Hi Sapper16E -
Good questions. I'll share the info I have - it's a lot of info and I know you want to zero in on specific studies, and that might do the trick for you - I'm not sure of the context for your post - people come here for a lot of different reasons. However, the best approach w/ an uninformed MD or one who is trying to avoid the right steps to diagnose you (for multiple possible reasons) is to fully wrap your head around where he/she might be coming from and the best way to do this is to understand ALL of the issues with the testing.
A lot of good info has come out of entities like LymeDisease.org that try to pull this highly technical and scientific info together and summarize it so that patients can better understand. Sometimes this comes with links to source info, sometimes not. And a lot of the info I have is about
the WB's failures, too.
First, for clarity, the ELISA is the first test usually administered out of a two-tiered testing process recommended by the CDC. The second test in the tier is the Western Blot. I explain the many issues with these tests in more detail below.
There is some complexity to what you're asking - in summary, the ELISA is notoriously inaccurate for diagnosing Lyme for several reasons but these also apply to the WB testing as well:
- problems with known characteristics of the Borrelia burgdorferi (Bb or Lyme) microbe and its ability to evade and/or disable immune function and the huge impact on accuracy of serological tests like the ELISA and WB for Lyme that both rely 100% on normal immune reactions to the Bb microbe.
- problems with the process by which the CDC recommends that MDs utilize the test in a two-tiered sequence, their function within CDC's surveillance criteria, and the design of both tests to that end - which doesn't support diagnosis
- the ELISA has sensitivity problems designed into the test itself
- the tests detect only Borrelia bufgdorferi sensu stricto B31 and will miss many other strains that cause Lyme-like issues
- problems with the misuse of the test and its results by uninformed and disinformed MDs, misunderstandings regarding the CDC's clear directives NOT to utilize the tests to solely diagnose
1) Over-reliance on testing to diagnose Lyme:
While the CDC has no formal medical authority whatsoever, it is what the medical industry follows. The CDC developed surveillance method criteria
to track trends in infectious diseases, including Lyme disease. To satisfy these surveillance proposes, the CDC developed a specific case definition for Lyme disease
that is used in qualifying "new Lyme cases" per the testing results.
"Surveillance methods" and "case definition" are two key concepts every Lyme patient needs to understand and need to be able to talk about
when MDs try to manipulate test results and/or simply are ignorant about
what they mean.
It is also critical to understand that EVERYTHING communicated/structured/guided/informed by the CDC regarding Lyme tests is geared to find "like" manifestations of Bb - cases where Bb microbe is similar and manifests itself into Lyme disease similarly, regardless of the host/patient - NOT to find ALL manifestations of Bb into Lyme disease
2) Misunderstanding of purpose of tests as part of CDC's criteria:
To this end (utilizing their "case definition" to implement their "surveillance" purposes) the CDC and IDSA (Infectious Diseases Society of America) developed a two-tiered serology testing "decision tree."
- The 1st tier ELISA is required
because it is intended to quickly and efficiently and economically screen for increased immune activity, and intended to be less specific but more sensitive. However, the test is notoriously inaccurate and there are many concerns over its sensitivity, particularly given the 50% accuracy rate.
- The 2nd tier WB test
is to be administered ONLY to confirm a positive 1st tier ELISA because it is possible for people who were vaccinated with the OspA Bb DNA to be "falsely positive" on the ELISA. Although in reality, this is rare, only a handful of the US population were administered the vaccines.
This suggests that the WB wasn't intended for the broader public, only for those receiving the vaccine. Also, the CDC/IDSA doesn't explain this logic to MDs, rarely includes it in their education about
Lyme testing for MDs, nor does the CDC recommend following up with a more specific test for people who have never had the vaccine yet tested negative on the ELISA, which is the majority of this country.
In addition to the gross misinterpretation of the CDC's criteria, very few MDs understand that the Bb have been proven to evade and/or inactivate the immune system, which is the primary reason that serology tests are inappropriate for LD diagnosis. The CDC doesn't inform MDs or patients of this, either.
