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UNLABELLED: Gonorrhea, caused by the bacterium Neisseria gonorrhoeae (Gc), is characterized by neutrophilic influx to infection sites. Gc has developed mechanisms to resist killing by neutrophils that include modifications to its surface lipooligosaccharide (LOS). One such LOS modification is sialylation: Gc sialylates its terminal LOS sugars with cytidine-5-monophosphate-N-acetylneuraminic acid, which is scavenged from the host using LOS sialyltransferase (Lst) since Gc cannot make its sialic acid. Sialylation enables sensitive strains of Gc to resist complement-mediated killing in a serum-dependent manner. However, little is known about the contribution of sialylation to complement-independent, direct Gc-neutrophil interactions. In the absence of complement, we found sialylated Gc expressing opacity-associated (Opa) proteins decreased the oxidative burst and granule exocytosis from primary human neutrophils. In addition, sialylated Opa+ Gc survived better than vehicle treated or Δlst Gc when challenged with neutrophils. However, Gc sialylation did not significantly affect Opa-dependent association with or internalization of Gc by neutrophils. Previous studies have implicated sialic acid-binding immunoglobulin-type lectins (Siglecs) in modulating neutrophil interactions with sialylated Gc. Blocking neutrophil Siglecs with antibodies that bind to their extracellular domains eliminated the ability of sialylated Opa+ Gc to suppress the oxidative burst and resist neutrophil killing. These findings highlight a new role for sialylation in Gc evasion of human innate immunity, with implications for the development of vaccines and therapeutics for gonorrhea. IMPORTANCE: Neisseria gonorrhoeae, the bacterium that causes gonorrhea, is an urgent global health concern due to increasing infection rates, widespread antibiotic resistance, and its ability to thwart protective immune responses. The mechanisms by which Gc subverts protective immune responses remain poorly characterized. One way N. gonorrhoeae evades human immunity is by adding sialic acid that is scavenged from the host onto its lipooligosaccharide, using the sialyltransferase Lst. Here, we found that sialylation enhances N. gonorrhoeae survival from neutrophil assault and inhibits neutrophil activation, independently of the complement system. Our results implicate bacterial binding of sialic acid-binding lectins (Siglecs) on the neutrophil surface, which dampens neutrophil antimicrobial responses. This work identifies a new role for sialylation in protecting N. gonorrhoeae from cellular innate immunity, which can be targeted to enhance the human immune response in gonorrhea.

Introduction: Bacterial urinary tract infections (UTI) and some sexually transmitted infections (STI) can have overlapping signs and symptoms or nonspecific findings, such as pyuria on urinalysis. Furthermore, results from the urine culture and the nucleic acid amplification test for an STI may not be available during the clinical encounter. We sought to determine whether gonorrhea, chlamydia, and trichomoniasis are associated with bacteriuria, information that might aid in the differentiation of STIs and UTIs.Methods: We used multinomial logistic regression to analyze 9,650 encounters of female patients whowere aged ≥18 years and who underwent testing for STIs. The ED encounters took place from April 18, 2014–March 7, 2017. We used a multivariable regression analysis to account for patient demographics, urinalysis findings, vaginal wet-mount results, and positive or negative (or no) findings from the urine culture and testing for Neisseria gonorrhoeae, Chlamydia trachomatis, or Trichomonas vaginalis.Results: In multivariable analysis, infection with T vaginalis, N gonorrhoeae, or C trachomatis was not associated with having a urine culture yielding 10,000 or more colony-forming units per mililiter (CFU/mL) of bacteria compared with a urine culture yielding less than 10,000 CFU/mL or no urine culture obtained. The diagnosis of a UTI in the ED was not associated with having a urine culture yielding 10,000 or more CFU/mL compared with a urine culture yielding less than 10,000 CFU/mL.Conclusion: After adjusting for covariates, no association was observed between urine culture results and testing positive for trichomoniasis, gonorrhea, or chlamydia. Our results suggest that having a concurrent STI and bacterial UTI is unlikely.

