ELISA and Western Blot: Lies that can kill you?

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ANTIBODIES ARE NOT A DIRECT MEASUREMENT OF ACTIVE INFECTION

ENTER THE WESTERN BLOT

MECHANISMS OF IMMUNE ESCAPE

REFUSAL TO ACCEPT A PATIENT'S SYMPTOMS AS PROOF OF INFECTION

LYME NEUROBORELIOSIS REPRESENTS PERSISTENT INFECTION WITH b. BURGDORFERI

BORRELIA BURGDORFERI CAN FIND SAFE HAVENS IN SEQUESTERED SITES

JUST A HANDFUL OF HUMAN STUDIES HAVE BEEN DONE USING BIOPSIES

POST-MORTEM LYME DISEASE TISSUE STUDIES

THERE HAS NEVER BEEN A CORRELATION BETWEEN ANTIBODY TITER AND THE NUMBERS OF LIVE ORGANISMS PRESENT.

THE CASE FOR SEQUESTERED PERSISTENT INFECTION

YALE PUTS MORE FAITH IN SEROLOGY TESTS THAN IN A PATIENT'S SYMPTOMS

ACCURACY of the WESTERN BLOT USING the NEW SUGGESTED CRITERIA

THE PROPOSED WESTERN BLOT REPORTING CRITERIA ARE GROSSLY INADEQUATE

LYME TESTS FAIL AGAIN

THE CURRENT NIH LONG-TERM TREATMENT STUDY HAS SHOWN FLAWS FROM THE VERY BEGINNING

Western Blot used to 'confirm' ELISA

EDITORIAL by THOMAS GRIER from SPOTLIGHT ON LYME, Newsletter of the Lyme Alliance.

ELISA and Western Blot test results: Lies that can kill you?

KEY WORDS:

Antibody -------- A protein produced by a white-blood-cell to attack bacteria and viruses

Titer ------------- Another word for level, as in level or amount of antibody measured in the blood

Seronegative --- Despite an infection there is an absence of antibodies in the blood or serum of the patient.

Spirochete ------ A spiral bacteria in the same family of bacteria as Syphilis.

Borrelia burgdorferi --- The spirochete bacteria that causes Lyme disease

Erythema Migrans ---- A red expanding rash on the skin caused by an infected tick bite. An EM rash is diagnostic for Lyme disease even in absence of a positive test.

Antigen ------------ refers to a foreign substance in our blood that is capable of causing an immune response

There isn't a disease in the past 100 years that has polarized the medical community more than Lyme disease.

From the very beginning Lyme disease was misunderstood. In the early 1970s two concerned mothers, Polly Murray and Judith Mensch, were convinced that the epidemic of Juvenile Rheumatoid Arthritis (JRA) cases that they were seeing in their neighborhoods, were being contracted as a result of some kind of environmental exposure rather than a genetic disorder.

After the State Health Department admitted that the JRA incidence rate in Old Lyme CT was at least eight times the national average, they somewhat reluctantly decided to investigate the observations of these two woman. (Murray and Mensch had to present actual patient case histories that they collected before an investigation was started.)

In 1975 a rheumatologist named Dr. Alan Steere first described these abnormal cases of "JRA" in the medical literature as a new type of arthritic disorder. He coined the term "Lyme Arthritis". This led to an immediate misunderstanding of the disease, and Lyme disease was incorrectly thought of for many years as strictly an arthritic disease.

Six years later in 1981 the actual cause of Lyme disease was discovered to be a new species of spirochetal bacteria that was transmitted to humans from the bite of infected "deer" ticks.

Almost ten years after Steere's description of Lyme disease as an arthritic disorder, it was now becoming recognized that Lyme Disease was in fact much more than just a new type of arthritis. Lyme disease was now being recognized as being equally capable of causing severe and devastating neurological disorders!

Pachner AR, Steere AC. The triad of neurologic manifestations of Lyme Disease: Meningitis, cranial neuritis, and radiculoneuritis. Neurology 1985;35:47-53

The cause of Lyme disease was discovered in 1981 to be caused by a bacteria transmitted by the bite of infected ticks. Dr. Willy Burgdorfer was the first to isolate the spirochetal bacteria from the midgut of Ixodes "Deer" Ticks from ticks from the Shelter Island Area. (Shelter Island is near the coast of New York and New Jersey)

Shortly after 1981 when the cause of "Lyme Arthritis" was known to be a bacteria, Lyme articles that appeared in the medical literature quickly assumed that the Lyme spirochete was similar to other bacterial infections. Many treatment studies based there protocols of antibiotic treatment on other bacterial infections such as strep throat.

The conclusions of most early studies that had short patient follow-ups concluded that you could expect Lyme disease to respond to 10-14 days of antibiotics. The antibiotics that were tested in the test tube and deemed to be effective at that time included: erythromycin, tetracycline, and penicillin.

From the very beginning treatment failures were seen in virtually every antibiotic study done. The longer the patient follow up the higher the incidence of treatment failure.

The medical community blamed early treatment failures on the older antibiotics, erythromycin, tetracycline, and penicillin and has long since accepted that these antibiotics are mostly ineffective at curing Lyme disease. What was being ignored was that the newer antibiotics were also consistently failing at preventing relapses of active infection.

Ever since these early treatment studies the concept that two weeks of antibiotic therapy is adequate treatment for Lyme disease has remained ingrained into the medical communities collective consciousness. This is despite the fact that in the first fifteen years since the discovery of the disease in 1975, virtually every antibiotic treatment study consistently recognized treatment failures.

