How the Orthodox Features of Orthopoxviruses Led to an Unorthodox Mpox Outbreak: What We've Learned, and What We Still Need to Understand.

Orthopoxviruses have repeatedly confounded expectations in terms of the clinical illness they cause and their patterns of spread. Monkeypox virus (MPXV), originally characterized in the late 1950s during outbreaks among captive primates, has been recognized since the 1970s to cause human disease (mpox) in West and Central Africa, where interhuman transmission has largely been associated with nonsexual, close physical contact. In May 2022, a focus of MPXV transmission was detected, spreading among international networks of gay, bisexual, and other men who have sex with men. The outbreak grew in both size and geographic scope, testing the strength of preparedness tools and public health science alike. In this article we consider what was known about mpox before the 2022 outbreak, what we learned about mpox during the outbreak, and what continued research is needed to ensure that the global public health community can detect, and halt further spread of this disease threat.

Modelling the impact of vaccination and sexual behaviour adaptations on mpox cases in the USA during the 2022 outbreak.

BACKGROUND: The 2022 mpox outbreak has infected over 30 000 people in the USA, with cases declining since mid-August. Infections were commonly associated with sexual contact between men. Interventions to mitigate the outbreak included vaccination and a reduction in sexual partnerships. Understanding the contributions of these interventions to decreasing cases can inform future public health efforts. METHODS: We fit a dynamic network transmission model to mpox cases reported by Washington DC through 10 January 2023. This model incorporated both vaccine administration data and reported reductions in sexual partner acquisition by gay, bisexual or other men who have sex with men (MSM). The model output consisted of daily cases over time with or without vaccination and/or behavioural adaptation. RESULTS: We found that initial declines in cases were likely caused by behavioural adaptations. One year into the outbreak, vaccination and behavioural adaptation together prevented an estimated 84% (IQR 67% to 91%) of cases. Vaccination alone averted 79% (IQR 64% to 88%) of cases and behavioural adaptation alone averted 25% (IQR 10% to 42%) of cases. We further found that in the absence of vaccination, behavioural adaptation would have reduced the number of cases, but would have prolonged the outbreak. CONCLUSIONS: We found that initial declines in cases were likely caused by behavioural adaptation, but vaccination averted more cases overall and was key to hastening outbreak conclusion. Overall, this indicates that outreach to encourage individuals to protect themselves from infection was vital in the early stages of the mpox outbreak, but that combination with a robust vaccination programme hastened outbreak conclusion.

Estimates of the Lifetime Productivity Costs of Chlamydia, Gonorrhea, and Syphilis in the United States.

BACKGROUND: Productivity costs of STIs reflect the value of lost time due to STI morbidity and mortality, including time spent travelling to, waiting for, and receiving STI treatment. The purpose of this study was to provide updated estimates of the average lifetime productivity cost for chlamydia, gonorrhea, and syphilis, per incident infection. METHODS: We adapted published decision tree models from recent studies of the lifetime medical costs of chlamydia, gonorrhea, and syphilis in the United States. For each possible outcome of infection, we applied productivity costs that we obtained based on published health economic studies. Productivity costs included the value of patient time spent to receive treatment for STIs and for related sequelae such as pelvic inflammatory disease in women. We used a human capital approach and included losses in market (paid) and non-market (unpaid) productivity. We conducted one-way sensitivity analyses and probabilistic sensitivity analyses. RESULTS: The average lifetime productivity cost per infection was $28 for chlamydia in men, $205 for chlamydia in women, $37 for gonorrhea in men, $212 for gonorrhea in women, and $411 for syphilis regardless of sex, in 2023 US dollars. The estimated lifetime productivity costs of these STIs acquired in the United States in 2018 was $795 million. CONCLUSIONS: These estimates of the lifetime productivity costs can help in quantifying the overall economic burden of STIs in the United States beyond just the medical cost burden and can inform cost-effectiveness analyses of STI prevention activities.

Vaccination May Be Economically and Epidemiologically Advantageous Over Frequent Screening for Gonorrhea Prevention.

