Diss. (sammanfattning) Linköping : Linköpings universitet, 2006. / Härtill 4 uppsatser.

Thesis (Ph. D.)--West Virginia University, 2005 / Title from document title page. Document formatted into pages; contains ix, 210 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.

Borrelia afzelii differential gene expression in the course of tick blood-feeding, and during chronic infection in mice was studied. Temperature effect on B. afzelii gene expression and infectivity was investigated. Infection rates of mice immunized with B. afzelii tick gut antigen at various stages of tick blood-intake were analyzed. This work was funded by the Grant Agency of the Czech Republic, Project No. 17-27393S to Radek Šíma.

Les maladies à tiques posent un problème majeur que se soit du point de vue de la santé animale ou de la santé humaine. Parmi ces pathologies, la borréliose de Lyme est la maladie à transmission vectorielle la plus fréquente de l’Hémisphère Nord et, en France, l’Alsace représente l’une des régions avec la plus forte incidence. Ce travail de thèse a eu pour objectif d’évaluer les densités en nymphes ainsi que les taux d’infection à Borrelia burgdorferi sl et Anaplasma phagocytophilum dans cette région. Nous avons comparé nos résultats à ceux établis dans cette même région en 2003 et 2004. De plus nous avons étudié les facteurs environnementaux potentiellement responsables de la variabilité inter-site de la densité en nymphes et également cartographié le risque de borréliose de Lyme en Alsace. Notre travail, qui pour l’instant a été conduit en Alsace, tend à s’étendre à d’autres régions de France. Il nous paraît pertinent de poursuivre les études de terrains sur certains sites pris en compte dans ce travail de façon à objectiver les tendances observées dans notre région. / Vector-borne diseases are today a major threat for human and animal health. Among those diseases, Lyme borreliosis is the most frequent vector-borne disease occurring in the Northern hemisphere, and the numbers of humans affected have been increasing in some parts of the world. In France, Lyme borreliosis is endemic to several regions including the Alsace region.The aim of this work was to investigate nymph densities and infection prevalence of Borrelia burgdoferi sl and Anaplasma phagocytophilum in this region. We compared our results to those obtained by Ferquel et al. in 2003 and 2004. We studied environmental factors involved in inter-site nymph density variability and mapped Lyme borreliosis nymph density in Alsace.For instance our work that has been conducted in Alsace, is now extended in other region of France. It will be interesting to validate our results with data from other area.

The prevalence of chronic Lyme disease (CLD) remains relatively unknown in Connecticut because there is not an agreement on what CLD is and how it should be diagnosed in addition to which pathological agent causes CLD. The aim of this quantitative study was to assess whether there were significant differences between two groups of primary care physicians (PCP) working in Connecticut from two different points in time regarding their knowledge in the diagnosis, treatment, and management of CLD. A knowledge, attitude, and practice model was used as the underlying theoretical framework for this study. A random cross-sectional survey was mailed out to the 1,726 PCPs found in the list of certified medical doctors in Connecticut of 2015. One hundred and forty-five PCPs responses (11.9% response rate) were received and compared to responses from previous data (a 2010 study) of 285 PCPs (39.1% response rate) from the list of certified medical doctors in 2006. The PCP estimated mean number of patients diagnosed and treated for CLD was not significantly different between 2006 and 2015. However, a significantly higher number of PCPs in 2015 reported knowing Lyme disease (LD) symptoms but not feeling comfortable diagnosing LD (χ� = 536.83, p < 0.001), and significantly more PCPs in 2015 reported knowing LD symptoms and feeling comfortable diagnosing CLD (χ� = 265.41, p < 0.001). This study can promote social change by encouraging Connecticut PCPs to recognize CLD as a diagnosis to enable the development of registries and case-control assessments. The findings of this study may also inspire future studies.

