Challenge of ending TB in China: tuberculosis control in primary healthcare sectors under integrated TB control model-a systematic review and meta-analysis.

BACKGROUND: China has the third-largest burden of tuberculosis (TB) cases in the world with great challenges towards ending TB. Primary health care (PHC) sectors play a critical role in TB prevention and control in communities under the Chinese integrated TB control model. However, there is a lack of comprehensive review of research evidence on TB control in PHC sectors under the integrated TB control model in China. METHODS: This review was conducted following the PRISMA guidelines. Articles published from 2012 to January 2022 were searched from four international and three Chinese databases. Studies conducted inside mainland China and relevant with TB control service in PHC sectors under the integrated model were included. After study selection, data extraction, and quality assessment, the meta-analysis was performed with RevMan using a random-effect model.When I2 was more than 50%, subgroup analysis was performed to explore possible reasons for heterogeneity. We also conducted a post hoc sensitivity analysis for outcomes after meta-analysis by exclusion of studies with a high risk of bias or classified as low quality. RESULTS: Forty-three studies from 16 provinces/municipalities in China were included in this review, and most studies included were of medium quality. PHC sectors in East China delivered TB control service better overall than that in West China, especially in tracing of patients and TB case management (TCM). In meta-analyses, both the pooled arrival rate of tracing and pooled TCM rate in East China were higher than those in West China. TB patients had a low degree of willingness to receive TCM provided by healthcare workers in PHC sectors nationwide, especially among migrant TB patients. There were 9 studies reporting factors related to TB control service in PHC sectors, 6 (2 in East and 4 in West China) of which indentified several characteristics of patients as associated factors. The context of PHC sectors was demonstrated to influence delivery of TB control service in PHC sectors in 5 studies (3 in East, 1 in Middle and 1 in West China). Most studies on strategies to promoting TB control services in PHC sectors were conducted in East China and some of these studies identified several online and offline interventions and strategies improving patients' treatment compliance [pooled OR (95% CI): 7.81 (3.08, 19.19] and awareness of TB [pooled OR (95% CI): 6.86 (2.16, 21.72)]. CONCLUSION: It is of urgent need to improve TB control in PHC sector in China, particularly in West China. Formative and implementation research with rigorous design are necessary to develop comprehensive, context-specific, and patient-centered TB control strategies to promote ending TB in China.

[Tobacco and tuberculosis: the nature of the links and the consequences of this association]. / Tabac et tuberculose : nature des liens et conséquences de cette association.

Tuberculosis and smoking are responsible for significant mortality worldwide. Smoking is spreading in emerging countries, and its prevalence is high in developed countries among socially disadvantaged populations; it could be the source of a resurgence of tuberculosis in future years. The aim of this review is to clarify the consequences of the association between smoking and tuberculosis, and the benefits of smoking cessation for smokers with tuberculosis.

Diagnostic delay, treatment duration and outcomes since the implementation of integrated model of tuberculosis control and their associated factors in a county in East China.

OBJECTIVE: This study assesses the diagnostic delay, treatment duration and treatment outcomes of tuberculosis (TB) patients since the implementation of the integrated model of TB control in a county in eastern China. It further identifies factors associated with diagnostic delay and treatment duration in the integrated model. METHODS: We collected data through the Chinese Tuberculosis Information Management System (TBIMS) for Cangnan County in Zhejiang Province. Chi-square and Mann-Whitney tests were adopted to identify factors associated with duration of treatment and treatment delay for TB patients within the integrated model. Multiple regression analysis was subsequently performed to confirm the identified factors. RESULTS: In the integrated model from 2012 to 2018, the median health system delay was maintained at 1 day, and the median patient delay decreased from 14 to 9 days and the median total delay decreased from 15 to 11 days. In addition, the proportion of patients who experienced patient delay > 14 days and total delay > 28 days decreased from 49% to 35% and from 32% to 29% respectively. However, the proportion of patients who had health system delay > 14 days increased from 0.2% to 13% from 2012 to 2018. The median treatment duration increased from 199 to 366 days and the number of TB patients lost to follow-up showed an overall upward trend from 2012 to 2018. The multivariable regression analysis indicated that migrant TB patients and TB patients initially diagnosed in hospitals at the prefectural level and above tended to experience total delay > 28 days (p < 0.001). Linear regression analysis confirmed that new TB patients>60 years tended to have longer treatment duration (p < 0.05). CONCLUSIONS: While our study may suggest the potential of the integrated model in early detection and diagnosis of TB, it also suggests the importance of strengthening supervision and management of designated hospitals to optimize the treatment duration and improve retention of patients in TB care. Enhancing health education for TB patients, especially amongst migrant patients, and training in TB identification and referral for non-TB doctors are also key for early TB detection and diagnosis in the integrated model.

