BACKGROUND: Syphilis can cause neurologic, ocular, or otic manifestations, possibly resulting in permanent disability or death. In 2018, CDC began collecting syphilis clinical manifestation data via the National Notifiable Diseases Surveillance System (NNDSS). We present the first reported U.S. syphilis neurologic, ocular, and otic manifestation prevalence estimates. METHODS: We reviewed 2019 NNDSS data to identify jurisdictions reporting ≥70% of syphilis cases ≥15 years old with clinical manifestation data (considered "complete reporting"). Among these jurisdictions, we determined reported neurologic, ocular, and otic manifestation prevalence, stratified by demographic, behavioral, and clinical characteristics. RESULTS: Among 41,187 syphilis cases in 16 jurisdictions with complete reporting, clinical manifestations were infrequently reported overall: neurologic (n = 445, 1.1%), ocular (n = 461, 1.1%), otic (n = 166, 0.4%), any (n = 807, 2.0%). Reported clinical manifestation prevalence was highest among cases ≥65 years old (neurologic: 5.1%; ocular: 3.5%; otic: 1.2%) and those reporting injection drug use (neurologic: 2.8%; ocular: 3.4%; otic: 1.6%). Although reported neurologic and ocular manifestation prevalence was slightly higher among HIV-infected vs. HIV-negative persons, approximately 40% of cases with manifestations were HIV-negative. Reported otic manifestation prevalence was similar regardless of HIV status. When stratifying by HIV status and syphilis stage, reported prevalence was highest among HIV-infected persons with unknown duration/late syphilis (neurologic: 3.0%; ocular: 2.3%; otic: 0.7%). CONCLUSIONS: Reported Neurologic, ocular, and otic manifestation prevalence was low among syphilis cases, but these data are likely an underestimate given potential underreporting. Reported clinical manifestation frequency, including among HIV-negative persons, emphasizes the importance of evaluating all syphilis cases for signs/symptoms of neurosyphilis, ocular syphilis, and otosyphilis.

BACKGROUND: Disseminated gonococcal infections (DGI) are thought to be uncommon; surveillance is limited and case reports are analyzed retrospectively or in case clusters. We describe the population-level burden of culture-confirmed DGI through the Active Bacterial Core surveillance (ABCs) system. METHODS: During 2015-2016, retrospective surveillance was conducted among residents in two ABCs areas and prospectively in three ABCs areas during 2017-2019. A DGI case was defined as isolation of Neisseria gonorrhoeae (Ng) from a normally sterile site. A case report form was completed for each case and antimicrobial susceptibility testing (AST) was performed on available isolates. RESULTS: During 2015-2019, 77 DGI cases were identified (~a rate of 0.13 cases per 100,000 population) and accounted for 0.06% of all reported gonorrhea cases in the three surveillance areas. Most DGI cases were male (64%), non-Hispanic Black (68%), and ranged from 16-67 years; blood (55%) and joint (40%) were the most common sterile sites. Among 29 isolates with AST results during 2017-2019, all were susceptible to ceftriaxone. CONCLUSIONS: DGI is an infrequent complication of Ng; since Ng can quickly develop antimicrobial resistance, continued DGI surveillance, including monitoring trends in antimicrobial susceptibility, could help inform DGI treatment recommendations.

Background: Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major health concerns globally. Increased global surveillance of gonococcal AMR is essential. We aimed to describe the 2017–18 data from WHO's global gonococcal AMR surveillance, and to discuss priorities essential for the effective management and control of gonorrhoea. Methods: We did a retrospective observational study of the AMR data of gonococcal isolates reported to WHO by 73 countries in 2017–18. WHO recommends that each country collects at least 100 gonococcal isolates per year, and that quantitative methods to determine the minimum inhibitory concentration of antimicrobials, interpreted by internationally standardised resistance breakpoints, are used. Findings: In 2017–18, 73 countries provided AMR data for one or more drug. Decreased susceptibility or resistance to ceftriaxone was reported by 21 (31%) of 68 reporting countries and to cefixime by 24 (47%) of 51 reporting countries. Resistance to azithromycin was reported by 51 (84%) of 61 reporting countries and to ciprofloxacin by all 70 (100%) reporting countries. The annual proportion of decreased susceptibility or resistance across countries was 0–21% to ceftriaxone and 0–22% to cefixime, and that of resistance was 0–60% to azithromycin and 0–100% to ciprofloxacin. The number of countries reporting gonococcal AMR and resistant isolates, and the number of examined isolates, have increased since 2015–16. Surveillance remains scarce in central America and the Caribbean and eastern Europe, and in the WHO African, Eastern Mediterranean, and South-East Asian regions. Interpretation: In many countries, ciprofloxacin resistance was exceedingly high, azithromycin resistance was increasing, and decreased susceptibility or resistance to ceftriaxone and cefixime continued to emerge. WHO's global surveillance of gonococcal AMR needs to expand internationally to provide imperative data for national and international management guidelines and public health policies. Improved prevention, early diagnosis, treatment of index patients and partners, enhanced surveillance (eg, infection, AMR, treatment failures, and antimicrobial use or misuse), and increased knowledge on antimicrobial selection, stewardship, and pharmacokinetics or pharmacodynamics are essential. The development of rapid, accurate, and affordable point-of-care gonococcal diagnostic tests, new antimicrobials, and gonococcal vaccines is imperative. Funding: None. © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

The COVID-19 pandemic impacted STD services. Of 59 U.S.-funded STD programs, 91% reported a great deal to moderate impact from staff reassignment in April 2020, with 28% of respondents reporting permanent reassignment of DIS staff. Telemedicine was implemented in 44%. Decreases in STD case reports were reported by most jurisdictions.

