ABSTRACT
Plasmids are diverse extrachromosomal elements significantly that contribute to interspecies dissemination of antimicrobial resistance (AMR) genes. However, within clinically important bacteria, plasmids can exhibit unexpected narrow host ranges, a phenomenon that has scarcely been examined. Here we show that pConj is largely restricted to the human-specific pathogen, Neisseria gonorrhoeae. pConj can confer tetracycline resistance and is central to the dissemination of other AMR plasmids. We tracked pConj evolution from the pre-antibiotic era 80 years ago to the modern day and demonstrate that, aside from limited gene acquisition and loss events, pConj is remarkably conserved. Notably, pConj has remained prevalent in gonococcal populations despite cessation of tetracycline use, thereby demonstrating pConj adaptation to its host. Equally, pConj imposes no measurable fitness costs and is stably inherited by the gonococcus. Its maintenance depends on the co-operative activity of plasmid-encoded Toxin:Antitoxin (TA) and partitioning systems rather than host factors. An orphan VapD toxin encoded on pConj forms a split TA with antitoxins expressed from an ancestral co-resident plasmid or a horizontally-acquired chromosomal island, potentially explaining pConj's limited distribution. Finally, ciprofloxacin can induce loss of this highly stable plasmid, reflecting epidemiological evidence of transient reduction in pConj prevalence when fluoroquinolones were introduced to treat gonorrhoea.
Subject(s)
Gonorrhea , Humans , Gonorrhea/drug therapy , Gonorrhea/genetics , Gonorrhea/epidemiology , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Plasmids/genetics , Neisseria gonorrhoeae/genetics , Drug Resistance, Bacterial/geneticsABSTRACT
Neisseria gonorrhoeae infection is an important public health issue, with an annual global incidence of 87 million. N. gonorrhoeae infection causes significant morbidity and can have serious long-term impacts on reproductive and neonatal health and may rarely cause life-threatening disease. Global rates of N. gonorrhoeae infection have increased over the past 20 years. Importantly, rates of antimicrobial resistance to key antimicrobials also continue to increase, with the United States Centers for Disease Control and Prevention identifying drug-resistant N. gonorrhoeae as an urgent threat to public health. This review summarizes the current evidence for N. gonorrhoeae vaccines, including historical clinical trials, key N. gonorrhoeae vaccine preclinical studies, and studies of the impact of Neisseria meningitidis vaccines on N. gonorrhoeae infection. A comprehensive survey of potential vaccine antigens, including those identified through traditional vaccine immunogenicity approaches, as well as those identified using more contemporary reverse vaccinology approaches, are also described. Finally, the potential epidemiological impacts of a N. gonorrhoeae vaccine and research priorities for further vaccine development are described.
Subject(s)
Anti-Infective Agents , Gonorrhea , Vaccines , Infant, Newborn , Humans , Neisseria gonorrhoeae , Gonorrhea/drug therapy , Gonorrhea/epidemiology , Gonorrhea/prevention & controlABSTRACT
Young men who have sex with men (YMSM) are disproportionately affected by HIV and bacterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet research into the immunologic effects of these infections is typically pursued in siloes. Here, we employed a syndemic approach to understand potential interactions of these infections on the rectal mucosal immune environment among YMSM. We enrolled YMSM aged 18-29 years with and without HIV and/or asymptomatic bacterial STI and collected blood, rectal secretions, and rectal tissue biopsies. YMSM with HIV were on suppressive antiretroviral therapy (ART) with preserved blood CD4 cell counts. We defined 7 innate and 19 adaptive immune cell subsets by flow cytometry, the rectal mucosal transcriptome by RNAseq, and the rectal mucosal microbiome by 16S rRNA sequencing and examined the effects of HIV and STI and their interactions. We measured tissue HIV RNA viral loads among YMSM with HIV and HIV replication in rectal explant challenge experiments among YMSM without HIV. HIV, but not asymptomatic STI, was associated with profound alterations in the cellular composition of the rectal mucosa. We did not detect a difference in the microbiome composition associated with HIV, but asymptomatic bacterial STI was associated with a higher probability of presence of potentially pathogenic taxa. When examining the rectal mucosal transcriptome, there was evidence of statistical interaction; asymptomatic bacterial STI was associated with upregulation of numerous inflammatory genes and enrichment for immune response pathways among YMSM with HIV, but not YMSM without HIV. Asymptomatic bacterial STI was not associated with differences in tissue HIV RNA viral loads or in HIV replication in explant challenge experiments. Our results suggest that asymptomatic bacterial STI may contribute to inflammation particularly among YMSM with HIV, and that future research should examine potential harms and interventions to reduce the health impact of these syndemic infections.
