Eradication Of Tuberculosis Research Articles

Proteomic analysis of drug-susceptible and multidrug-resistant nonreplicating Beijing strains of Mycobacterium tuberculosis cultured in vitro

The existence of latent tuberculosis infection (LTBI) is one of the main obstacles hindering eradication of tuberculosis (TB). To better understand molecular mechanisms and explore biomarkers for the pathogen during LTBI, we cultured strains of Mycobacterium tuberculosis (Mtb) under stress conditions, mimicking those in the host granuloma intracellular environment, to induce entry into the non-replicating persistence stage. The stresses included hypoxia, low pH (5.0), iron deprivation (100 μM of 2, 2’˗dipyridyl) and nutrient starvation (10% M7H9 medium). Three Mtb strains were studied: two clinical isolates (drug-susceptible Beijing (BJ) and multidrug-resistant Beijing (MDR-BJ) strains) and the reference laboratory strain, H37Rv. We investigated the proteomics profiles of these strains cultured in stressful conditions and then validated the findings by transcriptional analysis. NarJ (respiratory nitrate reductase delta chain) was significantly up-regulated at the protein level and the mRNA level in all three Mtb strains. The narJ gene is a member of the narGHJI operon encoding all nitrate reductase subunits, which play a role in nitrate metabolism during the adaptation of Mtb to stressful intracellular environments and the subsequent establishment of latent TB. The identification of up-regulated mRNAs and proteins of Mtb under stress conditions could assist development of biomarkers, drug targets and vaccine antigens.

82125 Multiple epidemics of multidrug-resistant tuberculosis revealed by spatial disease mapping and whole-genome sequencing analysis in urban China

ABSTRACT IMPACT: Our study will integrate state-of-the-art methods in pathogen genomics, epidemiology, and geospatial analysis to identify both host- and pathogen-factors driving the MDR-TB transmission and the study outcome can inform the design of targeted interventions OBJECTIVES/GOALS: The emergence of multidrug-resistant tuberculosis (MDR-TB) poses serious challenges for the global eradication of tuberculosis. Recent research has shown that transmission is now the dominant driver of MDR-TB. However, our limited understanding of where and among whom MDR-TB is transmitted hampers efforts to control person-to-person spread. METHODS/STUDY POPULATION: We used several analytic approaches to characterize the dynamics of MDR-TB transmission in Shanghai, China. We identified all culture-confirmed MDR cases between 2009-2016 in the city and 1) estimated individual-level risk factors for MDR disease; 2) mapped the TB cases by their home addresses and used a Bayesian spatial disease mapping method to identify regions with an elevated risk of MDR-TB; and 3) we sequenced all MDR isolates to understand whether transmission explained variance in risk that was not attributable to the distribution of individual or location-specific risk variates. RESULTS/ANTICIPATED RESULTS: There were 1034 MDR-TB cases among 16,315 culture-confirmed TB cases during the study period. Bayesian disease mapping identified spatial heterogeneity of MDR-TB and determined four hotspots with an elevated risk of MDR-TB, none of which were fully explained by individual or regional-covariates (Figure 1). Sequencing revealed that more than 40% of the MDR-TB strains were in genomic clusters, indicating recent MDR-TB transmission. Most importantly, MDR-TB cases in three of the four large clades (>8 isolates) were spatially concentrated in three strain-specific hotspots (Figure 2). DISCUSSION/SIGNIFICANCE OF FINDINGS: With the combination of traditional epidemiological tools, geographical, and genomic methods, this study revealed multiple loci of transmission of specific MDR-TB clades within a single city. Identification of where and among whom MDR-TB is transmitted can inform the design of targeted interventions.

Immunomodulatory Agents Combat Multidrug-Resistant Tuberculosis by Improving Antimicrobial Immunity.

