Enhancing tuberculosis vaccine development: a deconvolution neural network approach for multi-epitope prediction.

Tuberculosis (TB) a disease caused by Mycobacterium tuberculosis (Mtb) poses a significant threat to human life, and current BCG vaccinations only provide sporadic protection, therefore there is a need for developing efficient vaccines. Numerous immunoinformatic methods have been utilized previously, here for the first time a deep learning framework based on Deconvolutional Neural Networks (DCNN) and Bidirectional Long Short-Term Memory (DCNN-BiLSTM) was used to predict Mtb Multiepitope vaccine (MtbMEV) subunits against six Mtb H37Rv proteins. The trained model was used to design MEV within a few minutes against TB better than other machine learning models with 99.5% accuracy. The MEV has good antigenicity, and physiochemical properties, and is thermostable, soluble, and hydrophilic. The vaccine's BLAST search ruled out the possibility of autoimmune reactions. The secondary structure analysis revealed 87% coil, 10% beta, and 2% alpha helix, while the tertiary structure was highly upgraded after refinement. Molecular docking with TLR3 and TLR4 receptors showed good binding, indicating high immune reactions. Immune response simulation confirmed the generation of innate and adaptive responses. In-silico cloning revealed the vaccine is highly expressed in E. coli. The results can be further experimentally verified using various analyses to establish a candidate vaccine for future clinical trials.

Exploring opportunities to strengthen rural tuberculosis health service delivery: a qualitative study with health workers in Tibet autonomous region, China.

OBJECTIVES: This qualitative study aimed to explore opportunities to strengthen tuberculosis (TB) health service delivery from the perspectives of health workers providing TB care in Shigatse prefecture of Tibet Autonomous Region, China. DESIGN: Qualitative research, semi-structured in-depth interviews. SETTING: The TB care ecosystem in Shigatse, including primary and community care. PARTICIPANTS: Participants: 37 semi-structured interviews were conducted with village doctors (14), township doctors and nurses (14), county hospital doctors (7) and Shigatse Centre for Disease Control staff (2). RESULTS: The three main themes reported include (1) the importance of training primary and community health workers to identify people with symptoms of TB, ensure TB is diagnosed and link people with TB to further care; (2) the need to engage community health workers to ensure retention in care and adherence to TB medications; and (3) the opportunity for innovative technologies to support coordinated care, retention in care and adherence to medication in Shigatse. CONCLUSIONS: The quality of TB care could be improved across the care cascade in Tibet and other high-burden, remote settings by strengthening primary care through ongoing training, greater support and inclusion of community health workers and by leveraging technology to create a circle of care. Future formative and implementation research should include the perspectives of health workers at all levels to improve care organisation and delivery.

[The methodological approaches to evaluation of effect of tuberculosis as socially significant infection on decreasing of public health quality].

The study reveals main methodological approaches in monitoring and evaluating role of socially significant infectious diseases in reducing quality of public health in the Russian Federation. The article proposes at population level the grouping of main risk factors affecting quality of public health, exemplified by epidemiology of tuberculosis. The purpose of the study is to develop methodology of exploration of impact of socially significant infections on decreasing of quality of public health exemplified by epidemiology of tuberculosis as infectious disease that is well studied in medical social aspects and having fully functioning TB control and high level monitoring system. The informational analytical methodology was applied conjointly with critical analysis of national and foreign publications, normative legal acts, selected through scientific search systems PubMed, Medline, www.base-search.net, www.refseek.com, E-library, CiberLeninka, "Garant" and "ConsultantPlus". The depth of search was limited by 15 years and more. The data from the federal statistical observation form No. 8 "Information about diseases with active tuberculosis" for 2021 was also evaluated. For the first time, the grouping of main risk factors of socially significant infections , affecting decrease of quality of public health at population level are proposed. The mentioned factors are grouped as epidemiological; social economic (including economic damage caused directly by tuberculosis); demographic; behavioral; biomedical (presence of diseases not associated with tuberculosis, but reducing immunity); climatic geographical, etc. The further analysis and listing of specific indicators of each group of factors is required in order to monitor and quickly assess impact of socially significant infectious diseases on public health in the Russian Federation and its Subjects. The analysis of scientific literature demonstrated that, despite breadth of studying tuberculosis risk factors, they are non-systematized and fragmented. The methodological approaches to studying impact of socially significant infectious diseases on public health in foreign countries and in the Russian Federation, are practically absent. The compilation and actualization of listing of indicative indicators for each group of factors with the choice of statistical methods of their calculation, evaluation and interpretation will permit to develop methodological approaches to monitoring and assessing role of tuberculosis (hereinafter - HIV infection, parenteral viral hepatitis, etc.) in altering quality of public health in the Russian Federation with development of rapidly updated database of selected indicators at the level of each Subject of the Russian Federation.

