Background and Burden of Disease
Genital herpes is the leading cause of genital ulcer disease worldwide. Both herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) cause genital infection. However, HSV-2 is the more common cause of recurrent genital herpes. Despite a decline in the seroprevalence of HSV-2 from 21.2% in 1988 to 1994 to 15.5% in 2007 to 2010, genital herpes is among the most prevalent sexually transmitted infections in the United States, with approximately 50 million people infected. Based on data from the National Disease and Therapeutic Index, initial visits to physicians' offices related to genital herpes increased overall during 1966 to 2011, with approximately 300,000 visits in 2014 (Figure 1). In 2008, the lifetime direct medical cost for persons with HSV-2 in the United States was estimated at $540 million. This was significantly higher than the cost estimates for gonorrhea, syphilis, and trichomoniasis combined.[4,5]
Risk Factors for Genital HSV-2 Infection
Investigators have identified multiple risk factors for HSV-2 seropositivity, including female sex, black race, older age, and increasing number of lifetime sex partners.[2,6,7,8,9] In the National Health and Nutrition Examination Survey (NHANES) 2007 to 2010, HSV-2 seroprevalence was 2-fold higher in women (20.3%) compared with men (10.6%) and rates for both men and women were significantly higher in blacks than whites (Figure 2) . Data from NHANES shows racial disparities for HSV seroprevalence rates have steadily increased since 1988 and for the most recent time period (2007 to 2010), black females had 3.3 times the HSV seroprevalence rate of white females, and black males had 4.4 times the prevalence rate of white males (Figure 3).[2,9] The correlation of HSV-2 seroprevalence with age is shown by HSV-2 seroprevance rates of 1.5% among 14 to 19 year-olds to 25.6% among 40 to 49 year-olds; the seroprevalence rates rapidly rise in 20 to 29 year olds. In an earlier NHANES, HSV-2 seroprevalence rates were 3.8% among those who reported one lifetime sex partner, 20.8% among those with 5 to 9 lifetime sex partners, and 39.9% of those with 50 or more lifetime partners.
Risk Factors for Genital HSV-1 Infection
First-episode genital herpes caused by HSV-1 has increasingly been identified among young women, college students, and men who have sex with men (MSM).[8,10,11,12,13] Acquisition of genital HSV-1 can occur through genital-genital contact or via receptive oral sex.[14,15] In some settings, such as university campuses, HSV-1 has now replaced HSV-2 as the leading cause of first-episode genital herpes. One proposed reason for this shift is decreasing HSV-1 orolabial infection in childhood and early adolescence, with first exposure to HSV-1 occurring later in life with sexual activity. Changing sexual practices in young adults, namely an increase in oral-genital sex, may also contribute to the changing epidemiology of genital herpes.