Seroprevalence of IgG antibodies against pertussis toxin in the Chinese population: A systematic review and meta-analysis.

Pertussis is a vaccine-preventable infectious disease; however, data on pertussis antibody levels in a nationwide population are still limited in China. We aimed to pool the seropositivity rates of IgG antibodies against pertussis toxin (PT-IgG) across the country. We systematically searched PubMed, Web of Science, Embase, and the China National Knowledge Infrastructure Database for studies published between January 1, 2010, and June 30, 2023. Studies reporting the seroprevalence of PT-IgG among a healthy Chinese population were included. Pooled estimates were obtained using random-effects meta-analyzes. The meta-analysis included 39 studies (47,778 participants) reporting anti-PT IgG seropositivity rates. The pooled rate for all ages was 7.06% (95% CI, 5.50%-9.07%). Subgroup analyzes showed rates ranging from 6.36% to 12.50% across different age groups. This meta-analysis indicated a low anti-PT IgG seropositivity rate in the Chinese population, particularly among school-aged children and young adults. This finding underscores the urgent need to refine immunization strategies.

Knowledge and awareness of viral hepatitis and influencing factors among the general population aged 15-69 years in Zhejiang Province, China.

This study aimed to determine the level of viral hepatitis knowledge as well as the self-awareness of hepatitis B virus surface antigen (HBsAg) positive individuals, to provide data support for the next steps in viral hepatitis prevention and control. We conducted a cross-sectional survey to assess the knowledge of viral hepatitis among the general population aged 15-69 years in Zhejiang Province, China. A total of 3,626 individuals were surveyed with 10 questions. The knowledge level of the participants is reflected by the scores from the survey. Adequate knowledge was defined as a score of ≥ 6. The knowledge rate was defined as the ratio of the number of individuals with adequate knowledge to the total number of individuals. The knowledge rate of viral hepatitis among the general population aged 15-69 years in Zhejiang Province was 52.34% (mean score, 5.23). The majority of participants (52.51%) had adequate knowledge of viral hepatitis. Multiple logistic regression analysis showed that medical staff had the best knowledge of viral hepatitis, followed by individuals with university or higher education, those aged 40-49 years, and those with a history of hepatitis B vaccination. 34.16% of HBsAg positive participants were aware of their infection status before. The mean score of knowledge of viral hepatitis was significantly lower among HBsAg-positive than HBsAg-negative individuals. Knowledge of viral hepatitis in Zhejiang Province was still low, especially among HBsAg-positive individuals with no awareness of their infection status. More effort should be needed to improve public awareness of viral hepatitis.

Immuno-persistence of the different primary polio vaccine schedules and immunogenicity of the booster dose by sabin inactivated or bivalent oral poliovirus vaccine in children aged 4 years: an open-label, randomised, controlled phase 4 trial in China.

Background: Sabin inactivated and bivalent oral poliovirus vaccine (sIPV, bOPV) were commonly used in China since 2016. We conducted an open-label, randomised, controlled phase 4 trial to assess immune persistence following sequential immunisation with sIPV or bOPV, and immunogenicity and safety of a booster dose of poliovirus vaccine in children aged 4 years. Methods: Participants from a previous clinical trial with three different sequential schedules with sIPV (I) or bOPV (B) at ages 2, 3, and 4 months (Groups I-B-B, I-I-B, I-I-I) in 2017 were followed-up. The children were further divided into five subgroups after sIPV was given for Group I-B-B, and sIPV or bOPV randomly given for Group I-I-B and Group I-I-I (128 children in Groups I-B-B-I, 60 in Group I-I-B-B, 64 in Group I-I-B-I, 68 in Group I-I-I-B, 67 in Group I-I-I-I). Immune persistence and immunogenicity were assessed by measuring poliovirus type-specific antibodies, and safety were analysed in all children who received the booster dose. Findings: Between Dec 5, 2020 and Jun 30, 2021, we respectively enrolled 381 participants in the immune persistence analysis, and 352 participants in per protocol (PP) analysis of the immunogenicity of the booster immunisation. Seropositivity rates of antibodies against poliovirus types 1 and 3 were all >90% four years after primary immunisation, while for poliovirus type 2 were 46.83%, 75.41%, and 90.23% (χ2 = 60.948, P < 0.001) for Groups I-B-B, I-I-B, and I-I-I, respectively. After the booster dose, seropositivity rates were 100% for all three serotypes in Group I-B-B-I, I-I-B-I and I-I-I-I; In Group I-I-B-B and I-I-I-B, the seropositivity rates for types 1 and 3 were all 100%, for type 2 were 92.59% and 98.46%. The geometric mean titres (GMTs) against poliovirus 1 and 3 were all high in five groups (>1860.73), and the GMTs against type 2 were significantly lower in groups booster with bOPV: Group I-I-B-B (50.60) and Group I-I-I-B (247.84). There was no significant difference in seropositivity rates or GMTs for all three serotypes (P > 0.05) between Group I-I-B-I and I-I-I-I. No serious adverse events occurred during the study. Interpretation: Our findings suggest that at least two sIPV doses are needed in the current routine poliovirus immunisation schedule, and schedules containing 3 or 4 doses of sIPV provide better protection against poliovirus type 2 than the current sIPV-sIPV-bOPV-bOPV schedule in China. Funding: Medical and Health Science and Technology of Zhejiang Province (2021KY118). This trial was registered with ClinicalTrials.gov (NCT04576910).

