Assessing thresholds of resistance prevalence at which empiric treatment of gonorrhea should change among men who have sex with men in the US: A cost-effectiveness analysis.

BACKGROUND: Since common diagnostic tests for gonorrhea do not provide information about susceptibility to antibiotics, treatment of gonorrhea remains empiric. Antibiotics used for empiric therapy are usually changed once resistance prevalence exceeds a certain threshold (e.g., 5%). A low switch threshold is intended to increase the probability that an infection is successfully treated with the first-line antibiotic, but it could also increase the pace at which recommendations are switched to newer antibiotics. Little is known about the impact of changing the switch threshold on the incidence of gonorrhea, the rate of treatment failure, and the overall cost and quality-adjusted life-years (QALYs) associated with gonorrhea. METHODS AND FINDINGS: We developed a transmission model of gonococcal infection with multiple resistant strains to project gonorrhea-associated costs and loss in QALYs under different switch thresholds among men who have sex with men (MSM) in the United States. We accounted for the costs and disutilities associated with symptoms, diagnosis, treatment, and sequelae, and combined costs and QALYs in a measure of net health benefit (NHB). Our results suggest that under a scenario where 3 antibiotics are available over the next 50 years (2 suitable for the first-line therapy of gonorrhea and 1 suitable only for the retreatment of resistant infections), changing the switch threshold between 1% and 10% does not meaningfully impact the annual number of gonorrhea cases, total costs, or total QALY losses associated with gonorrhea. However, if a new antibiotic is to become available in the future, choosing a lower switch threshold could improve the population NHB. If in addition, drug-susceptibility testing (DST) is available to inform retreatment regimens after unsuccessful first-line therapy, setting the switch threshold at 1% to 2% is expected to maximize the population NHB. A limitation of our study is that our analysis only focuses on the MSM population and does not consider the influence of interventions such as vaccine and common use of rapid drugs susceptibility tests to inform first-line therapy. CONCLUSIONS: Changing the switch threshold for first-line antibiotics may not substantially change the health and financial outcomes associated with gonorrhea. However, the switch threshold could be reduced when newer antibiotics are expected to become available soon or when in addition to future novel antibiotics, DST is also available to inform retreatment regimens.

The Impact of Rapid Drug Susceptibility Tests on Gonorrhea Burden and the Life Span of Antibiotic Treatments: A Modeling Study Among Men Who Have Sex With Men in the United States.

Rapid point-of-care tests that diagnose gonococcal infections and identify susceptibility to antibiotics enable individualized treatment. This could improve patient outcomes and slow the emergence and spread of antibiotic resistance. However, little is known about the long-term impact of such diagnostics on the burden of gonorrhea and the effective life span of antibiotics. We used a mathematical model of gonorrhea transmission among men who have sex with men in the United States to project the annual rate of reported gonorrhea cases and the effective life span of ceftriaxone, the recommended antibiotic for first-line treatment of gonorrhea, as well as 2 previously recommended antibiotics, ciprofloxacin and tetracycline, when a rapid drug susceptibility test that estimates susceptibility to ciprofloxacin and tetracycline is available. The use of a rapid drug susceptibility test with ≥50% sensitivity and ≥95% specificity, defined in terms of correct ascertainment of drug susceptibility and nonsusceptibility status, could increase the combined effective life span of ciprofloxacin, tetracycline, and ceftriaxone by at least 2 years over 25 years of simulation. If test specificity is imperfect, however, the increase in the effective life span of antibiotics is accompanied by an increase in the rate of reported gonorrhea cases even under perfect sensitivity.

The US COVID-19 Trends and Impact Survey: Continuous real-time measurement of COVID-19 symptoms, risks, protective behaviors, testing, and vaccination.

The US COVID-19 Trends and Impact Survey (CTIS) is a large, cross-sectional, internet-based survey that has operated continuously since April 6, 2020. By inviting a random sample of Facebook active users each day, CTIS collects information about COVID-19 symptoms, risks, mitigating behaviors, mental health, testing, vaccination, and other key priorities. The large scale of the survey-over 20 million responses in its first year of operation-allows tracking of trends over short timescales and allows comparisons at fine demographic and geographic detail. The survey has been repeatedly revised to respond to emerging public health priorities. In this paper, we describe the survey methods and content and give examples of CTIS results that illuminate key patterns and trends and help answer high-priority policy questions relevant to the COVID-19 epidemic and response. These results demonstrate how large online surveys can provide continuous, real-time indicators of important outcomes that are not subject to public health reporting delays and backlogs. The CTIS offers high value as a supplement to official reporting data by supplying essential information about behaviors, attitudes toward policy and preventive measures, economic impacts, and other topics not reported in public health surveillance systems.

