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In pandemic conditions, situation of active and uncontrolled use by population of antimicrobial preparations treating COVID-19 occurs. So, new risks of development of medication resistance among patients with various infectious diseases, tuberculosis included, appear. The purpose of the study is to characterize prevalence of antimicrobial preparations use by population in relationship with development of medication resistance in patients with tuberculosis during COVID-19 pandemic. Material and methods. The analysis of sales of antimicrobial medicines was implemented on the basis of published official data from the joint-stock company DSM Group presenting monthly audit of the Russian pharmaceutical market. The determination of primary antibiotic resistance was carried out in 2018-2020 on 3312 patients with tuberculosis. The modified method of proportions on liquid nutrient medium in system with automated accounting of microorganisms growth, the method of absolute concentrations and the method of polymerase chain reaction with real-time detection were applied. The results of the study. It was established that the most demanding antimicrobial medications among population were ceftriaxone, azithromycin, levofloxacin, moxifloxacin, azithromycin. At the same time, the maximum increase in sales in 2020 up to 150% as compared with of 2019 was determined in medications derived from quinolone moxifloxacin, levofloxacin, which began to be used in treatment of coronavirus infection. At the same time, these medications are traditionally used in tuberculosis treatment. But in 2020, alarming trend was established that limits treatment of tuberculosis patients. The primary resistance of mycobacteria was also established in newly diagnosed tuberculosis patients, also for the same antimicrobial medications of quinolone derivatives, and increasing in proportion of patients with primary medication resistance to levofloxacin, moxifloxacin in 2020 as compared to 2018 was 189-480%. At the same time, increasing of resistance to other antibiotics made up to 60.8% on average. Conclusion. The study results imply alarming scenario of medication resistance shifts towards very virulent and highly medication-resistant genotypes. This trend can result in conditions of successful transmission of deadly medication-resistant mutants that can seriously undermine effectiveness of implemented programs of struggle with tuberculosis worldwide.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), which is a major threat to global public health. Currently, β-lactam antibiotics are rarely used in the treatment of TB, since Mtb naturally expresses β-lactamase (Blac) which renders Mtb resistant to such antibiotics due to β-lactam cleavage. Fortunately, antibiotic resistance can be overcome when β-lactam antibiotics are combined with a Blac inhibitor. With the current research, a near-infrared fluorescent probe LXMB was developed for the real-time detection and imaging of endogenous Blac activity in Mtb. Furthermore, a high-throughput screening platform was established using LXMB to screen Blac inhibitors from herbal medicines. Guided by the visual bioassay, Tannic acid was isolated from Galla Chinensis as a potential Blac inhibitor and was further evaluated in combination with several β-lactam antibiotics which resulted in an enhanced inhibitory effect toward M. tuberculosis H37Ra. Finally, LXMB was used to label live M. tuberculosis H37Ra phagocytosed within macrophages. Consequently, LXMB was a useful fluorescent tool to explore the mechanism of drug resistance based on Blac and can assist in the development of new tuberculosis treatments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Tuberculosis is a chronic respiratory disease caused by Mycobacterium tuberculosis. The common treatment regimens of tuberculosis are lengthy with adverse side effects, low patient compliance, and antimicrobial resistance. Drug delivery systems (DDSs) can overcome these limitations., Objective: This review aims to summarize the latest DDSs for the treatment of tuberculosis. In the first section, the main pharmacokinetic and pharmacodynamic challenges posed by the innate properties of the drugs are put forth. The second section elaborates on the use of DDS to overcome the disadvantages of the current treatment of tuberculosis., Conclusion: We reviewed research articles published in the last 10 years. DDSs can improve the physicochemical properties of anti-tuberculosis drugs, improving solubility, stability, and bioavailability, with better control of drug release and can target alveolar macrophages. However, more pre-clinical studies and robust bio-relevant analyses are needed for DDSs to become a feasible option to treat patients and attract investors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: To appropriately treat tuberculosis (TB) with regimens that combine novel and older drugs, evidence-based, context-specific strategies for drug-susceptibility testing (DST) will be required., Methods: We created a Markov state-transition model of 100 000 adults with TB receiving a novel, fluoroquinolone (FQ)-containing regimen. We estimated clinical outcomes and resource utilization with no FQ-DST, universal FQ-DST, or FQ-DST only for patients with rifampin-resistant TB ("targeted FQ-DST"). We considered scenarios of stronger (South Africa) and weaker (Southeast Asia) correlation of fluoroquinolone resistance with rifampin resistance, with sensitivity analysis for other setting and regimen characteristics., Results: Relative to no FQ-DST, targeted FQ-DST increased cure of FQ-resistant TB by 7.5% (interquartile range [IQR], 6.7%-9.2%) in South Africa and 1.7% (IQR, 0.7%-2.5%) in Southeast Asia. However, rare FQ resistance among the more prevalent rifampin-susceptible TB accounted for 50% of FQ-resistant TB in South Africa and 83% in Southeast Asia. As a result, universal FQ-DST further increased cure of FQ-resistant TB by 3.4% (IQR, 2.3%-5.4%) in South Africa and 5.8% (IQR, 5.1%-6.3%) in Southeast Asia. With targeted FQ-DST, 1 additional patient was cured per 50 (IQR, 42-70) tests in South Africa and 44 (IQR, 37-51) in Southeast Asia. When expanding from targeted to universal FQ-DST, 1 additional cure required 3500 (IQR, 2300-5500) tests in South Africa and 410 (IQR, 370-450) in Southeast Asia., Conclusions: FQ-DST improved patient outcomes and was particularly important for high-risk patient groups and less robust regimens. A universal strategy was favored in generalized epidemics of fluoroquinolone resistance., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Tuberculosis has been reaffirmed as the infectious disease causing most deaths in the world. Co-infection with HIV and the increase in multi-drug resistant Mycobacterium tuberculosis strains complicate treatment and increases mortality rates, making the development of new drugs an urgent priority. In this study we have identified a promising candidate by screening antimicrobial peptides for their capacity to inhibit mycobacterial growth. This non-toxic peptide, NZX, is capable of inhibiting both clinical strains of M. tuberculosis and an MDR strain at therapeutic concentrations. The therapeutic potential of NZX is further supported in vivo where NZX significantly lowered the bacterial load with only five days of treatment, comparable to rifampicin treatment over the same period. NZX possesses intracellular inhibitory capacity and co-localizes with intracellular bacteria in infected murine lungs. In conclusion, the data presented strongly supports the therapeutic potential of NZX in future anti-TB treatment., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: To evaluate the utility of Simultaneous Amplification and Testing (SAT-TB) Method for monitoring anti-TB treatment response., Methods: Serial morning sputum specimens were obtained from 377 active pulmonary tuberculosis (PTB) cases at baseline, weeks 2, months 2, 5 and 6 (newly diagnosed patients) or 8 (previously treated patients) for AmpSure assay, smear fluorescence microscopy (FM) and BACTEC MGIT 960 culture assay., Results: After treatment of 2 weeks, sputum culture was positive in 280 patients (74.27%). Among whom, 219 patients tested positive for SAT-TB assay and 143 patients smear FM positive. The detection rate of SAT-TB (78.21%) was significantly higher than sputum FM (51.07%, χ2 = 45.128, P < 0.001). At the end of the second month of treatment, 157 patients (41.64%) were still culture-positive, 115 patients of them SAT-TB positive and 79 smear FM positive. The difference of detection rate between SAT-TB (73.25%) and sputum FM (50.32%) was significant (χ2 = 17.480, P < 0.001). When patients underwent five months of treatment, 65 patients (17.24%) with sputum culture positive was defined as treatment failure. Among whom, 60 patients (92.31%) were SAT-TB positive and 38 patients (58.46%) were smear FM positive. The detection rate of SAT-TB assay was significantly higher than sputum FM (χ2 = 17.333, P < 0.001)., Conclusion: Results of AmpSure assays for monitoring treatment responses can be obtained without waiting for the results of BACTEC MGIT 960 assays and most patients with treatment failures could be detected after 5 months.

