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.

Factors Associated With Delays in Presentation and Treatment of Gonorrhea, Massachusetts 2015-2019.

BACKGROUND: Rates of gonorrhea are increasing across the United States. Understanding and addressing contributing factors associated with longer time to diagnosis and treatment may shorten the duration of infectiousness, which in turn may limit transmission. METHODS: We used Massachusetts data from the US Centers for Disease Control and Prevention Sexually Transmitted Disease Surveillance Network collected between July 2015 and September 2019, along with routinely reported surveillance data, to assess time from gonorrhea symptom onset to presentation to care, and time from presentation to care to receipt of treatment. Factors associated with longer time to presentation (TTP) and time to treatment (TTT) were assessed using Cox proportional hazard models with a constant time variable. RESULTS: Among symptomatic patients (n = 672), 31% did not receive medical care within 7 days of symptom onset. Longer TTP was associated with younger age, female gender, reporting cost as a barrier to care, and provider report of proctitis. Among patients with symptoms and/or known contact to gonorrhea (n = 827), 42% did not receive presumptive treatment. Longer TTT was associated with female gender, non-Hispanic other race/ethnicity, and clinics with less gonorrhea treatment experience. Among asymptomatic patients without known exposure to STI (n = 235), 26% did not receive treatment within 7 days. Longer TTT was associated with sexually transmitted disease clinic/family planning/reproductive health clinics and a test turnaround time of ≥3 days. CONCLUSIONS: Delays in presentation to care and receipt of treatment for gonorrhea are common. Factors associated with longer TTP and TTT highlight multiple opportunities for reducing the infectious period of patients with gonorrhea.

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.

Estimation of the Lifetime Quality-Adjusted Life Years (QALYs) Lost Due to Syphilis Acquired in the United States in 2018.

BACKGROUND: The purpose of this study was to estimate the health impact of syphilis in the United States in terms of the number of quality-adjusted life years (QALYs) lost attributable to infections in 2018. METHODS: We developed a Markov model that simulates the natural history and management of syphilis. The model was parameterized by sex and sexual orientation (women who have sex with men, men who have sex with women [MSW], and men who have sex with men [MSM]), and by age at primary infection. We developed a separate decision tree model to quantify health losses due to congenital syphilis. We estimated the average lifetime number of QALYs lost per infection, and the total expected lifetime number of QALYs lost due to syphilis acquired in 2018. RESULTS: We estimated the average number of discounted lifetime QALYs lost per infection as 0.09 (95% uncertainty interval [UI] .03-.19). The total expected number of QALYs lost due to syphilis acquired in 2018 was 13 349 (5071-31 360). Although per-case loss was the lowest among MSM (0.06), MSM accounted for 47.7% of the overall burden. For each case of congenital syphilis, we estimated 1.79 (1.43-2.16) and 0.06 (.01-.14) QALYs lost in the child and the mother, respectively. We projected 2332 (1871-28 250) and 79 (17-177) QALYs lost for children and mothers, respectively, due to congenital syphilis in 2018. CONCLUSIONS: Syphilis causes substantial health losses in adults and children. Quantifying these health losses in terms of QALYs can inform cost-effectiveness analyses and can facilitate comparisons of the burden of syphilis to that of other diseases.

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.

Evaluating spatially adaptive guidelines for the treatment of gonorrhea to reduce the incidence of gonococcal infection and increase the effective lifespan of antibiotics.

In the absence of point-of-care gonorrhea diagnostics that report antibiotic susceptibility, gonorrhea treatment is empiric and determined by standardized guidelines. These guidelines are informed by estimates of resistance prevalence from national surveillance systems. We examined whether guidelines informed by local, rather than national, surveillance data could reduce the incidence of gonorrhea and increase the effective lifespan of antibiotics used in treatment guidelines. We used a transmission dynamic model of gonorrhea among men who have sex with men (MSM) in 16 U.S. metropolitan areas to determine whether spatially adaptive treatment guidelines based on local estimates of resistance prevalence can extend the effective lifespan of hypothetical antibiotics. The rate of gonorrhea cases in these metropolitan areas was 5,548 cases per 100,000 MSM in 2017. Under the current strategy of updating the treatment guideline when the prevalence of resistance exceeds 5%, we showed that spatially adaptive guidelines could reduce the annual rate of gonorrhea cases by 200 cases (95% uncertainty interval: 169, 232) per 100,000 MSM population while extending the use of a first-line antibiotic by 0.75 (0.55, 0.95) years. One potential strategy to reduce the incidence of gonorrhea while extending the effective lifespan of antibiotics is to inform treatment guidelines based on local, rather than national, resistance prevalence.

