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Publications & Conference Presentations

 

35 + PUBLICATIONS & CONFERENCE PRESENTATIONS

RESULTING FROM

LYME DISEASE ASSOCIATION, INC

FUNDING OR SUPPORT

 

As of July 2013

 

 

  1. Int J Med Sci 2013; 10(7):915-931. doi:10.7150/ijms.6273

 

Lyme Borreliosis in Human Patients in Florida and Georgia, USA

 

Kerry L. Clark1, Brian Leydet1,2, Shirley Hartman3

1. Department of Public Health, University of North Florida, 1 UNF Drive, Jacksonville, Florida USA 32224;
2. Current address: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana USA 70803;
3. Mandarin Wellness Center, Jacksonville, Florida, USA 32257.

 

ABSTRACT: The aim of this study was to determine the cause of illness in several human patients residing in Florida and Georgia, USA, with suspected Lyme disease based upon EM-like skin lesions and/or symptoms consistent with early localized or late disseminated Lyme borreliosis. Using polymerase chain reaction (PCR) assays developed specifically for Lyme group Borrelia spp., followed by DNA sequencing for confirmation, we identified Borrelia burgdorferi sensu lato DNA in samples of blood and skin and also in lone star ticks (Amblyomma americanum) removed from several patients who either live in or were exposed to ticks in Florida or Georgia. This is the first report to present combined PCR and DNA sequence evidence of infection with Lyme Borrelia spp. in human patients in the southern U.S., and to demonstrate that several B. burgdorferi sensu lato species may be associated with Lyme disease-like signs and symptoms in southern states. Based on the findings of this study, we suggest that human Lyme borreliosis occurs in Florida and Georgia, and that some cases of Lyme-like illness referred to as southern tick associated rash illness (STARI) in the southern U.S. may be attributable to previously undetected B. burgdorferi sensu lato infections.

  1. Psychosomatics 2013

Correlates of Perceived Health-Related Quality of Life in Post-treatment Lyme Encephalopathy

Avinash M.Chandra,B.A., John G. Keilp, Ph.D., Brian A. Fallon, M.D. 

 

Columbia University

ABSTRACT: Background – Marked functional impairment has been reported by patients with post-treatment Lyme disease syndrome (PTLDS). Objective: We sought to identify but the clinical features that contribute most strongly to the impaired health status associated with PTLDS. Methods: Enrolled patients had a well-documented history of Lyme disease, prior treatment with at least 3 weeks with intravenous ceftriaxone, a positive IgG Western blot, and objective problems with memory. An index score to capture aggregate cognitive functioning, Short-Form 36 physical and mental component summer scores, and scores on other clinical and demographic measures were examined. Multiple linear regressions were performed to determine significant predictors of perceptions of impaired life functioning as delineated by theShort-Form36.Results: Fatigue was the most important contributor to perceived impairments in overall physical functioning, and fatigue and depression significantly predicted perceived impairments in overall mental functioning. Conclusions: Because fatigue and depression contribute prominently to reports of impaired physical functioning and mental functioning among patients with PTLDS, clinicians should assess patients for these symptoms and consider targeting these symptoms in the selection of treatment interventions. Future controlled studies should examine the effectiveness of such agents for patients with PTLDS.

 

 

  1. International Journal of Medical Sciences 2013

 

Lyme Borreliosis in Human Patients in Florida and Georgia, USA

 

Kerry L. Clark-1, Brian Leydet-1,2, Shirley Hartman-3

 

1-University of North Florida, 2-Louisiana State University, 3-Mandarin Wellness Center, Florida

 

ABSTRACT: The aim of this study was to determine the cause of illness in several human patients residing in Florida and Georgia, USA, with suspected Lyme disease based upon EM-like skin lesions and/or symptoms consistent with early localized or late disseminated Lyme borreliosis. Using polymerase chain reaction (PCR) assays developed specifically for Lyme group Borrelia spp., followed by DNA sequencing for confirmation, we identified Borrelia burgdorferi sensu lato DNA in samples of blood and skin and also in lone star ticks (Amblyomma americanum) removed from several patients who either live in or were exposed to ticks in Florida or Georgia. This is the first report to present combined PCR and DNA sequence evidence of infection with Lyme Borrelia spp. in human patients in the southern U.S., and to demonstrate that several B. burgdorferi sensu lato species may be associated with Lyme disease-like signs and symptoms in southern states. Based on the findings of this study, we suggest that human Lyme borreliosis occurs in Florida and Georgia, and that some cases of Lyme-like illness referred to as southern tick associated rash illness (STARI) in the southern U.S. may be attributable to previously undetected B. burgdorferi sensu lato infections.