Further, the longer patients were followed up after they received antibiotic treatment, the higher the relapse rates would climb. (See Nantucket Island Study Dr. Nancy Shadick et al.)

The Long-Term Follow-up of Lyme Disease: A Population-Based Retrospective Cohort Study Authors: Shadick NA; Phillips CB; Sangha O et al. Ann Intern Med 1999 Dec 21;131(12):919-26

* Data from the Nantucket Island study was presented By Dr. Nancy Shadick at an International Lyme Symposia. Those patients in the study that were followed for up to 5.2 years after initial antibiotic treatment had ever climbing relapse rates. Relapse rates in patients that received two weeks of IV Rocephin (ceftriaxone) could expect a relapse rate to exceed 50% after 5 years.

Other factors that contribute to relapse post treatment seem to include length of infection before diagnosis, choice of antibiotic used, and the severity of symptoms at time of evaluation.

While from the very beginning there have been thousands of patients that have complained of still being sick and symptomatic despite supposed adequate antibiotic treatments, most of the medical community has ignored the patient's observations, and labeled them as being cured. This is despite the fact that they still have most of the same symptoms that brought them to their doctors in the first place?

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SO WHAT DETERMINES A CURE IF THE PATIENT STILL HAS THE SYMPTOMS OF THE DISEASE?

In many cases it is not the patient's disability that determines the disease state but rather the presence or absence of natural immune factors or antibodies. THE PROBLEM IS ANTIBODIES ARE NOT A DIRECT MEASUREMENT OF ACTIVE INFECTION EITHER.

How could this have happened?

Part of the problem was the newly emerging science and technology of antibody serology testing known as ELISA tests. (Enzyme Linked Immuno Sera Assays)

ELISA tests look for an enzymatic color change that indicates the presence or absence of Lyme antibodies in a patient's serum.

If you still see a color change when a patient's serum is diluted with 512 parts water then it is said a patient has a dilution titer of 1:512

NOTE - higher titer numbers do not have any correlation to how sick a patient is feeling! In fact a high number indicates the presence of lots of immunity. A patient with a high titer is better able to fight the infection than someone who is producing low numbers of antibody or has a borderline or even negative titer.

Not only was it clear that ELISA tests were quick and easy to develop, but they were cheap and easy to administer. The convenience of ELISA tests was a powerful enticement to both doctors and patients. Let's face it 10 CCs of blood is more convenient than having several brain, skin, bladder or heart, biopsies that would cost thousands of dollars!

The problem was that from the very beginning it was assumed and generally accepted that these tests were a better diagnostic tool than patient evaluations based on symptoms and a response to treatment.

It was erroneously accepted that the absence of antibodies in the blood meant no infection was present anywhere in the patient's body.

Even more disturbing was the incorrect assumption that the drop in antibody levels during treatment indicated a microbiological cure. Thus, many studies concluded that patients were cured if they eventually tested negative for Lyme antibodies.

Both assumptions were and continue to be incorrect!

It certainly looks good on paper for a doctor if he can tell a patient that based on the test that they are negative for Lyme disease, but in reality the more accurate statement is that the patient is simply negative for the presence of those antibodies for which that particular test is sensitive for! But absence of antibodies does not mean the patient cannot have active infection.

ELISA TESTS CAN VARY GREATLY FROM LAB TO LAb. Since each lab holds there own patent on their own test, they are all competing to say they have the best test. It is a competitive business, and certain buzz words like specificity, sensitivity, efficacy, and accuracy are used to try and out sell one competitor's lab test over another.

This gives rise to many methods of testing efficacy, which are implemented by competing labs to be able to say that their test is better than the competition's tests. This is usually based on predetermined laboratory standards.

Unfortunately, laboratory methods of determining an ELISA test's efficacy and accuracy does not directly correlate to accuracy of determining infection in a human being.

If a laboratory tests its ELISA test on 100 test tubes of an identical known sample, and simultaneously on 100 test tubes of distilled water (the control group), and it picks up 99 of the 100 samples and only one of the control samples the lab can claim their test is 99% accurate. It had a 1% rate of false negatives and a 1% rate of false positives. (The lab chooses what dilution titer it accepts as positive. For one lab it maybe 1:256 for others it is as high as 1:1024)

A 99% sensitivity sounds great and most doctors and lay people would say if they heard this data that this ELISA test is 99% effective, and accurate.

But these tests cannot tell you if a patient who is infected but makes no antibodies (seronegative patients) has active Lyme disease. Also there is evidance that in humans with high titers the tests can still be as high as 55% inaccurate!

The admission that the Lyme bacteria is alive and sequestered in some seronegative patients is not welcome news to the developers of these tests. But rather than do the type of autopsy and tissue studies to truly compare their tests, the manufacturers have chosen to manufacture PATIENT STUDIES THAT DON'T COMPARE THEIR TESTS TO TISSUE STUDIES BUT INSTEAD TO OTHER EQUALLY BAD SERUM TESTS.

If a carpenter only has a yard stick 29 inches long, and he only tests its precision with another yardstick 29 inches long it will always appear that his yardstick is accurate!

So how do the lab's claims to the efficacy of these tests actually stand up in the real world for the diagnosis of Lyme disease?

Hundreds of labs and ELISA tests were evaluated by an independent sources, and were found several times to be less that 65% accurate. (This was based on triple-paired identical positive serum samples that were sent to 516 labs across the US) In some cases some labs were far below this average.