After the failure of the vaccines a few decades ago, none of this testing methodology was updated.
3) Misinterpretation of results:
As part of the surveillance protocol, the CDC developed a specific list of bands that are required in order for the tests to qualify as "CDC-positive" according to the "case definition" necessary to fulfill their "surveillance" requirements. This is explained below.
The CDC CLEARLY states that this criteria should NOT be utilized for diagnostic purposes, which is exactly what MDs all over the country are using them for. And the CDC states specifically that two Lyme-specific bands kDa 31 and 34 OspA and B were used for the creation of a vaccine so they have removed these two bands from possible bands people can react to, which essentially eliminates two very Lyme-specific bands, making it even more elusive for people's immune response to register as "positive" on the CDC's surveillance criteria.
Buried at the very bottom of this web page is the CDC's recommendation that LD be a clinical diagnosis:
It states that:"Surveillance case definitions establish uniform criteria for disease reporting and should not be used as the sole criteria for establishing clinical diagnoses, determining the standard of care necessary for a particular patient, setting guidelines for quality assurance, or providing standards for reimbursement." www.cdc.gov/lyme/stats/survfaq.html
Of course, the primary issue with expecting all MDs to clinically a Lyme case is that 95% of MDs are not qualified to do this, do not seek qualifications or education to support this, and with the attack on specialists who ARE qualified and successfully treat Lyme, most MDs are not willing to take the risks involved in treating patients. It's MUCH more convenient, given the problems with the testing and the system and the governance of Lyme info, to simply avoid diagnosing Lyme in patients.
The issues above are explained in more detail below and this is where I included most of the links:
First and foremost:Lyme Case Surveillance
The CDC wants the medical industry to follow its CASE SURVEILLANCE DEFINITION METHODOLOGY for testing for Lyme disease and offers no other approved means for testing. This is problematic on many levels as the tests have been studied to be about
50% reliable. The CDC reports that Lyme is the fastest-growing infectious disease
. Yet, find ANY other infectious disease where the tests promoted by the CDC are 50% reliable.
1) CDC’s CASE DEFINITION METHODOLOGY RELIES ON SEROLOGY DIAGNOSTICS, WHICH ARE INAPPROPRIATE FOR A BACTERIAL PATHOGEN THAT CAN TURN OFF THE IMMUNE PROCESS:
Over 200 studies show that Bb can evade and/or disable the immune response once the microbe is in the body. Over 700 articles also support these findings. This, alone, begs the need for improved testing for Lyme other than serology tests.
The infected tick's saliva includes an immunosuppressive component to prevent the body from shutting off the blood supply to it. So Borrelia & co take advantage of this window to establish themselves in the body before the immune system can create the correct and necessary antibodies. During that time of multiple days to multiple weeks, lyme and co moves away from the blood stream into the bone, tissue, and muscles.
