Virome survey of the bat, Rhinolophus affinis, in Hainan Province, China.

Bats are important mammal reservoirs of zoonotic pathogens. However, due to research limitations involving species, locations, pathogens, or sample types, the full diversity of viruses in bats remains to be discovered. We used next-generation sequencing technology to characterize the mammalian virome and analyze the phylogenetic evolution and diversity of mammalian viruses carried by bats from Haikou City and Tunchang County in Hainan Province, China. We collected 200 pharyngeal swab and anal swab samples from Rhinolophus affinis, combining them into nine pools based on the sample type and collection location. We subjected the samples to next-generation sequencing and conducted bioinformatics analysis. All samples were screened via specific PCR and phylogenetic analysis. The diverse viral reads, closely related to mammals, were assigned into 17 viral families. We discovered many novel bat viruses and identified some closely related to known human/animal pathogens. In the current study, 6 complete genomes and 2 partial genomic sequences of 6 viral families and 8 viral genera have been amplified, among which 5 strains are suggested to be new virus species. These included coronavirus, pestivirus, bastrovirus, bocavirus, papillomavirus, parvovirus, and paramyxovirus. The primary finding is that a SADS-related CoV and a HoBi-like pestivirus identified in R. affinis in Hainan Province could be pathogenic to livestock. This study expands our understanding of bats as a virus reservoir, providing a basis for further research on the transmission of viruses from bats to humans.

CD8+ T cell response in QuantiFERON-TB Gold Plus testing was associated with tuberculosis recurrence: a 2-year prospective study.

BACKGROUND: Recurrence posed an important challenge to pulmonary tuberculosis (PTB) control in China. The prospective study aimed to identify potential risk factors and to explore the value of QuantiFERON-TB Gold Plus (QFT-Plus) in identifying at-risk individuals with treated prior PTB history. METHODS: All eligible individuals aged ≥18 years who had been diagnosed with PTB before 2016 in Zhongmu County, where with an average level of TB prevalence in China, were included and received baseline survey including chest radiography, QuantiFERON-TB Gold In-Tube (QFT-GIT) and QFT-Plus, then PTB recurrence was tracked through a 2-year follow-up. RESULTS: Half of 1068 (52.34%, 559/1068) included eligible participants were QFT-Plus positive at baseline and 21 of them recurred active TB in 2-year follow-up. Individuals aged ≥ 60 years, who had a recent history of TB and smokers were associated with increased risk of TB recurrence with an adjusted odds ratio (aOR) of 3.97 (95% confidence interval (CI): 1.29-12.24), 7.71 (95% CI: 1.74-34.25) and 4.56 (95% CI: 1.62-12.83), respectively. Compared to QFT-Plus negatives, those who were TB2+/TB1- (aOR = 15.34) exhibited stronger association with the risk of TB recurrence than those who were TB1+/TB2+ (aOR = 6.06). A dose response relationship was also found between the risk of TB recurrence with the baseline level of TB2-TB1 (p for trend < 0.001). CONCLUSIONS: High burden of TB infection and high risk of PTB recurrence were observed in the study population. Those with recent onset of prior TB, elderly smokers and QFT-Plus positives especially with TB2 single positive deserved further attention in active TB surveillance.

Cost-effectiveness of latent tuberculosis infection testing and treatment with 6-week regimen among key population in rural communities in China: a decision analysis study.

PURPOSE: Several model studies suggested the implementation of latent tuberculosis infection (LTBI) testing and treatment could greatly reduce the incidence of tuberculosis (TB) and achieve the 2035 target of the "End TB" Strategy in China. The present study aimed to evaluate the cost-effectiveness of LTBI testing and TB preventive treatment among key population (≥ 50 years old) susceptible to TB at community level in China. METHODS: A Markov model was developed to investigate the cost-effectiveness of LTBI testing using interferon gamma release assay (IGRA) and subsequent treatment with 6-month daily isoniazid regimen (6H) (as a standard regimen for comparison) or 6-week twice-weekly rifapentine and isoniazid regimen (6-week H2P2) in a cohort of 10,000 adults with an average initial age of 50 years. RESULTS: In the base-case analysis, LTBI testing and treatment with 6H was dominated (i.e., more expensive with a lower quality-adjusted life year (QALY)) by LTBI testing and treatment with 6-week H2P2. LTBI testing and treatment with 6-week H2P2 was more effective than no intervention at a cost of $20,943.81 per QALY gained, which was below the willingness-to-pay (WTP) threshold of $24,211.84 per QALY gained in China. The one-way sensitivity analysis showed the change of LTBI prevalence was the parameter that most influenced the results of the incremental cost-effectiveness ratios (ICERs). CONCLUSION: As estimated by a Markov model, LTBI testing and treatment with 6-week H2P2 was cost-saving compared with LTBI testing and treatment with 6H, and it was considered to be a cost-effective option for TB control in rural China.

