GENERAL TICK-BORNE ILLNESS RESEARCH ISSUES

Priorities for Lyme Disease Research
Written by Sherrill Franklin, Focus – Opinions and Features item from LymeDisease.org, Chico, California
www.lymedisease.org/sherrill-franklin/
Almost 40 years have passed since the Lyme disease bacterium was identified, yet there are still no reliable diagnostics and no definitive treatments, especially for those with persistent symptoms. While Lyme disease research funding has always languished somewhere between hay fever and headaches, CDC/NIH grant money did add up to over $450 million between 1998 and 2016. Over 18 years, that’s about $25 million annually.

Lyme Disease: A Bioethical Morass
Neha Jariwala, Erum Ilyas and Herbert B Allen
Journal of Clinical Research & Bioethics, online first October 24, 2016.
http://www.omicsonline.org/clinical-research-bioethics-abstract.php?abstract_id=81033
“Primum non nocere”, “first do no harm” is a medical dictum based in antiquity. Yet, in nearly everything related to Lyme disease, it seems almost entirely disregarded. How ethical is it that we follow the guidelines of the CDC regarding diagnosis when those guidelines require erythema migrans that is clearly recognizable only in one (“bullseye rash”) of its multiple presentations? Further, how ethical is it that we are held to guidelines regarding a positive serology that is positive (at best) only 40% of the time? Another questionable ethical situation is the use of a bacteriostatic antibiotic that barely meets the MIC for Borrelia burgdorferi in its ordinarily prescribed regimen. It is also dependent on compliance which is a huge issue because of the gastrointestinal side effects. This antibiotic may clear the rash, but seemingly does little to prevent late findings of the disease. The sub lethal antibiotic dose can be important in the subsequent development of biofilms that lead to a chronic disease state. Lastly, how ethical is it that we have nearly abandoned our patient advocacy and permitted the insurance companies to dictate allowable treatment? And, in as much as Borrelia organisms were found in the brains of Alzheimer’s disease patients over 25 yrs ago and those spirochetes have recently been shown to produce biofilms, how ethical is it that we ignore research underpinning the pathogenesis of this disease?

The fight against Lyme disease
James G. Logan
NATURE, VOL 552, 14 DECEMBER 2017
It occurs in more than 80 countries and is the most commonly reported vectorborne disease in the Northern Hemisphere. In the United States alone, it spawns 300,000 new cases each year. Yet Lyme disease—caused by species of Borrelia bacteria carried by ticks of the Ixodes genus — remains one of the most poorly understood infections. It has divided researchers, clinicians and patients, and triggered intense public suspicion and confusion.

Lyme and associated tick-borne diseases: global challenges in the context of a public health threat.
Running title: Global challenges of Lyme disease
Christian Perronne
Frontiers in Cellular and Infection Microbiology, 4:74.
http://doi.org/10.3389/fcimb.2014.00074
The lack of a gold standard for diagnosis makes producing accurate statistics difficult. Some pathogenic strains belonging to the B. burgdorferi sensu lato complex have a worldwide distribution, yet they are rarely considered or tested for. Borrelia miyamotoi, for instance, phylogenetically close to relapsing fever borreliae, is now recognized as a cause of Lyme-like disease and relapsing fever in Asia, Europe and North America. It usually does not cross react with B. burgdorferi tests. A novel isolate of Borrelia has been isolated by PCR in a post-treatment serum from a patient with neurologic Lyme disease. These recent historical, geographical and microbial data should prompt the medical community to realize that cases of persisting post tick-bite syndromes are probably due to multiple pathogens and that these occult infections will require a new approach if not an actual paradigm shift.

