[POPULATION MORBIDITY BY INFECTIONS TRANSMITIED VIA IXODES PER- SULCATUS IN THE NORTH AND SOUTH OF IRKUTSK REGION].

AIM: Evaluate the degree of epidemic risk of emergence of tick-borne encephalitis (TBE) and ixodes ticks' borreliosis (ITB) in municipalities (MPs) of Irkutsk region with various natural- climate conditions. MATERIALS AND METHODS: Morbidity was compared for TBE and ITB during 2001 - 2015 in MPs of Irkutsk region located, to the north or south of the 55th parallel, i.e. in the con- ditions of different severity of sharply continental climate. 5-year average data were analyzed. RESULTS: ITB morbidity was 2 - 3 times higher than TBE for all the 5-year periods in the north of the region, whereas in the south -differences were not present. Moreover, in MPs located to the north of the 55th parallel in 2001 - 2015 a decrease of TBE and ITB morbidity did not occur, as in the south of the region. CONCLUSION: The lack of population morbidity reduction by TBE and ITB in the north and prevalence of the latter nosoform requires enhancement of a complex of prophylaxis measures in these MPs with an accent in development of non-specific means, includ- ing acaricidic treatment, enhancement of operations of centers of express diagnostics of transmissible infections, familiarizing of the population with the use of protective suits during periods of high activity of ticks.

Vaccination with the variable tick protein of the relapsing fever spirochete Borrelia hermsii protects mice from infection by tick-bite.

BACKGROUND: Tick-borne relapsing fevers of humans are caused by spirochetes that must adapt to both warm-blooded vertebrates and cold-blooded ticks. In western North America, most human cases of relapsing fever are caused by Borrelia hermsii, which cycles in nature between its tick vector Ornithodoros hermsi and small mammals such as tree squirrels and chipmunks. These spirochetes alter their outer surface by switching off one of the bloodstream-associated variable major proteins (Vmps) they produce in mammals, and replacing it with the variable tick protein (Vtp) following their acquisition by ticks. Based on this reversion to Vtp in ticks, we produced experimental vaccines comprised on this protein and tested them in mice challenged by infected ticks. METHODS: The vtp gene from two isolates of B. hermsii that encoded antigenically distinct types of proteins were cloned, expressed, and the recombinant Vtp proteins were purified and used to vaccinate mice. Ornithodoros hermsi ticks that were infected with one of the two strains of B. hermsii from which the vtp gene originated were used to challenge mice that received one of the two Vtp vaccines or only adjuvant. Mice were then followed for infection and seroconversion. RESULTS: The Vtp vaccines produced protective immune responses in mice challenged with O. hermsi ticks infected with B. hermsii. However, polymorphism in Vtp resulted in mice being protected only from the spirochete strain that produced the same Vtp used in the vaccine; mice challenged with spirochetes producing the antigenically different Vtp than the vaccine succumbed to infection. CONCLUSIONS: We demonstrate that by having knowledge of the phenotypic changes made by B. hermsii as the spirochetes are acquired by ticks from infected mammals, an effective vaccine was developed that protected mice when challenged with infected ticks. However, the Vtp vaccines only protected mice from infection when challenged with that strain producing the identical Vtp. A vaccine containing multiple Vtp types may have promise as an oral vaccine for wild mammals if applied to geographic settings such as small islands where the mammal diversity is low and the Vtp types in the B. hermsii population are defined.

Borrelia miyamotoi: a widespread tick-borne relapsing fever spirochete.

Borrelia miyamotoi is a relapsing fever spirochete that has only recently been identified as a human pathogen. Borrelia miyamotoi is genetically and ecologically distinct from Borrelia burgdorferi sensu lato, while both are present in Ixodes ticks. Over 50 patients with an acute febrile illness have been described with a B. miyamotoi infection, and two infected immunocompromised patients developed a meningoencephalitis. Seroprevalence studies indicate exposure in the general population and in specific risk groups, such as patients initially suspected of having human granulocytic anaplasmosis. Here, we review the available literature on B. miyamotoi, describing its presence in ticks, reservoir hosts, and humans, and discussing its potential impact on public health.