Disruption of Bacterial Thiol-Dependent Redox Homeostasis by Magnolol and Honokiol as an Antibacterial Strategy.

Some traditional Chinese medicines (TCMs) possess various redox-regulation properties, but whether the redox regulation contributes to antibacterial mechanisms is not known. Here, ginger juice processed Magnoliae officinalis cortex (GMOC) was found to show strong antibacterial activities against some Gram-positive bacteria, but not Gram-negative bacteria including E. coli, while the redox-related transcription factor oxyR deficient E. coli mutant was sensitive to GMOC. In addition, GMOC and its main ingredients, magnolol and honokiol, exhibited inhibitory effects on the bacterial thioredoxin (Trx) system, a major thiol-dependent disulfide reductase system in bacteria. The effects of magnolol and honokiol on cellular redox homeostasis were further verified by elevation of the intracellular ROS levels. The therapeutic efficacies of GMOC, magnolol and honokiol were further verified in S. aureus-caused mild and acute peritonitis mouse models. Treatments with GMOC, magnolol and honokiol significantly reduced the bacterial load, and effectively protected the mice from S. aureus-caused peritonitis infections. Meanwhile, magnolol and honokiol produced synergistic effects when used in combination with several classic antibiotics. These results strongly suggest that some TCMs may exert their therapeutic effects via targeting the bacterial thiol-dependent redox system.

Assessing COVID-19 Vaccine Booster Hesitancy Using the Modified 5C Scale in Zhejiang Province, China: A Cross-Sectional Study.

Following the rollout of a booster campaign to promote immunity against COVID-19 in China, this study aimed to assess booster hesitancy among adults who were fully vaccinated with primary doses across Zhejiang Province. Firstly, the modified 5C scale developed by a German research team was assessed for reliability and validity via a pre-survey in Zhejiang Province. Then, a 30-item questionnaire was established to conduct online and offline surveys during 10 November to 15 December 2021. Demographic characteristics and information on previous vaccination experience, vaccine type of primary doses, attitudes towards booster doses and awareness of SARS-CoV-2 infection were collected. Chi-square tests, pairwise comparison and multivariate logistic regression were performed in data analysis. In total, 4039 valid questionnaires were analyzed, with booster hesitancy of 14.81%. Dissatisfaction with previous vaccination experience of primary doses (ORs = 1.771~8.025), less confidence in COVID-19 vaccines (OR = 3.511, 95%CI: 2.874~4.310), younger age compared to the elderly aged 51-60 years old (2.382, 1.274~4.545), lower education level (ORs = 1.707~2.100), weaker awareness of social responsibility of prevention and control of COVID-19 (1.587, 1.353~1.859), inconvenience of booster vaccination (1.539, 1.302~1.821), complacency regarding vaccine efficacy as well as self-health status (1.224, 1.056~1.415) and excessive trade-offs before vaccination (1.184, 1.005~1.398) were positively associated with booster hesitancy. Therefore, intelligent means should be strengthened to optimize vaccination services. More influential experts and other significant figures should be supported to promote timely evidence-based information via various media platforms to reduce public hesitancy and increase booster uptake.

The decline in immunity and circulation of pertussis among Chinese population during the COVID-19 pandemic: A cross-sectional sero-epidemiological study.

