Revealed Analysis Funded by LDA 1996 to 2023

Revealed Analysis Funded by LDA 1996 to 2023

Table of Contents


The LDA has a protracted historical past of funding/supporting analysis initiatives that result in actual outcomes. Beneath is the record of hyperlinks to peer-reviewed articles that acknowledge LDA’s funding/assist.

Click on on the 12 months to see the article authors, summary, and a hyperlink to the publication itself when attainable.  Authors LDA supplied funding to are bolded.

61 Publications

(3) Antibiotics 2023, 2020, 2017
Journal of Medical Entomology 2022
Healthcare (Basel) 2022, 2018
The Journal of Nervous and Psychological Illness 2022
Journal of Vector Ecology 2021
Frontiers in Neurology 2021
(2) Frontiers in Medication 2020, 2019
Mind, Habits, & Immunity – Well being 2020
Meta Gene 2019
Ticks and Tick-Borne Ailments 2018
Archives of Scientific Neuropsychology 2018
(2) Psychosomatics 2018, 2013
Bio-Protocol 2017
(5) PLOS One 2017, 2012 (2), 2011, 2010
The FEBS Journal 2017
ACS Chemical Biology 2017
Biochemistry 2017
(2) Frontiers in Microbiology October 2016May 2016
Park Science (NPS, Division of Inside) 2016
FEMS Microbiology Letters 2015
Scientific Infectious Illness 2014
Veterinary Sciences 2014
Worldwide Journal of Medical Sciences 2013
Northeastern Naturalist, 2013
(3)Journal of Neuropsychiatry & Scientific Neurosciences 2013, 2003, 2001
Open Neurology Journal 2012
Journal of Bacteriology 2011
Genetics 2011
Journal of Medical Entomology 2010
Neurobiology of Illness 2010
Archives Basic Psychiatry 2009
Gene 2009
(2) Neurology 2008, 1999
Rising Infectious Ailments 2008
Minerva Medica October 2008
Microbial Pathogenesis 2008
Journal of Worldwide Neuropsychological Soc. 2006
An infection & Immunity 2006
Journal of Scientific Microbiology 2005
Professional Assessment of Anti-Infective Remedy 2004
The Proceedings of Nationwide Academy of Science 2004
(2) JSTBD 2002, 1999
Medscape Infectious Ailments April 2000
Journal of American Medical Affiliation (JAMA) 1999
Psychiatric Clinics of North America 1998
(2) An infection 1998, 1996


Click on right here to see an entire record of all publications from LDA-funded analysis and brief LDA summaries.

View list of all Publications from LDA-Funded Research


Click on right here to see a pattern of convention shows from researchers who’ve obtained LDA funding for his or her work.

Conference Presentations Resulting from LDA-Funding


Journal Articles Beneath

61. Antibiotics March 6, 2023 

Assessment – Disulfiram: Mechanisms, Functions, and Challenges

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Jenna Lanz 1 , Nicholas Biniaz-Harris 1 , Mara Kuvaldina 1 , Samta Jain 2 , Kim Lewis 2 and Brian A. Fallon 1,3,*

1 Lyme & Tick-Borne Ailments Analysis Heart, Division of Psychiatry, Vagelos Faculty of Physicians and Surgeons, Columbia College Irving Medical Heart, Columbia College, New York, NY 10032, USA

2 Antimicrobial Discovery Heart, Division of Biology, Northeastern College, Boston, MA 02115, USA

3 New York State Psychiatric Institute, New York, NY 10032, USA

* Correspondence: [email protected]

Summary: Background: Since disulfiram’s discovery within the Nineteen Forties and its FDA approval for alcohol use dysfunction, different indications have been investigated. This evaluate describes potential medical purposes, related dangers, and challenges. Strategies: For this narrative evaluate, a PubMed search was carried out for articles addressing in vivo research of disulfiram with an emphasis on drug repurposing for the remedy of human ailments. The important thing search phrases have been “disulfiram” and “Antabuse”. Animal research and in vitro research highlighting vital mechanisms and issues of safety have been additionally included. Outcomes: In whole, 196 sources addressing our analysis focus spanning 1948–2022 have been chosen for inclusion. Along with alcohol use dysfunction, rising information assist a possible position for disulfiram within the remedy of different addictions (e.g., cocaine), infections (e.g., micro organism corresponding to Staphylococcus aureus and Borrelia burgdorferi, viruses, parasites), inflammatory circumstances, neurological ailments, and cancers. The unwanted side effects vary from minor to life-threatening, with decrease doses conveying much less danger. Warning in human use is required because of the appreciable inter- topic variability in disulfiram pharmacokinetics. Conclusions: Whereas disulfiram has promise as a “repurposed” agent in human illness, its danger profile is of concern. Animal research and well-controlled medical trials are wanted to evaluate its security and efficacy for non-alcohol-related indications.

60. Journal of Medical Entomology, August 2022

Tick-Borne Pathogens in Questing Blacklegged Ticks (Acari: Ixodidae) From Pike County, Pennsylvania 3 August 2022

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Sarah Schwartz,1, Elizabeth Calvente,1, Emily Rollinson,2, Future Pattern Koon Koon,1, and Nicole Chinnici1,3

1Dr. Jane Huffman Wildlife Genetics Institute, East Stroudsburg College of Pennsylvania, 562 Independence Street, Suite 114,East Stroudsburg, PA 18301, USA

2East Stroudsburg College, 200 Prospect Avenue, East Stroudsburg, PA 18301, USA
3
Corresponding creator, e-mail: [email protected]

Summary
: Lively surveillance was carried out by amassing questing ticks from vegetation by means of a 2-yr survey in Pike County, Pennsylvania. Over a thousand blacklegged ticks (Ixodes scapularis Say) and American canine ticks (Dermacentor variabilis Say) have been collected. A single specimen of the next species was collected: lone star tick (Amblyomma americanum L.), rabbit tick (Haemaphysalis leporispalustris Packard), and an Asian longhorned tick (Haemaphysalis longicornis Neumann). This examine represents the biggest county-wide examine in Pennsylvania, surveying 988 questing I. scapularis grownup and nymphs. Molecular detection of 5 distinct tick-borne pathogens was screened by means of real-time PCR at a single tick decision. Respectively, the general 2-yr grownup and nymph prevalence have been highest with Borrelia burgdorferi (Spirochaetales: Spirochaetacceae) (45.99%, 18.94%), Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae) (12.29%, 7.95%) the place the
variant-ha (8.29%, 3.03%) was general extra prevalent than the variant-v1 (2.49%, 4.17%),
Babesia microti (Piroplasmida: Babesiidae) (4.97%, 5.30%), Borrelia miyamotoi (Spirochaetales: Spirochaetaceae) (1.38%, 1.89%), and Powassan virus lineage II [POWV]/deer tick virus (DTV) (2.07%, 0.76%). Grownup and nymph coinfection prevalence of B. burgdorferi and B. microti (3.03%, 4.97%) and grownup coinfection of B. burgdorferi and A. phagocytophilum or A. phagocytophilum and B. microti have been considerably greater than the impartial infection price anticipated naturally. This examine highlights the urgency to conduct various surveillance research with massive pattern sizes to higher perceive the human danger for tick-borne ailments inside small geographical space.

59. Healthcare (Basel) 2022 July 22

Kundalini Yoga for Put up-Therapy Lyme Illness: A Preliminary Randomized Research

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Lilly Murray 1,2,* , Charles Alexander 3, Clair Bennett 1,2, Mara Kuvaldina 1,2, Gurucharan Khalsa 4 and Brian Fallon 1,2,*

1 Lyme & Tick-Borne Ailments Analysis Heart, Division of Psychiatry, Columbia College Irving Medical Heart, New York, NY 10032, USA; [email protected] (C.B.); [email protected] (M.Ok.)

2 New York State Psychiatric Institute, New York, NY 10032, USA

3 Non-public Apply, Southport, CT 06890, USA; [email protected]

4 Fish Interfaith Heart, Chapman College, Orange, CA 92866, USA; [email protected]

* Correspondence: [email protected] (L.M.); [email protected] (B.F.)

Summary: This examine examined the adherence to and the potential good thing about Kundalini yoga (KY) for post-treatment Lyme disease syndrome (PTLDS). Contributors have been randomly assigned to eight weeks of a KY small-group intervention or a waitlist management (WLC). Adherence was measured as attendance at KY group periods. Main outcomes assessed ache, ache interference, fatigue, and international well being. Secondary outcomes assessed multisystem symptom burden, temper, sleep, bodily and social functioning, cognition, and mindfulness. Linear combined fashions have been used to check adjustments in outcomes over time as a perform of group task; intercepts for members have been modeled as random results. Though the goal pattern dimension was 40 members, the examine concluded with 29 members as a consequence of recruitment challenges. No KY members dropped out of the examine, and members attended 75% of group periods on common, however WLC retention was poor (57%). Concerning major outcomes, there was no vital interplay between group and time. Concerning secondary outcomes, there was a major interplay between group and time for multisystem symptom burden (p < 0.05) and cognition (p < 0.01); KY members reported improved multisystem symptom burden and cognition over the course of the examine in comparison with WLC members. To reinforce recruitment and retention, future trials could contemplate increasing geographic entry and together with supportive procedures for WLC members. This preliminary examine helps the necessity for a bigger examine to find out if KY reduces multisystem symptom burden and enhances cognition amongst folks with PTLDS

58. The Journal of Nervous and Psychological Illness: Could 2022 – Quantity 210 – Challenge 5
Persistent Signs, Lyme Illness, and Prior Trauma
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Mustafiz, Fayel BA∗,†; Moeller, James PhD∗,†; Kuvaldina, Maria PhD∗,†;
Bennett, Clair DPsych (Clin)∗,†; Fallon, Brian A. MD∗,†
∗Columbia Psychiatry, Columbia College Irving Medical Heart
†New York Psychiatric Institute, New York, New York.

Correspondence: Fayel Mustafiz, BA, 1051 Riverside Drive, Unit 69, New
York, NY 10032. E-mail: [email protected]

Summary: One prior examine means that traumatic occasions earlier than Lyme disease play an vital position in symptom severity. We examined this speculation amongst 60 people with persistent signs after Lyme disease utilizing validated measures of trauma historical past, psychological and bodily signs, and useful standing. Evaluation of variance with Tukey-Kramer a number of comparisons check revealed {that a} better variety of traumatic occasions have been considerably related to better symptom severity on the scales of temper (stress, melancholy, and anxiousness), cognition, multisystem symptom burden, and useful standing (psychological and bodily), however not on measures of ache and fatigue. The impact sizes—significant however not massive (0.17–0.29)—have been largely produced by comparability with people reporting a number of prior traumatic occasions, representing half of the posttreatment Lyme disease syndrome (PTLDS) group. In conclusion, though PTLDS could also be exacerbated by previous trauma, trauma performs a task in solely a subgroup of PTLDS. Whether or not addressing prior trauma can enhance outcomes on this subgroup requires examine.


57. Journal of Vector Ecology, Vol. 46, Challenge, Nov 2021
Institution of Amblyomma americanum populations and new information of Borrelia burgdorferi-infected Ixodes scapularis in South Dakota

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Holly Black 1,2, Rashaun Potts 2, Jayden Fiechtner 2, Jose E. Pietri 2, Hugh B. Britten 1

1 Division of Biology, College of South Dakota, Vermillion, SD, U.S.A.
2 Sanford College of Medication, College of South Dakota, Vermillion, SD, U.S.A.

Summary: Tick-borne ailments are an rising public well being menace in the US, however surveillance is missing in some areas. To advance present data of the ecology of ticks and tick-borne ailments in South Dakota, we carried out a survey in the summertime of 2019, specializing in the japanese counties of the state. We collected and recognized 266 ticks and a subset have been examined for the presence of Borrelia burgdorferi by polymerase chain response (PCR). Dermacentor variabilis, a ubiquitous species within the state, was essentially the most generally recognized tick, current in all counties surveyed. Nonetheless, we additionally recognized 15 Amblyomma americanum from three totally different areas, offering the primary proof of established populations within the state and increasing the vary of this species. As well as, we recognized 22 Ixodes scapularis from 5 totally different areas, confirming a earlier report of a longtime inhabitants within the state. Two grownup I. scapularis from two totally different websites have been discovered to harbor B. burgdorferi, together with a person from Lincoln County, suggesting the continuing presence of the pathogen in tick populations within the state and representing its southwestern-most detection within the midwest United States. These findings present vital info for assessing and monitoring the general public well being danger from tick-borne ailments in an space the place surveillance is missing.


56. Frontiers in Neurology, Could 10, 2021
Detecting Borrelia Spirochetes: A Case Research With Validation Amongst Post-mortem Specimens

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Shiva Kumar Goud Gadila1, Gorazd Rosoklija2,3, Andrew J. Dwork2,3,4,5, Brian A. Fallon2* and Monica E. Embers1*

1 Division of Immunology, Tulane Nationwide Primate Analysis Heart, Tulane College Well being Sciences, Covington, LA, United States
2 Division of Psychiatry, Columbia College, New York, NY, United States
3 Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, United States
4 Macedonian Academy of Sciences and Arts, Skopje, Macedonia
5 Division of Pathology and Cell Biology, Columbia College, New York, NY, United States

*Correspondence: Brian A. Fallon, [email protected]; Monica E. Embers, [email protected]

Summary: The complicated etiology of neurodegenerative illness has prompted research on a number of mechanisms together with genetic predisposition, mind biochemistry, immunological responses, and microbial insult. Specifically, Lyme disease is commonly related to neurocognitive impairment with variable manifestations between sufferers. We sought to develop strategies to reliably detect Borrelia burgdorferi, the spirochete micro organism answerable for Lyme disease, in post-mortem specimens of sufferers with a historical past of neurocognitive illness. On this report, we describe the usage of a number of molecular detection methods for this pathogen and its utility to a case examine of a Lyme disease affected person. The affected person had a historical past of Lyme disease, was handled with antibiotics, and years later developed continual signs together with dementia. The affected person’s pathology and medical case description was in step with Lewy physique dementia. B. burgdorferi was recognized by PCR in a number of CNS tissues and by immunofluorescent staining within the spinal twine. These research provide proof of the precept that persistent an infection with the Lyme disease spirochete could have lingering penalties on the CNS.


55. Frontiers in Medication (Lausanne), Oct 27, 2020
Borrelia miyamotoi Serology in a Scientific Inhabitants With Persistent Signs and Suspected Tick-Borne Sickness
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Shannon L. Delaney,1,2,* Lilly A. Murray,1,2 Claire E. Aasen,1 Clair E. Bennett,1,2 Ellen Brown,1,2 and Brian A. Fallon1,2

1 Lyme & Tick-Borne Ailments Analysis Heart, Columbia College Irving Medical Heart, New York, NY, United States
2 New York State Psychiatric Institute, Columbia College Irving Medical Heart, New York, NY, United States Edited by: Ying Zhang, Zhejiang College, China Reviewed by: Pallab Ghosh, Harvard Medical College, United States; Raymond James Dattwyler, New York Medical Faculty, United States

*Correspondence: Shannon L. Delaney [email protected]

Summary: Eighty-two sufferers looking for session for long-term sequalae after suspected tick-borne sickness have been consecutively examined for Borrelia miyamotoi antibodies utilizing a recombinant glycerophosphodiester phosphodiesterase (GlpQ) enzyme immunoassay. Twenty-one of the 82 sufferers (26%) examined constructive on the GlpQ IgG ELISA. Practically all the sufferers (98%) had no prior B. miyamotoi testing, indicating that clinicians hardly ever check for this rising tick-borne pathogen. In comparison with sufferers who solely examined constructive for Lyme disease antibodies, sufferers with B. miyamotoi antibodies offered with considerably extra sleepiness and ache. A potential examine is required to determine the connection between the presence of B. miyamotoi antibodies and chronic signs.


54. Antibiotics (Basel). Could 25, 2020

Impact of Borrelia burgdorferi Outer Membrane Vesicles on Host Oxidative Stress Response

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Keith Wawrzeniak, Gauri Gaur, Eva Sapi, and Alireza G. Senejani*

Division of Biology and Environmental Science, College of New Haven, West Haven, CT 06516, USA; [email protected] (Ok.W.); [email protected] (G.G.); [email protected] (E.S.)

