TOUCHED BY LYME: Where money for Lyme research goes
22 August, 2010
http://www.lymedisease.org/news/touchedbylyme/534.html
When we started publicizing that the 2010 CALDA Lymewalks are raising money for research, many people asked us what kind of research we are funding. It’s a fair question. Here’s a run-down on current research projects funded by CALDA.
CALDA has a committee made up of researchers, doctors and patients, who evaluate applications for research grants with an eye for projects that are patient-oriented. Our goal is to fund research that will do the most to help patients. (Typically, CALDA doesn’t fund the entire project. Researchers usually get support from a variety of sources.)
Here are current projects being funded in part by CALDA.
* Stanford University. Clinical manifestations of Lyme disease.
How is chronic Lyme defined? The diagnosis of Lyme disease is complicated because of the diversity of its clinical manifestations, with symptoms reflecting involvement of the brain, nerves, joints, muscles or heart. This research project focuses on the diverse manifestations of Lyme disease that are underrepresented in treatment research. The primary goal of this research is to establish a preliminary case control definition of chronic Lyme disease that recognizes the diversity of symptom patterns and the limitations of standard diagnostic tests. Knowledge gleaned from this study should help doctors do a better job of diagnosing and treating Lyme, and pave the way for more extensive research of chronic Lyme.
* University of California, Davis, vet school. Mechanisms of Bartonella transmission between ticks and dogs.
Bartonella transmission is not well understood. This study seeks to gain insight into the role of ticks in the transmission of Bartonella (a co-infection plaguing many Lyme patients.)
* Stony Brook University, New York. Profiling the Humoral Response to Bb Infection with Protein Microarrays. Looking for more effective antibiotic treatments for Lyme disease.
* University of New Haven, CT
Antibiotic susceptibility of the spirochete and other morphologies of Borrelia burgdorferi. Looking for treatments to eliminate all forms of Bb (spirochete, L-form, and cyst).
This project is being carried out by Dr. Eva Sapi, who is doing important work about a variety of aspects of Lyme disease. You can see a 10-minute interview with her about her work on YouTube.
http://www.youtube.com/watch?v=AmvgOfIN_8c
* Johns Hopkins University, Baltimore, MD
Molecular Basis of Borrelia burgdorferi L-form Formation.
Perfecting a technique for culturing L-forms of Bb in the laboratory, which could lead to more effective treatments.
These five projects are important steps, but there is still much work to be done. Won’t you help us raise money for more research by participating in the 2010 CALDA Lymewalks? If you are unable to attend in person, you can still create your own fundraising page or donate via somebody’s else’s page. Click here for more information.
http://www.lymedisease.org/activism/lyme_events.html
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Turn the Corner: 2009 Grant Recipients
http://www.turnthecorner.org/2009grants-2.html
These innovative research projects will have a monumental impact in regard to the treatment and diagnosis of Lyme disease. Your donation helps scientists and doctors study various approaches that can one day “turn the corner” on Lyme disease.
* M. Karen Newell, Ph.D. Colorado Springs, CO
One ground-breaking research project that TTC is funding in 2009 is headed by M. Karen Newell, Ph.D. at the University of Colorado at Colorado Springs. Her research has implications for improving quality of life for Lyme patients in the future. This study examines the genetics of chronic inflammation, which is a characteristic of every stage of Lyme disease. Using targeted peptides aimed at those that have the particular “immune response” genes associated with disease, Dr. Newell will attempt to reduce the inflammation caused by the Borrelia bacteria.
* Eva Sapi, Ph.D. West Haven, CT
Dr. Sapi, entering the second year of her two-year grants, has been studying the role of biofilms and nematodes in Borrelia burgdorferi, the bacterial agent of Lyme disease. Dr. Sapi has confirmed that the Borrelia bacteria is capable of hiding within a complex covering called biofilm, which increases its resistance to antibiotic treatment. The next step is to test which agents will ensure that Borrelia cannot hide in biofilm during and after antibiotic therapy. Dr. Sapi strongly believes this research will be vital to treating patients with chronic Lyme disease.