BackgroundMultidrug-resistant (MDR) tuberculosis has low treatment success rates, and new treatment strategies are needed. We explored whether treatment with active vitamin D3 (vitD) and phenylbutyrate (PBA) could improve conventional chemotherapy by enhancing immune-mediated eradication of Mycobacterium tuberculosis.MethodsA clinically relevant model was used consisting of human macrophages infected with M. tuberculosis isolates (n = 15) with different antibiotic resistance profiles. The antimicrobial effect of vitD+PBA, was tested together with rifampicin or isoniazid. Methods included colony-forming units (intracellular bacterial growth), messenger RNA expression analyses (LL-37, β-defensin, nitric oxide synthase, and dual oxidase 2), RNA interference (LL-37-silencing in primary macrophages), and Western blot analysis and confocal microscopy (LL-37 and LC3 protein expression).ResultsVitD+PBA inhibited growth of clinical MDR tuberculosis strains in human macrophages and strengthened intracellular growth inhibition of rifampicin and isoniazid via induction of the antimicrobial peptide LL-37 and LC3-dependent autophagy. Gene silencing of LL-37 expression enhanced MDR tuberculosis growth in vitD+PBA–treated macrophages. The combination of vitD+PBA and isoniazid were as effective in reducing intracellular MDR tuberculosis growth as a >125-fold higher dose of isoniazid alone, suggesting potent additive effects of vitD+PBA with isoniazid.ConclusionsImmunomodulatory agents that trigger multiple immune pathways can strengthen standard MDR tuberculosis treatment and contribute to next-generation individualized treatment options for patients with difficult-to-treat pulmonary tuberculosis.

Does Mycobacterium tuberculosis var. bovis Survival in the Environment Confound Bovine Tuberculosis Control and Eradication? A Literature Review.

Bovine tuberculosis (bTB) is one of the globe's most common, multihost zoonoses and results in substantial socioeconomic costs for governments, farming industries, and tax payers. Despite decades of surveillance and research, surprisingly, little is known about the exact mechanisms of transmission. In particular, as a facultative intracellular pathogen, to what extent does survival of the causative agent, Mycobacterium tuberculosis var. bovis (M. bovis), in the environment constitute an epidemiological risk for livestock and wildlife? Due largely to the classical pathology of cattle cases, the received wisdom was that bTB was spread by direct inhalation and exchange of bioaerosols containing droplets laden with bacteria. Other members of the Mycobacterium tuberculosis complex (MTBC) exhibit differing host ranges, an apparent capacity to persist in environmental fomites, and they favour a range of different transmission routes. It is possible, therefore, that infection from environmental sources of M. bovis could be a disease transmission risk. Recent evidence from GPS-collared cattle and badgers in Britain and Ireland suggests that direct transmission by infectious droplets or aerosols may not be the main mechanism for interspecies transmission, raising the possibility of indirect transmission involving a contaminated, shared environment. The possibility that classical pulmonary TB can be simulated and recapitulated in laboratory animal models by ingestion of contaminated feed is a further intriguing indication of potential environmental risk. Livestock and wildlife are known to shed M. bovis onto pasture, soil, feedstuffs, water, and other fomites; field and laboratory studies have indicated that persistence is possible, but variable, under differing environmental conditions. Given the potential infection risk, it is timely to review the available evidence, experimental approaches, and methodologies that could be deployed to address this potential blind spot and control point. Although we focus on evidence from Western Europe, the concepts are widely applicable to other multihost bTB episystems.

Deletion of pknG Abates Reactivation of Latent Mycobacterium tuberculosis in Mice.

Eradication of tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), has been a challenge due to its uncanny ability to survive in a dormant state inside host granulomas for decades. Mtb rewires its metabolic and redox regulatory networks to survive in the hostile hypoxic and nutrient-limiting environment, facilitating the formation of drug-tolerant persisters. Previously, we showed that protein kinase G (PknG), a virulence factor required for lysosomal escape, aids in metabolic adaptation, thereby promoting the survival of nonreplicating mycobacteria. Here, we sought to investigate the therapeutic potential of PknG against latent mycobacterium. We show that inhibition of PknG by AX20017 reduces mycobacterial survival in in vitro latency models such as hypoxia, persisters, and nutrient starvation. Targeting PknG enhances the bactericidal activity of the frontline anti-TB drugs in peritoneal macrophages. Deletion of pknG resulted in 5- to 15-fold-reduced survival of Mtb in chronically infected mice treated with anti-TB drugs. Importantly, in the Cornell mouse model of latent TB, the deletion of pknG drastically attenuated Mtb's ability to resuscitate after antibiotic treatment compared with wild-type and complemented strains. This is the first study to investigate the sterilizing activity of pknG deletion and inhibition for adjunct therapy against latent TB in a preclinical model. Collectively, these results suggest that PknG may be a promising drug target for adjunct therapy to shorten the treatment duration and reduce disease relapse.

