Tuberculosis remains a major global public health threat. While whole-genome sequencing has transformed our understanding of the causative agent, Mycobacterium tuberculosis (MTB), existing genomic databases are highly fragmented and often underrepresent structural variations (SVs). Furthermore, critical population-genetic statistics are rarely integrated with phylogenetic and geographic context, forcing researchers to reconcile separate datasets manually. To address this gap, we developed TBpop (https://tbpop.chinacdc.cn), an open-access, integrated population genomics portal. TBpop is built from 420 clinical MTB isolates selected from the first national drug resistance baseline survey in China. The portal integrates isolate metadata, pangenome categories, SNPs, SVs, IS6110 insertion sites, strain phylogeny, and gene-level statistics, and provides three interactive explorer modules: the Population Explorer, the Statistics Explorer, and the Variation Explorer. Additionally, a User Analysis module allows researchers to run population genetic workflows on their own alignments. TBpop provides an integrated platform for exploring genome plasticity, signatures of positive selection, and conservation patterns of functionally important genes in MTB.

Introduction: Tuberculosis (TB) remains a major public health challenge in China, which ranks fourth among the 30 high-burden countries worldwide. Individuals with asymptomatic Pulmonary TB (aPTB) may act as "silent transmitters", contributing to undetected community transmission and hindering progress toward the End-TB goals. This study examined the epidemiological characteristics of patients with aPTB in China from 2021 to 2024 to inform targeted control strategies. Methods: Data were obtained from the China Information System for Disease Control and Prevention for the period 2021-2024 and included TB cases with complete symptom records. aPTB was defined as cases without recorded cough symptoms, whereas symptomatic TB was defined as cases with recorded cough symptoms. Descriptive statistical analyses compared the demographic, clinical, and healthcare-seeking characteristics of patients with aPTB and symptomatic TB. Results: Among 973,299 PTB cases with complete symptom records, 16.66% were classified as aPTB. This proportion remained relatively stable throughout the study period, with a slight peak observed in 2022. Higher proportions of aPTB were observed among individuals aged 55-64 years (17.07%), 65-74 years (15.51%), and 15-24 years (14.03%), and among farmers and herders (50.87%). A mild seasonal trend was observed. Geographically, high-incidence areas were concentrated in western and southwestern China. Conclusions: aPTB constitutes a substantial component of the total TB burden in China. Strengthening active case detection in high-risk populations, optimizing medical resources in western China, and integrating aPTB control programs into national prevention and control plans for TB to mitigate hidden transmissions and advance national End-TB objectives.

Background: The proportion and epidemiological profile of asymptomatic tuberculosis (TB) vary widely depending on symptom criteria, yet no standardized case definition exists. Understanding how definitional differences impact surveillance estimates and risk factor associations is critical for accurate burden assessment and targeted intervention. This study compares two common symptom-based definitions of asymptomatic TB and evaluates their influence on estimated prevalence, risk factor associations, temporal trends, and geographic distribution in China. Methods: We analyzed national TB surveillance data (January 2021–December 2024, n=1,037,934). Asymptomatic TB was defined as: D1: absence of all TB-related symptoms; D2: absence of cough, expectoration, or hemoptysis. We compared case proportions (McNemar’s test), assessed risk factors (logistic regression), and analyzed temporal and spatial trends (segmented regression and geographic mapping). Findings: D2 identified nearly twice as many asymptomatic cases as D1 (14.74% vs. 8.29%, difference +6.45%, p<0.001), reclassifying 67,022 (6.5%). Risk factor associations were attenuated under D2: odds ratios for 41/46 subgroups shifted toward 1.0, reducing discriminative power. Temporal trends showed a national peak in early 2022 then decline, with marked provincial heterogeneity. Geographic disparities were more pronounced under D1, revealing a strong south-to-north gradient. Interpretation: Asymptomatic TB definition choice affects epidemiological estimates, risk factor identification, and geographic patterns. The stricter definition (D1) better captures screening-relevant populations and should be considered for standardizing surveillance and guiding active case-finding in high-burden settings.