High risk of tick bites in Dutch gardens.

Lyme borreliosis is the most prevalent tick-borne disease throughout the Northern Hemisphere. Because the disease has large socioeconomic consequences, there is an urgent need to further educate the public to stimulate preventive behavior. Unfortunately, risk factors for tick bites are poorly known. In this study, we determined the habitats and activities at risk for tick bites for people of different age categories using reports of Dutch citizens. Most people, 43%, were bitten in the forest, and an unexpected large number of people reported tick bites from their gardens (31%). Hiking, hobby gardening, and playing were the most-mentioned activities during which tick bites were received; people aged from 50 to 69 and children below 10 were bitten most. Different age categories were bitten in different habitats and during different activities. People aged from 0 to 60 reported most tick bites related to visiting a forest and hiking, whereas people older than 60 were mainly bitten in gardens. The percentage of garden and hobby gardening tick bites increased with age, but was also high for children less than 10 years of age. We suggest that these findings should be taken into account for the development of prevention strategies aiming to decrease the number of Lyme borreliosis cases.

Actualización acerca de Borrelia burgdorferi sensu lato y enfermedad de Lyme / Update on Borrelia burgdorferi sensu lato and Lyme disease

Introducción: Borrelia burgdorferi sensu lato es el agente etiológico de la enfermedad de Lyme, zoonosis emergente de difícil diagnóstico, prevención y control, reportada fundamentalmente en el hemisferio norte. Objetivo: facilitar información actualizada acerca de Borrelia burgdorferi. Métodos: se realizó una revisión de la literatura científica y especializada sobre los principales aspectos relacionados con este agente y su enfermedad; como son las características de las borrelias y el ciclo de vida, epidemiología, manifestaciones clínicas en humanos, diagnóstico de laboratorio, definición actual de caso, tratamiento, profilaxis, prevención y control. Resultados: se expone información actualizada y valiosa sobre los temas seleccionados, útil para el personal interesado en las enfermedades infecciosas transmitidas por vectores. Se muestra además información sobre los estudios realizados en Cuba. Conclusiones: se aporta información de utilidad para el manejo epidemiológico, clínico y microbiológico de casos con sospechas de la infección por Borrelia burgdorferi sensu lato(AU)

Introduction: Borrelia burgdorferi sensu lato is the causative agent of Lyme disease, an emerging zoonosis, whose diagnosis, prevention and control are difficult and it is mainly reported in the northern hemisphere. Objective: to provide updated information about Borrelia burgdorferi. Methods: a review of scientific and specialized literature on the key aspects of this agent and the disease such as characteristics and life cycle of borrelias, epidemiology, clinical manifestations in humans, laboratory diagnosis, current case definition, treatment, prophylaxis, prevention and control. Results: current valuable information on selected items was set forth, which is useful for the personnel involved in vector-borne infectious diseases. Additionally, information about studies conducted in Cuba was provided. Conclusions: this paper offers updated information for the epidemiological, clinical and microbiological management of suspected cases of infection with Borrelia burgdorferi sensu lato(AU)

Actualización acerca de Borrelia burgdorferi sensu lato y enfermedad de Lyme / Update on Borrelia burgdorferi sensu lato and Lyme disease

Introducción: Borrelia burgdorferi sensu lato es el agente etiológico de la enfermedad de Lyme, zoonosis emergente de difícil diagnóstico, prevención y control, reportada fundamentalmente en el hemisferio norte. Objetivo: facilitar información actualizada acerca de Borrelia burgdorferi. Métodos: se realizó una revisión de la literatura científica y especializada sobre los principales aspectos relacionados con este agente y su enfermedad; como son las características de las borrelias y el ciclo de vida, epidemiología, manifestaciones clínicas en humanos, diagnóstico de laboratorio, definición actual de caso, tratamiento, profilaxis, prevención y control. Resultados: se expone información actualizada y valiosa sobre los temas seleccionados, útil para el personal interesado en las enfermedades infecciosas transmitidas por vectores. Se muestra además información sobre los estudios realizados en Cuba. Conclusiones: se aporta información de utilidad para el manejo epidemiológico, clínico y microbiológico de casos con sospechas de la infección por Borrelia burgdorferi sensu lato