Subject(s)
Chlamydia Infections , Gonorrhea , HIV Infections , Sexual and Gender Minorities , Sexually Transmitted Diseases , Male , Humans , Sexually Transmitted Diseases/complications , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/therapy , Homosexuality, Male , RNA, Ribosomal, 16S , Chlamydia Infections/complications , HIV Infections/complications , Gonorrhea/epidemiologyABSTRACT
BACKGROUND: Data on the epidemiology of sexually transmitted infections (STIs) among transgender women (TGW) with and without human immunodeficiency virus (HIV) are limited. METHODS: We analyzed baseline data collected from a cohort of adult TGW across 6 eastern and southern US cities between March 2018 and August 2020 (n = 1018). Participants completed oral HIV screening, provided self-collected rectal and urogenital specimens for chlamydia and gonorrhea testing, and provided sera specimens for syphilis testing. We assessed associations with ≥1 prevalent bacterial STI using modified Poisson regression. RESULTS: Bacterial STI prevalence was high and differed by HIV status: 32% among TGW with HIV and 11% among those without HIV (demographic-adjusted prevalence ratio = 1.91; 95% confidence interval = 1.39-2.62). Among TGW without HIV, bacterial STI prevalence differed by geographic region, race and ethnicity, and gender identity, and was positively associated with reporting >1 sexual partner, hazardous alcohol use, homelessness, having safety concerns regarding transit to health care, and no prior receipt of gender-affirming health services. Among TGW with HIV, older age was inversely associated with bacterial STI. CONCLUSIONS: TGW had a high prevalence of bacterial STIs. The prevalence and correlates of bacterial STI differed by HIV status, highlighting the unique needs and risks of TGW with and without HIV. Tailored interventions may reduce sexual health-related inequities.
Subject(s)
HIV Infections , Sexually Transmitted Diseases , Transgender Persons , Humans , Female , Adult , Transgender Persons/statistics & numerical data , Prevalence , HIV Infections/epidemiology , Sexually Transmitted Diseases/epidemiology , Young Adult , United States/epidemiology , Adolescent , Middle Aged , Gonorrhea/epidemiology , Male , Sexual Partners , Southeastern United States/epidemiology , Chlamydia Infections/epidemiology , Syphilis/epidemiology , Sexual Behavior , Risk FactorsABSTRACT
BACKGROUND: Antimicrobial resistance (AMR) of Neisseria gonorrhoeae is a threat to public health as strains have developed resistance to antimicrobials available for the treatment of gonorrhea. Whole genome sequencing (WGS) can detect and predict antimicrobial resistance to enhance the control and prevention of gonorrhea. Data on the molecular epidemiology of N. gonorrhoeae is sparse in Zambia. This study aimed to determine the genetic diversity of N. gonorrhoeae isolated from patients attending sexually transmitted infection (STI) clinics in Lusaka, Zambia. METHODS: A cross-sectional study that sequenced 38 N. gonorrhoeae isolated from 122 patients with gonorrhea from 2019 to 2020 was conducted. The AMR profiles were determined by the E-test, and the DNA was extracted using the NucliSens easyMaG magnetic device. Whole genome sequencing was performed on the Illumina NextSeq550 platform. The Bacterial analysis pipeline (BAP) that is readily available at: https://cge.cbs.dtu.dk/services/CGEpipeline-1.1 was used for the identification of the species, assembling the genome, multi-locus sequence typing (MLST), detection of plasmids and AMR genes. Phylogeny by single nucleotide polymorphisms (SNPs) was determined with the CCphylo dataset. RESULTS: The most frequent STs with 18.4% of isolates each were ST7363, ST1921 and ST1582, followed by ST1583 (13%), novel ST17026 (7.9%), ST1588 (7.9%), ST1596 (5.3%), ST11181 (5.3%), ST11750 (2.6/%) and ST11241 (2.6%) among the 38 genotyped isolates. The blaTeM-1B and tetM (55%) was the most prevalent combination of AMR genes, followed by blaTeM-1B (18.4%), tetM (15.8%), and the combination of blaTeM-1B, ermT, and tetL was 2.6% of the isolates. The AMR phenotypes were predicted in ciprofloxacin, penicillin, tetracycline, azithromycin, and cefixime. The combination of mutations 23.7% was gryA (S91F), parC (E91G), ponA (L421) and rpsJ (V57M), followed by 18.4% in gyrA (S91F), ponA (L421P), rpsJ (V57M), and 18.4% in gyrA (D95G, S91F), ponA (L421P), and rpsJ (V57M). The combinations in gyrA (D95G, S91F) and rpsJ (V57M), and gyrA (D95G, S91F), parC (E91F), ponA (L421P) and rpsJ (V57M) were 13.2% each of the isolates. Plasmid TEM-1 (84.2%), tetM (15.8%), and gonococcal genetic island (GGI) was detected in all isolates. CONCLUSION: This study revealed remarkable heterogeneity of N. gonorrhoeae with blaTEM-1, tetM, ponA, gyrA, and parC genes associated with high resistance to penicillin, tetracycline, and ciprofloxacin demanding revision of the standard treatment guidelines and improved antimicrobial stewardship in Zambia.
