Archive for the ‘research’ Category

Will Two Pills of Doxy Prevent Lyme?

Created by Lyme Action Network

Only one study in 2001 tested this hypothesis at one hospital in New York.

For the study, the bullseye rash was the diagnostic criteria to determine if doxy prevented LD. The study actually showed that people bitten by nymphs were more likely to develop a bullseye rash and therefore diagnosed with LD in comparison with those bitten by an adult tick. None of those bitten by adult ticks developed a bullseye rash.

The Bullseye is a poor indicator of LD.

Only 50% with LD got any kind of rash and only 9% developed a bullseye.

Two pills used at the time of tick bite by a nymph prevented people from getting the bullseye – so they were not diagnosed as having LD and were excluded from the study.

So, will 2 pills of doxy prevent Lyme?

No.

Category:

Lyme, research, Testing, Ticks, Treatment

Controversies in Chronic LD

http://www.nursingcenter.com/journalarticle?Article_ID=3874121&Journal_ID=237151&Issue_ID=3874037

Journal of Infusion Nursing Volume 39, Number 6, Nov/Dec 2016

Elizabeth L. Maloney, MD

ABSTRACT
The Centers for Disease Control and Prevention estimates that more than 300, 000 new cases of Lyme disease occur each year in the United States and that 10% to 20% of these patients will remain symptomatic despite receiving appropriate antibiotictherapy. Many elements of the disease are poorly understood and have generated considerable controversy. This paper discusses the medical controversies related to posttreatment manifestations and their potential impact on infusion nurses.

An executive summary of the article

In an article to infusion nurses, Dr. Maloney points out that less than 20% of all EM rashes have the “classic” bullseye pattern. Infection often involves several tissue types or systems and there is a wide variety of nonspecific disease manifestations. Dissemination can happen quickly but signs may not appear for weeks, months, or even years, and it is not unusual for patients to initially present with Late-stage disease.

In other words, it is quite illogical to think you can quickly pin this thing down & tie a pink ribbon on it.

The article goes on to delineate the existing controversies in Chronic Lyme Disease.

Controversy #1 – Lack of universally understood terminology

Maloney states that initially the word “Chronic” was neutrally used to simply mean that the disease could be long-standing, but that this term over time was denoted by the Infectious Diseases Society of America (IDSA) to a negative connotation when they dismissed the very idea of chronic infection with Lyme Disease and came up with the term Post-Lyme disease syndrome (PLDS), also endorsed by the CDC. Maloney states that their assumption of PLDS lacks proof as there are no tests of cure for Lyme or biomarkers that can identify PLDS.

Controversy #2 – Validity of persistent manifestations being attributable to LD

The bulk of evidence supports the idea that persistent symptoms are related to an active infection or Lyme-induced immune dysregulation, yet again the IDSA and CDC discount this. Maloney sites study after study, particularly recent evidence clearly showing distinct differences in cerebral spinal fluid proteins of patients with chronic LD and those with chronic fatigue, and a longitudinal study of positive EM patients which found that only 1% developed fibromyalgia, which is lower than the general population.

Controversy #3 Significance of LD Persistence

Maloney states the evidence is clear: the physical, social, and economic costs of chronic LD is substantial and is a burden for the whole country. LD patients in study after study had significant physical impairments that interfered with functioning including abnormal sensory ability and motor deficits with pain levels matching post surgical patients, fatigue similar to MS patients, and physical functioning similar to patients with congestive heart failure. In one study, 39% spent at least $5,000 out of pocket for treatment and had to stop working, while another 28% reduced their hours at work.

Controversy #4 Testing in Chronic Lyme

Evidence shows that there are no tests to determine if a patient has an ongoing infection, yet some doctors use serology to decide if a person has chronic Lyme. Current testing DOES NOT identify the bacterium, but rather looks for antibodies to the bacterium. Elevated levels indicate exposure; however, levels in the body change over time. Positive serology in treated patients doesn’t necessarily mean they have an active infection just as negative results are not indicative of cure.

Controversy #5 Uncertain causation of Chronic Lyme

Several causes for chronic Lyme have been suggested but supporting evidence is lacking and include:
1) Other infections
2) Post infectious state
3) Permanent or temporary tissue damage
4) Secondary conditions triggered by initial infection and persisting despite Bb eradication
5) Immune dysfunction either to autoantibodies or unregulated inflammation                       6) Persistent Bb infection

Many doctors acknowledge all of these potential causes except persistent infection despite much evidence to the contrary including an NIH sponsored study demonstrating documented uninfected ticks becoming infected after feeding on a chronically infected patient who had been treated for LD over a year earlier. Also, evidence for 1 cause of persistence does not rule out all others as well as it may be numerous mechanisms working together.

