Genomic and spatial analysis reveal the transmission dynamics of tuberculosis in areas with high incidence of Zhejiang, China: A prospective cohort study.

In the mountainous, rural regions of eastern China, tuberculosis (TB) remains a formidable challenge; however, the long-term molecular epidemiological surveillance in these regions is limited. This study aimed to investigate molecular and spatial epidemiology of TB in two mountainous, rural counties of Zhejiang Province, China, from 2015 to 2021, to elucidate the recent transmission and drug-resistance profiles. The predominant Lineage 2 (L2) Beijing family accounted for 80.1% of total 532 sequenced Mycobacterium tuberculosis (Mtb) strains, showing consistent prevalence over seven years. Gene mutations associated with drug resistance were identified in 19.4% (103/532) of strains, including 47 rifampicin or isoniazid-resistant strains, eight multi-drug-resistant (MDR) strains, and five pre-extensively drug-resistant (pre-XDR) strains. Genomic clustering revealed 53 distinct clusters with an overall transmission clustering rate of 23.9% (127/532). Patients with a history of retreatment and those infected with L2 strains had a higher risk of recent transmission. Spatial and epidemiological analysis unveiled significant transmission hotspots, especially in densely populated urban areas, involving various public places such as medical institutions, farmlands, markets, and cardrooms. The study emphasizes the pivotal role of Beijing strains and urban-based TB transmission in the western mountainous regions in Zhejiang, highlighting the urgent requirement for specific interventions to mitigate the impact of TB in these unique communities.

Associations of genetic variants within TYK2 with pulmonary tuberculosis among Chinese population.

BACKGROUND: Pulmonary tuberculosis (PTB) is a common infectious disease caused by mycobacterium tuberculosis (MTB) and the present study aims to explore the associations of genetic variants within tyrosine kinases 2 (TYK2) with PTB incidence. METHODS: A population-based case control study including 168 smear-positive PTB cases and 251 controls was conducted. Five single nucleotide polymorphisms (SNPs) including rs280520, rs91755, rs2304256, rs12720270, rs280519 located within TYK2 gene were selected and MassARRAY® MALDI-TOF system was employed for genotyping. SPSS 19.0 was adopted for statistical analysis, non-conditional logistic regression was conducted. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed to estimate their contributions to PTB incidence. RESULTS: In the overall study population, rs91755 TT and rs280519 AA genotypes were found to be associated with reduced PTB risk (OR = 0.34, 95% CI: 0.16-0.72; OR = 0.38, 95% CI: 0.18-0.79, respectively). After stratification for sex, we found that among the male population, rs91755TG/TT, rs12720270AG/GG and rs280519AG/AA genotypes were associated with reduced PTB risk (OR = 0.41, 95% CI: 0.21-0.80; OR = 0.44, 95% CI: 0.21-0.94; OR = 0.42, 95% CI: 0.21-0.82, respectively). After stratification for age, we found that among those aged <60 years, rs91755TT and rs280519AA genotype were associated with reduced PTB risk (OR = 0.29, 95% CI: 0.09-0.90; OR = 0.34, 95% CI: 0.11-1.08, respectively); while rs2304256AC/AA genotype was associated with increased PTB risk (OR = 2.68, 95% CI: 1.05-6.85). Haplotype analysis revealed that AGAAG and ATCGA (Combined with rs280520, rs91755, rs2304256, rs12720270 and rs280519) were associated with increased (OR = 1.54, 95% CI: 1.01-2.37) and decreased PTB risk (OR = 0.70, 95% CI: 0.52-0.94), respectively. CONCLUSIONS: The genetic variants located within TYK2 including rs91755, rs12720270 and rs280519 were found to be associated with modified PTB risk and the SNPs had potential to be the biomarkers to predict PTB incidence risk.

Evaluation of nucleotide MALDI-TOF-MS for the identification of Mycobacterium species.

