Aporphine and amide alkaloids from Illigera parviflora.

Three undescribed alkaloids (+)-9-hydroxy-N-acetylnordicentrine (1), illigeparvinine (2), and deca-(2E,4Z)-2,4-dienoic acid 4-hydroxy-2-phenethyl amide (3), along with 19 known analogues (4-22), were isolated from the ethnic medicinal plant Illigera parviflora. Their structures were established using NMR, MS, and other spectroscopic analyses as well as X-ray diffraction. Moderate inhibition of human gastric carcinoma (MGC-803) and breast adenocarcinoma (T-47D) cell lines proliferation was observed for actinodaphnine (4) with IC50 values of 28.74 and 11.65 µM, respectively. These findings contribute new anticancer potential compounds and expand the chemical diversity known from the valuable traditional medicinal plant I. parviflora.

Treatment of maternal syphilis for preventing congenital syphilis: an observational study of adherence to treatment recommendation in Suzhou, China, 2019-2021.

BACKGROUND: China is one of the countries that set the goal to eliminate mother-to-child transmission (EMTCT) of syphilis by a target date. Active screening for syphilis among pregnant women, followed by effective treatment of maternal syphilis, is critical for achieving the goal. The China health authority issued national implementation protocols to guide EMTCT practice in health facilities. METHODS: Within a cohort of infants born to mothers infected with syphilis, we obtained the data of regimens used for treatment of maternal syphilis from the National Information System of Prevention of Mother-to-Child Transmission of HIV, Syphilis and Hepatitis B, and analysed the physician's treatment behaviour and its associated factors in a public hospital in Suzhou of China. RESULTS: A total of 450 pregnant women who were positive for treponemal or non-treponemal antibody, or had previous infection with syphilis were included into the study for analysis. Of them, 260 (57.8%) were positive for both treponemal and non-treponemal antibodies (syphilis seropositivity), and 353 (78.4%) were treated for syphilis according to the protocol in which 123 (34.8%) were treated with two courses. Non-adherence to treatment recommended by the protocol for maternal syphilis was significantly associated with antenatal visits in the third trimester (AOR 6.65, 95% CI 2.20-20.07, P =0.001), being positive only for a treponemal test (AOR 5.34, 95% CI 3.07-9.29, P <0.001) or having a syphilis infection before the pregnancy (AOR 2.05, 95% CI 1.14-3.69, P =0.017), whereas the uptake of treatment for two treatment courses was associated with attending antenatal care in 2020 or before (AOR 3.49, 95% CI 1.89-6.42, P <0.001), being positive for treponemal and non-treponemal tests (AOR 5.28, 95% CI 2.78-10.06, P <0.001) or having non-treponemal antibody titre of ≥1:8 (AOR 3.71, 95% CI 1.77-7.78, P =0.001). CONCLUSIONS: Implementation of the current recommendation to offer a universal treatment for syphilis among all pregnant women who are shown to be positive for a treponemal test alone is challenging in some clinical settings in China.

Associations of Chlamydia trachomatis serology with fertility-related and pregnancy adverse outcomes in women: a systematic review and meta-analysis of observational studies.

BACKGROUND: Chlamydia trachomatis (CT) infection has an increased risk for fertility-related and pregnancy adverse outcomes partly due to mechanisms related to a pro-inflammatory response to CT-, or cHSP60-induced delayed hypersensitivity. This study aimed to assess the evidence on the association between CT serology and adverse outcomes. METHODS: PubMed/Medline, Embase and Web of Science databases were searched for observational studies on the association of CT-specific antibodies (e. g. IgG, IgA, IgM, etc.) with infertility, tubal factor infertility (TFIF), ectopic pregnancy (EP), spontaneous abortion (SA), or preterm labor (PL) that were published from database inception to 31 August 2022. Pooled adjusted odds ratios or relative risks with corresponding 95% confidence intervals were calculated using a random effects model. This study was registered with PROSPERO (CRD42022368366). FINDINGS: We identified 128 studies that met the inclusion criteria, comprising 87 case-control, 34 cross-sectional and 7 cohort studies, for a total of 167 records involving 128,625 women participants included into the meta-analyses. Based on the adjusted estimates, it was found that CT-specific IgG was significantly associated with TFIF (pooled adjusted OR = 2.09, 95% CI 1.33-3.27, I2 = 63.8%) or EP (pooled adjusted OR = 3.00, 95% CI 1.66-5.40, I2 = 93.0%). Analyses of the unadjusted estimates indicated significant associations between CT-specific IgG and infertility, TFIF, EP or SA (four pooled unadjusted ORs ranging between 1.60 and 5.14, I2 ranging between 40% and 83%); IgA and infertility, TFIF, EP (three pooled unadjusted ORs ranging between 3.64 and 4.91, I2 ranging between 0% and 74%); IgM and TFIF (pooled unadjusted OR = 5.70, 95% CI 1.58-20.56, I2 = 56%); or cHSP60 and TFIF (pooled unadjusted OR = 7.83, 95% CI 5.42-11.31, I2 = 49%). INTERPRETATION: A broad range of CT-specific antibodies have been studied in association with fertility-related and pregnancy adverse outcomes. However, our study identified a low- or moderate-quality evidence for an association of CT serology with the outcomes. There are substantial research gaps in relation to the clinical implications of CT serological biomarkers. FUNDING: The work was supported by the Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2016-I2M-3-021).

