Exploring How Epidemic Context Influences Syphilis Screening Impact: A Mathematical Modeling Study.

BACKGROUND: The current syphilis epidemic in the United States is concentrated in gay, bisexual, and other men who have sex with men (MSM), but substantial heterosexual transmission is reported in some parts of the country. Using the US states of Louisiana and Massachusetts as case studies, we investigated how epidemic context influences the impact of population screening approaches for syphilis control. METHODS: We constructed a compartmental metapopulation model parameterized to describe observed patterns of syphilis transmission. We estimated the impact of different approaches to screening, including perfect adherence to current US screening guidelines in MSM. RESULTS: In Louisiana, where syphilis cases are more evenly distributed among MSM and heterosexual populations, we projected that screening according to guidelines would contribute to no change or an increase in syphilis burden, compared with burden with current estimated screening coverage. In Massachusetts, which has a more MSM-focused outbreak, we projected that screening according to guidelines would be as or more effective than current screening coverage in most population groups. CONCLUSIONS: Men who have sex with men-focused approaches to screening may be insufficient for control when there is substantial transmission in heterosexual populations. Epidemic characteristics may be useful when identifying at-risk groups for syphilis screening.

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.

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.

Infectious disease implications of large-scale migration of Venezuelan nationals.

Background: The ongoing economic and political crisis in Venezuela has resulted in a collapse of the healthcare system and the re-emergence of previously controlled or eliminated infectious diseases. There has also been an exodus of Venezuelan international migrants in response to the crisis. We sought to describe the infectious disease risks faced by Venezuelan nationals and assess the international mobility patterns of the migrant population. Methods: We synthesized data on recent infectious disease events in Venezuela and among international migrants from Venezuela, as well as on current country of residence among the migrant population. We used passenger-level itinerary data from the International Air Transport Association to evaluate trends in outbound air travel from Venezuela over time. We used two parameter-free mobility models, the radiation and impedance models, to estimate the expected population flows from Venezuelan cities to other major Latin American and Caribbean cities. Results: Outbreaks of measles, diphtheria and malaria have been reported across Venezuela and other diseases, such as HIV and tuberculosis, are resurgent. Changes in migration in response to the crisis are apparent, with an increase in Venezuelan nationals living abroad, despite an overall decline in the number of outbound air passengers. The two models predicted different mobility patterns, but both highlighted the importance of Colombian cities as destinations for migrants and also showed that some migrants are expected to travel large distances. Despite the large distances that migrants may travel internationally, outbreaks associated with Venezuelan migrants have occurred primarily in countries proximate to Venezuela. Conclusions: Understanding where international migrants are relocating is critical, given the association between human mobility and the spread of infectious diseases. In data-limited situations, simple models can be useful for providing insights into population mobility and may help identify areas likely to receive a large number of migrants.

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.

Can enhanced screening of men with a history of prior syphilis infection stem the epidemic in men who have sex with men? A mathematical modelling study.

OBJECTIVES: The aim of this study is to determine the transmission impact of using prior syphilis infection to guide a focused syphilis screening intervention among men who have sex with men (MSM). METHODS: We parameterised a deterministic model of syphilis transmission in MSM to reflect the 2011-2015 syphilis outbreak in Winnipeg, Canada. Enhanced screening of 75% of men with prior syphilis every 3 months (A) was compared with distributing equivalent number tests to all MSM (B) or those with the highest partner number (C). We compared early syphilis incidence, diagnoses and prevalence after 10 years, relative to a base case of 30% of MSM screened annually. RESULTS: Strategy A was expected to avert 52% of incident infections, 44% of diagnosed cases and reduce early syphilis prevalence by 89%. Strategy B had the least impact. Strategy C was most effective, averting 59% of incident cases. When screening frequency was semiannual or annual, strategy A was the most effective. CONCLUSIONS: Enhanced screening of MSM with prior syphilis may efficiently reduce transmission, especially when identification of high-risk men via self-reported partner numbers or high-frequency screening is difficult to achieve.

Cost-effectiveness of enhanced syphilis screening among HIV-positive men who have sex with men: a microsimulation model.

