The predictive value of TNF family for pulmonary tuberculosis: a pooled causal effect analysis of multiple datasets.

Objective: Despite extensive research on the relationship between pulmonary tuberculosis (PTB) and inflammatory factors, more robust causal evidence has yet to emerge. Therefore, this study aims to screen for inflammatory proteins that may contribute to the susceptibility to PTB in different populations and to explain the diversity of inflammatory and immune mechanisms of PTB in different ethnicity. Methods: The inverse variance weighted (IVW) model of a two-sample Mendelian Randomization (MR) study was employed to conduct causal analysis on data from a genome-wide association study (GWAS). This cohort consisting PTB GWAS datasets from two European and two East Asian populations, as well as 91 human inflammatory proteins collected from 14,824 participants. Colocalization analysis aimed to determine whether the input inflammatory protein and PTB shared the same causal single nucleotide polymorphisms (SNPs) variation within the fixed region, thereby enhancing the robustness of the MR Analysis. Meta-analyses were utilized to evaluate the combined causal effects among different datasets. Results: In this study, we observed a significant negative correlation between tumor necrosis factor-beta levels (The alternative we employ is Lymphotoxin-alpha, commonly referred to as LT) (P < 0.05) and tumor necrosis factor receptor superfamily member 9 levels (TNFRSF9) (P < 0.05). These two inflammatory proteins were crucial protective factors against PTB. Additionally, there was a significant positive correlation found between interleukin-20 receptor subunit alpha levels (IL20Ra) (P < 0.05), which may elevate the risk of PTB. Colocalization analysis revealed that there was no overlap in the causal variation between LT and PTB SNPs. A meta-analysis further confirmed the significant combined effect of LT, TNFRSF9, and IL20Ra in East Asian populations (P < 0.05). Conclusions: Levels of specific inflammatory proteins may play a crucial role in triggering an immune response to PTB. Altered levels of LT and TNFRSF9 have the potential to serve as predictive markers for PTB development, necessitating further clinical validation in real-world settings to ascertain the impact of these inflammatory proteins on PTB.

Exploring the causal correlations between 486 serum metabolites and systemic lupus erythematosus: a bidirectional Mendelian randomization study.

Objective: The observational association between circulating metabolites and systemic lupus erythematosus (SLE) has been well documented. However, whether the association is causal remains unclear. In this study, bidirectional Mendelian randomization (MR) was introduced to analyse the causal relationships and possible mechanisms. Methods: We conducted a two-sample bidirectional MR study. A genome-wide association study (GWAS) with 7,824 participants provided data on 486 human blood metabolites. Outcome information was obtained from a large-scale GWAS summary, which contained 5,201 single nucleotide polymorphisms (SNPs) cases and 9,066 control cases of Europeans and yielded a total of 7,071,163 SNPs. The inverse variance weighted (IVW) model was recruited as the primary two-sample MR analysis approach, followed by sensitivity analyses such as the heterogeneity test, horizontal pleiotropy test, leave-one-out analysis, and linkage disequilibrium score (LDSC) regression. Results: In this study, we discovered that 24 metabolites belonging to the lipid, carbohydrate, xenobiotic and amino acid superpathways may increase the risk of SLE occurrence (p < 0.05). In addition, the metabolic disorders of 51 metabolites belonging to the amino acid, energy, xenobiotics, peptide and lipid superpathways were affected by SLE (p < 0.05). Palmitoleate belonging to the lipid superpathway and isobutyrylcarnitine and phenol sulfate belonging to the amino acid superpathway were factors with two-way causation. The metabolic enrichment pathway of bile acid biosynthesis was significant in the forward MR analysis (p = 0.0435). Linolenic acid and linoleic acid metabolism (p = 0.0260), betaine metabolism (p = 0.0314), and glycerolipid metabolism (p = 0.0435) were the significant metabolically enriched pathways in the reverse MR analysis. Conclusion: The levels of some specific metabolites may either contribute to the immune response inducing SLE, or they may be intermediates in the development and progression of SLE. These metabolites can be used as auxiliary diagnostic tools for SLE and for the evaluation of disease progression and therapeutic effects.