So without even arguing that some Lyme patient's blood can be antibody negative despite an active infection, even in the patient whose blood is highly positive, that patient still runs as much as a 45% chance or higher of still testing negative with an ELISA test.

So a patient can be antibody negative and still have infection, but they can also have loads of antibody and still test negative simply by virtue of the lab's inability to deliver consistently accurate results.

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[ENTER THE WESTERN BLOT]

Now consider this. By today's diagnostic criteria if you test negative by ELISA you don't have Lyme disease. But if you test positive you still do not have Lyme disease until you test positive by Western Blot.

I will cite a recent study that shows that the Western Blot can be less than 50% accurate too. So statistically if the ELISA test is 65% accurate and a Western Blot is 50% accurate if you multiply these probabilities there is now less than a 33% chance of testing positive using the TWO TIERED TESTING APPROACH!

The biggest problem for Lyme patients today is that the medical community still by and large makes the same two incorrect assumptions about blood based testing.

This includes the more recent PCR [polymerase chain reaction] DNA blood tests, which still have the same pitfalls as antibody serologies in that the absence of infection of the bloodstream does not mean absence of infection in the body.

Two important points to remember about Antibody and PCR testing:

1) The absence of antibody (or bacterial DNA) does not prove absence of infection.

2) The drop in antibodies (or the absence of Bb DNA) does not guarantee that a patient is cured, and that the patient won't relapse from active infection.

Illustrated example: Let's consider that antibodies or bacterial DNA in the patient's serum are like hailstones you see during a hail storm. If you go out in your front yard during a hailstorm with a 5-gallon pail. You stand there for several seconds but you don't collect a single hailstone. What can you conclude about whether it is hailing out?

The absence of a hail stone in a small bucket doesn't exclude that it could have been hailing in your backyard. We can use a larger bucket and increase our odds, but what if the hailstorm is just on one corner of your yard? Likewise a small 10 cc vial of blood may be inadequate to find an infection that isn't even in the blood!

A very important observation: There is a history in medical literature of symptomatic seronegative Lyme patients that have received aggressive long-term antibiotic therapy that have been culture positive for active infection post therapy! So tests can be and are fallible, and the infection can persist despite lengthy and aggressive antibiotic therapy.

Other persistent infection studies have shown the presence of Borrelia burgdorferi antigens, bacterial particles, bacterial DNA/RNA, and found the presence of the bacteria in tissue biopsies in patients despite antibiotic therapy.

Using staining techniques that are sensitive for spirochetes, researchers have found the bacteria in the tissue biopsies from both in living patients, and sequestered in patient's tissues at autopsy.

All of these methods are a much more direct measurement of the presence of the Lyme bacteria than antibody blood tests. But they are impractical tests for the average doctor to perform on a daily basis.

Why can an infection be present in the body without the immune system making measurable antibodies?

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MECHANISMS OF IMMUNE ESCAPE:

Without the infection being in constant contact with the (blood-borne) immune system, the body shuts off antibody production. Antibody levels will fall even despite the fact that the infection is still sequestered deep in the body such as the brain, tendons, heart, nerves, bladder, eyes, and joints.

How do we know this?

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Because the MEDICAL COMMUNITY HAS BY AND LARGE REFUSED TO ACCEPT A PATIENT'S SYMPTOMS AS PROOF OF INFECTION, and have continually based their diagnosis of Lyme disease on Lyme serologies, there has been an ever growing schism between so called "Chronic Lyme Patients", and a medical community that refuses to accept their claims as still having active infection post treatment.

In many cases not only are serologies used to determine the diagnosis but the drop in antibodies is often used to indicate a biological cure.

It has been the variable nature of the disease and its wide range of symptoms, and the reliance on unreliable tests that has given rise to two different camps concerning the diagnosis and treatment of Lyme disease. The evolution of these two opposed paradigms of diagnosis and treatment will be discussed in the next section.

PART TWO "The Need For A Post-Mortem Lyme Disease Syudy" by Tom Grier

"The Need For A Post-Mortem Lyme Study"

The medical community is unevenly divided into two opposing camps on three major issues concerning Lyme Disease:

1) What constitutes a proper diagnosis of Lyme disease?

2) What constitutes proper treatment for patients with Lyme disease who have symptoms that persist beyond four weeks of antibiotic therapy?

3) What role should Lyme tests play in both diagnosis and treatment?

The first camp, which I will call Camp A, represents the majority of the medical community and is spearheaded by researchers from Yale Medical, the American College of Physicians (ACP), and several other major medical institutions.

In general terms, this camp believes that Lyme disease is best diagnosed through the use of two consecutive serology tests; the ELISA test followed by a confirming Western Blot. This is known as TWO-TIERED testing. (With very little opposition by the medical community, two-tiered testing has now become the diagnostic standard of most major medical centers.)

Camp A also maintains that Lyme disease, despite the stage or severity, is usually cured with just a few weeks of oral antibiotics. (This is the by far the most popular position within the medical community and the health insurance industry at this time.)

How does Camp A make a diagnosis of Lyme Disease? In the past a history of a tick bite followed by a bull's-eye skin rash or erythema migrans rash was diagnostic of the disease, but a diagnosis based on the rash and symptoms alone has come under increasing attack by several advocates of TWO TIERED testing including Yale Medical (see Yale Medical Report) and the ACP.

A video training tape by the ACP is quite explicit in its portrayal of Lyme patients that in the absence of an erythema migrans (EM) rash, the diagnosis must be made by dual serologies and more than two weeks of antibiotics is almost always unnecessary.