BACKGROUND: We investigated differences in gonococcal antimicrobial susceptibility by anatomic site among cisgender men who have sex with men (MSM) using specimens collected through CDC's enhanced Gonococcal Isolate Surveillance Project (eGISP) and Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). METHODS: During January 1, 2018-December 31, 2019, 12 eGISP and 8 SURRG sites collected urogenital, pharyngeal, and rectal isolates from cisgender MSM in STD clinics. Gonococcal isolates were sent to regional laboratories for antimicrobial susceptibility testing by agar dilution. To account for correlated observations, linear mixed-effects models were used to calculate geometric mean minimum inhibitory concentrations (MICs) and mixed-effects logistic regression models were used to calculate the proportion of isolates with elevated or resistant MICs; comparisons were made across anatomic sites. RESULTS: Participating clinics collected 3,974 urethral, 1,553 rectal, and 1,049 pharyngeal isolates from 5,456 unique cisgender MSM. There were no significant differences in the geometric mean MICs for azithromycin, ciprofloxacin, penicillin, and tetracycline by anatomic site. For cefixime and ceftriaxone, geometric mean MICs for pharyngeal isolates were higher compared to anogenital isolates (p < 0.05). The proportion of isolates with elevated ceftriaxone MICs (≥0.125 μg/ml) at the pharynx (0.67%) was higher than at rectal (0.13%) and urethral (0.18%) sites (p < 0.05). CONCLUSIONS: Based on data collected from multi-jurisdictional sentinel surveillance projects, antimicrobial susceptibility patterns of N. gonorrhoeae isolates may differ among MSM at extragenital sites, particularly at the pharynx. Continued investigation into gonococcal susceptibility patterns by anatomic site may be an important strategy to monitor and detect the emergence of antimicrobial resistant gonorrhea over time.

BACKGROUND AND OBJECTIVES: During 2014-2018, reported congenital syphilis (CS) cases in the United States increased 183%, from 462 to 1306 cases. We reviewed infants diagnosed with CS beyond the neonatal period (>28 days) during this time. METHODS: We reviewed surveillance case report data for infants with CS delivered during 2014-2018 and identified those diagnosed beyond the neonatal period with reported signs or symptoms. We describe these infants and identify possible missed opportunities for earlier diagnoses. RESULTS: Of the 3834 reported cases of CS delivered during 2014-2018, we identified 67 symptomatic infants diagnosed beyond the neonatal period. Among those with reported findings, 67% had physical examination findings of CS, 69% had abnormal long-bone radiographs consistent with CS, and 36% had reactive syphilis testing in the cerebrospinal fluid. The median serum nontreponemal titer was 1:256 (range: 1:1-1:2048). The median age at diagnosis was 67 days (range: 29-249 days). Among the 66 mothers included, 83% had prenatal care, 26% had a syphilis diagnosis during pregnancy or at delivery, and 42% were not diagnosed with syphilis until after delivery. Additionally, 24% had an initial negative test result and seroconverted during pregnancy. CONCLUSIONS: Infants with CS continue to be undiagnosed at birth and present with symptoms after age 1 month. Pediatric providers can diagnose and treat infants with CS early by following guidelines, reviewing maternal records and confirming maternal syphilis status, advocating for maternal testing at delivery, and considering the diagnosis of CS, regardless of maternal history.

BACKGROUND: To describe changes in reported sexually transmitted diseases (STDs) during the U.S. coronavirus disease 2019 pandemic, we compared the weekly number of reported nationally notifiable STDs in 2020 to 2019. METHODS: We reviewed cases of chlamydia, gonorrhea, and primary & secondary (P&S) syphilis reported to the U.S. National Notifiable Disease Surveillance System in 2020. For each STD, we compare the number of 2020 cases reported for a given Morbidity and Mortality Weekly Report (MMWR) week to the number of 2019 cases reported in the same week, expressing 2020 cases as a percentage of 2019 cases. We also calculated the percent difference between 2020 and 2019 cumulative case totals as of MMWR week 50 (week of December 9). RESULTS: During MMWR weeks 1-11 (week of December 29, 2019-March 11, 2020), the weekly number of cases of STDs reported in 2020 as a percentage of the cases in the same week in 2019 were similar. However, 2020 numbers were much lower than 2019 numbers in week 15 (week of April 8; chlamydia, 49.8%; gonorrhea, 71.2%; and P&S syphilis, 63.7%). As of week 50, the 2020 cumulative totals compared to 2019 were 14.0% lower for chlamydia, 7.1% higher for gonorrhea, and 0.9% lower for P&S syphilis. CONCLUSION: During March-April 2020, national case reporting for STDs dramatically decreased compared to 2019. However, resurgence in reported gonorrhea and syphilis cases later in the year suggest STD reporting may have increased during 2020, underscoring the importance of continued STD prevention and care activities.

