HHV-6 Testing

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Overview on Testing for HHV-6 infection

Nearly 100% of us are infected with HHV-6 by early childhood. This initial infection has caused our bodies to develop HHV-6 antibodies to fight against future HHV-6 viral infection or reactivation. In addition, at least 30% of us have small but consistently detectable levels of inactive (latent) HHV-6 virus that persist harmlessly in the blood into adulthood—many times never reactivating or becoming active over the course of a lifetime. Therefore, the relevant question when testing for HHV-6 infection is not whether you have HHV-6 virus or antibodies present in your blood, but rather is the virus active or latent? Unfortunately, this is not an easy question to answer. Two signs of an active infection are (1) viral DNA in your plasma or serum (as opposed to blood), and (2) unusually elevated antibody titers, on an IFA test. A PCR test on blood identifies both latent and active infections, so it is not helpful in answering this question unless it is a quantitative test.

TEST

Can it differentiate active from latent infection?

Comments

ELISA IgG test

Example: “positive >1.0″

No. These results are intended to give only “yes/no” answers to whether you are exposed to the virus in the past. An ELISA> 5 in an adult MIGHT be a clue of an active infection, but only the antibody tests done by IFA can tell you with precision how elevated the antibodies are.

IFA IgG test

Example: Titer 1:640

If the titer is highly elevated relative to healthy controls, it means that the patient may have had a recent infection or has a current chronic infection. Titers vary by laboratory. Focus Diagnostics (Quest) has a median antibody titer between 1:80 and 1:160 for controls. Other labs have much lower control titers. If the patient has an immune deficiency with low total IgG, then the antibody titer will not be elevated.  If HHV-6 is the only antibody titer out of five viruses to be elevated above average, then this indicates possible HHV-6 infection.

IgM test

(ELISA or IFA)

Yes. IgM only appears during an active infection or for 2-3 months after an active infection. The absence of an IgM antibody does not mean you do not have a active infection. Chronic infections in various tissues can persist with no evidence of IgM.

PCR DNA test on plasma or serum

(qualitative or quantitative)

Yes. HHV-6 is never found in plasma or serum unless there is an active infection  (or the individual has ciHHV-6). However, the absence of HHV-6 DNA in the plasma/serum does not mean that there isn’t a low-level persistent infection in the tissues (e.g. heart, thyroid, brain). HHV-6 DNA is not found in the plasma/serum except during the initial infection and transiently during an acute infection. Any positive test result should be repeated with a quantitative test. Also, a whole blood test should be ordered to rule out chromosomally integrated HHV-6 which occurs in <1% of the population. (See CIHHV-6) Someone who inherits HHV-6 integration will always be positive in the serum, whether the HHV-6 is active or not.

ddPCR or Digital Droplet PCR to confirm ciHHV-6 status

 

This ddPCR test is done on whole blood and was introduced in 2013 by University of Washington specifically to identify ciHHV6. Currently it cannot identify active infection, although this may change at some point in the future.  This test is an extremely accurate and sensitive third generation PCR test. Patients should request this test only if they have previously tested positive on a quantitative PCR DNA test for HHV-6 on plasma or serum.

Quantitative PCR DNA test on whole blood

Example: 1200 copies/ml

Yes. If the viral load is >200 copies per ml or 20 copies per microgram of DNA then this is an active infection. Healthy persons will have very low viral loads, typically less than 20 copies/ml in the whole blood. Usually this level is not detectable in a commercial lab.

Qualitative PCR DNA test on whole blood

Example: “Positive”  with no numerical value given

No. This test is useless for differentiating active from latent infection. Almost all healthy individuals have low levels of latent HHV-6B in the blood. On a sensitive nested PCR tests, at least a third of the normal population should test positive for HHV6 latent DNA. This test may be useful for determining if you have HHV-6A or HHV-6B but can’t tell you if the virus is active.

 

While both LabCorp and Quest laboratories offer a basic qualitative ELISA test for HHV-6, additional testing is necessary to determine a proper diagnosis of HHV-6 infection for the reasons listed above.  FOCUS Diagnostics, a division of Quest Laboratories, offers many of the above tests that may help to properly identify an HHV-6 infection. Patients may have blood drawn at any Quest laboratory, and request that these specific testing inquiries be forwarded to FOCUS Diagnostics to ensure proper results. 

 

HHV-6 in CNS Disease Overview

Overview of HHV-6 in CNS Disease

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