Impact of fine particulate matter on latent tuberculosis infection and active tuberculosis in older adults: a population-based multicentre cohort study.

Evidence showed that air pollution was associated with an increased risk of tuberculosis (TB). This study aimed to study the impact of long-term exposure to ambient particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) on the acquisition of LTBI and on the risk of subsequent active disease development among rural older adults from a multicentre cohort, which have not yet been investigated to date. A total of 4790 older adults were included in a population-based, multicentre, prospective cohort study (LATENTTB-NSTM) from 2013 to 2018. The level of long-term exposure to PM2.5 for each participant was assessed by aggregating satellite-based estimates. Logistic regression and time-varying Cox proportional hazards models with province-level random intercepts were employed to assess associations of long-term exposures to PM2.5 with the risk of LTBI and subsequent development of active TB, respectively. Out of 4790 participants, 3284 were LTBI-free at baseline, among whom 2806 completed the one-year follow-up and 127 developed newly identified LTBI. No significant associations were identified between PM2.5 and the risk of LTBI. And among 1506 participants with LTBI at baseline, 30 active TB cases were recorded during the 5-year follow-up. Particularly, an increment of 5 µg/m3 in 2-year moving averaged PM2.5 was associated with a 50.6% increased risk of active TB (HR = 1.506, 95% CI: 1.161-1.955). Long-term air pollution might be a neglected risk factor for active TB development from LTBI, especially for those living in developing or less-developed areas where the air quality is poor.

Diversity and independent evolutionary profiling of rodent-borne viruses in Hainan, a tropical island of China.

The risk of emerging infectious diseases (EID) is increasing globally. More than 60% of EIDs worldwide are caused by animal-borne pathogens. This study aimed to characterize the virome, analyze the phylogenetic evolution, and determine the diversity of rodent-borne viruses in Hainan Province, China. We collected 682 anal and throat samples from rodents, combined them into 28 pools according to their species and location, and processed them for next-generation sequencing and bioinformatics analysis. The diverse viral contigs closely related to mammals were assigned to 22 viral families. Molecular clues of the important rodent-borne viruses were further identified by polymerase chain reaction for phylogenetic analysis and annotation of genetic characteristics such as arenavirus, coronavirus, astrovirus, pestivirus, parvovirus, and papillomavirus. We identified pestivirus and bocavirus in Leopoldoms edwardsi from Huangjinjiaoling, and bocavirus in Rattus andamanensis from the national nature reserves of Bangxi with low amino acid identity to known pathogens are proposed as the novel species, and their rodent hosts have not been previously reported to carry these viruses. These results expand our knowledge of viral classification and host range and suggest that there are highly diverse, undiscovered viruses that have evolved independently in their unique wildlife hosts in inaccessible areas.

Declining incidence rate of tuberculosis among close contacts in five years post-exposure: a systematic review and meta-analysis.