Gaps in HIV Preexposure Prophylaxis Continuum of Care Following State Partner Services for Massachusetts Primary and Secondary Syphilis Cases, 2017 to 2018.

BACKGROUND: Human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) reduces HIV acquisition. We used a PrEP continuum of care to measure impact of field epidemiologist-facilitated referrals for PrEP-naive infectious syphilis cases across multiple clinical and pharmacy sites of care. METHODS: Retrospective analysis of 2017 to 2018 primary and secondary syphilis cases, medical charts, and pharmacy data to identify PrEP education, referral offer, referral acceptance, first visit, prescription pickup (PrEP initiation) and 2 to 3 months (PrEP persistence). The HIV seroconversion was determined using database match at syphilis diagnosis date and at 12 months. χ 2 or Fisher's exact tests were used to compare demographic characteristics associated with steps with lower progression rates. RESULTS: Of 1077 syphilis cases, partner services engaged 662 of 787 (84%) HIV-negative cases; 490 were PrEP-naive, 266 received education, 166 were offered referral, 67 accepted referral, 30 attended an initial appointment, and 22 were prescribed PrEP. Of 16 with pharmacy data, 14 obtained medication, and 8 persisted on PrEP at 2 to 3 months. Continuum progression was lowest from (1) PrEP-naïve to receiving PrEP education, (2) offered referral to referral acceptance, and (3) referral acceptance to initial PrEP appointment. Men with male partners were more likely to receive PrEP education or accept a referral. Higher social vulnerability was associated with increased PrEP referral acceptance. CONCLUSIONS: Few individuals accepted PrEP referrals and persisted on PrEP. Field and clinic data capture were inconsistent, possibly underestimating referral volume and impact of field engagement. Efforts aimed at increasing referral acceptance and clinic attendance may improve PrEP uptake especially among women and heterosexual men with syphilis.

Can Machine Learning Help Identify Patients at Risk for Recurrent Sexually Transmitted Infections?

BACKGROUND: A substantial fraction of sexually transmitted infections (STIs) occur in patients who have previously been treated for an STI. We assessed whether routine electronic health record (EHR) data can predict which patients presenting with an incident STI are at greatest risk for additional STIs in the next 1 to 2 years. METHODS: We used structured EHR data on patients 15 years or older who acquired an incident STI diagnosis in 2008 to 2015 in eastern Massachusetts. We applied machine learning algorithms to model risk of acquiring ≥1 or ≥2 additional STIs diagnoses within 365 or 730 days after the initial diagnosis using more than 180 different EHR variables. We performed sensitivity analysis incorporating state health department surveillance data to assess whether improving the accuracy of identifying STI cases improved algorithm performance. RESULTS: We identified 8723 incident episodes of laboratory-confirmed gonorrhea, chlamydia, or syphilis. Bayesian Additive Regression Trees, the best-performing algorithm of any single method, had a cross-validated area under the receiver operating curve of 0.75. Receiver operating curves for this algorithm showed a poor balance between sensitivity and positive predictive value (PPV). A predictive probability threshold with a sensitivity of 91.5% had a corresponding PPV of 3.9%. A higher threshold with a PPV of 29.5% had a sensitivity of 11.7%. Attempting to improve the classification of patients with and without repeat STIs diagnoses by incorporating health department surveillance data had minimal impact on cross-validated area under the receiver operating curve. CONCLUSIONS: Machine algorithms using structured EHR data did not differentiate well between patients with and without repeat STIs diagnosis. Alternative strategies, able to account for sociobehavioral characteristics, could be explored.

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.

More Screening or More Disease? Gonorrhea Testing and Positivity Patterns Among Men in 3 Large Clinical Practices in Massachusetts, 2010-2017.

