycoprotein E2.

Yagnik AT,  Lahm A,  Meola A,  Roccasecca RM,  Ercole BB,  Nicosia A,  Tramontano A.

[Article in English]

Istituto di Ricerche di Biologia Molecolare P. Angeletti, Pomezia (Rome), Italy.

Several experimental studies on hepatitis C virus (HCV) have suggested the envelope glycoprotein E2 as a key antigen for an effective vaccine against the virus. Knowledge of its structure, therefore, would present a significant step forward in the fight against this disease. This paper reports the application of fold recognition methods in order to produce a model of the HCV E2 protein. Such investigation highlighted the envelope protein E of Tick Borne Encephalitis virus as a possible template for building a model of HCV E2. Mapping of experimental data onto the model allowed the prediction of a composite interaction site between E2 and its proposed cellular receptor CD81, as well as a heparin binding domain. In addition, experimental evidence is provided to show that CD81 recognition by E2 is isolate or strain specific and possibly mediated by the second hypervariable region (HVR2) of E2. Finally, the studies have also allowed a rough model for the quaternary structure of the envelope glycoproteins E1 and E2 complex to be proposed. Proteins 2000;40:355-366.

MeSH Terms:

• Amino Acid Sequence
• Antigens, CD/metabolism
• Antigens, Viral/*chemistry
• Binding Sites
• Comparative Study
• Computer Simulation
• Dimerization
• Glycoproteins/*chemistry
• Heparin/metabolism
• Hepatitis C-Like Viruses/*chemistry
• Models, Molecular
• Molecular Sequence Data
• Protein Structure, Secondary
• Receptors, Virus/metabolism
• Sequence Alignment
• Sequence Homology, Amino Acid
• Support, Non-U.S. Gov't
• Surface Properties
• Viral Envelope Proteins/*chemistry

Substances:

• 0 (Antigens, CD)
• 0 (Antigens, Viral)
• 0 (Glycoproteins)
• 0 (Receptors, Virus)
• 0 (TAPA-1 antigen)
• 0 (Viral Envelope Proteins)
• 145420-18-4 (glycoprotein E, flavivirus)
• 157184-61-7 (hepatitis C virus envelope 2 protein)
• 9005-49-6 (Heparin)

WHO Expert Committee on Biological Standardization.

[No authors listed].

[Article in English]

This report presents the recommendations of a WHO Expert Committee commissioned to coordinate activities leading to the adoption of international requirements for the production and control of vaccines and other biologicals and the establishment of international biological reference materials. The report starts with a discussion of general issues brought to the Committee's attention and provides information on the status and development of reference materials for various antibodies, antibiotics, antigens, blood products and related substances, cytokines and growth factors and other substances for which the Committee has discerned a need for international reference materials. The second part of the report, of particular relevance of manufacturers and national control authorities, contains guidelines for the production and control of synthetic peptide vaccines, requirements for tick-borne encephalitis vaccine (inactivated), guidelines for thromboplastins and plasma used to control oral anticoagulant therapy, an amendment to the requirements for hepatitis B vaccine made by recombinant DNA techniques and a report on the standardization and calibration of cytokine immunoassays.

Publication Types:

• Guideline
• Technical Report

MeSH Terms:

• Biological Products/*standards
• *Consumer Product Safety
• Cytokines/analysis
• Cytokines/standards
• Hemostatics/standards
• Human
• Immunoassay/standards
• *International Cooperation
• Quality Control
• Reference Standards
• Thromboplastin/standards
• Vaccines/standards
• Vaccines, DNA
• *World Health Organization

Substances:

• 0 (Biological Products)
• 0 (Cytokines)
• 0 (Hemostatics)
• 0 (Vaccines)
• 0 (Vaccines, DNA)
• 9035-58-9 (Thromboplastin)

[The characteristics of detecting the tick-borne encephalitis virus antigen in the ELISA and indirect hemagglutination reaction by means of scanning electron microscopy]

Stronin OV,  Miller AA,  Podoplekina LE.

[Article in Russian]

Research Institute of Vaccines and Sera, Research and Production Group Virion, Tomsk, Russia.

The surface of polystyrene plates was studied at different stages of the enzyme immunoassay (EIA) and the passive hemagglutination (PHA) test by the method of scanning electron microscopy in the detection of tick-borne encephalitis (TBE) virus antigen. The study revealed that in the process of EIA larger antigens were washed away from the plate surface. The objects detected on the polystyrene surface were identified as conglomerations of the virions of TBE virus, but whole virions were shown to play no decisive role in EIA. The conclusion was made that, due to some specific features of this method, EIA was more sensitive in reaction with small antigens (individual glycoproteids, their small complexes). And, respectively, the PHA test was more sensitive in reaction with large antigenic complexes (whole virions, their conglomerations, immune complexes).

MeSH Terms:

• Antigens, Viral/*blood
• Antigens, Viral/ultrastructure
• Comparative Study
• Encephalitis Viruses, Tick-Borne/*immunology
• Enzyme-Linked Immunosorbent Assay/instrumentation
• Enzyme-Linked Immunosorbent Assay/*methods
• Hemagglutination Tests/instrumentation
• Hemagglutination Tests/*methods
• Human
• Microscopy, Electron, Scanning/*methods
• Particle Size
• Sensitivity and Specificity
• Surface Properties
• Virion/immunology

Substances:

• 0 (Antigens, Viral)

Human recombinant laminin-binding protein: isolation, purification, and crystallization.

Sorokin AV,  Mikhailov AM,  Kachko AV,  Protopopova EV,  Konovalova SN,  Andrianova ME,  Netesov SV,  Kornev AN,  Loktev VB.

[Article in English]

Institute of Molecular Biology, State Research Center for Virology and Biotechnology "Vector", Koltsovo, Novosibirsk Region, Russia.

The mRNA of the precursor of laminin-binding protein (LBP) was isolated from a human embryo kidney cell line and cloned. The determined sequence of the LBP gene showed complete identity with the LBP genes isolated from human lung and large intestine cells. The human LBP was expressed by E. coli cells, and it was purified using Ni-NTA-Sepharose chromatography. The mobility of the homogeneous recombinant human laminin-binding protein on SDS-PAGE was 43 kD. A mixture of eight murine monoclonal antibodies, the MPLR Pool against LBP, reacted with the recombinant LBP in Western blot. The interaction of the antiidiotypical antibodies 10H10 and E6B provided evidence that the epitope binding to protein E of the tick-borne encephalitis (TBE) virus is also preserved on the human recombinant LBP. Enzyme immunoassay confirmed the ability of the recombinant LBP to interact with protein E of TBE virus. The biological activity of the recombinant LBP allowed us to perform X-ray analysis of the spatial arrangement of the LBP molecule using the recombinant protein. For this purpose, crystals of the human LBP were obtained by the standing drop version of the pore diffusion technique. The crystals appropriate for X-ray structural analysis were 0.3 x 0.1 x 0.05 mm in size. The X-ray diffraction field of the crystal extended to 2.5 A.

MeSH Terms:

• Base Sequence
• Cloning, Molecular
• Crystallization
• Crystallography, X-Ray
• DNA Primers
• Electrophoresis, Polyacrylamide Gel
• Escherichia coli/genetics
• Human
• Kidney/chemistry
• Protein Binding
• Receptors, Laminin/chemistry
• Receptors, Laminin/genetics
• Receptors, Laminin/*isolation & purification
• Receptors, Laminin/metabolism
• Recombinant Proteins/chemistry
• Recombinant Proteins/genetics
• Recombinant Proteins/isolation & purification
• Recombinant Proteins/metabolism
• Support, Non-U.S. Gov't
• Support, U.S. Gov't, Non-P.H.S.
• Viral Envelope Proteins/metabolism

Substances:

• 0 (DNA Primers)
• 0 (Receptors, Laminin)
• 0 (Recombinant Proteins)
• 0 (Viral Envelope Proteins)
• 145420-18-4 (glycoprotein E, flavivirus)

[Early-summer meningo-encephalitis (ESME) and ESME-vaccination: status 2000]

Kunze U,  Bernhard G,  Bohm G,  Groman E.

[Article in German]

Institut fur Sozialmedizin, Universitat Wien. Sozialmedizin@univie.ac.at

Tick-borne encephalitis (TBE) is a public health problem very well under control in Austria because of a vaccination programme using a safe, efficient and well tolerated vaccine and a carefully designed social marketing concept. The Austrian vaccine underwent another technological updating and is now marketed under a new brand name (TicoVac) on the basis of an EU registration. A second product is also available (Encepur), but some limitations of use have to be taken into account. To improve the epidemiological situation even further (only 41 hospital cases in 1999) special attention has to be given to the age group 50 years and older as this is the segment of the population where the majority of cases is observed. TBE is a growing international health problem as awareness increases and cases are identified in many European countries, even in regions where TBE so far was not diagnosed. An "International Scientific Working-group on Tick-borne encephalitis (ISW-TBE)" was established to coordinate research and public health activities.

Publication Types:

• Journal Article
• Review
• Review, Tutorial

MeSH Terms:

• Adult
• Aged
• Austria/epidemiology
• Child
• Encephalitis, Tick-Borne/*epidemiology
• Encephalitis, Tick-Borne/mortality
• Encephalitis, Tick-Borne/*prevention & control
• Europe/epidemiology
• Human
• Meningoencephalitis/*epidemiology
• Meningoencephalitis/mortality
• Meningoencephalitis/*prevention & control
• Middle Age
• Practice Guidelines
• *Seasons
• Travel
• Vaccines, Inactivated/administration & dosage
• Viral Vaccines/*administration & dosage

Substances:

• 0 (Vaccines, Inactivated)
• 0 (Viral Vaccines)

Tick-borne encephalitis.

Dumpis U,  Crook D,  Oksi J.