A second study focuses on filarial nematodes, a microscopic worm found in deer ticks, the type that are known to spread Lyme disease. The researchers have identified that at least 40% of the tested deer ticks had this pathogen. The goal of this study is to provide a new means to test Lyme patients for a novel infection and to develop different therapeutic protocols, especially for those patients who are not responding to antibiotics.
* Lyme Literacy Programs for Patients, Washington, DC
TTC sponsored several projects to increase awareness of Lyme, including a legislative forum in the nation’s capital, led by the National Capital Lyme and Tick-Borne Disease Association. The forum helped build unity in the Lyme community and to educate many people about the legislative process and what they could do in order for chronic Lyme to be recognized by the United States Congress.
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Turn the Corner: 2009 Initiatives
http://www.turnthecorner.org/2009Initiatives.html
Your support has helped fund many much-needed initiatives in the world of Lyme disease. Turn the Corner Foundation (TTC) is so pleased to convert your donations into programs that make a difference in people’s lives.
* Under Our Skin
As many of you are aware, Turn the Corner (TTC) is the official Outreach Partner for the documentary Under Our Skin. The film investigates the shocking human, medical, and political dimensions of Lyme disease. We are extremley excited and proud to announce its theatrical release!
The film opened in New York City on June 19th at the IFC Center and will continue to be shown across the country in the coming months. Please join TTC in celebrating the film’s achievement and support the movie by spreading the word to family and friends and coming to the NYC showing.
This prestigious film has already earned many awards, including Best in Infectious Diseases at the International Health and Medical Media Awards, and has been selected as a finalist for the Audience Choice Award at the Tribeca Film Festival (2008). The film’s theatrical release is a huge accomplishment and testament to the importance of the film, Lyme disease, and everything we fight for.
Turn the Corner thanks you for your continuing support of Lyme disease awareness and the film Under Our Skin.
http://www.underourskin.com/
* Lyme and Associated Diseases Registry™
Dr. Burrascano, a member of TTC’s Medical Advisory Board, has been compiling data on diagnosis and treatment of Lyme disease. Results from this critical research will be a key element for all treating physicians and this information will be published and disseminated worldwide. We are pleased to announce that the top-performing doctors in this program are Dr. Chandra Swami, Dr. Steven Harris, Dr. Cheryl Ortel, Dr. Ann Corson, and Dr. Daniel Cameron. Encourage your physician to participate in the database program today and help standardize treatment techniques for Lyme patients.
Why Participate?
* Streamlines doctor/patient visits.
* Tabulates and analyzes hidden information in patient charts.
* Addresses clinical issues that doctors and patients face.
* Resolves dilemma of the “unknowns” in TBD care.
* Spearheads the standardization of TBD diagnosis and treatment
* Results in publishable data.
* Participation is easy, and simple to implement in office.
You have the power to make a critical difference in the Lyme community. Seize this opportunity to revolutionize the future of TBD treatment!
If you are a doctor or medical assistant and would like to participate in the program, please contact Colleen Nicholson at Jcn4jc@aol.com or 516.286.7196 end_of_the_skype_highlighting.
* Physicians Training Program
This groundbreaking program provides medical practitioners the opportunity to study with a Lyme-literate health care professional to recognize and treat Lyme disease successfully. In about two weeks, trainees become Lyme-literate through watching mentoring doctors in action with patients, reviewing different cases, and learning their individual approaches to diagnosis and treatment. These professionals bring this skill set back to their community in order to better care for their patients.Over 100 doctors have already been trained through this program, helping thousands of people with Lyme disease.
Click here for more information about the Physicians Training Program [open to European physicians also]
http://www.ilads.org/lyme_programs/lyme_training.html
Click here to read quotes from doctors who participated in the program.
http://www.turnthecorner.org/PhysiciansTrainingProgramReviews.htm
Click here to make a donation that helps doctors from all over the world become Lyme-literate.
http://www.turnthecorner.org/donate.htm
* Create Footprints
This national program allows volunteers across the country to plan a walk to raise funds for Lyme disease research and initiatives through Turn the Corner Foundation. You can become an organizer of an event and raise money in your own neighborhood. Create Footprints gives you everything you need, including forms and step-by-step instructions, to execute a successful fundraising walk no matter where you live. anning a walk to benefit Lyme disease research and awareness in your area.