Biomarkers for tuberculosis treatment outcome will assist in guiding individualized treatment and evaluation of new therapies. To identify candidate biomarkers, RNA sequencing of whole blood from a well-characterized TB treatment cohort was performed. Application of a validated transcriptional correlate of risk for TB revealed symmetry in host gene expression during progression from latent TB infection to active TB disease and resolution of disease during treatment, including return to control levels after drug therapy. The symmetry was also seen in a TB disease signature, constructed from the TB treatment cohort, that also functioned as a strong correlate of risk. Both signatures identified patients at risk of treatment failure 1-4 weeks after start of therapy. Further mining of the transcriptomes revealed an association between treatment failure and suppressed expression of mitochondrial genes before treatment initiation, leading to development of a novel baseline (pre-treatment) signature of treatment failure. These novel host responses to TB treatment were integrated into a five-gene real-time PCR-based signature that captures the clinically relevant responses to TB treatment and provides a convenient platform for stratifying patients according to their risk of treatment failure. Furthermore, this 5-gene signature is shown to correlate with the pulmonary inflammatory state (as measured by PET-CT) and can complement sputum-based Gene Xpert for patient stratification, providing a rapid and accurate alternative to current methods., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ethionamide (ETH) and prothionamide (PTH), both thioamides, have proven efficacy in clinical studies and form important components for multidrug-resistant tuberculosis treatment regimens and for treatment of tuberculous meningitis in adults and children. ETH and PTH are pro-drugs that, following enzymatic activation by mycobacterial EthA inhibit InhA, a target shared with isoniazid (INH), and subsequently inhibit mycolic acid synthesis of Mycobacterium tuberculosis. Co-resistance to INH and ETH is conferred by mutations in the mycobacterial inhA promoter region; mutations in the ethA gene often underlie ETH and PTH monoresistance. An oral daily dose of ETH or PTH of 15-20 mg/kg with a maximum daily dose of 1000 mg is recommended in children to achieve adult-equivalent serum concentrations shown to be efficacious in adults, although information on optimal pharmacodynamic targets is still lacking. Gastrointestinal disturbances, and hypothyroidism during long-term therapy, are frequent adverse effects observed in adults and children, but are rarely life-threatening and seldom necessitate cessation of ETH therapy. More thorough investigation of the therapeutic effects and toxicity of ETH and PTH is needed in childhood TB while child-friendly formulations are needed to appropriately dose children., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Time to liquid culture positivity (TTP) is a technically accessible and widely available measure of viable mycobacterial load in sputum samples. We describe the ability of TTP to predict colony forming unit counts of Mycobacterium tuberculosis from sputum samples collected before or during the first 14 days of antituberculosis therapy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

C3HeB/FeJ mice infected with Mycobacterium tuberculosis were used in an experimental animal model mimicking active tuberculosis in humans to evaluate the effect of antiinflammatory agents. No other treatment but ibuprofen was given, and it was administered when the animals' health started to deteriorate. Animals treated with ibuprofen had statistically significant decreases in the size and number of lung lesions, decreases in the bacillary load, and improvements in survival, compared with findings for untreated animals. Because antiinflammatory agents are already on the market, further clinical trials should be done to evaluate this effect in humans as soon as possible, to determine their suitability as coadjuvant tuberculosis treatment.