Background: The accurate identification of the Mycobacterium tuberculosis complex (MTBC) and different nontuberculous mycobacteria (NTM) species is crucial for the timely diagnosis of NTM infections and for reducing poor prognoses. Nucleotide matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has been extensively used for microbial identification with high accuracy and throughput. However, its efficacy for Mycobacterium species identification has been less studied. The objective of this study was to evaluate the performance of nucleotide MALDI-TOF-MS for Mycobacterium species identification. Methods: A total of 933 clinical Mycobacterium isolates were preliminarily identified as NTM by the MPB64 test. These isolates were identified by nucleotide MALDI-TOF-MS and Sanger sequencing. The performance of nucleotide MALDI-TOF MS for identifying various Mycobacterium species was analyzed based on Sanger sequencing as the gold standard. Results: The total correct detection rate of all 933 clinical Mycobacterium isolates using nucleotide MALDI-TOF-MS was 91.64% (855/933), and mixed infections were detected in 18.65% (174/933) of the samples. The correct detection rates for Mycobacterium intracellulare, Mycobacterium abscessus, Mycobacterium kansasii, Mycobacterium avium, MTBC, Mycobacterium gordonae, and Mycobacterium massiliense were 99.32% (585/589), 100% (86/86), 98.46% (64/65), 94.59% (35/37), 100.00% (34/34), 95.65% (22/23), and 100% (19/19), respectively. For the identification of the MTBC, M. intracellulare, M. abscessus, M. kansasii, M. avium, M. gordonae, and M. massiliense, nucleotide MALDI-TOF-MS and Sanger sequencing results were in good agreement (k > 0.7). Conclusion: In conclusion, nucleotide MALDI-TOF-MS is a promising approach for identifying MTBC and the most common clinical NTM species.

A Privacy-Preserving Trajectory Publishing Method Based on Multi-Dimensional Sub-Trajectory Similarities.

With the popularity of location services and the widespread use of trajectory data, trajectory privacy protection has become a popular research area. k-anonymity technology is a common method for achieving privacy-preserved trajectory publishing. When constructing virtual trajectories, most existing trajectory k-anonymity methods just consider point similarity, which results in a large dummy trajectory space. Suppose there are n similar point sets, each consisting of m points. The size of the space is then mn. Furthermore, to choose suitable k- 1 dummy trajectories for a given real trajectory, these methods need to evaluate the similarity between each trajectory in the space and the real trajectory, leading to a large performance overhead. To address these challenges, this paper proposes a k-anonymity trajectory privacy protection method based on the similarity of sub-trajectories. This method not only considers the multidimensional similarity of points, but also synthetically considers the area between the historic sub-trajectories and the real sub-trajectories to more fully describe the similarity between sub-trajectories. By quantifying the area enclosed by sub-trajectories, we can more accurately capture the spatial relationship between trajectories. Finally, our approach generates k-1 dummy trajectories that are indistinguishable from real trajectories, effectively achieving k-anonymity for a given trajectory. Furthermore, our proposed method utilizes real historic sub-trajectories to generate dummy trajectories, making them more authentic and providing better privacy protection for real trajectories. In comparison to other frequently employed trajectory privacy protection methods, our method has a better privacy protection effect, higher data quality, and better performance.

Bedaquiline Resistance and Molecular Characterization of Rifampicin-Resistant Mycobacterium Tuberculosis Isolates in Zhejiang, China.

Purpose: This study aimed to determine the prevalence and molecular characterization of bedaquiline (BDQ) resistance among rifampicin-resistant tuberculosis (RR-TB) isolates collected from Zhejiang, China. Patients and Methods: A total of 245 RR-TB isolates were collected from 19 municipal TB hospitals in Zhejiang province, China between January and December 2021. Microplate assays were used to determine the minimum inhibitory concentrations (MIC) of BDQ. Whole-genome sequencing (WGS) was performed on isolates with MIC values for BDQ ≥ 0.25 µg/mL. Results: Five (2.04%) BDQ-resistant strains were isolated from 245 tuberculosis patients. The resistance rate of BDQ was not correlated to the sex, age, treatment history, or occupation of patients. Four BDQ-resistant isolates and three BDQ-sensitive isolates were found to carry Rv0678 mutations, and one BDQ-resistant strain carried both Rv0678 and pepQ mutations. No mutations within the atpE and Rv1979c genes were observed. Conclusion: BDQ demonstrated strong in vitro antibacterial activity against RR-TB isolates, and the Rv0678 gene was identified as the primary mechanism contributing to BDQ resistance among RR-TB isolates from Zhejiang, China. Furthermore, in addition to the four currently known resistance-associated genes (atpE, Rv0678, Rv1979c, and pepQ), other mechanisms of resistance to BDQ may exist that need further study.

