Zugl.: Giessen, Univ., Diss., 2008

Würzburg, Univ., Diss., 2009

Thesis (Ph. D.)--University of Chicago, Dept. of Ecology and Evolution. / Includes bibliographical references. Also available on the Internet.

Thesis (Ph.D.) -- University of Rhode Island, 2009. / Typescript. Includes bibliographical references (leaves 188-202).

Despite the fact that eight cases of Lyme disease were diagnosed in San Luis Obispo County between 2005-2013, the identity of wildlife hosts serving as sources for tick infection in this region remained unidentified. The primary cause of Lyme disease in the U.S. is the spirochetal bacterium Borrelia burgdorferi sensu stricto, and this agent had not been previously isolated from the region. Borrelia bissettii, a related species that has not been implicated as a common causative agent of Lyme disease, was isolated in small rodents inhabiting coastal scrub and chaparral habitats in a previous San Luis Obispo County study. However, B. burgdorferi was not detected. In northwestern California, B. burgdorferi has been primarily associated with high populations of the tick vector Ixodes pacificus in dense woodlands or hardwood-conifer habitats, particularly in the western gray squirrel reservoir host, Sciurus griseus. My study investigated the role of S. griseus and other associated rodents as potential reservoirs for B. burgdorferi in central coastal California woodland habitats. Rodents were live-trapped at four sites in San Luis Obispo County in oak and mixed woodland. Rodent ear samples were tested for B. burgdorferi genospecies by bacterial culture and PCR. Ticks were collected from captured rodents and surrounding environments and tested by PCR for the presence of Borrelia. Of 119 captured rodents, seven were positive for Borrelia infection (5.9%) and of these, six were positive for B. burgdorferi (5.0%). There were multiple infected rodent species that included two western gray squirrels, three deer mice (Peromyscus maniculatus), and one brush mouse (P. boylii). Borrelia spp. were not detected by PCR from the 81 ticks recovered from the environment and rodents. Here, for the first time, we verify the presence of B. burgdorferi sensu stricto in San Luis Obispo county rodents. However, in contrast to previous Northern California studies, the western gray squirrel may not be the primary reservoir host for B. burgdorferi in this region. Multiple rodent species in oak woodlands may be involved in spirochete maintenance in San Luis Obispo County.

Since its initial identification in 1975, Lyme disease has become a public health concern in the U.S.  Increased concern is sparked by the rapid rate at which the disease is emerging into new areas.  One area of disease emergence is the state of Virginia which has been experiencing exponentially increasing rates of the disease.  This research studies Virginia's landscape-level habitats to explore demographic and environmental variables related to the spread of Lyme disease. The land cover data came from the National Land Cover Database (2006), demographic data came from the U.S. census (2010), and Lyme disease case data came from the Virginia Department of Health (2006-2010).  Key variables examined in this statewide study include the percentages of landscape types measured inside each census tract, measures of forest fragmentation, and measures of land cover interspersion inside state census tracts. Analysis was carried out using a spatial Poisson regression model.  Of the original 15 variables, 10 were significantly correlated to Lyme disease.  The six that were positively correlated with disease incidence include percent herbaceous land, percent water, two edge contrast measurements of herbaceous-forest land, median age, and average income.  The four that were negatively correlated were percent developed, population density, and two edge contrast measurements of developed-herbaceous land. Overall results indicate that specific environmental and demographic variables are associated with increased disease incidence as Lyme disease emerges in Virginia.  Results from this study could help create a predictive statewide map for Lyme disease incidence and aid in disease awareness and resource allocation. / Master of Science

