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The effect of micro-nutrients on malnutrition, immunity and therapeutic effect in patients with pulmonary tuberculosis: A systematic review and meta-analysis of randomised controlled trials.
Haiqing Cai, , Chen, L, Yin, C, Liao, Y, Meng, X, Lu, C, Tang, S, Li, X, Wang, X
Tuberculosis (Edinburgh, Scotland). 2020;:101994
Abstract
OBJECTIVE Micro-nutrients are closely related to pulmonary tuberculosis (PTB). Most patients with PTB suffer from micro-nutrients deficiency. We aimed to evaluate the efficacy of micro-nutrients support on clinical therapy and chronic inflammation in patients with PTB. METHODS We searched Pubmed, Springer link, Web of Science, Cochrane, Wan Fang and CNKI databases for randomised controlled trials (RCTs). The patients with anti-TB treatments were divided into two groups, the control group with nutritional advice or placebo, and the experimental group with micro-nutrients support for more than 2 weeks. Two reviewers conducted data extraction and quality assessment of the studies independently, and ReviewManager 5.2 software was used to input and analyse the data. The dichotomous variable was expressed in the risk ratios (RRS) and 95% CI, the continuous data were expressed in the mean difference (MD) and 95% CI, and the heterogeneity of subgroup was evaluated by I (Kerantzas and Jacobs, Jr., 2017) [2] test. RESULTS A total of 13 trials (2847 participants) were included. First, micro-nutrients improved sputum smears or culture negative conversion rates (OR 0.16 0.03-0.77, 2.29; MD -2.36, -4.72~-0.01, z = 1.97). Meanwhile, micro-nutrients support increased lymphocytes and decreased leukocytes, neutrophils, CRP and ESR (MD 0.20, 0.06-0.35, z = 2.78; MD -0.42, -0.65~-0.18, z = 3.48; MD -0.66, -1.12~-0.20, z = 2.82). However it had not impact on body weight, MUAC, haemoglobin, albumin or monocytes (p > 0.05). CONCLUSION Micro-nutrients support can reduce chronic inflammation and improve sputum smears or culture conversions to contribute to anti-TB treatment.
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A review on anti-tuberculosis peptides: Impact of peptide structure on anti-tuberculosis activity.
Yathursan, S, Wiles, S, Read, H, Sarojini, V
Journal of peptide science : an official publication of the European Peptide Society. 2019;(11):e3213
Abstract
Antibiotic resistance is a major public health problem globally. Particularly concerning amongst drug-resistant human pathogens is Mycobacterium tuberculosis that causes the deadly infectious tuberculosis (TB) disease. Significant issues associated with current treatment options for drug-resistant TB and the high rate of mortality from the disease makes the development of novel treatment options against this pathogen an urgent need. Antimicrobial peptides are part of innate immunity in all forms of life and could provide a potential solution against drug-resistant TB. This review is a critical analysis of antimicrobial peptides that are reported to be active against the M tuberculosis complex exclusively. However, activity on non-TB strains such as Mycobacterium avium and Mycobacterium intracellulare, whenever available, have been included at appropriate sections for these anti-TB peptides. Natural and synthetic antimicrobial peptides of diverse sequences, along with their chemical structures, are presented, discussed, and correlated to their observed antimycobacterial activities. Critical analyses of the structure allied to the anti-mycobacterial activity have allowed us to draw important conclusions and ideas for research and development on these promising molecules to realise their full potential. Even though the review is focussed on peptides, we have briefly summarised the structures and potency of the various small molecule drugs that are available and under development, for TB treatment.
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Spatial Network Mapping of Pulmonary Multidrug-Resistant Tuberculosis Cavities Using RNA Sequencing.
