https://www.ncbi.nlm.nih.gov/m/pubmed/29954419/

Multilocus sequence typing of clinical Borreliella afzelii strains: population structure and differential ability to disseminate in humans.

Gallais F, et al.
Parasit Vectors. 2018 Jun 28;11(1):374. doi: 10.1186/s13071-018-2938-x.

Abstract

BACKGROUND: Lyme borreliosis in humans results in a range of clinical manifestations, thought to be partly due to differences in the pathogenicity of the infecting strain. This study compared European human clinical strains of Borreliella afzelii (previously named Borrelia afzelii) using multilocus sequence typing (MLST) to determine their spatial distribution across Europe and to establish whether there are associations between B. afzelii genotypes and specific clinical manifestations of Lyme borreliosis. For this purpose, typing was performed on 63 strains, and data on a further 245 strains were accessed from the literature.

RESULTS: All 308 strains were categorized into 149 sequence types (STs), 27 of which are described here for the first time. Phylogenetic and goeBURST analyses showed short evolutionary distances between strains. Although the main STs differed among the countries with the largest number of strains of interest (Germany, the Netherlands, France and Slovenia), the B. afzelii clinical strains were less genetically structured than those previously observed in the European tick population. Two STs were found significantly more frequently in strains associated with clinical manifestations involving erythema migrans, whereas another ST was found significantly more frequently in strains associated with disseminated manifestations, especially neuroborreliosis.

CONCLUSIONS: The MLST profiles showed low genetic differentiation between B. afzelii strains isolated from patients with Lyme borreliosis in Europe. Also, clinical data analysis suggests the existence of lineages with differential dissemination properties in humans.

 

 

 

 

 

 

 

https://www.linkedin.com/pulse/worlds-first-french-cfs-association-decides-evaluate-manuel-gea-/

World’s first: The French ME/CFS Association decides to clinically evaluate the CFS pathogenesis model produced by Bio-Modeling Systems

Published on July 17, 2018
Manuel GEA – Bio-Modeling Systems

BMSystems has constructed a CADI™ model that, by integrating immunological dysregulations with their systemic metabolic, physiological and cognitive consequences, describes and explains the causal CFS mechanisms and their modes ofclinical progression, leading to the formulation of potential targeted treatments.

Paris, France July 10, 2018: The Scientific Committee of the French Chronic Fatigue Syndrome Association (ASFC) has decided to evaluate in clinic the CADI™ (Computer Assisted Deductive Integration) model of CFS pathogenesis mechanisms produced by Bio-Modeling Systems (BMSystems) to bring novel diagnostic and therapeutic strategies faster to patients. The two organizations will combine their competencies to improve understanding of the physiopathology and to accelerate treatment discovery for this poorly served, debilitating disorder for which challenges are considerable and therapeutic approaches non-satisfactory. To this end, the partners have launched an innovative research program which combines the scientific and clinical know-how of the Scientific and Medical teams attached to the Association with BMSystems’ heuristic CADI™ Discovery modeling platform and the scientific talents of its team of biologists.

More specifically, BMSystems has constructed a CADI™ model that, by integrating immunological dysregulations with their systemic metabolic, physiological and cognitive consequences, describes and explains the causal CFS mechanisms and their modes of clinical progression, leading to the formulation of potential targeted treatments. The purpose of this collaboration is to evaluate in the clinic the CADI™ model’s predictions and open new avenues that will be decisive for the understanding, the diagnosis and the treatment of the disease. The CADI™ model construction was entirely self-financed by BMSystems, revealing its confidence to jointly identify and characterize mechanisms that will quicker provide specific combined therapies to the patients.

The scientific program is placed under the shared leadership of Pr. Jean-Dominique de Korwin (Department of Internal Medicine, University Hospital of Nancy, Lorraine University) President of the Scientific Committee of the ASFC, Dr. François Iris, founder & CSO of BMSystems and Dr. Thanos Beopoulos, Integrative Biologist at BMSystems.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a major, yet severely under-estimated public health burden that needs novel, disruptive conceptual reconsideration that can drive the renewal and the evolution of therapies.

