Global Tuberculosis Research Articles

Socialization of TB Zero Program During The COVID-19 Pandemic for Residents of Islamic Center Residences in Kediri

Tuberculosis (TB) problem is still a challenge for Indonesia today. The World Health Organization reports that Indonesia is the third country with the highest TB burden globally. All component of society must take a role in dealing with the global TB problem to achieve Zero TB in 2050. As the implementation, the Pesantren 2 Primary Health Care conducted socialization in the Wali Barokah Islamic Center, Kediri City. Socialization about knowledge to residents of Islamic Center, this study aims to determine the essential characteristics of Islamic Center residents against TB disease. Questionnaires related to knowledge were filled out before and after explanation using PowerPoint and leaflet media. By using purposive, sampling method obtained 100 respondents. The survey results showed a significant increase in the knowledge of Islamic Center residents about TB disease after socialization in terms of signs and symptoms of the disease (p < 0.02), modes of transmission (p < 0.02), and methods of prevention of transmission (p < 0.01). Negative attitudes are still visible by stigmatizing TB sufferers from being ostracized (62.7%). The majority of subjects will go to health facilities (6.9%), but subjects still choose not to go for treatment (68%). The presentation of material about TB leads to reduce the burden of TB disease in TB endemic communities by modifying attitudes and behavior.

Miniaturized Rapid Electrochemical Immunosensor Based on Screen Printed Carbon Electrodes for Mycobacterium tuberculosis Detection.

In 2019, over 21% of an estimated 10 million new tuberculosis (TB) patients were either not diagnosed at all or diagnosed without being reported to public health authorities. It is therefore critical to develop newer and more rapid and effective point-of-care diagnostic tools to combat the global TB epidemic. PCR-based diagnostic methods such as Xpert MTB/RIF are quicker than conventional techniques, but their applicability is restricted by the need for specialized laboratory equipment and the substantial cost of scaling-up in low- and middle-income countries where the burden of TB is high. Meanwhile, loop-mediated isothermal amplification (LAMP) amplifies nucleic acids under isothermal conditions with a high efficiency, helps in the early detection and identification of infectious diseases, and can be performed without the need for sophisticated thermocycling equipment. In the present study, the LAMP assay was integrated with screen-printed carbon electrodes and a commercial potentiostat for real time cyclic voltammetry analysis (named as the LAMP-Electrochemical (EC) assay). The LAMP-EC assay was found to be highly specific to TB-causing bacteria and capable of detecting even a single copy of the Mycobacterium tuberculosis (Mtb) IS6110 DNA sequence. Overall, the LAMP-EC test developed and evaluated in the present study shows promise to become a cost-effective tool for rapid and effective diagnosis of TB.

Prevalence and Predictors of Pulmonary Tuberculosis among Prison Inmates in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

Prisoners in Sub-Saharan Africa (SSA) are at a high risk of tuberculosis (TB) infection due to overcrowding and poor ventilation. Consequently, TB is a leading cause of morbidity and mortality in prison, and many inmates face a number of barriers to TB control and had limited information in the region. Thus, the aim of this systematic review and meta-analysis was to estimate the overall pooled prevalence of pulmonary TB and predictors among prison inmates in SSA. From 2006 to 2019, a systematic review and meta-analysis was conducted using various databases, including PubMed, Embase, Web of Science, and Scopus. The data were extracted in Microsoft Excel using a standardized data extraction format, and the analysis was carried out with STATA version 14. To detect heterogeneity across studies, the I2 and the Cochrane Q test statistics were computed. To determine the overall prevalence of TB and predictors among prison populations, a random effect meta-analysis model was used. Of the 3,479 retrieved articles, 37studies comprising 72,844 inmates met the inclusion criteria. The pooled prevalence of pulmonary TB among prison inmates in SSA was 7.74% (95% CI: 6.46-8.47). In the subgroup analysis, the highest prevalence was found in the Democratic Republic Congo (DRC) (19.72%) followed by Zambia (11.68%) and then Ethiopia (9.22%). TB/HIV coinfection (OR 4.99 (95% CI: 2.60-9.58)), Body mass index (BMI < 18.5) (OR 3.62 (95% CI: 2.65-6.49)), incarceration (OR 4.52 (95% CI: 2.31-5.68)), and previous TB exposure (OR 2.43 (95% CI: 1.61-3.56)) had higher odds of pulmonary TB among inmates. The prevalence of pulmonary TB among SSA prison inmates was found to be high as compared to total population. TB/HIV coinfection, BMI, incarceration duration, and TB exposure were all predictors with pulmonary tuberculosis in prison inmates. As a result, emphasizing early screening for prisoners at risk of pulmonary TB is an important point to achieving global TB commitments in resource-limited settings.

