I wrote this recently as a Letter to the Editor of my local paper, The Bethel Citizen, after they wrote a small piece about the CDC’c protocol for testing and wrote it in such a way as the accuracy of the tests was never in question or even open for discussion. I must add it was after a much longer piece about two friends of mine with chronic Lyme who have organized the first annual Western Maine Lyme Disease Awareness Day:
I believe that it is irresponsible to report about the “Accuracy of Testing” (Lyme Disease) using the Federal Centers for Disease Control as a source when the CDC (Federal Center for Disease Control and Prevention) website states:
“Lyme disease is diagnosed on the basis of physician-observed clinical manifestations and a history of probable exposure to infected ticks . Laboratory tests are neither suggested nor required to confirm diagnosis for patients with recent onset (2–3 weeks) of a characteristic EM rash. However, positive results of recommended two-tiered serologic testing can provide confirmation of infection in patients with musculo-skeletal, neurologic, or cardiac symptoms. Testing methods that have not been adequately validated can be misleading and are not recommended.”
The big problem that is at the heart of every medical debate about chronic Lyme disease, and the accurate statistical data count for disease control is the accepted criteria for determining whether a person is infected with Lyme disease.
There is currently no reliable test to confirm the existence of Lyme disease.
The CDC refers to the recommended two-tiered serologic testing to provide confirmation of Lyme disease (even though they say that is NOT how it is diagnosed in the first line), but they know very well how unreliable these tests are.
The two-tiered testing refers to testing the blood of a patient when Lyme is suspected with first the ELISA assay, and if it comes back positive then taking another sample of blood and having a Western Blot test performed. The likelihood of a person with Lyme disease actually having both tests come back positive are about 50% depending on the lab, the strain of Babesiosis, and the length of time between the tick bite and your blood tests. Many believe it is much lower than that.
The CDC continues to say that the evidence of an EM rash proves the exposure to Lyme disease conclusively. And yet scientists found out years ago that some ticks leave a rash that infects human skin but never invades the organs, while other ticks do not leave a rash and infect the body aggressively and completely. (SUNY, Dr. Luft, Dr. Wei Gang Qiu)
The Enzyme-Linked Immunosorbant Serum Assay (ELISA) is the simplest, least expensive, easiest to perform, and most common Lyme test ordered. It is a test based on detecting the antibodies that our bodies make in response to being exposed to Borrelia burgdorferi (Bb). It is a preferred test by laboratories, not because it is more accurate than other Lyme tests, but because it is automated. Many different patient samples can be performed by a single machine simultaneously. This allows for a faster turnover, less costs, and theoretically, standardized test results that are consistent from lab to lab.
We are told by manufacturers, health departments and clinics that the Lyme ELISA tests are good, useful tests, but in two blinded studies that tested laboratories for accuracy, they failed miserably. Lorie Bakken, MS/MPH, showed in her studies that there was not only inaccuracy and inconsistency between competing laboratories, but also between identical triple samples sent to the same lab. In other words, identical samples often resulted in different results. In the first study, forty-five labs correctly identified the samples only 55% of the time.
In the latest study by the College of American Pathologists, 516 labs were tested. The overall result was terrible. There were almost equal numbers of false positives as false negatives. Overall, the labs were 55% inaccurate. The labs could only give a correct result 45% of the time.
The ELISA test sounds simple and straight forward, but it has a couple of major flaws. Borrelia species are some of the most polymorphic bacteria known to exist. In other words, most Borrelia species can significantly change its surface proteins enough during cell division as to evade our immune system, and may differ from laboratory strains enough to result in negative tests, even if antiBb antibodies are present. In Europe, this problem is intensified because they have recognized three species of Borrelia that cause Lyme disease, and so they have available three separate ELISA tests. The questions in America are: 1) Have we recognized all the strains and species of Borrelia that cause Lyme disease symptoms, and 2) are we incorporating them into our tests? The answer is no. Convenience and expedience has chosen that we don’t prime our ELISA tests with wild strains, but use a laboratory strain.
When a lab reports that their ELISA test has had high specificity and high sensitivity, it is usually interpreted by doctors as being a more accurate test, but the doctors don’t know what the lab is actually measuring. One of the hidden problems of serologic Lyme tests is the fact that the tests must be primed with a source of bacteria to create the reactions with the patient’s antibodies. To do this, virtually all labs rely on a laboratory strain of Bb known as strain B-31.Taking purified antigens from strain B-31 and injecting them into mice, they then can extract a monoclonal antibody to each antigen, or a polyvalent antibody soup. This antibody is concentrated and purified, and then added to the ELISA test to test the efficacy and performance of the test.
