Comparison of yield and relative costs of different screening algorithms for tuberculosis in active case-finding: a cross-section study.

BACKGROUND: Part of tuberculosis (TB) patients were missed if symptomatic screening was based on the main TB likely symptoms. This study conducted to compare the yield and relative costs of different TB screening algorithms in active case-finding in the whole population in China. METHODS: The study population was screened based on the TB likely symptoms through a face-to-face interview in selected 27 communities from 10 counties of 10 provinces in China. If the individuals had any of the enhanced TB likely symptoms, both chest X-ray and sputum tests were carried out for them furtherly. We used the McNemar test to analyze the difference in TB detection among four algorithms in active case-finding. Of four algorithms, two were from WHO recommendations including 1a/1c, one from China National Tuberculosis Program, and one from this study with the enhanced TB likely symptoms. Furthermore, a two-way ANOVA analysis was performed to analyze the cost difference in the performance of active case-finding adjusted by different demographic and health characteristics among different algorithms. RESULTS: Algorithm with the enhanced TB likely symptoms defined in this study could increase the yield of TB detection in active case-finding, compared with algorithms recommended by WHO (p < 0.01, Kappa 95% CI: 0. 93-0.99) and China NTP (p = 0.03, Kappa 95% CI: 0.96-1.00). There was a significant difference in the total costs among different three algorithms WHO 1c/2/3 (F = 59.13, p < 0.01). No significant difference in the average costs for one active TB case screened and diagnosed through the process among Algorithms 1c/2/3 was evident (F = 2.78, p = 0.07). The average costs for one bacteriological positive case through algorithm WHO 1a was about two times as much as the costs for one active TB case through algorithms WHO 1c/2/3. CONCLUSIONS: Active case-finding based on the enhanced symptom screening is meaningful for TB case-finding and it could identify more active TB cases in time. The findings indicated that this enhanced screening approach cost more compared to algorithms recommend by WHO and China NTP, but the increased yield resulted in comparative costs per patient. And it cost much more that only smear/bacteriological-positive TB cases are screened in active case-finding.

Added Value of Comprehensive Program to Provide Universal Access to Care for Sputum Smear-Negative Drug-Resistant Tuberculosis, China.

The increase in drug-resistant tuberculosis in China calls for scaling up rapid diagnosis. We evaluated introduction of rapid resistance testing by line-probe assay for all patients with a diagnosis of pulmonary tuberculosis in 2 prefectures in middle and eastern China. We analyzed sputum samples for smear-positive patients and cultures for smear-negative patients. We used a before-after comparison of baseline and intervention periods (12 months each) and analyzed data for 5,222 baseline period patients and 4,364 intervention period patients. The number of patients with rifampin resistance increased from 30 in the baseline period to 97 in the intervention period for smear-positive patients and from 0 to 13 for smear-negative patients, reflecting a low proportion of positive cultures (410/2,844, 14.4%). Expanding rapid testing for drug resistance for smear-positive patients resulted in a 3-fold increase in patients with diagnoses of rifampin-resistant tuberculosis. However, testing smear-negative patients had limited added value because of a low culture-positive rate.

Functional Genetic Variants of PPARx03B3; and PPARα Encoding Peroxisome Proliferator-Activated Receptors and Susceptibility to Ischemic Stroke in Chinese Han Population.

BACKGROUND: PPARx03B3; and PPARα belong to a receptor family of ligand-activated transcription factors involved in the regulation of inflammation, cellular glucose uptake, protection against atherosclerosis and endothelial cell function. Through these effects, they might be involved with the ischemic stroke (IS). METHODS: One thousand two hundred ninety-six subjects from the Chinese Han Population were chosen to assess the nature of the functional polymorphisms of PPARs and any links with IS. Multivariate logistic regression analysis was used to examine the association between PPARx03B3; and PPARα genotypes and a diagnosis of IS. RESULTS: Pro/Ala carriage may be associated with the decreased risk of IS in Hans (OR 0.542, 95% CI 0.346-0.850). The 162Val allele frequency at the DNA-binding region of PPARα was extremely rare in Chinese Han population. CONCLUSIONS: PPARx03B3; 12Pro/Ala resulting in an amino acid exchange in N-terminal sequence may be an independent protective factor for IS in the Chinese Han population. However, more populations are warranted to validate our findings.