In the context of the evolving global health landscape shaped by the COVID-19 pandemic, tuberculosis (TB) is gaining renewed attention as a reemerging threat even in low-endemic countries. Immunological tests such as the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) are pivotal in identifying tuberculosis infection (TBI). However, their inability to distinguish between past and ongoing infection poses a diagnostic challenge, possibly leading to the unnecessary treatment of a significant portion of the population with potential side effects. This review delves into the concept of incipient tuberculosis (ITB), a dynamic, presymptomatic stage characterized by heightened Mycobacterium tuberculosis complex (MTC) metabolic activity and replication that result in minimal radiological changes, signifying a transitional state between TBI and TB. Key focus areas include epidemiological factors, underlying pathogenesis, imaging findings, and the ongoing challenges in the identification of individuals with ITB through the development of new biomarkers and the use of whole-genome sequencing-based analyses to implement early treatment strategies. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis complex (MTBC). Antituberculosis drugs given to active TB sufferers consist of 3 or 4 combinations. Tuberculosis treatment is divided into intensive phase treatment (2 weeks) and continuation phase (16 weeks / 4 months). Interferon gamma (IFN γ) is a protein belonging to the cytokine family which plays a role in eliminating MTB bacteria through a cell-mediated immunity mechanism. The aim of this study was to analyze differences in gamma interferon levels in the intensive phase and advanced phase of tuberculosis treatment. This research method is an analytical observational study with a cross-sectional design (cross sectional study). The research design used was a randomized post test only control group design. Data were analyzed using the Kruskal Wallis test with statistical test results obtained with a p value of 0.033 (> 0.05), meaning there was a difference in IFN γ levels in the intensive phase and advanced phase of tuberculosis treatment. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is a prevalent bacterial infection caused by Mycobacterium tuberculosis (Mtb), primarily affecting the lungs, with rising incidence rates. Drug-resistant TB strains, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) types, pose challenges with poor treatment success rates and increased mortality. Demographic factors and genomic patterns contribute to drug resistance, emphasizing the need for new drugs targeting specific genomic patterns. Methods: This study analyzes the impact of demographics, treatment outcomes, and genomic mutations on drug-resistant TB using pattern identification techniques and whole-genome sequencing to discover therapeutic targets. This study primarily focused on the identification and analysis of MDR and XDR strains, considering various demographic characteristics and treatment outcomes. A dataset comprising 2,602 observations was utilized, and pattern recognition techniques were employed to identify significant features. Additionally, the study employs the whole-genome sequencing (WGS) pipeline to identify single nucleotide polymorphisms (SNPs) that result in new mutations in drug-resistant Mtb strains. Results: The findings of the study revealed that XDR and MDR non-XDR TB were the most prevalent types of drug resistance, and they were associated with unfavorable treatment outcomes, including death or treatment failure. Males exhibited a higher susceptibility to both XDR and MDR non-XDR TB compared to females. The age of onset for both types of resistance was approximately 40 years. Among the observed variants in 31 commonly occurring genes. Conclusion: These findings introduce a novel set of therapeutic targets specific to MDR and XDR Mtb types, which warrant further investigation for potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Blitar district was in the last second position in East Java Province, achieving low Tuberculosis recovery and treatment of the national target by 2022. Therefore, it is necessary to support surveillance systems as a prerequisite for providing information as decision-making material. Purpose: to describe the quality of the tuberculosis surveillance system based on its approach and attributes. Methods: This research was an evaluation study design on the tuberculosis surveillance system in 2022. Respondents totaled 19 people. Data was collected by interview using a questionnaire and document study using a checklist. Data was analyzed by comparing the system approach and surveillance attributes to existing guidelines. The data was presented in tables and narratives. Results: Evaluation of tuberculosis surveillance systems based on input, process, and output was available by surveillance guidelines. Evaluation of the surveillance attributes showed that the flexible system has high data quality, high sensitivity, timeliness, and high stability. However, the system is not simple in operation, has low acceptability of the network, and has low positive predictive value because the suspect detection is too loose and not representative. Conclusion: The implementation of the tuberculosis surveillance system has largely been carried out well, supported by several complete surveillance attributes. It is necessary to provide standard operational procedures for recording and reporting, improve coordination with the network to manually and electronically report suspected tuberculosis, and optimize the Mantoux test in children. [ABSTRACT FROM AUTHOR]

Global tuberculosis (TB) eradication is undermined by increasing prevalence of emerging resistance to available drugs, fuelling ongoing demand for more complex diagnostic and treatment strategies. Early detection of TB drug resistance coupled with therapeutic decision making guided by rapid characterisation of pre-treatment and treatment emergent resistance remains the most effective strategy for averting Drug-Resistant TB (DR-TB) transmission, reducing DR-TB associated mortality, and improving patient outcomes. Solid- and liquid-based mycobacterial culture methods remain the gold standard for Mycobacterium tuberculosis (MTB) detection and drug susceptibility testing (DST). Unfortunately, delays to result return, and associated technical challenges from requirements for specialised resource and capacity, have limited DST use and availability in many high TB burden resource-limited countries. There is increasing availability of a variety of rapid nucleic acid-based diagnostic assays with adequate sensitivity and specificity to detect gene mutations associated with resistance to one or more drugs. While a few of these assays produce comprehensive calls for resistance to several first- and second-line drugs, there is still no endorsed genotypic drug susceptibility test assay for bedaquiline, pretomanid, and delamanid. The global implementation of regimens comprising these novel drugs in the absence of rapid phenotypic drug resistance profiling has generated a new set of diagnostic challenges and heralded a return to culture-based phenotypic DST. In this review, we describe the available tools for rapid diagnosis of drug-resistant tuberculosis and discuss the associated opportunities and challenges. [ABSTRACT FROM AUTHOR]

This paper discusses the stability analysis of the model for the spread of tuberculosis and the effects of treatment. It is shown the analyze the dynamic behavior of the model to investigate the local stability properties of the model equilibrium point. The Routh-Hurwitz criterion is used to analyze local stability at the disease-free equilibrium point, while the Transcritical Bifurcation theorem is used to investigate the local stability properties of the endemic equilibrium point. The discussion results show that the equilibrium point's stability properties depend on the value of the basic reproduction number, which is calculated based on the Next Generation Matrix (NGM). When the basic reproduction number value is less than one, then the disease-free equilibrium point is locally asymptotically stable, whereas if it is more than one, then the endemic equilibrium point is locally asymptotically stable. Numerical simulations are included to explain the dynamic behavior of disease spread and to understand the effectiveness of tuberculosis treatment in a given population. The simulation results show that treatment in the infected individual phase is known to be more effective than treatment in latent individuals. [ABSTRACT FROM AUTHOR]