Mycobacterium microti: Not Just a Coincidental Pathogen for Cats.

Public interest in animal tuberculosis is mainly focused on prevention and eradication of bovine tuberculosis in cattle and wildlife. In cattle, immunodiagnostic tests such as the tuberculin skin test or the interferon gamma (IFN-γ) assay have been established and are commercially available. Feline tuberculosis is rather unknown, and the available diagnostic tools are limited. However, infections with Mycobacterium tuberculosis complex members need to be considered an aetiological differential diagnosis in cats with granulomatous lymphadenopathy or skin nodules and, due to the zoonotic potential, a time-efficient and accurate diagnostic approach is required. The present study describes 11 independent cases of Mycobacterium microti infection in domestic cats in Switzerland. For three cases, clinical presentation, diagnostic imaging, bacteriological results, immunodiagnostic testing, and pathological features are reported. An adapted feline IFN-γ release assay was successfully applied in two cases and appears to be a promising tool for the ante mortem diagnosis of tuberculosis in cats. Direct contact with M. microti reservoir hosts was suspected to be the origin of infection in all three cases. However, there was no evidence of M. microti infection in 346 trapped wild mice from a presumptive endemic region. Therefore, the source and modalities of infection in cats in Switzerland remain to be further elucidated.

Probing the dual inhibitory mechanisms of novel thiophenecarboxamide derivatives against Mycobacterium tuberculosis PyrG and PanK: an insight from biomolecular modeling study

The growing occurrence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (Mtb) strains underscores an urgent need for new antibiotics. The development of more bioactive antibiotics against drug-resistant organisms with a different mode of action could be a game-changer for the cure and eradication of tuberculosis (TB). Pantothenate Kinase (PanK) and CTP synthetase (PyrG) are both essential for RNA, DNA, and Lipids biosynthesis pathways. Given the extensive knowledge on these biosynthesis pathways inhibition of Mtb growth and survival, these enzymes present a fascinating opportunity for anti-mycobacterial drug discovery. Recently, it was experimentally established that the active metabolite 11426026 of compound 7947882 (a prodrug activated by EthA monooxygenase, 5-methyl-N-(4-nitrophenyl) thiophene-2-carboxamide) inhibits the activities of PyrG and PanK to indicate novel multitarget therapy aimed at discontinuing Mtb growth. However, the molecular mechanisms of their selective inhibition remain subtle. In this work, molecular dynamics simulations were employed to investigate the inhibitory mechanism as well as the selectivity impact of the active metabolite inhibitor of these enzymes. Computational modeling of the studied protein-ligand systems reveals that the active metabolite can potentially inhibit both PanK and PyrG, thereby creating a pathway as a double target approach in tuberculosis treatment. Communicated by Ramaswamy H. Sarma

Metformin and Rifampicin combination augments active to latent tuberculosis conversion: A computational study

Tuberculosis, a global threat, is a highly infectious disease intensified by the emergence of drug-resistant strains. In tuberculosis disease spectrum, a typical situation is a dormant or latent phase where a person exposed to Mycobacterium tuberculosis has the reservoir of the disease that may or may not result in an active state. Existence of the dormant state is retarding the eradication of tuberculosis. Transcription of several genes helps M. tuberculosis to survive in nonreplicative mode. DosR transcription factor is the hallmark for this genesis. Diabetes mellitus is a predisposition factor leading to the development of tuberculosis and latent tuberculosis. High plasma insulin concentrations in the prediabetic state can increase the tuberculosis bacterium. On the other hand, antidiabetic drug metformin is known to reduce active tuberculosis disease when provided in combination with antitubercular therapy. However, the effect of the same on latent tuberculosis is still unknown. In the present work using tools of computational biology, we have tried to find the consequence of adding metformin in combination with rifampicin, a well-known antitubercular drug, on molecular mechanisms of latent tuberculosis. We have investigated whether metformin and rifampicin interact with DosR machinery or not. Our results indicate that if metformin-bound DosR-DNA complex binds with rifampicin, it will result in the conversion of active tuberculosis to latent tuberculosis.

Economic aspects of control and eradication of bovine tuberculosis and the managerial costs associated: Review

Given its importance in veterinary medicine and its impact on human health, bovine tuberculosis demands attention on animal health programs in several countries. New ante- and post-mortem diagnosis protocols are available and facilitate disease detection and control. However, besides the known advantages and disadvantages of each protocol, there is little mention of their costs. This study intends to provide an overview of the economic aspects of diagnostic tests for the control and eradication of bovine tuberculosis.