 

 

  1. 2013 Northeastern Naturalist 20(1):197–204

 

Distribution of Ticks & Prevalence of Borrelia burgdorferi in the Upper 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 College VT, 2-Analytical Services, Inc. VT

 

ABSTRACT: Ixodes scapularis (Black-legged Tick) has expanded its range in recent decades. To establish baseline data on the abundance of the Black-legged Tick and Borrelia burgdorferi (the causative agent of Lyme disease) at the edge of a putative range expansion, we collected 1398 ticks from five locations along the Connecticut River in Vermont. Collection locations were approximately evenly distributed between the villages of Ascutney and Guildhall. Relative abundance and distribution by species varied across sites. Black-legged Ticks dominated our collections (= 1348, 96%), followed by Haemaphysalis leporispalustris (Rabbit Tick; = 45, 3%), and Dermacentor variabilis (American Dog Tick; = 5, <1%). Black-legged Tick abundance ranged from 6198 ticks per survey hectare (all life stages combined) at the Thetford site to zero at the Guildhall site. There was little to no overlap of tick species across sites. Phenology of Black-legged Ticks matched published information from other regions of the northeastern USA. Prevalence of B. burgdorferi in adult Black-legged Ticks was 8.9% (= 112).

 

 

  1. Microbial Pathogenesis Nov-Dec 2008


Profiling the humoral immune response to Borrelia burgdorferi infection with protein microarrays


Yun Xu, John F. Bruno, Benjamin J. Luft


ABSTRACT: To determine the cell envelope proteins of Borrelia burgdorferi recognized by immune sera of patients with late Lyme disease, we developed a Borrelia microarray containing proteins encoded by 90 cell envelope genes and their homologs described in the annotated genomic sequence of B. burgdorferi, strain B31. The protein microarray was used to profile the humoral immune response using sera from 13 patients with late Lyme disease and four normal controls. Although there was considerable heterogeneity in the individual sera responses, 25 of the cell envelope proteins were recognized by seven or more samples. Sera from non-infected individuals lacked reactivity against any of the proteins on the array. Among the most antigenic envelope proteins, BLAST search revealed little sequence homology to known microbial proteins from other species. The proteins that were highly seropositive included several members of the Erp gene families, BBA24 (decorin binding protein A (DbpA)) and members of the Borrelia gene family Pfam113 that code for the Mlp lipoprotein gene family. Several novel, uncharacterized B. burgdorferi antigens identified in this study were BBA14, BBG23, BB0108, BB0442 and BBQ03. The accurate diagnosis of Lyme disease depends on correlating objective clinical abnormalities with serological evidence of exposure to B. burgdorferi. A protein array of the envelope proteins of Borrelia burgdorferi may be very useful in specifically identifying patients with Lyme disease. This approach could contribute to a more rapid discovery of antigens not expressed in vitro that may be useful for the development of vaccine and diagnostics.

 

 

  1. Grant Title: Profiling the humoral response to Borrelia burgdorferi infection with protein microarrays


Presented at LDA Columbia University Lyme & Other Tick-Borne Diseases: Solutions through Cutting Edge Science 2008

 

Benjamin J Luft PhD Stony Brook University

New Insights from the Borrelia Genome

ABSTRACT: Dr. Luft spoke about studies including studies of different strains of Bb to identify virulence markers, which have investigated gene expression in B. Burgdorferi. He reported that under laboratory conditions around half of the potential 1400 Borrelia proteins are expressed. Conditions such as pH and temperature can be varied and the effects on gene expression can be studied. 

 

 

  1. PLoS ONE 7(10): e48277. doi:10.1371/journal.pone.0048277

 

Characterization of Biofilm Formation by Borrelia burgdorferi In Vitro

 

Sapi E, Bastian SL, Mpoy CM, Scott S, Rattelle A, et al. (2012)

 