Dheda, K, Lenders, L, Srivastava, S, Magombedze, G, Wainwright, H, Raj, P, Bush, SJ, Pollara, G, Steyn, R, Davids, M, et al
American journal of respiratory and critical care medicine. 2019;(3):370-380
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Abstract
Rationale: There is poor understanding about protective immunity and the pathogenesis of cavitation in patients with tuberculosis.Objectives: To map pathophysiological pathways at anatomically distinct positions within the human tuberculosis cavity.Methods: Biopsies were obtained from eight predetermined locations within lung cavities of patients with multidrug-resistant tuberculosis undergoing therapeutic surgical resection (n = 14) and healthy lung tissue from control subjects without tuberculosis (n = 10). RNA sequencing, immunohistochemistry, and bacterial load determination were performed at each cavity position. Differentially expressed genes were normalized to control subjects without tuberculosis, and ontologically mapped to identify a spatially compartmentalized pathophysiological map of the cavity. In silico perturbation using a novel distance-dependent dynamical sink model was used to investigate interactions between immune networks and bacterial burden, and to integrate these identified pathways.Measurements and Main Results: The median (range) lung cavity volume on positron emission tomography/computed tomography scans was 50 cm3 (15-389 cm3). RNA sequence reads (31% splice variants) mapped to 19,049 annotated human genes. Multiple proinflammatory pathways were upregulated in the cavity wall, whereas a downregulation "sink" in the central caseum-fluid interface characterized 53% of pathways including neuroendocrine signaling, calcium signaling, triggering receptor expressed on myeloid cells-1, reactive oxygen and nitrogen species production, retinoic acid-mediated apoptosis, and RIG-I-like receptor signaling. The mathematical model demonstrated that neuroendocrine, protein kinase C-θ, and triggering receptor expressed on myeloid cells-1 pathways, and macrophage and neutrophil numbers, had the highest correlation with bacterial burden (r > 0.6), whereas T-helper effector systems did not.Conclusions: These data provide novel insights into host immunity to Mycobacterium tuberculosis-related cavitation. The pathways defined may serve as useful targets for the design of host-directed therapies, and transmission prevention interventions.
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Severe disseminated tuberculosis in HIV-negative refugees.
Suárez, I, Maria Fünger, S, Jung, N, Lehmann, C, Reimer, RP, Mehrkens, D, Bunte, A, Plum, G, Jaspers, N, Schmidt, M, et al
The Lancet. Infectious diseases. 2019;(10):e352-e359
Abstract
In high-income countries, the presentation of tuberculosis is changing, primarily because of migration, and understanding the specific health needs of susceptible populations is becoming increasingly important. Although disseminated tuberculosis is well documented in HIV-positive patients, the disease is poorly described and less expected in HIV-negative individuals. In this Grand Round, we report eight HIV-negative refugees, who presented with extensively disseminated tuberculosis. We discuss the multifactorial causes, such as deprivations during long journeys, precarious living conditions, and the experience of violence, which might add to nutritional factors and chronic disorders, eventually resulting in a state of predisposition to immune deficiency. We also show that disseminated tuberculosis is often difficult to diagnose when pulmonary symptoms are absent. Communication difficulties between refugees and health-care workers are another major hurdle, and every effort should be made to get a valid patient history. This medical history is crucial to guide imaging and other diagnostic procedures to establish a definite diagnosis, which should be confirmed by a positive tuberculosis culture. Because many of these patients are at risk for multidrug-resistant tuberculosis, drug susceptibility testing is imperative to guide therapy. In the absence of treatment guidelines for this entity, clinicians can determine treatment duration according to recommendations provided for extrapulmonary tuberculosis and affected organs. Paradoxical expansion of tuberculous lesions during therapy should be treated with corticosteroids. In many cases, treatment duration must be individualised and might even exceed 12 months.
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Changes in Host Response to Mycobacterium tuberculosis Infection Associated With Type 2 Diabetes: Beyond Hyperglycemia.
