Non-Tuberculous Mycobacterial isolates from Panama: A retrospective 5-year analysis (2017-2021).

BACKGROUND: The genus Mycobacterium includes well-known bacteria such as M. tuberculosis causing tuberculosis and M. leprae causing leprosy. Additionally, various species collectively termed non-tuberculous mycobacteria (NTM) can cause infections in humans and animals, affecting individuals across all age groups and health conditions. However, information on NTM infection prevalence in Panama is limited. METHODS: This study conducted a retrospective analysis of clinical records from 2017 to 2021, specifically focusing on patients with NTM isolates. Data were categorized by variables like sex, age, HIV status, and sample source. RESULTS: Among the 4430 clinical records analyzed, 698 were linked to patients with NTM isolates. Of these patients, 397 were male, and 301 were female. Most female patients with NTM isolates (n = 190) were aged >45 to 85 years, while most male patients (n = 334) fell in the >25 to 75 years age group. A noteworthy proportion of male patients (n = 65) were aged 25-35 years. A significant age difference between male (median [min-max] = 53 years [3-90]) and female (median [61 years [6-94]) patients was observed (p < 0.001). Regarding HIV status, 77 positive individuals were male, and 19 were female (p < 0.001). Most samples (n = 566) were sputum samples, with additional pulmonary-associated samples such as broncho-alveolar lavage, tracheal secretions, and pleural fluid samples. Among extrapulmonary isolates (n = 48), sources included catheter secretions, intracellular fluids, peritoneal fluid, blood cultures, cerebrospinal fluid, bone marrow samples, and capillary transplant lesions. Specifically, the analysis identified the pathogenic microorganisms responsible for mycobacteriosis in Panama during the specific period 2017-2021, as M. fortuitum (34.4%), M. intracellulare (20.06%), and M. abscessus (13.75%), respectively. CONCLUSIONS: This study highlights the growing public health concern of NTM infections in Panama. The research provides valuable insights into the prevalence and distribution of NTM species in the country, offering a foundation for the development and implementation of effective prevention and control strategies for NTM infections in Panama.

Why do we use 100†mg of clofazimine in TB and NTM treatment?

Current tuberculosis and non-tuberculous mycobacterial disease guidelines recommend the use of clofazimine in a 100 mg once-daily dose. The rationale behind this exact dose is not provided. I performed a literature review to determine the reasoning behind the current dosing regimen. The current 100 mg once-daily dose of clofazimine stems from a deliberate attempt to find the minimum effective daily dose in leprosy treatment, driven by efficacy, economical and toxicity considerations. While this dose is safe, economical and practical, a higher dose with a loading phase may add relevant efficacy and treatment-shortening potential to both tuberculosis and non-tuberculous mycobacterial disease treatment. We need to revisit dose-response and maximum tolerated dose studies to get the best out of this drug, while continuing efforts to generate more active r-iminophenazine molecules that accumulate less in skin and intestinal tissues and have pharmacokinetic properties that do not require loading doses.

Epidemiology and treatment outcomes of recurrent tuberculosis in Tanzania from 2018 to 2021 using the National TB dataset.

