Diagnosis

Serologic assays (IgG antibodies) can be used to establish evidence of latent HHV-6 infection (past exposure) (31). IgM antibodies may be useful in the diagnosis of primary infection (31). The use of IgM serology to detect reactivation has shown variable results and probably lacks in sensitivity and specificity. The detection of active HHV-6 infection is more difficult (28, 31). Traditional viral cultures to assess for cytopathic effect are cumbersome and not rapid enough for routine clinical use (28). A rapid viral culture technique has been developed, in which the patient’s leukocytes are co-cultured with fibroblasts. Active infection is determined by staining the fibroblast layer with a monoclonal stain specific for an immediate early antigen, thus looking for cross infection of the fibroblasts. This method has sensitivity in the range of 80-85%, with specificity of nearly 100% (28). DNA detection by PCR methodology on cellular specimens (PBMC) cannot always reliably differentiate between latent and active infection. DNA detection on acellular specimens (serum, plasma, CSF), is probably more reliable for active infection, however the presence of "inhibitors" create problems with false negative results (decreased sensitivity). Reverse transcriptase PCR assays (messenger RNA detection) appear to be very promising for detection of active HHV-6 infection with excellent sensitivity and specificity (76). However, such assays are not commercially available at present. In the studies with our patient populations described herein, we used the rapid culture to reliably assess active HHV-6 infection. This test, in our opinion, is the best current assay system for active infection, particularly in view of the high degree of specificity. Accurately differentiating between latent infection and active / productive infection is of paramount importance in defining this disease process as well as clinical diagnosis. At present, there are not commercially available methods to distinguish HHV-6 variant A from variant B by these laboratory tests. Hopefully, accurate testing to separate out which variant is present will be forthcoming.