BACKGROUND: Gonorrhea's rapid development of antimicrobial resistance underscores the importance of new prevention modalities. Recent evidence suggests that a serogroup B meningococcal vaccine may be partially effective against gonococcal infection. However, the viability of vaccination and the role it should play in gonorrhea prevention are an open question. METHODS: We modeled the transmission of gonorrhea over a 10-year period in a heterosexual population to find optimal patterns of year-over-year investment of a fixed budget in vaccination and screening programs. Each year, resources could be allocated to vaccinating people or enrolling them in a quarterly screening program. Stratifying by mode (vaccination vs. screening), sex (male vs. female), and enrollment venue (background screening vs. symptomatic visit), we consider 8 different ways of controlling gonorrhea. We then found the year-over-year pattern of investment among those 8 controls that most reduced the incidence of gonorrhea under different assumptions. A compartmental transmission model was parameterized from existing literature in the US context. RESULTS: Vaccinating men with recent symptomatic infection, which selected for higher sexual activity, was optimal for population-level gonorrhea control. Given a prevention budget of $3 per capita, 9.5% of infections could be averted ($299 per infection averted), decreasing gonorrhea sequelae and associated antimicrobial use by similar percentages. These results were consistent across sensitivity analyses that increased the budget, prioritized incidence or prevalence reductions in women, or lowered screening costs. Under a scenario where only screening was implemented, just 5.5% of infections were averted. CONCLUSIONS: A currently available vaccine, although only modestly effective, may be superior to frequent testing for population-level gonorrhea control.

Serial Interval and Incubation Period Estimates of Monkeypox Virus Infection in 12 Jurisdictions, United States, May-August 2022.

Using data from 12 US health departments, we estimated mean serial interval for monkeypox virus infection to be 8.5 (95% credible interval 7.3-9.9) days for symptom onset, based on 57 case pairs. Mean estimated incubation period was 5.6 (95% credible interval 4.3-7.8) days for symptom onset, based on 35 case pairs.

Using infection prevalence, seroprevalence and case report data to estimate chlamydial infection incidence.

OBJECTIVES: To measure the effectiveness of chlamydia control strategies, we must estimate infection incidence over time. Available data, including survey-based infection prevalence and case reports, have limitations as proxies for infection incidence. We therefore developed a novel method for estimating chlamydial incidence. METHODS: We linked a susceptible infectious mathematical model to serodynamics data from the National Health and Nutritional Examination Survey, as well as to annual case reports. We created four iterations of this model, varying assumptions about how the method of infection clearance (via treatment seeking, routine screening or natural clearance) relates to long-term seropositivity. Using these models, we estimated annual infection incidence for women aged 18-24 and 25-37 years in 2014. To assess model plausibility, we also estimated natural clearance for the same groups. RESULTS: Of the four models we analysed, the model that best explained the empirical data was the one in which longer-lasting infections, natural clearance and symptomatic infections all increased the probability of long-term seroconversion. Using this model, we estimated 5910 (quartile (Q)1, 5330; Q3, 6500) incident infections per 100 000 women aged 18-24 years and 2790 (Q1, 2500; Q3, 3090) incident infections per 100 000 women aged 25-37 years in 2014. Furthermore, we estimated that natural clearance rates increased with age. CONCLUSIONS: Our method can be used to estimate the number of chlamydia infections each year, and thus whether infection incidence increases or decreases over time and after policy changes. Furthermore, our results suggest that clearance via medical intervention may lead to short-term or no seroconversion, and the duration of untreated chlamydial infection may vary with age, underlining the complexity of chlamydial infection dynamics.

Estimated Incidence and Prevalence of Gonorrhea in the United States, 2006-2019.

