NEEMA Funded Projects - STD

NEEMA 2.0 (2019-2024)

Modeling dynamic sexual networks and syphilis epidemiology

Men who have sex with men (MSM) are disproportionately impacted by syphilis. In 2019, 56.7% of all primary and secondary (P&S) syphilis infections among men were among MSM. Rates of P&S syphilis have increased more rapidly among MSM than any other subpopulation, from 20.6 per 100,000 in 2000 to 272.8 per 100,000 in 2015. Untreated syphilis can lead to severe medical complications, including infertility, severe neurological and ocular complications. However, little is known about how temporal changes in sexual network structures among MSM may influence syphilis epidemiology, promote racial/ethnic disparities, and hinder efforts to control syphilis with traditional network-informed interventions, including contact tracing. This project aims to bridge gaps in current knowledge and understanding of syphilis epidemiology among MSM using a prospective longitudinal cohort study called the Network Epidemiology of Syphilis Transmission Study (NEST) to model the individual-level and network-level factors contributing to epidemic syphilis among MSM in the U.S.

Predictive modeling for targeted prevention and surveillance of STDs

Identifying geographic areas of populations at risk for higher and worsening rates of STDs or poor health outcomes from these infections can help to prioritize resource allocations and prevention efforts. Drawing on similar work in evaluating county-level vulnerability to HIV and hepatitis C outbreaks and on more recent work on vulnerability to outbreaks of congenital syphilis, this project will use multilevel regression modeling to identify indicators predictive of (i) gonorrhea cases that are most likely to be antibiotic-resistant and (ii) jurisdictions that have increased vulnerability to STD increases and outbreaks.

Cost-effectiveness of chlamydia screening in women and men who have sex with women

The U.S. Preventive Services Task Force recommends annual screening for chlamydia in sexually active women under age 25. Evidence suggests that chlamydia screening may be protective against pelvic inflammatory disease (PID). PID can lead to more severe health outcomes, like tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. In men, chlamydia can cause urethritis and epididymitis. Previous studies suggest that chlamydia screening can be cost-effective; however, no transmission model has assessed cost-effectiveness of chlamydia screening in the United States at the levels that have been achieved up to the present. This project will use a calibrated chlamydia transmission model to estimate the number of sequelae averted and quality-adjusted life years gained by chlamydia screening during 2000-2015 and assess the cost-effectiveness of chlamydia screening.

Cost-effectiveness and HIV prevention impact of screening men who have sex with men (MSM) for chlamydia and gonorrhea

Sexually transmitted infections (STIs) can increase the risk of getting or transmitting HIV. A previous study found that overall, an estimated 10% of HIV infections were attributable to gonorrhea and chlamydia infection. This project builds on the previous study to estimate the probability of gonorrhea or chlamydia infection leading to an HIV infection. This project also aims to estimate the cost-effectiveness of gonorrhea and chlamydia screening programs on reducing HIV incidence among MSM in the United States.

Burden of STIs in terms of quality-adjusted life years lost

Estimates of the quality-of-life impacts of STIs are needed to quantify the health burden of STIs and to inform cost-effectiveness analyses of STI prevention interventions. Use of quality-adjusted life years (QALYs) enables comparison across a wide range of conditions and outcomes. The purpose of this project is to develop estimates of the expected lifetime number of QALYs lost per infection for major STIs: chlamydia, gonorrhea, syphilis, herpes simplex virus type 2 (HSV-2), and trichomoniasis. In addition to informing cost-effectiveness analyses of STI prevention interventions, this project’s results, when combined with estimates of STI incidence, will provide estimates of the overall population health burden of each STI. This project will build on the previously developed probability tree model, formal evidence synthesis, and literature review to estimate and value downstream consequences of infection across different racial/ethnic groups in the U.S. This project will update a gonorrhea analysis initiated in NEEMA 1.0 to compute QALYs lost for chlamydia and trichomoniasis. A Markov modeling approach and evidence synthesis will be used to compute QALYs lost for syphilis and HSV-2.

Estimating number of sexually active adults and adolescents in the U.S.