Eradication of Tuberculosis– Current Status and the Way Forward

It is estimated that about 25% of humanity is infected with the bacterium Mycobacterium tuberculosis. Thatis about 2 billion people. Several new vaccines will pass Phase I clinical trials in the next few years. Thispaper briefly summarizes past and present challenges to developing a vaccine against tuberculosis as well astreating tuberculosis. TB is a pathogen that infects more individuals globally than any other communicabledisease. TB is particularly devastating in poor developing countries, notably in Africa and Southeast Asia.Despite the WHO’s efforts to overcome TB, Multi Drug Resistant (MDR) TB and Extremely Drug Resistant(XDR) TB are huge challenges.

Trading with risk: associating bovine Tuberculosis to cattle commodities in risk-based trading

ABSTRACT The trading of cattle across England poses challenges to the control and eradication of the cattle disease bovine Tuberculosis (bTB). To encourage the consideration of risk in the practice of cattle trading in England, Cattle Health Certification Standards (CHeCS) were introduced in 2016 to associate cattle commodities with bTB. However, CHeCS has only been adopted by approximately 60 farmers and there is no evidence to suggest it is encouraging risk-based trading of cattle. In this article, I use three empirical cases to analyse how disease risk was calculated, how it was framed through CHeCS as a quantifiable quality that could be associated with cattle, and how it failed to be taken up in the market. Drawing on the work of Callon and others, I conceive this failure to be an overflow of the efforts of qualculation. Building on their work, I argue that attaching a quality to a commodity requires effort, is an unstable process and is ultimately prone to failure.

Using Bayesian spatial models to map and to identify geographical hotspots of multidrug-resistant tuberculosis in Portugal between 2000 and 2016

Multidrug-resistant tuberculosis (MDR-TB) is a major threat to the eradication of tuberculosis. TB control strategies need to be adapted to the necessities of different countries and adjusted in high-risk areas. In this study, we analysed the spatial distribution of the MDR- and non-MDR-TB cases across municipalities in Continental Portugal between 2000 and 2016. We used Bayesian spatial models to estimate age-standardized notification rates and standardized notification ratios in each area, and to delimitate high- and low-risk areas, those whose standardized notification ratio is significantly above or below the country’s average, respectively. The spatial distribution of MDR- and non-MDR-TB was not homogeneous across the country. Age-standardized notification rates of MDR-TB ranged from 0.08 to 1.20 and of non-MDR-TB ranged from 7.73 to 83.03 notifications per 100,000 population across the municipalities. We identified 36 high-risk areas for non-MDR-TB and 8 high-risk areas for MDR-TB, which were simultaneously high-risk areas for non-MDR-TB. We found a moderate correlation (ρ = 0.653; 95% CI 0.457–0.728) between MDR- and non-MDR-TB standardized notification ratios. We found heterogeneity in the spatial distribution of MDR-TB across municipalities and we identified priority areas for intervention against TB. We recommend including geographical criteria in the application of molecular drug resistance to provide early MDR-TB diagnosis, in high-risk areas.

A retrospective study of tuberculosis prevalence amongst patients attending a tertiary hospital in Riyadh, Saudi Arabia

Tuberculosis (TB) is a public health challenge that affects all genders and age groups and is a single leading infectious disease killer globally. We retrospectively investigated the prevalence of TB and anti-TB drug resistance among patients treated at the Prince Sultan Military Medical City (PSMMC) between the years 2000 and 2017. Patient demographic variables and drug susceptibility test results were obtained from TB notification records located in the TB laboratory at PSMMC. A total of 58,141 records were reviewed of which 1123 (2%) specimens were positive for Mycobacterium tuberculosis. Of the positive, 621 (55%) were from pulmonary specimens. Males over the age of 15 years accounted for 60% of the positive specimens. Drug resistance to at least one drug was detected in 90 (8%) of which 60 (5.3%), 24 (2%) 6 (0.5%) patients were mono-drug-resistant, poly-drug resistant and multidrug resistant (MDR-TB) respectively. Resistance to isoniazid and streptomycin were the most frequently found among first-line tuberculosis drugs, accounting for 4.5% and 3.8% of drug resistance cases respectively. Our findings show low prevalence of tuberculosis and multidrug resistant TB among patients treated at PSMMC over a 17-year period. Nationwide assessment is needed to get a clear picture of the TB burden across Saudi Arabia and inform national policies for eradication of TB.