Comparison of active tuberculosis occurrence associated with Janus kinase inhibitors and biological DMARDs in rheumatoid arthritis.

OBJECTIVES: This study aimed to evaluate the risk of tuberculosis associated with the use of Janus kinase (JAK) inhibitors or biological disease-modifying antirheumatic drugs (bDMARDs) in patients diagnosed with rheumatoid arthritis (RA) in South Korea. METHODS: In this nationwide matched-cohort study, we retrospectively identified adult patients with new-onset RA from the National Health Insurance Service database who were prescribed bDMARDs or JAK inhibitors and recently underwent latent tuberculosis infection (LTBI) screening during 2012‒2021, and followed them up until the end of 2022 for the development of active tuberculosis. HRs were estimated using Cox proportional hazards regression in a propensity score-matched cohort. RESULTS: Among 16 760 matched patients with RA (3352 JAK inhibitor users and 13 408 bDMARD users), 18.8% received tuberculosis preventive therapy for LTBI. Overall, JAK inhibitor users had a significantly lower risk of tuberculosis than bDMARD users (HR (95% CI)=0.37 (0.22 to 0.62)). Among the patients treated for LTBI, patients with low treatment adherence had a significantly higher risk than those without LTBI (HR (95% CI)=2.78 (1.74 to 4.44)). Patients without LTBI and using JAK inhibitors had a significantly lower risk of tuberculosis across all ages and sexes compared with bDMARD users. CONCLUSION: Patients with RA using JAK inhibitors have a significantly lower risk of active tuberculosis than bDMARD users in South Korea; however, patients with RA having LTBI are equally at risk regardless of the treatment received (JAK inhibitor vs bDMARD). Therefore, vigilant tuberculosis monitoring, especially in patients with low adherence to tuberculosis preventive therapy, is essential.

Global analysis of an age-structured tuberculosis model with an application to Jiangsu, China.

Diagnostic delay for TB infected individuals and the lack of TB vaccines for adults are the main challenges to achieve the goals of WHO by 2050. In order to evaluate the impacts of diagnostic delay and vaccination for adults on prevalence of TB, we propose an age-structured model with latent age and infection age, and we incorporate Mycobacterium TB in the environment and vaccination into the model. Diagnostic delay is indicated by the age of infection before receiving treatment. The threshold dynamics are established in terms of the basic reproduction number R 0 . When R 0 < 1 , the disease-free equilibrium is globally asymptotically stable, which means that TB epidemic will die out; When R 0 = 1 , the disease-free equilibrium is globally attractive; there exists a unique endemic equilibrium and the endemic equilibrium is globally attractive when R 0 > 1 . We estimate that the basic reproduction number R 0 = 0.5320 (95% CI (0.3060, 0.7556)) in Jiangsu Province, which means that TB epidemic will die out. However, we find that the annual number of new TB cases by 2050 is 1,151 (95%CI: (138, 8,014)), which means that it is challenging to achieve the goal of WHO by 2050. To this end, we evaluate the possibility of achieving the goals of WHO if we start vaccinating adults and reduce diagnostic delay in 2025. Our results demonstrate that when the diagnostic delay is reduced from longer than four months to four months, or 20% adults are vaccinated, the goal of WHO in 2050 can be achieved, and 73,137 (95%CI: (23,906, 234,086)) and 54,828 (95%CI: (15,811, 206,468)) individuals will be prevented from being infected from 2025 to 2050, respectively. The modeling approaches and simulation results used in this work can help policymakers design control measures to reduce the prevalence of TB.