BACKGROUND: Individuals in close contact with active pulmonary tuberculosis (TB) patients showed a high risk of recent infection and, once infected, higher risk of developing active TB in the following years post-exposure. But the peak time of active disease onset is unclear. This study aims to estimate post exposure TB incidence risk among close contacts to provide reference for clinical and public health strategies. METHODS: We searched PubMed, Web of Science, and EMBASE for articles published until December 1, 2022. The incidence rates were quantitatively summarized by means of meta-analysis using the random-effect model. RESULTS: Of the 5616 studies, 31 studies included in our analysis. For baseline close contacts results, the summarized prevalence of Mycobacterium tuberculosis (MTB) infection and active TB was found to be 46.30% (95% CI: 37.18%-55.41%) and 2.68% (95% CI: 2.02%-3.35%), respectively. During the follow-up, the 1-year, 2-year and 5-year cumulative incidence of TB in close contacts were 2.15% (95% CI: 1.51%-2.80%), 1.21% (95% CI: 0.93%-1.49%) and 1.11% (95% CI: 0.64%-1.58%), respectively. Individuals with a positive result of MTB infection testing at baseline showed significantly higher cumulative TB incidence as compared to those negatives (3.80% vs. 0.82%, p < 0.001). CONCLUSIONS: Individuals with close contact to active pulmonary TB patients are bearing significant risk of developing active TB, particularly within the first-year post-exposure. Population with recent infections should be an important priority for active case finding and preventive intervention worldwide.

Tuberculosis preventive treatment among individuals with inactive tuberculosis suggested by untreated radiographic abnormalities: a community-based randomized controlled trial.

Epidemiological and interventional studies have been rarely conducted among those with positive interferon-γ release assay (IGRA) results and radiologically inactive tuberculosis (TB) lesions on chest radiograph. This study aimed to estimate the effectiveness and safety of a six-week twice-weekly regimen (rifapentine plus isoniazid) among this key population in rural China. First, chest digital radiography was conducted to screen individuals with inactive TB lesions. Then, the identified participants were further evaluated and eligible participants with IGRA-positive results were included in subsequent randomized controlled trial (RCT). Of 44,500 recruited residents, 2,988 presented with radiographically inactive TB among 43,670 with complete results of chest radiography and questionnaire, and 28.61% (855/2,988) tested IGRA positive. Subsequently, 677 eligible participants were included in this RCT (345 in the preventive treatment group and 332 in the untreated control group). The treatment completion rate was 80.00% (276/345), and 11.88% (41/345) participants reported side-effects including two cases of hepatotoxicity (0.58%, 2/345). In the intention-to-treat analysis, the cumulative incidence rate of microbiologically confirmed active TB during a two-year follow-up was 1.16 (95% confidence interval [CI]: 0.03-2.29) in the preventive treatment group and 1.51 (95% CI: 0.20-2.82) in the control group (p = .485). Subgroup analyses showed that the protective rates were 55.42% (95% CI: 10.33-93.07%) and 80.17% (95% CI: 25.36-97.96%) for participants with fibrosis and for those aged ≥60 years, respectively. The expected treatment effect was not observed for the six-week regimen in this study. Future studies with sufficient sample size are needed to verify our findings.

Serial testing of latent tuberculosis infection in patients with diabetes mellitus using interferon-gamma release assay, tuberculin skin test, and creation tuberculin skin test.

Background: Diabetes mellitus (DM) patients with latent tuberculosis infection (LTBI) have an increased risk of developing active tuberculosis (TB) due to impaired immunity. The performance of currently available immune response-based assays for identification of TB infection had been rarely evaluated in patients with type 2 DM (T2DM) in China. Methods: A prospective study was conducted to investigate the status of LTBI in patients with confirmed T2DM. At the baseline survey, the prevalence of LTBI was tested using interferon-gamma release assay (IGRA), tuberculin skin test (TST) and creation tuberculin skin test (C-TST) in parallel. After a 3-month interval, the participants were retested by the three assays to estimate their performance in the serial testing. Results: A total of 404 participants with T2DM were included in the study. At baseline, after excluding active TB, the prevalence of LTBI identified by TST (≥ 10 mm), C-TST (≥ 5 mm) and IGRA (≥ 0.35 IU/ml) were 9.65% (39/404), 10.40% (42/404) and 14.85% (60/404), respectively. The concordance of TST and C-TST results with IGRA results was 86.39% (349/404) and 92.08% (372/404) with a Kappa coefficient of 0.37 [95% confidence interval (CI): 0.24- 0.50] and 0.64 (95% CI: 0.53- 0.76), respectively. After a 3-month interval, the continuous results of TST, C-TST and IGRA were observed to be increased with testing conversion for 50, 26 and 27 patients, respectively. For TST and C-TST conversions, the distribution of their quantitative results in serial tests varied significantly when further classified by baseline IGRA dichotomous results. Conclusion: In studied patients with T2DM, C-TST showed higher consistency with IGRA as compared to TST. The present of conversion observed in serial testing suggested that boosting effect of skin testing should be considered for identify of LTBI in patients with T2DM.

