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Key Clinical Updates in Human Herpesviruses

Hyponatremia is a predictive marker for HSV-1 encephalitis before lumbar puncture data are available.

Atypical presentations for HSV encephalitis, which include the absence of pleocytosis, unremarkable early CT presentations, and unusual MRI findings (global edema), are reported from Germany.

In pregnancy, HSV hepatitis is infrequently (18% in one series) associated with a rash and carries a mortality up to 39%.

Herpesviruses cause a wide spectrum of human disease. Eight identified human herpesviruses (HHV) include herpes simplex virus (HSV) (type 1), HSV (type 2), varicella zoster virus (VZV) (type 3), Epstein-Barr (EBV) infectious mononucleosis virus (type 4), and cytomegalovirus (CMV) (type 5). A sixth type (HHV-6) is identified as the causative agent of roseola (exanthema subitum), and a seventh (HHV-7) is serologically associated with several syndromes. Finally, human herpesvirus 8 (HHV-8) is linked with Kaposi sarcoma (see Chapter 31), primary effusion lymphoma, and some cases of multicentric Castleman disease. Herpes B virus is a zoonotic herpesvirus that infects macaques and causes approximately 80% mortality in untreated humans. Subclinical primary infection with the herpesviruses is more common than clinically manifest illness. Each persists in a latent state for the remainder of the person's life. With HSV and VZV, virus remains latent in sensory ganglia. Upon reactivation, lesions appear in the distal sensory nerve distribution. As a result of disease, drug, or radiation-induced immunosuppression, virus reactivation may lead to widespread lesions in affected organs such as the viscera or the central nervous system (CNS). Severe or fatal illness may occur in infants and immunodeficient persons. Herpesviruses can induce cell transformation, hence the association with certain malignancies, such as Burkitt lymphoma and nasopharyngeal carcinoma (with EBV) or primary effusion lymphoma, multicentric Castleman disease, and Kaposi sarcoma (with HHV-8).


  • Spectrum of illness: stomatitis, urogenital lesions, Bell palsy, encephalitis.

  • Variable intervals between exposure and clinical disease, since herpes simplex virus (HSV) causes both primary (often subclinical) and reactivation disease.

General Considerations

HSV-1 and HSV-2 affect primarily the oral and genital areas, respectively. Risk factors for HSV transmission include black race, female gender, a history of sexually transmitted infections, an increased number of partners, contact with commercial sex workers, lower socioeconomic status, young age at onset of sexual activity, and total duration of sexual activity. Seroprevalence of both viruses increases with age, and the seroprevalence of HSV-2 increases with sexual activity. In a German study, 79% of the population is HSV-1 seropositive by age 28–30. Among the adult population in the United States, HSV-1 seropositivity is 47.8% and HSV-2 seropositivity is 11.9%. Only 2.5% of women in a Canadian herpes vaccine study were HSV-2 seropositive compared with 29% among women aged 18–34 years in Kenya. In Germany 13.6% were seropositive, but only up to one-quarter of these were symptomatic. Asymptomatic shedding of either virus is common, but it is more common with HSV-2 and from genital areas, with most infected ...

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