BACKGROUND: In recent years, the resurgence of pertussis has posed a public health challenge in many countries. This study aimed to evaluate the immunity levels against pertussis among populations of different ages in China. METHODS: We conducted a cross-sectional serological survey in Zhejiang Province, China in 2020. Serum IgG antibodies against pertussis toxin (anti-PT), filamentous hemagglutinin (anti-FHA), and pertactin (anti-PRN) were quantitatively measured. The geometric mean concentration (GMC) of three antibodies was calculated. An anti-PT level < 5 IU/mL was considered undetectable, ≥20 IU/mL as seropositive and ≥80 IU/mL as an indicator of recent infection. Mathematical models were fitted for anti-PT concentrations over time in children after four doses of the pertussis vaccination. RESULTS: A total of 4459 participants aged 0-59 years were included in the analyses. The overall positivity rate of anti-PT was 29.80% with the highest (81.44%) rate in the 1-2 years old and the lowest (4.72%) in 10-14 years old. The GMCs of anti-PT, anti-FHA and anti-PRN for the whole participants were 9.67 (95%CI: 9.25-10.10),18.93 (18.24-19.67), and 8.99 (8.61-9.38) IU/mL, respectively. Over 50% of subjects aged ≥ 7 years had undetectable anti-PT IgG antibodies (<5IU/mL). The proportions of the populations with anti-PT IgG ≥ 80 IU/mL were approximately 0.9%, 0.3% and 1.1% among the 10-14, 15-29, and 40-59 years old groups, respectively. The power regression equation of the attenuation model after last dose of pertussis vaccine was y = 41.088x-1.238 (R2 = 0.935, p < 0.001). The fitted anti-PT concentrations was only 5.60 IU/mL at 5 years following the last vaccination dose. CONCLUSION: The prevalence of pertussis decreased during the study period in the COVID-19 pandemic; however, there was still a certain proportion of adolescents and adults with evidence of recent infection. The decline in antibody levels after pertussis vaccination was observed, and booster doses are in urgent need in China.

Mitochondrial Glrx2 Knockout Augments Acetaminophen-Induced Hepatotoxicity in Mice.

Acetaminophen (APAP) is one of the most widely used drugs with antipyretic and analgesic effects, and thus hepatotoxicity from the overdose of APAP becomes one of the most common forms of drug-induced liver injury. The reaction towards thiol molecules, such as GSH by APAP metabolite, N-acetyl-p-benzo-quinonimine (NAPQI), is the main cause of APAP-induced hepatotoxicity. However, the role of many other thiol-related regulators in toxicity caused by APAP is still unclear. Here we have found that knockout of the Glrx2 gene, which encodes mitochondrial glutaredoxin2 (Grx2), sensitized mice to APAP-caused hepatotoxicity. Glrx2 deletion hindered Nrf2-mediated compensatory recovery of thiol-dependent redox systems after acetaminophen challenge, resulting in a more oxidized cellular state with a further decrease in GSH level, thioredoxin reductase activity, and GSH/GSSG ratio. The weakened feedback regulation capacity of the liver led to higher levels of protein glutathionylation and thioredoxin (both Trx1 and Trx2) oxidation in Glrx2-/- mice. Following the cellular environment oxidation, nuclear translocation of apoptosis-inducing factor (AIF) was elevated in the liver of Glrx2-/- mice. Taken together, these results demonstrated that mitochondrial Grx2 deficiency deteriorated APAP-induced hepatotoxicity by interrupting thiol-redox compensatory response, enhancing the AIF pathway-mediated oxidative damage.

Establishment and Validation of a Non-invasive Diagnostic Nomogram to Identify Heart Failure in Patients With Coronary Heart Disease.