Trends and Patterns of Antibiotic Prescriptions in Primary Care Institutions in Southwest China, 2017-2022.

Purpose: To explore the prescription patterns and usage trends of antibiotics within primary care institutions located in underdeveloped regions of China from 2017 to 2022. Methods: A retrospective analysis of antibiotic prescriptions was conducted from 25 primary care institutions in Guizhou Province during the period of 2017-2022. Antibiotic prescriptions were categorized into appropriate and inappropriate use. Appropriate use is further categorized into preferred medication, and antibiotics can be used or substituted. Inappropriate use is further categorized into unnecessary use, incorrect spectrum of antibiotics and combined use of antibiotics. Factors associated with inappropriate use were investigated using generalized estimation equations. Holt-Winters and SARIMA models were employed to predict the number of inappropriate antibiotic prescriptions as the alternative model. Results: A total of 941,924 prescriptions were included, revealing a decreasing trend in both the number and inappropriate rates of antibiotic prescriptions from 2017 to 2022. Diseases of the respiratory system (70.66%) was the most frequent target of antibiotic use, with acute upper respiratory infections of multiple and unspecified sites representing 52.04% of these cases. The most commonly used antibiotics were penicillins (64.44%). Among all prescriptions, inappropriate antibiotic prescriptions reached 66.19%. Physicians aged over 35, holding the title of associate chief physician and possessing more than 11 years of experience were more likely to prescribe antibiotics inappropriately. The phenomenon of inappropriate antibiotic use was commoner among children aged five or younger. By comparing model parameters, it was determined that the SARIMA model outperforms the Holt-Winters model in predicting the number of inappropriate antibiotic prescriptions among primary care institutions. Conclusion: The number and inappropriate rates of antibiotic prescriptions in southwest China exhibited a downward trend from 2017 to 2022, but inappropriate prescription remains a serious problem in primary care institutions. Therefore, future efforts should focus on strengthening physician education, training, and clinical practice. Additionally, physicians' awareness of common misconceptions about inappropriate antibiotic use must be improved, and the prescribing behavior of physicians who fulfill patients' expectations by prescribing antibiotics needs to be modified.

Development and Application of a Reference Manual for Diagnosis and Rational Use of Antimicrobial Agents for Outpatient Primary Care (Digestive System Part): A Delphi Study.

Purpose: To establish a concise and easy-to-understand reference manual for outpatient primary care providers, promoting correct diagnosis of digestive system diseases and rational antimicrobial use. Methods: The establishment of the manual encompassed two processes: the development of a draft manual and the validation of the manual. The development process was based on a literature review and expert discussion. The manual comprises portions for disease diagnosis and rationality of antimicrobial use. The validation process employed a two-round Delphi technique, collecting consensus through paper-based or mail-based communications. The response of the Delphi group was assessed by the level of authority and commitment of the panelists and the degree of agreement among them. Furthermore, the manual was preliminarily applied among primary care physicians. Results: A total of 29 panelists completed the Delphi working process. They were authoritative in their professional fields with authority coefficients of 0.813 and 0.818 for the two portions of the manual, respectively. The level of commitment of the panelists was measured by response rates, which were 100.00% and 96.67% for Round 1 and 2. After two rounds, a consensus was achieved with the consensus rates for the two portions of the manual being greater than 65% and 70%, respectively. Kendall W-tests had P-values < 0.001 in both rounds. This reference manual provides 200 diagnostic indicators for 29 common digestive diseases and recommendations for the rational use of antimicrobial agents for 13 categories of digestive diseases. The primary care physicians who used the reference manual reported high satisfaction and frequent usage. Conclusion: Based on a collective consensus of professionals, a reference manual has been established, to provide a concise and easy-to-understand guide specifically for physicians and pharmacists in outpatient primary care. It could facilitate rapid learning to improve the accuracy of diagnosis and treatment for digestive disorders.

Effects of a feedback intervention on antibiotic prescription control in primary care institutions based on a Health Information System: a cluster randomized cross-over controlled trial.