Drug resistance patterns, treatment outcomes and factors affecting unfavourable treatment outcomes among extensively drug resistant tuberculosis patients in Pakistan; a multicentre record review.

Background: Extensively drug resistant tuberculosis (XDR-TB) is considered as a major threat to global health. This study aimed to analyse the treatment outcomes and identify the factors significantly associated with unfavourable treatment outcomes among XDR-TB patients. Methods: We conducted a retrospective observational study at 10 Programmatic Management Units of the National Tuberculosis Control Program of Pakistan. The Electronic Nominal Recording Reporting System records were used to collect data of all eligible XDR-TB patients registered at the study sites between March 2012 and August 2018. Treatment outcomes were analysed as per the standard criteria. Factors associated with unfavourable treatment outcomes were analysed by using multivariate binary logistic regression analysis. Results: Out of the total 184 patients, 59 (32.1%) completed their treatment successfully. Whereby, 83 patients (45.1%) died, 24 (13%) had treatment failure, and 11 (6%) were lost to follow-up. Treatment outcomes were not evaluated in 7 (3.8%) patients. Factors significantly associated with unfavourable treatment outcomes included; conventional therapy with bedaquiline, unfavourable interim treatment outcomes and occurrence of adverse drug events (negative association). Conclusion: Treatment success rate in the study cohort was sub-optimal (i.e., <75%). The poor success rate and high mortality are concerning, and requires immediate attention of the program managers and clinicians.

Diagnostic and treatment delay among new pulmonary tuberculosis patients in Southern India: A cross-sectional study.

Background: Delay in diagnosis and treatment enhances tuberculosis (TB) transmission and mortality. Understanding causes for delay can help in TB elimination by 2025, the stated goal of India. Objectives: Estimate diagnostic and treatment delay in Ernakulam district of Kerala, identify associated factors, and determine health-seeking behavior and knowledge regarding TB among new pulmonary TB patients. Materials and Methods: Community-based cross-sectional study among the new pulmonary TB patients registered under Revised National TB Control Program. Patients interviewed in-person and data collected using pretested semi-structured questionnaire. Descriptive statistics expressed as frequency, percent, interquartile range, median, and mean. The Chi-square test was used to assess statistical significance (P < 0.05) of association. Backward conditional method logistic regression done using variables with P < 0.2 in univariate analysis and adjusting for possible confounders. Results: Two hundred and twenty-nine patients interviewed and the median patient, health-care system, and treatment delay were 25 days, 22 days, and 1 day, respectively. While the patient delay (>30 days) and treatment delay (>2 days) were seen in 47.6% and 41% of patients, respectively, health-care system delay was seen in 79.9% of the patients. Choosing pharmacy for initial treatment (adjusted odds ratio [aOR] = 5.217), unskilled occupation (aOR = 3.717), female gender (aOR = 3.467), previously not heard about TB (aOR = 3.410), and lower education level (aOR = 2.774) were the independent predictors of the patient delay. Visiting two or more doctors (aOR = 5.855) and initially visiting a doctor of undergraduate qualification (aOR = 3.650) were the independent predictors of health-care system delay. The diagnosis in private sector (aOR = 8.989), not being admitted (aOR = 3.441), and age above 60 years (aOR = 0.394) was the independent predictors of treatment delay. Conclusion: Initial treatment from pharmacy, consulting multiple physicians, and diagnosis by private sector cause significant delay in diagnosis and treatment of pulmonary TB.