Background: Heart failure (HF) is an end-stage manifestation of and cause of death in coronary heart disease (CHD). The objective of this study was to establish and validate a non-invasive diagnostic nomogram to identify HF in patients with CHD. Methods: We retrospectively analyzed the clinical data of 44,772 CHD patients from five tertiary hospitals. Univariate logistic regression analyses and least absolute shrinkage and selection operator (LASSO) regression analyses were used to identify independent factors. A nomogram based on the multivariate logistic regression model was constructed using these independent factors. The concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC) were used to evaluate the predictive accuracy and clinical value of this nomogram. Results: The predictive factors in the multivariate model included hypertension, age, and the total bilirubin, uric acid, urea nitrogen, triglyceride, and total cholesterol levels. The area under the curve (AUC) values of the nomogram in the training set, internal validation set, external validation set1, and external validation set2 were 0.720 (95% CI: 0.712-0.727), 0.723 (95% CI: 0.712-0.735), 0.692 (95% CI: 0.674-0.710), and 0.655 (95% CI: 0.634-0.677), respectively. The calibration curves indicated that the nomogram had strong calibration. DCA and CIC indicated that the nomogram can be used as an effective tool in clinical practice. Conclusion: The developed predictive model combines the clinical and laboratory factors of patients with CHD and is useful in individualized prediction of HF probability for clinical decision-making during treatment and management.

In-patient Expenditure Between 2012 and 2020 Concerning Patients With Liver Cirrhosis in Chongqing: A Hospital-Based Multicenter Retrospective Study.

Background: Liver cirrhosis is a major global health and economic challenge, placing a heavy economic burden on patients, families, and society. This study aimed to investigate medical expenditure trends in patients with liver cirrhosis and assess the drivers for such medical expenditure among patients with liver cirrhosis. Methods: Medical expenditure data concerning patients with liver cirrhosis was collected in six tertiary hospitals in Chongqing, China, from 2012 to 2020. Trends in medical expenses over time and trends according to subgroups were described, and medical expenditure compositions were analyzed. A multiple linear regression model was constructed to evaluate the factors influencing medical expenditure. All expenditure data were reported in Chinese Yuan (CNY), based on the 2020 value, and adjusted using the year-specific health care consumer price index for Chongqing. Results: Medical expenditure for 7,095 patients was assessed. The average medical expenditure per patient was 16,177 CNY. An upward trend in medical expenditure was observed in almost all patient subgroups. Drug expenses were the largest contributor to medical expenditure in 2020. A multiple linear regression model showed that insurance type, sex, age at diagnosis, marital status, length of stay, smoking status, drinking status, number of complications, autoimmune liver disease, and the age-adjusted Charlson comorbidity index score were significantly related to medical expenditure. Conclusion: Conservative estimates suggest that the medical expenditure of patients with liver cirrhosis increased significantly from 2012 to 2020. Therefore, it is necessary to formulate targeted measures to reduce the personal burden on patients with liver cirrhosis.

Burden of whooping cough in China (PertussisChina): study protocol of a prospective, population-based case-control study.

INTRODUCTION: Pertussis is one of the top 10 diseases of children under 10 years of age, and the few vaccine-preventable diseases who is on a rise in China in recent years; however, the true burden of pertussis, including age-stratified incidence and risk factors of severe sequelae, are under-recognised. We aim to estimate the health burden of laboratory-confirmed pertussis by age groups, considering the setting of illness onset (ie, in community, outpatient and inpatient), in a Chinese population (~2.23 million in total) at two sites. METHODS AND ANALYSIS: This paper describes the study design of a 1-year, prospective, age-stratified and population-based case-control study, including site selection, study population, case registry, ascertainment and enrolment, control recruitment, follow-up of case, microbiological methods, data collection, quality control activities and statistical methods used to generate incidence estimates. During June 2021 through May 2022, registry of suspected pertussis cases (namely chronic/persistent cough) will be conducted in several participating hospitals (SHs) at the two sites, which are selected based on Healthcare Utilisation and Attitudes Surveys (HUAS) carried out before study initiation. A case-control study will be conducted in the SHs and we aim to enrol a total of 1000 suspected pertussis cases (ie, all hospital admissions and the first 1-3 outpatient visits each week each hospital) and 2000 frequency matched healthy controls in community. Our primary study outcome, the laboratory-confirmed Bordetella pertussis infection, will be determined by a comprehensive laboratory methods and procedures (ie, culture, PCR and serological tests) in both cases and controls at enrolment and during 60-day's follow-up visits. Finally, data from HUAS (ie, population size), case registry (ie, the total number of suspected pertussis cases) and case-control study (ie, the prevalence or population attributable fraction of Bordetella pertussis) will be combined to calculate incidence and its 95% CI through bootstrap method. Epidemiological analyses will be conducted to determine the risk factors associated with severe sequelae of pertussis. ETHICS AND DISSEMINATION: This study has been approved by Chinese Centre for Disease Control and Prevention's Institutional Review Board (no. ICDC-202110). Results will be disseminated via academic presentations and publication in peer-reviewed journals, and will provide valuable scientific data and some new insights into the incidence, aetiology and risk factors for severe sequelae of pertussis to academic societies and the public health authorities who is currently struggling and fighting against this burdensome disease worldwide.

