Genital herpes simplex virus type 2 (HSV-2) is one of the most prevalent sexually transmitted infections (STIs) in the United States, with an estimated 17.0% of all adolescents and adults infected.1 Most individuals infected with HSV-2 are asymptomatic; however, when symptoms do occur, genital herpes is characterized by painful, recurrent ulcerative and vesicular lesions in the anogenital region that can facilitate both transmission and acquisition of HIV infection and disease progression of HIV/AIDS.2,3 Herpes simplex virus type 2 infection can cause substantial morbidity during pregnancy, including spontaneous abortion, prematurity, and neonatal herpes, a potentially fatal infection.4 Herpes simplex virus type 2 remains incurable and, as a lifelong infection, can lead to psychological distress, interfering with current and future sexual partnerships. Unfortunately, public health interventions with proven effectiveness to prevent and control HSV-2 transmission remain limited.5
Non-Hispanic blacks in the United States have a disproportionate burden of STIs, including HSV-2.6 Based on data for other sexually transmitted diseases, individual-level factors alone do not account for these disparities. Social determinants of health (eg, poverty and access to health care), sexual, and social network patterns, all play an important role in HIV/STI transmission and may help to explain the disproportionately high prevalence of STIs among non-Hispanic blacks.7,8 Racial disparities in HSV-2 seroprevalence and diagnosis have been well documented.6,9
Serosurveys provide one of the best approaches to study the epidemiology of HSV-2 infections. Herpes simplex virus type 2 is a lifelong infection; seroprevalence increases with age, and prevalence in a specific age group is a reflection of cumulative incidence through that age. Since 1976, the Centers for Disease Control and Prevention (CDC) has monitored HSV-2 seroprevalence in the United States through the National Health and Nutrition Examination Surveys (NHANES). To determine whether racial disparities in HSV-2 seroprevalence and diagnosis have changed over time, we analyzed serological results from persons aged 14 to 49 years, overall and by age group, in NHANES from 1988 through 2010.
MATERIALS AND METHODS
The NHANES are a series of cross-sectional national surveys conducted by the National Center for Health Statistics of the CDC. The surveys are designed to be nationally representative of the civilian, noninstitutionalized US population. Consenting participants have a household interview followed by a physical health examination. More details of the survey methods have been published previously.9,10 NHANES III was conducted from 1988 to 1994. In 1999, NHANES was redesigned to become a continuous survey; usually data from 2 or more years are combined to achieve adequate sample sizes for analyses.
Participants from NHANES are categorized into 3 racial/ethnic categories (non-Hispanic white, non-Hispanic black, and Mexican American). This study focused on evaluating disparities between non-Hispanic blacks and non-Hispanic whites. Race/Ethnicity was defined by self-report. Sexual history information was self-reported by participants aged 14 to 49 years using face-to-face interviews (1988–1994) and audio computer-assisted self-interview (1999–2010). In this analysis, we evaluated the number of lifetime sexual partners and age at first sex. Persons 18 years or older were asked the question, “Has a doctor or other health care professional ever told you that you had genital herpes?” to determine if participants had a history of diagnosed genital herpes.
Purified glycoproteins specific for HSV-1 or HSV-2 were used as antigens to detect type-specific antibodies using solid-phase enzymatic immunodot assays. The same assay was used in all surveys. The immunodot assays are highly sensitive and accurately discriminate between HSV-1 and HSV-2.9,11
For this study, we analyzed HSV-2 seroprevalence data from the 4 most recent years available, 2007 to 2010, and report seroprevalence by self-reported demographics and sexual behaviors. We also analyzed trends in HSV-2 seroprevalence racial disparities using data from NHANES III (1988–1994) and 3 periods in continuous survey: 1999–2002, 2003–2006, and 2007–2010.
We analyzed these data according to NHANES sample survey design. All seroprevalence estimates were weighted to represent the noninstitutionalized US civilian population and to account for oversampling and nonresponse to the interview and the examination.12 All prevalence estimates were adjusted by age according to the 2000 US population. Variances of the estimates were calculated using the Taylor series expansion method, and the confidence intervals (CIs) of the estimates were calculated through a logarithmic transformation.13,14 We used the adjusted Wald F test to assess the differences between 2 proportions and the Cochran-Mantel-Haenszel test when these differences were stratified by a third variable. We used Cochran-Mantel-Haenszel test for trend to assess the significance of the trend over time. Prevalence estimates with relative standard errors greater than 30% are noted and considered unstable and should be interpreted with caution. Prevalence ratios and 95% CIs were also calculated. SUDAAN software version 11.0 (Research Triangle Institute, Cary, NC) was used for statistical analyses.