Tuberculosis screening costs and cost-effectiveness in high-risk groups: a systematic review.

BACKGROUND: Systematic screening for active tuberculosis (TB) is a strategy which requires the health system to seek out individuals, rather than waiting for individuals to self-present with symptoms (i.e., passive case finding). Our review aimed to summarize the current economic evidence and understand the costs and cost-effectiveness of systematic screening approaches among high-risk groups and settings. METHODS: We conducted a systematic review on economic evaluations of screening for TB disease targeting persons with clinical and/or structural risk factors, such as persons living with HIV (PLHIV) or persons experiencing homelessness. We searched three databases for studies published between January 1, 2010 and February 1, 2020. Studies were included if they reported cost and a key outcome measure. Owing to considerable heterogeneity in settings and type of screening strategy, we synthesized data descriptively. RESULTS: A total of 27 articles were included in our review; 19/27 (70%) took place in high TB burden countries. Seventeen studies took place among persons with clinical risk factors, including 14 among PLHIV, while 13 studies were among persons with structural risk factors. Nine studies reported incremental cost-effectiveness ratios (ICERs) ranging from US$51 to $1980 per disability-adjusted life year (DALY) averted. Screening was most cost-effective among PLHIV. Among persons with clinical and structural risk factors there was limited evidence, but screening was generally not shown to be cost-effective. CONCLUSIONS: Studies showed that screening is most likely to be cost-effective in a high TB prevalence population. Our review highlights that to reach the "missing millions" TB programmes should focus on simple, cheaper initial screening tools (i.e., symptom screen and CXR) followed by molecular diagnostic tools (i.e., Xpert®) among the highest risk groups in the local setting (i.e., PLHIV, urban slums). Programmatic costs greatly impact cost-effectiveness thus future research should provide both fixed and variable costs of screening interventions to improve comparability.

Delayed diagnosis of active pulmonary tuberculosis - potential risk factors for patient and healthcare delays in Portugal.

BACKGROUND: Early diagnosis and treatment of pulmonary tuberculosis (PTB) is essential for an effective control of the tuberculosis (TB) epidemic. Delayed diagnosis and treatment of TB increases the chance of complications and mortality for the patients, and enhances TB transmission in the population. Therefore, the aim of this study was to characterize patient, healthcare and total delay in diagnosing PTB and assess the effect of clinical and sociodemographic factors on the time until first contact with healthcare or reaching a PTB diagnosis. METHODS: Retrospective cohort study that included active PTB patients notified in the National Tuberculosis Surveillance System (SVIG-TB), between 2008 and 2017. Descriptive statistics, Kaplan-Meier estimates, logrank test and Cox proportional hazards model were used to characterize patient, healthcare and total delay and estimate the effect of clinical and sociodemographic variables on these delays. Significance level was set at 0.05. RESULTS: Median patient, healthcare and total delays was 37 days (Interquartile range (IQR): 19-71), 8 days (IQR: 1-32) and 62 days (IQR: 38-102), respectively. The median patient delay showed a constant increase, from 33 days in 2008 to 44 days in 2017. The median total delay presented a similar trend, increasing from 59 days in 2008 to 70 days in 2017. Healthcare delay remained constant during the study period. More than half of the PTB cases (82.9%) had a delay > 1 month between symptom onset and diagnosis. In the final Cox model, alcohol abuse, unemployment and being from a high TB incidence country were factors significantly associated with longer patient delay, while being female, having more than 45 years, oncologic and respiratory diseases were associated with longer healthcare delay. Being female, having more than 45 years and being from a high TB incidence country were associated with longer total delay. CONCLUSIONS: Patient delay and total delay have increased in recent years. Older patients, patients with alcohol problems, other comorbidities, unemployed or from countries with high TB incidence would benefit from the development of specific public health strategies that could help reduce the delay in TB diagnosis observed in our study. This study emphasizes the need to promote awareness of TB in the general population and among the healthcare community, especially at ambulatory care level, in order to reduce the gap between beginning of symptoms and TB diagnosis.