Large-scale health disparities associated with Lyme disease and human monocytic ehrlichiosis in the United States, 2007-2013
Springer YP, Johnson PTJ.
PLoS One. 2018 Sep 27;13(9):e0204609. eCollection 2018.
https://doi.org/10.1371/journal.pone.0204609
Results suggested that the incidence of Lyme disease was highest in counties with relatively higher proportions of white and more educated persons and lower poverty and crime rates; the incidence of human monocytic ehrlichiosis was highest in counties with relatively higher proportions of white and less educated persons, higher unemployment rates and lower crime rates. The percentage of housing units vacant was a strong positive predictor for both diseases with a magnitude of association comparable to those between incidence and the ecological variables.
Our findings indicate that racial/ethnic and socioeconomic disparities in disease incidence appear to be epidemiologically important features of Lyme disease and human monocytic ehrlichiosis in the United States. Steps to mitigate encroachment of wild flora and fauna into areas with vacant housing might be warranted to reduce disease risk.

Removing the Mask of Average Treatment Effects in Chronic Lyme Disease Research Using Big Data and Subgroup Analysis
Johnson L, Shapiro M, Mankoff J.
Healthcare. 2018 Oct 12;6(4). pii: E124.
https://doi.org/10.3390/healthcare6040124
Using patient-reported outcome data from the MyLymeData online patient registry, we show that sub-group analysis techniques can unmask valuable information that is hidden if averages alone are used. In our analysis, this approach revealed treatment effectiveness for up to a third of patients with Lyme disease. This study is important because it can help open the door to more individualized patient care using patient-centered outcomes and real-world evidence.

Genomic insights into the ancient spread of Lyme disease across North America
Katharine S. Walter, Giovanna Carpi, Adalgisa Caccone & Maria A. Diuk-Wasser
Nature Ecology & Evolution, 1569–1576 (2017) doi:10.1038/s41559-017-0282-8 Published online:28 August 2017
https://www.nature.com/articles/s41559-017-0282-8
Here, we show that B. burgdorferi s.s. has a complex evolutionary history with previously undocumented levels of migration. Diversity is ancient and geographically widespread, well pre-dating the Lyme disease epidemic of the past ~40 years, as well as the Last Glacial Maximum ~20,000 years ago. This means the recent emergence of human Lyme disease probably reflects ecological change—climate change and land use changes over the past century—rather than evolutionary change of the bacterium.

Lyme disease: the next decade.
Stricker RB, Johnson L.
Infection and Drug Resistance, 2011; 4:1-9. Online before print, January 7, 2011.
http://dx.doi.org/10.2147/IDR.S15653
Recognition of the importance of CWD forms and biofilms in persistent B. burgdorferi infection should stimulate pharmaceutical research into new antimicrobial agents that target these mechanisms of chronic infection with the Lyme spirochete. Concurrent clinical implementation of proteomic screening offers a chance to correct significant deficiencies in Lyme testing. Advances in these areas have the potential to revolutionize the diagnosis and treatment of Lyme disease in the coming decade.

Seven provocative findings on Lyme disease, brains and placentas …and what they mean to Medicine and Patients
Dr. Paul Duray Research Fellowship Endowment Inc, Naples, Florida
By Thomas Grier, Microbiologist
July 27, 2016
The Seven Provocative Findings of the Dr. Paul Duray Research Fellowship Foundation
1. Mother-to-child transmission of Borrelia across the womb
2. Finding Borrelia burgdorferi and miyamotoi associated with Amyloid Plaques in Alzheimer’s disease brains
3. Finding Borrelia in Lewy Body Dementia
4. Nematode worms found in the CSF (spinal fluid) of Multiple Sclerosis patients
5. Nematode worms found in Alzheimer’s brains
6. Borrelia found in five deadly brain tumors (Glioblastoma multiforme)
7. Borrelia Mayonii and Borrelia burgdorferi found in human testicle
Since 1975 when Lyme disease was first introduced to the medical literature, it has been surrounded by controversy and misunderstandings. Much of the problem stemmed from trying to understand this disease entirely through antibody tests (serology) based entirely on just one species – Borrelia burgdorferi.

