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American Family Physician Dec 2021Septic arthritis must be considered and promptly diagnosed in any patient presenting with acute atraumatic joint pain, swelling, and fever. Risk factors for septic...
Septic arthritis must be considered and promptly diagnosed in any patient presenting with acute atraumatic joint pain, swelling, and fever. Risk factors for septic arthritis include age older than 80 years, diabetes mellitus, rheumatoid arthritis, recent joint surgery, hip or knee prosthesis, skin infection, and immunosuppressive medication use. A delay in diagnosis and treatment can result in permanent morbidity and mortality. Physical examination findings and serum markers, including erythrocyte sedimentation rate and C-reactive protein, are helpful in the diagnosis but are nonspecific. Synovial fluid studies are required to confirm the diagnosis. History and Gram stain aid in determining initial antibiotic selection. Staphylococcus aureus is the most common pathogen isolated in septic arthritis; however, other bacteria, viruses, fungi, and mycobacterium can cause the disease. After synovial fluid has been obtained, empiric antibiotic therapy should be initiated if there is clinical concern for septic arthritis. Oral antibiotics can be given in most cases because they are not inferior to intravenous therapy. Total duration of therapy ranges from two to six weeks; however, certain infections require longer courses. Consideration for microorganisms such as Neisseria gonorrhoeae, Borrelia burgdorferi, and fungal infections should be based on history findings and laboratory results.
Topics: Anti-Bacterial Agents; Arthralgia; Arthritis, Infectious; Blood Sedimentation; Borrelia burgdorferi; Fever; Humans; Neisseria gonorrhoeae; Staphylococcus aureus; Synovial Fluid
PubMed: 34913662
DOI: No ID Found -
Nature Reviews. Rheumatology Aug 2021Infectious agents can trigger autoimmune responses in a number of chronic inflammatory diseases. Lyme arthritis, which is caused by the tick-transmitted spirochaete... (Review)
Review
Infectious agents can trigger autoimmune responses in a number of chronic inflammatory diseases. Lyme arthritis, which is caused by the tick-transmitted spirochaete Borrelia burgdorferi, is effectively treated in most patients with antibiotic therapy; however, in a subset of patients, arthritis can persist and worsen after the spirochaete has been killed (known as post-infectious Lyme arthritis). This Review details the current understanding of the pathogenetic events in Lyme arthritis, from initial infection in the skin, through infection of the joints, to post-infectious chronic inflammatory arthritis. The central feature of post-infectious Lyme arthritis is an excessive, dysregulated pro-inflammatory immune response during the infection phase that persists into the post-infectious period. This response is characterized by high amounts of IFNγ and inadequate amounts of the anti-inflammatory cytokine IL-10. The consequences of this dysregulated pro-inflammatory response in the synovium include impaired tissue repair, vascular damage, autoimmune and cytotoxic processes, and fibroblast proliferation and fibrosis. These synovial characteristics are similar to those in other chronic inflammatory arthritides, including rheumatoid arthritis. Thus, post-infectious Lyme arthritis provides a model for other chronic autoimmune or autoinflammatory arthritides in which complex immune responses can be triggered and shaped by an infectious agent in concert with host genetic factors.
Topics: Autoimmune Diseases; Autoimmunity; Borrelia burgdorferi; Humans; Inflammation; Lyme Disease
PubMed: 34226730
DOI: 10.1038/s41584-021-00648-5 -
Current Issues in Molecular Biology 2021Lyme disease (Lyme borreliosis) is a tick-borne, zoonosis of adults and children caused by genospecies of the sensu lato complex. The ailment, widespread throughout the...
Lyme disease (Lyme borreliosis) is a tick-borne, zoonosis of adults and children caused by genospecies of the sensu lato complex. The ailment, widespread throughout the Northern Hemisphere, continues to increase globally due to multiple environmental factors, coupled with increased incursion of humans into habitats that harbor the spirochete. sensu lato is transmitted by ticks from the complex. In North America, causes nearly all infections; in Europe, and are most associated with human disease. The spirochete's unusual fragmented genome encodes a plethora of differentially expressed outer surface lipoproteins that play a seminal role in the bacterium's ability to sustain itself within its enzootic cycle and cause disease when transmitted to its incidental human host. Tissue damage and symptomatology (i.e., clinical manifestations) result from the inflammatory response elicited by the bacterium and its constituents. The deposition of spirochetes into human dermal tissue generates a local inflammatory response that manifests as erythema migrans (EM), the hallmark skin lesion. If treated appropriately and early, the prognosis is excellent. However, in untreated patients, the disease may present with a wide range of clinical manifestations, most commonly involving the central nervous system, joints, or heart. A small percentage (~10%) of patients may go on to develop a poorly defined fibromyalgia-like illness, post-treatment Lyme disease (PTLD) unresponsive to prolonged antimicrobial therapy. Below we integrate current knowledge regarding the ecologic, epidemiologic, microbiologic, and immunologic facets of Lyme disease into a conceptual framework that sheds light on the disorder that healthcare providers encounter.
