Validity of the CDC 2-tiered Test for Late Lyme Borreliosis

Medical topics with questions, information and discussion related to Lyme disease and other tick-borne diseases.
radicale
Posts: 134
Joined: Fri 4 May 2012 16:51

Re: Validity of the CDC 2-tiered Test for Late Lyme Borrelio

Post by radicale » Mon 6 May 2013 23:19

It is useless guys, when someone is sent to a forum to maintain and/or protect the status quo you can be sure they won't change their mind. I think the time has come to embrace the Amish tradition of shunning, for the sake of maintaining some sanity. It would be wonderful if studies existed which utilized only culture-positive late Lyme disease patients, but they don't and as a result it is impossible to say how sensitive/specific the current 2-tier tests are for these patients.

Having said this it is fair to say that both over and under diagnosis occur, by the ILADS and ISDA camp respectively.

Henry
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Re: Validity of the CDC 2-tiered Test for Late Lyme Borrelio

Post by Henry » Mon 6 May 2013 23:54

"... when someone is sent to a forum to maintain and/or protect the status quo"... ? An example of a small mind at play. If you can't provide convincing evidence to make your point, there's always the ad hominen argument -- which seems to be alive and thriving in Lymeland. Yah think one reason why such patients haven't been considered might just be that they are extremely rare -- if they exist at all? I know it's not because attempts were not made to culture Borrelia from such patients. It has been tried many, many times.....all without success.

radicale
Posts: 134
Joined: Fri 4 May 2012 16:51

Re: Validity of the CDC 2-tiered Test for Late Lyme Borrelio

Post by radicale » Tue 7 May 2013 0:06

Henry wrote:"... when someone is sent to a forum to maintain and/or protect the status quo"... ? An example of a small mind at play. If you can't provide convincing evidence to make your point, there's always the ad hominen argument -- which seems to be alive and thriving in Lymeland. Yah think one reason why such patients haven't been considered might just be that they are extremely rare -- if they exist at all? I know it's not because attempts were not made to culture Borrelia from such patients. It has been tried many, many times.....all without success.
Give me a break. We have had a long discussion regarding the sensitivity and specificity of the 2-tier testing. During this discussion plenty of evidence was provided. I suppose I need to bring it up in its entirety every time I post? Because that's what you do right...

Lorima
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Re: Validity of the CDC 2-tiered Test for Late Lyme Borrelio

Post by Lorima » Tue 7 May 2013 4:08

Regarding Steere et al. 2008: 

Aside from the circularity issue, there is another problem I find equally egregious. Note that of the 31 patients billed as having "Persistent infection (Stage 3) Arthritis or chronic neurologic involvement", there is only ONE late-stage neurological patient included: the other 30 late-stage patients had arthritis, with its famously high IgG levels, so useful for passing the 2T test. See Table 1, footnote e. Quite well-buried, isn't it? 
"I have to understand the world, you see."
Richard Feynman

TicksSuck
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Re: Validity of the CDC 2-tiered Test for Late Lyme Borrelio

Post by TicksSuck » Tue 7 May 2013 17:04

It's also surprising that this one late-stage neurological patient was not considered false positive. I wonder why...

Lorima
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Re: Validity of the CDC 2-tiered Test for Late Lyme Borrelio

Post by Lorima » Tue 7 May 2013 17:39

They had to have a token late-stage neuro patient, so they could claim that they had shown that the 2T test was 100% sensitive in all late-stage disease, not just in arthritis. Even so, it would be interesting to know exactly what that patient's characteristics were, wouldn't it?
"I have to understand the world, you see."
Richard Feynman

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LHCTom
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Re: Validity of the CDC 2-tiered Test for Late Lyme Borrelio

Post by LHCTom » Thu 9 May 2013 20:48

Just an FYI: The reliability of the Western Blot in HIV testing has had a similar history of problems.

http://www.youtube.com/watch?v=7Lm93axmD70

Antibodies are specific to epitopes and NOT antigens. An epitope is a portion of a molecule to which an antibody binds. Each Borrelia surface antigen has multiple epitopes. Each surface antigen has a set of epitopes. Antibodies are produced by B cells with paratopes that match and bind to each epitope. So there are typically multiple antibodies with unique paratopes matching unique epitopes on each surface antigen. OspC seems to be the surface antigen with the least variation in epitopes which has made it a target for a "better" test since the epitope set variation is the basis for the Western Blot strain or species sensitivity. The B31 strain has a very specific set of epitopes on each of its surface antigens. A widely genetically diverse strain from B31 or another species will have a different epitope set for the same surface antigen.