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Research GRANTS
To access list of 2010 Lyme & tick-borne diseases research grants go to:
Ticks:
https://sites.google.com/site/marylandlyme/research-grants/tick-related-2010
Lyme:
https://sites.google.com/site/marylandlyme/research-grants/borrelia-grants-2010
https://sites.google.com/site/marylandlyme/research-grants/chronic-lyme-2010
https://sites.google.com/site/marylandlyme/research-grants/post-lyme-syndrome
https://sites.google.com/site/marylandlyme/research-grants/wormser2010
Co-infections:
https://sites.google.com/site/marylandlyme/research-grants/2010-babesia
https://sites.google.com/site/marylandlyme/research-grants/bartonella-grants-2010
https://sites.google.com/site/marylandlyme/research-grants/ehrlichia-anaplasma-2010
https://sites.google.com/site/marylandlyme/research-grants/rocky-mountain-spotted-fever-2010
Misc:
https://sites.google.com/site/marylandlyme/research-grants/misc-grants-2010
https://sites.google.com/site/marylandlyme/research-grants/past-grants
https://sites.google.com/site/marylandlyme/research-grants/ny-medical-college-2010
NB: This site also has links to chronic Lyme, Paediatric Lyme, Sam Donta, Dr Jones, misdiagnoses, sexual transmission, tick studies, Lyme controversies etc. etc – some very interesting stuff..
https://sites.google.com/site/marylandlyme/research-grants
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2010 Grants and Initiatives
International Lyme and Associated Diseases Society (ILADS)
Turn the Corner made a grant to ILADS for the world renown Physicians Training Program (PTP). Founded and exclusively funded by TTC, the PTP continues to foster excellence in care for Lyme disease and tick-borne disease patients by providing medical practitioners the opportunity to study with Lyme-literate healthcare professionals. In 2010 TTC proudly trained our 100th program graduate. Thousands of patients have been properly diagnosed and properly treated thanks to our groundbreaking signature program. Read More About the Physicians Training Program. http://www.turnthecorner.org/node/23
Turn the Corner made a grant to ILADS for the 2010 ILADS Conference in London, England. The first European conference was held in June and attracted over 65 attendees. TTC received praise from ILADS. “We are so very grateful for the support TTC has given us. The meeting was a tremendous success!”
ILADS 2012 London Conference attendees included: Carsten Nicolaus, MD; Chrisitan Perrone, MD; Sarrah Chisell, MD (organizer and graduate of ILADS/TTC Physician Training Program); Ann Corson, MD (graduate of ILDS/TTC Physician Training Program); Leo Shea III, Ph.D (TTC Medical Advisory Board Member)
Turn the Corner made a grant to ILADS for a new unique and innovative program – the Specialty Education program (SEP). SEP will underwrite the expenses associated with sending a Lyme-literate ILADS representative to attend medical specialty conferences to present or disseminate information regarding Lyme disease and tick-borne diseases. It is TTC’s belief that specialty physicians should have a greater awareness of the clinical diagnosis of Lyme and tick borne diseases.
Turn the Corner made a grant to Cheryl Koopman. Ph.D. at Stamford Univeristy to continue the “Multi-Method Examination of Diverse Manifestations of Lyme Disease”
Dr. Koopman and her Stanford University team seek to identify diverse manifestations of Lyme disease to help explain the complexity of this illness. They intend to use clinical and laboratory findings of Lyme disease patients to show how conclusions from prior studies may not adequately generalize to the typical Lyme disease patient population.
There are two main goals: 1) To identify patterns of symptoms that describe different groups of Lyme disease patients as seen in clinical practice; and 2) to establish a case-controlled definition of chronic Lyme disease.
For the first phase of the project, they obtained data from a large private practice in California that specializes in treating tick-borne illnesses. Over 1,000 medical records were reviewed and data recorded include: demographics, recollection of tick bite and bulls-eye rash, length of time since onset of symptoms to initial visit, co-morbid infections and illnesses, test results, and prior/current medication use. The team is excited about the results of this first phase of the research, which will be revealed as soon as they publish the results.