In one of the video scenarios, the tape suggests to treating physicians that patients who insist that they have persistent symptoms post-treatment should be referred to psychiatrists. The logic of this psychiatric referral stems from the premise that since antibiotics are accepted as curative, any persistence of symptoms has to be purely psychological. So if a patient doesn't feel better post treatment, send them to a shrink!

The second camp, often referred to as "LYME ADVOCATES," and which I will call Camp B, believes that most of the persistent symptoms post-antibiotic treatment are caused by persistent infection.

This camp maintains that antibody serologies are poor at detecting a spirochetal bacterial infection that has sequestered in deep tissues and no longer found within the bloodstream.

They believe spirochetes that have found sequestered, or privileged, sites tend to hide in the body and are poorly detected by any means. As proof of their position, this camp offers numerous studies which have shown persistence of Borrelia infection post-antibiotic treatment.

Listed below are several of these published cases of persistent infection in humans and animals post-treatment as confirmed by either culture or tissue biopsy and stain: (For further information, please refer to the compendium of references to the persistence or relapse of Lyme disease at Lyme Links .

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"These data suggest that LYME NEUROBORELIOSIS REPRESENTS PERSISTENT INFECTION WITH b. BURGDORFERI."

The study used nonhuman primates as a model for human neuroborreliosis, and used a special PCR technique to detect the presence of Borrelia DNA within specific structures of the brains of five rhesus monkeys. The monkeys were injected with strain N40Br of Borrelia burgdorferi, and later autopsied for analysis.

ABSTRACT SUMMARIES:

To do these kind of tissue studies of sequestered spirochetal infections takes nearly heroic efforts in time, costs, and diligence. Yet the few times that these types of studies have been applied to humans have suggested that Borrelia burgdorferi can indeed survive and thrive within the human body despite a complete course - or even several courses - of antibiotic therapy.

Camp A maintains that Lyme disease is relatively easy to diagnose by means of serology and is easily cured with antibiotics. So it follows that any study proving active infection post-antibiotics would disprove their position.

Yet despite several such studies and case histories, Camp A still maintains that persistence of symptoms post-antibiotic treatment of Lyme disease is not due to persistence of infection.

Why? How can they maintain this position if it has been repeatedly disproved?

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Compared to the literally thousands of CHEAP AND EASY LYME SEROLOGY TESTS that have been done, (many performed by drug companies and medical centers to prove efficacy of their Lyme tests), JUST A HANDFUL OF HUMAN STUDIES HAVE BEEN DONE USING BIOPSIES, cultures, and tissue stains post-antibiotic treatment. Many are single patient case histories that were submitted as abstracts, but never published.

The reason so many more studies use serologies instead of biopsies is time and money. It is simply easier to do blood tests. And, if you accept the premise that blood tests as accurate, then you must also accept the results that you get with those tests. Unfortunately, the medical community has decided to accept the blood tests despite their proven flaws. (see Bakken: ELISA / Western Blot accuracy testing)

Remember the yardstick analogy? If you continue to test the ability of Lyme blood tests to diagnose Lyme based on more blood tests you always get the same conclusion that Lyme is over diagnosed and over treated and that a few weeks of antibiotics is adequate.

But those few times when Lyme patients have been biopsied we have seen repeated evidence that the Lyme spirochete can indeed persist in the human body despite months of high dose antibiotics.

A large part of the reason why doctors prefer a blood test to other diagnostic methods is because a blood test looks definitive on paper, it satisfies insurance companies, and patient compliance to submit to a simple blood test is high.

If your doctor asked you for either a blood sample or several brain biopsies, which would you opt for? If you were a researcher and you could afford to do five patients using the biopsy method or 100 patients using blood tests, which would sound more appealing as a publishable study? A five patient study or a 100 patient study?

So you can see why researchers have latched onto the easy sampling methods as their diagnostic tool of choice. Once a researcher has repeatedly based his conclusions on the serology method only (thousands of serologies) then it becomes increasingly difficult to throw out all of his conclusions and theories based on just a handful of other researcher's tissue biopsies!.

Changing paradigms of thinking is difficult! It took 14 years to accept the Australian research that most stomach ulcers were caused by bacteria!

IF the results of those same tissue biopsies also threaten to affect

THEN it become increasingly more difficult to accept the concept that PERSISTENT INFECTION POST TREATMENT IS NOT ONLY POSSIBLE BUT MAY BE COMMON.

Early treatment studies often estimated that the number of treatment failures was as high as 10%, but those studies that had at least a six month follow up of patients suggest that treatment failures maybe as high as 30-57% if followed for six months to five years post treatment!

If this new data adversely affects the reputation of the doctor who failed to treat thousands of patients because of his serology-based belief system, then you see it becomes almost impossible to shift diagnostic paradigms.

There is now a question of professional reputation at stake as well as millions of dollars in tests, patents, and potentially millions in malpractice lawsuits.

It may not even be up to just the doctor anymore to make this kind of decision. He may be under severe peer pressure to curtail his opposing viewpoints for the sake of the institution he works for and the welfare of his fellow doctors who are not yet ready to accept that they have allowed patients with central nervous system infections to go untreated.

We have all heard the stories of doctors who treated Lyme patients that were told by their peers and / or HMO to cut costs and to not accept Lyme patients. HMOs have often used team bonus incentives to CURB THE ALTRUISTIC DOCTORS FROM TAKING PATIENTS THAT ARE COSTLY.

