scholarly journals A new Borrelia on the block: Borrelia miyamotoi – a human health risk?

2019 ◽  
Vol 24 (18) ◽  
Author(s):  
Sally Cutler ◽  
Muriel Vayssier-Taussat ◽  
Agustín Estrada-Peña ◽  
Aleksandar Potkonjak ◽  
Andrei Daniel Mihalca ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Human Health Risk ◽  
Case Series ◽  
Human Infection ◽  
Future Research ◽  
Borrelia Miyamotoi ◽  
Relapsing Fever ◽  
Pathogenic Potential ◽  
In Vivo Models

Background Borrelia miyamotoi clusters phylogenetically among relapsing fever borreliae, but is transmitted by hard ticks. Recent recognition as a human pathogen has intensified research into its ecology and pathogenic potential. Aims We aimed to provide a timely critical integrative evaluation of our knowledge on B. miyamotoi, to assess its public health relevance and guide future research. Methods This narrative review used peer-reviewed literature in English from January 1994 to December 2018. Results Borrelia miyamotoi occurs in the world’s northern hemisphere where it co-circulates with B. burgdorferi sensu lato, which causes Lyme disease. The two borreliae have overlapping vertebrate and tick hosts. While ticks serve as vectors for both species, they are also reservoirs for B. miyamotoi. Three B. miyamotoi genotypes are described, but further diversity is being recognised. The lack of sufficient cultivable isolates and vertebrate models compromise investigation of human infection and its consequences. Our understanding mainly originates from limited case series. In these, human infections mostly present as influenza-like illness, with relapsing fever in sporadic cases and neurological disease reported in immunocompromised patients. Unspecific clinical presentation, also occasionally resulting from Lyme- or other co-infections, complicates diagnosis, likely contributing to under-reporting. Diagnostics mainly employ PCR and serology. Borrelia miyamotoi infections are treated with antimicrobials according to regimes used for Lyme disease. Conclusions With co-infection of tick-borne pathogens being commonplace, diagnostic improvements remain important. Developing in vivo models might allow more insight into human pathogenesis. Continued ecological and human case studies are key to better epidemiological understanding, guiding intervention strategies.

scholarly journals The Relapsing Fever Spirochete Borrelia hermsiiContains Multiple, Antigen-Encoding Circular Plasmids That Are Homologous to the cp32 Plasmids of Lyme Disease Spirochetes

2000 ◽  
Vol 68 (7) ◽  
pp. 3900-3908 ◽  
Author(s):  
Brian Stevenson ◽  
Stephen F. Porcella ◽  
Katrina L. Oie ◽  
Cecily A. Fitzpatrick ◽  
Sandra J. Raffel ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Direct Detection ◽  
Human Infection ◽  
Relapsing Fever ◽  
Borrelia Hermsii ◽  
Functional Studies ◽  
Dna Library ◽  
Multiple Antigen ◽  
Antigenic Proteins

ABSTRACT Borrelia hermsii, an agent of tick-borne relapsing fever, was found to contain multiple circular plasmids approximately 30 kb in size. Sequencing of a DNA library constructed from circular plasmid fragments enabled assembly of a composite DNA sequence that is homologous to the cp32 plasmid family of the Lyme disease spirochete,B. burgdorferi. Analysis of another relapsing fever bacterium, B. parkeri, indicated that it contains linear homologs of the B. hermsii and B. burgdorfericp32 plasmids. The B. hermsii cp32 plasmids encode homologs of the B. burgdorferi Mlp and Bdr antigenic proteins and BlyA/BlyB putative hemolysins, but homologs of B. burgdorferi erp genes were absent. Immunoblot analyses demonstrated that relapsing fever patients produced antibodies to Mlp proteins, indicating that those proteins are synthesized by the spirochetes during human infection. Conservation of cp32-encoded genes in differentBorrelia species suggests that their protein products serve functions essential to both relapsing fever and Lyme disease spirochetes. Relapsing fever borreliae replicate to high levels in the blood of infected animals, permitting direct detection and possible functional studies of Mlp, Bdr, BlyA/BlyB, and other cp32-encoded proteins in vivo.