Estimating the size of sexually active adult and adolescent populations at a sub-national level (e.g., county) would improve the local understanding of disease burden of STIs. These estimates would also facilitate comparisons of disease rates, such as HIV and syphilis, between MSM and other populations. Building on the methods used to estimate the size of the MSM population, this project will develop state and county-level estimates for the population of men who have sex with women (exclusively), women who have sex with men, and sexually active adolescent sexual minority males, overall and by race and ethnicity. These estimates can then be used to generate estimates of disease rates for each of these population groups.

Impact of extragenital infections and screening on gonorrhea and chlamydia in heterosexual populations

Diagnoses of gonorrhea and chlamydia are on the rise among both women and men in the U.S., but the reasons for this are not fully clear. Improvements in diagnostics explain an unknown amount of this change, as might changes in clinic care. However, behavior change is also likely a key driver, although the magnitude of this effect is unknown, either overall or with sub-populations by age, race/ethnicity or region. Surveys like the National Survey of Family Growth (NSFG) have gathered large nationally representative samples that provide us with data on the underlying behaviors that might be expected to changes in bacterial STI rates. Mathematical modeling can be used to determine the patterns of change expected in incidence over time as a result of changes in these behaviors. A better understanding of the drivers of these changes – and clarification of where they do or do not seem consistent with behavioral data – helps to understand the extent which trends in diagnoses are due to positive developments (better screening) versus increases in sexual risk behavior, how that may vary by sub-population, and thus what forms and foci are optimal for both novel behavior change efforts and additional surveillance. This project will (i) analyze data from NSFG to identify key points of behavior change overall and by race/ethnicity and/or age group; and (ii) develop a model that explores major components of behavioral change among behaviorally heterosexual populations over time as revealed in the analyses from (i), alongside changes in diagnosis and treatment as obtained from STD surveillance.

Population estimates for STD/HIV modeling

This effort builds off a prior NEEMA/CAMP 1.0 project that estimated the county-level population of MSM and has proven to be very useful in estimating STI/HIV rates and disparities, as well as sizes of populations indicated for HIV pre-exposure prophylaxis. Aside from men who have sex with men (MSM), sub-national estimates of the sizes of sexually active adults do not exist but would help “complete” our local understanding of the disease burden of STIs, particularly given the low availability of sex-of-sex-partner data aside from syphilis, and HIV. Furthermore, such estimates would facilitate relative comparisons of syphilis and HIV burden between MSM and other populations. This project will create analogous denominators for sexually active men who have sex with women, and women who have sex with men, at the state level, and by race/ethnicity. This information will be synthesized into updated rates and rate ratios of HIV and STI diagnosis rates for updated measures of racial/ethnic disparities.

Enhancement of STI cost and resource allocation models

CDC's Division of STD Prevention has two existing cost modeling tools (STIC Figure and SPACE Monkey) that state and local STI programs can use for planning, resource allocation decisions, and advocacy for additional state resources (i.e., by demonstrating the return on investment for public health activities to treat cases and contacts). This project aims to update and enhance these tools to incorporate the most recent scientific information and meet the usability requirements and information needs of end-users. Activities include collecting updated model estimates, soliciting end users' input on model enhancements, creating enhanced models that incorporate updated scientific research and end users' feedback into the interface, and testing model prototypes to ensure they meet design requirements.

Aberration detection tool for STD case notifications

The National Notifiable Diseases Surveillance System (NNDSS) is used by local and state jurisdictions to send STD case notification data to CDC. Trends in NNDSS data are influenced by changes in incidence and changes in reporting practices. DSTDP monitors trends in NNDSS case data, reaching out to jurisdictions when an aberration is detected to see if data quality improvement activities are indicated or if the jurisdiction needs outbreak assistance. Although DSTDP engages in multiple activities to identify data quality and morbidity aberrations, there is an opportunity to develop a modeling tool that can identify a wider range of data aberrations more efficiently and effectively. In turn, this can improve data quality and outbreak response. This project will develop a SAS-based aberration detection tool that DSTDP can apply to weekly NNDSS syphilis case report data to quickly identify and summarize significant changes in data transmitted by jurisdictions that indicate shifts in syphilis morbidity or actionable data quality issues.