Remote Supervision of Basic Management Units for Tuberculosis Care During Covid-19 Period: An Innovative Experience from Benin Republic.

INTRODUCTION: Contingency measures taken by governments with movement restrictions during the COVID-19 pandemic may create difficulties in conducting some field activities for TB control especially the supervision of Basic Management Units (BMUs). We described in this paper an innovative initiative to conduct remote supervision (Esupervision) using Information and Communication Technology tools. SETTING AND METHOD: This initiative was conducted in Benin Republic. To carry out the activity, we used smartphone, WhatsApp® for messaging, CamScanner for scanning (both free applications); and internet connection. BMUs were asked to scan their reports and all necessary documents and sent them by WhatsApp® after scanning. On the day planned for the supervision, the supervisors of each section (clinic, laboratory, food delivery supervision) calls the BMUs health professionals via WhatsApp® video to conduct the activity according to the National Tuberculosis Programme guidelines. RESULTS: Overall, all the main objectives of a supervision were achieved despite some difficulties mainly related to the quality of internet connection. The reports from the different sections were validated for each BMU. For the laboratory activities, general aspects as well as the stock of reagents were evaluated; microcopy fields with an ordinary microscope were visualized. The management of tuberculosis patients was assessed by visualizing the results of bacteriological exams, treatment records, and stocks of medicines. CONCLUSION: Even though, this activity will probably not replace the traditional face-to-face supervision, it could be used in settings where movements are restricted for several reasons including COVID-19 pandemic, conflicts and natural disasters.

INTRODUCTION: Les mesures d'urgence prises par les gouvernements avec des restrictions de mouvements dans le cadre de la pandémie du COVID-19 peuvent créer des difficultés dans la conduite de certaines activités de terrain pour le contrôle de la tuberculose, en particulier la supervision des centres de dépistage et de traitement de la tuberculose (CDT). Nous avons décrit dans cet article, une initiative novatrice pour effectuer la supervision à distance (E-supervision) en utilisant les outils des Technologies de l'Information et de la Communication au Bénin. CADRE ET MÉTHODE: Cette initiative a été conduite en République du Bénin. Pour mener à bien cette activité, nous avons utilisé : smartphone, WhatsApp pour la messagerie et CamScanner ® pour le scannage (deux applications gratuites) ; et la connexion internet. Les agents des CDT ont été invités à envoyer tous les documents aux équipes de supervision via WhatsApp ® après les avoir scannés. Le jour prévu pour la supervision, les superviseurs de chaque section (clinique, laboratoire, gestion des vivres) ont appelé par WhatsApp ® video les acteurs des CDT pour dérouler les différentes séquences de la supervision selon les recommandations du Programme. RÉSULTATS: Dans l'ensemble, tous les principaux objectifs d'une supervision ont été atteints malgré quelques difficultés liées principalement à la qualité de la connexion internet. Les rapports des différentes sections (clinique, laboratoire et gestion des aliments) ont été validés pour chaque CDT. Pour les activités de laboratoire, l'aspect général ainsi que le stock de réactifs ont été évalués ; les champs de microcopie avec un microscope ordinaire ont été visualisés. La gestion des patients tuberculeux a été évaluée en visualisant les résultats des examens bactériologiques, les dossiers de traitement, les stocks de médicaments. CONCLUSION: Bien que cette activité ne remplacera probablement pas la supervision traditionnelle en face à face, elle pourrait être utilisée dans des contextes où les mouvements sont limités pour plusieurs raisons, notamment la pandémie COVID-19, les conflits, les catastrophes naturelles. MOTS CLÉS: Lutte contre la tuberculose, COVID-19, supervision, centres antituberculeux.

Impact of the Ebola virus disease outbreak (2014-2016) on tuberculosis surveillance activities by Guinea's National Tuberculosis Control Program: a time series analysis.

