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Introduction: Neisseria gonorrhoeae (Ng) has successively developed resistance to all previously recommended antimicrobial therapies, with ceftriaxone being the last option for monotherapy of gonorrhea. Global emergence and international spread of the FC428 clone derived mosaic penA-60 allele, associated with highlevel ceftriaxone minimum inhibitory concentrations (MICs) in non FC428 clone Ng lineages, has become an increasing concern. The penA60 allele carrying Ng was first identified in the U.S. in Las Vegas, Nevada (2019; GCWGS-102723), with a multi-locus sequence type (MLST)-1901 strain, in a non FC428 clone Ng lineage, which is associated with a historically ceftriaxone susceptible core genogroup. Later in 2022, an allele genetically similar to penA-60, mosaic penA-237, was identified in the UK (H22-722) and France (F92) with high-level ceftriaxone MICs and both belonged to MLST-1901. Methods: In this study, we assessed phylogenomic relatedness and antimicrobial resistance (AMR) determinant profiles of these three isolates with high-level ceftriaxone MICs among a global collection of 2,104 genomes belonging to the MLST-1901 core genome cluster group 31, which includes strains separated by a locus threshold of 200 or fewer differences (Ng_cgc_200). Recombination events in and around the penA coding region were catalogued and potential sources of inter species recombinant DNA were also inferred. Results: The global population structure of MLST-1901 core genogroup falls into 4 major lineages. Isolates GCWGS-10723, F92, and H22-722 clustered within Lineage 1, which was dominated by non-mosaic penA-5 alleles. These three isolates formed a clade within Lineage 1 that consisted of isolates from North America and southeast Asia. Neisseria subflava and Neisseria sicca were identified as likely progenitors of two independent recombination events that may have led to the generation of mosaic penA-60 and penA-237, within a possible non-mosaic penA-5 background. Discussions: Our study suggests that there are multiple evolutionary pathways that could generate concerning mosaic penA alleles via homologous recombination of historically susceptible Ng lineages with Neisseria commensals. Enhanced surveillance of gonococcal strains and Neisseria commensals is crucial for understanding of the evolution of AMR, particularly in less-studied regions (e.g., Asia), where high-level ceftriaxone MICs and multi-drug resistance are more prevalent. [ABSTRACT FROM AUTHOR]

The "Keep It Simple" package, which includes a short animated film (available online for streaming or download), a lesson plan, and supporting materials, was designed to be used with adolescents ages 15-19 to empower them to seek sexual and reproductive health care, and emphasize the availability of long-acting reversible contraception (LARCs). The materials in the package can be used together to deliver a 45 minute educational session that provides information to teens about the sexual health services available to them at local health centers, their rights to obtain those services, and how they can link to high quality and adolescent friendly sexual health care. The animation can also be used as a standalone product. All components of the "Keep It Simple" package are available for free and are also offered in Spanish as "No te compliques." Contains a bibliography.

Disseminated gonococcal infection (DGI) is a rare complication caused by the systemic dissemination of Neisseria gonorrhoeae to normally sterile anatomical sites. Little is known about the genetic diversity of DGI gonococcal strains and how they relate to other gonococcal strains causing uncomplicated mucosal infections. We used whole genome sequencing to characterize DGI isolates (n = 30) collected from a surveillance system in Georgia, United States, during 2017–2020 to understand phylogenetic clustering among DGI as well as uncomplicated uro- and extragenital gonococcal infection (UGI) isolates (n = 110) collected in Fulton County, Georgia, during 2017–2019. We also investigated the presence or absence of genetic markers related to antimicrobial resistance (AMR) as well as surveyed the genomes for putative virulence genetic factors associated with normal human-serum (NHS) resistance that might facilitate DGI. We found that DGI strains demonstrated significant genetic variability similar to the population structure of isolates causing UGI, with sporadic incidences of geographically clustered DGI strains. DGI isolates contained various AMR markers and genetic mechanisms associated with NHS resistance. DGI isolates had a higher frequency of the porB1A allele compared with UGI (67% vs 9%, P  < .0001); however, no single NHS resistance marker was found in all DGI isolates. Continued DGI surveillance with genome-based characterization of DGI isolates is necessary to better understand specific factors that promote systemic dissemination. [ABSTRACT FROM AUTHOR]