Economic analysis of disease investigation specialists to support 21^st century outbreak responses

DIS play a critical role in partner notification, counseling, and referral services for HIV and other STDs and such programs are integral components of HIV/STD prevention activities by state and local health departments. With rising rates of STDs, emerging infections such as COVID-19, and an evolving role of DIS, numerous questions can be addressed through economic analysis such as quantifying the return on investment of DIS activities, determining the budget requirements to deliver partner services to all eligible populations, or developing a prioritization model for allocating DIS resources. This two-phase project will include both a systematic literature review of the existing evidence on the costs and outcomes of DIS and partner services across diseases and an economic analysis.

Evaluating a diagnostic test that informs susceptibility to multiple antibiotics for gonorrhea treatment

While the COVID-19 pandemic has generally disrupted public health surveillance and non-life-threatening health care delivery, it has disrupted sentinel surveillance for antimicrobial resistant gonorrhea (ARGC) in particular. Fewer isolates are available at ARGC sentinel surveillance sites due to the reduction of STD clinic services at some of these sites. More broadly, healthcare seeking has been impacted in most parts of the country, limiting the opportunity for patients to be screened or receive diagnostic testing for STDs. In particular, the reduction in screening and treatment (and the shift from injectable to oral treatment for gonorrhea in response to clinic closures) may increase the incidence and prevalence of ARGC. People likely have also shifted their behaviors in ways that may either reduce or increase transmission. This project will adapt an existing model for the spread of antimicrobial-resistant gonococcal infection to project the effective lifespan of five antibiotics (ciprofloxacin, ceftriaxone, azithromycin, penicillin, and tetracycline) if rapid point-of-care diagnosis were to become widely available.

Exploring STD program impact

Estimating the return on investments in STD programs is an important priority. Previous work has analyzed program impact for syphilis, chlamydia, and gonorrhea. The results suggest that funding STD control activities is associated with reduced STD diagnoses in subsequent years at the state-level, with the strongest association observed for gonorrhea and syphilis. The regression modeling framework is not amenable to identifying the mechanisms through which the impact of funding is achieved, and as a non-dynamic model using ecological data, there is uncertainty around the estimated impact. This project will triangulate results across different modeling frameworks to compare and validate earlier findings to estimate the impact of STD Prevention and Control for Health Departments-funded STD prevention activities.

Establishing thresholds for antimicrobial-resistant gonorrhea screening

Antimicrobial-resistant gonorrhea (ARGC) has been identified as a serious public health threat. Previous NEEMA modeling by PPML has explored ways to optimize sentinel surveillance and extend the life of current treatments. This analysis will continue this work by exploring how screening for ARGC on a programmatic level would impact the spread of AMR gonorrhea and the effective lifespan of antibiotics. Rather than just relying on sentinel surveillance, this project will evaluate the impact increasing ARGC screening on a programmatic level has on the incidence of overall and AMR gonorrhea, as well as the effective lifespan of antibiotics used in the first-line treatment of gonorrhea.

Cost-effectiveness of sentinel surveillance for antimicrobial-resistant gonorrhea

Antimicrobial-resistant gonorrhea (ARGC) has been identified as a serious public health threat. CDC has used sentinel surveillance since 1986 to monitor Neisseria gonorrhoeae’s susceptibility to antimicrobials. Optimizing the use of sentinel surveillance could improve its effectiveness at detecting emerging resistance and therefore extending the life of effective treatments. In previous NEEMA work, we showed that increasing the scale of sentinel surveillance (i.e., the number of isolates tested each month) could increase the effective lifespan of antibiotics used for the treatment of gonorrhea. Evidence is lacking about the cost-effectiveness of this strategy and other strategies that change the number of isolates tested dynamically in response to prior periods’ estimates of resistance prevalence. This project aims to identify cost-effective strategies to inform the annual number of isolates tested for drug susceptibility in sentinel surveillance.