Neuropathogenicity of non-viable Borrelia burgdorferi ex vivo

Even after appropriate treatment, a proportion of Lyme disease patients suffer from a constellation of symptoms, collectively called Post-Treatment Lyme Disease Syndrome (PTLDS). Brain PET scan of patients with PTLDS have demonstrated likely glial activation indicating persistent neuroinflammatory processes. It is possible that unresolved bacterial remnants can continue to cause neuroinflammation. In previous studies, we have shown that non-viable Borrelia burgdorferi can induce neuroinflammation and apoptosis in an oligodendrocyte cell line. In this follow-up study, we analyze the effect of sonicated remnants of B. burgdorferi on primary rhesus frontal cortex (FC) and dorsal root ganglion (DRG) explants. Five FC and three DRG tissue fragments from rhesus macaques were exposed to sonicated B. burgdorferi and analyzed for 26 inflammatory mediators. Live bacteria and medium alone served as positive and negative control, respectively. Tissues were also analyzed for cell types mediating inflammation and overall apoptotic changes. Non-viable B. burgdorferi induced significant levels of several inflammatory mediators in both FC and DRG, similar to live bacteria. However, the levels induced by non-viable B. burgdorferi was often (several fold) higher than those induced by live ones, especially for IL-6, CXCL8 and CCL2. This effect was also more profound in the FC than in the DRG. Although the levels often differed, both live and dead fragments induced the same mediators, with significant overlap between FC and DRG. In the FC, immunohistochemical staining for several inflammatory mediators showed the presence of multiple mediators in astrocytes, followed by microglia and oligodendrocytes, in response to bacterial remnants. Staining was also seen in endothelial cells. In the DRG, chemokine/cytokine staining was predominantly seen in S100 positive (glial) cells. B. burgdorferi remnants also induced significant levels of apoptosis in both the FC and DRG. Apoptosis was confined to S100 + cells in the DRG while distinct neuronal apoptosis was also detected in most FC tissues in response to sonicated bacteria. Non-viable B. burgdorferi can continue to be neuropathogenic to both CNS and PNS tissues with effects likely more profound in the former. Persistence of remnant-induced neuroinflammatory processes can lead to long term health consequences.

Ecology of Ixodes pacificus Ticks and Associated Pathogens in the Western United States

Lyme disease is the most important vector-borne disease in the United States and is increasing in incidence and geographic range. In the Pacific west, the western black-legged tick, Ixodes pacificus Cooley and Kohls, 1943 is an important vector of the causative agent of Lyme disease, the spirochete, Borrelia burgdorferi. Ixodes pacificus life cycle is expected to be more than a year long, and all three stages (larva, nymph, and adult) overlap in spring. The optimal habitat consists of forest cover, cooler temperatures, and annual precipitation in the range of 200–500 mm. Therefore, the coastal areas of California, Oregon, and Washington are well suited for these ticks. Immature stages commonly parasitize Western fence lizards (Sceloporus occidentalis) and gray squirrels (Sciurus griseus), while adults often feed on deer mice (Peromyscus maniculatus) and black-tailed deer (Odocoileus h. columbianus). Ixodes pacificus carry several pathogens of human significance, such as Borrelia burgdorferi, Bartonella, and Rickettsiales. These pathogens are maintained in the environment by many hosts, including small mammals, birds, livestock, and domestic animals. Although a great deal of work has been carried out on Ixodes ticks and the pathogens they transmit, understanding I. pacificus ecology outside California still lags. Additionally, the dynamic vector–host–pathogen system means that new factors will continue to arise and shift the epidemiological patterns within specific areas. Here, we review the ecology of I. pacificus and the pathogens this tick is known to carry to identify gaps in our knowledge.

Extraction and Fractionation of Bioactives from Dipsacus fullonum L. Leaves and Evaluation of Their Anti-Borrelia Activity

Lyme disease (LD) is a tick-borne bacterial disease that is caused by Borrelia burgdorferi. Although acute LD is treated with antibiotics, it can develop into relapsing chronic form caused by latent forms of B. burgdorferi. This leads to the search for phytochemicals against resistant LD. Therefore, this study aimed to evaluate the activity of Dipsacus fullonum L. leaves extract (DE) and its fractions against stationary phase B. burgdorferi in vitro. DE showed high activity against stationary phase B. burgdorferi (residual viability 19.8 ± 4.7%); however, it exhibited a noticeable cytotoxicity on NIH cells (viability 20.2 ± 5.2%). The iridoid-glycoside fraction showed a remarkable anti-Borrelia effect and reduced cytotoxicity. The iridoid-glycoside fraction was, therefore, further purified and showed to contain two main bioactives—sylvestrosides III and IV, that showed a considerable anti-Borrelia activity being the least toxic to murine fibroblast NIH/3T3 cells. Moreover, the concentration of sylvestrosides was about 15% of DE, endorsing the feasibility of purification of the compounds from D. fullonum L. leaves.

Pediatric unilateral knee swelling: a case report of a complicated differential diagnosis and often overlooked cause

Lyme disease is the most common vector-borne illness in the United States. However, Lyme arthritis is a diagnosis that is often missed, even in children, who are the population with the highest incidence of Lyme disease. Lyme arthritis, which presents in the later stage of Borrelia burgdorferi infection, needs to be recognized and managed promptly, especially in endemic areas or when exposure to ticks is known. We present a case of a 3-year-old female presenting to the emergency department with a history of limping for 2 weeks. The mother of the child recognized a tick bite. However, the child was not taken to seek care expeditiously, because she had not developed any rashes. Test results demonstrated that the patient was IgG positive and IgM negative for Lyme disease, with Western blot confirming the diagnosis of Lyme arthritis. Most patients presenting with Lyme arthritis do not recall having a tick bite, making it difficult to differentiate it from other pediatric conditions. When this diagnosis is missed, it can result in long-term morbidity, which is generally refractory to intravenous antibiotic therapy, oftentimes requiring synovectomy. Hence, this underscores the importance of the consideration of Lyme arthritis as a differential diagnosis in patients presenting with joint effusion.