Comment in: 

• Clin Infect Dis. 2000 Jun;30(6):987-8

[Article in English]

Nuffield Department of Medicine, University of Oxford, United Kingdom.

Tick-borne encephalitis (TBE) is a zoonotic arbovirus infection endemic to Russia and Eastern and Central Europe. Despite being a common and serious life-threatening disease for which a mass vaccination program was implemented in Austria, there is only limited reference to this disease in the English-language literature. TBE is transmitted to humans usually by the bite of a tick (either Ixodes persulcatus or Ixodes ricinus); occasionally, cases occur following consumption of infected unpasteurized milk. Transmission is seasonal and occurs in spring and summer, particularly in rural areas favored by the vector. TBE is a serious cause of acute central nervous system disease, which may result in death or long-term neurological sequelae. Effective vaccines are available in a few countries. The risk for travelers of acquiring TBE is increasing with the recent rise in tourism to areas of endemicity during spring and summer.

Publication Types:

• Journal Article
• Review
• Review, Tutorial

MeSH Terms:

• Animal
• Arachnid Vectors/virology
• Encephalitis Viruses, Tick-Borne
• *Encephalitis, Tick-Borne/diagnosis
• *Encephalitis, Tick-Borne/epidemiology
• *Encephalitis, Tick-Borne/therapy
• *Encephalitis, Tick-Borne/transmission
• Human
• Ixodes/virology
• Support, Non-U.S. Gov't

[A comparison of the immune response induced by DNA or by an inactivated vaccine against tick-borne encephalitis]

Morozova OV,  Popova RV,  Maksimova TG,  Mitrofanova EE,  Bakhvalova VN.

[Article in Russian]

Institute of Bioorganic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia.

BALB/c mice were immunized with recombinant plasmid DNA pSVK3-ENS1 and pcDNAI-NS3 containing, respectively, genes E-NS1 and NS3 of tick-borne encephalitis (TBE) virus. Antibodies to TBE virus proteins were detected in the blood sera of the immunized animals by the method of the enzyme immunoassay. Though the titers of virus-specific antibodies in the sera of mice immunized with protein vaccines exceeded those registered after immunization with DNA vaccines, essential protective immunity was observed after the use of both vaccines.

MeSH Terms:

• Animal
• Antibodies, Viral/blood
• Comparative Study
• Drug Evaluation, Preclinical
• Encephalitis Viruses, Tick-Borne/genetics
• Encephalitis Viruses, Tick-Borne/*immunology
• Encephalitis Viruses, Tick-Borne/pathogenicity
• Encephalitis, Tick-Borne/immunology
• Encephalitis, Tick-Borne/*prevention & control
• Female
• Glycoproteins/immunology
• Immunization/methods
• Lethal Dose 50
• Mice
• Mice, Inbred BALB C
• Vaccines, DNA/*immunology
• Vaccines, Inactivated/immunology
• Viral Nonstructural Proteins/immunology
• Viral Structural Proteins/immunology
• Viral Vaccines/*immunology

Substances:

• 0 (Antibodies, Viral)
• 0 (Glycoproteins)
• 0 (Vaccines, DNA)
• 0 (Vaccines, Inactivated)
• 0 (Viral Nonstructural Proteins)
• 0 (Viral Structural Proteins)
• 0 (Viral Vaccines)

Vaccines for preventing tick-borne encephalitis.

Demicheli V,  Graves P,  Pratt M,  Jefferson T.

[Article in English]

Dept of Preventive Medicine & Biometrics, University of Colorado Health Sciences Center, Box C 245, 4200 E Ninth Ave, Denver, CO 80262, USA. Patricia.Graves@uchsc.edu

BACKGROUND: Tick-borne encephalitis is a disease of the central nervous system caused by a virus. Other than the vaccine, there is no treatment for the disease. OBJECTIVES: The objective of this review was to assess the effects of vaccines to prevent tick-borne encephalitis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Vaccine Fields Trials Register, the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles. We also handsearched the journal Vaccine. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing tick-borne encephalitis vaccines against placebo, control vaccines or comparisons of different doses or schedules of tick-borne encephalitis vaccines. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied inclusion criteria. A panel of six assessors examined trial quality. MAIN RESULTS: Five trials were included. They could not be combined for meta-analysis because of differences in comparisons and outcomes. Four types of tick-borne encephalitis vaccines were used. All the vaccines gave seroconversion rates of over 87%. There were frequent reports of systemic and local adverse effects. REVIEWER'S CONCLUSIONS: Tick-borne encephalitis vaccines appear to be highly immunogenic, but the relationship between seroconversion and clinical protection has not been established. Although adverse effects were commonly reported, none were severe or life threatening.

Publication Types:

• Journal Article
• Review
• Review, Academic

MeSH Terms:

• Child
• Encephalitis, Tick-Borne/immunology
• Encephalitis, Tick-Borne/*prevention & control
• Human
• Infant
• Vaccines/*therapeutic use

Substances:

• 0 (Vaccines)

Laboratory findings in tick-borne encephalitis--correlation with clinical outcome.

Kaiser R,  Holzmann H.

Comment in: 

• Infection. 2000 Mar-Apr;28(2):65-67

[Article in English]

Dept. of Neurology, University of Freiburg, Germany. kaiser@nz.ukl.uni-freiburg.de

Infection with the tick-borne encephalitis virus (TBEV) can result in various neurological complications. At present, there are little data available on laboratory findings that might help predict the clinical course and prognosis of tick-borne encephalitis (TBE). In the present study 100 patients with TBE were examined in respect to various laboratory parameters potentially characteristic for the disease and indicative for the prognosis in TBE. Pleocytosis, impairment of the blood-CSF barrier and intrathecal synthesis of immunoglobulins (IgM > IgG, IgA) were common findings in most patients. On admission to the hospital, 84% of the patients presented with an intrathecal synthesis of TBEV-specific IgM and/or IgG antibodies in the CSF. At follow-up, intrathecal synthesis of TBEV-specific antibodies was demonstrated in all patients studied within 15 days after the first examination, but changes of CSF parameters did not correlate with the clinical course of disease. In contrast to those with moderate course of disease, patients with severe courses of TBE displayed higher cell counts in the CSF and lower concentrations of neutralizing antibodies in serum, and more frequently revealed an intrathecal synthesis of total IgG. TBE-specific oligoclonal IgG antibodies in the CSF were demonstrated only in three patients with prior, incomplete, vaccination against TBE. The severe course of disease in individual patients with TBE may result from a slow or low production of neutralizing antibodies. In these patients, the more intense damage of the CNS tissue is reflected by higher cell counts in the CSF. At onset of disease the presence of a low concentration of neutralizing antibodies in serum and a high cell count in the CSF might indicate an unfavorable course of TBE.

MeSH Terms:

• Adolescence
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Viral/*blood
• Antibodies, Viral/*cerebrospinal fluid
• Diagnosis, Differential
• Encephalitis Viruses, Tick-Borne/*immunology
• Encephalitis, Tick-Borne/blood
• Encephalitis, Tick-Borne/cerebrospinal fluid
• Encephalitis, Tick-Borne/*pathology
• Enzyme-Linked Immunosorbent Assay
• Female
• Human
• Immunization/standards
• Immunization, Passive
• Male
• Meningitis, Viral/*virology
• Middle Age
• Prognosis
• Severity of Illness Index
• Support, Non-U.S. Gov't

Substances:

• 0 (Antibodies, Viral)

Comparison of the epidemiological and clinical features of tick-borne encephalitis in children and adults.

Logar M,  Arnez M,  Kolbl J,  Avsic-Zupanc T,  Strle F.

Comment in: 

• Infection. 2000 Mar-Apr;28(2):65-7

[Article in English]

Dept. of Infectious Diseases, University Medical Centre, Ljubljana, Slovenia. Mateja.Logar@mf.uni-lj.si

The aim of this prospective study was to compare epidemiological data and clinical features in children and adults with tick-borne encephalitis (TBE). Patients with aseptic meningitis diagnosed at the University Medical Centre, Department of Infectious Diseases, Ljubljana, Slovenia, from June to August 1997, in whom the diagnosis of TBE was ascertained by the presence of serum IgM antibodies against TBE virus, who were serologically negative for Borrelia burgdorferi sensu lato and had a negative PCR CSF result on enteroviral infection, were included in the study. Out of 213 patients with aseptic meningitis, 80 (37.56%) fulfilled inclusion criteria. There were 20 children and 60 adults. In both groups males predominated. Virtually all patients had headache and fever, and more than 50% suffered from vomiting. The majority of patients in both groups recalled a tick bite, had a biphasic course of the illness, and was found to have obviously expressed meningeal signs. In both groups the median CSF leukocyte count was somewhat lower than 100 x 10(6)/l with a predominance of lymphocytes. Children were more often given antibiotics during the initial phase of TBE than adults (p = 0.0095). Several other statistically significant distinctions (p < 0.05) were found including the frequency of fatigue, malaise, vertigo, photophobia, myalgias, arthralgias, as well as elevated CSF albumin and protein concentration, elevated albumin quotient and IgG quotient; all these findings were more often present in adults. In addition a longer duration of fever, more frequent need for anti-edematous treatment and longer hospitalization were found in adults. Direct comparison of clinical and epidemiological characteristics of TBE in children and adults revealed differences in several clinical and laboratory features and corroborates the previous conclusion that TBE in childhood is a milder illness than TBE in adults.