Introduction: The incidence of sexually transmitted infections (STI) increased in the United States between 2017–2021. There is limited data describing STI co-testing practices and the prevalence of STI co-infections in emergency departments (ED). In this study, we aimed to describe the prevalence of co-testing and co-infection of HIV, hepatitis C virus (HCV), syphilis, gonorrhea, and chlamydia, in a large, academic ED.Methods: This was a single-center, retrospective cross-sectional study of ED patients tested for HIV, HCV, syphilis, gonorrhea or chlamydia between November 27, 2018–May 26, 2019. In 2018, the study institution implemented an ED-based infectious diseases screening program in which any patient being tested for gonorrhea/chlamydia was eligible for opt-out syphilis screening, and any patient 18–64 years who was having blood drawn for any clinical purpose was eligible for opt-out HIV and HCV screening. Weanalyzed data from all ED patients ≥13 years who had undergone STI testing. The outcomes of interest included prevalence of STI testing/co-testing and the prevalence of STI infection/co-infection. We describe data with simple descriptive statistics.Results: During the study period there were 30,767 ED encounters for patients ≥13 years (mean age: 43 ± 14 years, 52% female), and 7,866 (26%) were tested for at least one of HIV, HCV, syphilis, gonorrhea, or chlamydia. We observed the following testing frequencies (and prevalence of infection): HCV, 7,539 (5.0%); HIV, 7,359 (0.9%); gonorrhea, 574 (6.1%); chlamydia, 574 (9.8%); and syphilis, 420 (10.5%). Infectious etiologies with universal testing protocols (HIV and HCV) made up the majority of STI testing. In patients with syphilis, co-infection with chlamydia (21%, 9/44) and HIV (9%, 4/44) was high. In patients with gonorrhea, co-infection with chlamydia (23%, 8/35) and syphilis (9%, 3/35) was high, and in patients with chlamydia, co-infection with syphilis (16%, 9/56) and gonorrhea (14%, 8/56) was high. Patients with HCV had low co-infection proportions (

BACKGROUND: Neisseria gonorrheae and Chlamydia trachomatis are associated with mucosal inflammation and human immunodeficiency virus 1 (HIV-1) transmission. We assessed levels of inflammatory cytokines in men who have sex with men (MSM) with and without rectal gonorrhea and/or chlamydia in Lima, Peru. METHODS: We screened 605 MSM reporting condomless receptive anal intercourse for rectal N. gonorrheae/C. trachomatis using nucleic acid testing. We identified 101 cases of gonorrhea and/or chlamydia and randomly selected 50 N. gonorrheae/C. trachomatis positive cases and matched 52 negative controls. We measured levels of IL-1β, IL-6, IL-8, and TNF-α in rectal secretions. Tests for HIV-1, rectal N. gonorrheae/C. trachomatis, and mucosal cytokines were repeated after 3 and 6 months. Cytokine levels in cases and uninfected controls were compared using Wilcoxon rank-sum tests and linear regression. RESULTS: MSM with gonorrhea/chlamydia had elevated levels of all cytokines in rectal mucosa compared with matched controls (all P values .05). DISCUSSION: Rectal gonorrhea/chlamydia infection is associated with transient mucosal inflammation and cytokine recruitment. Our data provide proof of concept for rectal sexually transmitted infection screening as an HIV prevention strategy for MSM. Clinical Trials Registration. NCT03010020.