scholarly journals Blood Smears Have Poor Sensitivity for ConfirmingBorrelia miyamotoiDisease

2019 ◽  
Vol 57 (3) ◽  
Author(s):  
Sam R. Telford ◽  
Heidi K. Goethert ◽  
Philip J. Molloy ◽  
Victor Berardi
Keyword(s):  
Lyme Disease ◽  
Morphological Evidence ◽  
Hard Tick ◽  
Borrelia Miyamotoi ◽  
Relapsing Fever ◽  
Main Mode ◽  
Blood Samples ◽  
Content Type ◽  
Blood Smears ◽  
Thick Smear

ABSTRACTBorrelia miyamotoidisease (BMD) is a newly recognized borreliosis that is cotransmitted by ticks wherever Lyme disease is zoonotic. UnlikeBorrelia burgdorferisensu lato, the agent of Lyme disease,B. miyamotoiis closely related to relapsing fever spirochetes, such asBorrelia hermsii. Some authors have suggested that the disease caused byB. miyamotoishould be considered a hard-tick-transmitted relapsing fever, and thus, the main mode of confirming a diagnosis for that infection, microscopy to analyze a blood smear, may have clinical utility. To determine whether blood smears may detectB. miyamotoiin the blood of acute BMD patients, we made standard malariological thick smears from anticoagulated blood samples that were previously determined to contain this agent (by PCR) and analyzed them for morphological evidence of spirochetes. Spirochetes were not detected in the blood smears from 20 PCR positive patient blood samples after examination of 100 thick smear fields and only 2 of 20 demonstrated spirochetes when the examination was extended to 300 thick smear fields. Inoculation of severe combined immunodeficient (SCID) mice yielded isolates from 5 of 5 samples, but 0 of 3 BALB/c mice became infected. We conclude that in strong contrast to the diagnosis of typical relapsing fever, microscopy of blood smears is not sensitive enough for confirming a diagnosis of BMD but that SCID mouse inoculation could be a useful complement to PCR.

scholarly journals Photodynamic therapy with new sublingual sensitiser Photosoft®E4 for cancer: a case series

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 161
Author(s):  
Karin Ried ◽  
Avni Sali ◽  
Michelle Wang ◽  
Brian Meade ◽  
Donald Murphy
Keyword(s):  
Photodynamic Therapy ◽  
Case Series ◽  
Disease Status ◽  
Future Research ◽  
Tissue Pharmacokinetics ◽  
Light Delivery ◽  
Number Of Patients ◽  
Cancer Types ◽  
Developed World

Background: An increasing number of patients seek complementary therapies for cancer treatment, the leading cause of death in the developed world. Photodynamic therapy (PDT), the combination of light and a photosensitiser agent, has provided some promising results in cancer therapy. New photosensitiser agents are continuously being developed to improve tolerability and effectiveness. There is a need to objectively evaluate clinical data from PDT patients.Methods: Here we report a case series using the new sublingually administered, chlorophyll-based photosensitiser Photosoft®E4 and an external laser light in a group of ten adult cancer patients not undergoing other concurrent therapies. PDT was administered for three treatment cycles with an average of 14 light treatments per patient, consisting of agent administration and laser treatment on alternate days over 3 months. Safety, tolerability and effectiveness on tumour palliation were monitored. Results: Patients in this study presented with a variety of cancer types and stages; half of the patients had breast cancer, and 40% had metastases. We found Photosoft®E4 to be safe and highly tolerable. However, overall disease status was not improved in our group of patients. Conclusions: Future research is required to determine the bioavailability of Photosoft®E4 and its uptake in tumour tissue, pharmacokinetics and dosing regimen, as well as the best mode of light delivery for the in vivo sensitiser activation.