BACKGROUND: Reactive syphilis serologies are investigated by health departments to determine if they represent new infection, reinfection, or treatment failure. Serologies prioritized for investigation based on nontreponemal test titer and age (using a 'reactor grid') undergo manual record search and review. We developed a computerized algorithm that automates the record search and review. METHODS: We developed and tested the algorithm using a Florida Department of Health dataset containing serologies reported January 2016-December 2018 and previous records linked to each individual. The algorithm was based on the syphilis case definition, which requires (except primary cases with signs and symptoms) 1) a positive treponemal test and a newly positive nontreponemal test or, 2) a 4-fold increase in nontreponemal test titer. Two additional steps were added to avoid missing cases. New York City Department of Health and Mental Hygiene validated this algorithm. RESULTS: The algorithm closed more investigations (49.9%) than the reactor grid (27.0%). The algorithm opened 99.4% of the individuals investigated and labeled as cases by the health department; it missed 75 cases. Many investigations opened by the algorithm were closed by the 'reactor grid'; we could not assess how many would have been cases. In New York City, the algorithm closed 70.9% of investigations, likely because more individuals had previous test in the database (88.2%) compared to Florida (56.5%). CONCLUSIONS: The automated algorithm successfully searched and reviewed records to help identify cases of syphilis. We estimate the algorithm would have saved Florida 590 workdays over 3 years.

BACKGROUND: The prevalence of Neisseria gonorrhoeae (GC) isolates with elevated minimum inhibitory concentrations (MICs) to various antibiotics continues to rise in the U.S. and globally. Genomic analysis provides a powerful tool for surveillance of circulating strains, antimicrobial resistance determinants, and understanding of transmission through a population. METHODS: GC isolates collected from the U.S. Gonococcal Isolate Surveillance Project (GISP) in 2018 (n=1479) were sequenced and characterized. Whole genome sequencing was used to identify sequence types, antimicrobial resistance profiles, and phylogenetic relationships across demographic and geographic populations. RESULTS: Genetic characterization identified that (1) 80% of the GC isolates were represented in 33 multilocus sequence types, (2) isolates clustered in 23 major phylogenetic clusters with select phenotypic and demographic prevalence, and (3) common antimicrobial resistance determinants associated with low-level or high-level decreased susceptibility or resistance to relevant antibiotics. CONCLUSIONS: Characterization of this 2018 GISP genomic dataset, which is the largest U.S. whole genome sequence data set to date, sets the basis for future prospective studies, and establishes a genomic baseline of GC populations for local and national monitoring.

The field of sexually transmitted infection (STI) prevention depends heavily on having current estimates of the health and economic burden of STIs. These estimates guide priorities in research, public health decisions, and governmental policies. Recent estimates have been cited in crucial public health and policy documents, such as STI treatment guidelines,1 STI surveillance reports,2 public health recommendations,3,4 and government budget justifications and priorities.5 Publishing these estimates is one of the most important contributions of the journal, Sexually Transmitted Diseases (STD), to the field.

During the 2017-2018 National Health and Nutrition Examination Survey, urine samples from participants aged 14-59 years were tested for Mycoplasma genitalium infection. Overall prevalence was 1.7% (95% CI: 1.1%, 2.7%). Prevalence was similar between males (1.8%, 95% CI: 0.9%, 3.1%) and females (1.7%, 95% CI: 0.8%, 3.0%).

BACKGROUND: The most recent estimates of the number of prevalent and incident sexually transmitted infections (STIs) in the United States (US) were for 2008. We provide updated estimates for 2018 using new methods. METHODS: We estimated the total number of prevalent and incident infections in the US for eight STIs: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, human papillomavirus (HPV), sexually transmitted hepatitis B, and sexually transmitted HIV. Updated per capita prevalence and incidence estimates for each STI were multiplied by the 2018 full resident population estimates to calculate the number of prevalent and incident infections. STI-specific estimates were combined to generate estimates of the total number of prevalent and incident STIs overall, and by gender and age group. Primary estimates are represented by medians and uncertainty intervals are represented by the 25th (Q1) and 75th (Q3) percentiles of the empirical frequency distributions of prevalence and incidence for each STI. RESULTS: In 2018, there were an estimated 67.6 (Q1=66.6, Q3=68.7) million prevalent and 26.2 (Q1=24.0, Q3=28.7) million incident STIs in the US. Chlamydia, trichomoniasis, genital herpes, and HPV comprised 97.6% of all prevalent and 93.1% of all incident STIs. Persons aged 15-24 years comprised 18.6% (12.6 million) of all prevalent infections; however, they comprised 45.5% (11.9 million) of all incident infections. CONCLUSIONS: The burden of STIs in the US is high. Almost half of incident STIs occurred in persons aged 15-24 years in 2018. Focusing on this population should be considered essential for national STI prevention efforts.