The Efficacy and Safety of Bedaquiline in the Treatment of Pulmonary Tuberculosis Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Bedaquiline (BDQ) has been designated as a Group A drug by the World Health Organization (WHO) for the management of multi-drug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). This systematic review and meta-analysis aim to evaluate the efficacy and safety of BDQ-containing regimens for the treatment of patients with pulmonary TB. METHODS: PubMed (MEDLINE), Elton B. Stephens Company (EBSCO) database, the Cochrane Register of Controlled Trials, and the China National Knowledge Infrastructure (CNKI) database were initially searched on 15 June 2022 and again on 20 March 2023. We included randomized controlled trials (RCTs) and non-randomized studies (NRSs) that administered BDQ to TB patients. The outcomes of interest were as follows: (1) efficacy, including the rate of sputum culture conversion at 8 weeks, 24 weeks, and during follow-up, as well as the rates of completion cure, death, treatment failure, and loss at follow-up and at the end of the treatment; and (2) safety, which encompassed the incidences of cardiotoxicity, hepatotoxicity, and grade 3-5 adverse events during the treatment period. RESULTS: A total of 29 articles were included in this meta-analysis, representing 23,358 individuals. Patients who were treated with BDQ were compared with patients who were not exposed to BDQ. The use of BDQ-containing regimens demonstrated improved rates of sputum conversion in RCTs at 24 weeks (RR = 1.27, 95% CI: 1.10 to 1.46) and during follow-up (RR = 1.33, 95% CI: 1.06 to 1.66). Additionally, BDQ-containing regimens showed increased cure rates (RR = 1.60, 95% CI: 1.13 to 2.26) and decreased failure rates (RR = 0.56, 95% CI: 0.56 to 0.88). In NRSs, BDQ-containing regimens improved the sputum culture conversion rate during follow-up (RR = 1.53, 95% CI: 1.07 to 2.20), increased the rate of cure (RR = 1.86, 95% CI: 1.23 to 2.83), reduced deaths from all causes (RR = 0.68, 95% CI: 0.48 to 0.97), and reduced failure rates (RR = 0.57, 95% CI: 0.46 to 0.71). However, the use of BDQ-containing regimens was associated with increased incidences of cardiotoxicity (RR = 4.54, 95% CI: 1.74 to 11.87) and grade 3-5 adverse events (RR = 1.42, 95% CI: 1.17 to 1.73) in RCTs. NRSs also showed an association between BDQ-containing regimens and cardiotoxicity (RR = 6.00, 95% CI: 1.32 to 27.19). No significant differences were observed between intervention groups and control groups with respect to other outcomes. CONCLUSIONS: Data from both RCTs and NRSs support the efficacy of BDQ for the treatment of pulmonary tuberculosis. However, the use of BDQ is associated with a higher incidence of cardiotoxicity and serious adverse events. Comparative data on efficacy and safety are limited, and further confirmation is required, due to potential bias and discrepancies in the available studies.

Whole-Genome Sequencing to Predict Mycobacterium tuberculosis Drug Resistance: A Retrospective Observational Study in Eastern China.