Spatial-temporal analysis of pulmonary tuberculosis in Hubei Province, China, 2011-2021.

BACKGROUND: Pulmonary tuberculosis (PTB) is an infectious disease of major public health problem, China is one of the PTB high burden counties in the word. Hubei is one of the provinces having the highest notification rate of tuberculosis in China. This study analyzed the temporal and spatial distribution characteristics of PTB in Hubei province for targeted intervention on TB epidemics. METHODS: The data on PTB cases were extracted from the National Tuberculosis Information Management System correspond to population in 103 counties of Hubei Province from 2011 to 2021. The effect of PTB control was measured by variation trend of bacteriologically confirmed PTB notification rate and total PTB notification rate. Time series, spatial autonomic correlation and spatial-temporal scanning methods were used to identify the temporal trends and spatial patterns at county level of Hubei. RESULTS: A total of 436,955 cases were included in this study. The total PTB notification rate decreased significantly from 81.66 per 100,000 population in 2011 to 52.25 per 100,000 population in 2021. The peak of PTB notification occurred in late spring and early summer annually. This disease was spatially clustering with Global Moran's I values ranged from 0.34 to 0.63 (P< 0.01). Local spatial autocorrelation analysis indicated that the hot spots are mainly distributed in the southwest and southeast of Hubei Province. Using the SaTScan 10.0.2 software, results from the staged spatial-temporal analysis identified sixteen clusters. CONCLUSIONS: This study identified seasonal patterns and spatial-temporal clusters of PTB cases in Hubei province. High-risk areas in southwestern Hubei still exist, and need to focus on and take targeted control and prevention measures.

Digitizing tuberculosis treatment monitoring in Wuhan city, China, 2020-2021: Impact on medication adherence.

Introduction: Digital technologies can improve adherence to tuberculosis (TB) treatment. We studied the impact of digitizing TB treatment monitoring on adherence among TB patients in Wuhan, China, during 2020-2021. Methods: We compared an electronic system introduced to monitor TB medication adherence (e-Patient Service System; e-PSS) with the p paper-based standard of care (TB Control Information System; TCIS) in terms of prescribed TB treatment doses taken by patients and patient outcome after six months of follow up. We designed a cross sectional study using retrospective data for all drug susceptible pulmonary TB patients recorded on both systems. The main indicators were: compliant first follow up visit (within 3 days of start of treatment); medication adherence (80% or more of monthly doses taken); and end of treatment success ratio. Results: A total of 1,576 TB patients were recorded in TCIS in July September, 2020 and 1,145 TB cases were included in e-PSS in January March, 2021. The distribution of patient demographic and clinical features was similar between the two groups. A larger proportion from the e-PSS group visited the community doctor in the first three days compared with the TCIS group (48.91 versus 29. 76 % respectively). Medication adherence was also higher in the e-PSS group during the 6 months of treatment than in the TCIS group (84. 28 versus 80.3 3 % respectively). Treatment success was 92.52% in the e-PSS group and 92.07% in the TCIS group. Multivariate logistic regress ion analysis demonstrated that adjusted odds ratios for compliant first follow up visit, medication adherence and favorable treatment outcome in the e-PSS versus TCIS groups were 2.94 (95% 2.47 3.50), 1.33 (95% 1.08 1.63), and 1. 12 (95% CL: 0.79 1.57) respectively. Discussion: This study revealed improvements in TB care following an intervention to monitor treatment digitally in patients in Wuhan, China.

Corrigendum: Digitizing tuberculosis treatment monitoring in Wuhan city, China, 2020-2021: Impact on medication adherence.

[This corrects the article DOI: 10.3389/fpubh.2023.1033532.].

The Potential Role of Vitamin D in the Development of Tuberculosis in Chinese Han Population: One Case-Control Study.