BACKGROUND: Syphilis is a genital ulcerative disease caused by the bacterium Treponema pallidum that is associated with significant complications if left untreated and can facilitate the transmission and acquisition of HIV infection. The last prevalence and incidence estimates of the burden of syphilis in the United States were for 2008. METHODS: We generate syphilis prevalence and incidence estimates for 2018 among adults aged 14-49 years. We fit a simple mathematical model to 2018 case report data to generate 10,000 sets of estimates for age and sex subpopulations and summarize our estimates by their median (50th percentile); uncertainty intervals are characterized by their 25th (Q1) and 75th (Q3) percentiles. We also used our methodology to re-estimate 2008 prevalence and incidence estimates. RESULTS: In 2018, there were an estimated 156,000 (Q1=132,000, Q3=184,000) prevalent and 146,000 (Q1=126,000, Q3=170,000) incident syphilitic infections in people aged 14-49 years. Men accounted for roughly 70% of prevalent infections and more than 80% of incident infections. In both sexes, there were more prevalent and incident infections in 25-49-year-olds than 14-24-year-olds. Using these methods to re-analyze 2008 data, syphilis prevalence and incidence estimates have increased 164% and 175%, respectively, between 2008 and 2018. DISCUSSION: Although not as common as other sexually transmitted infections, syphilis should be monitored due to its devastating sequelae. As it continues to increase in frequency, it will be important for future work to continue to track its trajectory and burden.

Most estimates of the combined burden and cost of sexually transmitted infections (STIs) in the United States have focused on eight common STIs with established national surveillance strategies (chlamydia, gonorrhea, syphilis, trichomoniasis, genital herpes, human papillomavirus, and sexually transmitted HIV and hepatitis B). However, over 30 STIs are primarily sexually transmitted or sexually transmissible. In this manuscript, we review what is known about the burden of "other STIs" in the United States, including those where sexual transmission is not the primary transmission route of infection. Although the combined burden of these other STIs may be substantial, accurately estimating their burden due to sexual transmission is difficult due to diagnostic and surveillance challenges. Developing better estimates will require innovative strategies, such as leveraging existing surveillance systems, partnering with public health and academic researchers outside of the STI field, and developing methodology to estimate the frequency of sexual transmission, particularly for new and emerging STIs.Monitoring the burden of sexually transmitted infections (STIs) in the United States is critical to inform and evaluate interventions and guide public health action. Most estimates of the combined burden of STIs in the United States have focused on eight common STIs with established national surveillance strategies (chlamydia, gonorrhea, syphilis, trichomoniasis, genital herpes, human papillomavirus [HPV], and sexually-transmitted HIV and hepatitis B); (1-5) however, there are over 30 pathogens that are sexually transmitted or transmissible (6-8) and these combined estimates underestimate the total burden and economic impact of STIs. "Other STIs" include infections that are primarily sexually transmitted in adults, but their public health significance has not been well established or there are no specific prevention or control programs for them (e.g., pubic lice, Mycoplasma genitalium) and infections where sexual transmission is not the primary transmission route (e.g., shigella, Zika). In this manuscript, we describe what is known about the burden (e.g., prevalence or incidence) of "other STIs" in the US based on a review of published manuscripts and surveillance reports and identify strategies that could be used to better estimate their burden.

Sexually transmitted infections (STIs) caused by the bacteria Neisseria gonorrhoeae (gonococcal infections) have increased 63% since 2014 and are a cause of sequelae including pelvic inflammatory disease, ectopic pregnancy, and infertility and can facilitate transmission of human immunodeficiency virus (HIV) (1,2). Effective treatment can prevent complications and transmission, but N. gonorrhoeae's ability to acquire antimicrobial resistance influences treatment recommendations and complicates control (3). In 2010, CDC recommended a single 250 mg intramuscular (IM) dose of ceftriaxone and a single 1 g oral dose of azithromycin for treatment of uncomplicated gonococcal infections of the cervix, urethra, and rectum as a strategy for preventing ceftriaxone resistance and treating possible coinfection with Chlamydia trachomatis (4). Increasing concern for antimicrobial stewardship and the potential impact of dual therapy on commensal organisms and concurrent pathogens (3), in conjunction with the continued low incidence of ceftriaxone resistance and the increased incidence of azithromycin resistance, has led to reevaluation of this recommendation. This report, which updates previous guidelines (5), recommends a single 500 mg IM dose of ceftriaxone for treatment of uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. If chlamydial infection has not been excluded, concurrent treatment with doxycycline (100 mg orally twice a day for 7 days) is recommended. Continuing to monitor for emergence of ceftriaxone resistance through surveillance and health care providers' reporting of treatment failures is essential to ensuring continued efficacy of recommended regimens.

In November 2019, the Southern Nevada Public Health Laboratory of the Southern Nevada Health District (SNHD) identified a male urethral gonococcal isolate later demonstrating reduced susceptibility to cefixime (minimum inhibitory concentration [MIC] = 2.0 μg/mL) and ceftriaxone (MIC = 1.0 μg/mL) but susceptible to azithromycin (MIC = 0.25 μg/mL). Molecular testing by CDC in the United States revealed the emerging mosaic penA60 allele, first identified in Japan in 2016 (1), which confers reduced susceptibility to cephalosporins and increases the risk for treatment failure. The penA60 allele has been identified in China (2), Canada (3,4), Denmark (5), Australia (6), France (7), and the United Kingdom (8). The Nevada case is the first identified case of a Neisseria gonorrhoeae isolate harboring the mosaic penA60 allele reported in the United States.

