The diversity of Borreliaspecies discovered in California appears to be particularly high. A divergent group of Borreliastrains collected from Ixodes ticks in California was described by Postic and co-workers and designated ‘genomospecies 2’ (Postic D, Garnier M, Baranton G. Int J Med Microbiol2007;297:263–271; Postic D, Ras NM, Lane RS, Hendson M, Baranton G. J Clin Microbiol1998;36:3497–3504). We performed multilocus sequence analysis (MLSA) using eight housekeeping loci (clpA, clpX, nifS, pepX, pyrG, recG, rplB and uvrA) on 12 strains of this Borreliagenospecies to confirm that these strains form a distinct group within the Borreliaburgdorferis. l. complex (Margos G, Hojgaard A, Lane RS, Cornet M, Fingerle V et al. Ticks Tick Borne Dis 2010;1:151–158). Phylogenetic and genetic distance analyses based on sequences of the MLSA housekeeping genes corroborated the distinctness of this group; genetic distances to all other members of the B. burgdorferis.l. complex were 96 % or lower. We propose the name Borrelia lanei sp. nov. for this genospecies in honor of Professor Robert S. Lane, University of California Berkeley, for his contributions to Borreliaand tick research. The type strain for Borrelia lanei sp. nov., strain CA28-91T, has been deposited to two culture collections (=DSM 17992T=CIP 109135T).
This could also explain why California Lyme patients are discarded like yesterday’s trash. They very probably have these yet to be discovered strains of borrelia that no CDC two tiered test is going to pick up in a trillion years.
Much work needs to be done not only in discovering these strains but also the other pathogens involved that make our cases much more complex than the average GP understands. These factors could well explain why we aren’t testing positively and why we are not getting better with the mono therapy of doxycycline.
Panelists Peter L. Salgo, MD; Robert C. Bransfield, MD, DLFAPA; Leonard Sigal, MD; Samuel Shor, MD, FACP; and Patricia V. Smith share their thoughts on what needs to happen before a consensus can be reached in Lyme disease.
Peter L. Salgo, MD: Moving to consensus: yes or no? The first step, if you’re going to make the diagnosis and treat it, is 2 to 4 weeks of antibiotics to kill the spirochete. Yes, no, what?
Robert C. Bransfield, MD, DLFAPA: No.
Peter L. Salgo, MD: No. Bob, why not?
Robert C. Bransfield, MD, DLFAPA: Well, I think I’ve seen some people for whom that works, but I think there’s always the outlier in the bell curve. There are some people where a few weeks do not work for some reason. Maybe they have a complex infection. There’s more than one pathogen.
Peter L. Salgo, MD: I said first step, would that be the first step for most people?
Robert C. Bransfield, MD, DLFAPA: Yes, I think that would be.
Leonard Sigal, MD: That would depend on the manifestation though. If somebody comes to you with meningitis, you’re not going to give them 2 weeks of doxycycline.
Robert C. Bransfield, MD, DLFAPA: No.
Samuel Shor, MD, FACP: No, but you’re not going to give them more than 8 weeks probably.
Leonard Sigal, MD: But my point being is that it depends.
Robert C. Bransfield, MD, DLFAPA: You’re right, it depends.
Samuel Shor, MD, FACP: Yes.
Peter L. Salgo, MD: OK. Consensus or not—my guess is going to be no, by the way—what do we do for the subset of patients who continue to experience symptoms after this 2 to 4 to 6 weeks of antibiotics?
Samuel Shor, MD, FACP: Careful differential diagnosis and careful empathetic review of their clinical picture.
Leonard Sigal, MD: And not telling them that it’s all in their head.
Samuel Shor, MD, FACP: Right, and being supportive.
Leonard Sigal, MD: Absolutely.
Samuel Shor, MD, FACP: With the recognition that there are going to be those of us who feel a greater percentage of patients probably have active infection as opposed to another group of people who do not, such that the recommendations coming out of that review is going to be different.
Leonard Sigal, MD: And to reiterate, looking for other potential explanations.
Samuel Shor, MD, FACP: Differential diagnosis.
Leonard Sigal, MD: Absolutely.
Robert C. Bransfield, MD, DLFAPA: And don’t just give antibiotics to treat the symptoms as well. We need to do both.
Peter L. Salgo, MD: Let’s boil it down. I’m trying to get at least some clarity, here, for the rationale for or against using a longer course of antibiotics in patients who have persistent symptoms.