Introduction: Borrelia burgdorferi sensu lato is the causative agent of Lyme disease, an emerging zoonosis, whose diagnosis, prevention and control are difficult and it is mainly reported in the northern hemisphere. Objective: to provide updated information about Borrelia burgdorferi. Methods: a review of scientific and specialized literature on the key aspects of this agent and the disease such as characteristics and life cycle of borrelias, epidemiology, clinical manifestations in humans, laboratory diagnosis, current case definition, treatment, prophylaxis, prevention and control. Results: current valuable information on selected items was set forth, which is useful for the personnel involved in vector-borne infectious diseases. Additionally, information about studies conducted in Cuba was provided. Conclusions: this paper offers updated information for the epidemiological, clinical and microbiological management of suspected cases of infection with Borrelia burgdorferi sensu lato

[Diseases transmitted by ticks locally and abroad]. / Maladies transmises par des tiques d'ici et d'ailleurs.

This article provides a brief overview of some diseases transmitted by ticks. These vectors do not transmit only Lyme disease and tickborne-encephalitis, even in Switzerland. Several tick-borne diseases cause nonspecific flu-like symptoms. Nevertheless sometimes severe, some of these diseases can be treated with specific treatments. Repellents, appropriate clothes impregnated with permethrine and prompt removal of the tick are effective preventive measures to limit the risk of infection. There is an effective vaccine which protects against tick-borne encephalitis.

A multimodal bait for trapping blood-sucking arthropods.

Artificial baits constitute important tools for the detection and sampling of blood-sucking arthropods, in particular those that are vectors of parasites affecting human health. At present, many different devices have been proposed to attract blood-sucking arthropods, mostly based on the attractiveness of particular chemicals or blends. However, most of them revealed themselves as unpractical (e.g. they require an electrical supply), expensive (e.g. gas bottles) or not efficient enough. On the other hand, the use of living baits is as effective but it has practical constraints and/or raises ethical questions. We present here a multimodal lure to attract blood-sucking arthropods designed taking into account both practical constraints and costs. The main characteristics of our bait are: (1) artificiality (no living-host); (2) multimodality (it associates heat, carbon dioxide and chemical attractants); (3) independency from any energy source; (4) no need for gas bottles; (5) easy to prepare and use in the field; (6) low cost. We tested the ability of the bait to attract blood-sucking arthropods in the laboratory and in the field, using capture sticky-traps. Our bait evinced to be almost as efficient as live hosts (mice) for the capture of Chagas disease and Borrelia vectors in Bolivia. The multimodal lure here presented is a generalist bait, i.e. effective for attracting different haematophagous species.

Interleukin 10 protects the brain microcirculation from spirochetal injury.

Spirochetal infections are an important cause of neurological disease. In previous studies of the pathogenesis of spirochetal brain infection, mice inoculated with Borrelia turicatae, an agent of tick-borne relapsing fever in North America, developed mild meningitis and parenchymal activation/infiltration by interleukin 10 (IL-10)-producing microglia/macrophages. Here, we investigated the neuroprotective effects of IL-10 during spirochetal infection by comparing the outcomes of B. turicatae infection in wild-type and IL-10-deficient RAG2-deficient mice. Mice were infected with either serotype 1 (Bt1), which causes more brain infection but lower bacteremia, or Bt2, which causes less brain infection but higher bacteremia. Interleukin 10 deficiency resulted in early death from subarachnoid/intraparenchymal brain hemorrhage in Bt2-infected mice. These mice had marked apoptosis of brain microvascular endothelial cells as assessed by terminal transferase-mediated DNA nick end-labeling staining. In contrast, Bt1 infection caused milder subarachnoid hemorrhage. Neuronal apoptosis was observed in mice infected with both serotypes and was prominent in the cerebellum. Neutralization of tumor necrosis factor prevented death and reduced morbidity and brain injury in mice infected by both serotypes. We conclude that IL-10 plays a critical role protecting the cerebral microcirculation from spirochetal injury possibly by inhibition effects of tumor necrosis factor.