Phylogenetic relationships investigation of Mycobacterium caprae strains from sympatric wild boar and goats based on whole genome sequencing.

Tuberculosis (TB) in wildlife challenges epidemiological surveillance and disease control. An outbreak of TB was detected in a free‐ranging wild boar population of a Natural Park in Catalonia (Spain) and the outbreak investigation was conducted in the area. During the study period (2015–2020), 278 wild boars were analysed by gross pathology, histopathology, mycobacterial culture and DVR‐spoligotyping. In addition, all cattle (49) and goat (47) herds of the area were tested with tuberculin skin test. TB compatible lesions were detected in 21 wild boars, and Mycobacterium caprae was isolated in 17 of them with two different spoligotypes: SB0415 (13) and SB1908 (4). Only two goat herds showed TB positive animals that were subsequently slaughtered. M. caprae with the spoligotypes SB0416 and SB0415 were isolated from these animals. To investigate the phylogenetic relationships and the transmission chain of the outbreak, nine strains isolated from six wild boars and three goats of the study area were analysed by whole genome sequencing (WGS) followed by single nucleotide polymorphism (SNP) analysis by maximum likelihood and median‐joining network inference methods. Results indicated that infected wild boars maintained M. caprae strains circulation in their own population and have likely transmitted the infection to goats, thus acting as TB reservoirs, compromising the success of livestock TB eradication campaigns and posing a risk for public health. The results also highlighted the usefulness of WGS followed by SNP analysis in providing relevant epidemiological information when detailed contact data are missing.

Analysis of Putative Epitope Candidates of Mycobacterium tuberculosis Against Pakistani Human Leukocyte Antigen Background: An Immunoinformatic Study for the Development of Future Vaccine.

Tuberculosis (TB), a chronic disease caused by Mycobacterium tuberculosis (Mtb), is a global health issue across the world. Pakistan ranks fifth among the countries, which are facing, a significantly great number of mortalities and morbidities due to TB. Unfortunately, all previously reported treatments are not successful for the eradication of TB. Here in this study, we report an emerging treatment option for this disease. We have applied immunoinformatics to predict highly conserved B and T-cell epitopes from Mtb, showing significant binding affinities to the frequent HLA alleles in the Pakistani population. A total of ten highly referenced and experimentally validated epitopes were selected from the Immune Epitope Database (IEDB), followed by their conservancy analysis using weblogos. The consensus sequences and variants derived from these sequences were examined, for their binding affinities, with prevalent HLA alleles of Pakistan. Moreover, the antigenic and allergenic natures of these peptides were also evaluated via Vaxijen and AllerTOP, respectively. Consequently, all potentially allergenic and non-antigenic, peptide fragments, were excluded from the analysis. Among all putative epitopes, three CD8 + T-cell epitopes were selected, as ideal vaccine candidates and, population coverage analysis revealed that the combination of these three peptides was covering, 67.28% Pakistani Asian and 57.15% mixed Pakistani populations. Likewise, eleven linear and six conformational or discontinuous B-cell epitopes were also marked as potential vaccine candidates based on their prediction score, non-allergenic nature, and antigenic properties. These epitopes, however, need the final validation via wet-lab studies. After their approval, these epitopes would be effective candidates for the future designing of epitope-based vaccines against Mtb infections in Pakistan.Electronic supplementary materialThe online version of this article (10.1007/s10989-020-10111-w) contains supplementary material, which is available to authorized users.

Artemisia annua and Artemisia afra extracts exhibit strong bactericidal activity against Mycobacterium tuberculosis