In the second phase of the study now, Dr. Koopman and her team are recruiting persons diagnosed with Lyme disease by California Bay Area physicians and matching them to a group of healthy controls to compare their test assays, symptoms, and quality of life indices. The sensitivity and specificity of IGeneX Western Blots, Mardex Western Blots, PCR and ELISA will be compared to each other for their ability to detect chronic Lyme disease. They will examine how these tests and indices are related to the symptom clusters found in the first phase of the study. This will help to establish a preliminary set of case-controlled criteria to characterize persons with chronic Lyme disease on alternative test assays and to further understand the diverse manifestations of this illness.
This research study is being conducted at Stanford University. The research team consists of the following: Cheryl Koopman, PhD, Principal Investigator; Tyson Holmes, PhD, Biostatistician; Yvonne Lin, PA-C, Project Director; Lila Castillo, MA, Project Coordinator; and Alexandra Aylward, Jill Whisnant, and Casey Brodhead, Research Coordinators. The expert panel is comprised of Daniel Cameron, MD; Christine Green, MD; and Raphael Stricker, MD. This project’s Scientific and Community Advisory Board includes physicians, researchers, and advocates.
Turn the Corner made a grant to Steven Phillips, M.D. to study an innovative treatment for Lyme and tick-borne diseases – rife technology. This study will be examining the effects on human cells of exposure to the types of radiofrequencies used in a particular rife machine. Extensive research has already been conducted on the effects on human cells by exposure to the frequencies used for cell phones, but this type of research has not been done for the radiofrequencies used for rife machines. This study will examine lymphocytes from patients with chronic Lyme disease who have not used a rife machine, patients with chronic Lyme disease who have been using a rife machine, and healthy controls. The lymphocytes will be examined for DNA damage by both the COMET assay and micronucleus test.
In this way, it may be possible to quantitate and compare the risk, or lack thereof, of rife machine radiofrequency exposure.
Turn the Corner made a grant to BLAST ! Lyme Disease Prevention Program.
BLAST is a health education initiative focused on the 5 most important science-based behaviors for keeping individuals safe from tick-borne diseases. The program focus is on prevention and education. BLAST has received accolades from the Centers for Disease Control and Prevention, the Connecticut Public Health Association, Fairfield County health departments and hospitals, universities and local school systems. The program has been recognized as a model Community Health education Program that is simple and affordable for the public to replicate. BLAST is based in Ridgefiled,CT and can be contacted at blastlyme@ridgefieldct.org. Their website is www.ridgefieldct.org and information is available here on our site. http://www.drupal.turnthecorner.org/content/tips-protect-your-loved-ones
Turn the Corner continues to support the research of Dr. Eva Sapi, University of New Haven.
Dr. Sapi, has been studying the role of biofilms and nematodes in Borrelia burgdorferi, the bacterial agent of Lyme disease. Dr. Sapi has confirmed that the Borrelia bacteria is capable of hiding within a complex covering called biofilm, which increases its resistance to antibiotic treatment. The next step is to test whichagents will ensure that Borrelia cannot hide in biofilm during and after antibiotic therapy. Dr. Sapi strongly believes this research will be vital to treating patients with chronic Lyme disease. Read a recent article about Dr. Sapi’s research at www.townsendletter.com/July2010/sapi0710.html
Turn the Corner is pleased to offer a video tape of the 2010 Lyme Disease Symposium “The Challenges of Lyme Disease: Emerging Research and Pediatric Care” hosted by Dr. Sapi at the University of New Haven.
Turn the Corner made a grant to Dr. Joseph Burrascano for his continuing work to create a Lyme and Associated Diseases Registry database.