Pulmonary tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB). Whole-genome sequencing (WGS) holds great promise as an advanced technology for accurately predicting anti-TB drug resistance. The development of a reliable method for detecting drug resistance is crucial in order to standardize anti-TB treatments, enhance patient prognosis, and effectively reduce the risk of transmission. In this study, our primary objective was to explore and determine the potential of WGS for assessing drug resistance based on genetic variants recommended by the World Health Organization (WHO). A total of 1105 MTB strains were selected from samples collected from 2014-2018 in Zhejiang Province, China. Phenotypic drug sensitivity tests (DST) of the anti-TB drugs were conducted for isoniazid (INH), rifampicin (RFP), streptomycin, ethambutol, fluoroquinolones (levofloxacin and moxifloxacin), amikacin, kanamycin, and capreomycin, and the drug-resistance rates were calculated. The clean WGS data of the 1105 strains were acquired and analyzed. The predictive performance of WGS was evaluated by the comparison between genotypic and phenotypic DST results. For all anti-TB drugs, WGS achieved good specificity values (>90%). The sensitivity values for INH and RFP were 91.78% and 82.26%, respectively; however, they were ≤60% for other drugs. The positive predictive values for anti-TB drugs were >80%, except for ethambutol and moxifloxacin, and the negative predictive values were >90% for all drugs. In light of the findings from our study, we draw the conclusion that WGS is a valuable tool for identifying genome-wide variants. Leveraging the genetic variants recommended by the WHO, WGS proves to be effective in detecting resistance to RFP and INH, enabling the identification of multi-drug resistant TB patients. However, it is evident that the genetic variants recommended for predicting resistance to other anti-TB drugs require further optimization and improvement.

TransFlow: a Snakemake workflow for transmission analysis of Mycobacterium tuberculosis whole-genome sequencing data.

MOTIVATION: Whole-genome sequencing (WGS) is increasingly used to aid the understanding of Mycobacterium tuberculosis (MTB) transmission. The epidemiological analysis of tuberculosis based on the WGS technique requires a diverse collection of bioinformatics tools. Effectively using these analysis tools in a scalable and reproducible way can be challenging, especially for non-experts. RESULTS: Here, we present TransFlow (Transmission Workflow), a user-friendly, fast, efficient and comprehensive WGS-based transmission analysis pipeline. TransFlow combines some state-of-the-art tools to take transmission analysis from raw sequencing data, through quality control, sequence alignment and variant calling, into downstream transmission clustering, transmission network reconstruction and transmission risk factor inference, together with summary statistics and data visualization in a summary report. TransFlow relies on Snakemake and Conda to resolve dependencies among consecutive processing steps and can be easily adapted to any computation environment. AVAILABILITY AND IMPLEMENTATION: TransFlow is free available at https://github.com/cvn001/transflow. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Drug resistance patterns and dynamics of tuberculosis in Zhejiang Province, China: Results from five periodic longitudinal surveys.

Background: As one of the high multi-drug resistance tuberculosis countries, it is critical for China to understand patterns of drug resistance to better formulate effective treatment regimens. Methods: The anti-TB Drug resistance surveillance has been conducted in Zheijang Province in years 1999, 2004, 2008, 2013, and 2018 respectively. We compared the prevalence of DR-TB from the latest survey with that of the previous four surveys in terms of all four first-line anti-TB drugs. We also examined the prevalence of rifampin-resistant TB (RR-TB) between the last two surveys and routine surveillance data. Results: Among 996 patients surveyed in 2018, the prevalence of RR-TB in new and previously treated TB cases was 2.5 and 4.3%, respectively. The prevalence of RR-TB among previously treated cases was much higher than for new cases in the four surveys from 1999 to 2013, while there was no significant difference between these groups in the 2018 survey. The percentage of TB cases resistant to fluoroquinolones in new patients was 3.8%. The prevalence of non-tuberculous mycobacteria increased over time; the prevalence of RR-TB among new cases slowly decreased. The prevalence of RR-TB in both new and previously treated TB cases from the latest two surveys was consistent with routine surveillance data. Conclusions: This consistency between routine surveillance and periodic surveys for TB cases implies that with universal testing in Zhejiang Province, data from routine surveillance could be used instead of periodic surveys to improve access to timely and appropriate treatment for DR-TB. Levels of resistance were lower than whole-country and global estimates, further indicating the value of universal drug susceptibility testing.

The burden and predictors of latent tuberculosis infection among elder adults in high epidemic rural area of tuberculosis in Zhejiang, China.