*Correspondence: [email protected]

Summary: Outer membrane vesicles (OMVs) are spherical our bodies containing proteins and nucleic acids which might be launched by Gram-negative micro organism, together with Borrelia burgdorferi, the causative agent of Lyme disease. The useful relationship between B. burgdorferi OMVs and host neuron homeostasis just isn’t nicely understood. The target of this examine was to look at how B. burgdorferi OMVs influence the host cell setting. First, an in vitro mannequin was established by co-culturing human BE2C neuroblastoma cells with B. burgdorferi B31. B. burgdorferi was capable of invade BE2C cells inside 24 h. Regardless of internalization, BE2C cell viability and ranges of apoptosis remained unchanged, however resulted in dramatically elevated manufacturing of MCP-1 and MCP-2 cytokines. Elevated secretion of MCP-1 has beforehand been related to adjustments in oxidative stress. BE2C cell mitochondrial superoxides have been decreased as early as 30 min after publicity to B. burgdorferi and OMVs. To rule out whether or not BE2C cell antioxidant response is the reason for decline in superoxides, superoxide dismutase 2 (SOD2) gene expression was assessed. SOD2 expression was decreased upon publicity to B. burgdorferi, suggesting that B. burgdorferi is perhaps answerable for superoxide discount. These outcomes counsel that B. burgdorferi modulates cell antioxidant protection and immune system response in response to the bacterial an infection. In abstract, these outcomes present that B. burgdorferi OMVs serve to instantly counter superoxide manufacturing in BE2C neurons, thereby ‘priming’ the host setting to assist B. burgdorferi colonization.

53. Mind, Habits, & Immunity – Well being, January 7, 2020 https://www.sciencedirect.com/science/article/pii/S2666354619300158?via%3Dihub
Anti-lysoganglioside and different anti-neuronal autoantibodies in post-treatment Lyme Illness and Erythema Migrans after repeat an infection Brian A.Fallon a,b,* Barbara Strobino, a,b, SeanReim c, JulieStoner d, Madeleine W. Cunningham c a Columbia Psychiatry, Columbia College Irving Medical Heart, New York, USA b New York State Psychiatric Institute, 1051 Riverside Drive, New York, USA c Division of Microbiology and Immunology, College of Oklahoma Well being Sciences Heart, Oklahoma Metropolis, USA d Division of Biostatistics, College of Oklahoma Well being Sciences Heart, Oklahoma Metropolis, USA

*Corresponding creator: Brian A. Fallon, Columbia College, 1051 Riverside Drive, Unit 69, New York, NY, 10032, USA.

Summary: Background: Molecular mimicry focusing on neural tissue has been reported after Borrelia burgdorferi(Bb) an infection. Herein, we examine whether or not antineuronal autoantibodies are elevated and whether or not antibody-mediated signaling of neuronal cells is elevated in a cohort of symptomatic adults with a historical past of Lyme Illness (LD). Strategies: Contributors (n = 179) included 24 with latest Erythema Migrans (EM) with out prior LD, 8 with latest EM and prior LD (EM + prior LD), 119 with persistent post-treatment LD signs (PTLS), and 28 seronegative endemic controls with no prior LD historical past. Antineuronal immunoglobulin G (IgG) titers have been measured by commonplace ELISA and in contrast with imply titers of regular age-matched sera in opposition to lysoganglioside, tubulin, and dopamine receptors (D1R and D2R). Antibody-mediated signaling of calcium calmodulin dependent protein kinase II (CaMKII) exercise in a human neuronal cell line (SK-N-SH) was recognized in serum. Outcomes: EM + prior LD instances had greater antibody titers than controls for anti-lysoganglioside GM1 (p = 0.002), anti-tubulin (p = 0.03), and anti-D1R (p = 0.02), in addition to greater expression within the useful antibody-mediated CaMKII Assay (p = 0.03). The EM instances with no prior historical past confirmed no vital variations on any measures. The PTLS instances demonstrated considerably greater titers (p = 0.01) than controls on anti-lysoganglioside GM1, however not for the opposite measures. Conclusion: The discovering of elevated anti-neuronal autoantibodies in our small pattern of these with a previous historical past of Lyme disease however not in these with out prior Lyme disease, if replicated in a bigger pattern, suggests an immune priming impact of repeated an infection; the CaMKII activation means that antineuronal antibodies have useful significance. The elevation of anti-lysoganglioside antibodies amongst these with PTLS is of specific curiosity given the established position of anti-ganglioside antibodies in peripheral and central neurologic ailments. Future potential research can decide whether or not these autoantibodies emerge after Bb an infection and whether or not their emergence coincides with persistent neurologic or neuropsychiatric signs.

52. Frontiers in Medication, December 6, 2019

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The Basic Symptom Questionnaire-30 (GSQ-30): A Transient Measure of Multi-System Symptom Burden in Lyme Illness
Brian A. Fallon 1,2*, Nevena Zubcevik 3,4, Clair Bennett 1,2, Shreya Doshi 1,2, Alison W. Rebman 5, Ronit Kishon 1,2, James R. Moeller 1,2, Nadlyne R. Octavien 3 and John N. Aucott 5

1 Division of Psychiatry, Lyme and Tick-Borne Ailments Analysis Heart, Columbia College Irving Medical Heart, New York, NY, United States
2 Division of Psychiatry, New York State Psychiatric Institute, New York, NY, United States
3 Division of Bodily Medication and Rehabilitation, Dean Heart for Tick borne Sickness, Harvard Medical College, Spaulding Rehabilitation Hospital, Boston, MA, United States
4 Division of Bodily Medication and Rehabilitation, Massachusetts Basic Hospital, Boston, MA, United States
5 Division of Rheumatology, Division of Medication, Lyme Illness Analysis Heart, Johns Hopkins College of Medication, Baltimore, MD, United States

*Correspondence: Brian A. Fallon, [email protected]

Summary: Introduction: The multi-system signs accompanying acute and post-treatment Lyme disease syndrome pose a problem for time-limited evaluation. The Basic Symptom Questionnaire (GSQ-30) was developed to fill the necessity for a quick patient-reported measure of multi-system symptom burden. On this examine we assess the psychometric properties and sensitivity to alter of the GSQ-30. Supplies and Strategies: 342 grownup members comprised 4 diagnostic teams: Lyme disease (post-treatment Lyme disease syndrome, n = 124; erythema migrans, n = 94); melancholy, n = 36; traumatic brain injury, n = 51; wholesome, n = 37. Contributors have been recruited from medical analysis amenities in Massachusetts, Maryland, and New York. Validation measures for the GSQ-30 included the Affected person Well being Questionnaire-4 for melancholy and anxiousness, visible analog scales for fatigue and ache, the Sheehan Incapacity Scale for useful impairment, and one international well being query. To evaluate sensitivity to alter, 53 sufferers with erythema migrans accomplished the GSQ-30 earlier than remedy and 6 months after 3 weeks of remedy with doxycycline. Outcomes: The GSQ-30 demonstrated wonderful inner consistency (Cronbach α = 0.95). The issue construction displays 4 core domains: ache/fatigue, neuropsychiatric, neurologic, and viral-like signs. Symptom burden was considerably related to melancholy (rs = 0.60), anxiousness (rs = 0.55), ache (rs = 0.75), fatigue (rs = 0.77), useful impairment (rs = 0.79), and normal well being (rs = −0.58). The GSQ-30 detected vital change in symptom burden earlier than and after antibiotic remedy; this transformation correlated with change in useful impairment. The GSQ-30 whole rating considerably differed for erythema migrans vs. three different teams (post-treatment Lyme disease syndrome, melancholy, wholesome controls). The GSQ-30 whole scores for traumatic brain injury and melancholy weren’t considerably totally different from post-treatment Lyme disease syndrome. Conclusions and Relevance: The GSQ-30 is a legitimate and dependable instrument to evaluate symptom burden amongst sufferers with acute and post-treatment Lyme disease syndrome and is delicate within the detection of change after remedy amongst sufferers with erythema migrans. The GSQ-30 ought to show helpful in medical and analysis settings to evaluate multi-system symptom burden and to watch change over time. The GSQ-30 can also show helpful in future precision medication research as a medical measure to correlate with disease-relevant biomarkers.


51. Meta Gene, Quantity 21, September 2019. On-line Could 2019

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Genetic Variation within the ABCB1 Gene Related to Put up Therapy Lyme Illness Syndrome Standing
Joanna Lyon 1, Hyunuk Seung 2

1 Superior Scientific Pharmacist, College of Maryland College of Pharmacy, United States of America [email protected]
2 Division of Pharmacy Apply and Science, College of Maryland College of Pharmacy, United States of America [email protected]

Summary: Put up Therapy Lyme Illness Syndrome (PTLDS) poses a obscure well being subject. This multi-centered, randomized management trial studied the attainable correlation between ABCB1 (MDR1) gene variants and the incidence of PTLDS in affected sufferers. Genomic DNA was remoted and analyzed for 4 ABCB1 gene SNPs (rs1128503, rs1045642, rs2235067, and rs4148740). Vital findings embody the affiliation of rs1128503 TC variant with PTLDS standing. Moreover, the rs1128503+ rs1045642+ rs2235067 SNP mixture elevated rs1128503 genotype TC significance to three.83 occasions the rs1128503 genotype CC. The TT variant of rs4148740 along side rs1128503 decreased the chances ratio and appeared to convey a PTLDS protecting standing to the rs1128503 TC variant.


50. Ticks and Tick-Borne Ailments, 2018 Nov 27

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Regional prevalences of Borrelia burgdorferi, Borrelia bissettiae, and Bartonella henselae in Ixodes affinis, Ixodes pacificus and Ixodes scapularis within the USA.
Maggi RG 1, Toliver M 2, Richardson T 3, Mather T 4, Breitschwerdt EB 5

1 Intracellular Pathogens Analysis Laboratory, Comparative Medication Institute, Faculty of Veterinary Medication, North Carolina State College (NCSU), 1060 William Moore Drive, Raleigh, NC 27607. [email protected]
2 Public Well being Pest Administration Part, NC Division of Atmosphere and Pure Assets, 10005 Waterford Court docket, Raleigh, NC 27613. [email protected]
3 Intracellular Pathogens Analysis Laboratory, Comparative Medication Institute, Faculty of Veterinary Medication, North Carolina State College (NCSU), 1060 William Moore Drive, Raleigh, NC 27607. [email protected]
4 Division of Plant Sciences and Entomology, Heart for Vecto-Borne Illness, Faculty of the Atmosphere and Life Sciences, College of Rhode Island, 231 Woodward Corridor, Kingston, RI 02881. [email protected]
5 Intracellular Pathogens Analysis Laboratory, Comparative Medication Institute, Faculty of Veterinary Medication, North Carolina State College (NCSU), 1060 William Moore Drive, Raleigh, NC 27607. [email protected]

ABSTRACT: The target of this work was to find out the prevalence of Borrelia and Bartonella species in Ixodes spp. ticks collected from 16 USA states. Genus PCR amplification and sequence evaluation of Bartonella and Borrelia 16SsRNA-23SsRNA intergenic areas have been carried out on DNA extracted from 929 questing grownup ticks (671 Ixodes scapularis, 155 Ixodes affinis, and 103 Ixodes pacificus). Total, 129/929 (13.9%) Ixodes ticks have been PCR constructive for Borrelia burgdorferi sensu stricto, 48/929 for B. bissettiae whereas 23/929 (2.5%) have been PCR constructive for a Bartonella henselae. Borrelia bissettiae or B. burgdorferi s.s. and B. henselae co-infections have been present in I. affinis from North Carolina at a price of 4.5%; in a single I. scapularis from Minnesota, however not in I. pacificus. For each bacterial genera, PCR constructive charges have been extremely variable relying on geographic location and tick species, with Ixodes affinis (n = 155) collected from North Carolina, being the tick species with the best prevalence’s for each Borrelia spp. (63.2%) and B. henselae (10.3%). Based mostly on the outcomes of this and different printed research, improved understanding of the enzootic cycle, transmission dynamics, and vector competence of Ixodes species (particularly I. affinis) for transmission of Borrelia spp. and B. henselae must be a public well being analysis precedence.


49. Archives of Scientific Neuropsychology, Nov 12, 2018
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Neurocognition in Put up-Therapy Lyme Illness and Main Depressive Dysfunction Keilp JG 1,2,3*, Corbera Ok 1, Gorlyn M 2, Oquendo MA 2,3,4, Mann JJ 2,3

Fallon BA 1,2,3 *Corresponding creator at: New York State Psychiatric Institute and Division of Psychiatry, Columbia College Faculty of Physicians and Surgeons, Field 42, NYSPI, 1051 Riverside Drive, New York, NY 10032, USA. Tel.: 1-646-774-7509. E-mail: [email protected] (J.G. Keilp)

1 Lyme Illness Analysis Heart, Columbia College Faculty of Physicians and Surgeons, New York, NY
2 Division of Psychiatry, Columbia College Faculty of Physicians and Surgeons, New York, NY
3 Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY
4 Division of Psychiatry, Perelman College of Medication, College of Pennsylvania, Philadelphia, PA

Dr. John Keilp, senior neuropsychologist for the Columbia Lyme & Tick-borne Ailments Analysis Heart’, studies that the cognitive profile of sufferers with publish remedy Lyme disease is meaningfully totally different from the profile of sufferers with main melancholy. It is a neurocognitive biomarker or fingerprint of post-treatment Lyme disease. Though each teams may need fatigue and psychological fogginess, the Lyme group extra usually studies issues with verbal reminiscence and verbal fluency whereas the depressed (non-Lyme) group extra usually studies slower processing velocity and poor consideration. These outcomes spotlight the worth of neurocognitive testing in serving to to tease out the potential causes of cognitive issues in sufferers with post-treatment Lyme disease.


48. Psychosomatics 59(5) · Sept/Oct 2018 https://www.ncbi.nlm.nih.gov/pubmed/29606281
Depressive Signs and Suicidal Ideation Amongst Symptomatic Sufferers with a Historical past of Lyme Illness Versus Two Comparability Teams
Shreya Doshi M.A 1*., John G. Keilp Ph.D 2., Barbara Strobino Ph.D. 1, Martin McElhiney Ph.D. 1, Judith Rabkin Ph.D. 1, Brian A. Fallon M.D. 1

1 Division of Scientific Therapeutics, Division of Psychiatry, New York State Psychiatric Institute, New York, NY 2 Division of Molecular Imagining and Neuropathology, Division of Psychiatry, New York State Psychiatric Institute, New York, NY *[email protected]

ABSTRACT: Background: Melancholy has been reported in 8–45% of sufferers with posttreatment Lyme signs (PTLS), however little is understood about suicidal ideation in these sufferers. Methodology: Melancholy and suicidal ideation have been assessed utilizing the Beck Melancholy Stock (BDI-II). Scores from the PTLS group (n = 81) have been in comparison with these from 2 different teams: HIV+ sufferers being handled for fatigue (n = 70), and a nonpatient comparability group (NPCG; n = 44). ANOVA and t-tests have been used to check teams; logistic regression was used to establish the strongest correlates of suicidal ideation. Outcomes: Imply BDI-II scores fell within the mildly depressed vary for PTLS and HIV+ sufferers, with each teams having greater melancholy scores than the NPCG. Suicidal ideation was reported by 19.8% of the PTLS sufferers and 27.1% of the HIV+ sufferers, a nonsignificant distinction. Amongst these with gentle or no melancholy, suicidal ideation was unusual (6.5% PTLS and 11.9% HIV+). Among the many sufferers with moderate-to-severe melancholy, suicidal ideation was extra frequent (63.2% of 19 PTLS and 50% of 28 HIV+); amongst these, 2 with PTLS and 1 with HIV+ expressed suicidal intent. Additional, 4.5% (n = 2) of the NPCG had suicidal ideation, every had scores within the moderate-to-severe melancholy vary. Increased scores on the cognitive signs subscale of the BDI-II predicted better chance of suicidal ideation throughout affected person teams. Conclusion:As anticipated, suicidal ideation is elevated amongst sufferers who’re depressed. The truth that 1 in 5 sufferers with PTLS reported suicidal ideation highlights the significance of screening for melancholy and suicidality to optimize affected person care.


