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Using data from 12 US health departments, we estimated mean serial interval for monkeypox virus infection to be 8.5 (95% credible interval 7.3-9.9) days for symptom onset, based on 57 case pairs. Mean estimated incubation period was 5.6 (95% credible interval 4.3-7.8) days for symptom onset, based on 35 case pairs.

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.

Mathematical modeling suggests that rapid diagnostics that report antibiotic susceptibility have the potential to extend the usefulness of existing antibiotics for treatment of gonorrhea compared with the current guidelines for empiric 2-drug treatment. Abstract Background Increasing antibiotic resistance limits treatment options for gonorrhea. We examined the impact of a hypothetical point-of-care (POC) test reporting antibiotic susceptibility profiles on slowing resistance spread. Methods A mathematical model describing gonorrhea transmission incorporated resistance emergence probabilities and fitness costs associated with resistance based on characteristics of ciprofloxacin (A), azithromycin (B), and ceftriaxone (C). We evaluated time to 1% and 5% prevalence of resistant strains among all isolates with the following: (1) empiric treatment (B and C), and treatment guided by POC tests determining susceptibility to (2) A only and (3) all 3 antibiotics. Results Continued empiric treatment without POC testing was projected to result in >5% of isolates being resistant to both B and C within 15 years. Use of either POC test in 10% of identified cases delayed this by 5 years. The 3 antibiotic POC test delayed the time to reach 1% prevalence of triply-resistant strains by 6 years, whereas the A-only test resulted in no delay. Results were less sensitive to assumptions about fitness costs and test characteristics with increasing test uptake. Conclusions Rapid diagnostics reporting antibiotic susceptibility may extend the usefulness of existing antibiotics for gonorrhea treatment, but ongoing monitoring of resistance patterns will be critical.

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. 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. 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.

Despite declining HIV infection rates, persistent racial and ethnic disparities remain. Appropriate calculations of diagnosis rates by HIV transmission category, race and ethnicity, and geography are needed to monitor progress towards reducing systematic disparities in health outcomes. We estimated the number of heterosexually active adults (HAAs) by sex and state to calculate appropriate HIV diagnosis rates and disparity measures within subnational regions. The analysis included all HIV diagnoses attributed to heterosexual transmission in 2018 in the United States, in 50 states and the District of Columbia. Logistic regression models estimated the probability of past-year heterosexual activity among adults in three national health surveys, by sex, age group, race and ethnicity, education category, and marital status. Model-based probabilities were applied to estimated counts of HAAs by state, which were synthesized through meta-analysis. HIV diagnoses were overlaid to calculate racial- and ethnic-specific rates, rate differences (RDs), and rate ratios (RRs) among HAAs by sex and state. Nationally, HAA women have a two-fold higher HIV diagnosis rate than HAA men (rate per 100,000 HAAs, women: 6.57; men: 3.09). Compared to White non-Hispanic HAAs, Black HAAs have a 20-fold higher HIV diagnosis rate (RR, men: 21.28, women: 19.55; RD, men: 15.40, women: 31.78) and Hispanic HAAs have a 4-fold higher HIV diagnosis rate (RR, men: 4.68, RD, women: 4.15; RD, men: 2.79, RD, women: 5.39). Disparities were ubiquitous across regions, with >75% of states in each region having Black-to-White RR ≥10. The racial and ethnic disparities across regions suggests a system-wide failure particularly with respect to preventing HIV among Black and Hispanic women. Pervasive disparities emphasize the role for coordinated federal responses such as the current Ending the HIV Epidemic (EHE) initiative.

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. 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. 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.

Context: Each year, millions of U.S. youth acquire sexually transmitted diseases (STDs). Estimates of the economic burden of STDs can help to quantify the impact of STDs on the nation's youth and on the payers of the cost of their medical care. Methods: We synthesized the existing literature on STD costs to estimate the lifetime medical cost per case of eight major STDs-HIV, human papillomavirus (HPV), genital herpes simplex virus type 2, hepatitis B, chlamydia, gonorrhea, trichomoniasis and syphilis. We then estimated the total burden of disease by multiplying these cost-per-case estimates by the approximate number of new cases of STDs acquired by youth aged 15-24. Results: The total estimated burden of the nine million new cases of these STDs that occurred among 15-24-year-olds in 2000 was $6.5 billion (in year 2000 dollars). Viral STDs accounted for 94% of the total burden ($6.2 billion), and nonviral STDs accounted for 6% of the total burden ($0.4 billion). HIV and HPV were by far the most costly STDs in terms of total estimated direct medical costs, accounting for 90% of the total burden ($5.9 billion). Conclusions: The large number of infections acquired by persons aged 15-24 and the high cost per case of viral STDs, particularly HIV, create a substantial economic burden.