OBJECTIVES: Overuse and misuse of antibiotics are major factors in the development of antibiotic resistance in primary care institutions of rural China. In this study, the effectiveness of a Health Information System-based, automatic, and confidential antibiotic feedback intervention was evaluated. METHODS: A randomized, cross-over, cluster-controlled trial was conducted in primary care institutions. All institutions were randomly divided into two groups and given either a three-month intervention followed by a three-month period without any intervention or vice versa. The intervention consisted of three feedback measures: a real-time pop-up warning message of inappropriate antibiotic prescriptions on the prescribing physician's computer screen, a 10-day antibiotic prescription summary, and distribution of educational manuals. The primary outcome was the 10-day inappropriate antibiotic prescription rate. RESULTS: There were no significant differences in inappropriate antibiotic prescription rates (69.1% vs. 72.0%) between two groups at baseline (P = 0.072). After three months (cross-over point), inappropriate antibiotic prescription rates decreased significantly faster in group A (12.3%, P < 0.001) compared to group B (4.4%, P < 0.001). At the end point, the inappropriate antibiotic prescription rates decreased in group B (15.1%, P < 0.001) while the rates increased in group A (7.2%, P < 0.001). The characteristics of physicians did not significantly affect the rate of antibiotic or inappropriate antibiotic prescription rates. CONCLUSION: A Health Information System-based, real-time pop-up warnings, a 10-day prescription summary, and the distribution of educational manuals, can effectively reduce the rates of antibiotic and inappropriate antibiotic prescriptions.

Tuberculosis among Ambulatory People Living with HIV in Guangxi Province, China: A Longitudinal Study.

BACKGROUND: This study aims to determine the prevalence of TB among ambulatory people living with HIV in Guangxi Province, which experienced the biggest HIV epidemic in China. METHODS: We undertook a longitudinal study in five HIV/AIDS designated hospitals randomly selected from Guangxi Province; all newly diagnosed HIV/AIDS outpatients from 2019 to 2021 were screened for TB and interviewed with a questionnaire. RESULTS: A total of 4539 HIV/AIDS outpatients were enrolled, with 2886 (63.6%) men and 1653 (26.4%) women. The prevalence of TB/HIV coinfection was 0.8%, with a clear downward trend from 1.3% in 2019 to 0.4% in 2021 (p = 0.0011). The prevalence of LTBI was 24.3%, with no significant differences from 2019 to 2021. The percentages of AIDS, comorbidity, nine symptoms and abnormal chest X-ray of TB were higher than those of the other PLWH. CONCLUSION: The prevalence of TB among ambulatory people with HIV in Guangxi Province was 14 times higher than the general population, and the annual declined TB prevalence indicated the effectiveness of TB and HIV control and prevention over recent years. The findings proved that symptom screening was insufficient for TB diagnosis and highlighted the importance of systematic TB screening at every visit to a health facility.

Effect of unifaceted and multifaceted interventions on antibiotic prescription control for respiratory diseases: A systematic review of randomized controlled trials.

BACKGROUND: The global health system is improperly using antibiotics, particularly in the treatment of respiratory diseases. We aimed to examine the effectiveness of implementing a unifaceted and multifaceted intervention for unreasonable antibiotic prescriptions. METHODS: Relevant literature published in the databases of Pubmed, Embase, Science Direct, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure and Wanfang was searched. Data were independently filtered and extracted by 2 reviewers based on a pre-designed inclusion and exclusion criteria. The Cochrane collaborative bias risk tool was used to evaluate the quality of the included randomized controlled trials studies. RESULTS: A total of 1390 studies were obtained of which 23 studies the outcome variables were antibiotic prescription rates with the number of prescriptions and intervention details were included in the systematic review. Twenty-two of the studies involved educational interventions for doctors, including: online training using email, web pages and webinar, antibiotic guidelines for information dissemination measures by email, postal or telephone reminder, training doctors in communication skills, short-term interactive educational seminars, and short-term field training sessions. Seventeen studies of interventions for health care workers also included: regular or irregular assessment/audit of antibiotic prescriptions, prescription recommendations from experts and peers delivered at a meeting or online, publicly reporting on doctors' antibiotic usage to patients, hospital administrators, and health authorities, monitoring/feedback prescribing behavior to general practices by email or poster, and studies involving patients and their families (n = 8). Twenty-one randomized controlled trials were rated as having a low risk of bias while 2 randomized controlled trials were rated as having a high risk of bias. Six studies contained negative results. CONCLUSION: The combination of education, prescription audit, prescription recommendations from experts, public reporting, prescription feedback and patient or family member multifaceted interventions can effectively reduce antibiotic prescription rates in health care institutions. Moreover, adding multifaceted interventions to educational interventions can control antibiotic prescription rates and may be a more reasonable method. REGISTRATIONS: This systematic review was registered in PROSPERO, registration number: CRD42020192560.