Algorithms for Screening for Active Tuberculosis among Individuals with Latent Tuberculosis Infection in a Rural Community in China.

Screening for active tuberculosis (TB) among individuals with latent tuberculosis infection (LTBI) is important for the initiation and evaluation of TB preventive treatment. The performances of different tools and their combinations had rarely been studied in community-level screening among individuals with LTBI in China. This study aimed to explore appropriate algorithms for screening for active TB among individuals with LTBI in rural China. Three sputum samples were collected from each participant for smear microscopy, culture, and an Xpert MTB/RIF assay. Chest digital radiography and TB symptoms were investigated as well. The performances of different testing algorithms were compared with that of sputum culture as the gold standard. Overall, 1,564 study participants with LTBI were investigated, with a final diagnosis of 20 TB cases by sputum culture. Compared with other tests, the Xpert MTB/RIF assay detected 80.00% (95% confidence interval [CI], 58.40% to 91.93%) of culture-positive cases, with the highest sensitivity. When tests were combined using "or," "and," or "step" algorithms, the highest sensitivity reached 90.00% (95% CI, 69.90% to 97.21%) for the combination of the Xpert MTB/RIF assay and chest radiography, but the positive predictive value (PPV) decreased to 22.22% (95% CI, 14.54% to 32.41%). The Xpert MTB/RIF assay alone showed the best agreement with sputum culture, with a kappa value of 0.840. Pathogen molecular detection alone showed good performance compared to the other algorithms, for ruling out active TB in general LTBI, but the high cost might be a challenge for scaling it up. Identifying those with a high risk for progression to TB more precisely and establishing a cost-effective screening algorithm deserve further exploration. IMPORTANCE Enhancing community-wide active case screening in target LTBI populations is important for achieving the early treatment of active TB, and ruling active TB out is a prerequisite for initiating preventive treatment. The current study evaluated the performances of multiple tests and their combinations in screening for active TB among individuals with LTBI at the community level. Compared with the classical "TB symptoms and chest radiography" algorithm, the application of Xpert MTB/RIF improved the sensitivity from 45% to 80%. When the Xpert MTB/RIF assay was combined with chest radiography, the sensitivity was further improved to 90.00%, which achieved the World Health Organization (WHO) target product profiles. However, the algorithm requires caution as the PPV decreased from 88.89% for Xpert MTB/RIF alone to 22.22% for the combination. Xpert MTB/RIF alone offered remarkable sensitivity without compromising the PPV but would have major resource implications. Thus, identifying target populations for LTBI treatment more precisely and developing cost-effective and high-throughput screening tools and algorithms deserve further efforts.

Whole transcriptome sequencing reveals neutrophils' transcriptional landscape associated with active tuberculosis.

Neutrophils have been recognized to play an important role in the pathogenesis of tuberculosis in recent years. Interferon-induced blood transcriptional signatures in ATB are predominantly driven by neutrophils. In this study, we performed global RNA-seq on peripheral blood neutrophils from active tuberculosis patients (ATB, n=15); latent tuberculosis infections (LTBI, n=22); and healthy controls (HC, n=21). The results showed that greater perturbations of gene expression patterns happened in neutrophils from ATB individuals than HC or those with LTBI, and a total of 344 differentially expressed genes (DEGs) were observed. Functional enrichment analysis showed that besides the interferon signaling pathway, multiple pattern recognition receptor pathways were significantly activated in ATB, such as NOD-like receptors and Toll-like receptors. Meanwhile, we also observed that the expression of genes related to endocytosis, secretory granules, and neutrophils degranulation were downregulated. Our data also showed that the NF-κB signaling pathway might be inhibited in patients with ATB, which could increase Mycobacterium tuberculosis survival and lead to active tuberculosis status. Furthermore, we validated the accuracy of some differentially expressed genes in an independent cohort using quantitative PCR, and obtained three novel genes (RBM3, CSRNP1, SRSF5) with the ability to discriminate active tuberculosis from LTBI and HC.