BACKGROUND: We extend recent work estimating incidence and prevalence of gonococcal infections among men and women aged 15 to 39 years in the United States in 2018 by applying the same modeling framework to estimate gonococcal incidence and prevalence during 2006 to 2019. METHODS: The model is informed by cases from the Nationally Notifiable Disease Surveillance System, data from the National Survey of Family Growth, and data on other factors known to impact gonococcal incidence and prevalence. We use Monte Carlo simulation to account for uncertainty in input parameters. Results are reported as median annual per-capita incidence and prevalence; uncertainty intervals are characterized by the 25th and 75th simulated percentiles. RESULTS: There were 1,603,473 (1,467,801-1,767,779) incident cases of gonorrhea estimated in 2019. Per-capita incidence increased 32%, from 1101 (1002-1221) to 1456 (1333-1605) infections per 100,000 persons. This trend in per-capita incidence had 3 phrases: an initial decline during 2006 to 2009, a plateau through 2013, and a rapid increase of 66% through 2019. Men aged 25 to 39 years experienced the greatest increase in incidence (125%, 541 [467-651] to 1212 infections [1046-1458] per 100,000 men). Women aged 25 to 39 years had the lowest incidence in 2019, with 1040 infections (882-1241) per 100,000 women. Prevalence increased more slowly among those aged 25 to 39 years versus 15 to 24 years. The incidence ratio comparing men with women aged 25 to 39 years increased from 0.76 to 1.18. CONCLUSIONS: The burden of gonorrhea has increased among men and women aged 15 to 39 years since 2013. An increasing proportion of incident infections are among men. Additional biomedical and behavioral interventions are needed to control gonococcal transmission.

Changes in Oral and Anal Sex With Opposite-Sex Partners Among Sexually Active Females and Males Aged 15 to 44 Years in the United States: National Survey of Family Growth, 2011-2019.

BACKGROUND: Oral and anal sex with opposite-sex partners is common and associated with sexually transmitted infection (STI) transmission. Trends in these behaviors over the last decade, during which bacterial STI diagnoses have reached historic highs while HIV diagnoses have decreased, are not well understood. We examined recent trends in oral and anal sex and associated condom use with opposite-sex partners among females and males. METHODS: We analyzed data from 16,926 female and 13,533 male respondents aged 15 to 44 years who reported sex with an opposite-sex partner in the past 12 months from the National Survey of Family Growth, 2011-2019. We used survey-weighted linear or logistic regression to evaluate linear temporal trends in oral and anal sex behaviors. RESULTS: From 2011-2013 to 2017-2019, reports of oral sex and number of oral sex partners in the past 12 months increased among females (85.4% in 2011-2013 to 89.4% in 2017-2019; odds ratio [OR], 1.05 [95% confidence interval {CI}, 1.02-1.09], and ß = 0.014 [95% CI, 0.005-0.023]; respectively) but not males (ranges, 87.9%-89.1%; 1.27-1.31). Condom use at last oral sex decreased among both females and males (6.3%-4.3%: OR, 0.93 [95% CI, 0.88-0.99]; 5.9%-4.4%: OR, 0.95 [95% CI, 0.91-1.00]). Anal sex (ranges, 21.0%-23.3% [females] and 23.3%-24.6% [males]), number of anal sex partners (females, 0.22-0.25; males, 0.26-0.30), and condom use at last anal sex (females, 15.3%-18.2%; males, 27.0%-28.7%) remained stable. CONCLUSIONS: The frequency of oral and anal sex with opposite-sex partners among U.S. 15- to 44-year-olds, paired with limited and-for oral sex-decreasing condom use, demonstrates the need to understand the role of these behaviors in increasing STI diagnosis rates and the potential role of extragenital screening and condoms in reducing STI transmission.

Potential for Recurrent Mpox Outbreaks Among Gay, Bisexual, and Other Men Who Have Sex with Men - United States, 2023.

More than 30,000 monkeypox (mpox) cases have been diagnosed in the United States since May 2022, primarily among gay, bisexual, and other men who have sex with men (MSM) (1,2). In recent months, diagnoses have declined to one case per day on average. However, mpox vaccination coverage varies regionally, suggesting variable potential risk for mpox outbreak recurrence (3). CDC simulated dynamic network models representing sexual behavior among MSM to estimate the risk for and potential size of recurrent mpox outbreaks at the jurisdiction level for 2023 and to evaluate the benefits of vaccination for preparedness against mpox reintroduction. The risk for outbreak recurrence after mpox reintroduction is linearly (inversely) related to the proportion of MSM who have some form of protective immunity: the higher the population prevalence of immunity (from vaccination or natural infection), the lower the likelihood of recurrence in that jurisdiction across all immunity levels modeled. In contrast, the size of a potential recurrent outbreak might have thresholds: very small recurrences are predicted for jurisdictions with mpox immunity of 50%-100%; exponentially increasing sizes of recurrences are predicted for jurisdictions with 25%-50% immunity; and linearly increasing sizes of recurrences are predicted for jurisdictions with <25% immunity. Among the 50 jurisdictions examined, 15 are predicted to be at minimal risk for recurrence because of their high levels of population immunity. This analysis underscores the ongoing need for accessible and sustained mpox vaccination to decrease the risk for and potential size of future mpox recurrences.