BACKGROUND: The number of cases of gonorrhoea in the USA and worldwide caused by Neisseria gonorrhoeae is increasing (555 608 reported US cases in 2017, and 87 million cases worldwide in 2016). Many countries report declining in vitro susceptibility of azithromycin, which is a concern because azithromycin and ceftriaxone are the recommended dual treatment in many countries. We aimed to identify strain types associated with decreased susceptibility to azithromycin. METHODS: We did a genomic analysis of N gonorrhoeae isolates obtained by the US Gonococcal Isolate Surveillance Project. Isolates were whole-genome sequenced based on decreased susceptibility to azithromycin (minimal inhibitory concentration [MIC] ≥2 μg/mL, using agar dilution antibiotic susceptibility testing) and geographical representation. Bioinformatic analyses established genomic diversity, strain population dynamics, and antimicrobial resistance profiles. FINDINGS: 410 isolates were sorted into more than 20 unique phylogenetic clades. One predominant persistent clade (consisting of 97 isolates) included the most isolates with azithromycin MICs of 2 μg/mL or higher (61 of 97 [63%] vs 59 of 311 [19%]; p<0·0001) and carried a mosaic mtr (multiple transferable resistance) locus (68 of 97 [70%] vs two of 313 [1%]; p<0·0001). Of the remaining 313 isolates, 57 (18%) had decreased susceptibility to azithromycin (MIC ≥4 μg/mL), which was attributed to 23S rRNA variants (56 of 57 [98%]) and formed phylogenetically diverse clades, showing various levels of clonal expansion. INTERPRETATION: Reduced azithromycin susceptibility was associated with expanding and persistent clades harbouring two well described resistance mechanisms, mosaic mtr locus and 23S rRNA variants. Understanding the role of recombination, particularly within the mtr locus, on the fitness and expansion of strains with decreased susceptibility has important implications for the public health response to minimise gonorrhoea transmission. FUNDING: US Centers for Disease Control and Prevention (CDC), CDC Combating Antibiotic Resistant Bacteria initiative, Oak Ridge Institute for Science Education, US Department of Energy/CDC/Emory University, National Institutes of Health, and Biomedical Laboratory Research and Development Service of the US Department of Veterans Affairs.

In 2018, 21 (41%) jurisdictions had begun reporting gender identity for sexually transmitted disease case notifications sent to the Centers for Disease Control and Prevention. Among jurisdictions with ≥70% of cases with reported gender identity and sex, 1.0% of primary and secondary syphilis cases were identified as transgender and 71% of transgender women with syphilis were concurrently coded as being male sex.

Congenital syphilis is an infection with Treponema pallidum in an infant or fetus, acquired during pregnancy from a mother with untreated or inadequately treated syphilis. Congenital syphilis can cause miscarriage, stillbirth, or early infant death, and infected infants can experience lifelong physical and neurologic problems. Although timely identification and treatment of maternal syphilis during pregnancy can prevent congenital syphilis (1,2), the number of reported congenital syphilis cases in the United States increased 261% during 2013-2018, from 362 to 1,306. Among reported congenital syphilis cases during 2018, a total of 94 resulted in stillbirths or early infant deaths (3). Using 2018 national congenital syphilis surveillance data and a previously developed framework (4), CDC identified missed opportunities for congenital syphilis prevention. Nationally, the most commonly missed prevention opportunities were a lack of adequate maternal treatment despite the timely diagnosis of syphilis (30.7%) and a lack of timely prenatal care (28.2%), with variation by geographic region. Congenital syphilis prevention involves syphilis prevention for women and their partners and timely identification and treatment of pregnant women with syphilis. Preventing continued increases in congenital syphilis requires reducing barriers to family planning and prenatal care, ensuring syphilis screening at the first prenatal visit with rescreening at 28 weeks' gestation and at delivery, as indicated, and adequately treating pregnant women with syphilis (2). Congenital syphilis prevention strategies that implement tailored public health and health care interventions to address missed opportunities can have substantial public health impact.

BACKGROUND: Azithromycin (AZI) is recommended with ceftriaxone (CRO) for treatment of uncomplicated gonococcal urethritis and cervicitis in the United States, and an AZI-susceptibility breakpoint is needed. Neither the Food and Drug Administration (FDA) nor the Clinical and Laboratory Standards Institute (CLSI) has set interpretive breakpoints for AZI susceptibility. As a result, AZI antimicrobial susceptibility testing (AST) cannot be interpreted using recognized standards. This has contributed to increasingly unavailable clinical laboratory AST, although gonorrhea is on the rise with >550 000 US gonorrhea cases reported to the Centers for Disease Control and Prevention in 2017, the highest number of cases since 1991. METHODS: This article summarizes the rationale data reviewed by the CLSI in June 2018. RESULTS: The CLSI decided to set a susceptible-only interpretive breakpoint at the minimum inhibitory concentration of </=1 microg/mL. This is also the epidemiological cutoff value (ECV) (ie, the end of the wild-type susceptibility distribution). This breakpoint presumes that AZI (1-g single dose) is used in an approved regimen that includes an additional antimicrobial agent (ie, CRO 250 mg, intramuscular single dose). CONCLUSIONS: Having a breakpoint can improve patient care and surveillance and allow future development and FDA regulatory approval of modernized AST to guide treatment. The breakpoint coincides with a European Committee on AST decision to remove previously established, differing AZI breakpoints and use the ECV as guidance for testing. The CLSI breakpoint is now the recognized standard that defines AZI susceptibility for gonococcal infections.