Association Between Plasma Exosomes S100A9/C4BPA and Latent Tuberculosis Infection Treatment: Proteomic Analysis Based on a Randomized Controlled Study.

Background: Identifying host plasma exosome proteins associated with host response to latent tuberculosis infection (LTBI) treatment might promote our understanding of tuberculosis (TB) pathogenesis and provide useful tools for implementing the precise intervention. Methods: Based on an open-label randomized controlled trial (RCT) aiming to evaluate the short-course regimens for LTBI treatment, plasma exosomes from pre- and post-LTBI treatment were retrospectively detected by label-free quantitative protein mass spectrometry and validated by a parallel reaction monitoring method for participants with changed or not changed infection testing results after LTBI treatment. Eligible participants for both screening and verification sets were randomly selected from the based-RCT in a 1:1 ratio by age and gender. Reversion was defined as a decrease in IFN-γ levels from >0.70 IU/ml prior to treatment to 0.20 IU/ml within 1 week of treatment. The predictive ability of the candidate proteins was evaluated by receiver operating characteristic (ROC) analysis. Results: Totally, two sample sets for screening (n = 40) and validation (n = 60) were included. Each of them included an equal number of subjects with persistent positive or reversed QuantiFERON-TB Gold In-Tube (QFT) results after LTBI. A total of 2,321 exosome proteins were detected and 102 differentially expressed proteins were identified to be associated with QFT reversion. Proteins with high confidence and original values intact were selected to be further verified. Totally, 9 downregulated proteins met the criteria and were validated. After verification, C4BPA and S100A9 were confirmed to be still significantly downregulated (fold change <0.67, p < 0.05). The respective areas under the ROC curve were 0.73 (95% CI: 0.57-0.89) and 0.69 (95% CI: 0.52-0.86) for C4BPA and S100A9, with a combined value of 0.78 (95% CI: 0.63-0.93). The positive and negative predictive values for combined markers were 70.10% (95% CI: 50.22-86.30%) and 55.63% (95% CI: 29.17-61.00%). Conclusion: Our findings suggest that downregulated C4BPA and S100A9 in plasma exosomes might be associated with a host positive response to LTBI treatment. Further studies are warranted to verify the findings and potential underlying mechanisms in varied populations with a larger sample size.

The Association between Circulating microRNAs and the Risk of Active Disease Development from Latent Tuberculosis Infection: a Nested Case-Control Study.

Tuberculosis (TB) remains one of the deadliest communicable diseases. Biomarkers predicting the risk of active disease development from latent tuberculosis infection (LTBI) are urgently needed for precise intervention. This study aimed to identify potential circulating microRNAs (miRNAs) playing such a role in Chinese population. Based on a prospective study aiming to track the development of active TB among rural residents with LTBI, the baseline levels of circulating miRNAs were retrospectively compared between those who developed TB (case group) and those age-gender matched controls remain free of TB (contraol group) during the follow-up. Agilent human miRNA microarray were used to select differently expressed circulating miRNAs and verified by subsequent real-time quantitative PCR (RT-qPCR). Six candidate miRNAs were expressed at statistically significant levels between the two groups at the baseline, as determined by microarray. Following verification among 150 study participants by RT-qPCR, the levels of hsa-miR-16-5p (P < 0.001) and hsa-miR-451a (P < 0.001) were found to be significantly lower in case group compared to control group. The combined areas under curves (AUCs) and precision-recall curves (PRCs) were 0.84, 0.86 and 0.85, 0.87 for hsa-miR-16-5p and hsa-miR-451a, respectively. hsa-miR-451a combined with body mass index (BMI) and prior history of TB presented the best performance, with a sensitivity of 80.82% and an acceptable specificity of 79.22%. After adjusting the two co-variables, the AUC of hsa-miR-451a was 0.78. Circulating levels of hsa-miR-451a showed potential to predict development of active TB from LTBI in a Chinese population. Further studies are warranted to verify these findings in varied study settings. IMPORTANCE Approximately a quarter of the world population are infected with M. tuberculosis and about 5% to 10% of these might develop active disease in their lifetime. Preventive treatment could effectively protect individuals at a high risk of developing active disease from LTBI, and is regarded as a critical component of End TB Strategies. Biomarkers which could accurately identify high-risk population and predict the risk of disease development are urgently needed for developing local guidelines of LTBI management and precise intervention. A nested case-control study was designed to explore possible microRNAs related with TB occurrence based on a previous prospective study, which aimed to track the development of active TB among rural residents with LTBI. The baseline circulating levels of hsa-miR-16-5p and hsa-miR-451a were significantly lower in TB cases compared to those in LTBI controls. Further receiver operator characteristic (ROC) curve analysis found that hsa-miR-451a showed considerable potential to predict the development of active TB from LTBI.