BACKGROUND: Most countries in Subsaharan Africa have well-established National Tuberculosis Control Programs with relatively stable routine performances. However, major epidemiological events may result in significant disruptions. In March 2014, the World Health Organization announced the outbreak of Ebola virus disease in Guinea, a country with a high incidence of TB and HIV. Our study aimed to assess the impact of the Ebola virus disease outbreak on TB notification, treatment, and surveillance, using main indicators. METHODS: This is a retrospective cohort study that compared TB trends using surveillance data from the periods before (2011-2013), during (2014-2016), and after (2017-2018) Ebola virus disease outbreak. A time-series analysis was conducted to investigate the linkages between the decline in TB notification and the Ebola virus disease outbreak through cross-correlation. The lag in the cross-correlation test was evaluated using ANCOVA type II delayed variable dependent model. The surveillance system was assessed using TB surveillance standards and benchmarks and vital registration systems recommended by WHO, compared with those of 2015 during the Ebola virus disease. RESULTS: The rate of reporting of TB declined from 120 cases per 100,000 in 2011 to 100 cases per 100,000 in 2014, at the peak of the Ebola virus disease outbreak. The time-series cross-correlation test of all notified cases of TB and Ebola showed a significant lag of - 0.4 (40%), reflecting a drop in the rate of notification (F-value = 5.7 [95% CI: 0.2-21.3]). The Ebola virus disease had no negative impact on patient treatment outcomes (F-value = 1.3 [95% CI: 0.0-8.8]). Regarding the surveillance system, five out of 13 WHO standards and benchmarks were met following their evaluation in 2019, after the Ebola virus disease outbreak, compared to three in 2015. CONCLUSION: Major epidemics such as the Ebola virus disease outbreak may have a significant impact on well-established TB control programs as shown in the example of Guinea. Sudden disruptions of routine performance may lead programs to improve their surveillance system. The experience acquired in the fight against EVD and the investments made should make it possible to prepare the health system in a coherent manner for the other probable episodes.

Determination of related factors about diagnostic and treatment delays in patients with smear-positive pulmonary tuberculosis in Turkey

Background/aim: This study aimed to analyze delays in diagnosis and treatment by defining the related demographic and clinical factors, to reveal obstacles, and to develop essential attempts to help reduce treatment delays. Materials and methods: We created a questionnaire on the subject of delays in diagnosis and treatment in tuberculosis (TB) control to be administered to the patients. The forms were distributed to dispensaries across the country by the General Directorate of Public Health via an official letter. Results: The study included 853 new patients with smear-positive pulmonary TB. The mean patient delay was 18.06 ± 22.27 days, the mean diagnosis delay was 35.63 ± 34.86 days, and the mean treatment delay was 0.90 ± 2.39 days. We found no association between sex, age, literacy, residential location, the presence of chronic respiratory diseases, and patient delay. It was determined that patient delay was shorter for patients with hemoptysis, fever, dyspnoea, and chest pain. In women, the diagnosis delay was longer than in men. Conclusion: In the diagnosis process of patients with tuberculosis, it was determined that there was an improvement in the patient delay; however, the improvement in the diagnosis delay was still not acceptable as an ideal duration.

Health technology assessment of fixed-dose combination regimen in treatment of newly diagnosed smear-positive pulmonary tuberculosis: A meta-analysis.