Subject(s)
Anti-Bacterial Agents , Gonorrhea , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Neisseria gonorrhoeae/genetics , Gonorrhea/drug therapy , Gonorrhea/epidemiology , Gonorrhea/microbiology , Multilocus Sequence Typing , Zambia/epidemiology , Cross-Sectional Studies , Drug Resistance, Bacterial/genetics , Tetracycline , Ciprofloxacin , Penicillins , Microbial Sensitivity TestsABSTRACT
After lifting of all COVID-19 preventive measures in England in July 2021, marked, widespread increases in gonorrhea diagnoses, but not testing numbers, were observed, particularly in persons 15-24 years of age. Continued close surveillance and public health messaging to young persons are needed to control and prevent gonorrhea transmission.
Subject(s)
COVID-19 , Gonorrhea , Humans , COVID-19/prevention & control , Gonorrhea/epidemiology , Gonorrhea/prevention & control , SARS-CoV-2 , Public Health , England/epidemiologyABSTRACT
We reviewed data obtained in October 2021-May 2023 from youth who reported a history of sexual activity upon admission to 1 of 12 juvenile justice facilities in Utah, USA, that offered screening for Chlamydia trachomatis and Neisseria gonorrhoeae. Urinalysis revealed C. trachomatis positivity of 10.77%, N. gonorrhoeae positivity of 1.08%, and coinfection C. trachomatis N. gonorrhoeae) of 0.90%. Prevalence of infection was similar for youths in rural and urban facilities. A total of 12.01% of those identifying as male and 14.01% of those identifying as female tested positive for C. trachomatis, N. gonorrhoeae, or coinfection. Of young adults who tested positive, 74.65% received their results while incarcerated, all of whom accepted treatment. Our research underscores the feasibility of providing prompt C. trachomatis/N. gonorrhoeae screening and treatment in juvenile correctional facilities. The pervasiveness of infection emphasizes the urgent need for early identification and treatment for C. trachomatis and N. gonorrhoeae in incarcerated youth nationwide.
Subject(s)
Chlamydia Infections , Coinfection , Gonorrhea , Young Adult , Adolescent , Male , Female , Humans , Gonorrhea/diagnosis , Gonorrhea/epidemiology , Gonorrhea/prevention & control , Chlamydia Infections/diagnosis , Chlamydia Infections/epidemiology , Utah/epidemiology , Coinfection/epidemiology , Neisseria gonorrhoeae , Chlamydia trachomatis , Correctional Facilities , Prevalence , Mass Screening/methodsABSTRACT
To determine antimicrobial susceptibility of Neisseria gonorrhoeae, we analyzed phenotypes and genomes of 72 isolates collected in Cambodia in 2023. Of those, 9/72 (12.5%) were extensively drug resistant, a 3-fold increase from 2022. Genomic analysis confirmed expansion of newly emerging resistant clones and ongoing resistance emergence across new phylogenetic backbones.