Unlike the wild strains, B-31 grows well in culture, and this makes it a perfect choice as a consistent and inexpensive source of Bb. But the affinity the mouse monoclonal antibody has to B-31 antigen is quite different from the affinity the patients’ antibodies have to the same antigen. This means the test may register as negative because the test cannot detect the slightly different antibody profile that a wild strain of Bb can produce. In other words, the labs are really comparing apples to oranges! This is why, when the American College of Pathologists used human sera to test the accuracy of 516 different laboratories ELISA tests nationwide, the overall accuracy was only 45%.
In the quest for specificity, most ELISA tests have become so specific that the test may fail to detect antibodies from related strains of Borrelia. This would include different genospecies that cause Lyme disease, as well as different Borrelia species that cause Tickborne Relapsing Fever. Would a cross reaction to the Borrelia species that cause Tick-borne Relapsing Fever be so bad?
The real Achilles’ Heal of an ELISA Test is that it can only detect free antibody. It cannot detect any antibody that has become mixed with antigen.
The ELISA test depends on the active, free antibodies to attach to the free antigens that have been embedded on the walls of the test tube. If the antibodies in the serum being tested are already attached to antigens, then the enzyme reaction cannot take place. If we think of antibodies as sort of keys that fit into locks, and that on the surface of the bacteria are specific locks we now call antigens, you can see that once a key is inserted into a lock, the key is no longer available to open any other locks.
What makes this test so misleading is that many doctors accept high readings as an indication that the patient must really be sick. This logic is exactly backwards. If a patient is really infected with lots of bacteria, that means they have a lot of bacterial antigens floating around in the blood. So, as free antigen increases, free antibody decreases.
Since the ELISA test detects only free antibody, a negative test might actually indicate a MORE serious infection. Many times totally asymptotic patients with ELISA titers over 1000 will be treated as though they were on death’s doorstep simply because they had a high titer, while patients with borderline titers who are practically disabled are ignored, because a low titer is perceived as meaning LESS infected! These conclusions are erroneous and actually opposite to the truth, which is that a high titer means greater natural immunity.
What a high ELISA test may be a better indicator of is what level of immunity is the patient capable of mounting against this infection? A high titer is the same thing as saying the patient has a high natural immunity, and a low can mean that the patient may be overwhelmed by infection.
In one year-long study by Dr. Sam Donta, MD, (in Boston) did on chronic Lyme patients, the initial ELISA tests proved to be more than 66+% inaccurate (1996 LDF Conference lecture). Other researchers have also found the ELISA tests to be inaccurate. Using a 45-panel diagnostic testing protocol from the NIH for testing the efficacy of the ELISA and Western Blot, researchers found the accuracy of the Lyme ELISA varied from about 5075%, and were routinely inconsistent. The CDC’s ELISA test did no better on average than any other ELISA. It is the CDC ELISA test which is used for surveillance of emerging Lyme disease in the United States, yet the test was correct only about two out every three tests. Too often, a single negative ELISA test can prevent a sick patient from getting treatment, even despite having serious symptoms.
Now assuming you have a positive ELISA (Tier One), then you run the Western Blot gauntlet (Tier Two.)
The Western Blot is a much more complex test that essentially makes a map some of the different antibodies the immune system produces to the bacteria. The map separates the antibodies by the weight of their respective antigens and are reported in units called kilo daltons or kDa.
For example, a Western Blot may report bands at 22, 23, 25, 31, 34, 39, and 41 kDa. Each of these bands represents an antibody response to a specific protein found on the spirochete. The 41 band indicates an antibody to the flagella 41 kDa protein and is nonspecific. The 31 kDa band represents the OSPA protein and is specific for just a few species of Borrelia, as is the 34 band OSPB, and 23 kDa OSPC.
In 1994, the Association of State and Territorial Public Health Laboratory Directors, under a CDC grant, decided that there should be consistency between labs reporting Lyme disease Western Blots, and that a specific reporting criteria should be established. The consensus committee, chaired by Dr. Michael Osterholm, Ph.D., MN, set nationwide standards for Western Blot reporting. This sounds good, but one could argue they made a bad situation worse. Prior to the hearing, virtually every lab had accepted bands 22, 23, 25, 31, and 34 kDa as specific and significant, and reported them as positive for exposure to Borrelia burgdorferi. Not only are these bands specific for Borrelia species, but they represent all of the major outer surface proteins being used to develop the Lyme vaccines.