BACKGROUND: A rapid and affordable point-of-care test is a priority for Neisseria gonorrhoeae control. WHO and Foundation for Innovative New Diagnostics (FIND) have a target product profile for a non-molecular N gonorrhoeae rapid point-of-care test that requires a clinical sensitivity of greater than 80% and a specificity over 95% to be considered useful in syndromic management; test turnaround time should be 30 min or under, and the test should cost less than US$3. A novel lateral flow assay (LFA) was developed to achieve that profile. METHODS: In this cross-sectional study we evaluated the performance of the novel N gonorrhoeae lateral flow assay (NG-LFA) at the primary health-care level in South Africa. Male patients with urethral discharge syndrome and female patients with vaginal discharge syndrome were recruited from five primary health-care facilities in the Buffalo City Metropolitan Municipality health district of South Africa. First-void urine specimens and nurse-collected vaginal swabs were tested in-facility with the NG-LFA and Xpert CT/NG PCR assay. N gonorrhoeae multi-antigen sequence typing (NG-MAST) was performed on all LFA positive specimens. FINDINGS: Between March 7, and Sept 19, 2022, we enrolled 200 male patients with urethral discharge and 200 female patients with vaginal discharge. The median age of male patients was 24 years (IQR 21-31 years), and the median age of female patients was 25 years (IQR 21-32 years). In addition, 23 male patients and 12 female patients who presented at the facility with a partner notification slip were enrolled of whom one (4%) and five (42%) were symptomatic, respectively. NG-LFA and Xpert results were available for all participants. In urine specimens, NG-LFA sensitivity was 96·1% (Wilson 95% CI 91·2-98·3; 123 LFA-positive among 128 PCR-positive specimens) and 91·7% in vaginal swab specimens (78·2-97·1; 33 LFA-positive among 36 PCR-positive). The specificity was 97·2% in urine specimens (90·4-99·2; 70 LFA-negative among 72 PCR-negative) and 96·3% in vaginal specimens (92·2-98·3; 158 LFA-negative among 164 PCR-negative). In 156 LFA-positive specimens, NG-MAST showed 93 different sequence types. INTERPRETATION: The novel NG-LFA had excellent clinical sensitivity and specificity in symptomatic male and female patients. The test met the optimal requirement for sensitivity and the minimal requirement for specificity specified in the target product profile. NG-LFA could provide an important tool to optimise clinical management and reduce excess antibiotic use in settings without direct access to laboratory testing. FUNDING: Global Antimicrobial Resistance Innovation Fund (GAMRIF) via FIND and National Institutes of Health.

While ceftriaxone remains the first-line treatment for gonorrhea, the US Centers for Disease Control and Prevention recommended cefixime as a second-line treatment in 2021. We tested 1176 Neisseria gonorrhoeae isolates among clients attending the Melbourne Sexual Health Centre in 2021 and 2022. The prevalence of cefixime resistance was 6.3% (74/1176), azithromycin resistance was 4.9% (58/1176), and ceftriaxone resistance was 0% (0/1176). Cefixime resistance was highest among women (16.4%, 10/61), followed by men who have sex with women (6.4%, 7/109) and men who have sex with men (5.8%, 57/982). The prevalence of cefixime-resistant N gonorrhoeae exceeds the threshold of the 5% resistance level recommended by the World Health Organization; thus, cefixime treatment would have limited benefits in Australia. [ABSTRACT FROM AUTHOR]

Introduction: This research aimed to explore the determinants of cervical HPV infection and evaluate how cervical cancer screening outcomes influence sexual functioning and anxiety among women across three provinces in China. Methods: Study participants were categorized into HPV-positive or HPV-negative groups, after which they completed the General Characteristics Questionnaire and the SAS Anxiety Scale. The HPV-positive cohort was further divided into four subgroups: Subgroup 1 consisted of individuals with HPV types 16 or 18 but no cytological abnormalities. Subgroup 2 included those with cytological abnormalities and infections with HPV types 16 or 18. Subgroup 3 included participants infected with high-risk HPV types other than 16 and 18, who did not show cytological abnormalities, while Subgroup 4 encompassed individuals with both cytological abnormalities and infections with high-risk HPV types other than 16 and 18. All participants were assessed using the Female Sexual Function Index Scale (FSFI), which measures sexual function across these subgroups. Results: A total of 531 questionnaires were analyzed. Logistic regression identified several risk factors for HPV infection, including manual labor, service occupations, other occupations, low- and middle-income groups, and cervical columnar epithelial ectasia, as well as an increase in the number of previous sexual partners. Conversely, protective factors included condom use during sexual activity and mutual genital hygiene prior to intercourse. The incidence of lower genital tract infections was significantly higher in the HPV-positive group compared to the HPV-negative group, with rates of chlamydia (13.3% versus 4.6%, P<0.001), gonococcal infections (5.2% versus 0.4%, P<0.001), and mycobacterial diseases (38.9% versus 23.4%, P<0.001). Additionally, anxiety levels were significantly higher in the HPVpositive group compared to the HPV-negative group (p<0.005). Anxiety levels and cytological outcomes were significantly correlated across the four HPV-positive subgroups (p<0.05), with type 16/18 infections being associated with notably lower FSFI scores compared to other high-risk HPV types (p<0.05). Conclusions: The findings suggest that infections with HPV type 16/18, especially when accompanied by abnormal cytological findings,significantly elevate anxiety and distress in women and are associated with reduced FSFI scores. These results highlight the complex impact of HPV infection on women's sexual health and psychological well-being with HPV type 16/. [ABSTRACT FROM AUTHOR]

