“Lyme On The Brain” (part 2) by Tom Grier
“Lyme On the Brain” continued…
Lecture Notes of Tom Grier: Tom Grier (Microbiologist from Minnesota) spoke at Lac Court Oreilles Convention Center in Hayward, WI. Tom’s life work is to do further research and bring awareness of this illness to everyone. For more info about Tom and his work checkout http://www.mibdec.com
The heart and soul of the mechanism of infection, or the pathogenisis of Borrelia bacteria that cause Relapsing Fever and Lyme Disease is its ability to attach to the lining of blood vessels and cause gaps or holes to appear between the endothelial cells.
The endothelial cells themselves release digestive substances, as well as our own white blood cells releasing blood-born immune factors such as tissue plasminogen, TNF-alpha, IL-1, Il-6, histamines, vaso-active amines and MMP-9 that facilitates cell penetration through any and all blood vessels, but especially important is the immediate transit of Borrelia burgdorferi through the blood-brain-barrier.
Animal models including dogs and primates show conclusively that this is not just a random occurrence, but rather a very specific mechanism that facilitates both the immediate and long-term survival of Borrelia within mammalian systems. In dog-models, the uninfected dog’s blood protein albumin was tagged with radioactive Iodine, and then traced using radio-detection of entering the brain and spinal-fluid. After infected ticks were allowed to feed on the dogs, this “leaky-brain-effect” took less than 24-48 hours to reach its full potential.
We can measure and observe this leaky-brain-effect in dogs, hamsters, rabbits, and primates within hours, and we can see and detect in many other animal models including guinea pigs, mice, hamsters, and rabbits the actual transit of Borrelia into the brain of these animals within days of tick-bite, yet our own USA health-care experts are saying without equivocation that infected ticks have to be attached for at least 36-48 hours (YALE Medical Report, IDSA-Lyme Treatment Guidelines)
Why is there such an absolute dictatorship in our guidelines when we have direct animal studies since 1989 that suggest that not only does Borrelia bacteria penetrate blood vessels and enter the brain, but once the blood-brain-barrier closes up 10-14 days after initial infection; the sequestered bacterial infection within the brain is undetectable by serology tests.
Our current serology tests that detect antibodies to the Lyme bacteria; require at least 4-6 weeks after exposure to produce significant antibodies to the Lyme bacterium. By then the infection can be resting dormant and quiescently within the host’s brain, undetected, undetectable, and creating changes within the brain that are subtle and perhaps for awhile negligible.
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Consider these other short-comings of the
current antibody based Lyme serology tests:
- To create these tests we need a representative source of the wild bacteria as a source for specific antigens that can be used to detect the specific antibodies that patients produce as a result of an infection from their local area.
Since Borrelia bacteria are genetically equipped to change their antigenic appearance (strain variation) it is important to use tests that are designed using the best representation of the bacteria that is found in the local area. There can be tremendous variation in Borrelia isolates even those found within close proximity to each other. There are well over 1000 Borrelia isolates of Borrelia burgdorferi that are strain variations in the USA alone. This is not even counting the greater variation that we see if we look at other related geno-species such as Borrelia lonestarrii in Missouri, or Relapsing Fever Borrelia in the SW USA, or the genospecies Borrelia garinii and Borrelia afzelii found in Europe, or the dozens of other related bacteria in the world that cause Lyme-like or Relapsing-Fever-Like diseases caused by various variant strains of Borrelia bacteria. Once you see this global picture you can never look at Lyme as an isolated disease ever again. It is part of a global-pandemic called Borreliosis.
But the tests that have been chosen for us, and dictated that we use are not based on any Borrelia found in nature! Why?
Since Borrelia identity changes quickly by inserting variant plasmid genes into its larger linear chromosome, the bacteria will always have built in variation unless you eliminate plasmids.
(Borrelia burgdorferi has about 31 circular or linear plasmid-chromosomes that facilitate genetic variation, it is estimated that over 60 genes can insert in at least three different chromosome loci resulting in over sixty to the 3rd power variations in the bacteria or potentially over 200,000 possible variations that could be predicted based on what we currently know.)
