Unexpected occasional persistence of high levels of HHV-6 DNA in sera: detection of variants A and B.

Previously it was thought that in the immunocompetent human herpesvirus-6 [HHV-6] DNA was present transiently in serum during early primary infection but not thereafter. In this study, HHV-6 serum IgG avidity was detected by immunofluorescence and HHV-6 variants A/B [HHV-6A/B] serum DNA by semi-quantitative PCR [titre-log(10) copies/ml] in: (a) young children <3 years old from an encephalitis Survey, and a control Anonymised Serum Bank and (b) children/adults referred for diagnosis. The results showed that 11 out of 15 children [all <2 years] with primary infection proven by seroconversion had transient low levels of serum HHV-6B DNA [mean titre 2.6]. However, 3.3% (6/184) of Survey Children had significantly higher levels [mean titre 5.3; 2 HHV-6A; 4 HHV-6B; P < 0.001]. Similarly high level serum DNA [mean titre 4.0; 4 HHV-6A; 6 HHV-6B] was found in 1.5% (10/653) of the Serum Bank Children. Moreover, seven young children <3 years old [four Survey Children and three referred for diagnosis] had high titre serum HHV-6 DNA [mean 4.8] persisting i.e., in all available samples [median 186 days]. Three older children >3 years old and 4 adults [3 of whom were the mothers of 3 of the young children with persisting HHV-6] also had persisting high titre viral DNA [mean 4.2; median 108 days]. Thus in contrast to acute primary infection, where only HHV-6B DNA is found transiently, both HHV-6A and B DNA persist in serum at high titre in occasional individuals of all ages. The significance of this newly described phenomenon in relation to diagnosis, clinical consequences and congenital infection are discussed.