Practical Models of Pharmaceutical Care for Improving Tuberculosis Patient Detection and Treatment Outcomes: A Systematic Scoping Review.

Decreasing global tuberculosis (TB) notifications indicate problems related to TB patient detection and treatment outcomes. Pharmaceutical care (PC) has potential roles in managing these issues. However, PC practices have not yet become widespread in the real world. This systematic scoping review aimed to identify and analyze the current literature on practical models of pharmaceutical care for improving tuberculosis patient detection and treatment outcomes. We then discussed the present challenges and future considerations for the successful implementation of PC services in TB. A systematic scoping review was performed to identify the practice models of PC in TB. Systematic searches and screening were used to identify relevant articles in the PubMed and Cochrane databases. We then discussed the challenges and recommendations for successful implementation using a framework to improve professional healthcare practice. Our analysis included 14 of 201 eligible articles. We identified that the focuses in the PC of TB are on increasing patient detection (four articles) and improving TB treatment outcomes (ten articles). Practices cover services in the community and hospital settings, such as screening and referring people with presumptive TB, tuberculin test services, collaborative practices for treatment completion, directly observed treatment, the solution of drug-related problems, reporting and managing adverse drug reactions, and medication adherence programs. Although PC services positively increase TB patient detection and treatment outcomes, hidden challenges in the actual practice are analyzed. Several factors should be comprehensively considered in successful implementation, such as guidelines, individual pharmacy personnel, patient, professional interaction, organizational capacity, regulation, incentive, and resource factors. Hence, a collaborative PC program that involves all related stakeholders should be considered to create successful and sustainable PC services in TB.

Cartridge Based Nucleic Acid Amplification Test, an Important Diagnostic Tool for Tuberculosis both Pulmonary and Extra-Pulmonary Tuberculosis

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB), one of the top 10 causes of death worldwide (ranking above HIV/AIDS). About a quarter of the world's population is infected with TB and thus at risk of developing TB disease. The Global TB Report 2019 states that in 2018 a total of 1.5 million people died from TB, an estimated 10 million (range, 9.0–11.1 million) people fell ill worldwide.(1) Eight countries accounted for two-thirds of the total, with India leading the count, followed by China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh, and South Africa.(1) Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health security threat. The WHO estimates that there were 484 000 new cases with resistance to rifampicin (RIF) – the most effective first-line drug, which accounts for 78% MDR-TB cases. The MDR-TB burden largely falls on three countries – India, China, and the Russian Federation. About 6.2% of MDR-TB cases had extensively drug-resistant TB (XDR-TB) in 2018. Worldwide, only 56% of MDR-TB patients are currently successfully treated. Globally, TB incidence is falling at about 2% per year. This needs to accelerate to a 4%–5% annual decline to reach the 2020 milestones of the End TB Strategy.

Amorphous Drug Nanoparticles for Inhalation Therapy of Multidrug-Resistant Tuberculosis.