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Indiana University-Purdue University Indianapolis (IUPUI) / Lyme disease, the most prevalent vector-borne illness in the United States, is a multisystem inflammatory disorder caused by infection with the spirochete Borrelia burgdorferi (Bb). This spirochete is maintained in nature through an enzootic cycle involving ticks and small mammals. The Bb genome encodes a large number of surface lipoproteins, many of which are expressed during mammalian infection. One of these lipoproteins is the major outer surface protein C (OspC) whose production is induced during transmission as spirochetes transition from ticks to mammals. OspC is required for Bb to establish infection in mice and has been proposed to facilitate evasion of innate immunity. However, the exact biological function of OspC remains elusive. Our studies show the ospC-deficient spirochete could not establish infection in NOD-scid IL2rγnull mice that lack B cells, T cells, NK cells, and lytic complement, whereas the wild-type spirochete was fully infectious in these mice. The ospC mutant also could not establish infection in SCID and C3H mice that were transiently neutropenic during the first 48 h post-challenge. However, depletion of F4/80+ phagocytes at the skin-site of inoculation in SCID mice allowed the ospC mutant to establish infection in vivo. In phagocyte-depleted SCID mice, the ospC mutant was capable to colonize the joints and triggered neutrophilia during dissemination in a similar pattern as wild-type bacteria. We then constructed GFP-expressing Bb strains to evaluate the interaction of the ospC mutant with phagocytes. Using flow cytometry and fluorometric assay for phagocytosis, we found that phagocytosis of GFP-expressing ospC mutant spirochetes by murine peritoneal macrophages and human THP-1 cells was significantly higher than parental wild-type Bb strains, suggesting that OspC has an anti-phagocytic property. This enhancement in phagocytosis was not mediated by MARCO and CD36 scavenger receptors and was not associated with changes in mRNA levels of TNFα, IL-1β, and IL-10. Phagocytosis assays with HL60 neutrophil-like cells showed that uptake of Bb strains was independent to OspC. Together, our findings reveal that F4/80+ phagocytes are important for clearance of the ospC mutant, and suggest that OspC promotes spirochetes' evasion of macrophages in the skin of mice during early Lyme borreliosis.

There are about 1500 cases of Lyme borreliosis (LB) registered annually in Lithuania, the average morbidity rate was 34/100 000 in 1991-2006. The high incidence of LB determines the high attention to the epidemiological situation. The analysis of the diseases patterns and causative factors is needed for management of the situation, development of disease preventive strategies, improving the diagnostics, providing recommendations and etc. The aim of the study is to assess epidemiological patterns of LB and the main factors (natural-climatic and social) leading to them in Lithuania 1995-2006. In this study LB incidence trends and risk factors are evaluated, correlation of various risk factors with LB incidence and abundance of ticks are assessed, the prevalence of tick bites and risk factors among the population are determined. This study has evaluated the possible ecological significance of newly formed biotope‘s to the LB spread. After molecular tests the prevalence and genotypes of Borrelia in Ixodes ricinus nymphs collected from different biotopes was determined. This study succeeded to detect until now not detected in Lithuania Borrelia miyamotoi belonging to relapsing fever group. The study results showed that nymps’ infectivity in Lithuania is 14.8%. The climatic (air temperature and snow cover) risk factors are the most important ones influencing the LB. LB natural habitat has the property to expand at the expense of areas where the incidence rate was previously low. / Lietuvoje kasmet registruojama apie 1500 susirgimų Laimo borelioze (LB), 1991-2006 m. vidutinis sergamumo rodiklis buvo 34/100 000 gyventojų. Aukštas sergamumo LB lygis sąlygoja didelį dėmesį šios ligos epidemiologinei situacijai. Jos dėsningumų ir priežastinių veiksnių analizė reikalinga situacijos valdymui, planuojant ir rengiant prevencines strategijas, gerinant diagnostiką, teikiant rekomendacijas visuomenei ir kt. Šio darbo tikslas – įvertinti LB epidemiologinius dėsningumus ir juos sąlygojančius svarbiausius veiksnius (gamtinius-klimatinius ir socialinius) Lietuvoje 1995–2006 m. Darbe išnagrinėti ir aprašyti LB sergamumo dėsningumai, įvertintos sergamumo tendencijos, atlikta LB rizikos veiksnių analizė ir nustatytos sąsajos su LB sergamumu ir erkių gausa, nustatytas erkių įkandimų ir rizikos veiksnių paplitimas tarp Lietuvos gyventojų. Šiame darbe įvertinta naujai susiformavusių biotopų galima ekologinė reikšmė LB plitimui, atlikus molekulinius tyrimus, nustatytas borelijų paplitimas ir genotipai Ixodes ricinus nimfose, surinktose skirtinguose biotopuose bei išaiškinta nauja, iki šiol Lietuvoje neaptikta grįžtamosios karštinės borelijų grupei priklausanti Borrelia miyamotoi. Šio darbo rezultatai parodė, kad nimfų infekuotumas Lietuvoje yra 14,8 proc.; svarbiausi sergamumą LB sąlygojantys rizikos veiksniai yra klimatiniai (vidutinė oro temperatūra bei sniego danga); LB gamtinis arealas turi savybę plėstis teritorijų, kuriuose sergamumas anksčiau buvo žemas, sąskaita.