Objective: Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis, which causes disease in all organs, 80% of which are in the lungs, and can sometimes spread to other organs. It can lead to death in untreated or inadequately treated patients. Treatment of tuberculosis is very difficult due to the resistance of mycobacteria to many chemicals and disinfectants, antibiotics, and chemotherapeutics, especially in immunocompromised patients (HIV, Human Immunodeficiency Virus); this disease is very common. Therefore, in recent years, the search for new drugs to be used to treat tuberculosis has increased worldwide. We aim to determine the effect of orientin and vitexin on M. tuberculosis strains. Materials and Methods: In this study, the effects of orientin and vitexin against M. tuberculosis standard strains (M. tuberculosis H37Ra and M. tuberculosis H37Rv) and six-clinical M. tuberculosis strains. The inoculum was prepared using a positive BACTEC "Mycobacteria Growth Indicator Tube" containing 7H9 Broth. Microplate Presto Blue Method and rifampicin were used as standard antibiotics in the anti-mycobacterial assay. Results: Orientin and vitexin showed a mycobactericidal effect on tuberculosis strains depending on the concentration. Orientin and vitexin have not been tested on current clinical strains of M. tuberculosis before. In this respect, it is the first report describing the anti-mycobacterial activity of both orientin and vitexin. Conclusion: These results indicate that orientin and vitexin may be helpful for further investigations into their role in inhibiting M. tuberculosis. They have a possibility of new anti-mycobacterial drug candidates in the near future. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb). Mtb affects not only the respiratory system but also other body organs, such as the lungs, leading to pulmonary and extrapulmonary TB, the brain, and the spine. Aspilia pluriceta from Meru Betiri National Park in Indonesia is one plant with potential for Mycobacterium tuberculosis. This study aimed to determine the antituberculosis activity of extracts and fractions of Aspilia pluriceta against Mycobacterium tuberculosis H37Rv. Aspilia pluriceta was extracted by maceration with methanol, and the crude methanol extract was fractionated successively with hexane, dichloromethane (DCM), and ethyl acetate. The phytochemical of the crude extract was determined by TLC and visualised by spraying with appropriate staining reagents. The crude extract and fractions of Aspilia pluriceta at concentrations 25, 100, 500, and 1000 µg/mL, respectively, were tested against the H37Rv strain of Mycobacterium tuberculosis using the resazurin method and analysed by an ELISA reader. Isoniazid, a first-line drug used in the treatment of tuberculosis, was used as the positive control agent. The phytochemical screening test revealed the presence of saponins, alkaloids, tannins, flavonoids, and terpenes. The results of anti-TB showed that the ethyl acetate fraction exhibited the most potent activity against Mycobacterium tuberculosis H37Rv with an IC50 value of 0.48 µg/mL. The crude extract and other fractions exhibited low activity against the tested organism. The findings showed that the plant holds potential for phytochemicals with antituberculosis activity, which could be further explored through bioactivity-guided isolation for leads against Mycobacterium tuberculosis. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to analyze the demographic, clinical, histopathological, diagnosis, treatment, and follow‐up data on the occurrence of oral and maxillofacial tuberculosis (OMTB). Methods: Electronic searches without publication date restrictions were undertaken in four databases. Case reports and case series describing the occurrence of OMTB were included. Critical evaluation of studies was done using the Joanna Briggs Institute – University of Adelaide tool for case reports or case series. Results: A total of 217 studies were included in the qualitative synthesis, for a total of 301 cases of OMTB. Of these patients, 192 (63.7%) were male, with an average age of 39.6 ± 19.8 (15 months to 81 years). The tongue (n = 80/26.6%) represented the most common affected site, followed by the mandible (n = 43/14.3%). The clinical presentation consisted mainly of a painful ulcerated lesion (n = 156/56.5%). Histopathological analysis showed a granulomatous inflammation in most cases (n = 156/63.1%). The main diagnostic methods used were sputum test (n = 53/26.8%), culture (n = 49/24.7%) and purified protein derivative (PPD), or Mantoux test (n = 49/24.7%). Antituberculosis therapy was used in 244 cases (100.0%) and 5.2% of patients died. Conclusions: This systematic review provided clinical, demographic data and information about diagnostic methods of OMTB lesions and served as an important guide to assist health professionals in the early diagnosis of these lesions. [ABSTRACT FROM AUTHOR]

Background Drug-resistant tuberculosis (DR-TB) is a global challenge. Owing to its high annual mortality and morbidity rates, as stated in the annual global TB reports provided by WHO, the prevalence of multidrug-resistant tuberculosis (MDR-TB) or rifampicin-resistant tuberculosis was shown to be increasing worldwide in 2021. Patients with tuberculosis from 2018 to 2022 represented ~40 million individuals, including 1.5 million with DR-TB. The study's goal was to identify MDR-TB prevalence and risk factors in Jazan, Saudi Arabia. Patients and methods The research was done on 114 patients diagnosed with pulmonary TB in Jazan Chest Hospital from January to April, 2019. Demographic data were collected. Monteux test, chest radiograph, sputum smear, and Lowenstein–Jensen culture were performed for all patients with pulmonary TB. Patients were allocated in either group A, with 103 (90.4%) patients, if they had Mycobacterium tuberculosis-susceptible isolates, or in group B, with 11 (9.7%) patients, if they had M. tuberculosis-resistant isolates. Results The observed overall DR-TB prevalence was 9.7%. The proportion of MDR isolates was 7%, polyresistant isolate TB was 0.9%, rifampicin-resistant tuberculosis was 0.9%, and ethambutol-resistant TB was 0.9%. Females were more in group B (54.5%) than in group A (26.2%). Unmarried patients were higher in group A (60.2%) than in group B (29.3%). Comorbidities had significant values in the drug-resistant groups (90.9%). Conclusion The study showed that screening and treatment of DR-TB are crucial for the control of TB in Jazan and Saudi Arabia as a whole. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a significant public health concern in the 21st century, especially due to drug resistance, coinfection with diseases like immunodeficiency syndrome (AIDS) and coronavirus disease 2019, and the lengthy and costly treatment protocols. In this review, we summarize the pathogenesis of TB infection, therapeutic targets, and corresponding modulators, including first‐line medications, current clinical trial drugs and molecules in preclinical assessment. Understanding the mechanisms of Mycobacterium tuberculosis (Mtb) infection and important biological targets can lead to innovative treatments. While most antitubercular agents target pathogen‐related processes, host‐directed therapy (HDT) modalities addressing immune defense, survival mechanisms, and immunopathology also hold promise. Mtb's adaptation to the human host involves manipulating host cellular mechanisms, and HDT aims to disrupt this manipulation to enhance treatment effectiveness. Our review provides valuable insights for future anti‐TB drug development efforts. [ABSTRACT FROM AUTHOR]