MeSH Terms:

• Adolescence
• Adult
• Aged
• Antibodies, Viral/*blood
• Child
• Child, Preschool
• Comparative Study
• Diagnosis, Differential
• Encephalitis Viruses, Tick-Borne/*immunology
• Encephalitis, Tick-Borne/blood
• Encephalitis, Tick-Borne/cerebrospinal fluid
• Encephalitis, Tick-Borne/*diagnosis
• Encephalitis, Tick-Borne/*epidemiology
• Enzyme-Linked Immunosorbent Assay
• Female
• Human
• Male
• Meningitis, Aseptic/*virology
• Middle Age
• Prospective Studies
• Slovenia/epidemiology

Substances:

• 0 (Antibodies, Viral)

Tick-borne viral encephalitis--the threat of summer.

Ruef C.

Comment on: 

• Infection. 2000 Mar-Apr;28(2):74-7
• Infection. 2000 Mar-Apr;28(2):78-84

[Article in English]

Publication Types:

• Comment
• Editorial
• Review
• Review, Tutorial

MeSH Terms:

• *Disease Outbreaks
• *Encephalitis Viruses, Tick-Borne
• Encephalitis, Tick-Borne/*epidemiology
• Encephalitis, Tick-Borne/prevention & control
• Encephalitis, Tick-Borne/transmission
• Europe/epidemiology
• Human
• Seasons

[An analysis of geographical differences in the appearance of tick-borne encephalitis]

Bolotin EI.

[Article in Russian]

Reasons of differences in clinical forms of tick-borne encephalitis within certain regions and throughout all area are analysed. It is supposed that the epidemic potential of natural focus depends upon temperature conditions during the winter period.

MeSH Terms:

• Animal
• Arachnid Vectors/virology
• Disease Reservoirs
• Encephalitis Viruses, Tick-Borne/pathogenicity
• Encephalitis, Tick-Borne/*epidemiology
• Encephalitis, Tick-Borne/transmission
• Encephalitis, Tick-Borne/virology
• Human
• Morbidity/trends
• Russia/epidemiology
• Seasons
• Temperature
• Ticks/virology

Clinical distinction between human granulocytic ehrlichiosis and the initial phase of tick-borne encephalitis.

Lotric-Furlan S,  Petrovec M,  Avsic-Zupanc T,  Strle F.

[Article in English]

Department of Infectious Diseases, University Medical Centre, Ljubljana, Slovenia.

OBJECTIVES: The aim of our study was to establish clinical and laboratory differences between patients with acute human granulocytic ehrlichiosis (HGE) and patients with the initial phase of tick-borne encephalitis (TBE). METHODS: Clinical features and laboratory results of four patients with acute HGE (established by the presence of the specific DNA sequences of the HGE agent in whole blood by polymerase chain reaction and/or by seroconversion to the HGE agent by indirect immunofluorescence assay) and 12 patients with the initial phase of TBE (demonstrated by the presence of serum IgM antibodies to TBE virus) were compared. All these patients were uncovered at the Department of Infectious Diseases, University Medical Centre, Ljubljana, Slovenia, during 1995-1996, in a prospective study on the aetiology of febrile illnesses occurring within 6 weeks after a tick bite. RESULTS: Findings were similar for the majority of the examined parameters including severity of illness, level and duration of fever, presence of headache, leukopenia, thrombocytopenia, and liver - function test abnormalities. Statistically significant differences were found only for arthralgia (P=0.026) and elevated concentration of C-reactive protein (P=0.003); both variables were found more often in patients with acute HGE. CONCLUSIONS: In a patient residing in the central part of Slovenia, who reports a tick bite followed by a febrile illness with leukopenia and/or thrombocytopenia, the presence of arthralgias and/or an elevated C-reactive protein value directs toward the diagnosis of acute HGE and against the initial phase of TBE.

MeSH Terms:

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Bacterial/blood
• Diagnosis, Differential
• Ehrlichia/genetics
• Ehrlichia/immunology
• Ehrlichia/isolation & purification
• Ehrlichiosis/*diagnosis
• Ehrlichiosis/microbiology
• Ehrlichiosis/physiopathology
• Encephalitis Viruses, Tick-Borne/immunology
• Encephalitis Viruses, Tick-Borne/isolation & purification
• Encephalitis, Tick-Borne/*diagnosis
• Encephalitis, Tick-Borne/physiopathology
• Encephalitis, Tick-Borne/virology
• Female
• Human
• Male
• Middle Age
• Support, Non-U.S. Gov't

Substances:

• 0 (Antibodies, Bacterial)

Effects of multiple sclerosis and other inflammatory CNS disorders on tick-borne encephalitis serology.

Woessner R,  Grauer MT,  Haass A,  Gaertner B,  Holzer G,  Mueller-Reiland D,  Mueller-Lantzsch N,  Treib J.

[Article in English]

Department of Neurology, University Hospital of the Saarland, Homburg/Saar, Germany.

The goal of the present study was to investigate whether a direct association exists between false-positive recognition of IgG antibodies and inflammatory changes in the central nervous system (CNS) and whether inflammatory diseases of the CNS affect the specificity of the enzyme-linked immunosorbent assay (ELISA) of tick-borne encephalitis (TBE) virus. A group of patients (1,815), treated in the Department of Neurology, University Hospital of the Saarland, Homburg/Saar, Germany, were tested forTBE IgG antibodies by ELISA. Several subgroups of patients with and without inflammatory changes in the CSF as well as patients with and without confirmed multiple sclerosis (MS) were investigated. Overall, 4.5% of all the 1,815 patients and 4.8% of the patients with inflammatory changes in the CSF but without MS had TBE IgG antibodies. In the subgroup with inflammatory changes in the CSF and MS, 4.4% of the patients were TBE IgG-positive. In the subgroup without inflammatory changes in the CSF, 3.8% of the patients without MS were TBE IgG-positive and 4.9% of the patients with MS were TBE IgG-positive. The rate of TBE IgG positivity was not significantly different in the subgroups with and without inflammatory changes in the CSF (P = 0.45). The comparison of the subgroups with and without MS showed no significant difference in the TBE IgG titer (P = 0.83) as well. This indicates that the specificity of the ELISA was affected neither by inflammatory changes in the CSF nor by MS.

MeSH Terms:

• Antibodies, Viral/blood
• Central Nervous System Diseases/*immunology
• Encephalitis, Tick-Borne/blood
• Encephalitis, Tick-Borne/epidemiology
• Encephalitis, Tick-Borne/*immunology
• Germany/epidemiology
• Human
• Multiple Sclerosis/*immunology

Substances:

• 0 (Antibodies, Viral)

Molecular detection of pathogen DNA in ticks (Acari: Ixodidae): a review.

Sparagano OA,  Allsopp MT,  Mank RA,  Rijpkema SG,  Figueroa JV,  Jongejan F.

[Article in English]

Division of Parasitology and Tropical Veterinary Medicine, Faculty of Veterinary Medicine, Utrecht University, The Netherlands. O.A.E.Sparagano@hw.ac.uk

Ticks play an important role in human and veterinary medicine, in particular due to their ability to transmit a wide spectrum of pathogenic micro-organisms of protozoal, rickettsial, bacterial and viral origin. Pathogens in ticks can be identified by conventional methods such as indirect immunofluorescence, isolation in cell culture or by using histological staining techniques. However, the advent of the polymerase chain reaction (PCR) has resulted in tremendous improvements in the specific and sensitive detection of pathogen DNA in ticks. In this paper, literature on DNA extraction methods, PCR protocols, primers and probes, which are in use for the successful detection and identification of pathogens in ticks, are critically reviewed. Some recommendations are also given towards the end of this review.

Publication Types:

• Journal Article
• Review
• Review, Tutorial

MeSH Terms:

• Anaplasma/genetics
• Anaplasma/isolation & purification
• Animal
• Arachnid Vectors/*microbiology
• Arachnid Vectors/parasitology
• Arachnid Vectors/virology
• Babesia/genetics
• Babesia/isolation & purification
• Borrelia/genetics
• Borrelia/isolation & purification
• Cowdria/genetics
• Cowdria/isolation & purification
• DNA Primers/chemistry
• DNA, Bacterial/chemistry
• DNA, Bacterial/*isolation & purification
• DNA, Protozoan/chemistry
• DNA, Protozoan/*isolation & purification
• DNA, Viral/chemistry
• DNA, Viral/*isolation & purification
• Ehrlichia/genetics
• Ehrlichia/isolation & purification
• Encephalitis Viruses, Tick-Borne/genetics
• Encephalitis Viruses, Tick-Borne/isolation & purification
• Nairobi Sheep Disease Viruses/genetics
• Nairobi Sheep Disease Viruses/isolation & purification
• Polymerase Chain Reaction/methods
• Polymerase Chain Reaction/veterinary
• Support, Non-U.S. Gov't
• Theileria/genetics
• Theileria/isolation & purification
• Tick-Borne Diseases/transmission
• Tick-Borne Diseases/*veterinary
• Ticks/*microbiology
• Ticks/parasitology
• Ticks/virology

Substances:

• 0 (DNA Primers)
• 0 (DNA, Bacterial)
• 0 (DNA, Protozoan)
• 0 (DNA, Viral)

[Tick-borne encephalitis]

Takashima I,  Hayasaka D.

[Article in Japanese]

Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.

Publication Types:

• Journal Article
• Review
• Review, Multicase
• Review, Tutorial

MeSH Terms:

• Amino Acid Sequence
• Animal
• Base Sequence
• Encephalitis Viruses, Tick-Borne/genetics
• Encephalitis Viruses, Tick-Borne/pathogenicity
• *Encephalitis, Tick-Borne/epidemiology
• *Encephalitis, Tick-Borne/virology
• Human
• Japan/epidemiology
• Phylogeny
• Russia/epidemiology
• Serologic Tests
• Support, Non-U.S. Gov't
• Ticks/virology
• Viral Envelope Proteins/chemistry
• Viral Envelope Proteins/genetics

Substances:

• 0 (Viral Envelope Proteins)

The role of lambs in louping-ill virus amplification.