A-79 Case Series Evaluating Quantitative Electroencephalograph and Neuropsychological Function in Neurological Lyme Disease

2021 ◽  
Vol 36 (6) ◽  
pp. 1123-1124
Author(s):  
Alexandra Rudd-Barnard ◽  
Sarah Jarvandi ◽  
Roxanne Rapoport ◽  
Sue Smith ◽  
Natalia Witkowska
Keyword(s):  
Lyme Disease ◽  
Slow Wave ◽  
Case Series ◽  
Quantitative Eeg ◽  
Wave Activity ◽  
Slow Wave Activity ◽  
Future Research ◽  
Eyes Closed ◽  
Neuropsychological Status ◽  
Eyes Open

Abstract Objectives The purpose of this study was to investigate the characteristics of physician diagnosed Neurological Lyme disease (NLD) using Quantitative EEG and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We hypothesize that findings would include more slow wave (Delta/Theta) activity that is consistent with the severity reported dysfunction. Methods Subjects consisted of four adult females with a physician provided diagnosis of NLD. EEG was recorded from 21 sites during an eyes open and eyes-closed resting conditions. Raw EEG data was made quantifiable (qEEG) through Fourier transformation to determine z-score derived cortical and subcortical slow wave activity. The RBANS was used to assess each subject’s functioning. Results (See Imaging). Subject 1. Theta: 3.7. Alpha: 2.3. Theta: 3.2. Alpha: 2.5. RBANS - 96. Subject 2. Theta: 1.9. Alpha: 3.1. Theta: 2.3. Alpha: 4.4. RBANS - 76. Subject 3. Theta: 3.4. Alpha: 2.8. Theta: 3.5. Alpha: 2.1. RBANS - 110. Subject 4. Theta: 3.6. Alpha: 3.0. Theta: 3.3. Alpha: 2.8. RBANS - 100. Conclusions NLD subjects within this study all demonstrated elevated subcortical frontal and frontotemporal theta and alpha. Elevation in cortical slow wave activity was found for subjects with greater reported symptomatology and may suggest either less severe course of disease or serve as a recovery marker. RBANS assessment variables were not completely sensitive in detection of subject reported challenges. Implications for conceptualization, treatment, and disease monitoring are highlighted. Directions for future research will also be discussed.

scholarly journals BBK07 Immunodominant Peptides as Serodiagnostic Markers of Lyme Disease

2010 ◽  
Vol 18 (3) ◽  
pp. 406-413 ◽  
Author(s):  
Adam S. Coleman ◽  
Evelyn Rossmann ◽  
Xiuli Yang ◽  
Haichen Song ◽  
Chinta M. Lamichhane ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Bacterial Pathogen ◽  
Surface Protein ◽  
Human Infection ◽  
Full Length ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lower Sensitivity ◽  
Serum Samples ◽  
Amino Terminal

ABSTRACTLyme disease (LD) is a tick-borne infection caused by the bacterial pathogenBorrelia burgdorferi. Current diagnostic tests mostly use borrelial lysates or select antigens to detect serum antibodies againstB. burgdorferi. These immunoassays are not entirely effective, especially for detection of early infection. We have recently characterized anin vivo-induced antigen, BBK07, as a serodiagnostic marker for LD. We now report that in a line blot assay, recombinant BBK07 protein-based detection is 90% sensitive and nearly 100% specific againstB. burgdorferiinfection in humans. Using an overlapping peptide library of 23 peptides encompassing full-length BBK07, we identified the immunodominant epitopes of BBK07 during human infection. We show that a select combination of amino-terminal peptides significantly enhanced BBK07-based diagnostic accuracy compared to that with the full-length protein. Although in enzyme-linked immunosorbent assay (ELISA) studies BBK07 peptides had overall lower sensitivity than established serodiagnostic peptides, such as the VlsE peptide C6 and OspC peptide pepC10, for the detection of early human LD, a subset of serum samples that failed to recognize either VlsE or OspC peptides were preferentially reactive to BBK07 peptides. These results highlight the fact that BBK07 peptides could be useful to complement the efficacy of VlsE and OspC peptide-based serodiagnostic assays. Finally, using a panel of canine sera, we show that BBK07 peptide is also effective for LD diagnosis in infected dogs. Together, our data show that peptides from theB. burgdorferisurface protein BBK07 are highly specific and sensitive serodiagnostic markers, and we suggest their future use in LD diagnostic assays.

scholarly journals Pneumocystis carinii: A Review of an Important Opportunistic Pathogen in AIDS

