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Herpesviruses cause a wide spectrum of human disease. Eight identified human herpesviruses (HHV) include herpes simplex virus-1 (HSV-1) (type 1), HSV-2 (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. The World Health Organization (WHO) reports that, in 2016, an estimated 491.5 million people were living with HSV-2 (13.2% of the world's population aged 15- to 49 years-old) and an estimated 3752.0 million people were living with HSV-1 (66.6% of the world's population aged 0- to 49 years-old). Asymptomatic shedding of either virus is common, but it is more common with HSV-2 and from genital areas, with most infected individuals shedding virus at least once a month, which may be responsible for transmission. Asymptomatic HSV-2–infected individuals shed the virus less often than those with symptomatic infection. Clinical disease typically indicates reactivation. Total and subclinical shedding of HSV-2 virus decrease after the first year of initial infection, although viral shedding continues for years thereafter. HSV-2 lesions occur at higher-than-expected rates among women during the postpartum period and among women who have sex with women.

Although HSV-2 ...

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