As of 2024, more than 50,000 people suffer from Lyme arthritis — a debilitating late-stage symptom of Lyme disease. Symptoms remain even after the completion of antibiotic therapy and when there is no longer any indication of an active infection. Studies have found that a portion of the bacterial cell wall from the causative agent, Borrelia burgdorferi, is a persistent antigen in Lyme arthritis patients, lingering within the synovial fluid. This antigen, peptidoglycan, is recognized by the immune system in numerous ways. Multiple publications have shown that peptidoglycan is proinflammatory and can cause arthritis when injected in vivo. The same was found to be true for B. burgdorferi peptidoglycan. Studies focused on the structure of peptidoglycan from B. burgdorferi have shown atypical differences in both glycan and peptide chemistry that likely alter immune recognition. Due to a lack of necessary enzymes and transporters B. burgdorferi are unable to recycle their peptidoglycan as they elongate and produce daughter cells. This leads to a 45% reduction of their total cell wall that is released into the environment. The work detailed below focuses on this antigen to further our knowledge as to its in vivo biodistribution pattern, half-life, and ability to induce arthritis. For these experiments B. burgdorferi peptidoglycan (pBb PG) was purified, fluorescently labeled, and tracked in vivo to study its clearance pattern and rate. Three different mouse models for Lyme arthritis were utilized in these studies and all experienced persistence of B. burgdorferi peptidoglycan in their liver for upward of 20 days. There were differences in the rate of clearance between types of mice, suggesting the involvement of host genetics. Serum collected weekly throughout this experiment showed over a log fold change in the abundance of ALT and AST levels, which indicates liver dysfunction. Proteomic analysis of the livers of mice post pBb PG injection showed altered levels of proteins important for mitochondrial function and iron homeostasis. When human PBMCs were stimulated with PG from various bacteria it was found that at 12 h pBb PG differentially expressed genes involved in energy metabolic pathways, including oxidative phosphorylation and the citric acid cycle. A subset of Lyme disease patients continue to experience symptomology even after completion of multiple rounds of antibiotics. These patients are termed to have post treatment Lyme disease syndrome and typically experience fatigue as their most common symptom. This symptom in combination with the findings of this dissertation regarding the link between pBb PG and energy metabolism warrants further investigation. Especially since this biopolymer has been found to persist in the synovial fluid of Lyme arthritis patients. Better understanding how these processes are connected could allow for the eventual development of a way to target this material for clearance, or ways to inactivate it. Both options have the potential to help alleviate the devastating symptomology experienced by patients. / Doctor of Philosophy / Lyme disease is the most common human disease originating from a nonhuman host in the United States, with the estimated number of cases ~500,000 each year. This disease is caused by the bacterium Borrelia burgdorferi, that is transmitted by the black legged tick. This disease usually causes flu-like symptoms and if left untreated can cause more severe symptomology like arthritis, carditis, and neurological symptoms. Lyme arthritis is the most common late-stage symptom of this disease. Current areas of weakness within the field include ways to diagnose this disease, the treatment options, and our understanding of how these bacteria cause the symptoms they do. Recent work has made strides in studying Lyme arthritis, suggesting a major contributing factor to be a specific component of the bacterial cell wall that continues to persist. This component is called peptidoglycan and has been found in Lyme arthritis patients even after they've finished antibiotic therapy. Studies have also shown that the structure of this cell wall component is unique in comparison to other well-known bacteria. The research conducted as a part of this dissertation aims to investigate how this bacterial peptidoglycan is able to persist within patients for so long. To study this we utilized three mouse models of Lyme disease that all develop different severities of Lyme arthritis. By isolating the peptidoglycan from B. burgdorferi and labeling it with a molecule that fluoresces, we were able to track it over time in mice. We found that in all three mouse backgrounds peptidoglycan from B. burgdorferi persists for extended periods of times in the liver. We tested peptidoglycan from other common bacteria and found that they rapidly clear the mice. This suggests that there is something about the structure of B. burgdorferi's peptidoglycan that allows it to go unnoticed by the body for so long. Since this material is persisting within the liver we wanted to test if these mice had altered liver function. We found increased serum levels of enzymes that are indicators of overall liver health, suggesting some form of dysregulation. We also measured the total abundance of proteins in the livers of these mice in comparison to healthy controls. The mice injected with B. burgdorferi peptidoglycan had changes in the level of proteins involved in energy production and iron utilization. By measuring changes in gene expression, we confirm the specificity of these results to peptidoglycan from B. burgdorferi, even when using cells isolated from humans. One of the major conundrums of Lyme disease are the patients who continue to experience symptomology even after treatment, who are referred to as having post treatment Lyme disease syndrome. The primary symptom affecting these patients is fatigue, drawing an interesting parallel to our recent studies showing that B. burgdorferi peptidoglycan seems to be impacting energy metabolism. These findings warrant further investigation into the exact way in which B. burgdorferi peptidoglycan is affecting this process, which will hopefully lead to the generation of more targeted therapies to help alleviate this symptomology.