Background and aims: Spinal serum 25-hydroxyvitamin D [25[OH]D] status plays an important role in mediating innate immune responses by acting as a cofactor for induction of antimycobacterial activity and is thus involved in the development of Tuberculosis (TB). Results reported regarding the association of vitamin D with TB remained controversial. We aimed to identify any common association between 25[OH]D status and TB in the Chinese Han population. Methods: 280 subjects (70 TB patients and 210 matched controls) were recruited. TB cases were diagnosed based on the presence of acid-fast bacilli on smears from sputum and MTB isolation. Healthy controls were randomly selected from four local community-based populations. 25[OH]D was detected by electrochemiluminescence immunoassay (ECLIA) on Roche Elecsys before the initial treatment. Multivariable logistic regression analysis was used to examine the association of Vitamin D with TB. Results: There was no significant difference in the serum vitamin D level between total cases and controls, but we found a strong tendency toward a higher serum vitamin D level in male population (P < 0.05) with TB but not in females. High serum vitamin D increased the risk of TB in the Chinese Han population (OR = 1.035, 95%CI: 1.001-1.070, P < 0.05). The serum vitamin D level was significantly decreased with age increasing in cases and controls (all P < 0.001). Conclusions: High serum vitamin D may be an independent risk factor for TB in the Chinese Han population.

Prevalence, Incidence, and Characteristics of Tuberculosis Among Known Diabetes Patients - A Prospective Cohort Study in 10 Sites, 2013-2015.

What is already known about this topic?: The association of diabetes mellitus (DM) with both increased risk of tuberculosis (TB) and unfavorable treatment outcomes has been identified by many studies (1). However, epidemic data for TB cases in DM patients is absent in China. What is added by this report?: This current population-based prospective cohort study, conducted in ten counties located in eastern, central, and western China during 2013-2015, revealed a high prevalence and incidence of TB in known DM patients. Most TB cases were captured by active case-finding and a much higher presence of being asymptomatic among TB/DM patients was obtained. What are the implications for public health practice?: Active case-finding should be carried out in DM patients and populations at high risk for developing TB. A TB symptom screening-based case-finding strategy is not enough; chest radiography check should be done once a year for these patients.

A Tuberculosis Outbreak During the COVID-19 Pandemic - Hubei Province, China, 2020.

What is already known about topic? Multidrug-resistant tuberculosis (MDR-TB) has become a growing threat to public health. There were few reports about family-to-school MDR-TB outbreaks in China, especially during the coronavirus disease 2019 (COVID-19) pandemic. What is added by this report? A tuberculosis (TB) outbreak happened in Hubei Province during the COVID-19 pandemic. The transmission chain was probably from a father （MDR-TB case）with retreated TB history to his daughter, who then spread TB to her classmates. What are the implications for public health practice? We should enhance TB control both in schools and households, including strengthening TB/MDR-TB detection, health education, and ventilation. The TB contact screening cannot only be limited to outside school settings and should be conducted in the school when a TB student is absent from school for 2 or 3 months, or even longer especially during the COVID-19 pandemic.

Incidence and risk factors of tuberculosis among the elderly population in China: a prospective cohort study.

BACKGROUND: China is facing challenges of the shifting presentation of tuberculosis (TB) from younger to elderly due to an ageing population, longer life expectancy and reactivation disease. However, the burden of elderly TB and influence factors are not yet clear. To fill the gap, we generated a cohort study to measure the magnitude of TB incidence and associated factors among the elderly population aged 65 years and above in China. METHODS: In this cohort established in 2013 through a prevalence survey conducted in selected sites, a total of 34 076 elderlies without TB were enrolled into two-year follow-up. We used both active and passive case findings to find out all TB patients among them. The person-year (PY) incidence rates for both bacteriologically positive TB and active TB were calculated. Cox proportional regression model was performed to test effect of risk factors, and the population attributable fraction (PAF) of each risk factor contributing to incident TB among elderlies was calculated. RESULTS: Over the two-year follow-up period, a total of 215 incident active TB were identified, 62 of which were bacteriologically positive. The incidence rates for active TB and bacteriologically positive TB were 481.8 per 100 000 PY (95% CI: 417.4-546.2 per 100 000 PY) and 138.9 per 100 000 PY (95% CI: 104.4-173.5 per 100 000 PY), respectively. Incident cases detected by active case finding were significantly higher (P < 0.001). Male, non-Han nationality, previously treated TB, ex/current smoker and body mass index (BMI) < 18.5 presented as independent predictors for developing TB disease. For developing bacteriologically positive TB, the biggest contribution was from self-reported ex or current smoker (18.06%). And, for developing active TB, the biggest contribution was from non-Han nationality (35.40%), followed by male (26.80%) and age at 75 years and above (10.85%). CONCLUSIONS: Ageing population in China had a high TB incidence rate and risk to develop TB disease, implying that National TB Program (NTP) needs to prioritize for elderly. Active case finding should be applied capture more active TB cases among this particular population, especially for male, non-Han nationality, and those with identified risk factors.