47. Healthcare (Basel) 2018 Jun; 6(2): 69. A Neighborhood Research of Borrelia burgdorferi Antibodies amongst People with Prior Lyme Illness in Endemic Areas https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023339/

Barbara Strobino 1,2,* Katja Steinhagen 3, Wolfgang Meyer 3, Thomas Scheper 3, Sandra Saschenbrecker 3, Wolfgang Schlumberger 3, Winfried Stöcker 3, Andrea Gaito 4 and Brian A. Fallon 1.

1 Division of Psychiatry, Lyme and Tick-Borne Ailments Analysis Heart, Columbia College Irving Medical Heart, New York, NY 10032, USA; [email protected]
2 Analysis Basis for Psychological Hygiene, Inc., New York, NY 10032, USA
3 Institute for Experimental Immunology, Euroimmun, 23560 Lübeck, Germany; [email protected] (Ok.S.); [email protected] (W.M.); [email protected] (T.S.); [email protected] (S.S.); [email protected] (Wo.S.); [email protected] (Wi.S.)
4 Impartial Researcher, Basking Ridge, NJ 07920, USA; [email protected]

* Correspondence: [email protected]; Tel.: +1-646-774-8052

Summary: The target was to look at the prevalence of Borrelia antibodies amongst symptomatic people with latest and previous Lyme disease in endemic communities utilizing commonplace assays and novel assays using next-generation antigenic substrates. Single- and two-tiered algorithms included totally different anti-Borrelia ELISAs and immunoblots. Antibody prevalence was examined in sera from 32 people with latest erythema migrans (EM), 335 people with persistent signs following remedy for Lyme disease (PTLS), and 41 group controls with out a historical past of Lyme illness. Amongst convalescent EM instances, sensitivity was highest utilizing the C6 ELISA (93.8%) in contrast to different single assays; specificity was 92.7% for the C6 ELISA vs. 85.4–97.6% for different assays. The two-tiered ELISA-EUROLINE IgG immunoblot mixtures enhanced case detection considerably in comparison with the respective ELISA-IgGWestern blot mixtures (75.0% vs. 34.4%) regardless of comparable specificity (95.1% vs. 97.6%, respectively). For PTLS cohorts, two-tier ELISA-IgG-blot positivity ranged from 10.1% to 47.4%, relying upon assay mixture, time from preliminary an infection, and medical historical past. For controls, the two-tier positivity price was 0–14.6% throughout assays. A two-tier algorithm of two-ELISA assays yielded a excessive positivity price of 87.5% amongst convalescent EM instances with specificity of 92.7%. For convalescent EM, mixtures of the C6 ELISA with a second-tier ELISA or line blot could present helpful options to WB-based testing algorithms.


46. Bio-Protocol. Vol 7, Iss 23, December 05, 2017 DOI: 10.21769/BioProtoc.2643.
https://bio-protocol.org/e2643
Lentiviral Knockdown of Transcription Issue STAT1 in Peromyscus leucopus to Assess Its Function within the Restriction of Tick-borne Flaviviruses
Adaeze O. Izuogu,1 and R. Travis Taylor1,* *[email protected]

1 Division of Medical Microbiology and Immunology, College of Toledo Faculty of Medication and Life Sciences, Toledo, Ohio, USA

ABSTRACT: Mobile an infection with tick-borne flaviviruses (TBFVs) ends in activation of the interferon (IFN) signaling pathway and subsequent upregulation of quite a few genes termed IFN stimulated genes (ISGs) (Schoggins et al., 2011). Many ISGs perform to forestall virus pathogenesis by appearing in a broad or particular method by means of protein-protein interactions (Duggal and Emerman, 2012). The efficiency of the IFN signaling response determines the end result of TBFV an infection (Finest, 2017; Carletti et al., 2017). Curiously, information from our lab present that TBFV replication is considerably restricted in cells of the reservoir species Peromyscus leucopus thereby suggesting a potent antiviral response (Izuogu et al., 2017). We assessed the relative contribution of IFN signaling to resistance in P. leucopus by pulling down a serious transcription issue within the IFN response pathway. Sign transducer and activator of transcription 1 (STAT1) was particularly focused in P. leucopus cells by shRNA know-how. We additional examined the influence of gene knockdown on the power of cells to reply to IFN and prohibit virus replication; the outcomes point out that when STAT1 expression is altered, P. leucopus cells have a decreased response to IFN stimulation and are considerably extra vulnerable to TBFV replication.


45. FEBS J. 2017 Nov;284(21):3662-3683. Epub 2017 Sep 30. https://www.ncbi.nlm.nih.gov/pubmed/28892294
Nuclease exercise provides an edge to host-defense peptide piscidin 3 over piscidin 1, rendering it simpler in opposition to persisters and biofilms.
Libardo MDJ1, Bahar AA2, Ma B3, Fu R4, McCormick LE5, Zhao J6, McCallum SA7, Nussinov R3,8, Ren D2,9,10,11, Angeles-Boza* AM1, Cotten* ML12. *[email protected], *[email protected]

1 Division of Chemistry, College of Connecticut, Storrs, CT, USA.
2 Division of Biomedical and Chemical Engineering, Syracuse College, NY, USA.
3 Primary Science Program, Leidos Biomedical Analysis, Inc. Most cancers and Irritation Program, Nationwide Most cancers Institute, Frederick, MD, USA.
4 Nationwide Excessive Magnetic Subject Laboratory, Tallahassee, FL, USA.
5 Hamilton Faculty, Division of Chemistry, Clinton, NY, USA.
6 Most cancers and Irritation Program, Nationwide Most cancers Institute, Frederick, MD, USA.
7 Rennselaer Polytechnic Institute, Heart for Biotechnology & Interdisciplinary Research, Troy, NY, USA.
8 Sackler Institute of Molecular Medication, Division of Human Genetics and Molecular Medication, Sackler College of Medication, Tel Aviv College, Israel.
9 Syracuse Biomaterials Institute, Syracuse College, NY, USA.
10 Division of Civil and Environmental Engineering, Syracuse College, NY, USA. 11 Division of Biology, Syracuse College, NY, USA. 12 Division of Utilized Science, Faculty of William and Mary, Williamsburg, VA, USA.

ABSTRACT: Host-defense peptides (HDPs) characteristic evolution-tested efficiency in opposition to life-threatening pathogens. Whereas piscidin 1 (p1) and piscidin 3 (p3) are homologous and potent fish HDPs, solely p1 is strongly membranolytic. Right here, we hypothesize that one other mechanism imparts p3 robust efficiency. We display that the N-termini of each peptides coordinate Cu2+ and p3-Cu cleaves remoted DNA at a price on par with free Cu2+ however considerably sooner than p1-Cu. On planktonic micro organism, p1 is extra antimicrobial however solely p3 options copper-dependent DNA cleavage. On biofilms and persister cells, p3-Cu is extra lively than p1-Cu, commensurate with stronger peptide-induced DNA harm. Molecular dynamics and NMR present that extra DNA-peptide interactions exist with p3 than p1, and the peptides undertake conformations concurrently poised for metal- and DNA-binding. These outcomes generate a number of vital conclusions. First, homologous HDPs can’t be assumed to have similar mechanisms since p1 and p3 eradicate micro organism by means of distinct relative contributions of membrane and DNA-disruptive results. Second, the nuclease and membrane actions of p1 and p3 present that naturally occurring HDPs can inflict not solely physicochemical but additionally covalent harm. Third, robust nuclease exercise is crucial for biofilm and persister cell eradication, as proven by p3, the homolog extra particular towards micro organism and extra expressed in vascularized tissues. Fourth, p3 combines a number of physicochemical properties (e.g., Amino Terminal Copper and Nickel binding motif; quite a few arginines; reasonable hydrophobicity) that confer low membranolytic results, sturdy copper-scavenging functionality, robust interactions with DNA, and quick nuclease exercise. This new data might assist design novel therapeutics lively in opposition to hard-to-treat persister cells and biofilms.


44. ACS Chem. Biol., 2017, 12 (5), pp 1170–1182 Publication Date (Internet): March 29, 2017 https://pubs.acs.org/doi/abs/10.1021/acschembio.7b00237
Membrane Oxidation in Cell Supply and Cell Killing Functions
Ting-Yi Wang,†,⊥ M. Daben J. Libardo,‡,⊥ Alfredo M. Angeles-Boza,*,‡ and Jean-Philippe Pellois*,†,§ †Division of Biochemistry and Biophysics, Texas A&M College, Faculty Station, Texas 77843, United States ‡Division of Chemistry, College of Connecticut, Storrs, Connecticut 06269, United States §Division of Chemistry, Texas A&M College, Faculty Station, Texas 77843, United States *E-mail: [email protected]., *E-mail: [email protected].

ABSTRACT: Cell supply or cell killing processes usually contain the crossing or disruption of mobile membranes. We evaluate how, by modifying the composition and properties of membranes, membrane oxidation will be exploited to boost the supply of macromolecular cargoes into reside human cells. We additionally describe how membrane oxidation will be utilized to attain environment friendly killing of micro organism by antimicrobial peptides. Lastly, we current latest proof highlighting how membrane oxidation is intimately engaged in pure organic processes corresponding to antigen supply in dendritic cells and within the killing of micro organism by antimicrobial peptides. Total, the insights which have been lately gained on this space ought to facilitate the event of simpler supply applied sciences andantimicrobial therapeutic approaches.


43. Biochemistry, 2017, 56 (10), pp 1403–1414 Publication Date (Internet): February 22, 2017 https://pubs.acs.org/doi/abs/10.1021/acs.biochem.6b01046
Exploration of the Innate Immune System of Styela clava: Zn2+ Binding Enhances the Antimicrobial Exercise of the Tunicate Peptide Clavanin A
Samuel A. Juliano†, Scott Pierce†, James A. deMayo‡, Marcy J. Balunas‡, and Alfredo M. Angeles-Boza*† † Division of Chemistry, College of Connecticut, Storrs, Connecticut 06269-3060, United States ‡ Division of Medicinal Chemistry, Division of Pharmaceutical Sciences, College of Connecticut, Storrs, Connecticut 06269, United States *E-mail: [email protected]

ABSTRACT: Tunicates have been used as primitive fashions for understanding cellmediated and humoral immunity. Clavanin A (ClavA) is one member of a household of antimicrobial peptides produced by the solitary tunicate Styela clava. On this work, we display that ClavA makes use of Zn2+ ions to potentiate its antimicrobial exercise not solely by decreasing the focus at which the peptide inhibits the expansion of micro organism but additionally by rising the speed of killing. Membrane depolarization, β-galactosidase leakage, and potassium leakage assays point out that ClavA is membrane lively, kinds small pores, however induces cell loss of life by focusing on an intracellular element. ClavA and ClavA-Zn2+ added to Escherichia coli and imaged by confocal microscopy translocate throughout the cell membrane. E. coli mutants missing the useful Zn2+ import system are much less vulnerable to ClavA, suggesting that the synergistic exercise between ClavA and Zn2+ has a cytoplasmic goal, which is additional supported by its nucleolytic exercise. Total, these research establish a exceptional new mechanism by which zinc contributes to the immune response within the tunicate S. clava.


42. PLoS One, June 26, 2017;12(6)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484488/
Interferon Signaling in Peromyscus Leucopus Confers a Potent and Particular Restriction to Vector-borne Flaviviruses
Adaeze O. Izuogu1, Kristin L. McNally2, Stephen E. Harris3, Brian H. Youseff1, John B. Presloid1, Christopher Burlak4, Jason Munshi-South5, Sonja M. Best2, R. Travis Taylor1*

1 Division of Medical Microbiology and Immunology, College of Toledo Faculty of Medication and Life Sciences, Toledo, Ohio, United States of America,
2 Innate Immunity and Pathogenesis Unit, Laboratory of Virology, Rocky Mountain Laboratories, DIR, NIAID, NIH, Hamilton, Montana, United States of America,
3 The Graduate Heart, Metropolis College of New York, New York, New York, United States of America,
4 Division of Surgical procedure, College of Minnesota, Minneapolis, Minnesota, United States of America,
5 Louis Calder Heart-Organic Subject Station, Fordham College, Armonk, New York, United States of America * [email protected]

Summary: Tick-borne flaviviruses (TBFVs), together with Powassan virus and tick-borne encephalitis virus trigger encephalitis or hemorrhagic fevers in people with case-fatality charges starting from 1-30%. Regardless of extreme illness in people, TBFV an infection of pure rodent hosts has little noticeable impact. At the moment, the idea for resistance to illness just isn’t recognized. We hypothesize that the coevolution of flaviviruses with their respective hosts has formed the evolution of potent antiviral elements that suppress virus replication and defend the host from deadly an infection. Within the present examine, we in contrast virus an infection between reservoir host cells and associated vulnerable species. An infection of major fibroblasts from the white-footed mouse (Peromyscus leucopus, a consultant host) with a panel of vector-borne flaviviruses confirmed as much as a ten,000-fold discount in virus titer in comparison with management Mus musculus cells. Replication of vesicular stomatitis virus was equal in P. leucopus and M. musculus cells suggesting that restriction was flavivirus-specific. Step-wise comparability of the virus an infection cycle revealed a major block to viral RNA replication, however not virus entry, in P. leucopus cells. To know the position of the kind I interferon (IFN) response in virus restriction, we knocked down sign transducer and activator of transcription 1 (STAT1) or the kind I IFN receptor (IFNAR1) by RNA interference. Lack of IFNAR1 or STAT1 considerably relieved the block in virus replication in P. leucopus cells. The foremost IFN antagonist encoded by TBFV, nonstructural protein 5, was useful in P. leucopus cells, thus ruling out ineffective viral antagonism of the host IFN response. Collectively, this work demonstrates that the IFN response of P. leucopus imparts a powerful and virus-specific barrier to flavivirus replication. Future identification of the IFN-stimulated genes answerable for virus restriction particularly in P. leucopus will yield mechanistic perception into environment friendly management of virus replication and will inform the event of antiviral therapeutics.


41. Antibiotics, March 22, 2017
http://www.mdpi.com/2079-6382/6/1/10/pdf
Exercise of Sulfa Medicine and Their Combos in opposition to Stationary Part B. burgdorferi In Vitro Jie Feng, Shuo Zhang, Wanliang Shi and Ying Zhang * Division of Molecular Microbiology and Immunology, Bloomberg College of Public Well being, Johns Hopkins College, Baltimore, MD 21205, USA *Writer to whom correspondence must be addressed. [email protected]

Summary: Lyme disease is a commonest vector-borne illness within the US. Though the vast majority of Lyme sufferers will be cured with the usual two- to four-week antibiotic remedy, at the least 10%–20% of sufferers proceed to endure from extended post-treatment Lyme disease syndrome (PTLDS). Whereas the trigger for that is unclear, one chance is that persisting organisms will not be killed by present Lyme antibiotics. In our earlier research, we screened an FDA drug library and an NCI compound library on B. burgdorferi and located some drug hits together with sulfa medicine as having good exercise in opposition to B. burgdorferi stationary section cells. On this examine, we evaluated the relative exercise of three generally used sulfa medicine, sulfamethoxazole (Smx), dapsone (Dps), sulfachlorpyridazine (Scp), and in addition trimethoprim (Tmp), and assessed their mixtures with the generally prescribed Lyme antibiotics for actions in opposition to B. burgdorferi stationary section cells. Utilizing the identical molarity focus, dapsone, sulfachlorpyridazine and trimethoprim confirmed very comparable exercise in opposition to stationary section B. burgdorferi enriched in persisters; nevertheless, sulfamethoxazole was the least lively drug among the many three sulfa medicine examined. Curiously, opposite to different bacterial techniques, Tmp didn’t present synergy in drug mixtures with the three sulfa medicine at their clinically related serum concentrations in opposition to B. burgdorferi. We discovered that sulfa medicine mixed with different antibiotics have been extra lively than their respective single medicine and that four-drug mixtures have been extra lively than three-drug mixtures. 4-drug mixtures dapsone + minocycline + cefuroxime + azithromycin and dapsone + minocycline + cefuroxime + rifampin confirmed one of the best exercise in opposition to stationary section B. burgdorferi in these sulfa drug mixtures. Nonetheless, these four-sulfa-drug–containing mixtures nonetheless had significantly much less exercise in opposition to B. burgdorferi stationary section cells than the Daptomycin + cefuroxime + doxycycline used as a constructive management which utterly eradicated B. burgdorferi stationary section cells. Future research are wanted to judge and optimize the sulfa drug mixtures in vitro and in addition in animal fashions.