University of New Haven, CT

ABSTRACT: Borrelia burgdorferi, the causative agent of Lyme disease, has long been known to be capable of forming aggregates and colonies. It was recently demonstrated that Borrelia burgdorferi aggregate formation dramatically changes the in vitro response to hostile environments by this pathogen. In this study, we investigated the hypothesis that these aggregates are indeed biofilms, structures whose resistance to unfavorable conditions are well documented. We studied Borrelia burgdorferi for several known hallmark features of biofilm, including structural rearrangements in the aggregates, variations in development on various substrate matrices and secretion of a protective extracellular polymeric substance (EPS) matrix using several modes of microscopic, cell and molecular biology techniques. The atomic force microscopic results provided evidence that multilevel rearrangements take place at different stages of aggregate development, producing a complex, continuously rearranging structure. Our results also demonstrated that Borrelia burgdorferi is capable of developing aggregates on different abiotic and biotic substrates, and is also capable of forming floating aggregates. Analyzing the extracellular substance of the aggregates for potential exopolysaccharides revealed the existence of both sulfated and non-sulfated/carboxylated substrates, predominately composed of an alginate with calcium and extracellular DNA present. In summary, we have found substantial evidence that Borrelia burgdorferi is capable of forming biofilm in vitro. Biofilm formation by Borrelia species might play an important role in their survival in diverse environmental conditions by providing refuge to individual cells.

 

 

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

 

A Reappraisal of the U.S. Clinical Trials of Post-Treatment Lyme Disease Syndrome

 

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

 

Columbia University

 

ABSTRACT: Four federally funded randomized placebo-controlled treatment trials of post-treatment Lyme syndrome in the United States have been conducted. Most international treatment guidelines summarize these trials as having shown no acute or sustained benefit to repeated antibiotic therapy. The goal of this paper is to determine whether this summary conclusion is supported by the evidence.

Methods: The methods and results of the 4 U.S. treatment trials are described and their critiques evaluated.

Results: 2 of the 4 U.S. treatment trials demonstrated efficacy of IV ceftriaxone on primary and/or secondary outcome measures.

Conclusions: Future treatment guidelines should clarify that efficacy of IV ceftriaxone for post-treatment Lyme fatigue was demonstrated in one RCT and supported by a second RCT, but that its use was not recommended primarily due to adverse events stemming from the IV route of treatment. While repeated IV antibiotic therapy can be effective, safer modes of delivery are needed.

 

 

  1. Northeast Natural History Conference, Syracuse, NY 2012

 

A Survey of Tick Populations Along the Connecticut River in Vermont

 

A.C. Serra, A.R. Giese, Lyndon State College (VT)

 

ABSTRACT (see publication above)

____________________________________________________________________________________________

  1. PLOS One 2012

 

Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi PlasmidsLyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33–40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi 900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short ≤20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant.

 

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

 

1-University of Utah School of Medicine, 2-University of Maryland School of Medicine, 3-Hunter College of the City University of New York, 4-Stony Brook University, NY, 5- New Jersey Medical School, 6-J. Craig Venter Institute, MD, 7-Brookhaven National Laboratory, NY

 

ABSTRACT: Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33–40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi ~900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short ≤20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant.

 

 

  1. Journal of Bacteriology 2011

Whole-Genome Sequences of Thirteen 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-University of Medicine and Dentistry of New Jersey—New Jersey Medical School, 2-Institute for Genome Sciences, University of Maryland, School of Medicine, 3-University of Utah Medical School, 4- Hunter College of the City University of New York, 5-Brookhaven National Laboratory, Upton, New York 6-Stony Brook University

 

ABSTRACT: Borrelia burgdorferi is a causative agent of Lyme disease in North America and Eurasia. The first complete genome sequence of B. burgdorferi strain 31, available for more than a decade, has assisted research on the pathogenesis of Lyme disease. Because a single genome sequence is not sufficient to understand the relationship between genotypic and geographic variation and disease phenotype, we determined the whole-genome sequences of 13 additional B. burgdorferi isolates that span the range of natural variation. These sequences should allow improved understanding of pathogenesis and provide a foundation for novel detection, diagnosis, and prevention strategies.

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  1. PLoS ONE 6(2): e17287. doi:10.1371/journal.pone.0017287 2011

 

Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic 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 K. Holland-3, Jonas Bergquist-5, Patricia K. Coyle-6, Richard D. Smith-4, Brian A. Fallon-7, Benjamin H. Natelson-2,8

1-Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, United States of America, 2 Department of Neurology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, United States of America, 3 Division of Biostatistics and Epidemiology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, United States of America, 4 Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, United States of America, 5 Department of Physical and Analytical Chemistry, Uppsala University, Uppsala, Sweden, 6 Department of Neurology, State University of New York-Stony Brook, Stony Brook, New York, United States of America, 7 Department of Psychiatry, Columbia University Medical Center, New York, New York, United States of America, 8 Department of Pain Medicine and Palliative Care and Beth Israel Medical Center, Albert Einstein School of Medicine, Bronx, New York, United States of America

ABSTRACT: Neurologic Post Treatment Lyme disease (nPTLS) and Chronic Fatigue (CFS) are syndromes of unknown etiology. They share features of fatigue and cognitive dysfunction, making it difficult to differentiate them. Unresolved is whether nPTLS is a subset of CFS.

