Qiao Liu

Background: Recent Mycobacterium tuberculosis infection ( MTB ) carries a higher risk of progression to active tuberculosis (TB) than MTB infection, but the immune features that distinguish these stages remain unclear. Methods: In this multicenter observational study in Jiangsu Province, China, we enrolled 228 participants with MTB infection ( n = 88), recent infection ( n = 44), or active TB ( n = 96). Twelve plasma cytokines and chemokines were quantified using a multiplex Luminex platform. Group differences were assessed using non-parametric tests with a two-stage false discovery rate (FDR) correction and age- and sex-adjusted residual models. Biomarker performance was evaluated by repeated Monte Carlo cross-validation using an ensemble feature-selection framework. Post-hoc power analyses were conducted to evaluate the robustness of subgroup comparisons. Results: Age, but not sex, differed across groups. After age- and sex-adjusted comparisons, six markers differed across groups. While recent infection exhibited a trend toward higher IL-23 and IL-12 concentrations compared to remote infection, post-hoc analysis revealed these subgroup differences had small effect sizes and were statistically underpowered. In the combined infection-vs.-TB comparison, IL-8 and CCL1 were higher in active TB, whereas IL-23, IL-12, IL-10, and IL-1ra were lower. Among multivariable models, XGBoost performed best (mean AUC 0.866), followed by the ensemble model (0.865) and random forest (0.861). Decision curve analysis suggested potential clinical utility across exploratory threshold probabilities, although no clinically validated operating point was predefined. Conclusion: Active TB exhibits a distinct peripheral cytokine pattern compared to MTB infection. Recent infection may represent an exploratory trend toward preserved Th1/Th17 signaling, though larger longitudinal cohorts are required for confirmation. Peripheral cytokine profiles integrated into multivariable models may provide complementary triage information, although external validation is required before clinical application.

A large number of tuberculosis patients manifest with minimal or no symptoms, and the infectiousness of these individuals is not well characterized. Index cases were consecutively enrolled from the four health centers in Jiangsu Province. Symptoms among index cases were assessed covering the 3 months prior to diagnostic evaluation, in addition to those present at the time of diagnosis. Concurrently, one control community was selected for QuantiFERON screening. Mycobacterium tuberculosis infection was measured through QuantiFERON for all groups. 1,050 contacts of 473 tuberculosis patients, and 560 unexposed controls were included. Asymptomatic tuberculosis among index cases varied from 15% (no symptoms), to 24% (no cough), and 44% (no prolonged cough). The relative risk of QuantiFERON positivity was higher than controls compared to contacts of both asymptomatic (aRR; 2.06; 1.28–3.33) and symptomatic tuberculosis patients (aRR; 2.23; 1.66–3.01). When using alternative QuantiFERON cutoffs, the relative risk was consistently higher among both contact groups compared to controls. When comparing contacts of symptomatic and asymptomatic tuberculosis patients, similar rates of QuantiFERON and ESAT6-CFP10 skin test levels were seen, regardless of the cutoff. This study suggests that tuberculosis patients that are minimally symptomatic or without recognized symptoms may be infectious.

Background: Tuberculosis (TB) remains a major public health concern. Despite improved diagnostic tools, delays in TB diagnosis persist and hinder control efforts. Objective: This study aims to investigate the spatiotemporal patterns of TB diagnostic delay and identify individual and spatial risk factors in Jiangsu Province, China, from 2011 to 2021. Methods: This study included 332,091 patients with TB who reported in Jiangsu Province from 2011 to 2021, using data obtained from the Jiangsu TB Information Management System, and diagnostic delay was defined as an interval of more than 28 days between symptom onset and diagnosis. Logistic regression was used to evaluate individual-level factors associated with delayed status, while a Bayesian spatiotemporal Beta model was used to analyze county-level TB diagnostic delay rates and assess spatial correlation using the global Moran I . The panel Granger causality analysis explored the temporal dynamics of delay rate transitions. Results: Male patients, educators, and those diagnosed at the local Centers for Disease Control and Prevention had lower odds of diagnostic delay, whereas the older adults, agricultural workers, migrants, clinically diagnosed cases, and those diagnosed at community health centers had higher odds of delay. Spatial clustering in TB diagnostic delay rates was significant from 2015 onward (Moran I =0.110-0.193; all P <.05), excluding 2018 when Moran I was 0.054. The Bayesian spatiotemporal Beta model, which accounted for 31.8% of the total variation due to spatial structure, indicated that for each 1-unit increase in the proportion of local patients and for each 100,000-person increase in resident population, the TB diagnostic delay rate decreased by 33.9% (95% CI 0.128-0.498) and 2% (95% CI 0.005-0.033), respectively. The panel Granger causality analysis indicated that TB incidence and health care technicians significantly influenced temporal changes in delay rates. Conclusions: TB diagnostic delays in Jiangsu were influenced by both individual and spatial factors, with the proportion of local patients and resident population size contributing significantly to spatiotemporal variation. Tailored interventions targeting high-risk groups and health care settings are needed.

