Fwd: CDC/NIH Webinar: Lyme research moves in wrong direction

----- Original Message -----
From: Tom
To: MinnesotaLyme@yahoogroups.com
Sent: Monday, November 26, 2012 6:12 PM
Subject: [MinnesotaLyme] CDC/NIH Webinar: Lyme research moves in wrong direction

Observations and opinions on the CDC/NIH Webinar on Lyme Disease Testing

By Tom Grier

IgM = The earliest of antibodies produced in new infections. IgM can rise and fall as infections wax and wane

IgG = Late antibody that is more specific to the infection but take 4-6 weeks to be produced

Awhile back I viewed the taxpayer paid CDC webinar October 1st , 2012 on Lyme disease testing and future research directions. I was quite disappointed at both the direction of research and the analysis of current testing.

http://www.cdc.gov/lyme/diagnosistreatment/index.html

In the beginning Dr. Joseph Breen of the NIH encouragingly stated that because Lyme serology tests are indirect tests, that they cannot be used to determine cure and that they are striving to find a way to determine cure after antibiotics. Dr Breen also noted that antibodies in Lyme patients only appear after the optimum time to treat has already passed. He then went on to say that Lyme disease is difficult to accurately stage into categories such as Skin manifistations as stage one, Neurological manifestations as stage two or Arthritis as stage three, yet later on these three stages are used to access the accuracy of Lyme serology testing.

A mission statement if there is one seems to be to determine if Lyme persists after antibiotic treatment, but there is absolutely no mention of pathology, culturing or staining mentioned as part of that quest. The two animal models and studies that are mentioned that were done in mice and Non Human Primates I believe are the studies that have already done by Embers and Barthold. (Which have been heavily criticized by the very institutions that are now holding them up as research models?) and not new studies being funded.

The future direction the CDC and NIH seem to be taking with Lyme disease testing, is to create Four Research Initiatives that will last 2 years. With grants of approximately $150,000/year and any grants that are extended will be increased to perhaps $250,000.

Unfortunately three of the four initiatives are even more indirect testing than current Lyme serology testing.

Although Dr. Breen says culturing is the gold standard for detection and identification of active Lyme disease he goes on to say culturing is slow, expensive and variable in accuracy. Culturing does not appear to have a future with tax payer paid studies, nor does microscopy like con-focal laser microscopy that has huge potential for Lyme research.

The "New Direction" of Lyme testing is heavily based on Lymphokine, cytokine responses by immune cells and is an indirect analysis of whether a patient has been exposed to Lyme disease. Since several labs are already doing lymphokine response testing, one wonders if there will be patent infringement as these taxpayer paid initiatives proceed? Will the researchers who get these grants, soon apply for new patents involving lymphokine response Lyme testing? One thing is for certain, if these tests are accepted as proof "cure" without offering any supporting pathology, then Lyme patients can expect to be denied treatment by health providers with tests even less direct than antibody serology. Maybe that is a goal of this research ???

Only one of the four initiatives ever mentions the new emerging species of Borrelia that cause Lyme disease and STARI in the USA. That grant goes to Dr. Alan Barbour and the grant application description is simply:
"Informative Immunodiagnostics of Lyme Disease" which also sounds like vague indirect immune response analysis.

(Currently of the 10 species that cause Lyme disease world-wide, none are used in creating Lyme tests. Only lab strain Borrelia burgdorferi B-31 strain is used in serology testing, Pasteur Institute has repeatedly pointed out the short sightedness of accepting this as a world-wide standard of testing, and shown its inaccuracies when compared to tests using local wild strain isolates.)

The most disturbing aspect of the webinar was the way they analyzed IgM Western Blots to show a 27% false positive rate and why it is not a good test.

Dr. Joseph Brren begins by saying that in the first 30 days of infection that only the IgM Western Blot is effective and the EIA/ELISA tests are not yet sensitive to detect adequate antibody response. After 30 days EIA and IgG Western Blots can be and should be used.

None of the patient analysis addressed studies that show patients that have been seronegative but culture or PCR positive, or addressed antibody-antigen complexes that are not detectible by serology, nor did Breen address that all ELISA tests used by the CDC are whole cell preparations using laboratory strain B-31 and not one single new genospecies of Lyme like Borrellia bissetti or Borellia spielmani, B. andersoni, B. Americana. are being included in test preparations.

The CDC tests for Americans are not prepared with whole cell isolates of any of the European strains or newly emerging American strains. So we judge the inaccuracy of IgM Western Blots with ELISA tests with several built in flaws.

Since both patients and ticks migrate and travel it seems likely that a patient returning from Norway, the UK, Germany, France, Romania, or a dozen other countries with Lyme-like disease would likely test negative by CDC two-tiered testing and be told they cannot be treated. So are these patients false negatives? The CDC never discussed that scenario.

Here is where bad science from our own CDC and NIH really becomes a problem to the health and welfare of USA Lyme patients: IgM Western Blots are 27 % False Positives. Here is how they determined this figure.

First the general problems of Western Blots are three main areas: 1) faint bands are reported as positive, 2) Alignment of blotting strips could mean some labs report incorrect bands, 3) The complexity of interpreting Western Blots allows doctors to influence the tests to be positive.