Using pooled urogenital, anorectal and oropharyngeal specimens to detect Chlamydia trachomatis and Neisseria gonorrhoeae among men who have sex with men in China: a multisite diagnostic accuracy study.

OBJECTIVES: Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at both urogenital and extragenital sites has been recommended in many countries. Testing of the infections using pooled specimens from urogenital and extragenital sites offer the opportunity to shorten the testing time and reduce the testing cost. Ex-ante pooling is placing the original single-site specimens in a tube with transport media, while ex-post pooling is making a pool of the transport media from both anorectal and oropharyngeal specimens and the urine. This study aimed to conduct a multisite performance evaluation of two pool-specimen approaches (ex-ante and ex-post) in detection of CT and NG using the Cobas 4800 platform among men who have sex with men (MSM) in China. DESIGN: Diagnostic accuracy study. SETTING, PARTICIPANTS AND OUTCOME MEASURES: Participants were recruited from MSM communities at six cities in China. Two oropharyngeal and anorectal swabs collected by clinical staff and 20 mL first-void urine collected by the participant himself were used for evaluating sensitivity and specificity. RESULTS: A total of 1311 specimens were collected from 437 participants in six cities. The sensitivities of ex-ante pooling approach as compared with single-specimen approach (reference standard) were 98.7% (95% CI, 92.7% to 100.0%) for detection of CT and 89.7% (95% CI, 75.8% to 97.1%) for NG, and the specificities were 99.5% (95% CI, 98.0% to 99.9%) and 98.7% (95% CI, 97.1% to 99.6%), respectively. The sensitivities of ex-post pooling approach were 98.7% (95% CI, 92.7% to 100.0%) for CT and 100.0% (95% CI, 91.0% to 100.0%) for NG, and the specificities were 100.0% (95% CI, 99.0% to 100.0%) and 100.0% (95% CI, 99.1% to 100.0%), respectively. CONCLUSIONS: The ex-ante and ex-post pooling approaches show good sensitivity and specificity in detecting urogenital and extragenital CT and/or NG, indicating that these approaches can be used in epidemiological surveillance and clinical management of CT and NG infections, particularly among MSM population.

Knowledge on Chlamydia trachomatis and Acceptance to Testing for It Among Young Students in China.

BACKGROUND: Actively screening for Chlamydia trachomatis (CT) is important for young people because of a high prevalence of asymptomatic infection in this population. This study aimed to investigate knowledge on CT and preference to the screening services for CT among young students in China. METHODS: From June to July 2022, a web-based questionnaire survey was conducted to collect information on sociodemographic characteristics, sexual behaviors, knowledge of CT, previous testing for CT, and preference to platform of testing for CT among Chinese young students. An online home-based self-sampling test (HBSST) service was offered free of charge if the participant was willing to be tested for CT. Statistical analyses included descriptive analysis, χ 2 test, and multivariable logistic regression. RESULTS: Of 520 participants, 419 (80.6%) were aged between 16 and 24 years, 235 (45.2%) reported having sexual experience in the past, and 27 (5.2%) being tested before for CT. Slightly higher than 10% (57/520) of students were knowledgeable about CT. About one-third (36.9%) expressed their willingness to have a testing for CT but majority of them (63.1%) preferred to a free testing. Having sexual experience was significantly associated with the willingness to take the HBSST service (adjusted odds ratio, 2.96; 95% confidence interval, 1.92-4.58). A total of 139 (26.7%) participants requested the HBSST service online and 43.2% (60/139) returned the specimen for testing, in which 2 positives (3.3%) were found. CONCLUSIONS: The knowledge on CT and the previous uptake or current willingness to have a testing for CT was low among Chinese young students.

Prevalence of anatomically specific infections with Chlamydia trachomatis among men who have sex with men in China: protocol for a nationwide cross-sectional study as part of Disease Burden Surveillance of Infections with Chlamydia (DBSIC).