Space-Time Distribution Characteristics of Tuberculosis and Its Socioeconomic Factors in Southern China from 2015 to 2019.

Purpose: Guangxi is a high prevalence area of tuberculosis (TB) in China, urgent needing of further TB reduction. Our purpose is to analyze the epidemiological characteristics of TB in Guangxi and analyze the relationship between socioeconomic factors and TB from the dimensions of time and space to provide evidence to effectively prevent and control TB. Patients and Methods: We performed a retrospective analysis of the epidemiology of TB. Moran's index (I) was used for spatial autocorrelation analysis, and space-time scanning was used to detect temporal, space, and space-time clusters of TB. A Bayesian space-time model was used to analyze related factors of the TB epidemic at the county level in Guangxi. Results: From 2015 to 2019, a total of 233,623 TB cases were reported in Guangxi. The majority of TB cases were in males; the reported incidence of TB was the highest in people aged ≥65 years. By occupation, farmers were the most frequently affected. The overall reported incidence of TB decreased by 4.95% during this period. Tuberculosis occurs all year round, but the annual reporting peak is usually from March to July. Spatial autocorrelation analysis showed that the reported incidence of TB in 2015-2019 was spatially clustered (Moran's I > 0, P < 0.05); Kulldorff's scan revealed that the space-time cluster (log-likelihood ratio = 2683.76, relative risk = 1.60, P < 0.001) was mainly concentrated in northern Guangxi. Using Bayesian space-time modeling, socioeconomic and healthcare factors are related to the high prevalence of TB. Conclusion: The prevalence of TB is influenced by a space-time interaction effect and is associated with socioeconomic and healthcare status. It is necessary to improve the economic development and health service in areas with a high TB prevalence.

Changing antibiotic prescribing practices in outpatient primary care settings in China: Study protocol for a health information system-based cluster-randomised crossover controlled trial.

BACKGROUND: The overuse and abuse of antibiotics is a major risk factor for antibiotic resistance in primary care settings of China. In this study, the effectiveness of an automatically-presented, privacy-protecting, computer information technology (IT)-based antibiotic feedback intervention will be evaluated to determine whether it can reduce antibiotic prescribing rates and unreasonable prescribing behaviours. METHODS: We will pilot and develop a cluster-randomised, open controlled, crossover, superiority trial. A total of 320 outpatient physicians in 6 counties of Guizhou province who met the standard will be randomly divided into intervention group and control group with a primary care hospital being the unit of cluster allocation. In the intervention group, the three components of the feedback intervention included: 1. Artificial intelligence (AI)-based real-time warnings of improper antibiotic use; 2. Pop-up windows of antibiotic prescription rate ranking; 3. Distribution of educational manuals. In the control group, no form of intervention will be provided. The trial will last for 6 months and will be divided into two phases of three months each. The two groups will crossover after 3 months. The primary outcome is the 10-day antibiotic prescription rate of physicians. The secondary outcome is the rational use of antibiotic prescriptions. The acceptability and feasibility of this feedback intervention study will be evaluated using both qualitative and quantitative assessment methods. DISCUSSION: This study will overcome limitations of our previous study, which only focused on reducing antibiotic prescription rates. AI techniques and an educational intervention will be used in this study to effectively reduce antibiotic prescription rates and antibiotic irregularities. This study will also provide new ideas and approaches for further research in this area. TRIAL REGISTRATION: ISRCTN, ID: ISRCTN13817256. Registered on 11 January 2020.