Samuel Shor, MD, FACP: If you feel that there is a threshold that you’ve achieved and that there is active infection—and we’ve all discussed what that means, and that threshold is different for individuals. If you feel that’s the case, then by not doing that, you potentially run the risk of not having adequate therapeutic gains. The other component—and this goes to the MS patients. A number of them, actually all 3 of them, were recommended by the neurologists to be on immune-suppressive drugs, which could have made their conditions worse had they not been identified as having an infection.
Peter L. Salgo, MD: Now, we’ve had an awful lot of bomb-throwing here today. There’s an awful lot of grenades flying through the air out there. What do we need to reach a better consensus on the issues that we’ve discussed?
Samuel Shor, MD, FACP: Better testing.
Peter L. Salgo, MD: Better testing. What kind of testing are we looking for?
Leonard Sigal, MD: Let’s back up for a second. We need better science, looking at clinical markers, biomarkers as you were saying; looking at better testing; and looking at what the sensitive questions are that we can ask. I don’t mean sensitive in the sense of, “I’m caring for you,” that’s important, too, but sensitive in the sense of statistics. I think what we need to do is put down the grenades, put down the bombs, stop accusing each other of somehow having nefarious interest, and let’s have a civil conversation. I realize this is the United States in the year 2017, so the word civil has been thrown out the door. But maybe in this microcosm, we can be civil, have a conversation about this, and make the best of everybody’s talents and experiences.
Robert C. Bransfield, MD, DLFAPA: One solution is having more programs like this. This is great. I think when it’s face-to-face and collegial, we can help to reconcile these differences and iron them out. We’re coming at it from very different angles.
Leonard Sigal, MD: Yes.
Samuel Shor, MD, FACP: Right.
Robert C. Bransfield, MD, DLFAPA: I think this is very useful and I think better disease definition is critical.
Patricia V. Smith: I was just going to say that, over the years, many times, we have asked to have more dialogue. We’ve contacted the IDSA, we’ve tried to sit down with them. We actually had them at our LDA Columbia CME Conference several years ago. It was the first time they were on the same stage. Believe it or not, we’ve advocated for that for decades, to get people together to have a discussion. But, unfortunately, there’s been unwillingness, and I was very happy that Dr. Sigal agreed to come in today and sit at the same table as us, because it doesn’t happen very often.
Leonard Sigal, MD: But it goes the other way around, you know.I’ve invited people.
Patricia V. Smith: Excuse me, but who?
Leonard Sigal, MD: I’ve invited clinicians in New Jersey, who see hundreds of patients with Lyme disease, to sit down with me to come up with research studies that would allow us to understand what’s going on in those people, understand how they respond to antibiotics, and understand what biomarkers might be useful. And the last time I saw them was when they walked out the door. They didn’t follow through on their interest.
Patricia V. Smith: The reason for that may be because, for a number of decades, our physicians have been gone after by medical boards just for treatment, long-term, of patients with Lyme disease. That has been very problematic, and we have a number of physicians who have had sanctions and so on, so a climate of fear has existed. If they’re really the practicing physicians, they don’t want to put themselves out there, because they are brought up on charges.
Leonard Sigal, MD: Well, I’m not sure that’s the explanation. The BME, the Board of Medical Examiners in the state of New Jersey, has looked at many, many clinicians.
Patricia V. Smith: I know what they look at.
Leonard Sigal, MD: Yes, you know, unfortunately. But what I was asking was, “If you see these patients, let’s do a clinical study so we can understand what’s going on with these patients,” and they were never forthcoming. All I can do is invite and, in a civil manner, try to encourage them to be part of a scientific trial.
Patricia V. Smith: I think part of the problem is also that when there have been clinical trials—and sometimes the treating physicians have supported those trials, and they have said to patients, “Maybe you should enter those trials”—those trials always end up that the patients are basically not being helped by antibiotics. Again, broad brush conclusions. And so, those physicians and those patients don’t want to even participate in those trials.
Peter L. Salgo, MD: Let me see if I understand that point. There are trials that are undergoing, that are underway, and patients get enrolled in these trials, but the results are that antibiotics may not be the right answer. They didn’t give you the answer you wanted. Does that mean that the trial was bad?
Patricia V. Smith: No, that isn’t the situation. The conclusions that were drawn in some of these studies, in the 4 from the NIH—and Sam alluded to 2 of them before—were broad brush. It should have said that in this subset of patients who were in this trial, with these particular antibiotics for this duration of therapy, the antibiotics maybe did not help them—or in 2 cases antibiotics actually did, but they said that they didn’t. So, that is the broad brush.