The Estimated Lifetime Quality-Adjusted Life-Years Lost Due to Chlamydia, Gonorrhea, and Trichomoniasis in the United States in 2018.

BACKGROUND: Comprehensive evaluation of the quality-adjusted life-years (QALYs) lost attributable to chlamydia, gonorrhea, andtrichomoniasis in the United States is lacking. METHODS: We adapted a previous probability-tree model to estimate the average number of lifetime QALYs lost due to genital chlamydia, gonorrhea, and trichomoniasis, per incident infection and at the population level, by sex and age group. We conducted multivariate sensitivity analyses to address uncertainty around key parameter values. RESULTS: The estimated total discounted lifetime QALYs lost for men and women, respectively, due to infections acquired in 2018, were 1541 (95% uncertainty interval [UI], 186-6358) and 111 872 (95% UI, 29 777-267 404) for chlamydia, 989 (95% UI, 127-3720) and 12 112 (95% UI, 2 410-33 895) for gonorrhea, and 386 (95% UI, 30-1851) and 4576 (95% UI, 13-30 355) for trichomoniasis. Total QALYs lost were highest among women aged 15-24 years with chlamydia. QALYs lost estimates were highly sensitive to disutilities (health losses) of infections and sequelae, and to duration of infections and chronic sequelae for chlamydia and gonorrhea in women. CONCLUSIONS: The 3 sexually transmitted infections cause substantial health losses in the United States, particularly gonorrhea and chlamydia among women. The estimates of lifetime QALYs lost per infection help to prioritize prevention policies and inform cost-effectiveness analyses of sexually transmitted infection interventions.

Regional and country-level trends in cervical cancer screening coverage in sub-Saharan Africa: A systematic analysis of population-based surveys (2000-2020).

BACKGROUND: Sub-Saharan Africa (SSA) has the highest cervical cancer (CC) burden globally-worsened by its HIV epidemics. In 2020, the World Health Organization (WHO) introduced a CC elimination strategy with goals for vaccination, screening, and treatment. To benchmark progress, we examined temporal trends in screening coverage, percent screened at least twice by the age of 45, screening coverage among women living with HIV (WLHIV), and pre-cancer treatment coverage in SSA. METHODS AND FINDINGS: We conducted a systematic analysis of cross-sectional population-based surveys. It included 52 surveys from 28 countries (2000 to 2020) with information on CC screening among women aged 25 to 49 years (N = 151,338 women). We estimated lifetime and past 3-year screening coverage by age, year, country, and HIV serostatus using a Bayesian multilevel model. Post-stratification and imputations were done to obtain aggregate national, regional, and SSA-level estimates. To measure re-screening by age 45, a life table model was developed. Finally, self-reported pre-cancer treatment coverage was pooled across surveys using a Bayesian meta-analysis. Overall, an estimated 14% (95% credible intervals [95% CrI]: 11% to 21%) of women aged 30 to 49 years had ever been screened for CC in 2020, with important regional and country-level differences. In Eastern and Western/Central Africa, regional screening coverages remained constant from 2000 to 2020 and WLHIV had greater odds of being screened compared to women without HIV. In Southern Africa, however, screening coverages increased and WLHIV had equal odds of screening. Notably this region was found to have higher screening coverage in comparison to other African regions. Rescreening rates were high among women who have already been screened; however, it was estimated that only 12% (95% CrI: 10% to 18%) of women had been screened twice or more by age 45 in 2020. Finally, treatment coverage among 4 countries with data was 84% (95% CrI: 70% to 95%). Limitations of our analyses include the paucity of data on screening modality and the few countries that had multiple surveys. CONCLUSION: Overall, CC screening coverage remains sub-optimal and did not improve much over the last 2 decades, outside of Southern Africa. Action is needed to increase screening coverage if CC elimination is to be achieved.