Increasing the interaction of Borrelia burgdorferi with decorin significantly reduces the 50 percent infectious dose and severely impairs dissemination.

Tight regulation of surface antigenic expression is crucial for the pathogenic strategy of the Lyme disease spirochete, Borrelia burgdorferi. Here, we report the influence of increasing expression of decorin-binding protein A (DbpA), one of the most investigated spirochetal surface adhesins, on the 50% infectious dose (ID(50)), dissemination, tissue colonization, pathogenicity, and persistence of B. burgdorferi in the murine host. Our in vitro assays showed that increasing DbpA expression dramatically increased the interaction of B. burgdorferi with decorin and sensitivity to growth inhibition/killing by anti-DbpA antibodies; however, this increased interaction did not affect spirochetal growth and replication in the presence of decorin. Increasing DbpA expression significantly reduced ID(50) values and severely impaired dissemination in severe combined immunodeficiency (SCID) and immunocompetent mice. During infection of SCID mice, B. burgdorferi with increased DbpA expression was able to effectively colonize heart and skin tissues, but not joint tissues, completely abrogating arthritis virulence. Although increasing DbpA expression did not affect spirochetal persistence in the skin, it diminished the ability of B. burgdorferi to persist in the heart and joint tissues during chronic infection of immunocompetent mice. Taken together, the study highlights the importance of controlling surface antigen expression in the infectivity, dissemination, tissue colonization, pathogenicity, and persistence of B. burgdorferi during mammalian infection.

Anti-interleukin-15 prevents arthritis in Borrelia-vaccinated and -infected mice.

We showed previously that interleukin-17 (IL-17) plays a significant role in the induction of arthritis associated with Borrelia vaccination and challenge. Little information, however, is available about the chain of immunologic events that leads to the release of IL-17. The production of IL-17 has been linked to stimulation of memory cells by IL-15. Therefore, we hypothesized that IL-15 is involved in the induction of arthritis associated with Borrelia vaccination and infection of mice. Here we present evidence that treatment of Borrelia-vaccinated and -infected mice with anti-IL-15 antibody prevents swelling of the hind paws. More importantly, both anti-IL-15 antibody- and recombinant IL-15 receptor alpha-treated Borrelia-vaccinated and -infected mice were free of major histopathologic indications of arthritis, including hyperplasia, hypertrophy, and vilus formation of the synovium. Similarly, the synovial space and perisynovium were free of inflammatory cells. By contrast, the synovium of nontreated Borrelia-vaccinated and -infected mice had overt hyperplasia, hypertrophy, and vilus formation. Moreover, the synovial space and perisynovium were infiltrated with neutrophils, macrophages, and lymphocytes. Finally, we show that recombinant IL-15 stimulates the release of IL-17 from lymph node cells obtained near the arthritic site. These results suggest that IL-15 plays a major role in orchestrating IL-17 induction of arthritis associated with Borrelia-vaccinated and -infected mice.

[Tick-borne encephalitis in the Russian Federation: state-of-the-art and prevention policy].

The last quarter of the 20th century in the Russian Federation was marked by an unprecedented increase in the incidence of tick-borne encephalitis (TBE) with its peaks in 1996 and 1999 when as high as 10,000 cases of the disease were notified. Its highest incidence was recorded in the Regions of the Urals and Siberia. As many as 70-80% of the persons who felt ill were urban dwellers who had been infected mainly in the anthropurgic foci occurring in abundance in the environs of cities and towns. It was found that the area of TBE had been expanded and virus-infected ticks had actively penetrated into the urban parks and small public gardens. There were as many as 70 TBE-endemic regions. As of now, it has been ascertained that TBE foci are generally combined with other infections transmitted by Ixodes ticks and caused by viruses, bacteria, rickettsia and protozoa. This result is the occurrence of mixed infections, which requires new approaches to their diagnosis, treatment, and prevention. The prevention of TBE is conventionally based on vaccination of high-risk groups comprising mainly "forest" occupations. Under the present conditions, the strategy of TBE control should be radically revised towards mass vaccination of the population living in the highly endemic areas, which will drastically reduced morbidity in the country.