OBJECTIVES:Whole-genome sequencing (WGS) enables comprehensive characterization of Mycobacterium tuberculosis (MTB), but its routine clinical use is limited by the lack of standardized and multicenter-validated analytical workflows. METHODS:We developed TB-Genaly, a user-friendly and secure bioinformatics pipeline for MTB WGS analysis. Performance of drug-resistance prediction was evaluated using a multicenter, population-based cohort comprising 461 clinical MTB isolates from four centers, each with paired phenotypic drug susceptibility testing (pDST) results. Sensitivity and specificity were calculated to assess concordance between genotypic predictions and pDST. RESULTS:TB-Genaly demonstrated high predictive performance for anti-tuberculosis drug resistance. For first-line drugs, it achieved sensitivity and specificity of 95.8% and 92.6% for rifampicin, 95.5% and 92.4% for isoniazid, 91.8% and 99.4% for pyrazinamide, and 87.3% and 92.7% for ethambutol. For second-line drugs, sensitivity and specificity ranged from 87.8% to 94.7% and 97.5% to 98.0%. The mean values of sensitivity and specificity for predicting MDR-TB were 95.4% (95%CI 92.3%-97.7%) and 93.5% (95%CI 91.1-95.5%), respectively. Receiver operating characteristic (ROC) curve analysis further confirmed excellent discriminatory power, with area under the curve (AUC) values of 0.999, 0.997, 0.995 and 0.969 for the four agents. Additionally, TB-Genaly supports automated generation of standardized clinical reports and transmission network visualizations. CONCLUSION:TB-Genaly provides accurate, standardized WGS-based drug-resistance prediction across multiple centers. Its usability and comprehensive reporting facilitate integration into clinical diagnostics and public health surveillance, highlighting its potential to support clinical decision-making and tuberculosis control efforts.

Whole-genome sequencing (WGS) is an increasingly adopted platform for predicting drug resistance in Mycobacterium tuberculosis; however, diagnostic accuracy varies substantially across bioinformatic tools and analytical frameworks, generating considerable uncertainty for clinical laboratory implementation. We conducted a prospectively registered (PROSPERO: CRD420261342739), PRISMA-DTA-compliant systematic review and meta-analysis of diagnostic accuracy studies. PubMed (MEDLINE), Embase, Web of Science, and Cochrane CENTRAL were searched from 1 January 2000 through 28 January 2026. Primary overall sensitivity and specificity were estimated using a tool-level bivariate random-effects model. Exploratory subgroup analyses and meta-regression examined the association between algorithm category and diagnostic-performance heterogeneity. Twenty-eight drug-level evaluations from seven tools (rifampicin, isoniazid, ethambutol, and pyrazinamide for each tool) were compiled from the extracted 2 × 2 data. For the primary tool-level composite analysis, pooled sensitivity was 0.930 (95% CI: 0.907–0.948) and pooled specificity was 0.962 (95% CI: 0.929–0.981). In secondary drug-specific analyses, sensitivity was highest for rifampicin (0.960, 95% CI: 0.934–0.976) and isoniazid (0.933, 95% CI: 0.906–0.953), and lowest for pyrazinamide (0.860, 95% CI: 0.800–0.904). Exploratory tool-level comparisons produced pooled sensitivity estimates of 0.920 for rule-based tools, 0.899 for machine learning tools, and 0.951 for hybrid tools. These comparisons involved only seven tool-level analytic units and cannot disentangle algorithm type from individual tool identity, training data, mutation catalogue version, or validation population. WGS-based bioinformatic tools provide highly specific and generally sensitive predictions of Mycobacterium tuberculosis resistance for first-line drugs across diverse clinical settings. Exploratory differences between tool categories should not be interpreted as causal effects of algorithmic architecture. Future studies should use prospective head-to-head evaluations on shared, geographically diverse isolate collections, alongside continued improvement of resistance catalogues and external validation.

