Late-stage borreliosis and substance abuse.

Background: Infectious diseases can contribute to substance abuse. Here, a fatal case of borreliosis and substance abuse is reported. This patient had a history of multiple tick bites and increasing multisystem symptoms, yet diagnosis and treatment were delayed.

A comparison of Bartonella henselae infection in immunocompetent and immunocompromised mice.

Bartonellosis refers to disease caused by the Bartonella genus of bacteria. The breadth of disease manifestations associated with Bartonella is currently expanding and includes regional lymphadenopathy, rheumatic, ocular, and neurological disorders. The dearth of knowledge regarding diagnosis, treatment and pathogenesis of this disease can be partially attributed to the lack of a reliable small animal model for the disease.

Evaluation of the available animal models for infections.

The diseases caused by the genus of bacteria are clinically diverse, and can be challenging to cure. The study of bartonellosis has been hampered by the lack of a suitable animal model. Preclinical studies for novel therapeutics and a competent host for vector transmission studies are needed to fill critical knowledge gaps.

Direct Detection of Borrelia Species in Tissues.

Among the controversies in Lyme disease is the potential for Borrelia spirochetes to persist after guideline-directed antimicrobial therapy. Direct detection of the spirochetes has been essential to explore this phenomenon, given that the infection is often occult and infrequently observed in blood and other body fluids. In addition, the role of spirochetal infection has been examined in the etiology of neurodegenerative diseases through detection in affected tissues.

Superior efficacy of combination antibiotic therapy versus monotherapy in a mouse model of Lyme disease.

Lyme disease (LD) results from the most prevalent tick-borne infection in North America, with over 476,000 estimated cases annually. The disease is caused by which transmits through the bite of Ixodid ticks. Most cases treated soon after infection are resolved by a short course of oral antibiotics.

Targeting Borrelia burgdorferi HtpG with a berserker molecule, a strategy for anti-microbial development.

Conventional antimicrobial discovery relies on targeting essential enzymes in pathogenic organisms, contributing to a paucity of new antibiotics to address resistant strains. Here, by targeting a non-essential enzyme, Borrelia burgdorferi HtpG, to deliver lethal payloads, we expand what can be considered druggable within any pathogen. We synthesized HS-291, an HtpG inhibitor tethered to the photoactive toxin verteporfin.

The Probable Infectious Origin of Multiple Sclerosis.

Multiple sclerosis (MS) is an immune inflammatory disease that causes demyelination of the white matter of the central nervous system. It is generally accepted that the etiology of MS is multifactorial and believed to be a complex interplay between genetic susceptibility, environmental factors, and infectious agents. While the exact cause of MS is still unknown, increasing evidence suggests that disease development is the result of interactions between genetically susceptible individuals and the environment that lead to immune dysregulation and CNS inflammation.

Lyme disease and the pursuit of a clinical cure.

Lyme disease, caused by the spirochete , is the most common vector-borne illness in the United States. Many aspects of the disease are still topics of controversy within the scientific and medical communities. One particular point of debate is the etiology behind antibiotic treatment failure of a significant portion (10-30%) of Lyme disease patients.

Repeated Tick Infestations Impair Transmission in a Non-Human Primate Model of Tick Feeding.

The blacklegged tick, , is the predominant vector of , the agent of Lyme disease in the USA. Natural hosts of such as are repeatedly infested by these ticks without acquiring tick resistance. However, upon repeated tick infestations, non-natural hosts such as guinea pigs, mount a robust immune response against critical tick salivary antigens and acquire tick resistance able to thwart tick feeding and transmission.

Direct Capture and Early Detection of Lyme Disease Spirochete in Skin with a Microneedle Patch.

sensu lato family of spirochetes causes Lyme disease (LD) in animals and humans. As geographic territory of ticks expands across the globe, surveillance measures are needed to measure transmission rates and provide early risk testing of suspected bites. The current standard testing of LD uses an indirect two-step serological assay that detects host immune reactivity.

Migration Assays for Evaluation of Chemoattractants in Tick Saliva.

Uptake of the Lyme disease spirochete by its tick vector requires not only chemical signals present in the tick's saliva but a responsive phenotype by the living in the mammalian host. This is the principle behind xenodiagnosis, wherein pathogen is detected by vector acquisition. To study migration of toward tick saliva, with the goal of identifying chemoattractant molecules, we tested multiple assays and compared migration of host-adapted spirochetes to those cultured in vitro.

Identification of microRNAs in the Lyme Disease Vector .

MicroRNAs (miRNAs) are a class of small non-coding RNAs involved in many biological processes, including the immune pathways that control bacterial, parasitic, and viral infections. Pathogens probably modify host miRNAs to facilitate successful infection, so they might be useful targets for vaccination strategies. There are few data on differentially expressed miRNAs in the black-legged tick after infection with , the causative agent of Lyme disease in the United States.

Characterization of Immunological Responses to Immunogenic Protein A (BipA), a Species-Specific Antigen for North American Tick-Borne Relapsing Fever.

Tick-borne relapsing fever (TBRF) is a neglected vector-borne bacterial disease distributed worldwide. Borrelia turicatae, Borrelia parkeri, and Borrelia hermsii are three argasid-borne TBRF species previously implicated in human disease in North America. TBRF is likely underdiagnosed due to its nonspecific symptoms and poorly developed diagnostic tests.