INTRODUCTION: Chlamydia trachomatis (CT) causes the most prevalent bacterial sexually transmitted infection in the world, and men who have sex with men (MSM) are considered as a high-risk population for this infection. Data regarding the prevalence of CT infection in China are limited and fragmented. In this study, we aim to determine at the national level the anatomically specific CT prevalence and genotype distribution of CT strains among MSM, recruiting from the venues where MSM commonly seek sexual partners. METHODS AND ANALYSIS: The study will be a nationwide cross-sectional survey to estimate the prevalence of chlamydial infections among MSM who meet the inclusion criteria over a period of 6 months (May-October 2022). A total of 2429 participants will be recruited from the venues where MSM most often seek sex partners in 14 cities of the 7 geographical regions in China. A mobile phone app-based anonymous self-administered questionnaire will be used to collect sociodemographic and behavioural data, and specimens of urine, anorectal and pharyngeal swabs will be collected for identifying the infections of CT and Neisseria gonorrhoeae and genotypes of CT. The data will be analysed using the IBM SPSS program V.20 ETHICS AND DISSEMINATION: The study protocol has been approved by the Medical Ethics Committee of the Chinese Academy of Medical Sciences Institute of Dermatology and the National Center for STD Control on 9 October 2021 (approval number 2021-KY-037). The study is based on voluntary participation and a written informed consent process. The study results will be submitted for publication in peer-reviewed journals and reported in conferences. The relevant data will be made available to development of control programmes and used as health education materials to disseminate to the community. The dataset will be deposited in a public repository. TRIAL REGISTRATION NUMBER: ChiCTR2100052869.

High Prevalence of Rectal Chlamydia trachomatis Infection With the Same Genotype as Urogenital Infection in Female Outpatients in Sexually Transmitted Disease Clinics in China.

BACKGROUND: Little is known about rectal Chlamydia trachomatis (CT) infection in outpatients attending sexually transmitted disease (STD) clinics in China. In this study, we aimed to explore the clinical and epidemiologic features of rectal CT infection in this population. METHODS: A cross-sectional study was conducted among patients attending STD clinics in Tianjin and Guangxi provinces of China from June 2018 to August 2020. Bivariate and multivariate logistic regression analysis were developed to explore the association of different risk factors for urogenital and rectal CT infection. RESULTS: The prevalence of urogenital and rectal CT was 11.2% (154/1374) and 4.9% (68/1377), respectively. The rectal CT prevalence among female and male patients was 7.8% (60/767) and 1.3% (8/610), respectively. The most common genotype in urogenital CT-positive samples was genotype E (29.9%), while the most common genotype among rectal CT-positive samples was genotype J (23.4%). More than 85% (52/60) of women infected with rectal CT were co-infected with urogenital CT. About 90.0% (36/40) of women shared similar genotypes between rectal and urogenital samples. Females and patients infected with urogenital CT were deemed to be at an increased risk for rectal CT infection. A high proportion of rectal CT infection had concurrent urogenital CT infection, especially in women, and most of the co-infections were shared among the same genotypes. CONCLUSIONS: It would be prudent to encourage awareness and introduce detection tests and treatment strategies for rectal CT infection particularly in female patients visiting STD clinics in China.

Evaluation of the Accuracy of Various Disks and Strips for Rapid Culture-Based Gonococcal Antimicrobial Susceptibility Screening Tests in China.

PURPOSE: Neisseria gonorrhoeae, resistant to the first-line treatment option ceftriaxone, is widespread in China from 2016. Nowadays, diverse reagents of disks and strips for rapid gonococcal antimicrobial susceptibility tests used in clinics are culture-based disks diffusion and gradient strips methods. This study aimed to evaluate the accuracy, quality, and availability of almost all disks and strips acquired in the Chinese market and serve as a reference for clinical selection. METHODS: We tested the performance of 15 commercial disks and 9 commercial gradient strips acquired in China, compared with traditional agar dilution method. The overall performance was evaluated by the categorical agreement. The reagent accuracy of gradient strips was assessed by the essential agreement. RESULTS: A total of 167 gonococcal isolates were used to evaluate antimicrobial disks from three brands. The overall categorical agreements were 71.7% to 81.8% for ceftriaxone, less than 58% for cefixime, 100% for spectinomycin, over 98% for ciprofloxacin, below 70.5% for penicillin, and 73.3% to 81.8% for tetracycline. A total of 81 isolates were tested for different gradient strips. Categorical agreements were over 96% for ceftriaxone, 86.2% for azithromycin, 62.3% to 67.1% for penicillin, 41.9% to 67.5% for tetracycline, and 95% for ciprofloxacin. Essential agreements were 57.7% to 87.3% for ceftriaxone, 70% for azithromycin, 64.9% to 68.4% for penicillin, 51.8% to 71.2% for tetracycline, and 91.3% for ciprofloxacin. CONCLUSION: Rapid test reagents of disks and strips based on gonococcal culture have suboptimal performance. Disk diffusion for spectinomycin or ciprofloxacin can be recommended for clinical individualized prescription. The gradient strips are of great value to identify ceftriaxone-resistant gonococcal strains. Furthermore, abundant improvements are required for many reagents to further optimize their accuracy till the fulfillment of molecular detection.

