Discussion about Armin labs (Split Thread).

[Vitalic]

Prof. Edwards would you care to expound on the reasons you suspect Armin's test(s) to be unreliable? I do recall you made a generalised post about the pitfalls of LTT as a testing methodology but I do not recall seeing anything specific to Lyme or Armin. I am particularly interested since I received a positive LTT Elispot result on a retest after the initial test was negative, and although I have been clinically assessed by KDM I am yet to be even close to convinced that it is a correct diagnosis, since as I am seronegative the only evidence appears to be limited to LTT results plus KDM's interpretation of my immune profile being consistent with other Lyme patients + animal models. I already took the leap of faith and underwent IV antibiotic treatment which did not help, and yet he is still convinced there is an active Borrelia infection which will require further treatment. An agent said in the film The Matrix, "there are levels of survival we are prepared to accept", well there are levels of evidence we are prepared to accept in a situation where there is no imperfect solution much less a perfect one, but I certainly have reason to be skeptical about my diagnosis and by extension the diagnosis of presumably a subset of other ME patients that have been led down the Lyme path on grounds that are flaky at best. (I say subset advisedly, and really it is a subset within a subset, because I am very aware that some people have made significant improvements and even recovered by treating late stage Lyme).

I also have my own doubts about Armin after seeing him give presentations at events seemingly arranged to hawk Nutramedix products and the fact he is now advising patients on Lyme treatment, it rather gives the impression he has realised what a potential goldmine this is and that just selling tests doesn't quite tap into it enough.

 

[justy]

See here http://lymediseaseuk.com/wp-content/uploads/2015/12/Statement_regarding_DAKKS_Accreditation.pdf
For a statement from Armin Schwarzbach and his team at Armin labs about accreditation of their tests, after inaccurate comments made by Lyme Disease Action.

 

[trickthefox]

From what I have gathered from all the sources I listen to it seems very likely that Armin labs are producing false positive results and people are taking treatment unnecessarily.

Jonathan can you point to sources that back up this statement as it is a pretty huge statement given the people on the forum that are treating based on these results

 

[Jonathan Edwards]

I am afraid I am not prepared to say much more. The view I express is the view of what appear to be sensible specialists in the field who are just ordinary people going about their work with no axes to grind. And the whole set up with these commercial labs rings danger bells for me anyway. There are times when particular individuals in the medical world are ahead of the game and the standard wisdom is out of date. But in my experience you can tell when people are ahead of the game because they have everything openly documented and in general make no special claims, simply give their case. The controversial Lyme testing labs in no way fit that picture to me. There are a whole lot of other reasons why I take the view I do but they are best kept confidential.

I am not suggesting anybody takes my opinion as carrying weight, simply that other opinions may be ill-founded and that it is sensible to consult with specialists who have no financial interest in the matter.

 

[msf]

I would say that the LTT-ELISPOT has been openly documented, since they have published a study showing it´s sensitivity and specificity. As for special claims, surely being ahead of the game means that by giving your case you are making special claims?

 

[msf]

I think we can speculate the same thing about the labs in question. They will be happy to keep running the tests, making money off of patients all without validating the test which might turn out to be bogus.

Of course I am speculating about this.

Barb

How do they validate their own test externally?

 

[Jonathan Edwards]

How do they validate their own test externally?

If there is no gold standard to check the test by then it is not validatable and that is the end of it.

If there is a gold standard they get other labs to send them blinded samples that have been found positive and negative on the gold standard. They send out their blinded results for the inspecting labs to compare with the gold standard findings, breaking the code. They also send out kits with instructions to several other labs and send those labs samples they have deemed positive and negative, again blinded. If the test performs reliably then the results will be replicated. And there are other variations to check for reproducibility across various other variables. It is all routine for government service labs. When my mother ran the virus reference lab at the Central Public Health Laboratory Unit at Colindale that sort of thing was much of the workload. Unfortunately, even in the NHS pathology is increasingly subcontracted out to commercial labs.

 

[paolo]

I am unable to judge if LTT technology is realiable in Lyme disease. And I fear that nobody can. This test deserves further studies to be validated.

But it is worth noting that the same author who participated in a paper about the usefulness of LTT in the diagnosis of active Lyme infection, has recently worked with Fluge and Mella on autoimmunity against beta adrenergic receptors in CFS (this is the paper, that you all know).

The name of this scientist is Hans-Dieter Volk, and he is from Charité University Medicine of Berlin. So if you dicredit his work on LTT in Lyme disease, you have to question also Fluge's work on autoimmunity in ME.

 

[Daffodil]

demeirleir's team already confirmed autoimmunity in CFS via tissue sampling. what I'd like to know is, why were the proteins different in spinal fluid with CFS vs Lyme??

 

[msf]

Because it was CFS, not ME?

 

[Jonathan Edwards]

I am unable to judge if LTT technology s realiable in Lyme disease. And I fear that nobody can. This test deserves further studies to be validated.

But it is worth noting that the same author who participated in a paper about the usefulness of LTT in the diagnosis of active Lyme infection, has recently worked with Fluge and Mella on autoimmunity against beta adrenergic receptors in CFS (this is the paper, that you all know).

The name of this scientist is Hans-Dieter Volk, and he is from Charité University Medicine of Berlin. So if you dicredit his work on LTT in Lyme disease, you have to question also Fluge's work on autoimmunity in ME.

I think this oversimplifies. The Norwegians strenuously avoid making any claims about clinical application of their work. Tests that are not validated as clinical tools can still be of interest in the research arena.

