43 < Back to Research Top Published Date 02/09/2020 Targeted metagenomics for clinical detection and discovery of bacterial tickborne pathogens Journal Journal of Clinical Microbiology Citation J Clin Microbiol 2020 Sep 2; JCM.00147-20 DOI 10.1128/JCM.00147-20 Authors Kingry L 4, Sheldon S, Oatman S, Pritt B, Anacker M, Bjork J, Neitzel D, Strain A, Berry J, Sloan L, Respicio-Kingry L, Dietrich E, Bloch K, Moncayo A, Srinivasamoorthy G, Hu B, Hinckley A, Mead P, Kugeler K, Petersen J Abstract Tickborne diseases, due to a diversity of bacterial pathogens, represent a significant and increasing public health threat throughout the northern hemisphere. A high-throughput 16S V1-V2 rDNA-based metagenomics assay was developed and evaluated using >13,000 residual samples from patients suspected of tickborne illness and >1000 controls. Taxonomic predictions for tickborne bacteria were exceptionally accurate, as independently validated by secondary testing. Overall, 881 specimens were positive for bacterial tickborne agents. Twelve tickborne bacterial species were detected, including two novel pathogens, representing a 100% increase in the number of tickborne bacteria identified compared to what was possible by initial PCR testing. In three blood specimens, two tickborne bacteria were simultaneously detected. Seven bacteria, not known to be tick-transmitted, were also confirmed unique to samples from persons suspected of tickborne illness. These results indicate 16S V1-V2 metagenomics can greatly simplify diagnosis and accelerate discovery of bacterial tickborne pathogens. URL Previous https://jcm.asm.org/content/58/11/e00147-20.long No Review Needed? Next

279 < Back to Research Top Published Date 18/12/2010 'Rare' infections mimicking multiple sclerosis: consider Lyme disease Journal Clinical Neurology and Neurosurgery Citation Clin Neurol Neurosurg. 2011 Apr;113(3):259-60 DOI 10.1016/j.clineuro.2010.11.017 Authors Stricker RB , Johnson L Abstract URL Previous https://www.ncbi.nlm.nih.gov/pubmed/21168953 No Review Needed? Next

288 < Back to Research Top Published Date 12/05/2010 Morgellons disease: Analysis of a population with clinically confirmed microscopic subcutaneous fibers of unknown etiology Journal Clinical, Cosmetic and Investigational Dermatology Citation Clin Cosmet Investig Dermatol. 2010 May 13;3:67-78 DOI Authors Savely VR, Stricker RB Abstract BACKGROUND: Morgellons disease is a controversial illness in which patients complain of stinging, burning, and biting sensations under the skin. Unusual subcutaneous fibers are the unique objective finding. The etiology of Morgellons disease is unknown, and diagnostic criteria have yet to be established. Our goal was to identify prevalent symptoms in patients with clinically confirmed subcutaneous fibers in order to develop a case definition for Morgellons disease. METHODS: Patients with subcutaneous fibers observed on physical examination (designated as the fiber group) were evaluated using a data extraction tool that measured clinical and demographic characteristics. The prevalence of symptoms common to the fiber group was then compared with the prevalence of these symptoms in patients with Lyme disease and no complaints of skin fibers. RESULTS: The fiber group consisted of 122 patients. Significant findings in this group were an association with tick-borne diseases and hypothyroidism, high numbers from two states (Texas and California), high prevalence in middle-aged Caucasian women, and an increased prevalence of smoking and substance abuse. Although depression was noted in 29% of the fiber patients, pre-existing delusional disease was not reported. After adjusting for nonspecific symptoms, the most common symptoms reported in the fiber group were: crawling sensations under the skin; spontaneously appearing, slow-healing lesions; hyperpigmented scars when lesions heal; intense pruritus; seed-like objects, black specks, or "fuzz balls" in lesions or on intact skin; fine, thread-like fibers of varying colors in lesions and intact skin; lesions containing thick, tough, translucent fibers that are highly resistant to extraction; and a sensation of something trying to penetrate the skin from the inside out. CONCLUSIONS: This study of the largest clinical cohort reported to date provides the basis for an accurate and clinically useful case definition for Morgellons disease. URL Previous https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047951 No Review Needed? Next