Antimicrobial Susceptibility of Ertapenem in Neisseria gonorrhoeae Isolates Collected Within the China Gonococcal Resistance Surveillance Programme (China-GRSP) 2018.

PURPOSE: This study aimed to determine the minimum inhibitory concentrations (MICs) of ertapenem on Neisseria gonorrhoeae collected from eight Chinese provinces in 2018. METHODS: The MICs of ertapenem on 503 Neisseria gonorrhoeae isolates (415 isolates selected randomly and 88 isolates selected with preference) were measured using the agar dilution method. For comparison, the MICs of ceftriaxone and azithromycin were detected. RESULTS: Among 415 randomly selected isolates, the MIC range for ertapenem was from ≤0.008 mg/L to 0.5 mg/L. The corresponding MIC50 and MIC90 were 0.06 and 0.125 mg/L, respectively. Twelve of 415 isolates (2.9%) exhibited MIC values ≥0.25 mg/L, and only one isolate (0.2%) had a MIC of 0.5 mg/L. By comparing all 503 tested isolates, a correlation of r = 0.487 (P <0.001) between ertapenem and ceftriaxone MIC was observed, and the correlation between MICs of ertapenem and azithromycin was low (r = -0.12, P = 0.007). In 24 ceftriaxone-decreased susceptibility isolates, four isolates (16.7%) showed a MIC ≥0.25 mg/L for ertapenem. In 85 azithromycin resistant isolates, three isolates (3.5%) showed a MIC ≥0.25 mg/L for ertapenem. CONCLUSION: The in vitro results suggest that ertapenem has satisfactory susceptibility in isolates collected from eight provinces in China; hence, it might be a promising treatment option for resistant gonococcal infections.

Performance of point-of-care tests for the detection of chlamydia trachomatis infections: A systematic review and meta-analysis.

BACKGROUND: Chlamydia trachomatis (CT) is one of the most prevalent bacterial sexually transmitted infections (STIs) globally but has been inadequately detected for intervention. Introduction of point-of-care tests (POCTs) for CT is critical for filling the intervention gaps. We conducted a systematical review and meta-analysis on diagnostic performance of POCTs for CT to assist in guiding the application of these assays in CT screening and detection. METHODS: We searched PubMed/Medline and Embase databases, from January 2004 to May 2021, for studies reporting the performance of POCTs for identifying CT using specimens collected from urethral, vaginal, cervical, anorectal, or pharyngeal site or of urine. Two investigators independently screened and extracted data for controlling the quality of data extraction. Any discrepancies in study selection and data extraction were resolved through consensus. We only included studies with sufficient data to estimate sensitivity and specificity, and used laboratory-based nucleic acid amplification test (NAAT) as the reference standard. The main outcomes were pooled sensitivity, specificity, and diagnostic odds ratio (DOR) and their corresponding 95% confidence intervals (CIs). Summary estimates were calculated using a random-effects model and summary receiver operator curves (SROCs) were generated using the Moses-Littenberg method. STATA 14.0 and Meta-DiSc 1.4 were used for statistical analysis. The study protocol is registered with PROSPERO, number CRD42019140544. FINDINGS: Of 3,038 records identified, 39 studies (42,336 specimens) were included in the study, including 14 studies on evaluation of antigen detection (AD)-based and 25 on NAAT-based POCTs. The overall pooled sensitivity, specificity and DOR were 56% (95% CI 45%-67%), 99% (95% CI 98%-99%) and 86 (95% CI 46-163), respectively, for AD-based POCTs and corresponding values for NAAT-based POCTs were 94% (95% CI 91%-96%), 99% (95% CI 99%-99%) and 1,933(95% CI 1,018-3,669), respectively. The pooled sensitivity of AD-based POCTs varied across the types of specimens, indicating 46% for cervical swabs (95% CI 37%-56%; range 22.7%-71.4%), 52% for vaginal swabs (95% CI 34%-70%; range 17.1%-86.8%) and 57% for male urine (95% CI 36%-75%; range 20.0%-82.6%). For NAAT-based POCTs, the pooled sensitivity was 94% (95% CI 90%-96%) for cervical swabs, 94% (95% CI 86%-98%) for vaginal swabs, 95% (95% CI 91%-97%) for urine specimens and 93% (95% CI 87%-96%) for anorectal swabs. INTERPRETATION: NAAT-based POCTs for CT have a significantly better performance particularly in sensitivity for diagnosing the infection with CT than the AD-based POCTs. Screening strategy with AD-based POCTs may potentially result in a substantial under-detection of the infections.