BACKGROUND: Patients with recurrent TB have an increased risk of higher mortality, lower success rate, and a relatively feeble likelihood of treatment completion than those with new-onset TB. This study aimed to assess the epidemiology of recurrent TB in Tanzania; specifically, we aim to determine the prevalence of TB recurrence and factors associated with unfavourable treatment outcomes among patients with recurrent TB in Tanzania from 2018 to 2021. METHODS: In this cross-sectional study, we utilized Tanzania's routinely collected national TB program data. The study involved a cohort of TB patients over a fixed treatment period registered in the TB and Leprosy case-based District Health Information System (DHIS2-ETL) database from 2018 to 2021 in Tanzania. We included patients' sociodemographic and clinical factors, facility characteristics, and TB treatment outcomes. We conducted bivariate analysis and multivariable multi-level mixed effects logistic regression of factors associated with TB recurrence and TB treatment outcomes to account for the correlations at the facility level. A purposeful selection method was used; the multivariable model included apriori selected variables (Age, Sex, and HIV status) and variables with a p-value <0.2 on bivariate analysis. The adjusted odds ratio and 95% confidence interval were recorded, and a p-value of less than 0.05 was considered statistically significant. FINDINGS: A total of 319,717 participants were included in the study; the majority were adults aged 25-49 (44.2%, n = 141,193) and above 50 years (31.6%, n = 101,039). About two-thirds were male (60.4%, n = 192,986), and more than one-fifth of participants (22.8%, n = 72,396) were HIV positive. Nearly two in every hundred TB patients had a recurrent TB episode (2.0%, n = 6,723). About 10% of patients with recurrent TB had unfavourable treatment outcomes (9.6%, n = 519). The odds of poor treatment outcomes were two-fold higher for participants receiving treatment at the central (aOR = 2.24; 95% CI 1.33-3.78) and coastal zones (aOR = 2.20; 95% CI 1.40-3.47) than the northern zone. HIV-positive participants had 62% extra odds of unfavourable treatment outcomes compared to their HIV-negative counterparts (aOR = 1.62; 95% CI 1.25-2.11). Bacteriological TB diagnosis (aOR = 1.39; 95% CI 1.02-1.90) was associated with a 39% additional risk of unfavourable treatment outcomes as compared to clinical TB diagnosis. Compared to community-based DOT, patients who received DOT at the facility had 1.39 times the odds of poor treatment outcomes (aOR = 1.39; 95%CI 1.04-1.85). CONCLUSION: TB recurrence in Tanzania accounts for 2% of all TB cases, and it is associated with poor treatment outcomes. Unfavourable treatment outcomes were recorded in 10% of patients with recurrent TB. Poor TB treatment outcome was associated with HIV-positive status, facility-based DOT, bacteriologically confirmed TB and receiving treatment at the hospital level, differing among regions. We recommend post-treatment follow-up for patients with recurrent TB, especially those coinfected with HIV. We also propose close follow-up for patients treated at the hospital facility level and strengthening primary health facilities in TB detection and management to facilitate early treatment initiation.

Spatial distribution and temporal trends of tuberculosis case notifications, Uganda: a ten-year retrospective analysis (2013-2022).

BACKGROUND: Uganda has a high incidence and prevalence of tuberculosis (TB). Analysis of spatial and temporal distribution of TB is an important tool for supporting spatial decision-making, planning, and policy formulations; however, this information is not readily available in Uganda. We determined the spatial distribution and temporal trends of tuberculosis notifications in Uganda, 2013-2022. METHODS: We conducted a retrospective analysis of routinely-generated program data reported through the National TB and Leprosy Programme (NTLP) surveillance system. We abstracted data on all TB cases diagnosed from 2013 to 2022 by district and region. We drew choropleth maps for Uganda showing the TB case notification rates (CNR) per 100,000 and calculated the CNR using the cases per district as the numerator and individual district populations as the denominators. Population estimates were obtained from the 2014 National Population and Housing Census, and a national growth rate of 3% was used to estimate the annual population increase. RESULTS: Over the entire study period, 568,957 cases of TB were reported in Uganda. There was a 6% annual increase in TB CNR reported from 2013 (134/100,000) to 2022 (213/100,000) (p-value for trend p < 0.00001). Cases were reported from all 12 Ministry of Health regions during the entire period. The distribution of CNR was heterogeneous throughout the country and over time. Moroto, Napak and Kampala districts had consistently high CNR throughout the ten years. Kalangala district had lower CNR from 2013 to 2018 but high CNR from 2019 to 2022. Moroto region, in the northeast, had consistently high CNR while Mbale and Soroti regions in Eastern Uganda had the lowest CNR throughout the ten years. CONCLUSION: There was an overall increasing trend in TB CNR from 2013 to 2022. We recommend that the National TB program institutes intensified measures aided by more funding to mitigate and reverse the negative impacts of the COVID-19 pandemic on TB.

Health Screening Strategies for Artisanal and Small-Scale Miners for Tuberculosis, Human Immunodeficiency Virus and Silicosis: A Case of the USAID-Supported Kunda Nqob'iTB Project in Zimbabwe.