Costs, Health Benefits, and Cost-Effectiveness of Chlamydia Screening and Partner Notification in the United States, 2000-2019: A Mathematical Modeling Analysis.

BACKGROUND: Chlamydia remains a significant public health problem that contributes to adverse reproductive health outcomes. In the United States, sexually active women 24 years and younger are recommended to receive annual screening for chlamydia. In this study, we evaluated the impact of estimated current levels of screening and partner notification (PN), and the impact of screening based on guidelines on chlamydia associated sequelae, quality adjusted life years (QALYs) lost and costs. METHODS: We conducted a cost-effectiveness analysis of chlamydia screening, using a published calibrated pair formation transmission model that estimated trends in chlamydia screening coverage in the United States from 2000 to 2015 consistent with epidemiological data. We used probability trees to translate chlamydial infection outcomes into estimated numbers of chlamydia-associated sequelae, QALYs lost, and health care services costs (in 2020 US dollars). We evaluated the costs and population health benefits of screening and PN in the United States for 2000 to 2015, as compared with no screening and no PN. We also estimated the additional benefits that could be achieved by increasing screening coverage to the levels indicated by the policy recommendations for 2016 to 2019, compared with screening coverage achieved by 2015. RESULTS: Screening and PN from 2000 to 2015 were estimated to have averted 1.3 million (95% uncertainty interval [UI] 490,000-2.3 million) cases of pelvic inflammatory disease, 430,000 (95% UI, 160,000-760,000) cases of chronic pelvic pain, 300,000 (95% UI, 104,000-570,000) cases of tubal factor infertility, and 140,000 (95% UI, 47,000-260,000) cases of ectopic pregnancy in women. We estimated that chlamydia screening and PN cost $9700 per QALY gained compared with no screening and no PN. We estimated the full realization of chlamydia screening guidelines for 2016 to 2019 to cost $30,000 per QALY gained, compared with a scenario in which chlamydia screening coverage was maintained at 2015 levels. DISCUSSION: Chlamydia screening and PN as implemented in the United States from 2000 through 2015 has substantially improved population health and provided good value for money when considering associated health care services costs. Further population health gains are attainable by increasing screening further, at reasonable cost per QALY gained.

Modeling the Cost-Effectiveness of Express Multisite Gonorrhea Screening Among Men Who Have Sex With Men in the United States.

BACKGROUND: Men who have sex with men (MSM) experience high rates of gonococcal infection at extragenital (rectal and pharyngeal) anatomic sites, which often are missed without asymptomatic screening and may be important for onward transmission. Implementing an express pathway for asymptomatic MSM seeking routine screening at their clinic may be a cost-effective way to improve extragenital screening by allowing patients to be screened at more anatomic sites through a streamlined, less costly process. METHODS: We modified an agent-based model of anatomic site-specific gonococcal infection in US MSM to assess the cost-effectiveness of an express screening pathway in which all asymptomatic MSM presenting at their clinic were screened at the urogenital, rectal, and pharyngeal sites but forewent a provider consultation and physical examination and self-collected their own samples. We calculated the cumulative health effects expressed as gonococcal infections and cases averted over 5 years, labor and material costs, and incremental cost-effectiveness ratios for express versus traditional scenarios. RESULTS: The express scenario averted more infections and cases in each intervention year. The increased diagnostic costs of triple-site screening were largely offset by the lowered visit costs of the express pathway and, from the end of year 3 onward, this pathway generated small cost savings. However, in a sensitivity analysis of assumed overhead costs, cost savings under the express scenario disappeared in the majority of simulations once overhead costs exceeded 7% of total annual costs. CONCLUSIONS: Express screening may be a cost-effective option for improving multisite anatomic screening among US MSM.

Potential for Point-of-Care Tests to Reduce Chlamydia-associated Burden in the United States: A Mathematical Modeling Analysis.