A Fluorescent Probe to Detect Quick Disulfide Reductase Activity in Bacteria.

The Trx and Grx systems, two disulfide reductase systems, play critical roles in various cell activities. There are great differences between the thiol redox systems in prokaryotes and mammals. Though fluorescent probes have been widely used to detect these systems in mammalian cells. Very few methods are available to detect rapid changes in the redox systems of prokaryotes. Here we investigated whether Fast-TRFS, a disulfide-containing fluorescent probe utilized in analysis of mammalian thioredoxin reductase, could be used to detect cellular disulfide reducibility in bacteria. Fast-TRFS exhibited good substrate qualities for both bacterial thioredoxin and GSH-glutaredoxin systems in vitro, with Trx system having higher reaction rate. Moreover, the Fast-TRFS was used to detect the disulfide reductase activity in various bacteria and redox-related gene null E. coli. Some glutaredoxin-deficient bacteria had stronger fast disulfide reducibility. The Trx system was shown to be the predominant disulfide reductase for fast disulfide reduction rather than the Grx system. These results demonstrated that Fast-TRFS is a viable probe to detect thiol-dependent disulfide reductases in bacteria. It also indicated that cellular disulfide reduction could be classified into fast and slow reaction, which are predominantly catalyzed by E. coli Trx and Grx system, respectively.

Post-vaccination serologic testing of infants born to hepatitis B surface antigen-positive mothers is more cost-effective in Zhejiang Province, China: A Markov chain analysis.

To evaluate the cost-effectiveness of the post-vaccination serologic testing (PVST) plus active-passive immunoprophylaxis of infants born to hepatitis B surface antigen (HBsAg)-positive mothers, a Markov model was constructed by R 4.0.1 to compare the current strategy (three-dose HepB plus HBIG) and the PVST strategy (post-vaccination serologic testing plus the current strategy) for infants of HBsAg-positive mothers. Costs and utility scores were assessed from a field survey. Other model inputs were extracted from published literature and unpublished data from the Zhejiang provincial center for disease control and prevention (Zhejiang CDC). We calculated the incremental cost-effectiveness ratio (ICER) as the main result within 1-year cycle length with a 81 horizon among 50,000 infants and performed one-way sensitivity analysis and probabilistic sensitivity analysis to explore the reliability of outcome. The ICER was -4130.18 yuan/quality-adjusted life year (QALY) for the PVST strategy compared with the current strategy from the societal perspective. It was estimated that the PVST strategy would save about 3,809,546 yuan and prevent loss of 922.37 QALYs within 81 cycles among 50,000 infants. ICER was most sensitive to the discount rate, and the cost-effectiveness acceptability curves showed that the PVST strategy reached a probability of being 100% cost-effective below willing to pay (107,624 yuan). In conclusion, the PVST strategy had increased the utility and reduced cost among infants born to HBsAg-positive mothers. The PVST strategy is a more cost-effective choice for infants born to HBsAg-positive mothers than the current strategy, and further promotion of the PVST project is recommended.

Antifungal Therapy with Azoles Induced the Syndrome of Acquired Apparent Mineralocorticoid Excess: a Literature and Database Analysis.

We aimed to estimate the risk of varied antifungal therapy with azoles causing the syndrome of acquired apparent mineralocorticoid excess (AME) in real-world practice. First, we conducted a disproportionality analysis based on data from the FDA Adverse Event Reporting System (FAERS) database to characterize the signal differences of triazoles-related AME. Second, a systematic review was conducted, and clinical features of AME cases reported in clinical practice were described. In the FAERS database, we identified 27 cases of triazoles-AME, posaconazole [ROR = 865.37; 95%CI (464.14; 1613.45)], and itraconazole [ROR = 556.21; 95% (303.05; 1020.85)] significantly increased the risk of AME events, while fluconazole, voriconazole, and isavuconazole did not affect any of the mineralocorticoid excess targets. Eighteen studies with 39 cases raised evidence of AME following posaconazole and itraconazole treatment, and another 27 cases were identified by analysis of the description of clinical features in the FAERS database. The average age of 66 patients was 55.5 years (6-87 years). AME mainly occurs in patients with posaconazole concentrations above 3 µg/mL (mean = 4.4 µg/mL, range 1.8∼9.5 µg/mL), and is less likely to occur when levels are below 2 µg/mL (6%). The median time to event onset was 11.5 weeks, and 50% of the adverse events occurred within 3 months for posaconazole. The presented study supports very recent findings that posaconazole and itraconazole, but not the other three azole antifungals investigated, are associated with AME and that the effects are dose-dependent, which allows for a dose de-escalation strategy and for substitution with fluconazole, isavuconazole, or voriconazole to resolve the adverse effects.

