Knowledge of Tuberculosis preventive treatment among people living with HIV: A cross-sectional survey in selected regions of Tanzania.

BACKGROUND: Tuberculosis remains a significant global health concern, especially for People Living with HIV, who are at an increased risk of severe TB disease. Despite the availability of TB Preventive Treatment, knowledge gaps persist among People Living with HIV regarding its importance, accessibility, and administration. The study aimed to assess TPT knowledge levels and determinants among People Living with HIV in Tanzania. METHODS: A cross-sectional survey was conducted from April to May 2023 in 12 regions of mainland Tanzania. The study included PLHIV aged 18 years and above, receiving HIV care in selected Care and Treatment Centers. Data were collected through face-to-face interviews using a semi-structured questionnaire covering sociodemographic characteristics and Tuberculosis preventive treatment knowledge. Descriptive statistics, chi-square tests, and logistic regression analyses were employed for data analysis. RESULTS: Out of the 391 People Living with HIV interviewed, 71.4% demonstrated adequate Tuberculosis preventive treatment knowledge. Female participants, those attending urban health facilities, and individuals with longer durations of HIV care exhibited higher Tuberculosis preventive treatment knowledge levels. However, knowledge disparities persisted based on demographic characteristics such as gender and location of health facilities. CONCLUSION: While a considerable portion of People Living with HIV demonstrated adequate higher Tuberculosis preventive treatment knowledge, addressing gaps among those with lower understanding is crucial. Targeted education campaigns tailored to the needs of People Living with HIV, especially in rural areas and among male populations, are essential. Collaborative efforts between national health programs and community organizations are vital to integrate Tuberculosis preventive treatment awareness effectively into comprehensive HIV care programs, ultimately reducing the burden of Tuberculosis among People Living with HIV and the general population.

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.

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.

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.

Assessment of health promotion action for tuberculosis of end tuberculosis action plan (2019-2022) in China.

BACKGROUND: Tuberculosis is a chronic infectious disease that endangers people's health, and China is a country with a high burden of tuberculosis. To accelerate the progress towards ending TB, the Chinese government implemented the End TB Action Plan (2019-2022), which consists of six actions. Among the End TB Action Plan, health promotion was conducted to improve the awareness of TB knowledge among Chinese people. The purpose of this study is to evaluate the effectiveness of implementing TB health promotion activities outlined in the End TB Action Plan, and to provide recommendations for future TB prevention and control plan. METHODS: A cross-sectional study was conducted in nine Chinese provinces in 2022. A total of 11,920 Chinese people filled out the questionnaire. Logistic regression analysis was used to explore that overall awareness of TB core information is associated with whether they received TB health education. RESULTS: The study involved 11,920 Chinese participants. The overall awareness rate of the core information of TB was 84.2%, which does not reach the 85% goal of the End TB Action Plan. The single awareness rate that TB is a chronic infectious disease and that the vast majority of TB patients can be cured were 75.3% and 76.0%. Participants who received TB health education had a higher awareness rate of TB core information. Participants who were elderly, retired or had a primary school education or below had poor awareness of the core information of TB. Participants who were elderly, lived in urban areas, were equipment operators or had a primary school education or below received less TB health education. Participants mainly received TB health education through TV (44.6%) and Internet (37.8%), preferred TV, broadcasts or movies (58.9%) and Internet advertising (54.7%). Participants preferred illustrated (46.2%) and audio-visual (44.8%) advertising materials. The common sources used to answer health-related questions on the internet were We-Medias (48.3%) and search engines (38.9%). Participants preferred to use short-form videos (66.8%) and illustrations (53.1%) to answer health-related questions. CONCLUSIONS: Health promotion action for TB had a positive effect in China, but the awareness of TB was inadequate among Chinese people, and it is necessary to strengthen TB health education for those people. Moreover, TB prevention and control institutions should advertise TB more in audio-visual and illustrated forms on the Internet and audio-visual media. Health-related questions should be published in short-form video and illustrated forms in the We-Media and search engine more.

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.

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.

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.

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.

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.

The seroconversion history to SARS-CoV-2 in Indigenous people from Brazil - the interplay between exposure, vaccination, and tuberculosis.

