Strategies for isoniazid preventive therapy in HIV-positive patients who consume alcohol.

WHO guidance to defer isoniazid preventive therapy (IPT) among those with regular alcohol use because of hepatotoxicity concerns may exclude many people living with HIV (PLWH) at high TB risk in these settings.To evaluate hepatotoxicity during TB preventive therapy (TPT) in PLWH who report alcohol use in Uganda over 10 years.We developed a Markov model of latent TB infection, isoniazid preventive therapy (IPT - a type of TPT), and TB disease using data from the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) study. We modeled several treatment scenarios, including no IPT, IPT with liver enzyme monitoring (AST/ALT) during treatment, and IPT with pre-screening using the tuberculin skin test (TST).The no IPT scenario had 230 TB deaths/100,000 population over 10 years, which is more than that seen in any IPT scenario. IPT, even with no monitoring, was preferred over no IPT when population TB disease incidence was >50 in 100,000.For PLWH who report alcohol use in high TB burden settings, IPT should be offered, ideally with regular AST/ALT monitoring. However, even if regular monitoring is not possible, IPT is still preferable to no IPT in almost every modeled scenario..

A public health development intervention between acceptability and feasibility: descriptive-interpretive discussion of an example.

Introduction: the National Tuberculosis Control Program (NTP) in Cameroon participated between 2016 and 2018 in a multi-country operational study of the Union against Tuberculosis and Lung Disease (The UNION) aiming at demonstrating the efficiency and feasibility of systematic tuberculosis preventive treatment (TPT) with 3 months of an isoniazid/rifampicin (3RH) combination in under-five child contacts of bacilliferous TB patients. Cameroon was one of the participating countries of the study. Despite the promising results communicated following this study, the coverage of TPT with 3RH in Cameroon remains low. We explored the intervention under aspects of acceptability and perceived feasibility. Methods: key participants and stakeholders in this descriptive interpretative study in Cameroon were interviewed in five focus groups or individually (31 individuals). The Focus Group Discussion (FGD) and interview transcripts were analysed for different components of acceptability using a theoretical framework and the results discussed confronting them with the main objective of the study, i.e. demonstrating feasibility. Results: the children's parents expressed overall positive feelings about and acceptance of the intervention, emphasizing the unexpected empathy shown by the health staff. The involved field staff, too, showed unreserved acceptance. On the other hand, managers at the intermediate and central levels showed scepticism as to the process of initiation of the study as well as to its feasibility in the given context, neglecting aspects of resources necessary for a scaling-up and of prioritisation. Conclusion: the adoption of a public health strategy, also internationally recognized as an effective and efficient intervention, requires more than the demonstration of its acceptability or feasibility during the term of a showcase project introduced by an external development partner. Adoption is conditioned by adoption and circumspect planning involving at each stage the stakeholders on all levels of the program.

The ΔfbpAΔsapM candidate vaccine derived from Mycobacterium tuberculosis H37Rv is markedly immunogenic in macrophages and induces robust immunity to tuberculosis in mice.

Tuberculosis (TB) remains a significant global health challenge, with approximately 1.5 million deaths per year. The Bacillus Calmette-Guérin (BCG) vaccine against TB is used in infants but shows variable protection. Here, we introduce a novel approach using a double gene knockout mutant (DKO) from wild-type Mycobacterium tuberculosis (Mtb) targeting fbpA and sapM genes. DKO exhibited enhanced anti-TB gene expression in mouse antigen-presenting cells, activating autophagy and inflammasomes. This heightened immune response improved ex vivo antigen presentation to T cells. Subcutaneous vaccination with DKO led to increased protection against TB in wild-type C57Bl/6 mice, surpassing the protection observed in caspase 1/11-deficient C57Bl/6 mice and highlighting the critical role of inflammasomes in TB protection. The DKO vaccine also generated stronger and longer-lasting protection than the BCG vaccine in C57Bl/6 mice, expanding both CD62L-CCR7-CD44+/-CD127+ effector T cells and CD62L+CCR7+/-CD44+CD127+ central memory T cells. These immune responses correlated with a substantial ≥ 1.7-log10 reduction in Mtb lung burden. The DKO vaccine represents a promising new approach for TB immunization that mediates protection through autophagy and inflammasome pathways.

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.

Ag85B with c-di-AMP as mucosal adjuvant showed immunotherapeutic effects on persistent Mycobacterium tuberculosis infection in mice.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.

Host and pathogen genetic diversity shape vaccine-mediated protection to Mycobacterium tuberculosis.