Diagnosis and treatment of latent tuberculosis infection (LTBI) is critical to tuberculosis (TB) control. Identifying the risk factors associated with LTBI can contribute to developing an optimized strategy for LTBI management. We conducted a survey of adults aged 65 years and older living in rural areas in Zhejiang Province during July 2021, followed by a one-year follow-up period to determine TB incidence. Participants underwent a physical examination and 5-6 mL of blood was drawn to test for Mycobacterium tuberculosis infection A total of 1856 individuals participated in the study, of whom 50.5% were men and 80.1% were married. Most participants (96.8%) often opened windows for ventilation at home. One-third (33.4%) of participants had abnormal chest radiographs and 34.9% had LTBI. Nine participants (0.5%) developed active TB patients during the one-year follow-up period. People who frequented closed entertainment places such as chess and card rooms had a relatively high percentage of LTBI (39.5%). Factors associated with a higher risk of LTBI in multivariable logistic regression analysis included being male (odds ratio [OR]:1.32; 95% confidence interval [CI] =:1.01-1.72), smoking (OR: 1.43; 95% CI:1.04-1.97), not opening windows for ventilation at home frequently (OR: 1.88; 95% CI: 1.10-3.22), and abnormal chest radiographs (OR; 1.48; 95% CI; 1.20-1.81). LTBI was prevalent among the elder adults living in high-epidemic rural areas of TB in Zhejiang province. Men, people who smoke, and people without the habit of ventilating at home should be targeted for LTBI screening to accelerate the decline of the TB epidemic in Zhejiang Province.

Identification and characterization of nontuberculous mycobacteria isolated from suspected pulmonary tuberculosis patients in eastern china from 2009 to 2019 using an identification array system.

OBJECTIVE: Nontuberculous mycobacteria (NTM) species are increasingly being isolated and have become a key factor affecting public health by causing pulmonary diseases. Most NTM species do not respond to conventional tuberculosis (TB) drugs. This study aimed to identify NTM isolated from suspected pulmonary TB patients from the Zhejiang province and analyze their distribution in the region. METHODS: A total of 1,113 NTM isolates from patients suspected to be suffering from acid-fast bacilli-positive tuberculosis were identified at the species level, using the CapitalBio Mycobacterium identification array and polymerase chain reaction amplification and sequencing of 16S-23S gene internal transcribed spacer (ITS), 16S rRNA, and hsp65. RESULTS: Of the 23,138 isolates, we identified 1,102 NTM (4.8%), mainly including Mycobacterium intracellulare (54.81%, 604/1,102), M. chelonae-M. abscessus (16.52%, 182/1,102), M. avium (13.16%, 145/1,102), M. kansasii (8.17%, 90/1,102), and M. gordonae (3.27%, 36/1,102). CONCLUSION: The distribution of NTM species observed in patients with suspected pulmonary tuberculosis provides guidance for the diagnosis and treatment of NTM pulmonary diseases.

Identification and characterization of nontuberculous mycobacteria isolated from suspected pulmonary tuberculosis patients in eastern china from 2009 to 2019 using an identification array system

Abstract Objective Nontuberculous mycobacteria (NTM) species are increasingly being isolated and have become a key factor affecting public health by causing pulmonary diseases. Most NTM species do not respond to conventional tuberculosis (TB) drugs. This study aimed to identify NTM isolated from suspected pulmonary TB patients from the Zhejiang province and analyze their distribution in the region. Methods A total of 1,113 NTM isolates from patients suspected to be suffering from acid-fast bacilli-positive tuberculosis were identified at the species level, using the CapitalBio Mycobacterium identification array and polymerase chain reaction amplification and sequencing of 16S-23S gene internal transcribed spacer (ITS), 16S rRNA, and hsp65. Results Of the 23,138 isolates, we identified 1,102 NTM (4.8%), mainly including Mycobacterium intracellulare (54.81%, 604/1,102), M. chelonae-M. abscessus (16.52%, 182/1,102), M. avium (13.16%, 145/1,102), M. kansasii (8.17%, 90/1,102), and M. gordonae (3.27%, 36/1,102). Conclusion The distribution of NTM species observed in patients with suspected pulmonary tuberculosis provides guidance for the diagnosis and treatment of NTM pulmonary diseases.