Tuberculosis (TB) is one of the most prevalent infectious diseases. The global TB situation is further complicated by increasing patient numbers infected with Mycobacterium tuberculosis (M.tb.) strains resistant to either one or two of the first-line therapeutics, promoted by insufficient treatment length and/or drug levels due to adverse reactions and reduced patient compliance. An intriguing approach to improve anti-TB therapy relates to nanocarrier-based drug-delivery systems, which enhance local drug concentrations at infection sites without systemic toxicity. Recently developed anti-TB antibiotics, however, are lipophilic and difficult to transport in aqueous systems. Here, the very lipophilic TB-antibiotics bedaquiline (BDQ) and BTZ (1,3-benzothiazin-4-one 043) are prepared as high-dose, amorphous nanoparticles via a solvent-antisolvent technique. The nanoparticles exhibit mean diameters of 60 ± 13 nm (BDQ) and 62 ± 44 nm (BTZ) and have an extraordinarily high drug load with 69% BDQ and >99% BTZ of total nanoparticle mass plus a certain amount of surfactant (31% for BDQ, <1% for BTZ) to make the lipophilic drugs water-dispersible. Suspensions with high drug load (4.1 mg/mL BDQ, 4.2 mg/mL BTZ) are stable for several weeks. In vitro and in vivo studies employing M.tb.-infected macrophages and susceptible C3HeB/FeJ mice show promising activity, which outperforms conventional BDQ/BTZ solutions (in DMF or DMSO) with an up to 50% higher efficacy upon pulmonary delivery. In vitro, the BDQ/BTZ nanoparticles demonstrate their ability to cross the different biological barriers and to reach the site of the intracellular mycobacteria. In vivo, high amounts of the BDQ/BTZ nanoparticles are found in the lung and specifically inside granulomas, whereas only low BDQ/BTZ-nanoparticle levels are observed in spleen or liver. Thus, pulmonary delivered BDQ/BTZ nanoparticles are promising formulations to improve antituberculosis treatment.

When should we be able to divert the cost of tuberculosis to other diseases?

Dear Editor, A country’s development and progress are based on its economy and gross domestic product (GDP). A recently published article in your journal introduces the past, present, and future of the Indian economy specifically related to healthcare. The author has nicely described the high burden of communicable and noncommunicable diseases. The authors have covered tuberculosis (TB) under communicable disease. We want to add some perspective to point out the status of TB burden on the Indian health economy.[1] Southeast Asian countries share more than 40% of the global TB burden and India is one of them. India belongs to the bracket of lower-middle-income countries.[2] Each and every single expenditure thing will have an effect on our country’s economy, either the share market or the healthcare system. As per recently published data, the Indian economy cost around $32 billion every year in TB-related fatalities.[1] TB is an old and infectious disease that makes a patient immunocompromised. TB patients have more chance to get other infectious diseases which makes patient’s life more troublesome in health and wealth both ways. The World Health Organization (WHO) and Government provide free testing and treatment for TB patients but this is not enough to control and eliminate the disease.[3] Majority of the patients belong to the lower and lower-middle-class family, which does not have the facility to get proper nutritious food; due to malnourishment, the patient does not get the treatment benefits that they need. Various studies revealed that several risk factors are responsible for the development of TB specifically drug-resistant TB and malnutrition, low body mass index, and low economy are few of them.[4] The Indian government is giving some amount to the patient to comply with treatment but that is not enough. To get benefits from the government, patients need to pass various documentary processes. Many patients stop the treatment in between due to these hectic procedures.[5] WHO and the government had the goal of END TB program to eradicate TB from India by the year 2025. Government and supportive people are on the right way but coronavirus disease 2019 (COVID-19) pandemic took us back foot.[6] TB not only is a fatal disease but also puts a lot of stress on the treasury. So, if TB is eliminated, a lot of funds can then be diverted to take care of other infectious diseases. So realistically, we can eliminate TB maybe by 2030. Out of all the programs mentioned, maybe TB is one entity, we can believe can be taken care of monetarily. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Expedited diagnosis of pediatric tuberculosis using Truenat MTB-Rif Dx and GeneXpert MTB/RIF

Rapid, cost-effective, and sensitive diagnostic assays are essential for global tuberculosis (TB) control, especially in high TB burden, resource-limited settings. The current study was designed to evaluate diagnostic accuracy of Truenat MTB-Rif Dx (MolBio) in children less than 18 years of age, with symptoms suggestive of TB. Gastric aspirate, induced sputum, and broncho-alveolar lavage samples were subjected simultaneously to AFB-smear, GeneXpert MTB/RIF, liquid culture (MGIT-960) and Truenat MTB-Rif Dx. The index-test results were evaluated against microbiological reference standards (MRS). Truenat MTB-Rif Dx had a sensitivity of 57.1%, specificity of 92% against MRS. The sensitivity and specificity of the Truenat MTB-RIF Dx compared with liquid culture was 58.7% and 87.5% while GeneXpert MTB/RIF was 56% and 91.4%. The performance of both GeneXpert MTB/RIF and Truenat MTB-Rif Dx are comparable. Result of our study demonstrates that Truenat MTB-Rif can aid in early and efficient diagnosis of TB in children.