Rectal Mycoplasma genitalium in Patients Attending Sexually Transmitted Disease Clinics in China: An Infection That Cannot Be Ignored.

BACKGROUND: Previous studies have investigated rectal Mycoplasma genitalium (MG) in men who have sex with men (MSM), while little is known about the prevalence of rectal MG infection in individuals attending sexually transmitted disease (STD) clinics in China. We aimed to estimate the prevalence of rectal MG infection in this population and identified the potential risk factors for rectal MG infection. METHODS: A cross-sectional study was conducted among individuals attending STD clinics located in China from June 2018 to August 2020. Univariate and multivariate logistic regression analyses were conducted to explore the association of different risk factors for rectal MG infection. RESULTS: A total of 1,382 patients were included in the final analyses. A total of 30 of 1377 rectal swabs (2.2%) and 77 of 1374 urogenital samples (5.6%) were positive for MG. In Guangxi, 18 of 47 patients (38.3%) infected with urogenital MG and 5 of 19 patients (26.3%) infected with rectal MG received the recommended treatment. Factors found to be significantly associated with rectal MG infection included: male (adjusted odds ratio (AOR) 0.232, [95% CI: 0.072-0.745]) compared to female, homosexual or bisexual (AOR 40.427, [95% CI: 3.880-421.196]) compared to heterosexual, and those infected with urogenital MG (AOR 7.215, [95% CI: 2.898-17.965]) compared to those who did not get infected with urogenital MG. CONCLUSION: Rectal MG infection should be thought of not only in MSM population but also in STD clinic patients, especially females who have urogenital MG infection. Appropriate strategy for rectal MG screening and treatment needs to be developed for these patients in China.

Clinical Performance of the Xpert® CT/NG Test for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae: A Multicenter Evaluation in Chinese Urban Hospitals.

Background: We aimed to evaluate the clinical performance of the GeneXpert® (Xpert) CT/NG assay for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) using urine and cervical swabs collected from patients in China. Methods: This study was conducted from September 2016 to September 2018 in three Chinese urban hospitals. The results from the Xpert CT/NG test were compared to those from the Roche cobas® 4800 CT/NG test. Discordant results were confirmed by DNA sequence analysis. Results: In this study, 619 first void urine (FVU) specimens and 1,042 cervical swab specimens were included in the final dataset. There were no statistical differences between the results of the two tests for the detection of CT/NG in urine samples (p > 0.05), while a statistical difference was found in cervical swabs (p < 0.05). For CT detection, the sensitivity and specificity of the Xpert test were 100.0% (95%CI = 96.8-99.9) and 98.3% (95%CI = 96.6-99.2) for urine samples and 99.4% (95%CI = 96.5-100.0) and 98.6% (95%CI 97.5-99.2) for cervical swabs, respectively. For NG detection, the sensitivity and specificity of the Xpert test were 99.2% (95%CI = 94.9-100.0) and 100.0% (95%CI = 99.0-100.0) for urine and 100% (95%CI = 92.8-100.0) and 99.7% (95%CI = 99.0-99.9) for cervical swabs, respectively. Conclusion: The Xpert CT/NG test exhibited high sensitivity and specificity in the detection of CT and NG in both urine and cervical samples when compared to the reference results. The 90-min turnaround time for CT and NG detection at the point of care using Xpert may enable patients to receive treatment promptly.

Evaluation of Drugs with Therapeutic Potential for Susceptibility of Neisseria Gonorrhoeae Isolates from 8 Provinces in China from 2018.