Study on Flow Velocity Distribution in Open Channel With Flexible Vegetation.

Ecological management of river channels is a hot topic for current sustainable development and flow measurement of ecological river is an important part. In this article, a flow velocity distribution model of the channel containing flexible vegetation is constructed from the vegetation riverbed theory and the bursting phenomenon to reveal the microscopic mechanism of the flow velocity distribution in the upper layer of vegetation. In the vegetation riverbed law, the effect of flexible vegetation is evaluated by the mixed length formula. The bursting phenomenon law considers the influence of the channel sidewalls on the flow and a two-dimensional velocity model is established by introducing the concept of average turbulence structure. The mechanism of the downward shift of the maximum flow velocity point on the channel sidewall is explained. The verification of the calculated velocity profiles is carried out based on data obtained in laboratory experiments. The results show that the combination of the two models can well describe the velocity distribution of the whole channel. At the end, the phenomenon of flow velocity zoning in open channel is discussed, which provides a solution for flow measurement in ecological channel.

Quantum private set intersection cardinality based on bloom filter.

Private Set Intersection Cardinality that enable Multi-party to privately compute the cardinality of the set intersection without disclosing their own information. It is equivalent to a secure, distributed database query and has many practical applications in privacy preserving and data sharing. In this paper, we propose a novel quantum private set intersection cardinality based on Bloom filter, which can resist the quantum attack. It is a completely novel constructive protocol for computing the intersection cardinality by using Bloom filter. The protocol uses single photons, so it only need to do some simple single-photon operations and tests. Thus it is more likely to realize through the present technologies. The validity of the protocol is verified by comparing with other protocols. The protocol implements privacy protection without increasing the computational complexity and communication complexity, which are independent with data scale. Therefore, the protocol has a good prospects in dealing with big data, privacy-protection and information-sharing, such as the patient contact for COVID-19.

Treatment outcomes of patients with multidrug and extensively drug-resistant tuberculosis in Zhejiang, China.

BACKGROUND: The aim of this study was to assess the treatment outcomes of multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) in Zhejiang, China and to evaluate possible risk factors associated with poor outcomes of M/XDR-TB. METHODS: Two-hundred-and-sixty-two patients having M/XDR-TB who received the diagnosis and treatment at nine referral hospitals from 1 January 2016 to 31 December 2016 in Zhejiang, China were included. All patients received second-line regimens recommended by WHO under the DOTS-Plus strategy. RESULTS: Among the 262 patients, the treatment success rate was 55.34% (n = 145) with 53.44% (n = 140) cured and 1.91% (n = 5) who completed treatment, 62 (23.66%) failed, 27 (10.31%) died, 16 (6.11%) defaulted and 12 (4.58%) transferred out. Forty (64.52%) of the 62 M/XDR-TB patients who failed treatment were due to adverse effects in the first 10 months of treatment. Eighteen patients (6.37%) had XDR-TB. Treatment failure was significantly higher among patients with XDR-TB at 50% than that among patients with non-XDR-TB at 21.72% (P = 0.006). Failure outcomes were associated with a baseline weight less than 50 kg (OR, 8.668; 95% CI 1.679-44.756; P = 0.010), age older than 60 years (OR, 9.053; 95% CI 1.606-51.027; P = 0.013), hemoptysis (OR, 8.928; 95% CI 1.048-76.923; P = 0.045), presence of cavitary diseases (OR, 10.204; 95% CI 2.032-52.631; P = 0.005), or treatment irregularity (OR, 47.619; 95% CI 5.025-500; P = 0.001). CONCLUSION: Treatment outcomes for M/XDR-TB under the DOTS-Plus strategy in Zhejiang, China were favorable but still not ideal. Low body weight (< 50 kg), old age (> 60 years), severe symptoms of TB including cavitary disease, hemoptysis and irregular treatment were independent prognostic factors for failure outcomes in patients with M/XDR-TB.

Associations of genetic variants at TAP1 and TAP2 with pulmonary tuberculosis risk among the Chinese population.