 

Pooled cerebrospinal fluid (CSF) samples from nPTLS patients, CFS patients, and healthy volunteers were comprehensively analyzed using high-resolution mass spectrometry (MS), coupled with immunoaffinity depletion methods to reduce protein-masking by abundant proteins. Individual patient and healthy control CSF samples were analyzed directly employing a MS-based label-free quantitative proteomics approach. We found that both groups, and individuals within the groups, could be distinguished from each other and normals based on their specific CSF proteins (p<0.01). CFS (n=43) had 2,783 non-redundant proteins, nPTLS (n=25) contained 2,768 proteins, and healthy normals had 2,630 proteins. Preliminary pathway analysis demonstrated that the data could be useful for hypothesis generation on the pathogenetic mechanisms underlying these two related syndromes. nPTLS and CFS have distinguishing CSF protein complements. Each condition has a number of CSF proteins that can be useful in providing candidates for future validation studies and insights on the respective mechanisms of pathogenesis. Distinguishing nPTLS and CFS permits more focused study of each condition, and can lead to novel diagnostics and therapeutic interventions.

 

 

  1. Genetics: Published Articles Ahead of Print, published on September 2, 2011 as 10.1534/genetics.111.130773 Copyright 2011

 

Pervasive Recombination and Sympatric Genome Diversification Driven by Frequency-Dependent Selection in Borrelia burgdorferi, the Lyme disease Bacterium

 

James Haven-1,†, Levy C. Vargas2, Emmanuel F. Mongodin-3, Vincent Xue-4, Yozen Hernandez-2, Pedro Pagan-2, Claire M. Fraser-Liggett-3, Steven E. Schutzer-5, Benjamin J. Luft-6, Sherwood R. Casjens-7, and Wei-Gang Qiu-1,2,8

 

ABSTRACT: How genomic diversity within bacterial populations originates and is maintained in thepresence of frequent recombination is a central problem in understanding bacterial evolution. Natural populations of Borrelia burgdorferi, the bacterial agent of Lyme disease, consist of diverse genomic groups co-infecting single individual vertebrate hosts and tick vectors. To understand mechanisms of sympatric genome differentiation in B. burgdorferi, we sequenced and compared 23 genomes representing major genomic groups in North America and Europe. Linkage analysis of over 13,500 single nucleotide polymorphisms revealed pervasive horizontal DNA exchanges. Although three times more frequent than point mutation, recombination is localized and weakly affects genome-wide linkage disequilibrium. We show by computer simulations that, while enhancing population fitness, recombination constrains neutral and adaptive divergence among sympatric genomes through periodic selective sweeps. In contrast, simulations of frequency-dependent selection with recombination produced the observed pattern of a large number of sympatric genomic groups associated with major sequence variations at the selected locus. We conclude that negative frequency-dependent selection targeting a small number of surface-antigen loci (ospC in particular) sufficiently explains the maintenance of sympatric genome diversity in B. burgdorferi without adaptive divergence. In fact, pervasive recombination makes it unlikely for local B. burgdorferi genomic groups to achieve host specialization. B. burgdorferi genomic groups in northeastern United States are thus best viewed as constituting a single bacterial species, whose generalist nature is a key to its rapid spread and

human virulence.

 

 

  1. Journal of Medical Entomology 47(1):89-94. 2010

 

Extraction of Total 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 Road, Carlsbad, CA 92008 (e-mail: meshoo@ibisbio.com), 2 -University of Medicine and Dentistry of New Jersey, Dept. of Medicine, 185 South Orange Ave., Newark, NJ 07103.

 

ABSTRACT: Ticks harbor numerous bacterial, protozoal, and viral pathogens that can cause serious infections in humans and domestic animals. Active surveillance of the tick vector can provide insight into the frequency and distribution of important pathogens in the environment. Nucleic-acid based detection of tick-borne bacterial, protozoan, and viral pathogens requires the extraction of both DNA and RNA (total nucleic acids) from ticks. Traditional methods for nucleic acid extraction are limited to extraction of either DNA or the RNA from a sample. Here we present a simple bead-beating based protocol for extraction of DNA and RNA from a single tick and show detection of Borrelia burgdorferi and Powassan virus from individual, infected Ixodes scapularis ticks. We determined expected yields for total nucleic acids by this protocol for a variety of adult tick species. The method is applicable to a variety of arthropod vectors, including fleas and mosquitoes, and was partially automated on a liquid handling robot.