BACKGROUND: Point-of-care testing (POCT) assays for chlamydia are being developed. Their potential impact on the burden of chlamydial infection in the United States, in light of suboptimal screening coverage, remains unclear. METHODS: Using a transmission model calibrated to data in the United States, we estimated the impact of POCT on chlamydia prevalence, incidence, and chlamydia-attributable pelvic inflammatory disease (PID) incidence, assuming status quo (Analysis 1) and improved (Analysis 2) screening frequencies. We tested the robustness of results to changes in POCT sensitivity, the proportion of patients getting treated immediately, the baseline proportion lost to follow-up (LTFU), and the average treatment delay. RESULTS: In Analysis 1, high POCT sensitivity was needed to reduce the chlamydia-associated burden. With a POCT sensitivity of 90%, reductions from the baseline burden only occurred in scenarios in which over 60% of the screened individuals would get immediate treatment and the baseline LTFU proportion was 20%. With a POCT sensitivity of 99% (baseline LTFU 10%, 2-week treatment delay), if everyone were treated immediately, the prevalence reduction was estimated at 5.7% (95% credible interval [CrI] 3.9-8.2%). If only 30% of tested persons would wait for results, the prevalence reduction was only 1.6% (95% CrI 1.1-2.3). POCT with 99% sensitivity could avert up to 12 700 (95% CrI 5000-22 200) PID cases per year, if 100% were treated immediately (baseline LTFU 20% and 3-week treatment delay). In Analysis 2, when POCT was coupled with increasing screening coverage, reductions in the chlamydia burden could be realized with a POCT sensitivity of 90%. CONCLUSIONS: POCT could improve chlamydia prevention efforts if test performance characteristics are significantly improved over currently available options.

Population-level Benefits of Extragenital Gonorrhea Screening Among Men Who Have Sex With Men: An Exploratory Modeling Analysis.

BACKGROUND: Men who have sex with men (MSM) are disproportionately burdened by gonorrhea and face high rates of extragenital (rectal and pharyngeal) infection, which is mostly asymptomatic and often missed by urogenital-only screening. Extragenital screening likely remains below Centers for Disease Control and Prevention-recommended levels. Because increasing screening coverage is often resource-intensive, we assessed whether improved extragenital screening among men already presenting at clinics could lead to substantial reductions in prevalence and incidence. METHODS: We calibrated an agent-based model of site- and race-specific gonorrhea infection in MSM to explicitly model multisite infection within an individual and transmission via anal, orogenital, and ororectal sex. Compared with current screening levels, we assessed the impact of increasing screening at (1) both extragenital sites, (2) only the rectal site, and (3) only the pharyngeal site among men already being urogenitally screened. RESULTS: All scenarios reduced prevalence and incidence, with improved screening at both extragenital sites having the largest effect across outcomes. Extragenitally screening 100% of men being urogenitally screened reduced site-specific prevalence by an average of 42% (black MSM) and 50% (white MSM), with these values dropping by approximately 10% and 20% for each race group when targeting only the rectum and only the pharynx, respectively. However, increasing only rectal screening was more efficient in terms of the number of screens needed to avert an infection as this avoided duplicative screens due to rectum/pharynx multisite infection. CONCLUSIONS: Improved extragenital screening substantially reduced site-specific gonorrhea prevalence and incidence, with strategies aimed at increasing rectal screening proving the most efficient.

The Potential Population-Level Impact of Different Gonorrhea Screening Strategies in Baltimore and San Francisco: An Exploratory Mathematical Modeling Analysis.

BACKGROUND: Baltimore and San Francisco represent high burden areas for gonorrhea in the United States. We explored different gonorrhea screening strategies and their comparative impact in the 2 cities. METHODS: We used a compartmental transmission model of gonorrhea stratified by sex, sexual orientation, age, and race/ethnicity, calibrated to city-level surveillance data for 2010 to 2017. We analyzed the benefits of 5-year interventions which improved retention in care cascade or increased screening from current levels. We also examined a 1-year outreach screening intervention of high-activity populations. RESULTS: In Baltimore, annual screening of population aged 15 to 24 years was the most efficient of the 5-year interventions with 17.9 additional screening tests (95% credible interval [CrI], 11.8-31.4) needed per infection averted while twice annual screening of the same population averted the most infections (5.4%; 95% CrI, 3.1-8.2%) overall with 25.3 (95% CrI, 19.4-33.4) tests per infection averted. In San Francisco, quarter-annual screening of all men who have sex with men was the most efficient with 16.2 additional (95% CrI, 12.5-44.5) tests needed per infection averted, and it also averted the most infections (10.8%; 95% CrI, 1.2-17.8%). Interventions that reduce loss to follow-up after diagnosis improved outcomes. Depending on the ability of a short-term outreach screening to screen populations at higher acquisition risk, such interventions can offer efficient ways to expand screening coverage. CONCLUSIONS: Data on gonorrhea prevalence distribution and time trends locally would improve the analyses. More focused intervention strategies could increase the impact and efficiency of screening interventions.