BACKGROUND: Syphilis co-infection risk has increased substantially among HIV-infected men who have sex with men (MSM). Frequent screening for syphilis and treatment of men who test positive might be a practical means of controlling the risk of infection and disease sequelae in this population. PURPOSE: We evaluated the cost-effectiveness of strategies that increased the frequency and population coverage of syphilis screening in HIV-infected MSM receiving HIV care, relative to current standard of care. METHODS: We developed a state-transition microsimulation model of syphilis natural history and medical care in HIV-infected MSM receiving care for HIV. We performed Monte Carlo simulations using input data derived from a large observational cohort in Ontario, Canada, and from published biomedical literature. Simulations compared usual care (57% of the population screened annually) to different combinations of more frequent (3- or 6-monthly) screening and higher coverage (100% screened). We estimated expected disease-specific outcomes, quality-adjusted survival, costs, and cost-effectiveness associated with each strategy from the perspective of a public health care payer. RESULTS: Usual care was more costly and less effective than strategies with more frequent or higher coverage screening. Higher coverage strategies (with screening frequency of 3 or 6 months) were expected to be cost-effective based on usually cited willingness-to-pay thresholds. These findings were robust in the face of probabilistic sensitivity analyses, alternate cost-effectiveness thresholds, and alternate assumptions about duration of risk, program characteristics, and management of underlying HIV. CONCLUSIONS: We project that higher coverage and more frequent syphilis screening of HIV-infected MSM would be a highly cost-effective health intervention, with many potentially viable screening strategies projected to both save costs and improve health when compared to usual care. The baseline requirement for regular blood testing in this group (i.e., for viral load monitoring) makes intensification of syphilis screening appear readily practicable.

Screen more or screen more often? Using mathematical models to inform syphilis control strategies.

BACKGROUND: Syphilis incidence among men who have sex with men (MSM) continues to rise despite attempts to increase screening and treatment uptake. We examined the marginal effect of increased frequency versus increased coverage of screening on syphilis incidence in Toronto, Canada. METHODS: We developed an agent-based, network model of syphilis transmission, representing a core population of 2,000 high-risk MSM. Epidemiological and biological parameters were drawn from regional surveillance data and literature-derived estimates. The pre-intervention period of the model was calibrated using surveillance data to identify 1000 credible simulations per strategy. Evaluated strategies included: annual syphilis screening at baseline coverage, increased screening frequency at baseline coverage, and increased coverage of annual screening. Intervention impact was measured as annual prevalence of detected infectious cases and syphilis incidence per year over 10 years. RESULTS: Of the strategies evaluated, increasing the frequency of syphilis screening to every three months was most effective in reducing reported and incident syphilis infections. Increasing the fraction of individuals tested, without increasing test frequency, resulted a smaller decline in incidence, because reductions in infectious syphilis via treatment were counterbalanced by increased incident syphilis among individuals with prior latent syphilis. For an equivalent number of additional tests performed annually, increased test frequency was consistently more effective than improved coverage. CONCLUSIONS: Strategies that focus on higher frequency of testing in smaller fractions of the population were more effective in reducing syphilis incidence in a simulated MSM population. The findings highlight how treatment-induced loss of immunity can create unexpected results in screening-based control strategies.

Estimation of the burden of disease and costs of genital Chlamydia trachomatis infection in Canada.

BACKGROUND: Rates of Chlamydia trachomatis (CT) infection in Canada have been increasing since the mid-1990s. We sought to estimate the burden of CT in this population. METHODS: We developed an age- and sex-structured mathematical model parameterized to reproduce trends in CT prevalence between 1991 and 2009 in the Canadian population aged 10 to 39 years. Costs were identified, measured, and valued using a modified societal perspective and converted to year 2009 Canadian dollars. Cost-effectiveness of the implemented policy of enhanced screening for asymptomatic infections was estimated by comparison with model-projected trends in the absence of increased screening. Main outcome measures were current net cost and burden of illness attributable to CT infection, and incremental cost-effectiveness ratios. RESULTS: Under base case model assumptions, there was a trend of increasing detection of CT cases (due to increases in screening), despite an underlying stabilization of actual CT infections. Average estimated costs associated with CT infection over this period were $51.4 million per year. Costs of screening and treatment of asymptomatic infections as a proportion of total CT costs were estimated to have increased over time, whereas costs of long-term sequelae associated with untreated infections declined over the same period. Compared with no change in screening, enhanced screening was estimated to be highly cost-effective, with an incremental cost-effectiveness ratio of $2910 per quality-adjusted life year. CONCLUSIONS: Despite increases in screening, the economic burden of CT in Canada remains high. Further investigation of trends in chlamydia-associated complications is required to better understand the impact of screening on incidence.