Nearly 100% of humans are exposed to HHV-6 by the age of three. After the primary infection, the HHV-6 DNA appears briefly in the serum (and spinal fluid) and then a small amount of virus establishes latency. Small amounts of DNA can be found in the white blood cells and saliva in children and adults at the initial infection, but is only found in serum or plasma (the liquid surrounding the blood cells), during active infection.

HHV-6 active infections can persist in the brain tissue long after all traces of the virus have disappeared from the blood (Caserta 2004) and can be found in large quantities in the brain tissues with barely a trace in the spinal fluid (Fotheringham 2007).

There are no serological (IgG) assays that can differentiate HHV-6A from HHV-6B, so very little is known about the prevalence of HHV-6A and HHB-6B in various populations. Studies of biopsy tissues can offer helpful clues regarding the prevalence of HHV-6A. In a US study of lung tissue samples, both variants were found in 67% of transplant patients and 54% of controls (Cone 1996).

HHV-6 primary infections account for nearly 20% of all emergency room visits for infants with fever in the US. Although rare, HHV-6 encephalitis can cause serious complications and death. A survey of HHV-6 encephalitis in Japan revealed a surprisingly high rate of permanent neurological disability (47%) and death (2.5%) (Yoshikawa 2009).