> "No serological test can rule out LD and LD cannot be adequately diagnosed by serology alone. Studies show potent immune suppression induced by Borrelia, which interferes with an appropriate immune response by design so most people don’t produce enough antibodies for the tests to register."(Elsner RA, Hastey CJ, Olsen KJ, Baumgarth N (2015) Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection. PLoS Pathog 11(7): e1004976. doi:10.1371/journal.ppat.1004976) journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004976
> "If this spirochete is evolved enough to attack our B-lymphocytes, then it may also be evolved in other ways that we do not yet understand. It is for certain that its ability to kill B-lymphocytes evolved as part of a defense mechanism to evade its own destruction. The observation that it can use the B-cell's own membrane as camouflage indicates that it may be able to go undetected by our immune system. The way our immune system is supposed to work is that it recognizes foreign invaders as being different from self, and attacks the infection."(The Complexities of Lyme Disease: A Microbiology Tutorial: Part 1, By Thomas M. Grier, MS, Excerpt from the Lyme Disease Survival Manual 1997.)www.lymeneteurope.org/info/the-complexities-of-lyme-disease
> "The structure of the Lyme spirochete is unlike any other bacteria that has ever been studied before. Spirochetes have an extra layer of glyco-proteins may act like a stealthy coat of armor that protects and hides the bacteria from the immune system. The human immune system uses proteins that are on the surface of the bacteria as markers, and sends attacking antibodies and killer T-cells to those markers, called outer surface protein antigens (OSP antigens). This nearly invisible layer is rarely seen in washed cultures, but can be seen regularly in tissue biopsies."(Sigal LH, Tatu AH. Lyme Disease patient's serum contains LgM antibodies to Borrelia burgdorferi that cross react with neuronal antigens. Neurology 1988;38:1439-1442)www.lymeneteurope.org/info/the-complexities-of-lyme-disease
> "The structure of the Lyme spirochete is unlike any other bacteria that has ever been studied before. Spirochetes have an extra layer of glyco-proteins may act like a stealthy coat of armor that protects and hides the bacteria from the immune system. The human immune system uses proteins that are on the surface of the bacteria as markers, and sends attacking antibodies and killer T-cells to those markers, called outer surface protein antigens (OSP antigens). This nearly invisible layer is rarely seen in washed cultures, but can be seen regularly in tissue biopsies."Sigal LH, Tatu AH. Lyme Disease patient's serum contains LgM antibodies to Borrelia burgdorferi that cross react with neuronal antigens. Neurology 1988;38:1439-1442 www.lymeneteurope.org/info/the-complexities-of-lyme-disease
> "People who have the worst infections may have the lowest antibody titers, and test negative. Note: It takes four weeks from the tick bite to test positive."www.lymeneteurope.org/info/the-complexities-of-lyme-disease
2) CDC'S CASE DEFINITION IS BASED ON NEEDS FOR SURVEILLANCE PURPOSES, NOT FOR DIAGNOSTICS AND TREATMENT
The CDC’s primary function is to report statistics of disease in this country as reported to them (contrary to what most people believe, the CDC is not a medical entity of any authority nor does it have jurisdiction over the FDA, which regulates testing, etc.). Generally, labs report to state health depts., which in turn report to CDC. But even the CDC states that valid LD cases could be excluded by their own reporting criteria—the strictness of criteria for surveillance purposes can result in under-reporting.
The CDC’s reporting criteria drives its method of case definition required for the purposes of surveillance and is based on "uniformity, simplicity and timeliness." The CDC’s case definition is not based on science but was designed to serve its primary function (reporting trends in diseases) and also to promote commercial interests.
In other words, the criteria is geared to identify all similar manifestations of the Bb microbe, not to capture all of the manifestations of the Bb microbe.
The CDC website itself acknowledges that Lyme is a clinical diagnosis yet most MDs are unqualified to do it. Dr. David Volkman, Ph.D., M.D. (Emeritus Professor of Medicine and Pediatrics at SUNY, Stony Brook, Board certified in Immunology, Diagnostic Laboratory Immunology and Internal Medicine, and Board Eligible in Infectious Diseases), was a member of the original Committee (along with IDSA’s Wormser) to Develop a Surveillance Case Definition for Lyme Disease and helped write the surveillance definition.
Volkman states that “the CDC explicitly cautioned against using this restrictive case definition or clinical diagnosis and reiterated this proscription with every re-issuing of it’s ‘Surveillance Definition.’
It has been a source of frustration and confusion that some in the medical community wrongly insist that a LD patient must satisfy CDC criteria.”georgialymedisease.org/yahoo_site_admin/assets/docs/ws_-Volkman_1_comments_IDSA_guidelines.100215315.pdf
And, according to Daniel Cameron, president of the International Lyme and Associated Diseases Society, "In epidemiology, every time you have a surveillance system, you always at least have a tenfold underreporting. There have been studies that show it might be as much as 40 times that."
He also questions the fact that 95 percent of the reported cases come from just 13 states, mostly in the Northeast, along with Minnesota, Virginia, and Wisconsin. People in other states are less likely to report cases if the official view is that Lyme is rare and geographically restricted, according to Cameron. "That's a little bit of a reporting problem."