BACKGROUND: Evidence-based policy decision-making is introduction of newer technology that it is 'not inferior' to existing technology. Multiple randomised clinical trials (RCTs) on tuberculosis (TB) treatment have shown mixture of favourable, unfavourable and non-significant changes in outcomes with the use of fixed-dose combination (FDC) regimens. The aim of this study was to assess clinical effectiveness of FDC regimen as compared to the use of separate drugs in anti-TB treatment. METHODS: Systematic literature search was carried out. RCTs with newly diagnosed smear-positive pulmonary TB cases were included. Defined outcomes were smear conversion, relapse, adverse reactions and patient compliance. RESULTS: Initial search revealed 457 articles, out of which 7 were included for meta-analysis. Pooled risk ratio for smear conversion rate at the end of intensive phase was 1.01 (95% confidence interval [CI], 0.99-1.03; p = 0.40). Similarly, smear conversion rate at the end of treatment showed no significant difference (relative risk (RR) = 1.01; 95% CI, 0.99-1.02; p = 0.45). Pooled risk ratio for combined smear conversion rates was 1.01 (95% CI, 0.99-1.02). However, relapse rates showed marginally higher trend with FDC regimens (RR, 1.56; 95% CI, 0.95-2.56; p = 0.49). Pooled analysis for adverse events showed no significant difference (RR = 0.98; 95% CI, 0.86-1.11; p = 0.70). Analysis of patient compliance showed marginal increase among FDC group (RR = 1.02; 95% CI, 0.96-1.09; p = 0.47)). CONCLUSION: Fixed-dose combination (FDC) formulations are not inferior in treatment outcomes. It may also ease programme managers and patients by improving compliance. However, increase in relapse rates needs further evaluation through large multicentric studies before implementing policy change in the national programme.

Anti-tuberculosis drug concentrations in tuberculosis patients with and without diabetes mellitus.

PURPOSE: The aim of the study was to compare plasma concentrations of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) between tuberculosis (TB) patients with and without diabetes mellitus (DM). METHODS: Two-hour post-dosing concentrations of RMP, INH and PZA were determined in adult TB patients that were studied with (n = 452) and without DM (n = 1460), treated with a thrice-weekly regimen in India. Drug concentrations were estimated by HPLC. RESULTS: The median (IQR) INH [6.6 (3.9-10.0) and 7.8 (4.6-11.3)] and PZA [31.0 (22.3-38.0) and 34.1 (24.6-42.7)] microgram per milliliter concentrations were significantly lower in diabetic than non-diabetic TB patients (p < 0.001 for both drugs). Blood glucose was negatively correlated with plasma INH (r = -0.09, p < 0.001) and PZA (r = -0.092, p < 0.001). Multiple linear regression analysis showed RMP, INH and PZA concentrations were influenced by age and drug doses, INH and PZA by DM, RMP by alcohol use and PZA by gender and category of ATT. DM reduced INH and PZA concentrations by 0.8 and 3.0 µg/ml, respectively. CONCLUSIONS: TB patients with DM had lower INH and PZA concentrations. Negative correlation between blood glucose and drug concentrations suggests delayed absorption/faster elimination of INH and PZA in the presence of elevated glucose.

Strengthening tuberculosis control overseas: who benefits?

BACKGROUND: Although tuberculosis is a major cause of morbidity and mortality worldwide, available funding falls far short of that required for effective control. Economic and spillover consequences of investments in the treatment of tuberculosis are unclear, particularly when steep gradients in the disease and response are linked by population movements, such as that between Papua New Guinea (PNG) and the Australian cross-border region. OBJECTIVE: To undertake an economic evaluation of Australian support for the expansion of basic Directly Observed Treatment, Short Course in the PNG border area of the South Fly from the current level of 14% coverage. METHODS: Both cost-utility analysis and cost-benefit analysis were applied to models that allow for population movement across regions with different characteristics of tuberculosis burden, transmission, and access to treatment. Cost-benefit data were drawn primarily from estimates published by the World Health Organization, and disease transmission data were drawn from a previously published model. RESULTS: Investing $16 million to increase basic Directly Observed Treatment, Short Course coverage in the South Fly generates a net present value of roughly $74 million for Australia (discounted 2005 dollars). The cost per disability-adjusted life-year averted and quality-adjusted life-year saved for PNG is $7 and $4.6, respectively. CONCLUSIONS: Where regions with major disparities in tuberculosis burden and health system resourcing are connected through population movements, investments in tuberculosis control are of mutual benefit, resulting in net health and economic gains on both sides of the border. These findings are likely to inform the case for appropriate investment in tuberculosis control globally.