An Outbreak of Multidrug-Resistant Tuberculosis in a Secondary School - Hubei Province, 2019.

What is already known about this topic? Multidrug-resistant tuberculosis (MDR-TB) is a type of tuberculosis with resistance to common treatments such as isoniazid and rifampicin. MDR-TB is a major global health challenge and needs to be controlled tightly through prevention measures, early diagnosis, and full treatment and management. What is added by this report? This outbreak was the first MDR-TB related public health emergency in Hubei Province. In total, five MDR-TB cases and nine clinically diagnosed cases were identified within one class in a secondary school. Students and teachers from other classes were monitored, but no other cases were found. What are the implications for public health practice? The implementation of TB prevention and control measures in schools is important to increase knowledge on TB and to raise awareness on protecting personal wellbeing. The Automatic Early Warning Information System alerted the local health department and allowed for a timely response to prevent further disease spread.

Determinants of Health Care-Seeking Delay among Tuberculosis Patients in Rural Area of Central China.

Background The prevalence of tuberculosis (TB) in low and middle-income countries is a significant public health and social concern. TB is a common infectious disease caused by the Mycobacterium tuberculosis infection, which has a widespread infection rate. Health care-seeking delay maybe one of the most important neglected risk factors for the spread of TB. Objectives The aim of this study was to understand the situation of health care-seeking delay among rural tuberculosis patients in Hubei Province, and explore its risk factors. Methods A total of 1408 rural tuberculosis patients were surveyed using a standard structured questionnaire in three cities of Hubei Province during the past two years. Results For the 1408cases of pulmonary tuberculosis, 39.70% of them were health care-seeking delayed. Logistic regressions indicate that the Han nationality, farming careers, the over 45 min walk to the township's hospital, and awareness of the national TB free treatment policy, were significantly associated with higher odds of a delay in care seeking. Conclusions The prevalence of health care-seeking delay among tuberculosis patients was high in rural areas. It is essential to take comprehensive targeted interventions to reduce care-seeking delay.

The impact of the new cooperative medical scheme on financial burden of tuberculosis patients: evidence from six counties in China.

BACKGROUND: Tuberculosis (TB) patients in China encounter heavy financial burdens throughout the course of their treatment and it is unclear how China's health insurance systems affect the alleviation of this burden under the integrated approach. This study aimed to measure reimbursement for TB services under the New Cooperative Medical Scheme (NCMS) in rural China and to evaluate changes in catastrophic health expenditure (CHE) caused by the reimbursement policies. METHODS: Reimbursement data were obtained from routine data systems for the NCMS in Yichang (YC) and Hanzhong (HZ). 1884 TB inpatients reimbursed by NCMS from 2010 to 2012 were included. Household surveys were conducted. A total of 494 TB patients under the NCMS were selected in this paper. 12 Focus Group Discussions (FGDs) were held. We measured the impact of the NCMS by counterfactual analysis, which analyzed the financial burden alleviation. Equity was assessed by Concentration Index (CI), and disaggregated by project sites. RESULTS: TB inpatients were reimbursed with an effective reimbursement rate of 57.3 %. Average out-of-pocket (OOP) payments for outpatient and inpatient services after diagnosis were 1413 yuan and 430 yuan, and 3572 yuan and 3013 yuan in YC and HZ, respectively. The reimbursement level for TB outpatient care after diagnosis was very low due to a limited outpatient quota. TB patients in HZ incurred higher effective reimbursement rates, but the incidence of CHE remained higher. The reduction of CHE incidence after the NCMS showed no difference statistically (P > 0.05). The severity of CHE was alleviated slightly. CIs after reimbursement were all below zero and their absolute values were higher than those before reimbursement. CONCLUSIONS: Low reimbursement for TB patients could lead to heavy financial burden. Poor TB patients incurred high rates of CHE. The NCMS was found to be a protective factor for CHE, but the impact was modest and the equity of CHE did not improve. The NCMS reimbursement policies should be improved in the future to include a more comprehensive coverage of care. Supplemental programs may be necessary to expand coverage for TB care.

Association of functional genetic variants in PPARδ encoding peroxisome proliferator-activated receptor delta with ischemic stroke in Chinese Uyghur population.