3) CDC’s CASE DEFINITION METHODOLOGY RELIES ON AN INSENSITIVE "TWO-TIERED TESTING DECISION TREE" OR SCREENING PROCESS BUT QUALIFYING CRITERIA FOR "CDC POSITIVE" RESULTS ARE GEARED TOWARD THEIR SURVEILLANCE NEEDS, AND NOT TO BE INTERPRETED FOR DIAGNOSTIC PURPOSES:www.cdc.gov/lyme/healthcare/clinician_twotier.html
1st tier test ELISA (Enzyme-linked Immunosorbent Assay) with confirmatory 2nd tier test Western Blot (immunoblot). The first issue with these tests is that these are both serology tests that they aren't detecting the Bb microbe itself but instead they rely 100% on detecting antibodies to the Bb microbe that can be produced only by a healthy immune system.
Other issues with these two serology tests:
The ELISA is highly questionable for early localized disease. This very general test is intended to detect general immune activity (looks for a collection of the B31 strain antibodies), not a response to a specific infection. The CDC's intent was to reduce false positives since the ELISA an show possible reaction associated with those who were vaccinated back in the early 90s. However, the unintended result is that there are far more false negative results.
Only if the ELISA is positive, which is difficult to achieve the sicker you are as explained above, does the CDC recommend that MDs follow up with the more specific 2nd tier Western Blot test. Therefore, many people who test falsely negative with the ELISA never get retested with a more specific and accurate Western Blot.
The 2nd tier Western Blot test also looks for immune response but more specifically identifies antibodies for a specific Borrelia strain (looks for 5 out of 10 possible B31 strain antibodies produced by your body). Subsequently, since most MDs are unfamiliar with the multiple issues contributing to inaccuracy issues of these tests and often misinterpret the CDC’s methodology to prohibit
follow up for a negative ELISA, they will refuse to administer the more specific 2nd tier and tell patients they couldn’t possibly have LD because the 1st tier ELISA was negative.
And since insurance companies generally follow the more restrictive CDC surveillance protocol (even for diagnostic purposes), insurance generally won’t pay for a 2nd tier test after the 1st tier is negative, even if the 2nd tier results are positive for LD, which also discourages MDs from ordering tests and patients from taking them.
Another source of confusion is that the serology tests shouldn't be administered in the first 4-6 weeks after possible initial Bb infection so that the body has a chance to mount an effective and detectable immune response. However, the most effective impact against the infection and preventing it from proliferating throughout the body requires antibiotic prophylactics immediately after you’ve been infected. So, for those who are fortunate enough to notice a tick bite and get to an MD who is willing to consider possible Lyme infection, the tests do nothing at all to help MDs decide that yes, you’ve likely been infected and you need antibiotic therapy before being able to administer a test to confirm your infection.
And of course, even when MDs wait long enough and do administer the tests, the tests are still inaccurate 50% of the time.
Most often general MDs who know very little about
early onset symptoms and the much broader realities for possible transmission, will refuse to administer antibiotics until or unless a test confirms infection. You could be waiting a very long time for that.
The unintended consequences are that these tests generally produce false negatives, not false positives and when the guidelines are followed, many infected patients fall through the cracks.
