Best Lyme&co-infect. lab/doc in Europe ?

Medical topics with questions, information and discussion related to Lyme disease and other tick-borne diseases.
Post Reply
Anushka
Posts: 34
Joined: Tue 4 Nov 2014 17:54

Best Lyme&co-infect. lab/doc in Europe ?

Post by Anushka » Wed 3 Jun 2015 7:54

Hi all,

I am the author of moms4science.wordpress.com (an old ME pt/mom).

Recent developments on the ME scene (KDM finding more Lyme&co-infections in ME pt's), and immune marker studies which I follow closely, lead me to believe that there might be the possibility that ME and "chronic" Lyme are the same or at least caused by similar pathogens. (I am not convinced, but looking at the possibility.)

I would like to hear, in a nutshell, from the more experienced "chronic" Lyme pt, which lab/doc you think is the best in Europe to test for Lyme & co-infections. (Especially looking for newer testing methods/labs for co-infection/strains -- like Babesia)

Not looking for personal accounts or treatment advise, but a quick comprehensive overview on testing and best docs to dx chronic infection.

(Especially looking for newer testing methods/labs for co-infection/strains -- like Babesia)

Thank you
Anushka
Anushka

User avatar
LHCTom
Posts: 341
Joined: Mon 22 Oct 2012 4:18

Re: Best Lyme&co-infect. lab/doc in Europe ?

Post by LHCTom » Thu 4 Jun 2015 4:13

I cannot speak for Europe with personal experience but the same principles apply and the European Lyme antibody tests are better designed and more modern than the US tests. So here are a few thoughts.

There are a number of tests that have pro and cons. The best way to be sure is too find a doctor that will run a number of tests and then evaluate the underlying details of the results to decide if you have or had Lyme or Babesia.

For both Lyme and Babesia, there are multiple genospecies that are endemic to different parts of the world. You need to be sure that whatever form of test is being done is able to detect the most likely genospecies in your area. The only exception is culture for Lyme is not as genospecies sensitive and microscopic examination of red blood cells for Babesia is the same for each genospecies.

Most people get the doctors favorite test and are given a positive or negative and they run with that. Don't do that. You need to understand the test and arrange for multiple tests and based on the underlying details, the probability of having Lyme or Babesia can be estimated. Sometimes its obvious one way or the other but many have wildly varying results which make it more difficult to analyze.

For Lyme those include:

Indirect - antibody based testing - the most vetted but needs careful analysis of the specifics and the very best lab and test manufacturers.

The EUROIMMUN antibody tests are very good and their printout shows the exact optical levels of the band intensities of each antibody for each of the antigens including Vlse which provides similar testing as the C6 in the US which looks for certain epitopes on the Vlse surface antigen.

http://www.euroimmun.ch/fileadmin/user_ ... UK_A02.pdf

The Mikrogen system would be a very good European alternate test to compare to the Euroimmun results.
http://www.mikrogen.de/english/deutschl ... igg-1.html
Euroline Printout.JPG
Euroline Printout.JPG (57.45 KiB) Viewed 2173 times
As you can see in the EUROIMMUN report, it accounts for multiple genospecies, has an improved set of antigens plus the optical level shows gives a quantitative level for each antibody. In the US, they typically don't account for multiple genospecies and show no data on specific bands. The bands are not all created equal. Strain and genospecies can effect which antibodies are produced. So knowing the optical level of the bands indicates approximate antibody levels. It will also show if its barely negative which would not be reported in the US. That in turn can be compared with Mikrogen for consistency.

I would start by arranging for both the EUROIMMUN and Mikrogen IgG and IgM blots and compare them.


Direct - PCR and culture
Both culture and PCR are far less validated so would only be used if the two antibody tests were so discordant, you needed more information. PCR is typically not useful for disseminated Lyme since finding spirochete DNA in blood is a very low probability since spirochetes only use blood for traversing the body. During the early EM rash, the EM skin can be both cultured and tested with PCR effectively. But the EM only occurs early and in half the cases.

The US Sapi/Advanced Laboratory Labs culture may be a good test but needs additional validation to be sure.
http://www.advanced-lab.com/spirochete.php

For Babesia those include:

Indirect - antibody based testing - the most vetted but needs careful analysis of the specifics and the very best lab and test manufacturers.

I'm not sure of the European Baesia testing based on antibodies but a little research should allow you to find the two best systems to allow them to be compared again. Antibody testing is genospecies sensitive so in Europe Babesia divergens is most common. But in the US Babesia microti and Babesia duncani/Wa1 appear on East and West Coast respectively. Make sure the antibody test takes any reasonable genospecies into account.

Direct - PCR and Microscopic examination of the red blood cells

If a competant microscopic examination of your red blood cells shows some of the cells infected by the maltese cross of Baesia, that is very powerful evidence. Babesia often is subclinical and only infects a small number of red blood cells so it takes a lot of luck and someone very competant at microscopy identification of Babesia in a blood smear.