PPARδ belongs to a receptor family of ligand-activated transcription factors involved in the regulation of inflammation, cellular glucose uptake, protection against atherosclerosis and endothelial cell function. Through these effects, they might be involved with the ischemic stroke (IS). We recruited 200 subjects (100 IS patients diagnosed by CTs or/and magnetic resonance imaging (MRI) and 100 normal healthy controls from Chinese Uyghur population) to assess the nature of the functional polymorphisms of PPARδ +294T/C and any links with IS in this unique population. We found that the C allele of the PPARδ +294T/C polymorphism was more common in controls than IS subjects in the Uyghur population. C allele carriage may be associated with an increased risk of IS in Uyghurs with a strong trend (OR 1.79, 95% CI: 1.11-2.89). Additionally, the PPARδ CC and TC genotypes were less frequent in Uyghur population than in Han population. Our population and ethnic-based study demonstrates that the PPARδ +294C allele maybe an independent risk of IS in Chinese Uyghurs especially in the male (OR 1.99, 95%CI:1.06-3.72) and obesity populations (OR 2.36, 95%CI: 1.19-4.67), which were consistent with Tunisian Population. Moreover, total cholesterol, fasting blood glucose, waist-to-hip ratio, hypertension, history of heart diseases, and negative events may increase the risk of IS, with a trend for HDL to be a protective factor for IS in the Uyghur population. However, larger populations are warranted to validate our findings.

The NLRP3 inflammasome and stroke.

Inflammasome pattern recognition receptors, which belong to the family of multi-meric proteins, play an important role in innate immunity, including NLRPs, NLRC, and NAIP. Among these receptors, NLRP3 (nucleotide-binding domain (NOD)-like receptor protein 3) inflammasome may activate the inflammation and participate in atherosclerosis, pathophysiology of myocardial infarction, resultin ischemia/reperfusion injury and stroke and other cardiovascular diseases. Effective regulation of NLRP3 may help prevent or even treat stroke. In recent years, the role of inflammation in stroke has attracted much attention, and the in-depth study of its mechanism of action is gradually clear. This mini-review focuses on the association of regulatory mechanisms of NLRP3 inflammasome with the development of stroke, which may supply some clues for future therapies and novel drug targets for stroke.

A tailed primers protocol to identify the association of eNOS gene variable number of tandem repeats polymorphism with ischemic stroke in Chinese Han population by capillary electrophoresis.

Endothelial nitric oxide synthase (eNOS) plays an important role in mediating endothelium-dependent vasodilatation and antithrombotic action and is thus involved in the development of ischemic stroke (IS). Controversial results regarding the association of eNOS gene variable number of tandem repeats (VNTR) polymorphism with IS have been reported by conventional PCR-polyacrylamide gel electrophoresis methods. We aimed to identify any common association of eNOS gene VNTR polymorphism with IS in Chinese Han population by capillary electrophoresis (CE). The VNTR polymorphism of 27 bp within the eNOS intron-4 was determined by CE with specially designed tailed primers in Chinese Han patients with IS (n=457) and matched elderly controls without IS (n=457). Significant differences in BMI, WHR, hypertension, diabetes, smoking, TG, HDL, LDL, LDL, and FBG were observed between cases and controls. The distributions of eNOS VNTR polymorphism were not significantly associated with IS after adjustment for cardiovascular risk factors (OR=1.18, 95% CI: 0.82-1.69). This finding was consistent with the further meta-analysis in Asians. The meta-analysis in Americans demonstrated that 4a/4b+4a/4a genotype was significantly associated with IS risk with an OR of 1.54 (95% CI, 1.09-2.17) compared with the 4b/4b genotype. Our data suggests that BMI, WHR, hypertension, diabetes, smoking, TG, LDL, and FBG may increase the risk of IS. However, eNOS VNTR polymorphism may be not an independent major contributor for IS in Chinese Han population. The VNTR polymorphism might be associated with IS in Americans based on meta-analysis.

Lack of association between two key SNPs on chromosome 12p13 and ischemic stroke in Chinese Uyghur population.

Recent genome-wide association studies (GWAS) have identified two key SNPs (rs11833579 and rs12425791) on chromosome 12p13 that were significantly associated with stroke in Caucasians. However, the validity of the association has remained controversial. We performed genetic association analyses in a very unique population which has 60% European ancestry and 40% East Asian ancestry. No significant association between these two SNPs and ischemic stroke was detected in this Chinese Uyghur population.