Evaluation of the diagnostic performance of an immunochromatographic test for Chlamydia trachomatis.

Objectives: To evaluate the diagnostic performance of different brands of immunochromatographic test (ICT) reagents for Chlamydia trachomatis using homogenized samples to provide a reference for reagent quality control. Methods: Eight commercially available ICT reagents were evaluated, of which three used the latex method and five used the colloidal gold method. Analytical performance evaluation using a pure culture broth of C. trachomatis, as well as clinical application validation using cervical epithelial cell samples acquired from the research subjects, were conducted. The concentration of C. trachomatis was quantified using a nucleic acid amplification test. Results: The limit of detection (LOD) of different ICT reagents in the analytical performance evaluation varied from 9.5 × 103 to 1 × 105 IFU/mL, and only one reagent met the LOD specified in the manufacturer's instructions. Likewise, only one reagent in the clinical application validation achieved the analytical LOD, four reagents were 2.1-4.2-fold of the analytical LODs, and three reagents failed to detect positive results in clinical samples. Conclusions: The diagnostic performance of different methods and different brands of ICT reagents in clinical practice was different from the manufacturer's instructions and the results of laboratory evaluation. The diagnostic performance of reagents should be evaluated before they are actually used in clinical practice.

Short-term effectiveness of single-dose intranasal spray COVID-19 vaccine against symptomatic SARS-CoV-2 Omicron infection in healthcare workers: a prospective cohort study.

Background: The pivotal phase 3 efficacy clinical trial has demonstrated that a two-dose regimen of dNS1-RBD (Beijing Wantai Biological Pharmacy Enterprise, Beijing, China) is well-tolerated and provides wide protection against SARS-CoV-2 infection. However, the effectiveness of a single-dose regimen is still unknown. We aimed to estimate the effectiveness of one-dose of dNS1-RBD against symptomatic Omicron infections in real-world conditions. Methods: This prospective cohort study was conducted during an Omicron outbreak among healthcare workers in Xiamen, China, from December 22, 2022 to January 16, 2023. Participants chose to receive single-dose of dNS1-RBD or remain unvaccinated based on personal preference. Healthcare workers daily validated their SARS-CoV-2 infection status, using either RT-PCR or rapid antigen test. A survey questionnaire was conducted to gather information on acute symptoms from individuals infected with SARS-CoV-2. The primary outcome was the symptomatic SARS-CoV-2 infections after enrollment in the dNS1-RBD recipients or the control group among all participants and by prior COVID-19 vaccination status. Findings: On December 22, 2022, a total of 1391 eligible participants without a history of prior SARS-CoV-2 infection were enrolled. Among them, 550 received single-dose of dNS1-RBD, while 841 remained unvaccinated. In the total cohort, the range of follow-up time was 1∼26 days. During the study period, a total of 880 symptomatic SARS-CoV-2 infections were identified in the total cohort. The adjusted vaccine effectiveness against symptomatic SARS-CoV-2 infections and the infections requiring medical attention were 19.0% (95% CI: 6.7, 29.7, P = 0.004) and 59.4% (95% CI: 25.1, 78.0, P = 0.004) in the total cohort, 11.6% (95% CI: -2.4, 23.7, P = 0.100) and 55.3% (95% CI: 15.3, 76.4, P = 0.014) in the participants with inactivated COVID-19 vaccination history, as well as 87.0% (95% CI: 72.6, 93.9, P < 0.001) and 84.2% (95% CI: -41.8, 98.2, P = 0.099) in the naïve participants, respectively. Interpretation: When administered as a booster to individuals with a history of inactivated COVID-19 vaccination, a single-dose of dNS1-RBD provides protection against infections requiring medical attention at least in the short-term after vaccination. The data also showed that a single-dose of dNS1-RBD is protective against symptomatic SARS-CoV-2 infections as a primary immunization for individuals without prior exposure, but due to the limited sample size of naïve participants, further research with a larger sample size is needed to make a solid conclusion. Funding: Xiamen Science and Technology Bureau 2022 General Science and Technology Plan Project and the Bill & Melinda Gates Foundation.

Association between treatment failure in patients with early syphilis and penicillin resistance-related gene mutations of Treponema pallidum: Protocol for a multicentre nested case-control study.