A new series of symmetric acridin-9-yl-bis-benzothiazol-2-yl-amines have been synthesized in good to excellent yields by intra-molecular cyclization of 1-acridin-9-yl-1-benzothiazol-2-yl-3-aryl thiourea and screened for their in vitro antitubercular activity against Mycobacterium tuberculosis by BACTEC radiometric method. The synthesis of new analogues bearing an acridine-linked chloro-substituted benzothiazole has demonstrated enhanced antituberculosis activity. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a disease of public health concern in Nigeria as the country is listed among the 30 high TB burden countries in the world. It is caused by Mycobacterium tuberculosis, an airborne pathogen. Tuberculosis disease is a manifestation of an active state of the infection when host immune response has been overwhelmed. Leucocytes participate in immune response, and traditionally, the total and differential counts have been useful in offering general outlook on inflammation as well as immunodeficiency. Lately, leucocyte derivatives such as neutrophil-tolymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) have been reported as better markers of inflammation in some disease conditions. This study assessed total and differential leucocyte counts together with the derivatives in active tuberculosis infection among 80 tuberculosis patients and equal number of matched controls. Total and differential leucocyte counts were determined using standard haematology autoanalyzer, while the ratios were mathematically derived. Data were analyzed and hypotheses tested using student's t-test on statistical package for social sciences (SPSS) version 21. A p-value of ≤0.05 was considered as statistically significant. Neutrophil-lymphocyte ratio was significantly higher in TB patients, while lymphocyte-monocyte ratio was significantly lower in TB patients than the control. Furthermore, neutrophil-lymphocyte ratio was significantly higher, while the lymphocytemonocyte ratio was significantly lower in TB patients at diagnosis (n=26) in comparison with those on treatment (n=54). There is derangement in leucocyte derivatives in association with tuberculosis. These derivatives improved significantly as anti-TB treatment progressed. Therefore, these variables could serve as useful indicators in the monitoring of treatment for TB patients. [ABSTRACT FROM AUTHOR]

We have studied the antimycobacterial efficacy of the liposomal preparation of mycobacteriophage D29 on models of tuberculous granuloma in vitro and in the experiment on laboratory mice of the relatively resistant strain C57BL/6, infected with the virulent strain of M. tuberculosis H37Rv. We have shown the preparation of liposomal preparation of the lytic mycobacteriophages and its characteristics. The experiments showed a significant lytic effect of the liposomal form of mycobacteriophage D29 both on the model of tuberculous granuloma formed by human blood mononuclear cells in vitro, which is formed in the presence of Mycobacterium tuberculosis and on the model of tuberculous infection in C57BL/6 mice. Keywords: mycobacteriophage D29, M. tuberculosis, liposomes, tuberculous granuloma in vitro, tuberculosis infection and its treatment. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (MT) is a widespread bacterium which usually attacks the lungs causing tuberculous pneumonia, but it can also occupy any other part of our body. One of the MT strains discovered in 1995 in China, known as the Beijing type, is extremely dangerous because of its increased antibiotic resistance. The most efficient method to properly identify this strain is genotyping which is based on the analysis of the MT genome. Symptoms of tuberculosis caused by the Beijing type may be similar to normal MT strain; however, there are some discrepancies. The most significant step in the diagnostic process is to determine the range of antibiotic resistance. These strains usually show a multi-drug resistant or extremely drug resistant phenotype. [ABSTRACT FROM AUTHOR]

Tuberculosis (T.B.) is a disease that occurs due to infection by the bacterium, Mycobacterium tuberculosis (Mtb), which is responsible for millions of deaths every year. Due to the emergence of multidrug and extensive drug-resistant Mtb strains, there is an urgent need to develop more powerful drugs for inclusion in the current tuberculosis treatment regime. In this study, 1778 molecules from four medicinal plants, Azadirachta indica, Camellia sinensis, Adhatoda vasica, and Ginkgo biloba, were selected and docked against two chosen drug targets, namely, Glutamine Synthetase (G.S.) and Isocitrate Lyase (I.C.L.). Molecular Docking was performed using the Glide module of the Schrӧdinger suite to identify the best-performing ligands; the complexes formed by the best-performing ligands were further investigated for their binding stability via Molecular Dynamics Simulation of 100 ns. The present study suggests that Azadiradione from Azadirachta indica possesses the potential to inhibit Glutamine Synthetase and Isocitrate Lyase of M. tuberculosis concomitantly. The excellent docking score of the ligand and the stability of receptor-ligand complexes, coupled with the complete pharmacokinetic profile of Azadiradione, support the proposal of the small molecule, Azadiradione as a novel antitubercular agent. Further, wet lab analysis of Azadiradione may lead to the possible discovery of a novel antitubercular drug. [ABSTRACT FROM AUTHOR]

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Rationale: Completion of preventive therapy is a major bottleneck in global tuberculosis control. Long-acting injectable drug formulations would shorten therapy administration and may thereby improve completion rates. Recently, a long-acting formulation of bedaquiline demonstrated antituberculosis activity for up to 12 weeks after injection in a validated mouse model of preventive therapy. Objectives: The objectives of this study were to 1) determine the total duration of activity after an injection of long-acting bedaquiline and 2) evaluate the activity of regimens comprised of long-acting bedaquiline plus short (2-4 wk) oral companion courses of bedaquiline, with or without rifapentine, using the validated mouse model of tuberculosis preventive therapy. Methods: After the establishment of a stable Mycobacterium tuberculosis lung infection in bacillus Calmette-Guérin (BCG)-immunized BALB/c mice, treatment was initiated with 1 of 12 randomly assigned regimens. In addition to positive and negative controls, six regimens included one or two injections of long-acting bedaquiline (alone or with oral bedaquiline with or without rifapentine), and four comparator regimens consisted of oral agents only. Lung bacterial burden was measured monthly for up to 28 weeks. Measurements and Main Results: One injection of long-acting bedaquiline at 160 mg/kg exerted antituberculosis activity for 12 weeks. Compared with the positive control (daily isoniazid-rifapentine for 4 wk), six regimens had equivalent bactericidal activity (including two all-oral comparator regimens), and two regimens had superior sterilizing activity: one injection with 2 weeks of oral bedaquiline and high-dose rifapentine; and two injections with 4 weeks of oral bedaquiline. Conclusions: Long-acting injectable bedaquiline has significant potential for shortening tuberculosis preventive therapy. [ABSTRACT FROM AUTHOR]