Ethnopharmacological relevanceEmergence of drug-resistant and multidrug-resistant Mycobacterium tuberculosis (Mtb) strains is a major barrier to tuberculosis (TB) eradication, as it leads to longer treatment regimens and in many cases treatment failure. Thus, there is an urgent need to explore new TB drugs and combinations, in order to shorten TB treatment and improve outcomes. Here, we evaluated the potential of two Asian and African traditional medicinal plants, Artemisia annua, a natural source of artemisinin (AN), and Artemisia afra, as sources of novel antitubercular agents. Aim of the studyOur goal was to measure the activity of A. annua and A. afra extracts against Mtb as potential natural and inexpensive therapies for TB treatment, or as sources of compounds that could be further developed into effective treatments. Materials and methodsThe minimum inhibitory concentrations (MICs) of A. annua and A. afra dichloromethane extracts were determined, and concentrations above the MICs were used to evaluate their ability to kill Mtb and Mycobacterium abscessus in vitro. ResultsPrevious studies showed that A. annua and A. afra inhibit Mtb growth. Here, we show for the first time that Artemisia extracts have a strong bactericidal activity against Mtb. The killing effect of A. annua was much stronger than equivalent concentrations of pure AN, suggesting that A. annua extracts kill Mtb through a combination of AN and additional compounds. A. afra, which produces very little AN, displayed bactericidal activity against Mtb that was substantial but weaker than that of A. annua. In addition, we measured the activity of Artemisia extracts against Mycobacterium abscessus. Interestingly, we observed that while A. annua is not bactericidal, it inhibits growth of M. abscessus, highlighting the potential of this plant in combinatory therapies to treat M. abscessus infections. ConclusionOur results indicate that Artemisia extracts have an enormous potential for treatment of TB and M. abscessus infections, and that these plants contain bactericidal compounds in addition to AN. Combination of extracts with existing antibiotics may not only improve treatment outcomes but also reduce the emergence of resistance to other drugs.

Accuracy of tuberculosis diagnostic tests in small ruminants: A systematic review and meta-analysis

Tuberculosis (TB) in small ruminants is a neglected disease despite its major impact on goat and sheep production and the global public health. The awareness of the role of small ruminants in the epidemiology of animal TB has increased in the last two decades, however, there is a lack of standardization of procedures and robust quantitative estimates on the accuracy of diagnostic TB tests in the scientific literature. To address this knowledge gap, all the available information regarding the use of ante-mortem diagnostic techniques in small ruminants was collected and summarized through a systematic review process. Furthermore, a random-effects meta-analysis was conducted to separately estimate the sensitivity (Se) and specificity (Sp) of cell-based tests among the retrieved studies in goats. Studies included in the meta-analysis were also evaluated using the Quality Assessment of Diagnostic Accuracy Studies included in systematic reviews adapted for animal diagnostic tests (VETQUADAS). Median pooled Se estimates of the single intradermal tuberculin (SIT) test (ranged from 0.51 to 0.59), the comparative intradermal tuberculin (CIT) test (ranged from 0.30 to 0.50) and the interferon-gamma (IFN-γ) release assay (IGRA) (ranged from 0.66 to 0.72) were lower than that reported previously in cattle, regardless the interpretation criteria and the reporting of MAP infection or vaccination. However, the specificity was adequate for all the tests (ranged from 0.95 to 0.99), except for the SIT test in MAP vaccinated herds (ranged from 0.78 to 0.90). This study provides an overview of the accuracy of diagnostic tests for TB in goats, however, the considerable between-study heterogeneity found hampered the conclusive interpretation of the pooled Se and Sp estimates. Therefore, further studies in small ruminants are necessary to optimize the diagnostic Se, which could help to design effective control strategies, accelerate the eradication of TB in these species and harmonize test procedures.

Karakteristik dan Upaya Pencegahan Penularan Pada Penderita Tuberkulosis Paru

Pulmonary tuberculosis is still a global priority health problem because it is the leading cause of death in the world for infectious diseases. According to WHO, Indonesia ranks third in the world after India and China. Estimated cases of pulmonary tuberculosis in Indonesia in 2019, as many as 845,000 people, while the prevalence of patients with pulmonary tuberculosis is 142 per 100 thousand population, Jambi ranked 5th in Indonesia. Lung tuberculosis is highly contagious, and can have a devastating effect on family members who live in the same house as people with pulmonary tuberculosis, if prevention efforts are not made by those with pulmonary tuberculosis. The purpose of this study was to identify the characteristics and efforts to prevent transmission in patients with pulmonary tuberculosis. This research is a descriptive study, with a total sampling technique, conducted on 42 people with pulmonary TB in the work area of PKM Putri Ayu Jambi City. Use demographic and transmission prevention instruments. Data collection was carried out by guided interviews. The results showed. The highest age in patients with pulmonary tuberculosis is productive age (23.8%) with male sex (57.1%) the highest education is basic education (40.5%) and employment is IRT (31.0%). Whereas prevention of transmission for more than half (54.8%) is good. It is expected that patients with pulmonary tuberculosis can increase their knowledge related to the knowledge of pulmonary tuberculosis, how to treat and prevent pulmonary tuberculosis transmission and to be actively involved in the eradication of pulmonary tuberculosis, while the health center staff and cadres can conduct counseling about efforts to prevent transmission of pulmonary tuberculosis to increase public knowledge about lung tuberculosis eradication, while the health center staff and cadres can conduct counseling about efforts to prevent the transmission of pulmonary tuberculosis prevention of pulmonary tuberculosis, as well as periodically do homevisit to the place of residence of tubulosis patients to monitor the condition of pulmonary tuberculosis sufferers.