76 < Back to Research Top Published Date 04/02/2020 Lymelight: forecasting Lyme disease risk using web search data Journal Nature Partner Journal Digital Medicine Citation 03:16 DOI 10.1038/s41746-020-0222-x Authors Sadilek A, Hswen Y, Bavadekar S, Shekel T, Brownstein JS, Gabrilovich E Abstract Lyme disease is the most common tick-borne disease in the Northern Hemisphere. Existing estimates of Lyme disease spread are delayed a year or more. We introduce Lymelight-a new method for monitoring the incidence of Lyme disease in real-time. We use a machine-learned classifier of web search sessions to estimate the number of individuals who search for possible Lyme disease symptoms in a given geographical area for two years, 2014 and 2015. We evaluate Lymelight using the official case count data from CDC and find a 92% correlation (p < 0.001) at county level. Importantly, using web search data allows us not only to assess the incidence of the disease, but also to examine the appropriateness of treatments subsequently searched for by the users. Public health implications of our work include monitoring the spread of vector-borne diseases in a timely and scalable manner, complementing existing approaches through real-time detection, which can enable more timely interventions. Our analysis of treatment searches may also help reduce misdiagnosis of the disease. URL Previous https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000681/ No Review Needed? Next

187 < Back to Research Top Published Date 24/07/2015 Biofilm formation by Borrelia burgdorferi sensu lato Journal FEMS Microbiology Letters Citation FEMS Microbiol Lett. 2015 Aug;362(15):fnv120 DOI 10.1093/femsle/fnv120 Authors Timmaraju VA, Theophilus PA, Balasubramanian K, Shakih S, Luecke DF, Sapi E Abstract Bacterial biofilms are microbial communities held together by an extracellular polymeric substance matrix predominantly composed of polysaccharides, proteins and nucleic acids. We had previously shown that Borrelia burgdorferi sensu stricto, the causative organism of Lyme disease in the United States is capable of forming biofilms in vitro. Here, we investigated biofilm formation by B. afzelii and B. garinii, which cause Lyme disease in Europe. Using various histochemistry and microscopy techniques, we show that B. afzelii and B. garinii form biofilms, which resemble biofilms formed by B. burgdorferi sensu stricto. High-resolution atomic force microscopy revealed similarities in the ultrastructural organization of the biofilms form by three Borrelia species. Histochemical experiments revealed a heterogeneous organization of exopolysaccharides among the three Borrelia species. These results suggest that biofilm formation might be a common trait of Borreliagenera physiology. URL Previous https://academic.oup.com/femsle/article/362/15/fnv120/550276 No Review Needed? Next

132 < Back to Research Top Published Date 25/07/2018 Far-Reaching Dispersal of Borrelia burgdorferi Sensu Lato-Infected Blacklegged Ticks by Migratory Songbirds in Canada Journal Healthcare (Basel, Switzerland) Citation Healthcare (Basel). 2018 6, 89. DOI 10.3390/healthcare6030089 Authors Scott JD, Clark KL, Foley JE, Bierman BC, Durden LA Abstract Lyme disease has been documented in northern areas of Canada, but the source of the etiological bacterium, Borrelia burgdorferi sensulato (Bbsl) has been in doubt. We collected 87 ticks from 44 songbirds during 2017, and 24 (39%) of 62 nymphs of the blacklegged tick, Ixodes scapularis, were positive for Bbsl. We provide the first report of Bbsl-infected, songbird-transported I. scapularis in Cape Breton, Nova Scotia; Newfoundland and Labrador; north-central Manitoba, and Alberta. Notably, we report the northernmost account of Bbsl-infected ticks parasitizing a bird in Canada. DNA extraction, PCR amplification, and DNA sequencing reveal that these Bbsl amplicons belong to Borrelia burgdorferi sensu stricto (Bbss), which is pathogenic to humans. Based on our findings, health-care providers should be aware that migratory songbirds widely disperse B. burgdorferi-infected I. scapularis in Canada's North, and local residents do not have to visit an endemic area to contract Lyme disease. URL Previous https://www.mdpi.com/2227-9032/6/3/89 No Review Needed? Next