The red blood cells infected with Babesia looks like this:
http://www.ufrgs.br/imunovet/molecular_ ... abesia.jpg

Lyme in Europe can be caused by B. garinii, B. afzelii or B. burgdorferi and its possible but unlikly that another genospecies might have caused the infection.

The EUROIMMUN and Mikrogen blots take all three genospecies into account.

http://www.euroimmun.ch/fileadmin/user_ ... UK_A02.pdf

I would start with two different antibody tests for each and see if they agree. If they are both positive or both negative, they are probably correct because the European criteria was designed to be more sensitive than the US version which is so controversial. If you do this and get discordant results, then you might consider the US culture and a Babesia blood smear to see what it shows.
The greater the ignorance, the greater the dogmatism.

Attributed to William Osler, 1902

User avatar
ChronicLyme19
Posts: 564
Joined: Mon 11 Aug 2014 17:42
Location: NY, USA

Re: Best Lyme&co-infect. lab/doc in Europe ?

Post by ChronicLyme19 » Thu 4 Jun 2015 4:41

I'll second everything that LHCTom has said.

Also I'd add that some of us with persistent Lyme/tick borne infections also have immunogloublin immune deficiencies in IgA, IgM, and IgG. These deficiencies may cause us to test false negative. Your total globulin level in basic blood work may be normal so the doctors might not think to check for this.
Half of what you are taught is incorrect, but which half? What if there's another half missing?

User avatar
LHCTom
Posts: 341
Joined: Mon 22 Oct 2012 4:18

Re: Best Lyme&co-infect. lab/doc in Europe ?

Post by LHCTom » Thu 4 Jun 2015 5:27

There are a number of tests promoted by the Lyme community like the CD57 and Elispot-LTT but I've been unable to find any basis for the CD57 and the Elispot-LTT has not been validated.

I too have low IgG subclasses and suspect it might cause a bias lowering some IgG based tests like the Western Blot and ELISA which rely on quantities of the right IgG subclass associated with the type of infection.

My Immunetics C6 has hovered around 2.0 for 5 years where above .9 and above is positive but my level is lower than many others. I have tested it yearly since showing positive for Lyme and my last test earlier this year at StonyBrook using an Immunetics kit was negative. Some research suggests the C6 drops when the infection has resolved.

I also did the ALS culture which was positive and I got a copy of my cultures pyrG gene. When I looked it up in NCBI, it was novel but the closest match was a CA strain of Bb. So the ALS culture might be ok but only further validation will tell us for sure.

I believe IgG subclass 3 is the relevant IgG for a spirochetal infection. My IgG subclass 3 was 30 where the normal range at Labcorp is 41-129. My IgG subclass 1 was also low at 388 with a normal range of 422-1292. This is a quantitative measure of all the IgG subclass combined and I have not been able to find any research on its effect on ELISA or Blot levels. I suspect it does somewhat. Its also not Lyme specific but can effect test results if the doctor is unaware of it.
The greater the ignorance, the greater the dogmatism.

Attributed to William Osler, 1902

Anushka
Posts: 34
Joined: Tue 4 Nov 2014 17:54

Re: Best Lyme&co-infect. lab/doc in Europe ?

Post by Anushka » Thu 4 Jun 2015 22:59

@LHCTom

Thank you 4 compiling all this information for me. I will go through it and than most probably have some
more questions later on.

@ChronicLyme19 , I think the topic immune deficiency in patients with chronic Lyme has been under researched and appreciated; especially regarding reliability of antibody tests.

I will be back with some questions.

Thank you all
Anushka

Anushka
Posts: 34
Joined: Tue 4 Nov 2014 17:54

Re: Best Lyme&co-infect. lab/doc in Europe ?

Post by Anushka » Mon 15 Jun 2015 15:18

Hi again,

I have a few more questions.
Direct - PCR and culture
Both culture and PCR are far less validated so would only be used if the two antibody tests were so discordant, you needed more information. PCR is typically not useful for disseminated Lyme since finding spirochete DNA in blood is a very low probability since spirochetes only use blood for traversing the body. During the early EM rash, the EM skin can be both cultured and tested with PCR effectively. But the EM only occurs early and in half the cases.
PCR on synovial fluid has shown a sensitivity of up to >90% (when using four different primer sets) in patients with untreated or partially treated Lyme arthritis, making it a helpful confirmatory test in these patients. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1195970/
Why are you saying that PCR and culture is fare less validated ? Any specific reason ?

So far I have not heard from anyone on forums that they had a synovial fluid aspiration done, or that this topic is even being discussed among chronic Lyme pts. Why ?