To assess the prevalence and genetic basis of pretomanid (Pa) resistance, further to generate additional MIC data to support ECOFF/breakpoint setting in the microdilution system. Mycobacterium tuberculosis (MTB) isolates were collected from national drug resistance surveillance regions, with no prior pretomanid exposure. All strains were sub-cultured on Löwenstein-Jensen medium and tested against 12 anti-tuberculosis drugs with the Sensititre® MYCOTB plate. Pretomanid was serially diluted in 7H9 broth supplemented with 10

To characterize the mutation profile of the ahpC gene in isoniazid resistance (INHr) Mycobacterium tuberculosis (MTB) isolates and to evaluate the correlation between specific mutations and resistance levels, a total of 1,337 INHr MTB isolates were collected through the Chinese Drug Resistance Surveillance Program (2013-2020). The minimum inhibitory concentrations (MICs) for INH, rifampicin (RIF), and ethionamide were determined by broth microdilution, followed by whole-genome sequencing analysis. Among 1,337 INHr-MTB isolates, 45.5% (608/1,337) were multidrug-resistant (MDR), and 54.5% (729/1,337) were RIF-sensitive cases, with lineage 2 predominating (1,013/1,337, 75.8%). Resistance mutations were identified in 79.1% (1,058/1,337) of strains, primarily katG Ser315Thr (65.5%, 695/1,058) and inhA C-777T (19.7%, 208/1,058). Notably, 5.3% (56/1,058) isolates harbored standalone ahpC mutations, with 83.3% (5/6) C-81T, 60.0% (9/15) G-48A, 57.1% (4/7) C-54T, 50.0% (3/6) C-57T, and 42.1% (8/19) C-52T mutations showing high-level INH resistance. Accordingly, 91.7% (11/12) dual katG315+inhA mutations conferred high-level INH resistance, while ahpC C-57T mutants universally exhibited MDR. The ahpC mutations are associated with high-level INH resistance in variants without concurrent katG or inhA mutations. This finding significantly advances our understanding of tuberculosis resistance profiling, enabling more comprehensive detection of INHr-MTB and optimizing therapeutic strategies.IMPORTANCEAmong INH-resistant MTB clinical isolates, mutations in the ahpC promoter region have been considered to occur in combination with other mutations, such as katG and inhA, in a compensatory role. While the ahpC mutations have been incorporated into the World Health Organization (WHO)-recommended rapid diagnostic test, Xpert MTB/extensively drug-resistant tuberculosis (XDR), it has been still ambiguous about the standalone effects on INH resistance spectrum. Our findings demonstrate that the ahpC mutations are associated with high-level INH resistance in variants without concurrent katG or inhA mutations. This finding significantly advances our understanding of TB resistance profiling, enabling a more comprehensive detection of INHr-MTB and optimizing therapeutic strategies.

What is already known about this topic?:Tuberculosis preventive treatment (TPT) is critical in preventing latent tuberculosis infection (LTBI) progression to active tuberculosis. China has integrated TPT into national Tuberculosis (TB) control; however, systematic national data on TPT implementation in China are scarce. What is added by the report?:TPT recipient number in China increased 2.5-fold (2022-2025), with around 79% using short-course regimens. Among 2,676 individuals with LTBI, TPT acceptance and completion rates were 45.14% and 85.18%, respectively. Key acceptance factors included age, ethnicity, occupation, treatment institution, immunocompromised status, and purified protein derivative results. What are the implications for public health practice?:To improve TPT effectiveness, public health strategies should integrate TPT into routine clinics, promote short-course regimens, and target high-risk groups (e.g., immunocompromised individuals and the elderly) to increase acceptance rates and reduce disparities to achieve TB elimination.