Topics: Animals; Arthropod Vectors; Borrelia burgdorferi; Disease Management; Disease Susceptibility; Host-Pathogen Interactions; Humans; Life Cycle Stages; Lyme Disease; Organ Specificity; Ticks
PubMed: 33303701
DOI: 10.21775/cimb.042.333 -
Clinical Infectious Diseases : An... Apr 2020Lyme disease, caused by some Borrelia burgdorferi sensu lato, is the most common tick-borne illness in the Northern Hemisphere and the number of cases, and geographic... (Clinical Trial)
Clinical Trial
Lyme disease, caused by some Borrelia burgdorferi sensu lato, is the most common tick-borne illness in the Northern Hemisphere and the number of cases, and geographic spread, continue to grow. Previously identified B. burgdorferi proteins, lipid immunogens, and live mutants lead the design of canonical vaccines aimed at disrupting infection in the host. Discovery of the mechanism of action of the first vaccine catalyzed the development of new strategies to control Lyme disease that bypassed direct vaccination of the human host. Thus, novel prevention concepts center on proteins produced by B. burgdorferi during tick transit and on tick proteins that mediate feeding and pathogen transmission. A burgeoning area of research is tick immunity as it can unlock mechanistic pathways that could be targeted for disruption. Studies that shed light on the mammalian immune pathways engaged during tick-transmitted B. burgdorferi infection would further development of vaccination strategies against Lyme disease.
Topics: Animals; Borrelia burgdorferi; Humans; Ixodes; Lyme Disease; Ticks; Vaccination; Vaccines
PubMed: 31620776
DOI: 10.1093/cid/ciz872 -
Cell Oct 2021Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently...
Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria. We therefore sought to identify a compound acting selectively against B. burgdorferi. A screen of soil micro-organisms revealed a compound highly selective against spirochetes, including B. burgdorferi. Unexpectedly, this compound was determined to be hygromycin A, a known antimicrobial produced by Streptomyces hygroscopicus. Hygromycin A targets the ribosomes and is taken up by B. burgdorferi, explaining its selectivity. Hygromycin A cleared the B. burgdorferi infection in mice, including animals that ingested the compound in a bait, and was less disruptive to the fecal microbiome than clinically relevant antibiotics. This selective antibiotic holds the promise of providing a better therapeutic for Lyme disease and eradicating it in the environment.
Topics: Animals; Anti-Bacterial Agents; Borrelia burgdorferi; Calibration; Cinnamates; Drug Evaluation, Preclinical; Feces; Female; HEK293 Cells; Hep G2 Cells; Humans; Hygromycin B; Lyme Disease; Mice; Microbial Sensitivity Tests; Microbiota
PubMed: 34619078
DOI: 10.1016/j.cell.2021.09.011 -
Nature Reviews. Microbiology Oct 2020Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted to vertebrate hosts by Ixodes spp. ticks. The spirochaete relies heavily on its arthropod... (Review)
Review
Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted to vertebrate hosts by Ixodes spp. ticks. The spirochaete relies heavily on its arthropod host for basic metabolic functions and has developed complex interactions with ticks to successfully colonize, persist and, at the optimal time, exit the tick. For example, proteins shield spirochaetes from immune factors in the bloodmeal and facilitate the transition between vertebrate and arthropod environments. On infection, B. burgdorferi induces selected tick proteins that modulate the vector gut microbiota towards an environment that favours colonization by the spirochaete. Additionally, the recent sequencing of the Ixodes scapularis genome and characterization of tick immune defence pathways, such as the JAK-STAT, immune deficiency and cross-species interferon-γ pathways, have advanced our understanding of factors that are important for B. burgdorferi persistence in the tick. In this Review, we summarize interactions between B. burgdorferi and I. scapularis during infection, as well as interactions with tick gut and salivary gland proteins important for establishing infection and transmission to the vertebrate host.
Topics: Animals; Arachnid Vectors; Arthropod Proteins; Borrelia burgdorferi; Gene Expression Regulation; Genome; Host-Pathogen Interactions; Humans; Intestines; Ixodes; Lyme Disease; Protein-Tyrosine Kinases; STAT Transcription Factors; Salivary Glands; Salivary Proteins and Peptides; Signal Transduction
PubMed: 32651470
DOI: 10.1038/s41579-020-0400-5 -
German Medical Science : GMS E-journal 2020Lyme borreliosis is the most common tick-borne infectious disease in Europe. A neurological manifestation occurs in 3-15% of infections and can manifest as...