> "False-negative results can impact diagnosis and treatment of LD, and this study indicates that for early-stage disease false-negative results are 66.8% for a single-stage test increasing to 74.9% for the two-tier test. By comparison, HIV testing results in 1.4% false negatives for the worst-case single test and 0.095% false positives with sensitive tests used with a two-step methodology. LD testing in early-/acute-stage disease generated 56 times more false-negative test results than HIV testing, and when neurological/arthralgia symptoms were present, LD testing generated ~180 times more false-negative test results than the two-step HIV tests."/www.ncbi.nlm.nih.gov/pmc/articles/PMC5391870/
> "55% of 516 laboratories could not accurately identify serum samples from Lyme disease patients. containing antibody against Borrelia burgdorferi""LORI L. BAKKEN, STEVEN M. CALLISTER, PHILIP J. WAND, AND RONALD F. SCHELL
> "Recently, two independent researchers in the UK conducted a systematic meta-analysis (literature review) of 20 years of published data regarding commercial test kits for Lyme disease. The comprehensive review determined that the mean sensitivity of all test kits used was only 59.5%. The analysis showed that the Lyme disease test with the highest sensitivity is the Western blot alone, with a mean sensitivity of 62.4%. The mean sensitivity for the ELISA Is 62.3%. In the end, it was determined that the overall sensitivity of the FDA-approved two-tier test for Borrelia burgdorferi is only 53.7%."/www.lymedisease.org/lyme-sci-testing//www.dovepress.com/commercial-test-kits-for-detection-of-lyme-borreliosis-a-meta-analysis-peer-reviewed-article-IJGM
> A Johns Hopkins study 2005 found CDC 2-tiered testing missed 75% of positive Lyme cases
> The table mid-page of this article by the leading LD organization indicates the frequency of “false positives” (high specificity) and “false negatives (low sensitivity) – the two-tiered testing misses 44% of positive cases:www.ncbi.nlm.nih.gov/pmc/articles/PMC2078675/
> A study showing the tests are as much as 75% inaccurate:/www.ncbi.nlm.nih.gov/pmc/articles/PMC5391870/
> 22 Reasons tests are wrong:whatislyme.com/22-reasons-why-your-lyme-test-may-be-wrong/
> Virginia Governor Bob McDonnell and Secretary of Health and Human Resources 2011 Lyme Disease Task Force Report/www.cga.ct.gov/2012/rpt/2012-R-0149.htm
> (Molloy, Berardi, Persing, Sigal Detection of Multiple Reactive Protein Species by Immunoblotting after Recumbant Outer Surface Protein A Lyme Disease Vaccination) m.cid.oxfordjournals.org/content/31/1/42.full
4) CDC SURVEILLANCE CASE DEFINITION INCLUDES SPECIFIC REQUIREMENTS FOR CERTAIN BANDS TO BE PRESENT TO QUALIFY AS “POSITIVE”This “qualifying bands” criteria for the two-tiered testing methodology are intended for surveillance purposes, only, and were not intended to be utilized in confirming the presence of the infection for effective diagnostics purposes.
Regardless, the tests are being used incorrectly to diagnose Lyme. The Western Blot essentially makes a map of the different antibodies we make to the bacteria. The map separates the antibodies by size and weight, and is reported in units called kilo daltons or kDa.
Most Western Blot tests will list the DNA “bands” against which the test found detectable levels of antibodies that your body generated and the test will indicate if you are positive or not and also if you are “CDC positive” or not. Of course, the “CDC positive” result is intended for surveillance and tracking, not for diagnostics but uneducated MDs will use it to diagnose.
For example, a Western Blot may report bands at 22, 25, 31, 34, 39, and 41 kDa. Each of these bands represents an antibody response to a specific protein found on the Borrelia spirochete. The 41 band indicates an antibody to the flagella protein, and is non-specific and therefore can also indicate a crossover reaction to dental spirochetes, for example and on its own, 41 does not always indicate an immune response to Bb. However, there are Lyme-specific bands, which means that these bands indicate an immune response to Borrelia DNA and are understood to be Lyme-specific bands that can react to nothing else - just like you can't be "sorta pregnant". The 31-kDa band represents the OSP-A protein and is specific for Borrelia, as is the 34 band OSP-B and 25 kDa OSP-C. Bands 31 and 34 were so specific for Bb they were used to develop the vaccines.
For surveillance purposes, the CDC generated a list of bands that they deem to be lyme-specific DNA and determined that a person needs to have at least 5 reactive bands (of a specific group of bands) in order to be “CDC positive”. Tests that had four or fewer reactive bands, even if those bands are deemed “lyme-specific” bands, will receive test results back from the labs with a “CDC negative” indication. Misinformed MDs then tell patients they couldn’t possibly have LD. Again, this criteria was developed to identify a specific manifestation of Bb, not all manifestations of Bb.