Revised nomenclature and SNP barcode for Mycobacterium tuberculosis lineage 2.

Mycobacterium tuberculosis (Mtb) lineage 2 (L2) strains are present globally, contributing to a widespread tuberculosis (TB) burden, particularly in Asia where both prevalence of TB and numbers of drug resistant TB are highest. The increasing availability of whole-genome sequencing (WGS) data worldwide provides an opportunity to improve our understanding of the global genetic diversity of Mtb L2 and its association with the disease epidemiology and pathogenesis. However, existing L2 sublineage classification schemes leave >20 % of the Modern Beijing isolates unclassified. Here, we present a revised SNP-based classification scheme of L2 in a genomic framework based on phylogenetic analysis of >4000 L2 isolates from 34 countries in Asia, Eastern Europe, Oceania and Africa. Our scheme consists of over 30 genotypes, many of which have not been described before. In particular, we propose six main genotypes of Modern Beijing strains, denoted L2.2.M1-L2.2.M6. We also provide SNP markers for genotyping L2 strains from WGS data. This fine-scale genotyping scheme, which can classify >98 % of the studied isolates, serves as a basis for more effective monitoring and reporting of transmission and outbreaks, as well as improving genotype-phenotype associations such as disease severity and drug resistance. This article contains data hosted by Microreact.

Interaction analysis of Mycobacterium tuberculosis between the host environment and highly mutated genes from population genetic structure comparison.

ABSTRACT: We aimed to investigate the genetic and demographic differences and interactions between areas where observed genomic variations in Mycobacterium tuberculosis (M. tb) were distributed uniformly in cold and hot spots.The cold and hot spot areas were identified using the reported incidence of TB over the previous 5 years. Whole genome sequencing was performed on 291 M. tb isolates between January and June 2018. Analysis of molecular variance and a multifactor dimensionality reduction (MDR) model was applied to test gene-gene-environment interactions. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were computed to test the extent to which genetic mutation affects the TB epidemic using a multivariate logistic regression model.The percentage of the Beijing family strain in hot spots was significantly higher than that in cold spots (64.63% vs 50.69%, P = .022), among the elderly, people with a low BMI, and those having a history of contact with a TB patient (all P < .05). Individuals from cold spot areas had a higher frequency of out-of-town traveling (P < .05). The mutation of Rv1186c, Rv3900c, Rv1508c, Rv0210, and an Intergenic Region (SNP site: 3847237) showed a significant difference between cold and hot spots. (P < .001). The MDR model displayed a clear negative interaction effect of age groups with BMI (interaction entropy: -3.55%) and mutation of Rv0210 (interaction entropy: -2.39%). Through the mutations of Rv0210 and BMI had a low independent effect (interaction entropy: -1.46%).Our data suggests a statistically significant role of age, BMI and the polymorphisms of Rv0210 genes in the transmission and development of M. tb. The results provide clues for the study of susceptibility genes of M. tb in different populations. The characteristic strains showed a local epidemic. Strengthening genotype monitoring of strains in various regions can be used as an early warning signal of epidemic spillover.

A genome epidemiological study of mycobacterium tuberculosis in subpopulations with high and low incidence rate in Guangxi, South China.

BACKGROUND: Tuberculosis (TB) is caused by a bacterium called Mycobacterium tuberculosis (Mtb). China is the third in top 8 high TB burden countries and Guangxi is one of the high incidence areas in South China. Determine bacterial factors that affected TB incidence rate is a step toward Ending the TB epidemic. RESULTS: Genomes of M. tuberculosis cultures from a relatively high and low incidence region in Guangxi have been sequenced. 347 of 358(96.9%) were identified as M. tuberculosis. All the strains belong to Lineage 2 and Lineage 4, except for one in Lineage 1. We found that the genetic structure of the M. tuberculosis population in each county varies enormously. Low incidence rate regions have a lower prevalence of Beijing genotypes than other regions. Four isolates which harbored mutT4-48 also had mutT2-58 mutations. It is suggested that strains from the ancestors of modern Beijing lineage is circulating in Guangxi. Strains of modern Beijing lineage (OR=2.04) were more likely to acquire drug resistances than Lineage 4. Most of the lineage differentiation SNPs are related to cell wall biosynthetic pathways. CONCLUSIONS: These results provided a higher resolution to better understand the history of transmission of M. tuberculosis from/to South China. And the incidence rate of tuberculosis might be affected by bacterial population structure shaped by demographic history. Our findings also support the hypothesis that Modern Beijing lineage originated in South China.