Multiplex LNA probe-based RAP assay for rapid and highly sensitive detection of rifampicin-resistant Mycobacterium tuberculosis.

The World Health Organization (WHO) Global tuberculosis Report 2021 stated that rifampicin-resistant tuberculosis (RR-TB) remains a major public health threat. However, the in-practice diagnostic techniques for RR-TB have a variety of limitations including longer time, lack of sensitivity, and undetectable low proportion of heterogeneous drug resistance. Here we developed a multiplex LNA probe-based RAP method (MLP-RAP) for more sensitive detection of multiple point mutations of the RR-TB and its heteroresistance. A total of 126 clinical isolates and 78 sputum samples collected from the National Tuberculosis Reference Laboratory, China CDC, were tested by MLP-RAP assay. In parallel, qPCR and Sanger sequencing of nested PCR product assay were also performed for comparison. The sensitivity of the MLP-RAP assay could reach 5 copies/μl using recombinant plasmids, which is 20 times more sensitive than qPCR (100 copies/μl). In addition, the detection ability of rifampicin heteroresistance was 5%. The MLP-RAP assay had low requirements (boiling method) for nucleic acid extraction and the reaction could be completed within 1 h when placed in a fluorescent qPCR instrument. The result of the clinical evaluation showed that the MLP-RAP method could cover codons 516, 526, 531, and 533 with good specificity. 41 out of 78 boiled sputum samples were detected positive by MLP-RAP assay, which was further confirmed by Sanger sequencing of nested PCR product assay, on the contrary, qPCR was able to detect 32 samples only. Compared with Sanger sequencing of nested PCR product assay, both the specificity and sensitivity of the MLP-RAP assay were 100%. MLP-RAP assay can detect RR-TB infection with high sensitivity and specificity, indicating that this assay has the prospect of being applied for rapid and sensitive RR-TB detection in general laboratories where fluorescent qPCR instrument is available.

Geographical evolutionary pathway of global tuberculosis incidence trends

BackgroundsTuberculosis (TB) remains a serious public health and human development problem, especially in developing countries. Despite the effectiveness of directly observed therapy, short course programs in reducing transmission and progression of TB, poverty reduction and socioeconomic development remain crucial factors in decreasing TB incidence. However, the geographical pathway on the planet is not yet clear.ObjectivesThis study was to reconstruct the geographical evolutionary process of TB in 173 countries and territories from 2010 to 2019 to analyze the socioeconomic determinants that impact the global TB epidemic. In addition, the TB incidence in 2030 was predicted.MethodsThis study analyses TB incidence data from 173 countries and territories between 2010 and 2019. The Geotree model would be used to reconstruct the geographical evolutionary process of TB, which provides a simplified schema for geo-visualizing the trajectories of TB incidence and their socioeconomic drivers. Additionally, to estimate the future TB incidence in 2030, a multilevel model was utilized in conjunction with the hierarchical nature of the Geotree based on a stratified heterogeneity analysis.ResultsGlobal TB incidence was found to be associated with the country type and development stages. Between 2010 and 2019, the average TB incidence rate in 173 countries and territories was -27.48%, with marked spatially stratified heterogeneity by country type and development stage. Low-income and lower-middle-income countries were most vulnerable to TB. Upper-middle-income countries experienced a faster decline in TB incidence than high-income countries, and TB incidence generally decreased as the development stage increased, except for the lower-middle development stage in 2019.The highest average rate of decline in TB incidence was observed in the upper-middle development stage of high-income countries, with a reduction of 45.24%. Meanwhile, 37 high-income countries in the high development stage demonstrated an average rate of change of -13.93%. Socioeconomic determinants, including gross domestic product per capita, urbanization rate, and sociodemographic index, were found to inhibit TB incidence. Based on current trends, the predicted average global TB incidence in 2030 is 91.581 per 100,000 population.ConclusionsThe trajectories of the global TB incidence have been reconstructed to formulate targeted public health responses. To eliminate TB, countries at similar development stage can draw on the experiences of countries at higher development stages that are tailored to their unique characteristics. By learning from successful TB control strategies, countries can take strategic steps toward eradicating TB and improving public health outcomes.