Non-prescription antibiotic use for cough among Chinese children under 5 years of age: a community-based cross-sectional study.

OBJECTIVE: This study aimed to investigate the non-prescription use of antibiotics for cough among children under 5 years in China. DESIGN: A community-based cross-sectional survey. SETTING: A face-to-face interview based on a standard questionnaire in the community from October to December 2019. PARTICIPANTS: A total of 3102 children under 5 years of age were enrolled with probability proportionate to size sampling method. The children's caregivers provided the responses as their agents. OUTCOME MEASURES: Cough in the past month, non-prescription use of antibiotics after cough. RESULTS: 1211 of 3102 children were reported to have a cough in the past month. Of these, 40.2% (487/1211) were medicated with antibiotics, and 18.7% (91/487) of these were not prescribed. Cephalosporins were the most frequently used antibiotic (52.8%), and community pharmacies were the main source (53.7%). Children who coughed for 1-2 weeks (OR 1.73, 95% CI 1.03 to 2.90) or 3-4 weeks (OR 2.39, 95% CI 1.08 to 4.97), with runny nose (OR 1.86, 95% CI 1.13 to 3.19) or those whose family annual income between ¥50 000 and ¥100 000 (OR 4.44, 95% CI 1.52 to 18.95) had a higher risk of non-prescription use of antibiotics than those coughing for <1 week, without runny nose or with family annual income <¥50 000. CONCLUSIONS: Our findings indicated that a high proportion of infants and young children had been treated with antibiotics for cough, and nearly one in five of them were used without prescription. More public health campaigns and further education on the appropriate use of antibiotics are needed to ensure the rational treatment of cough in children.

Laboratory parameters between multisystem inflammatory syndrome in children and Kawasaki disease.

Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been described to partially overlap with Kawasaki disease (KD) with regard to clinical symptoms, but they are unlikely to share the same disease entity. We conducted a systematic review and meta-analysis to characterize the laboratory parameters of MIS-C compared with those of KD and Kawasaki disease shock syndrome (KDSS). Databases were searched for studies on laboratory parameters of MIS-C (hematology, inflammatory markers, cardiac markers, and biochemistry) through May 31, 2021. Twelve studies with 3073 participants yielded 969 MIS-C patients. In terms of hematology, MIS-C patients had lower levels of leukocytes, absolute lymphocyte count and platelet count (PLT) than KD patients and had similar absolute neutrophil count (ANC) and hemoglobin (Hb) levels. In terms of inflammatory markers, MIS-C patients had higher levels of C-reactive protein, D-dimer and ferritin than KD patients and had similar levels of procalcitonin and erythrocyte sedimentation rate (ESR). In terms of cardiac markers, MIS-C patients had higher CPK levels than KD patients. The levels of N-terminal pro-brain natriuretic peptide, troponin and aspartate aminotransferase were not significantly different between MIS-C and KD patients. In terms of biochemistry, MIS-C patients had lower levels of albumin, sodium and alanine aminotransferase and higher levels of creatinine than KD patients. In addition, MIS-C patients had lower levels of PLT, Hb and ESR and higher levels of ANC than KDSS patients. Measurement of laboratory parameters might assist clinicians with accurate evaluation of MIS-C and further mechanistic research.

Non-prescriptionxx antibiotic use for people aged 15 years or older for cough in China: a community-based survey.