Minimally invasive far lateral debridement combined with posterior instrumentation for thoracic and lumbar tuberculosis without severe kyphosis

BackgroundAnti-tuberculous therapy (ATT) alone cannot easily cure spine tuberculosis (STB) though it is the most essential treatment. Many studies have confirmed the efficacy of the surgical treatment of STB through anterior, anterolateral, posterior debridement, and intervertebral fusion or combined with internal fixation. However, the conventional surgical approach requires extensive exposure of the affected areas with high rates of morbidity and mortality. Recently, minimally invasive surgery has come into use to reduce iatrogenic trauma and relevant complications. Here, we introduced a novel technique for the treatment of thoracic and lumbar spine tuberculosis: minimally invasive far lateral debridement and posterior instrumentation (MI-FLDPI). In this study, we evaluated the technical feasibility, the clinical outcomes, and the postoperative complications.MethodsWe did a prospective, non-randomized study on this new technique. Twenty three patients (13 males) with thoracic or lumbar spine tuberculosis who underwent minimally invasive far lateral debridement and posterior instrumentation were included in the study. The preoperative comorbidities, operation duration, intra-operative hemorrhage, Cobb’s angles, and postoperative complications were recorded and analyzed. Clinical outcomes were evaluated by Visual Analog Scale (VAS), Oswestry Disability Index (ODI), neurological recovery, and eradication of tuberculosis. Radiological outcomes were evaluated by changes in Cobb’s angle and fusion status of the affected segments.ResultsThe patients were followed for an average of 19 months (ranging from 12 to 36 months). At the final follow-up, CRP and ESR of all patients were normal. The VAS and ODI were significantly improved compared with preoperative values (P < 0.05). No evident progression of the kyphotic deformity was found after surgery. Twenty two patients showed spontaneous peripheral interbody fusion 1 year after surgery. There were no failure of the instrumentation even though a young female with drug-resistant tuberculosis showed no sign of interbody fusion at the third year follow-up. All the patients with preoperative neurological deficit showed complete recovery at the final follow-up.ConclusionsMI-FLDPI using expandable tubular retractor could be recommended to treat thoracic and lumbar spine tuberculosis for the advantages of less trauma, earlier recovery, and less complications. Spontaneous peripheral interbody fusion was observed in nearly all the cases even without bone grafting.

Recent Developments in the Application of Flow Cytometry to Advance our Understanding of Mycobacterium tuberculosis Physiology and Pathogenesis.

The ability of the bacterial pathogen Mycobacterium tuberculosis to adapt and survive within human cells to disseminate to other individuals and cause active disease is poorly understood. Research supports that as M. tuberculosis adapts to stressors encountered in the host, it exhibits variable physiological and metabolic states that are time and niche‐dependent. Challenges associated with effective treatment and eradication of tuberculosis (TB) are in part attributed to our lack of understanding of these different mycobacterial phenotypes. This is mainly due to a lack of suitable tools to effectively identify/detect heterogeneous bacterial populations, which may include small, difficult‐to‐culture subpopulations. Importantly, flow cytometry allows rapid and affordable multiparametric measurements of physical and chemical characteristics of single cells, without the need to preculture cells. Here, we summarize current knowledge of flow cytometry applications that have advanced our understanding of the physiology of M. tuberculosis during TB disease. Specifically, we review how host‐associated stressors influence bacterial characteristics such as metabolic activity, membrane potential, redox status and the mycobacterial cell wall. Further, we highlight that flow cytometry offers unprecedented opportunities for insight into bacterial population heterogeneity, which is increasingly appreciated as an important determinant of disease outcome. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.