Neisseria gonorrhoeae multilocus sequence type (ST) 9363 core-genogroup isolates have been associated with reduced azithromycin susceptibility (AZMrs) and show evidence of clonal expansion in the United States. Here, we analyze a global collection of ST-9363 core-genogroup genomes to shed light on the emergence and dissemination of this strain. The global population structure of ST-9363 core-genogroup falls into three lineages: Basal, European, and North American; with 32 clades within all lineages. Although, ST-9363 core-genogroup is inferred to have originated from Asia in the mid-19th century; we estimate the three modern lineages emerged from Europe in the late 1970s to early 1980s. The European lineage appears to have emerged and expanded from around 1986 to 1998, spreading into North America and Oceania in the mid-2000s with multiple introductions, along with multiple secondary reintroductions into Europe. Our results suggest two separate acquisition events of mosaic mtrR and mtrR promoter alleles: first during 2009–2011 and again during the 2012–2013 time, facilitating the clonal expansion of this core-genogroup with AZMrs in the United States. By tracking phylodynamic evolutionary trajectories of clades that share distinct demography as well as population-based genomic statistics, we demonstrate how recombination and selective pressures in the mtrCDE efflux operon granted a fitness advantage to establish ST-9363 as a successful gonococcal lineage in the United States and elsewhere. Although it is difficult to pinpoint the exact timing and emergence of this young core-genogroup, it remains critically important to continue monitoring it, as it could acquire additional resistance markers. [ABSTRACT FROM AUTHOR]

Background: Reduced antibiotic susceptibility (RS) in Neisseria gonorrhoeae (GC) may increase treatment failure. Conducting tests of cure (TOC) for patients with RS-GC may facilitate identification of treatment failures.Methods: We examined 2018 to 2019 data from 8 jurisdictions participating in the US Centers for Disease Control and Prevention's Strengthening US Response to Resistant Gonorrhea project. Jurisdictions collected GC isolates and epidemiological data from patients and performed antimicrobial susceptibility testing. Minimum inhibitory concentrations of ceftriaxone, 0.125 μg/mL or greater; cefixime, 0.250 μg/mL or greater; or azithromycin, 2.0 μg/mL or greater were defined as RS. Patients with RS infections were asked to return for a TOC 8 to 10 days posttreatment. We calculated a weighted TOC return rate and described time to TOC and suspected reasons for any positive TOC results.Results: Overall, 1165 patients were diagnosed with RS infections. Over half returned for TOC (weighted TOC, 61%; 95% confidence interval, 50.1%-72.6%; range by jurisdiction, 32%-80%). Test of cure rates were higher among asymptomatic (68%) than symptomatic patients (53%, P = 0.001), and men who have sex with men (62%) compared with men who have sex with women (50%; P < 0.001). Median time between treatment and TOC was 12 days (interquartile range, 9-16). Of the 31 (4.5%) TOC patients with positive results, 13 (42%) were suspected because of reinfection and 11 (36%) because of false-positive results. There were no treatment failures suspected to be due to RS-GC.Conclusions: Most patients with a RS infection returned for a TOC, though return rates varied by jurisdiction and patient characteristics. Test of cure can identify and facilitate treatment of reinfections, but false-positive TOC results may complicate interpretation and clinical management. [ABSTRACT FROM AUTHOR]

Background: Responding effectively to outbreaks of antibiotic-resistant gonorrhea (ARGC) in the future will likely prove challenging. Tabletop exercises (TTXs) may assist local, state, and federal public health officials evaluate existing ARGC outbreak response plans, strengthen preparedness and response effectiveness, and identify critical gaps to address before an outbreak.Methods: In 2018 to 2019, Centers for Disease Control and Prevention (CDC) collaborated with state partners to develop and implement TTXs to simulate a public health emergency involving an ARGC outbreak. Before the TTXs, 2 state-local health department pairs developed ARGC outbreak response plans. During each 1-day exercise (in Indiana and Illinois), participants discussed roles, clinical management, public health response, and communication based on predeveloped response plans. Observers identified outbreak response strengths and gaps, and participants completed feedback forms.Results: Forty-one (Illinois) and 48 people (Indiana) participated in each TTX, including sexually transmitted disease clinical staff, laboratorians, public health infectious disease program staff, and CDC observers. Strengths and gaps varied by jurisdiction, but identified gaps included: (1) local access to gonorrhea culture and timely antimicrobial susceptibility testing, (2) protocols for clinical management of suspected treatment failures, (3) communication plans, and (4) clarity regarding state and local responsibilities. The CDC observers identified opportunities to provide national-level technical assistance, foster local antimicrobial susceptibility testing, and develop further response guidance. Tabletop exercises summary reports were used to guide modifications to local response plans to address gaps.Conclusions: The TTXs allowed participants to practice responding to a simulated public health emergency and may have enhanced local response capacity. Centers for Disease Control and Prevention made TTX implementation materials publicly available. [ABSTRACT FROM AUTHOR]