A novel multi-component protein vaccine ECP001 containing a protein polypeptide antigen nPstS1 riching in T-cell epitopes showed good immunogenicity and protection in mice.

Tuberculosis (TB) is an infectious disease that seriously affects human health. Until now, the only anti-TB vaccine approved for use is the live attenuated Mycobacterium bovis (M. bovis) vaccine - BCG vaccine, but its protective efficacy is relatively low and does not provide satisfactory protection against TB in adults. Therefore, there is an urgent need for more effective vaccines to reduce the global TB epidemic. In this study, ESAT-6, CFP-10, two antigens full-length and the T-cell epitope polypeptide antigen of PstS1, named nPstS1, were selected to form one multi-component protein antigens, named ECP001, which include two types, one is a mixed protein antigen named ECP001m, the other is a fusion expression protein antigen named ECP001f, as candidates for protein subunit vaccines. were prepared by constructing one novel subunit vaccine by mixing or fusing the three proteins and combining them with aluminum hydroxide adjuvant, and the immunogenicity and protective properties of the vaccine was evaluated in mice. The results showed that ECP001 stimulated mice to produce high titre levels of IgG, IgG1 and IgG2a antibodies; meanwhile, high levels of IFN-γ and a broad range of specific cytokines were secreted by mouse splenocytes; in addition, ECP001 inhibited the proliferation of Mycobacterium tuberculosis in vitro with a capacity comparable to that of BCG. It can be concluded that ECP001 is a novel effective multicomponent subunit vaccine candidate with potential as BCG Initial Immunisation-ECP001 Booster Immunisation or therapeutic vaccine for M. tuberculosis infection.

A study of analysis on prevalence, serological marker and prognosis of tuberculosis in tertiary care hospital

BackgroundTuberculosis is an infectious disease responsible for a significant cause of ill health. According to the WHO global tuberculosis report 2021. 9.9 million cases fell sick with TB in 2020. Significantly, the prevalence of tuberculosis in India is 25%. ObjectiveTo analyze the prevalence of tuberculosis in the suburban areas of the metropolitan city in South India. To analyze the serological marker and prognosis of tuberculosis among males and females. To determine the importance of molecular testing - PCR confirmation on TB after AFB smear. MethodsA retrospective study to analyze 462 patients enrolled by the respiratory medicine department on suspecting pulmonary- 356 (M−264 & F-92) and extra-pulmonary-106 (M-73&F-33) patients and diagnosed Zhiel-Neelsen staining, Mantoux test, Chip-based RT-PCR test, Erythrocyte sedimentation rate, and analyzed serological test such as C-Reactive Protein, Chemiluminescence immune assay. Results23 patients were positive in Ziehl-Neelsen staining, 65 were positive in molecular True-Nat PCR test, Mantoux skin test induration in 10 patients, 98 TB Positive patients examined in the serological analysis, 1 & 3 patients reacted in HIV/HBsAg, and HBsAg test respectively, by chemiluminescence immunoassay, 8 PTB and 4 EPTB and 47 non-TB patients were positive in C-reactive protein, 46 TB and 94 non-TB patients detected abnormal values out of these 160 patients in ESR test. ConclusionThe Prevalence of tuberculosis is significantly rising, especially in the middle-aged population. The rapid molecular diagnostics to detect TB are highly sensitive and specific. Serological markers are essential for the analysis of disease prognosis and need to focus on the guidance of DOTS and RNTCP to End TB.

Synthesis of plant-based, self-adjuvanted, dual antigen specific to Mycobacterium tuberculosis as a novel tuberculosis subunit vaccine that elicits immunogenicity in rabbit.