PURPOSE: The study aimed to evaluate meropenem, fosfomycin, berberine hydrochloride, and doxycycline minimum inhibitory concentrations (MICs) of Neisseria gonorrhoeae collected from eight provinces in China in 2018. METHODS: The MICs of 540 Neisseria gonorrhoeae isolates (451 isolates selected randomly and 89 isolates selected with preference) were determined to meropenem, fosfomycin, berberine hydrochloride, and doxycycline using the agar dilution method, and the MICs of ceftriaxone and azithromycin were detected for comparison. RESULTS: Among 451 randomly selected isolates, the MIC90 was 0.06 mg/L for meropenem, 64 mg/L for fosfomycin, 64 mg/L for berberine hydrochloride, and 16 mg/L for doxycycline. All isolates showed the MIC ≤ 0.125 mg/L to meropenem, 13 isolates (2.9%) showed MIC > 64 mg/L to fosfomycin, 8 isolates (1.8%) demonstrated MIC > 64 mg/L to berberine hydrochloride, and 271 isolates (60.1%) demonstrated MIC > 1 mg/L to doxycycline. Comparing all 540 tested isolates, a correlation of r = 0.50 (P < 0.001) between meropenem and ceftriaxone MIC was observed. In 24 ceftriaxone-decreased susceptibility isolates, all isolates showed an MIC ≤ 0.125 mg/L for meropenem, 1 isolate (4.2%) showed an MIC > 64 mg/L for fosfomycin, 1 isolate (4.2%) showed an MIC > 64 mg/L for berberine hydrochloride, and 13 isolates (54.2%) showed an MIC > 1 mg/L for doxycycline. In 87 azithromycin resistant isolates, all isolates showed an MIC ≤ 0.125 mg/L for meropenem, 2 isolates (2.3%) showed an MIC > 64 mg/L for fosfomycin, 4 isolates (4.6%) showed an MIC > 64 mg/L for berberine hydrochloride, and 64 isolates (73.6%) showed an MIC > 1 mg/L for doxycycline. CONCLUSION: The in vitro results suggest that meropenem might be a promising treatment option for resistant gonococcal infections, while the effects of fosfomycin and berberine hydrochloride should be further evaluated as potential therapeutic agents. The effectiveness of these drugs in animal experiments and clinical use may need further study.

Enhancing gonorrhea surveillance in China by testing females in gynecology clinics: Lessons learned from a pilot survey.

OBJECTIVES: China has a high burden of gonorrhea, but an imbalanced male-to-female (M/F) ratio of reported cases. Therefore, the prevalence of gonorrhea in China may be underestimated due to inadequate testing of potentially infected females. The objective of this study is to investigate the cause of this imbalanced M/F ratio and develop strategies to enhance gonorrhea surveillance, particularly among females. METHODS: The national center for STD control (NCSTDC) of China CDC collected data in Zhongshan city over the year 2018 from the National Notifiable Disease Report System (NNDRS) and the Hospital and Laboratory Information Systems (HIS and LIS) that obtains information from 24 hospitals. RESULTS: Analysis of 1,542 reported cases of gonorrhea and the case distribution among different hospitals showed that most of the female cases (80.31%) were reported by gynecological clinics. The M/F ratio of reported cases varied between different hospitals and was dependent on the intensity of testing of females by their gynecological clinics. CONCLUSIONS: This study showed a significant correlation between M/F ratios and the relative contribution of female gonorrhea testing, especially in gynecology clinics. Enhancing gonorrhea testing among females should be advocated to improve surveillance in China.

Surveillance and molecular epidemiology of Neisseria gonorrhoeae isolates in Shenzhen, China, 2010-2017.

OBJECTIVES: The development and emergence of antimicrobial resistance in Neisseria gonorrhoeae (NG) have become a major public-health problem worldwide. This study aimed to analyse the antimicrobial susceptibility and molecular characteristics of NG isolates in Shenzhen, China. METHODS: A total of 1282 NG isolates were consecutively collected between 2010 and 2017. Patient demographic information was also collected. MICs of ceftriaxone, spectinomycin, ciprofloxacin, azithromycin and penicillin were determined by agar dilution. Isolates were genotyped using N. gonorrhoeae multi-antigen sequence typing (NG-MAST). RESULTS: Among the isolates, 97.4% were resistant to ciprofloxacin and 68.2% to penicillin. Moreover, 5.0% showed decreased susceptibility to ceftriaxone (CROD) and 17.3% were resistant to azithromycin (AZM-R); 1.3% were simultaneously CROD and AZM-R. All isolates were susceptible to spectinomycin. Increasing ceftriaxone MICs were found from 2010 to 2017. A total of 427 sequence types (STs) and 68 genogroups were identified from 724 isolates. ST5061, ST3741 and ST1766 were observed across the study years. ST14638 (n = 3) was predominant among 32 CROD isolates. Prevalent STs were ST5061 (n = 6), ST1866 (n = 5) and ST11133 (n = 5) among 96 AZM-R isolates. CONCLUSIONS: A high prevalence of isolates resistant to ciprofloxacin and penicillin was found in this study. Azithromycin, one antimicrobial of dual antimicrobial therapy recommended by the WHO, showed a high prevalence of resistance. The other, ceftriaxone, can be used continuously in this region owing to lower resistance levels. However, the emergence of CROD and decreasing susceptibility to ceftriaxone indicate that continuous antimicrobial resistance surveillance is essential.