However, the committee, without any clear reasoning, disqualified those bands as even being reportable. Thus, after the consensus meeting, those bands were no longer acceptable, and the result was that what had been a fair-to-good test for detecting Lyme disease had now become poor, or even worse, arguably useless.
Many scientists have questioned these new reporting criteria, and several wrote letters of protest to both the committee and to laboratory journals. Many labs stopped reporting the actual bands and instead, simply reported the test as positive or negative, thus preventing any further interpretations.
How badly did the Lab Directors bootstrap this test? The following is an analysis of the new guidelines presented as an abstract and lecture at the 1995 Rheumatology Conference in Texas, chaired by Dr. Alan Steere, MD. (1995 Rheumatology Symposia Abstract #1254, Dr. Paul Fawcett, et al.)
This was a study designed to test the recently proposed changes to Western Blot interpretation by the Second National Conference on Serological Testing for Lyme Disease, sponsored by the CDC. The committee proposed limiting the bands that could be reported in a Western Blot for diagnosis of Lyme disease. Out of a possible 25 bands, 10 specific bands were selected as being reportable. An lgG Western Blot must have five or more of these bands: 18, 21,28, 30, 39, 41,,45, 58, 66 and 93 kDa. An lgM Western Blot must have two or more of the following three bands: 23, 39, 41.
Conspicuously absent are the most important bands, 22, 23, 25, 31, and 34, which include OSPA, OSP-B and OSP-C antigens – the three most widely accepted and recognized Bb antigens. These include proteins from the strain “B31” which researchers have found to be the most virulent and vicious. How is this going to help us diagnose the disease or track the epidemic?
An abstract was performed using 66 children who tested positive under the old test, but under the new criteria only 20 children were now considered positive. That means 46 children who were all symptomatic would have been sent home untreated. That’s an accuracy rate of only 31%.
The conclusion of the researchers was: “the proposed Western Blot reporting criteria are grossly inadequate, because it excluded 69% of the infected children.”
I believe this new criteria is criminal, and completely opposed to the Hippocratic Oath. It is self serving to doctors that want to control popular opinion rather than by doctors who want to find the truth and protect people from harm. There are children that are being infected every day with an incurable disease and doctors who refuse to give hospitals or labs the tools to adequately diagnose the disease before serious damage is done. Years are being lost to millions of people, but certainly we must all agree its the worst for the children who never will have the chance to live a normal childhood.
But the problem with these tests is actually even worse than all of the above. The Second Committee based all assumptions on a possible 25 proteins (antibodies), and yet researchers have known for quite some time that the Borrelia species morph from one strain into another. This has been shown repeatedly in labs where animals without Borreliosis were injected with a specific strain, and several weeks later were found to have a completely different strain active in their body. Additionally, according to Molecular Biology there are at least 40 known species of Borrelia that we know of, (then add to that the unlimited number of mutations. )
According to Dr. Luft at SUNY School of Medicine, to make the Western Blot accurate, every genome in every known species of Borrelia would have to be mapped – 1800 proteins in all – a far cry from 25!
NOTE: From Feb 2011 to Jan 2012 (and ongoing) Dr. Luft and his team of scientists have been mapping these enormous genomes and currently have published their results in the “Journal of Bacteriology”: Strain 31 with 13 variations, another Borrellia sensu variation from Finland, four more species (four isolates from two of the Borrelia species that cause human Lyme disease, B. afzelii isolates ACA-1 and PKo and B. garinii isolates PBr and Far04), and three species B. valaisiana VS116, B. spielmanii A14S, and B. bissettii DN127. That is a total of 21 species of Borrelia thus far. (GO SUNY)
Other hopeful news is that recently, a Chinese study found that changing western blot criteria to detect the prevalent strain of Lyme bacteria in their region increased the accuracy of the tests. Another study in the United States proved that mixing two infectious Borrelia strains in a western blot assay increased the test’s sensitivity. If simply adding other strains of the same Lyme species increases the western blot’s sensitivity, the changes needed in order to detect various Lyme species may be incredible. course all of these changes make an expensive and co plex test even more expensive and complex.
To read the full article I wrote on my blog go to http://lymediseaseresource.com/wordpress/is-the-western-blot-capable-of-more-accuracy-2/
How did I end up writing a blog on Lyme disease?