BACKGROUND: Non-prescription antibiotic use at community is a main driver of antimicrobial resistance. Cough is a common condition and prevalent in all townships, including China. This study aims to investigate the non-prescription antibiotic use for cough in China and explore to which extent antibiotic use knowledge was correctly instructed in communities. METHODS: A probability-proportionate-to-size sampling method was adopted to survey from all 14 townships in Yiwu city, China. All participants were investigated by face-to-face interview on Portable Android Devices. The continuous variables were presented by mean and standard deviation or medium and inter-quartile range (IQR). The categorical variables were presented using percentage or constituent ratio. Chi-square test for univariate analysis and logistic regression for multivariate analysis were conducted to assess the odds ratios and 95% confidence intervals, respectively. RESULTS: A total of 3034 respondents across all the 14 townships and the 50 natural villages/streets completed all key items of the questionnaire. Of 2400 (79.10%) respondents stated that they experienced cough in the past 12 months with the medium age of 36.5 (IQR: 26-49) and 12.21% (293/2400) respondents had the non-prescription antibiotic use behavior. Among those 293 respondents, the proportion of non-prescription antibiotic use for cough peaked at around 16% among people aged 30-39 years old. The major sources of antibiotics were pharmacy (77.70%) and/or family storage (43.92%). CONCLUSIONS: Non-prescription antibiotics use for cough is prevalent in the community, especially among people in their thirties. Strengthened drug purchase regulation and well-trained professional pharmacists would be promising alternatives to ameliorate AMR. Moreover, penetrating antibiotics knowledge to common citizens and is an urgent task to alleviate antimicrobial resistance. Therefore, proactive policies and regulations should be made to improve current situations.

Influencing factors and necessity of post-vaccination serologic testing follow-up for HBsAg-positive mothers and their infants: A 5-year prospective study in Zhejiang Province, China (2016-2020).

In 2016, China officially proposed for the first time that infants born to HBsAg-positive mothers should be tested for HBsAg and anti-HBs 1-2 months after their third dose of HepB, also known as the post-vaccination serological testing programme. This study aimed to systematically evaluate the implementation and influencing factors of PVST to further reduce HBV infection risk in infants and improve the protective effect of HepB to the greatest extent. A prospective observational study was conducted to investigate the interruption of MTCT of hepatitis B. Univariate and multivariate analyses were applied to explore factors associated with the PVST follow-up rate among HBsAg-positive mothers and their infants. Additionally, bivariate analysis was performed on HBsAg and anti-HBs results in infants born to HBsAg-positive mothers. Here, the participation rate of PVST was 67.08% among 2120 pairs of positive mothers and infants. The HBsAg-positive rate among participants was 0.77%, whereas the anti-HBs positive rate was 96.84%, and both negative rates were 2.39%. Among infants with double negative results (34), only 15 completed three doses of HepB and PVST again, and 14 (93.33%) of which the antibody test results turned positive. Older mothers with high educational levels who reside in the local area were the most likely to PVST follow-up. The PVST programme is necessary to evaluate the HepB response status of newborns after vaccination. Moreover, revaccination for susceptible infants can effectively improve the MTCT-blocking rate of hepatitis B. Therefore, the scope of PVST projects in Zhejiang and China should be expanded.

Economic and disease burden of Japanese encephalitis in Zhejiang Province, 2013-2018.

BACKGROUND: Japanese encephalitis (JE) is a mosquito-borne disease and associated with high mortality and disability rate among symptomatic cases. In the absence of local data, this study estimated the economic burden and the disability-adjusted life years (DALYs) due to JE in Zhejiang Province, China during 2013-2018, to increase disease awareness and provide evidence for effective health policy. METHODOLOGY/PRINCIPLE FINDINGS: We merged multiple data sources, including National Notifiable Disease Registry System (NNDRS), patient interviews and medical records from corresponding hospitals for JE cases which occurred during 2013-2018 in Zhejiang Province. Direct costs were extracted from hospitals' billing systems and patient interviews. Indirect costs and disease burden were calculated based on questionnaire survey from patient interviews and follow-up assessment by general practitioners. Given under-reporting, an expansion factor (EF) was applied to extrapolate the JE burden to the provincial level. The total economic burden of JE during 2013-2018 was estimated at US $12.01 million with an EF = 3. Of this, $8.32 million was due to direct economic cost and $3.69 million to indirect cost. The disease burden of JE was 42.75 DALYs per million population (28.44 YLD, 14.28 YLL) according to the 1990 Global Burden of Disease (GBD 1990) methodology and 80.01 DALYs (53.67YLD, 26.34YLL) according to the GBD 2010 methodology. Sensitivity analysis demonstrated that the overall economic burden varied from US$ 1.73-36.42 million. The greatest variation was due to the prognosis of illness (-85.57%-203.17%), followed by occupation (-34.07%-134.12%) and age (-72.97%-47.69%). CONCLUSIONS/SIGNIFICANCE: JE imposes a heavy burden for families and society in Zhejiang Province. This study provides comprehensive empirical estimates of JE burden to increase awareness and strengthen knowledge of the public. These data may support provincial level public health decision making for prevention and control of JE. Ongoing surveillance for acute meningitis and encephalitis syndrome (AEMS) in sentinel hospitals, is needed to further refine estimates of JE burden.