BACKGROUND:TB continues to pose considerable threats to elderly populations worldwide. Drawing on the Global Burden of Disease 2021 dataset spanning 3 decades, this investigation explores how TB burden has shifted among Chinese seniors aged 60 and above. METHODS:Standardized epidemiological metrics for incidence, prevalence, mortality, disability-adjusted life years, age-standardized rate and average annual percent change were calculated. Joinpoint regression analysis was applied to identify periods manifesting notable changes and an age-period-cohort framework was employed to estimate the age, period, and cohort effects. Modifiable contributors were measured through attributable fraction analysis, and Bayesian modeling were used to predict long-term trends to 2041. RESULTS:Drug-susceptible TB declined steadily (-8.07%), whereas drug-resistant TB escalated dramatically, with XDR-TB rising 2133.81% and MDR-TB increasing by and 20.29% relative to 1990, respectively. Men carried roughly twice the disease burden of women, driven largely by smoking and alcohol. Conversely, obesity and diabetes became the prominent drivers among older women after 2006. HIV-associated TB in the elderly patients showed no signs of abating. Projections suggest drug-susceptible TB will keep declining, whereas drug-resistant TB will keep growing. CONCLUSIONS:Older Chinese adults confront a multifaceted TB epidemic marked by declining drug-susceptible TB cases, rising drug‑resistant cases, gender-specific risk profiles, and an emerging HIV-TB syndemic. Addressing sex-differentiated risk profiles and strengthening resistance surveillance are essential steps toward national elimination goals.

Background: Patients with systemic autoimmune diseases (sAIDs) are susceptible to active tuberculosis (ATB), especially in high-burden countries and regions. However, a comprehensive overview of the ATB burden across the full spectrum of sAIDs remains lacking. Methods: In this nationwide retrospective cohort study, we linked individual-level data from the Chinese Rheumatism Data Center (CRDC), the Infectious Disease Reporting System (IDRS), and the Tuberculosis Information Management System (TBIMS). Patients of all ages registered in CRDC between 2016 and 2023, with a confirmed diagnosis of 1 of 10 sAIDs, including rheumatoid arthritis, systemic lupus erythematosus, spondyloarthritis, primary Sjögren's disease, idiopathic inflammatory myopathies, undifferentiated connective tissue disease, systemic sclerosis, Behçet's disease (BD), Takayasu arteritis (TAK), and ANCA-associated vasculitis (AAV), were included. We estimated incidence rates, point prevalence, cumulative incidence, and age- and gender-adjusted standardized incidence ratios (SIRs) for ATB, and examined associations between SIRs and region-level socioeconomic indicators using Cox proportional hazards models. Findings: Among 255,103 eligible patients, 2,775 incident ATB cases were confirmed across all 10 sAIDs. The overall ATB incidence rate in 2023 was 157.79 per 100,000 person-years. Point prevalence of ATB among patients with sAIDs rose from 393.83 per 100,000 people in 2016 to 904.65 per 100,000 people in 2023. Cumulative incidence exceeded 1% within 10 years of sAID diagnosis. Patients with TAK (7.60, 95% CI 4.92-11.22), AAV (6.96, 4.90-9.59), BD (6.30, 4.25-9.00) carried the highest relative risks of ATB, and male and female patients exhibited comparable ATB susceptibility compared with general population. At the area level, higher urbanization was associated with increased ATB risk in patients with sAIDs, whereas higher educational attainment was protective. Interpretations: Patients with sAIDs constitute a distinctly high-risk population for ATB, with a burden substantially exceeding that of the general population and marked heterogeneity across diseases and socioeconomic context. These findings support the systematic integration of targeted TB screening and preventive strategies into routine rheumatology care, particularly in TB-endemic settings.