Turn the Corner volunteers proudly answers inquiries from Lyme patients throughout the world and provide free information about Lyme-Literate medical professionals. Thousands of patients have been helped with the information provided by Turn the Corner’s wonderful and caring volunteers. Inquiries can be made at medicalinfo@turnthecorner.org
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2011 Grants and Initiatives
Turn the Corner awards a grant to the International Lyme and Associated Diseases Society (ILADS) for the world renown Physicians Training Program (PTP). Founded and exclusively funded by TTC, the PTP continues to foster excellence in care for Lyme disease and tick-borne disease patients by providing medical practitioners the opportunity to study with Lyme-literate healthcare professionals. Over 100 medical practioners have been trained and thousands of patients have been properly diagnosed and properly treated thanks to our groundbreaking signature program. Read More About the Physicians Training Program. http://www.turnthecorner.org/content/physicians-training-program
Turn the Corner awards a grant to Eva Sapi, Ph.D., University of New Haven. Since 2008, Turn the Corner has supported the research of Dr. Sapi. Dr. Sapi and her students at the University of New Haven have been studying the role of biofilms and nematodes in Borrelia burgdorferi, the bacterial agent of Lyme disease. Dr. Sapi has confirmed that the Borrelia bacteria is capable of hiding within a complex covering called biofilm, which increases its resistance to antibiotic treatment. Currently she is testing which agents will ensure that Borrelia cannot hide in biofilm during and after therapy. Dr. Sapi strongly believes this research will be vital to treating patients with chronic Lyme disease. Read a recent article about Dr. Sapi’s research at www.townsendletter.com/July2010/sapi0710.html Turn the Corner is pleased to offer a video tape of the 2010 Lyme Disease Symposium “The Challenges of Lyme Disease: Emerging Research and Pediatric Care” hosted by Dr. Sapi at the University of New Haven. http://www.turnthecorner.org/content/dr-sapi-conference-new-haven-ct-2010
Turn the Corner awards a grant to M. Karen Newell, Ph.D., Texas A & M University Since 2009, Turn the Corner has supported Dr. Newell’s ground-breaking research project that has implications for improving quality of life for Lyme patients in the future. This study examines the genetics of chronic inflammation, which is a characteristic of every stage of Lyme disease. Using targeted peptides aimed at those that have the particular “immune response” genes associated with disease, Dr. Newell will attempt to reduce the inflammation caused by the Borrelia bacteria.
Through cytometric and computational analyses and tissue typing of peripheral blood from patients with Lyme disease, Dr. Newell has successfully determined that B and activated T lymphocytes, compared with peripheral blood white cells from uninfected individuals, exhibit the characteristics of polyclonal B and T cell activation and have MHC class I or II molecules filled with self-antigens. This reaffirms the prediction of a statistically significant association between the binding affinity of the peptide CLIP to the MHC class II, but not MHC class I. Further research requires parallel analysis of lymph node cells from at least 15 chronic Lyme patients in order to demonstrate statistical significance.
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3 interesting projects:
Project Number: 5R01AI073911-04
Contact Principal Investigator: BARTHOLD, STEPHEN WILLIAM
Title: HUMORAL RESPONSES TO LYME BORRELIOSIS: A MOUSE MODEL Awardee Organization: UNIVERSITY OF CALIFORNIA DAVIS
http://projectreporter.nih.gov/project_info_description.cfm?aid=8012860&icde=7716963
This disease is caused by B. burgdorferi (Bb) and is the most commonly reported arthropod-borne illness in the US and Europe with the number of reported infections raising each year. The spirochetes cause persistent infections and chronic disease with bouts of arthritis and carditis in untreated patients. Our long-term objective is to delineate the mechanisms with which Bb evades effective immunity during persistent infection of fully immunocompetent hosts.
PUBLIC HEALTH RELEVANCE: Lyme Disease is a chronic disabling disease resulting from a tick-bite. The tick transfers a bacterium, Borrelia burgdorferi, to the patient, which can persist in various organs, including the joints and heart, where it can cause disabling disease such as chronic arthritis and heart muscle disease. The body develops an immune response that can initially fend off disease but cannot clear the infection. Thus, if infections are not treated continuing disease is common. This proposal aims to determine why the immune response that is sufficient to help to reduce disease ultimately fails to clear the infection. Such information is necessary to develop vaccines and treatments for this increasingly prevalent disease.