Progress Toward Equitable Mpox Vaccination Coverage: A Shortfall Analysis - United States, May 2022-April 2023.

More than 30,000 monkeypox (mpox) cases were reported in the United States during the 2022 multinational outbreak; cases disproportionately affected gay, bisexual, and other men who have sex with men (MSM). Substantial racial and ethnic disparities in incidence were also reported (1). The national mpox vaccination strategy* emphasizes that efforts to administer the JYNNEOS mpox vaccine should be focused among the populations at elevated risk for exposure to mpox (2). During May 2022-April 2023, a total of 748,329 first JYNNEOS vaccine doses (of the two recommended) were administered in the United States.† During the initial months of the outbreak, lower vaccination coverage rates among racial and ethnic minority groups were reported (1,3); however, after implementation of initiatives developed to expand access to mpox vaccination,§ coverage among racial and ethnic minority groups increased (1,4). A shortfall analysis was conducted to examine whether the increase in mpox vaccination coverage was equitable across all racial and ethnic groups (5). Shortfall was defined as the percentage of the vaccine-eligible population that did not receive the vaccine (i.e., 100% minus the percentage of the eligible population that did receive a first dose). Monthly mpox vaccination shortfalls were calculated and were stratified by race and ethnicity; monthly percent reductions in shortfall were also calculated compared with the preceding month's shortfall (6). The mpox vaccination shortfall decreased among all racial and ethnic groups during May 2022-April 2023; however, based on analysis of vaccine administration data with race and ethnicity reported, 66.0% of vaccine-eligible persons remained unvaccinated at the end of this period. The shortfall was largest among non-Hispanic Black or African American (Black) (77.9%) and non-Hispanic American Indian or Alaska Native (AI/AN) (74.5%) persons, followed by non-Hispanic White (White) (66.6%) and Hispanic or Latino (Hispanic) (63.0%) persons, and was lowest among non-Hispanic Asian (Asian) (38.5%) and non-Hispanic Native Hawaiian and other Pacific Islander (NH/OPI) (43.7%) persons. The largest percentage decreases in the shortfall were achieved during August (17.7%) and September (8.5%). However, during these months, smaller percentage decreases were achieved among Black persons (12.2% and 4.9%, respectively), highlighting the need for a focus on equity for the entirety of a public health response. Achieving equitable progress in JYNNEOS vaccination coverage will require substantial decreases in shortfalls among Black and AI/AN persons.

Racial and Ethnic Disparities in Mpox Cases and Vaccination Among Adult Males - United States, May-December 2022.

As of December 31, 2022, a total of 29,939 monkeypox (mpox) cases* had been reported in the United States, 93.3% of which occurred in adult males. During May 10-December 31, 2022, 723,112 persons in the United States received the first dose in a 2-dose mpox (JYNNEOS)† vaccination series; 89.7% of these doses were administered to males (1). The current mpox outbreak has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) and racial and ethnic minority groups (1,2). To examine racial and ethnic disparities in mpox incidence and vaccination rates, rate ratios (RRs) for incidence and vaccination rates and vaccination-to-case ratios were calculated, and trends in these measures were assessed among males aged ≥18 years (males) (3). Incidence in males in all racial and ethnic minority groups except non-Hispanic Asian (Asian) males was higher than that among non-Hispanic White (White) males. At the peak of the outbreak in August 2022, incidences among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) males were higher than incidence among White males (RR = 6.9 and 4.1, respectively). Overall, vaccination rates were higher among males in racial and ethnic minority groups than among White males. However, the vaccination-to-case ratio was lower among Black (8.8) and Hispanic (16.2) males than among White males (42.5) during the full analytic period, indicating that vaccination rates among Black and Hispanic males were not proportionate to the elevated incidence rates (i.e., these groups had a higher unmet vaccination need). Efforts to increase vaccination among Black and Hispanic males might have resulted in the observed relative increased rates of vaccination; however, these increases were only partially successful in reducing overall incidence disparities. Continued implementation of equity-based vaccination strategies is needed to further increase vaccination rates and reduce the incidence of mpox among all racial and ethnic groups. Recent modeling data (4) showing that, based on current vaccination coverage levels, many U.S. jurisdictions are vulnerable to resurgent mpox outbreaks, underscore the need for continued vaccination efforts, particularly among racial and ethnic minority groups.

