Most sexually active people will be infected with a sexually transmitted infection (STI) at some point in their lives,1,2 yet many are unaware of the high prevalence and incidence of STIs in the United States and their associated health consequences and financial costs.3 Weinstock et al.4 previously estimated the number of STIs in calendar year 2000 in the United States. Given the availability of newer data and the continued need to monitor the burden of STIs to describe the public health impact, this article presents estimates of the number of STIs in the United States for calendar year 2008.
GENERAL METHODS AND DATA SOURCES
We estimated the number of incident and prevalent infections in the United States in 2008 for 8 common STIs: 3 bacterial (chlamydia, gonorrhea, syphilis), 4 viral (herpes simplex virus type 2 [HSV-2], human papillomavirus [HPV], hepatitis B virus [HBV], and human immunodeficiency virus [HIV]), and 1 protozoan (trichomoniasis). For each infection, only the proportion thought to be sexually transmitted was included. Data sources identified for use in calculations included national surveys, nationally notifiable disease case report data (National Electronic Disease Surveillance System [NEDSS]), and data from special projects, published and unpublished (Table 1). Calculation methods for each infection are described within the disease-specific sections.
TABLE 1: Summary of Data Sources Used to Calculate the Number of Incident and Prevalent STIs in the United States, 2008
The primary data source used to estimate the prevalence of most infections was the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the noninstitutionalized, civilian population of the United States that includes collection and testing of biologic specimens for STIs.5–11 To estimate prevalent infections, we multiplied NHANES prevalence estimates, where available, by postcensal population estimates from the midpoint of the 2007 and 2008 Community Population Surveys.12 We report 95% confidence intervals (CIs) for each NHANES point prevalence estimate. All NHANES prevalence estimates had relative standard error (RSE) values of 30% or less (indicating estimate stability), unless otherwise indicated. In particular, NHANES is not well powered for subgroup analyses for low-prevalence diseases; thus, RSE values are higher in some sex/age combinations. Additional methods for estimating incident infections varied by STI and are described separately.
Prevalent and incident infections were estimated for 5 US population groups: the total population, all women, all men, women aged 15 to 24 years, and men aged 15 to 24 years. All counts were rounded to 3 significant digits. Because a person may have more than 1 STI at a given time (e.g., coinfection with HPV and chlamydia), or more than 1 episode of a single STI (e.g., repeat chlamydial infection), this article presents the estimated total number of infections in the calendar year, rather than the number of persons who have an infection. The only exception to this rule is HPV; HPV estimates are framed at the individual level as the number of persons with an HPV infection. Estimates presented in this article are infections, which may or may not result in clinical disease.
Prevalence estimates produced using NHANES data were generated under several assumptions. First, we assumed that NHANES is broadly representative of the total US population. Second, we used the most recent available NHANES data, combining data from multiple years when necessary for estimate stability, and assumed that population prevalence was stable through 2008. Third, we assumed that prevalence estimates reflect both symptomatic and asymptomatic infections. Finally, when STI testing was limited to NHANES participants within a certain age range, we assumed that no prevalent or incident infections occurred outside this age range.
Estimates were made using the highest-quality evidence available, and a strength of estimate rating was given to each estimate presented.4 On the basis of the relative quality and reliability of the data sources used to create each estimate, ratings of good (level I), fair (level II), or poor (level III) were given. Ratings for total estimates were determined based on the lowest component rating. Table 2 summarizes the criteria for these ratings. Tables 3 and 4 show each STI-specific estimate and the corresponding strength of estimate rating.