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Project Number: 5R01AI085798-02
Contact Principal Investigator: BOCKENSTEDT, LINDA K
Title: REAL-TIME IMAGING ANALYSIS OF VECTOR-BORNE LYME BORRELIOSIS PATHOGENESIS & PERSIS Awardee Organization: YALE UNIVERSITY
http://projectreporter.nih.gov/project_info_description.cfm?aid=8034220&icde=7716963
Although usually amenable to antibiotic therapy, Bb infection can be followed by prolonged clinical symptoms, especially if treatment is delayed. Recent studies in mice reveal that under some circumstances, spirochetes can persist in connective tissue for extended periods after antibiotic treatment. Central to resolving the clinical issue of spirochete persistence after antibiotic therapy is an understanding of how Bb evades the normal host defenses that should complement antibiotic effects.
PUBLIC HEALTH RELEVANCE: Lyme disease, due to infection with the tick-transmitted spirochete Borrelia burgdorferi (Bb), is the most common vector-borne disease in North America. The mechanisms whereby Bb infects, disseminates and persists in mammals are poorly understood. This application will use state-of-the-art imaging approaches, including multiphoton microscopy, to study features of the outer membrane of Bb and Bb motility patterns that may allow it to escape immune and antibiotic-mediated destruction in vivo.
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Project Number: 1R41AI092978-01
Contact Principal Investigator: BOCKENSTEDT, LINDA K
Title: T CELL CYTOKINE ASSAY FOR THE DIAGNOSIS OF DISSEMINATED LYME BORRELIOSIS Awardee Organization: L2 DIAGNOSTICS, LLC
http://projectreporter.nih.gov/project_info_description.cfm?aid=8058201&icde=7716963
Serologic tests (ELISA and immunoblot) that detect B. burgdorferi-reactive antibodies are the most widely used tests, but have lower sensitivity and specificity in early infection and can be indeterminate in later stages, particularly if antibiotics have been administered. In addition, current Lyme serologic tests do not distinguish previous exposure to B. burgdorferi from active infection, and no serologic test to date can be used to assess response to therapy. This Phase 1 proposal seeks to improve upon the currently available Lyme diagnostic tests
PUBLIC HEALTH RELEVANCE: Lyme disease, due to infection with the tick-borne spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States. Timely diagnosis of infection is important for optimal response to therapy and to prevent long-term sequelae. This project will assess the utility of a T cell cytokine assay for the detection of disseminated B. burgdorferi infection and for monitoring efficacy of treatment.
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Evaluation of in-vitro antibiotic susceptibility of different morphological forms of Borrelia burgdorferi
Authors:
Sapi E, Kaur N, Anyanwu S, Luecke DF, Datar A, Patel S, Rossi M, Stricker RB
Published Date May 2011 , Volume 2011:4 Pages 97 – 113 DOI 10.2147/IDR.S19201
Background: Lyme disease is a tick-borne illness caused by the spirochete Borrelia burgdorferi. Although antibiotic therapy is usually effective early in the disease, relapse may occur when administration of antibiotics is discontinued. Studies have suggested that resistance and recurrence of Lyme disease might be due to formation of different morphological forms of B. burgdorferi, namely round bodies (cysts) and biofilm-like colonies. Better understanding of the effect of antibiotics on all morphological forms of B. burgdorferi is therefore crucial to provide effective therapy for Lyme disease.
Methods: Three morphological forms of B. burgdorferi (spirochetes, round bodies, and biofilm-like colonies) were generated using novel culture methods. Minimum inhibitory concentration and minimum bactericidal concentration of five antimicrobial agents (doxycycline, amoxicillin, tigecycline, metronidazole, and tinidazole) against spirochetal forms of B. burgdorferi were evaluated using the standard published microdilution technique. The susceptibility of spirochetal and round body forms to the antibiotics was then tested using fluorescent microscopy (BacLight™ viability staining) and dark field microscopy (direct cell counting), and these results were compared with the microdilution technique. Qualitative and quantitative effects of the antibiotics against biofilm-like colonies were assessed using fluorescent microscopy and dark field microscopy, respectively.