BACKGROUND: Gonorrhea diagnosis rates in the United States increased by 75% during 2009-2017, predominantly in men. It is unclear whether the increase among men is being driven by more screening, an increase in the prevalence of disease, or both. We sought to evaluate changes in gonorrhea testing patterns and positivity among men in Massachusetts. METHODS: The analysis included men (aged ≥15 years) who received care during 2010-2017 in 3 clinical practice groups. We calculated annual percentages of men with ≥1 gonorrhea test and men with ≥1 positive result, among men tested. Log-binomial regression models were used to examine trends in these outcomes. We adjusted for clinical and demographic characteristics that may influence the predilection to test and probability of gonorrhea disease. RESULTS: On average, 306 348 men had clinical encounters each year. There was a significant increase in men with ≥1 gonorrhea test from 2010 (3.1%) to 2017 (6.4%; adjusted annual risk ratio, 1.12; 95% confidence interval, 1.12-1.13). There was a significant, albeit lesser, increase in the percentage of tested men with ≥1 positive result (1.0% in 2010 to 1.5% in 2017; adjusted annual risk ratio, 1.07; 95% confidence interval, 1.04-1.09). CONCLUSIONS: We estimated significant increases in the annual percentages of men with ≥1 gonorrhea test and men with ≥1 positive gonorrhea test result between 2010 and 2017. These results suggest that observed increases in gonorrhea rates could be explained by both increases in screening and the prevalence of gonorrhea.

Adaptive guidelines for the treatment of gonorrhea to increase the effective life span of antibiotics among men who have sex with men in the United States: A mathematical modeling study.

BACKGROUND: The rise of gonococcal antimicrobial resistance highlights the need for strategies that extend the clinically useful life span of antibiotics. Because there is limited evidence to support the current practice of switching empiric first-line antibiotic when resistance exceeds 5% in the population, our objective was to compare the impact of alternative strategies on the effective life spans of antibiotics and the overall burden of gonorrhea. METHODS AND FINDINGS: We developed and calibrated a mathematical model of gonorrhea transmission among men who have sex with men (MSM) in the United States. We calibrated the model to the estimated prevalence of gonorrhea, the rate of gonorrhea cases, and the proportion of cases presenting symptoms among MSM in the US. We used this model to project the effective life span of antibiotics and the number of gonorrhea cases expected under current and alternative surveillance strategies over a 50-year simulation period. We demonstrate that compared to the current practice, a strategy that uses quarterly (as opposed to yearly) surveillance estimates and incorporates both the estimated prevalence of resistance and the trend in the prevalence of resistance to determine treatment guidelines could extend the effective life span of antibiotics by 0.83 years. This is equivalent to successfully treating an additional 80.1 (95% uncertainty interval: [47.7, 111.9]) gonorrhea cases per 100,000 MSM population each year with the first-line antibiotics without worsening the burden of gonorrhea. If the annual number of isolates tested for drug susceptibility is doubled, this strategy could increase the effective life span of antibiotics by 0.94 years, which is equivalent to successfully treating an additional 91.1 (54.3, 127.3) gonorrhea cases per 100,000 MSM population each year without increasing the incidence of gonorrhea. Study limitations include that our conclusions might not be generalizable to other settings because our model describes the transmission of gonorrhea among the US MSM population, and, to better capture uncertainty in the characteristics of current and future antibiotics, we chose to model hypothetical drugs with characteristics similar to the antibiotics commonly used in gonorrhea treatment. CONCLUSIONS: Our results suggest that use of data from surveillance programs could be expanded to prolong the clinical effectiveness of antibiotics without increasing the burden of the disease. This highlights the importance of maintaining effective surveillance systems and the engagement of policy makers to turn surveillance findings into timely and effective decisions.

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.

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.

Opioid Use Fueling HIV Transmission in an Urban Setting: An Outbreak of HIV Infection Among People Who Inject Drugs-Massachusetts, 2015-2018.