The geno-spatio analysis of Mycobacterium tuberculosis complex in hot and cold spots of Guangxi, China.

BACKGROUND: At present, there are few studies on polymorphism of Mycobacterium tuberculosis (Mtb) gene and how it affects the TB epidemic. This study aimed to document the differences of polymorphisms between tuberculosis hot and cold spot areas of Guangxi Zhuang Autonomous Region, China. METHODS: The cold and hot spot areas, each with 3 counties, had been pre-identified by TB incidence for 5 years from the surveillance database. Whole genome sequencing analysis was performed on all sputum Mtb isolates from the detected cases during January and June 2018. Single nucleotide polymorphism (SNP) of each isolate compared to the H37Rv strain were called and used for lineage and sub-lineage identification. Pairwise SNP differences between every pair of isolates were computed. Analyses of Molecular Variance (AMOVA) across counties of the same hot or cold spot area and between the two areas were performed. RESULTS: As a whole, 59.8% (57.7% sub-lineage 2.2 and 2.1% sub-lineage 2.1) and 39.8% (17.8% sub-lineage 4.4, 6.5% sub-lineage 4.2 and 15.5% sub-lineage 4.5) of the Mtb strains were Lineage 2 and Lineage 4 respectively. The percentages of sub-lineage 2.2 (Beijing family strains) are significantly higher in hot spots. Through the MDS dimension reduction, the genomic population structure in the three hot spot counties is significantly different from those three cold spot counties (T-test p = 0.05). The median of SNPs distances among Mtb isolates in cold spots was greater than that in hot spots (897 vs 746, Rank-sum test p < 0.001). Three genomic clusters, each with genomic distance ≤12 SNPs, were identified with 2, 3 and 4 consanguineous strains. Two clusters were from hot spots and one was from cold spots. CONCLUSION: Narrower genotype diversity in the hot area may indicate higher transmissibility of the Mtb strains in the area compared to those in the cold spot area.

Spatiotemporal patterns and ecological factors of tuberculosis notification: A spatial panel data analysis in Guangxi, China.

BACKGROUND: Guangxi is one of the provinces having the highest notification rate of tuberculosis in China. However, spatial and temporal patterns and the association between environmental diversity and tuberculosis notification are still unclear. OBJECTIVE: To detect the spatiotemporal pattern of tuberculosis notification rates from 2010 to 2016 and its potential association with ecological environmental factors in Guangxi Zhuang autonomous region, China. METHODS: We performed a spatiotemporal analysis with prediction using time series analysis, Moran's I global and local spatial autocorrelation statistics, and space-time scan statistics to detect temporal and spatial clusters of tuberculosis notifications in Guangxi between 2010 and 2016. Spatial panel models were employed to identify potential associating factors. RESULTS: The number of reported cases peaked in spring and summer and decreased in autumn and winter. The predicted number of reported cases was 49,946 in 2017. Moran's I global statistics were greater than 0 (0.363-0.536) during the study period. The most significant hot spots were mainly located in the central area. The eastern area exhibited a low-low relation. By the space-time scanning, the clusters identified were similar to those of the local autocorrelation statistics, and were clustered toward the early part of 2016. Duration of sunshine, per capita gross domestic product, the treatment success rate of tuberculosis and participation rate of the new cooperative medical care insurance scheme in rural areas had a significant negative association with tuberculosis notification rates. CONCLUSION: The notification rate of tuberculosis in Guangxi remains high, with the highest notification cluster located in the central region. The notification rate is associated with economic level, treatment success rate and participation in the new cooperative medical care insurance scheme.

Hot and Cold Spot Areas of Household Tuberculosis Transmission in Southern China: Effects of Socio-Economic Status and Mycobacterium tuberculosis Genotypes.