Disk-Diffusion Testing Is an Inappropriate Screening Tool for Cephalosporin-Resistant Gonorrhoea Strains in Clinical Practice in China.

PURPOSE: Injectable ceftriaxone and oral cefixime are the last agents effective against Neisseria gonorrhoeae. In vitro antimicrobial-susceptibility testing (AST) is done to identify the most efficacious antibiotic needed to combat the infection in that particular individual. The objective of this study was to evaluate whether Kirby-Bauer (KB) disk-diffusion tests can detect N. gonorrhoeae isolates that have decreased susceptibility to ceftriaxone and cefixime for appropriate clinical management. METHODS: A total of 1,633 consecutive clinical isolates of N. gonorrhoeae were collected from January 1, 2013 to December 31, 2017 from seven dermatology clinics located in five provinces in China. Consistency between KB disk-diffusion tests and the agar-dilution method, as well as sensitivity of the KB test for detecting N. gonorrhoeae isolates with decreased susceptibility to ceftriaxone and cefixime, were determined using 1,306 clinical isolates that had been recovered to complete agar-dilution AST. RESULTS: The prevalence of isolates with decreased susceptibility to ceftriaxone and cefixime was 12.1% (198 of 1,633) and 12.7% (208 of 1,633), respectively, using KB disk-diffusion tests. The prevalence of isolates with decreased susceptibility was 9.9% (129 of 1,306) for ceftriaxone and 9.9% (129 of 1,305) for cefixime using agar-dilution AST. The categorical agreement of these two methods was 80.9% for both ceftriaxone and cefixime. Compared to agar-dilution AST, the sensitivity of the KB test for detecting N. gonorrhoeae isolates with decreased susceptibility was 22.5% (29 of 129) for ceftriaxone and 29.5% (38 of 129) for cefixime, and its specificity 87.3% (1,028 of 1,177) for ceftriaxone and 86.7% (1,018 of 1,176) for cefixime. CONCLUSION: Although KB tests are easy to carry out in clinical practice, their ability to detect cephalosporin-resistant gonorrhoea strains is limited. This method is not an appropriate selection for screening cephalosporin-resistant gonorrhoea strains in clinical practice in China.

Improving the coverage and accuracy of syphilis testing: The development of a novel rapid, point-of-care test for confirmatory testing of active syphilis infection and its early evaluation in China and South Africa.

BACKGROUND: Current point-of-care tests (POCT) for syphilis, based on the detection of Treponema pallidum (TP) total antibodies, have limited capacity in distinguishing between active and past/treated syphilis. We report the development and early evaluation of a new prototype POCT based on the detection of TP-IgA antibodies, a novel biomarker for active syphilis. METHODS: The TP-IgA POCT (index test) was developed in response to the World Health Organisation (WHO) target product profile (TPP) for a POCT for confirmatory syphilis testing. Two sub-studies were conducted consecutively using 458 pre-characterised stored plasma samples in China (sub-study one, addressing the criteria for the WHO TPP), and 503 venous blood samples collected from pregnant/postpartum women in South Africa (sub-study two, addressing potential clinical utility). Performance of the index test was assessed against standard laboratory-based serology using a combination of treponemal (TPHA) and non-treponemal (rapid plasma reagin [RPR]) tests. FINDINGS: In sub-study one, the index test demonstrated 96·1% (95%CI=91·7%-98·5%) sensitivity and 84·7% (95%CI=80·15-88·6%) specificity for identification of active syphilis (TPHA positive, RPR positive). It correctly identified 71% (107/150) samples of past-treated syphilis (TPHA positive, RPR negative). In sub-study two, the index test achieved 100% (95%CI=59%-100%) sensitivity for active syphilis and correctly identified all nine women with past syphilis. INTERPRETATION: The TP-IgA POCT has met the WHO TPP for a POCT for diagnosis of active syphilis and demonstrated its potential utility in a clinical setting. Future studies are warranted to evaluate field performance of the final manufactured test. FUNDING: Saving Lives at Birth: Grand Challenge for Development, Thrasher Research Fund, and the Victorian Government Operational Infrastructure Scheme.

Comparison of Microdilution Method with Agar Dilution Method for Antibiotic Susceptibility Test of Neisseria gonorrhoeae.