TABLE 2: Criteria for Strength of Evidence Ratings for National Estimates of Incidence and Prevalence of STIs
TABLE 3: Estimated Number of Prevalent STIs and Strengths of Evidence—United States, 2008
TABLE 4: Estimated Number of Incident STIs and Strengths of Evidence—United States, 2008
CHLAMYDIA
To estimate prevalent chlamydia infections (Chlamydia trachomatis) in 2008, we analyzed NHANES data from 2005 to 2008. National Health and Nutrition Examination Survey participants are tested only for genital chlamydia infections, and results do not reflect oropharyngeal or rectal chlamydia infections. Among women aged 15 to 24 years, prevalence was 3.21% (95% CI, 2.26%–4.52%) corresponding to an estimated 660,000 prevalent chlamydia infections nationally. Among men in the same age range, there were an estimated 342,000 prevalent infections (1.66% prevalence; 95% CI, 1.07%–2.55%). Among persons aged 25 to 39 years, there were an additional estimated 264,000 prevalent infections among women (0.87% prevalence; 95% CI, 0.40%–1.86%; RSE, 38%) and 303,000 prevalent infections among men (1.01% prevalence; 95% CI, 0.56%–1.81%). In total, there were approximately 924,000 prevalent chlamydia infections in 2008 among women and 645,000 infections among men.
We calculated the number of estimated incident infections using the formula incidence rate (IR) = prevalence/duration. To determine the average duration of infection, we updated parameters used in a previously published estimate13 to better reflect current knowledge of chlamydia natural history and screening coverage (see Supplementary Material, at https://links.lww.com/OLQ/A59). For women, we assumed that the duration of infection was 0.69 years for ages 15 to 24 years and 0.79 years for ages 25 to 39 years. For men, we assumed that the duration of infection was 0.41 years for all ages. Thus, among those aged 15 to 39 years, there were an estimated 1.29 million incident chlamydia infections among women and 1.57 million infections among men. Among those aged 15 to 24 years, there were an estimated 957,000 infections among women and 833,000 infections among men.
GONORRHEA
To obtain stable estimates of prevalent gonorrhea infections (Neisseria gonorrhoeae), we analyzed NHANES data from 1999 to 2008. The prevalence of gonorrhea among women aged 15 to 39 years was 0.32% (95% CI, 0.16%–0.57%), corresponding to an estimated 163,000 prevalent gonorrhea infections in 2008.11 Among women aged 15 to 24 years, there were 128,000 prevalent infections (0.62% prevalence; 95% CI, 0.38%–1.03%). Prevalence among men aged 15 to 39 years was 0.21% (95% CI, 0.08%–0.43%; RSE, 37%), corresponding to an estimated 107,000 prevalent gonorrhea infections. Among men aged 15 to 24 years, prevalence was 0.32% (95% CI, 0.12%–0.84%; RSE, 49%), for a total of 67,300 estimated prevalent infections.
We calculated the number of estimated incident infections using the formula IR = prevalence/duration. To determine the average duration of infection, we summed the duration of symptomatic infection and the duration of asymptomatic infection weighted by the proportion of infections that are symptomatic. For women, we assumed an average duration of infection of 0.46 years (0.58 years for asymptomatic infection14 and 0.08 years for symptomatic infection with 25% of women symptomatic). For men, we assumed an average duration of infection of 0.23 years (0.38 years for asymptomatic infection14 and 0.08 years for symptomatic infection with 50% of men symptomatic). Thus, among those aged 15 to 39 years, there were 354,000 incident infections among women and 466,000 incident infections among men. Among those aged 15 to 24 years, there were 277,000 incident infections among women and 293,000 incident infections among men.
SYPHILIS
To estimate prevalent syphilis infections (Treponema pallidum), we analyzed NHANES data from 2001 to 2004, the most recent years in which this testing was conducted.6 Among 18- to 49-year-old women and men, 0.08% (95% CI, 0.03%–0.2%; RSE, >30%) of the population had a positive treponemal test result and a nontreponemal titer of 1:8 or greater,6 which we assumed reflected active disease. Thus, there were an estimated 117,000 prevalent syphilis infections in 2008. Because 27.8% of all reported syphilis cases occurred among women in 2008, we calculated that 32,500 prevalent infections occurred among women and 84,400 occurred among men. Furthermore, because 20% of all reported syphilis cases occurred among those aged 15 to 24 years, we calculated that there were 6500 prevalent infections among women and 16,900 prevalent infections among men in this age group.