Knowledge, attitudes, and practice toward tuberculosis in high school students in Qingdao, China.

INTRODUCTION: The purpose of this study is to assess the levels of knowledge, attitude, and practice (KAP) related to TB, and to analyze the differences among various demographic groups. METHODOLOGY: A total of 621 students enrolled in Qingdao High School, coming from high TB burden settings. The cross-sectional study was conducted from May to July of 2022. Participants completed an online questionnaire. Differences in knowledge and practice based on participant characteristics were analyzed using the Wilcoxon rank test and Kruskal-Wallis rank test. Group differences were assessed using a rank-based analysis of variance. RESULTS: The mean percentage of correct answers for TB knowledge and practice was 82.09% and 83.25%, respectively. Grade Three students showed higher knowledge and practice scores than Grade One or Grade Two students (t = -3.9935, p = 0.0002, t = 3.4537, p = 0.0018. 8.58 vs 7.94, 8.58 vs 8.23. t = 3.4562, p = 0.0018, t = -2.8688, p = 0.0128. 1.78 vs 1.61, 1.78 vs 1.64). A significant majority (78.42%) of students expressed fear of being affected by TB. 49.28% of the students would support and help TB patients. 88.08% of participants had heard of TB, with 72.94% learning about it at school, mainly through visual aids like posters. Information was predominantly obtained from online sources (websites, microblogs, WeChat, etc.). CONCLUSIONS: It is recommended to develop a TB curriculum for lower-grade students to enhance awareness of TB prevention through various means, including the internet and social media.

Disparities in Tuberculosis Incidence by Race and Ethnicity Among the U.S.-Born Population in the United States, 2011 to 2021 : An Analysis of National Disease Registry Data.

BACKGROUND: Elevated tuberculosis (TB) incidence rates have recently been reported for racial/ethnic minority populations in the United States. Tracking such disparities is important for assessing progress toward national health equity goals and implementing change. OBJECTIVE: To quantify trends in racial/ethnic disparities in TB incidence among U.S.-born persons. DESIGN: Time-series analysis of national TB registry data for 2011 to 2021. SETTING: United States. PARTICIPANTS: U.S.-born persons stratified by race/ethnicity. MEASUREMENTS: TB incidence rates, incidence rate differences, and incidence rate ratios compared with non-Hispanic White persons; excess TB cases (calculated from incidence rate differences); and the index of disparity. Analyses were stratified by sex and by attribution of TB disease to recent transmission and were adjusted for age, year, and state of residence. RESULTS: In analyses of TB incidence rates for each racial/ethnic population compared with non-Hispanic White persons, incidence rate ratios were as high as 14.2 (95% CI, 13.0 to 15.5) among American Indian or Alaska Native (AI/AN) females. Relative disparities were greater for females, younger persons, and TB attributed to recent transmission. Absolute disparities were greater for males. Excess TB cases in 2011 to 2021 represented 69% (CI, 66% to 71%) and 62% (CI, 60% to 64%) of total cases for females and males, respectively. No evidence was found to indicate that incidence rate ratios decreased over time, and most relative disparity measures showed small, statistically nonsignificant increases. LIMITATION: Analyses assumed complete TB case diagnosis and self-report of race/ethnicity and were not adjusted for medical comorbidities or social determinants of health. CONCLUSION: There are persistent disparities in TB incidence by race/ethnicity. Relative disparities were greater for AI/AN persons, females, and younger persons, and absolute disparities were greater for males. Eliminating these disparities could reduce overall TB incidence by more than 60% among the U.S.-born population. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Coverage of BCG Vaccination for children aged until 7 years old and its determinants in French Guiana.