About ME/CFS: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome remains a debilitating condition for the patient and a confusing one for the physicians, both because of diagnostic difficulties and poorly codified management. Despite numerous studies, its pathophysiology remains unclear, but a multifactorial origin is suspected with triggering (infections) and maintenance (psychological) factors as well as the persistence of inflammatory (low-grade inflammation, microglial activation…), immunologic (decrease of NK cells, abnormal cytokine production, reactivity to a variety of allergens, role of estrogens…) and muscular (mitochondrial dysfunction and failure of bioenergetic performance) abnormalities at the origin of multiple dysfunctions (endocrine, neuromuscular, cardiovascular, digestive…). The frequency of CSF is variously appreciated, depending on the criteria of definition, with prevalence between 0.2 and 2.6% in Western countries. The ratio of women to men is 4/1, with predominance in young adults (20-40 years) but with possible attack at any age and a genetic predisposition. Between 836,000 and 2.5 million Americans and between 150,000 and 300,000 French people would suffer from CFS with often severe degrees of disability generating high health costs and distress.

About Bio-Modeling Systems (BMSystems):

Bio-Modeling Systems, an innovative company founded in 2004, is the first and, to date, only company to successfully create in-silico heuristic models validated in-vivo. BMSystems’ models have been built by its biologists using an integrated IT solution called CADI ™ (Computer Assisted Deductive Integration) and have led to discoveries and patents in the fields of infectious diseases, oncology, neurology, psychiatry, dermatology, immunology, metabolic disorders, innovative bioprocesses for industrial biotech and the creation of new companies exploiting these patents. BMSystems’ models describe the biological phenomena involved in pathological states and provide novel mechanistic integrations to explain the cause of certain diseases, identify and select predictive biomarkers, offer new combinations of molecules and new therapeutic strategies, thereby contributing to the development of Mechanism-Based Medicine.

For more information and access to presentations & publications, please visit http://www.bmsystems.net.

About the French Chronic Fatigue Syndrome Association (ASFC):

ASFC is the only association representing patients with ME/CFS approved by the French Ministry of Health in 2015. The association provides a phone hotline and organizes regular meetings between patients and volunteers everywhere in France, and an annual meeting with expert scientists. ASFC welcomes everyone suffering from unexplained chronic fatigue and ME/CFS, informs and refers them to specialized centres for an accurate diagnosis. The main missions of the Scientific Council are to inform and advise the ASFC on the development of knowledge on ME/CSF and patient care, to propose research protocols and strategic directions for recognition of ME/CFS in France.

President of ASFC: Mr. Robert SCHENK

Members of the Scientific Committee of the ASFC involved in the project: Pr. François-Jérôme AUTHIER, Pr. Ingrid BANOVIC, Dr. Grégoire COZON (PhD), Dr. Stéphane DELLIAUX (PhD), Mrs Isabelle FORNASIERI (PhD), Dr. Alaa GHALI, Pr. Yves JAMMES, Mrs Emmanuelle JOUET (PhD), Pr. Jean-Dominique de KORWIN, Pr. Bernard LEBLEU, Dr. Frédérique RETORNAZ.

For more information, please visit http://www.asso-sfc.org

_________________

**Comment**

There is no doubt in my mind that technology like this will be the wave of medicine.  I’m no expert on ME/CFS but regarding Lyme/MSIDS, psychiatric issues need to be put in the equation.  

Also, this technology is only as good as those inputting the markers and in the case of Lyme/MSIDS there is a vast polarization in the medical community of those who believe it to be a benign illness cured by 21 days of doxycycline and those who believe it can infiltrate every organ of the body eventually leading to death without proper long-term treatment.  Technology must include all sides and it must adapt and change to new information.

