Chlamydia trachomatis seroassays used in epidemiologic research: a narrative review and practical considerations.

Chlamydia trachomatis (CT) is a sexually transmitted infection that can lead to adverse reproductive health outcomes. CT prevalence estimates are primarily derived from screening using nucleic acid amplification tests (NAATs). However, screening guidelines in the United States only include particular subpopulations, and NAATs only detect current infections. In contrast, seroassays identify past CT infections which are important for understanding the public health impacts of CT, including pelvic inflammatory disease and tubal factor infertility. Older seroassays have been plagued by low sensitivity and specificity and have not been validated using a consistent reference measure, making it challenging to compare studies, define the epidemiology of CT and determine the effectiveness of control programs. Newer seroassays have better performance characteristics. This narrative review summarizes the "state of the science" for CT seroassays that have been applied in epidemiologic studies and provides practical considerations for interpreting the literature and employing seroassays in future research.

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.

The Congenital Syphilis Prevention Cascade: Reimagining a Missed Prevention Opportunities Framework for Effective Intervention.

ABSTRACT: Congenital syphilis (CS) rates have risen in the United States since 2013. Prevention of CS requires testing and treatment of pregnant and pregnancy-capable persons at high risk for syphilis. We developed a CS Prevention Cascade to assess how effectively testing and treatment interventions reached pregnant persons with a CS outcome.

Trends in Patient's Use of Sexual Health Services During COVID-19 in a Network of STD Clinics, STD Surveillance Network, 2019 to 2021.

BACKGROUND: The initial years of the COVID-19 pandemic disrupted sexual health care clinic's services. We describe use patterns by patient characteristics, and the use of telehealth (TH) services among a network of sexually transmitted disease (STD) clinics. METHODS: Data were collected using a survey to assess the impact of COVID-19 from March to December 2020 among 7 jurisdictions who contribute STD visit-level data as part of the STD Surveillance Network. As a complement to the survey, retrospective data from January 2019 to December 2021 from these 7 STD clinics in the same 7 jurisdictions were examined for monthly utilization trends by overall visits, patient characteristics, and TH visits. RESULTS: Survey results indicated 7 clinics prioritized patients for in-person visits and 4 jurisdictions reported urgent care centers were the most common referral location. In April 2020 (relative to April 2019) clinic visits and unique patients decreased by 68.0% and 75.8%, respectively. Telehealth were documented in 4 clinics, beginning in March 2020, peaking in December 2020, and tapering until December 2021. We observed the number of clinic visits (-12.2%) and unique patients presenting for care (-27.2%) in December 2021 had yet to return to levels to that seen in December 2019. CONCLUSIONS: Sexually transmitted disease clinics showed fragility and resiliency in their adjustment to the pandemic; allowing for the continuation of services. Overall patient census has been slow to return to prepandemic levels, and many patients may still not be seeking timely care. This could result in missed opportunities to screen and treat STIs and increasing the possibility of harmful sequelae.

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.

Assessing the National Representativeness of Estimates of Antimicrobial-Resistant Urogenital Neisseria gonorrhoeae in US Men, Gonococcal Isolate Surveillance Project, 2008-2018.

BACKGROUND: The percentage of Neisseria gonorrhoeae (GC) isolates with resistance or elevated minimum inhibitory concentrations to antimicrobials has steadily increased. Current estimates are based on the Gonococcal Isolate Surveillance Project (GISP), a sentinel surveillance study of male GC in the United States. This analysis seeks to assess for adjustment before treating aggregated GISP estimates as nationally representative of all reported male urogenital infections. METHODS: We used multilevel regression with poststratification (MRP) to compute national estimates of the proportion of antimicrobial resistance (AMR) (defined as exceeding minimum inhibitory concentration thresholds) in male GC using data from 2008 to 2018 GISP and case reports. Sensitivity analyses investigated the impact of analysis assumptions and unmeasured variables. We additionally produced estimates of 2018 AMR GC cases among US men. RESULTS: National estimates were consistent with unweighted estimates. The estimated proportion of incident AMR GC infections in men with urogenital GC in 2018 was 51.5% (95% confidence interval [CI], 50.1%-52.9%), equating to an estimated 366,300 incident AMR GC infections in US men aged 15 to 39 years. Estimates of AMR for tested antimicrobials in male GC infections in 2018 ranged from 0.16% (95% CI, 0.08%-0.24%) for ceftriaxone to 29.9% (95% CI, 28.6%-31.1%) for ciprofloxacin. Sensitivity analyses revealed that unmeasured data on sex of sex partners could substantially impact weighted estimates. CONCLUSIONS: Antimicrobial resistance among reported incident male urogenital GC infections remains rare for ceftriaxone, the current standard of care. Aggregated GISP data are generally representative of men in the US who are reported with urogenital gonorrhea.

