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Background Although diagnosis and treatment services for tuberculosis (TB) are provided free of charge in most countries, direct non-medical and indirect costs due to absenteeism, also place a significant burden on patients and their families. Sichuan Province has the second highest incidence of TB in China, with an incidence of approximately 100 cases per 100 000 people. However, there are limited research on out-of-pocket expenditure (OOPE) and its influencing factors in TB patients in Sichuan Province. Methods A retrospective cross-sectional study was conducted on TB patients in designated medical institutions for TB in Sichuan Province from 2017-2021. A face-to-face questionnaire was conducted to obtain the information related to hospitalization of patients, and the multi-level regression model was used to analyse the factors that influence OOPE and total out-of-pocket expenditure (TOOPE) of TB patients. Results A total of 2644 patients were investigated, and 74.24% of TB patients and their families experienced catastrophic total costs due to TB. The median total cost was 9223.37 CNY (1429.98 USD), in which the median direct and indirect costs of TB patients were 10185.00 CNY (1579.07 USD) and 2400.00 CNY (372.09 USD), respectively, and indirect costs contributed to 43% of total costs. The median OOPE and TOOPE costs were 6024.00 CNY (933.95 USD) and 11890.50 CNY (1843.49 USD), respectively. OOPE and TOOPE had common influencing factors including whether the patient's family had four or more members, a history of hospitalization, combination with other types of TB, the number of visits before diagnosis, and co-occurrence with chronic disease. Conclusions The OOPE and TOOPE for TB patients and their families in Sichuan Province are still heavy. In the long run, it is necessary to strengthen education and awareness campaigns on TB related knowledge, disseminate basic medical knowledge to the public, improve healthcare-seeking behavior, and enhance the healthcare infrastructure to improve the accuracy of TB diagnosis and reduce the significant OOPE and TOOPE faced by TB patients and their families in Sichuan Province.

Background Multidrug- or rifampicin-resistant tuberculosis (TB; MDR/RR-TB) is a significant public health threat. However, the mechanisms involved in its transmission in Sichuan, China are unclear. To provide a scientific basis for MDR/RR-TB control and prevention, we investigated the drug-resistance characteristics, genetic diversity, and transmission dynamics and analyzed the demographic and clinical characteristics of patients to identify risk factors for the acquisition of MDR/RR-TB in Sichuan, Western China. Methods Whole-genome sequencing was performed using a sample comprised of all MDR/RR-TB strains isolated from patients with pulmonary TB (≥ 15 years) at the 22 surveillance sites in Sichuan province between January 2019 and December 2021, to analyze genotypic drug resistance and genetic diversity. Moreover, we performed statistical analyses of the epidemiological characteristics and risk factors associated with the transmission dynamics of MDR/RR-TB. Results The final analysis included 278 MDR/RR TB strains. Lineage 2.2, the major sub-lineage, accounted for 82.01% (228/278) of isolates, followed by lineage 4.5 (9.72%, 27/278), lineage 4.4 (6.83%, 19/278), and lineage 4.2 (1.44%, 4/278). The drug resistance rates, ranging from high to low, were as follows: isoniazid (229 [82.37%]), streptomycin (177 [63.67%]), ethambutol (144 [51.80%]), pyrazinamide (PZA, 119 [42.81%]), fluoroquinolones (FQs, 93 [33.45%]). Further, the clofazimine, bedaquiline, and delamanid resistance rates were 2.88, 2.88, and 1.04%, respectively. The gene composition cluster rate was 32.37% (90/278). In addition, 83.81% (233/278) of MDR/RR-TB cases were determined to be likely caused by transmission. Finally, patients infected with lineage two strains and strains with the KatG S315T amino acid substitution presented a higher risk of MDR/RR-TB transmission. Conclusion Transmission plays a significant role in the MDR/RR-TB burden in Sichuan province, and lineage 2 strains and strains harboring KatG S315T have a high probability of transmission. Further, high levels of FQ and PZA drug resistance suggest an urgent need for drug susceptibility testing prior to designing therapeutic regimens. New anti-TB drugs need to be used standardly and TB strains should be regularly monitored for resistance to these drugs.