For example in a clinic with 200 doctors: If the doctors get rid of the one doctor in the clinic who is "overdiagnosing and overtreating" his Lyme patients then the group bonus would go from say nothing back to $30,000. What kind of pressure do you think the Lyme treating physician would be under from his 199 peers?

It would take real character for a doctor to admit that he has told thousands of patients, based on inaccurate tests and the denial of contrary evidence, that they aren't sick despite the patient's repeated insistence that they are in fact still sick.

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[POST-MORTEM LYME DISEASE TISSUE STUDIES]

In today's litigious society where administrations dictate policy, I feel many doctors have simply acquiesced and have taken the path of least resistance. A serology based diagnosis looks safest on paper. Safest, that is, unless a post-mortem Lyme disease tissue study proves otherwise!

Let me give you a local example in Duluth MN: A man phoned me and told me about his strange untreatable Rheumatoid arthritis, he mentioned he and his brother and his father were all avid sportsman from an area rife with Lyme disease.

When he told me his brother had non-remitting MS [multiple sclerosis] and his father was in a nursing home with Alzheimer's, I started to see a pattern. Despite the different diagnosis's they all shared similar symptoms that were consistent with Lyme disease.

Shared Symptoms: Sensitivity to bright lights, migrating joint pain, head aches, muscle twithches, stiff crunchy neck, floaters in the eyes, heart palpitations and chest pains, depression, hearing disturbances, night sweats, strange burning skin sensations, sensitivity to noise, urinary frequency/urgency but decreased urinary volume and many more.

Both the sons in their 30s responded slowly but steadily to constant antibiotics, and neither one has either MS or arthritis. When they asked their father's physicians to test for or treat their father for Lyme disease the doctors became furious and refused to not only treat, but refused to even do a single Lyme test.

Despite the strong family history and symptoms and life-long exposure to infected ticks, the doctors refused to even entertain the possibility that the man dying in the nursing home of senile "Alzheimer's like" dementia could possibly have Lyme disease.

Why? What did the doctors have to lose with this patient?

I believe they were afraid of exactly what the autopsy tests showed! The boys wanted to be absolutely sure one way or another if their father had long standing untreated Lyme disease.

After all TRUE ALZHEIMER'S MAY HAVE A GENETIC COMPONENT, BUT LYME DISEASE IS TREATABLE!

When their dad died they sent his brain to a pathologist who specializes in brain sectioning, and silver stain.

In virtually every cross section of the cerebral cortex spirochetes were found. Further they were consistent with Borrelia burgdorferi and even more astoundingly, in a serial cross section where several slides were made of the same brain cell and bacteria, a spirochete was found half in and out of a human neuron.

This is important because although we have seen in-vitro penetration of human fibroblast cells, macrophage, B-cells, and rodent neurons, we have never seen in-vivo evidence ever before of intracellular spirochetes in any human cell let alone human brain cells. This was a huge discovery.

When the son of this man tried to see the doctor to discuss the autopsy findings he flatly refused, and in fact became quite agitated and said that it meant nothing and meant he probably died of Syphilis!

The son and his entire family including his mother had Syphilis tests which all were negative and once again tried to see the doctor. Almost immediately a restraining order was placed against the patient's son.

He only wanted to know why the doctor didn't test for Syphilis if he thought it was Syphilis? Why hadn't father hadn't been given a Syphilis test or treated for syphilis? [See Jim Forris story LA Spotlight])

[ELISA and WESTERN BLOT test results may be LIES THAT CAN KILL YOU]

Everyone wants a cheap and easy blood test, but the reality is that despite the manufacturer's claims, is that these tests are poor and have continued to be about the same degree of inconsistency for nearly two decades.

Many manufacturers who claimed their tests were 90% or better in accuracy found that when their tests were independently tested on known samples, their accuracy averaged 45-65%. (See Bakken: The American College of Pathologist's Proficiency Testing)

The few studies which have proven persistent infection post-treatment simply have not been enough to fend off the overwhelming numbers of cheap and easy serology studies that erroneously conclude the absence of antibodies means the absence of infection.

Many early Lyme treatment studies actually used the drop in antibodies in a patient to determine a biological cure and an endpoint to treatment. These studies are still being quoted today.

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BUT THERE HAS NEVER BEEN A CORRELATION BETWEEN ANTIBODY TITER AND THE NUMBERS OF LIVE ORGANISMS PRESENT.

So these studies, which have often claimed high cure rates, were based on a false assumption that the absence of antibodies meant the absence of infection.

(Remember the hail-stone analogy? The absence of a hailstone in your bucket cannot prove that it isn't hailing somewhere on you property!)

The adoption of TWO-TIERED antibody testing as diagnosis still relies on the same false assumption that high levels of antibody mean active infection.

If antibodies drop with treatment you are cured, so you would think then that a high positive test post infection would mean a continuance of infection? But this is not allowed! Persistent antibodies just means a previous exposure to the bacteria and does not mean that you have an active infection remaining post treatment.

The ACP and other medical institutions have maintained that positive antibody titers don't necessarily mean the presence of active infection. So, a patient who still has high antibodies post-treatment can be ignored and should not be retreated, despite persistent symptoms. So PERSISTENTLY HIGH ANTIBODIES CAN BE FOREVER DISMISSED IN A PATIENT THAT HAS BEEN PREVIOUSLY TREATED.

Despite numerous studies showing culture positive patients can have virtually no measurable antibodies, we still accept TWO-TIERED testing as the diagnostic standard.

