Implantação de triagem para clamídia e gonorreia na Cidade de São Paulo - 12º Seminário de Pesquisas

Como está sendo o projeito de Implantação de triagem para Chlamydia trachomatis e Neisseria gonohrroeae em Centros de Testagem e Aconselhamento (CTAs) e Serviço de Atenção Especializada (SAE) no Município de São Paulo para usuários de PrEP? Um projeto pioneiro para criar um protocolo de abordagem etiológica para detecção e tratamento de gonorreia e clamídia, duas das ISTs mais comuns no mundo. Os servidores que estão à frente do processo contam: Cristina de Paula - Gerente do CTA Pirituba; Vitória Vieira - Enfermeira do CTA Pirituba; Kathia Dutra Tabacow - Gerente do CTA Santo Amaro, Carlos Amadeu Biondi - Gerente do SAE Alexandre Kalil Yasbeck, e Andréia de Araujo - Gerente do SAE Fidelis Ribeiro. Essa palestra foi gravada para o 12º Seminário de Pesquisas em IST/Aids da Cidade de São Paulo, realizado no dia 04 de dezembro de 2020.

Substituted salicylic acid analogs offer improved potency against multidrug-resistant Neisseria gonorrhoeae and good selectivity against commensal vaginal bacteria.

Drug-resistant Neisseria gonorrhoeae represents a major threat to public health; without new effective antibiotics, untreatable gonococcal infections loom as a real possibility. In a previous drug-repurposing study, we reported that salicylic acid had good potency against azithromycin-resistant N. gonorrhoeae. We now report that the anti-gonococcal activity in this scaffold is easily lost by inopportune substitution, but that select substituted naphthyl analogs (3b, 3o and 3p) have superior activity to salicylic acid itself. Furthermore, these compounds retained potency against multiple ceftriaxone- and azithromycin-resistant strains, exhibited rapid bactericidal activity against N. gonorrhoeae, and showed high tolerability to mammalian cells (CC50 > 128 µg/mL). Promisingly, these compounds also show very weak growth inhibition of commensal vaginal bacteria.

Antibiotic prophylaxis for ophthalmia neonatorum in Italy: results from a national survey and the Italian intersociety new position statements.

BACKGROUND: Ophthalmia neonatorum is an acute conjunctivitis that occurs in newborns within the first month of life. The most serious infections are due to Chlamydia trachomatis and Neisseria gonorrhoeae, that may cause permanent damages. The use of ophthalmic prophylaxis varies widely around the world, according to the different health and socio-economic contexts. To date in Italy there is no a clear legislation regarding ophthalmia neonatorum prophylaxis at birth. METHODS: We invited all birth centers in Italy to carry out a retrospective survey relating the last three years. We collected data regarding demographics of neonates, drugs used for ophthalmic prophylaxis and results of the screening of pregnant women for Chlamydia trachomatis and Neisseria gonorrhoeae vaginal infections. RESULTS: Among 419 birth centers, 302 (72,1%) responded to the survey. Overall 1041384 neonates, 82,3% of those born in the three years considered, received ophthalmic prophylaxis. Only 4,585 (0,4%) of them received one of the drugs recommended by the WHO. The Centers that participated to the survey reported 12 episodes of Chlamydial conjunctivitis and no Gonococcal infection in the three years. Only 38% of the Centers performed vaginal swabs to pregnant women: 2,6% screened only for Neisseria, 9,6% only for Chlamydia and 25,8% for both germs. CONCLUSIONS: The data obtained from the survey showed a low incidence of neonatal conjunctivitis due to either Neisseria gonorrhoeae or Chlamydia trachomatis in Italy. Due to the lack of legislation regulating the prophylaxis of ophthalmia neonatorum in newborns, the Italian Society of Neonatology, the Italian Society of Obstetrics and Gynecology and the Italian Society of Perinatal Medicine have recently issued new recommendations on this topic.