Segura-Cerda, CA, López-Romero, W, Flores-Valdez, MA
Frontiers in cellular and infection microbiology. 2019;:342
Abstract
Tuberculosis (TB) remains as the first cause of death among infectious diseases worldwide. Global incidence of tuberculosis is in part coincident with incidence of type 2 diabetes (T2D). Incidence of T2D is recognized as a high-risk factor that may contribute to tuberculosis dissemination. However, mechanisms which favor infection under T2D are just starting to emerge. Here, we first discuss the evidences that are available to support a metabolic connection between TB and T2D. Then, we analyze the evidences of metabolic changes which occur during T2D gathered thus far for its influence on susceptibility to M. tuberculosis infection and TB progression, such as hyperglycemia, increase of 1AC levels, increase of triglycerides levels, reduction of HDL-cholesterol levels, increased concentration of lipoproteins, and modification of the activity of some hormones related to the control of metabolic homeostasis. Finally, we recognize possible advantages of metabolic management of immunity to develop new strategies for treatment, diagnosis, and prevention of tuberculosis.
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Conventional polymerase chain reaction and amplification refractory mutation system-multi-gene/ multi-primer PCR in the diagnosis of female genital tuberculosis.
Bhanothu, V, Venkatesan, V
Archives of microbiology. 2019;(3):267-281
Abstract
This review mainly summarizes disease, immune-pathology and the clinical usefulness, advances, potential applications and limitations of new, cutting-edge technology (MG/MP-PCR and/or ARMS-MG/MP-PCR) in the detection of female genital tuberculosis (FGTB) disease and gene polymorphism among infertile patients. The investigation was set in the Department of Zoology, Osmania University and National Institute of Nutrition, Hyderabad, India. Desired articles were critically reviewed and analysed. Keywords and NET searches were conducted in all electronic databases starting from September, 2006. Full-text English-language reviews and research articles describing FGTB, infertility, gene polymorphism, conventional polymerase chain reaction (PCR) and multigene (MG)/multiprimer (MP)-PCR were included. The current review provides a comprehensive overview on the PCR and types (multiplex, nested, RT etc.) including the reagents, cycling conditions and pitfalls in the detection of FGTB disease and gene polymorphism among infertile patients. It provides limited information on MG/MP-PCR. At present, conventional PCR, MG/MP-PCR and/or amplification refractory mutation system (ARMS)-MG/MP-PCR have emerged as scientific innovations and perform significant function in medical research, mutational analysis and clinical investigations. This review admits that MG/MP-PCR and/or ARMS-MG/MP-PCR has the capacity to diagnose disease rapidly and to genotype a large number of samples. MG/MP-PCR and/or ARMS-MG/MP-PCR are considered as simple, reliable, non-isotopic, low-cost, fast, accurate and relatively easy-to-perform procedure. This review suggests that this method needs to be critically evaluated using huge number of clinical samples occurring across the world and then can be accredited for clinical utilization.
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Undernutrition and Tuberculosis: Public Health Implications.
Sinha, P, Davis, J, Saag, L, Wanke, C, Salgame, P, Mesick, J, Horsburgh, CR, Hochberg, NS
The Journal of infectious diseases. 2019;(9):1356-1363
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Abstract
Almost 800 million people are chronically undernourished worldwide, of whom 98% are in low- and middle-income countries where tuberculosis is endemic. In many tuberculosis-endemic countries, undernutrition is a driver of tuberculosis incidence and associated with a high population attributable fraction of tuberculosis and poor treatment outcomes. Data suggest that undernutrition impairs innate and adaptive immune responses needed to control Mycobacterium tuberculosis infection and may affect responses to live vaccines, such as BCG. Given its impact on tuberculosis, addressing undernutrition will be a vital component of the World Health Organization End TB strategy. This narrative review describes the effect of undernutrition on the immune response, vaccine response, and tuberculosis incidence, severity, and treatment outcomes.
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Potential Effect of Statins on Mycobacterium tuberculosis Infection.