Another additional indirect tool to prove an ongoing joint or bone disease of any kind would be a nuclear scintigraphy. Is this tool not being used routinely in LYME pt with joint swelling or complains ?
Direct - PCR and Microscopic examination of the red blood cells.

The only exception is culture for Lyme is not as genospecies sensitive and microscopic examination of red blood cells for Babesia is the same for each genospecies.

If a competent microscopic examination of your red blood cells shows some of the cells infected by the maltese cross of Baesia, that is very powerful evidence. Babesia often is subclinical and only infects a small number of red blood cells so it takes a lot of luck and someone very competent at microscopy identification of Babesia in a blood smear.
What do you mean by "very competent" ?

How good and specialized does a microbiologist have to be to find Bb or Babesia, or any protozoa in general, and in which kind of other tissue would one expect to find Bb or Babesia ?
Anushka

User avatar
LHCTom
Posts: 341
Joined: Mon 22 Oct 2012 4:18

Re: Best Lyme&co-infect. lab/doc in Europe ?

Post by LHCTom » Tue 16 Jun 2015 7:51

Hi again,

I have a few more questions.
Direct - PCR and culture
Both culture and PCR are far less validated so would only be used if the two antibody tests were so discordant, you needed more information. PCR is typically not useful for disseminated Lyme since finding spirochete DNA in blood is a very low probability since spirochetes only use blood for traversing the body. During the early EM rash, the EM skin can be both cultured and tested with PCR effectively. But the EM only occurs early and in half the cases.



PCR on synovial fluid has shown a sensitivity of up to >90% (when using four different primer sets) in patients with untreated or partially treated Lyme arthritis, making it a helpful confirmatory test in these patients. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1195970/
The key word is confirmatory.

That's only patients who were CDC positive on US ELISA and Western Blot and have obvious Lyme arthritis. When your Knees or other joints are swollen and you are CDC positive and have not been treated, synovial fluid will contain spirochetes and even their dead DNA after treatment. But that is a rare case. Not everyone and not all genospecies cause Lyme arthritis.

PCR in the blood fails because the number of spirochetes is so low and that combined with the very small PCR test sample. With the exception of of a few lab versions of PCR, the typical sensitivity is in the 10% range. That's pretty lousy.

Wormser acheived about 40% sensitivity on CDC positive blood cultures. That's pretty lousy odds for a diagnostic.

Both PCR and culture can be used with a relapsing fever during the peaks of spirochetemia in the blood. But those are odd cases also.



Why are you saying that PCR and culture is fare less validated ? Any specific reason ?
Cultures with the exception of thne Sapi/ALS are only used in research labs and are not standardized nor have they been validated as a diagnosis tool as opposed to research tool. Same with PCR with the exception of special cases.

I'm talking about broad first level testing and not third level confirmatory based on earlier tests and other facts. That's a fr more complicated question as it requires all the possible disgnois facts and paths.
So far I have not heard from anyone on forums that they had a synovial fluid aspiration done, or that this topic is even being discussed among chronic Lyme pts. Why ?
I've never heard of someone with chronic Lyme having swollen joints/ arthritis. Once it becomes chronic, the immune system gets it under control but just cannot kill it. Arthritis out of control spirochetes growing in joints before treatment or adaptive immune system control.

Its just that very few people have the conditions where culture an PCR work well. If you are talking about walking into your doctor and want to know if your symptoms are Lyme and you didn't have an EM, are antibody positive and have big swollen joints, the antibody tests are the best general broad sweep. If you are antibody negative but have a history of a bite that was attached a reasonable time and you live in an endemic area ( or travel), other conditions ruled out, then other tests are ways of looking at more specific situtaions like arthritis or obvious brain involvment.
Another additional indirect tool to prove an ongoing joint or bone disease of any kind would be a nuclear scintigraphy. Is this tool not being used routinely in LYME pt with joint swelling or complains ?
I don't know what it is but what testing route one takes is dependent on the situtaion. There are many situations and variables and diagnostic algorithms based on history, examination, symptoms, ruling out other conditions etc...Given a particular situation, one chooses the best test to learn something based on a dianosis hypothesis based on the situation and what has been learned.
What do you mean by "very competent" ?
It takes experience .

When someone looks through a microscope trying to identify an organism, its not an easy thing to do.

http://www.ncbi.nlm.nih.gov/books/NBK26880/

http://www.bio.davidson.edu/people/dawe ... 2lab2.html

http://water.me.vccs.edu/courses/env195 ... _print.htm

How good and specialized does a microbiologist have to be to find Bb or Babesia, or any protozoa in general, and in which kind of other tissue would one expect to find Bb or Babesia ?
The only sensible place to look for Babesia is red blood cells. But there are a lot of procedural details to properly identifying what is inside the red blood cell.
The greater the ignorance, the greater the dogmatism.

Attributed to William Osler, 1902

Post Reply