Artisanal and small-scale mining is characterized by excessive exposure to physical, chemical, ergonomic, psychosocial and biological hazards. There is a high burden of tuberculosis (TB), human immunodeficiency virus (HIV) infections and silicosis among artisanal and small-scale miners (ASMs). The aim of this project report is to describe lessons learned from strategies implemented to reach ASMs with screening services for TB, HIV and silicosis in Zimbabwe through the Kunda-Nqob'i TB (KNTB) project supported by the United States Agency for International Development (USAID). The intervention package for screening ASMs for TB, HIV and silicosis included service provision through two occupational health clinics at two provincial hospitals and a mobile workplace-based screening (WBS) facility at the mining sites. From 1 October 2020 to 30 September 2023, 10,668 ASMs were screened, with a high number of cases of silicosis (21%) and TB (7.4%). There was a high burden of HIV (30%) in ASMs attending the occupational health clinics. The two occupational health clinics screened 3453 ASMs, while the mobile WBS activities screened 7215 ASMs during the period. A total of 370 healthcare workers (doctors/clinical officers, nurses, environmental health technicians and district tuberculosis and Leprosy control officers) were trained on TB and the fundamental diagnostic principles of silicosis. The KNTB project has been successful in reaching out to many ASMs operating in remote and hard-to-reach mining areas. The KNTB project has brought to light the positive health-seeking behavior of ASMs operating in remote areas. The project has brought to the fore the effectiveness of multi-stakeholder engagement and collaboration in reaching out to ASMs in remote areas with health screening services. There is a high burden of TB, HIV and silicosis in ASMs. Screening for TB, HIV and silicosis using workplace-based screening and occupational health clinics is an effective strategy and should be rolled out to all areas with high artisanal and small-scale mining activity.

Private practitioners' practices for tuberculosis management in a city largely served by the private health sector in Uganda.

BACKGROUND: Globally, tuberculosis (TB) remains a significant cause of morbidity and mortality having caused 1.6 million deaths in 2021. Uganda is a high TB burden country with a large private sector that serves close to 60% of the urban population. However, private for-profit health facilities' involvement with the National TB and Leprosy Program (NTLP) activities remains poor. This study evaluated the practices of diagnosis and treatment of pulmonary tuberculosis (PTB) and associated factors among practitioners in private for-profit (PFP) healthcare facilities in Kampala, Uganda. METHODS: We conducted a cross-sectional study among randomly selected private practitioners in Uganda's largest city, Kampala. A structured questionnaire was used for data collection. Descriptive statistics and generalized linear models with log Poisson link were used to analyze data. Practices were graded as standard or substandard. RESULTS: Of the 630 private practitioners studied, 46.2% (95% confidence interval (CI): 26.6 to 67.1) had overall standard practices. Being a laboratory technician (prevalence ratio (PR) = 2.7, p< 0.001) or doctor (PR = 1.2, p< 0.001), a bachelor's degree level of qualification (PR = 1.1, p = 0.021), quarterly supervision by the national TB program (PR = 1.3, p = 0.023), and acceptable knowledge of the practitioner about TB (PR = 1.8, p<0.001) were significantly associated with standard practices. CONCLUSIONS: The practices of TB management for practitioners from the PFP facilities in Kampala are suboptimal and this poses a challenge for the fight against TB given that these practitioners are a major source of primary health care in the city.

ESX-3 secretion system in Mycobacterium: An overview.