My only other concern is that doctors use this as only one of many tools in their differential diagnoses because particularly with Lyme/MSIDS, people fall through the cracks due to “atypical” or “rare” presentations.  In my experience these aren’t “atypical” or “rare” at all but have simply not been reported on – therefore, doctors and researchers just aren’t aware of them.  In the case of Lyme/MSIDS the worst thing a researcher could use would be old Lyme/MSIDS research (and yes, even new meta-analysis from past research) as that would only represent the Lyme Cabal and their pigeon-holing this complex illness into a square of their own making which leaves out a huge chunk of suffering patients.  They also smugly state that this chunk is only 10-20% of patients.  I say the percentage is much higher and is growing daily.

 

https://www.nj.com/news/index.ssf/2018/07/this_is_how_dna_helps_rutgers_scientists_crack_the.html

It spreads SFTS (sever fever with thrombocytopenia syndrome), “an emerging hemorrhagic fever,” causing fever, fatigue, headache, nausea, muscle pain, diarrhea, vomiting, abdominal pain, disease of the lymph nodes, and conjunctival congestion, but the potential impact of this tick on tickborne illness is not yet known. In other parts of the world, this Longhorned tick, also called the East Asian or bush tick, has been associated with several tickborne diseases, such as spotted fever rickettsioses, Anaplasma, Ehrlichia, and Borrelia, the causative agent of Lyme Disease.

For a 2016 literature review on SFTS: http://infectious-diseases-and-treatment.imedpub.com/research-advances-on-epidemiology-of-severefever-with-thrombocytopenia-syndrome-asystematic-review-of-the-literature.php?aid=17986
Although the clinical symptoms of SFTS and HGA are similar to each other, but the treatment methods of the two diseases are totally different. Doctors notice that the biggest difference between the clinical symptom of SFTS and HGA is that SFTS patients generally without skin rash, the dermorrhagia is also not seriously, and few massive hemorrhage cases were reported [23]. It is also reported that SFTS patients had gastrointestinal symptoms, such as nausea, vomiting, and diarrhea, which are rarely observed in HGA patients [2]. So these differences can be used as the auxiliary basis of differential diagnosis.
At present, there is still no specific vaccine or antiviral therapy for SFTSV infection. Supportive treatment, including plasma, platelet, granulocyte colony stimulating factor (GCSF), recombinant human interleukin 11, and gamma globulin is the most essential part of case treatment [44]. Meanwhile, some measures were taken to maintain water, electrolyte balance and treat complications are also very important.
Ribavirin is reported to be effective for treating Crimean-Congo Hemorrhagic Fever (CCHF) infections and hemorrhagic fever with renal syndrome, but it is still inadequate to judge the effect of ribavirin on SFTS patients because of the study limitation without adequate parameters were investigated [45]. Host immune responses play an important role in determining the severity and clinical outcome in patients with infection by SFTSV.
For Viral treatment options: https://madisonarealymesupportgroup.com/2016/03/28/combating-viruses/

And lastly, please know ticks parasitize one another, potentially spreading all manner of diseases to humans.  This fact also shoots holes in the regurgitated mantra that only certain ticks carry certain pathogens.  If they are feasting on one another, they can potentially infect each other and then us:  https://madisonarealymesupportgroup.com/2018/03/07/tick-bites-tick-hyperparasitism/

 

 

G. Magnotta Research Lab at the University of Guelph – Melanie Wills, Research Associate

https://www.thestar.com/news/gta/2017/06/14/university-of-guelph-receives-14m-grant-for-lyme-disease-lab.html

The University of Guelph in Ontario received a $1.4 million dollar grant from the G. Magnotta Foundation for Vector-Borne Diseases, named for Magnotta Winery co-founder Gabe Magnotta.  This lab is dedicated to improving testing and treatment for Lyme disease. 

Magnotta died in 2009 from complications of Lyme disease. His wife and business partner Rossana Magnotta created the non-profit foundation in 2012.

“Lyme disease is increasingly recognized as a substantial threat across the country, and there is a profound need for high-quality science that can improve the lives of afflicted Canadians,” said Melanie Wills, a research associate in the school’s molecular and cellular biology department, who will head the new lab.