Changes in Sexual Behaviors with Opposite-Sex Partners and Sexually Transmitted Infection Outcomes Among Females and Males Ages 15-44 Years in the USA: National Survey of Family Growth, 2008-2019.

Rates of reported gonorrhea and chlamydial infections have increased substantially over the past decade in the USA and disparities persist across age and race/ethnicity. We aimed to understand potential changes in sexual behaviors, sexual network attributes, and sexually transmitted infection (STI) screening that may be contributing to these trends. We analyzed data from 29,423 female and 24,605 male respondents ages 15-44 years from the National Survey of Family Growth, 2008-2019. We used survey-weighted linear or logistic regression to evaluate linear temporal trends in sexual behaviors with opposite-sex partners, network attributes, and STI testing, treatment, and diagnosis. Significant declines were observed in condom use at last vaginal sex, mean number of vaginal sex acts, proportion of condom-protected sex acts in the past 4 weeks, and racial/ethnic homophily with current partners among males and females from 2008-2010 through 2017-2019. Among males, mean number of female partners in the past 12 months and concurrency also declined, while the percent reporting ever having sex with another male increased. Past-year testing for chlamydia and any STI increased among females. Research is needed to understand how these changes interact and potentially contribute to increasing reported gonorrhea and chlamydia diagnoses and identify avenues for future intervention.

Incidence of Monkeypox Among Unvaccinated Persons Compared with Persons Receiving ≥1 JYNNEOS Vaccine Dose - 32 U.S. Jurisdictions, July 31-September 3, 2022.

Human monkeypox is caused by Monkeypox virus (MPXV), an Orthopoxvirus, previously rare in the United States (1). The first U.S. case of monkeypox during the current outbreak was identified on May 17, 2022 (2). As of September 28, 2022, a total of 25,341 monkeypox cases have been reported in the United States.* The outbreak has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) (3). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series with doses administered 4 weeks apart, was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and monkeypox infection (4). U.S. distribution of JYNNEOS vaccine as postexposure prophylaxis (PEP) for persons with known exposures to MPXV began in May 2022. A U.S. national vaccination strategy† for expanded PEP, announced on June 28, 2022, recommended subcutaneous vaccination of persons with known or presumed exposure to MPXV, broadening vaccination eligibility. FDA emergency use authorization (EUA) of intradermal administration of 0.1 mL of JYNNEOS on August 9, 2022, increased vaccine supply (5). As of September 28, 2022, most vaccine has been administered as PEP or expanded PEP. Because of the limited amount of time that has elapsed since administration of initial vaccine doses, as of September 28, 2022, relatively few persons in the current outbreak have completed the recommended 2-dose series.§ To examine the incidence of monkeypox among persons who were unvaccinated and those who had received ≥1 JYNNEOS vaccine dose, 5,402 reported monkeypox cases occurring among males¶ aged 18-49 years during July 31-September 3, 2022, were analyzed by vaccination status across 32 U.S. jurisdictions.** Average monkeypox incidence (cases per 100,000) among unvaccinated persons was 14.3 (95% CI = 5.0-41.0) times that among persons who received 1 dose of JYNNEOS vaccine ≥14 days earlier. Monitoring monkeypox incidence by vaccination status in timely surveillance data might provide early indications of vaccine-related protection that can be confirmed through other well-controlled vaccine effectiveness studies. This early finding suggests that a single dose of JYNNEOS vaccine provides some protection against monkeypox infection. The degree and durability of such protection is unknown, and it is recommended that people who are eligible for monkeypox vaccination receive the complete 2-dose series.

Reduced Risk for Mpox After Receipt of 1 or 2 Doses of JYNNEOS Vaccine Compared with Risk Among Unvaccinated Persons - 43 U.S. Jurisdictions, July 31-October 1, 2022.