The COVID-19 pandemic caused a significant loss of human lives and a worldwide decline in quality of life. Although our understanding of the pandemic has improved significantly since the beginning, the natural history of COVID-19 and its impacts on under-represented populations, such as Indigenous people from America, remain largely unknown. We performed a retrospective serological survey with two Brazilian Indigenous populations (n=624), Tupiniquim and Guarani-Mbyá. Samples were collected between September 2020 and July 2021: a period comprising the dissemination of SARS-CoV-2 variants and the beginning of COVID-19 vaccination in Brazil. Seroconversions against S and N antigens were assessed using three different commercially available ELISA kits. Samples were also used to assess the prevalence of tuberculosis (TB) in the same population (n=529). Seroconversion against SARS-CoV-2 antigens was considered positive if at least one of the three ELISA kits detected levels of specific antibodies above the threshold specified by the manufacturer. In this sense, we report 56.0% (n=349/623) of seroconverted individuals. Relative seroconversion peaked after introduction of the Coronavac vaccine in February 2021. Vaccination increased the production of anti-S IgG from 3.9% to 48.6%. Our results also indicated that 11.0% (n=46/417) of all individuals were positive for TB. Seroconversion to SARS-CoV-2 was similar between individuals with positive tuberculosis test results to those with negative test results. Most vaccinated individuals seroconverted to SARS-CoV-2, indicating that Coronavac may be as protective in individuals from these indigenous groups as observed in the general Brazilian population. COVID-19 severity was minimal regardless of incomplete vaccine coverage, suggesting that vaccination may not be the only factor protecting individuals from severe COVID-19. Tuberculosis is highly prevalent and not associated with increased seroconversion to SARS-CoV-2.

Estimating the Potential Public Health Value of BCG Revaccination.

An upcoming trial may provide further evidence that adolescent/adult-targeted BCG revaccination prevents sustained Mycobacterium tuberculosis infection, but its public health value depends on its impact on overall tuberculosis morbidity and mortality, which will remain unknown. Using previously calibrated models for India and South Africa, we simulated BCG revaccination assuming 45% prevention-of-infection efficacy, and we evaluated scenarios varying additional prevention-of-disease efficacy between +50% (reducing risk) and -50% (increasing risk). Given the assumed prevention-of-infection efficacy and range in prevention-of-disease efficacy, BCG revaccination may have a positive health impact and be cost-effective. This may be useful when considering future evaluations and implementation of adolescent/adult BCG revaccination.

Airborne infection prevention and control implementation: A positive deviant organisational case study of tuberculosis and COVID-19 at a South African rural district hospital.

There are many examples of poor TB infection prevention and control (IPC) implementation in the academic literature, describing a high-risk environment for nosocomial spread of airborne diseases to patients and health workers. We developed a positive deviant organisational case study drawing on Weick's theory of organisational sensemaking. We focused on a district hospital in the rural Eastern Cape, South Africa and used four primary care clinics as comparator sites. We interviewed 18 health workers to understand TB IPC implementation over time. We included follow-up interviews on interactions between TB and COVID-19 IPC. We found that TB IPC implementation at the district hospital was strengthened by continually adapting strategies based on synergistic interventions (e.g. TB triage and staff health services), changes in what value health workers attached to TB IPC and establishing organisational TB IPC norms. The COVID-19 pandemic severely tested organisational resilience and COVID-19 IPC measures competed instead of acted synergistically with TB. Yet there is the opportunity for applying COVID-19 IPC organisational narratives to TB IPC to support its use. Based on this positive deviant case we recommend viewing TB IPC implementation as a social process where health workers contribute to how evidence is interpreted and applied.

Valuation of knowledge, attitude, practices of tuberculosis among the health care workers from Islamabad Pakistan.