Article here:  https://www.guelphtoday.com/local-news/new-lyme-disease-lab-to-study-elusive-bacteria-643135

Telling quote from Melanie Wills in the Department of Molecular and Cellular Biology:

“I could not turn my back on the conflicting research or on the suffering I was witnessing,” she said.

Also:

The new lab will place the patient “as a key partner in the center of an interdisciplinary study,” she said.

The non-profit founder, Rossana Magnotta, stated:

“We need a new diagnostic test,” Magnotta added. “The current one misses too many people, and it is not broad enough to pick up the many strains of Borrelia. The Canadian tests are not accurate, and the chances of getting a false negative are very high. You will be told you don’t have Lyme, but you will get sicker and sicker everyday, and you won’t know why.”

“We need the truth,” she added. “We need to understand the true rate of Lyme disease, and the true rate of misdiagnosis.”

Her husband not only fought Lyme disease, but also:

“a health care system that seemed unwilling to accept and understand what my husband was going through.”

https://w.soundcloud.com/player/?url=https%3A//api.soundcloud.com/tracks/393025281&color=006341“>

This story is produced and presented by The University of Vermont Medical Center

Globally, more than 300 million people of all ages suffer from depression. It’s the leading cause of disability and a major contributor to the overall global burden of disease. Yet treatment for depression can be limited by effectiveness, cost, availability and side effects. Now, a new clinical trial done at the University of Vermont shows that magnesium may be a safe, effective, and less expensive treatment option for mild to moderate depression. Read or listen to our interview above with one of the leaders of this clinical trial, Emily Tarleton, PhD, RD, CD. She is a Bionutrition Research Manager at the University of Vermont’s Clinical Research Center.

Your clinical trial finds a link between depression and magnesium intake. What have you discovered through your work?

Emily Tarleton: We were following up on some cross-sectional and prospective trials. I found an inverse association between magnesium intake and depression, so we conducted a randomized clinical trial with the aim of determining whether supplemental magnesium really does influence symptoms of depression. And we found that over a six-week period of time, symptoms of both depression and anxiety improved significantly. And this was the case regardless of age, gender, baseline severity of depression, baseline magnesium status, or use of other treatments for depression, such as counseling or antidepressants. And we also found that it was really well-tolerated, and a majority of participants indicated that they would use it in the future, which was one of our main outcomes.

So for anyone who is a little bit new to the research world, what exactly is a randomized controlled trial?

Emily Tarleton: Right. So a randomized controlled trial is a trial in which we … in this case, we were comparing people to themselves, so we gave them a treatment for the six weeks, which in this case was the magnesium supplement, and then we followed them the same way for another six weeks without the magnesium supplement so we could compare how they responded while on the supplement, but also what happened while they were off of the supplement. And it’s randomized because they either started the supplements at week one or at week seven, so it’s sort of a crossover design.

And this was just here in Vermont? Are these Vermonters who participated?

Emily Tarleton: Yes. We started small for this trial, and we used outpatient primary care clinics to recruit from through physicians and people had to have a baseline of still suffering from depression, so people who are currently experiencing symptoms, and we were able to do our study over the phone for the most part, and it was really … people really liked the opportunity to try something new.

And magnesium is something that you can just buy, right, in the store? It’s over the counter?

Emily Tarleton: Right. And magnesium is also found in a lot of foods that we eat, so the reason we don’t tend to get enough is because it’s the healthy food people don’t really like to eat a lot of, so things like green leafy vegetables and whole grains and nuts and legumes. As a society, unfortunately those aren’t foods that we over-consume- so people tend to not get as much magnesium as they should.

Is this something where, outside of the world of mild to moderate depression, anyone could benefit from?

Emily Tarleton: Yes. Because magnesium is in these healthy foods, certainly anybody would benefit from consuming more of those foods in general. But magnesium has also been found to help with other chronic diseases. It’s been associated with cardiovascular disease and diabetes. People with migraines sometimes take magnesium. Also the big connection is with muscle cramping, so some people who tend to have a lot of muscle cramping, leg cramps, will take magnesium and that seems to help for them as well.

