@nerd, would you know the gold standard test used to detect EBV reactivation?
If the sensitivity of VCA IgM for reactivated EBV infection is 5.8%, then that figure must have been obtained by comparing the results of VCA IgM to the gold standard.
Unfortunately, I don't have access to Wiley's paywall. But they write the following in the abstract.
IgM directed against Epstein‐Barr virus (EBV) early antigen (IgM‐EA) has been established as an early marker of EBV infection and IgG directed against Epstein‐Barr virus nuclear antigen 1 (IgG‐EBNA‐1) as a late marker. Simultaneous seropositivity to IgM‐EA and IgG‐EBNA has therefore been proposed as indicating reactivation of latent EBV infection.
Besides VCA IgM, the only acute marker they mention is EA IgM. I assume their "seropositive" definition is simultaneous EA IgM and EBNA IgG. I don't think this is considered the current gold standard, though, because most sources only mention EA-D IgA or IgG.
This paper clarifies these questions in the introduction:
De Paschale M, Clerici P. Serological diagnosis of Epstein-Barr virus infection: Problems and solutions.
World J Virol. 2012;1(1):31-43.
10.5501/wjv.v1.i1.31
They mention the abovementioned study and its validity, pointing out that EA IgM is just not used because it is also sensitive to the initial (and not reactivating) infection. If you already know that you had your initial infection before because you already had a positive ENBA IgG and VCA IgG test in the past, EA IgM should still be a reliable marker because IgM have the shortest half-life and aren't oversensitive as EA-D IgG is because some patients have these antibodies for many years. So if you'd like to know if you likely had a reactivation phase in the recent time, when your initial infection is far in the past, EA-D IgG is the gold standard. If you'd like to check for a current ongoing reactivation phase, EA IgM is the better way.
But the study also mentions other types of tests and which is indicative of which EBV-induced condition. They differentiate initial infection, chronic active EBV (CAEBV), and reactivated EBV. Interestingly, they also mention other pathogens that cause IM (but usually isn't called this way).
I think in the future, we'll only have gene expression profiles because they are cheap and fast. Thanks to Illumina and other new drivers of this technology, any doctor can do these tests in their own lab and have the results while the patient can wait. Moreover, it provides extensive profiles of all cataloged diseases and pathogens in a single small blood probe. If your lytic EBV genes are elevated, you would immediately know that your EBV is reactivating again. I think this will be the future gold standard. The hardware technology already exists. It's affordable. Statistical analysis and gene matching tools already exist as well. The missing piece is a large study that provides a huge test set to enable neural networks to get sufficient significance from the data.
But I imagine that the MD lobby will try to prevent this because it will make some of their jobs obsolete or reduce their practical application. Not that it matters to them that we urgently need more MDs anyway.
You can already do such tests, I had some done of some EBV genes in my own case. But it's not in the guidelines because their indicative ranges are based on correlation studies. What does it really mean when your latent genes are 20x elevated above the average healthy range? Obviously, it is of pathological significance in some way. But it might also be associated with SLE, MS, lymphomas, and not just with IM. And due to the lack of data, there is insufficient significance for the differentiation of all these EBV-associated conditions based on gene expression.