Background: The widespread occurrence of syphilis remains a global public health problem. Although penicillin has been recommended as the first-line therapy for syphilis for more than 70 years, treatment failure occurs in 10-20% of patients with early syphilis. Recent studies have reported varied single-nucleotide polymorphisms (SNPs) of Treponema pallidum related to penicillin resistance. The clinical relevance of these SNPs to treatment failure in patients with early syphilis is unresolved. In this work, a protocol is developed to evaluate the association between treatment failure in patients with early syphilis and penicillin resistance-related gene mutations of T. pallidum. Methods: A multicentre nested case-control study is designed, and patients who are diagnosed with early syphilis and treated with penicillin will be recruited for the study cohort. Before the first treatment, baseline information and biological specimens will be collected from the subjects, and serological tests for syphilis will be performed. Each participant will be followed up at 1, 3, 6, 9, and 12 months after the first treatment, and the clinical manifestations and serum non-treponemal test titres will be evaluated at each follow-up. Patients who will fail treatment are defined as cases, and those who will respond to treatment are defined as controls. Tests for SNPs related to penicillin-binding proteins and Tp47 will be performed in these cases and controls. Survival analysis is used performed to identify gene mutations of T. pallidum related to penicillin resistance and their combinations associated with treatment failure. Discussion: This protocol provides a practical clinical study design that illustrates the role of gene mutations of T. pallidum related to penicillin resistance in the treatment outcome of patients with early syphilis.

Association between the overall burden of comorbidity and Ct values among the older patients with Omicron infection: Mediated by inflammation.

Objectives: To investigate the associations between the overall burden of comorbidity, inflammatory indicators in plasma and Ct values among the elderly with COVID-19. Methods: We conducted a retrospective observational study. The results of each nucleic acid test of during hospitalization were obtained. Linear regression models assessed the associations between the overall burden of comorbidity, inflammatory indicators in plasma and Ct values among the elderly. A causal mediation analysis was performed to assess the mediation effects of inflammatory indicators on the association between the overall burden of comorbidity and Ct values. Results: A total of 767 COVID-19 patients aged ≥ 60 years were included between April 2022 and May 2022. Patients with a high burden of comorbidity had significantly lower Ct values of the ORF gene than subjects with a low burden of comorbidity (median, 24.81 VS 26.58, P < 0.05). Linear regression models showed that a high burden of comorbidity was significantly associated with higher inflammatory responses, including white blood cell count, neutrophil count and C-reactive protein. Also, white blood cell count, neutrophil count, C-reactive protein and the overall burden of comorbidity assessed by age-adjusted Charlson comorbidity index were independent risk factors for the Ct values. A mediation analysis detected the mediation effect of white blood cells on the association between the burden of comorbidity and Ct values, with the indirect effect estimates of 0.381 (95% CI: 0.166, 0.632, P < 0.001). Similarly, the indirect effect of C-reactive protein was -0.307 (95% CI: -0.645, -0.064, P = 0.034). White blood cells and C-reactive protein significantly mediated the relationship between the burden of comorbidity and Ct values by 29.56% and 18.13% of the total effect size, respectively. Conclusions: Inflammation mediated the association between the overall burden of comorbidity and Ct values among elderly with COVID-19, which suggests that combined immunomodulatory therapies could reduce the Ct values for such patients with a high burden of comorbidity.

Effectiveness of Inactivated Vaccine against SARS-CoV-2 Delta Variant Infection in Xiamen, China-A Test-Negative Case-Control Study.

OBJECTIVE: Vaccine effectiveness can measure herd immunity, but the effectiveness of inactivated vaccines in Xiamen remains unclear. Our study was designed to understand the herd immunity of the COVID-19 inactivated vaccine against the SARA-CoV-2 Delta variant in the real world of Xiamen. METHODS: We carried out a test-negative case-control study to explore the vaccine's effectiveness. Participants aged over 12 years were recruited. A logistic regression was used to estimate the odds ratio (OR) of the vaccine among cases and controls. RESULTS: This outbreak began with factory transmission clusters, and spread to families and communities during the incubation period. Sixty percent of cases were confirmed in a quarantine site. A huge mass of confirmed cases (94.49%) was identified within three days, and nearly half of them had a low Ct value. Following an adjustment for age and sex, a single dose of inactivated SARS-CoV-2 vaccine yielded the vaccine effectiveness (VE) of the overall case, of 57.01% (95% CI: -91.44~86.39%), the fully VE was 65.72% (95% CI: -48.69~88.63%) against COVID-19, 59.45% against moderate COVID-19 and 38.48% against severe COVID-19, respectively. The VE of fully vaccinated individuals was significantly higher in females than in males (73.99% vs. 46.26%). The VE among participants aged 19~40 and 41~61 years was 78.75% and 66.33%, respectively, which exceeds the WHO's minimal threshold. Nevertheless, the VE in people under 18 and over 60 years was not observed because of the small sample size. CONCLUSIONS: The single-dose vaccine had limited effectiveness in preventing infection of the Delta variant. The two doses of inactivated vaccine could effectively prevent infection, and clinical mild, moderate, and severe illness caused by the SARS-CoV-2 Delta variant in people aged 18-60 years in the real world.