40. Frontiers in Microbiology, October 19, 2016 http://journal.frontiersin.org/article/10.3389/fmicb.2016.01744/pdf
Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-like Microcolony B. burgdorferi Persisters Which Are Sterilized by Daptomycin/Doxycycline/Cefuroxime Drug Mixture with out Pulse Dosing
Jie Feng1, Shuo Zhang1, Wanliang Shi1, Ying Zhang1*

1Department of Molecular Microbiology and Immunology, Bloomberg College of Public Well being, Johns Hopkins College, USA *Corresponding creator: Ying Zhang, MD, PhD Division of Molecular Microbiology and Immunology, Bloomberg College of Public Well being, Johns Hopkins College, Baltimore, MD 21205, USA [email protected]

Summary: Though the vast majority of Lyme disease sufferers will be cured, at the least 10-20% of the sufferers proceed to endure from persisting signs corresponding to fatigue, muscular and joint ache, and neurologic impairment after commonplace 2-4 week antibiotic remedy. Whereas the causes for this post-treatment Lyme disease signs are unclear, one chance is because of B. burgdorferi persisters that aren’t successfully killed by present antibiotics corresponding to doxycycline or amoxicillin used to deal with Lyme disease. A earlier examine confirmed that 4 rounds of ceftriaxone pulse dosing remedy eradicated B. burgdorferi persisters in vitro utilizing a comparatively younger late log section tradition (5 day previous). On this examine, we investigated if ceftriaxone pulse dosing might additionally eradicate B. burgdorferi persisters in older stationary section cultures (10 day previous) enriched with extra resistant microcolony type of persisters. We discovered that ceftriaxone pulse dosing might solely eradicate planktonic log section B. burgdorferi spirochetal kinds and spherical physique kinds however no more resistant aggregated biofilm-like microcolony persisters enriched in stationary section cultures. Furthermore, we discovered that not all medicine are appropriate for pulse dosing, with bactericidal medicine ceftriaxone and cefuroxime being extra acceptable for pulse dosing than bacteriostatic drug doxycycline and persister drug daptomycin. We additionally confirmed that drug mixture pulse dosing remedy was simpler than single drug pulse dosing. Importantly, we display that pulse dosing remedy impaired the exercise of the persister drug daptomycin and its drug mixture in opposition to B. burgdorferi persisters and that the best technique to kill the extra resistant biofilm-like microcolonies is the daptomycin/doxycycline/ceftriaxone triple drug mixture with out pulse dosing. Our findings point out pulse dosing could not all the time work as a normal precept however quite is determined by the particular medicine used, with cidal medicine being extra acceptable for pulse dosing than static or persister medicine, and that drug mixture strategy with persister medicine is simpler at killing the extra resistant microcolony type of persisters than pulse dosing. These observations could have implications for simpler remedy of Lyme disease. Future research are required to validate these findings in animal fashions of B. burgdorferi persistence.


39. Frontiers in Microbiology, Could 23, 2016 http://journal.frontiersin.org/article/10.3389/fmicb.2016.00743/full
A Drug Mixture Display Identifies Medicine Lively in opposition to Amoxicillin-Induced Spherical Our bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library Ying Zhang,
Jie Feng, Wanliang Shi, Shuo Zhang, David Sullivan, Paul G. Auwaerter, Johns Hopkins

Summary: Though presently beneficial antibiotics for Lyme disease corresponding to doxycycline or amoxicillin remedy the vast majority of the sufferers, about 10–20% of sufferers handled for Lyme disease could expertise lingering signs together with fatigue, ache, or joint and muscle aches. Beneath experimental stress circumstances corresponding to hunger or antibiotic publicity, Borrelia burgdorferi can develop spherical physique kinds, that are a kind of persister micro organism that seem resistant in vitro to customary first-line antibiotics for Lyme disease. To establish simpler medicine with exercise in opposition to the spherical physique type of B. burgdorferi, we established a spherical physique persister mannequin induced by publicity to amoxicillin (50 μg/ml) after which screened the Meals and Drug Administration drug library consisting of 1581 drug compounds and in addition 22 drug mixtures utilizing the SYBR Inexperienced I/propidium iodide viability assay. We recognized 23 drug candidates which have greater exercise in opposition to the spherical our bodies of B. burgdorferi than both amoxicillin or doxycycline. Eleven particular person medicine scored higher than metronidazole and tinidazole which have been beforehand described to be lively in opposition to spherical our bodies. On this amoxicillin-induced spherical physique mannequin, some drug candidates corresponding to daptomycin and clofazimine additionally displayed enhanced exercise which was just like a earlier display screen in opposition to stationary section B. burgdorferi persisters not publicity to amoxicillin. Further candidate medicine lively in opposition to spherical our bodies recognized embody artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug mixtures had the best exercise in opposition to amoxicillin-induced spherical our bodies and stationary section B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings verify and prolong earlier findings that sure drug mixtures have superior exercise in opposition to B. burgdorferi persisters in vitro, even when pre-treated with amoxicillin. These findings could have implications for improved remedy of Lyme disease.


38. Park Science (NPS, Division of Inside) March 2016 http://www.nature.nps.gov/ParkScience/Archive/PDF/Article_PDFs/ParkScience32(1)Summer2015_36-41_Ford_et_al_3819.pdf
Tick surveillance and illness prevention on the Appalachian Path (Additionally printed in Appalachian Path Journeys, The Journal of the Appalachian Path Conservancy, Could/June 2014)

Karl Ford, Robyn Nadolny, Ellen Stromdahl, and Graham Hickling Summary: The Appalachian Nationwide Scenic Path (AT) runs 3,520 km (2,187 mi) from northern Georgia to northern Maine, traversing 14 states the place Lyme disease and different tickborne ailments are endemic or rising. Roughly 2–3 million guests hike the AT yearly, together with through-hikers who spend 5 to 6 months on the path in spring by means of early fall, when frequent tick species are lively. Illness vector tick surveillance was carried out from April by means of August 2013 at 42 randomly chosen AT shelter areas alongside a south-to-north transect protecting the complete size of the AT. Tick abundance at shelters and tenting areas was in contrast with tick abundance on the AT itself, and the collected ticks have been examined for frequent bacterial pathogens. Human-biting tick species collected comprised Ixodes scapularis, Amblyomma americanum, Amblyomma maculatum, and Dermacentor variabilis. Human pathogens Borrelia burgdorferi and Rickettsia montanensis have been detected in examined ticks. Tick abundance on the path was low general (2.8 ticks per 1,000 m2 sampled), however exceeded tick abundance in shelters and tenting areas by 14.5 occasions. No ticks have been collected south of Virginia or north of Massachusetts, or above 829 m (2,720 ft) in elevation, which means that season and elevation are vital determinants of the chance of hiker publicity to questing ticks on the AT. Such info must be included in future well being messaging to hikers together with preventive measures. Administration points are mentioned.


37. FEMS Microbiology Letters Advance Entry, July 24, 2015 http://femsle.oxfordjournals.org/content/early/2015/07/23/femsle.fnv120
Biofilm formation by 1 Borrelia sensu lato Arun Timmaraju1,2,†, Priyanka A.S. Theophilus1,†, Kunthavai Balasubramanian1,3, Shafiq Shakih1, David F. Leucke1 and Eva Sapi1,*

1 Lyme disease analysis group, Division of Biology and Environmental Science, College of New Haven, West Haven, CT, USA
2 Current tackle: Interpace Diagnostics, New Haven, CT, 06519 3 Current tackle: Division of Hematology, Yale College of Medication, New Haven, CT, 06520 † Contributed equally * Correspondence: Eva Sapi Ph.D., Division of Biology and Environmental Sciences, College of New Haven, 1211 Campbell Avenue, Charger Plaza LL16. West Haven, CT, 06516, USA. [email protected]

Summary: Bacterial biofilms are microbial communities held collectively by an extracellular polymeric substance matrix predominantly composed of polysaccharides, proteins and nucleic acids. We had beforehand proven that Borrelia burgdorferi sensu stricto, the causative organism of Lyme disease in the US is able to forming biofilms in vitro. Right here, we investigated biofilm formation by Borrelia afzelii and Borrelia garinii, which trigger Lyme disease in Europe. Utilizing numerous histochemistry and microscopy methods, we present that Borrelia afzelii and Borrelia garinii type biofilms, which resemble biofilms fashioned by Borrelia burgdorferi sensu stricto. Excessive-resolution atomic power microscopy revealed similarities within the ultra-structural group of the biofilms type by three Borrelia species. Histochemical experiments revealed a heterogeneous group of exopolysaccharides among the many three Borrelia species. These outcomes counsel that biofilm formation is perhaps a typical trait of Borrelia genera physiology.


36. Scientific Infectious Ailments Advance Entry, September 2, 2014 http://www.ncbi.nlm.nih.gov/pubmed/25182244
A comparability of Lyme disease serologic check outcomes from 4 laboratories in sufferers with persistent signs after antibiotic remedy Brian A. Fallon1, Martina Pavlicova2, Samantha W. Coffino3, Carl Brenner4

1 Division of Psychiatry, Columbia College, New York NY
2 Division of Biostatistics, Mailman College of Public Well being, Columbia College, New York, NY
3 Division of Neurology, Columbia College, New York, NY 4 Lamont-Doherty Earth Observatory of Columbia College, Palisades, NY Abstract: In sufferers with post-treatment Lyme syndrome, charges of constructive serologic check outcomes have been typically comparable amongst a college laboratory, a industrial laboratory, and two Lyme specialty laboratories, though interlaboratory variability was excessive and the IgM Western Blot carried out poorly.

Summary: Background – Because the incidence of Lyme disease (LD) has elevated, various “Lyme specialty laboratories” have emerged, claiming singular experience in LD testing. We investigated the diploma of interlaboratory variability of a number of LD serologic assessments—entire cell sonicate (WCS) enzyme-linked immunosorbent assay (ELISA), IgM and IgG Western blots (WB), and an ELISA primarily based on the conserved sixth area of VlsE (C6)—carried out at one college laboratory, one industrial laboratory and two laboratories focusing on LD testing.


35. Veterinary Sciences, 2014
www.mdpi.com/2306-7381/1/1/5
Filarial Nematode An infection in Ixodes scapularis Ticks Collected from Southern Connecticut Pabbati Namrata, Jamie M. Miller, Madari Shilpa, Patlolla Raghavender Reddy, Cheryl Bandoski, Michael J. Rossi and Eva Sapi* Division of Biology and Environmental Science, College of New Haven, West Haven, CT 06516, USA

*Writer to whom correspondence must be addressed.

Summary: It was lately demonstrated that the lone star tick Amblyomma americanum might harbor filarial nematodes inside the genus Acanthocheilonema. On this examine, Ixodes scapularis (deer) ticks collected from Southern Connecticut have been evaluated for his or her potential to harbor filarial nematodes. Non-engorged nymphal and grownup stage Ixodes scapularis ticks have been collected in Southern Connecticut utilizing the usual drag methodology. In situ hybridization with filarial nematode particular sequences demonstrated the presence of filarial nematodes in Ixodes ticks. Filarial nematode particular DNA sequences have been amplified and confirmed by direct sequencing in Ixodes nymphal and grownup ticks utilizing both normal filarial nematode or Onchocercidae household particular PCR primers. Phylogenetic evaluation of the 12S rDNA gene sequence indicated that the filarial nematode infecting Ixodes scapularis ticks is most carefully associated to the species present in Amblyomma americanum ticks and belongs to the genus of Acanthocheilonema. Our information additionally demonstrated that an infection price of those filarial nematode in Ixodes ticks is comparatively excessive (about 22% and 30% in nymphal and grownup Ixodes ticks, respectively). In abstract, the outcomes from our research demonstrated that filarial nematode an infection was present in Ixodes ticks just like what has been present in Amblyomma americanum ticks. Vet. Sci. 2014, 1, 5-15; doi:10.3390/vetsci1010005


34. Psychosomatics 2013
http://www.psychosomaticsjournal.com/article/S0033-3182%2813%2900078-9/fulltext
Correlates of Perceived Well being-Associated High quality of Life in Put up-treatment Lyme Encephalopathy Avinash M.Chandra , B.A.-1, John G. Keilp, Ph.D.-2, Brian A. Fallon*, M.D.-2

1 Division of Psychiatry, Columbia College, New York, NY.
2 Division of Scientific Therapeutics of the New York State Psychiatric Institute, New York, NY *Corresponding Writer: Brian A. Fallon, M.D [email protected]

ABSTRACT: Background – Marked useful impairment has been reported by sufferers with post-treatment Lyme disease syndrome (PTLDS). Goal: We sought to establish however the medical options that contribute most strongly to the impaired well being standing related to PTLDS. Strategies: Enrolled sufferers had a well-documented historical past of Lyme disease, prior remedy with at the least 3 weeks with intravenous ceftriaxone, a constructive IgG Western blot, and goal issues with reminiscence. An index rating to seize mixture cognitive functioning, Brief-Type 36 bodily and psychological element summer season scores, and scores on different medical and demographic measures have been examined. A number of linear regressions have been carried out to find out vital predictors of perceptions of impaired life functioning as delineated by theShort-Form36.Outcomes: Fatigue was a very powerful contributor to perceived impairments in general bodily functioning, and fatigue and melancholy considerably predicted perceived impairments in general psychological functioning. Conclusions: As a result of fatigue and melancholy contribute prominently to studies of impaired bodily functioning and psychological functioning amongst sufferers with PTLDS, clinicians ought to assess sufferers for these signs and contemplate focusing on these signs within the number of remedy interventions. Future managed research ought to look at the effectiveness of such brokers for sufferers with PTLDS.


33. Worldwide Journal of Medical Sciences 2013 http://www.medsci.org/v10p0915.htm
Lyme Borreliosis in Human Sufferers in Florida and Georgia, USA
Kerry L. Clark-1, Brian Leydet-1,2, Shirley Hartman-3 1-College of North Florida, 2-Louisiana State College, 3-Mandarin Wellness Heart, Florida Corresponding creator: Kerry L. Clark, M.P.H., Ph.D., Division of Public Well being, College of North Florida, 1 UNF Drive, Jacksonville, FL 32224. Cellphone: (904) 620-1427. Fax: (904) 620-2848. E-mail: [email protected]

ABSTRACT: The intention of this examine was to find out the reason for sickness in a number of human sufferers residing in Florida and Georgia, USA, with suspected Lyme disease primarily based upon EM-like pores and skin lesions and/or signs in step with early localized or late disseminated Lyme borreliosis. Utilizing polymerase chain response (PCR) assays developed particularly for Lyme group Borrelia spp., adopted by DNA sequencing for affirmation, we recognized Borrelia burgdorferi sensu lato DNA in samples of blood and pores and skin and in addition in lone star ticks (Amblyomma americanum) faraway from a number of sufferers who both reside in or have been uncovered to ticks in Florida or Georgia. That is the primary report back to current mixed PCR and DNA sequence proof of an infection with Lyme Borrelia spp. in human sufferers within the southern U.S., and to display that a number of B. burgdorferi sensu lato species could also be related to Lyme disease-like indicators and signs in southern states. Based mostly on the findings of this examine, we propose that human Lyme borreliosis happens in Florida and Georgia, and that some instances of Lyme-like sickness known as southern tick related rash sickness (STARI) within the southern U.S. could also be attributable to beforehand undetected B. burgdorferi sensu lato infections.


32. Northeastern Naturalist 2013; 20(1):197–204.
http://www.bioone.org/doi/abs/10.1656/045.020.0116
Distribution of Ticks & Prevalence of Borrelia burgdorferi within the Higher Connecticut River Valley of Vermont
Abigail C. Serra-1, Paul S. Warden-2, Colin R. Fricker-2, and Alan R. Giese-1,*

1-Lyndon State Faculty VT, 2-Analytical Providers, Inc. VT
Corresponding creator – [email protected] edu.