Immune responses to Neisseria gonorrhoeae and implications for vaccine development.

Neisseria gonorrheoae is the causative agent of gonorrhea, a sexually transmitted infection responsible for a major burden of disease with a high global prevalence. Protective immunity to infection is often not observed in humans, possible due to high variability of key antigens, induction of blocking antibodies, or a large number of infections being relatively superficial and not inducing a strong immune response. N. gonorrhoeae is a strictly human pathogen, however, studies using mouse models provide useful insights into the immune response to gonorrhea. In mice, N. gonorrhoea appears to avoid a protective Th1 response by inducing a less protective Th17 response. In mouse models, candidate vaccines which provoke a Th1 response can accelerate the clearance of gonococcus from the mouse female genital tract. Human studies indicate that natural infection often induces a limited immune response, with modest antibody responses, which may correlate with the clinical severity of gonococcal disease. Studies of cytokine responses to gonococcal infection in humans provide conflicting evidence as to whether infection induces an IL-17 response. However, there is evidence for limited induction of protective immunity from a study of female sex workers in Kenya. A controlled human infection model (CHIM) has been used to examine the immune response to gonococcal infection in male volunteers, but has not to date demonstrated protection against re-infection. Correlates of protection for gonorrhea are lacking, which has hampered the progress towards developing a successful vaccine. However, the finding that the Neisseria meningitidis serogroup B vaccines, elicit cross-protection against gonorrhea has invigorated the gonococcal vaccine field. More studies of infection in humans, either natural infection or CHIM studies, are needed to understand better gonococcal protective immunity.

Web-Based STI/HIV Testing Services Available for Access in Australia: Systematic Search and Analysis.

BACKGROUND: Sexually transmitted infection (STI) rates continue to rise in Australia, and timely access to testing and treatment is crucial to reduce transmission. Web-based services have been viewed as a way to improve timely access to STI/HIV testing and have proliferated in recent years. However, the regulation of these services in Australia is minimal, leading to concerns about their quality. The purpose of this review was to systematically identify web-based STI/HIV testing services available in Australia and assess them on aspects of quality, reliability, and accessibility. OBJECTIVE: We aim to systematically identify and assess web-based STI/HIV testing services available in Australia. METHODS: A Google search of Australian web-based services was conducted in March 2022 and repeated in September 2022 using Boolean operators and search terms related to test services (eg, on the internet or home), STIs (eg, chlamydia or gonorrhea), and test type (eg, self-test). The first 10 pages were assessed, and services were categorized as self-testing (ST; test at home), self-sampling (SS; sample at home and return to laboratory), or self-navigated pathology (SNP; specimens collected at pathology center). Website reliability was assessed against the Health on the Net Foundation code of conduct, and service quality was assessed using a scorecard that was developed based on similar reviews, Australian guidelines for in-person services, and UK standards. Additionally, we looked at measures of accessibility including cost, rural access, and time to test results. RESULTS: Seventeen services were identified (8 ST, 2 SS, and 7 SNP). Only 4 services offered recommended testing for all 4 infections (chlamydia, gonorrhea, syphilis, and HIV) including genital, anorectal, and oropharyngeal sites, and 5 offered tests other than those recommended by Australian testing guidelines (eg, Ureaplasma). Nine services (1 SNP, 8 self-test) had no minimum age requirements for access. Reliability scores (scale 0-8) were similar between all services (range 4.75-8.0). Quality weighted scores (scale 0-58) were similar between SNP and SS services (average 44.89, SD 5.56 and 44.75, SD 1.77, respectively) but lower for ST services (22.66, SD 8.93; P=.002). Government-funded services were of higher quality than private services (43.54, SD 6.71 vs 29.43, SD 13.55; P=.03). The cost for services varied between SNP (Aus $0-$595; ie, US $0-$381.96), self-sample (Aus $0; ie, US $0), and ST (Aus $0-$135; ie, US $0-$86.66). The time to test results was much shorter for SNP services (~4 days) than for SS (~12 days) and ST (~14 days). CONCLUSIONS: This review identified considerable variability in the quality and reliability of the web-based STI/HIV testing services in Australia. Given the proliferation and use of these services will likely increase, it is imperative that Australia develops national standards to ensure the standard-of-care offered by web-based STI/HIV testing services is appropriate to protect Australian users from the impact of poorly performing and inappropriate tests.