 

 

  1. PLoS ONE 5(5) 2010

 

Genotypic variation and Mixtures of Lyme Borrelia in Ixodes Ticks from North America and Europe

 

Chris Crowder-1, Heather Mathews -1, Steven Schutzer-2 et al

 

1 -Ibis Biosciences, 1896 Rutherford Road, Carlsbad, CA 92008 (e-mail: meshoo@ibisbio.com), 2 -University of Medicine and Dentistry of New Jersey, Dept. of Medicine, 185 South Orange Ave., Newark, NJ 07103.

 

 

ABSTRACT: Lyme disease, caused by various species of Borrelia, is transmitted by Ixodes ticks in North America and Europe. Studies have shown the genotype of Borrelia burgdorferi sensu stricto (s.s.) or the species of B. burgdorferi sensu lato (s.l.) affects the ability of the bacteria to cause local or disseminated infection in humans.

Methodology/Principal Findings: We used a multilocus PCR electrospray mass spectrometry assay to determine the species and genotype Borrelia from ticks collected in New York, Connecticut, Indiana, Southern Germany, and California and characterized isolates from parts of the United States and Europe. These analyses identified 53 distinct genotypes of B. burgdorferi sensu stricto with higher resolution than ospC typing. Genotypes of other members of the B. burgdorferi sensu lato complex were also identified and genotyped including B. afzelii, B. garinii, B. lusitaniae, B. spielmanii, and B. valaisiana. While each site in North America had genotypes unique to that location, we found genotypes shared between individual regions and two genotypes found across the United States. Significant B. burgdorferi s.s. genotypic diversity was observed between North America and Europe: only 6.6% of US genotypes (3 of 45) were found in Europe and 27% of the European genotypes (3 of 11) were observed in the US. Interestingly, 39% of adult Ixodes scapularis ticks from North America were infected with more than one genotype of B. burgdorferi s.s. and 22.2% of Ixodes ricinus ticks from Germany were infected with more than one genotype of B. burgdorferi s.l.

Conclusions/Significance: The presence of multiple Borrelia genotypes in ticks increases the probability that a person will be infected with more than one genotype of B. burgdorferi, potentially increasing the risks of disseminated Lyme disease. Our study indicates that the genotypic diversity of Borrelia in ticks in both North America and Europe is higher then previously reported and can have potential clinical consequences.

___________________________________________________________________________________________

 

  1. Kerry Clark, PHD University of N. Florida

 

Investigations of Human Borreliosis in the Southern US

 

Presented at 2009 Columbia University/LDA national Lyme & Tick-Borne Diseases: 34 Years From Lyme Connecticut Across the Nation scientific conference and at Jacksonville State University Spring 2010 conference.

 

ABSTRACT: This study address the hypothesis that lone star ticks (Amblyomma americanum), in addition to blacklegged ticks (Ixodes scapularis), serve as vectors of Bbsl to humans. The study results are expected to confirm a previously unrecognized genetic group of Bbsl as the cause of a significant portion of LB cases in the U.S., to estimate the rate of infection in ticks biting humans in the southern U.S., to provide evidence of the tick species responsible for transmitting Lyme Borrelia to humans in southern states, and to provide improved methods for DNA testing and identification of Lyme Borrelia in human patient samples.

 

History: Dr. Clark’s research is focused on the ecology and epidemiology of Lyme disease and other tick-borne diseases in the southern U.S. He collaborated with investigators at Georgia Southern University in several studies, including those leading to the first isolations and characterizations of B. burgdorferi in South Carolina. Dr. Clark and colleagues have documented the presence of several Lyme Borrelia species infecting small mammals, ticks, and lizards in Florida and South Carolina. He was the first to ever report finding Lyme disease spirochetes infecting wild reptiles. More recently, he has focused his investigative efforts on the cause of Lyme-like illness in humans in the southern U.S.

 

Objectives: The primary objectives of his research and service activities are the following: (1) to learn more about the ecology and epidemiology of Lyme and other tick-borne diseases affecting humans in the U.S.; (2) to improve early detection and diagnosis by developing better diagnostic tests; and (3) to educate clinicians, public health personnel and the general public about the presence, identification, and prevention of tick-borne infections.