AbstractObjectiveStudy designMethodsResultsConclusionOur objective was to assess trends in three sexually transmitted infections (STIs) – gonorrhoea, chlamydia and syphilis – in Spain, by age group and sex from 2016 to 2022.Retrospective observational studyData from epidemiological surveillance system were used to calculate the incidence rate for each STIs by age group and sex. Poisson regression was employed to examine the trends for 2016 to 2022.For gonorrhoea, higher incidence rates were observed among men than women for all period. The incidence rate ratio (IRR) varied between 1.14 (95% CI 1.12–1.16) for the 15–19 age group to 1.24 (1.23–1.25) for the 35–44 age group among men, and between 1.14 (1.09–1.19) for 55 years or more to 1.27 (1.24–1.29) for the 15–19 age group among women. For chlamydia, women showed higher incidence rate for all age groups than men during the period. Individuals aged 55 years and over showed the highest increase, IRR = 1.30 (1.27–1.34) for men, while it was the lowest for women, IRR = 1.22 (1.16–1.27). The incidence rates for syphilis were lower than for the other STIs. IRR values varied between 1.04 (1.02–1.06) in the 20–24 age group and 1.15 (1.14–1.16) in the 35–44 age group for males; and between 1.13 (1.06–1.16) for the 25–34 age group and 1.18 (1.13–1.25) for the 25–34 age group for females.STIs are more frequent in people aged 25–34 and are increasing in all age groups. However, the rise is most pronounced among older men and among younger women. [ABSTRACT FROM AUTHOR]

Objective To describe Neisseria gonorrhoeae treatment failure to the recommended antimicrobial regimens (azithromycin, cefixime and ceftriaxone). Methods Our study was a longitudinal analysis of treatment failures from an observational open cohort of gonococcal infection cases collected in Québec, Canada (n  = 2547) between September 2015 and December 2019. Epidemiological and clinical data were collected using a self-administered questionnaire, direct case interviews and chart reviews. Antimicrobial susceptibility testing was performed using the agar dilution method. To be retained as a treatment failure, cases must have had (i) a laboratory-confirmed gonococcal infection; (ii) a documented treatment; (iii) a positive test of cure (TOC) performed within a defined period and (iv) no sexual contact (vaginal, oral or anal), even protected with a condom, between the beginning of treatment and the positive TOC. A broader definition, including suspected cases, was also examined. Results Among 1593 cases where a TOC was performed, 83 had a positive TOC: 11 were retained as treatment failure, and 6 were considered suspected cases (overall = 17/1593; 1.1%). Possible explanations for retained or suspected treatment failure included resistance to the antibiotics used for treatment (n  = 1), pharyngeal infection (n  = 9, of which 5 had been treated with ceftriaxone and 4 with other regimens); and azithromycin monotherapy (n  = 1). Some cases had more than one potential explanation. Conclusions Treatment failure occurred in 1.1% of cases of Neisseria gonorrhoeae infection for which a TOC was performed, including some cases of pharyngeal infection treated with ceftriaxone. [ABSTRACT FROM AUTHOR]