INTRODUCTION: The overall incidence of tuberculosis (TB) in France is low; thus, BCG vaccination is no longer mandatory. In French Guiana - a French overseas territory - BCG vaccination is strongly recommended because the incidence of TB is high in the context of mass immigration from endemic countries with low BCG vaccination rates. Thus, it is important to assess Bacillus Calmette-Guérin (BCG) vaccination coverage and its predictors. METHODS: We used data from the 2014 French Guiana Yellow Fever survey, which was conducted by the Observatoire Régional de la Santé de Guyane. Demographic and immunization data from eligible children and their families were collected using a questionnaire. Children who had an immunization card and who were no older than 7 years of age at the time of the survey were eligible. The Coverage for BCG and other mandatory vaccines were estimated; the delay in BCG vaccination was also computed. Univariate and multivariate analyses identified predictors associated with BCG immunization and BCG delayed immunization (after 2 months of age). RESULTS AND CONCLUSION: Overall, 469 children were eligible for this study. The total BCG coverage was 79.5 %, and the proportion of children vaccinated with delay was 50.7 %. The multivariate analysis indicated that BCVA was significantly greater among children younger than 3 years of age, whose household head was employed and whose education level was greater. None of the predictors were associated with the delay of BCG vaccination.

Gendered gaps to tuberculosis prevention and care in Kenya: a political economy analysis study.

BACKGROUND: Tuberculosis (TB) remains a public health concern in Kenya despite the massive global efforts towards ending TB. The impediments to TB prevention and care efforts include poor health systems, resource limitations and other sociopolitical contexts that inform policy and implementation. Notably, TB cases are much higher in men than women. Therefore, the political economy analysis (PEA) study provides in-depth contexts and understanding of the gender gaps to access and successful treatment for TB infection. DESIGN: PEA adopts a qualitative, in-depth approach through key informant interviews (KII) and documentary analysis. SETTING AND PARTICIPANTS: The KIIs were distributed among government entities, academia, non-state actors and community TB groups from Kenya. RESULTS: The themes identified were mapped onto the applied PEA analysis framework domains. The contextual and institutional issues included gender concerns related to the disconnect between TB policies and gender inclusion aspects, such as low prioritisation for TB programmes, limited use of evidence to inform decisions and poor health system structures. The broad barriers influencing the social contexts for TB programmes were social stigma and cultural norms such as traditional interventions that negatively impact health-seeking behaviours. The themes around the economic situation were poverty and unemployment, food insecurity and malnutrition. The political context centred around the systemic and governance gaps in the health system from the national and devolved health functions. CONCLUSION: Broad contextual factors identified from the PEA widen the disparity in targeted gender efforts toward men. Following the development of effective TB policies and strategies, it is essential to have well-planned gendered responsive interventions with a clear implementation plan and monitoring system to enhance access to TB prevention and care.

Lessons Learned from Public Health and State Prison Collaborations during COVID-19 Pandemic and Multifacility Tuberculosis Outbreak, Washington, USA.

The large COVID-19 outbreaks in prisons in the Washington (USA) State Department of Corrections (WADOC) system during 2020 highlighted the need for a new public health approach to prevent and control COVID-19 transmission in the system's 12 facilities. WADOC and the Washington State Department of Health (WADOH) responded by strengthening partnerships through dedicated corrections-focused public health staff, improving cross-agency outbreak response coordination, implementing and developing corrections-specific public health guidance, and establishing collaborative data systems. The preexisting partnerships and trust between WADOC and WADOH, strengthened during the COVID-19 response, laid the foundation for a collaborative response during late 2021 to the largest tuberculosis outbreak in Washington State in the past 20 years. We describe challenges of a multiagency collaboration during 2 outbreak responses, as well as approaches to address those challenges, and share lessons learned for future communicable disease outbreak responses in correctional settings.

A new neonatal BCG vaccination pathway in England: a mixed methods evaluation of its implementation.