Laurenson MK,  Norman R,  Reid HW,  Pow I,  Newborn D,  Hudson PJ.

[Article in English]

Institute of Biological Sciences, University of Stirling. karen.laurenson@ed.ac.uk

In some areas of Scotland, the prevalence of louping-ill virus has not decreased despite the vaccination of replacement ewes for over 30 years. The role of unvaccinated lambs in viral persistence was examined through a combination of an empirical study of infection rates of lambs and mathematical modelling. Serological sampling revealed that most lambs were protected by colostral immunity at turnout in May/June but were fully susceptible by the end of September. Between 8 and 83% of lambs were infected over the first season, with seroconversion rates greater in late rather than early summer. The proportion of lambs that could have amplified the louping-ill virus was low, however, because high initial titres of colostral antibody on farms with a high force of infection gave protection for several months. A simple mathematical model suggested that the relationship between the force of infection and the percentage of lambs that became viraemic was not linear and that the maximum percentage of viraemic lambs occurred at moderately high infection rates. Examination of the conditions required for louping-ill persistence suggested that the virus could theoretically persist in a sheep flock with over 370 lambs, if the grazing season was longer than 130 days. In practice, however, lamb viraemia is not a general explanation for louping-ill virus persistence as these conditions are not met in most management systems and because the widespread use of acaracides in most tick-affected hill farming systems reduces the number of ticks feeding successfully.

MeSH Terms:

• Animal
• Antibodies, Viral/blood
• Colostrum/immunology
• Disease Susceptibility/veterinary
• Encephalitis Viruses, Tick-Borne/*growth & development
• Encephalitis Viruses, Tick-Borne/immunology
• Encephalitis, Tick-Borne/blood
• Encephalitis, Tick-Borne/epidemiology
• Encephalitis, Tick-Borne/*veterinary
• Female
• Hemagglutination Inhibition Tests/veterinary
• Immunity, Maternally-Acquired
• *Models, Biological
• Scotland/epidemiology
• Seroepidemiologic Studies
• Sheep
• Sheep Diseases/blood
• Sheep Diseases/epidemiology
• Sheep Diseases/*virology
• Support, Non-U.S. Gov't
• Ticks
• Vaccination/veterinary
• Viral Vaccines/immunology
• Viremia/veterinary

Substances:

• 0 (Antibodies, Viral)
• 0 (Viral Vaccines)

Infectious cDNA clones of Langat tick-borne flavivirus that differ from their parent in peripheral neurovirulence.

Campbell MS,  Pletnev AG.

[Article in English]

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.

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.

MeSH Terms:

• Amino Acid Substitution/genetics
• Animal
• Cell Line
• *Cloning, Molecular
• Comparative Study
• Consensus Sequence/genetics
• DNA Mutational Analysis
• DNA, Complementary/genetics
• Encephalitis Viruses, Tick-Borne/*genetics
• Encephalitis Viruses, Tick-Borne/isolation & purification
• Encephalitis Viruses, Tick-Borne/*pathogenicity
• Encephalitis Viruses, Tick-Borne/physiology
• Encephalitis, Tick-Borne/mortality
• Encephalitis, Tick-Borne/pathology
• Encephalitis, Tick-Borne/*virology
• Genome, Viral
• Lethal Dose 50
• Mice
• Mice, SCID
• Mutation/genetics
• Neurons/pathology
• Neurons/*virology
• Reverse Transcriptase Polymerase Chain Reaction
• Transfection
• Variation (Genetics)/genetics
• Virulence/genetics
• Virus Replication/physiology

Substances:

• 0 (DNA, Complementary)

Membrane fusion activity of tick-borne encephalitis virus and recombinant subviral particles in a liposomal model system.

Corver J,  Ortiz A,  Allison SL,  Schalich J,  Heinz FX,  Wilschut J.

[Article in English]

Laboratory of Molecular Virology, University of Groningen and Academic Hospital, Groningen, Ant. Deusinglaan 1, 9713 AV, The Netherlands.

We present a kinetic analysis of the membrane fusion activity of tick-borne encephalitis (TBE) virus and TBE-derived recombinant subviral particles (RSPs) in a liposomal model system. Fusion was monitored using a fluorescence assay involving pyrene-labeled phospholipids. Fusion was strictly dependent on low pH, with the optimum being at pH 5.3-5.5 and the threshold at pH 6.8. Fusion did not require a protein or carbohydrate receptor in the target liposomes. Preexposure to low pH of the virus alone resulted in inactivation of its fusion activity. At the optimum pH for fusion and 37 degrees C, the rate and extent of fusion were very high, with more than 50% of the virus fusing within 2 s and the final extent of fusion being 70%. Lowering of the temperature did not result in a significant decrease in the rate and extent of fusion, suggesting that TBE virus fusion is a facile process with a low activation energy, possibly due to the flat orientation of the E glycoprotein on the viral surface facilitating the establishment of direct intermembrane contact. The fusion characteristics of TBE virus and RSPs were similar, indicating that RSPs provide a reliable and convenient model for further study of the membrane fusion properties of TBE virus.

MeSH Terms:

• Animal
• Cells, Cultured
• Chick Embryo
• Cholesterol/metabolism
• Encephalitis Viruses, Tick-Borne/chemistry
• Encephalitis Viruses, Tick-Borne/genetics
• Encephalitis Viruses, Tick-Borne/*metabolism
• Fluorescent Dyes/metabolism
• Hydrogen-Ion Concentration
• Kinetics
• Liposomes/chemistry
• Liposomes/*metabolism
• *Membrane Fusion
• Membrane Glycoproteins/genetics
• Membrane Glycoproteins/metabolism
• Models, Biological
• Phosphatidylcholines/metabolism
• Phosphatidylethanolamines/metabolism
• Pyrenes/metabolism
• Recombinant Proteins/genetics
• Recombinant Proteins/metabolism
• Sphingomyelins/metabolism
• Support, Non-U.S. Gov't
• Support, U.S. Gov't, P.H.S.
• Thermodynamics
• Viral Envelope Proteins/genetics
• Viral Envelope Proteins/metabolism
• Viral Structural Proteins/genetics
• Viral Structural Proteins/*metabolism

Substances:

• 0 (Fluorescent Dyes)
• 0 (Liposomes)
• 0 (Membrane Glycoproteins)
• 0 (Phosphatidylcholines)
• 0 (Phosphatidylethanolamines)
• 0 (Pyrenes)
• 0 (Recombinant Proteins)
• 0 (Sphingomyelins)
• 0 (Viral Envelope Proteins)
• 0 (Viral Structural Proteins)
• 129-00-0 (pyrene)
• 57-88-5 (Cholesterol)

Grant Support:

• HL-16660/HL/NHLBI

[Tick-borne encephalitis and Lyme disease: the epizootiological parallels and monitoring]

Naumov RL.

[Article in Russian]

Publication Types:

• Journal Article
• Review
• Review, Tutorial

MeSH Terms:

• Animal
• Arachnid Vectors/microbiology
• Arachnid Vectors/virology
• Borrelia/pathogenicity
• Disease Reservoirs
• Encephalitis Viruses, Tick-Borne/pathogenicity
• Encephalitis, Tick-Borne/*epidemiology
• Encephalitis, Tick-Borne/microbiology
• Encephalitis, Tick-Borne/parasitology
• Encephalitis, Tick-Borne/virology
• Human
• Ixodes/microbiology
• Ixodes/virology
• Lyme Disease/*epidemiology
• Lyme Disease/microbiology
• Lyme Disease/parasitology
• Lyme Disease/virology
• Support, Non-U.S. Gov't
• Time Factors

[The biodiversity dynamics of the causative agents of diseases transmitted by ticks in the genus Ixodes: an analysis of multiyear data]

Dubinina EV,  Alekseev AN.

[Article in Russian]

Fauna of pathogen's met in the organism of the primary tick-borne disease vectors--Ixodes persulcatus Schulze and Ixodes ricinus (L.) was observed. Prevalence of Borrelia mono- and poly-infection in the I. persulcatus ticks within a season of the vector activity was analyzed and increase of the number of the dual infected specimens during the season was demonstrated. The first determination of Ehrlichia infected I. ricinus and I. persulcatus collected in the Baltic region of Russia was stated. The triple infection of Ixodes ticks in was proved: infection by the two species of Borrelia and Ehrlichia; infection by the three species of Borrelia and infection by the tick-borne encephalitis virus and two species of Borrelia. The first determination of the tick-borne encephalitis virus in I. ricinus in the recreational zone of Kaliningrad Province (Courland [correction of Curonian] Spit) was described. Dipetalonema sp. was detected in the St. Petersburg population of I. persulcatus. The prevalence of poly-infection among I. persulcatus ticks was stated.

MeSH Terms:

• Animal
• *Arachnid Vectors/microbiology
• *Arachnid Vectors/parasitology
• *Arachnid Vectors/virology
• *Ecosystem
• Human
• *Ixodes/microbiology
• *Ixodes/parasitology
• *Ixodes/virology
• Russia
• Seasons
• Support, Non-U.S. Gov't
• Tick-Borne Diseases/microbiology
• Tick-Borne Diseases/parasitology
• Tick-Borne Diseases/*transmission
• Tick-Borne Diseases/virology

[Protective effect of a new antiviral preparation of phosprenyl in experimental tick-borne encephalitis]

Ozherelkov SV,  Timofeev AV,  Novikova GP,  Deeva AV,  Narovlianskii AN,  Sanin AV,  Pronin AV.