Phase IIb trials of tuberculosis therapy rely on early biomarkers of treatment effect. Despite limited predictive ability for clinical outcomes, culture conversion, the event in which an individual previously culture positive for Mycobacterium tuberculosis yields a negative culture after initiating treatment, is a commonly used endpoint. Lack of consensus on how to define the outcome and corresponding measure of treatment effect complicates interpretation and limits between-trial comparisons. We review common analytic approaches to measuring treatment effect and introduce difference in restricted mean survival times as an alternative to identify faster times to culture conversion and express magnitude of effect on the time scale. Findings from the PanACEA MAMS-TB trial are reanalyzed as an illustrative example. In a systematic review we demonstrate variability in analytic approaches, sampling strategies, and outcome definitions in phase IIb tuberculosis trials. Harmonization would allow for larger meta-analyses and may help expedite advancement of new tuberculosis therapeutics. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) are present in elevated numbers in tuberculosis patients and have been found to be permissive for Mycobacterium tuberculosis proliferation. To determine whether depletion of MDSCs may improve host control of tuberculosis, we used a novel diphtheria toxin-based fusion protein DABIL-4 that targets and depletes interleukin 4 (IL-4) receptor-positive cells. We show that DABIL-4 depletes both polymorphonuclear MDSCs and monocytic MDSCs, increases interferon-γ + T cells, and reduces the lung bacillary burden in a mouse tuberculosis model. These results indicate that MDSC-depleting therapies targeting the IL-4 receptor are beneficial in tuberculosis and offer an avenue towards host-directed tuberculosis therapy. [ABSTRACT FROM AUTHOR]

Eastern countries are a major source of medicinal plants, which set up a rich source of ethnopharmacologically known medicines used in the treatment of various diseases. These traditional medicines have been known as complementary, alternative, or nonconventional therapy across globe for ages. Tuberculosis (TB) poses a huge global burden and leads to maximum number of deaths due to an infectious agent. Treatment of TB using Directly Observed Treatment Short-course (DOTS) therapy comprises multiple antibiotics is quite lengthy and causes serious side-effects in different organs. The length of the TB treatment leads to withdrawal from the patients, which paves the way for the emergence of drug resistance in the bacterial population. These concerns related to therapy need serious and immediate interventions. Traditional medicines using phytochemicals has shown to provide tremendous potential in TB treatment,mainly in the eradication of Mycobacterium tuberculosis (M.tb), increasing natural immunity, and managing the side effects of anti-TB drugs. This review describes the antituberculosis potential of selected ethnopharmacologically important phytochemicals as potential immune-modulator and as an adjunct-therapy in TB. This review will be a useful reference for researchers working on ethnopharmacology and will open the door for the discovery of novel agents as an adjunct-therapy to tuberculosis. [ABSTRACT FROM AUTHOR]

Multidrug resistance tuberculosis (MDR-TB) associated with the development of resistance to fluoroquinolones (FQs) especially ofloxacin is a matter of concern, as they had been earlier recommended drugs for usage in the MDR-TB treatment regimens, and moxifloxacin and other quinolones are still on the list. Mycobacterium tuberculosis acquires resistance to FQs mainly through mutations in the quinolone resistance determining regions (QRDRs) of the gyrA gene and less frequently in the gyrB gene. A literature search on the geographical distribution of ofloxacin resistance in TB shows that there is a mild surge in reporting of the resistance to ofloxacin in tuberculosis patients. Molecular tests demonstrating mutations in gyrA and gyrB genes is widely used to detect ofloxacin resistance and the broadly available commercial assay for the rapid detection of second-line-drug resistance, including FQ resistance, the GenoType MTBDRsl assay (Hain Life science, Nehren, Germany), detects the most common mutations found in the QRDR of gyrA while its new version 2.0 detects mutations in the gyrB as well. It has been shown that on reviewing the frequency and geographic distribution of gyrA and gyr B mutations associated with FQ resistance, there do exist geographic differences in the frequencies within and across countries. Cross-resistance to FQs is an area of concern, although some studies show that concordance in resistance among the FQ agents, lower level of cross-resistance has also been reported. The presence of ofloxacin resistance is an alarm signal while Moxifloxacin and other FQs are still the recommended drugs for the resistant TB cases. The WHO recommendation that ofloxacin be phased out from MDR-TB regimens is well justified. It is important that rationale usage of ofloxacin is needed for preventing ofloxacin resistance, to aid in the management of tuberculosis. [ABSTRACT FROM AUTHOR]

With an estimated 25% of the global population infected with Mycobacterium tuberculosis (Mtb), tuberculosis (TB) remains a leading cause of death by infectious diseases. Humoral immunity following TB treatment is largely uncharacterized, and antibody profiling could provide insights into disease resolution. Here we focused on the distinctive TB-specific serum antibody features in active TB disease (ATB) and compared them with latent TB infection (LTBI) or treated ATB (txATB). As expected, di-galactosylated glycan structures (lacking sialic acid) found on IgG-Fc differentiated LTBI from ATB, but also discriminated txATB from ATB. Moreover, TB-specific IgG4 emerged as a novel antibody feature that correlated with active disease, elevated in ATB, but significantly diminished after therapy. These findings highlight 2 novel TB-specific antibody changes that track with the resolution of TB and may provide key insights to guide TB therapy. [ABSTRACT FROM AUTHOR]

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SapM is a secreted virulence factor from Mycobacterium tuberculosis critical for pathogen survival and persistence inside the host. Its full potential as a target for tuberculosis treatment has not yet been exploited because of the lack of potent inhibitors available. By screening over 1500 small molecules, we have identified new potent and selective inhibitors of SapM with an uncompetitive mechanism of inhibition. The best inhibitors share a trihydroxy-benzene moiety essential for activity. Importantly, the inhibitors significantly reduce mycobacterial burden in infected human macrophages at 1 µM, and they are selective with respect to other mycobacterial and human phosphatases. The best inhibitor also reduces intracellular burden of Francisella tularensis, which secretes the virulence factor AcpA, a homologue of SapM, with the same mechanism of catalysis and inhibition. Our findings demonstrate that inhibition of SapM with small molecule inhibitors is efficient in reducing intracellular mycobacterial survival in host macrophages and confirm SapM as a potential therapeutic target. These initial compounds have favourable physico-chemical properties and provide a basis for exploration towards the development of new tuberculosis treatments. The efficacy of a SapM inhibitor in reducing Francisella tularensis intracellular burden suggests the potential for developing broad-spectrum antivirulence agents to treat microbial infections. [ABSTRACT FROM AUTHOR]

Humans have been infected with Mycobacterium tuberculosis (Mtb) for thousands of years. While tuberculosis (TB), one of the deadliest infectious diseases, is caused by uncontrolled Mtb infection, over 90% of presumed infected individuals remain asymptomatic and contain Mtb in a latent TB infection (LTBI) without ever developing disease, and some may clear the infection. A small number of heavily Mtb-exposed individuals appear to resist developing traditional LTBI. Because Mtb has mechanisms for intracellular survival and immune evasion, successful control involves all of the arms of the immune system. Here, we focus on immune responses to Mtb in humans and nonhuman primates and discuss new concepts and outline major knowledge gaps in our understanding of LTBI, ranging from the earliest events of exposure and infection to success or failure of Mtb control. [ABSTRACT FROM AUTHOR]