Adolescents are underprioritized in tuberculosis (TB) control, and the effect of TB preventive therapy (TPT) in this group is unstudied in China. This study evaluated the protective effect of TPT in Chinese adolescents during TB outbreaks. Data on TB outbreaks and contact screening in six cities (2019–2021) were collected. Adolescents eligible for TPT were identified via tuberculin skin test or interferon-gamma assay and grouped by TPT. Follow-up until 31 December 2023, tracked TB onset. The protective effect was analyzed using KM survival curves and COX models. From January 2019 to December 2021, 136 school TB outbreaks were reported, involving 10,837 adolescent contacts. Among these, 624 adolescent contacts met the criteria for TPT (latent TB infection) at baseline; 277 (44.4%) initiated a 3-month isoniazid plus rifampicin preventive therapy (TPT group), while 347 (55.6%) did not receive TPT (non-TPT group). By 31 December 2023, 11 of these 624 adolescent contacts developed active TB, with 1 patient in the TPT group and 10 patients in the non-TPT group. The cumulative incidence of TB was 0.36% in the TPT group vs. 2.88% in the non-TPT group (χ² = 5.65, p = 0.017). This corresponds to an approximate 87% reduction in TB incidence among adolescent contacts who received TPT compared to those who did not. TPT reduced TB incidence by ~90% among adolescent contacts. Timely, comprehensive, and standardized TPT is recommended to minimize TB risks in educational settings and achieve a TB-free campus.

The COVD-19 pandemic has led to major impacts on population-level transmission of respiratory viral illnesses. However, the impact of the pandemic on Mycobacterium tuberculosis transmission is unknown. Schoolchildren from 12 cities in Jiangsu Province were administered tuberculin skin tests at school matriculation from 2017–2021. We conducted an interrupted time-series analysis to compare trends from annual tuberculin surveys before (2017–2019) and during pandemic-related social restrictions (2020–2021). We compared observed trends in tuberculin positivity during restrictions to a counterfactual model assuming background trends prior to restrictions continued linearly. From 2017–2021, 1,940,735 schoolchildren from 1,427 schools were administered a skin test. Among middle school students, tuberculin positivity was largely consistent from 2017–2019 (9.3%, 9.6%, 10.0%), but reduced in 2020 and 2021 (8.0% and 7.0%). There was a reduction in the annual risk of infection of 24.7% (95% predictive interval [PI], −27.2, −21.2) and 37.0% (95% PI, −40.8, −33.3) compared to the counterfactual model in 2020 and 2021. Among high school students, similar but more modest reductions in the annual risk of infection were seen in post-pandemic years (19.8% reduction in 2021). There have been substantial population-level decreases in M tuberculosis transmission among adolescents in eastern China.