Furthermore; those patients who test positive to both tests can in some cases be dismissed as false positive by reason of previous treatment despite their positive antibody titers or lingering symptoms.

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THE CASE FOR SEQUESTERED PERSISTENT INFECTION:

The idea that antibiotics can clear the blood stream of the infection but not privileged sites has given rise to the theory of "re-seeding" infections. These are infections that for periods of time after treatment can appear to be cured, but will reoccur when the infection "load" once again build up and re-enters the blood stream.

The absence of spirochetes from the bloodstream and the subsequent lack of contact with white blood cells results in the decreased production of antibodies in the blood.

The patients test negative, but metabolically inactive bacteria can still remain in protected sites in the body. Eventually, when conditions are right, the hidden bacteria will reproduce and reintroduce bacteria back into the bloodstream, or "re-seed" the infection back into the circulatory system.

While opponents of this theory say the absence of antibody is equated with the absence of active infection, they also maintain that the persistence of antibody is a residual effect of previous infection.

This, too, is an emphasized point by Yale and the ACP. A synopsis of this view point can be found in the Yale Medicine Report, May 15, 1996 in an article by Marc Woortman which states that: (Excerpts from page 11, Yale Medicine, May 15th, 1996)

`` If you suspect the tick was attached for at least 36 hours, observe the site of the bite for development of the characteristic skin rash, erythema chronica migrans (sic), usually a circular red patch, or expanding "bull's eye," that appears between three days and one month after the bite.

Not all rashes at the site of the bite are due to Lyme disease. Allergic reactions to tick saliva are common. Preventative antibiotic treatment is not necessary, is costly, and may cause side effects.

If symptoms of later-stage Lyme disease develop, such as arthritic swelling of a joint, most often the knee, or facial nerve palsy, have a test done. If the test is positive, have a more precise test done. Only if this test proves positive should a course of antibiotic therapy begin. Expect some symptoms to linger up to three months. No further antibiotic treatment is necessary. '' ...

It is clear that the Yale perspective on diagnosing Lyme disease is that LATE STAGE LYME SYMPTOMS, including a swollen knee and Bell's Palsy, do not warrant antibiotic treatment despite a positive ELISA test!

The statement from the second paragraph tells us the intentions, "Only if this [second] test proves positive should a course of antibiotic therapy begin.".

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This statement tells us that YALE PUTS MORE FAITH IN SEROLOGY TESTS THAN IN A PATIENT'S SYMPTOMS:

Even symptoms that include

must all be ignored because antibiotics are costly and could cause side effects!

Apparently no one told this to dermatologists who often prescribe tetracycline for acne for years at a cost of about $10 a month.

I have to ask; What motivates these doctors to deny treatment to a symptomatic patient who has a rash and a positive ELISA serology?

If a doctor's kid had a documented history of a tick bite (less than 36 hours), an EM rash, Bell's palsy, a swollen knee etc. And then had a positive ELISA test but a negative Western Blot, I have to believe that that family member is going to get antibiotics despite the negative second test! Further I would consider it gross negligence not to do so.

So then can Yale be serious about this protocol? Yes. They have made it repeatedly clear in writing that THEY ARE; and several patients referred to clinics using the TWO TIERED protocol have been DENIED further antibiotic treatment because of the acceptance that symptoms and a single positive test can be ignored if a confirmatory second test is negative. Some clinics even require two positive tests within two weeks of each other!

We know the limitations of the ELISA test when independently tested but WHAT ABOUT THE RELIABILITY OF THE WESTERN BLOT TEST? (If it is so good why don't we just skip the time and expense of the ELISA test and just go straight to the Western Blot?)

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ACCURACY of the WESTERN BLOT USING the NEW SUGGESTED CRITERIA

Western Blot and False Negatives in Children: 1995 Rheumatology Symposia Abstract # 1254 Dr. Paul Fawcett et al.

This was a study designed to test the adopted changes to Western Blot Interpretation and reporting by the Second National Conference on serological Testing for Lyme Disease.

Changes in reporting included the limiting of the bands that could be reported on a Western Blot for diagnosis to: IgG Western Blot- must have five or more of these bands: 18, 23-25,28, 30, 39, 41, 45, 58, 66, and 93 kda. The IgM Western Blot must have two or more bands of the following three bands: 23, 39, 41.

Conspicuously absent are the most important bands 22, 25, 31, and 34 which include OSP-A (outer surface protein A), and OSP-B antigens. Two of the most widely accepted and recognized antigens.

These antigens are so immuno reactive that they were the antigens chosen for human vaccine trials. Yet they are not considered important enough to include in the diagnostic criteria? Why?

This abstract showed that under the old reporting criteria, all of 66 pediatric patients 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 BE DENIED TREATMENT.

Remember the Yale Medicine Report which has told us not to treat just on the basis of rashes? Yet here 46 children who had bull's-eye rashes tested positive with the old Western Blot reporting criteria (Including having antibody bands that can only occur in Borrelia infections!),

BUT

Clearly two thirds of these kids would have been excluded if we ignored the rash and excepted the negative Western Blots using the newly adopted reporting criteria. DO YOU WANT YOUR KIDS TO HAVE TO MAKE IT THROUGH THOSE STANDARDS?

Let's review the suggested criteria from Yale:

This is all inferred from an article which earlier refers to their staff as the "Lyme Dream Team" of doctors!

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The conclusion of the researchers Fawcett et al was: "THE PROPOSED WESTERN BLOT REPORTING CRITERIA ARE GROSSLY INADEQUATE, because it excluded 66% of the infected children."