Several studies have evaluated the association between killer-cell immunoglobulin-like receptors (KIR) genes and susceptibility risk to tuberculosis (TB) infection. Nonetheless, their outcomes have not been conclusive and consistent. Here we implemented a systematic review and meta-analysis of KIR genes association to susceptibility risk of pulmonary TB (PTB) infection to attain a clear understanding of the involvement of these genes in susceptibility to PTB infection. A systematic search was conducted in the MEDLINE/PubMed and Scopus databases to find case-control studies published before November 2020. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated to determine the association between KIR genes and risk of PTB infection. After comprehensive searching and implementing the inclusion and exclusion criteria, 10 case-control studies were included in the meta-analysis. Four KIR genes were found to have significant positive association with PTB susceptibility risk of infection, including 2DL3 (OR = 1.454, 95% CI = 1.157–1.827; P = 0.001), 2DS1 (OR = 1.481, 95% CI = 1.334–1.837; P < 0.001), 2DS4 (OR = 1.782, 95% CI = 1.273–2.495; P = 0.001) and 3DL1 (OR = 1.726, 95% CI = 1.277–2.333; P < 0.001). However, the results showed that the remaining KIR genes (2DS2-4, 2DL1, 2, 4, 3DL1-2) and two pseudogenes (2DP1 and 3DP1) did not have significant associations with risk of PTB infection. This meta-analysis provides reliable evidence that the KIR genes 2DL3, 2DS1, 2DS4, and 3DL1 may be associated with an increased risk of PTB infection. [ABSTRACT FROM AUTHOR]

Evidence is limited for infection prevention and control (IPC) measures reducing Mycobacterium tuberculosis (MTB) transmission in health facilities. This systematic review, 1 of 7 commissioned by the World Health Organization to inform the 2019 update of global tuberculosis (TB) IPC guidelines, asked: do triage and/or isolation and/or effective treatment of TB disease reduce MTB transmission in healthcare settings? Of 25 included articles, 19 reported latent TB infection (LTBI) incidence in healthcare workers (HCWs; absolute risk reductions 1%–21%); 5 reported TB disease incidence in HCWs (no/slight [high TB burden] or moderate [low burden] reduction) and 2 in human immunodeficiency virus-positive in-patients (6%–29% reduction). In total, 23/25 studies implemented multiple IPC measures; effects of individual measures could not be disaggregated. Packages of IPC measures appeared to reduce MTB transmission, but evidence for effectiveness of triage, isolation, or effective treatment, alone or in combination, was indirect and low quality. Harmonizing study designs and reporting frameworks will permit formal data syntheses and facilitate policy making. [ABSTRACT FROM AUTHOR]

Tuberculosis is the leading cause of death among people living with HIV (PLH). Preventive tuberculosis therapy reduces mortality in PLH, especially in those with a positive tuberculin skin test (TST). New, more specific technologies for detecting latent tuberculosis infection (LTBI) are now commercially available. We sought to analyse the cost-effectiveness of four different strategies for the diagnosis of LTBI in PLH in Brazil, from the Brazilian public health care system perspective. We developed a Markov state-transition model comparing four strategies for the diagnosis of LTBI over 20 years. The strategies consisted of TST with the currently used protein purified derivative (PPD RT 23), two novel skin tests using recombinant allergens (Diaskintest [Generium Pharmaceutical, Moscow, Russia] and EC [Zhifei Longcom Biologic Pharmacy Co., Anhui, China]), and the QuantiFERON-TB-Gold-Plus (Qiagen, Hilden, Germany). The main outcome was cost (in 2020 US dollars) per quality-adjusted life years (QALY). For the base case scenario, the Diaskintest was dominant over all other examined strategies. The cost saving estimate per QALY was US $1375. In sensitivity analyses, the Diaskintest and other newer tests remained cost-saving compared to TST. For PLH, TST could be replaced by more specific tests in Brazil, considering the current national recommendations. [ABSTRACT FROM AUTHOR]

This article outlines the significant scientific progress reported in 2019 that has led to the development of new drugs and therapeutic regimens, vaccine candidates, and diagnostics for the prevention and treatment of tuberculosis. In 2020, it will be important to build on this momentum and continue to advance basic and clinical research to develop improved tools and interventions, simultaneously optimizing their implementation in national control programs. To successfully achieve the goal to end tuberculosis within a generation, a concerted, collective, and collaborative effort is required, involving government, academia, industry and civil society at all levels. [ABSTRACT FROM AUTHOR]

Objectives. This study is aimed at evaluating the clinical application value of RNA simultaneous amplification and testing method for Mycobacterium tuberculosis (SAT-TB) combined with acid-fast staining in the diagnosis and treatment of pulmonary tuberculosis (PTB). Methods. This paper included 168 suspected and confirmed PTB sufferers admitted to The Sixth People's Hospital of Wenzhou from December 2018 to December 2019, whose sputum was collected and tested using SAT-TB, smear acid-fast staining method, and the BACTEC MGIT 960 system. With the MGIT 960 culture test method as the gold standard, the application value of SAT-TB, acid-fast staining, or SAT-TB combined with acid-fast staining in the diagnosis and treatment of PTB was assessed. Results. With the MGIT 960 culture as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of SAT-TB for the diagnosis of PTB were 57.3%, 92.5%, 84.3%, and 73.5%, respectively. The conformity was 76.8%, and the Kappa value was 0.515, suggesting a statistically significant difference ( χ 2 = 7.314 , p < 0.05) and a general consistency degree. Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value of SAT-TB combined with sputum smear acid-fast staining were 81.3%, 86.0%, 88.4%, and 80.8%, respectively, with the MGIT 960 culture still the gold standard. The conformity and Kappa value were 83.9% and 0.672, respectively, showing no statistically significant difference ( χ 2 = 0.438 , p > 0.05) and a relatively high consistency degree. Conclusion. SAT-TB combined with acid-fast staining had a similar detection rate to that of the MGIT 960 culture test with a high consistency degree, which could be applied in the diagnosis of PTB efficiently and accurately. [ABSTRACT FROM AUTHOR]