Subject(s)
Anti-Bacterial Agents , Gonorrhea , Microbial Sensitivity Tests , Neisseria gonorrhoeae , World Health Organization , Neisseria gonorrhoeae/drug effects , Neisseria gonorrhoeae/genetics , Cambodia/epidemiology , Humans , Gonorrhea/microbiology , Gonorrhea/epidemiology , Gonorrhea/drug therapy , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Phylogeny , Male , Female , AdultABSTRACT
Ceftriaxone-resistant Neisseria gonorrhoeae FC428-like strains have disseminated across the Asia-Pacific region, with a continuous rise in prevalence during 2015-2022. To mitigate the effect of these strains, we advocate for enhanced molecular diagnostics, expanded surveillance networks, and a regionally coordinated effort to combat the global spread of FC428-like strains.
Subject(s)
Anti-Bacterial Agents , Ceftriaxone , Drug Resistance, Bacterial , Gonorrhea , Neisseria gonorrhoeae , Neisseria gonorrhoeae/drug effects , Neisseria gonorrhoeae/genetics , Ceftriaxone/pharmacology , Humans , Gonorrhea/microbiology , Gonorrhea/epidemiology , Gonorrhea/drug therapy , Asia/epidemiology , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Prevalence , History, 21st CenturyABSTRACT
BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.
Subject(s)
Anti-Bacterial Agents , Cost-Benefit Analysis , Gonorrhea , Homosexuality, Male , Quality-Adjusted Life Years , Humans , Gonorrhea/drug therapy , Gonorrhea/epidemiology , Gonorrhea/economics , Gonorrhea/diagnosis , Male , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/economics , Prevalence , United States/epidemiology , Neisseria gonorrhoeae/drug effects , Drug Resistance, Bacterial , Cost-Effectiveness AnalysisABSTRACT
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.
Subject(s)
Gonorrhea , Sexual and Gender Minorities , Male , Humans , United States/epidemiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Gonorrhea/drug therapy , Gonorrhea/epidemiology , Ceftriaxone/therapeutic use , Ceftriaxone/pharmacology , Homosexuality, Male , Longevity , Neisseria gonorrhoeae , Microbial Sensitivity Tests , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Tetracycline/pharmacology , Tetracycline/therapeutic use , Drug Resistance, BacterialABSTRACT
PURPOSE OF REVIEW: The rise in antimicrobial resistance in several STI pathogens such as Neisseria gonorrhoeae has become a public health threat as only one first-line treatment remains. Reducing screening interval for gonorrhoea and chlamydia in high-prevalence populations has been proposed to address antimicrobial stewardship, but this remains controversial. This review aimed to revisit the epidemiology of infections at the oropharynx and review the current screening recommendations and treatment guidelines in different populations. RECENT FINDINGS: Emerging evidence suggests that the oropharynx is the primary anatomical site for gonorrhoea transmission but maybe not for chlamydia transmission. Most international guidelines recommend 3-monthly oropharyngeal gonorrhoea and chlamydia screening for high-prevalence populations (e.g. men who have sex with men) but not low-prevalence populations (e.g. heterosexuals) given the clinical and public health benefits of screening in low-prevalence populations are still unclear. Doxycycline remains the first-line treatment for oropharyngeal chlamydia in most guidelines. However, some countries have moved from dual therapy (ceftriaxone and azithromycin) to monotherapy (ceftriaxone) for oropharyngeal gonorrhoea treatment to address antimicrobial stewardship. SUMMARY: The transmission of gonorrhoea and chlamydia is still not fully understood. Further work will be required to evaluate the benefits and harms of reducing screening in high-prevalence populations.
