Laboratory diagnosis of primary Human Herpesvirus-6 (HHV6) and -7 (HHV7) infection on the acute blood sample

Abstract

Human Herpesvirus (HHV) 6 causes roseola, febrile seizure and acute febrile illnesses in young children. HHV 7 is closely related to HHV6 but its clinical role is less clear. The current methods of documenting primary HHV infection by culture of leukocytes or seroconversion are not rapid enough to have any clinical impact. We hypothesized that demonstration of viral DNA in the blood combined with negative serology indicates a primary infection. IgG antibodies to HHV6 and HHV7 were detected by immunofluorescence. Viral DNA was detected by PCR in whole blood and plasma. Ninety children under 3 years of age admitted to our pediatric unit with fever (T>38.5 rectal) without a clinically apparent bacterial illness were recruited. Acute and convalescent blood samples were obtained in 40 patients. An acute blood sample only was available in 50 patients. The discharge diagnoses were made 'blinded' to the laboratory investigator. Thirty-two patients had an alternative microbiologie diagnosis (eg., Influenza, Parainfluenza, Respiratory Syncytial virus etc). Of the remaining 58 patients, 33 had paired blood samples. We found seroconversion with a fourfold rise of HHV6 IgG in 36 patients, 15 of whom also had a characteristic profile of leukocyte positive for HHV6 DNA with a negative HHV6 IgG in the acute samples. Only 12 were also plasma positive. Eleven of these 16 patients had a diagnosis of Roseola. Seroconversion with a fourfold rise of HHV7 IgG with PCR positive leukocytes and plasma was also seen in 3 of these 16 patients. Of the 25 patients with only an acute blood sample with no alternative diagnosis, 9 had the characteristic profile for primary HHV6 infection, 5 of whom had Roseola. None of the 32 patients with an alternative diagnosis had seroconversion of HHV-6 or -7, nor the characteristic profile in the acute blood sample. The sensitivity and specificity of this profile in the acute blood for diagnosing primary HHV6 infection was 94% and 100% respectively.