1991 ◽  
Vol 2 (1) ◽  
pp. 12-18
Author(s):  
M John Gill ◽  
Ron Read
Keyword(s):  
Pneumocystis Carinii ◽  
Opportunistic Pathogen ◽  
Human Infection ◽  
Clinical Disease ◽  
Immunofluorescent Staining ◽  
T Helper ◽  
In Vivo Models ◽  
Noninvasive Test

Since the first report of human infection withPneumocystis cariniiin 1942, cases of pneumonia due to this opportunistic pathogen have become increasingly common. Animal studies and clinical observations show that a significant depletion or dysfunction of T helper lymphocytes predisposes to clinical disease. Individuals with damaged T helper cells secondary to malignancies (eg, Hodgkin’s lymphoma), drugs (eg, cyclosporine, steroids), or certain infections (eg, human immunodeficiency virus) are at particular risk. Serological studies suggest that disease is most often secondary to the reactivation of an asymptomatic infection, usually acquired during childhood. Increasing shortness of breath, a nonproductive cough and hypoxia often preceded by several weeks of lethargy, fever and weight loss are the classical features ofP cariniipneumonia in acquired immune deficiency syndrome. Bronchoalveolar lavage is usually the optimal diagnostic test. Immunofluorescent staining on liquified sputum induced by nebulized saline appears to be a promising and noninvasive test. Early empiric therapy with trimethoprim-sulphamethoxazole (trimethoprim 5 mg-sulphamethoxazole 25 mg/kg/day every 6 h) or intravenous pentamidine (4 mg/kg/day) for 21 days is usually effective, but infection is not eradicated, and clinical disease is likely to recur. Prophylaxis using aerosolized pentamidine reduces the risk of pulmonary disease but can predispose to extrapulmonary infection. Improved in vitro and in vivo models of human pneumocystis infection would significantly increase understanding of the molecular biology of the organism, the pathogenesis of disease, and the optimal therapeutic regimens.

scholarly journals The biology of cutaneous neurofibromas

Neurology ◽  
2018 ◽  
Vol 91 (2 Supplement 1) ◽  
pp. S14-S20 ◽  
Author(s):  
Jean-Philippe Brosseau ◽  
Dominique C. Pichard ◽  
Eric H. Legius ◽  
Pierre Wolkenstein ◽  
Robert M. Lavker ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Research Priorities ◽  
Future Research ◽  
In Vivo Models ◽  
Cells Of Origin ◽  
Group Members ◽  
Multiple Levels

ObjectiveA group of experts in dermatology, genetics, neuroscience, and regenerative medicine collaborated to summarize current knowledge on the defined factors contributing to cutaneous neurofibroma (cNF) development and to provide consensus recommendations for future research priorities to gain an improved understanding of the biology of cNF.MethodsThe group members reviewed published and unpublished data on cNF and related diseases via literature search, defined a set of key topic areas deemed critical in cNF pathogenesis, and developed recommendations in a series of consensus meetings.ResultsFive specific topic areas were identified as being relevant to providing an enhanced understanding of the biology of cNF: (1) defining the human cells of origin; (2) understanding the role of the microenvironment, focusing on neurons, mast cells, and fibroblasts; (3) defining the genetic and molecular differences between the cNFs, focusing on size and number; (4) understanding if sex hormones are critical for cNF development or progression; and (5) identifying challenges in establishing in vitro and in vivo models representing human cNF.ConclusionsThe complexity of cNF biology stems from its heterogeneity at multiple levels including genetic, spatial involvement, temporal development, and cellular composition. We propose a unified working model for cNF that builds a framework to address the key questions about cNF that, when answered, will provide the necessary understanding of cNF biology to allow meaningful development of therapies.

scholarly journals The Role of the Gut-Brain Axis in Neurodegenerative Diseases and Relevance of the Canine Model: A Review

2019 ◽  
Author(s):  
Yoko Ambrosini ◽  
Dana Borcherding ◽  
Anumantha Kanthasamy ◽  
Hyun Jung Kim ◽  
Albert Jergens ◽  
...  
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Gut Microbiome ◽  
Individual Variability ◽  
Future Research ◽  
In Vivo Models ◽  
Advantages And Disadvantages ◽  
Amyloid A