ABSTRACT: Ixodes scapularis (Black-legged Tick) has expanded its vary in latest many years. To ascertain baseline information on the abundance of the Black-legged Tick and Borrelia burgdorferi (the causative agent of Lyme disease) on the fringe of a putative vary enlargement, we collected 1398 ticks from 5 areas alongside the Connecticut River in Vermont. Assortment areas have been roughly evenly distributed between the villages of Ascutney and Guildhall. Relative abundance and distribution by species different throughout websites. Black-legged Ticks dominated our collections (n = 1348, 96%), adopted by Haemaphysalis leporispalustris (Rabbit Tick; n = 45, 3%), and Dermacentor variabilis (American Canine Tick; n = 5, <1%). Black-legged Tick abundance ranged from 6198 ticks per survey hectare (all life phases mixed) on the Thetford web site to zero on the Guildhall web site. There was little to no overlap of tick species throughout websites. Phenology of Black-legged Ticks matched printed info from different areas of the northeastern USA. Prevalence of B. burgdorferi in grownup Black-legged Ticks was 8.9% (n = 112)


31. J Neuropsychiatry Clin Neurosci. 2013 Feb 27. doi: 10.1176/appi.neuropsych.12090223. http://www.ncbi.nlm.nih.gov/pubmed/23446551

Put up-Therapy Lyme Syndrome and Central Sensitization.

Batheja S, Nields JA, Landa A, Fallon BA*. Division of Psychiatry, Columbia College, and The New York State Psychiatric Institute.
*Ship correspondence to Dr. Fallon; e-mail: [email protected]

ABSTRACT: Central sensitization is a course of that hyperlinks quite a lot of continual ache problems which might be characterised by hypersensitivity to noxious stimuli and ache in response to non-noxious stimuli. Amongst these problems, remedies that act centrally could have better efficacy than remedies appearing peripherally. As a result of many people with post-treatment Lyme syndrome (PTLS) have an identical symptom cluster, central sensitization could also be a course of mediating or exacerbating their sensory processing. This text evaluations central sensitization, studies new information on sensory hyperarousal in PTLS, explores the potential position of central sensitization in symptom chronicity, and suggests new instructions for neurophysiologic and remedy analysis.


30. The Open Neurology Journal 2012: 6, (Suppl 1-M2) 79-87

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474942/
A Reappraisal of the U.S. Scientific Trials of Put up-Therapy Lyme Illness Syndrome

Brian A. Fallon*,1, Eva Petkova2, John G. Keilp3 and Carolyn B. Britton4

1 Columbia College, Dept. of Psychiatry, Division of Scientific Therapeutics, USA
2 New York College, Dept. of Youngster and Adolescent Psychiatry, Division of Biostatistics, USA
3 Columbia College, Dept. of Psychiatry, Division of Neuroscience, USA
4 Columbia College, Dept. of Neurology, USA *Ship correspondence to Dr. Fallon; e-mail: [email protected]

ABSTRACT: 4 federally funded randomized placebo-controlled remedy trials of post-treatment Lyme syndrome in the US have been carried out. Most worldwide remedy tips summarize these trials as having proven no acute or sustained profit to repeated antibiotic remedy. The objective of this paper is to find out whether or not this abstract conclusion is supported by the proof. Strategies: The strategies and outcomes of the 4 U.S. remedy trials are described and their critiques evaluated. Outcomes: 2 of the 4 U.S. remedy trials demonstrated efficacy of IV ceftriaxone on major and/or secondary consequence measures. Conclusions: Future remedy tips ought to make clear that efficacy of IV ceftriaxone for post-treatment Lyme fatigue was demonstrated in a single RCT and supported by a second RCT, however that its use was not beneficial primarily as a consequence of adversarial occasions stemming from the IV route of remedy. Whereas repeated IV antibiotic remedy will be efficient, safer modes of supply are wanted.


29. PLoS ONE 7(10) 2012: e48277. doi:10.1371/journal.pone.0048277 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0048277
Characterization of Biofilm Formation by Borrelia burgdorferi In Vitro

Eva Sapi*, Scott L. Bastian, Cedric M. Mpoy, Shernea Scott, Amy Rattelle, Namrata Pabbati, Akhila Poruri, Divya Burugu, Priyanka A. S. Theophilus, Truc V. Pham, Akshita Datar, Navroop Ok. Dhaliwal, Alan MacDonald, Michael J. Rossi, David F. Luecke (Lyme Illness Analysis Group, Division of Biology and Environmental Sciences, College of New Haven, West Haven, Connecticut, United States of America); Saion Ok. Sinha (Division of Physics, College of New Haven, West Haven, Connecticut, United States of America).

*Corresponding Writer E-mail: Eva Sapi, [email protected]

ABSTRACT: Borrelia burgdorferi, the causative agent of Lyme disease, has lengthy been recognized to be able to forming aggregates and colonies. It was lately demonstrated that Borrelia burgdorferi mixture formation dramatically adjustments the in vitro response to hostile environments by this pathogen. On this examine, we investigated the speculation that these aggregates are certainly biofilms, buildings whose resistance to unfavorable circumstances are nicely documented. We studied Borrelia burgdorferi for a number of recognized hallmark options of biofilm, together with structural rearrangements within the aggregates, variations in growth on numerous substrate matrices and secretion of a protecting extracellular polymeric substance (EPS) matrix utilizing a number of modes of microscopic, cell and molecular biology methods. The atomic power microscopic outcomes supplied proof that multilevel rearrangements happen at totally different phases of mixture growth, producing a posh, constantly rearranging construction. Our outcomes additionally demonstrated that Borrelia burgdorferi is able to creating aggregates on totally different abiotic and biotic substrates, and can be able to forming floating aggregates. Analyzing the extracellular substance of the aggregates for potential exopolysaccharides revealed the existence of each sulfated and non-sulfated/carboxylated substrates, predominately composed of an alginate with calcium and extracellular DNA current. In abstract, we’ve discovered substantial proof that Borrelia burgdorferi is able to forming biofilm in vitro. Biofilm formation by Borrelia species would possibly play an vital position of their survival in various environmental circumstances by offering refuge to particular person cells.


28. PLOS One 2012
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0033280
Genome Stability of Lyme Illness Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

Sherwood R. Casjens1*, Emmanuel F. Mongodin2, Wei-Gang Qiu3, Benjamin J. Luft4, Steven E. Schutzer5, Eddie B. Gilcrease1, Wai Mun Huang1, Marija Vujadinovic1, John Ok. Aron1, Levy C. Vargas3, Sam Freeman3, Diana Radune6, Janice F. Weidman6, George I. Dimitrov6, Hoda M. Khouri6, Julia E. Sosa6, Rebecca A. Halpin6, John J. Dunn7, Claire M. Fraser2

1-College of Utah College of Medication,
2-College of Maryland College of Medication,
3-Hunter Faculty of the Metropolis College of New York,
4-Stony Brook College, NY,
5- New Jersey Medical College,
6-J. Craig Venter Institute, MD,
7-Brookhaven Nationwide Laboratory, NY

*Corresponding Writer E-mail: [email protected]

ABSTRACT: Lyme disease is the commonest tick-borne human sickness in North America. With a purpose to perceive the molecular pathogenesis, pure variety, inhabitants construction and epizootic unfold of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a significantly better understanding of the pure variety of its genome will likely be required. In the direction of this finish we current a comparative evaluation of the nucleotide sequences of the quite a few plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains have been chosen as a result of they embody the three mostly studied laboratory strains, and since they signify totally different main genetic lineages and so are informative relating to the genetic variety and evolution of this organism. A singular characteristic of Borrelia genomes is that they carry numerous linear and round plasmids, and this work exhibits that strains N40, JD1, 297 and B31 carry associated however non-identical units of 16, 20, 19 and 21 plasmids, respectively, that comprise 33–40% of their genomes. We deduce that there are at the least 28 plasmid compatibility sorts among the many 4 strains. The B. burgdorferi ~900 Kbp linear chromosomes are evolutionarily exceptionally secure, apart from a brief ≤20 Kbp plasmid-like part on the proper finish. A couple of of the plasmids, together with the linear lp54 and round cp26, are additionally very secure. We present right here that the opposite plasmids, particularly the linear ones, are significantly extra variable. Practically all the linear plasmids have undergone a number of substantial inter-plasmid rearrangements since their final frequent ancestor. Despite these rearrangements and variations in plasmid contents, the general gene complement of the totally different isolates has remained comparatively fixed.


27. Journal of Bacteriology 2011 http://jb.asm.org/content/193/4/1018.long Complete-Genome Sequences of 13 Isolates of Borrelia burgdorferi Steven E. Schutzer1,*, Claire M. Fraser-Liggett2, Sherwood R. Casjens3,*, Wei-Gang Qiu4, John J. Dunn5, Emmanuel F. Mongodin2, and Benjamin J. Luft6 1-College of Medication and Dentistry of New Jersey—New Jersey Medical College, 2-Institute for Genome Sciences, College of Maryland, College of Medication, 3-College of Utah Medical College, 4- Hunter Faculty of the Metropolis College of New York, 5-Brookhaven Nationwide Laboratory, Upton, New York 6-Stony Brook College *Corresponding creator. Mailing tackle for Steven E. Schutzer: Division of Medication, College of Medication and Dentistry of New Jersey—New Jersey Medical College, Newark, NJ 07103. E-mail: [email protected] Mailing tackle for Sherwood R. Casjens: Division of Pathology, College of Utah Medical College, Room 2200 EEJMRB, 15 North Medical Dr. East, Salt Lake Metropolis, UT 84112. E-mail: [email protected] ABSTRACT: Borrelia burgdorferi is a causative agent of Lyme disease in North America and Eurasia. The primary full genome sequence of B. burgdorferi pressure 31, obtainable for greater than a decade, has assisted analysis on the pathogenesis of Lyme disease. As a result of a single genome sequence just isn’t enough to know the connection between genotypic and geographic variation and illness phenotype, we decided the whole-genome sequences of 13 further B. burgdorferi isolates that span the vary of pure variation. These sequences ought to permit improved understanding of pathogenesis and supply a basis for novel detection, analysis, and prevention methods.


26. PLoS ONE 6(2): e17287. doi:10.1371/journal.pone.0017287 2011 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017287
Distinct Cerebrospinal Fluid Proteomes Differentiate Put up-Therapy Lyme Illness from Continual Fatigue Syndrome

Steven E. Schutzer-1#*, Thomas E. Angel-4#, Tao Liu-4#, Athena A. Schepmoes-4, Therese R. Clauss-4, Joshua N. Adkins-4, David G. Camp II-4, Bart Ok. Holland-3, Jonas Bergquist-5, Patricia Ok. Coyle-6, Richard D. Smith-4, Brian A. Fallon-7, Benjamin H. Natelson-2,8

1-Division of Medication, College of Medication and Dentistry of New Jersey-New Jersey Medical College, Newark, New Jersey, United States of America,
2 Division of Neurology, College of Medication and Dentistry of New Jersey-New Jersey Medical College, Newark, New Jersey, United States of America,
3 Division of Biostatistics and Epidemiology, College of Medication and Dentistry of New Jersey-New Jersey Medical College, Newark, New Jersey, United States of America,
4 Organic Sciences Division, Pacific Northwest Nationwide Laboratory, Richland, Washington, United States of America,
5 Division of Bodily and Analytical Chemistry, Uppsala College, Uppsala, Sweden,
6 Division of Neurology, State College of New York-Stony Brook, Stony Brook, New York, United States of America,
7 Division of Psychiatry, Columbia College Medical Heart, New York, New York, United States of America, 8 Division of Ache Medication and Palliative Care and Beth Israel Medical Heart, Albert Einstein College of Medication, Bronx, New York, United States of America

*Corresponding Writer E-mail: [email protected] #These authors contributed equally to this work

ABSTRACT: Neurologic Put up Therapy Lyme disease (nPTLS) and Continual Fatigue (CFS) are syndromes of unknown etiology. They share options of fatigue and cognitive dysfunction, making it tough to distinguish them. Unresolved is whether or not nPTLS is a subset of CFS. Pooled cerebrospinal fluid (CSF) samples from nPTLS sufferers, CFS sufferers, and wholesome volunteers have been comprehensively analyzed utilizing high-resolution mass spectrometry (MS), coupled with immunoaffinity depletion strategies to scale back protein-masking by ample proteins. Particular person affected person and wholesome management CSF samples have been analyzed instantly using a MS-based label-free quantitative proteomics strategy. We discovered that each teams, and people inside the teams, could possibly be distinguished from one another and normals primarily based on their particular CSF proteins (p<0.01). CFS (n = 43) had 2,783 non-redundant proteins, nPTLS (n = 25) contained 2,768 proteins, and wholesome normals had 2,630 proteins. Preliminary pathway evaluation demonstrated that the info could possibly be helpful for speculation era on the pathogenetic mechanisms underlying these two associated syndromes. nPTLS and CFS have distinguishing CSF protein enhances. Every situation has various CSF proteins that may be helpful in offering candidates for future validation research and insights on the respective mechanisms of pathogenesis. Distinguishing nPTLS and CFS permits extra targeted examine of every situation, and may result in novel diagnostics and therapeutic interventions.


25. Genetics: Revealed Articles Forward of Print, printed on September 2, 2011 as 0.1534/genetics.111.130773 Copyright 2011 http://www.genetics.org/content/189/3/951.long
Pervasive Recombination and Sympatric Genome Diversification Pushed by Frequency-Dependent Choice in Borrelia burgdorferi, the Lyme disease Bacterium
James Haven*,1, Levy C. Vargas†, Emmanuel F. Mongodin‡, Vincent Xue§, Yozen Hernandez†, Pedro Pagan†, Claire M. Fraser-Liggett‡, Steven E. Schutzer**, Benjamin J. Luft††, Sherwood R. Casjens‡‡, and Wei-Gang Qiu†*, §§, 2 *Division of Biology, The Graduate Heart, Metropolis College of New York, New York, New York 10016 †Division of Organic Sciences and The Heart for Gene Construction and Perform and §Division of Pc Science, Hunter Faculty, Metropolis College of New York, New York, New York 10065 ‡Institute for Genome Sciences, College of Maryland BioPark, Baltimore, Maryland 21201 **Division of Medication, College of Medication and Dentistry of New Jersey–New Jersey Medical College, Newark, New Jersey 07103 ††Division of Medication, Well being Science Heart, Stony Brook College, Stony Brook, New York 11794 ‡‡Division of Pathology, Division of Molecular Cell Biology and Immunology, College of Utah College of Medication, Salt Lake Metropolis, Utah 84112 §§Nationwide Evolutionary Synthesis Heart, Durham, North Carolina 27705 1 Current tackle: Odum College of Ecology, College of Georgia, Athens, GA 30602. 2 Corresponding creator: Division of Organic Sciences, Hunter Faculty of the Metropolis College of New York, 695 Park Ave., New York, NY 10065. E-mail: [email protected]

ABSTRACT: How genomic variety inside bacterial populations originates and is maintained in thepresence of frequent recombination is a central drawback in understanding bacterial evolution. Pure populations of Borrelia burgdorferi, the bacterial agent of Lyme disease, include various genomic teams co-infecting single particular person vertebrate hosts and tick vectors. To know mechanisms of sympatric genome differentiation in B. burgdorferi, we sequenced and in contrast 23 genomes representing main genomic teams in North America and Europe. Linkage evaluation of over 13,500 single nucleotide polymorphisms revealed pervasive horizontal DNA exchanges. Though 3 times extra frequent than level mutation, recombination is localized and weakly impacts genome-wide linkage disequilibrium. We present by laptop simulations that, whereas enhancing inhabitants health, recombination constrains impartial and adaptive divergence amongst sympatric genomes by means of periodic selective sweeps. In distinction, simulations of frequency-dependent choice with recombination produced the noticed sample of numerous sympatric genomic teams related to main sequence variations on the chosen locus. We conclude that detrimental frequency-dependent choice focusing on a small variety of surface-antigen loci (ospC specifically) sufficiently explains the upkeep of sympatric genome variety in B. burgdorferi with out adaptive divergence. The truth is, pervasive recombination makes it unlikely for native B. burgdorferi genomic teams to attain host specialization. B. burgdorferi genomic teams in northeastern United States are thus finest seen as constituting a single bacterial species, whose generalist nature is a key to its fast unfold and human virulence.