Genitourinary tuberculosis (GUTB) is associated with significant morbidity and mortality. As patients with GUTB have no specific symptoms or clinical features, early diagnosis and treatment of GUTB is clinically challenging. The present study assessed the current spectrum of clinical presentation, urinary findings and radiological signs of patients with GUTB. Patients with confirmed GUTB (n = 53) were analysed for clinical presentation, diagnostic tests and management. Data about demographic details, clinical presentation, urine routine examination, urine acid-fast bacillus (AFB) smear test, urine Mycobacterium tuberculosis culture, routine blood investigations, radiological, cystoscopic and histopathological examinations were recorded for all study patients. Various surgical interventions were performed on the basis of the site involved. After surgical procedure, patients were treated with chemotherapy and followed up for one year to till date. The present study patients were from the age range of 19–75 years with female preponderance. The most common clinical presentation was irritative voiding symptoms (69.81%), haematuria and flank pain (56.60%, each). The most commonly affected organ was kidney (62.26%) following ureter (30.19%), urinary bladder (24.53%), prostate (9.43%) and epididymis (1.89%). The urine AFB smear and urine culture for M. tuberculosis tests were positive in 13.18% and 54.71% of patients, respectively. Surgical interventions were done in majority (75.47%) of patients. Accurate and early diagnosis is vital for the better management of patients with GUTB. Apart from the available course of chemotherapy, surgical intervention is also required for complete management. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is one of the diseases causing high rate of morbidity and mortality worldwide. Amongst high TB burden countries Pakistan ranks fifth, with an estimated new TB cases of 510,000 emerging each year. Worldwide resistance to anti-tubercular drugs is a serious public health issue. Objective: This study was aimed to determine Mycobacterium tuberculosis (MTB) prevalence both in respiratory and non-respiratory clinical samples, their resistance to the first line Anti-tubercular drug especially to Rifampicin, hence to determine Multidrug resistant Tuberculosis prevalence in the region. Method: This study was carried out to elucidate Mycobacterium tuberculosis (MTB) prevalence and their Rifampicin resistance among patients of Ayub teaching hospital and nearby districts in Hazara division of Pakistan from July 2017 to September 2019. Total 276 clinical samples were collected (both respiratory and non-respiratory) and screened by Zeihl-Neelsen (ZN) staining initially for the presence of Acid-Fast bacilli (AFB). Samples were further subjected to GeneXpert assay for detection of Mycobacterium Tuberculosis and Rifampicin resistance. Results: Out of 276 samples, 68 (24.64%) were AFB smear positive while MTB was detected in 28 (20.29%) respiratory samples and 9 (6.52%) in nonrespiratory samples. Rifampicin resistance detected in 2 pulmonary samples (1.45%) and nil (0%) in non-respiratory samples. Conclusion: The possible reason of low prevalence rate of resistance to Rifampicin in current study is due to small sample size and mixing of new and retreated cases. Still the study could play its role to help government and health governing bodies in formulating sufficient plans regarding drug resistant TB control. [ABSTRACT FROM AUTHOR]

In infections caused by Mycobacterium tuberculosis (Mtb), the clinical evolution is dissimilar, so it is important to achieve a quick and correct diagnosis, it is necessary to implement new diagnostic tools. In the present study, a comparison was made between the molecular technique GeneXpert MTB / RIF, an important diagnostic tool that also allows the detection of sensitivity and / or resistance to Rifampicin, and the established conventional diagnostic techniques; smear microscopy (BK) and culture in Löwenstein-Jensen (L-J), to demonstrate its diagnostic applicability from clinical samples. 287 samples from symptomatic patients were analyzed, 146 (50.9%) were HIV / AIDS patients. The highest percentage of Mtb detection was obtained by the GeneXpert MTB / RIF molecular technique, however, if we observe the difference between the percentage obtained by Xpert MTB / RIF and the bacteriological culture, it was not statistically significant, obtaining a value of p = 0.2324. It is important to note that Xpert MTB / RIF allowed us to detect resistance to Rifampicin in 3 patients. The BK was the technique that obtained the lowest percentage of positivity. This study reaffirmed the applicability of this molecular tool for the diagnosis of TB in both pulmonary and extrapulmonary samples; the shortening of the diagnostic time allows the clinician to start specific treatment, avoiding the spread of the infection in the patient. [ABSTRACT FROM AUTHOR]

Background: The gene expert MTB-Rif assay is available in the department of Pulmonology NMU Hospital Multan from November 2011, It is working in collaboration with National TB control program (NTP). As per NTP guidelines, it is advisable to high risk groups only & not as a primary diagnostic tool. These high risk groups include retreatment cases, treatment after default, treatment failure & even in new cases who are high risk e.g DM, HIV, Long standing use of steroids, those having malignant disease, health care providers & contacts of MDR-XTR TB patients Objective: Objective of the present study was to audit the results of sputum smear microscopy & gene expert and DST in NMU, Hospital Multan. Methodology: It was a descriptive study in which non probability consecutive sampling method was used. It was conducted in MDR clinic of department of pulmonology. From November 2011 to February 2018 total 12924 tests have been performed, sputum smear microscopy has already been performed for years & is being continued in the presence of gene expert as well. In selected cases, where gene expert MTB is detected & Rif resistance is also present and the patient are either non affording these cases are funded by NTP for culture and DST. It is considered worthwhile to simply audit the results of sputum smear microscopy, gene expert & DST and share this data of ourPMDTclinic. Results: A total of 12924 gene experts were performed. MTB were detected in 5100, Rif resistance were detected in 789, sputum smear was positive in 4502 & negative in 8422 cases. The gene expert showed error in 478 cases out of them 200 were re-checked which showed expert positive in 98 cases & Rif resistance in 12 cases. Conclusion: The gene expert MTB Rif-Asaay is an effective & revolutionary tool to diagnose the MDR TB patients and it minimizes the time to start MDR treatment. Our unit is being benefited very effectively from this game-changer and that's why we wanted to share our data & perspective. [ABSTRACT FROM AUTHOR]

The article discusses a study on bedaquiline-resistant tuberculosis(TB). It mentions that the World Health Organization (WHO) estimated that approximately 5.6 percent of the 10 million new TB cases in 2017 were caused by Mycobacterium tuberculosis complex (MTBC) strains showing resistance against rifampicin (RR-TB) or against rifampicin and isoniazid (multidrug-resistant tuberculosis.