As of October 28, 2022, a total of 28,244* monkeypox (mpox) cases have been reported in the United States during an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series (with doses administered 4 weeks apart), was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and mpox disease (2); an FDA Emergency Use Authorization issued on August 9, 2022, authorized intradermal administration of 0.1 mL per dose, increasing the number of persons who could be vaccinated with the available vaccine supply† (3). A previous comparison of mpox incidence during July 31-September 3, 2022, among unvaccinated, but vaccine-eligible men aged 18-49 years and those who had received ≥1 JYNNEOS vaccine dose in 32 U.S. jurisdictions, found that incidence among unvaccinated persons was 14 times that among vaccinated persons (95% CI = 5.0-41.0) (4). During September 4-October 1, 2022, a total of 205,504 persons received JYNNEOS vaccine dose 2 in the United States.§ To further examine mpox incidence among persons who were unvaccinated and those who had received either 1 or 2 JYNNEOS doses, investigators analyzed data on 9,544 reported mpox cases among men¶ aged 18-49 years during July 31-October 1, 2022, from 43 U.S. jurisdictions,** by vaccination status. During this study period, mpox incidence (cases per 100,000 population at risk) among unvaccinated persons was 7.4 (95% CI = 6.0-9.1) times that among persons who received only 1 dose of JYNNEOS vaccine ≥14 days earlier and 9.6 (95% CI = 6.9-13.2) times that among persons who received dose 2 ≥14 days earlier. The observed distribution of subcutaneous and intradermal routes of administration of dose 1 among vaccinated persons with mpox was not different from the expected distribution. This report provides additional data suggesting JYNNEOS vaccine provides protection against mpox, irrespective of whether the vaccine is administered intradermally or subcutaneously. The degree and durability of such protection remains unclear. Persons eligible for mpox vaccination should receive the complete 2-dose series to optimize strength of protection†† (5).

Estimates of the Prevalence and Incidence of Syphilis in the United States, 2018.

BACKGROUND: Syphilis is a genital ulcerative disease caused by the bacterium Treponema pallidum that is associated with significant complications if left untreated and can facilitate the transmission and acquisition of HIV infection. The last prevalence and incidence estimates of the burden of syphilis in the United States were for 2008. METHODS: We generate syphilis prevalence and incidence estimates for 2018 among adults aged 14 to 49 years. We fit a simple mathematical model to 2018 case report data to generate 10,000 sets of estimates for age and sex subpopulations and summarize our estimates by their median (50th percentile); uncertainty intervals are characterized by their 25th (Q1) and 75th (Q3) percentiles. We also used our methodology to reestimate 2008 prevalence and incidence estimates. RESULTS: In 2018, there were an estimated 156,000 (Q1, 132,000; Q3, 184,000) prevalent and 146,000 (Q1, 126,000; Q3, 170,000) incident syphilitic infections in people aged 14 to 49 years. Men accounted for roughly 70% of prevalent infections and more than 80% of incident infections. In both sexes, there were more prevalent and incident infections in 25- to 49-year-olds than 14- to 24-year-olds. Using these methods to reanalyze 2008 data, syphilis prevalence and incidence estimates have increased 164% and 175%, respectively, between 2008 and 2018. DISCUSSION: Although not as common as other sexually transmitted infections, syphilis should be monitored because of its devastating sequelae. As it continues to increase in frequency, it will be important for future work to continue to track its trajectory and burden.

Estimates of the Prevalence and Incidence of Genital Herpes, United States, 2018.