BACKGROUND: Tuberculosis (TB) as a foremost infectious disease adds massive burden to morbidity and mortality rate, despite of well-structured TB control programs around the globe. Inappropriate health care management system and poor implementation on standard in relevance to TB, remain some reasons causative to TB prevalence and its rising antimicrobial resistance. Health Care Workers (HCWs) laboring as a part of TB control system, are the vital warriors in achieving the goals of TB End Strategy by 2035. Their performance is influenced by their knowledge, attitude, and practices (KAP) toward this infectious disease. This study aimed to signify the role of KAP score of health care Workers in the better control and prevention of TB in the Islamabad Capital Territory (ICT), Pakistan. METHODS: A cross-sectional study on Knowledge, Attitude and Practice study of Tuberculosis (TB) among health care Workers, was done in ICT, which is the capital of Pakistan. The KAP of TB was collected for the 306 Health Care Workers from all the Islamabad TB referring health facilities which refer the TB patients for testing to the National Reference Laboratory, Islamabad Pakistan. Eligible health care workers were requested to respond on KAP questionnaire after informed consent. KAP questionnaire comprised of knowledge, attitude, and practices section including demographic information. All the data was analyzed using IBM SPSS statistics 21. One Way Analysis of Variance (ANOVA) was applied to calculate KAP mean score against different variables. On the significant data sets of ANOVA output, Tukey's Multiple Comparison Test was applied for pairwise comparison. Pearson correlation coefficient was utilized to explore the association between two qualitative variables. The non-parametric tests were applied to evaluate difference of KAP score in relation to demographic covariates individually. RESULTS: From June to July 2023, we conducted TB KAP study among Health Care Workers of ICT, Pakistan. The average age was 33 years (range 26-30 years). Majority of the recruited subjects were not being trained for dealing with TB infection. The results demonstrated that Health Care Workers working were lacking their knowledge about mode of TB transmission, best diagnostic technique, and contraction of TB infections. The mean knowledge, attitude and practices mean scores were 15.05 (SD = 3.96), 83.68 (SD = 15.74) and 6.31 (SD = 2.21), respectively. Mean knowledge score of Health Care Workers were significantly related to their educational level and occupation while no significant association was declared with working experience as TB staff. Pearson coefficient of attitude score with knowledge of Health Care Workers was of weak level (0.28). Practice mean score was correlated to knowledge mean score at a moderate level (r = 0.40). On the other hand, practice score was r = 0.29 with attitude mean score had shown weak level correlation. A number of demographic factors were strongly linked to each of the mean score of knowledge, attitude, and practices. CONCLUSION: These findings highlighted the significant involvement of education, profession, and professional trainings in the better knowledge, attitude, and practices of the TB related health care Workers. For a better management system of infectious diseases like TB, a well-trained and professionally competent staff of Health Care Workers is important so as to achieve the goal of TB-End strategy by 2035 from Pakistan, which is the 5th highest burden country for TB.

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..

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.

Comparative analysis of genomic characteristics and immune response between Mycobacterium tuberculosis strains cultured continuously for 25 years and H37Rv.

Tuberculosis (TB) continues to pose a significant global health challenge, emphasizing the critical need for effective preventive measures. Although many studies have tried to develop new attenuated vaccines, there is no effective TB vaccine. In this study, we report a novel attenuated Mycobacterium tuberculosis (M. tb) strain, CHVAC-25, cultured continuously for 25 years in the laboratory. CHVAC-25 exhibited significantly reduced virulence compared to both the virulent H37Rv strain in C57BL/6J and severe combined immunodeficiency disease mice. The comparative genomic analysis identified 93 potential absent genomic segments and 65 single nucleotide polymorphic sites across 47 coding genes. Notably, the deletion mutation of ppsC (Rv2933) involved in phthiocerol dimycocerosate synthesis likely contributes to CHVAC-25 virulence attenuation. Furthermore, the comparative analysis of immune responses between H37Rv- and CHVAC-25-infected macrophages showed that CHVAC-25 triggered a robust upregulation of 173 genes, particularly cytokines crucial for combating M. tb infection. Additionally, the survival of CHVAC-25 was significantly reduced compared to H37Rv in macrophages. These findings reiterate the possibility of obtaining attenuated M. tb strains through prolonged laboratory cultivation, echoing the initial conception of H37Ra nearly a century ago. Additionally, the similarity of CHVAC-25 to genotypes associated with attenuated M. tb vaccine positions it as a promising candidate for TB vaccine development.

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.