INTRODUCTION: The introduction of a national evaluation of newborn screening for Severe Combined Immunodeficiency (SCID) in England triggered a change to the selective Bacillus Calmette-Guerin (BCG) vaccination programme delivery pathway, as this live attenuated vaccine is contraindicated in infants with SCID. The neonatal BCG vaccination programme is a targeted programme for infants at increased risk of tuberculosis and used to be offered shortly after birth. Since September 2021 the BCG vaccine is given to eligible infants within 28 days of birth, when the SCID screening outcome is available. We explore the experiences of those implementing the new pathway, and how they made sense of, engaged with, and appraised the change. METHODS: A mixed-methods evaluation was conducted between October 2022 and February 2023. This involved national online surveys with BCG commissioners and providers and qualitative semi-structured interviews with commissioners, providers, and Child Health Information System stakeholders in two urban areas. Survey data was analysed using descriptive statistics and interview data was analysed thematically. The data was triangulated using Normalization Process Theory as a guiding framework. RESULTS: Survey respondents (n = 65) and qualitative interviewees (n = 16) revealed that making sense of the new pathway was an iterative process. Some expressed a desire for more direction on how to implement the new pathway. The perceived value of the change varied from positive, ambivalent, to concerned. Some felt well-prepared and that improvements to data capture, eligibility screening, and accountably brought by the change were valuable. Others were concerned about the feasibility of the 28-day target, reductions in vaccination coverage, increased resource burden, and the outcome of the SCID evaluation. New collaborations and communities of practice were required to facilitate the change. Three main challenges in implementing the pathway and meeting the 28-day vaccination target were identified: appointment non-attendance; appointment and data systems; and staffing and resourcing. Feedback mechanisms were informal and took place in tandem with implementation. CONCLUSION: The new NHS neonatal BCG service specification has created an effective structure for monitoring and managing the BCG vaccination programme, but further work is required to support delivery of the 28-day vaccination target and improve uptake rates.

HtpG-A Major Virulence Factor and a Promising Vaccine Antigen against Mycobacterium tuberculosis.

Tuberculosis (TB) is the leading global cause of death f rom an infectious bacterial agent. Therefore, limiting its epidemic spread is a pressing global health priority. The chaperone-like protein HtpG of M. tuberculosis (Mtb) is a large dimeric and multi-domain protein with a key role in Mtb pathogenesis and promising antigenic properties. This dual role, likely associated with the ability of Heat Shock proteins to act both intra- and extra-cellularly, makes HtpG highly exploitable both for drug and vaccine development. This review aims to gather the latest updates in HtpG structure and biological function, with HtpG operating in conjunction with a large number of chaperone molecules of Mtb. Altogether, these molecules help Mtb recovery after exposure to host-like stress by assisting the whole path of protein folding rescue, from the solubilisation of aggregated proteins to their refolding. Also, we highlight the role of structural biology in the development of safer and more effective subunit antigens. The larger availability of structural information on Mtb antigens and a better understanding of the host immune response to TB infection will aid the acceleration of TB vaccine development.

A proposal to evaluate the management of tuberculosis programs: a qualitative, evaluability assessment in the border region of Brazil and Venezuela.

This study aims to analyze the feasibility of building an evaluative model for the management of the Tuberculosis Prevention and Control Program in the State of Roraima, located on the border between Brazil and Venezuela. This is an evaluability assessment, a type of study used as a pre-evaluation of the development and implementation stages of a program, as well as throughout its execution. The study was developed in stages comprising the: (i) definition of the intervention to be analyzed and its objectives and goals; (ii) construction of the intervention logical model; (iii) screening of parties interested in the evaluation; (iv) definition of the evaluative questions; and (v) design of the evaluation matrix. Four priority components were defined for the evaluation: management of the organization and implementation of tuberculosis (TB) prevention and control policy; epidemiological surveillance management; care network management; and management of expected/achieved results. In this model, and based on theoretical references, we defined the necessary resources, activities, outputs, outcomes, and the expected impact for each of the policy management components. The management of the TB control program is feasible for evaluation based on the design of its components, the definition of structure and process indicators, and relevant results for the analysis of the management of TB prevention and control actions, as well as its influence on compliance with the agreed indicators and targets aiming at eradicating the disease by 2035.