Mpox stigma among men who have sex with men in the Netherlands: Underlying beliefs and comparisons across other commonly stigmatized infections.

People with or at risk for mpox are likely to be stigmatized because of analogies to other sexually transmitted infections. Stigma is driven by beliefs about the perceived severity of the condition and perceived responsibility for acquiring the condition, both in broader society and individual responsibility. We explored these beliefs and compared them across mpox, human immunodeficiency virus (HIV), syphilis, gonorrhoea, and chlamydia in an online survey, conducted in July 2022, with 394 men-who-have-sex-with-men in the Netherlands. We compared mean scores between infections using repeated measures analysis of variance and conducted hierarchical regression analyses to identify determinants of both mpox perceived responsibility endpoints. Results showed that participants expected that mpox would be seen as a "gay disease" and will be used to blame gay men. Compared to other infections, mpox was considered less severe than HIV, but more severe than syphilis, gonorrhoea, and chlamydia. Perceived responsibility was comparable across infections, but, for each infection, participants perceived attributed responsibility to be higher in society than individual responsibility. Both perceived responsibility endpoints were highly correlated with each other and with other stigma beliefs. These results provide insight on the underlying determinants of mpox stigma and demonstrate that anticipated mpox stigma is present in the Netherlands.

Two cases of extensively drug-resistant (XDR) Neisseria gonorrhoeae infection combining ceftriaxone-resistance and high-level azithromycin resistance, France, November 2022 and May 2023.

We report two extensively drug-resistant (XDR) Neisseria gonorrhoeae (NG) isolates combining high-level resistance to azithromycin and resistance to ceftriaxone, obtained in France from two heterosexual patients, one of whom returned from Cambodia. Whole genome sequencing identified MLST ST16406, the mosaic penA-60.001 which caused ceftriaxone resistance in the internationally spreading FC428 clone, and the A2059G mutation in the 23S rRNA gene. The NG isolates F93 and F94 were related to XDR isolates detected in Austria and the United Kingdom in 2022.

Peptide barcode of multidrug-resistant strains of Neisseria gonorrhoeae isolated from patients in Thailand.

The emergence of multidrug-resistant strains of Neisseria gonorrhoeae constitutes a serious threat to public health. The present study aimed to investigate peptidome-based biomarkers of multidrug-resistant N. gonorrhoeae, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and liquid chromatography tandem mass spectrometry (LC-MS). The peptide barcode database of multidrug resistant N. gonorrhoeae was generated from the whole-cell peptides of 93 N. gonorrhoeae isolated from patients in Thailand. The dendrogram of 93 independent isolates of antibiotic-resistant N. gonorrhoeae revealed five distinct clusters including azithromycin resistance group (AZ), ciprofloxacin resistance group (C), ciprofloxacin and penicillin resistance group (CP), ciprofloxacin and tetracycline resistance group (CT), ciprofloxacin, penicillin and tetracycline resistance group (CPT). The peptidomes of all clusters were comparatively analyzed using a high-performance liquid chromatography-mass spectrometry method (LC-MS). Nine peptides derived from 9 proteins were highly expressed in AZ (p value < 0.05). These peptides also played a crucial role in numerous pathways and showed a strong relationship with the antibiotic resistances. In conclusion, this study showed a rapid screening of antibiotic-resistant N. gonorrhoeae using MALDI-TOF MS. Additionally, potential specific peptidome-based biomarker candidates for AZ, C, CP, CT and CPT-resistant N. gonorrhoeae were identified.