Hainan Province, the only tropical province in China, remains a high-burden area for tuberculosis (TB). However, up-to-date data on the prevalence and demographic disparities of TB cases are lacking. To address these gaps, we conducted a population-based TB prevalence survey. We conducted a population-based, cross-sectional survey using a multistage stratified random cluster sampling design. The study included adults (aged ≥15 years) who had resided in their households for at least six months in Hainan. Screening and diagnostic procedures followed World Health Organization (WHO) guidelines. We calculated the crude prevalence of active PTB among participants with valid results and applied inverse probability weighting combined with multiple imputation to account for missing data. Prevalence estimates were compared by rural–urban residence, age group, sex, and ethnicity. In 2023, a total of 67,681 individuals were enumerated, of whom 35,219 (52.0

To evaluate the performance of the iFIND INH/FQ, a low-complexity molecular assay, for the rapid and simultaneous detection of resistance to isoniazid (INH) and fluoroquinolones (FQs) in Mycobacterium tuberculosis. Frozen sputum specimens stored at the Chengde Center for Disease Control and Prevention laboratory were used. Phenotypic drug susceptibility testing (pDST) and DNA sequencing served as reference standards. The limit of detection (LOD) was determined using probit regression with spiked samples. The assay's ability to detect resistance-conferring mutations in katG, inhA, and gyrA genes was assessed using genotypically characterized strains. Diagnostic accuracy was evaluated against pDST. The LOD was 20.79 CFU/mL for INH and 9.34 CFU/mL for FQs. The assay detected all targeted mutations except ahpC c.-6 associated with INH resistance. Compared to pDST, the iFIND INH/FQ assay demonstrated a sensitivity of 97.59% (95% confidence interval [CI]: 91.63-99.34%) and specificity of 98.10% (95% CI: 94.57-99.35%) for INH resistance. For FQ resistance, sensitivity was 92.16% (95% CI: 81.50-96.91%) for levofloxacin and 92.00% (95% CI: 81.16-96.85%) for moxifloxacin, with specificities of 97.33% (95% CI: 93.89-98.85%) and 96.81% (95% CI: 93.21-98.53%), respectively. Sequencing confirmed iFIND results in the majority of discrepant cases (100% for INH and 55.65% for FQs). The iFIND INH/FQ LC-aNAAT is a highly accurate and rapid molecular assay for simultaneous detection of INH and FQ resistance. It is a promising tool for scaling up rapid drug susceptibility testing in clinical and peripheral laboratory settings.IMPORTANCEAs a low-complexity automated nucleic acid amplification test, the iFIND assay achieves the goal of simultaneously detecting isoniazid and fluoroquinolone resistance in approximately 90 min, perfectly meeting the TPP's core requirements for "rapid" and "simple operation." Its fully integrated system minimizes manual steps and contamination risk, making it highly suitable for use in resource-limited, lower-biosafety-level primary laboratories.

Transmission of rifampicin-resistant and multidrug-resistant tuberculosis (MDR/RR-TB) is a major driver of the global drug-resistant TB epidemic, yet the contribution of compensatory mutations to its spread remains uncertain. We analyzed 206 non-duplicate MDR/RR-TB isolates collected from five surveillance sites in Hunan Province, China, between 2013 and 2020 using whole-genome sequencing. Transmission clusters were defined by ≤12 single-nucleotide polymorphism (SNP) differences, and compensatory mutations in rpoA, rpoB, and rpoC were identified through a curated mutation catalog and phylogenetic evidence. Clusters were further classified based on whether compensatory mutations predated transmission (C-type), arose after transmission (M-type), or were absent (N-type), with M-type clusters excluded to reduce confounding. Among the 206 isolates, 63 (30.6%) carried at least one compensatory mutation, predominantly in rpoC, and 27 clusters (32.5%) were identified, ranging from 2 to 6 isolates. No significant difference was observed in clustering frequency between compensated and non-compensated strains (21.7% vs 32.8%, P = 0.113), nor in cluster size between C-type and N-type clusters (P = 0.961). These findings demonstrate that compe nsatory mutations do not significantly affect transmission clustering at the population level; instead, prolonged infectious periods associated with diagnostic delays and treatment challenges are more likely to sustain MDR/RR-TB spread, underscoring the importance of rapid detection, timely effective therapy, and robust patient management to curb transmission.IMPORTANCEUnderstanding the drivers of multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) transmission is critical for global TB control. Compensatory mutations in RNA polymerase subunits have been proposed as key contributors to the success of drug-resistant strains, yet population-level evidence has been limited. In this population-based genomic study of 206 MDR/RR-TB isolates collected over 8 years in Hunan Province, China, we systematically examined the association between compensatory mutations and transmission clustering. Our results show that compensatory mutations did not significantly increase clustering frequency or cluster size, indicating a limited impact on the spread of MDR/RR-TB in the community. These findings challenge the prevailing assumption that compensatory evolution is a major determinant of transmission success and provide robust genomic evidence to refine our understanding of drug-resistant TB epidemiology.