Testing of the Biocan B inj. ad us. vet. vaccine and development of the new recombinant vaccine against canine borreliosis.

Verification of the efficacy of Biocan B inj. ad us. vet. (Bioveta, a.s.) was done by challenge testing. Ticks collected in the nature were used as natural vectors of the infection. Six beagles and two control ones were used in the test. Formation of outer surface protein A specific antibodies (OspA antibodies) and borrelia specific immonoglobulins (IgG) was measured by Western blot and EIA in the sera samples. The tissue samples were used for detection of borreliae by cultivation method and dark field microscopy (DFM). Formation of IgG antibodies and OspA antibodies after vaccination was observed. The maximum titer level of antibodies was reached between 21. and 49. day after vaccination and then slowly decreased. Presence of borreliae was detected only in skin biopsies of non-vaccinated dogs. The post mortem tissue samples showed presence of borreliae in all of the samples of the non-vaccinated dogs. The tissues of the vaccinated dogs were not infected with borreliae, except for two samples of dog with low titer levels of OspA antibodies. The development of the new vaccine is based on preparation of recombinant outer surface proteins (e.g. rOspA and rOspC) of B. afzelii, B. burgdorferi and B. garinii origin. Chosen recombinant proteins were successfully expressed in E. coli. The obtained purified proteins are currently being tested on laboratory BALB/c mice. Formation of specific antibodies against some recombinant proteins has been confirmed. These proteins are suitable candidates for preparation of a vaccine prototype and they will be subsequently used in challenge tests.

Glycerol-3-phosphate acquisition in spirochetes: distribution and biological activity of glycerophosphodiester phosphodiesterase (GlpQ) among Borrelia species.

Relapsing-fever spirochetes achieve high cell densities (>10(8)/ml) in their host's blood, while Lyme disease spirochetes do not (<10(5)/ml). This striking contrast in pathogenicity of these two groups of bacteria suggests a fundamental difference in their ability to either exploit or survive in blood. Borrelia hermsii, a tick-borne relapsing-fever spirochete, contains orthologs to glpQ and glpT, genes that encode glycerophosphodiester phosphodiesterase (GlpQ) and glycerol-3-phosphate transporter (GlpT), respectively. In other bacteria, GlpQ hydrolyzes deacylated phospholipids to glycerol-3-phosphate (G3P) while GlpT transports G3P into the cytoplasm. Enzyme assays on 17 isolates of borreliae demonstrated GlpQ activity in relapsing-fever spirochetes but not in Lyme disease spirochetes. Southern blots demonstrated glpQ and glpT in all relapsing-fever spirochetes but not in the Lyme disease group. A Lyme disease spirochete, Borrelia burgdorferi, that was transformed with a shuttle vector containing glpTQ from B. hermsii produced active enzyme, which demonstrated the association of glpQ with the hydrolysis of phospholipids. Sequence analysis of B. hermsii identified glpF, glpK, and glpA, which encode the glycerol facilitator, glycerol kinase, and glycerol-3-phosphate dehydrogenase, respectively, all of which are present in B. burgdorferi. All spirochetes examined had gpsA, which encodes the enzyme that reduces dihydroxyacetone phosphate (DHAP) to G3P. Consequently, three pathways for the acquisition of G3P exist among borreliae: (i) hydrolysis of deacylated phospholipids, (ii) reduction of DHAP, and (iii) uptake and phosphorylation of glycerol. The unique ability of relapsing-fever spirochetes to hydrolyze phospholipids may contribute to their higher cell densities in blood than those of Lyme disease spirochetes.