Mycobacteria are microorganisms distributed in the environment worldwide, and some of them, such as Mycobacterium tuberculosis or M. leprae, are pathogenic. The hydrophobic mycobacterial cell envelope has low permeation and bacteria need to export products across their structure. Mycobacteria possess specialized protein secretion systems, such as the Early Secretory Antigenic Target 6 secretion (ESX) system. Five ESX loci have been described in M. tuberculosis, called ESX-1 to ESX-5. The ESX-3 secretion system has been associated with mycobacterial metabolism and growth. The locus of this system is highly conserved across mycobacterial species. Metallo-proteins regulate negative ESX-3 transcription in high conditions of iron and zinc. Moreover, this secretion system is part of an antioxidant regulatory pathway linked to Zinc. EccA3, EccB3, EccC3, EccD3, and EccE3 are components of the ESX-3 secretion machinery, whereas EsxG-EsxH, PE5-PPE4, and PE15-PPE20 are proteins secreted by this system. In addition, EspG3 and MycP3 are complementary proteins involved in transport and proteolysis respectively. This system is associated to mycobacterial virulence by releasing the bacteria from the phagosome and inhibiting endomembrane damage response. Furthermore, components of this system inhibit the host immune response by reducing the recognition of M. tuberculosis-infected cells. The components of the ESX-3 secretion system play a role in drug resistance and cell wall integrity. Moreover, the expression data of this system indicated that external and internal factors affect ESX-3 locus expression. This review provides an overview of new findings on the ESX-3 secretion system, its regulation, expression, and functions.

Deciphering drug discovery and microbial pathogenesis research in tuberculosis during the two decades of postgenomic era using entity mining approach.

We examined literature on Mycobacterium tuberculosis (Mtb) subsequent to its genome release, spanning years 1999-2020. We employed scientometric mapping, entity mining, visualization techniques, and PubMed and PubTator databases. Most popular keywords, most active research groups, and growth in quantity of publications were determined. By gathering annotations from the PubTator, we determined direction of research in the areas of drug hypersensitivity, drug resistance (AMR), and drug-related side effects. Additionally, we examined the patterns in research on Mtb metabolism and various forms of tuberculosis, including skin, brain, pulmonary, extrapulmonary, and latent tuberculosis. We discovered that 2011 had the highest annual growth rate of publications, at 19.94%. The USA leads the world in publications with 18,038, followed by China with 14,441, and India with 12,158 publications. Studies on isoniazid and rifampicin resistance showed an enormous increase. Non-tuberculous mycobacteria also been the subject of more research in effort to better understand Mtb physiology and as model organisms. Researchers also looked at co-infections like leprosy, hepatitis, plasmodium, HIV, and other opportunistic infections. Host perspectives like immune response, hypoxia, and reactive oxygen species, as well as comorbidities like arthritis, cancer, diabetes, and kidney disease etc. were also looked at. Symptomatic aspects like fever, coughing, and weight loss were also investigated. Vitamin D has gained popularity as a supplement during illness recovery, however, the interest of researchers declined off late. We delineated dominant researchers, journals, institutions, and leading nations globally, which is crucial for aligning ongoing and evolving landscape of TB research efforts. Recognising the dominant patterns offers important information about the areas of focus for current research, allowing biomedical scientists, clinicians, and organizations to strategically coordinate their efforts with the changing priorities in the field of tuberculosis research.

The geographical distribution and socioeconomic risk factors of COVID-19, tuberculosis and leprosy in Fortaleza, Brazil.

BACKGROUND: Fortaleza (Brazil) is high endemic for coronavirus disease 2019 (COVID-19), tuberculosis (TB) and leprosy. These three diseases share respiratory droplets through coughing or sneezing as the main mode of transmission but differ in incubation time, with COVID-19 having a short and leprosy a long incubation time. Consequently, contacts of a patient are at higher risk of infection and developing these diseases. There might be scope for combined preventive measures, but a better understanding of the geographical distribution and relevant socioeconomic risk factors of the three diseases is needed first. This study aims to describe the geographic distribution of COVID-19, TB and leprosy incidence and to identify common socioeconomic risk factors. METHODS: The total number of new cases of COVID-19, TB and leprosy, as well as socioeconomic and demographic variables, were retrieved from official registers. The geographical distribution of COVID-19, TB and leprosy rates per neighbourhood was visualised in Quantum GIS, and spatial autocorrelation was measured with Moran's I in GeoDa. A spatial regression model was applied to understand the association between COVID-19, TB, leprosy rates, and socioeconomic factors. RESULTS: COVID-19 and TB showed a more homogenous distribution, whereas leprosy is located more in the south and west of Fortaleza. One neighbourhood (Pedras) in the southeast was identified as high endemic for all three diseases. Literacy was a socioeconomic risk factor for all three diseases: a high literacy rate increases the risk of COVID-19, and a low literacy rate (i.e., illiteracy) increases the risk of TB and leprosy. In addition, high income was associated with COVID-19, while low income with TB. CONCLUSIONS: Despite the similar mode of transmission, COVID-19, TB and leprosy show a different distribution of cases in Fortaleza. In addition, associated risk factors are related to wealth in COVID-19 and to poverty in TB and leprosy. These findings may support policymakers in developing (partially combined) primary and secondary prevention considering the efficient use of resources.