 

 

  1. Neurobiology of Disease 2010

 

Inflammation and central nervous system Lyme disease.

 

Brian Fallon, MD, David Hardesty, MD et al

 

Columbia University

 

ABSTRACT: Neurologic manifestations of Lyme disease occur in 10-15% of individuals with untreated Lyme.  This paper discusses the symptoms of neurologic Lyme and reviews experimental studies that provide insight into the possible mechanisms of inflammation following Borrelia infection and contributing risk factors.

 

 

  1. Arch Gen Psychiatry. 2009;66(5):554-563.

 

Regional Cerebral Blood Flow and Metabolic Rate 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

 

Columbia University

ABSTRACT

Main Outcome Measures: 

Patients with persistent Lyme encephalopathy were compared with age-, sex-, and education-matched controls. Fully quantified assessments of rCBF and rCMR for glucose were obtained while subjects were medication-free using positron emission tomography. The CBF was assessed in 2 resting room air conditions (without snorkel and with snorkel) and 1 challenge condition (room air enhanced with carbon dioxide, ie, hypercapnia).

Results:

Statistical parametric mapping analyses revealed regional abnormalities in all rCBF and rCMR measurements that were consistent in location across imaging methods and primarily reflected hypoactivity. Deficits were noted in bilateral gray and white matter regions, primarily in the temporal, parietal, and limbic areas. Although diminished global hypercapnic CBF reactivity (< .02) was suggestive of a component of vascular compromise, the close coupling between CBF and CMR suggests that the regional abnormalities are primarily metabolically driven. Patients did not differ from controls on global resting CBF and CMR measurements.

Conclusions:

Patients with persistent Lyme encephalopathy have objectively quantifiable topographic abnormalities in functional brain activity. These CBF and CMR reductions were observed in all measurement conditions. Future research should address whether this pattern is also seen in acute neurologic Lyme disease.

 

  1. Gene 2009

 

Fast, adaptive evolution at a bacterial host-resistance locus: The PFam54 gene array in Borrelia burgdorferi”

 

*Wywial E. Haven J, Casjens SR, Hernandez YA, Singh S, Mongodin EF, Fraser-Liggett CM, Luft BJ, Schutzer SE, Qiu WG.

 

ABSTRACT: Microbial pathogens have evolved sophisticated mechanisms for evasion of host innate and adaptive immunities. PFam54 is the largest paralogous gene family in the genomes of Borrelia burgdorferi, the Lyme disease bacterium. One member of PFam54, the complement-regulator acquiring surface proteins 1 (BbCrasp-1), is able to abort the alternative pathway of complement activation via binding human complement-regulator factor H (FH). The gene coding for BbCRASP-1 exists in a tandem array of PFam54 genes in the B. burgdorferi genome, a result apparently of repeated gene duplications. To help elucidate the functions of the large number of PFam54 genes, we performed phylogenomic and structural analyses of the PFam54 gene array from ten B. burgdorferi genomes. Analyses based on gene tree, genome synteny, and structural models revealed rapid adaptive evolution of this array through gene duplication, gene loss, and functional diversification. Individual PFam54 genes, however, do not show high intra-population sequence polymorphisms as genes providing evasion from adaptive immunity generally do. PFam54 members able to bind human FH are not monophyletic, suggesting that human FH affinity, however strong, is an incidental rather than main function of these PFam54 proteins. The large number of PFam54 genes existing in any single B. burgdorferi genome may target different innate-immunity proteins of a single host species or the same immune protein of a variety of host species. Genetic variability of the PFam54 gene array suggests that universally present PFam54 lineages such as BBA64, BBA65, BBA66, and BBA73 may be better candidates for the development of broad-spectrum vaccines or drugs than strain-restricted lineages such as BbCRASP-1.