Tuberculosis (TB) is a common infectious disease, and the present study aims to explore the associations of single nucleotide polymorphisms (SNPs) at rs1135216 and rs1057141 of transporter-associated antigen processing (TAP1) and rs2228396 of TAP2 with pulmonary tuberculosis (PTB) risk. A case-control study including 168 smear-positive PTB cases and 251 controls was conducted. Genotyping of the SNPs at rs1135216, rs1057141 and rs2228396 was performed, and their associations with PTB risk were analysed with SPSS software version 19.0. After conducting stratification for age, a significant association was detected for rs1057141 with increased PTB risk (OR = 0.17, 95% CI 0.04-0.79) among those aged ≥60 years. For those aged <60 years, a marginally significant association was detected between rs1135216 TC/CC and PTB risk (OR = 1.97, 95% CI 0.93-4.19). Haplotype analysis revealed that the haplotype AT at rs1135216 and rs2228396, as well as AAT at rs1057141, rs1135216 and rs2228396, was associated with increased PTB risk, and the ORs were 2.83 (95% CI 1.30-6.14) and 2.89 (95% CI 1.34-6.27), respectively. Rs1057141 is a genetic predictor of reduced PTB risk for those aged ≥60 years, while rs1135216 might be a potential genetic predictor for those aged <60 years. Haplotype AT at rs1135216 and rs2228396, as well as AAT at rs1057141, rs1135216 and rs2228396, is a genetic marker that may predict PTB risk.

Longitudinal Analysis of Prevalence and Risk Factors of Rifampicin-Resistant Tuberculosis in Zhejiang, China.

OBJECTIVES: To investigate the factors associated with rifampicin-resistant tuberculosis among drug resistant tuberculosis patients and to determine the correlation of rifampicin-resistant TB with MDR-TB in a high MDR-TB burden province of china. METHODS: A retrospective longitudinal analysis on four surveys of anti-TB drug resistance done in 1998, 2003, 2008, and 2013 in Zhejiang province, China. 4289 sputum-smear microscopy positive suspected tuberculosis patients were eligible at 30 investigation points, chosen by stratified random sampling at survey sites from all over the province. Culturing samples in L-J medium and the drug-susceptibility testing for the 4 first-line anti-TB drugs were performed to all patients. Multivariate logistic regression was carried out to determine the factors associated with the rifampicin-resistance in the study population. RESULTS: Overall, there were 3832 patients with positive mycobacterial cultures, and 2813 of the isolates (73.4%) were susceptible to all 4 first-line drugs. Analysis of rifampin monoresistant (RMR) TB indicated the prevalence was 1.1% in new cases and 3.4% in previously treated cases. Among the 359 rifampicin resistant TB (RR-TB) cases, 279 (77.7%) were also resistant to isoniazid, indicating MDR-TB. From 1998 to 2013, the proportion of MDR-TB among rifampicin-resistant TB cases varied between 80.0% and 87.5% (P for trend: 0.768) among previously treated cases and varied from 68.6% to 79.5% (P for trend: 0.403) among new cases. Among previously treated patients, those who received treatment for less than 6 months were less likely to have drug resistant TB (OR: 0.40, 95% CI: 0.16-0.97) or MDR-TB (OR: 0.24, 95% CI: 0.07-0.81). Patients who received anti-TB treatment in a general hospital were less likely to develop MDR-TB than those treated in a TB clinic (OR: 0.08, 95% CI: 0.01-0.72). CONCLUSION: This study highlights a high proportion of RMR-TB among new RR-TB cases in Zhejiang, China. The management of treatment with rapid and accurate diagnosis of MDR-TB other than only relying on RIF susceptibility testing is crucial for improving adherence and outcomes in patients with drug-resistant TB.