Background: Tuberculosis (TB) is a leading cause of death among people living with HIV (PLHIV). While body mass index (BMI) affects TB risk, its association with latent tuberculosis infection (LTBI) in PLHIV is unclear. High-transmission settings, such as prisons, may further increase LTBI risk, yet this relationship has not been studied across both prison and community populations of PLHIV. Methods: We conducted a dual cross-sectional study of PLHIV in Jiangsu Province, China, recruiting participants from a prison hospital in 2021 and community healthcare facilities from July to November 2023. BMI was calculated from measured height and weight. LTBI was identified by a positive ESAT6-CFP10 (EC) skin test or the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay. Logistic regression and generalized additive models (GAMs) assessed the association between BMI and LTBI, adjusting for demographic, clinical, and behavioral confounders. Results: A total of 1799 PLHIV were included in the analysis, of whom 343 (19.07%) were recruited from prison settings and 1456 (80.93%) from community-based screening. The overall prevalence of LTBI was 13.79% (n = 248). Obesity (BMI ≥ 28 kg/m²) was linked to a significantly lower risk of LTBI (adjusted OR = 0.47, 95% CI: 0.23–0.95, p = 0.036), particularly when identified by EC testing (adjusted OR = 0.13, 95% CI: 0.03–0.54, p = 0.005). The BMI–LTBI association followed a nonlinear “U-shaped” pattern, with the lowest prevalence in individuals who were obese. Among those with CD4+ T cell counts < 500 cells/μL, the inverse association between obesity and LTBI was even more marked (adjusted OR = 0.20, 95% CI: 0.05–0.83, p = 0.027). Conclusion: In summary, obesity is significantly associated with a lower risk of LTBI among PLHIV, with an approximate 54% risk reduction. This inverse relationship was most pronounced when using the EC skin test.

As an alternative to the tuberculin skin test (TST) or QuantiFERON-TB Gold In-Tube (QFT-GIT), ESAT6-CFP10 (EC) skin test is an emerging screening method; however, its value in the diagnosis of latent tuberculosis infection (LTBI) in detainees is still unclear in China. Newly admitted detainees meeting inclusion criteria were enrolled, with demographic/clinical data collected via structured questionnaires. TST, EC skin test, and QFT-GIT screenings were performed, documenting the diameter of skin indurations and/or redness at injection sites and blistering reactions at injection sites. In total, 1,038 detainees were enrolled in this study from October 2022 to October 2023 with 236 LTBI (22.7%). The positive rate of TST, EC skin test, and QFT-GIT was 18.1%, 10.6% and 11.9%. The area under the curve for EC was 0.820, indicating a strong concordance with QFT-GIT (κ = 0.673). Compared with QFT-GIT, the sensitivity of EC was 66.9%, and the specificity was 97.0%. The mean induration diameter or redness of EC was significantly larger than that of TST ( P < 0.001). In the regression model, no history of alcohol consumption (aOR = 0.433, 95% confidence interval [CI]: 0.200, 0.938), no history of surgical trauma (aOR = 0.731, 95% CI: 0.539, 0.991), and no drug use (aOR = 0.473, 95% CI: 0.233, 0.961) was identified as a protective factor for LTBI. The EC demonstrated both high specificity and sensitivity comparable to the QFT-GIT. When screening for LTBI among jail detainees in this setting, particular attention should be given to individuals with a history of alcohol consumption, surgical trauma, and drug use. IMPORTANCE: Jail detainees represent a vulnerable population with an elevated risk of tuberculosis. The EC skin test demonstrates promising potential as an alternative to traditional diagnostic methods, such as the TST and QFT-GIT assay, for LTBI screening. Targeted screening strategies can facilitate the early detection, diagnosis, and management of LTBI.

The low positive predictive value of tuberculin skin tests and interferon-γ release assays often results in unnecessary prophylaxis. This study aimed to identify antigen-specific biomarkers with high accuracy for predicting progression to active tuberculosis (ATB). QuantiFERON supernatants from a school tuberculosis outbreak cohort were analyzed, tracking students over two years to identify ATB cases. We assessed 67 cytokines using the Luminex Multiplex Array kit and applied LASSO and multivariate logistic regression to select predictors. A nomogram was developed from the coefficients of top predictors. Model performance was evaluated by AUC, C-index, and AIC. The levels of FGFbasic, GM-CSF, MPIF-1/CCL23, as well as the combinations of ratios of FGFbasic/GM-CSF and FGFbasic/MPIF-1/CCL23 were significantly associated with the risk of ATB. AUC values for the prediction models based on individual cytokines ranged from 0.607 to 0.713, notably lower than those of the fixed models based on the logistic regression (0.932) and LASSO regression (0.939). The LASSO regression model exhibited the best predictive performance, with a higher sensitivity (0.858 vs. 0.818) and specificity (0.949 vs.0.923), lower AIC (36.323 vs. 38.232), and equivalent C-index (0.939) compared to the traditional logistic regression model. The biomarkers identified in this study offer valuable insights for developing a more precise tool to identify individuals at high risk for rapid progression to ATB disease, enabling targeted interventions. The combination of multiple immune indicators shows significant promise in improving diagnostic accuracy.