Mathematical modeling study of school-based chlamydia screening: potential impact on chlamydia prevalence in intervention schools and surrounding communities.

BACKGROUND: Chlamydia screening in high schools offers a way to reach adolescents outside of a traditional clinic setting. Using transmission dynamic modeling, we examined the potential impact of high-school-based chlamydia screening programs on the burden of infection within intervention schools and surrounding communities, under varying epidemiological and programmatic conditions. METHODS: A chlamydia transmission model was calibrated to epidemiological data from three different settings. Philadelphia and Chicago are two high-burden cities with existing school-based screening programs. Rural Iowa does not have an existing program but represents a low-burden setting. We modeled the effects of the two existing programs to analyze the potential influence of program coverage and student participation. All three settings were used to examine a broader set of hypothetical programs with varying coverage levels and time trends in participation. RESULTS: In the modeled Philadelphia program, prevalence among the intervention schools' sexually active 15-18 years old population was 4.34% (95% credible interval 3.75-4.71%)after 12 program years compared to 5.03% (4.39-5.43%) in absence of the program. In the modeled Chicago program, prevalence was estimated as 5.97% (2.60-7.88%) after 4 program years compared to 7.00% (3.08-9.29%) without the program. In the broader hypothetical scenarios including both high-burden and low-burden settings, impact of school-based screening programs was greater in absolute terms in the higher-prevalence settings, and benefits in the community were approximately proportional to population coverage of intervention schools. Most benefits were garnered if the student participation did not decline over time. CONCLUSIONS: Sustained high student participation in school-based screening programs and broad coverage of schools within a target community are likely needed to maximize program benefits in terms of reduced burden of chlamydia in the adolescent population.

The Impact of Screening and Partner Notification on Chlamydia Prevalence and Numbers of Infections Averted in the United States, 2000-2015: Evaluation of Epidemiologic Trends Using a Pair-Formation Transmission Model.

Population-level effects of control strategies on the dynamics of Chlamydia trachomatis transmission are difficult to quantify. In this study, we calibrated a novel sex- and age-stratified pair-formation transmission model of chlamydial infection to epidemiologic data in the United States for 2000-2015. We used sex- and age-specific prevalence estimates from the National Health and Nutrition Examination Surveys, case report data from national chlamydia surveillance, and survey data from the Youth Risk Behavior Survey on the proportion of the sexually active population aged 15-18 years. We were able to reconcile national prevalence estimates and case report data by allowing for changes over time in screening coverage and reporting completeness. In retrospective analysis, chlamydia prevalence was estimated to be almost twice the current levels in the absence of screening and partner notification. Although chlamydia screening and partner notification were both found to reduce chlamydia burden, the relative magnitude of their estimated impacts varied in our sensitivity analyses. The variation in the model predictions highlights the need for further data collection and research to improve our understanding of the natural history of chlamydia and the pathways through which prevention strategies affect transmission dynamics.

Estimated Impact of Screening on Gonorrhea Epidemiology in the United States: Insights From a Mathematical Model.

The burden of gonorrhea infections in the United States is high. There are marked disparities by race/ethnicity and sexual orientation. We quantified the impact of screening and treatment on gonorrhea rates in the US population aged 15 to 39 years for the period 2000 to 2015 and estimated the impact that alternative screening strategies might have had over the same period. METHODS: We developed a national-level transmission model that divides the population by race/ethnicity, preferred gender of sex partners, age, gender, and sexual activity level. We compared our fitted model ("base case") to 4 alternative strategies: (i) no screening, (ii) full adherence to current screening guidelines, (iii) annual universal screening, or (iv) enhanced screening in groups with the highest infection burden. Main outcomes were incidence, infections averted, and incidence rate ratios by race/ethnicity. Mean values and 95% credible intervals were calculated from 1000 draws from parameter posterior distributions. RESULTS: The calibrated model reproduced observed trends in gonorrhea, including disparities in infection burden by race/ethnicity. We estimated that screening for gonorrhea from 2000 to 2015 averted 30% (95% credible intervals, 18-44%) of total infections that would otherwise have occurred. All alternative active screening strategies were estimated to further reduce, but not eliminate, gonorrhea infections relative to the base case, with differential impacts on the subpopulations of interest. CONCLUSIONS: Our model results suggest that screening has reduced gonorrhea incidence in the US population. Additional reductions in infection burden may have been possible over this period with increased screening, but elimination was unlikely.