 

  1. Emerging Infectious Diseases Volume 14, Number 7–July 2008

Wide Distribution of a High-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†

 

Hunter College of the City University of New York, New York, New York, USA; †Stony Brook University, Stony Brook, New York, USA; ‡Baxter Innovations GmBH, Orth/Donau, Austria; and §Centers for Disease Control and Prevention, Fort Collins, Colorado, USA

ABSTRACT: The A and B clones of Borrelia burgdorferi sensu stricto, distinguished by outer surface protein C (ospC) gene sequences, are commonly associated with disseminated Lyme disease. To resolve phylogenetic relationships among isolates, we sequenced 68 isolates from Europe and North America at 1 chromosomal locus (16S–23S ribosomal RNA spacer) and 3 plasmid loci (ospC,dbpA, and BBD14). The ospC-A clone appeared to be highly prevalent on both continents, and isolates of this clone were uniform in DNA sequences, which suggests a recent trans-oceanic migration. The genetic homogeneity of ospC-A isolates was confirmed by sequences at 6 additional chromosomal housekeeping loci (gap, alr, glpA, xylB, ackA, and tgt). In contrast, the ospC-B group consists of genotypes distinct to each continent, indicating geographic isolation. We conclude that the ospC-A clone has dispersed rapidly and widely in the recent past. The spread of the ospC-A clone may have contributed, and likely continues to contribute, to the rise of Lyme disease incidence.

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  1. Neurology May 2008

 

A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy

 

B. A. Fallon, MD, 2. J. G. Keilp, PhD, 3 K. M. Corbera, MD, 4. E. Petkova, PhD, 5. C. B. Britton, MD, 6. E. Dwyer, MD, 7. I. Slavov, PhD, 8. J. Cheng, MD, PhD, 9. J. Dobkin, MD, 10. D. R. Nelson, PhD and 11. H. A. Sackeim, PhD

 

From the Department of Psychiatry (B.A.F., J.G.K., K.M.C., E.P., I.S., J.C., H.A.S.), Department of Biostatistics (E.P.), Department of Neurology (C.B.B.), Department of Medicine (E.D., J.D.), and New York State Psychiatric Institute (B.A.F., J.G.K., K.M.C., E.P., I.S., J.C., H.A.S.), Columbia University, New York; and Department of Cell and Molecular Biology, University of Rhode Island, Kingston (D.R.N.).

ABSTRACT

Background: Optimal treatment remains uncertain for patients with cognitive impairment that persists or returns after standard IV antibiotic therapy for Lyme disease.

Methods: Patients had well-documented Lyme disease, with at least 3 weeks of prior IV antibiotics, current positive IgG Western blot, and objective memory impairment. Healthy individuals served as controls for practice effects. Patients were randomly assigned to 10 weeks of double-masked treatment with IV ceftriaxone or IV placebo and then no antibiotic therapy. The primary outcome was neurocognitive performance at week 12—specifically, memory. Durability of benefit was evaluated at week 24. Group differences were estimated according to longitudinal mixed-effects models.

Results: After screening 3368 patients and 305 volunteers, 37 patients and 20 healthy individuals enrolled. Enrolled patients had mild to moderate cognitive impairment and marked levels of fatigue, pain, and impaired physical functioning. Across six cognitive domains, a significant treatment-by-time interaction favored the antibiotic-treated group at week 12. The improvement was generalized (not specific to domain) and moderate in magnitude, but it was not sustained to week 24. On secondary outcome, patients with more severe fatigue, pain, and impaired physical functioning who received antibiotics were improved at week 12, and this was sustained to week 24 for pain and physical functioning. Adverse events from either the study medication or the PICC line were noted among 6 of 23 (26.1%) patients given IV ceftriaxone and among 1 of 14 (7.1%) patients given IV placebo; these resolved without permanent injury.

Conclusion: IV ceftriaxone therapy results in short-term cognitive improvement for patients with posttreatment Lyme encephalopathy, but relapse in cognition occurs after the antibiotic is discontinued. Treatment strategies that result in sustained cognitive improvement are needed.

 

 

  1. Presented at LDA-Columbia University Lyme & Other Tick-Borne Diseases: Solutions through Cutting Edge Science 2008

 

Profiling the humoral response to Borrelia burgdorferi infection with protein microarrays

 

Benjamin J Luft, et al Stony Brook University NY

 

New Insights from the Borrelia Genome

ABSTRACT: Dr. Luft spoke about studies including studies of different strains of Bb to identify virulence markers, which have investigated gene expression in B. Burgdorferi. He reported that under laboratory conditions around half of the potential 1400 Borrelia proteins are expressed. Conditions such as pH and temperature can be varied and the effects on gene expression can be studied.

 

 

  1. Infection and Immunity, January 2006

 

Identification of Borrelia burgdorferi outer surface proteins

 

Brooks CS; Vuppala SR; Jett AM; Akins DR Department of Microbiology and Immunology.