US gonorrhea rates are rising, and antibiotic-resistant Neisseria gonorrhoeae (AR-Ng) is an urgent public health threat. Since implementation of nucleic acid amplification tests for Ng identification, capacity for culturing Ng in the US has declined, along with the ability to perform culture-based antimicrobial susceptibility testing (AST). Yet, AST is critical for detecting and monitoring AR-Ng. In 2016, CDC established the Antibiotic Resistance Laboratory Network (AR Lab Network) to shore up national capacity for detecting several resistance threats including Ng. AR-Ng testing, a sub-activity of CDC's AR Lab Network, is performed in a tiered network of approximately 35 local laboratories, four regional laboratories (state public health laboratories in MD, TN, TX, WA), and CDC's national reference laboratory. Local laboratories receive specimens from approximately 60 clinics associated with the Gonococcal Isolate Surveillance Project (GISP), enhanced GISP (eGISP), and Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). They isolate and ship up to 20,000 isolates to regional laboratories for culture-based agar dilution AST with seven antibiotics and for whole genome sequencing of up to 5,000 isolates. The CDC further examines concerning isolates and monitors genetic AR markers. During 2017 and 2018, the network tested 8,214 and 8,628 Ng isolates, and CDC received 531 and 646 concerning isolates, and 605 and 3,159 sequences, respectively. In summary, the AR Lab Network supported laboratory capacity for Ng-AST and associated genetic marker detection, expanding pre-existing notification and analysis systems for resistance detection. Continued, robust AST and genomic capacity can help inform national public health monitoring and intervention.

During 2013-2017, the national annual rate of reported primary and secondary (P&S) syphilis cases in the United States increased 72.7%, from 5.5 to 9.5 cases per 100,000 population (1). The highest rates of P&S syphilis are seen among gay, bisexual, and other men who have sex with men (collectively referred to as MSM) (2), and MSM continued to account for the majority of cases in 2017 (1). However, during 2013-2017, the P&S syphilis rate among women increased 155.6% (from 0.9 to 2.3 cases per 100,000 women), and the rate among all men increased 65.7% (from 10.2 to 16.9 cases per 100,000 men), indicating increasing transmission between men and women in addition to increasing transmission between men (1). To further understand these trends, CDC analyzed national P&S syphilis surveillance data for 2013-2017 and assessed the percentage of cases among women, men who have sex with women only (MSW), and MSM who reported drug-related risk behaviors during the past 12 months. Among women and MSW with P&S syphilis, reported use of methamphetamine, injection drugs, and heroin more than doubled during 2013-2017. In 2017, 16.6% of women with P&S syphilis used methamphetamine, 10.5% used injection drugs, and 5.8% used heroin during the preceding 12 months. Similar trends were seen among MSW, but not among MSM. These findings indicate that a substantial percentage of heterosexual syphilis transmission is occurring among persons who use these drugs, particularly methamphetamine. Collaboration between sexually transmitted disease (STD) control programs and partners that provide substance use disorder services will be important to address recent increases in heterosexual syphilis.

Gonorrhea, the sexually transmitted disease (STD) caused by Neisseria gonorrhoeae, is the second most common notifiable disease in the United States after chlamydia; 468,514 cases were reported to state and local health departments in 2016, an increase of 18.5% from 2015 (1). N. gonorrhoeae has progressively developed resistance to most antimicrobials used to treat the infection (2). As a result, CDC recommends two antimicrobials (250 mg of ceftriaxone [IM] plus 1 g of azithromycin [PO]) for treating uncomplicated gonorrhea to improve treatment efficacy and, potentially, to slow the emergence and spread of antimicrobial resistance. To monitor adherence to the current CDC-recommended regimen for uncomplicated gonorrhea, CDC reviewed enhanced data collected on a random sample of reported cases of gonorrhea in seven jurisdictions participating in the STD Surveillance Network (SSuN) and estimated the proportion of patients who received the CDC-recommended regimen for uncomplicated gonorrhea, by patient characteristics and diagnosing facility type. In 2016, the majority of reported patients with gonorrhea (81%) received the recommended regimen. There were no differences in the proportion of patients receiving the recommended regimen by age or race/ethnicity; however, patients diagnosed with gonorrhea in STD (91%) or family planning/reproductive health (94%) clinics were more likely to receive this regimen than were patients diagnosed in other provider settings (80%). These data document high provider adherence to CDC gonorrhea treatment recommendations in specialty STD clinics, indicating high quality of care provided in those settings. Local and state health departments should monitor adherence with recommendations in their jurisdictions and consider implementing interventions to improve provider and patient compliance with gonorrhea treatment recommendations where indicated.

Preventing the emergence of ceftriaxone-resistant Neisseria gonorrhoeae can potentially avert hundreds of millions of dollars in direct medical costs of gonorrhea and gonorrhea-attributable HIV infections. In the illustrative scenario we examined, emerging ceftriaxone resistance could lead to 1.2 million additional N. gonorrhoeae infections within 10 years, costing $378.2 million.

