Find a proper lab for viral testing in Germany ?

[Markus83]

I would like to have a deeper look concerning reactivated virus infections which hasn't been done systematically in the past.

As far as I've read, CFS specialists (like Lerner, Montoya, etc.) use mainly the IgG response to distuingish between reactivated or past infection. They say "high" titers suggest a reactivated infection.

The problem is that they recommend either specialised labs in the US (Labcorp, etc.) or specific manufacturer testkits (like Diasorin) on which their interpretation guidlines focus. In Germany, the labs don't tell me, which manufacturer testkit they use. So I'm not sure what to do now. If I let the herpes family test in a normal lab, it will surely come back IgM negative and IgG positive, and then I don't know if this IgG is high or not in my case (the labs will of course say it's just normal and I don't know a CFS doctor here).

So what would you recommend me?

I can give you two examples. I tested for Varicella zoster a few years ago. It came back IgM negativ (normal < 22 U) and IgG positve with 2053 U (normal < 22 U). The lab says it's just fine. I don't know what to do with the results

I got tested in another lab for parvovirus B19: IgM negative, IgG 150 U (normal < 3 U). The lab doc says: remote infection. Then I asked him and said that the antibodies seems quite high for me. He said that's true, but it had no consequences. If I don't know how to interpret the results, the tests are not helpful for me.

 

[Hip]

This issue of viral testing in ME/CFS is a perennial problem. For patients in the US who have access to the ME/CFS specialist doctors, these doctors are able to interpret viral test results and diagnose chronic active infection, typically when IgG titers are high. But for patients in Europe and elsewhere, even if you are able to get the right test, there is no easy way to interpret the result.

In principle, interpretation should be straightforward. Dr Daniel Dantini for example uses a rule of thumb that if the IgG titers are at least 4 times higher than the average IgG titers the healthy general population get on a particular viral antibody test, then that indicates a chronic active infection in the context of ME/CFS.

This is a nice simple rule, but the problem is that the lab may not be able to tell you the average IgG titers for their tests. I wrote to a lab I used in London, and they could not tell me the average IgG titers.


In the case of the ARUP Lab enterovirus antibody tests, Dr John Chia actually validated and calibrated these tests using hundreds of healthy controls and ME/CFS patients; using this data he was able to accurately set the threshold titer for diagnosis of active enterovirus infection at 1:320. You can see his calibration data in this post.

Another perennial problem of viral testing for ME/CFS is that the only reliable blood test for enterovirus (coxsackievirus B and echovirus) is the antibody test by the neutralization method (other antibody testing methods such as ELISA, IFA and CFT are not really sensitive enough). And I am only aware of two labs that have an antibody neutralization test for coxsackievirus B: ARUP Lab in the US, and the Hellenic Pasteur Institute in Greece.

So that makes it difficult to test for enterovirus; although if you are tested at ARUP (and they do accept serum samples from abroad), at least you will know the exact threshold titer for diagnosis of active infection.

 

[Wonkmonk]

I can give you two examples. I tested for Varicella zoster a few years ago. It came back IgM negativ (normal < 22 U) and IgG positve with 2053 U (normal < 22 U). The lab says it's just fine. I don't know what to do with the results

I got tested in another lab for parvovirus B19: IgM negative, IgG 150 U (normal < 3 U). The lab doc says: remote infection. Then I asked him and said that the antibodies seems quite high for me. He said that's true, but it had no consequences. If I don't know how to interpret the results, the tests are not helpful for me.

If these were my results and all other viruses came back unsuspicious, I'd treat the Varicella test as indicating ongoing infection and try Valacyclvir, which is relatively low risk and costs are not too high. But I think for those who had chickenpox or were exposed to it as a child, a higher Varicella IgG titer isn't so unusual and might just indicated a good level of protection while the virus is in latency as it should be. But this should perhaps be validated with an infectious disease specialist.

Can't comment on the Parovirus, I never looked into this virus so far.

 

[Markus83]

I'm still unsure what to do. My doc took blood for EBV and CMV. I'll see what they come up with. The other tests I would have to pay on my own. But that's like throwing money out of a window without having a strict interpretation guideline. As Hip said, considering IgG four times higer than average does not help me, because probably no lab can tell me what the average is.

 

[Hip]

But that's like throwing money out of a window without having a strict interpretation guideline.

Indeed. In recent months I have been writing to some ME/CFS doctors in the US, asking for some guidelines about diagnosing chronic active infection in ME/CFS. So far, the replies I received have not really helped. But I need to write to more ME/CFS doctors.