Leonard Sigal, MD: One of the criticisms that I’ve heard of the “long-term” antibiotic trials is that the duration was insufficient, and had there been a longer trial of antibiotics, there might have been a better outcome. I’ve heard this from other people. I’m not putting words in your mouth, Sam. I just want to ask you about it.
Samuel Shor, MD, FACP: And that is a potential, but there are other confounding variables, such as in the Klempner study. Most people were sick for between 4-and-a-half and 5-and-a-half years, many of whom had gone through the very protocols that were used in the study, so you’re self-selecting failure. And it’s also a matter of not identifying treatment of co-infections.
Leonard Sigal, MD: See, you’re taking issue with the design of the study.
Samuel Shor, MD, FACP: Yes.
Leonard Sigal, MD: Had the study been a little bit more real-world oriented…
Samuel Shor, MD, FACP: Right. The problem is that you’ve got to control your variables, and there are so many variables that you’ve got to control.
Robert C. Bransfield, MD, DLFAPA: And PCR-positive patients were excluded from the study. They should have been the ones that were studied.
Leonard Sigal, MD: I agree with you.
Peter L. Salgo, MD: It sounds to me—not being involved in the creation of these studies, not being at the table—that if everybody got together and agreed a priori on the construction of the study and the goals and endpoints, everybody might agree better when they got the data.
Samuel Shor, MD, FACP: We’re in the process of actually doing that. There’s a work group of about 15 of us who are trying to put that together.
Leonard Sigal, MD: If I can be of assistance, let me know.
Peter L. Salgo, MD: I just want to point out, I haven’t seen this since the United Nations was formed.
Leonard Sigal, MD: In the pharmaceutical industry.
Samuel Shor, MD, FACP: Both schools of thought are involved.
Leonard Sigal, MD: In the pharmaceutical industry—and that’s not a dirty word—when you have a study of say a drug for rheumatoid arthritis, you have to come up with entry criteria that bring in patients who are as homogenous as possible, because you’re going to be randomizing them. If you randomize them and they’re not homogenous, you stand a chance of asymmetric distribution of patients and your study goes up in smoke.
Samuel Shor, MD, FACP: Right.
Leonard Sigal, MD: I’m not defending anybody’s study design, by the way. I’m just saying that when you do a study, you have to be really rigorous about bringing in as homogenous a population as possible. Now, for some reason, they decided to exclude PCR-positive patients. I don’t know what the reasoning was there. But the idea is to not make the entry criteria so small that you can’t get the real world in, but not so broad as to make it a garbage study. There has got to be some middle ground.
Purpose: Lyme disease is spreading worldwide, with multiple Borrelia species causing a broad range of clinical symptoms that mimic other illnesses. A validated Lyme disease screening questionnaire would be clinically useful for both providers and patients. Three studies evaluated such a screening tool, namely the Horowitz Multiple Systemic Infectious Disease Syndrome (MSIDS) Questionnaire. The purpose was to see if the questionnaire could accurately distinguish between Lyme patients and healthy individuals.
Methods: Study 1 examined the construct validity of the scale examining its factor structure and reliability of the questionnaire among 537 individuals being treated for Lyme disease. Study 2 involved an online sample of 999 participants, who self-identified as either healthy (N=217) or suffering from Lyme now (N=782) who completed the Horowitz MSIDS Questionnaire (HMQ) along with an outdoor activity survey. We examined convergent validity among components of the scale and evaluated discriminant validity with the Big Five personality characteristics. The third study compared a sample of 236 patients with confirmed Lyme disease with an online sample of 568 healthy individuals.
Results: Factor analysis results identified six underlying latent dimensions; four of these overlapped with critical symptoms identified by Horowitz – neuropathy, cognitive dysfunction, musculoskeletal pain, and fatigue. The HMQ showed acceptable levels of internal reliability using Cronbach’s coefficient alpha and exhibited evidence of convergent and divergent validity. Components of the HMQ correlated more highly with each other than with unrelated traits.
Discussion: The results consistently demonstrated that the HMQ accurately differentiated those with Lyme disease from healthy individuals. Three migratory pain survey items (persistent muscular pain, arthritic pain, and nerve pain/paresthesias) robustly identified individuals with verified Lyme disease. The results support the use of the HMQ as a valid, efficient, and low-cost screening tool for medical practitioners to decide if additional testing is warranted to distinguish between Lyme disease and other illnesses.
Multiple sclerosis is a terrible and debilitating disease where the body’s immune system is directed against the central nervous system. When that happens, according to the National MS Society:1
Within the CNS, the immune system attacks myelin — the fatty substance that surrounds and insulates the nerve fibers — as well as the nerve fibers themselves.
The damaged myelin forms scar tissue (sclerosis), which gives the disease its name.