Lyme Bacteria Hides Inside Parasitic Worms, Causing Chronic Brain Diseases
Patient Centered Care Advocacy Group
May 19, 2016, 07:00 ET
https://www.prnewswire.com/news-releases/lyme-bacteria-hides-inside-parasitic-worms-causing-chronic-brain-diseases-300270742.html
The examination of autopsied brain tissues from patients who died of serious neurological conditions has revealed that many tick-borne infections, such as Lyme disease, go undiagnosed and untreated. Board-certified pathologist, Alan B. MacDonald, MD, says his research shows “tick infections are not easily detected with routine tests, nor are they easily cured with short courses of antibiotics.” MacDonald found two Borrelia pathogens, including B. burgdorferi the causative agent of Lyme disease, thriving inside parasitic nematode worms, worm eggs or larvae in the brain tissue of nineteen deceased patients. These microscopic worms are endosymbionts, meaning the Borrelia bacteria dwell inside the worms. A tick bite delivers the nematode into the human body.

Gut dysbiosis, leaky gut, and intestinal epithelial proliferation in neurological disorders: towards the development of a new therapeutic using amino acids, prebiotics, probiotics, and postbiotics. Reviews in the neurosciences.
Reviews in the neurosciences · September 2018
Maguire, Mia & Maguire, Greg. (2018).
DOI: 10.1515/revneuro-2018-0024.
Here we offer a review of the evidence for a hypothesis that a combination of ingestible probiotics, prebiotics, postbiotics, and amino acids will help amelio-rate dysbiosis and degeneration of the gut, and therefore promote restoration of nervous system function in a number of neurological indications

Non-viable Borrelia burgdorferi induce inflammatory mediators and apoptosis in human oligodendrocytes.
Parthasarathy G, Fevrier HB, Philipp MT.
Neuroscience Letters, online before print 2013 Oct 21. pii: S0304-3940(13)00936-1.
http://dx.doi.org/10.1016/j.neulet.2013.10.032
In previous studies, exposure to live Borrelia burgdorferi was shown to induce inflammation and apoptosis of human oligodendrocytes. In this study we assessed the ability of non-viable bacteria (heat killed or sonicated) to induce inflammatory mediators and cell death. Both heat-killed and sonicated bacteria induced release of CCL2, IL-6, and CXCL8 from oligodendrocytes in a dose dependent manner. In addition, non-viable B. burgdorferi also induced cell death as evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and another cell viability assay. These results suggest that spirochetal residues left after bacterial demise, due to treatment or otherwise, may continue to be pathogenic to the central nervous system.

Health Care Costs, Utilization and Patterns of Care following Lyme Disease
Adrion ER, Aucott J, Lemke KW, Weiner JP.
PLoS One. 2015 Feb 4;10(2):e0116767. eCollection 2015.
http://doi.org/10.1371/journal.pone.0116767
Lyme disease is the most frequently reported vector borne infection in the United States. The Centers for Disease Control have estimated that approximately 10% to 20% of individuals may experience Post-Treatment Lyme Disease Syndrome – a set of symptoms including fatigue, musculoskeletal pain, and neurocognitive complaints that persist after initial antibiotic treatment of Lyme disease. Lyme disease is associated with $2,968 higher total health care costs (95% CI: 2,807-3,128, p<.001) and 87% more outpatient visits (95% CI: 86%-89%, p<.001) over a 12-month period, and is associated with 4.77 times greater odds of having any PTLDS-related diagnosis, as compared to controls (95% CI: 4.67-4.87, p<.001). Among those with Lyme disease, having one or more PTLDS-related diagnosis is associated with $3,798 higher total health care costs (95% CI: 3,542-4,055, p<.001) and 66% more outpatient visits (95% CI: 64%-69%, p<.001) over a 12-month period, relative to those with no PTLDS-related diagnoses.