Estimates of incident syphilis infections were based on national case reports of primary and secondary (P&S), early latent, and late and late latent syphilis. We assumed that all P&S cases reported in 2008 were acquired that year. In 2008, 2242 P&S cases were reported among women and 11,255 reported among men.15 The estimated average time from infection to early latency in untreated patients is 26 weeks16; we assumed that any cases of early latent syphilis reported during the second half of 2008 and the first half of 2009 were acquired in 2008. During this time interval, 3429 cases of early latent syphilis were reported among women, and 9522 were reported among men.15,17 Five-year moving averages of reported late and late latent syphilis (diagnosis >12 months after infection18) were fairly stable in 2003 to 2010. Therefore, we considered the average annual number of late and late latent syphilis cases in 2003 in 2010 to estimate incident infections from the year 2008 that would be reported more than 12 months after acquisition: 6416 cases of late and late latent syphilis cases among women and 11,438 cases among men. Finally, we assumed that 20% of all syphilis infections would never be diagnosed and therefore never reported.19 In total, there were an estimated 15,100 incident infections among women and 40,300 incident infections among men. Among 15- to 24-year-olds, there were 838 P&S, 1248 early latent, and an estimated 1144 late and late latent cases among women, and 2463 P&S, 1965 early latent, and an estimated 1327 late and late latent cases among men. Thus, there were an estimated 4040 total incident syphilis infections among women and 7190 total infections among men.
GENITAL HERPES (HSV-2)
Genital herpes prevalence estimates were based on HSV-2 antibody seroprevalence NHANES data from 2007 to 2008. Among those aged 15 to 49 years, there were 15.9 million prevalent infections among women (prevalence, 21.7%; 95% CI, 19.5%–23.9%) and an estimated 8.2 million infections among men (prevalence, 11.3%; 95% CI, 8.88%–13.7%). Thus, there were 24.1 million prevalent HSV-2 infections among women and men aged 15 to 49 years in the United States (prevalence, 16.5%; 95% CI,14.5–18.5). Assuming that HSV-2 prevalence in people 50 years or older was equal to that among 45- to 49 year-olds, there were an estimated 48.5 million prevalent infections in the entire US population. Among 15- to 24 year-olds, there were an estimated 1.69 million prevalent infections among women (prevalence, 8.20%; 95% CI, 4.39–12.0) and 812,000 infections among men (prevalence, 3.86%; 95% CI, 1.43–6.29; RSE, 32%).
We estimated HSV-2 incidence from age-specific prevalence data.20 Because HSV-2 infection is not curable, incident infections can only occur in individuals who have not been infected. We used preliminary catalytic models fitted to HSV-2 seroprevalence data from NHANES surveys (1988–2008)21 to estimate the force of infection (FOI; IR in the seronegative population; see Supplementary Material, at https://links.lww.com/OLQ/A59). Using modeled incidence, the age-specific prevalence of HSV-2 was estimated and compared with actual prevalence data from successive NHANES surveys. The models allowed FOI to vary by age, time, sex, and race/ethnicity (non-Hispanic whites, non-Hispanic blacks, and Mexican Americans). After estimating FOI, we calculated the IR for the whole population by solving the formula IR = [(number of new infections)/(population count)] * 100. To estimate the number of incident infections in other racial/ethnic groups, we applied the modeled FOI for the non-Hispanic white population (lowest risk) but used Community Population Surveys population count data for the “other” population. We estimated that there were 356,000 new HSV-2 infections among women aged 15 to 49 years in 2008 (IR = 0.49%) and 420,000 incident infections among men (IR = 0.58%). Among women aged 15 to 24 years, there were an estimated 208,000 incident infections in 2008 (IR = 1.01%); among men, there were an estimated 144,000 infections (IR = 0.69%).
HUMAN PAPILLOMAVIRUS
Estimates of prevalent HPV infections were based on NHANES data from 2003 to 2006 (before vaccine introduction) among women aged 15 to 59 years.7 Prevalence estimates reflect persons with detectable infections with any of 37 different HPV types; 21.6% of women were infected with more than 1 HPV type.22 Prevalence varied by age group from 32.9% (95% CI, 29.5%–36.5%) among 15- to 19 year-olds to 38.8% (95% CI, 33.9%–44.0%) among 50- to 59-year-olds, with a peak prevalence of 53.8% (95% CI, 45.9%–61.5%) among 20- to 24-year-olds. An estimated 39.9 million women had a prevalent HPV infection in 2008. Assuming that prevalence among men was the same as among women,23 an estimated 39.2 million men had a prevalent HPV infection in 2008. Among young women and men aged 15 to 24 years, an estimated 8.88 million women and 9.06 million men had a prevalent HPV infection.