OBJECTIVE: To estimate new HIV diagnosis rates among HIV negative MSM who are repeatedly tested for HIV in sexually transmitted disease (STD) clinics, and assess the impact of demographic and disease-specific characteristics that are associated with higher HIV diagnosis rates. STUDY DESIGN: Retrospective analysis using 2010-2013 data from the STD Surveillance Network (SSuN), a sentinel surveillance system comprised of health departments in 12 cities conducting sentinel surveillance in 40 STD clinics. We analyzed data from all MSM repeatedly (>/=2 times) tested for HIV, with an initial negative HIV test required for staggered cohort entry. Follow-up time was accrued from the date of the first negative HIV test to the most recent negative test or the first positive HIV test. STD diagnoses during the follow-up period were reviewed. We estimated HIV diagnoses rates (number of HIV diagnoses/total number of person-years at risk) by demographic and clinical characteristics with 95% confidence intervals (CI) using an inverse variance weighted random effects model, adjusting for heterogeneity between SSuN jurisdictions. RESULTS: Overall, 640 HIV diagnoses occurred among 14,824 individuals and 20,951.6 person-years (PY) of observation, for an adjusted incidence of HIV diagnosis of 3.0 per 100 PY (95% CI 2.6, 3.4). Rates varied across race/ethnicity groups with the highest rate among Blacks (4.7/100 PY; 95% CI 4.1-5.3) followed by Hispanics, Whites and persons of other races/ethnicities. MSM having a diagnosis of P&S syphilis on or after the first negative HIV test had a higher new HIV diagnosis rate (7.2/100 PY; 95% CI 5.8-9.0) compared to MSM who did not have a P&S syphilis diagnosis (2.8/100 PY; 95% CI 2.6-3.1). MSM who tested positive for rectal gonorrhea (6.3/100 PY; 95% CI 5.7-6.9) or rectal chlamydia (5.6/100 PY; 95% CI 4.6-6.6) had higher rates of new HIV diagnosis when compared to those with negative test results. CONCLUSIONS: MSM attending SSuN STD clinics have high rates of new HIV diagnoses, particularly those with a previous diagnosis of P&S syphilis, rectal chlamydia and/or gonorrhea. STD clinics continue to be important clinical setting for diagnosing HIV among MSM populations.

BACKGROUND: Recent increases in syphilis among men who have sex with men (MSM) are especially concerning, given the biologic and epidemiologic associations between syphilis and HIV infection. We sought to better describe the current epidemiology of primary and secondary (P&S) syphilis and the prevalence of HIV infection among reported P&S syphilis cases by demographic group, including sex of sex partner, in the United States in 2016. METHODS: We reviewed national P&S syphilis case report data from 2016, including available risk factor information such as sex of sex partner and HIV status. Data were extracted from the National Electronic Telecommunications System for Surveillance, the system through which CDC receives notifiable STD data from all 50 states and the District of Columbia. The proportion of cases with HIV co-infection was calculated using cases with known HIV status as the denominator. RESULTS: Of 27,814 P&S syphilis cases reported in 2016, 58.1% were among MSM, 13.9% were among men who have sex with women only (MSW), 11.0% were among women, and 16.9% were among men without data on sex of sex partners. Similar patterns were observed across geographic regions, race/ethnicity groups, and most age groups. Overall, 38.5% of reported P&S syphilis cases with known HIV status were co-infected with HIV. The prevalence of HIV co-infection was highest among MSM (47.0%) compared with MSW (10.7%) or women (4.1%). Among MSM with P&S syphilis, the prevalence of HIV co-infection was highest among black MSM, ranging from 33.8% among black MSM aged 15-19 years to 77.8% among black MSM aged 45-49 years. CONCLUSIONS: These data underscore the epidemiologic linkages between syphilis and HIV, particularly among MSM. P&S syphilis may represent an opportunity to prevent HIV infection among persons who are HIV-negative and identify and link to care persons living with HIV infection but not currently engaged in care.

The Anniston Community Health Survey, a cross-sectional study, was undertaken in 2005-2007 to study environmental exposure to polychlorinated biphenyl (PCB) and organochlorine (OC) pesticides and health outcomes among residents of Anniston, AL, United States. The examination of potential risks between these pollutants and metabolic syndrome, a cluster of cardiovascular risk factors (i.e., hypertension, central obesity, dyslipidemia and dysglycemia) was the focus of this analysis. Participants were 548 adults who completed the survey and a clinic visit, were free of diabetes, and had a serum sample for clinical laboratory parameters as well as PCB and OC pesticide concentrations. Associations between summed concentrations of 35 PCB congeners and 9 individual pesticides and metabolic syndrome were examined using generalized linear modeling and logistic regression; odds ratios (OR) and 95% confidence intervals (CI) are reported. Pollutants were evaluated as quintiles and as log transformations of continuous serum concentrations. Participants were mostly female (68%) with a mean age (SD) of 53.6 (16.2) years. The racial distribution was 56% white and 44% African American; 49% met the criteria for metabolic syndrome. In unadjusted logistic regression, statistically significant and positive associations across the majority of quintiles were noted for seven individually modeled pesticides (p,p'-DDT, p,p'-DDE, HCB, beta-HCCH, oxychlor, tNONA, Mirex). Following adjustment for covariables (i.e., age, sex, race, education, marital status, current smoking, alcohol consumption, positive family history of diabetes or cardiovascular disease, liver disease, BMI), significant elevations in risk were noted for p,p'-DDT across multiple quintiles (range of ORs 1.61 to 2.36), for tNONA (range of ORs 1.62-2.80) and for p,p'-DDE [OR (95% CI)] of 2.73 (1.09-6.88) in the highest quintile relative to the first. Significant trends were observed in adjusted logistic models for log10 HCB [OR=6.15 (1.66-22.88)], log10 oxychlor [OR=2.09 (1.07-4.07)] and log10 tNONA [3.19 (1.45-7.00)]. Summed PCB concentrations were significantly and positively associated with metabolic syndrome only in unadjusted models; adjustment resulted in attenuation of the ORs in both the quintile and log-transformed models. In conclusion, several OC pesticides were found to have significant associations with metabolic syndrome in the Anniston study population while no association was observed for PCBs.