To investigate how host and pathogen diversity govern immunity against Mycobacterium tuberculosis (Mtb), we performed a large-scale screen of vaccine-mediated protection against aerosol Mtb infection using three inbred mouse strains [C57BL/6 (B6), C3HeB/FeJ (C3H), Balb/c x 129/SvJ (C129F1)] and three Mtb strains (H37Rv, CDC1551, SA161) representing two lineages and distinct virulence properties. We compared three protective modalities, all of which involve inoculation with live mycobacteria: Bacillus Calmette-Guérin (BCG), the only approved TB vaccine, delivered either subcutaneously or intravenously, and concomitant Mtb infection (CoMtb), a model of pre-existing immunity in which a low-level Mtb infection is established in the cervical lymph node following intradermal inoculation. We examined lung bacterial burdens at early (Day 28) and late (Day 98) time points after aerosol Mtb challenge and histopathology at Day 98. We observed substantial heterogeneity in the reduction of bacterial load afforded by these modalities at Day 28 across the combinations and noted a strong positive correlation between bacterial burden in unvaccinated mice and the degree of protection afforded by vaccination. Although we observed variation in the degree of reduction in bacterial burdens across the nine mouse/bacterium strain combinations, virtually all protective modalities performed similarly for a given strain-strain combination. We also noted dramatic variation in histopathology changes driven by both host and bacterial genetic backgrounds. Vaccination improved pathology scores for all infections except CDC1551. However, the most dramatic impact of vaccination on lesion development occurred for the C3H-SA161 combination, where vaccination entirely abrogated the development of the large necrotic lesions that arise in unvaccinated mice. In conclusion, we find that substantial TB heterogeneity can be recapitulated by introducing variability in both host and bacterial genetics, resulting in changes in vaccine-mediated protection as measured both by bacterial burden as well as histopathology. These differences can be harnessed in future studies to identify immune correlates of vaccine efficacy.

Immunogenic profiling of Mycobacterium tuberculosis Rv1513 reveals its ability to switch on Th1 based immunity.

Tuberculosis (TB) is one of the infectious diseases caused by the pathogen Mycobacterium tuberculosis that continuously threatens the global human health. Bacillus Calmette-Guérin (BCG) vaccine is the only vaccine that has been used clinically to prevent tuberculosis in recent centuries, but its limitations in preventing latent infection and reactivation of tuberculosis do not provide full protection. In this study, we selected the membrane-associated antigen Rv1513 of Mycobacterium. In order to achieve stable expression and function of the target gene, the prokaryotic expression recombinant vector pET30b-Rv1513 was constructed and expressed and purified its protein. Detection of IFN- γ levels in the peripheral blood of TB patients stimulated by whole blood interferon release assay (WBIA) and multi-microsphere flow immunofluorescence luminescence (MFCIA) revealed that the induced production of cytokines, such as IFN-γ and IL-6, was significantly higher than that in the healthy group. Rv1513 combined with adjuvant DMT (adjuvant system liposomes containing dimethyldioctadecylammonium bromide (DDA), monophospholipid A (MPL), and trehalose-660-dibenzoic acid (TDB)) was used to detect serum specific antibodies, cytokine secretion from splenic suprasplenic cell supernatants, and multifunctional T-cell levels in splenocytes in immunised mice. The levels of IFN-γ, TNF-α, and IL-2 secreted by mouse splenocytes were found in the Rv1513+DMT group and the BCG+Rv1513+DMT group. The serum levels of IgG and its subclasses and the number of IFN-γ+T cells, TNF-α+T and IFN-γ+TNF-α+T cells in the induced CD4+/CD8+T cells in mice were significantly higher than those in the BCG group, and the highest levels were found in the BCG+Rv1513+DMT group. These findings suggest that Rv1513/DMT may serve as a potential subunit vaccine candidate that may be effective as a booster vaccine after the first BCG vaccination.

Quantifying Viable M. tuberculosis Safely Obviating the Need for High Containment Facilities.

Mycobacterium tuberculosis is an infectious pathogen that requires biosafety level-3 laboratory for handling. The risk of transmission is high to laboratory staff, and to manage the organism safely, it is necessary to construct high containment laboratory facilities at great expense. This limits the application of tuberculosis diagnostics to areas where there is insufficient capital to invest in laboratory infrastructure. In this method, we describe a process of inactivating sputum samples by either heat or guanidine thiocyanate (GTC) that renders them safe without affecting the quantification of viable bacteria. This method eliminates the need for level 3 containment laboratory for the tuberculosis molecular bacterial load assay (TB-MBLA) and is applicable in low- and middle-income countries.