To calculate the number of incident infections, age-specific estimates of the annual probability of HPV acquisition among women were obtained from a published mathematical model.24 Among women aged 15 to 59 years, the IR ranged from 25% (annual probability of acquiring a new infection) among 20- to 24-year-olds to 2% among 50- to 59-year-olds, corresponding to an estimated 7.06 million women with an incident HPV infection in 2008, of whom 3.42 million were aged 15 to 24 years. Assuming that the IR among men was the same as among women,25 there were an estimated 7.08 million men aged 15 to 59 years with an incident HPV infection in 2008, of whom 3.48 million men were aged 15 to 24 years.
HEPATITIS B (SEXUAL TRANSMISSION)
The weighted prevalence of chronic HBV in 3 cycles of NHANES data (2003–2008) was used to estimate the number of prevalent HBV infections for women (prevalence, 0.16%; 95% CI, 0.11%–0.26%) and men (prevalence, 0.45%; 95% CI, 0.30%–0.68%). This number was divided in half to estimate the number of infections that were sexually transmitted.26 From NHANES data, chronic HBV infection was defined as having total hepatitis B core antibody (anti-HBc) and hepatitis B surface antigen (HBsAg).9 We estimated that there were 123,000 sexually transmitted prevalent infections among women and 300,000 infections among men in the United States in 2008. Given the small number of NHANES participants in the 15- to 24-year age group who were chronically infected with HBV, the RSE greatly exceeded 30% (RSE, 100%). Therefore, we were not able to calculate the number of estimated prevalent cases for this group.
The number of estimated incident HBV infections was determined from published hepatitis national surveillance data (NEDSS).27 A full description of methods used to calculate new cases is available elsewhere.27 Briefly, reported cases were adjusted to account for underreporting and underdiagnosis. To estimate the number of cases that were sexually transmitted, we divided the adjusted number of reported cases in half because approximately 50% of HBV cases have been shown to be sexually transmitted26 Using this method, there were an estimated 7025 incident sexually transmitted HBV infections among women and 11,900 incident sexually transmitted HBV infections among men in the United States in 2008. Among 15- to 24-year-olds, an estimated 622 infections occurred among women and 825 occurred among men.
HIV (SEXUAL TRANSMISSION)
National HIV surveillance data were used to estimate prevalent and incident HIV infections. The number of persons living with HIV infection (prevalent infections) in the United States at the end of 2008 (both diagnosed and undiagnosed) was estimated using an extended back-calculation approach.28 This approach was based on diagnoses of HIV infection for persons 13 years or older at diagnosis from 40 states that have had confidential name-based HIV infection reporting since at least January 2006 and AIDS diagnoses from an additional 11 areas; data were reported to the Centers for Disease Control and Prevention (CDC) through June 2010 (see Supplementary Material, at https://links.lww.com/OLQ/A59).28 Surveillance data were adjusted for reporting delays, missing risk-factor information, and incomplete reporting.28 Of the estimated 1.18 million persons 13 years or older living with HIV infection at the end of 2008, 908,000 persons had infections attributable to sexual transmission (580,000 to male-to-male sexual contact and 328,000 to heterosexual contact). Of these, an estimated 217,000 persons living with HIV were women and 691,000 were men. Among persons aged 13 to 24 years, an estimated 68,600 persons were living with HIV at the end of 2008.28 To ensure a stable estimate, we were unable to stratify by sex or estimate HIV infections attributable to sexual transmission for this age group.