Subject(s)
Chlamydia Infections , Gonorrhea , Sexual and Gender Minorities , Male , Humans , Gonorrhea/diagnosis , Gonorrhea/drug therapy , Gonorrhea/epidemiology , Homosexuality, Male , Ceftriaxone/therapeutic use , Neisseria gonorrhoeae , Chlamydia Infections/diagnosis , Chlamydia Infections/drug therapy , Chlamydia Infections/epidemiology , OropharynxABSTRACT
INTRODUCTION: Antimicrobial resistance in Neisseria gonorrhoeae compromises gonorrhoea treatment and rapid antimicrobial susceptibility testing (AST) would be valuable. We have developed a rapid and accurate flow cytometry method (FCM) for AST of gonococci. METHODS: The 2016 WHO gonococcal reference strains, and WHO Q, R and S (nâ=â17) were tested against seven clinically relevant antibiotics (ceftriaxone, cefixime, azithromycin, spectinomycin, ciprofloxacin, tetracycline and gentamicin). After 4.5 h incubation of inoculated broth, the fluorescent dye Syto™ 9 was added, followed by FCM analysis. After gating, the relative remaining population of gonococci, compared with unexposed growth control samples, was plotted against antimicrobial concentration, followed by non-linear curve regression analysis. Furthermore, the response at one single concentration/tested antibiotic was evaluated with the intention to use as a screening test for detection of resistant gonococci. RESULTS: A dose-dependent response was seen in susceptible isolates for all tested antimicrobials. There was a clear separation between susceptible/WT and resistant/non-WT isolates for ceftriaxone, cefixime, spectinomycin, ciprofloxacin and tetracycline. In contrast, for azithromycin, only high-level-resistant isolates were distinguished, while resistant isolates with MICs of 4 mg/L were indistinguishable from WT (MICâ≤â1 mg/L) isolates. For gentamicin, all tested 17 isolates were WT and FCM analysis resulted in uniform dose-response curves. Using a single antibiotic concentration and a 50% remaining cell population cut-off, the overall sensitivity and specificity for resistance detection were 93% and 99%, respectively. CONCLUSIONS: By providing results in <5 h for gonococcal isolates, FCM-based AST can become a rapid screening method for antimicrobial resistance or antimicrobial susceptibility in gonococci.
Subject(s)
Anti-Infective Agents , Gonorrhea , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Neisseria gonorrhoeae , Azithromycin/pharmacology , Ceftriaxone/pharmacology , Spectinomycin/pharmacology , Cefixime/pharmacology , Flow Cytometry , Drug Resistance, Bacterial , Gonorrhea/epidemiology , Anti-Infective Agents/pharmacology , Ciprofloxacin/pharmacology , Tetracycline/pharmacology , Microbial Sensitivity Tests , Gentamicins/pharmacologyABSTRACT
BACKGROUND: Antimicrobial resistance in Neisseria gonorrhoeae is a global public health concern. Tetracycline resistance (TetR) increased from 39.4% to 75.2% between 2016 and 2021 in N. gonorrhoeae isolates collected through national surveillance in England, despite the absence of use of tetracyclines for the treatment of gonorrhoea. OBJECTIVES: We investigated whether there was correlation between bacterial sexually transmitted infection (STI) tests performed and treatment with antimicrobials, with increased TetR in N. gonorrhoeae. METHODS: We examined correlations between bacterial STI tests, antimicrobial treatment and TetR in N. gonorrhoeae, using national surveillance data from three large sexual health services (SHS) in London during 2016-20. Doxycycline prescribing data and antibiograms of a non-STI pathogen from distinct patient groups (sexual health, obstetric and paediatric), at a large London hospital, were analysed to identify if doxycycline use in SHS was associated with resistance in a non-STI organism. RESULTS: A substantial increase in TetR was observed, particularly in isolates from gay, bisexual and other MSM (GBMSM). Strong positive correlations were observed exclusively in GBMSM between N. gonorrhoeae TetR and both bacterial STI tests (râ=â0.97, Pâ=â0.01) and antimicrobial treatment (râ=â0.87, Pâ=â0.05). Doxycycline prescribing increased dramatically during the study period in SHS. Prevalence of TetR in Staphylococcus aureus was higher in isolates sourced from SHS attendees than those from other settings. CONCLUSIONS: Frequent screening of GBMSM at higher risk of STIs, such as those on pre-exposure prophylaxis (PrEP) leading to/and increased use of doxycycline for the treatment of diagnosed infections, may account for the increase in TetR in N. gonorrhoeae.