Colonization of Toxigenic Clostridium difficile Among Intensive Care Unit Patients: A Multi-Centre Cross-Sectional Study.

Background:Clostridium difficile (CD) is a major cause of healthcare-associated infections and antibiotic-associated diarrhea in hospitalized patients worldwide. Carriers of toxigenic CD (tCD) have a higher risk of developing CD infections and can transmit CD to the environment and susceptible patients. However, little is known regarding the carriers and transmission of tCD in China. Methods: A multi-center cross-sectional study of tCD colonization (tCDC) was conducted from October 24 to 31, 2014, at 33 hospitals in Shanghai, China. Rectal swabs or stool samples were collected and tested, and the clinical and demographic status, epidemiological data, and blood parameters of 531 participants were recorded. The status of tCDC was defined by a positive result on the nucleic acid amplification test for the tcdA (toxin A), tcdB (toxin B), and cdtAB (toxin CDT) genes after positive bacterial culture. Results: The overall prevalence of CD colonization (CDC) was 19.02%, tCDC accounted for 92.08%, and A+B+CDT- was the dominant genotype (87.13%). The CD infection (CDI) prevalence was 1.51%. Potential tCDC-associated factors were admission to secondary grade hospitals, a body mass index <18.5, hospitalization during the previous 30 days, underlying diseases (including hypertension, diabetes mellitus, coronary heart disease, and respiratory failure), diarrhea during the previous 7 days, and exposure to fluoroquinolones or lansoprazole. Conclusions: This study reveals the prevalence of CDC and tCDC in Shanghai, elucidates several associated factors, contributes to the awareness of the current epidemiology in parts of eastern China and provides new insights for further study and infection control practices.

The mechanism of ROS regulation of antibiotic resistance and antimicrobial lethality.

Misuse and overuse of antibiotics have led to serious resistance problems that pose a grave threat to human health. How to solve the increasing antibiotic resistance problem is a huge challenge. Besides the traditional strategy of developing novel antimicrobial agents, exploring ways to enhance the lethal activity of antibiotics currently available is another feasible approach to fight against resistance. Recent studies showed that ROS plays an important role in regulating both antibiotic resistance and antimicrobial lethality. ROS produced by sublethal levels of antibiotic induces antibiotic resistance through activating drug efflux pumps via MarR(Multiple antibiotic resistance repressor)-MarA(Multiple antibiotic resistance activator), triggers the protective function against stress via SoxR (Superoxide response transcriptional regulator)-SoxS (Superoxide response transcription factor), and promotes mutagenesis by induction of SOS system. On the contrary, ROS triggered by lethal levels of antibiotic promotes bacterial killing and suppresses resistance. In addition to the concentration of antibiotic, the role of ROS in mediating antimicrobial resistance and bacterial killing is also regulated by a series of genetic regulators (e.g. MazEF, Cpx, SoxR, MarRAB). Thus, how ROS contribute to antimicrobial resistance and bacterial killing is complex. In this review, we summarized the mechanism of ROS in regulating antibiotic resistance and antimicrobial lethality, which may provide references and guidance for finding new ways to enhance antimicrobial lethality of currently available antimicrobials and battling antibiotic resistance.

Dimethyl Sulfoxide Protects Escherichia coli from Rapid Antimicrobial-Mediated Killing.

The contribution of reactive oxygen species (ROS) to antimicrobial lethality was examined by treating Escherichia coli with dimethyl sulfoxide (DMSO), an antioxidant solvent frequently used in antimicrobial studies. DMSO inhibited killing by ampicillin, kanamycin, and two quinolones and had little effect on MICs. DMSO-mediated protection correlated with decreased ROS accumulation and provided evidence for ROS-mediated programmed cell death. These data support the contribution of ROS to antimicrobial lethality and suggest caution when using DMSO-dissolved antimicrobials for short-time killing assays.