Non-tuberculous mycobacteria (NTM) cause pulmonary diseases that resemble tuberculosis and are frequently misdiagnosed in TB-endemic settings, leading to inappropriate treatment. This study aimed to determine the prevalence of NTM pulmonary disease (NTMPD) among patients presumed to have pulmonary TB in China, and to evaluate the impact of ecological, climatic, and socioeconomic factors on NTMPD identification. Data on notification cases between January 1, 2011 and December 31, 2020 were from the National TB Information Management System (TBIMS). Joinpoint regression models were used to analyze temporal trends in NTMPD prevalence and its spatial variability. A random forest model was employed to assess the effects of ecological, climatic, and socioeconomic factors on NTMPD identification. NTMPD cases are concentrated primarily in the eastern and southeastern coastal regions of China. NTMPD prevalence shows an annual decline (AAPC = −1.64%, 95% CI: −2.76% to −0.51%). Random forest analysis identifies annual average temperature (mean importance = 5.51%, 95% CI: 3.50% to 7.53%), GDP (mean importance = 3.60%, 95% CI: 2.19% to 5.01%), and water coverage area (mean importance = 3.45%, 95% CI: 1.73% to 5.16%) as key predictors of NTMPD identification. In 2020, 573 counties remain classified as neglected high-risk areas. NTMPD in China exhibits spatial heterogeneity and a declining temporal trend, with identification influenced by ecological, climatic, and socioeconomic factors. These findings highlight the need for targeted surveillance and diagnostic capacity strengthening, particularly in neglected high-risk areas. Non-tuberculous mycobacteria can cause lung diseases similar to Mycobacterium tuberculosis and are often misdiagnosed in tuberculosis-endemic settings, leading to inappropriate treatment and delayed care. Understanding how common non-tuberculous mycobacteria pulmonary disease (NTMPD) is, and where it is concentrated, is important for improving diagnosis and patient management. We examined NTMPD among patients initially presumed to have pulmonary tuberculosis across China. We found that environmental, climatic, and socioeconomic factors were associated with NTMPD identification, and more than 500 counties remained classified as neglected high-risk areas. Li et al., use national surveillance data from 2011–2020, for analysis of trends and geographic patterns of non-tuberculous mycobacterial pulmonary disease (NTMPD) in China and assess ecological, climatic, and socioeconomic factors linked to its identification. NTMPD is concentrated in eastern and southeastern China, declines over time, and is most strongly associated with temperature, GDP, and water coverage, with 573 counties remaining neglected high-risk areas in 2020.