Influence of ceiling fan's speed and direction on efficacy of upperroom, ultraviolet germicidal irradiation: Experimental.

Increasing a ceiling fan's speed from its lowest setting of 61 rpm, which resulted in 0.77 m3/s of airflow, to its highest setting of 176 rpm, which resulted in 2.5 m3/s of airflow, or having the fan blow either upward or downward had no statistically significant effect on the efficacy of upper-room ultraviolet germicidal irradiation (UVGI). This outcome suggests that air circulation due to the ceiling fan was sufficient and that any additional increase would not improve efficacy. Numerous experimental studies on upper-room UVGI in which fans were used to provide air mixing have been published. However, none have quantified the air movement produced by these fans or described their tests in sufficient detail to allow results to be compared to predictions using computational fluid dynamics (CFD). The present work provides the required information. In addition to the usual boundary conditions needed for CFD, we made experimental measurements of UV susceptibility of the microorganisms used in the upper-room UVGI tests. We measured UV susceptibilities for Mycobacterium parafortuitum and Bacillus atrophaeus spores to be 0.074 and 0.018 m2/J, respectively. In a previous publication, we reported the spatial distribution of fluence rate, which is also needed for predicting efficacy from CFD. In a companion paper referred to as Part II, upper-room UVGI efficacy was predicted by both Eulerian and Lagrangian CFD and compared to the experimental results from the present study.

Multidrug-resistant and extensively drug-resistant tuberculosis: a review of current concepts and future challenges.

Multidrug-resistant and extensively drug-resistant tuberculosis are recent global health issues, which makes tuberculosis - after the success of short course treatment during the second half of the last century - a major health challenge. Globalisation, health inequalities, competing economic interests and political instability contribute substantially to the spread of drug-resistant strains, which are associated with high rates of morbidity and mortality. Issues such as increasing transmission of drug-resistant strains, poor diagnostic coverage and a lengthy, toxic treatment need to be overcome by innovative approaches to tuberculosis control, prevention, diagnostics and treatment. This review addresses recent developments and future concepts.

M. tuberculosis Infection Attributable to Exposure in Social Networks of Tuberculosis Cases in an Urban African Community.

Background: The persistence of tuberculosis today and its global disparity send a powerful message that effective tuberculosis control must respond to its regional epidemiology. Active case finding through contact investigation is a standard protocol used for tuberculosis control, but its effectiveness has not been established, especially in endemic areas. Methods: To quantify the potential effectiveness of contact investigation in Kampala, Uganda, we used a cross-sectional design to evaluate the social networks of 123 tuberculosis index cases and 124 controls without tuberculosis. Results: Tuberculous infection was present in 515 of 989 tuberculosis case contacts (52.1%) and 396 of 1026 control contacts (38.6%; adjusted prevalence ratio, 1.4; 95% CI, 1.3-1.6). The proportion of infected participants with known exposure within the social network of the tuberculosis case was 35%. The population-attributable fraction was 11.1% for any known exposure, with 7.3% attributable to household exposure and 3.4% attributable to extrahousehold exposure. Conclusions: This low population-attributable fraction indicates that contact tracing in the social networks of index cases will have only a modest effect in reducing tuberculous infection in a community. New approaches to community-level active case finding are needed.

A conceptual framework on determinants of the integrated tuberculosis control model implementation in China.

Improving the provision of tuberculosis (TB) care is both urgent and imperative to achieve the goals outlined in the End TB Strategy. China has initiated the integrated TB control model to enhance the quality of TB care Since 2012. Despite these efforts, the integrated TB control health system encounters numerous challenges in delivering effective TB care. The factors influencing TB care provision are intricate, and a conceptual framework to comprehend these potential determinants is currently lacking. To bridge this gap, this article proposed a conceptual framework that was developed through insights from the fields of both public management and health services, adjustment of PRISM model and elements, reference to the blocks of health system and reference to the framework of outcome indicators in implementation research. This conceptual framework included 4 modules which can be coherently and logically deduced, offered a multi-perspective understanding of the determinants to TB care, and hypothesized that the TB control services provided by the integrated TB control model is a public service and must be "patient-centered"; determinants of the integrated TB control model implementation can be divided into seven domains; the evaluation of the integrated TB control model implementation covers implementation outcomes and service outcomes. This framework offers the potential to guide empirical investigations, aiding in the understanding and identification of determinants, including barriers and facilitators, associated with the implementation of the integrated TB control health model. Furthermore, it serves as a valuable tool for developing interventions that address system-level barriers, drawing insights from the realms of public management and health services.