The Use of Mathematical Models of Chlamydia Transmission to Address Public Health Policy Questions: A Systematic Review.

BACKGROUND: Mathematical models of chlamydia transmission can help inform disease control policy decisions when direct empirical evaluation of alternatives is impractical. We reviewed published chlamydia models to understand the range of approaches used for policy analyses and how the studies have responded to developments in the field. METHODS: We performed a literature review by searching Medline and Google Scholar (up to October 2015) to identify publications describing dynamic chlamydia transmission models used to address public health policy questions. We extracted information on modeling methodology, interventions, and key findings. RESULTS: We identified 47 publications (including two model comparison studies), which reported collectively on 29 distinct mathematical models. Nine models were individual-based, and 20 were deterministic compartmental models. The earliest studies evaluated the benefits of national-level screening programs and predicted potentially large benefits from increased screening. Subsequent trials and further modeling analyses suggested the impact might have been overestimated. Partner notification has been increasingly evaluated in mathematical modeling, whereas behavioral interventions have received relatively limited attention. CONCLUSIONS: Our review provides an overview of chlamydia transmission models and gives a perspective on how mathematical modeling has responded to increasing empirical evidence and addressed policy questions related to prevention of chlamydia infection and sequelae.

Vaccination and Voting Patterns in the U.S.: Analysis of COVID-19 and Flu Surveys From 2010 to 2022.

INTRODUCTION: The study assessed the relationship between COVID-19 and influenza (flu) vaccination and voting patterns during the pandemic and the time trends between flu vaccination and voting patterns. METHODS: Flu and COVID-19 vaccination coverage were analyzed using National Immunization Surveys for flu (Years 2010-2022) and COVID-19 (National Immunization Surveys Adult COVID-19 Module 2021-2022), Centers for Disease Control and Prevention surveillance of COVID-19 vaccination coverage (2021-2022) and U.S. COVID-19 Trends and Impact Survey (2021-2022). The study described the correlations between state-level COVID-19 and flu vaccination coverage, examined individual-level characteristics of vaccination for COVID-19 and for flu using logistic regression (COVID-19 Trends and Impact Survey May-June 2022), and analyzed flu vaccination coverage by age (National Immunization Surveys for flu 2010-2022) and its relationship with voting patterns. RESULTS: There was a strong correlation between state-level COVID-19 vaccination coverage and voting share for the Democratic candidate in the 2020 presidential elections. COVID-19 vaccination coverage in June 2022 was higher than flu vaccination coverage, and it had a stronger correlation with voting patterns (R=0.90 vs R=0.60 in COVID-19 Trends and Impact Survey). Vaccinated people were more likely to be living in a county where the majority voted for the Democratic candidate in 2020 elections both for COVID-19 (adjusted OR=1.77, 95% CI=1.71, 1.84) and for flu (adjusted OR=1.27, 95% CI=1.23, 1.31). There is a longstanding correlation between voting patterns and flu vaccination coverage, which varies by age, with the strongest correlation in the youngest ages. CONCLUSIONS: There are existing prepandemic patterns between vaccination coverage and voting patterns. The findings align with research that has identified an association between adverse health outcomes and the political environment in the U.S.

Resistance-minimising strategies for introducing a novel antibiotic for gonorrhoea treatment: a mathematical modelling study.