The primary viruses linked to ME/CFS are: coxsackievirus B, echovirus, EBV, HHV-6, cytomegalovirus and parvovirus B19. And the intracellular bacterium Chlamydia pneumoniae is linked to ME/CFS.

So these are the main ones that ME/CFS specialists test for. In the case of active coxsackievirus B or echovirus, oxymatrine can be used as a treatment. In the case of active EBV, HHV-6 or cytomegalovirus, Valtrex or Valcyte can be used. In the case of active parvovirus B19, that responds to IVIG.

Then viruses like varicella, herpes simplex and HHV-7 are of secondary importance, as there is not much evidence linking them to ME/CFS.

As Hip said, considering IgG four times higer than average does not help me, because probably no lab can tell me what the average is.

I am not sure if there is any validity to this, but on ARUP Lab coxsackievirus B test, which we know the threshold IgG titer for active infection is 1:320, this titer is 64 times the threshold titer for a negative infection.

(If you look at the CVB test information page, it says that the threshold titer for a negative infection is < 1:10. The next titer down is 1:5, so 1:5 is the threshold titer for a negative infection. The ratio of 1:5 to 1:320 is 64.)

So I was wondering whether it might be possible to use an approximate rule of thumb that a chronic active infection in ME/CFS might be diagnosed when you have an IgG titer of at least 64 times the threshold titer for a negative infection. However, there may be no validity to this whatsoever.

 

[Markus83]

I think these threshold titers have to be taken with caution, even when it comes from specialists. I don't think that they validated them, for example by testing PCR positive patients. Or did they?

I think ones immune system must be able to detect the virus and build sufficient amounts of anibodies, to apply the rule "high titer == active infection". I could imagine, that the IS in many people is so outraged that they are not able to build sufficient amounts of antibodies anymore.

In my case I have total IgG in serum of about 10 gm/l, which is in the lower normal range (I think normal range is between 8 - 16 gm/l). But we have to keep in mind that reference ranges are made from healty people. If you have several chronic infections ongoing, I would think one should have total serum IgG in the higher or even above the reference range.

 

[Hip]

I don't think that they validated them, for example by testing PCR positive patients. Or did they?

PCR blood tests are generally not the best way to test for infections in ME/CFS: Dr Chia found that in patients with enterovirus-associated ME/CFS, even under the best conditions, PCR will only come out positive in around on third of cases, meaning that two-thirds will get a false negative.

In the case of enterovirus, we know from numerous studies that in ME/CFS this infection in found in the tissues (muscle, intestine and brain tissues), with not much virus actually in the blood. This is why blood PCR is often negative in ME/CFS.

Antibody testing is different, because unlike PCR, it does not try to detect the virus directly, but measures the immune response to the virus. So even if the infection is hidden in the tissues, you still get an antibody response.

Dr Chia considers the gold standard test for enterovirus to be via a stomach tissue, where the tissue itself is tested for enterovirus.

 

[Wonkmonk]

The other tests I would have to pay on my own. But that's like throwing money out of a window without having a strict interpretation guideline.

But there might also be a very clear result where it is obvious that the titers are elevated. In my case, I had HSV-1 titers >1:20,000 on three separate occasions in the past year. Regardless where the actual cutoff is, this is a wildly elevated titer and justifies a trial with antivirals.

 

[Wonkmonk]

In the case of enterovirus, we know from numerous studies that in ME/CFS this infection in found in the tissues (muscle, intestine and brain tissues), with not much virus actually in the blood. This is why blood PCR is often negative in ME/CFS.

This is also consistent with Dr Lerner's theory which states that there is an abortive ongoing infection in which no complete virions are formed, therefore PCR (and often IgM) is negative.

 

[Hip]

This is also consistent with Dr Lerner's theory which states that there is an abortive ongoing infection in which no complete virions are formed, therefore PCR (and often IgM) is negative.

Yes, just as for enterovirus-associated ME/CFS, numerous studies found non-cytolytic enterovirus infection inside the cells of ME/CFS patients (a type of infection which produces no new viral particles), likewise, in the case of herpesvirus-associated ME/CFS, Dr Lerner proposed there are abortive herpesvirus infections inside the cells of ME/CFS patients, and these again do not produce new viral particles.

Although Lerner's theory lacks supporting evidence, it could explain why you get high IgG titers in ME/CFS, but often find no infection in the blood when you test by PCR.

 

[Markus83]

I made a new thread with my lab results, maybe you can help me: http://forums.phoenixrising.me/inde...lts-help-me-with-interpretation-please.59380/