The tests also indicate the “level” of DNA found by noting with “IND” (indeterminate), or an individual or series of “+” or “-“. Because the tests aren’t confusing enough, there is also much confusion over whether or not “IND” indicates “enough” of the Borrelia DNA to be considered positive. Currently, the CDC criteria ignores the “IND” results but again, this is like being “kind of” pregnant if these bands are Lyme-specific. Unfortunately, there is less solid information available to help people navigate IND responses on their WBs, which is why it's important to be able to argue your way around the tests' inaccuracies more comprehensively.Lyme-specific bands were excluded from the testing criteria because they were used in vaccine development
Because the CDC eliminated the two bands from their qualifying list of “CDC-positive” bands, some people who DO have Lyme and have a WB reaction to those bands (yet were never administered the vaccination) and might lack reaction to enough bands - will be considered “negative” for Lyme. Not only were the vaccinations unsuccessful, the misadventure now leaves the primary testing methodologies without enough Lyme-specific bands, which would help test accuracy. Here are few older articles about
this - the "system" has known about
the testing problems for decades:
> Prior to a 1994 NIH hearing to develop conformity amongst labs, every lab accepted bands 25, 31, and 34 as Lyme-specific and significant in diagnoses. Without any clear reasoning, during what has come to be known as the infamous 1994 Dearborn meeting, the NIH disqualified those bands from being reportable. The result was that what had been a fair good test had now become poor or even useless.1995 Rheumatology Conference in Texas. (1995 Rheumatology Symposia Abstract # 1254 Dr. Paul Fawcett et al.)
> When the CDC developed its surveillance case definition it included specific requirements for certain "bands" to be present on the confirmatory western blot. However, two “lyme-specific” bands (kDa 31 and 34, or outer surface proteins—Osp A & Osp B) were excluded. Why? These bands are so specific for LD that they were used for vaccine development. They removed them from the testing criteria otherwise people who had been vaccinated would all be positive for those bands and falsely positive on tests.www.lymeneteurope.org/info/the-complexities-of-lyme-disease
> 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."1995 Rheumatology Conference in Texas. (1995 Rheumatology Symposia Abstract # 1254 Dr. Paul Fawcett et al.)
> The table mid-page of this article by the leading LD organization indicates the frequency of “false positives” (high specificity) and “false negatives (low sensitivity) – the two-tiered testing misses 44% of positive cases:www.ncbi.nlm.nih.gov/pmc/articles/PMC2078675/
There are additional nuances in the disinfo spread amongst MDs about
Lyme diagnosis and testing:
The WB tests most MDs are administering are detecting IgM and IgG antibodies--for MOST immune responses, the IgM antibodies indicate an newer immune response to an infection or a reactivated response to a previous infection, and eventually the body transitions IgM antibodies into IgG antibodies. IgG antibodies are generally older immune responses to an infection. However, this rule just doesn't apply for Lyme - over 200 studies have shown that the Bb microbe can interfere with normal immune function.
Most people don't generate an Erythema Migrans or bullseye rash but many MDs incorrectly insist this must be present in order for a possible infection to occur. Alternatively, an EM rash is one of the definitive signs that a Bb infection has occurred. Unfortunately, the EM rash can look nothing like the classic bullseye and is often misdiagnosed.
The IGeneX Western Blot has been preferred for a long time because IGeneX processes over 20,000 Lyme tests a year, and can adhere to a more specialized structure than the CDC regulations. IGeneX includes band 31 in their testing, and also offers 30-31kDa confirmation-these bands are often positive due to cross-reactivity with other viruses, and IGeneX uses highly specific recombination antigens to validate results. In addition, IgG needs only 2 bands present (instead of 5), and the IgM needs 2 (like the Western Blot).
Hope this is helpful -
Post Edited (Pirouette) : 10/25/2017 4:26:44 PM (GMT-6)