[Article in Russian]

Antiviral activity of phosprenyl was studied in BALB/c mice infected with tick-borne encephalitis (TBE) virus. Up to 60% animals infected with TBE virus survived after 1-3 intramuscular injections of phosprenyl. The mortality in the untreated group infected with the virus was 100%. Direct antiviral effect of phosprenyl was studied in sensitive SPEV cells infected with TBE virus. The titer of the virus decreased 10-fold in the cells treated with the drug vs. untreated control cells. Phosprenyl stimulates some interleukins: gamma-interferon, tumor necrosis factor-alpha, and interleukin-6. The stimulating effect of the drug manifests in intact animals and in those infected with TBE virus and treated with phosprenyl. The prospects of further trials of the drug as a therapeutic and prophylactic agent in TBE are discussed.

MeSH Terms:

• Animal
• Antiviral Agents/administration & dosage
• Antiviral Agents/*therapeutic use
• Cytokines/biosynthesis
• Encephalitis, Tick-Borne/*prevention & control
• Injections, Intramuscular
• Mice
• Mice, Inbred BALB C
• Polyisoprenyl Phosphates/administration & dosage
• Polyisoprenyl Phosphates/*therapeutic use

Substances:

• 0 (Antiviral Agents)
• 0 (Cytokines)
• 0 (Polyisoprenyl Phosphates)
• 0 (phosprenyl)

Proceedings of the 5th International Potsdam Symposium on Tick-borne Diseases: Tick-borne Encephalitis and Lyme Borreliosis. Berlin, Germany, February 26-27, 1999.

[No authors listed].

[Article in English]

Publication Types:

• Congresses
• Overall

MeSH Terms:

• Animal
• *Encephalitis, Tick-Borne
• Human
• *Lyme Disease

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.

Fleeton MN,  Liljestrom P,  Sheahan BJ,  Atkins GJ.

[Article in English]

Microbiology and Tumorbiology Center, Karolinska Institute, S-171 77 Stockholm, Sweden.

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.

MeSH Terms:

• Animal
• Antibodies, Viral/biosynthesis
• Antigens, Viral/*genetics
• Cell Line
• Comparative Study
• Encephalitis Viruses, Tick-Borne/*genetics
• Encephalitis Viruses, Tick-Borne/*immunology
• Encephalitis Viruses, Tick-Borne/pathogenicity
• Encephalitis, Tick-Borne/immunology
• Encephalitis, Tick-Borne/pathology
• Encephalitis, Tick-Borne/prevention & control
• Hamsters
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Models, Biological
• Plasmids/genetics
• Recombination, Genetic
• Semliki Forest Virus/*genetics
• Semliki Forest Virus/*immunology
• Support, Non-U.S. Gov't
• Vaccines, DNA/genetics
• Vaccines, DNA/immunology
• Vaccines, Inactivated/genetics
• Vaccines, Inactivated/immunology
• Vaccines, Synthetic/*genetics
• Vaccines, Synthetic/*immunology
• Viral Vaccines/*genetics
• Viral Vaccines/*immunology

Substances:

• 0 (Antibodies, Viral)
• 0 (Antigens, Viral)
• 0 (Plasmids)
• 0 (Vaccines, DNA)
• 0 (Vaccines, Inactivated)
• 0 (Vaccines, Synthetic)
• 0 (Viral Vaccines)

An accelerated schedule for tick-borne encephalitis vaccine: the American Military experience in Bosnia.

Craig SC,  Pittman PR,  Lewis TE,  Rossi CA,  Henchal EA,  Kuschner RA,  Martinez C,  Kohlhase KF,  Cuthie JC,  Welch GE,  Sanchez JL.

[Article in English]

Directorate of Epidemiology and Disease Surveillance, U.S. Army Center for Health Promotion and Preventive Medicine, Aberdeen Proving Ground (EA), Maryland 21010, USA.

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.

MeSH Terms:

• Adult
• Antibodies, Viral/blood
• Bosnia-Herzegovina
• Cohort Studies
• Encephalitis Viruses, Tick-Borne/*immunology
• Encephalitis, Tick-Borne/immunology
• Encephalitis, Tick-Borne/*prevention & control
• Enzyme-Linked Immunosorbent Assay
• Female
• Human
• Immunization Schedule
• Male
• Military Medicine/methods
• *Military Personnel
• Occupational Diseases/*prevention & control
• United States
• Vaccines, Inactivated/administration & dosage
• Vaccines, Inactivated/adverse effects
• Viral Vaccines/*administration & dosage
• Viral Vaccines/adverse effects

Substances:

• 0 (Antibodies, Viral)
• 0 (Vaccines, Inactivated)
• 0 (Viral Vaccines)

Diffuse reversible alopecia in patients with Lyme meningitis and tick-borne encephalitis.

Cimperman J,  Maraspin V,  Lotric-Furlan S,  Ruzic-Sabljic E,  Avsic-Zupanc T,  Strle F.

[Article in English]

University Medical Centre, Ljubljana, Slovenia.

Alopecia occurring after febrile bacterial and viral infection is a phenomenon well known since the beginning of the century. To evaluate the occurrence of alopecia in tick transmitted disease, 23 adult patients with Lyme meningitis and 71 patients with tick-borne encephalitis were included in a prospective study and were followed up for one year. Diffuse alopecia occurred within three months after the outbreak of disease in 3 out of 23 (13%) patients with Lyme meningitis and in 40 out of 71 (56.3%) patients with tick-borne encephalitis. The mean duration of alopecia was 2 to 3 months and alopecia was reversible in all patients.

MeSH Terms:

• Adolescence
• Adult
• Aged
• Alopecia/*diagnosis
• Encephalitis, Tick-Borne/*diagnosis
• Female
• Follow-Up Studies
• Human
• Lyme Disease/*diagnosis
• Male
• Meningitis, Bacterial/*diagnosis
• Middle Age
• Prospective Studies

Lyme meningitis: a one-year follow up controlled study.

Cimperman J,  Maraspin V,  Lotric-Furlan S,  Ruzic-Sabljic E,  Strle F.

[Article in English]

Department of Infectious Diseases, University Medical Centre, Ljubljana, Slovenia.

Thirty-six patients with Lyme meningitis diagnosed at the Department of Infectious Diseases, University Medical Centre, Ljubljana in 1993 and 1994 were enrolled in a prospective study. All patients had lymphocytic meningitis, negative serum IgM antibody titres to tick-borne encephalitis virus and met at least one of the following four criteria: i) isolation of Borrelia burgdorferi sensu lato from cerebrospinal fluid (2 patients), ii) intrathecal borrelial antibody production (22 patients) iii) seroconversion to borrelial antigens (3 patients) and/or iv) erythema migrans in the period of four months prior to the onset of neurological involvement (21 patients). All patients underwent antibiotic treatment and were followed up for one year. The results of our study revealed that Lyme meningitis frequently occurs without meningeal signs and is often accompanied by additional neurological and/or other manifestations of Lyme borreliosis. During the first year after antibiotic treatment, minor and major manifestations of Lyme borreliosis persisted or occurred for the first time in several patients. They were not infrequent even at the examination performed one year after therapy.

Publication Types:

• Clinical Trial
• Journal Article

MeSH Terms:

• Adult
• Aged
• Aged, 80 and over
• Antibiotics/adverse effects
• Antibiotics/*therapeutic use
• Antibodies, Bacterial/cerebrospinal fluid
• Borrelia burgdorferi/immunology
• Female
• Follow-Up Studies
• Human
• IgG/cerebrospinal fluid
• IgM/cerebrospinal fluid
• Lyme Disease/diagnosis
• Lyme Disease/*drug therapy
• Lyme Disease/immunology
• Male
• Meningitis, Bacterial/diagnosis
• Meningitis, Bacterial/*drug therapy
• Meningitis, Bacterial/immunology
• Middle Age

Substances:

• 0 (Antibiotics)
• 0 (Antibodies, Bacterial)
• 0 (IgG)
• 0 (IgM)

Impact of climatic change on the northern latitude limit and population density of the disease-transmitting European tick Ixodes ricinus.

Lindgren E,  Talleklint L,  Polfeldt T.

[Article in English]

Natural Resources Management, Department of Systems Ecology, Stockholm University, Stockholm, Sweden. elisa@system.ecology.su.se

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.

MeSH Terms:

• Animal
• Arachnid Vectors/*growth & development
• Climate
• Discriminant Analysis
• Encephalitis, Tick-Borne/*prevention & control
• Geography
• Human
• Ixodes/*growth & development
• Lyme Disease/*prevention & control
• Population Density
• Support, Non-U.S. Gov't
• Sweden

Infections with flaviviridae.

Neyts J,  Leyssen P,  De Clercq E.

[Article in English]

Rega Institute for Medical Research, KULeuven.

The family of the Flaviviridae contains 3 genera: (i) the hepaciviruses, to which belongs Hepatitis C virus (HCV), (ii) the flaviviruses and (iii) the pestiviruses. Over 140 million people, more than four times the number of HIV-positive individuals, are chronically infected with the HCV. Hepatitis G virus (HGV) has not yet been assigned to a genus. The impact of this recently discovered virus is yet to be established. Infections with flaviviruses such as Yellow Fever virus (YFV), Dengue Fever virus (DENV), Japanese Encephalitis virus (JEV) and Tick-borne Encephalitis virus (TBEV) are emerging world-wide. The Pestiviruses, Bovine Viral Diarrhea virus (BVDV), Classical Swine Fever virus (CSFV) and Border Disease virus (BDV) have a serious impact on life-stock. At present, only treatment with interferon, alone or combined with ribavirin, has been approved for the treatment of HCV infections. No specific antivirals are available for the treatment of infections with Hepaci-, Flavi- or Pestiviruses. Possible targets for inhibition of the replication of Flaviviridae are the binding to, and the uptake of the virus in the cell; the internal ribosomal entry site (IRES) of Hepaci- and Pestiviruses; viral proteases; the viral RNA-dependent RNA polymerase and the viral helicase. The search for specific inhibitors of HCV replication is hindered by the absence of an efficient cell culture system for propagation of this virus. In addition, small laboratory animals, including mice, are not susceptible to HCV infection. Flaviviruses may cause infection in mice, but do so mainly following direct intracerebral inoculation. We have established a small animal model for flavivirus infections in SCID mice inoculated peripherally with the murine flavivirus Modoc.