This creates an economic and practical dilemma for manufactures of Lyme serology tests who want consistency and reproducibility without the expense of isolating local bacteria from local ticks and growing them in the lab which is very difficult, time consuming, inconsistent and expensive. For this reason manufacturers use a strain that was developed in a lab that resists variation.
Strain B-31 that was originally isolated from the NE USA ticks, and was created through high-passage selection until it remained consistent from division to division.
B-31 is never found in nature, and when B-31 tests were compared and tested by independent researchers in Madison WI, France, Austria, and United Kingdom, B-31 had short comings and never had the essential antibody detection that the tests developed from local wild-strains produced. One can make an argument for B-31 consistency, but never for its local strain selectivity.
What makes this discussion about what strain we use to make Lyme serology tests completely moot; is the one fact that we completely ignore in the United States:
Once Borrelia bacteria breach the brain’s defenses, absolutely no Lyme serology test short of an autopsy can rule out infection within the human brain!
Here are some other considerations about Lyme test shortcomings:
- Dr. Lori Bakken Madison WI tested 516 labs across the USA using Lyme ELISA tests, and found them seriously lacking and only about 50 % accurate in consistency of positive tests. She used triple paired identical blinded samples. This independent test illustrates the fallibility of the Lyme ELISA test yet incredibly the ELISA is demanded by so called experts and medical authorities to be used as one of two screening tests used for the diagnosis of Lyme disease.
(Bakken LL, Callister SM, Wand PJ, Schell RF. Interlaboratory Comparison of Test Results for the Detection of Lyme Disease by 516 Participants in the Wisconsin State Lab of Hygiene/College of American Pathologists Proficiency Testing Progrm. J Clin Microbiol 1997; Vol 35, No 3:537-543
Bakken LL, Case KL, Callister SM et al. Performance of 45 Laboratories participating in a proficiency testing program for Lyme disease serology. JAMA 1992;268:891-895
Now consider the second screening test: The Western Blot was once a useful tool for diagnosing Lyme disease when used properly, but the National Western Blot Criteria meeting held in Dearborn MI changed this test from somewhat useful to useless and the logic and science behind it is so poor we have to ask ourselves what agenda did the committee of state epidemiologists and concerned patent-owners have? Yes people and institutions who had conflicts of financial interest had input into the two-tiered system of diagnosis that we currently use.
The nearly arbitrary decision to eliminate species specific antibody-bands from the reporting of the Western Blot tests definitely made the Western-Blot test less accurate. This change in accuracy did not come about from changing the actual test but rather by enforcing a reporting-bureaucracy that made the test less sensitive. Make no mistake the labs that do this test still see the positive bands that are banned from reporting, but are legally unable to report them.
Then to further cloud the already muddy waters of accuracy it was decided that all laboratories across the USA have to report all Western Blots as either positive or negative and not report the essential bands.
Not reporting significant Western Blot Band is to a scientist, tantamount to saying:
There are no contaminates in
your drinking water, so please don’t waste your time testing the well water, and if you do test the waters and find something that we haven’t reported, we have already deemed that the contaminates are unimportant and benign.
Well the contaminates (bands 31, and 34) aren’t as benign as we are told. Let’s look at the old Western Blot reporting criteria on 66 kids with a tick-bite and bull’s-eye rash compared with the new reporting criteria. This is the same test and same patients, but we are now using the Dearborn MI “Dressler” criteria for Western Blot reporting.
Western Blot and False Negatives in Children: 1995 Rheumatology Symposia Abstract # 1254 Dr. Paul Fawcett et al. This abstract showed that under the old criteria, all of 66 pediatric patients with a history of a tick bite and, Bull’s Eye rash who were symptomatic, were accepted as positive under the old Western Blot interpretation. Under the newly proposed criteria only 20 were now considered positive. That means 46 children who were all symptomatic, would probably under the previously mention YALE Criteria be denied treatment! That’s a success rate of only 31 %.
66 Children with Bull’s Eye rash Old W. Blot Criteria 100 % positive
New NIH Criteria 31% positive
The number of false positives under both criteria was ZERO %
* Note: A misconception about Western Blots is that they have as many false positives as false negatives. This is not true. False positives are rare.