Host contributions to the force of Borrelia burgdorferi and Babesia microti transmission differ at edges of and within a small habitat patch

In the northeastern United States, the emergence of Lyme disease has been associated, in part, with the increase of small forest patches. Such disturbed habitat is exploited by generalist species, such as white-footed mice, which are considered the host with the greatest reservoir capacity for the agents of Lyme disease ( Borrelia burgdorferi sensu stricto) and human babesiosis ( Babesia microti ). Spatial risk analyses have identified edge habitat as particularly risky. Using a retrotransposon-based quantitative PCR assay for host bloodmeal remnant identification, we directly measured whether the hosts upon which vector ticks fed differed at the edge or within the contiguous small habitat patch. Questing nymphal deer ticks, Ixodes dammini , the northern clade of Ixodes scapularis , were collected from either the edge or within a thicket on Nantucket Island over 3 transmission seasons and tested for evidence of infection as well as bloodmeal hosts. Tick bloodmeal hosts significantly differed by site as well as by year. Mice and deer were identified most often (49.9%), but shrews, rabbits and birds were also common. Ticks from the edge fed on a greater diversity of hosts than those from the thicket. Surprisingly, mice were not strongly associated with either infection at either sampling site (OR<2 for all). Although shrews were not the most common host utilized by ticks, they were highly associated with both infections at both sites (OR= 4.5 and 7.9 B. burgdorferi and 7.9 and 19.0 B. microti , edge and thicket). We conclude that reservoir hosts may differ in their contributions to infecting ticks between edge and contiguous vegetated patches. Importance Habitat fragmentation is thought to be a main factor in the emergence of Lyme disease and other of the deer tick-transmitted infections. The patchwork of forest and edges promotes altered biodiversity, favoring the abundance of generalist rodents such as white footed mice, heretofore considered a key tick and reservoir host in the northeastern U.S. We used tick bloodmeal analyses to directly identify the hosts from which nymphal deer ticks became infected. We demonstrate that there is considerable microfocality in host contributions to the cohort of infected ticks and that shrews, although they fed fewer ticks than mice, disproportionately influenced the force of pathogen transmission in our site. The venue of transmission of certain deer tick-transmitted agents may comprise a habitat scale of 10 meters or fewer and depend on alternative small mammal hosts such as shrews.

Disulfiram: A repurposed drug in preclinical and clinical development for the treatment of infectious diseases

This article reviews preclinical and clinical studies on the repurposed use of disulfiram (Antabuse) as an antimicrobial agent. Preclinical research covered on the alcohol sobriety aid include uses as an anti-MRSA agent, a carbapenamase inhibitor, antifungal drug for candidiasis, and a treatment for parasitic diseases due to protozoa (e.g., giardiasis, leishmaniasis, malaria) and helminthes (e.g., schistosomiasis, trichuriasis). Past, current, and pending clinical studies on disulfiram as a post-Lyme disease syndrome (PTLDS) therapy, an HIV latency reversal agent, and an intervention for COVID-19 infections are also reviewed.

The Impact of a Pandemic COVID-19 on the Incidence of Borreliosis in Poland

Purpose Lyme disease is the most common tick-borne disease, caused by spirochetes of the genus Borrelia, transmitted by ticks of the Ixodes genus in Poland. The purpose of this analysis was whether the COVID-19 outbreak had a significant impact on the number of reported Lyme disease cases. Materials and Methods The data included in the World Health Organization (WHO) and the data from the “Reports on incidence of infectious diseases, infections and poisoning in Poland” presented by the Department of Epidemiology NIZP-PZH were analyzed. Results To the end of 2020, there were registered 12, 524 Lyme disease cases. In the same period, in 2018 and 2019 were registered, respectively, 20, 150 and 20, 614 Lyme disease cases. The overall number of Lyme disease cases in 2018 and 2019 was at a similar level. The monthly increase in the number of cases was also at a similar level. The year 2020 in January and February was characterized by the same increase in the number of cases as in previous years. The difference started to be noticeable in March and the lowered growth compared to the previous years has been maintained to this day. In December, about 8, 000 fewer cases of Lyme disease were registered than in previous years. Conclusion The reduced number of cases of Lyme disease coincided with the beginning of the COVID-19 epidemic in Poland in March 2020. Every year, the incidence of Lyme disease in Poland is at a similar level with a similar monthly increase. The outbreak of the COVID-19 pandemic had a significant impact on the number of cases recorded, which could have catastrophic consequences for people who did not receive treatment in the right time.

Baptism of fire: Modeling the effects of prescribed fire on tick-borne disease

Recently, tick-borne illnesses have been trending upward and are an increasing source of risk to people's health in the United States. This is due to range expansion in tick habitats as a result of climate change. Thus, it is imperative to find a practical and cost-efficient way of managing tick populations. Prescribed burns are a common form of land management that can be cost efficient if properly managed and can be applied across large amounts of land. In this study, we present a compartmental model for ticks carrying Lyme disease and uniquely incorporate the effects of prescribed fire using an impulsive system to investigate the effects of prescribed fire intensity (high and low) and the duration between burns. Our study found that fire intensity has a larger impact in reducing tick population than the frequency between burns. Furthermore, burning at high intensity is preferable to burning at low intensity whenever possible, although high intensity burns may be unrealistic due to environmental factors. Annual burns resulted in the most significant reduction of infectious nymphs, which are the primary carriers of Lyme disease.