Leprosy and tuberculosis control scenario of the national program for the improvement of access and quality of primary care in Brazil.

BACKGROUND: In Brazil, despite advances in public health policies aimed at eliminating and controlling infectious and parasitic diseases, the incidence of neglected diseases is still high. The epidemiological scenario in Brazil of diseases such as tuberculosis and leprosy evidences a public policy agenda that has not been resolute in terms of control, nor in terms of elimination. OBJECTIVE: To analyze the actions of diagnosis and treatment of leprosy and tuberculosis in the context of primary health care. METHODS: In this ecological study, data from the third cycle of the Program for the Improvement of Access and Quality of Primary Care were extracted from electronic address of the Primary Health Care Secretariat of Brazil in the area of Actions, Programs and Strategies. A total of 37,350 primary health care teams were that answered the questionnaire were eligible, with variables extracted from leprosy and tuberculosis control actions. The municipalities were grouped according to the characteristic of the Brazilian municipality. The partition chi-square and the Residuals Test were used to assess whether there was a difference in the proportion of tuberculosis and leprosy actions between types of municipalities. Statistics were carried out using Minitab 20 and Bioestat 5.3. RESULTS: Regarding the leprosy treatment location, there is a higher proportion of people referred to be treated at the reference in adjacent rural (p = 0.0097) and urban (p < 0.0001) municipalities; monitoring of people with leprosy referred to the service network (p. = 0.0057) in remote rural areas. Lower proportion of teams requesting bacilloscopy in remote rural areas (p = 0.0019). Rural areas have a higher proportion of teams that diagnose new cases (p = 0.0004). Regarding the actions of diagnosis and treatment of tuberculosis. There is a higher proportion of teams that carry out consultations at the unit itself in rural areas when compared to adjacent intermediaries (p = 0.0099) and urban (p < 0.0001); who requested sputum smear microscopy in adjacent intermediaries (p = 0.0021); X-ray in adjacent intermediaries (p < 0.0001) and urban (p < 0.0001); collection of the first sputum sample in urban (p < 0.0001) and adjacent rural areas (p < 0.0001); directly observed treatment (p < 0.0001) in adjacent rural municipalities. CONCLUSION: There are inequalities in the diagnosis and treatment of leprosy and tuberculosis among the types of municipalities.

Immune Targeting of Mycobacteria through Cell Surface Glycan Engineering.

Mycobacteria and other organisms in the order Mycobacteriales cause a range of significant human diseases, including tuberculosis, leprosy, diphtheria, Buruli ulcer, and non-tuberculous mycobacterial (NTM) disease. However, the intrinsic drug tolerance engendered by the mycobacterial cell envelope undermines conventional antibiotic treatment and contributes to acquired drug resistance. Motivated by the need to augment antibiotics with novel therapeutic approaches, we developed a strategy to specifically decorate mycobacterial cell surface glycans with antibody-recruiting molecules (ARMs), which flag bacteria for binding to human-endogenous antibodies that enhance macrophage effector functions. Mycobacterium-specific ARMs consisting of a trehalose targeting moiety and a dinitrophenyl hapten (Tre-DNPs) were synthesized and shown to specifically incorporate into outer-membrane glycolipids of Mycobacterium smegmatis via trehalose metabolism, enabling recruitment of anti-DNP antibodies to the mycobacterial cell surface. Phagocytosis of Tre-DNP-modified M. smegmatis by macrophages was significantly enhanced in the presence of anti-DNP antibodies, demonstrating proof-of-concept that our strategy can augment the host immune response. Because the metabolic pathways responsible for cell surface incorporation of Tre-DNPs are conserved in all Mycobacteriales organisms but absent from other bacteria and humans, the reported tools may be enlisted to interrogate host-pathogen interactions and develop immune-targeting strategies for diverse mycobacterial pathogens.