Intention to accept pertussis vaccination among Chinese people older than age 5.

Background: The intention of Chinese people older than age 5 to accept the pertussis vaccination is unknown, which is important for the future design of an effective pertussis vaccination program in China.Method: We conducted a cross-sectional survey among people older than age 5 in China. A 24-item questionnaire was used to explore the determinants of intention to accept a pertussis vaccination, and for children and adolescents (≦15 years old), their guardian was required to help answer the questionnaire on their behalf. Univariate and multivariate logistic regression was used to analyze the influencing factors of intention.Results: A total of 3,041 individuals participated in our survey and 3025 completed the questionnaire, among which 1938 (64.07%) reported a positive intention to be vaccinated. A multiple logistic regression analysis revealed that the main positive factors for the intention to accept pertussis vaccination were younger age (Odd ratio [OR] 0.838, P < .001), higher educational attainment (OR 1.171, P = .002), no hospitalization because of the most recent cough (OR 2.468, P < .001), awareness about pertussis (OR 1.958, P < .001), and consideration of pertussis vaccination to be safe (OR 1.450, P = .026).Conclusion: There is a relatively high level of intention to receive the pertussis vaccine among people older than age 5 in China. Future pertussis vaccination strategies geared at them should consider focusing on middle-aged and older individuals and those with a low education as well as strengthen the promotion of disease characteristics, vaccine effectiveness, and safety.

Serological and molecular epidemiology of Japanese Encephalitis in Zhejiang, China, 2015-2018.

BACKGROUND: Shifts have occurred in the epidemiological characteristics of Japanese encephalitis (JE), extending from the molecular level to the population level. The aim of this study was to investigate the seroprevalence of JE neutralizing antibodies in healthy populations from different age groups in Zhejiang Province, and to conduct mosquito monitoring to evaluate the infection rate of Japanese encephalitis virus (JEV) among vectors, as well as the molecular characteristics of the E gene of isolated JEV strains. METHODOLOGY/PRINCIPAL FINDINGS: A total of 1190 sera samples were screened by a microseroneutralization test, including 429 infants (28d-11m) and 761 participants (2y-82y). For those under 1 year old, the geometric mean titers (GMTs) of the JE neutralizing antibody was 9.49 at birth and significantly declined as the age of month increased (r = -0.225, P<0.001). For those above 1-year old, seropositive proportions were higher in subjects aged 1-3 years old as well as ≥25 years old (65%-75%), and relatively lower in subjects aged between 4-25 years old (22%-55%). Four or more years after the 2nd dose of JEV-L (first dose administered at 8 months and the second at 2 years of age), the seropositive proportion decreased to 32.5%, and GMTs decreased to 8.08. A total of 87,201 mosquitoes were collected from livestock sheds in 6 surveillance sites during 2015-2018, from which 139 E gene sequences were successfully amplified. The annual infection rate according to bias-corrected maximum likelihood estimation of JEV in Culex tritaeniorhynchus was 1.56, 2.36, 5.65 and 1.77 per 1000, respectively. JEV strains isolated during 2015-2018 all belonged to Genotype I. The E gene of amplified 139 samples differed from the JEV-L vaccine strain at fourteen amino acid residues, including the eight key residues related to virulence and virus attenuation. No divergence was observed at the sites related to antigenicity. CONCLUSIONS/SIGNIFICANCE: Zhejiang Province was at a high risk of JE exposure due to relatively lower neutralizing antibody levels among the younger-aged population and higher infection rates of JEV in mosquitoes. Continuous, timely and full coverage of JE vaccination are essential, as well as the separation of human living areas and livestock shed areas. In addition, annual mosquito surveillance and periodic antibody level monitoring are important for providing evidence for improvement in JE vaccines and immunization schedules.