Epidemiology of and programmatic response to tuberculosis in Solomon Islands: analysis of surveillance data, 2016-2022.

Objective: To identify progress and challenges in the national response to tuberculosis (TB) in Solomon Islands through an epidemiological overview of TB in the country. Methods: A descriptive analysis was conducted using the national TB surveillance data for 2016-2022. Case notifications, testing data, treatment outcomes and screening activities were analysed. Results: The number of case notifications was 343 in 2022, with an average annual reduction of the case notification rate between 2016 and 2022 of 4.7%. The highest case notification rate was reported by Honiara City Council (126/100 000 population) in 2022. The number of people with presumptive TB tested by Xpert® rapidly increased from zero in 2016 to 870 in 2022. Treatment success rate remained consistently high between 2016 and 2022, ranging from 92% to 96%. Screening for HIV and diabetes mellitus (DM) among TB patients in 2022 was 14% and 38%, respectively. Most patients (97%) were hospitalized during the intensive phase of treatment in 2022; in contrast, during the continuation phase, the proportion of patients treated at the community level increased from 1% in 2016 to 63% in 2022. Despite an increase in household contact investigations, from 381 in 2016 to 707 in 2021, the uptake of TB preventive treatment (TPT) was minimal (7% among eligible child contacts). Discussion: This epidemiological analysis in Solomon Islands reveals both notable achievements and challenges in the country's TB programme. One major achievement is a potential actual reduction in TB incidence. Challenges identified were potential underdetection of cases in rural areas, suboptimal community-based care, and insufficient contact tracing and uptake of TPT. It is crucial to address these challenges (e.g. by optimizing resources) to advance the national TB response.

[Annual progress of immunotherapy for tuberculosis in 2023].

As a chronic infectious disease, tuberculosis (TB) is closely related to immune regulation and immune effect. Immunotherapy which can improve the curative effect of tuberculosis and control the spread of tuberculosis, is one of the important means for the comprehensive treatment of tuberculosis. From October 2022 to September 2023, research on the immunotherapy of tuberculosis at home and abroad continues to increase, providing new opportunities for the treatment of multidrug-resistant and extensively drug-resistant tuberculosis. Host-targeted therapy and therapeutic vaccines are new directions for research into TB adjuvant therapy.

"Harm reduction approach for tuberculosis and substance use disorders: A review of approaches and implications in the Indian context".

There are limitations to traditional treatment approaches in addressing the needs of individuals with dual comorbidity of TB and SUD. The concept of harm reduction as a distinct approach to addressing substance use, focusing on minimising the negative consequences associated with it rather than advocating for complete abstinence. Different harm reduction strategies, such as opioid substitution therapy, needle and syringe programmes, testing for viral infections etc. have been effectively employed for SUDs in past. Similarly, TB risk minimization approaches like improving housing and nutrition and focused testing strategies are considered as harm reduction strategies for TB management. The relationship between tuberculosis (TB) and substance use disorders (SUDs) involves a complex interplay of biopsychosocial factors. It is crucial to prioritise integrated and closely monitored care in order to address the treatment challenges and potential drug interactions that may arise. In light of the acknowledged challenges like limited awareness, infrastructure, drug resistance, and stigma, it is imperative to explore potential avenues for the implementation of harm reduction strategies targeting individuals with comorbid TB and SUD in India. Potential strategies for addressing the issue includes a range of measures, such as augmenting investments in healthcare, integrating policies, tackling social determinants, and establishing shared platforms for psychosocial rehabilitation.

India marching towards TB elimination: How far we are.