BACKGROUND: Although there are more recent estimate of genital herpes prevalence, incidence estimates in the United States (US) have not been updated since 2008. METHODS: We estimated genital herpes prevalence and incidence for 2018 among adults aged 18 to 49 years. We estimated prevalence using 2015-2018 National Health and Nutrition Examination Survey herpes simplex virus type 2 (HSV-2) seroprevalence data among the noninstitutionalized civilian population and extrapolated this prevalence to the full US population using 2018 American Community Survey data. We estimated incidence using 2011 to 2018 National Health and Nutrition Examination Survey HSV-2 data as inputs to a simple mathematical model. We used Monte Carlo simulation to generate 10,000 input parameter sets for age and sex subpopulations and summarized our estimates by their median; uncertainty intervals for these estimates are characterized by their first (Q1) and third (Q3) quartiles. We conducted sensitivity analyses investigating the impact of HSV type 1 (HSV-1) infection on estimates of genital herpes burden. RESULTS: In 2018, there were an estimated 18.6 (Q1 = 18.1, Q3 = 19.0) million prevalent and 572,000 (Q1 = 479,000, Q3 = 673,000) incident genital herpes infections among 18- to 49-year-olds. Women accounted for two thirds of prevalent infections with an estimated 12.1 (Q1 = 11.9, Q3 = 12.5) million infections. Incidence was highest among 18- to 24-year-olds with an estimated 242,000 (Q1 = 210,000, Q3 = 274,000) infections. Sensitivity analyses indicated that HSV-1 could be responsible for millions more prevalent genital herpes infections, and tens of thousands of additional incident genital herpes infections, depending on the percentage of HSV-1 infections that are genital. DISCUSSION: Genital herpes is a common sexually transmitted disease in the United States. Future research to understand the burden of genital infections attributable to HSV-1 would refine estimates of genital herpes burden.

The Estimated Lifetime Medical Cost of Chlamydia, Gonorrhea, and Trichomoniasis in the United States, 2018.

BACKGROUND: The purpose of this study was to provide updated estimates of the average lifetime medical cost per infection for chlamydia, gonorrhea, and trichomoniasis. METHODS: We adapted a published decision tree model that allowed for 7 possible outcomes of infection: (1) symptomatic infection, treated, no sequelae; (2) symptomatic infection, not treated, sequelae; (3) symptomatic infection, not treated, no sequelae; (4) asymptomatic infection, treated, sequelae; (5) asymptomatic infection, treated, no sequelae; (6) asymptomatic infection, not treated, sequelae; and (7) asymptomatic infection, not treated, no sequelae. The base case values and ranges we applied for the model inputs (i.e., the probability and cost assumptions) were based on published studies. RESULTS: The estimated lifetime medical costs per infection for men and women, respectively, were $46 (95% credibility interval, $32-$62) and $262 ($127-$483) for chlamydia, $78 ($36-$145) and $254 ($96-$518) for gonorrhea, and $5 ($1-$14) and $36 ($17-$58) for trichomoniasis. Cost estimates for men were most sensitive to assumptions regarding the probability that the infection is symptomatic, the probability of treatment if asymptomatic, and the cost of treatment of infection. Cost estimates for chlamydia and gonorrhea in women were most sensitive to assumptions regarding the probability and cost of subsequent pelvic inflammatory disease. CONCLUSIONS: These estimates of the lifetime medical cost per infection can inform updated estimates of the total annual cost of sexually transmitted infections in the United States, as well as analyses of the value and cost-effectiveness of sexually transmitted infection prevention interventions.

Estimates of the Prevalence and Incidence of Chlamydia and Gonorrhea Among US Men and Women, 2018.

BACKGROUND: The most recent prevalence and incidence estimates for chlamydia and gonorrhea, the 2 most reported sexually transmitted infections in the United States, were for 2008. We present updated estimates of the number of prevalent and incident chlamydial and gonococcal infections for 2018. METHODS: We estimated chlamydial prevalence directly from the 2015 to 2018 cycles of the National Health and Nutrition Examination Survey and chlamydial incidence using a mathematical model primarily informed by National Health and Nutrition Examination Survey and case report data. Total and antimicrobial-resistant gonococcal prevalence and incidence were estimated using mathematical models primarily informed by case report and Gonococcal Isolate Surveillance Program data. Estimates were calculated for the total population, all women, and all men aged 15 to 39 years, stratified by age group. Primary estimates represent medians and uncertainty intervals represent the 25th (Q1) and 75th (Q3) percentiles of the empirical frequency distributions of prevalence and incidence for each infection. RESULTS: Among persons aged 15 to 39 years in the United States in 2018, we estimate 2.35 (Q1, 2.20; Q3, 2.51) million prevalent and 3.98 (Q1, 3.77; Q3, 4.22) million incident chlamydial infections, and an estimated 209,000 (Q1, 183,000; Q3, 241,000) prevalent and 1.57 (Q1, 1.44; Q3, 1.72) million incident gonococcal infections. Of all gonococcal infections, there were 107,000 (Q1, 94,000; Q3, 124,000) prevalent and 804,000 (Q1, 738,000; Q3, 883,000) incident infections demonstrating antimicrobial resistance or elevated minimum inhibitory concentrations to selected antibiotics. CONCLUSIONS: Chlamydia and gonorrhea were very common in the United States in 2018. Estimates show that more than 800,000 newly acquired gonococcal infections in 2018 demonstrated resistance or elevated minimum inhibitory concentrations to currently or previously recommended antibiotics.