National Health and Nutrition Examination Surveys 2007–2010
Overall, HSV-2 seroprevalence in NHANES 2007–2010 was 15.5% (Table 1). Seroprevalence increased with age ranging from 1.5% among those aged 14 to 19 years to 25.6% among those aged 40 to 49 years (P < 0.001). Herpes simplex virus type 2 seroprevalence was higher among females (20.3%) than among males (10.6%). Herpes simplex virus type 2 seroprevalence among non-Hispanic blacks was 41.8% compared with 11.3% among non-Hispanic whites, (P < 0.001). Among non-Hispanic black males, HSV-2 seroprevalence was 31.7% compared with 7.2% among non-Hispanic white males (P < 0.001). Among non-Hispanic black females, HSV-2 seroprevalence was 49.9% compared with 15.3% among non-Hispanic white females (P < 0.001). Examination of behavioral variables demonstrated that even among respondents who reported having 1 lifetime sex partner, this disparity persisted; HSV-2 seroprevalence was 11.1% among non-Hispanic blacks with 1 lifetime sex partner compared with 3.0% among non-Hispanic whites (P < 0.05).
Trends in HSV-2 Seroprevalence and Racial Disparities
Overall, HSV-2 seroprevalence decreased in the United States between 1988 to 1994 and 2007 to 2010, from 21.2% to 15.5%. However, racial disparities in HSV-2 seroprevalence significantly increased (Fig. 1). Although seroprevalence decreased among non-Hispanic white males (13.7% [1988–1994] to 7.2% [2007–2010], P < 0.001), HSV-2 seroprevalence remained stable among non-Hispanic black males (32.9% [1988–1994] and 31.7% [2007–2010], P = 0.9). The black/white prevalence ratio increased from 2.4 (95% CI, 1.9–2.9) in 1988 to 1994 to 4.4 (95% CI, 3.3–5.8) in 2007 to 2010 (P = 0.001). Similarly, in females there was a significant decrease in HSV-2 seroprevalence over time among non-Hispanic white females (19.5% [1988–1994] to 15.3% [2007–2010], P < 0.001), but seroprevalence remained stable among non-Hispanic black females (52.5% [1988–1994] to 49.9% [2007–2010], P = 0.1). The black/white prevalence ratio increased from 2.7 (95% CI, 2.4–3.0) in 1988 to 1994 to 3.3 (95% CI, 2.9–3.7) in 2007 to 2010 (P = 0.01).
Several differences in age-specific trends were observed (Fig. 2). Herpes simplex virus type 2 seroprevalence among non-Hispanic black males aged 14 to 19 years decreased over time, from 6.5% (1988–1994) to 0.45% (2007–2010; P < 0.001), yielding a black/white prevalence ratio that decreased from 1.6 (95% CI, 0.6–4.1) in 1988 to 1994 to 0.75 (95% CI, 0.06–9.4) in 2007 to 2010 (P = 0.50). Among all other age groups, the black/white prevalence ratio increased over time, most notably among men aged 20 to 29 years. In this age group, the prevalence ratio increased from 2.2 (95% CI, 1.3–3.7) in 1988 to 1994 to 6.8 (95% CI, 3.6–12.9; P < 0.01). Among females, in all age groups, the black/white prevalence ratio remained stable or slightly increased over time with no statistically significant changes.
History of Clinical Diagnosis of Genital Herpes
The overall percentage of HSV-2–seropositive survey participants who reported never being told by a doctor or health care professional that they had genital herpes did not change significantly between 1988 to 1994 and 2007 to 2010 and remained high (90.7% and 87.4%, respectively; Table 2). Among non-Hispanic black females, the percentage who were unaware of their infection decreased significantly, from 96.4% in 1988 to 1994 to 85.4% in 2007 to 2010 (P < 0.001). However, among non-Hispanic black males, there was no change; 96.2% of HSV-2–seropositive black males reported that they had never been told they had genital herpes in 1988 to 1994 compared with 94.9% in 2007 to 2010 (P = 0.61). Between 1988 to 1994 and 2007 to 2010, there were no significant changes in the proportion of HSV-2–seropositive participants who reported no history of genital herpes among non-Hispanic white males or females.
