HHV-6 Infection - IgG or IgM?

[Learner1]

@Learner1
Valcyte vs Valtrex?

Been on Valtrex (500mg 3x/day) for 1 month now. I feel decent energy levels the majority of the days. But in past 30 days (since starting Valtrex), there have been 3 times where I was exhausted. Each time, the exhaustion lasted 24-48 hrs.

That sounds hopeful. With EBV, my doctors (one is a top ME/CFS specialist) wanted me on 3g a day of valacyclovir (Valtrex). My insurance wouldn't approve it, but they somehow were ok with 1.8g of valganciclovir a day. Lerner put patients on 4g of valacyclovir a day.

 

[mitoMAN]

@Hip @Learner1
I have done quantitative PCR of HHV-6 and EBV.
The results came in negative.

Somehow its almost impossible to get a IFT Titer check for HHV-6 and EBV in Austria.
All the labs told me that this technique is not used anymore (?!)..
So all I got is ELISA or useless positive / negative IgG / IgM checks..

I'm stuck in Germany right now due to Corona and will try to find an IFA/IFT Lab here for exact Titers.
However:
Would the negative qPCR of HHV-6 and EBV rule out any of these two as possible cause?

 

[Hip]

Would the negative qPCR of HHV-6 and EBV rule out any of these two as possible cause?

As far as I know, these negative results on your qPCR blood test would not rule out the possibility of getting high antibody levels for herpesvirus on an antibody test.

In the case of enterovirus, I know that Dr Chia has used the most sensitive PCR available, and often gets negative results on a blood test, even though the ME/CFS patient's antibody levels are very high.

 

[mitoMAN]

Thank you Hip, I finally found the link in your roadmap to testing via IFA at the IMD Berlin and will do so next week. (HHV-6 IgG IFA to get the correct titers).

Again. Thank you so much for this incredible roadmap!

 

[SuhasSN]

Interesting, I've never seen that statement from the HHV-6 Foundation before.

Generally when I've seen studies that examine the sensitivity of antibody tests, the order of sensitivity is this:

• Neutralization test (various types of neutralization test: micro-neutralization test, plaque reduction neutralization test, cytopathic effect neutralization test).
• EIA (enzyme immunoassay) and ELISA (enzyme-linked immunosorbent assay). ELISA is a specific type of EIA.
• IFA (immunofluorescence assay, or immunofluorescence test), also called IFT, IF.
• CFT (complement fixation test), also called CF.

Neutralization is the gold-standard most sensitive, followed by EIA/ELISA, with IFA being similarly sensitive to EIA, but IFA typically lagging slightly behind the sensitivity of EIA.

If you take a virus like coxsackievirus B, which is one of the hardest viruses to detect in chronic infections, only a neutralization antibody test can reliably detect it. This is what Dr Chia found.

EIA and IFA might sometimes detect chronic CVB, but will often miss it. And CFT is completely useless for chronic coxsackievirus B, and will never detect such chronic infections, as CFT is completely insensitive in the chronic infection context (CFT is only suitable for detecting acute infections).



I just Googled, and came across this old paper from 1996, which found ELISA was more sensitive than IFA. But maybe techniques have changed since then.

There is one more standard for EBV and HHV 6 that is CLIA In India the labs told Me that it is at par with ELISA or even more sensitive then ELISA
Please share your opinion on this ?

 

[Hip]

There is one more standard for EBV and HHV 6 that is CLIA

I have never heard of this, can you provide a link? The only thing I can find is Clinical Laboratory Improvement Amendments (CLIA), which is a set of regulatory standards for clinical laboratory testing.

 

[Cipher]

I have never heard of this, can you provide a link? The only thing I can find is Clinical Laboratory Improvement Amendments (CLIA), which is a set of regulatory standards for clinical laboratory testing.

I think the lab is referring to chemiluminescence immunoassay.

Wellinghausen et al., (2018). MiQ. Immunological methods for the detection of Infectious Diseases. Instand. e.V. ISBN 978-3-87185-518-4

5.9 Chemiluminescence immunoassay
The detection principle of chemiluminescence immunoassays (CLIA or LIA) is similar to that of ELISA.
The antibodies or antigens are detected by measuring the specific wavelength of light produced
through a chemical reaction. Chemiluminescent substrates include acridin ester or isoluminol which
oxidize in the presence of hydrogen peroxide and a catalyzer to produce the luminescence signal.

The electro-chemiluminescence immunoassay (ECLIA) is a further development of CLIA. As with CLIA,
ECLIA uses a chemiluminescence reaction to detect the antibodies or antigens being tested for,
however the chemiluminescent substrate (luminophore) oxidizes by applying an electrical current
rather than as a result of a chemical reaction. Luminophores that are used include a ruthenium
complex that reacts with a tripropylamine radical. The activated ruthenium then breaks down,
releasing a photon.

The detection sensitivity of the CLIA and ECLIA methods is higher than for ELISA and ELFA (detection
limits of 10 –18 to 10 –20 mol/assay) [315]. However, a direct comparison can only be made when other
assay factors, e.g. the detection antigens and antibodies that are used, are identical. Additional
advantages of the CLIA and ECLIA methods include a shorter analysis time than with ELISA, and
automatable processing. Interfering factors are comparable to those of traditional ELISAs (see above).
CLIAs and ECLIAs are currently used in fully automated analysis systems produced by various
manufacturers.

 

[Hip]

I think the lab is referring to chemiluminescence immunoassay.

Interesting.