Impact of the COVID-19 Pandemic on Centers for Disease Control and Prevention-Funded Sexually Transmitted Disease Programs.

ABSTRACT: The COVID-19 pandemic impacted sexually transmitted disease (STD) services. Of 59 US-funded STD programs, 91% reported a great deal to moderate impact from staff reassignment in April 2020, with 28% of respondents reporting permanent reassignment of disease intervention specialist staff. Telemedicine was implemented in 47%. Decreases in STD case reports were reported by most jurisdictions.

The Burden of and Trends in Pelvic Inflammatory Disease in the United States, 2006-2016.

BACKGROUND: Pelvic inflammatory disease (PID) is an infection of the upper genital tract that has important reproductive consequences to women. We describe the burden of and trends in PID among reproductive-aged women in the United States during 2006-2016. METHODS: We used data from 2 nationally representative probability surveys collecting self-reported PID history (National Health and Nutrition Examination Survey, National Survey of Family Growth); 5 datasets containing International Classification of Diseases, Ninth/Tenth Revision codes indicating diagnosed PID (Healthcare Utilization Project; National Hospital Ambulatory Medical Care Survey, emergency department component; National Ambulatory Medical Care Survey; National Disease Therapeutic Index; MarketScan); and data from a network of sexually transmitted infection (STI) clinics (Sexually Transmitted Disease Surveillance Network). Trends during 2006-2016 were estimated overall, by age group and, if available, race/ethnicity, region, and prior STIs. RESULTS: An estimated 2 million reproductive-aged women self-reported a history of PID. Three of 4 nationally representative data sources showed overall declines in a self-reported PID history, and PID emergency department and physician office visits, with small increases observed in nearly all data sources starting around 2015. CONCLUSIONS: The burden of PID in the United States is high. Despite declines in burden over time, there is evidence of an increase in recent years.

Sexually Transmitted Infections Among US Women and Men: Prevalence and Incidence Estimates, 2018.

BACKGROUND: The most recent estimates of the number of prevalent and incident sexually transmitted infections (STIs) in the United States were for 2008. We provide updated estimates for 2018 using new methods. METHODS: We estimated the total number of prevalent and incident infections in the United States for 8 STIs: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, human papillomavirus, sexually transmitted hepatitis B, and sexually transmitted HIV. Updated per-capita prevalence and incidence estimates for each STI were multiplied by the 2018 full resident population estimates to calculate the number of prevalent and incident infections. STI-specific estimates were combined to generate estimates of the total number of prevalent and incident STIs overall, and by sex and age group. Primary estimates are represented by medians, and uncertainty intervals are represented by the 25th (Q1) and 75th (Q3) percentiles of the empirical frequency distributions of prevalence and incidence for each STI. RESULTS: In 2018, there were an estimated 67.6 (Q1, 66.6; Q3, 68.7) million prevalent and 26.2 (Q1, 24.0; Q3, 28.7) million incident STIs in the United States. Chlamydia, trichomoniasis, genital herpes, and human papillomavirus comprised 97.6% of all prevalent and 93.1% of all incident STIs. Persons aged 15 to 24 years comprised 18.6% (12.6 million) of all prevalent infections; however, they comprised 45.5% (11.9 million) of all incident infections. CONCLUSIONS: The burden of STIs in the United States is high. Almost half of incident STIs occurred in persons aged 15 to 24 years in 2018. Focusing on this population should be considered essential for national STI prevention efforts.

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 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.

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.

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.

An Evaluation of Infertility Among Women in the Republic of Palau, 2016.