Healthcare access and burden of care for patients with Lyme disease: A large United States survey.
Johnson L, Aylward A, Stricker RB.
Health Policy. published online before print, 2011 Jun 13.
http://www.ncbi.nlm.nih.gov/pubmed/21676482
Responses from 2424 patients were included in the study. Half of the respondents reported seeing at least seven physicians before the diagnosis of Lyme disease was made. Nearly half had Lyme disease for more than 10 years and traveled over 50 miles to obtain treatment. Most respondents experienced symptoms lasting six months or more despite receiving at least 21 days of antibiotic treatment. A quarter of respondents had been on public support or received disability benefits due to Lyme disease symptoms, and over half had visited an emergency room at least once as a result of these symptoms.

Relevance of Chronic Lyme Disease to Family Medicine as a Complex Multidimensional Chronic Disease Construct: A Systematic Review
Liesbeth Borgermans, Geert Goderis, Jan Vandevoorde, and Dirk Devroey
International Journal of Family Medicine, Volume 2014 (2014), Article ID 138016.
http://dx.doi.org/10.1155/2014/138016
Because of the absence of solid evidence on prevalence, causes, diagnostic criteria, tools and treatment options, the role of autoimmunity to residual or persisting antigens, and the role of a toxin or other bacterial-associated products that are responsible for the symptoms and signs, chronic Lyme disease (CLD) remains a relatively poorly understood chronic disease construct. The role and performance of family medicine in the detection, integrative treatment, and follow-up of CLD are not well studied either. The purpose of this paper is to describe insights into the complexity of CLD as a multidimensional chronic disease construct and its relevance to family medicine by means of a systematic literature review.

Tick-borne pathogen – reversed and conventional discovery of disease
Tijsse-Klasen E, Koopmans MP, Sprong H.
Frontiers in Public Health. 2014 Jul 7;2:73. eCollection 2014.
http://doi.org/10.3389/fpubh.2014.00073
Molecular methods have increased the number of known microorganisms associated with ticks significantly. Some of these newly identified microorganisms are readily linked to human disease while others are yet unknown to cause human disease. The face of tick-borne disease discovery has changed with more diseases now being discovered in a “reversed way,” detecting disease cases only years after the tick-borne microorganism was first discovered. Compared to the conventional discovery of infectious diseases, reverse order discovery presents researchers with new challenges. Estimating public health risks of such agents is especially challenging, as case definitions and diagnostic procedures may initially be missing.

There Is a Method to the Madness: Strategies to Study Host Complement Evasion by Lyme Disease and Relapsing Fever Spirochetes
Marcinkiewicz AL, Kraiczy P, Lin YP.
Frontiers in Microbiology. 2017 Mar 2;8:328. eCollection 2017.
https://doi.org/10.3389/fmicb.2017.00328
Following transmission, spirochetes survive in the blood to induce bacteremia at the early stages of infection, which is thought to promote evasion of the host complement system. The complement system acts as an important innate immune defense mechanism in humans and vertebrates. Upon activation, the cleaved complement components form complexes on the pathogen surface to eventually promote bacteriolysis.

A Novel Multivalent OspA Vaccine against Lyme Borreliosis is Safe and Immunogenic in an Adult Population Previously Infected with Borrelia burgdorferi sensu lato.
Wressnigg N, Barrett PN, Pöllabauer EM, O’Rourke M, Portsmouth D, Schwendinger MG, Crowe BA, Livey I, Dvorak T, Schmitt B, Zeitlinger M, Kollaritsch H, Esen M, Kremsner PG, Jelinek T, Aschoff R, Weisser R, Naudts IF, Aichinger G.
Clinical and Vaccine Immunology, online before print 2014 Sep 3. pii: CVI.00406-14.
http://doi.org/10.1128/CVI.00406-14
Lyme borreliosis (LB) patients who recover, as well as previously infected asymptomatic individuals, remain vulnerable to re-infection with Borrelia burgdorferi sensu lato (s.l.). There is limited information available about OspA vaccines in this population. Participants received three, monthly, priming immunizations, with either 30µg or 60µg alum-adjuvanted OspA antigen, and a booster vaccination either 6 months or 9-12 months after the first immunization. Antibody responses to the six OspA serotypes included in the vaccine were evaluated. Adverse events were predominantly mild and transient, and were similar in the seronegative and seropositive populations.