Guerra-De-Blas, PDC, Torres-González, P, Bobadilla-Del-Valle, M, Sada-Ovalle, I, Ponce-De-León-Garduño, A, Sifuentes-Osornio, J
Journal of immunology research. 2018;:7617023
Abstract
Tuberculosis is one of the 10 leading causes of death in the world. The current treatment is based on a combination of antimicrobials administered for six months. It is essential to find therapeutic agents with which the treatment time can be shortened and strengthen the host immune response against Mycobacterium tuberculosis. M. tuberculosis needs cholesterol to infect and survive inside the host, but the progression of the infection depends to a large extent on the capacity of the immune response to contain the infection. Statins inhibit the synthesis of cholesterol and have pleiotropic effects on the immune system, which have been associated with better results in the treatment of several infectious diseases. Recently, it has been reported that cells treated with statins are more resistant to M. tuberculosis infection, and they have even been proposed as adjuvants in the treatment of M. tuberculosis infection. The aim of this review is to summarize the immunopathogenesis of tuberculosis and its mechanisms of evasion and to compile the available scientific information on the effect of statins in the treatment of tuberculosis.
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Vitamin C: A Natural Inhibitor of Cell Wall Functions and Stress Response in Mycobacteria.
Syal, K, Chatterji, D
Advances in experimental medicine and biology. 2018;:321-332
Abstract
Tuberculosis, caused by Mycobacterium tuberculosis, has re-emerged as a threat to human race. Conventional antibiotic treatments are failing due to different stress response strategies adopted by bacterial pathogens. Since time immemorial, Vitamin C is known to protect against pathogens by boosting immunity in humans. Recently, Vitamin C has been shown to directly kill M. tuberculosis including multiple drug-resistant strains by generation of oxidative radicals through Fenton's reaction. Concurrently, it inhibits (p)ppGpp-mediated stringent response thus effectively shutting down long-term survival and persistence in mycobacteria. Here, we have discussed historical perspective and recent evidences on Vitamin C-mediated inhibition of several key pathways of M. tuberculosis such as (p)ppGpp synthesis and mycobacterial cell wall function. Several cell wall components including mycolic acids are critical for mycobacterial virulence. We observed downregulation of various mycolic acids in M. smegmatis upon treatment with Vitamin C, and data have been presented here. Vitamin C has been shown to inhibit the biofilm growth as well as disrupt the formed biofilm in mycobacteria. Additionally, Vitamin C role in cell-mediated and humoral immunity has been elucidated. Vitamin C is toxic at high concentration; therefore we have proposed the idea of derivatizing Vitamin C in order to lower the minimal inhibition concentration (MIC) necessary to target M. tuberculosis.
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The Synergistic Effects of the Glutathione Precursor, NAC and First-Line Antibiotics in the Granulomatous Response Against Mycobacterium tuberculosis.
Teskey, G, Cao, R, Islamoglu, H, Medina, A, Prasad, C, Prasad, R, Sathananthan, A, Fraix, M, Subbian, S, Zhong, L, et al
Frontiers in immunology. 2018;:2069
Abstract
Mycobacterium tuberculosis (M. tb), the causative bacterial agent responsible for tuberculosis (TB) continues to afflict millions of people worldwide. Although the human immune system plays a critical role in containing M. tb infection, elimination proves immensely more challenging. Consequently, there has been a worldwide effort to eradicate, and limit the spread of M. tb through the conventional use of first-line antibiotics. Unfortunately, with the emergence of drug resistant and multi-drug resistant strains of M. tb the archetypical antibiotics no longer provide the same ascendancy as they once did. Furthermore, when administered, these first-line antibiotics commonly present severe complications and side effects. The biological antioxidant glutathione (GSH) however, has been demonstrated to have a profound mycobactericidal effect with no reported adverse consequences. Therefore, we examined if N-Acetyl Cysteine (NAC), the molecular precursor to GSH, when supplemented in combination with suboptimal levels of standalone first-line antibiotics would be sufficient to completely clear M. tb infection within in vitro derived granulomas from healthy subjects and individuals with type 2 diabetes (T2DM). Our results revealed that by virtue of immune modulation, the addition of NAC to subprime levels of isoniazid (INH) and rifampicin (RIF) was indeed capable of inducing complete clearance of M. tb among healthy individuals.