Identifying appropriate animal models is critical in developing translatable in vitro and in vivo systems for therapeutic development and investigating disease pathophysiology. These animal models should have direct biological and translational relevance to the underlying disease they are supposed to mimic. Aging dogs naturally develop a cognitive decline in many aspects including learning and memory, but also exhibit human-like individual variability in the aging process. Neurodegenerative processes that can be observed in both human and canine brains include the progressive accumulation of β-amyloid (Aβ) found as diffuse plaques in the prefrontal cortex, including the gyrus proreus, the hippocampus, and in the cerebral vasculature. A growing body of epidemiological data shows that human patients with neurodegenerative diseases have concurrent intestinal lesions, and histopathological changes in the gastrointestinal (GI) tract occurs decades that evolve before neurodegenerative changes. Gut microbiome alterations also have been observed in many neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases, and inflammatory CNS diseases. Interestingly, only recently has the dog gut microbiome been recognized to more closely resemble in composition and in functional overlap with the human gut microbiome as compared to rodent models. This article aims to review the physiology of the gut-brain axis (GBA), and its involvement with neurodegenerative diseases in dogs and humans. Additionally, we outline the advantages and disadvantages of traditional in vitro and in vivo models and discuss future research directions investigating major human neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases using dogs.

scholarly journals Genetic characterization of the human relapsing fever spirochete Borrelia miyamotoi in vectors and animal reservoirs of Lyme disease spirochetes in France

2014 ◽  
Vol 7 (1) ◽  
pp. 233 ◽  
Author(s):  
Jean-François Cosson ◽  
Lorraine Michelet ◽  
Julien Chotte ◽  
Evelyne Le Naour ◽  
Martine Cote ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Genetic Characterization ◽  
Borrelia Miyamotoi ◽  
Relapsing Fever ◽  
Animal Reservoirs

Cell-Enhanced Acellular Nerve Allografts for Peripheral Nerve Reconstruction: A Systematic Review and a Meta-Analysis of the Literature

Neurosurgery ◽  
2018 ◽  
Vol 85 (5) ◽  
pp. 575-604 ◽  
Author(s):  
Francesca Alice Pedrini ◽  
Filippo Boriani ◽  
Federico Bolognesi ◽  
Nicola Fazio ◽  
Claudio Marchetti ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Case Reports ◽  
Case Series ◽  
Future Research ◽  
Nerve Reconstruction ◽  
Level Of Evidence ◽  
Promising Alternative ◽  
Positive Effects

Abstract BACKGROUND Peripheral nerve reconstruction is a difficult problem to solve. Acellular nerve allografts (ANAs) have been widely tested and are a promising alternative to the autologous gold standard. However, current reconstructive methods still yield unpredictable and unsuccessful results. Consequently, numerous studies have been carried out studying alternatives to plain ANAs, but it is not clear if nerve regeneration potential exists between current biological, chemical, and physical enrichment modes. OBJECTIVE To systematically review the effects of cell-enhanced ANAs on regeneration of peripheral nerve injuries. METHODS PubMed, ScienceDirect, Medline, and Scopus databases were searched for related articles published from 2007 to 2017. Inclusion criteria of selected articles consisted of (1) articles written in English; (2) the topic being cell-enhanced ANAs in peripheral nerve regeneration; (3) an in vivo study design; and (4) postgrafting neuroregenerative assessment of results. Exclusion criteria included all articles that (1) discussed central nervous system ANAs; (2) consisted of xenografts as the main topic; and (3) consisted of case series, case reports or reviews. RESULTS Forty papers were selected, and categorization included the animal model; the enhancing cell types; the decellularization method; and the neuroregenerative test performed. The effects of using diverse cellular enhancements combined with ANAs are discussed and also compared with the other treatments such as autologous nerve graft, and plain ANAs. CONCLUSION ANAs cellular enhancement demonstrated positive effects on recovery of nerve function. Future research should include clinical translation, in order to increase the level of evidence available on peripheral nerve reconstruction.

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