Incident HIV infections were estimated using data from 16 states and 2 cities (see Supplementary Material, at https://links.lww.com/OLQ/A59) that had confidential name-based HIV infection reporting and continuous implementation of HIV incidence surveillance since 2006, with at least 15% completeness of serologic testing algorithm for recent HIV seroconversion (STARHS) results annually. Analysis included new diagnoses of HIV infection for persons 13 years or older at diagnosis in 2008 reported to CDC through June 2010 from the 18 jurisdictions. Data on STARHS results and history of HIV testing and antiretroviral use for these persons were reported to CDC through January 2011.29 New diagnoses were classified as of recent or long-standing duration based on STARHS results; information on history of HIV testing and antiretroviral use was used to classify individuals as those testing HIV positive on their first HIV test and those testing negative for HIV before HIV diagnosis.29 Multiple imputation was used to assign a transmission category to those reported without risk information,30 and imputed transmission category values were used to impute missing STARHS results and testing history information.29,31 HIV incidence was estimated using a stratified extrapolation approach based on concepts borrowed from sample survey methodology; details are described elsewhere.29,31,32 Incidence estimates were adjusted to account for reporting delay, but not incomplete reporting.33 Estimated incidence within the 18 jurisdictions was extrapolated to the remaining US areas and the District of Columbia to obtain a population-based national HIV incidence estimate.29
An estimated 47,800 incident HIV infections occurred in United States in 2008. Of these, an estimated 41,400 incident HIV infections were attributed to sexual transmission (26,900 to male-to-male sexual contact and 14,500 to heterosexual contact).29 Among black/African American, Hispanic/Latino, and white males, an estimated 30,100 incident HIV infections were attributed to male-to-male sexual contact and heterosexual contact. Among females of the same racial/ethnic groups, an estimated 9600 incident HIV infections were attributed to heterosexual contact. Overall, these 3 racial/ethnic groups accounted for 96% (45,700/47,800) of all incident HIV infections.29 Among persons aged 13 to 29 years, an estimated 18,600 incident HIV infections occurred in 2008; we were unable to stratify by sex or estimate infections attributed to sexual transmission for this age group.
TRICHOMONIASIS
To estimate prevalent Trichomonas vaginalis infections among women, we analyzed NHANES data collected from 2001 to 2004, the most recent years in which this testing was conducted.8 Among women aged 15 to 49 years, the weighted prevalence of infection was 3.15% (95% CI, 2.28%–4.35%), corresponding to an estimated 2.31 million prevalent infections nationally. Among women aged 15 to 24 years, prevalence was 1.50% (95% CI, 0.91%–2.44%), for an estimated 309,000 prevalent infections among young women.
To estimate incident infections among women, we used data from the National Disease and Therapeutic Index (NDTI), which generated national projections based on reports from 4140 office-based private practice physicians in 2008 of initial visits for vaginal trichomoniasis based on diagnostic International Classification of Diseases, Ninth Edition codes.15,34 We assumed that NDTI data represented only symptomatic infections in women. Furthermore, we assumed that 30% of women with a T. vaginalis infection had symptoms of trichomoniasis and would have sought care related to those symptoms.35 To determine the total number of incident infections and account for asymptomatic infections, we divided symptomatic infections projected from NDTI for the year 2008 (204,000) by the proportion of infections thought to have produced symptoms (30%). Thus, we calculated that there were an estimated 680,000 incident infections among women in the United States.
To estimate the number of prevalent and incident infections among men, we assumed that women were more commonly infected with T. vaginalis than men (prevalence ratio, 1.64; 95% CI, 1.25–2.15).36 Thus, we calculated that the estimated prevalence of infection among men aged 15 to 49 years was 1.92%, corresponding to 1.40 million prevalent infections among men. Dividing the total number of estimated incident infections among women by this same ratio resulted in an estimated 415,000 incident infections among men of all ages. Among men aged 15 to 24 years, we calculated the estimated prevalence of T. vaginalis infection to be 0.91%, corresponding to 191,000 prevalent infections among young men.
To estimate incident infections among young women and men, we multiplied the proportion of estimated prevalent infections occurring among those aged 15 to 24 years for both women and men in NHANES (13%) by the total number of incident infections, estimating that there were 90,800 incident infections among young women aged 15 to 24 years and 56,900 incident infections among young men of the same age group in the United States.
DISCUSSION
In total, we estimate that there were 110 million prevalent STIs in the United States in 2008. Of these, approximately 20% of infections (22.1 million) occurred among women and men aged 15 to 24 years. Prevalence estimates were based primarily on strong nationally representative data that are likely more accurate than less-representative data sources; however, given the generally cautious assumptions used to generate these estimates, these figures may be interpreted as conservative estimates, and the true prevalence of STIs in the United States could be even higher.