BACKGROUND: Gonorrhoea is a highly prevalent sexually transmitted infection and an urgent public health concern because of increasing antibiotic resistance in Neisseria gonorrhoeae. Only ceftriaxone remains as the recommended treatment in the USA. With the prospect of new anti-gonococcal antibiotics being approved, we aimed to evaluate how to deploy a new drug to maximise its clinically useful lifespan. METHODS: We used a compartmental model of gonorrhoea transmission in a US population of men who have sex with men (MSM) to compare strategies for introducing a new antibiotic for gonorrhoea treatment. The MSM population was stratified into three sexual activity groups (low, intermediate, and high) characterised by annual rates of partner change. The four introduction strategies tested were: (1) random 50-50 allocation, where each treatment-seeking infected individual had a 50% probability of receiving either drug A (current drug; a ceftriaxone-like antibiotic) or drug B (a new antibiotic), effective at time 0; (2) combination therapy of both the current drug and the new antibiotic; (3) reserve strategy, by which the new antibiotic was held in reserve until the current therapy reached a 5% threshold prevalence of resistance; and (4) gradual switch, or the gradual introduction of the new drug until random 50-50 allocation was reached. The primary outcome of interest was the time until 5% prevalence of resistance to each of the drugs (the new drug and the current ceftriaxone-like antibiotic); sensitivity of the primary outcome to the properties of the new antibiotic, specifically the probability of resistance emergence after treatment and the fitness costs of resistance, was explored. Secondary outcomes included the time to a 1% resistance threshold for each drug, as well as population-level prevalence, mean and range annual incidence, and the cumulative number of incident gonococcal infections. FINDINGS: Under baseline model conditions, a 5% prevalence of resistance to each of drugs A and B was reached within 13·9 years with the reserve strategy, 18·2 years with the gradual switch strategy, 19·2 years with the random 50-50 allocation strategy, and 19·9 years with the combination therapy strategy. The reserve strategy was consistently inferior for mitigating antibiotic resistance under the parameter space explored and was increasingly outperformed by the other strategies as the probability of de novo resistance emergence decreased and as the fitness costs associated with resistance increased. Combination therapy tended to prolong the development of antibiotic resistance and minimise the number of annual gonococcal infections (under baseline model conditions, mean number of incident infections per year 178 641 [range 177 998-181 731] with combination therapy, 180 084 [178 011-184 405] with the reserve strategy). INTERPRETATION: Our study argues for rapid introduction of new anti-gonococcal antibiotics, recognising that the feasibility of each strategy must incorporate cost, safety, and other practical concerns. The analyses should be revisited once robust estimates of key parameters-ie, the likelihood of emergence of resistance and fitness costs of resistance for the new antibiotic-are available. FUNDING: US Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases.

Lifetime quality-adjusted life years lost due to genital herpes acquired in the United States in 2018: a mathematical modeling study.

Background: Genital herpes (GH), caused by herpes simplex virus type 1 and type 2 (HSV-1, HSV-2), is a common sexually transmitted disease associated with adverse health outcomes. Symptoms associated with GH outbreaks can be reduced by antiviral medications, but the infection is incurable and lifelong. In this study, we estimate the long-term health impacts of GH in the United States using quality-adjusted life years (QALYs) lost. Methods: We used probability trees to model the natural history of GH secondary to infection with HSV-1 and HSV-2 among people aged 18-49 years. We modelled the following outcomes to quantify the major causes of health losses following infection: symptomatic herpes outbreaks, psychosocial impacts associated with diagnosis and recurrences, urinary retention caused by sacral radiculitis, aseptic meningitis, Mollaret's meningitis, and neonatal herpes. The model was parameterized based on published literature on the natural history of GH. We summarized losses of health by computing the lifetime number of QALYs lost per genital HSV-1 and HSV-2 infection, and we combined this information with incidence estimates to compute the total lifetime number of QALYs lost due to infections acquired in 2018 in the United States. Findings: We estimated 0.05 (95% uncertainty interval (UI) 0.02-0.08) lifetime QALYs lost per incident GH infection acquired in 2018, equivalent to losing 0.05 years or about 18 days of life for one person with perfect health. The average number of QALYs lost per GH infection due to genital HSV-1 and HSV-2 was 0.01 (95% UI 0.01-0.02) and 0.05 (95% UI 0.02-0.09), respectively. The burden of genital HSV-1 is higher among women, while the burden of HSV-2 is higher among men. QALYs lost per neonatal herpes infection was estimated to be 7.93 (95% UI 6.63-9.19). At the population level, the total estimated lifetime QALYs lost as a result of GH infections acquired in 2018 was 33,100 (95% UI 12,600-67,900) due to GH in adults and 3,140 (95% UI 2,260-4,140) due to neonatal herpes. Results were most sensitive to assumptions on the magnitude of the disutility associated with post-diagnosis psychosocial distress and symptomatic recurrences. Interpretation: GH is associated with substantial health losses in the United States. Results from this study can be used to compare the burden of GH to other diseases, and it provides inputs that may be used in studies on the health impact and cost-effectiveness of interventions that aim to reduce the burden of GH. Funding: The Center for Disease Control and Prevention.