Changes of awareness of tuberculosis and access to tuberculosis-related information among students in Zhejiang Province in the year of 2014 and 2018 / 中国学校卫生

Objective@#To explore the changes of awareness of tuberculosis and access to tuberculosis-related information among students in Zhejiang Province.@*Methods@#There were 554 students younger than 30 y were included in the study during April to sept. of 2014 and during sept. to Nov. of 2018. Univariate and multivariate Logistic regression were conducted to find the related factors of knowing about tuberculosis and related knowledge. Chi-square test was used to analyze the changes of ways access to tuberculosis-related information.@*Results@#There were 440 participants (79.4%) aware of tuberculosis, including 215(85.7%) in 2014 and 225(74.3%) in 2018. The factors affecting awareness on tuberculosis were female ( AOR=1.60, 95%CI =1.04-2.47) vs male; and junior middle school( AOR=1.99, 95%CI =1.03-3.85), high school( AOR=3.27, 95%CI =1.57-6.81), college or higher ( AOR=6.73，95%CI =2.55-17.76) vs primary school or lower; year 2018 ( AOR=0.50, 95%CI =0.31-0.80) vs 2014. There was no significant statistical difference in the overall knowledge scores of tuberculosis between the students in the two surveys. In 2018, the proportion of tuberculosisrelated information accessed from the Internet (forum, WeChat, Weibo.) and community activities (assembly promotion)(75.10%, 26.70%) was higher than that of 2014(36.20%, 13.10%)( χ 2=68.88, 12.79, P <0.05).@*Conclusion@#The proportion of students aware of tuberculosis and TB control in Zhejiang Province were not significantly improved. Higher proportion of students get tuberculosis-related information from the new media. Therefore, it is necessary to strengthen health education of tuberculosis in schools, especially through the usage of new media apart from traditional pathways.

An efficient and adaptive data-hiding scheme based on secure random matrix.

There is a vivid research on securely deliver a secret message by using a data hiding technique in digital images. However, most existing solutions of data-hiding need to encrypt secret data first, and embed the encrypt message into cover image, which is not promising any security once the embedding algorithm is leaked. In this paper, an efficient and adaptive data hiding scheme is presented which is based on a new reference matrix named secure reference matrix. The scheme is flexible enough to meet different data hiding capacities and image quality as needed, and we allow the reference matrix to be more secure since it is randomly generated each time and make it much harder for being attack with exhaustive manner by extending the possible solution. We give the detail protocol for our scheme and provide the practical test and performance analysis. Experimental results show that our scheme has a better flexibility and efficiency in embedding process, and the average value of Peak Signal to Noise Ratio (PSNR) for the stego-images which are generated by our scheme have a higher visual quality for different embedding capacities, and our scheme is more efficient compared with related work.

Is rifampin resistance a reliable predictive marker of multidrug-resistant tuberculosis in China: A meta-analysis of findings.

OBJECTIVES: Systematic review of multidrug-resistant tuberculosis (MDR-TB) prevalence among rifampicin (RIF)-resistant tuberculosis (RR-TB) patients in 34 provinces of China was conducted to correlate RIF resistance with concurrent isoniazid (INH) resistance. METHODS: Database searches (PubMed, Embase, China National Knowledge Infrastructure, Chinese Scientific Journal, Wanfang), identified drug resistance surveillance studies conducted between January 1, 2000 and June 30, 2018. Of 1554 records, random-effects meta-analysis of 34 studies of adequate methodological quality yielded 108,366 TB cases for MDR-TB prevalence analysis of RR-TB cases. RESULTS: MDR-TB prevalence among RR-TB cases varied from 57% (Xinjiang; 95% CI 47%, 67%) to 95% (Taiwan; 95% CI 92%, 98%), for a pooled national rate of 77% (95% CI 75%, 80%). Subgroup and meta-regression analyses revealed greater MDR-TB prevalence in previously treated versus new RR-TB cases (P < 0.001), with no significant differences of regional initial drug resistance rates or sampling methods. Regional MDR-TB prevalence among RR-TB cases was lowest (69%) in the Northeast Region (95% CI 65%, 73%) and highest (90%) in Hong Kong, Macao and Taiwan (95% CI 81%, 98%). CONCLUSIONS: In China, ∼77% of RR-TB cases are MDR-TB. Thus, RIF resistance cannot effectively predict MDR-TB. Highly variable RR-TB prevalence across China warrants improved TB management.