24. Journal of Medical Entomology 47(1):89-94. 2010 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837073/
Extraction of Whole Nucleic Acids from Ticks for the Detection of Bacterial & Viral Pathogens
Chris D. Crowder-1, Megan A. Rounds-1, Curtis A. Phillipson-1, John M. Picuri-1, Heather E. Matthews-1, Justina Halverson-1, Steven E. Schutzer-2, David J. Ecker-1, and Mark W. Eshoo-1 1-Ibis Biosciences, 1896 Rutherford Street, Carlsbad, CA 92008 (Mark W. Eshoo e-mail: [email protected]), 2-College of Medication and Dentistry of New Jersey, Dept. of Medication, 185 South Orange Ave., Newark, NJ 07103.]

ABSTRACT: Ticks harbor quite a few bacterial, protozoal, and viral pathogens that may trigger severe infections in people and home animals. Lively surveillance of the tick vector can present perception into the frequency and distribution of vital pathogens within the setting. Nucleic-acid primarily based detection of tick-borne bacterial, protozoan, and viral pathogens requires the extraction of each DNA and RNA (whole nucleic acids) from ticks. Conventional strategies for nucleic acid extraction are restricted to extraction of both DNA or the RNA from a pattern. Right here we current a easy bead-beating primarily based protocol for extraction of DNA and RNA from a single tick and present detection of Borrelia burgdorferi and Powassan virus from particular person, contaminated Ixodes scapularis ticks. We decided anticipated yields for whole nucleic acids by this protocol for quite a lot of grownup tick species. The tactic is relevant to quite a lot of arthropod vectors, together with fleas and mosquitoes, and was partially automated on a liquid dealing with robotic.


23. PLoS ONE 5(5) 2010 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010650 Genotypic variation and Mixtures of Lyme Borrelia in Ixodes Ticks from North America and Europe
Chris D. Crowder, Heather E. Matthews, Megan A. Rounds, Curtis A. Phillipson, Feng Li, Ranga Sampath, David J. Ecker, Mark W. Eshoo* – Ibis Biosciences, Carlsbad, California, United States of America; Scott R. Campbell – Suffolk County Division of Well being Providers, Yaphank, New York, United States of America; Benjamin J. Luft – Division of Medication, State College of New York at Stony Brook, Stony Brook, New York, United States of America; Oliver Nolte – Laboratory of Dr. Brunner, Constance, Germany; Steven Schutzer – Division of Medication, College of Medication and Dentistry of New Jersey, Newark, New Jersey, United States of America *Corresponding Writer E-mail: Mark W. Eshoo [email protected]

ABSTRACT: Lyme disease, brought on by numerous species of Borrelia, is transmitted by Ixodes ticks in North America and Europe. Research have proven the genotype of Borrelia burgdorferi sensu stricto (s.s.) or the species of B. burgdorferi sensu lato (s.l.) impacts the power of the micro organism to trigger native or disseminated an infection in people. Methodology/Principal Findings: We used a multilocus PCR electrospray mass spectrometry assay to find out the species and genotype Borrelia from ticks collected in New York, Connecticut, Indiana, Southern Germany, and California and characterised isolates from components of the US and Europe. These analyses recognized 53 distinct genotypes of B. burgdorferi sensu stricto with greater decision than ospC typing. Genotypes of different members of the B. burgdorferi sensu lato complicated have been additionally recognized and genotyped together with B. afzelii, B. garinii, B. lusitaniae, B. spielmanii, and B. valaisiana. Whereas every web site in North America had genotypes distinctive to that location, we discovered genotypes shared between particular person areas and two genotypes discovered throughout the US. Vital B. burgdorferi s.s. genotypic variety was noticed between North America and Europe: solely 6.6% of US genotypes (3 of 45) have been present in Europe and 27% of the European genotypes (3 of 11) have been noticed within the US. Curiously, 39% of grownup Ixodes scapularis ticks from North America have been contaminated with multiple genotype of B. burgdorferi s.s. and 22.2% of Ixodes ricinus ticks from Germany have been contaminated with multiple genotype of B. burgdorferi s.l. Conclusions/Significance: The presence of a number of Borrelia genotypes in ticks will increase the chance that an individual will likely be contaminated with multiple genotype of B. burgdorferi, doubtlessly rising the dangers of disseminated Lyme disease. Our examine signifies that the genotypic variety of Borrelia in ticks in each North America and Europe is greater then beforehand reported and may have potential medical penalties.


22. Neurobiology of Illness 2010 http://www.sciencedirect.com/science/article/pii/S0969996109003386 Irritation and central nervous system Lyme disease.
Brian A. Fallon*-a, d, Elizabeth S. Levin-b, Pernilla J. Schweitzer-b, David Hardestya-c a Division of Psychiatry, Columbia College, New York, NY, USA b Faculty of Physicians and Surgeons, Columbia College, New York, NY, USA c Division of Neurology, Columbia College, New York, NY, USA d New York State Psychiatric Institute, New York, NY, USA

*Corresponding Writer, Dr. Fallon, Columbia College Medical Heart, 1051 Riverside Drive, New York, NY 10032, United States. Fax: +1 212 543 6515. [email protected]

ABSTRACT: Lyme disease, brought on by the bacterium Borrelia burgdorferi, may cause multi-systemic indicators and signs, together with peripheral and central nervous system illness. This evaluate examines the proof for and mechanisms of irritation in neurologic Lyme disease, with a selected give attention to the central nervous system, drawing upon human research and managed analysis with experimentally contaminated rhesus monkeys. Instructions for future human analysis are prompt which will assist to make clear the position of irritation as a mediator of the continual persistent signs skilled by some sufferers regardless of antibiotic remedy for neurologic Lyme disease.


21. Arch Gen Psychiatry. 2009;66(5):554-563. 
http://archpsyc.jamanetwork.com/article.aspx?articleid=483068
Regional Cerebral Blood Circulation and Metabolic Charge in Persistent Lyme Encephalopathy
Brian A. Fallon, MD*; Richard B. Lipkin, BA; Kathy M. Corbera, MD; Shan Yu, PhD; Mitchell S. Nobler, MD; John G. Keilp, PhD; Eva Petkova, PhD; Sarah H. Lisanby, MD; James R. Moeller, PhD; Iordan Slavov, PhD; Ronald Van Heertum, MD; Brett D. Mensh, MD, PhD; Harold A. Sackeim, PhD Writer Affiliations: Departments of Psychiatry (Drs Fallon, Corbera, Yu, Keilp, Petkova, Lisanby, Moeller, Slavov, Mensh, and Sackeim), Radiology (Drs Van Heertum and Sackeim), and Biostatistics (Dr Petkova), Faculty of Physicians and Surgeons of Columbia College, New York, New York; the New York State Psychiatric Institute, New York (Drs Fallon, Corbera, Yu, Nobler, Keilp, Petkova, Lisanby, Moeller, Slavov, Mensh, and Sackeim); the Division of Neural and Behavioral Science, State College of New York at Downstate, New York (Mr Lipkin); and the Division of Psychiatry and Behavioral Sciences, New York Medical Faculty, New York (Dr Nobler). *Corresponding Writer – Brian A. Fallon, MD, Division of Psychiatry, Faculty of Physicians and Surgeons of Columbia College, New York, New York 10032, USA. [email protected]

ABSTRACT: Principal End result Measures: Sufferers with persistent Lyme encephalopathy have been in contrast with age-, sex-, and education-matched controls. Absolutely quantified assessments of rCBF and rCMR for glucose have been obtained whereas topics have been medication-free utilizing positron emission tomography. The CBF was assessed in 2 resting room air circumstances (with out snorkel and with snorkel) and 1 problem situation (room air enhanced with carbon dioxide, ie, hypercapnia). Outcomes: Statistical parametric mapping analyses revealed regional abnormalities in all rCBF and rCMR measurements that have been constant in location throughout imaging strategies and primarily mirrored hypoactivity. Deficits have been famous in bilateral grey and white matter areas, primarily within the temporal, parietal, and limbic areas. Though diminished international hypercapnic CBF reactivity (P < .02) was suggestive of a element of vascular compromise, the shut coupling between CBF and CMR means that the regional abnormalities are primarily metabolically pushed. Sufferers didn’t differ from controls on international resting CBF and CMR measurements. Conclusions: Sufferers with persistent Lyme encephalopathy have objectively quantifiable topographic abnormalities in useful mind exercise. These CBF and CMR reductions have been noticed in all measurement circumstances. Future analysis ought to tackle whether or not this sample can be seen in acute neurologic Lyme disease.


 20. Gene 2009
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743244/
Quick, adaptive evolution at a bacterial host-resistance locus: The PFam54 gene array in Borrelia burgdorferi”
Ewa Wywial,1,2,* James Haven,1,3,* Sherwood R. Casjens,4 Yozen A. Hernandez,3 Shaneen Singh,1,2 Emmanuel F. Mongodin,5 Claire M. Fraser-Liggett,5 Benjamin J. Luft,6 Steven E. Schutzer,7 and Wei-Gang Qiu1,3,§ 1 Division of Biology, The Graduate Heart of the Metropolis College of New York, 365 Fifth Avenue, New York, NY 10016, USA 2 Division of Biology, Brooklyn Faculty, Metropolis College of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA 3 Division of Organic Sciences and the Heart for Gene Construction and Perform, Hunter Faculty, Metropolis College of New York, 695 Park Avenue, New York, NY 10065, USA 4 Division of Pathology, Division of Molecular Cell Biology and Immunology, College of Utah College of Medication, Salt Lake Metropolis, UT 84112, USA 5 Institute for Genome Sciences, College of Maryland BioPark, 801 West Baltimore Avenue, Baltimore, MD 21201, USA 6 Division of Medication, Well being Science Heart, Stony Brook College, Stony Brook, NY 11794, USA 7 Division of Medication, College of Medication and Dentistry of New Jersey-New Jersey Medical College, 185 South Orange Avenue, Newark, NJ 07103, USA § Corresponding Writer: Weigang Qiu, Division of Organic Sciences, Hunter Faculty of the Metropolis College of New York, 695 Park Avenue, New York, NY 10065, USA, Cellphone: 1-212-772-5296, Fax: 1-212-772-5227, E-mail: [email protected]

*Each authors contributed equally to the analysis

ABSTRACT: Microbial pathogens have developed subtle mechanisms for evasion of host innate and adaptive immunities. PFam54 is the biggest paralogous gene household within the genomes of Borrelia burgdorferi, the Lyme disease bacterium. One member of PFam54, the complement-regulator buying floor proteins 1 (BbCrasp-1), is ready to abort the choice pathway of complement activation by way of binding human complement-regulator issue H (FH). The gene coding for BbCRASP-1 exists in a tandem array of PFam54 genes within the B. burgdorferi genome, a end result apparently of repeated gene duplications. To assist elucidate the capabilities of the massive variety of PFam54 genes, we carried out phylogenomic and structural analyses of the PFam54 gene array from ten B. burgdorferi genomes. Analyses primarily based on gene tree, genome synteny, and structural fashions revealed fast adaptive evolution of this array by means of gene duplication, gene loss, and useful diversification. Particular person PFam54 genes, nevertheless, don’t present excessive intra-population sequence polymorphisms as genes offering evasion from adaptive immunity typically do. PFam54 members capable of bind human FH will not be monophyletic, suggesting that human FH affinity, nevertheless robust, is an incidental quite than important perform of those PFam54 proteins. The big variety of PFam54 genes present in any single B. burgdorferi genome could goal totally different innate-immunity proteins of a single host species or the identical immune protein of quite a lot of host species. Genetic variability of the PFam54 gene array means that universally current PFam54 lineages corresponding to BBA64, BBA65, BBA66, and BBA73 could also be higher candidates for the event of broad-spectrum vaccines or medicine than strain-restricted lineages corresponding to BbCRASP-1.


19. Neurology Could 2008 http://www.neurology.org/content/70/13/992.long
A randomized, placebo-controlled trial of repeated IV antibiotic remedy for Lyme encephalopathy
B. A.
Fallon, MD
*, J. G. Keilp, PhD, Ok. M. Corbera, MD, E. Petkova, PhD, C. B. Britton, MD, E. Dwyer, MD, I. Slavov, PhD, J. Cheng, MD, PhD, J. Dobkin, MD, D. R. Nelson, PhD and H. A. Sackeim, PhD From the Division of Psychiatry (B.A.F., J.G.Ok., Ok.M.C., E.P., I.S., J.C., H.A.S.), Division of Biostatistics (E.P.), Division of Neurology (C.B.B.), Division of Medication (E.D., J.D.), and New York State Psychiatric Institute (B.A.F., J.G.Ok., Ok.M.C., E.P., I.S., J.C., H.A.S.), Columbia College, New York; and Division of Cell and Molecular Biology, College of Rhode Island, Kingston (D.R.N.).

*Dr. Fallon – Columbia College, 1051 Riverside Drive, Unit 69, New York, NY 10032, USA. [email protected]

ABSTRACT: Background: Optimum remedy stays unsure for sufferers with cognitive impairment that persists or returns after commonplace IV antibiotic remedy for Lyme disease. Strategies: Sufferers had well-documented Lyme disease, with at the least 3 weeks of prior IV antibiotics, present constructive IgG Western blot, and goal reminiscence impairment. Wholesome people served as controls for observe results. Sufferers have been randomly assigned to 10 weeks of double-masked remedy with IV ceftriaxone or IV placebo after which no antibiotic remedy. The first consequence was neurocognitive efficiency at week 12—particularly, reminiscence. Sturdiness of profit was evaluated at week 24. Group variations have been estimated in keeping with longitudinal mixed-effects fashions. Outcomes: After screening 3368 sufferers and 305 volunteers, 37 sufferers and 20 wholesome people enrolled. Enrolled sufferers had gentle to reasonable cognitive impairment and marked ranges of fatigue, ache, and impaired bodily functioning. Throughout six cognitive domains, a major treatment-by-time interplay favored the antibiotic-treated group at week 12. The advance was generalized (not particular to area) and reasonable in magnitude, however it was not sustained to week 24. On secondary consequence, sufferers with extra extreme fatigue, ache, and impaired bodily functioning who obtained antibiotics have been improved at week 12, and this was sustained to week 24 for ache and bodily functioning. Hostile occasions from both the examine remedy or the PICC line have been famous amongst 6 of 23 (26.1%) sufferers given IV ceftriaxone and amongst 1 of 14 (7.1%) sufferers given IV placebo; these resolved with out everlasting harm. Conclusion: IV ceftriaxone remedy ends in short-term cognitive enchancment for sufferers with posttreatment Lyme encephalopathy, however relapse in cognition happens after the antibiotic is discontinued. Therapy methods that end in sustained cognitive enchancment are wanted.


18. Rising Infectious Ailments Quantity 14, Quantity 7–July 2008 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600328/
Extensive Distribution of a Excessive-Virulence Borrelia burgdorferi Clone in Europe & North America. Wei-Gang Qiu,* John F. Bruno,† William D. McCaig,* Yun Xu,† Ian Livey,‡ Martin E. Schriefer,§ and Benjamin J. Luft† Sequencing Group acknowledged (Schutzer) *Hunter Faculty of the Metropolis College of New York, New York, New York, USA; †Stony Brook College, Stony Brook, New York, USA; ‡Baxter Improvements GmBH, Orth/Donau, Austria; and §Facilities for Illness Management and Prevention, Fort Collins, Colorado, USA Deal with for correspondence: Wei-Gang Qiu, Division of Organic Sciences, Hunter Faculty of the Metropolis College of New York, 695 Park Ave, New York, NY 10065, USA; e-mail: [email protected]

ABSTRACT: The A and B clones of Borrelia burgdorferi sensu stricto, distinguished by outer floor protein C (ospC) gene sequences, are generally related to disseminated Lyme disease. To resolve phylogenetic relationships amongst isolates, we sequenced 68 isolates from Europe and North America at 1 chromosomal locus (16S–23S ribosomal RNA spacer) and three plasmid loci (ospC,dbpA, and BBD14). The ospC-A clone seemed to be extremely prevalent on each continents, and isolates of this clone have been uniform in DNA sequences, which suggests a latest trans-oceanic migration. The genetic homogeneity of ospC-A isolates was confirmed by sequences at 6 further chromosomal housekeeping loci (hole, alr, glpA, xylB, ackA, and tgt). In distinction, the ospC-B group consists of genotypes distinct to every continent, indicating geographic isolation. We conclude that the ospC-A clone has dispersed quickly and broadly within the latest previous. The unfold of the ospC-A clone could have contributed, and sure continues to contribute, to the rise of Lyme disease incidence.