Immunoinformatics and structural aided approach to develop multi-epitope based subunit vaccine against Mycobacterium tuberculosis.

Tuberculosis is a highly contagious disease caused by Mycobacterium tuberculosis (Mtb), which is one of the prominent reasons for the death of millions worldwide. The bacterium has a substantially higher mortality rate than other bacterial diseases, and the rapid rise of drug-resistant strains only makes the situation more concerning. Currently, the only licensed vaccine BCG (Bacillus Calmette-Guérin) is ineffective in preventing adult pulmonary tuberculosis prophylaxis and latent tuberculosis re-activation. Therefore, there is a pressing need to find novel and safe vaccines that provide robust immune defense and have various applications. Vaccines that combine epitopes from multiple candidate proteins have been shown to boost immunity against Mtb infection. This study applies an immunoinformatic strategy to generate an adequate multi-epitope immunization against Mtb employing five antigenic proteins. Potential B-cell, cytotoxic T lymphocyte, and helper T lymphocyte epitopes were speculated from the intended proteins and coupled with 50 s ribosomal L7/L12 adjuvant, and the vaccine was constructed. The vaccine's physicochemical profile demonstrates antigenic, soluble, and non-allergic. In the meantime, docking, molecular dynamics simulations, and essential dynamics analysis revealed that the multi-epitope vaccine structure interacted strongly with Toll-like receptors (TLR2 and TLR3). MM-PBSA analysis was performed to ascertain the system's intermolecular binding free energies accurately. The immune simulation was applied to the vaccine to forecast its immunogenic profile. Finally, in silico cloning was used to validate the vaccine's efficacy. The immunoinformatics analysis suggests the multi-epitope vaccine could induce specific immune responses, making it a potential candidate against Mtb. However, validation through the in-vivo study of the developed vaccine is essential to assess its efficacy and immunogenicity profile, which will assure active protection against Mtb.

Global stability and optimal control of an age-structured SVEIR epidemic model with waning immunity and relapses.

The efficacy of vaccination, incomplete treatment and disease relapse are critical challenges that must be faced to prevent and control the spread of infectious diseases. Age heterogeneity is also a crucial factor for this study. In this paper, we investigate a new age-structured SVEIR epidemic model with the nonlinear incidence rate, waning immunity, incomplete treatment and relapse. Next, the asymptotic smoothness, the uniform persistence and the existence of interior global attractor of the solution semi-flow generated by the system are given. We define the basic reproduction number R 0 and prove the existence of the equilibria of the model. And we study the global asymptotic stability of the equilibria. Then the parameters of the model are estimated using tuberculosis data in China. The sensitivity analysis of R 0 is derived by the Partial Rank Correlation Coefficient method. These main theoretical results are applied to analyze and predict the trend of tuberculosis prevalence in China. Finally, the optimal control problem of the model is discussed. We choose to take strengthening treatment and controlling relapse as the control parameters. The necessary condition for optimal control is established.

Recent efforts in the development of glycoconjugate vaccine and available treatment for tuberculosis.

Tuberculosis (TB) continues to pose a grave threat to global health, despite relentless eradication efforts. In 1882, Robert Koch discovered that Mycobacterium tuberculosis (Mtb) is the bacterium responsible for causing tuberculosis. It is a fact that tuberculosis has claimed the lives of more than one billion people in the last few decades. It is imperative that we must take immediate and effective action to increase resources for TB research and treatment. Effective TB treatments demand an extensive investment of both time and finances, often requiring 6-9 months of rigorous antibiotic therapy. The most efficient way to control tuberculosis is by receiving a childhood Bacillus Calmette-Guérin (BCG) vaccination. Despite years of research on vaccine development, we still do not have any new approved vaccine for tuberculosis, except BCG, which is partially effective in young children. This review discusses briefly the available treatment for tuberculosis and remarkable advancements in glycoconjugate-based TB vaccine developments in recent years (2013-2024) and offers valuable direction for future research priorities.

Completion of tuberculosis preventive therapy and associated factors among clients on antiretroviral therapy at Debre Berhan town health facilities, North Shoa Zone, Ethiopia.