Objectives Neisseria gonorrhoeae strains associated with the high-level ceftriaxone-resistant FC428 clone or containing its main resistance determinant, penA allele 60.001, have shown global transmission. In Hangzhou, China, 10% of the isolates were associated with the FC428 clone in 2019. Here, we investigated ceftriaxone resistance and the prevalence of FC428-associated strains in Hangzhou in 2020–22. Methods A total of 209 gonococcal isolates were investigated for antimicrobial susceptibility to ceftriaxone and other antibiotics by agar dilution method. Sequence types and penA alleles were determined by PCR and sequence analysis. Results Resistance to ceftriaxone (MIC > 0.125 mg/L) was observed for 16% (33/209) of the isolates, whereas 6.7% (14/209) of the isolates displayed high-level ceftriaxone resistance (MIC = 1 mg/L). These 14 high-level ceftriaxone-resistant isolates and another isolate displaying an MIC = 0.25 mg/L contained penA allele 60.001, with eight of these isolates, all from 2020 to 2021 belonging to MLST ST1903, the sequence type commonly associated with the original FC428 clone. Importantly, the six penA allele 60.001-containing isolates from 2022 belonged to MLST ST8123, ST7365 and ST7367, which are among the most frequently encountered sequence types found in China. Therefore, these results indicate that endemic lineages in China have acquired penA allele 60.001. Conclusions Here, we report continued transmission of gonococcal strains associated with the FC428 clone or containing penA allele 60.001 in Hangzhou. A major concern for public health is the acquisition of penA allele 60.001 by successful endemic lineages, which might enhance the transmission of this high-level ceftriaxone resistance trait. [ABSTRACT FROM AUTHOR]

The multi drug-resistant Neisseria gonorrhoeae has been classified by the World Health Organisation (WHO) as a high-priority global public health problem. This underlines the need for better understanding of the transmission dynamics and proposing an optimal intervention strategy to control the disease. In this article, a deterministic mathematical model for the transmission dynamics of gonorrhoea as an antibiotic resistant disease in a population with an imperfect vaccination is proposed and analysed. The model incorporates the classes of vaccinated individuals and individuals equipped with self protection interventions to reduce antibiotic resistant cases. The threshold parameter R 0 , the basic reproduction number, for the analysis of the model is calculated. In the given setting, the model exhibits a backward bifurcation for R 0 < 1. However, if the efficacy of the vaccine is 100% without a waning effect, the model is shown to be without a backward bifurcation and the disease-free equilibrium is globally asymptotically stable whenever R 0 < 1. The global sensitivity analysis of the model to variations in parameter values is also performed to determine the most influential parameters on the disease transmission. Moreover, the optimal control analysis of the full model is presented and the optimal intervention strategies are proposed. The proposed intervention strategies are shown to be able to control the disease within a relatively shorter period of time. Finally, numerical experiments are presented to support the theoretical analysis of the model. • Imperfect vaccination is not helpful to eradicate the disease from the population. • Awareness campaign about the antibiotic resistant strain can reduce the transmission of the disease. • Sensitive parameters for the transmission dynamics of the disease are identified. • With the use of the optimal control analysis, cost effective intervention measures are proposed. [ABSTRACT FROM AUTHOR]

