Human Herpesvirus6

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Epidemiology and Risk Factors. Human herpesvirus- 6 (HHV-6) is the causative agent of the common childhood infection roseola infantum (exanthem subitum). '133 The virus was first isolated in 1986 from the peripheral blood lymphocytes of patients with AIDS and those with lymphoproliferative disorders. It is a member of the human herpesvirus family and shares some DNA sequence homology with the cytomegalovirus. W Saliva may be the major mode of transmission of HHV-6. Primary infection may be symptomatic or asymptomatic; the virus is then able to become

latent in the host and reactivates in the presence of immunosuppression. The majority of the population is exposed to HHV-6 in infancy, and by the age of 2 years, most children are seropositive.^

Pathogenesis and Pathophysiology. HHV-6 DNA has been detected by PCR in six of nine (66 percent) normal brain tissue specimens in one study, and in the CSF of nine of ten patients with exanthem subitum and neurological symptoms.[135] , [136] Human T-lymphocytes are the primary cell type infected by HHV-6, but HHV-6 has also been shown to infect cells of neuronal and glial origin in vitro. [135] The detection of HHV-6 DNA by PCR in children with exanthem subitum and neurological symptoms suggests that HHV-6 invades the brain during acute infection. [136| The presence of HHV-6 DNA in normal brain tissue specimens is evidence of the persistence or latency of HHV-6 in the central nervous system. [135] Reactivation of latent HHV-6 infection has been demonstrated in children and in immunocompromised adults.W1 , [138]

Clinical Features and Associated Findings. As previously stated, HHV-6 is the etiological agent of childhood exanthem subitum. The most common CNS complications of primary HHV-6 infection are seizures, meningoencephalitis, and encephalopathy. W1 HHV-6 has been reported as the etiological agent of focal encephalitis in a bone marrow transplant recipient and in immunocompetent adults with focal encephalitis in whom the clinical presentation suggested herpes simplex virus encephalitis. W , W1 CNS infection with HHV-6 has also been associated with diffuse or multifocal demyelination and a clinical picture of fulminant multiple sclerosis.[139] Disseminated HHV-6 infection has been reported in children and adults with AIDS. [140] , [141]

Exanthem Subitum. Roseola infantum or exanthem subitum is a common disease of infancy characterized by high fever for a few days followed by the appearance of a generalized maculopapular rash when the fever subsides. Febrile convulsions in this disease have a reported incidence of 13 to 30 percent, children 12 to 15 months of age being at highest risk. [133] , [136]

Encephalitis and Focal Encephalitis. HHV-6 DNA has been recovered from the brain of a patient at autopsy who died of encephalitis 5 months after undergoing allogeneic bone marrow transplantation.[138] Three of 37 patients with a clinical presentation suggestive of herpes simplex encephalitis and 6 of 101 patients with clinical and laboratory evidence of herpes simplex encephalitis were found to have HHV-6 DNA in their CSF when samples of CSF were sent to the University of Alabama for the purpose of undergoing diagnostic PCR analysis for possible herpes simplex encephalitis. The spectrum of disease ranged from mild encephalitis with complete resolution to severe neurological dysfunction and death. [134] A dense and disseminated active HHV-6 infection was found in the brain tissue of a young woman with a fulminant demyelinative disease that was clinically and histopathologically diagnosed as acute multiple sclerosis. W

Differential Diagnosis. Primary HHV-6 infection is diagnosed by culture of peripheral blood mononuclear cells and a concomitant fourfold or greater rise in IgG titer between the acute and convalescent sera. CSF can be analyzed by PCR to detect HHV-6 DNA. IgM antibody may be present during reactivation, and therefore its presence does not differentiate a primary infection from reactivation. W1

Management. Limited information is available on the susceptibility of HHV-6 to antiviral agents. The pattern of antiviral inhibition of HHV-6, however, resembles that of the human cytomegalovirus, suggesting that ganciclovir and foscarnet may be effective for the treatment of HHV-6 infections. [142]

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