257 < Back to Research Top Published Date 01/02/2012 Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here? Journal Quality of Life Research Citation Qual Life Res. 2013 Feb;22(1):75-84 DOI 10.1007/s11136-012-0126-6 Authors Aucott JN, Rebman AW, Crowder LA, Kortte KB Abstract PURPOSE: A subset of patients treated for Lyme disease report persistent or recurrent symptoms of unknown etiology named post-treatmentLyme disease syndrome (PTLDS). This study aims to describe a cohort of participants with early, untreated Lyme disease, and characterize post-treatment symptomatology and functional impact of PTLDS over time. METHODS: Sixty-three participants with erythema migrans and systemic symptoms were enrolled in a prospective cohort study. Participants underwent physical exams and clinical assessments, and completed the SF-36 (daily life functioning) and the Beck Depression Inventory, Second Edition (BDI-II) (depression), at each of five visits over a period of 6 months. RESULTS: Signs of Lyme disease disappeared post-treatment; however, new-onset patient-reported symptoms increased or plateaued over time. At 6 months, 36% of patients reported new-onset fatigue, 20% widespread pain, and 45% neurocognitive difficulties. However, less than 10% reported greater than "minimal" depression across the entire period. Those with PTLDS (36%) did not differ significantly from those without with respect to demographics, pre-treatment SF-36, and BDI-II scores. Statistically significant differences were found over time on the Role Physical, Vitality, Social Functioning, Role Emotional, and Mental Health subscales (with a trend toward significance for the remaining three subscales of Physical Functioning, Bodily Pain, and General Health) of the SF-36 between those with an eventual PTLDS diagnosis and those without when measured at 6 months. CONCLUSIONS: Unlike clinical signs of Lyme disease, new-onset symptoms are reported by a subset of participants without evidence of depressive symptomatology. Patients who developed PTLDS had significantly lower life functioning compared to those without PTLDS. We propose future avenues for researching infection-triggered symptoms resulting from multiple mechanisms. URL Previous https://link.springer.com/article/10.1007%2Fs11136-012-0126-6 No Review Needed? Next

101 < Back to Research Top Published Date 27/06/2019 Characteristics of transfusion-transmitted Babesia microti, American Red Cross 2010-2017 Journal Transfusion Citation Transfusion. 2019 Jun 27 DOI 10.1111/trf.15425 Authors L Tonnetti, RL Townsend, RY Dodd, SL Stramer Abstract BACKGROUND: Babesia microti, a red blood cell (RBC) parasite transmitted naturally to vertebrate hosts by ixodid ticks, is endemic to the northeastern and upper midwestern United States, with the geographic range of infected ticks expanding. B. microti is a blood safety issue with >200 transfusion-transmissions reported. METHODS: The American Red Cross's Hemovigilance program investigated hospital-reported transfusion-transmitted babesiosis (TTB) cases. Follow-up samples from involved donors were tested for B. microti antibodies and parasite DNA, the latter by real-time polymerase chain reaction (PCR). Test-positive donors were permanently deferred from future donations. RESULTS: B. microti-positive donors were implicated in 77 of 143 suspect TTB cases investigated from 2010 through 2017. In four cases, two positive donors were identified for a total of 81 positive donors. In three cases, a RBC unit was split and components transfused multiple times to the same pediatric recipient. RBCs were the transmitting product in all cases. At follow-up, all involved donors were antibody positive; 25 donors were also PCR positive. Positive donations were collected throughout the year, peaking in the summer. Most donors (78) were resident of, or traveled to (2), an endemic state. One donor resided in a non-endemic state without relevant travel history. One fatality listed babesia as a contributing factor. No implicated donation was screened by an investigational protocol. CONCLUSIONS: Babesiosis remains a blood safety issue. Prior to FDA-licensed screening test availability and final FDA Guidance, blood collectors in endemic states investigationally tested none, a portion, or all collections. Future expanded testing will reduce the frequency of TTB cases. URL Previous https://www.ncbi.nlm.nih.gov/pubmed/31250463 No Review Needed? Next

134 < Back to Research Top Published Date 17/05/2018 Human Babesiosis Caused by Babesia duncani Has Widespread Distribution across Canada Journal Healthcare (Basel, Switzerland) Citation Healthcare (Basel). 2018 May 17;6(2). pii: E49 DOI 10.3390/healthcare6020049 Authors Scott JD, Scott CM Abstract Human babesiosis caused by Babesia duncani is an emerging infectious disease in Canada. This malaria-like illness is brought about by a protozoan parasite infecting red blood cells. Currently, controversy surrounds which tick species are vectors of B. duncani. Since the availability of a serological or molecular test in Canada for B. duncani has been limited, we conducted a seven-year surveillance study (2011?2017) to ascertain the occurrence and geographic distribution of B. duncani infection country-wide. Surveillance case data for human B. duncani infections were collected by contacting physicians and naturopathic physicians in the United States and Canada who specialize in tick-borne diseases. During the seven-year period, 1119 cases were identified. The presence of B. duncani infections was widespread across Canada, with the highest occurrence in the Pacific coast region. Patients with human babesiosis may be asymptomatic, but as this parasitemia progresses, symptoms range from mild to fatal. Donors of blood, plasma, living tissues, and organs may unknowingly be infected with this piroplasm and are contributing to the spread of this zoonosis. Our data show that greater awareness of human babesiosis is needed in Canada, and the imminent threat to the security of the Canadian blood supply warrants further investigation. Based on our epidemiological findings, human babesiosis should be a nationally notifiable disease in Canada. Whenever a patient has a tick bite, health practitioners must watch for B. duncani infections, and include human babesiosis in their differential diagnosis. URL Previous https://www.mdpi.com/2227-9032/6/2/49 No Review Needed? Next