Relationship between DNA Methylation Profiles and Active Tuberculosis Development from Latent Infection: a Pilot Study in Nested Case-Control Design.

Individuals with latent tuberculosis infection (LTBI) were regarded as an enormous reservoir of cases with active tuberculosis (TB). To strengthen LTBI management, biomarkers and tools are urgently required for identifying and ruling out active TB in a fast and effective way. Based on an open-label randomized controlled trial aiming to explore short-course LTBI treatment regimens, DNA methylation profiles were retrospectively detected to explore potential biomarkers, which could discriminate active TB from LTBI. The Infinium MethylationEPIC BeadChip array was used to analyze genomewide DNA methylation levels for 15 persons with LTBI who later developed active TB and for 15 LTBI controls who stayed healthy. The differentially methylated CpGs (dmCpGs) located in the promoter regions pre- and post-TB diagnosis were selected (P < 0.05 and |Δß|>0.10) and evaluated by receiver operating characteristic (ROC) analysis. Eight dmCpGs were identified to be associated with TB occurrence; six were located in hypermethylated genes (cg02493602, cg02206980, cg02214623, cg12159502, cg14593639, and cg25764570), and two were located in hypomethylated genes (cg02781074 and cg12321798). ROC analysis indicated that the area under curve (AUC) of these eight dmCpGs ranged from 0.72 to 0.84. Given 90% sensitivity, the specificity was highest for cg14593639 at 66.67%. The combination analysis indicated that "cg02206980 + cg02214623 + cg12159502 + cg12321798" showed the best performance, with an AUC of 0.88 (95% confidence interval [CI]: 0.72, 0.97), a sensitivity of 93.33% (95% CI: 70.18%, 99.66%), and a specificity of 86.67% (95% CI: 62.12%, 97.63%). Our preliminary results indicate the potential value of the DNA methylation level as a diagnostic biomarker for discriminating active disease in LTBI testing. This finding requires further verification in independent populations with large sample sizes. IMPORTANCE Approximately a quarter of the world population had been infected with Mycobacterium tuberculosis, and about 5 to 10% of these individuals might develop active disease in their lifetimes. As a critical component of the "end TB strategies," preventive treatment was shown to protect 60 to 90% of high-risk LTBIs from developing active disease. Developing new TB screening tools based on blood-based biomarkers, which could identify and rule out active TB from LTBI, are prerequisite before initialing intervention. We tried to explore potential DNA methylation diagnostic biomarkers through retrospectively detected DNA methylation profiles pre- and post-TB diagnosis. Eight dmCpGs were identified, and the combination of "cg02206980 + cg02214623 + cg12159502 + cg12321798" showed a sensitivity of 93.33% and a specificity of 86.67%. The preliminary results provided new insight into detecting the DNA methylation level as a potential tool to distinguish TB from LTBI.

Protective efficacy of 6-week regimen for latent tuberculosis infection treatment in rural China: 5-year follow-up of a randomised controlled trial.