In general there aren’t a lot of great studies or randomized clinical trials on showing a cause and effect of magnesium in these uses, but their research is ongoing.

In this study, and I just want to get a better understanding for what some of these participants went through, how often did they have to take the magnesium?

Emily Tarleton: We had them take the tablets every day. We suggested they take two in the morning and two in the evening just to avoid that stomach upset. Some people took all four at once, and that was fine for them. Other people liked to split it up. It really didn’t seem to make a difference.

Another thing we found was that the effect was significant regardless of overall compliance, so at the end of the study we did a pill count to see how compliant they were with taking the supplements, and the lower the compliance, people still had a good reaction, a good decrease in their symptoms. So, in a future study we could look at using even less of the supplement.

Are there plans for a future study?

Emily Tarleton: We would love to do another study. There’s lots of … of course, we’d like to do a longer-term, bigger randomized controlled trial with a more diverse population to really show that this happened. We didn’t really have enough people. While I mentioned that we saw the effect regardless of age and gender and all those other little sub-studies, we didn’t really have enough people to really prove that or not, so we’d love to do a bigger study to show if there is a difference by race or gender. Age is another big one we’d like to look at.

So as we talked about a little bit earlier, the treatment for depression is complex. It can be limited by cost, availability. There are side effects. It’s a very complicated thing. What do you think … and I realize that the study and the research is somewhat in its infancy. What do you think is the promise of magnesium as a treatment for people?

Emily Tarleton: Yeah. As you mentioned, we’re just getting started and even within our study, magnesium of course like any other treatment didn’t work for everyone. But, because of the positive effects that we saw and because they worked quickly with very few side effects, it can be an option that patients can explore with their primary care or any other healthcare provider that they’re seeing. There really is little risk to taking magnesium because, like I said, the side effects are few. We also saw the change in symptoms of depression within two weeks of taking the supplements, so if within two weeks you don’t see … you’re not feeling any better or you happen to be even feeling worse, you can certainly stop taking them. Because it’s a mineral, it doesn’t stay within the body for a long period of time. After a day or two, any extra magnesium you have will be flushed out. If for some reason you feel like, “Oh, I don’t know. For some reason it’s making me feel worse,” it comes out of the body really quickly as well.

As I mentioned, we were able to decrease those side effects just by changing the timing of the dose or decreasing the dose to less than we had originally started at. It’s also inexpensive. You mentioned the cost. About a month’s supply of the magnesium chloride that we used in the study is only about $12 to $14 a month. And over-the-counter so you can get it on Amazon.

Another aspect people liked about the magnesium was the lack of stigma associated with taking it. Some people just really don’t want to start an antidepressant for that reason. And you know, even people who start antidepressants oftentimes are put in a tough situation where they may be feeling a little bit better, but not where they want to be.

Now they’re in a position where they need to either increase their dosage or add another medication increasing those risks of side effects, or they’re left with the other option which is stay where they are and not feel as good as they wanted to. That’s just not a great position to be in. We did have people in our study that were already taking an antidepressant and we did see that there might be what we call this adjunct relationship where the magnesium actually helps the antidepressant work even better. And there are a couple of other studies to support that idea.

This is another direction we can certainly go in. It could be an option in that sense too like, “Hey, I just really don’t want to risk increasing my side effects,” or “I just really don’t feel I’m feeling at the point where I want to start an antidepressant yet.” Magnesium might be an option.

For people who are maybe feeling depressed and who haven’t seen their doctor yet or haven’t really talked to anyone yet, what’s the step for them? Is this something where they go to the grocery store and pick some of this up? What would they do next?

Emily Tarleton: Magnesium does actually interact with some medications, so you would want to talk to your healthcare provider before starting it. But, as we mentioned, it’s also found in really healthy foods, and there are some theories that just certain nutrients in combination might help with depression as well. And we’ve seen studies on things like fish oils, vitamin B. We’ve looked at vitamin D as well. Zinc, folic acid, all these different nutrients people have found some sort of association as well. Eating healthy foods that have all of these nutrients may help, may be beneficial, and may help you feel good in general just because you’re taking care of yourself in that sense.