Lyme bacteria settled in North America far earlier than we thought
Insight into the disease’s ancient origins points toward the causes of the current epidemic
By Jen Monnier, Science Line, New York University, New York City, New York
November 29, 2017
www.scienceline.org/2017/11/lyme-bacteria-settled-north-america-far-earlier-thought/
While the Lyme disease outbreak in people dates back only about 40 years, the bacterium that causes this disease has called North America home for more than 20,000 years, according to a study published in August in the journal Nature Ecology and Evolution.

Nature vs. Nurture: Navigating Neuroepigenetics
A4M Blog
posted in Discoveries on November 9, 2018 by Nathalie Gedeon.

Nature vs. Nurture: Navigating Neuroepigenetics


The debate regarding the origins of human behavior, and the conflict between nature versus nurture, has been philosophized, researched, and argued for over a millennium. In the last 30 years, however, a field of genetic-biology has positioned itself to wholly restructure the fundamental basis for the debate: neuroepigenetics. Neuroepigenetics is the study of how dynamic epigenetic changes affect the nervous system, and concurrently, neurological behaviors. Within this emerging field, scientists have increasingly found that the dichotomy between nurture and nature has been widely misunderstood. Rather, as pharmacology professor and neurobiology expert J. David Sweatt explains, “It is now clear that there is a dynamic interplay between genes and experience, a clearly delineated and biochemically driven mechanistic interface between nature and nurture.”

Future Microbiology
May 2009, Vol. 4, No. 4, Pages 457-469.
Dean T Nardelli?, Erik L Munson?, Steven M Callister? & Ronald F Schell
http://dx.doi.org/10.2217/fmb.09.17
The development of a vaccine for Lyme disease was intensely pursued in the 1990s. However, citing a lack of demand, the first human Lyme disease vaccine was withdrawn from the market less than 5 years after its approval. The public’s concerns about the vaccine’s safety also likely contributed to the withdrawal of the vaccine. Nearly a decade later, no vaccine for human Lyme disease exists. The expansion of Lyme disease’s endemic range, as well as the difficulty of diagnosing infection and the disease’s steady increase in incidence in the face of proven preventative measures, make the pursuit of a Lyme disease vaccine a worthwhile endeavor. Many believe that the negative public perception of the Lyme disease vaccine will have tarnished any future endeavors towards its development. Importantly, many of the drawbacks of the Lyme disease vaccine were apparent or foreseeable prior to its approval. These pitfalls must be confronted before the construction of a new, effective and safe human Lyme disease vaccine.

Borrelia burgdorferi: Cell Biology and Clinical Manifestations in Latent Chronic Lyme.
Smith, A. , Oertle, J. and Prato, D.
Open Journal of Medical Microbiology, 4, 210-223,(2014).
http://www.scirp.org/journal/PaperInformation.aspx?PaperID=51411
Chronic Lyme disease is predicated by an infection with Borrelia burgdorferi via tick vector. B. burgdorferi has been extensively researched with regard to its genome and cell biology. There are many unique characteristics to the bacteria itself; however, serological diagnostics and diagnosis based on symptoms can be complicated and potentially misleading. Other promising diagnostics were also evaluated in this review. Treatment of the chronic Lyme disease can be complicated and at times ineffective.

Whole-Genome Sequences of Borrelia bissettii, Borrelia valaisiana, and Borrelia spielmanii.
Schutzer SE, Fraser-Liggett CM, Qiu WG, Kraiczy P, Mongodin EF, Dunn JJ, Luft BJ, Casjens SR.
Journal of Bacteriology, January 2012, vol. 194, no. 2, 545-54.
http://jb.asm.org/content/194/2/545.full
It has been known for decades that human Lyme disease is caused by the three spirochete species Borrelia burgdorferi, Borrelia afzelii, and Borrelia garinii. Recently, Borrelia valaisiana, Borrelia spielmanii, and Borrelia bissettii have been associated with Lyme disease. We report the complete genome sequences of B. valaisiana VS116, B. spielmanii A14S, and B. bissettii DN127.