BACKGROUND: Enlarging tuberculosis (TB) preventive treatment among at-risk populations is a critical component of the End TB Strategy. There is an urgent need to develop suitable latent tuberculosis infection (LTBI) testing and treatment tools according to the local TB epidemic and available resources worldwide. METHODS: Based on an open-label randomised controlled trial conducted since 2015 in China among rural residents aged 50-70 years with LTBI, the protective efficacy of a 6-week twice-weekly regimen of rifapentine plus isoniazid was further evaluated in a 5-year follow-up survey. RESULTS: 1298 treated participants and 1151 untreated controls were included in the 5-year protective efficacy analysis. In the per-protocol analysis, the incidence rate was 0.49 (95% CI 0.30-0.67) per 100 person-years in the untreated control group and 0.19 (95% CI 0.07-0.32) per 100 person-years in the treated group; the protection rate was 61.22%. Subgroup analysis showed that the protection rate was 76.82% in the per-protocol analysis among participants with baseline interferon (IFN)-γ levels in the highest quartile (≥3.25 IU·mL-1). Multiple logistic regression analysis indicated that participants with baseline body mass index <18.5 kg·m-2 and with pulmonary fibrotic lesions had increased hazard of developing active disease with an adjusted hazard ratio (aHR) of 3.64 (95% CI 1.20-11.00) and 5.99 (95% CI 2.20-16.27), respectively. In addition, individuals with higher baseline IFN-γ levels showed an increased risk of TB occurrence (aHR 2.27, 95% CI 1.13-4.58). CONCLUSIONS: Our findings suggest the 6-week twice-weekly regimen of rifapentine plus isoniazid for LTBI treatment might be an optional tool for TB control in the Chinese population.

The Association Between Mycobacteria-Specific Antigen-Induced Cytokines and Host Response to Latent Tuberculosis Infection Treatment in a Chinese Population.

OBJECTIVES: Exploring biomarkers monitoring latent tuberculosis infection (LTBI) treatment effectiveness would benefit optimizing the therapeutic regimen. This study aims to identify potential mycobacteria-specific antigen-induced cytokines associated with host responses to preventive treatment. METHODS: Based on a randomized controlled trial on LTBI treatment among individuals with chest radiography abnormalities suggestive of prior tuberculosis (TB), the dynamically changed cytokine levels in QuantiFERON-TB Gold In-Tube (QFT) supernatants were estimated during the treatment by bead-based multiplex assays and enzyme-linked immunosorbent assay. RESULTS: In total, 63 treated participants and 32 untreated controls were included in the study. The levels of 13 background-corrected mycobacteria-specific antigen-stimulated cytokines [basic fibroblast growth factor (FGF), growth-regulated oncogene (GRO)-α, interleukin (IL)-1α, IL-1ra, IL-12 (p70), stem cell factor (SCF), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), IL-8, interferon (IFN)-α2, IL-5, IL-12 (p40), leukemia inhibitory factor (LIF), and IL-17A] were found to be statistically different between before and after treatment in treated participants, while no statistically differences were observed in untreated controls. Among these 13 cytokines, the level of IL-8 was significantly lower in the QFT reversed group than that in the non-reversed group (p = 0.028) among treated participants, while such a difference was not found for untreated controls (p = 0.292). CONCLUSION: Our results suggested that the lower level of mycobacteria-specific antigen-induced IL-8 might be associated with the host's positive response to LTBI treatment.

The effect of WeChat-based training on improving the knowledge of tuberculosis management of rural doctors.

BACKGROUND: In China, rural doctors played a crucial role in TB cases referral and management. The current study aimed to evaluate the effect of WeChat-based training program on improving the rural doctors' knowledge on TB management. METHODS: A One-year WeChat-based training was conducted among registered rural doctors from Zhongmu County, located in middle China, by means of releasing original contents (in forms of text, poster, video or cartoon) through WeChat subscription account (WeChat SA) once a week. Pre-and-post-training offline tests were hold using the same self-administered questionnaire to evaluate the training effect. RESULTS: A total of 467 rural doctor were included in the study. During the training, 60 original articles were posted through WeChat SA. With respect to the two tests, the median score increased from 50 (40.0-60.0) to 60 (53.0-70.0) (p < 0.001) after training. As compared with posters, the median readings were significantly higher for released contents in forms of text, video and cartoon (p < 0.001). Female's test performance improved better than male's. In addition, a positive relation was observed between education level and the test performance regardless of training. CONCLUSIONS: Our results indicated that WeChat-based training improved the knowledge of rural doctors on TB management to a certain extent. It is worthy to explore more effective new media-based training methods to promote TB control in rural China.