The only approved vaccine, Bacillus Calmette Guérin (BCG) used in global tuberculosis (TB) immunization programmes has been very effective in childhood TB but not in adult pulmonary and latent TB. Moreover, the emergence of multi-drug resistance-TB cases demands either to increase efficiency of BCG or replace it with the one with improved efficacy. A novel combination of two most effective secreted protein antigens specific for Mycobacterium tuberculosis (Mtb), ESAT-6 and MPT-64 (but not present in BCG strains) fused with a cholera toxin B subunit (CTB) and tagged with 6xHis was expressed for the first time in Escherichia coli as well as in transgenic cucumber plants developed using Agrobacterium tumefaciens-mediated transformation. The recombinant fusion protein (His6x.CTB-ESAT6-MPT64) expressed in E. coli was purified by a single-step affinity chromatography and used to produce polyclonal antibodies in rabbit. The transgenic cucumber lines were confirmed by polymerase chain reaction (PCR), Southern blot hybridization, reverse transcriptase PCR (RT-PCR), real-time PCR (qRT-PCR) and expression of recombinant fusion protein by western blot analysis and its quantification by enzyme-linked immunosorbent assay (ELISA). A maximum value of the fusion protein, 478ng.g-1 (0.030% of the total soluble protein) was obtained in a transgenic cucumber line. Rabbit immunized orally showed a significant increase in serum IgG levels against the fusion protein as compared to the non-immunized rabbit. Stable expression of Mtb antigens with CTB in edible cucumber plants (whose fruits are eaten raw) in sufficient amount possibly would facilitate development of a safe, affordable and orally delivered self-adjuvanted, novel dual antigen based subunit vaccine against TB.

Exploration of the diversity of multi-drug resistant Mycobacterium tuberculosis complex in Lagos, Nigeria using WGS: Distribution of lineages, drug resistance patterns and genetic mutations

Multidrug-resistant (MDR) or extensively drug-resistant (XDR) Tuberculosis (TB) is a major challenge to global TB control. Therefore, accurate tracing of in-country MDR-TB transmission are crucial for the development of optimal TB management strategies. This study aimed to investigate the diversity of MTBC in Nigeria. The lineage and drug-resistance patterns of the clinical MTBC isolates of TB patients in Southwestern region of Nigeria were determined using the WGS approach. The phenotypic DST of the isolates was determined for nine anti-TB drugs. The sequencing achieved average genome coverage of 65.99X. The most represented lineages were L4 (n = 52, 83%), L1 (n = 8, 12%), L2 (n = 2, 3%) and L5 (n = 1, 2%), suggesting a diversified MTB population. In term of detection of M/XDR-TB, while mutations in katG and rpoB genes are the strong predictors for the presence of M/XDR-TB, the current study also found the lack of good genetic markers for drug resistance amongst the MTBC in Nigeria which may pose greater problems on local tuberculosis management efforts. This high-resolution molecular epidemiological data provides valuable insights into the mechanistic for M/XDR TB in Lagos, Nigeria.

Global prevalence of hepatitis B or hepatitis C infection among patients with tuberculosis disease: systematic review and meta-analysis

There is a substantial overlap in the epidemiology of chronic hepatitis B (HBV), hepatitis C (HCV) and tuberculosis (TB) due to overlapping risk factors. Testing for viral hepatitis is not widely recommended for patients with TB. The aim of this systematic review was to evaluate the global prevalence of chronic viral hepatitis infection among patients with TB. MEDLINE, EMBASE, Web of Science, Cochrane Library, African Journals Online, LILACS, and country TB reports were searched for studies published between January 1st, 2011 and June 17th 2021. Random-effects meta-analyses for proportions were conducted to obtain pooled prevalences. The prevalence of chronic HBV/HCV infection among patients with TB was also compared to that in the general population. The protocol was registered on PROSPERO (CRD42021276468). This analysis included 127 studies (83 for both HBV and HCV, 28 for HBV only, and 25 for HCV only) and data from 94,936 patients. The global pooled seroprevalence was 5.8% (95% CI 5.0-6.8) for HBs-antigen and 10.3% (95% CI 8.4-12.3) for HCV-antibodies. Pooled prevalence was highest in the WHO African Region for HBV at 7.8% (95% CI 5.2-10.9) and in the WHO European Region at 17.5% (95% CI 12.2-23.5) for HCV. In studies among TB patients who inject drugs, HCV prevalence was 92.5% (95% CI 80.8-99.0). Pooled HCV-antibody seroprevalence among patients with TB was higher than in the general population in all six WHO regions while HBs-antigen seroprevalence was higher in 3/6 regions. This review highlights the syndemicity of chronic viral hepatitis and TB and suggests that routine testing for hepatitis upon TB diagnosis may be justified. The prevalence of chronic HBV and HCV infections was higher among patients with TB than in the general population. This study was study was funded by the Global Tuberculosis Programme, World Health Organization.