Subject(s)
Anti-Bacterial Agents , Doxycycline , Gonorrhea , Microbial Sensitivity Tests , Neisseria gonorrhoeae , Tetracycline Resistance , Neisseria gonorrhoeae/drug effects , Neisseria gonorrhoeae/isolation & purification , Humans , Gonorrhea/microbiology , Gonorrhea/epidemiology , Gonorrhea/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , England/epidemiology , Male , Female , Doxycycline/therapeutic use , Doxycycline/pharmacology , Adult , London/epidemiology , Tetracycline/pharmacology , Tetracycline/therapeutic useABSTRACT
OBJECTIVES: Regular quality-assured WGS with antimicrobial resistance (AMR) and epidemiological data of patients is imperative to elucidate the shifting gonorrhoea epidemiology, nationally and internationally. We describe the dynamics of the gonococcal population in 11 cities in Brazil between 2017 and 2020 and elucidate emerging and disappearing gonococcal lineages associated with AMR, compare to Brazilian WGS and AMR data from 2015 to 2016, and explain recent changes in gonococcal AMR and gonorrhoea epidemiology. METHODS: WGS was performed using Illumina NextSeq 550 and genomes of 623 gonococcal isolates were used for downstream analysis. Molecular typing and AMR determinants were obtained and links between genomic lineages and AMR (determined by agar dilution/Etest) examined. RESULTS: Azithromycin resistance (15.6%, 97/623) had substantially increased and was mainly explained by clonal expansions of strains with 23S rRNA C2611T (mostly NG-STAR CC124) and mtr mosaics (mostly NG-STAR CC63, MLST ST9363). Resistance to ceftriaxone and cefixime remained at the same levels as in 2015-16, i.e. at 0% and 0.2% (1/623), respectively. Regarding novel gonorrhoea treatments, no known zoliflodacin-resistance gyrB mutations or gepotidacin-resistance gyrA mutations were found. Genomic lineages and sublineages showed a phylogenomic shift from sublineage A5 to sublineages A1-A4, while isolates within lineage B remained diverse in Brazil. CONCLUSIONS: Azithromycin resistance, mainly caused by 23S rRNA C2611T and mtrD mosaics/semi-mosaics, had substantially increased in Brazil. This mostly low-level azithromycin resistance may threaten the recommended ceftriaxone-azithromycin therapy, but the lack of ceftriaxone resistance is encouraging. Enhanced gonococcal AMR surveillance, including WGS, is imperative in Brazil and other Latin American and Caribbean countries.
Subject(s)
Anti-Bacterial Agents , Azithromycin , Drug Resistance, Bacterial , Gonorrhea , Microbial Sensitivity Tests , Neisseria gonorrhoeae , Whole Genome Sequencing , Neisseria gonorrhoeae/genetics , Neisseria gonorrhoeae/drug effects , Neisseria gonorrhoeae/classification , Brazil/epidemiology , Humans , Gonorrhea/microbiology , Gonorrhea/epidemiology , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/genetics , Azithromycin/pharmacology , Male , Genome, Bacterial , Female , Adult , Molecular Epidemiology , Young Adult , Genomics , RNA, Ribosomal, 23S/genetics , Middle Aged , Ceftriaxone/pharmacology , Adolescent , Multilocus Sequence Typing , Cefixime/pharmacologyABSTRACT
Numbers of infections with Neisseria gonorrhoeae are among the top three sexually transmitted infections (STI) worldwide. In addition, the emergence and spread of antimicrobial resistance (AMR) in Neisseria gonorrhoeae pose an important public-health issue. The integration of genomic, phenotypic and epidemiological data to monitor Neisseria gonorrhoeae fosters our understanding of the emergence and spread of AMR in Neisseria gonorrhoeae and helps to inform therapy guidelines and intervention strategies. Thus, the Gonococcal resistance surveillance (Go-Surv-AMR) was implemented at the Robert Koch Institute in Germany in 2021 to obtain molecular, phenotypic and epidemiological data on Neisseria gonorrhoeae isolated in Germany. Here, we describe the structure and aims of Go-Surv-AMR. Furthermore, we point out future directions of Go-Surv-AMR to improve the integrated genomic surveillance of Neisseria gonorrhoeae. In this context we discuss current and prospective sequencing approaches and the information derived from their application. Moreover, we highlight the importance of combining phenotypic and WGS data to monitor the evolution of AMR in Neisseria gonorrhoeae in Germany. The implementation and constant development of techniques and tools to improve the genomic surveillance of Neisseria gonorrhoeae will be important in coming years.