BackgroundAccurate and cost-effective screening for Mycobacterium tuberculosis (Mtb) infection remains a global challenge. While Interferon-γ Release Assays (IGRAs) offer high specificity, their widespread deployment is hindered by high costs and technical complexity. Conversely, the traditional Tuberculin Skin Test (TST) lacks specificity due to BCG cross-reactivity. Emerging recombinant skin tests predominantly rely on the ESAT6-CFP10 antigen combination. To potentially broaden the antigenic repertoire and enhance diagnostic sensitivity, we developed a novel recombinant fusion protein incorporating MPT64 (from Region of Difference 2, RD2) alongside ESAT-6. This study represents the first-in-human evaluation of the ESAT6-MPT64 (EM) skin test.MethodsThis single-center, randomized, open-label, dose-escalation Phase 1 clinical trial (Registration: ChiCTR2500112887) enrolled 60 participants, comprising 30 healthy controls and 30 patients with active pulmonary tuberculosis (TB). Participants were stratified and randomized into low-, medium-, and high-dose cohorts (n = 10 per cohort/group). The primary endpoint was safety and tolerability. Secondary endpoints included diagnostic performance (sensitivity and specificity) and concordance with the T-SPOT.TB assay (IGRA).ResultsThe EM skin test demonstrated an excellent safety profile. Adverse events were predominantly mild (Grade 1–2), transient, and self-limiting, with no serious adverse events (SAEs) related to the investigational product reported. In terms of diagnostic performance, the test exhibited robust immunogenicity in active TB patients, achieving a peak sensitivity of 87.0% at 48 hours and maintaining 82.6% at 72 hours post-injection. In healthy controls, the test showed high specificity with a low rate of non-specific reactions (13.3%). Receiver Operating Characteristic (ROC) analysis indicated high diagnostic accuracy, with Area Under the Curve (AUC) values exceeding 0.80 across all dose groups at both 48- and 72-hour reading windows. Furthermore, the EM skin test demonstrated substantial concordance (κ > 0.60) with IGRA results, confirming that the specific DTH response is distinct from BCG vaccination background.ConclusionThe recombinant EM skin test is safe, well-tolerated, and demonstrates preliminary diagnostic accuracy comparable to IGRAs. By successfully validating the translational utility of the MPT64 (RD2) antigen in a human cohort, this study provides a strong proof-of-concept for the EM skin test as a scalable, specific, and cost-effective immunodiagnostic tool.

Objective:To determine the proportions of drug-resistant tuberculosis (TB), its trends, and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China. Methods:The data of patients with pulmonary TB were retrieved from a national drug-resistant TB survey for analysis. Joinpoint regression software was used to analyze time trends. We also used whole genome sequencing to analyze the lineages and drug resistance-conferring mutations of 621 isolates. Results:Among 4,235 patients with pulmonary TB, the proportion of new cases of multidrug-resistant tuberculosis (MDR-TB) was 3.18% (95% confidence interval [ CI]: 2.37-4.15) for adolescents and 3.76% (95% CI: 3.03-4.60) for young adults; for previously treated patients, MDR-TB accounted for 11.25% (95% CI: 5.28-20.28) of adolescents and 11.05% (95% CI: 6.88-16.55) of young adults. The proportion of patients with MDR-TB remained stable among both new and previously treated patients aged 10-24 years during the study period. Through whole genome sequencing, we found that the most common mutations in the MDR-TB strains were Ser315Thr in the katG gene (71.74%) and Ser450Leu in the rpoB gene (50.00%). Conclusion:This study revealed a high proportion of MDR-TB among adolescents and young adults, indicating that urgent and comprehensive measures are needed to reduce the emergence and transmission of drug-resistant TB among this population in China.