BACKGROUND: Tuberculosis preventive therapy is vital in caring for HIV-positive individuals, as it prevents the progression from latent tuberculosis infection to tuberculosis disease. The aim of the study is to assess the completion of tuberculosis preventive therapy and associated factors among clients receiving antiretroviral therapy in Debre Berhan town, Ethiopia, in 2022. METHOD: Institutional based cross sectional study was conducted. Random sampling methods were used to select both study participants and health facilities. Both bivariate and multivariate logistic regression analyses were performed. P-values less than 0.05 were statistically significant. RESULT: The study found that, 83% of participants were completed tuberculosis preventive therapy. Completed tuberculosis preventive therapy was associated with no adverse drug events, taking first-line ART, and good ART adherence. CONCLUSION: According to the Ethiopian ART guidelines, the study found a low completion rate of tuberculosis preventive therapy among HIV-positive clients on antiretroviral therapy. Factors like no adverse drug events, first-line antiretroviral regimen, and good adherence were significantly associated with completing tuberculosis preventive therapy.

An Effective Health System Approach to End TB: Implementing the Double X Strategy in Vietnam.

Countries that are high burden for TB must reverse the COVID-19 pandemic's devastating effects to accelerate progress toward ending TB. Vietnam's Double X (2X) strategy uses chest radiography (CXR) and GeneXpert (Xpert) rapid diagnostic testing to improve early detection of TB disease. Household contacts and vulnerable populations (e.g., individuals aged 60 years and older, smokers, diabetics, those with alcohol use disorders, and those previously treated for TB) with and without TB symptoms were screened in community campaigns using CXRs, followed by Xpert for those with a positive screen. In public non-TB district facilities, diabetics, respiratory outpatients, inpatients with lung disease, and other vulnerable populations underwent 2X evaluation. During COVID-19 restrictions in Vietnam, the 2X strategy improved access to TB services by decentralization to commune health stations, the lowest level of the health system, and enabling self-screening using a quick response mobile application. The number needed to screen (NNS) with CXRs to diagnose 1 person with TB disease was calculated for all 2X models and showed the highest yield among self-screeners (11 NNS with CXR), high yield for vulnerable populations in communities (60 NNS) and facilities (19 NNS), and moderately high yield for household contacts in community campaigns (154 NNS). Computer-aided diagnosis for CXRs was incorporated into community and facility implementation and improved physicians' CXR interpretations and Xpert referral decisions. Integration of TB infection and TB disease evaluation increased eligibility for TB preventive treatment among household contacts, a major challenge during implementation. The 2X strategy increased the rational use of Xpert, employing a health system-wide approach that reached vulnerable populations with and without TB symptoms in communities and facilities for early detection of TB disease. This strategy was effectively adapted to different levels of the health system during COVID-19 restrictions and contributed to post-pandemic TB recovery in Vietnam.

Progress Toward Tuberculosis Elimination and Tuberculosis Program Performance - National Tuberculosis Indicators Project, 2016-2022.