This study investigated drug-resistant tuberculosis (DR-TB) in the Yi ethnic group. The study was designed to identify risk factors for DR-TB and its relationship with HIV/AIDS. To establish the resistance to antituberculosis drugs, whole-genome sequencing (WGS) was performed using culture-positive Mycobacterium tuberculosis samples collected from people of the Yi ethnic group from March 2019 to March 2021. Baseline characteristics were obtained from China’s tuberculosis surveillance system. A total of 116 M. tuberculosis strains were included in the final analysis. Lineage 2.2 (75.86%) was the dominant sublineage, followed by lineage 4.5 (18.97%) and lineage 4.4 (5.17%). The rates of rifampicin-resistant (RR-TB), multidrug-resistant (MDR-TB), and preextensively drug-resistant TB (pre-XDR-TB) were 18.97%, 10.34%, and 6.03%, respectively. Drug-resistant strains were not found in the elderly (age≥65 years). The proportions of RR/MDR-TB and pre-XDR-TB cases among re-treatment patients were higher than those among new patients (χ2=12.155, P=0.003; χ2=22.495, P=0.001, respectively). The pre-XDR-TB case proportions were higher among female patients than among males and higher among referred patients (χ2=5.456, P=0.032; χ2=15.134, P=0.002, respectively). The rates of RR/MDR-TB and pre-XDR-TB did not differ appreciably among groups with different HIV infection statuses nor lineage populations. DR-TB poses a serious challenge to the Yi ethnic group. Re-treatment patients, women, and referred patients were at high risk of MDR/RR-TB or pre-XDR-TB while HIV and lineage 2 had negligible association with drug resistance. Whole-genome sequencing should be used to guide the design of treatment regimens and to tailor public interventions.

Background The disease burden caused by pulmonary tuberculosis (TB) in Sichuan province still persisted at a high level, and large spatial variances were presented across regional distribution disparities. The socio-economic factors were suspected to affect the population of TB notification, we aimed to describe TB case notification rate (CNR) and identify which factors influence TB epidemic are necessary for the prevention and control of the disease in Sichuan province. Methods A retrospective cross-sectional study and an ecological spatial analysis was conducted to quantify the presence and location of spatial clusters of TB by the Moran’s I index and examined these patterns with socio-economic risk factors by hierarchical Bayesian spatio-temporal model. Results A total of 630,009 pulmonary TB cases were notified from 2006 to 2015 in 181 counties of Sichuan province. The CNR decreased year by year since 2007, from 88.70 to 61.37 per 100,000 persons. The spatial heterogeneities of CNR were observed during the study periods. Global Moran’s I index varied from 0.23 to 0.44 with all P -value < 0.001. The Bayesian spatio-temporal model with parametric spatio-temporal interactions was chosen as the best model according to the minimum of Deviance Information Criterion ( DIC )(19,379.01), and in which the quadratic form of time was taken. The proportion of age group and education year were all associated with CNR after adjusting the spatial effect, temporal effect and spatio-temporal interactions. TB CNR increased by 10.2% [95% credible interval ( CI ): 6.7–13.7%] for every 1-standard-deviation increase in proportion of age group and decreased by 23% (95% CI : 13.7–32.7%) for every 1-standard-deviation increase in education year. Conclusions There were spatial clusters of TB notification rate in Sichuan province from 2006 to 2015, and heavy TB burden was mainly attributed to aging and low socioeconomic status including poor education. Thus, it is more important to pay more attention to the elderly population and improve socioeconomic status including promoting education level in Sichuan province to reduce the TB burden.