LRC Key Achievements 2022 - 2024

245 < Back to Research Top Published Date 05/10/2012 The Psychoimmunology of Lyme/Tick-Borne Diseases and its Association with Neuropsychiatric Symptoms Journal The Open Neurology Journal Citation Open Neurol J. 2012;6:88-93 DOI 10.2174/1874205X01206010088 Authors Bransfield RC Abstract Disease progression of neuropsychiatric symptoms in Lyme/tick-borne diseases can be better understood by greater attention to psychoimmunology. Although there are multiple contributors that provoke and weaken the immune system, infections and persistent infections are significant causes of pathological immune reactions. Immune mediated effects are a significant contributor to the pathophysiological processes and disease progression. These immune effects include persistent inflammation with cytokine effects and molecular mimicry and both of these mechanisms may be present at the same time in persistent infections. Sickness syndrome associated with interferon treatment and autoimmune limbic encephalopathies are models to understand inflammatory and molecular mimicry effects upon neuropsychiatric symptoms. Progressive inflammatory reactions have been proposed as a model to explain disease progression in depression, psychosis, dementia, epilepsy, autism and other mental illnesses and pathophysiological changes have been associated with oxidative stress, excitotoxicity, changes in homocysteine metabolism and altered tryptophan catabolism. Lyme disease has been associated with the proinflammatory cytokines IL-6, IL-8, IL-12, IL-18 and interferon-gamma, the chemokines CXCL12 and CXCL13 and increased levels proinflammatory lipoproteins. Borrelia burgdorferi surface glycolipids and flagella antibodies appear to elicit anti-neuronal antibodies and anti-neuronal antibodies and Borrelia burgdorferi lipoproteins can disseminate from the periphery to inflame the brain. Autism spectrum disorders associated with Lyme/tick-borne diseases may be mediated by a combination of inflammatory and molecular mimicry mechanisms. Greater interaction is needed between infectious disease specialists, immunologists and psychiatrists to benefit from this awareness and to further understand these mechanisms. URL Previous https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474947 No Review Needed? Next

35 < Back to Research Top Published Date 29/09/2020 Effect of dapsone alone and in combination with intracellular antibiotics against the biofilm form of B. burgdorferi Journal BMC Research Notes Citation 13(1):455. DOI 10.1186/s13104-020-05298-6 Authors Horowitz RI, Murali K, Gaur G, Freeman PR, Sapi E Abstract Objective: Lyme disease is a tick-borne, multisystemic disease caused by Borrelia burgdorferi. Standard treatments for early Lyme disease include short courses of oral antibiotics but relapses often occur after discontinuation of treatment. Several studies have suggested that ongoing symptoms may be due to a highly antibiotic resistant form of B. burgdorferi called biofilms. Our recent clinical study reported the successful use of an intracellular mycobacterium persister drug used in treating leprosy, diaminodiphenyl sulfone (dapsone), in combination therapy for the treatment of Lyme disease. In this in vitro study, we evaluated the effectiveness of dapsone individually and in combination with cefuroxime and/or other antibiotics with intracellular activity including doxycycline, rifampin, and azithromycin against Borrelia biofilm forms utilizing crystal violet biofilm mass, and dimethyl methylene blue glycosaminoglycan assays combined with Live/Dead fluorescent microscopy analyses. Results: Dapsone, alone or in various combinations with doxycycline, rifampin and azithromycin produced a significant reduction in the mass and protective glycosaminoglycan layer and overall viability of B. burgdorferi biofilm forms. This in vitro study strongly suggests that dapsone combination therapy could represent a novel and effective treatment option against the biofilm form of B. burgdorferi. Keywords: Biofilm; Borrelia burgdorferi; Dapsone; Lyme disease. URL Previous https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-020-05298-6 No Review Needed? Next