Background: Pharyngeal infection is more difficult to diagnose and treat than genital or rectal infection and can act as a reservoir for gonococcal infection. We determined the prevalence of pharyngeal gonorrhea in Korean men with urethritis and analyzed the molecular characteristics and antimicrobial susceptibility of the isolates. Methods: Seventy-two male patients with symptoms of urethritis who visited a urology clinic in Wonju, Korea, between September 2016 and March 2018 were included. Urethral and pharyngeal gonococcal cultures, antimicrobial susceptibility testing, Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST), and multiplex real-time PCR (mRT-PCR) were performed. Results: Among the 72 patients, 59 tested positive for gonococcus by mRT-PCR. Of these 59 patients, 18 (30.5%) tested positive in both the pharynx and urethra, whereas 41 tested positive only in the urethra. NG-MAST was feasible in 16 out of 18 patients and revealed that 14 patients had the same sequence types in both urethral and pharyngeal specimens, whereas two patients exhibited different sequence types between the urethra and pharynx. Of the 72 patients, 33 tested culture-positive. All patients tested positive only in urethral specimens, except for one patient who tested positive in both. All culture-positive specimens also tested positive by mRT-PCR. All isolates were susceptible to azithromycin and spectinomycin, but resistance rates to ceftriaxone and cefixime were 2.9% and 14.7%, respectively. Conclusions: The prevalence of pharyngeal gonorrhea in Korean men with gonococcal urethritis is as high as 30.5%, highlighting the need for pharyngeal screening in high-risk groups. Ceftriaxone is the recommended treatment for pharyngeal gonorrhea. [ABSTRACT FROM AUTHOR]

Neisseria gonorrhoeae is widespread globally. Primary prevention is unsuccessful and antimicrobial resistance threatens optimal management. There is no specific vaccine and natural infection studies show that N gonorrhoeae can avoid and suppress immune responses. In addition to extensive variation in expression and specificity of many gonococcal surface antigens, it induces a robust inflammatory response through the Th17 pathway with a large influx of neutrophils and inflammatory cytokines but evades macrophages. The Th1- and Th2-mediated response is suppressed, resulting in low, short-lived antibody titers. Real-world evidence suggests that gonorrhea cases are reduced among recipients of Neisseria meningitidis group B vaccines containing outer membrane vesicles (OMVs). Although the first randomized trial of an OMV-containing MenB vaccine against N gonorrhoeae infection did not show statistically significant vaccine efficacy, ongoing trials might shed further light. Several candidate vaccine antigens for a gonococcal-specific vaccine are being evaluated preclinically but only one has reached clinical trials. [ABSTRACT FROM AUTHOR]

There is an urgent need for vaccines against Neisseria gonorrhoeae , the causative agent of gonorrhea. Vaccination with an outer membrane vesicle–based Neisseria meningitidis vaccine provides some protection from N. gonorrhoeae ; however, the mechanisms underlying this cross-protection are unknown. To address this need, we developed multiplexed bead-based assays for the relative quantification of human and mouse IgG and IgA against N gonorrhoeae antigens. The assays were evaluated for analyte independence, dilutional linearity, specificity, sensitivity, intra- and interassay variability, and robustness to sample storage conditions. The assay was then used to test samples from mice and humans immunized with an N meningitidis outer membrane vesicle vaccine. [ABSTRACT FROM AUTHOR]

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Background. Although there has been growth in online STI testing services, more attention is needed to understand how to facilitate effective treatment pathways for users. This study investigated where young people want to be treated for gonorrhoea and syphilis if they test positive using an online service. Methods. We conducted an online survey of Australians aged 16-29 years that included multiple choice and free-text questions about their preferred location for receiving injectable antibiotics. Multivariable multinomial logistic regression examined associations between respondent characteristics and service preferences. Content analysis was used to code free-text responses. Results. Among 905 survey respondents, 777 (85.9%) answered questions on treatment preferences. Respondents most commonly preferred injectable antibiotics provided by a sexual health clinic (294; 37.8%) or a nurse in a pharmacy (208; 26.8%). Gender/sexually diverse respondents were more likely to select sexual health clinics over general practice (MSM RRR 2.5, 95% CI 1.1-5.7; WSW RRR 2.6, 95% CI 1.1-5.7; trans/non-binary RRR 2.5; 95% CI 1.0-6.0). Older respondents (aged 25-29 years) were more likely to choose all alternatives over general practice, with the reverse found for those who had previously tested. From open-text answers, pharmacies were valued for their convenience, and sexual health clinics for providing non-judgemental, free services by specialists. Conclusions. Differences in treatment preferences by certain groups of young people suggest that different service offerings may influence treatment-seeking outcomes from online STI testing services. [ABSTRACT FROM AUTHOR]