Tuberculosis continues to be the leading cause of death worldwide. India shares twenty five percent of total tuberculosis population. Programmatic approach to fight against tuberculosis started in this country in the form of National Tuberculosis Program (NTP). In due course of time India adopted many strategic changes in its fight against tuberculosis. The current program named National tuberculosis elimination program (NTEP) has been set up to eliminate TB by 2025. There are some challenges which India need to overcome to achieve its target five years ahead of the sustainable development goals. Insufficient budget, inadequate diagnostic facilities, under-reporting, low success rate, high dropout rate, social stigma are some of the major challenges in the path to achieve a TB elimination status. Besides that, all the backlogs demand for swift performance in identification, notification, and treatment of TB cases. India has all the potential to eliminate tuberculosis. Strengthening of health system, mainstreaming of private sectors, enhancing diagnostic facilities, inclusion of latest diagnostic techniques, addressing social hindrances, and advocacy for higher budget are some of the program strengthening measures, if followed properly, can take India towards a TB free status.

Recombinant mycobacterial DNA-binding protein 1 with post-translational modifications boosts IFN-gamma production from BCG-vaccinated individuals' blood cells in combination with CpG-DNA.

Tuberculosis remains a large health threat, despite the availability of the tuberculosis vaccine, BCG. As BCG efficacy gradually decreases from adolescence, BCG-Prime and antigen-booster may be an efficient strategy to confer vaccine efficacy. Mycobacterial DNA-binding protein 1 (MDP1, namely Rv2986c, hupB or HU) is a major Mycobacterium tuberculosis protein that induces vaccine-efficacy by co-administration with CpG DNA. To produce MDP1 for booster-vaccine use, we have created recombinant MDP1 produced in both Escherichia coli (eMDP1) and Mycolicibacterium smegmatis (mMDP1), an avirulent rapid-growing mycobacteria. We tested their immunogenicity by checking interferon (IFN)-gamma production by stimulated peripheral blood cells derived from BCG-vaccinated individuals. Similar to native M. tuberculosis MDP1, we observed that most lysin resides in the C-terminal half of mMDP1 are highly methylated. In contrast, eMDP1 had less post-translational modifications and IFN-gamma stimulation. mMDP1 stimulated the highest amount of IFN-gamma production among the examined native M. tuberculosis proteins including immunodominant MPT32 and Antigen 85 complex. MDP1-mediated IFN-gamma production was more strongly enhanced when combined with a new type of CpG DNA G9.1 than any other tested CpG DNAs. Taken together, these results suggest that the combination of mMDP1 and G9.1 possess high potential use for human booster vaccine against tuberculosis.

Geographic Equity and Environmental Sustainability of Conference Models: Results of a Comparative Analysis.

We conducted a comparative analysis of in-person, virtual, and hybrid conferences on tuberculosis hosted by Keystone Symposia and examined the number of participants, their country of residence, carbon dioxide equivalents (CO2e) produced, and participant impressions regarding scientific quality. Data were available from three in-person meetings, one virtual meeting, and one hybrid. The virtual conference hosted 2.5-fold more participants compared with the in-person conferences (842 versus an average of 328) from more than double the number of countries (68 versus an average of 33). The virtual conference attracted 4.5-fold more participants from countries with a high burden of tuberculosis, compared with the average in-person conference (209 versus an average of 46). For in-person meetings, an average of 79% of participants were based in high-income countries. For the virtual meeting, 53% of participants were from high-income countries, and 47% from low- and middle-income countries. For the hybrid conference, there were 465 participants from 43 countries, of which 289 attended in person from a total of 20 countries, and 176 participated virtually from 34 countries. Of those who took part in person, 91% were from high-income countries. The average CO2e emissions from an in-person conference was 696 tons of CO2e, with 96.0% from air travel. The virtual meeting produced 0.48 ton of CO2e from electricity usage, a 1,450-fold decrease compared with in-person events. Virtual conferences scored a content quality rating of 87.3% to 90.8% compared with a range of 86.4% to 92.2% for in-person conferences.