Implementation factors of tuberculosis control program in primary healthcare settings in China: a mixed-methods using the Consolidated Framework for Implementation Research framework.

BACKGROUND: Tuberculosis (TB) is a major cause of death worldwide, and Chinese TB burden ranked the second globally. Chinese primary healthcare (PHC) sectors implement the TB Control Program (TCP) to improve active case finding, referral, treatment adherence, and health education. This study aimed to identify barriers and enablers of TCP implementation in high TB burden regions of West China. METHODS: We conducted a representative study using mixed-methods in 28 counties or districts in Chongqing Municipality and Guizhou Province of West China from October 2021 to May 2022. Questionnaire surveys and semi-structured in-depth interviews were conducted with 2720 TB healthcare workers (HCWs) and 20 interviewees in PHC sectors. Descriptive statistical analysis was used to investigate TB HCWs' characteristics, and path analysis model was utilized to analyze the impact of associated factors on TCP implementation. Thematic framework analysis was developed with the guide of the adapted Consolidated Framework for Implementation Research (CFIR) on factors of TCP implementation. RESULTS: This study found that 84.6% and 94.1% of community and village HCWs had low professional titles. Based on the results of multiple regression analysis and correlation analysis, lower TB core knowledge scores (-0.09) were identified as barriers for TCP implementation in community PHC sectors, and low working satisfaction (-0.17) and low working willingness (-0.10) are barriers for TPC implementation in village PHC sectors. The results of in-depth interviews reported barriers in all domains and enablers in four domains of CFIR. There were identified 19 CFIR constructs associated with TCP implementation, including 22 barriers such as HCWs' heavy workload, and 12 enablers such as HCWs' passion towards TCP planning. CONCLUSIONS: With the guide of the CFIR framework, complex factors (barriers and enablers) of TCP implementation in PHC sectors of West China were explored, which provided important evidences to promote TB program in high TB burden regions. Further implementation studies to translate those factors into implementation strategies are urgent needed.

Identification and molecular characterization of Mycobacterium bovis DNA in GeneXpert® MTB/RIF ultra-positive, culture-negative sputum from a rural community in South Africa.

This study investigated the presence of Mycobacterium bovis (M. bovis) DNA in archived human sputum samples previously collected from residents who reside adjacent to the M. bovis-endemic Hluhluwe-iMfolozi wildlife park, South Africa (SA). Sixty-eight sputum samples were GeneXpert MTB/RIF Ultra-positive for M. tuberculosis complex (MTBC) DNA but culture negative for M. tuberculosis. Amplification and Sanger sequencing of hsp65 and rpoB genes from DNA extracted from stored heat-inactivated sputum samples confirmed the presence of detectable amounts of MTBC from 20 out of the 68 sputum samples. Region of difference PCR, spoligotyping and gyrB long-read amplicon deep sequencing identified M. bovis (n = 10) and M. tuberculosis (n = 7). Notably, M. bovis spoligotypes SB0130 and SB1474 were identified in 4 samples, with SB0130 previously identified in local cattle and wildlife and SB1474 exclusively in African buffaloes in the adjacent park. M. bovis DNA in sputum, from people living near the park, underscores zoonotic transmission potential in SA. Identification of spoligotypes specifically associated with wildlife only and spoligotypes found in livestock as well as wildlife, highlights the complexity of TB epidemiology at wildlife-livestock-human interfaces. These findings support the need for integrated surveillance and control strategies to curb potential spillover and for the consideration of human M. bovis infection in SA patients with positive Ultra results.