Introduction: The Centers for Disease Control and Prevention implemented Strengthening the US Response to Resistant Gonorrhea (SURRG) to build local detection and response capacity and evaluate responses to antibiotic-resistant gonorrhea outbreaks, including partner services for gonorrhea. We evaluated outcomes of traditional partner services conducted under SURRG, which involved (1) counseling index patients and eliciting sexual partners; (2) interviewing, testing, and treating partners; and (3) providing partner services to partners newly diagnosed with gonorrhea. We also evaluated outcomes of enhanced partner services, which additionally involved interviewing and testing partners of persons who tested negative, and social contacts of index patients and partners.Methods: We analyzed partner services investigation data from 8 jurisdictions participating in SURRG from 2017 to 2019. We summed total index patients, partners from traditional partner services, and partners and contacts from enhanced partner services, and calculated partner services outcomes among partners and contacts. We also visualized sexual networks from partner services data.Results: Of 1242 index patients identified, 506 named at least 1 sexual partner. Traditional partner services yielded 1088 sexual partners, and 105 were newly diagnosed with gonorrhea. Enhanced partner services yielded an additional 59 sexual partners and 52 social contacts. Of those partners and contacts, 3 were newly diagnosed with gonorrhea. Network visualization revealed sparse networks with few complex partnership clusters.Conclusions: Traditional partner services for gonorrhea may be useful for eliciting, notifying, and diagnosing partners of index patients in an outbreak setting. Enhanced partner services are unlikely to be effective for eliciting, notifying, and diagnosing a substantial number of additional people. [ABSTRACT FROM AUTHOR]

Background: In 2016, Centers for Disease Control and Prevention initiated Strengthening the US Response to Resistant Gonorrhea (SURRG) in multiple jurisdictions to enhance antibiotic resistant gonorrhea rapid detection and response infrastructure and evaluate the impact of key strategies.Methods: Eight jurisdictions were funded to establish or enhance local gonococcal culture specimen collection in sexually transmitted disease and community clinics, conduct rapid antimicrobial susceptibility testing (AST) in local laboratories, modify systems for enhanced data collection and rapid communication of results, and initiate enhanced partner services among patients with gonorrhea demonstrating elevated minimum inhibitory concentrations (MICs) to ceftriaxone, cefixime or azithromycin.Results: Grantees incorporated genital, pharyngeal, and rectal gonococcal culture collection from all genders at participating clinics. During 2018 to 2019, grantees collected 58,441 culture specimens from 46,822 patients and performed AST on 10,814 isolates (representing 6.8% [3412] and 8.9% [4883] of local reported cases in 2018 and 2019, respectively). Of isolates that underwent AST, 11% demonstrated elevated azithromycin MICs; fewer than 0.5% demonstrated elevated ceftriaxone or cefixime MICs. Among patients whose infections demonstrated elevated MICs, 81.7% were interviewed for partner elicitation; however, limited new cases were identified among partners and contacts.Conclusions: As a public health model to build capacity to slow the spread of emerging resistance, SURRG successfully expanded culture collection, implemented rapid AST, and implemented an enhanced partner services investigation approach in participating jurisdictions. Findings from SURRG may enhance preparedness efforts and inform a longer-term, comprehensive, and evidence-based public health response to emerging gonococcal resistance. Continued development of innovative approaches to address emerging resistance is needed. [ABSTRACT FROM AUTHOR]

Background Since 2014, Neisseria gonorrhoeae azithromycin (AZM) susceptibility has declined in the United States, but high-level AZM resistance (HL-AZMR) has been infrequent and sporadic. We describe a cluster of 14 N. gonorrhoeae isolates with HL-AZMR identified in Indianapolis over 13 months. Methods N. gonorrhoeae culture specimens (genital and extragenital) were collected from attendees of the Bell Flower Clinic. Isolates underwent antimicrobial susceptibility testing (AST) using Etest. AZM minimum inhibitory concentrations ≥256 µg/mL were classified as HL-AZMR. Local disease intervention specialists interviewed patients whose isolates demonstrated HL-AZMR and conducted partner services. Relatedness of isolates was investigated by genomic analyses. Results During 2017–2018, AST was performed in 1016 N. gonorrhoeae isolates collected at the Bell Flower Clinic. Fourteen isolates (1.4%) from 12 men collected over 13 months demonstrated HL-AZMR; all were cephalosporin susceptible. Of the 12 men, 9 were white and reported male sex partners. Nine of the men were able to be retested; all were cured with 250-mg ceftriaxone plus 1-g AZM. Two men named each other as partners; no other partners in common were reported. Genomic analysis demonstrated close relatedness of the HL-AZMR isolates and a novel combination of a mosaic- mtr R promoter along with 23S ribosomal RNA mutations that appear to have emerged from circulating strains. Conclusions The close genetic relatedness with limited epidemiologic linkages between patients highlights the challenges of gonorrhea partner investigations and suggests undetected local transmission. Local AST, rapid public health action, and epidemiologic investigations combined with genomic analysis provides a multipronged approach to understanding an outbreak of sexually transmitted disease. [ABSTRACT FROM AUTHOR]