Maintenance and recall of memory T cell populations against tuberculosis: Implications for vaccine design.

Despite the widespread use of standardised drug regimens, advanced diagnostics, and Mycobacterium bovis Bacille-Calmette-Guérin (BCG) vaccines, the global tuberculosis (TB) epidemic remains uncontrollable. To address this challenge, improved vaccines are urgently required that can elicit persistent immunologic memory, the hallmark of successful vaccines. Nonetheless, the processes underlying the induction and maintenance of immunologic memory are not entirely understood. Clarifying how memory T cells (Tm cells) are created and survive long term may be a crucial step towards the development of effective T cell-targeted vaccines. Here, we review research findings on the memory T cell response, which involves mobilization of several distinct Tm cell subsets that are required for efficient host suppression of M. tuberculosis (Mtb) activity. We also summaries current knowledge related to the T cell response-based host barrier against Mtb infection and discuss advantages and disadvantages of novel TB vaccine candidates.

Exploring biogenic chalcones as DprE1 inhibitors for antitubercular activity via in silico approach.

Cases of drug-resistant tuberculosis (TB) have increased worldwide in the last few years, and it is a major threat to global TB control strategies and the human population. Mycobacterium tuberculosis is a common causative agent responsible for increasing cases of TB and as reported by WHO, approximately, 1.5 million death occurred from TB in 2020. Identification of new therapies against drug-resistant TB is an urgent need to be considered primarily. The current investigation aims to find the potential biogenic chalcone against the potential targets of drug-resistant TB via in silico approach. The ligand library of biogenic chalcones was screened against DprE1. Results of molecular docking and in silico ADMET prediction revealed that ZINC000005158606 has lead-like properties against the targeted protein. Pharmacophore modeling was done to identify the pharmacophoric features and their geometric distance present in ZINC000005158606. The binding stability study performed using molecular dynamics (MD) simulation of the DprE1-ZINC000005158606 complex revealed the conformational stability of the complex system over 100ns with minimum deviation. Further, the in silico anti-TB sensitivity of ZINC000005158606 was found to be higher as compared to the standards against Mycobacterium tuberculosis. The overall in silico investigation indicated the potential of identified hit to act as a lead molecule against Mycobacterium tuberculosis.

Prevalence and factors associated with tuberculosis among the mining communities in Mererani, Tanzania.

Tuberculosis (TB) is among diseases of global health importance with Sub Saharan Africa (SSA) accounting for 25% of the global TB burden. TB prevalence among miners in SSA is estimated at 3,000-7,000/100,000, which is about 3 to 10-times higher than in the general population. The study's objective was to determine the prevalence of TB and associated risk factors among mining communities in Mererani, northern Tanzania. This was a cross-sectional study conducted from April 2019 to November 2021 involving current Small Scale Miners (SSM) and the General Community (GC). A total of 660 participants, 330 SSM and 330 GC were evaluated for the presence of TB. Data were analysed using Statistical Package for the Social Sciences (SPSS) database (IBM SPSS Statistics Version 27.0.0.0). Binary logistic regression (Generalized Linear Mixed Model) was used to determine the association between TB and independent predictors. Prevalence of TB was 7%, about 24-times higher than the national prevalence of 0.295%. Participants from the general community had higher prevalence of TB 7.9% than SSM (6.1%). Both for SSM and the GC, TB was found to be associated with: lower education level (aOR = 3.62, 95%CI = 1.16-11.28), previous lung disease (aOR = 4.30, 95%CI = 1.48-12.53) and having symptoms of TB (aOR = 3.24, 95%CI = 1.38-7.64). Specifically for the SSM, TB was found to be associated with Human Immunodeficiency Virus (HIV) infection (aOR = 8.28, 95%CI = 1.21-56.66). Though significant progress has been attained in the control of the TB epidemic in Tanzania, still hot spots with significantly high burden of TB exists, including miners. More importantly, populations surrounding the mining areas, are equally affected, and needs more engagement in the control of TB so as to realize the Global End TB targets of 2035.