Publication Types:

• Journal Article
• Review
• Review, Academic

MeSH Terms:

• Animal
• Cattle
• Disease Models, Animal
• Flaviviridae/*classification
• Flaviviridae/genetics
• Flaviviridae/pathogenicity
• *Flaviviridae Infections/classification
• *Flaviviridae Infections/epidemiology
• *Flaviviridae Infections/veterinary
• Human
• Mice
• Mice, SCID
• Support, Non-U.S. Gov't

[Report of the first congress of the "European Society for Emerging Infections".].

Huygelen C.

[Article in Dutch]

The first congress of the recently founded European Society for Emerging Infections was held in Budapest from 13 to 16 September 1998. About 200 physicians, veterinarians, biologists and microbiologists attended this meeting. The euphoria of the 1970's with respect to infectious diseases is now gone. During the last twenty years about thirty new infections agents have been identified and re-emergence of old diseases which had disappeared to a large extent, has been reported in many countries. Most newly emerging diseases in man are of zoonotic origin or are closely related to disease in animal (wild or domestic) showing a parallel pathology. The nature of the etiologic agents varies widely: prions, viruses, chlamydia, rickettsiae, bacteria, protozoa etc. Several factors play a role in the emergence: mutations of the agents themselves; changing habits of man as the host: travel, sexual habits, etc.; modifications of the climate or environment can influence the expansion of vectors. The subjects discussed at the congress covered a wide field of diseases and agents: plague, retroviruses, antibiotic-resistant bacteria, influenza, lyme borreliosis, tick-borne encephalitis, hantaviruses, rickettsioses and ehrlichiose, transmissible spongiform encephalopathies, Borna, lyssaviruses, E. coli, protozoa, chlamydia, etc.

Publication Types:

• Congresses

MeSH Terms:

• Animal
• Communicable Disease Control/*trends
• Communicable Diseases/*classification
• Communicable Diseases/*transmission
• Human

Detection of anterior horn lesions by MRI in central European tick-borne encephalomyelitis.

Beer S,  Brune N,  Kesselring J.

[Article in English]

Department of Neurology, Rehabilitation Center, Valens, Switzerland.

We report a case of central European tick-borne encephalitis with cervical myelitis presenting clinically as a lower motor neuron syndrome of the upper limbs with proximal asymmetrical pareses and atrophies. There were no sensory deficits nor signs of lesions of the spinal pathways or signs of encephalitis or meningitis. The affected motor fibers of the upper limbs were electrically inexcitable, but sensory findings were normal. Electromyography of the paralyzed muscles revealed pathological denervation activity without voluntary activation. The initial magnetic resonance imaging (MRI) showed a large hyperdense lesion in the anterior part of the cervical cord from C3 to T1. Despite the fact that MRI changes disappeared completely within 6 weeks the patient showed only little improvement in the paralyzed muscles after 6 months. To our knowledge, these MRI changes in patients with tick-borne encephalitis, consistent with an isolated anterior horn lesion, have never been reported previously. The course may have been aggravated by an initial antibiotic treatment with cephalosporins.

MeSH Terms:

• Adult
• Animal
• Case Report
• Electromyography
• Encephalomyelitis/*diagnosis
• Encephalomyelitis/physiopathology
• Encephalomyelitis/*virology
• Europe
• Human
• *Insect Vectors
• *Magnetic Resonance Imaging
• Male
• Spinal Cord/*pathology
• Ticks/*virology

Annual and seasonal variation of tick-borne encephalitis virus (TBEV) prevalence in ticks in selected hot spot areas in Germany using a nRT-PCR: results from 1997 and 1998.

Suss J,  Schrader C,  Abel U,  Voigt WP,  Schosser R.

[Article in English]

Bundesinstitut fur gesundheitlichen Verbraucherschutz und Veterinarmedizin, Berlin, Germany. j.suess@bgvv.de

The prevalence of tick-borne encephalitis virus (TBEV) in Ixodes ricinus tick populations in endemic areas of Germany with the highest TBE risk is unknown. Annual and seasonal differences in TBEV prevalence have also not been studied. Against this background, in May 1997 we started a systematic virus surveillance programme in ticks collected in locations known to have a high incidence of autochthonous TBE cases. These were 5 locations in Baden-Wurttemberg (Black Forest) and 8 locations in Bavaria (surrounding Passau). Field-collected ticks were randomly assigned to pools of 10 adults or 20 nymphs, respectively. The tick pools were tested for the presence of TBEV-RNA using a newly developed, sensitive nested reverse transcriptase polymerase chain reaction assay (nRT-PCR). The primer pairs were selected from the 5'-terminal noncoding region, a highly conserved part of the virus. The specificity was tested by computer homology searches of sequences, as well as by sequencing of the first and the second amplificates, by Southern blot hybridisation with a DIG-labelled oligonucleotide probe, and by restriction enzyme analysis. The method has proved to be very sensitive, with a detection limit of 20 fg of TBEV RNA per PCR run, or a single positive tick. Based on biostatistical considerations a sample size of at least 1000 ticks per estimation point was chosen. The estimated TBEV prevalence and confidence intervals (CI) were calculated from the nRT-PCR results of pooled samples (10 adults or 20 nymphs) using appropriate formulae for pooled testing. In order to identify the estimated TBEV prevalence as well as to assess the influence of annual and seasonal factors on TBEV prevalence, ticks were sampled twice a year (May and September) in 1997 and 1998 at exactly identical sites. These sites were selected because they were known to have had the highest incidence of autochthonous TBE cases during the previous 10 years. On sampling days, relevant local meteorological data were also noted. In total, 8500 I. ricinus ticks were investigated in this study, 4270 (3540 nymphs, 730 adults) from the Black Forest habitats, and 4230 (3680 nymphs, 550 adults) from the Bavarian locations. In the foci near Freiburg (Black Forest), the estimated virus prevalence was relatively high in the whole tick population, during 1997 with only slight seasonal differences [3.4% (confidence interval, CI, 2.3-4.8%) in May and 2.9% (CI 1.7-4.5%) in September]. In contrast, in 1998, in the same foci the estimated TBEV prevalence was considerably lower [1.1% (CI 0.5-2.0%) in May and 0.6% (CI 0.2-1.4%) in September]. Thus, while the seasonal differences again remained low, the annual variation was marked. In the Bavarian foci in 1997, the estimated virus prevalence of the whole tick population studied was lower than in the Black Forest foci and the seasonal fluctuations were low: in May 1997 0.9% (CI 0.4-1.8%) of the ticks were positive, in September 1.1% (CI 0.5-1.9%). In 1998, in May 2.0% (CI 1.1-3.3%) of the ticks were positive, and in September 1.1% (CI 0.5-2.1%). For the whole study period, every 50th to 100th I. ricinus nymph or adult in the Passau region was calculated to give a positive signal in the nRT-PCR. The TBEV prevalence data indicate that residents and visitors of areas in Germany known for high endemic activity take a significant risk of contracting TBEV infection, if bitten by ticks. In addition, the data suggest that annual fluctuations may exist in the whole tick population studied. Seasonal fluctuations of the virus prevalence in ticks were small.

MeSH Terms:

• Adult
• Animal
• Encephalitis Viruses, Tick-Borne/genetics
• Encephalitis Viruses, Tick-Borne/*isolation & purification
• Encephalitis, Tick-Borne/epidemiology
• Germany/epidemiology
• Human
• Ixodes/*virology
• Longitudinal Studies
• Nymph/virology
• RNA, Viral/analysis
• Reverse Transcriptase Polymerase Chain Reaction
• Risk Factors
• Seasons
• Time Factors

Substances:

• 0 (RNA, Viral)

Some epidemiological data on TBE and Lyme borreliosis in Croatia.

Borcic B,  Kaic B,  Kralj V.

[Article in English]

Croatian Institute of Public Health, Zagreb, Croatia.

TBE in Croatia was first discovered in 1953 but its mandatory reporting, as a distinct nosological entity, was instituted in 1987. Data presented here concern the 1989-1998 decade. During this period a total of 500 cases of TBE was recorded, ranging from 23 (1990) to 87 (1994) per year, with an average of 50 cases annually. There is only one natural focus in the northern part of the country, between the rivers Sava and Drava. Alleged cases of TBE, as occurring out of the focus (Zadar and Pula), have not been certified. The seasonal distribution of TBE cases is typical, most cases occurring from May to July (75%). As for the age distribution of TBE, a substantial rise is seen after the age of 20, only some 3% of cases occurring in children younger than 10 years. The first documented cases of human Lyme borreliosis in Croatia were published in 1986, its official compulsory reporting starting in 1991. Since then 1464 cases were recorded with an annual average of some 150 cases, varying from 93 (1992) up to 335 (1996). The age distribution is somewhat different from TBE, since the age group 0-9 years recruits 20% of all cases. Nevertheless, most of the diseased are of adult age. About 92% of the cases occur between May and August. The disease occurs mostly in the inland, above the 45th parallel, and only sporadically on the Adriatic coast.

MeSH Terms:

• Adolescence
• Adult
• Age Factors
• Child
• Child, Preschool
• Croatia/epidemiology
• Encephalitis, Tick-Borne/*epidemiology
• Human
• Infant
• Infant, Newborn
• Lyme Disease/*epidemiology
• Middle Age
• Prevalence
• Risk Factors
• Seasons

Main features of tick-borne encephalitis eco-epidemiology in Russia.

Korenberg EI,  Kovalevskii YV.