Objective:To evaluate the clinical diagnostic ability of iFIND TBR (iFIND) for Mycobacterium tuberculosis (MTB) and resistance to rifampicin (RIF). Methods:Sputum samples, prospectively collected from patients with suspected pulmonary tuberculosis between November 2023 and December 2024, were used for comprehensive laboratory testing, including smear microscopy, solid culture, Xpert MTB/RIF, iFIND assays, and proportion method drug susceptibility testing (DST). Results:Among the 452 patients, the positive rates of iFIND (80.31%) and Xpert (76.99%) were significantly higher than those of solid culture (65.49%). Based on solid culture as the reference standard, the sensitivity of iFIND for detection of MTB was slightly higher than that of Xpert, but no statistically significant difference was observed (p = 0.157). The sensitivity and specificity of iFIND for detection of MTB were 99.14 and 84.31% relative to the bacteriology reference standard, respectively. Based on the clinical diagnosis results as reference, the higher sensitivity of iFIND than Xpert was observed in detecting MTB (93.46% vs. 90.58%), although the difference was not statistically significant (p = 0.162). The rifampicin detection failure rate was significantly higher in low bacterial load specimens (1+) compared to those with moderate/high loads (≥2+) (p < 0.001). With the proportion method DST results as reference standard, no statistically significant differences were observed in the sensitivity and specificity between iFIND and Xpert. Conclusion:The iFIND assay is a rapid and automated assay with sensitivity and specificity comparable to Xpert for early TB diagnosis and drug resistance screening, making it particularly suitable for implementation in primary healthcare settings and general hospitals.

IntroductionDigital droplet PCR (ddPCR) offers high sensitivity and absolute quantification without standard curves, making it promising for tuberculosis (TB) detection in paucibacillary samples. This study evaluated the diagnostic performance of a ddPCR assay targeting IS6110 and 23S rRNA for pulmonary tuberculosis (PTB) and tuberculous pleurisy (TP).MethodsA total of 436 patients (245 suspected PTB, 191 suspected TP) were prospectively enrolled. ddPCR was performed on sputum, bronchoalveolar lavage fluid, and pleural effusion samples. Diagnostic performance was compared with Xpert MTB/RIF and culture.ResultsIn suspected PTB, ddPCR showed significantly higher sensitivity than Xpert (49.70% vs. 38.10%, p < 0.001), while Xpert showed higher specificity (98.65% vs. 87.70%). In suspected TP, ddPCR also demonstrated superior sensitivity (17.54% vs. 10.40%, p < 0.001). For NTM detection, ddPCR achieved 60% sensitivity and 99.58% specificity.DiscussionddPCR offers improved sensitivity for PTB and TP diagnosis, particularly in paucibacillary cases, though its lower specificity necessitates confirmatory testing. The dual-target design enables simultaneous MTB/NTM differentiation, providing clinical utility for guiding appropriate therapy.

Background:Tuberculosis (TB) remains a major public health challenge in China. Although meteorological factors are known to influence its transmission, their nonlinear and lagged impacts across regions and seasons remain unclear. We quantified these effects using the most detailed national data set available and explored how climate information can enhance TB prediction and control. Methods:We conducted a nationwide ecological time-series study by integrating weekly TB surveillance data (2005-19) with high-resolution meteorological and air pollution models. We assessed associations between TB incidence and meteorological factors using negative binomial regression and distributed lag nonlinear models to account for nonlinear and delayed effects. Results:From 2005 to 2019, TB cases in China decreased from 1.23 million to 0.75 million (estimated annual percent change <0 across all regions), with the burden remaining highest in western and southern China. Higher weekly mean temperature (incidence rate ratio (IRR) = 1.33) and precipitation (IRR = 1.03) increased TB risk, while greater temperature differences (IRR = 0.96) and relative humidity (IRR = 0.92) had protective effects. Temperature effects peaked in summer (IRR = 1.80; P < 0.05). Lagged analyses showed that extreme high temperatures and high wind speeds initially suppressed, but subsequently elevated TB risk, while higher precipitation and humidity showed delayed risk effects. Conclusions:By integrating fine-scale epidemiological and meteorological data, our study adds to our knowledge on TB epidemiology by more accurately characterising climate-disease interactions and enhancing the predictive capability of risk models. The findings provide empirical evidence to support the development of risk stratification tools and guide the implementation of proactive, phased intervention strategies aimed at mitigating the persistent TB burden in high-risk regions.