Controversy #6 Antibiotic Usage

The CDC and IDSA propagate the idea that antibiotic treatment is risky and doesn’t help patients, while others disagree. According to Maloney the evidence supports the selective use of antibiotics for chronic Lyme. She also states that the trials by Klempner et al should not be used to prove that antibiotics are not helpful as the study was biased and of poor design. She also points out that findings demonstrating effective retreatment that improved patient outcomes as well as complete recovery in some, has received little notice and that most doctors are not going to even know about them. She also wisely mentions that immune modulators may be useful but persistent infection needs to be ruled out because lowering the immune response risks triggering an active infection.

Maloney clearly admonishes infusion nurses that the science of chronic Lyme is constantly changing but that many doctors have wrongly entrenched themselves in a biased opinion despite the reasoned opinions of colleagues and that due to this they will probably find themselves in the thick of the argument. She says nurses can and should influence treatment decisions by advocating for the patient and by staying abreast of current science and giving accurate information that offers options to create a dialog between care giver and care receiver.

Author Affiliation: Partnership for Healing and Health, Wyoming, Minnesota.
Elizabeth L. Maloney, MD, is the president of Partnership for Health and Health, Ltd. She develops educational materials on tick borne illnesses, including accredited continuing medical education courses for physicians and nurses, and has published papers and letters on Lyme disease in peer-reviewed journals. The author has no conflicts of interest to disclose. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
Corresponding Author: Elizabeth L. Maloney, MD, President, Partnership for Health and Health Ltd, PO Box 84, Wyoming, MN 55092 ( md@phhmd.com ). Elizabeth L. Maloney , MD DOI: 10.1097/NAN.0000000000000195

Category:

research, Treatment

Spinal Fluid Cytokines

Cerebrospinal fluid cytokines in Lyme neuroborreliosis

Pietikäinen A, Maksimow M, Kauko T, Hurme S, Salmi M, Hytönen J.

Journal of Neuroinflammation, 2016 Oct 18;13(1):273.

http://doi.org/10.1186/s12974-016-0745-x

Abstract

Background
Lyme neuroborreliosis (LNB) is one of the manifestations of Lyme disease. Although it is known that immune reaction of LNB patients is dominated by Th1 and Th2 responses and patients have elevated numbers of B cells in their cerebrospinal fluid (CSF), not all the cells involved in inflammation and cytokine secretion have been characterized. The current diagnostics of LNB is based on intrathecal production of antibodies. In recent years, the measurement of chemokine CXCL13 concentration from the CSF has been introduced as a new promising diagnostic tool for LNB to complement the antibody-based diagnostic methods. A few other cytokines have also been analyzed as possible diagnostic markers. However, multiplex analyses simultaneously evaluating the concentrations of a large number of different cytokines in the CSF of LNB patients have been lacking thus far. Extensive cytokine profiling CSF samples of LNB patients would also help in understanding the complex immunopathogenesis of LNB.

Methods
CSF samples were analyzed from 43 LNB patients, 19 controls, 18 tick-borne encephalitis patients, and 31 multiple sclerosis patients. In addition, CSF samples from 23 LNB patients obtained after the antibiotic treatment were examined. Altogether, the concentrations of 49 different cytokines were determined from all of the samples. The concentrations of 48 different cytokines were analyzed by magnetic bead suspension array using the Bio-Plex Pro Human Cytokine 21- and 27-plex panels, and the concentration of CXCL13 was analyzed by an ELISA based method.

Results
Distinct cytokine profiles which were able to distinguish LNB patients from controls, tick-borne encephalitis patients, multiple sclerosis patients, and LNB patients treated with antibiotics were identified. LNB patients had elevated concentrations of all major T helper cell type cytokines (Th1, Th2, Th9, Th17, and Treg) in their CSF.

Conclusions
Despite the great differences in the CSF cytokine profiles of different patient groups, CXCL13 still remained as the best marker for LNB. However, IL-1ra might also be helpful as a marker for the antibiotic treatment response. Concerning the immunopathogenesis, this is the first report suggesting the involvement of Th9 cells in the immune response of LNB.