Results: Doxycycline reduced spirochetal structures ~90% but increased the number of round body forms about twofold. Amoxicillin reduced spirochetal forms by ~85%–90% and round body forms by ~68%, while treatment with metronidazole led to reduction of spirochetal structures by ~90% and round body forms by ~80%. Tigecycline and tinidazole treatment reduced both spirochetal and round body forms by ~80%–90%. When quantitative effects on biofilm-like colonies were evaluated, the five antibiotics reduced formation of these colonies by only 30%–55%. In terms of qualitative effects, only tinidazole reduced viable organisms by ~90%. Following treatment with the other antibiotics, viable organisms were detected in 70%–85% of the biofilm-like colonies.
Conclusion: Antibiotics have varying effects on the different morphological forms of B. burgdorferi. Persistence of viable organisms in round body forms and biofilm-like colonies may explain treatment failure and persistent symptoms following antibiotic therapy of Lyme disease.
Full paper available at:
http://www.dovepress.com/evaluation-of-in-vitro-antibiotic-susceptibility-of-different-morpholo-peer-reviewed-article-IDR
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Project Number: 5R01AI026815-23
Contact Principal Investigator: BARTHOLD, STEPHEN WILLIAM
Title: MOUSE MODEL OF LYME BORRELIOSIS
http://projectreporter.nih.gov/project_info_description.cfm?aid=7999251&icde=0
DESCRIPTION (provided by applicant): The overall objective of this project is to understand the pathogenesis of Lyme borreliosis, using a mouse model. This project will focus on mechanisms of antibody-mediated disease remission and mechanisms by which spirochetes evade immune clearance. Immune serum from persistently infected mice contains three measurable functional effects: protective, disease-resolving, and spirochete-reducing effects. …The functional state of spirochetes during persistent infection will be explored in order to determine the specific antigen-antibody interactions involved in maintaining disease quiescence and sequestration of spirochetes in collagen, and to determine if the persistent state is either static or dynamic, using parabiotic mice infected with co-isogenic strains of spirochetes. These studies are highly relevant to understanding how B. burgdorferi persists in the immunologically responsive host, and how the host maintains the host-parasite equilibrium. Lyme borreliosis is the most common vector-borne disease in the U.S., with significant morbidity, and its prevalence and geographic distribution are rising. These studies are needed to develop better strategies for effective management of patients with persistent infections.
Relevance: Pathogen persistence and evasion of host immunity are highly relevant issues for all chronic infectious diseases, but Lyme borreliosis in particular. The proposed studies will incisively investigate the mechanisms of Borrelia burgdorferi persistence, which will help lead to more effective treatment.
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Time for Lyme Charity – Active projects 2011
True to our mission statement, Time for Lyme promotes promising, innovative, cutting-edge research for the eradication of tick-borne illnesses. We are proud to showcase current research projects that we are funding wholly or in part:
It Starts with Prevention
Time for Lyme awarded a grant to Dr. Robert E. Thach, Professor of Biology at Washington University in St. Louis for his work on vertebrate reservoirs for tick-borne diseases in the central United States. According to Dr. Thach, “Future development and implementation of strategies to control tick-borne diseases depend on understanding how these disease-producing organisms that ticks transmit are maintained in the environment. Through novel analysis of nymphal tick gut blood, sources of the tick’s previous blood meals can be identified. In so doing, primary and secondary reservoirs can be determined. Discovering the carriers of the infected ticks will eventually help design methods to reduce human exposure to them and consequently, tick- borne diseases.” Dr. Thach has focused his work on the tick-borne disease Ehrlichiosis, a growing problem in the Midwest.
Better Diagnostic Tests
The Lyme and Tick-Borne Research Center at Columbia University has been particularly interested in identifying better diagnostic tests and better treatments for people with chronic persistent symptoms. Dr. Brian Fallon, director of the Center and Associate Professor at Columbia University, cites one of the Center projects, which involved evaluating the sensitivity and specificity of 6 new assays for Lyme disease. This community screening study took place in the spring/summer of 2009 and included those with typical and atypical cases of Lyme disease. The results of this study may help to enhance the likelihood that those with Lyme disease are detected and treated more quickly. For more information about the Center, see www.columbia-lyme.org.