We’ve talked about the study a lot, but I’m also kind of fascinated by your title. You’re a Bionutrition Research Manager. What are some of the other things you work on in your role here?

Emily Tarleton: Yeah. The Clinical Research Center is located on Shepardson 2 at the main hospital, and we do inpatient and outpatient research and really, any investigator within the UVM or UVM Medical Center community can utilize our services, and we have a metabolic kitchen, as well, that we can do food trials.

What’s a metabolic kitchen?

Emily Tarleton: It’s a kitchen that is specific to research where we create these very controlled meals. Whether an investigator wants to control for a certain nutrient or they want to just control the overall calories people are consuming at a given time. So we do some long-term feeding trials where sometimes we’re controlling the fatty acid content of the food, sometimes we’re looking at the different effects of dairy, sometimes we’re looking at the effects of glucose. So we’re involved in various studies throughout the community, and it’s really exciting to be involved at this level and sort of get to see the results of some of these other trials.

Is there anything else that you found in your research that you think it would be helpful for our listeners to hear?

Emily Tarleton: One of the things we found was that, as I alluded to, the US adult population really doesn’t consume enough magnesium, and so we took a closer look at this and tried to figure out some reasons why that might be. There have been changes in agricultural processes over the last century that has actually decreased the amount of magnesium in the soil, therefore there’s less magnesium absorbed by the plants and the vegetables that we eat. That’s one reason.

That also means that we have to increase the amounts of those vegetables to get the same amount of magnesium, but what we found was that our intake of vegetables has actually gone down slightly over the past couple of decades. So we’re getting less in the plant to begin with and then we’re consuming less of those vegetables which isn’t a great combination. Those are sort of changes in the way our consumption patterns are as adults. We’ve also just decreased our whole grains and we’re eating more processed vegetables, more processed grains and refined oils, which all have less magnesium as well. Socioeconomic status also plays a role in magnesium consumption, so those that are at the lower end of the socioeconomic status, they tend to not only eat more processed and refined foods, they also are less likely to take a supplement in general and a supplement that contains magnesium.

Is that because of cost or-?

Emily Tarleton: Usually it’s cost. Yeah. And just a side note that many multivitamins don’t have magnesium in them to begin with so if you’re taking a general multivitamin, you can look at the bottle but not all of them contain magnesium. You can look for one that does have some, and usually it’s a very small amount even if it does.

Finally, there’s also issues with absorption and excretion so we have to absorb the magnesium after we consume it, whether it’s from food or a supplement. And then we have to not excrete it all. We have to maintain some of that absorption. Things like alcohol consumption, smoking, medications and several chronic diseases actually affect the absorption or the excretion of magnesium. As we’ve seen an increase in things like diabetes over time, it’s actually known that people who have diabetes absorb less magnesium. There’s research ongoing in these areas, as well. There are many reasons why we’re not getting enough, and this is not only in the US but in other countries as well. They’ve seen the same trend.

We’ve just been talking with Emily Tarleton. She’s a PhD and a registered and certified dietician at the University of Vermont Medical Center. She’s a Bionutrition Research Manager at the University of Vermont Clinical Research Center. If you want to learn more about her studies and other things happening here, please visit uvmhealth.org/medcenter.

If you want to learn more about clinical trials and research currently happening at the University of Vermont and the University of Vermont Medical Center, visit our website.

Members of the editorial and news staff of the USA Today Network were not involved in the creation of this content.

______________

**Comment**

It’s pretty common for Lyme/MSIDS patients to suffer with depression at some point in their journey.  There are many potential reasons for this – including pain, isolation, fear, and loss of control of nearly everything.  I personally found a direct correlation between how I felt physically and how I felt mentally.  Thankfully good, appropriate, effective treatment of antimicrobials resolved this and I never had to take anything for depression.  (And my treatment wasn’t 21 days of doxycycline!)

For Lyme treatment ideas:  https://madisonarealymesupportgroup.com/2016/02/13/lyme-disease-treatment/