17. Minerva Medica October 2008;99(5):489-96.
http://www.ncbi.nlm.nih.gov/pubmed/18971914
Severity of Lyme disease with persistent signs. Insights from a double-blind placebo-controlled medical trial DanielCameron, MD, Northern Westchester Hospital, Mount Kisco, NY, USA. [email protected]

ABSTRACT: Lyme disease is a worldwide well being concern and is the world’s main tick borne an infection brought on by the spirochete, Borrelia burgdorferi, that has been related to quite a few neurologic, rheumatologic and psychiatric manifestations. The signs of Lyme disease have been characterised as both extreme or ”associated to the aches and pains of every day dwelling.” A randomized double-blind, placebo-controlled medical trial (RCT) was carried out in a major inner medication observe in Westchester County, New York, USA. A complete of 84 adults with Lyme disease with persistent signs (LDPS) have been studied; 52 obtained amoxicillin and 34 obtained placebo. The topics obtained both placebo or amoxicillin 3 g per day orally for 3 months. The SF-36 was used as the end result measure of the affected person’s perceived High quality of Life (QOL). For topics enrolling on this RCT, the typical SF-36 bodily element abstract (PCS) of QOL (40+/-9, vary 29-44) and psychological element abstract (MCS) of QOL (39+/-14, vary 23-46) have been worse than the overall USA inhabitants and worse than people with diabetes, coronary heart illness, melancholy, osteoarthritis or rheumatoid arthritis. The enhancements within the SF-36 measure of QOL for topics randomized to amoxicillin vs. placebo was vital (46% vs 18%, P=0.007). It is crucial for clinicians to remember that LDPS will be extreme. A major achieve within the QOL for topics randomized to amoxicillin on this RCT with out severe adversarial occasions is in step with the objective of bettering affected person’s QOL and consequently worthy of additional examine.


16. Microbial Pathogenesis Nov-Dec 2008 http://www.sciencedirect.com/science/article/pii/S0882401008001253
Profiling the humoral immune response to Borrelia burgdorferi an infection with protein microarrays Yun Xu, John F. Bruno*, Benjamin J. Luft – Division of Medication, State college of New York at Stony Brook, Stony Brook, NY 11794, USA *Corresponding creator – Division of Medication, T-15 Room 060, SUNY at Stony Brook, Stony Brook, NY 11794-8154, USA. Tel.: +1 631 444 2054; fax: +1 631 444 2493. [email protected]

ABSTRACT: To find out the cell envelope proteins of Borrelia burgdorferi acknowledged by immune sera of sufferers with late Lyme disease, we developed a Borrelia microarray containing proteins encoded by 90 cell envelope genes and their homologs described within the annotated genomic sequence of B. burgdorferi, pressure B31. The protein microarray was used to profile the humoral immune response utilizing sera from 13 sufferers with late Lyme disease and 4 regular controls. Though there was appreciable heterogeneity within the particular person sera responses, 25 of the cell envelope proteins have been acknowledged by seven or extra samples. Sera from non-infected people lacked reactivity in opposition to any of the proteins on the array. Among the many most antigenic envelope proteins, BLAST search revealed little sequence homology to recognized microbial proteins from different species. The proteins that have been extremely seropositive included a number of members of the Erp gene households, BBA24 (decorin binding protein A (DbpA)) and members of the Borrelia gene household Pfam113 that code for the Mlp lipoprotein gene household. A number of novel, uncharacterized B. burgdorferi antigens recognized on this examine have been BBA14, BBG23, BB0108, BB0442 and BBQ03. The correct analysis of Lyme disease is determined by correlating goal medical abnormalities with serological proof of publicity to B. burgdorferi. A protein array of the envelope proteins of Borrelia burgdorferi could also be very helpful in particularly figuring out sufferers with Lyme disease. This strategy might contribute to a extra fast discovery of antigens not expressed in vitro which may be helpful for the event of vaccine and diagnostics.


15. An infection and Immunity, January 2006 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1346608/ Identification of Borrelia burgdorferi outer floor proteins Brooks CS-1; Vuppala SR-2; Jett AM-2; Akins DR*-2 Sequencing Group acknowledged (Schutzer) 1Department of Biology, Austin Peay State College, Clarksville, Tennessee 37044, 2Department of Microbiology and Immunology, College of Oklahoma Well being Sciences Heart, Oklahoma Metropolis, Oklahoma 731042 *Corresponding creator – Mailing tackle: Division of Microbiology and Immunology, The College of Oklahoma Well being Sciences Heart, Oklahoma Metropolis, OK 73104. Cellphone: (405) 271-2133 ext. 46640. Fax: (405) 271-3117. E-mail: [email protected]

ABSTRACT: A number of Borrelia burgdorferi outer floor proteins have been recognized over the previous decade which might be up-regulated by temperature- and/or mammalian host-specific indicators as this spirochete is transmitted from ticks to mammals. Given the potential position(s) that these differentially up-regulated proteins could play in B. burgdorferi transmission and Lyme disease pathogenesis, a lot consideration has lately been positioned on figuring out further borrelial outer floor proteins. To establish uncharacterized B. burgdorferi outer floor proteins, we beforehand carried out a complete gene expression profiling evaluation of temperature-shifted and mammalian host-adapted B. burgdorferi. The mixed microarray analyses revealed that many genes encoding recognized and putative outer floor proteins are down-regulated in mammalian host-adapted B. burgdorferi. On the identical time, nevertheless, a number of totally different genes encoding putative outer floor proteins have been discovered to be up-regulated throughout the transmission and an infection course of. Among the many putative outer floor proteins recognized, biochemical and floor localization analyses confirmed that seven (Bb0405, Bb0689, BbA36, BbA64, BbA66, BbA69, and BbI42) are localized to the floor of B. burgdorferi. Moreover, enzyme-linked immunosorbent assay evaluation utilizing serum from tick-infested baboons indicated that every one seven outer floor proteins recognized are immunogenic and that antibodies are generated in opposition to all seven throughout a pure an infection. Particular antibodies generated in opposition to all seven of those floor proteins have been discovered to be bactericidal in opposition to B. burgdorferi, indicating that these newly recognized outer floor proteins are prime candidates for evaluation as second-generation Lyme disease vaccinogens.


14. J Int Neuropsychol Soc. 2006 Jan;12(1):119-29
http://www.ncbi.nlm.nih.gov/pubmed/16433951
WAIS-III and WMS-III efficiency in continual Lyme disease
John G. Keilp a1 a2 c1 , Kathy Corbera a1 a3 , Iordan Slavov a1 a3 , Michael J. Taylor a5 , Harold A. Sackeim a1 a4, and Brian A. Fallon a1 a3 a1 Columbia College Faculty of Physicians and Surgeons, Division of Psychiatry, New York, New York a2 New York State Psychiatric Institute, Division of Neuroscience, New York, New York a3 New York State Psychiatric Institute, Division of Therapeutics, New York, New York a4 New York State Psychiatric Institute, Division of Organic Psychiatry, New York, New York a5 Division of Psychiatry, College of California at San Diego, California c1 Reprint requests to: John Keilp, Ph.D., Columbia College Faculty of Physicians and Surgeons, Division of Psychiatry, Field 42, NYSPI, 1051 Riverside Drive, New York, NY 10032. E-mail: [email protected]

ABSTRACT: There’s controversy relating to the character and diploma of mental and reminiscence deficits in continual Lyme disease. On this examine, 81 members with rigorously recognized continual Lyme disease have been administered the most recent revisions of the Wechsler Grownup Intelligence Scale (WAIS-III) and Wechsler Reminiscence Scale (WMS-III), and in comparison with 39 nonpatients. On the WAIS-III, Lyme disease members had poorer Full Scale and Efficiency IQ’s. On the subtest stage, variations have been restricted to Info and the Processing Pace subtests. On the WMS-III, Lyme disease members carried out extra poorly on Auditory Fast, Fast, Auditory Delayed, Auditory Recognition Delayed, and Basic Reminiscence indices. Amongst WMS-III subtests, nevertheless, variations have been restricted to Logical Reminiscence (rapid and delayed) and Household Photos (delayed solely), a Visible Reminiscence subtest. Discriminant analyses counsel deficits in continual Lyme are finest characterised as a mixture of reminiscence issue and diminished processing velocity. Deficits have been modest, between one-third and two-thirds of a normal deviation, in step with earlier research. Melancholy severity had a weak relationship to processing velocity, however little different affiliation to check efficiency. Deficits in continual Lyme disease are in step with a refined neuropathological course of affecting a number of efficiency duties, though additional work is required to definitively rule out nonspecific sickness results. (JINS, 2006, 12, 119-129.).


13. Journal of Scientific Microbiology, February 2005
http://jcm.asm.org/content/43/2/850.long
Proof of Borrelia Autoimmunity-Induced Part of Lyme Carditis and Arthritis. Elizabeth S. Raveche1, Steven E. Schutzer,1*, Helen Fernandes1, Helen Bateman1, Brian A. McCarthy1, Steven P. Nickell2, and Madeleine W. Cunningham3. 1 Departments of Pathology and Medication, New Jersey Medical College, College of Medication and Dentistry of New Jersey, Newark, New Jersey, 2 Division of Molecular Genetics and Microbiology, College of New Mexico, Albuquerque, New Mexico, 3 College of Oklahoma Well being Sciences Heart, Oklahoma Metropolis, Oklahoma. *Corresponding creator. Mailing tackle: Division of Medication, New Jersey Medical College, College of Medication and Dentistry of New Jersey, MSB E543, 185 S. Orange Ave., Newark, NJ 07103. Cellphone: (973) 972-4872. Fax: (801) 383-8534. E-mail: [email protected].

ABSTRACT: We investigated the likelihood that manifestations of Lyme disease in sure hosts, corresponding to arthritis and carditis, could also be autoimmunity mediated as a consequence of molecular mimicry between the bacterium Borrelia burgdorferi and self-components. We first in contrast amino acid sequences of Streptococcus pyogenes M protein, a recognized inducer of antibodies which might be cross-reactive with myosin, and B. burgdorferi and located vital homologies with OspA protein. We discovered that S. pyogenes M5-specific antibodies and sera from B. burgdorferi-infected mice reacted with each myosin and B. burgdorferi proteins by Western blots and enzyme-linked immunosorbent assay. To analyze the connection between self-reactivity and the response to B. burgdorferi, NZB mice, fashions of autoimmunity, have been contaminated. NZB mice contaminated with B. burgdorferi developed greater levels of joint swelling and better anti-B. burgdorferi immunoglobulin M cross-reactive responses than different strains with similar main histocompatibility complicated (DBA/2 and BALB/c). These research reveal immunological cross-reactivity and counsel that B. burgdorferi could share frequent epitopes which mimic self-proteins. These implications could possibly be vital for sure autoimmunity-susceptible people or animals that turn into contaminated with B. burgdorferi.


12. Professional Assessment Anti-Infective Remedy 2004
http://www.ilads.org/lyme/ILADS_Guidelines.pdf
Proof-based tips for the administration of Lyme disease Worldwide Lyme & Related Ailments Society Lyme Illness Therapy Pointers ILADS Working Group: Dan Cameron, MD, MPH-1 [Internal Medicine and Epidemiology, Mt. Kisco, New York]; Andrea Gaito, MD [Rheumatology, Basking Ridge, New Jersey]; Nick Harris, PhD [Immunology, Palo Alto, California]; Gregory Bach, DO [Family and Integrative Medicine, Colmar, Pennsylvania]; Sandra Bellovin, MD [Family Practice, Portsmouth, Virginia]; Kenneth Bock, MD [Family Practice, Rhinebeck, New York]; Steven Bock, MD [Family Practice, Rhinebeck, New York]; Joseph Burrascano, MD [Internal Medicine, East Hampton, New York]; Constance Dickey, RN [Registered Nurse, Hampden, Maine]; Richard Horowitz [Internal Medicine, Hyde Park, New York]; Steven Phillips, MD [Internal Medicine, Ridgefield, Connecticut]; Lawrence Meer-Scherrer MD [Internal Medicine, Flamatt, Switzerland]; Bernard Raxlen, MD [Psychiatry, Greenwich, Connecticut]; Virginia Sher, MD [Psychiatry, Holland, Pennsylvania]; Harold Smith, MD [Emergency Medicine, Danville, Pennsylvania]; Pat Smith [President, Lyme Disease Association]*; Ray Stricker MD [Hematology and Immunotherapy, San Francisco, California] 1-ILADS, P.O. Field 341461, Bethesda, MD 20827-1461, USA. *Pat Smith, LDA, was co-author on article

ABSTRACT: This report, accomplished in November 2003, is meant to function a useful resource for physicians, public well being officers and organizations concerned within the analysis and remedy of Lyme disease.


11. Proceedings of the Nationwide Academy of Science, Sept. 2004 http://www.pnas.org/content/101/39/14150.long
Genetic alternate and plasmid transfers in Borrelia burgdorferi sensu stricto revealed by three-way genome comparisons and multilocus sequence typing. Wei-Gang Qiu *, †, Steven E. Schutzer ‡, John F. Bruno §, Oliver Attie *, Yun Xu §,John J. Dunn ¶, Claire M. Fraser ∥, Sherwood R. Casjens **, and Benjamin J. Luft § Writer Affiliations: *Division of Organic Sciences, Hunter Faculty of the Metropolis College of New York, 695 Park Avenue, New York, NY 10021; ‡Division of Medication, New Jersey Medical College, 185 South Orange Avenue, Newark, NJ 07103; §Division of Medication, Well being Science Heart, Stony Brook College, Stony Brook, NY 11794; ¶Biology Division, Brookhaven Nationwide Laboratory, Upton, NY 11793; ∥The Institute for Genomic Analysis, 9712 Medical Heart Drive, Rockville, MD 200850; and **Division of Pathology, Division of Molecular Cell Biology and Immunology, College of Utah Medical College, Salt Lake Metropolis, UT 84132

ABSTRACT: Comparative genomics of carefully associated bacterial isolates is a strong methodology for uncovering virulence and different vital genome components. We decided draft sequences (8-fold protection) of the genomes of strains JD1 and N40 of Borrelia burgdorferi sensu stricto, the causative agent of Lyme disease, and we in contrast the expected genes from the 2 genomes with these from the beforehand sequenced B31 genome. The three genomes are carefully associated and are evolutionarily roughly equidistant ( 0.5% pairwise nucleotide variations on the principle chromosome). We used a Poisson mannequin of nucleotide substitution to display screen for genes with elevated ranges of nucleotide polymorphisms. The three-way genome comparability allowed distinction between polymorphisms launched by mutations and people launched by recombination utilizing the strategy of phylogenetic partitioning. Assessments for recombination prompt that patches of high-density nucleotide polymorphisms on the chromosome and plasmids come up by DNA alternate. The position of recombination as the principle mechanism driving B. burgdorferi diversification was confirmed by multilocus sequence typing of 18 medical isolates at 18 polymorphic loci. A powerful linkage between the multilocus sequence genotypes and the foremost alleles of outer-surface protein C (ospC) prompt that balancing choice at ospC is a dominant power sustaining B. burgdorferi variety in native populations. We conclude that B. burgdorferi undergoes genome-wide genetic alternate, together with plasmid transfers, and former studies of its clonality are artifacts from the usage of geographically and ecological remoted samples. Frequent recombination implies a possible for fast adaptive evolution and a attainable polygenic foundation of B. burgdorferi pathogenicity.