Subject(s)
Gonorrhea , Neisseria gonorrhoeae , Humans , Neisseria gonorrhoeae/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Prospective Studies , Drug Resistance, Bacterial/genetics , Microbial Sensitivity Tests , Gonorrhea/drug therapy , Gonorrhea/epidemiology , Germany/epidemiologyABSTRACT
OBJECTIVES: Our objective was to obtain long-term data on the incidence of sexually transmitted infections (STIs) and their association with behavioural factors after widespread pre-exposure prophylaxis (PrEP) implementation. METHODS: This was a time-to-event analysis of a national PrEP cohort in Switzerland (SwissPrEPared study). Participants were people without HIV interested in taking PrEP with at least two STI screening visits. Primary outcomes were incidence rate of gonorrhoea, chlamydia, and syphilis. The association between behavioural factors and STI diagnosis was expressed using hazard ratios. We adjusted for testing frequency and calendar year. RESULTS: This analysis included 3907 participants enrolled between April 2019 and April 2022, yielding 3815.7 person-years of follow-up for gonorrhoea (15 134 screenings), 3802.5 for chlamydia (15 141 screenings), and 3858.6 for syphilis (15 001 screenings). The median age was 39 years (interquartile range [IQR] 32-47), 93.8% (n = 3664) identified as men who have sex with men (MSM). The incidence was 22.8 (95% confidence interval [CI] 21.3-24.4) per 100 person-years for gonorrhoea, 26.3 (95% CI 24.7-28.0) for chlamydia, and 4.4 (95% CI 3.8-5.1) for syphilis. Yearly incidence rates decreased between 2019 (all bacterial STIs: 81.6; 95% CI 59.1-109.9) and 2022 (all bacterial STIs: 49.8; 95% CI 44.6-55.3). Participants reporting chemsex substance use were at higher risk of incident STIs, as were those reporting multiple sexual partners. Younger age was associated with a higher risk of gonorrhoea and chlamydia. CONCLUSIONS: Incidence rates of bacterial STIs decreased over time. Young MSM, those with multiple partners, and those using chemsex substances were at increased risk of STIs.
Subject(s)
Gonorrhea , HIV Infections , Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Sexually Transmitted Diseases, Bacterial , Sexually Transmitted Diseases , Syphilis , Male , Humans , Adult , Incidence , Homosexuality, Male , Syphilis/epidemiology , Gonorrhea/epidemiology , HIV Infections/epidemiology , HIV Infections/prevention & control , Sexually Transmitted Diseases/epidemiology , Sexually Transmitted Diseases/prevention & control , Sexually Transmitted Diseases, Bacterial/epidemiologyABSTRACT
To investigate the progress of disparities in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), gonorrhea, and syphilis among children and adolescents aged 6-22 years in China during 2013-2021. A total of 614 325 cases data were extracted from the Chinese Information System for Infectious Diseases Control and Prevention during 2013-2021. Puberty health education data were drew from the Student Health Surveillance in 2021. Disparity patterns and average annual percentage changes (AAPCs) in sexually transmitted infections (STIs) incidence or new cases in China were examined using descriptive statistics and joinpoint regression. The incidence across 345 cities was stratified by gross domestic product (GDP). Between 2013 and 2021, there were 614 325 reported cases of HIV/AIDS, gonorrhea, and syphilis among children and adolescents aged 6-22, with an annual average incidence of 24.0967 per 100 000. The expansion of HIV/AIDS has halted, yet the surge in gonorrhea and syphilis remains notably pronounced. The ratio of male to female AIDS incidence increased from 2.75 (2.60, 2.90) to 7.13 (6.68, 7.62), but that of syphilis changed from 0.33 (0.32, 0.34) to 0.56 (0.55, 0.57). Students and out-of-school individuals aged 13-15 experienced a notably high increase in STI cases, surpassing other age groups, with an average annual percentage increase of 29.2% and 26.3%, respectively. Nonstudents consistently had a higher incidence rate than students, with an IRR reaching 31.80 (31.24, 32.37) in 2021. A noticeable clustering pattern of new cases emerged in the southeastern region of the Heihe-Tengchong line, extending inland from the coastal areas. Districts and counties with lower rates of puberty sexual health education tended to have higher average STI incidence rates. At the prefecture and city levels, there was a noticeable upward trend on average STI incidence rates in cities with per capita GDPs. Strategies to address those disparities include promoting equitable health education, and widespread sexual health education, particularly in areas with limited access to education and experiencing rapid economic development. The effectiveness of sexual health education intervention needs to be further evaluated in well-designed studies.