Better Treatments
Dr. Benjamin J. Luft, the Edmond Pellegrino Professor of Medicine at the State University of New York (SUNY), Stony Brook, is on a quest to find better antibiotic therapies for Lyme disease. We know that the Borrelia burgdorferi bacteria can remain viable in animals even after treatment with penicillin, tetracycline and macrolide antibiotics. Dr. Luft and his colleagues have discovered that the microbes possess something known as efflux pumps in their cell membranes, which help eliminate antibiotics and other toxins from inside the cell and thus help bacteria survive. Research is underway to determine the mechanisms of resistance and whether two already approved antibiotics could block these efflux pumps and allow antibiotics to build up inside the bacteria, thus insuring their demise.
Chronicling Chronic Lyme Disease
Dr. John Aucott, Principal Investigator for the Lyme Disease Research Foundation of Maryland, is conducting a longitudinal study in collaboration with scientists at the Johns Hopkins School of Medicine. The clinical research team will examine the course of infection by the Lyme organism and the resulting illness from the initial rash to the chronic persistent stage. His objectives are to measure risk factors, symptom pattern and severity, and immune system response over time in patients with chronic Lyme symptoms.
Treating Persistent Symptoms
Dr. Armin Alaedini, Assistant Professor of Neuroscience at the Weill Medical College of Cornell University, is conducting research to determine the relevance and role of the body’s immune system in chronic Lyme disease. To understand more fully how to help patients whose symptoms persist after antibiotic treatment, Dr. Alaedini is analyzing blood and spinal fluid for biomarkers that might correlate with various symptoms of the disease.
Diagnostic Biomarkers for Persisting Brain and Nervous System Symptoms in Lyme Disease
This study is led by Steven Schutzer, MD, a physician-scientist and Professor of Medicine at the University of Medicine and Dentistry-New Jersey Medical School. The study utilizes the most advanced mass spectrometry and protein separation techniques in the United States. Step 1 is to establish the comprehensive list of proteins in cerebrospinal fluid (CSF, the liquid window of the brain) of normal healthy people. Step 2 is to do the same in people with persisting brain and nervous system symptoms in Lyme disease. Step 1 has been completed. Step 2 (Lyme CSF proteome) will follow. Steps 1 and 2 are the Discovery Phase. We expect there will be a large number of potential biomarkers. This number can be narrowed down to the top ones in a Verification Phase using samples from separate individual patients. Once biomarkers are found, the same can be searched for in the blood, which would not be possible before CSF identification.
Understanding Chronic Lyme Disease Syndrome
Dr. Karen Newell, Associate Professor Department of Biology at the University of Colorado, Colorado Springs, Scientific Director of the CU Institute of Bioenergetics, and newly affiliated with Texas A & M University, believes that the genetic blueprint of an individual determines certain immune characteristics that can contribute to the elimination of disease, or its progression into chronic and persistent infection. In healthy individuals, self-peptides and/or their presenting cells are usually removed. Those with a blueprint that does not allow these self-peptides to be removed, tend to mount an auto-reactive or chronic inflammatory immune response. Her theory proposes a “targeted” peptide to replace/remove the self peptides and restore a healthy immune response. Her research thereby delves into the mechanism by which unchecked immunologic responses to infection result in chronic disease or inflammation. The results of Dr. Newell’s research may hold the key to unlocking the mystery behind chronic Lyme disease.
Model for Chronic Lyme Disease
Dr. Ying Zhang, professor of molecular microbiology and immunology at the Bloomberg School of Public Health at Johns Hopkins University, has reliably reproduced the culture of Borrelia burgdorferi in its L form. The L forms are morphologically, and perhaps chemically, different from the spirochetal form. L forms are known to be responsible for persistent infections among other bacteria. Now successful, the culture technique will allow antibiotic sensitivity testing in vitro, leading to more effective antibiotic therapies, and surface protein analysis, facilitating the development of vaccines against another form of Borrelia infection.