Free, full text (pdf file, 1.2 MB): https://jneuroinflammation.biomedcentral.com/track/pdf/10.1186/s12974-016-0745-x?site=jneuroinflammation.biomedcentral.com
or https://goo.gl/1wnP2D

Category:

Lyme, research

10 Million for Lyme Research

http://www.hopkinsmedicine.org/news/media/releases/johns_hopkins_awarded_10_million_cohen_foundation_grant_to_expand_current_lyme_disease_research_initiatives

Johns Hopkins University received a $10 million grant from the Steven and Alexandra Cohen Foundation to explore Lyme disease and develop potential new therapies to address the illness. Johns Hopkins is the only institution in the nation to receive multiple Lyme disease grants from the foundation.

The grant will be divided among three Johns Hopkins research teams led by John Aucott, M.D.; Ying Zhang, M.D., Ph.D.; and Brian Schwartz, M.D.

John Aucott, M.D.
John Aucott, M.D., assistant professor of medicine, and colleague Mark Soloski, Ph.D., professor of medicine, both of the Johns Hopkins University School of Medicine, received a five-year grant for $6 million to support the continuation of the Johns Hopkins Lyme Disease Research Center’s Study of Lyme Disease Immunology and Clinical Events, a longitudinal effort that identifies patients at the onset of Lyme disease, initiates standard treatment and follows them over a one-year period. The aim is to characterize those patients that develop post-treatment Lyme disease syndrome and analyze the immunological pathways triggered as the disease progresses in those patients.

“This grant allows us to expand our research and gain a better understanding of the disease,” Aucott says. “It also allows for greater diversity among participants so we can get more substantive information that can inform future developments in the field of Lyme research and discovery.”

Aucott and Soloski’s work will involve detailed clinical, immunological and molecular profiling, and will be done in collaboration with Joel Dudley, Ph.D., assistant professor of genetics and genomic sciences and director of biomedical informatics at the Icahn School of Medicine at Mount Sinai, in New York City. Dudley will support Aucott and Soloski by developing high-level computer modeling that will aid in the analysis of the large data sets.

With support from the grant, Aucott, director of the Johns Hopkins Lyme Disease Research Center, plans to open a new research site each year of the grant. For year one, he has already begun expanding the Green Spring Station clinical research site in Lutherville, Maryland, nearly doubling the number of exam rooms. Aucott also plans to build a Lyme research clinic at Johns Hopkins Bayview Medical Center. For the second year, he is looking to set up a site in Howard County, Maryland. For year three, he hopes to expand into Pennsylvania. His plans for years four and five will explore sites throughout the East Coast.

“As Lyme cases continue to increase in the U.S., there is an increasing need to understand the disease and its outcomes,” says Aucott. “We have no way of predicting who will recover and who won’t. This grant will allow us to explore why post-treatment Lyme disease syndrome exists, the mechanisms behind the disease and the pathways through which it causes symptoms so that one day, we can use that information to develop ways to prevent the disease or develop more effective drugs. Currently, we don’t have a full understanding of the disease or the most effective ways to treat those it impacts.”

Ying Zhang, M.D., Ph.D.
Ying Zhang, M.D., Ph.D., professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, received $2.5 million from the foundation for a five-year grant that will allow him and his team to test potential new ways to treat Lyme disease. The grant will support Zhang’s efforts to develop optimal drug combinations to more effectively combat post-treatment Lyme disease syndrome, focusing on developing effective oral drug combination regimens. First, Zhang and his team will develop an oral version of a triple-drug combination that currently is only available through IV. The oral drug combinations will then be tested in vitro (test tube) for effectiveness against Borrelia persisters using novel methodologies recently developed by his group. Next, the drug combinations will be tested in a mouse model of persistent Lyme disease to confirm efficacy, followed by validation in a monkey model, to be performed by his collaborator Monica Embers, Ph.D., from Tulane University.

“This grant is very important for us because it provides stability to the Lyme research program here at Johns Hopkins,” Zhang says. “It will allow us to advance potential new and more effective therapies for this complex and intriguing disease. There is currently no therapy available that effectively treats post-treatment Lyme disease syndrome. “We may be able to fast-track the development of new and better ways to treat the disease.”

Brian Schwartz, M.D.
Brian Schwartz, M.D., professor in the Department of Environmental Health and Engineering at the Johns Hopkins Bloomberg School of Public Health, received more than $1 million from the foundation to conduct a three-year, two-phase investigation of Lyme disease in Pennsylvania, one of the hardest-hit regions for the disease.

In phase I, Schwartz and colleagues will conduct a large-scale, population-based study of the epidemiology of Lyme disease using data from electronic health records from the Geisinger Clinic. These data are available for over 500,000 patients from 2001 to present. Schwartz and colleagues will link that information to community data on land use and land cover — for example, agricultural land, forested land and low-density suburban development. In addition, Schwartz will evaluate populations vulnerable to Lyme disease, delayed diagnosis and treatment by looking at these features by age, sex, race/ethnicity, family socioeconomic status, community socioeconomic status, and a variety of other community and environmental variables.