The conclusion of the researchers was: “the proposed Western Blot Reporting Criteria are grossly inadequate, because it excluded 69% of the infected children.”
More issues with serology testing in Lyme:
- The human body starts to make IgM antibody at 4-6 weeks after exposure to the pathogen, and does not make IgG antibodies for many months, yet some “Lyme Experts” want to eliminate IgM Western Blot reporting completely. This would almost certainly mean less early Lyme disease detection because most doctors who use “Two-Tiered” testing protocols will test within the first two months of tick bite and the negative Western Blots will demand that they not treat. (See Yale treatment protocols above)
D) The Lyme bacteria can hide almost immediately within the human body.
Without a large enough number of bacteria (infection load) that remains in the
bloodstream for a sufficient time for the immune system to recognize the
pathogen, the human immune response will be minimal or absent.
Intracellular localization of Borrelia burgdorferi within human endothelial cells. Ma Y, Sturrock A, Weis JJ. Infect Immun 1991 Feb; 59(2): 671-8. PMID:
Characterization of Borrelia burgdorferi invasion of cultured endothelial cells. Comstock LE, Thomas DD. Microb Pathog 1991 Feb; 10(2): 137-48. PMID:
Penetration of endothelial cell monolayers by Borrelia burgdorferi.
Comstock LE, Thomas DD. Infect Immun 1989 May; 57(5): 1626-8. PMID:
Although the antibody tests would be negative possibly for years, the infection can still be alive and cause problems where it survives such as in the: joints, heart, inside endothelial cells, and inside the brain and more specifically inside brain neurons and glial cells. These bacteria cannot be detected with indirect methods like Lyme antibody test including ELISA and Western Blots, nor is it likely that DNA-PCR can detect these infections without heroic efforts to obtain proper sampling that goes far beyond just blood and urine. Time, money and expediency has forced doctors to use tests that are inadequate for the task of determining the worst possible scenario which is a persistent infection within the brain.
For the simple reason that most patients are not obviously or immediately affected by their neurological infection, the medical system has ignored these ticking time-bomb patients that are seronegative, and symptom free. But the neuro-lyme patients will pay a severe price for having doctors who refuse to go back and connect all the dots after these patients reappear in their offices with severe disabling symptoms.
Untreated and improperly treated tick bites can lead to patient disasters. Yet the treatment guidelines are so black and white that we have to now ask ourselves: Are we going to hold the users of these treatment guidelines accountable for their lack of any flexibility?
Patients are not paid to be experts in any disease, but when an entire medical community has limited all the options for sick patients both in diagnosis and treatment, then can we not hold these professionals to the same standards we would expect from a plumber? If the pipes leak, at least try and understand why?
Here is an example of unrealistic expectations from the medical community. In Valhalla New York a temporary Lyme treatment center was created that used the ELISA test to screen patients. Using this inadequate test it was determined that about 30 % of all walk in patients had Lyme disease. But here is what one of the coordinators had to say about it:
There is great hysteria about Lyme disease… less than a third of the patients who walked in to our center actually had Lyme disease.
Would we hold the same standards of accurate self-diagnosis to cancer patients, or heart patients? Do we publicly chastise patients walking into a sexually transmitted disease center and say: “These people are wasting my time! Only a third of them have VD!!!”
Why then is there a double standard for people who are losing their jobs, their marriages and quality of life who are just seeking answers. No wonder so many patients turn to alternative treatments. The options for Lyme disease patients to get diagnosed and aggressively treated in America is extremely limited and only getting worse every year!
Now consider this: Recently a Lyme disease expert stated nationally that there is no evidence of transplacental transfer of active infection from mother to fetus.
We have actually observed in culture Borrelia burgdorferi penetrating umbilical vein.
We also have nine case histories 1987-1989 that confirmed by either culture or direct tissue staining that in fact Borrelia burgdorferi does cross the placenta, and has caused still-births including infections within the fetal brain.
