Herpes Genitalis

Gale R. Burstein

Kimberly A. Workowski

Genital herpes is a chronic lifelong viral disease. Herpes genitalis lesions are caused by a large DNA virus, herpes simplex virus (HSV), with two serotypes, HSV type 1 (HSV-1) and HSV type 2 (HSV-2). Most cases of recurrent genital herpes are caused by HSV-2; however, HSV-1 is becoming more prominent as a cause of first-episode genital herpes, especially in young women and men who have sex with men (MSM).¹,²,³ These viruses have the ability to become latent and reactivate. Although among adolescents and young adults (AYAs) HSV-2 infection prevalence has not changed significantly over the last decade, HSV-1 seroprevalence has decreased, leaving young people more susceptible to HSV disease and incident HSV-1 infections at sexual debut.³ Most HSV-1- and HSV-2-infected persons have not been diagnosed.²,⁴ They may have mild or unrecognized infections but shed virus intermittently in the genital tract. Most genital herpes infections are transmitted by persons unaware that they have the infection or who are asymptomatic when transmission occurs.

EPIDEMIOLOGY

Prevalence¹ and Incidence

The National Health and Nutrition Examination Surveys (NHANES) conducted between 1999 and 2010 identified overall decreases in HSV-1 seroprevalence, especially among 14- to 19-year-olds, with no significant changes in HSV-2 seroprevalence.³ As more youth lack HSV-1 antibodies at sexual debut, their susceptibility to genital HSV-1 increases.
- Among 14- to 19-year-olds, HSV-1 seroprevalence decreased by 23%, from 39% during 1999 to 2004, to 30% during 2005 to 2010, whereas HSV-2 seroprevalence did not change significantly (from 1.6% to 1.2%).
- Among 20- to 29-year-olds, HSV-1 seroprevalence decreased 9% over the 10-year period from 54% to 50%, whereas HSV-2 seroprevalence did not change significantly (from 11% to 10%).
HSV-1 and HSV-2 prevalence varies by age.³
- The prevalence of infection increases with age. In NHANES 2005 to 2010, approximately 30% of 14- to 19-year-olds and 50% of 20- to 29-year-olds were infected with HSV-1 and 1.2% of 14- to 19-year-olds and 9.9% of 20- to 29-year-olds were infected with HSV-2.³
Sociodemographic disparities exist with HSV-1 sero-prevalence.³,⁴
- HSV-1 seroprevalence varies by race, gender, and income: Among 14- to 29-year-olds, estimated HSV-1 seroprevalence was higher among Mexican Americans and non-Hispanic Blacks compared to non-Hispanic Whites, females compared to males, and those with lower incomes.³
- Similar disparities exist with HSV-2 seroprevalence.⁴
HSV-1 incident infections are more than twice as common as HSV-2 infections.² Among healthy, HSV-1/2 seronegative females aged 18 to 30 years followed in an HSV vaccine trial for 20 months, the rate of new infections with HSV-1 (2.5/100 person years) was more than twice that of HSV-2 (1.1/100 person years), and HSV-1 infections in the genital area appeared three times more frequently than HSV-2 genital infections.²
- Among females 18 to 22 years, HSV-1 incident infections were most common (3.2/100 person years) and more than twice the rate of incident HSV-2 infections (1.3/100 person years).²

Recurrent Episodes

Persons with symptomatic first-episode genital HSV-2 infection frequently experience recurrent genital lesions; recurrences are less frequent after initial genital HSV-1 infection. However, intermittent shedding can occur with either strain, even in those without visible lesions. Therefore, identification of the type of infecting strain may have prognostic importance to the individual and may be useful in counseling.⁵

Transmission

Mode of transmission is through sexual contact, either genital-genital or oral-genital, and by mucosal contact with infected secretions.
Humans are the sole known reservoir of infection.
Risk of transmission
- Demographics: HSV-2 disproportionately affects Black Americans, particularly Black females, who reside in communities with a higher prevalence of HSV-2 infection, placing them at greater risk of infection. There are also additional biologic factors placing females at greater risk for HSV-2 than males.⁴ The female genital tract has more exposed vascular, mucosal surface of the vagina and cervix compared to the male urethral meatus. Also, the female genital tract mucosa has more prolonged exposure to infected semen, which increases the probability of infection.
- The decreasing seroprevalence of HSV-1 antibodies among AYAs results in increased susceptibility to incident genital HSV-1 infections.³
- Although viral shedding is highest while genital lesions are present, most HSV-2 sexual transmission occurs on days when the source partner has no visible genital lesions.²,⁵
- HSV-2 viral shedding rates are increased among persons with HIV infection.⁶ HSV suppressive therapy in persons infected with HIV does not reduce the risk of HIV or HSV-2 transmission to susceptible sex partners.⁷,⁸

Infections by Serologic Type

HSV-1 infection typically manifests as oral-labial lesions, but the frequency of HSV-1 genital infections is increasing, especially among AYAs.²,³ Genital recurrences and subclinical shedding are much less frequent than with genital HSV-2 infection.
HSV-2 infection typically manifests as anogenital lesions. Oral HSV-2 infection is uncommon.²,⁹

PATHOGENESIS

Virus particles can be shed in salivary, cervical, urogenital, and anorectal secretions of infected individuals. The virus gains entry into the body through mucosal surfaces or abraded skin and replicates in the epidermal and dermal cells of a susceptible host. After replication, the virus spreads through contiguous cells to mucocutaneous projections of sensory nerves.

After resolution of the primary disease, the virus becomes latent. Latency appears to be lifelong but is interrupted by periods of viral reactivation, leading to silent viral shedding or clinically apparent recurrences. Reactivation of latent virus leads to transport of viral genomes to the skin surface, where replication occurs in the dermis and epidermis. Reactivation can be triggered by a variety of stimuli, such as ultraviolet light, immunosuppression, fever, pneumococcal pneumonia, stress, and local trauma. Frequency and clinical severity of reactivation depend on factors such as the host immunological status and the severity and viral type of the primary infection.

CLINICAL MANIFESTATIONS