Withaferin A Protects against Primary and Recurrent Tuberculosis by Modulating Mycobacterium-Specific Host Immune Responses.

The fate of Mycobacterium tuberculosis infection is governed by immune signaling pathways that can either eliminate the pathogen or result in tuberculosis (TB). Anti-TB therapy (ATT) is extensive and is efficacious only against active, drug-sensitive strains of M. tuberculosis. Due to severe side effects, ATT often causes impairment of host immunity, making it imperative to use novel immunotherapeutics for better clinical outcomes. In this study, we have explored the immunomodulatory potential of withaferin A (WA) as an immunotherapeutic against TB. Here, we demonstrate that WA can constrain intracellular drug-sensitive and -resistant strains of M. tuberculosis by augmenting host immune responses. We also established the potential of WA treatment in conjunction with isoniazid. We show that WA directs the host macrophages toward defensive M1 polarization and enhances TH1 and TH17 immune responses against M. tuberculosis infection. The reduced bacterial burden upon T cell adoptive transfer further corroborated the augmented T cell responses. Interestingly, WA stimulated the generation of T cell memory populations by instigating STAT signaling, thereby reducing the rate of TB recurrence due to reactivation and reinfection. We substantiate the prospects of WA as a potent adjunct immunomodulator that enriches protective memory cells by prompting STAT signaling and improves host defense against M. tuberculosis. IMPORTANCE Despite being extensive, conventional antituberculosis therapy (ATT) is barely proficient in providing sterile immunity to tuberculosis (TB). Failure to constrain the escalating global TB burden due to the emergence of drug-resistant bacterial strains and immune dampening effects of ATT necessitates adjunct immunotherapeutics for better clinical outcomes. We evaluated the prospects of withaferin A (WA), an active constituent of Withania somnifera, as an adjunct immunomodulator against diverse M. tuberculosis strains. WA efficiently restricts the progression of TB by stimulating antimycobacterial host responses, protective immune signaling, and activation of diverse immune cell populations. Protective effects of WA can be attributed to the enrichment of memory T cells by induction of STAT signaling, thereby enhancing resistance to reinfections and reactivation of disease. We ascertained the immunotherapeutic potential of WA in boosting host immune responses against M. tuberculosis.

Impact of COVID-19 on diagnosis of tuberculosis, multidrug-resistant tuberculosis, and on mortality in 11 countries in Europe, Northern America, and Australia. A Global Tuberculosis Network study

ObjectivesAlthough evidence is growing on the overall impact of the COVID-19 pandemic on tuberculosis (TB) services, global studies based on national data are needed to better quantify the extent of the impact and the countries’ preparedness to tackle the two diseases. The aim of this study was to compare the number of people with new diagnoses or recurrence of TB disease, the number of drug-resistant (DR)-TB, and the number of TB deaths in 2020 vs 2019 in 11 countries in Europe, Northern America, and Australia. MethodsTB managers or directors of national reference centers of the selected countries provided the agreed-upon variables through a validated questionnaire on a monthly basis. A descriptive analysis compared the incidence of TB and DR-TB and mortality of the pre-COVID-19 year (2019) vs the first year of the COVID-19 pandemic (2020). ResultsComparing 2020 vs 2019, lower number of TB cases (new diagnosis or recurrence) was notified in all countries (except USA-Virginia and Australia), and fewer DR-TB notifications (apart from France, Portugal, and Spain). The deaths among TB cases were higher in 2020 compared to 2019 in most countries with three countries (France, The Netherlands, USA-Virginia) reporting minimal TB-related mortality. ConclusionsA comprehensive evaluation of medium-term impact of COVID-19 on TB services would benefit from similar studies in multiple settings and from global availability of treatment outcome data from TB/COVID-19 co-infected patients.