The aims of the study were: (1) compare sociodemographic characteristics among active tuberculosis (TB) cases and their household contacts in cold and hot spot transmission areas, and (2) quantify the influence of locality, genotype and potential determinants on the rates of latent tuberculosis infection (LTBI) among household contacts of index TB cases. Parallel case-contact studies were conducted in two geographic areas classified as "cold" and "hot" spots based on TB notification and spatial clustering between January and June 2018 in Guangxi, China, using data from field contact investigations, whole genome sequencing, tuberculin skin tests (TSTs), and chest radiographs. Beijing family strains accounted for 64.6% of Mycobacterium tuberculosis (Mtb) strains transmitted in hot spots, and 50.7% in cold spots (p-value = 0.02). The positive TST rate in hot spot areas was significantly higher than that observed in cold spot areas (p-value < 0.01). Living in hot spots (adjusted odds ratio (aOR) = 1.75, 95%, confidence interval (CI): 1.22, 2.50), Beijing family genotype (aOR = 1.83, 95% CI: 1.19, 2.81), living in the same room with an index case (aOR = 2.29, 95% CI: 1.5, 3.49), travelling time from home to a medical facility (aOR = 4.78, 95% CI: 2.96, 7.72), history of Bacillus Calmette-Guérin vaccination (aOR = 2.02, 95% CI: 1.13 3.62), and delay in diagnosis (aOR = 2.56, 95% CI: 1.13, 5.80) were significantly associated with positive TST results among household contacts of TB cases. The findings of this study confirmed the strong transmissibility of the Beijing genotype family strains and this genotype's important role in household transmission. We found that an extended traveling time from home to the medical facility was an important socioeconomic factor for Mtb transmission in the family. It is still necessary to improve the medical facility infrastructure and management, especially in areas with a high TB prevalence.

Risk factors associated with Tuberculosis (TB) among people living with HIV/AIDS: A pair-matched case-control study in Guangxi, China.

BACKGROUND: As one of the poorest provinces in China, Guangxi has a high HIV and TB prevalence, with the annual number of TB/HIV cases reported by health department among the highest in the country. However, studies on the burden of TB-HIV co-infection and risk factors for active TB among HIV-infected persons in Guangxi have rarely been reported. OBJECTIVE: To investigate the risk factors for active TB among people living with HIV/AIDS in Guangxi Zhuang autonomous region, China. METHODS: A surveillance survey was conducted of 1 019 HIV-infected patients receiving care at three AIDS prevention and control departments between 2013 and 2015. We investigated the cumulative prevalence of TB during 2 years. To analyze risk factors associated with active TB, we conducted a 1:1 pair-matched case-control study of newly reported active TB/HIV co-infected patients. Controls were patients with HIV without active TB, latent TB infection or other lung disease, who were matched with the case group based on sex and age (± 3 years). RESULTS: A total of 1 019 subjects were evaluated. 160 subjects (15.70%) were diagnosed with active TB, including 85 clinically diagnosed cases and 75 confirmed cases. We performed a 1:1 matched case-control study, with 82 TB/HIV patients and 82 people living with HIV/AIDS based on surveillance site, sex and age (±3) years. According to multivariate analysis, smoking (OR = 2.996, 0.992-9.053), lower CD 4+ T-cell count (OR = 3.288, 1.161-9.311), long duration of HIV-infection (OR = 5.946, 2.221-15.915) and non-use of ART (OR = 7.775, 2.618-23.094) were independent risk factors for TB in people living with HIV/AIDS. CONCLUSION: The prevalence of active TB among people living with HIV/AIDS in Guangxi was 173 times higher than general population in Guangxi. It is necessary for government to integrate control planning and resources for the two diseases. Medical and public health workers should strengthen health education for TB/HIV prevention and treatment and promote smoking cessation. Active TB case finding and early initiation of ART is necessary to minimize the burden of disease among patients with HIV, as is IPT and infection control in healthcare facilities.

[Effect of antiretroviral therapy in reducing deaths among patients co-infected with Mycobacterium tuberculosis and human immunodeficiency virus in Guangxi].