Gifted Students and Lyme Disease What Educators, Counselors, and Parents Need to Know
Patricia A. Schuler, PhD
Gifted Child Today, January 2013, vol. 36, no. 1, 35-46.
http://dx.doi.org/10.1177/1076217512465288
Gifted and talented students, like all students, are susceptible to the effects of Lyme disease. However, their experiences may be more intense and life altering, depending on the severity of the Lyme disease. In this article, the phenomenological experience of two gifted boys with Lyme disease gives educators, counselors, and parents insight into how this disease impacts the intellectual functioning, social status, and identity of gifted children with this bacterial illness.

“Antibiotics give rise to new communities of harmful bacteria.” 
ScienceDaily. ScienceDaily, 23 February 2015.
University of North Carolina at Chapel Hill.
www.sciencedaily.com/releases/2015/02/150223164533.htm
“For a long time we’ve thought that bacteria make antibiotics for the same reasons that we love them — because they kill other bacteria,” said Shank, whose work appears in the February 23 Early Edition of the Proceedings of the National Academy of Sciences. “However, we’ve also known that antibiotics can sometimes have pesky side-effects, like stimulating biofilm formation.” Shank and her team now show that this side-effect — the production of biofilms — is not a side-effect after all, suggesting that bacteria may have evolved to produce antibiotics in order to produce biofilms and not only for their killing abilities.

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
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.

Severe life-threatening Ehrlichia chaffeensis infections transmitted through solid organ transplantation.
Sachdev SH, Joshi V, Cox ER, Amoroso A, Palekar S.
Transplant Infectious Disease, online before print, 2013 Dec 16.
http://doi.org/10.1111/tid.12172
Donor-derived infections from organ transplantation are rare occurrences with preoperative screening practices. Ehrlichia chaffeensis, a tick-borne illness, transmitted through solid organ transplantation has not been reported previously to our knowledge. We present cases of 2 renal allograft recipients who developed severe E.chaffeensis infection after receipt of organs from a common deceased donor. These cases demonstrate that tick-borne pathogens, such as E.chaffeensis, can be transmitted through renal transplantation. E. chaffeensis can be associated with excessive morbidity and mortality, commonly owing to delay in diagnosis and poor response to non-tetracycline antibiotics. In populations with endemic tick-borne illness, donors should be questioned about tick exposure, and appropriate antibiotics can be administered if indicated.

Screening for Babesia microti in the U.S. Blood Supply
Erin D. Moritz, Ph.D., Colleen S. Winton, S.B.B. (A.S.C.P.), Laura Tonnetti, Ph.D., Rebecca L. Townsend, B.A., Victor P. Berardi, Mary-Ellen Hewins, B.S., Karen E. Weeks, B.S., Roger Y. Dodd, Ph.D., and Susan L. Stramer, Ph.D.
New England Journal of Medicine 2016; 375:2236-2245. Online first, December 8, 2016.
http://doi.org/10.1056/NEJMoa1600897
Babesia microti, a tickborne intraerythrocytic parasite that can be transmitted by means of blood transfusion, is responsible for the majority of cases of transfusion-transmitted babesiosis in the United States. However, no licensed test exists for screening for B. microti in donated blood. Of 89,153 blood-donation samples tested, 335 (0.38%) were confirmed to be positive.

Bartonella henselae transmission by blood transfusion in mice
da Silva MN, Vieira-Damiani G, Ericson ME, Gupta K, Gilioli R, de Almeida AR, Drummond MR, Lania BG, de Almeida Lins K, Soares TC, Velho PE
Transfusion, online first, 2016 Mar 10.
http://doi.org/10.1111/trf.13545
Bartonella spp. are neglected fastidious Gram-negative bacilli. We isolated Bartonella henselae from 1.2% of 500 studied blood donors and demonstrated that the bacteria remain viable in red blood cell units after 35 days of experimental infection.