Would it be any surprise that the Health Insurance companies are in nearly complete support the new Western Blot reporting criteria?

Abstract # 1256 by K.K. McCartney et al: This study showed that the using the newly proposed Western Blot criteria resulted in 60% false negative results in children with both E.M. Rash, and Bell's Palsy.

A total of 23 patients with both a bull's-eye rash, and Bell's Palsy were tested using the new criteria for Western Blot as proposed by the NIH committee. Only nine of the 23 patients were considered positive with the new criteria.

So despite a diagnostic rash and a late-stage neurological symptom, the accuracy of the Western Blot was only 39%. Once again the old criteria was far more accurate with no false positives.

ACCURACY OF CLASSICAL DIAGNOSTIC CRITERIA IS CHALLENGED:

1995 Rheumatology Symposia Abstract # 1153 Dr. J. Sibilla et al:

French researchers studied 62 patients of suspected Lyme Disease. Using the standard diagnostic criteria for LD (Dressler's Criteria for ELISA and Western Blot) only 9 were found to meet the accepted criteria. However; by using the Polymerase Chain reaction Test on blood, CSF, and synovial knee-joint tissue on the remaining 53 patients, another 9 were detected.

That means the standard antibody tests using Dressler's Criteria missed half of the active Lyme Arthritis patients. The Conclusion: "as many as half of the Lyme Patients were being missed by adhering to the accepted diagnostic criteria."

Since PCR is not 100% other patients in the study may also have Lyme Disease. For example only one patient was detected by PCR of the blood, six were confirmed by PCR of the CSF, and 4 patients had PCR positive synovial tissue.

How many doctors that you know will order both a spinal fluid and a synovial biopsy? Many will only do blood because it is easier and has less cost and trauma to the patient, but what are the costs and morbidity of undiagnosed untreated Lyme disease?

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LYME TESTS FAIL AGAIN:

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 Laboratory of Hygiene/College of American Patologists Proficiency Testing Program. Journal of Clinical Microbiology, March 1997; 35(3):537-543

Analysis of 516 laboratories revealed that only 55% could correctly identify Lyme sera from patients that met the CDC criteria for seropositivity. The 516 participants had a high incidence of both false negatives, and false positives. The conclusion was that the currently available test kits must meet stronger criteria for approval, and laboratory procedure and consistency must improve.

In short the ELISA test WHOSE ACCURACY APPROACHED THAT OF FLIPPING A COIN, is almost worthless in a practical setting, and do not live up to manufacturers claims, or the claims of the labs reporting.

In a video tape, the ACP explains persistent elevations of antibody as residual immunity from prior infection and not indicative of active infection. Thus, any elevations post-treatment should be ignored, but then why make a patient pay for a Lyme test if your preset protocol insists on ignoring a positive result?

Please tell me why a patient should have to pay for a positive test that is going to be ignored? Yet if the test was negative it is used as an indication that the patient should not be treated.

By this logic, Lyme patients are far better not ever having antibody serology tests until the medical community changes their attitudes and criteria for diagnosis and treatment based on negative tests!

If the patient has been cured, why find out if Lyme antibodies are still elevated? The test is superfluous, yet it is repeatedly ordered and reordered and reordered. The repeated negative tests look like strong proof to the insurance companies not to treat.

There is no doubt that there is a lopsided division within the medical community about the diagnosis and treatment of Lyme disease.

I feel that there are already enough human tissue studies to support the claims of thousands of patients who say they are actively infected despite supposedly adequate antibiotic treatment.

It is clear, however, that these studies citing active infection post-treatment are not enough for the majority of the medical community to change their opinion that Lyme disease can persist post-treatment.

Rather than continuing to bandy the same old data back and forth, I suggest that we do the Lyme study that really needs to be done: a definitive multi-center, international, post-mortem Lyme disease tissue study.

The study must include multiple tissue biopsies including brain, heart, tendon, and bladder, and use multiple techniques including fluorescent immune antibody staining, silver stain, tissue culture, antigen detection, and PCR.

The study should also include another group of patients. Based on several extraordinary case histories of Alzheimer's patients done by Dr. Judit Miklossy, a multi-national tissue-spirochete study should also include a subset of non-Lyme patients who have dementia-type diseases including multiple sclerosis, Alzheimers, early senile dementia, Parkinson's, lupus, ALS, and similar disorders.

Even a 1% incidence or correlation to spirochetal infections could save billions in health care dollars if those patients could be targeted for early antibiotic therapy.

This study should be nonspecific and look for many genus of spirochetes, not just Borrelia burgdorferi! Based on the genetic diversity of the many disease causing Borrelia species, that no species of spirochete should be overlooked or excluded from the study.

Any study that would just target Borrelia burgdorferi species could miss a significant number of infections. Any spirochete in the brain is abnormal and significant!

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THE CURRENT NIH LONG-TERM TREATMENT STUDY HAS, in my opinion, SHOWN FLAWS FROM THE VERY BEGINNING. Not the least of which was when halfway through the study the head administrator Dr. Mark Klempner commented to the press that it was irrational for any Lyme patient to take months of antibiotics for persisting symptoms of Lyme disease.

This is not exactly a unbiased position for him to take. He should have been in my opinion reprimanded and forced to resign his position from this study.

How can a study evaluating the value of long-term treatment have any validity if the head researcher believes so strongly that he would make comments to the press that there is no value in long term antibiotic treatment?

He has presented a conclusion to a study which hasn't yet been completed!