Lietuvoje kasmet registruojama apie 1500 susirgimų Laimo borelioze (LB), 1991-2006 m. vidutinis sergamumo rodiklis buvo 34/100 000 gyventojų. Aukštas sergamumo LB lygis sąlygoja didelį dėmesį šios ligos epidemiologinei situacijai. Jos dėsningumų ir priežastinių veiksnių analizė reikalinga situacijos valdymui, planuojant ir rengiant prevencines strategijas, gerinant diagnostiką, teikiant rekomendacijas visuomenei ir kt. Šio darbo tikslas – įvertinti LB epidemiologinius dėsningumus ir juos sąlygojančius svarbiausius veiksnius (gamtinius-klimatinius ir socialinius) Lietuvoje 1995–2006 m. Darbe išnagrinėti ir aprašyti LB sergamumo dėsningumai, įvertintos sergamumo tendencijos, atlikta LB rizikos veiksnių analizė ir nustatytos sąsajos su LB sergamumu ir erkių gausa, nustatytas erkių įkandimų ir rizikos veiksnių paplitimas tarp Lietuvos gyventojų. Šiame darbe įvertinta naujai susiformavusių biotopų galima ekologinė reikšmė LB plitimui, atlikus molekulinius tyrimus, nustatytas borelijų paplitimas ir genotipai Ixodes ricinus nimfose, surinktose skirtinguose biotopuose bei išaiškinta nauja, iki šiol Lietuvoje neaptikta grįžtamosios karštinės borelijų grupei priklausanti Borrelia miyamotoi. Šio darbo rezultatai parodė, kad nimfų infekuotumas Lietuvoje yra 14,8 proc.; svarbiausi sergamumą LB sąlygojantys rizikos veiksniai yra klimatiniai (vidutinė oro temperatūra bei sniego danga); LB gamtinis arealas turi savybę plėstis teritorijų, kuriuose sergamumas anksčiau buvo žemas, sąskaita. / There are about 1500 cases of Lyme borreliosis (LB) registered annually in Lithuania, the average morbidity rate was 34/100 000 in 1991-2006. The high incidence of LB determines the high attention to the epidemiological situation. The analysis of the diseases patterns and causative factors is needed for management of the situation, development of disease preventive strategies, improving the diagnostics, providing recommendations and etc. The aim of the study is to assess epidemiological patterns of LB and the main factors (natural-climatic and social) leading to them in Lithuania 1995-2006. In this study LB incidence trends and risk factors are evaluated, correlation of various risk factors with LB incidence and abundance of ticks are assessed, the prevalence of tick bites and risk factors among the population are determined. This study has evaluated the possible ecological significance of newly formed biotope‘s to the LB spread. After molecular tests the prevalence and genotypes of Borrelia in Ixodes ricinus nymphs collected from different biotopes was determined. This study succeeded to detect until now not detected in Lithuania Borrelia miyamotoi belonging to relapsing fever group. The study results showed that nymps’ infectivity in Lithuania is 14.8%. The climatic (air temperature and snow cover) risk factors are the most important ones influencing the LB. LB natural habitat has the property to expand at the expense of areas where the incidence rate was previously low.

In North America, Borrelia burgdorferi is the primary causative agent of Lymedisease which is a growing health concern. The ability of B. burgdorferi to maintain chronic infection indicates that they are capable of immune evasion. A distinguishing characteristic of B. burgdorferi is the large number of sequences encoding predicted or known lipoproteins, including outer surface protein F (OspF). This study analyzes the specificity of the humoral immune response to B. burgdorferi B3 IMI OspF proteins during murine and human infection. Immunoblot analyses revealed a temporal expression of OspF proteins during infection and mapped the immunodominant epitopes which lie within the variable domains. To determine if OspF-related proteins are produced by other isolates, immunoblot analyses were performed using sera collected from mice and humans infected with diverse B. burgdorferi strains. Differences in the immunoreactivity profile to OspF proteins were seen among the infection sera tested. To identify the molecular basis of these differences, the ospF gene was isolated from several strains, sequenced and evolutionary analyses were conducted. These analyses revealed that OspF proteins show little diversity despite the separate geographic locations from which isolates originated. The high degree of OspF protein conservation seen in isolates from two distinct regions emphasizes the potential for OpsF proteins as vaccinogens or in serodiagnostic assays. Altogether, this study demonstrates the potential contribution of OspF proteins to immune evasion through its temporal expression during infection which may play specific roles at different stages of infection. Studies are underway to determine if inactivation of ospF genes through allelic exchange mutagenesis impacts on the pathogenicity of the Lyme disease spirochetes.