Millions of cases of sexually transmitted infections (STIs) occur in the United States each year, resulting in substantial medical costs to the nation. Previous estimates of the total direct cost of STIs are quite dated. We present updated direct medical cost estimates of STIs in the United States. We assembled recent (i.e., 2002-2011) cost estimates to determine the lifetime cost per case of 8 major STIs (chlamydia, gonorrhea, hepatitis B virus, human immunodeficiency virus (HIV), human papillomavirus, genital herpes simplex virus type 2, trichomoniasis and syphilis). The total direct cost for each STI was computed as the product of the number of new or newly diagnosed cases in 2008 and the estimated discounted lifetime cost per case. All costs were adjusted to 2010 US dollars. Results indicated that the total lifetime direct medical cost of the 19.7 million cases of STIs that occurred among persons of all ages in 2008 in the United States was $15.6 (range, $11.0-$20.6) billion. Total costs were as follows: chlamydia ($516.7 [$258.3-$775.0] million), gonorrhea ($162.1 [$81.1-$243.2] million), hepatitis B virus ($50.7 [$41.3-$55.6] million), HIV ($12.6 [$9.5-$15.7] billion), human papillomavirus ($1.7 [$0.8-$2.9] billion), herpes simplex virus type 2 ($540.7 [$270.3-$811.0] million), syphilis ($39.3 [$19.6-$58.9] million), and trichomoniasis ($24.0 [$12.0-$36.0] million). Costs associated with HIV infection accounted for more than 81% of the total cost. Among the nonviral STIs, chlamydia was the most costly infection. Sexually transmitted infections continue to impose a substantial cost burden on the payers of medical care in the United States. The burden of STIs would be even greater in the absence of STI prevention and control efforts.

The Centers for Disease Control and Prevention (CDC) recommends syphilis screening at least annually for sexually active men who have sex with men (MSM). The objective of this study is to assess the frequency of MSM testing for syphilis and how syphilis test results compared with results of rectal gonorrhea and chlamydia tests. In collaboration with a large US commercial laboratory, we identified men aged 15–60 years who had rectal chlamydia or gonorrhea tests during 09/01/2013–09/30/2015 as presumed MSM. We classified MSM as having current or past syphilis if during the study period they had (1) either a reactive qualitative non-treponemal test or at least a 1:1 quantitative non-treponemal test, and (2) they had a reactive treponemal test. Of 52,771 MSM, 14.3% had no syphilis testing, 4.8% had only treponemal testing (37.8% were reactive), 63.2% had only non-treponemal testing (2.0% were reactive), and 17.7% had both non-treponemal and treponemal testing (86.6% had current or past syphilis). Of those MSM who had reactive qualitative non-treponemal tests, at least 90% had no quantitative non-treponemal tests. Current or past syphilis was more common among MSM with positive rectal gonorrhea or chlamydia tests (24.1%) than MSM with negative rectal gonorrhea and chlamydia tests (13.0%, p < 0.005). Of MSM with any syphilis testing during 09/01/2013–09/30/2014, 64.8% also had annual repeat testing. Syphilis testing in general and repeat syphilis testing were frequent but suboptimal among MSM. It is important to continually monitor syphilis for MSM, especially for those MSM who had rectal chlamydia or gonorrhea infection.

BACKGROUNDSexually transmitted infections (STIs) are associated with an increased risk of human immunodeficiency virus (HIV) acquisition and transmission. We estimated the proportion of HIV incidence among men who have sex with men attributable to infection with the 2 most common bacterial STIs, Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT). METHODSWe used a stochastic, agent-based model of a sexual network of MSM with cocirculating HIV, NG, and CT infections. Relative risk (RR) multipliers, specific to anatomic site of infection, modified the risk of HIV transmission and acquisition based on STI status. We estimated the effect of NG and CT on HIV incidence overall and on HIV acquisition and HIV transmission separately. Each scenario was simulated for 10 years. The population attributable fraction (PAF) was determined for each combination of RRs by comparing the incidence in the final year of a scenario to a scenario in which the RRs associated with NG and CT were set to 1.0. RESULTSOverall, 10.2% (interquartile range [IQR], 7.9–12.4) of HIV infections were attributable to NG/CT infection. Then in sensitivity analyses, the PAF for HIV transmission ranged from 3.1% (IQR, 0.5–5.2) to 20.4% (IQR, 17.8–22.5) and the PAF for HIV acquisition ranged from 2.0% (IQR, −0.7 to 4.3) to 13.8% (IQR, 11.7–16.0). CONCLUSIONSDespite challenges in estimating the causal impact of NG/CT on HIV risk, modeling is an alternative approach to quantifying plausible ranges of effects given uncertainty in the biological cofactors. Our estimates represent idealized public health interventions in which STI could be maximally prevented, setting targets for real-world STI interventions that seek to reduce HIV incidence.