Here is the bad science.

1) Even though Dr. Breen stated that of all the Lyme serology tests that only the IgM Western Blot is useful in the first 30 days, but now in this analysis of false positives; if a patient has symptoms beyond 30 days and a positive IgM Western Blot: then the positive Western Blot has to be wrong because IgM antibodies should have declined. This is bad science and human interpretation is interfering with scientific observation. The analysis is based on an incorrect assumption that the IgM test is not useful after 30 days.

2) If you have a negative ELISA test but a positive IgM Western Blot, then the Western Blot is false positive. This is also bad science for many reasons; the most important is that the ELISA test is notoriously inaccurate. When institutions other than the CDC test the ELISA tests in real world conditions over 500 labs were only 50 % accurate (Lori Bakken College of Pathology and Lab Testing) I can site many more studies but to negate and ignore a sick and symptomatic patient and ignore a positive IgM Western Blot positive test on the basis of a predesigned standards that are based on bad science, is too much like the old witch trials where if the witch drowned she was not a witch.

You can't advance science and testing if you design into your testing-paradigm a flaw. Using a negative ELISA test to prove the Western Blot is false positive is bad science and bad study design.

3) Incorrect Interpretation of Bands is another source of false IgM Western Blots: Borrelia binding protein 39 kDa is a surface protein specific to Lyme. How does one reconcile a bacterial protein's presence as negligible? That is like catching a hailstone and being told it was not hailing because national weather radar didn't show any hail. Radar is less accurate than a hailstone in your hand, and likewise an IgM Western Blot 39kDa band is more decisive than an ELISA test with a high cut-off point of 512 or even greater. (Some major labs still use 1024 titers as a cutoff.)

A significant portion of the false positive rate for IgM Western Blot is assigned to incorrect bands are being reported which accounts for false positives. No one at the CDC has yet addressed the Deerborn MI or Dressler criteria of Western Blot reporting, it is simply assumed that if you report bands 31 and 34 or a single 39 band as significant then it has to be a false positive. This is bad science times 2x.

The Dressler criteria was not designed to diagnose Lyme as much as it was to eliminate patients who received the Lyme vaccine. Also the idea that the number of bands that are positive is important is quite arbitrary. A good scientist would say it is which bands you see and not how many. A good scientist would say a single case of a patient being culture positive but is negative by 2-tiered testing would show 2-tiered testing is not 100 % accurate in chronic neurological Lyme disease. We already have that data many times over, yet the CDC did not address the flaws in their study designs. If the paradigm of reasoning is wrong then so are the results.

When you eliminate the three reasons for Western Blot False Positives you have a test that has almost no false positives, just as shown by Dr. Paul Fawcett over a decade ago when addressing the pitfalls of the Dressler Western Blot Reporting Criteria in 66 kids with EM rashes. Old criteria 100 % positive with no false positives in the control group. Using the new Dressler Criteria on the same 66 kids Fawcett reported 33% positive IgM positive using the exact same blood samples.

The Dressler reporting criteria is partly based on arbitrary logic and often yields arbitrary responses.

Another distressing point of interest is that according to the CDC testing, two-tiered testing is 97-100 % accurate to detect chronic neurologic involvement. I don't know if this means they are admitting that chronic Lyme in the brain exists or not? What I am concerned with is the basis that they reach this figure of 100 % accuracy. It too is based on poor assumptions and bad science. There is no infection more serious than a brain infection yet they offer no brain pathology to support this claim. Yet once again we have that data that already exists and proves this claim of 100 % to be wrong. In my opinion as a nation we should be collecting more brain pathology and not wasting millions on Lymphokine profiling and immune responses that will be hailed as new break through tests, generate millions of dollars in patent rights and give patients nothing in return accept more indirect and inconclusive tests.

As usual the CDC will not redress their previous mistakes, nor are they moving in a direction that can shed new light on this disease nor move in a direction that truly helps patients already suffering.

I predict that in two years the newly proposed CDC/NIH testing initiatives as outlined will produce nothing significant towards the outcome of either diagnosis or treatment of Lyme disease or resolve the question of persistent infection with Borrelia after antibiotic treatment.

The new initiatives fail to address:

A) The long history of culture, and PCR positives in seronegatve Lyme patients
B) The continued use of B-31 strain and no attempt to use other new genospecies of Lyme
C) The refusal to look at the world-wide picture of Lyme and start to accept European strains in our local testing
D) The poor science behind the Dressler Criteria of Western Blot Reporting
E) A long-range research program that uses any pathology especially brain autopsy to address persistent infection post antibiotics or presence of CNS infection in seronegative patients.
F) The reliance of assumptions based on bad science and bad reasoning in serology testing such as ELISA tests are more accurate post 30 days than IgM Western Blots or that 2-tiered testing is 100% accurate in late "chronic" neurological Lyme when this has never been put to the test through pathology testing of the brain.
G) The development of more direct testing like antigen capture and laser microscopy.
H) Treatment guidelines that are rigid and may be harming Lyme patients.