INTRODUCTION: Antimicrobial resistance (AMR) of Neisseria gonorrhoeae (N. gonorrhoeae) becomes a grave public health problem in the world. A strengthened Antimicrobial Resistance Surveillance Program is needed to track the trend of AMR development. However, the lack of a proper antimicrobial susceptibility test (AST) method is a barrier to expand the AMR surveillance in China. Traditional agar dilution (AD) method is laborious and E-test strips have no approval license for clinical use. Herein, a Chinese group modified the microdilution (MD) method for clinical ASTs. The objective of this study is to compare the MD method with the AD method for N. gonorrhoeae AST. MATERIALS AND METHODS: A total of 166 clinical isolates were tested for antimicrobial susceptibility of ceftriaxone, spectinomycin, azithromycin, ciprofloxacin, tetracycline, and penicillin using MD and AD method simultaneously. Results of MD method were read manually or automatically. Rates of essential agreement (EA), category agreement (CA), minor error, and very major error were compared. RESULTS: The total EAs (compared with results read manually) of penicillin, tetracycline, ciprofloxacin, spectinomycin, ceftriaxone, and azithromycin were 90.4%, 97.0%, 85.5%, 100.0%, 94%, and 72.3%; and CAs were 82.5%, 94.0%, 100%, 100%, 95.2%, and 94%, respectively. CONCLUSION: We conclude that the MD method might be an alternative for clinical AST of N. gonorrhoeae in China. In particular, MD method has the potency of accurate differentiation of isolates resistant to ceftriaxone or azithromycin, which were empirically recommended for gonococcal treatment, but its quality remained suboptimal, and further improvement is needed for clinical use.

Novel education-based intervention to reduce inappropriate antibiotic prescribing for treatment of gonorrhoea in China: protocol for a cluster randomised controlled trial.

INTRODUCTION: Inappropriate use of antibiotics to treat gonorrhoea can lead to antibiotic resistance. Education programmes may be helpful for improving physician prescribing behaviours in accordance with treatment guidelines. As traditional education based on printed materials may have limited effect on guideline-based treatment, innovative education strategies are needed. The current trial aims to assess the effectiveness of a novel education intervention to increase guideline-based treatment of gonorrhoea in China. METHODS AND ANALYSIS: We will conduct a two-arm cluster randomised control trial at 144 hospitals (clusters) in eight Chinese provinces. The intervention will include an online training video developed on the WenJuanXing platform that covers workflows and requirements for managing a patient with uncomplicated gonorrhoea. Outpatient physicians in dermatology (dermatovenerology), urology, andrology and gynaecology will be given access to the video via a quick response code. In hospitals allocated to the control arm, physicians will continue to participate in their standard of care training programme. The primary outcome is the proportion of gonorrhoea antibiotic prescriptions adherent to Chinese national guidelines at the cluster level. In addition, to understand the reasons of physician's non-adherence to the intervention by conducting a questionnaire survey will be considered as the secondary outcome of the study. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Medical Ethics Committee of the Chinese Academy of Medical Sciences Institute of Dermatology (2020-LS-004). All physicians will provide an informed consent prior to participating in the study. Findings of the trial will be disseminated through conferences and peer-reviewed journals, and will be used to develop training programmes for physicians. TRIAL REGISTRATION NUMBER: ChiCTR2000029591.

Impact of the gonococcal FC428 penA allele 60.001 on ceftriaxone resistance and biological fitness.

Global dissemination of the Neisseria gonorrhoeae ceftriaxone-resistant FC428 clone jeopardizes the currently recommended ceftriaxone-based first-line therapies. Ceftriaxone resistance in the FC428 clone has been associated with the presence of its mosaic penA allele 60.001. Here we investigated the contribution penA allele 60.001 to ceftriaxone resistance and its impact on biological fitness. Gonococcal isolates expressing penA allele 60.001 and mosaic penA allele 10.001, which is widespread in the Asia-Pacific region and associated with reduced susceptibility to ceftriaxone and cefixime, were genetic engineered to exchange their penA alleles. Subsequent antimicrobial susceptibility analyses showed that mutants containing penA 60.001 displayed 8- to 16-fold higher ceftriaxone and cefixime minimal inhibitory concentrations (MICs) compared with otherwise isogenic mutants containing penA 10.001. Further analysis of biological fitness showed that in vitro liquid growth of single strains and in the competition was identical between the isogenic penA allele exchange mutants. However, in the presence of high concentrations of palmitic acid or lithocholic acid, the penA 60.001-containing mutants grew better than the isogenic penA 10.001-containing mutants when grown as single strains. In contrast, the penA 10.001 mutants outcompeted the penA 60.001 mutants when grown in competition at slightly lower palmitic acid or lithocholic acid concentrations. Finally, the penA 60.001 mutants were outcompeted by their penA 10.001 counterparts for in vivo colonization and survival in a mouse vaginal tract infection model. In conclusion, penA allele 60.001 is essential for ceftriaxone resistance of the FC428 clone, while its impact on biological fitness is dependent on the specific growth conditions.