IntroductionAs China is scaling up tuberculosis preventive therapy (TPT) for people living with HIV (PLHIV) in its national programmes, the objective of this study was to evaluate the feasibility and performance of 6-month regimen of isoniazid monotherapy (6H) in terms of preventive therapy acceptance, adherence, effectiveness and outcomes in minority areas with a high burden of tuberculosis (TB) and HIV/AIDS.MethodA prospective observational cohort study was initiated among 461 PLHIV in Butuo County after ruling out active TB (ATB) and followed up for up to 3 years to collect incidence events in real-world settings. TB incidence and protective rates were calculated. The risk factors related to acceptance and adherence were identified using a logistic regression model.ResultsOf the 688 PLHIV screened for TB, 115 (16.72 %) had ATB. Among the 461 participants eligible for 6H, 392 (85.03%) initiated 6H, and 277 (70.67%) completed the therapy. In total, 15 were identified as having ATB during follow-up. The incidence of ATB in the complete group was 0.62/100 person years (95% CI 0.20 to 1.45) as compared with the incomplete group 2.96/100 person years (95% CI 1.36 to 5.63) (p=0.005), and the protective rate of 6H was 79.05%. The protection rate between the complete and incomplete and refusal groups was 69.31%. In total, 142 (36.22%) patients experienced adverse drug reactions during isoniazid preventive therapy. The logistic regression model revealed several factors associated with 6H acceptance: first CD4+ T lymphocyte count was between 200 and 350 cells/mm3 (adjusted OR (aOR)=0.30, 95% CI 0.10 to 0.92) or>500 cells/mm3 (aOR=0.25, 95% CI 0.08 to 0.77). Factors associated with 6H adherence: 36–45 years old (aOR=2.76, 95% CI 1.49 to 5.10), middle school education (aOR=0.26, 95% CI 0.08 to 0.79) and history of prior TB (aOR=0.09, 95% CI 0.05 to 0.20).Conclusion6H can reduce the incidence of ATB in minority areas with high burdens of TB and HIV/AIDS. Periodic counselling of patients on adherence and retraining of the TPT staff are essential. Health monitoring and education for specific populations improve TPT acceptance and adherence.

To determine factors influencing the utilization and accessibility to bacteriologic-based tuberculosis (TB) diagnosis among sputum smear positive (SS+) retreatment TB patients, and to develop strategies for improving the case detection rate of MDR-TB in rural China. A cross-sectional study of SS+ TB retreatment patients was conducted in eight counties from three provinces with different implementation period and strategy of MDR-TB program in China. Demographic and socioeconomic parameters were collected by self-reporting questionnaires. Sputum samples were collected and cultured by the laboratory of county-designated TB clinics and delivered to prefectural Centers for Disease Prevention and Control (CDC) labs for DST with 4 first-line anti-TB drugs. Among the 196 SS+ retreatment patients, 61.22% received culture tests during current treatment. Patients from more developed regions (OR = 24.0 and 3.6, 95% CI: 8.6-67.3 and 1.1-11.6), with better socio-economic status (OR = 3. 8, 95% CI: 1.3-10.7), who had multiple previous anti-TB treatments (OR = 5.0, 95% CI: 1.6-15.9), and who failed in the most recent anti-TB treatment (OR = 2.6, 95% CI: 1.0-6.4) were more likely to receive culture tests. The percentage of isolates resistant to any of first-line anti-TB drugs and MDR-TB were 50.0% (95% CI: 39.8%-60.2%) and 30.4% (95% CI: 21.0%-39.8%) respectively. Retreatment SS+ TB patients, high risk MDR-TB population, had poor utilization of access to bacteriologic-based TB diagnosis, which is far from optimal. The next step of anti-TB strategy should be focused on how to make bacteriological-based diagnosis cheaper, safer and more maneuverable, and how to assure the DST-guided treatment for these high-risk TB patients.