 

[msf]

If there is no gold standard to check the test by then it is not validatable and that is the end of it.

If there is a gold standard they get other labs to send them blinded samples that have been found positive and negative on the gold standard. They send out their blinded results for the inspecting labs to compare with the gold standard findings, breaking the code. They also send out kits with instructions to several other labs and send those labs samples they have deemed positive and negative, again blinded. If the test performs reliably then the results will be replicated. And there are other variations to check for reproducibility across various other variables. It is all routine for government service labs. When my mother ran the virus reference lab at the Central Public Health Laboratory Unit at Colindale that sort of thing was much of the workload. Unfortunately, even in the NHS pathology is increasingly subcontracted out to commercial labs.

I´ve pointed out before that there is no gold standard, so therefore no Lyme tests are validatable, which means that you can´t say that the NHS tests are better than the LTT-ELISPOT.

 

[paolo]

I think this oversimplifies. The Norwegians strenuously avoid making any claims about clinical application of their work. Tests that are not validated as clinical tools can still be of interest in the research arena.

Yes, I see yor point, prof. Edwards.

From what I have studied, I think that from a patient's point of view to use Rituximab and see if it can help, is currently as legitimate as to analize one's own T cells activity against borrelia antigens with an experimental test like LTT.

 

[msf]

In Prof. Edward´s defence, though, he does not advise people to get Rituximab for ME.

 

[msf]

Two more of the authors of the LTT study (von Baehr V and Doebis) were also involved (along with Volk) in the Charite study on EBV responses in ME patients last year:

http://www.ncbi.nlm.nih.gov/pubmed/24454857

You´d think one of them would say to Scheibenbogan, ´we´ve got a test for you, Fluge and Mella to try on your patients...´

 

[msf]

I was just watching the video below, in which at around 14.00 he says that EUCALB (European Concerted Action for Lyme Borreliosis) recommend that the cut off value for an ELISA is adjusted so that...wait for it...less than 5% of healthy blood donors are positive for Lyme...is this the validated testing that I hear people talk about?

Also, check out the slide at 21.21...you´ve got to love that English Channel! First it kept the French out, then the Germans out, and now it´s keeping Lyme out!

 

[Hip]

Here is a nice little diagram graphically showing how, as you change the threshold or cutoff point for a positive test result, it affects the number of false positives and false negatives you get in your test:

Source: here.​

The pink curve on the top represents patients with the disease; the gray curve on the bottom represents patients without the disease.

The horizontal line in the middle of the graph represents your test result value (like titer for example), and as you move to the right on this line, the test result value (titer) increases.

The two vertical lines in the graph (one solid and one dotted) represent different cutoffs that you can choose for deciding the point where the test value (titer) signifies a positive result.

You can see that if you move your cutoff line left, you get less false negatives, but more false positives.

Labs like Arminlabs may have moved their cutoff line to the left to reduce false negatives, but at the expense of getting more false positives.

 

[Mel9]

Here is a nice little diagram graphically showing how, as you change the threshold or cutoff point for a positive test result, it affects the number of false positives and false negatives you get in your test:

View attachment 14322
Source: here.​

The pink curve on the top represents patients with the disease; the gray curve on the bottom represents patients without the disease.

The horizontal line in the middle of the graph represents your test result value (like titer for example), and as you move to the right on this line, the test result value (titer) increases.

The two vertical lines in the graph (one solid and one dotted) represent different cutoffs that you can choose for deciding the point where the test value (titer) signifies a positive result.

You can see that if you move your cutoff line left, you get less false negatives, but more false positives.

Labs like Arminlabs may have moved their cutoff line to the left to reduce false negatives, but at the expense of getting more false positives.

What is the possible serological mechanism for a false positive?

 

[Hip]

What is the possible serological mechanism for a false positive?

I am not sure of the precise biochemical dynamics, but the accuracy of medical tests is expressed in terms of their sensitivity and a specificity. If a test was 100% accurate every time, it would have both a sensitivity of 100%, and a specificity of 100%. But in the real world, tests are never perfect, so you never get a 100% figure.

Lyme tests for example have a sensitivity of up to around 80% for the best tests. That means 80% of patients actually infected with Borrelia will get a correct positive result on the test when tested. But 20% will get an incorrect negative result (a false negative).

And if the specificity of a Lyme test is around 95%, that means 95% of patients who are not infected with Borrelia will get a correct negative result on the test when tested. But 5% will get an incorrect positive result (a false positive).


This issue of false positives and false negatives is problem in Lyme testing because the testing technology is not very accurate.

If we compare to HIV testing, the HIV test is much more accurate, with a sensitivity of 99.7% and specificity of 98.5%. That means only 0.3% of patients (3 patients in 1000) tested for HIV will get a false negative, and 1.5% of patients (15 patients in 1000) tested will get a false positive.

 

[nandixon]

I am particularly interested since I received a positive LTT Elispot result on a retest after the initial test was negative, and although I have been clinically assessed by KDM I am yet to be even close to convinced that it is a correct diagnosis, since as I am seronegative the only evidence appears to be limited to LTT results plus KDM's interpretation of my immune profile being consistent with other Lyme patients + animal models. I already took the leap of faith and underwent IV antibiotic treatment which did not help, and yet he is still convinced there is an active Borrelia infection which will require further treatment.

At the time you tested positive for the second Elispot LTT, were you taking (or had you taken) any medications or supplements that were different than you'd taken when you tested negative for the first Elispot LTT? For example, did you undergo antibiotic treatment in between the two tests?