 

The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA,

 

ABSTRACT: Several Borrelia burgdorferi outer surface proteins have been identified over the past decade that are up-regulated by temperature- and/or mammalian host-specific signals as this spirochete is transmitted from ticks to mammals. Given the potential role(s) that these differentially up-regulated proteins may play in B. burgdorferi transmission and Lyme disease pathogenesis, much attention has recently been placed on identifying additional borrelial outer surface proteins. To identify uncharacterized B. burgdorferi outer surface proteins, we previously performed a comprehensive gene expression profiling analysis of temperature-shifted and mammalian host-adapted B. burgdorferi. The combined microarray analyses revealed that many genes encoding known and putative outer surface proteins are down-regulated in mammalian host-adapted B. burgdorferi. At the same time, however, several different genes encoding putative outer surface proteins were found to be up-regulated during the transmission and infection process. Among the putative outer surface proteins identified, biochemical and surface localization analyses confirmed that seven (Bb0405, Bb0689, BbA36, BbA64, BbA66, BbA69, and BbI42) are localized to the surface of B. burgdorferi. Furthermore, enzyme-linked immunosorbent assay analysis using serum from tick-infested baboons indicated that all seven outer surface proteins identified are immunogenic and that antibodies are generated against all seven during a natural infection. Specific antibodies generated against all seven of these surface proteins were found to be bactericidal against B. burgdorferi, indicating that these newly identified outer surface proteins are prime candidates for analysis as second-generation Lyme disease vaccinogens.

 

 

  1. J Int Neuropsychol Soc. 2006 Jan;12(1):119-29

 

WAIS-III and WMS-III performance in chronic Lyme disease

 

Keilp JG, Corbera K, Slavov I, Taylor MJ, Sackeim HA, Fallon BA.

 

Columbia University College of Physicians and Surgeons, Department of Psychiatry, NY, NY. New York State Psychiatric Institute, Department of Neuroscience, NY, NY.

 

ABSTRACT: There is controversy regarding the nature and degree of intellectual and memory deficits in chronic Lyme disease. In this study, 81 participants with rigorously diagnosed chronic Lyme disease were administered the newest revisions of the Wechsler Adult Intelligence Scale (WAIS-III) and Wechsler Memory Scale (WMS-III), and compared to 39 nonpatients. On the WAIS-III, Lyme disease participants had poorer Full Scale and Performance IQ’s. At the subtest level, differences were restricted to Information and the Processing Speed subtests. On the WMS-III, Lyme disease participants performed more poorly on Auditory Immediate, Immediate, Auditory Delayed, Auditory Recognition Delayed, and General Memory indices. Among WMS-III subtests, however, differences were restricted to Logical Memory (immediate and delayed) and Family Pictures (delayed only), a Visual Memory subtest. Discriminant analyses suggest deficits in chronic Lyme are best characterized as a combination of memory difficulty and diminished processing speed. Deficits were modest, between one-third and two-thirds of a standard deviation, consistent with earlier studies. Depression severity had a weak relationship to processing speed, but little other association to test performance. Deficits in chronic Lyme disease are consistent with a subtle neuropathological process affecting multiple performance tasks, although further work is needed to definitively rule out nonspecific illness effects. (JINS, 2006, 12, 119-129.).

 

 

  1. Daniel Cameron, MD. Presented to the 6th Annual Lyme & Other Tick-Borne Diseases: Emerging Tick-Borne Diseases Conference on October 28, 2005 in Philadelphia Pennsylvania

 

Results from Lyme Disease Clinical Treatment Trial

 

Lyme Disease Association and Columbia University, conference co-sponsors.

 

CONFERENCE ABSTRACT

Methods: Data were obtained from a randomized, double-blind placebo-controlled study of patients with recurrent Lyme disease. Patients received either amoxicillin 500mg. 3 times/day or placebo for 3 months. The Short Form-36 Health Survey, administered at baseline and at the conclusion, provided a Mental Component Summary (MCS) and a Physical Component Summary (PCS) for HRQOL. Baseline HRQOL scores were compared with the general US and chronically-ill populations. Patients with Lyme disease were divided into the lowest, moderate, and higher initial quality of life as measured by SF-36.

Results: The quality of life of Lyme disease was significantly lower than the US norm and chronically-ill patients on all SF-36 scales. Compared with patients who received placebo, patients treated with amoxicillin showed greater improvement on SF-36 physical function, general health perception, vitality, social function, and emotional health. Lyme disease patient presenting with the best initial quality of life had the highest success rate.