Objectives. To describe and control an outbreak of HIV infection among people who inject drugs (PWID).Methods. The investigation included people diagnosed with HIV infection during 2015 to 2018 linked to 2 cities in northeastern Massachusetts epidemiologically or through molecular analysis. Field activities included qualitative interviews regarding service availability and HIV risk behaviors.Results. We identified 129 people meeting the case definition; 116 (90%) reported injection drug use. Molecular surveillance added 36 cases to the outbreak not otherwise linked. The 2 largest molecular groups contained 56 and 23 cases. Most interviewed PWID were homeless. Control measures, including enhanced field epidemiology, syringe services programming, and community outreach, resulted in a significant decline in new HIV diagnoses.Conclusions. We illustrate difficulties with identification and characterization of an outbreak of HIV infection among a population of PWID and the value of an intensive response.Public Health Implications. Responding to and preventing outbreaks requires ongoing surveillance, with timely detection of increases in HIV diagnoses, community partnerships, and coordinated services, all critical to achieving the goal of the national Ending the HIV Epidemic initiative.

COVID-19-Associated Multisystem Inflammatory Syndrome in Children - United States, March-July 2020.

In April 2020, during the peak of the coronavirus disease 2019 (COVID-19) pandemic in Europe, a cluster of children with hyperinflammatory shock with features similar to Kawasaki disease and toxic shock syndrome was reported in England* (1). The patients' signs and symptoms were temporally associated with COVID-19 but presumed to have developed 2-4 weeks after acute COVID-19; all children had serologic evidence of infection with SARS-CoV-2, the virus that causes COVID-19 (1). The clinical signs and symptoms present in this first cluster included fever, rash, conjunctivitis, peripheral edema, gastrointestinal symptoms, shock, and elevated markers of inflammation and cardiac damage (1). On May 14, 2020, CDC published an online Health Advisory that summarized the manifestations of reported multisystem inflammatory syndrome in children (MIS-C), outlined a case definition,† and asked clinicians to report suspected U.S. cases to local and state health departments. As of July 29, a total of 570 U.S. MIS-C patients who met the case definition had been reported to CDC. A total of 203 (35.6%) of the patients had a clinical course consistent with previously published MIS-C reports, characterized predominantly by shock, cardiac dysfunction, abdominal pain, and markedly elevated inflammatory markers, and almost all had positive SARS-CoV-2 test results. The remaining 367 (64.4%) of MIS-C patients had manifestations that appeared to overlap with acute COVID-19 (2-4), had a less severe clinical course, or had features of Kawasaki disease.§ Median duration of hospitalization was 6 days; 364 patients (63.9%) required care in an intensive care unit (ICU), and 10 patients (1.8%) died. As the COVID-19 pandemic continues to expand in many jurisdictions, clinicians should be aware of the signs and symptoms of MIS-C and report suspected cases to their state or local health departments; analysis of reported cases can enhance understanding of MIS-C and improve characterization of the illness for early detection and treatment.

Using electronic health records to identify candidates for human immunodeficiency virus pre-exposure prophylaxis: An application of super learning to risk prediction when the outcome is rare.

Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) protects high risk patients from becoming infected with HIV. Clinicians need help to identify candidates for PrEP based on information routinely collected in electronic health records (EHRs). The greatest statistical challenge in developing a risk prediction model is that acquisition is extremely rare. METHODS: Data consisted of 180 covariates (demographic, diagnoses, treatments, prescriptions) extracted from records on 399 385 patient (150 cases) seen at Atrius Health (2007-2015), a clinical network in Massachusetts. Super learner is an ensemble machine learning algorithm that uses k-fold cross validation to evaluate and combine predictions from a collection of algorithms. We trained 42 variants of sophisticated algorithms, using different sampling schemes that more evenly balanced the ratio of cases to controls. We compared super learner's cross validated area under the receiver operating curve (cv-AUC) with that of each individual algorithm. RESULTS: The least absolute shrinkage and selection operator (lasso) using a 1:20 class ratio outperformed the super learner (cv-AUC = 0.86 vs 0.84). A traditional logistic regression model restricted to 23 clinician-selected main terms was slightly inferior (cv-AUC = 0.81). CONCLUSION: Machine learning was successful at developing a model to predict 1-year risk of acquiring HIV based on a physician-curated set of predictors extracted from EHRs.

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.