Cocrystallizing and Codelivering Complementary Drugs to Multidrugresistant Tuberculosis Bacteria in Perfecting Multidrug Therapy.

Bacteria cells exhibit multidrug resistance in one of two ways: by raising the genetic expression of multidrug efflux pumps or by accumulating several drug-resistant components in many genes. Multidrug-resistive tuberculosis bacteria are treated by multidrug therapy, where a few certain antibacterial drugs are administered together to kill a bacterium jointly. A major drawback of conventional multidrug therapy is that the administration never ensures the reaching of different drug molecules to a particular bacterium cell at the same time, which promotes growing drug resistivity step-wise. As a result, it enhances the treatment time. With additional tabletability and plasticity, the formation of a cocrystal of multidrug can ensure administrating the multidrug chemically together to a target bacterium cell. With properly maintaining the basic philosophy of multidrug therapy here, the synergistic effects of drug molecules can ensure killing the bacteria, even before getting the option to raise the drug resistance against them. This can minimize the treatment span, expenditure and drug resistance. A potential threat of epidemic from tuberculosis has appeared after the Covid-19 outbreak. An unwanted loop of finding molecules with the potential to kill tuberculosis, getting their corresponding drug approvals, and abandoning the drug after facing drug resistance can be suppressed here. This perspective aims to develop the universal drug regimen by postulating the principles of drug molecule selection, cocrystallization, and subsequent harmonisation within a short period to address multidrug-resistant bacteria.

CD11b+Gr-1low cells that accumulate in M.leprae-induced granulomas of the footpad skin of nude mice have the characteristics of monocytic-myeloid-derived suppressor cells.

CD11b+Gr-1low cells that are increased in the lungs of a Mycobacterium (M) tuberculosis-infection mouse model have the characteristics of monocytic (M)-myeloid-derived suppressor cells (MDSCs) and harbor M.tuberculosis. Interestingly, a high number of M-MDSCs have also been observed in skin lesions of patients with lepromatous leprosy. We hypothesized that CD11b+Gr-1low cells might be involved in the pathogenesis of leprosy, as they are in tuberculosis. In the current study, we investigated the issue of whether CD11b+Gr-1low cells accumulate in Mycobacterium (M) leprae-induced granulomas of the footpad skin of nude mice. Our results show that CD11b+Gr-1low cells began to accumulate in the 7-month-old M.leprae-induced granulomas and were replaced by other leukocytes, including CD11b+Gr-1high over time during M.leprae infections. CD11b + Gr-1low cells expressed the surface markers of M-MDSC, Ly6Chigh and Ly6Glow. In addition, CD11b+Gr-1low cells have the nuclei of a mononuclear cell type and expressed higher levels of arginase 1 (Arg1) and inducible NO synthetase (iNOS). Furthermore, they showed a higher infection rate by M.leprae. Taken together, our results indicate that the inoculation with M.leprae induced an accumulation of CD11b + Gr-1low at a relatively early stage, 7-month-old M.leprae-induced granulomas, and that CD11b+Gr-1low have the characteristics of M-MDSC and may act as a reservoir for M.leprae.

Redefining tuberculosis: an interview with Lalita Ramakrishnan.

Professor Lalita Ramakrishnan is at the forefront of modern tuberculosis (TB) research. She has developed vital tools, most notably a robust zebrafish model, to study this disease, leading to seminal discoveries uncovering bacterial and host interactions throughout infection. Her group has harnessed this knowledge to develop new treatments for TB and shape clinical research. By unveiling these complex interactions, they have also improved our understanding of fundamental biology of macrophages and other infectious diseases, such as leprosy.

Extemporaneously compounded liquid formulations of clofazimine.