Transfusion-associated Anaplasma phagocytophilum infection in a pregnant patient with thalassemia trait: a case report.
Shields K, Cumming M, Rios J, Wong MT, Zwicker JI, Stramer SL, Alonso CD.
Transfusion, online before print, 2014 Nov 11.
http://doi.org/10.1111/trf.12908
Human granulocytic anaplasmosis (HGA) is an acute nonspecific febrile illness caused by the bacterium Anaplasma phagocytophilum. Although usually transmitted via tick bite, HGA may rarely also be acquired through transfusion.

Two Cases of Transfusion-Transmitted Anaplasma phagocytophilum.
American Journal of Clinical Pathology. 2012 Apr;137(4):562-5.
Annen K, Friedman K, Eshoa C, Horowitz M, Gottschall J, Straus T.
http://dx.doi.org/10.1309/AJCP4E4VQQQOZIAQ
We report 2 additional cases of transfusion-transmitted A phagocytophilum in which leukocyte reduction of all transfused units failed to prevent microbial transmission.

A confirmed Ehrlichia ewingii infection likely acquired through platelet transfusion.
Regan J, Matthias J, Green-Murphy A, Stanek D, Bertholf M, Pritt B, Sloan L, Kelly A, Singleton J, McQuiston J, Hocevar SN, Whittle J.
Clinical Infectious Diseases, online before print, 2013 Mar 19.
http://dx.doi.org/10.1093/cid/cit177
Ehrlichiosis is a tick-borne disease that ranges in severity from asymptomatic infection to fatal sepsis. Ehrlichiosis acquired from transfusion of blood products has not been documented in the literature to date. A case of Ehrlichia ewingii infection likely transmitted by transfusion of leukoreduced platelets is described and public health implications discussed.

Is there a place for xenodiagnosis in the clinic?
Telford SR 3rd, Hu LT, Marques A.
Expert Review of Anti-infective Therapy. 2014 Nov;12(11):1307-10.
http://doi.org/10.1586/14787210.2014.966084
Whether Borrelia burgdorferi, the causative agent of Lyme disease, can persist after antibiotic therapy is an area of ongoing controversy. Our recent safety trial of xenodiagnosis demonstrates that ticks may be successfully fed on patients and may help determine the biological basis for post-treatment Lyme disease syndrome.

Protesting CDC’s biased reporting in PubMed Commons
LymeDisease.org, Chico, California
June 18, 2017
www.lymedisease.org/cdc-biased-report/
The CDC’s June 15 article in MMWR, which slams “chronic Lyme” treatments—and by extension, Lyme patients and the doctors who treat them—continues to draw sharp responses from the Lyme disease community. ILADS physician Raphael Stricker, MD, and his frequent co-author, LymeDisease.org CEO Lorraine Johnson, posted their rebuttal on PubMed Commons on June 17. Now, when anyone accesses the original article on PubMed, Stricker and Johnson’s reply will be shown right along with it.

Tick-borne infections–a growing public health threat to school-age children. Prevention steps that school personnel can take.
Hamlen R.
National Association of School Nurses: School Nurse. 2012 Mar; 27(2): 94-100.
http://dx.doi.org/10.1177/1942602X11427928
School nurses are experts in school health services and frequently front-line providers of care for school-age children presenting with symptoms of physical illness or behavioral, cognitive, learning, and/or psychological problems possibly due to tick-borne infections. School nurses need to know how to protect children on school property and during school sponsored outdoor activities from being bitten by ticks that can transmit diseases.

Medial prefrontal cortex stimulation accelerates therapy response of exposure therapy in acrophobia
Martin J. Herrmann’Correspondence information about the author Martin J. HerrmannEmail the author Martin J. Herrmann, Andrea Katzorke, Yasmin Busch, Daniel Gromer, Thomas Polak, Paul Pauli, Jürgen Deckert
PlumX Metrics
http://dx.doi.org/10.1016/j.brs.2016.11.007
This study provides first clinical evidence that high-frequency rTMS over the vmPFC improves exposure therapy response of acrophobia symptoms.