Problem/Condition: Elimination of tuberculosis (TB) is defined as reducing TB disease incidence in the United States to less than 1 case per million persons per year. In 2022, TB incidence in the United States was 2.5 TB cases per 100,000 persons. CDC's TB program developed a set of national TB indicators to evaluate progress toward TB elimination through monitoring performance of state and city TB program activities. Examining TB indicator data enables state- and city-level TB programs to identify areas for program evaluation and improvement activities. These data also help CDC identify states and cities that might benefit from technical assistance. Period Covered: The 5-year period for which the most recent data were available for each of five indicators: 1) overall TB incidence (2018-2022), 2) TB incidence among non-U.S.-born persons (2018-2022), 3) percentage of persons with drug susceptibility results reported (2018-2022), 4) percentage of contacts to sputum acid-fast bacillus (AFB) smear-positive TB patients with newly diagnosed latent TB infection (LTBI) who completed treatment (2017-2021), and 5) percentage of patients with completion of TB therapy within 12 months (2016-2020). Description of System: The National TB Indicators Project (NTIP) is a web-based performance monitoring tool that uses national TB surveillance data reported through the National TB Surveillance System and the Aggregate Reports for TB Program Evaluation. NTIP was developed to facilitate the use of existing data to help TB program staff members prioritize activities, monitor progress, and focus program improvement efforts. The following five indicators were selected for this report because of their importance in Federal TB funding allocation and in accelerating the decline in TB cases: 1) overall TB incidence in the United States, 2) TB incidence among non-U.S.-born persons, 3) percentage of persons with drug susceptibility results reported, 4) percentage of contacts to sputum AFB smear-positive TB cases who completed treatment for LTBI, and 5) percentage of patients with completion of TB therapy within 12 months. For this report, 52 TB programs (50 states, the District of Columbia, and New York City) were categorized into terciles based on the 5-year average number of TB cases reported to National TB Surveillance System. This grouping allows comparison of TB programs that have similar numbers of TB cases and allocates a similar number of TB programs to each category. The following formula was used to calculate the relative change by TB program for each indicator: [(% from year 5 - % from year 1 ÷ % from year 1) × 100]. Results: During the 5-year period for which the most recent data were available, most TB programs had improvements in reducing overall TB incidence (71.2%) and increasing the percentage of contacts receiving a diagnosis of LTBI who completed LTBI treatment (55.8%); the majority of programs (51.0%) also had improvements in reducing incidence among non-U.S.-born persons. The average percentage of persons with drug susceptibility results reported in most jurisdictions (28 of 52, [53.9%]) met or exceeded the 5-year national average of 97% (2018-2022). The percentage of contacts to sputum acid-fast bacillus (AFB) smear-positive TB patients with newly diagnosed latent TB infection (LTBI) who completed treatment increased in 29 of 52 (55.8%) jurisdictions from 2017 to 2021, signifying that, for most jurisdictions, steps have been taken to enhance performance in this area. The average percentage of patients with completion of TB therapy within 12 months was at or above the national average of 89.7% in approximately two-thirds (32 of 52 [61.5%]) of jurisdictions. Interpretation: This report is the first to describe a 5-year relative change for TB program performance. These results suggest that TB programs are making improvements in activities that help identify persons with TB and LTBI and ensure patients complete treatment in a timely manner. Public Health Action: Use of NTIP data from individual TB programs enables a more detailed examination of trends in program performance and identification of areas for program improvement. Assessing indicator trends by TB program provides an opportunity to gain a better understanding of program performance in comparison to other programs. It can also facilitate communication between programs regarding successes and challenges in program improvement. This information is valuable for TB programs to allocate resources effectively and provide additional context on TB control for public health policymakers.

Assessment of Isoniazid Preventive Therapy and Incidence of Tuberculosis among People Living with Human Immunodeficiency Virus Seeking Care in an Anti-retroviral Therapy Center, Puducherry.

BACKGROUND: One in three deaths among people living with human immunodeficiency virus (PLHIV) is due to Tuberculosis. Isoniazid preventive therapy (IPT) was implemented in antiretroviral therapy (ART) center Puducherry in July 2017. OBJECTIVES: We have determined the proportion of PLHIV who were eligible, initiated, completed IPT and also the incidence of tuberculosis before and after implementation of IPT. MATERIALS AND METHODS: It was a facility based longitudinal descriptive study. All PLHIV, aged 10 years and above, seeking care in ART Centers was included. The number of PLHIV eligible, initiated and completed IPT was summarized as proportion with 95% CI. RESULTS: Among the registered PLHIV (999), the proportion of PLHIV those were found eligible for IPT was 93% [95% CI (91.24%-94.67%)] and initiated on IPT was 92% [95% CI (90.20%-93.95%)]. Completion rate of IPT was 96.3% [95% CI (94.59%-97.63%)]. CONCLUSION: Initiation of IPT was relatively less among newly registered PLHIV as compared to older cohort of PLHIV.

Selenium nanoparticles enhance mucosal immunity against Mycobacterium bovis infection.

Selenium nanoparticles (SeNPs) enhance the immune response as adjuvants, increasing the efficacy of viral vaccines, including those for COVID-19. However, the efficiency of mucosal SeNPs in boosting vaccine-induced protective immunity against tuberculosis remains unclear. Therefore, this study aims to investigate whether the combination of SeNPs with the AH antigen (Ag85A-HspX) can boost respiratory mucosal immunity and thereby enhance the protective effects against tuberculosis. We synthesized SeNPs and assessed their impact on the immune response and protection against Mycobacterium bovis (M. bovis) as a mucosal adjuvant in mice, administered intranasally at a dose of 20 µg. SeNPs outperformed polyinosinic-polycytidylic acid (Poly IC) in stimulating the maturation of bone marrow-derived dendritic cells (BMDCs), which enhanced antigen presentation. SeNPs significantly activated and proliferated tissue-resident memory T cells (TRMs) and effector CD4+ T cells in the lungs. The vaccines elicited specific antibody responses in the respiratory tract and stimulated systemic Th1 and Th17 immune responses. Immunization with AH and SeNPs led to higher levels of mucosal secretory IgA in bronchoalveolar lavage fluid (BALF) and secretory IL-17 in splenocytes. Moreover, SeNPs immunized mice showed reduced M. bovis infection loads and inflammatory lesions in the lungs post-challenge. Notably, immunization with AH and SeNPs significantly reduced bacterial load in the lungs, achieving the lowest levels compared to all other tested groups. This study calls for pre-clinical investigation of AHB-SeNPs as an anti-bovine tuberculosis vaccine and for exploring its human vaccine potential, which is anticipated to aid in the development of innovative vaccines or adjuvants.