Correlates of Neisseria gonorrhoeae antimicrobial resistance: cross-sectional results from an open cohort sentinel surveillance network in Québec, Canada, 2016-2019.

OBJECTIVES: To examine correlates of Neisseria gonorrhoeae antimicrobial resistance (AMR) to first-line antimicrobials (azithromycin, cefixime and ceftriaxone). DESIGN AND SETTING: The sentinel surveillance network is an open cohort of gonococcal infection cases from Québec, Canada. Cross-sectional results are reported herein. PARTICIPANTS: Between 1 January 2016 and 31 December 2019, data from 886 individuals accounting for 941 gonorrhoea cases were included. METHODS: Epidemiological and clinical data were collected using an auto-administered questionnaire, direct case interviews and chart reviews. Antimicrobial susceptibility testing was performed using the agar dilution method. Generalised estimating equations were used for regression. RESULTS: The prevalence of azithromycin resistance with a minimal inhibitory concentration (MIC) of ≥2 mg/L was 21.3%. In 2016, men who have sex with men were more likely to be infected with an azithromycin-resistant N. gonorrhoeae isolate (adjusted prevalence ratio (aPR)=4.73, 95% CI 1.48 to 15.19) or with an isolate with increased third-generation cephalosporin (3GC) MIC (aPR=5.32, 95% CI 1.17 to 24.11 for cefixime (MIC≥0.06 mg/L) and aPR=4.38, 95% CI 1.53 to 12.54 for ceftriaxone (MIC≥0.03 mg/L)). However, these associations were not maintained between 2017 and 2019, with increased MIC observed in men who have sex exclusively with women and women. Overall, azithromycin resistance was significantly more likely in cases who self-reported HIV infection (aPR=1.65, 95% CI 1.00 to 2.71). Cefixime increased MIC were more likely in individuals 25-34 years old (aPR=2.23, 95% CI 1.18 to 4.21). Cefixime and ceftriaxone increased MIC were both more likely in cases who reported ≥5 sexual partners (cefixime: aPR=2.10, 95% CI 1.34 to 3.27 and ceftriaxone: aPR=1.62, 95% CI 1.14 to 2.30). CONCLUSION: Significant correlates of N. gonorrhoeae AMR to first-line antimicrobials were observed. Antimicrobial stewardship may be particularly important for 3GC. Active monitoring and interventions are critical for 3GC non-susceptible strains, especially considering the very low prevalence in Québec.

Identification of ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone and isolates harboring a novel mosaic penA gene in Chengdu in 2019-2020.

BACKGROUND: Antimicrobial resistance in gonorrhea has become a growing global public health burden. Neisseria gonorrhoeae isolates with resistance to ceftriaxone, the last remaining first-line option, represent an emerging threat of untreatable gonorrhea. METHODS: A total of ten ceftriaxone-resistant N. gonorrhoeae FC428 isolates and two isolates harboring a novel mosaic penA-232.001 allele from 160 gonococcal isolates in Chengdu in 2019-2020 was described in the present study. Multilocus sequence typing (MLST) and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were performed to characterize the isolates. Whole genome sequencing and maximum-likelihood method were performed to infer how the genetic phylogenetic tree of these isolates looks like. Recombination analysis was performed using the RDP4 software. This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100048771, registration date: 20210716). RESULTS: The genetic phylogeny showed that the ten FC428 isolates sporadically clustered into different phylogenetic clades, suggesting different introductions and local transmission of FC428. Two isolates showed close genetic relatedness to ceftriaxone-resistant clone A8806, which was only reported from Australia in 2013. Homologous recombination events were detected in penA between Neisseria gonorrhoeae and commensal Neisseria species (N. perflava and N. polysaccharea), providing evidence of commensal Neisseria species might serve as reservoirs of ceftriaxone resistance-mediating penA sequences in clinical gonococcal strains. CONCLUSIONS: Our results demonstrate further dissemination of FC428 in China and resurgence risks of sporadic ceftriaxone-resistant A8806 to become the next clone to spread.