BACKGROUND: Men who have sex with men (MSM) in the United States experience an approximately 100-fold greater rate of primary and secondary (P&S) syphilis diagnoses compared to men who have sex with women only. As in the general population, racial/ethnic disparities in P&S syphilis diagnosis rates may exist among MSM, but MSM-specific P&S syphilis rates by race/ethnicity are unavailable. We enhanced a published modeling approach to estimate area-level MSM populations by race/ethnicity and provide the first estimates of P&S syphilis among black and white non-Hispanic MSM. METHODS: We used data from the American Community Survey (ACS), published findings from the National Health and Nutrition Examination Survey (NHANES), and national syphilis surveillance data to estimate state-level rates of P&S syphilis diagnoses among MSM, overall and for black and white non-Hispanic MSM. We also used variability around ACS and NHANES estimates to calculate 95% confidence intervals for each rate. RESULTS: Among 11,359 cases of P&S syphilis among MSM with known race/ethnicity in 2014, 72.5% were among white (40.3%) or black (32.2%) MSM. The national rate of P&S syphilis diagnosis was 168.4/100,000 for white MSM and 583.9/100,000 for black MSM. Regional rates for black MSM ranged from 602.0/100,000 (South) to 521.5/100,000 (Midwest) and were consistently higher than those for white MSM. CONCLUSIONS: Although white MSM accounted for the majority of P&S syphilis diagnoses in 2014, when evaluating diagnoses based on rate per 100,000, black MSM had consistently and markedly higher rates than white MSM, with the highest-impacted states located in the US South.

In 2015, the rate of reported primary and secondary syphilis in the United States was 7.5 cases per 100,000 population, nearly four times the previous lowest documented rate of 2.1 in 2000. In 2015, 81.7% of male primary and secondary syphilis cases with information on the sex of the sex partner were among gay, bisexual, and other men who have sex with men (collectively referred to as MSM) (1). These data suggest a disproportionate incidence of disease among MSM. However, attempts to quantify this disparity have been hindered by limited data on the size of the MSM population at the state level. To produce the first estimates of state-specific rates of primary and secondary syphilis among MSM, CDC used MSM population estimates based on a new methodology and primary and secondary syphilis case counts reported in 2015 to the National Notifiable Diseases Surveillance System. Among 44 states reporting information on the sex of sex partners for ≥70% of male cases, the overall rate of primary and secondary syphilis among all men (aged ≥18 years) in the United States in 2015 was 17.5 per 100,000, compared with 309.0 among MSM and 2.9 among men who reported sex with women only. The overall rate of primary and secondary syphilis among MSM was 106.0 times the rate among men who have sex with women only and 167.5 times the rate among women.* These data highlight the disproportionate impact of syphilis among MSM and underscore the need for innovative and targeted syphilis prevention measures at the state and local level, especially among MSM. It is important that health care providers recognize the signs and symptoms of syphilis, screen sexually active MSM for syphilis at least annually, and provide timely treatment according to national sexually transmitted diseases treatment guidelines.

OBJECTIVES: To examine prevalence of low- and high-grade cervical lesions over time in a large cohort of US female adolescents and women. METHODS: We used health care claims data from 9 million privately insured female patients aged 15 to 39 years to estimate annual prevalence of cytologically detected cervical low-grade (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and high-grade histologically detected cervical intraepithelial neoplasia grades 2 and 3 (CIN2+) during 2007 through 2014. We restricted analyses to those who received cervical cancer screening in a given calendar year. RESULTS: Prevalence of HSIL and CIN2+ decreased significantly for those aged 15 to 19 years. Average annual percent change in prevalence in this group during 2007 through 2014 for HSIL and CIN2+ was -8.3% and -14.4%, respectively (P < .001 for both estimates). Prevalence of HSIL and CIN2+ also decreased significantly for women aged 20 to 24 years. No decreases were seen in women aged 30 to 39 years. CONCLUSIONS: Decreases in high-grade lesions reflected their greater association with human papillomavirus types 16 and 18, compared with low-grade lesions, providing ecological evidence of population effectiveness of human papillomavirus vaccination among young, privately insured women.