Antibodies bind to epitopes on antigens and not just antigens. So a widely diverse strain or species with a very different set of epitopes will lead to Western Blot blot binding failure to the primary B31 based antibody. The B31 primary antibodies have paratopes that match the B31 antigen epitopes. If the surface antigen has sufficiently different epitopes, then fewer antibodies will bind during blotting. This lowers the band darkness reducing sensitivity. Only the antibodies spread out into bands by gel electrophoresis that have epitopes matching the B31 antigen epitopes will blot. This is the underlying reason that using the US B31 based Western Blot fails to detect European species. It doesn't just apply to species. The distinction between a Borrelia strain or species is not based on its surface antigen epitope variation. As the genetic diversity increases as in strains or species, the surface antigens epitope sets eventually vary enough to cause the Western Blot to fail. This is when the test antigens are replaced with ones that match the Borrelia in the area such that this epitope set diversity is reset.

There is no magic epitope set difference boundary between Borrelia burgdorferi, Borrelia afzelii , Borrelia garinii, Borrelia miyamotoi etc... As the genetic diversity increases, the epitope set differences increase. Eventually this causes the blotting failure when the blotting primary antibody paratopes fail to bind to valid antigens. This is not a linear function since the immune system can prefer certain epitopes making them more dominant. But eventually, the match breaks down, the quantity of antibodies that match during blotting decreases and the test fails.

This is the reason for example, the tests outside the US use antigens from local Borrelia. All the Borrelia share the same set of surface antigens ErpA, REVA, DbpA, OspC, OspD, 30, OspA, OspB, BmpA, FlaB, VlsE, 45, BBK32, 58, 66 and P83/100. Unfortunately, the antibodies for each of these can differ by strain or species. This is because the epitopes on each of these vary as diversity varies. Otherwise it would be easy to have a universal test.

It is this underlying paratope->epitope matching across a whole set of epitopes on each surface antigen that is where the problems lies. This is also why the C6 test was pursued since its epitopes are highly conserved across strains and species that gave it some advantages. Even the C6 fails since the epitopes on C6 also vary making it fail for some cases.

Since most of the studies exploring the CDC 2T and C6 were done in the US Northeast, the underlying Borrelia strain diversity was biased leading to a bias in test results. Unless the studies are done with known underlying strain diversity, this epitope set problem will lead to biased results. This is why nearly every country has its own 2T like test with local antigens with closely matching epitopes and why the criteria vary.
The greater the ignorance, the greater the dogmatism.

Attributed to William Osler, 1902

rlstanley
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Re: Validity of the CDC 2-tiered Test for Late Lyme Borrelio

Post by rlstanley » Fri 10 May 2013 2:56

.
somebody said:
... I think the time has come to embrace the Amish tradition of shunning,...
How beyond bullying. How beyond ignorant. How fitting of LymeLand yapping.

Meh.
.

radicale
Posts: 134
Joined: Fri 4 May 2012 16:51

Re: Validity of the CDC 2-tiered Test for Late Lyme Borrelio

Post by radicale » Fri 10 May 2013 3:07

rlstanley wrote:.
somebody said:
... I think the time has come to embrace the Amish tradition of shunning,...
How beyond bullying. How beyond ignorant. How fitting of LymeLand yapping.

Meh.
.
How is that bullying or ignorant? What is perhaps more ignorant is to take a small snippet of my quote out of context to fit to some strange stereotype. Henry refuses to discuss real points of contention, so why exactly should anyone take him seriously.

He provides as conclusive evidence of the 100% sensitivity of the current 2-tier testing for late lyme disease a study with a token late lyme disease patient.

He refuses to acknowledge the effect of strain and species variations on the sensitivity of the 2-tier test, as shown by Dr. Wormser. Then when he sees fit accuses others of making unsubstantiated claims, again ignoring the said evidence.

rlstanley
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Joined: Mon 3 Dec 2007 2:53

Re: Validity of the CDC 2-tiered Test for Late Lyme Borrelio

Post by rlstanley » Fri 10 May 2013 3:28

.

When you start talking shunning people, you show how little ammo you have. Has nothing to do with Henry in the slightest. It's a loser.

Hey
Shun
Away

Me
Too?
Thank You.
.

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