Evaluation and optimization of the syndromic management of female genital tract infections in Nairobi, Kenya.

BACKGROUND: Genital tract infections pose a public health concern. In many low-middle-income countries, symptom-based algorithms guide treatment decisions. Advantages notwithstanding, this strategy has important limitations. We aimed to determine the infections causing lower genital tract symptoms in women, evaluated the Kenyan syndromic treatment algorithm for vaginal discharge, and proposed an improved algorithm. METHODS: This cross-sectional study included symptomatic non-pregnant adult women presenting with lower genital tract symptoms at seven outpatient health facilities in Nairobi. Clinical, socio-demographic information and vaginal swabs microbiological tests were obtained. Multivariate logistic regression analyses were performed to find predictive factors for the genital infections and used to develop an alternative vaginal discharge treatment algorithm (using 60% of the dataset). The other 40% of data was used to assess the performance of each algorithm compared to laboratory diagnosis. RESULTS: Of 813 women, 66% had an infection (vulvovaginal candidiasis 40%, bacterial vaginosis 17%, Neisseria gonorrhoea 14%, multiple infections 23%); 56% of women reported ≥ 3 lower genital tract symptoms episodes in the preceding 12 months. Vulvovaginal itch predicted vulvovaginal candidiasis (odds ratio (OR) 2.20, 95% CI 1.40-3.46); foul-smelling vaginal discharge predicted bacterial vaginosis (OR 3.63, 95% CI 2.17-6.07), and sexually transmitted infection (Neisseria gonorrhoea, Trichomonas vaginalis, Chlamydia trachomatis, Mycoplasma genitalium) (OR 1.64, 95% CI 1.06-2.55). Additionally, lower abdominal pain (OR 1.73, 95% CI 1.07-2.79) predicted sexually transmitted infection. Inappropriate treatment was 117% and 75% by the current and alternative algorithms respectively. Treatment specificity for bacterial vaginosis/Trichomonas vaginalis was 27% and 82% by the current and alternative algorithms, respectively. Performance by other parameters was poor to moderate and comparable between the two algorithms. CONCLUSION: Single and multiple genital infections are common among women presenting with lower genital tract symptoms at outpatient clinics in Nairobi. The conventional vaginal discharge treatment algorithm performed poorly, while the alternative algorithm achieved only modest improvement. For optimal care of vaginal discharge syndrome, we recommend the inclusion of point-of-care diagnostics in the flowcharts.

Prevalence of gonococcal and chlamydial infections among men who have sex with men in sub-Saharan Africa: protocol for a systematic review and meta-analysis.

BACKGROUND: Bacterial sexually transmitted infections (STIs) including Neisseria gonorrhoeae and Chlamydia trachomatis are common in men who have sex with men (MSM). These infections increase the risk of acquiring and transmitting human immunodeficiency virus (HIV) in this key population. Access to MSM in many countries in sub-Saharan Africa remains generally difficult due to discrimination or criminalization of their sexual orientation which could lead to depression and risky sexual practices associated with prevalence. This protocol therefore proposes to undertake a systematic review and meta-analysis of literature on the prevalence of gonococcal and chlamydial infections among MSM in Sub-Saharan Africa. METHODS: This review which aims to ascertain the pooled prevalence and risk factors of these infections in sub-Saharan Africa's MSM population will follow the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. The search strategy will review relevant articles from the following databases: PubMed, Scopus, ISI Web of Science and the Directory of Open Access Journals (DOAJ). Articles screening for eligibility and data extraction will be conducted by two independent reviewers. All discrepancies will be resolved by the third and fourth reviewers. Heterogeneity in studies will be evaluated using the I2 statistic and where heterogeneity is high and significant, a random effect model will be used to estimate the pooled prevalence. Publication bias will be assessed using the Doi plot. Extracted data will be analysed using MetaXL add-on for Microsoft excel. Data will be presented in tables and graphically presented in forest plots. DISCUSSION: In this study, we anticipate being able to systematically determine the prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis among MSM as well as explore possible risk factors associated with prevalence. The outcomes of the systematic review and meta-analyses will serve to support researchers and public health stakeholders in identifying healthcare priorities and in addressing issues pertaining to the overall wellbeing of the MSM community. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022327095.