O estudo objetivou realizar um levantamento de doenças transmitidas por carrapatos em amostras de humanos e animais domésticos oriundos do Estado do Espírito Santo. Foram estudadas as Riquétsioses, Erliquiose, Babesiose, Borreliose, e especificamente em cães a Hepatozoonose canina. Três expedições científicas foram realizadas, onde foram coletadas amostras de sangue de humanos (n=201), cães (n=92) e eqüídeos (n=27). As amostras foram testadas utilizando-se os ensaios de Imunofluorescência Indireta (RIFI) e ELISA Indireto, dependendo do antígeno de eleição. A Reação em Cadeia de Polimerase (PCR) foi realizada utilizando primers específicos para os gêneros dos agentes pesquisados. Foi possível concluir que os municípios estudados podem ser considerados endêmicos para as zoonoses pesquisadas / This study aimed to perform a survey on tick-borne diseases in blood samples from humans and domestic animals from the State of Espírito Santo. The following diseases were studied: Rickettsiosis, Ehrlichiosis, Babesiosis, Borreliosis, and specifically in dogs, Canine Hepatozoonosis. Three scientific expeditions were performed, where blood samples from humans (n=201), dogs (n=92) and equids (n=27) were collected. Samples were tested using Indirect Immunofluorescence Assays (IFA) and Indirect ELISA, depending on the antigen. Polymerase Chain Reactions (PCR) were performed using specific primers to the genera of the surveyed agents. We concluded that the studied municipalities can be considered endemic areas to the surveyed zoonosis

O estudo objetivou realizar um levantamento de doenças transmitidas por carrapatos em amostras de humanos e animais domésticos oriundos do Estado do Espírito Santo. Foram estudadas as Riquétsioses, Erliquiose, Babesiose, Borreliose, e especificamente em cães a Hepatozoonose canina. Três expedições científicas foram realizadas, onde foram coletadas amostras de sangue de humanos (n=201), cães (n=92) e eqüídeos (n=27). As amostras foram testadas utilizando-se os ensaios de Imunofluorescência Indireta (RIFI) e ELISA Indireto, dependendo do antígeno de eleição. A Reação em Cadeia de Polimerase (PCR) foi realizada utilizando primers específicos para os gêneros dos agentes pesquisados. Foi possível concluir que os municípios estudados podem ser considerados endêmicos para as zoonoses pesquisadas / This study aimed to perform a survey on tick-borne diseases in blood samples from humans and domestic animals from the State of Espírito Santo. The following diseases were studied: Rickettsiosis, Ehrlichiosis, Babesiosis, Borreliosis, and specifically in dogs, Canine Hepatozoonosis. Three scientific expeditions were performed, where blood samples from humans (n=201), dogs (n=92) and equids (n=27) were collected. Samples were tested using Indirect Immunofluorescence Assays (IFA) and Indirect ELISA, depending on the antigen. Polymerase Chain Reactions (PCR) were performed using specific primers to the genera of the surveyed agents. We concluded that the studied municipalities can be considered endemic areas to the surveyed zoonosis

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 4 uppsatser.