A post-mortem tissue study would eliminate any serology based biased interpretations.

It is sad to think that Lyme patients have to die to get this data, but I don't think the medical community has given us any other viable options. I would like to see this study financed by a multi-national fund to avoid any national bias.

Too often we have seen both the CDC and the NIH choose sides in this debate favoring the assumptions that serology tests are more important than patient's symptoms and comments; and, so far, CULTURES AND TISSUE STUDIES HAVE BEEN WHOLLY IGNORED.

The rift in the medical community is real, but until we do a definitive study, I don't see any chance of ending the argument. If we accept the assumptions that Lyme antibody serologies are definitive in determining both diagnosis, and cure, then Camp A wins.

If we accept the current case histories of patients that have been confirmed as having persistent infection by culture, then Camp A's argument that there is no such thing as "Chronic Lyme Disease" is already disproved.

However, if there isn't enough hard evidence to reach a consensus among the entire medical community (and it appears there isn't), then before any more state medical review boards condemn any more Lyme treating doctors, they should at least wait until the truly definitive study that can either prove or disprove persistent infection has been done.

No such study has yet been done and it is way over due. We now need to start compiling autopsy data that specifically looks for spirochetes in sequestered tissues ...

NINE REASONS FOR FALSE NEGATIVE LYME DISEASE BLOOD TESTS

The Lyme Disease Foundation (LDF), in their brochure entitled "LDF Frequently Asked Questions About Lyme Disease" lists the following nine reasons for false negative Lyme disease test results.

1. Antibodies against Bb are present, but the laboratory is unable to detect them. [Borrelia burgdorferi (Bb) is the Lyme disease bacteria.]

2. Antibodies against Bb may NOT be present in detectable levels in a patient with Lyme disease because the patient is currently on, or has recently taken, antibiotics. The antibacterial effect of antibiotics can reduce the body's production of antibodies.

3. Antibodies against Bb may NOT be present in detectable levels in a patient with Lyme disease because the patient is currently on or has previously taken anti-inflammatory steroidal drugs These can suppress a person's immune system, thus reducing or preventing an antibody response.

4. Antibodies against Bb may NOT be present in detectable levels in a patient with Lyme disease because the patient's antibodies may be bound with the bacteria with not enough free antibodies available for testing.

[For this reason, some of the worst cases of Lyme disease test negative -- too much bacteria for the immune system to handle.]

5. Antibodies against Bb may NOT be present in detectable levels in a patient with Lyme disease because the patient could be immunosuppressed for a number of other reasons, and the immune system is not reacting to the bacteria.

6. Antibodies against Bb may NOT be present in detectable levels in a patient with Lyme disease because the bacteria has changed its makeup (antigenic shift) limiting recognition by the patient's immune system.

7. Antibodies against Bb may NOT be present in detectable levels in a patient with Lyme disease because the patient's immune response has not been stimulated to produce antibodies, i.e., the blood test is taken too soon after the tick-bite (8-6 weeks).

Please do not interpret this statement as implying that you should wait for a positive test to begin treatment.

8. Antibodies against Bb may NOT be present in detectable levels in a patient with Lyme disease because the laboratory has raised its cutoff too high.

9. Antibodies against Bb may NOT be present in detectable levels in a patient with Lyme disease because the patient is reacting to the Lyme bacteria, but is not producing the "right" bands to be considered positive.

Lyme Disease Foundation
1 Financial Plaza
Hartford, CT 06103
(860)525-2000
fax (860)525-TICK
Lyme Disease National Hotline (800)886-LYME
mailto:lymefnd@aol.com

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Evaluation of a commercial enzyme-linked immunosorbent assay for detection of Borrelia burgdorferi exposure in dogs.

By Sheets JT, Rossi CA, Kearney BJ, Moore GE.

Veterinary Medicine Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702-5011, USA.

[ Fort Detrick is supposed to be our front line defense against biological warfare.]

OBJECTIVE:

To evaluate the effectiveness of a commercially available ELISA kit for detecting antibodies against Borrelia burgdorferi in dogs.

SAMPLE POPULATION:

Banked sera from 440 military working dogs were used for serologic analyses.

PROCEDURE:

Serum samples were analyzed for antibodies against B burgdorferi by use of a commercially available ELISA and subsequently by western blot analysis as a confirmatory test [joking?].

RESULTS:

Results from the ELISA indicated that 89 (20%) samples were positive for exposure to B burgdorferi or canine Lyme disease vaccine, and 351 (80%) were negative. Follow-up testing by western blot analysis indicated that results for 109 (25%) samples were positive and 331 (75%) were negative for exposure.

All samples that had positive results on the ELISA also had positive results on western blot analysis (true [wow!] positives). Of the 351 samples that had negative results on the ELISA, only 331 had negative results on western blot analysis (true [wow!] negatives). The remaining 20 samples had positive results on western blot analysis. [Truth is clearly in the eye of the beholder.]

By use of a standard 2 x 2 table, it was determined that the ELISA had a sensitivity of 82%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 94%. [Do these researchers really believe this? -- this brings to mind the remark about 'liars, damned liars, and statisticians']

CONCLUSIONS AND CLINICAL RELEVANCE:

The commercial ELISA kit evaluated in this study appeared to lack adequate sensitivity for detecting all potential cases of borreliosis in dogs.

The ELISA was also unable to discriminate natural exposure from exposure attributable to vaccination, which could complicate interpretation of positive results and treatment of dogs with clinical signs.

J Am Vet Med Assoc 2000 May 1;216(9):1418-22

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