Dynamics and optimal control of tuberculosis model with the combined effects of vaccination, treatment and contaminated environments.

Tuberculosis has affected human beings for thousands of years, and until today, tuberculosis still ranks third among 29 infectious diseases in China. However, most of the existing mathematical models consider a single factor, which is not conducive to the study of tuberculosis transmission dynamics. Therefore, this study considers the combined effects of vaccination, treatment, and contaminated environments on tuberculosis, and builds a new model with seven compartments of $ SVEITRW $ based on China's tuberculosis data. The study shows that when the basic reproduction number $ R_{0} $ is less than 1, the disease will eventually disappear, but when $ R_{0} $ is greater than 1, the disease may persist. In the numerical analysis part, we use Markov-chain Monte-Carlo method to obtain the optimal parameters of the model. Through the next generation matrix theory, we calculate that the $ R_{0} $ value of tuberculosis in China is $ 2.1102 $, that is, if not controlled, tuberculosis in China will not disappear over time. At the same time, through partial rank correlation coefficients, we find the most sensitive parameter to the basic reproduction number $ R_{0} $. On this basis, we combine the actual prevalence of tuberculosis in China, apply Pontryagin's maximum principle, and perform cost-effectiveness analysis to obtain the conditions required for optimal control. The analysis shows that four control strategies could effectively reduce the prevalence of TB, and simultaneously controlling $ u_{2}, u_{3}, u_{4} $ is the most cost-effective control strategy.

The impact of living conditions and health interventions on tuberculosis, Denmark, 1876 to 2022.

BackgroundDenmark possesses an exceptional historical data collection on tuberculosis (TB) from 1876 to the present, providing a unique opportunity to assess TB epidemiology over 147 years in Denmark.AimOur aim was to describe the TB disease burden in Denmark in relation to historical events, living conditions and health interventions during the past 147 years.MethodsWe performed a nationwide register-based ecological study including all persons with TB in Denmark from 1876 through 2022, correlating the TB incidence to social, economic and health indicators.ResultsIn Denmark, the overall TB incidence and mortality declined markedly over the past 147 years, only marginally influenced by specific TB interventions such as sanatoria, Bacillus Calmette-Guèrin (BCG) vaccination, mass screenings and antibiotics. Parallel to this decline, the country experienced improved living conditions, as illustrated by decreased infant mortality and increased life expectancy and wealth. In 1978, Denmark became a low-incidence country for TB with risk groups predominantly affected, and with a continuous change in demographics towards fewer Danish-born cases and relatively more migrant cases.ConclusionsThe decline over time in TB incidence and mortality in Denmark preceded specific TB interventions and can, first of all, be attributed to improved living conditions. TB has now become a rare disease in Denmark, predominantly occurring in particular risk groups. Future elimination of TB will require a combination of specific health interventions in these risk groups combined with a continued focus on improving socioeconomic status and living conditions.

[Smoking and tuberculosis]. / Tabac et tuberculose.

SMOKING AND TUBERCULOSIS. Tuberculosis and smoking are responsible for high mortality worldwide. Tuberculosis causes 9 million incident cases and 1.6 million deaths every year. Smoking increases the risk of infection by Mycobacterium tuberculosis and of severe tuberculosis disease with death or recurrence. Cessation of smoking improves the course of the disease, promoting adherence to anti-tuberculosis treatment and definitive cure. All health-care professionals involved in tuberculosis care must be involved to help smokers with tuberculosis to quit.

TABAC ET TUBERCULOSE. La tuberculose et le tabagisme sont à l'origine d'une importante mortalité dans le monde. La tuberculose cause 9 millions de cas incidents et 1,6 million de décès chaque année. Le tabagisme augmente les risques d'infection par Mycobacterium tuberculosis et de tuberculose maladie sévère avec décès ou récidive. L'arrêt du tabac améliore le cours de l'infection, favorisant l'adhésion des patients au traitement antituberculeux et la guérison définitive. Tous les professionnels de santé doivent s'investir dans la mission d'aide à l'arrêt du tabac des fumeurs atteints de tuberculose.