[Article in English]

Vector Laboratory, Gamaleya Research Institute for Epidemiology and Microbiology, Russian Academy of Medical Sciences, Moscow, Russia. focus@edkor.msk.ru

Tick-borne encephalitis (TBE) is a classic obligatorily transmissible viral infection with natural focality, which is widespread mainly in Eurasian forests of the temperate zone. Virus was discovered in the Russian Far East in 1937. Its main long-term reservoirs and vectors in natural foci are Ixodes persulcatus and I. ricinus ticks. Boundaries of the virus range and the location of natural foci within it are closely associated with the distribution pattern of these ticks. The largest categories of TBE range zoning are described. Each natural focus functions as a relatively autonomous parasitic system. The principal scheme of TBE virus circulation related to the development of three successive generations of the main vector is presented. The main parameter of epizootic activity and epidemic manifestation of natural foci and their long-term fluctuations in different regions are discussed. TBE morbidity in Russian and its dynamics during approximately 45 years are analysed.

Publication Types:

• Journal Article
• Review
• Review, Tutorial

MeSH Terms:

• Animal
• Disease Vectors
• *Ecology
• Encephalitis Viruses, Tick-Borne/physiology
• Encephalitis, Tick-Borne/*epidemiology
• Encephalitis, Tick-Borne/virology
• Host-Parasite Relations/physiology
• Human
• Ixodes/virology
• Prevalence
• Russia/epidemiology
• Time Factors
• Vertebrates/parasitology

Survival strategy of tick-borne encephalitis virus: cellular basis and environmental determinants.

Labuda M,  Randolph SE.

[Article in English]

Institute of Zoology, Slovak Academy of Sciences, Bratislava, Slovakia.

Although TBE virus can be transmitted in the laboratory by a wide variety of ixodid tick species to a wide variety of vertebrate host species, nevertheless in nature endemic cycles of TBE virus depend principally on just two tick species, Ixodes ricinus in the western and I. persulcatus in the eastern Palaearctic. A complete transmission cycle, from tick to tick via vertebrates, occurs most efficiently between co-feeding ticks in the absence of a systemic viraemia. This non-systemic route depends on TBE virus replication within particular immunocompetent cells in the skin, and only certain vertebrate species, notably Apodemus mice, are susceptible to this. Amongst the potential tick vectors in Europe, only I. ricinus has the correct host relationships and appropriate natural life cycle to support such non-systemic transmission cycles. Within the wide European distribution of this tick-host relationship, only in certain places do larval and nymphal ticks feed together on the same hosts with sufficient coincidence to ensure TBE virus survival. The environmental factors that determine this seasonal coincidence are being identified with the help of remotely-sensed meteorological satellite imagery to create predictive risk maps of TBE foci.

Publication Types:

• Journal Article
• Review
• Review, Tutorial

MeSH Terms:

• Animal
• Climate
• Disease Transmission
• Disease Vectors
• Encephalitis Viruses, Tick-Borne/*physiology
• Encephalitis, Tick-Borne/epidemiology
• Encephalitis, Tick-Borne/virology
• Host-Parasite Relations/*physiology
• Ixodes/*physiology
• Muridae/immunology
• Muridae/parasitology
• Muridae/virology
• Risk Factors
• Skin/immunology
• Skin/parasitology
• Skin/virology
• Support, Non-U.S. Gov't
• Vertebrates/immunology
• Vertebrates/*parasitology
• Vertebrates/virology

Tick-borne encephalitis virus: advances in molecular biology and vaccination strategy in the next century.

Heinz FX.

[Article in English]

Institute of Virology, University of Vienna, Austria.

Publication Types:

• Journal Article
• Review
• Review, Tutorial

MeSH Terms:

• Encephalitis Viruses, Tick-Borne/chemistry
• Encephalitis Viruses, Tick-Borne/*genetics
• Encephalitis Viruses, Tick-Borne/*immunology
• Encephalitis, Tick-Borne/epidemiology
• Encephalitis, Tick-Borne/*prevention & control
• Epidemiology, Molecular
• Europe/epidemiology
• Far East/epidemiology
• Human
• RNA, Viral/genetics
• Siberia/epidemiology
• Vaccines, Attenuated
• Vaccines, DNA
• Vaccines, Synthetic
• Viral Vaccines

Substances:

• 0 (RNA, Viral)
• 0 (Vaccines, Attenuated)
• 0 (Vaccines, DNA)
• 0 (Vaccines, Synthetic)
• 0 (Viral Vaccines)

Pathogen-tick-host interactions: Borrelia burgdorferi and TBE virus.

Nuttall PA.

[Article in English]

Institute of Virology & Environmental Microbiology, Oxford, UK.

Both tick-borne encephalitis (TBE) virus and Borrelia burgdorferi depend for their survival on a tick-borne transmission cycle involving diverse vertebrate hosts and ixodid (primarily Ixodes) tick species. Increasing evidence strongly suggests that a key factor in successful transmission is the ability of these pathogens to exploit the pharmacological properties of their vector tick's saliva. Proteins and other chemicals, secreted in tick saliva, control the vertebrate hosts' haemostatic, inflammatory and immune responses in order to facilitate blood-feeding. Such bioactive saliva molecules include immunoglobulin-binding proteins, histamine-binding proteins, natural killer cell and interferon regulators, and complement inhibitors. By unravelling the contents of tick saliva and understanding their interactions with host and pathogen, we may identify new strategies for disease control.

Publication Types:

• Journal Article
• Review
• Review, Tutorial

MeSH Terms:

• Animal
• Bacterial Vaccines/therapeutic use
• Birds/parasitology
• Borrelia burgdorferi/immunology
• Borrelia burgdorferi/*physiology
• Complement Inactivators/metabolism
• Disease Vectors
• Encephalitis Viruses, Tick-Borne/immunology
• Encephalitis Viruses, Tick-Borne/*physiology
• Encephalitis, Tick-Borne/prevention & control
• Encephalitis, Tick-Borne/virology
• Female
• Histamine/metabolism
• Host-Parasite Relations/*physiology
• IgG/metabolism
• Ixodes/*microbiology
• Ixodes/*physiology
• Killer Cells, Natural/metabolism
• Lyme Disease/prevention & control
• Lyme Disease/virology
• Male
• Proteins/metabolism
• Rodentia/parasitology
• Saliva/chemistry
• Saliva/microbiology
• Viral Vaccines/therapeutic use

Substances:

• 0 (Bacterial Vaccines)
• 0 (Complement Inactivators)
• 0 (IgG)
• 0 (Proteins)
• 0 (Viral Vaccines)
• 51-45-6 (Histamine)

Tick-borne encephalitis virus NS3 gene expression does not protect mice from homologous viral challenge.

Morozova OV,  Maksimova TG,  Bakhvalova VN.

[Article in English]

Novosibirsk Institute of Bioorganic Chemistry, Novosibirsk, Russia. MOV@niboch.nsc.ru

Tick-borne encephalitis virus (TBEV) NS3 gene has been subcloned into the expression vector pcDNAI and expressed in eukaryotic cells. Immunization of mice with the recombinant plasmid pcDNAI-NS3 induced antibodies against NS3 protein but did not protect from viral challenge.

MeSH Terms:

• Animal
• Antibodies, Viral/*blood
• Antibodies, Viral/immunology
• Cell Line
• Encephalitis Viruses, Tick-Borne/genetics
• Encephalitis Viruses, Tick-Borne/*immunology
• Encephalitis Viruses, Tick-Borne/pathogenicity
• Encephalitis, Tick-Borne/*prevention & control
• Encephalitis, Tick-Borne/virology
• Kidney/cytology
• Mice
• Mice, Inbred BALB C
• Plasmids/genetics
• Support, Non-U.S. Gov't
• Swine
• Transfection
• Vaccination
• Vaccines, DNA/*immunology
• Viral Nonstructural Proteins/*genetics
• Viral Nonstructural Proteins/*immunology
• Viral Nonstructural Proteins/metabolism
• Viral Vaccines/immunology

Substances:

• 0 (Antibodies, Viral)
• 0 (NS3 protein, flavivirus)
• 0 (Plasmids)
• 0 (Vaccines, DNA)
• 0 (Viral Nonstructural Proteins)
• 0 (Viral Vaccines)

[Assessment of selected parameters of non-specific cellular response in patients with tick borne encephalitis].

Izycka A,  Jablonska E,  Zajkowska J,  Hermanowska-Szpakowicz T,  Izycki T.

[Article in Polish]

Zakladu Immunopatologii Akademii Medycznej w Bialymstoku.

The aim of this study was the assessment of certain PMN functions involving migration, chemotaxis, phagocytic activity and intracellular oxygen-dependent killing in patients with TBE. The examination involved 47 persons treated in the Department of Infectious and Neuroinfectious Diseases Medical Academy in Bialystok. Two examinations were done: before and just after treatment. Control group contained 29 healthy persons. Migration and chemotaxis were assessed by agarose method of Nelson and al. and Glaser and al. Phagocytic activity was examined by microscopic method and intracellular oxygen-dependent killing by reduction test of NBT by Parks method. Analysis of results showed a decrease of all examined parameters both before and after treatment. It indicates a depression of non-specific cellular response in patients with Lyme meningoencephalitis.

MeSH Terms:

• Antibodies, Protozoan/immunology
• Cell Movement/physiology
• Chemotaxis, Leukocyte/physiology
• Encephalitis, Tick-Borne/*blood
• Encephalitis, Tick-Borne/diagnosis
• Encephalitis, Tick-Borne/immunology
• Female
• Human
• Leukocytes/pathology
• Macrophages/pathology
• Male
• Middle Age
• Phagocytosis/*physiology

Substances:

• 0 (Antibodies, Protozoan)

Seroprevalence of ehrlichiosis, Lyme borreliosis and tick-borne encephalitis infections in children and young adults in Slovenia.