BACKGROUND: Clofazimine (CFZ) is routinely used worldwide for the treatment of leprosy and TB. However, no liquid or dispersible tablet formulations of CFZ are currently available commercially for patients with challenges ingesting soft gelatin capsules or solid formulations. The aim of this research was to develop stable extemporaneous liquid formulations of CFZ that can be stored at room temperature for several weeks to enable practical dosing in the field. METHODS: Two formulations were prepared in syrup and sugar-free vehicles with CFZ tablets using a simple method that can be used in a routine pharmacy. Suspensions were stored at room temperature and at 30°C for 30 days. Formulation aliquots were tested on Days 0, 15 and 30 for appearance, pH, potency and microbial counts. RESULTS: Appearance remained unchanged during storage. The pH of both formulations was between 4.0 and 6.0. Potency was between 90% and 110% for 30 days in the syrup formulation and for 15 days in the sugar-free formulation. Microbial counts met United States Pharmacopeia 1111 limits for oral aqueous liquids and specific organisms were absent. CONCLUSIONS: A simple field-friendly method was successfully developed for the preparation of CFZ liquid formulations using commonly available ingredients. This will permit practical dosing and titration for children and other patients with swallowing challenges.

Mycobacterium smegmatis: The Vanguard of Mycobacterial Research.

The genus Mycobacterium contains several slow-growing human pathogens, including Mycobacterium tuberculosis, Mycobacterium leprae, and Mycobacterium avium. Mycobacterium smegmatis is a nonpathogenic and fast growing species within this genus. In 1990, a mutant of M. smegmatis, designated mc2155, that could be transformed with episomal plasmids was isolated, elevating M. smegmatis to model status as the ideal surrogate for mycobacterial research. Classical bacterial models, such as Escherichia coli, were inadequate for mycobacteria research because they have low genetic conservation, different physiology, and lack the novel envelope structure that distinguishes the Mycobacterium genus. By contrast, M. smegmatis encodes thousands of conserved mycobacterial gene orthologs and has the same cell architecture and physiology. Dissection and characterization of conserved genes, structures, and processes in genetically tractable M. smegmatis mc2155 have since provided previously unattainable insights on these same features in its slow-growing relatives. Notably, tuberculosis (TB) drugs, including the first-line drugs isoniazid and ethambutol, are active against M. smegmatis, but not against E. coli, allowing the identification of their physiological targets. Furthermore, Bedaquiline, the first new TB drug in 40 years, was discovered through an M. smegmatis screen. M. smegmatis has become a model bacterium, not only for M. tuberculosis, but for all other Mycobacterium species and related genera. With a repertoire of bioinformatic and physical resources, including the recently established Mycobacterial Systems Resource, M. smegmatis will continue to accelerate mycobacterial research and advance the field of microbiology.

Impact of nanoparticles on amyloid ß-induced Alzheimer's disease, tuberculosis, leprosy and cancer: a systematic review.

Nanotechnology is an interdisciplinary domain of science, technology and engineering that deals with nano-sized materials/particles. Usually, the size of nanoparticles lies between 1 and 100 nm. Due to their small size and large surface area-to-volume ratio, nanoparticles exhibit high reactivity, greater stability and adsorption capacity. These important physicochemical properties attract scientific community to utilize them in biomedical field. Various types of nanoparticles (inorganic and organic) have broad applications in medical field ranging from imaging to gene therapy. These are also effective drug carriers. In recent times, nanoparticles are utilized to circumvent different treatment limitations. For example, the ability of nanoparticles to cross the blood-brain barrier and having a certain degree of specificity towards amyloid deposits makes themselves important candidates for the treatment of Alzheimer's disease. Furthermore, nanotechnology has been used extensively to overcome several pertinent issues like drug-resistance phenomenon, side effects of conventional drugs and targeted drug delivery issue in leprosy, tuberculosis and cancer. Thus, in this review, the application of different nanoparticles for the treatment of these four important diseases (Alzheimer's disease, tuberculosis, leprosy and cancer) as well as for the effective delivery of drugs used in these diseases has been presented systematically. Although nanoformulations have many advantages over traditional therapeutics for treating these diseases, nanotoxicity is a major concern that has been discussed subsequently. Lastly, we have presented the promising future prospective of nanoparticles as alternative therapeutics. In that section, we have discussed about the futuristic approach(es) that could provide promising candidate(s) for the treatment of these four diseases.