Although HSV-2 seroprevalence has decreased overall, the decrease is most marked among non-Hispanic whites, and thus, racial disparities have significantly increased over time. Herpes simplex virus type 2 is an important public health problem because persons infected with HSV-2 are at greater risk for acquiring HIV,15,16 an epidemic that also disproportionately affects non-Hispanic blacks. These persistent disparities demonstrate the need for innovative prevention strategies among this at-risk population.
Although HSV-2 seroprevalence has not changed among non-Hispanic blacks, encouragingly, among non-Hispanic black adolescents, particularly among boys, seroprevalence has decreased substantially. One possible explanation could be that non-Hispanic black adolescents are less sexually active. Analysis of the National Youth Risk Behavior Survey found a significant decrease in the prevalence of current sexual activity occurring in black high school students in 1991 to 2011.17 Further investigation into possible changes over time in sexual risk behaviors among non-Hispanic black adolescents, including condom usage, age of sexual debut, and number of lifetime sexual partners, is warranted to further explore the decrease in HSV-2 seroprevalence and develop age-specific interventions.
Currently, there is no specific national program to control and prevent genital herpes. Primary prevention of HSV-2 infection is difficult given the absence of a highly effective prevention modality, such as a vaccine.5,18 Although some vaginal topical microbicides seem promising, these are still being investigated.19,20 Most HSV-2 transmission is from individuals with unrecognized infection.21 Our study found that 85% of non-Hispanic black females and 95% of non-Hispanic black males with HSV-2 were unaware of their infection. However, the role for HSV-2 screening in population-based prevention efforts remains controversial, and screening of the general population is not currently recommended by the CDC or the US Preventive Services Task Force.22,23 There are several complex issues related to HSV-2 screening, including concerns about test performance in low-prevalence populations and whether knowledge of seropositivity results in behavior changes such as increased condom usage, compliance with daily suppressive therapy, and disclosure of HSV-2 infection to sexual partners.5,24 Of note, research at an urban sexually transmitted disease clinic, found that non-Hispanic black clients were less likely to request HSV-2 testing compared with non-Hispanic white or Hispanic clients when testing was offered at a cost.25 Black women in that study were least likely to request testing, although they experience the largest burden of HSV-2 disease in the United States. Further investigation into the feasibility, acceptability, benefit, and cost-effectiveness of HSV-2 serological testing among non-Hispanic blacks is warranted.
One limitation of NHANES is that information on genital or prodromal symptoms is not collected. Individuals who have symptoms may be more likely to access health care and seek diagnostic testing; we could not explore if racial differences in HSV-2 symptomatic disease, genital herpes, exist. Another limitation of our study is the absence of questions about sexual network factors and detailed questions about condom use in NHANES. Although we report the magnitude of HSV-2 seroprevalence racial disparities, we could not evaluate the impact individual risk behaviors (ie, condom usage), sexual network factors (ie, concurrency), or social determinants of health have on these racial/ethnic differences.
Our finding that racial disparities in HSV-2 have significantly increased over time highlights the need for research that addresses prevention of HSV-2, in particular among non-Hispanic blacks. Prevention measures would be especially important for young adults in their early 20s, when incidence seems to increase dramatically. Research has shown that condoms reduce the transmission of HSV-2,26,27 that disclosure of genital herpes infection to sex partners increases time to acquisition of infection,28 and that taking daily suppressive therapy, recommended for symptomatic HSV-2–infected persons, reduces viral shedding and HSV-2 transmission to sex partners.29,30 It remains unknown if asymptomatic persons found to be HSV-2 seropositive would adopt these protective behaviors and, if so, whether behavior change is sustainable. Second, more information on factors and barriers associated with the acceptability of HSV-2 serological testing among all populations, including non-Hispanic blacks, is needed. Research that explores acceptability of HSV-2 serological testing and racial differences in recognition of genital HSV-2 symptoms may provide evidence to support educational interventions that increase awareness. Finally, research into the development of an efficacious HSV-2 vaccine should continue.
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