When any part of the myelin sheath or nerve fiber is damaged or destroyed, nerve impulses traveling to and from the brain and spinal cord are distorted or interrupted, producing a wide variety of symptoms.
Currently, there is no cure. Medication can often help make symptoms like double vision, blindness, as well as psychological or muscle issues more bearable but ultimately it robs people of their lives and shortens life expectancies. But that may all be changing.
Dr. Su Metcalfe believes that the attack on the nerve cells can be stopped thanks to a new medical development her company LIFNano has created. 2
She said in an interview:
“Some people get progressive MS, so go straight to the severe form of the disease, but the majority have a relapsing or remitting version.
It can start from the age of 30, and there’s no cure, so all you can do is suppress the immune response, but the drugs that do that have side effects, and you can’t repair the brain. The cost of those drugs is very high, and in the UK there are a lot of people who don’t get treated at all.” 3
Using the stem cell particle LIF, which is a part of the immune cell and is able to control and confine the attack on our bodies, she found a “small binary switch” which is able to regulate itself INSIDE the immune cell to NOT attack our body. However, it can attack when it needs to.
She went on to say,
“That LIF, in addition to regulating and protecting us against attack, also plays a major role in keeping the brain and spinal cord healthy. In fact it plays a major role in tissue repair generally, turning on stem cells that are naturally occurring in the body, making it a natural regenerative medicine, but also plays a big part in repairing the brain when it’s been damaged.” 4
Much more research needs to be done but this breakthrough seems quite promising and the team has set their sights on having found the cure by 2020.
Dr. Metcalfe also believes she and her team might be able to tackle dementia as well because LIF is a “major health factor for the brain.”5 Therefore, if they can get into the brain and protect it, it serves that they could prevent dementia.
**Comment**
This is indeed great news for Lyme/MSIDS patients due to the fact many with MS, dementia, and Alzheimer’s are initially misdiagnosed with those labels but are actually infected and vice versa. All in all, many autoimmune diseases will potentially benefit from this treatment.
Iowan, Jack Gordon, is a case discovery of 2 diseases NEVER found together before on 11.22.2015: Lewy Body Dementia, causing violent hallucinations, and Lyme Disease/MSIDS. Using his medical files, he was bitten by a tick 35 yrs. ago, but the doctors never acknowledged it by diagnosing or treating him.
Professor Holly Ahern, of State University of New York Adirondack, has extensive teaching and research experience in bacteriology and molecular biology. She’s the author of nationally published textbooks on microbiology, cell biology, and molecular biology. She’s also an expert on the scientific literature pertaining to Lyme disease and other tick-borne infections.
Professor Ahern came to her Lyme expertise the hard way, as the mother of a daughter with Lyme disease. Her professional knowledge was put to the practical test of having to navigate the complex care of a Lyme patient. She understands the science and has complete empathy for the suffering that tick-borne diseases inflict on patients and families.
Earlier this year, she gave an illuminating presentation at the Focus on Lyme Scientific Conference in Scottsdale, Arizona. Addressing the historical events that have contributed to the Lyme disease epidemic in the US, she reminds the audience of something they know too well— “we are not in a good place when it comes to Lyme disease.” Then, she answers the question: how did we get here?
Ahern clearly lays out the “alternative conclusions” that over past decades have perpetuated the idea that Lyme disease is “hard to catch and easy treat.” That misconception continues to be encouraged by the CDC and IDSA today.
She points out that, in fact:
Lyme is easy to catch: “Lyme disease is the second most common infectious disease in the United States.”
Testing for Lyme is highly inaccurate: “The recommended serological assays for Lyme disease are falsely negative more than half the time.”
Lyme infection can be chronic: “There are hundreds of peer-reviewed studies that show the relationship between bacterial infection and chronic disease, not just Lyme disease.”
Antibiotics do treat infection: “Of the clinical trials done to date, not one of them provides conclusive scientific evidence to prove antibiotics show no benefit to patients with chronic symptoms.”
Ahern reviews the epidemiology used in the discovery of Lyme disease and the science from the original studies of 40 years ago demonstrating the following facts:
Only 1 in 4 patients with Lyme will develop the bull’s-eye rash.
Only 50% of patients with Lyme will develop the antibodies needed for a positive test.
Only 50% of patients with Lyme will test positive using the CDC “gold standard” two-tier test.
Only 50% of patients treated with two weeks of antibiotics will get better.
Ahern uses humor and wit to describe the current scientific data which refutes the notion that patients with persistent symptoms from Lyme disease are not helped with longer term antibiotics.