The recent emergence of strains of Neisseria gonorrhoeae associated with treatment failures to ceftriaxone, the foundation of current treatment options, has raised concerns over a future of untreatable gonorrhea. Current global data on gonococcal strains suggest that several lineages, predominately characterized by mosaic penA alleles, are associated with elevated minimum inhibitory concentrations (MICs) to extended spectrum cephalosporins (ESCs). Here we report on whole genome sequences of 813 N. gonorrhoeae isolates collected through the Gonococcal Isolate Surveillance Project in the United States. Phylogenomic analysis revealed that one persisting lineage (Clade A, multi-locus sequence type [MLST] ST1901) with mosaic penA-34 alleles, contained the majority of isolates with elevated MICs to ESCs. We provide evidence that an ancestor to the globally circulating MLST ST1901 clones potentially emerged around the early to mid-20th century (1944, credibility intervals [CI]: 1935–1953), predating the introduction of cephalosporins, but coinciding with the use of penicillin. Such results indicate that drugs with novel mechanisms of action are needed as these strains continue to persist and disseminate globally. Resistance of Neisseria gonorrhoeae to extended spectrum cephalosporins is an increasing concern. Here, the authors conduct whole genome sequencing of isolates from the United States and find that most resistant isolates were associated with a persistent circulating lineage. [ABSTRACT FROM AUTHOR]

Background: Antibiotic-resistant gonorrhoea has been a chronic public health burden since the mid-1930s. Recent emergence of isolates resistant to the current recommended antibiotics for gonorrhoea further magnifies the threat of untreatable gonorrhoea. The lack of new, effective antibiotics highlights the need for better understanding of the population structure of Neisseria gonorrhoeae in order to provide greater insight on how to curtail the spread of antimicrobial-resistant N. gonorrhoeae.Objectives: To explore a potential application of MALDI-TOF MS to differentiate N. gonorrhoeae displaying different levels of susceptibility to the antibiotic azithromycin.Methods: We conducted MALDI-TOF MS using the Bruker Biotyper on 392 N. gonorrhoeae isolates collected through the Gonococcal Isolate Surveillance Project (GISP) and/or the Strengthening the United States Response to Resistant Gonorrhea (SURRG) project. The MALDI-TOF MS spectra were visually analysed to assess the presence of distinctive peak(s). Statistical analysis was performed to assess the relationship between gonococcal isolates with the distinct protein peak and antibiotic susceptibility.Results: In this study, we were able to differentiate N. gonorrhoeae isolates into two distinct subpopulations using MALDI-TOF MS. Isolates were distinguished by the presence or absence of a spectral peak at 11 300 Da. Notably, these two groups exhibited different levels of susceptibility to azithromycin.Conclusions: We have shown that in addition to its ability to identify N. gonorrhoeae, MALDI-TOF MS could also be used to differentiate gonococcal isolates with different levels of susceptibility to azithromycin. [ABSTRACT FROM AUTHOR]

Objectives. To examine long-term gonorrhea prevalence trends from a sentinel surveillance population of young people at elevated risk for gonorrhea. Methods. We analyzed annual cross-sectional urogenital gonorrhea screening data from 191 991 women (2000–2017) and 224 348 men (2003–2017) 16 to 24 years of age entering the National Job Training Program, a US vocational training program. We estimated prevalence among women using an expectation-maximization algorithm incorporated into a logistic regression to account for increases in screening test sensitivity; log-binomial regression was used to estimate prevalence among men. Results. The adjusted gonorrhea prevalence among women followed a U-shaped curve, falling from 2.9% to 1.6% from 2000 through 2011 before rising to 2.7% in 2017. The prevalence among men declined from 1.4% to 0.8% from 2003 through 2017. In the case of both women and men, the prevalence was highest across all study years among those who were Black or American Indian/Alaska Native and those who resided in the South or Midwest. Conclusions. Trends among National Job Training Program enrollees suggest that gonorrhea prevalence is rising among young women while remaining low and steady among young men. [ABSTRACT FROM AUTHOR]

The study reported here used data collected from participants in a Volunteer Income Tax Assistance (VITA) Program to better understand how families anticipated using their Earned Income Tax Credit (EITC) refunds and their use of direct deposit. Data were collected over 3 years. The most common use for a refund by participants was paying bills or debts. One-third of participants planned to use their refund for savings or asset accumulation. Direct deposit participation was not significantly associated with using the EITC refund for savings or asset accumulation, with the exception of one asset, which was a house. [ABSTRACT FROM AUTHOR]