Association of naturally acquired type-specific HPV antibodies and subsequent HPV re-detection: systematic review and meta-analysis.

BACKGROUND: Understanding the role of naturally acquired (i.e., infection-induced) human papillomavirus (HPV) antibodies against reinfection is important given the high incidence of this sexually transmitted infection. However, the protective effect of naturally acquired antibodies in terms of the level of protection, duration, and differential effect by sex remains incompletely understood. We conducted a systematic review and a meta-analysis to (1) strengthen the evidence on the association between HPV antibodies acquired through past infection and subsequent type-specific HPV detection, (2) investigate the potential influence of type-specific HPV antibody levels, and (3) assess differential effects by HIV status. METHODS: We searched Embase and Medline databases to identify studies which prospectively assessed the risk of type-specific HPV detection by baseline homologous HPV serostatus among unvaccinated individuals. Random-effect models were used to pool the measures of association of naturally acquired HPV antibodies against subsequent incident detection and persistent HPV positivity. Sources of heterogeneity for each type were assessed through subgroup analyses stratified by sex, anatomical site of infection, male sexual orientation, age group, and length of follow-up period. Evidence of a dose-response relationship of the association between levels of baseline HPV antibodies and type-specific HPV detection was assessed. Finally, we pooled estimates from publications reporting associations between HPV serostatus and type-specific HPV detection by baseline HIV status. RESULTS: We identified 26 publications (16 independent studies, with 62,363 participants) reporting associations between baseline HPV serostatus and incident HPV detection, mainly for HPV-16 and HPV-18, the most detected HPV type. We found evidence of protective effects of baseline HPV seropositivity and subsequent detection of HPV DNA (0.70, 95% CI 0.61-0.80, NE = 11) and persistent HPV positivity (0.65, 95% CI 0.42-1.01, NE = 5) mainly for HPV-16 among females, but not among males, nor for HPV-18. Estimates from 8 studies suggested a negative dose-response relationship between HPV antibody level and subsequent detection among females. Finally, we did not observe any differential effect by baseline HIV status due to the limited number of studies available. CONCLUSION: We did not find evidence that naturally acquired HPV antibodies protect against subsequent HPV positivity in males and provide only modest protection among females for HPV-16. One potential limitation to the interpretation of these findings is potential misclassification biases due to different causes.

Pathways and Intersections: Multifaceted Approaches to Engage Individuals From Underrepresented and Marginalized Communities in HIV Research and Career Development.

BACKGROUND: The underrepresentation of historically marginalized groups in the HIV research workforce is a barrier to reaching national Ending the Epidemic goals. SETTING: The Harvard University Center for AIDS Research (HU CFAR) Diversity Equity and Inclusion Working Group (DEI WG) uses a multifaceted approach to enhance the field's diversity. METHODS: We established a DEI WG to improve the recruitment, inclusion, and retention of underrepresented minorities (URMs) in HIV research. We use community-based, participatory processes to establish and expand education and outreach programs about HIV care and research to better connect the HU CFAR to communities affected by HIV. This article reports on the development of the WG in July 2022, progress in its first year, and future plans. RESULTS: We have built a network of >50 investigators across the university for monthly meetings; partnered with existing research pathway programs for high school, undergraduate, and graduate students, directly supporting 7 new trainees and linking CFAR investigators to additional mentorship opportunities; and created 2-year Scholar Awards for 5 URM investigators in HIV. Planned work includes needs assessments for early-stage investigators to understand factors contributing to inclusion and retention and new pathway and outreach programming being developed with community partner minority-serving institutions. CONCLUSIONS: The HU CFAR DEI WG strives to ensure that individuals from underrepresented, marginalized, and minoritized communities have an opportunity to contribute to HIV research and that research is informed by the needs of the communities affected by the epidemic. An intersectional approach should be incorporated into HIV research pathway initiatives.