Central Nervous System Mycobacterium Infection: Tuberculosis and Beyond.

Tuberculosis is a contagious infectious disease caused by Mycobacterium tuberculosis, and is the leading cause of death from a single infectious agent worldwide. Imaging plays an important role in the early diagnosis of central nervous system tuberculosis and may prevent unnecessary morbidity and mortality. This article presents an extensive review of pathogenesis, clinical symptoms, typical and atypical imaging appearances of intracranial and spinal tuberculosis, and advanced imaging of intracranial tuberculosis. Furthermore, we explore central nervous system infection of nontuberculous mycobacteria and leprosy and their imaging findings.

Factors associated with tuberculosis treatment success among tuberculosis and human immunodeficiency virus co-infected patients in Kelantan.

INTRODUCTION: Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection is a global public health issue among people living with HIV. The objective was to assess the prevalence of TB treatment outcomes (successful and unsuccessful) and associated factors with TB treatment success among TB and HIV co-infected patients in Kelantan for 5 years (2014-2018). The successful TB treatment was defined as the sum of cured patients and those who completed the treatment. The unsuccessful treatment was defined as the sum of treatment failed, died, and default. MATERIALS AND METHODS: A cross-sectional study was conducted at the TB/Leprosy Unit of the State Health Department of Kelantan (JKNK) using secondary data from January 2014 to December 2018 assessed in the MyTB online system. The data were analyzed using SPSS 25.0 and STATA 14. Ethics approvals were obtained from Medical Research Ethics Committee (MREC) and UniSZA Human Research Ethics Committee (UHREC). RESULTS: Kelantan had 6,313 TB cases from January 2014 to December 2018. There were 703 (11.1%) cases of TB and HIV co-infection. The prevalence of successful treatment among TB and HIV co-infected patients was 57.1%. The duration of treatment and anatomy of TB location was significantly associated with TB treatment success. CONCLUSION: This study's findings showed that the prevalence of TB treatment success rate was 57.1%, and the unsuccessful rate was 42.9%. The treatment duration and the TB location's anatomy were significantly associated with the treatment success rate. Improving TB treatment outcomes should be started with anti-TB treatment immediately after TB diagnosis. Therefore, the government should strengthen the TB/HIV collaborative efforts to achieve good treatment outcomes among these vulnerable patients.

Treatment outcomes of tuberculosis patients in a Directly Observed Treatment Short course (DOTS) Referral Centre in Delta State, Nigeria: a five-year review (2012 - 2016).

Introduction: The objective of this study is to observe the trend in treatment outcomes and identify determinants of treatment success among patients recruited into care through the DOTS strategy. Methodology: A retrospective record review of tuberculosis patients (2012-2016) was carried out at the Tuberculosis and Leprosy Referral Centre, Eku, Delta State, Nigeria. Results: Records of four hundred and twenty five (425) tuberculosis patients under DOTS were reviewed over five years. The highest number of cases under treatment, 102 (24.0%), was recorded in 2013. The mean age (SD) of patients was 37.3 (±16.5) years, majority of the patients were male (62.4%) and 18% had TB/HIV co-infection. Treatment outcomes of patients were cured (53.4%), completed (27.8%), died (6.8%), failed (2.4%), lost to follow up (4.9%), transferred out (1.2%) and not evaluated (3.5%). Over all, treatment success rate was 81.2% with a trend of 88.7% (2012), 87.3% (2013), 85.9% (2014), 65.0% (2015) and 65.8% (2016) respectively. Patient characteristics were not associated with treatment success. Conclusion: The treatment success rate was high and in line with the national recommendation of 80% and above. The trend showed a reduction in number of new cases enrolled into the DOTS programme, reduction in success rate with a concomitant increase in loss to follow up. There was no association between patient characteristics and TB treatment success. System strengthening on patient follow up, community health education and treatment adherence is recommended.