Fertility challenges are a personal and important part of a woman's reproductive health and are associated with health and lifestyle factors. Limited data exist on infertility among women in Palau. We describe the lifetime prevalence of self-reported infertility in a nationally representative sample of women in Palau and investigate the association between tobacco and/or betel nut use and infertility. During May-December 2016, a population-based survey of noncommunicable diseases was conducted in Palau using a geographically stratified random sample of households (N=2409). Men and women ≥18 years of age were chosen randomly from each selected household. The prevalence of a self-reported lifetime episode of infertility (having tried unsuccessfully to become pregnant for ≥12 months) was evaluated among 874 women aged ≥18 years by key health and lifestyle factors. Prevalence ratios (PR) and 95% confidence intervals (CI) were calculated. Of 315 women who ever tried to become pregnant, 39.7% (95% CI: 34.2%, 45.3%) reported a lifetime episode of infertility. Prevalence was higher in women of Palauan vs other ethnicity (PR=1.6, 95% CI: 1.1, 2.3), those who self-reported poor/not good vs. excellent/ very good health status (PR=2.1, 95% CI: 1.4, 3.3), and those with a body mass index (BMI) ≥30 vs <30 (PR=1.7, 95% CI: 1.3, 2.2). Adjusted models showed that tobacco and/or betel nut users were almost twice as likely to report infertility versus non-users (PR=1.8, 95% CI: 1.3, 2.5). More research is needed to understand the infertility experiences of women in Palau and to promote lifestyle factors contributing to optimal reproductive health.

USA300 methicillin-resistant Staphylococcus aureus bacteremia and the risk of severe sepsis: is USA300 methicillin-resistant Staphylococcus aureus associated with more severe infections?

USA300 methicillin-resistant Staphylococcus aureus (MRSA) is increasing as a cause of severe community-associated bacteremic infections. We assessed severe sepsis in response to infection in patients with USA300 MRSA compared to non-USA300 MRSA bacteremia. A cohort study was conducted from 1997 to 2008 comparing sepsis in response to infection in 271 patients with MRSA bacteremia from 4 VA hospitals. Sixty-seven (25%) patients with MRSA bacteremia were USA300 MRSA; 204 (75%) were non-USA300 MRSA. The proportion of MRSA bacteremia caused by USA300 MRSA increased over time (χ² P < 0.0001). Adjusting for age and nosocomial infection, patients with USA300 MRSA bacteremia were more likely to have severe sepsis or septic shock in response to infection than patients with non-USA300 MRSA bacteremia (adjusted relative risk = 1.82; 95% confidence interval, 1.16-2.87; P = 0.01). This suggests that patients with USA300 MRSA are more likely to develop severe sepsis in response to their infection, which could be due to host or bacterial differences.

Illicit drug use and risk for USA300 methicillin-resistant Staphylococcus aureus infections with bacteremia.

To assess the association of illicit drug use and USA300 methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, a multicenter study was conducted at 4 Veterans Affairs medical centers during 2004-2008. The study showed that users of illicit drugs were more likely to have USA300 MRSA bacteremia (in contrast to bacteremia caused by other S. aureus strains) than were patients who did not use illicit drugs (adjusted relative risk 3.0; 95% confidence interval 1.9-4.4). The association of illicit drug use with USA300 MRSA bacteremia decreased over time (p = 0.23 for trend). Notably, the proportion of patients with USA300 MRSA bacteremia who did not use illicit drugs increased over time. This finding suggests that this strain has spread from users of illicit drugs to other populations.

A simple and inexpensive particle agglutination test to distinguish recent from established HIV-1 infection.

OBJECTIVES: We sought to modify the Serodia HIV-1/HIV-2 particle agglutination assay (PA), a simple and cost-effective HIV assay that is used globally for the detection of HIV antibodies, as a sensitive/less sensitive test (S/LS) to identify recently infected individuals and to estimate HIV incidence. METHODS: The Serodia PA test was modified as an S/LS test (PA-LS) by using HIV antigen-coated gelatin particles at a dilution of 1:68 and a specific diluent, and calibrated using 37 HIV clade B seroconversion panels (309 samples) from Trinidad and from a commercial source that were tested at dilution intervals from 1:10 to 1:80,000. The greatest sensitivity for correctly classifying samples from recent and established infections was determined by receiver operator curve (ROC) analysis. RESULTS: At a 1:40,000 sample dilution and a days post-seroconversion cutoff of 190 days, the PA-LS test yielded a 97% sensitivity for classifying recent and established infection samples. Furthermore, at a 1:20,000 dilution, the positive predictive value for correctly identifying recently infected individuals was 99%. The PA-LS test offers a 30-44-fold cost saving over currently available S/LS tests. CONCLUSION: A modified, low cost and simple-to-perform PA test is appropriate for use in resource-limited countries, and has exhibited excellence in distinguishing recent from established HIV infection.