Tuberculosis (TB) and HIV are two worldwide public health concerns. Co-infection of these two diseases has been considered to be a major obstacle for the global efforts in reaching the goals for the prevention of HIV and TB. A comprehensive cross-sectional study was conducted to recruit TB patients in three provinces (Guangxi, Henan and Sichuan) of China between April 1 and September 30, 2010. A total of 1,032 consenting TB patients attended this survey during the study period. Among the participants, 3.30% were HIV positive; about one quarter had opportunistic infections. Nearly half of the participants were 50 years or older, the majority were male and about one third were from minority ethnic groups. After adjusting for site, gender and areas of residence (using the partial/selective Model 1), former commercial plasma donors (adjusted OR [aOR] = 33.71) and injecting drug users(aOR = 15.86) were found to have significantly higher risk of being HIV-positivity. In addition, having extramarital sexual relationship (aOR = 307.16), being engaged in commercial sex (aOR = 252.37), suffering from opportunistic infections in the past six months (aOR = 2.79), losing 10% or more of the body weight in the past six months (aOR = 5.90) and having abnormal chest X-ray findings (aOR = 20.40) were all significantly associated with HIV seropositivity (each p<0.05). HIV prevalence among TB patients was high in the study areas of China. To control the dual epidemic, intervention strategies targeting socio-demographic and behavioral factors associated with higher risk of TB-HIV co-infection are urgently called for.

Global food security is a major driver of population health, and food system collapse may have complex and long-lasting effects on health outcomes. We examined the effect of prenatal exposure to the Great Chinese Famine (1958–1962)—the largest famine in human history—on pulmonary tuberculosis (PTB) across consecutive generations in a major center of ongoing transmission in China. We analyzed >1 million PTB cases diagnosed between 2005 and 2018 in Sichuan Province using age–period–cohort analysis and mixed-effects metaregression to estimate the effect of the famine on PTB risk in the directly affected birth cohort (F1) and their likely offspring (F2). The analysis was repeated on certain sexually transmitted and blood-borne infections (STBBI) to explore potential mechanisms of the intergenerational effects. A substantial burden of active PTB in the exposed F1 cohort and their offspring was attributable to the Great Chinese Famine, with more than 12,000 famine-attributable active PTB cases (>1.23% of all cases reported between 2005 and 2018). An interquartile range increase in famine intensity resulted in a 6.53% (95% confidence interval [CI]: 1.19–12.14%) increase in the ratio of observed to expected incidence rate (incidence rate ratio, IRR) in the absence of famine in F1, and an 8.32% (95% CI: 0.59–16.6%) increase in F2 IRR. Increased risk of STBBI was also observed in F2. Prenatal and early-life exposure to malnutrition may increase the risk of active PTB in the exposed generation and their offspring, with the intergenerational effect potentially due to both within-household transmission and increases in host susceptibility

Ultrafast laser processing is particularly well-suited for the processing of heterogeneous materials due to its advantages such as a wide range of materials applicability and high machining quality. However, the ablation depth has been difficult to control via the axial feed. In this situation, excessive damage and non-uniform ablation will occur in laser processing. In-situ monitoring and control of the machining process is one of the most promising methods to solve the problems. In this paper, we report an innovative method for in-situ monitoring of the interface status and ablation depth in ultra-fast laser drilling of heterogeneous materials using optical coherence tomography (OCT). Firstly, the signal analysis and processing of the interference signal are developed for extracting the depth information. And then the interface detection of the heterogeneous materials and the measurement of the corresponding thickness before the drilling are demonstrated. Finally, the in-situ monitoring of the ablation depth is achieved. This study demonstrates the feasibility of utilizing spectral-domain optical coherence tomography (SD-OCT) for interface detection and in-situ monitoring of ablation depth in ultrafast laser drilling. The findings underscore the potential of SD-OCT in optimizing and achieving precise control of manufacturing processes. Keywords: laser processing, optical coherence tomography, in-situ monitoring, interface detection