Cizman M,  Avsic-Zupanc T,  Petrovec M,  Ruzic-Sabljic E,  Pokorn M.

[Article in English]

Department of Infectious Diseases, University Medical Center, Ljubljana, Slovenia. milan.cizman@mf.uni-lj.si

BACKGROUND: Little is known about the seroprevalence of ehrlichiosis in adults and much less about the same in children. METHODS: One hundred and forty-three healthy children and young adults (6-24 years of age, male to female ratio, 1:1) were assessed for the presence of antibodies to the agents of human granulocytic ehrlichiosis (HGE), human monocytic ehrlichiosis (HME), Borrelia burgdorferi sensu stricto (BB), and tick-borne encephalitis (TBE) virus in Slovenia, where tick-related infections are endemic. Antibodies to HGE and HME agents were assayed by indirect immunofluorescence, and antibodies to BB and TBE by enzyme-linked immunosorbent assay. A questionnaire about tick exposure was answered by all subjects. In the event of a positive result, a detailed interview was conducted. RESULTS: Of 143 study subjects, 22 (15.4%) had detectable antibodies to HGE agent, 22 (15.4%) were positive to BB, 18 (12.6%) were positive to TBE virus (12 of these were vaccinated) and 4 (2.8%) were positive to the HME agent. The history of persons seropositive to an HGE agent had been uneventful. CONCLUSIONS: Our study documents a high seroprevalence of HGE in children and young adults in Slovenia, similar to the seroprevalence of LB and higher than that of TBE and HME. Although the majority of these infections are probably asymptomatic or mild, active surveillance for acute HGE infections in children in areas endemic for tick-related infections is necessary.

MeSH Terms:

• Adult
• Animal
• Antibodies, Bacterial/*blood
• Antibodies, Viral/*blood
• *Bites and Stings
• Borrelia burgdorferi/immunology
• Child
• Ehrlichia chaffeensis/immunology
• Ehrlichiosis/diagnosis
• Ehrlichiosis/*epidemiology
• Encephalitis, Tick-Borne/diagnosis
• Encephalitis, Tick-Borne/*epidemiology
• *Endemic Diseases
• Enzyme-Linked Immunosorbent Assay
• Female
• Fluorescent Antibody Technique, Indirect
• Human
• Lyme Disease/diagnosis
• Lyme Disease/*epidemiology
• Male
• Questionnaires
• Seroepidemiologic Studies
• Slovenia/epidemiology
• *Ticks

Substances:

• 0 (Antibodies, Bacterial)
• 0 (Antibodies, Viral)

Perspectives for the treatment of infections with Flaviviridae.

Leyssen P,  De Clercq E,  Neyts J.

[Article in English]

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.

The family Flaviviridae contains three genera: Hepacivirus, Flavivirus, and Pestivirus. Worldwide, more than 170 million people are chronically infected with Hepatitis C virus and are at risk of developing cirrhosis and/or liver cancer. In addition, infections with arthropod-borne flaviviruses (such as dengue fever, Japanese encephalitis, tick-borne encephalitis, St. Louis encephalitis, Murray Valley encephalitis, West Nile, and yellow fever viruses) are emerging throughout the world. The pestiviruses have a serious impact on livestock. Unfortunately, no specific antiviral therapy is available for the treatment or the prevention of infections with members of the Flaviviridae. Ongoing research has identified possible targets for inhibition, including binding of the virus to the cell, uptake of the virus into the cell, the internal ribosome entry site of hepaciviruses and pestiviruses, the capping mechanism of flaviviruses, the viral proteases, the viral RNA-dependent RNA polymerase, and the viral helicase. In light of recent developments, the prevalence of infections caused by these viruses, the disease spectrum, and the impact of infections, different strategies that could be pursued to specifically inhibit viral targets and animal models that are available to study the pathogenesis and antiviral strategies are reviewed.

Publication Types:

• Journal Article
• Review
• Review, Academic

MeSH Terms:

• Animal
• Antiviral Agents/*therapeutic use
• Flaviviridae/genetics
• Flaviviridae/*physiology
• Flaviviridae Infections/drug therapy
• Flaviviridae Infections/*therapy
• Flaviviridae Infections/virology
• Gene Therapy
• Human
• Support, Non-U.S. Gov't
• Virus Replication/drug effects

Substances:

• 0 (Antiviral Agents)

[Viral encephalitis]

Bassetti C,  Sturzenegger M.

[Article in German]

Neurologische Universitatsklinik und Poliklinik, Inselspital, Bern.

Viral encephalitis presents with fever, headache, focal and generalized neurologic symptoms and signs, seizures, and CSF pleocytosis. Herpes simplex Virus (HSV) 1 and arboviruses (flaviruses) are the most common causes of encephalitis in Switzerland. The initial work-up in a suspected encephalitis includes CSF analysis, EEG, and brain CT or MRI. The identification of the responsible agent usually occurs with polymerase chain reaction or serology. The differential diagnosis to other infectious and non-infectious acute CNS-disorders may initially be arduous. A specific treatment is possible only in encephalitis caused by viruses of the herpes group. Active immunization should be considered in subjects at high risk for tick-borne encephalitis. With early treatment the prognosis may be satisfactory also in HSV encephalitis.

Publication Types:

• Journal Article
• Review
• Review, Tutorial

MeSH Terms:

• Antiviral Agents/*therapeutic use
• Diagnosis, Differential
• Encephalitis, Viral/*diagnosis
• Encephalitis, Viral/*drug therapy
• Encephalitis, Viral/epidemiology
• Human
• Prognosis
• Switzerland/epidemiology
• Tick-Borne Diseases/*diagnosis
• Tick-Borne Diseases/*drug therapy
• Tick-Borne Diseases/epidemiology
• Tick-Borne Diseases/virology

Substances:

• 0 (Antiviral Agents)

Characterization of tick-borne encephalitis virus from Latvia.

Mavtchoutko V,  Vene S,  Haglund M,  Forsgren M,  Duks A,  Kalnina V,  Horling J,  Lundkvist A.

[Article in English]

National Environmental Health Centre, Riga, Latvia.

Viruses of the tick-borne encephalitis (TBE) antigenic complex, within the family Flaviviridae, cause a variety of diseases including uncomplicated febrile illness, encephalitis, meningo-encephalitis, hemorrhagic fever and chronic disease in humans, domesticated animals or wildlife species. TBE is a serious problem in Latvia with up to a 1,000 patients confirmed serologically annually 1994-1995. No previous data had been reported on the causative agent of TBE in Latvia. In the present study, a virus was isolated from serum of a patient with clinical symptoms of an acute TBE infection. Nucleotide sequence information obtained by direct reverse transcription-polymerase chain reaction (RT-PCR) and the serological characteristics of the isolated virus strain, designated TBE-Latvia-1-96, indicated a closer relationship to the Vasilchenko strain, isolated in Novosibirsk (Siberia, Russia), as compared to the western European or far eastern subtypes of TBE viruses. In a mouse neurovirulence assay, a significant difference in survival rates (days) was shown between Latvia-1-96 and the western European TBE virus subtype.

MeSH Terms:

• Animal
• Antibodies, Monoclonal
• Brain/virology
• Cercopithecus aethiops
• Encephalitis Viruses, Tick-Borne/genetics
• Encephalitis Viruses, Tick-Borne/immunology
• Encephalitis Viruses, Tick-Borne/*isolation & purification
• Encephalitis Viruses, Tick-Borne/pathogenicity
• Encephalitis, Tick-Borne/immunology
• Encephalitis, Tick-Borne/*virology
• Female
• Human
• Latvia
• Mice
• Mice, Inbred Strains
• Microtinae
• Phylogeny
• RNA, Viral/analysis
• Reverse Transcriptase Polymerase Chain Reaction
• Sequence Alignment
• Serologic Tests
• Vero Cells
• Viral Envelope Proteins/*analysis
• Viral Envelope Proteins/genetics
• Viral Envelope Proteins/immunology
• Virulence

Substances:

• 0 (Antibodies, Monoclonal)
• 0 (RNA, Viral)
• 0 (Viral Envelope Proteins)

Impact of microclimate on immature tick-rodent host interactions (Acari: Ixodidae): implications for parasite transmission.

Randolph SE,  Storey K.

[Article in English]

Department of Zoology, University of Oxford, UK.

Rodents play a significant role in enzootic cycles of tick-borne pathogens, notably, in the northern hemisphere, tick-borne encephalitis virus and Lyme borreliosis spirochaetes. The relative numbers of nymphal and larval ticks feeding on rodents are crucial variables in determining the probability of rodent infection and the degree of amplification of infection prevalence in the tick population. Manipulation of the microclimate within quasinatural experimental arenas revealed that under increasingly dry conditions the numbers of unfed nymphal Ixodes ricinus L. questing in upper layers of the herbage decreased, whereas the rate of fat use and the numbers of nymphs feeding on small rodents, both increased. This is consistent with nymphs descending to the moist lower vegetation layers for water replenishment, where they would come into contact with small hosts. Very few larvae quested or fed on rodents under the dry conditions, but many more did so once the humidity increased, suggesting that larvae escape desiccation by becoming quiescent. The ratio of larvae to nymphs feeding on rodents thus increases with increasing humidity, contributing to the seasonal and geographical variation in disease transmission dynamics.

MeSH Terms:

• Animal
• Comparative Study
• Encephalitis, Tick-Borne/epidemiology
• Europe/epidemiology
• Geography
• *Host-Parasite Relations
• Human
• Ixodes/growth & development
• Ixodes/*physiology
• Life Cycle Stages
• Lyme Disease/epidemiology
• Microclimate
• Rodentia/*parasitology
• Support, Non-U.S. Gov't