Neutrophils Are Critical for Myelin Removal in a Peripheral Nerve Injury Model of Wallerian Degeneration
Jane A. Lindborg, Matthias Mack and Richard E. Zigmond
Journal of Neuroscience 25 October 2017, 37 (43) 10258-10277;
https://doi.org/10.1523/JNEUROSCI.2085-17.2017
The accepted view in the basic and clinical neurosciences is that the clearance of axonal and myelin debris after a nerve injury is directed primarily by inflammatory CCR2+ macrophages. However, we demonstrate that this clearance is nearly identical in WT and Ccr2−/− mice, and that neutrophils replace CCR2+ macrophages as the primary phagocytic cell. We find that neutrophils play a major role in myelin clearance not only in Ccr2−/− mice but also in WT mice, highlighting their necessity during nerve degeneration in the peripheral nervous system. These degeneration studies may propel improvements in nerve regeneration and draw critical parallels to mechanisms of nerve degeneration and regeneration in the CNS and in the context of peripheral neuropathies.

Persistence of neurological damage induced by dietary vitamin B-12 deficiency in infancy.
von Schenck, Bender-Götze C, Koletzko B.
Arch Dis Child. 1997 Aug;77(2):137-9.
https://www.ncbi.nlm.nih.gov/pubmed/9301352
A case is reported of a 14 month old boy with severe dietary vitamin B-12 deficiency caused by his mother’s vegan diet. Clinical, electroencephalography (EEG), and haematological findings are described. Cranial magnetic resonance imaging (MRI) showed severe frontal and frontoparietal cranial atrophy. Vitamin B-12 supplements led to a rapid improvement of haematological and neurological symptoms.

A natural Anopheles-associated Penicillium chrysogenum enhances mosquito susceptibility to Plasmodium infection
Yesseinia I. Angleró-Rodríguez, Benjamin J. Blumberg, Yuemei Dong, Simone L. Sandiford, Andrew Pike, April M. Clayton & George Dimopoulos
Scientific Reports 6, Article number: 34084 (2016)10.1038/srep34084
12 June 2016
https://www.nature.com/articles/srep34084
Whereas studies have extensively examined the ability of bacteria to influence Plasmodium infection in the mosquito, the tripartite interactions between non-entomopathogenic fungi, mosquitoes, and Plasmodium parasites remain largely uncharacterized. Here we report the isolation of a common mosquito-associated ascomycete fungus, Penicillium chrysogenum, from the midgut of field-caught Anopheles mosquitoes. Although the presence of Pe. chrysogenum in the Anopheles gambiae midgut does not affect mosquito survival, it renders the mosquito significantly more susceptible to Plasmodium infection through a secreted heat-stable factor.

Impact of GeneSight Psychotropic on Response to Psychotropic Treatment in Outpatients Suffering From a Major Depressive Disorder (MDD) and Having Had an Inadequate Response to at Least One Psychotropic Medication Included in GeneSight Psychotropic (RCT)
ClinicalTrials.gov Last Update Posted: September 18, 2017
Principal Investigator: John Greden, Ph.D, University of Michigan
https://clinicaltrials.gov/ct2/show/NCT02109939
This was the largest ever pharmacogenomics depression trial and primarily assessed Hamilton Depression Rating Scale 17 (HAMD-17) scores from baseline to eight weeks in patients receiving GeneSight-guided therapy compared to those receiving treatment-as-usual. The study was designed to evaluate three key endpoints relative to HAMD-17 scores: remission (HAMD-17 score ≤7), response (HAMD-17 reduction >50%), and symptom reduction.
Patients receiving the GeneSight test achieved a clinically meaningful and statistically significant improvement in both remission rates (p<0.01) and response rates (p=0.01) at eight weeks compared to the treatment-as-usual group.

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