Does Dementia Have a Microbial Cause?

The potential contribution of pathogenic microbes to dementia-inducing disease is a subject of considerable importance. Alzheimer's disease (AD) is a neurocognitive disease that slowly destroys brain function, leading to cognitive decline and behavioral and psychiatric disorders. The histopathology of AD is associated with neuronal loss and progressive synaptic dysfunction, accompanied by the deposition of amyloid-β (Aβ) peptide in the form of parenchymal plaques and abnormal aggregated tau protein in the form of neurofibrillary tangles.

Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease Syndromes.

The annual incidence of Lyme disease, caused by tick-transmitted Borreliella burgdorferi, is estimated to be at least 476,000 cases in the United States and many more worldwide. Ten to 20% of antimicrobial-treated Lyme disease patients display posttreatment Lyme disease syndrome (PTLDS), a clinical complication whose etiology and pathogenesis remain uncertain. Autoimmunity, cross-reactivity, molecular mimicry, coinfections, and borrelial tolerance to antimicrobials/persistence have been hypothesized and studied as potential causes of PTLDS.

An Exploratory Study on the Microbiome of Northern and Southern Populations of Ticks Predicts Changes and Unique Bacterial Interactions.

The black-legged tick () is the primary vector of , the causative agent of Lyme disease in North America. However, the prevalence of Lyme borreliosis is clustered around the Northern States of the United States of America. This study utilized a metagenomic sequencing approach to compare the microbial communities residing within populations from northern and southern geographic locations in the USA.

Improving rigor and reproducibility in nonhuman primate research.

Nonhuman primates (NHPs) are a critical component of translational/preclinical biomedical research due to the strong similarities between NHP and human physiology and disease pathology. In some cases, NHPs represent the most appropriate, or even the only, animal model for complex metabolic, neurological, and infectious diseases. The increased demand for and limited availability of these valuable research subjects requires that rigor and reproducibility be a prime consideration to ensure the maximal utility of this scarce resource.

Recent Progress in Lyme Disease and Remaining Challenges.

Lyme disease (also known as Lyme borreliosis) is the most common vector-borne disease in the United States with an estimated 476,000 cases per year. While historically, the long-term impact of Lyme disease on patients has been controversial, mounting evidence supports the idea that a substantial number of patients experience persistent symptoms following treatment. The research community has largely lacked the necessary funding to properly advance the scientific and clinical understanding of the disease, or to develop and evaluate innovative approaches for prevention, diagnosis, and treatment.

Antibiotic Susceptibility of Bartonella Grown in Different Culture Conditions.

Bartonellosis is caused by a Gram-negative intracellular bacterium with a zoonotic transmission. The disease, caused by any of several genospecies of can range from a benign, self-limited condition to a highly morbid and life-threatening illness. The current standard of care antibiotics are generally effective in acute infection; these include azithromycin or erythromycin, doxycycline, gentamicin, rifampin, and ciprofloxacin.

Report of the Pathogenesis and Pathophysiology of Lyme Disease Subcommittee of the HHS Tick Borne Disease Working Group.

An understanding of the pathogenesis and pathophysiology of Lyme disease is key to the ultimate care of patients with Lyme disease. To better understand the various mechanisms underlying the infection caused by , the Pathogenesis and Pathophysiology of Lyme Disease Subcommittee was formed to review what is currently known about the pathogenesis and pathophysiology of Lyme disease, from its inception, but also especially about its ability to persist in the host. To that end, the authors of this report were assembled to update our knowledge about the infectious process, identify the gaps that exist in our understanding of the process, and provide recommendations as to how to best approach solutions that could lead to a better means to manage patients with persistent Lyme disease.

Detecting Borrelia Spirochetes: A Case Study With Validation Among Autopsy Specimens.

The complex etiology of neurodegenerative disease has prompted studies on multiple mechanisms including genetic predisposition, brain biochemistry, immunological responses, and microbial insult. In particular, Lyme disease is often associated with neurocognitive impairment with variable manifestations between patients. We sought to develop methods to reliably detect , the spirochete bacteria responsible for Lyme disease, in autopsy specimens of patients with a history of neurocognitive disease.

Blocking Borrelia burgdorferi transmission from infected ticks to nonhuman primates with a human monoclonal antibody.

Disrupting transmission of Borrelia burgdorferi sensu lato complex (B. burgdorferi) from infected ticks to humans is one strategy to prevent the significant morbidity from Lyme disease. We have previously shown that an anti-OspA human mAb, 2217, prevents transmission of B.

Visualizing Borrelia burgdorferi Infection Using a Small-Molecule Imaging Probe.

diagnostic imaging of bacterial infections is currently reliant on targeting their metabolic pathways, an ineffective method to identify microbial species with low metabolic activity. Here, we establish HS-198 as a small-molecule fluorescent conjugate that selectively targets the highly conserved bacterial protein HtpG (high-temperature protein G), within Borrelia burgdorferi, the bacterium responsible for Lyme disease. We describe the use of HS-198 to target morphologic forms of B.