Urinary proteomic analysis to identify a potential protein biomarker panel for the diagnosis of tuberculosis.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is one of the primary causes of death worldwide. Rapid and accurate diagnosis of TB is one of the most direct means to reduce the incidence of TB. In this study, urinary proteomic profiling of TB patients and non-TB individual controls (HCs) was performed, and differentially expressed urinary proteins between TB and HCs were compared and exclusively expressed proteins in TB patients were selected to establish a clinically useful disease marker panel. In total, these top 11 targeted proteins with 265 peptides were scheduled for multiple reaction monitoring validation analysis by using urine samples from 52 TB patients and 52 HCs. The result demonstrated that a three-protein combination out of the five-protein panel (namely P22352, Q9P121, P15151, Q13291, and Q8NDA2) exhibited sensitivity rate of 82.7% in the diagnosis of TB. Furthermore, the three-protein combination could differentiate TB from the latent tuberculosis (LTB) effectively, which exhibited specificity rate of 92.3% for the diagnosis of TB from the LTB category. Although more numbers of clinical samples are required for further verification, the results provided preliminary evidence that this "three-protein combination" out of the five-protein panel could probably be a novel TB diagnostic biomarker in clinical application.

Application of artificial intelligence in digital chest radiography reading for pulmonary tuberculosis screening.

Currently, the diagnosis of tuberculosis (TB) is mainly based on the comprehensive consideration of the patient's symptoms and signs, laboratory examinations and chest radiography (CXR). CXR plays a pivotal role to support the early diagnosis of TB, especially when used for TB screening and differential diagnosis. However, high cost of CXR hardware and shortage of certified radiologists poses a major challenge for CXR application in TB screening in resource limited settings. The latest development of artificial intelligence (AI) combined with the accumulation of a large number of medical images provides new opportunities for the establishment of computer-aided detection (CAD) systems in the medical applications, especially in the era of deep learning (DL) technology. Several CAD solutions are now commercially available and there is growing evidence demonstrate their value in imaging diagnosis. Recently, WHO published a rapid communication which stated that CAD may be used as an alternative to human reader interpretation of plain digital CXRs for screening and triage of TB.

Urinary metabolomic analysis to identify potential markers for the diagnosis of tuberculosis and latent tuberculosis.

Tuberculosis (TB) is a serious infectious disease with high infection and mortality rates. 5%-10% of the latent tuberculosis infections (LTBI) are likely to develop into active TB, and there are currently no clinical biomarkers that can distinguish between LTBI, active TB and other non-tuberculosis populations. Therefore, it is necessary to develop rapid diagnostic methods for active TB and LTBI. In this study, urinary metabolome of 30 active TB samples and the same number of LTBI and non-TB control samples were identified and analyzed by UPLC-Q Exactive MS. In total, 3744 metabolite components were obtained in ESI- mode and 4086 in ESI + mode. Orthogonal partial least square discriminant analysis (OPLS-DA) and hierarchical cluster analysis (HCA) showed that there were significant differences among LTBI, active TB and non-TB. Six differential metabolites were screened in positive and negative mode, 3-hexenoic acid, glutathione (GSH), glycochenodeoxycholate-3-sulfate, N-[4'-hydroxy-(E)-cinnamoyl]-l-aspartic acid, deoxyribose 5-phosphate and histamine. The overlapping pathways differential metabolites involved were mainly related to immune regulation and urea cycle. The results showed that the urine metabolism of TB patients was disordered and many metabolic pathways changed. Multivariate statistical analysis revealed that GSH and histamine were selected as potential molecular markers, with area under curve of receiver operating characteristic curve over 0.75. Among the multiple differential metabolites, GSH and histamine changed to varying degrees in active TB, LTBI and the non-TB control group. The levels of GSH and histamine in 48 urinary samples were measured by ELISA in validation phase, and the result in our study provided the potential for non-invasive biomarkers of TB.

Conditional expanding post-exposure prophylaxis: a potential new tool for tuberculosis control.

For individuals with high risk of exposure and thereafter developing and transmitting active tuberculosis, conditional post-exposure prophylaxis might be a potential tool for tuberculosis control https://bit.ly/39qHHh4.