Subject(s)
Gonorrhea , Sexually Transmitted Diseases , Humans , Adolescent , Male , Female , China/epidemiology , Incidence , Child , Young Adult , Gonorrhea/epidemiology , Sexually Transmitted Diseases/epidemiology , HIV Infections/epidemiology , Syphilis/epidemiology , Acquired Immunodeficiency Syndrome/epidemiology , Epidemiological MonitoringABSTRACT
OBJECTIVES: We aimed to determine the prevalence of anorectal Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) among transgender women in Brazil, and to assess the performance and costs of various approaches for the diagnosis and management of anorectal NG/CT. METHODS: TransOdara was a multicentric, cross-sectional STI prevalence study among 1317 transgender women conducted in five capital cities representing all Brazilian regions. Participants aged >18 years were recruited using respondent-driven sampling (RDS), completed an interviewer-led questionnaire, offered an optional physical examination and given choice between self-collected or provider-collected samples for NG/CT testing. Performance and cost indicators of predetermined management algorithms based on the WHO recommendations for anorectal symptoms were calculated. RESULTS: Screening uptake was high (94.3%) and the estimated prevalence of anorectal NG, CT and NG and/or CT was 9.1%, 8.9% and 15.2%, respectively. Most detected anorectal NG/CT infections were asymptomatic (NG: 87.6%, CT: 88.9%), with a limited number of participants reporting any anorectal symptoms (9.1%). Of those who permitted anal examination, few had clinical signs of infection (13.6%). Sensitivity of the tested algorithms ranged from 1.4% to 5.1% (highest for treatment based on the reported anorectal discharge or ulcer and receptive anal intercourse (RAI) in the past 6 months) and specificity from 98.0% to 99.3% (highest for treatment based on the reported anorectal discharge with clinical confirmation or report of RAI). The estimated cost-per-true case of anorectal NG/CT infection treated varied from lowest providing treatment for anorectal discharge syndrome based on the reported RAI ($2.70-4.28), with algorithms including clinical examinations decreasing cost-effectiveness. CONCLUSIONS: High prevalence of mostly asymptomatic anorectal NG and CT was observed among Brazilian transgender women. Multi-site NG/CT screening should be offered to transgender women. Where diagnostic testing capacity is limited, syndromic management for those presenting with anorectal symptoms is recommended.
Subject(s)
Chlamydia Infections , Gastrointestinal Diseases , Gonorrhea , Transgender Persons , Humans , Female , Male , Gonorrhea/diagnosis , Gonorrhea/epidemiology , Gonorrhea/prevention & control , Brazil/epidemiology , Prevalence , Cross-Sectional Studies , Chlamydia Infections/diagnosis , Chlamydia Infections/epidemiology , Chlamydia Infections/prevention & control , Neisseria gonorrhoeae , Chlamydia trachomatis , Homosexuality, MaleABSTRACT
BACKGROUND: People who report sexual assault express concerns regarding contracting sexually transmitted infection (STI); however, published literature regarding the risk of STI transmission in this context is sparse. METHOD: We audited STI and blood-borne virus (BBV) testing at a forensic and medical sexual assault care service in the Australian Capital Territory between 2004 and 2022. Eligibility for testing among 1928 presentations was defined based on risk (eg, reported penetration). Testing at presentation included chlamydia and gonorrhoea 1850, syphilis and BBV 1472, and after 2-6 weeks, 890 out of 1928 (46.2%) and after 3 months 881 out of 1928 (45.7%), respectively. RESULTS: At presentation, 100 out of 1928 (5.2%) individuals were diagnosed with chlamydia, of those, 95 out of 1799 (5.3%) were female, and 5 out of 121 (4.1%) were male. Gonorrhoea was diagnosed in 7 out of 1920 (0.4%), 5 out of 95 female and 2 out of 5 male. Hepatitis B, which was all pre-existing, was diagnosed in 5 out of 1799 (0.3%). Overall, chlamydia prophylaxis was given to 203 out of 1928 (10.5%) and HIV post-exposure prophylaxis to 141 out of 1928 (7.3%).At 2-6 weeks of follow-up, 10 out of 890 (1.1%) individuals were diagnosed with chlamydia, with no gonorrhoea diagnosed. There were no cases of syphilis, hepatitis B or HIV diagnosed at 3-month serology testing in 881 individuals. Chlamydia detection at follow-up was more common in the group aged 15-29 years. Of those provided with chlamydia prophylaxis, 203 out of 1928, only 16 out of 203 (7.9%) were diagnosed with chlamydia. CONCLUSIONS: The offer of STI testing is almost universally accepted by individuals presenting for post-sexual assault care. There were no identifiable factors to justify the routine use of chlamydia prophylaxis. STI testing provided an opportunity for screening and should remain part of the clinical care of people who report sexual assault.