(See work and photo by Dr. Andrew Szycpanski Stony Brook Dept. of Pathology New York of Borrelia creating holes in umbilical vein.)
If I was a Obstetric Nurse or OB-GYN and told to repeat this factoid that Lyme does not cross the placenta as stated by our guiding experts on Lyme disease concerning pregnant patients, and then to also be forced by clinic administrations, insurance companies and peer pressure to rely on two-tiered testing, and follow published treatment guidelines that ignore our entire encyclopedia of knowledge on spirochetes, I would be worried! I would be worried that when the next fetal autopsy is done that I would be called to be accountable.
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This is a silver stained image of a Borrelia burgdorferi penetrating a fetal brain neuron at necropsy of a still-born fetus from a mother thought to be at low risk for Lyme disease and seronegative for Lyme antibodies on several lyme serology tests. Alan MacDonald
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If Lyme disease patients have early undetectable neurological infections that resist current antibiotic treatment regimens, then why haven’t we seen evidence of this?
First of all if you define treatment success by merely saying that the patient’s Lyme tests are now negative after treatment, you will by virtue of incredibly bad science never see treatment failures. This is because eliminating the infection from the blood is not the same as eliminating it from the heart, brain and joints. But serologies will fail to detect these areas of sequested infection where the bacteria fails to stimulate antibody production.
Next you have to look at follow-up. If you do a study that compares doxycycline to IV ceftriaxone and the only symptom is a bull’s-eye rash and your only determination of cure is the absence of rash and a negative ELISA test, and your only follow-up post treatment is two weeks. You will probably conclude that doxycycline is as effective as IV ceftriaxone, and insurance companies will smile and love you. (See M. Eckman )
Two things have been consistently true in nearly one dozen antibiotic treatment studies: The longer you treat the fewer relapses you have, and the sooner you treat after tick bite the better, and the longer you follow patients after treatment the higher the relapse rate will be. We have patients from Nantucket Island that were followed over five years after months of antibiotic treatment and still relapsed and it didn’t matter if intravenous drugs were used. What was more important was How long you treated and how soon after tick bite you treated. Overall the relapse rate after 5 years approached 50 %, but to get all the facts you had to go to a Lyme Conference because this final relapse rate was never published and conveniently left out
How antibiotics work:
In most cases bacterial lethal exposure occurs only during cell division. For a spirochete like Borrelia that is a slow divider (24 hours under good conditions) to get the same lethal exposure during cell-wall synthesis as say treating strep bacteria, you would have to treat for one year and five months. Using the old microbiology formulas for tuberculosis from the 1950s, we would expect both TB and Lyme disease to require in many cases over one year of antibiotics including combination therapy. Well we learned our lesson with Tuberculosis but not yet with Lyme disease.
Relapse or Failure %
Logigian (1990) 37% After 6 months, 10 of 27 patients treated relapsed or failed treatment. 17 (63%) improved, 6 (22 percent) improved, then relapsed, 4 (15%) had no response.”
Pfister (1991) 37% 33 patients with neuroborreliosis treated. After a mean of 8.1 months, 10 of 27 were symptomatic and borrelia persisted in the CSF of one patient:
Asch (1994) 28% 3.2 years after initial treatment: 28% relapsed with major organ involvement; 18% were reinfected. Persistent symptoms of arthralgia, arthritis, cardiac or neurologic involvement, were present in 114 (53%) patients.”
Shadick (1994) 26% 10 of the 38 patients …relapsed within 1 year of treatment and had had repeated antibiotic treatment.”
Shadick (1999) >37% 69 of 184 previously treated patients (37%) reported a previous relapse.
Treib (1998) >50% After 4.2 years, more than ½ of 44 treated patients with clinical signs of neuroborreliosis and specific intrathecal antibody production were symptomatic.
Valesova (1996) 38% At 36 months, 10 of 26 had relapsed or progressed: complete response or marked improvement in 19, relapse in 6, and new symptoms in 4.
End of Lecture Notes for Lyme on the Brain Part 2 by Tom Grier
COMING UP NEXT… Part 3 – A history of spirochetes in MS since 1911 to present day.
Madison Area Lyme Support Group 