10. The Journal of Neuropsychiatry & Scientific Neurosciences. 2003 http://neuro.psychiatryonline.org/article.aspx?articleid=101812
Regional Cerebral Blood Circulation and Cognitive Deficits in Continual Lyme Illness.
Brian A. Fallon, M.D., John Keilp, Ph.D., Isak Prohovnik, Ph.D., Ronald Van Heertum, M.D. and J. John Mann, M.D. From the Lyme Illness Analysis Program, The NYS Psychiatric Institute, New York, New York. Deal with correspondence to Dr. Brian A. Fallon, NYS Psychiatric Institute, 1051 Riverside Drive, #69, New York, NY 10032

ABSTRACT: This examine examined mind functioning in sufferers with Lyme encephalopathy. Eleven sufferers underwent neuropsychological assessments and Xenon133-regional cerebral blood move (rCBF) research, utilizing an exterior detector system. Every rCBF scan was age- and sex-matched to 2 archival, regular controls. Whereas few variations have been famous on gray-matter move indices (ISI, fg), Lyme sufferers demonstrated vital move reductions in white matter index (k2) (p=.004), notably within the posterior temporal and parietal lobes bilaterally (p=.003). Circulation reductions in white matter areas have been considerably related to deficits in reminiscence (r=.66, p=.027) and visuospatial group (r=.62, p=.041). Outcomes counsel that Lyme encephalopathy could also be a illness primarily affecting the cerebral white matter.


9. Journal of Spirochetal and Tick-borne Ailments. Spring/Summer time 2002
https://www.ilads.org/wp-content/uploads/2018/10/JSTBD-VOL9-SPRING-SUMMER-02-1.pdf
Borrelia burgdorferi Persists within the Gastrointestinal Tract of Youngsters and Adolescents with Lyme Illness.
Martin Fried, MD*; Dorothy Pietrucha, MD†, Gaye Madigan, RN‡, Aswine Bal, MD§ *Departments of Pediatric Gastroenterology, †Pediatric Neurology, ‡Tutorial Affairs, and §Pediatric Infectious Illness, Jersey Shore Medical Heart, Neptune, New Jersey

ABSTRACT: This examine paperwork the persistence of B burgdorferi DNA within the gastrointestinal tract of pediatric sufferers who’ve already been handled with antibiotics for Lyme disease. Ten consecutive sufferers between the ages of 9 and 13 years offered with an erythema migrans (EM) rash, a constructive western blot for Lyme disease, continual belly ache, heartburn, or shiny crimson blood within the stool. Endoscopy assessed the gastrointestinal (GI) mucosa for irritation and biopsies have been examined for B burgdorferi utilizing a Dieterle stain and with polymerase chain response (PCR) to the outer floor protein A (Osp A) of B burgdorferi. As controls, 10 consecutive sufferers with continual belly ache have been additionally examined by GI biopsies and with PCR. B burgdorferi persevered within the GI tract in all 10 sufferers with Lyme disease as proven by Dieterle stain of biopsies and with PCR. Not one of the management topics’ biopsies have been PCR constructive for B. burgdorferi. Continual gastritis, continual duodenitis, and continual colitis have been present in Lyme disease sufferers and related to the detection of B burgdorferi DNA within the GI tract regardless of prior antibiotic remedies. Now we have concluded that the DNA of B burgdorferi persevered in sufferers with Lyme disease even after antibiotic remedy.


8. Journal of Neuropsychiatry and Scientific Neurosciences. 2001 13:500-5-7 http://neuro.psychiatryonline.org/doi/pdf/10.1176/jnp.13.4.500
A Managed Research of Cognitive Deficits in Youngsters with Continual Lyme Illness.
Felice A Tager, PhD, Brian A Fallon, MD. From the Columbia College Division of Psychiatry, Division of Behavioral Medication, New York, New York. Deal with correspondence to Dr. Tager, Columbia Presbyterian Medical Heart, 622 West 168th Avenue, Field 427, New York, NY 10032. E-mail: [email protected]

ABSTRACT: Though neurologic Lyme disease is understood to trigger cognitive dysfunction in adults, little is understood about its long-term sequelae in kids. Twenty kids with a historical past of new-onset cognitive complaints after Lyme disease have been in contrast with 20 matched wholesome management topics. Every baby was assessed with measures of cognition and psychopathology. Youngsters with Lyme disease had considerably extra cognitive and psychiatric disturbances. Cognitive deficits have been nonetheless discovered after controlling for anxiousness, melancholy, and fatigue. Lyme disease in kids could also be accompanied by long-term neuropsychiatric disturbances, leading to psychosocial and educational impairments. Areas for additional examine are mentioned.


7. Medscape Infectious Ailments 2(1) April 2000
Preliminary in Vitro and in Vivo Findings of Hyperbaric Oxygen Therapy in Experimental Bb An infection.
http://www.medscape.com/viewarticle/432883#4
Charles Pavia, PhD NY Medical Faculty College of Medication. NYCOM Microbiology and Immunodiagnostic Laboratory of NYIT.

ABSTRACT: In these research, we evaluated repeated HBOT for its capability to kill Bb in vitro, and in vivo, in a murine mannequin of Lyme disease. A number of North American tick-derived and lately obtained affected person isolates have been studied individually in our assay techniques. To check for in vitro susceptibility, one-half to at least one million Bb have been cultured in a small quantity (0.1 – 0.2 ml) of BSK media utilizing small snap-cap check tubes. With the caps eliminated, these cultures have been then uncovered, for one hour (twice every day for two consecutive days), to pure, filtered oxygen pressurized to 2-3 occasions regular atmospheric circumstances. This was achieved utilizing a specifically constructed, miniaturized cylindrical chamber (size = 12 inches; diameter = 8 inches), outfitted to just accept any pressurized gasoline combination by means of its portal opening. After the ultimate HBOT, all cultures obtained an extra 0.5 ml of BSK media (making the ultimate quantity now 0.6 – 0.7 ml), and their caps have been snapped shut. Matching management cultures obtained no HBOT. All cultures have been incubated at 33° C for 2-3 days and have been examined microscopically for reside Bb. Our outcomes confirmed that 14 of 17 strains of Bb had their progress inhibited by 33-94%, whereas there was little or no inhibition of three Bb strains. For the in vivo research, separate teams of C3H or CO1 mice have been contaminated intradermally with 100,000 Bb. Two to 4 weeks later, one group of contaminated mice obtained two, 1.0-1.5 hour HBO exposures, for 2 consecutive or alternating days. The handled mice have been sacrificed someday after the final remedy, and extract cultures of their urinary bladders have been ready in BSK media. It was discovered that no Bb grew out of 80% of those extract cultures, whereas reside Bb organisms have been recoverable from 90% of extract cultures ready from matched, contaminated management mice not handled with HBO. These information counsel that HBOT could also be thought-about as a clinically helpful type of adjunct remedy within the remedy of Lyme disease.


6. Journal of Spirochetal and Tick-borne Ailments Fall/Winter 1999
https://www.ilads.org/wp-content/uploads/2018/10/JSTBD-VOL6-FALL-WINTER-99-3.pdf
Repeated Antibiotic Therapy in Continual Lyme Illness.
Brian A. Fallon, MD, Felice Tager, PhD, John Keilp, PhD, Nicola Weiss, PhD, Michael R. Liebowitz, MD, New York State Psychiatric Institute and Columbia College Division of Psychiatry, New York, New York; Lesley Fein, MD, Non-public Apply, West Caldwell, New Jersey; Kenneth Liegner, MD, Non-public Apply, West Caldwell, New Jersey.

ABSTRACT: Sufferers with continual Lyme disease who expertise persistent cognitive deficits regardless of having obtained the beneficial antibiotic remedy pose a therapeutic dilemma. This pilot examine was designed to evaluate whether or not further antibiotic remedy is helpful. Enrolled within the examine have been 23 sufferers with complaints of persistent reminiscence issues who had beforehand obtained 4-16 weeks of intravenous antibiotic remedy. Sufferers have been examined at baseline and 4 months later. Throughout this interval, the personal doctor decided remedy (intravenous, intramuscular, oral, or none). Assessments included standardized measures of cognition, melancholy, anxiousness, and useful standing. Between occasions 1 and a pair of, 5 sufferers got no antibiotics and 18 got further antibiotics: 7 intravenously, 4 intramuscularly, and seven orally. At time 1, there have been no statistically vital group variations in cognition, melancholy, or anxiousness between those that later obtained antibiotics and people who didn’t. At time 1, the 23 sufferers have been additionally functionally disabled. At time 2, in contrast with sufferers who obtained no antibiotics, sufferers given antibiotics scored higher on general and particular person measures of cognition. Sufferers given intravenous antibiotics confirmed the best useful enchancment (ache, bodily functioning, vitality) and essentially the most cognitive enchancment, even when controlling for baseline variations in cognition between the remedy teams. Sufferers who didn’t have a reactive Western blot presently or traditionally have been simply as probably to enhance cognitively as sufferers with reactive Western blot outcomes. This uncontrolled examine means that repeated antibiotic remedy will be helpful, even amongst sufferers who’ve been beforehand handled and even amongst sufferers who’re presently Western blot detrimental, with the intravenous route of remedy being the best. A double-blind placebo-controlled examine is required to verify these outcomes.


5. JAMA, Nov. 24, 1999, Vol.282, No.20
http://jama.jamanetwork.com/article.aspx?articleid=192130
Borrelia Burgdorferi–Particular Immune Complexes in Acute Lyme Illness. Steven E. Schutzer, MD; P. Ok. Coyle, MD; Patrick Reid, MS; Bart Holland, PhD Writer Affiliations: Division of Medication, Division of Allergy and Immunology (Dr Schutzer and Mr Reid) and Division of Preventive Medication (Dr Holland), College of Medication and Dentistry of New Jersey-New Jersey Medical College, Newark (Dr Schutzer and Mr Reid); and the Division of Neurology, State College of New York, Stony Brook (Dr Coyle).

ABSTRACT: Context Prognosis of an infection with Borrelia burgdorferi, the reason for Lyme disease (LD), has been impeded by the dearth of efficient assays to detect lively an infection. Goal: To find out whether or not B burgdorferi particular immune complexes are detectable throughout lively an infection in LD. Design, Setting, and Sufferers: Cross-sectional evaluation of serum samples from 168 sufferers fulfilling Facilities for Illness Management and Prevention surveillance standards for LD and 145 wholesome and different illness controls carried out over 8 years. Assessments have been carried out blinded. Principal End result Measure Detection of B burgdorferi immune complexes by enzyme-linked immunosorbent assay and Western blot. Outcomes: The B burgdorferi immune complexes have been present in 25 of 26 sufferers with early seronegative erythema migrans (EM) LD; 105 of 107 sufferers with seropositive EM LD; 6 of 10 sufferers who have been seronegative with culture-positive EM; 0 of 12 sufferers who have been handled and recovered from LD; and 13 of 13 sufferers with neurologic LD with out EM. Amongst 147 controls, B burgdorferi immune complicated was present in 0 of fifty wholesome people; 0 of 40 sufferers with persistent fatigue; 0 of seven people with frequent tick publicity; and a pair of of fifty sufferers with different ailments. Conclusion: These information counsel that B burgdorferi immune complicated formation is a typical course of in lively LD. Evaluation of the B burgdorferi immune complexes by a easy method has the potential to assist or exclude a analysis of early in addition to lively LD an infection Funding/Assist: This work was supported partially by grants A41518, NS34092, AI31561, and AR40470 from the Nationwide Institutes of Well being and grant U50/CCU206582 from the Facilities for Illness Management and Prevention, and by the Lyme Illness Affiliation of New Jersey.


4. Neurology, Oct 12, 1999 http://www.neurology.org/content/53/6/1340.long
Absence of Borrelia Burgdorferi-specific immune complexes in continual fatigue syndrome. Schutzer SE-1, Natelson BH. 1 Division of Medication, College of Medication and Dentistry, New Jersey Medical College, Newark 07103, USA. [email protected]

ABSTRACT: Continual fatigue syndrome (CFS) and Lyme disease usually share medical options, particularly fatigue, contributing to concern that Borrelia burgdorferi (Bb), the reason for Lyme disease, could underlie CFS signs. We examined 39 CFS sufferers and 40 wholesome controls with a Bb immune complicated check. Sufferers and controls have been nonreactive. Facilities for Illness Management and Prevention-defined CFS sufferers missing antecedent indicators of Lyme disease–erythema migrans, Bell’s palsy, or massive joint arthritis–will not be prone to have laboratory proof of Bb an infection.


 3. The Psychiatric Clinics of North America Vol. 21,#3, 9/98 http://www.psych.theclinics.com/article/S0193-953Xpercent2805percent2970032-0/fulltext
The Underdiagnosis of Neuropsychiatric Lyme Illness in Youngsters and Adults.
Brian A. Fallon, MD, MPH-1, Janice M. Kochevar, NP, Andrea Gaito, MD, Jenifer A. Nields, MD 1-Division of Psychiatry, Columbia College Medical Heart and the Lyme Illness Analysis Program, New York, New York (BAF), 2-private observe, Armonk, New York (JMK), 3-Division of Medication, Seton Corridor College, and personal observe, Basking Ridge, New Jersey (AG), 4-Division of Psychiatry, Yale College College of Medication, New Haven, Connecticut (JAN)

ABSTRACT: Lyme disease is a tick-borne sickness brought on by the spirochete Borrelia burgdorferi. Reported all through the US, the best incidence of Lyme disease happens in sure areas, such because the Northeast, the higher Midwest, and the Pacific Coastal states. It has been dubbed “The New Nice Imitator” as a result of, like one other spirochetal sickness neurosyphilis-the authentic Nice Imitator, Lyme disease has an enormous array of multisystem manifestations, together with neuropsychiatric ones.18 Failure to acknowledge Lyme disease early in its course can lead to the event of a continual sickness that’s solely quickly or partially aware of antibiotic remedy. The objective of this text is to current the everyday and atypical manifestations of Lyme disease in kids and adults to be able to assist the clinician extra quickly unmask the proper analysis behind the puzzling shows of some sufferers.


2. An infection. 1998 Nov-Dec:26(6):364-7
http://www.ncbi.nlm.nih.gov/pubmed/9861561?dopt=Abstract
A proposal for the dependable tradition of Borrelia burgdorferi from sufferers with continual Lyme disease, even from these beforehand aggressively handled.
Phillips SE-1, Mattman LH, Hulinska D, Moayad H 1Greenwich Hospital, CT 06830, USA.

ABSTRACT: Since tradition of Borrelia burgdorferi from sufferers with continual Lyme disease has been a very uncommon occasion, clarification of the character of the sickness and proving its etiology as infectious have been tough. A way for reliably and reproducibly culturing B. burgdorferi from the blood of sufferers with continual Lyme disease was subsequently sought by making a managed blood tradition trial learning 47 sufferers with continual Lyme disease. All had relapsed after long-term oral and intravenous antibiotics. 23 sufferers with different continual sickness fashioned the management group. Optimistic cultures have been confirmed by fluorescent antibody immuno-electron microscopy utilizing monoclonal antibody directed in opposition to Osp A, and Osp A PCR. 43/47 sufferers (91%) cultured constructive. 23/23 controls (100%) cultured detrimental. Though persistent an infection has been, so far, strongly prompt in continual Lyme disease by constructive PCR and antigen seize, there are main issues with these assessments. This new methodology for culturing B. burgdorferi from sufferers with continual Lyme disease actually defines the character of the sickness and establishes that it’s of continual infectious etiology. This discovery ought to assist to reestablish the gold commonplace in laboratory analysis of Lyme disease.


1. An infection 24 (1996) #5
http://www.ncbi.nlm.nih.gov/pubmed/8923044
Borrelia burgdorferi DNA within the Urine of Handled Sufferers with Continual Lyme Illness Symptom: A PCR Research of 97 Circumstances
Bayer ME-1, Zhang L, Bayer MH. 1-Fox Chase Most cancers Heart, Philadelphia, PA 19111, USA. Writer affiliation: Fox Chase Most cancers Heart, Philadelphia, PA 19111, USA

ABSTRACT: All sufferers had proven erythema chronica migrans following a deer tick chunk. A lot of the sufferers had been antibiotic-treated for prolonged intervals of time. …Of the 97 sufferers, 72 (74.2%) have been discovered with constructive PCR and the remainder with detrimental PCR. The 62 wholesome volunteers have been PCR detrimental. It’s proposed {that a} sizeable group of sufferers recognized on medical grounds as having continual Lyme disease should excrete Borrelia DNA, and will achieve this despite intensive antibiotic remedy.


∞ Lyme Illness Affiliation, Inc. June 2015 PO Field 1438 Jackson, NJ 08527 www.LymeDiseaseAssociation.org 888-366-6611

Orignally Revealed on: Sep 14, 2014



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