Association of Group B Meningococcal Vaccine Receipt With Reduced Gonorrhea Incidence Among University Students.

This case-control study examines reported cases of gonorrhea among recipients of meningococcal group B vaccine at 2 universities in Oregon.

Th1-polarized MtrE-based gonococcal vaccines display prophylactic and therapeutic efficacy.

ABSTRACTGlobal dissemination of high-level ceftriaxone-resistant Neisseria gonorrhoeae strains associated with the FC428 clone poses a threat to the efficacy ceftriaxone-based therapies. Vaccination is the best strategy to contain multidrug-resistant infections. In this study, we investigated the efficacy of MtrE and its surface Loop2 as vaccine antigens when combined with a Th1-polarizing adjuvant, which is expected to be beneficial for gonococcal vaccine development. Using in vitro dendritic cell maturation and T cell differentiation assays, CpG1826 was identified as the optimal Th1-polarizing adjuvant for MtrE and Loop2 displayed as linear epitope (Nloop2) or structural epitope (Intraloop2) on a carrier protein. Loop2-based antigens raised strongly Th1-polarized and bactericidal antibody responses in vaccinated mice. Furthermore, the vaccine formulations provided protection against a gonococcal challenge in mouse vaginal tract infection model when provided as prophylactic vaccines. Also, the vaccine formulations accelerated gonococcal clearance when provided as a single therapeutic dose to treat an already established infection, including against a strain associated with the FC428 clone. Therefore, this study demonstrated that MtrE and Loop 2 are effective gonococcal vaccine antigens when combined with the Th1-polarizing CpG1826 adjuvant.

The third nationwide surveillance of antimicrobial susceptibility against Neisseria gonorrhoeae from male urethritis in Japan, 2016-2017.

Neisseria gonorrhoeae is one of the important pathogens of sexually transmitted infections. N. gonorrhoeae is rapidly becoming antimicrobial resistant, and there are few drugs that are effective in the initial treatment of gonorrhea. To understand the trends of antimicrobial susceptibility of N. gonorrhoeae, the Surveillance Committee of the Japanese Society of Infectious Diseases, the Japanese Society for Chemotherapy, and the Japanese Society of Clinical Microbiology conducted the third nationwide antimicrobial susceptibility surveillance of N. gonorrhoeae isolated from male urethritis. The specimens were collected from male patients with urethritis at 30 facilities from May 2016 to July 2017. From the 159 specimens collected, 87 N. gonorrhoeae strains were isolated, and 85 were tested for susceptibility to 21 antimicrobial agents. All strains were non-susceptible to penicillin G. Seven strains (8.2%) were ß-lactamase-producing strains. The rates of susceptibility to cefixime and cefpodoxime were 96.5% and 52.9%, respectively. Three strains were non-susceptible with a minimum inhibitory concentration (MIC) of 0.5 mg/L for cefixime. None of the strains were resistant to ceftriaxone or spectinomycin. The susceptibility rate for ciprofloxacin was 23.5% (20 strains), and no strains showed intermediate susceptibility. The susceptibility rate against azithromycin was 81.2%, with one strain isolated with a MIC of 8 mg/L against azithromycin. The results of this surveillance indicate that ceftriaxone and spectinomycin, which are currently recommended for gonococcal infections in Japan, appear to be effective. It will be necessary to further expand the scale of the next surveillance to understand the current status of drug-resistant N. gonorrhoeae in Japan.