In contrast to prevalence estimates, nearly 50% (9.7 million) of the estimated 19.7 million total incident infections in 2008 occurred among women and men aged 15 to 24 years, demonstrating that STIs are disproportionately acquired by adolescents and young adults. Incidence estimates are not as strong as prevalence estimates. Although incident counts are based on stronger evidence than prior published estimates for most STIs, some estimates (e.g., strength of estimate rating III) are based on nonrepresentative data or relatively generous assumptions and could be inaccurate. In particular, there is a continued need for more accurate data on the duration of infection for many STIs.
The number of incident STIs estimated in 2008 may be slightly higher than what was reported in 2000 (19.7 million in 2008 and 18.8 million in 2000).4 However, different assumptions and data sources were used to generate the 2000 estimates, so comparisons should be made very cautiously and trends should not be inferred. In particular, NHANES prevalence data used to generate incidence estimates were not previously available for many STIs. National Health and Nutrition Examination Survey availability, in addition to improvements in test technology, may have had a large impact on differences observed in incident HPV (increase from 2000). Estimates of trichomoniasis incidence were also substantially different between 2000 (7.4 million incident infections) and 2008 (1.1 million incident infections); however, both estimates were of the lowest rating (III).
Based on our estimates, the majority of both incident and prevalent STIs in the United States were HPV infections. More than 71% of all prevalent infections and nearly 72% of all incident infections were caused by HPV. It is important to note that if the total number of HPV infections had been described (rather than the number of women with HPV infections), prevalence and incidence estimates would have appeared to be even higher because 21.6% of women were infected with multiple types of HPV infection at the same time.7 Clinically, however, as with many other STIs, most HPV infections are asymptomatic, transient, and do not result in sequelae.
Estimates presented in this study are subject to various limitations. Most importantly, conservative assumptions likely underestimate the overall number of STIs occurring annually in the United States. For instance, NHANES data only represent cervical or urethral infection and do not reflect oropharyngeal or rectal infections (chlamydia, gonorrhea, trichomoniasis). In addition, to calculate the STI estimates presented in this study, it was necessary to make a number of assumptions, particularly when calculating the number of incident cases; the combination of these assumptions and the lack of precision associated with some data used may amplify the overall uncertainty of the final estimated number of infections presented. Furthermore, for the formula IR = prevalence/duration to be used, we assumed that the IR and duration of infection were constant over the time frame covered by data used in the calculation. This assumption may not be valid given possible fluctuations in either scenario. In addition, the magnitude of our estimates does not reflect the relative morbidity associated with some STIs (e.g., HIV and syphilis).
Our findings highlight the ongoing need for better data. Although our prevalence estimates are strong, our incidence estimates, which use the best available data, are far from optimal. Of the 24 total sex- and disease-specific prevalence and incidence estimates, only 6 had the strongest rating (I, good), all of which were prevalence estimates based on NHANES data. Most of our estimates were rated fair (II). Four of our incidence estimates were given the lowest rating (III, poor), indicating a particular need for stronger data. Within each estimate calculation, the use of different assumptions could cause substantial variation in the resulting point estimate. For example, changing the duration of chlamydia infection among women by 1 month in either direction (0.69 ± 0.083 years for ages 15–24 years, 0.79 ± 0.083 years for ages 25–39 years) results in point estimates of the number of incident chlamydia infections among women of 1.16 million (increasing duration of infection) and 1.46 million (decreasing duration of infection), compared with the reported estimate of 1.29 million infections. The overall total estimates were rated as fair (prevalence) and poor (incidence), demonstrating a substantial lack of certainty.
Despite the uncertainly around the exact point estimates, our estimates demonstrate that STIs are common in the United States, particularly among adolescents and young adults. Prevalence estimates exceeding 110 million infections suggest that a large proportion of the population of the United States had an STI in 2008. With almost half of all new infections occurring among women and men aged 15 to 24 years, public health efforts to address STIs should continue to focus on prevention among adolescents and young adults to reduce the number and impact of STIs over the course of their lives.
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