THE ROLE OF HUMAN HERPES VIRUS 6 IN ENCEPHALITIS PATIENTS

Background: Primary infection with Human Herpesvirus 6 (HHV6) is usually asymptomatic in children but is most well known to cause exanthem subitum (roseola infantum). HHV6 has also been shown to cause a variety of severe neurological clinical manifestations, including encephalitis. The California Encephalitis Project (CEP), a referral-based service located in the Viral and Rickettsial Disease Laboratory, California Department of Public Health, was initiated to identify the etiological causes and characterize the epidemiological features of encephalitis, including the role of HHV6.

Materials and methods: Specimens from cases of encephalitis are referred from physicians throughout California to the CEP for a standardized panel of diagnostic tests. In March 2006, an in-house HHV6 real-time polymerase chain reaction (PCR) was performed on all cerebral spinal fluid (CSF) samples received and the clinical characteristics of cases with positive HHV6-PCR results were reviewed.

Results: Five hundred and ninety six CSF specimens were tested and HHV6 was identified in 15 (2.5%) of these. Co-infections were identified in two of these HHV6 (+) samples: HSV1 (1) and Coccidioides immitis (1). The median age of HHV6 (+) patients was 42 years (range: 7 months-80 years) and 9 (60%) were male. Ten (64%) HHV6 (+) cases presented with fever, 7 (50%) with seizures, 2 (14%) had rash, 1 (7%) became comatose, and 1 (7%) died. The initial CSF median white blood cell count was 70 cells/mm³ (range: 0-655), median CSF protein level was 56 mg/dL (range: 17-299), and a median CSF glucose was 59 mg/dL (range: 24-79). Compared to HSV1 (+) and Enterovirus (+) confirmed cases combined, there is no significant difference between the two groups with respect to demographic, clinical, or laboratory data, with the exception of CSF Glucose values being slightly higher in HSV1 (+) & EV (+) cases than in HHV6 (+) cases (67 mg/dL vs. 59 mg/dL, respectively; p-value=0.03).

Conclusions:  HHV6 appears to be important in a small, but significant number, of encephalitis cases. More adults than children were identified with CNS HHV-6 infection. The laboratory and clinical aspects of these cases are similar to other viral encephalitis etiologies.