Well, I crashed (physically speaking) badly in October of 2006 after being very active with my family, friends and riding my horses competitively (Scott and I even bred our mare that year so we had a new four-legged family member). My local doctor immediately suspected Lyme but the ELISA was negative.
I continued to get worse to the point that I could not get out of bed, (obviously couldn’t drive or ride my horses) could not tolerate light or noise of any kind, my skin hurt my joints ached, I felt feverish, I ached all over, I heard phantom voices and sounds, I cried uncontrollably for no reason, lost my ability to do simple math or remember simple words. My writing became illegible, my ability to think was…well, I felt like I was in my mind was mired in quicksand – they call it “Brain Fog” I would feel parts of my body shriek in pain as if someone were putting out a cigarette on my skin…and this is only half of my symptoms.
My family and friends insisted I go to Boston to see a Infectious Disease specialist, and thanks to a friend who pulled some strings I was able to see a ID MD who taught at Harvard – very respected – at the Lahey Clinic. He spent about 20 minutes with me, “You have all of the symptoms for Lyme disease but I don’t want to go fishing for a false positive. I just don’t believe in chronic Lyme disease.” (at this point my local doctor had me finish a course of 45 days of Doxycycline which according to this “expert” would have killed off any infection of Lyme disease I may have had.)
The doctor would not order a western blot because he felt that would be asking for a false positive – I asked him how it would be a false positive if I had all the symptoms and the test conformed the disease was present. He was stubborn and unyielding in spite of my obvious pain. My sister was there to take notes so that I wouldn’t forget anything he said. And he diagnosed me finally as depressed with fibromyalgia.
I asked him how he diagnosed me with fibromyalgia after studying about it afterwards and learning that there are 18 specific points on the body that are sore to the touch and yet this doctor never checked any of these points.
This is the kind of doctor who is teaching a new generation of doctors who will be facing ten to twenty times the numbers of sick people.
In my opinion, the ELISA test is worthless as a diagnostic tool in Lyme disease, and so is the Western Blot as it is now. They are inconsistent and inaccurate, and should be discontinued as tools to diagnose Lyme until they are made to be accurate. If the NIH and CDC truly believe, as they’ve stated, that the diagnosis of Lyme disease is to be made on the basis of symptoms, then these tests should be temporarily banned until a test is created that is more reliable.
What does all of this mean to the reader? First, please attend the first annual Western Maine Lyme Disease Awareness Conference on May 5 at Mountain Valley Middle School in Mexico to learn as much as you can about this rapidly spreading disease. It is the fastest growing vector-borne disease in the country even with the most conservative estimates.
Secondly, if you suspect that you have Lyme disease, find a doctor that specializes in treating Lyme disease. To be fair, most physicians do not have time after seeing patients every 15 minutes all day every day to keep up to date on the latest research on Lyme disease. They rely on the IDSA (Infectious Disease Society of America) guidelines for treating Lyme which is highly controversial, so much so, that Connecticut Attorney General Blumenthal issued an anti-trust investigation in 2006.
In 2008 the IDSA was ordered to revise their guidelines with the supervision of an independent outside arbiter stating financial conflict of interest and willfully ignoring medical evidence as just part of the charges against the Committee who appeared to be supporting the Insurance Companies interest of wanting to keep their costs down by limiting the length of time a patient could receive IV antibiotics even if they needed it longer. (See http://www.ct.gov/ag/cwp/view.asp?a=2795&q=414284 for full story)
For an idea of how unscrupulous this IDSA has become, even after hours of testimony from doctors and researchers all across the country the IDSA Committee voted to keep the guidelines “as is” until public opinion and pressure caused them to agree to change every guideline except one: They refused to redo the vote on the one recommendation that required the diagnosis of Lyme could only be made if there is a positive blood test (completely unreliable two-tiered seratological testing discussed above.) They also refuse to follow their own rules to update the regulations every five years, and this is with a disease that is spreading like wildfire and new research and evidence being brought to light on a monthly basis. Now Congress is seeking to force the IDSA by law to change the guidelines. Go to http://www.change.org/petitions/change-idsa-guidelines-so-lyme-patients-can-get-treatment to have your voice heard regarding blood tests for diagnosis in order to get treatment.
Thanks to Dr. Tom Grier MS at CanLyme for up to date facts and figures about ELISA and Western Blot.