OBJECTIVE: To understand the effect of antiretroviral therapy (ART) in reducing deaths among patients co-infected with Mycobacterium tuberculosis and human immunodeficiency virus (TB/HIV), and provide data-based evidence for improving ART in TB/HIV patients. METHODS: The information about TB patients who were HIV positive confirmed previously or recently in Guangxi were collected, and the TB/HIV patients were confirmed by using the related data from national AIDS prevention and treatment information system. Then a retrospective case control study was conducted to understand the survivals and deaths in the patients receiving ART or receiving no ART by using Kaplan-Meier method and estimate the ART protective rate within 1 year after TB treatment initiation. RESULTS: Among 519 TB/HIV patients, 100 received ART (19.3%); Among 84 TB/HIV patients who died within 1 year after TB treatment, 8 (9.5%) received ART, while 76 (90.5%) received no ART. Compared with the 18.7% mortality rate in non-ART group, TB/HIV patients mortality rate in ART group was only 8.08%, the difference was statistical significant (P < 0.05). Kaplan-Meier survival curve showed that the survival rate in patients receiving ART was higher than that in patients receiving no ART within 1 year after TB treatment, the difference was statistical significant (Log-rank = 4.96, P = 0.02). Compared with patients receiving ART, the OR value was 2.31 times higher than that in patients receiving no ART;ART could protect 56.7% of TB/HIV patients against death during the first year of anti-TB therapy. CONCLUSION: In the first year of anti-TB therapy, the risk of death in TB/HIV patients receiving no ART was much higher than that in TB/HIV patients receiving ART, and the survival time was longer in the patients receiving ART. The ART coverage should be expanded in TB/HIV patients.

[Feature analysis on patients died from co-infection of Mycobacterium tuberculosis and human immunodeficiency virus in Guangxi, from 2007 to 2012].

OBJECTIVE: To understand the general feature of patients with Mycobacterium tuberculosis (MTB) and human immunodeficiency virus (HIV) co-infectious (TB/HIV) in Guangxi, from 2007 to 2012. METHODS: Information regarding individuals that the contributory causes of death were due to MTB infection among HIV as the underlying cause of death from the Vital Registration System, together with bacterium smear or culture results, onset of TB, time that TB was diagnosed and entered an Internet base TB surveillance system was collected and checked. Data including information on time of death, age, occupation, the underlying cause of death among TB patients, bacterium distribution, average age of death, interval from onset to death, percentage of TB/HIV co-infection patients among all the patients etc, were all analysed. RESULTS: 203 patients died from HIV associated with TB from the Guangxi Vital Registration System were identified between 2007 and 2012. The average percentage of TB/HIV co-infection cases accounted for 8.24% (ranging from 3.94% in 2007 to 13.27% in 2012) among all the deaths of HIV infection while it accounted for 9.90% (ranging from 2.56% to in 2007 to 26.88% in 2012) among patients with MTB infection in the same period. The average percentage of deaths from TB/HIV co-infection in 2010 and 2012 accounted for 10.66% (ranging from 8.83% to 13.27%)and 22.17% (ranging from 20.60% to 26.88%)among patients died of HIV and TB infection respectively. The male-female ratio was 4.21 for 1, with the average age of death as 44.65 (44.65 ± 15.52) years;median time from TB symptoms onset to diagnosis as 37 (mean 94.31, standard deviation 206.07) days, record as (94.31 ± 206.07); median time from diagnosis to death as 46 (165.22 ± 282.19) days, 54.68% TB/HIV patients died within two months of being diagnosed with TB and the median time from TB symptoms onset to death as 131 (257.68 ± 340.79) days. 16.26% of the TB/HIV cases were bacterium confirmed TB cases. CONCLUSION: Compare to those TB patients without HIV, less bacterium evidence was found in TB/HIV patients. High burden caused by HIV disease was seen if they were co-infected with TB. An increasing proportion of deaths was noticed among patients co-infected with HIV and TB in the last three years, suggesting that the coverage of antiretroviral therapy be scaled up together with the strengthening of the capability on early TB case-finding among people live with HIV.