For phase II, a questionnaire-based study will be performed to assess vulnerabilities within the population. This will include aspects of individual, occupational and community risks, as well as an assessment of people’s knowledge, attitudes and practices regarding Lyme disease diagnosis, treatment and long-term prognosis. Investigators will also analyze who is getting Lyme disease and why, how long it takes until diagnosis, and appropriate treatment. This research will allow for the evaluation of Lyme disease risk, and assess diagnosis and treatment patterns, with a goal of identifying new management strategies to address Lyme disease.

Discovered more than four decades ago, Lyme disease has now spread rapidly throughout the East Coast and Midwest. It is estimated to afflict more than 300,000 people per year, becoming the sixth most common reportable infectious disease in the U.S. However, little is understood about the complex pathogenesis of the disease, which costs the U.S. economy up to $1.3 billion per year in treatment costs alone.

Related Stories:

First U.S. Center to Study Lyme Disease Launched at Johns Hopkins Medicine
On the Web:

Steven & Alexandra Cohen Foundation
Lyme Disease Research Center
FOR THE MEDIA

Contacts:

Helen Jones
410-502-9422
hjones49@jhmi.edu

Lauren Nelson
410-955-8725
laurennelson@jhmi.edu
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Category:

Lyme, research

Probable Transfusion-Transmission of Babesiosis

The Brief case: Probable transfusion-transmitted babesiosis in a transplant recipient

Kitt E, Keaton AA, Graf EH.
Journal of Clinical Microbiology 54:2632–2634.

http://dx.doi.org/10.1128/JCM.00981-16

Case

A 3-year-old immunocompromised male who had been hospitalized for 7 months in the cardiac intensive care unit developed fever and tachycardia in December. He was prenatally diagnosed with hypoplastic left heart syndrome and received right ventricle to pulmonary artery conduit surgery days after delivery. Due to worsening right ventricular function, after a hemi-Fontan procedure, he received an orthotopic heart transplant at the beginning of his 3rd year of life.

His posttransplant course was complicated by multiple episodes of rejection, cytomegalovirus (CMV) pneumonitis, and several central-line-associated bloodstream infections. As a result of the rejection, necessitating plasmapheresis as well as frequent blood draws for management, which led to anemia, he received 36 packed red blood cell transfusions over the course of 7 months posttransplantation. These transfusions were evenly spaced, and he remained hospitalized during the 7 months.

At the time of the febrile episode, he was on caspofungin, trimethoprim-sulfamethoxazole, and ganciclovir. The subsequent diagnostic workup included multiple sets of blood cultures, a urine culture, and a CMV viral load analysis. He was started on vancomycin and cefepime while awaiting microbiologic results. Other pertinent test results included a complete blood count (CBC) with differential showing pancytopenia and an aspartate transaminase (AST) level of 200 U/liter (reference range, 20 to 60 U/liter), an alanine aminotransferase (ALT) level of 84 U/liter (reference range, 5 to 45 U/liter), and a C-reactive protein level of 3.1 mg/dl (reference range, 0 to 0.9 mg/dl), which increased to 7.1 mg/dl over 4 days.

On the 5th day of fever, another CBC with differential was ordered and was noted by the hematopathologist to contain intraerythrocytic parasites. Immediately, a blood smear with Giemsa stain (Harleco Giemsa stain; EMD Millipore, Billerica, MA, USA) was performed by the microbiology laboratory, yielding the definitive diagnosis. Babesia species with a parasitemia level of 18% was reported to the clinical team. Real-time PCR testing, performed by a reference laboratory, provided the species-level identity of Babesia microti. All other infectious workups were negative. The patient was started on azithromycin plus atovaquone due to the contraindications against treatment with quinidine (QT interval prolongation in a heart transplant recipient with declining heart function).

Three days later, clindamycin was added when his parasitemia level did not decline. He was also given an exchange transfusion on day 4 after diagnosis in an attempt to reduce his parasitemia. After 14 days of therapy, his parasitemia became undetectable and he completed 6 full weeks of therapy, at which time he remained aparasitemic. Since transfusion was the child’s only known risk factor for Babesia infection, a complete investigation into the blood products used was conducted, but the infectious unit/donor could not be definitively identified. Banked products from the organ donor were also tested, and it was determined that the heart transplant was not the source of the Babesia infection.

Category:

Babesia, research, Treatment