Lyme borreliosis is the most common tick-borne infectious disease in Europe. A neurological manifestation occurs in 3-15% of infections and can manifest as polyradiculitis, meningitis and (rarely) encephalomyelitis. This S3 guideline is directed at physicians in private practices and clinics who treat Lyme neuroborreliosis in children and adults. Twenty AWMF member societies, the Robert Koch Institute, the German Borreliosis Society and three patient organisations participated in its development. A systematic review and assessment of the literature was conducted by the German Cochrane Centre, Freiburg (Cochrane Germany). The main objectives of this guideline are to define the disease and to give recommendations for the confirmation of a clinically suspected diagnosis by laboratory testing, antibiotic therapy, differential diagnostic testing and prevention.
Topics: Adult; Animals; Borrelia burgdorferi; Child; Clinical Laboratory Techniques; Diagnosis, Differential; Disease Vectors; Erythema Chronicum Migrans; Germany; Humans; Lyme Neuroborreliosis; Patient Care Management; Post-Lyme Disease Syndrome; Preventive Health Services
PubMed: 32341686
DOI: 10.3205/000279 -
BMC Microbiology Aug 2023With almost 700 000 estimated cases each year in the United States and Europe, Lyme borreliosis (LB), also called Lyme disease, is the most common tick-borne illness in... (Review)
Review
With almost 700 000 estimated cases each year in the United States and Europe, Lyme borreliosis (LB), also called Lyme disease, is the most common tick-borne illness in the world. Transmitted by ticks of the genus Ixodes and caused by bacteria Borrelia burgdorferi sensu lato, LB occurs with various symptoms, such as erythema migrans, which is characteristic, whereas others involve blurred clinical features such as fatigue, headaches, arthralgia, and myalgia. The diagnosis of Lyme borreliosis, based on a standard two-tiered serology, is the subject of many debates and controversies, since it relies on an indirect approach which suffers from a low sensitivity depending on the stage of the disease. Above all, early detection of the disease raises some issues. Inappropriate diagnosis of Lyme borreliosis leads to therapeutic wandering, inducing potential chronic infection with a strong antibody response that fails to clear the infection. Early and proper detection of Lyme disease is essential to propose an adequate treatment to patients and avoid the persistence of the pathogen. This review presents the available tests, with an emphasis on the improvements of the current diagnosis, the innovative methods and ideas which, ultimately, will allow more precise detection of LB.
Topics: Animals; Humans; Lyme Disease; Borrelia burgdorferi; Ixodes; Europe
PubMed: 37528399
DOI: 10.1186/s12866-023-02935-5 -
Virulence Dec 2023Infection with often triggers pathophysiologic perturbations that are further augmented by the inflammatory responses of the host, resulting in the severe clinical... (Review)
Review
Infection with often triggers pathophysiologic perturbations that are further augmented by the inflammatory responses of the host, resulting in the severe clinical conditions of Lyme disease. While our apprehension of the spatial and temporal integration of the virulence determinants during the enzootic cycle of is constantly being improved, there is still much to be discovered. Many of the novel virulence strategies discussed in this review are undetermined. Lyme disease spirochaetes must surmount numerous molecular and mechanical obstacles in order to establish a disseminated infection in a vertebrate host. These barriers include borrelial relocation from the midgut of the feeding tick to its body cavity and further to the salivary glands, deposition to the skin, haematogenous dissemination, extravasation from blood circulation system, evasion of the host immune responses, localization to protective niches, and establishment of local as well as distal infection in multiple tissues and organs. Here, the various well-defined but also possible novel strategies and virulence mechanisms used by to evade obstacles laid out by the tick vector and usually the mammalian host during colonization and infection are reviewed.
Topics: Animals; Humans; Borrelia burgdorferi; Virulence; Lyme Disease; Virulence Factors; Mammals
PubMed: 37814488
DOI: 10.1080/21505594.2023.2265015 -
Parasite Immunology May 2021The bacterial pathogen Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted to humans through an Ixodes tick vector. B. burgdorferi is able to... (Review)
Review
The bacterial pathogen Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted to humans through an Ixodes tick vector. B. burgdorferi is able to survive in both mammalian and tick hosts through careful modulation of its gene expression. This allows B. burgdorferi to adapt to the environmental and nutritional changes that occur when it is transmitted between the two hosts. Distinct interactions between the spirochete and its host occur at every step of the enzootic cycle and dictate the ability of the spirochete to survive until the next stage of the cycle. Studying the interface between B. burgdorferi, the Ixodes tick vector and the natural mammalian reservoirs has been made significantly more feasible through the complete genome sequences of the organisms and the advent of high throughput screening technologies. Ultimately, a thorough investigation of the interplay between the two domains (and two phyla within one domain) is necessary in order to completely understand how the pathogen is transmitted.
Topics: Animals; Arachnid Vectors; Borrelia burgdorferi; Gene Expression; Host Microbial Interactions; Humans; Ixodes; Lyme Disease; Mammals; Microbiota; Nymph; Salivary Glands
PubMed: 33368329
DOI: 10.1111/pim.12816