Incidence and Prevalence of Trichomonas vaginalis Infection Among Persons Aged 15 to 59 Years: United States, 2018.

BACKGROUND: Trichomonas vaginalis (TV) is a sexually transmitted parasite associated with multiple adverse outcomes in women. Estimating TV incidence is challenging because of its largely asymptomatic presentation. METHODS: Per-capita prevalence was estimated using the National Health and Nutrition Examination Survey, 2013 to 2018. Incidence was estimated using ordinary differential equations assuming static incidence at steady state and fit using Bayesian techniques. Model inputs included estimates of proportion of asymptomatic cases, natural clearance, and time to symptomatic treatment seeking. Posterior distributions were drawn, and uncertainty was reported, from 25th (Q1) to 75th (Q3) percentiles. Aggregated measures were estimated by combining component distributions. RESULTS: Among 15- to 59-year-olds in 2018, the number of prevalent TV infections was 2.6 (Q1, 2.4; Q3, 2.7) million overall, 470,000 (Q1, 414,000; Q3, 530,000) among men, and 2.1 (Q1, 2.0; Q3, 2.2) million among women; the numbers of incident infections were 6.9 (Q1, 6.2; Q3, 7.6) million, 3.3 (Q1, 2.8; Q3, 3.8) million, and 3.5 (Q1, 3.1; Q3, 4.0) million among all persons, men, and women, respectively. Persons aged 15 to 24 years comprised 15.6% and 16.3% of all prevalent and incident infections, respectively; prevalence and incidence in both sexes increased with age. Incidences in both sexes were highly dependent on estimates of natural clearance, which were based on few data. CONCLUSIONS: Prevalence and incidence of TV are substantial in the United States, particularly among those 25 years or older. Although estimated prevalence is higher in women, estimated incidence is similar in men and women. Data on key parameters of TV infection are limited; future research should focus on clarifying the natural history of TV.

The Estimated Direct Lifetime Medical Costs of Sexually Transmitted Infections Acquired in the United States in 2018.

BACKGROUND: We estimated the lifetime medical costs attributable to sexually transmitted infections (STIs) acquired in 2018, including sexually acquired human immunodeficiency virus (HIV). METHODS: We estimated the lifetime medical costs of infections acquired in 2018 in the United States for 8 STIs: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, human papillomavirus (HPV), hepatitis B, and HIV. We limited our analysis to lifetime medical costs incurred for treatment of STIs and for treatment of related sequelae; we did not include other costs, such as STI prevention. For each STI, except HPV, we calculated the lifetime medical cost by multiplying the estimated number of incident infections in 2018 by the estimated lifetime cost per infection. For HPV, we calculated the lifetime cost based on the projected lifetime incidence of health outcomes attributed to HPV infections acquired in 2018. Future costs were discounted at 3% annually. RESULTS: Incident STIs in 2018 imposed an estimated $15.9 billion (25th-75th percentile: $14.9-16.9 billion) in discounted, lifetime direct medical costs (2019 US dollars). Most of this cost was due to sexually acquired HIV ($13.7 billion) and HPV ($0.8 billion). STIs in women accounted for about one fourth of the cost of incident STIs when including HIV, but about three fourths when excluding HIV. STIs among 15- to 24-year-olds accounted for $4.2 billion (26%) of the cost of incident STIs. CONCLUSIONS: Incident STIs continue to impose a considerable lifetime medical cost burden in the United States. These results can inform health economic analyses to promote the use of cost-effective STI prevention interventions to reduce this burden.