Relevant bibliographies by topics / EXtremely Drug Resistant Tuberculosis

Academic literature on the topic 'EXtremely Drug Resistant Tuberculosis'

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Published: 6 September 2023

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Journal articles on the topic "EXtremely Drug Resistant Tuberculosis"

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Polsfuss, Silke, Sabine Hofmann-Thiel, Matthias Merker, David Krieger, Stefan Niemann, Holger Rüssmann, Nicolas Schönfeld, Harald Hoffmann, and Katharina Kranzer. "Emergence of Low-level Delamanid and Bedaquiline Resistance During Extremely Drug-resistant Tuberculosis Treatment." Clinical Infectious Diseases 69, no. 7 (February 2, 2019): 1229–31. http://dx.doi.org/10.1093/cid/ciz074.

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Abstract Two new drugs, delamanid and bedaquiline, have recently been approved for treatment of multidrug-resistant and extensively drug-resistant (XDR) tuberculosis. Here, we report a case of clofazimine, bedaquiline, and low-level delamanid resistances acquired during treatment of a patient with XDR tuberculosis.
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Migliori, G. B., R. Centis, L. D'Ambrosio, A. Spanevello, E. Borroni, D. M. Cirillo, and G. Sotgiu. "Totally Drug-Resistant and Extremely Drug-Resistant Tuberculosis: The Same Disease?" Clinical Infectious Diseases 54, no. 9 (April 9, 2012): 1379–80. http://dx.doi.org/10.1093/cid/cis128.

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Antonenko, Kate, Valentin Kresyun, and Peter Antonenko. "Mutations leading to drug-resistant Mycobacterium tuberculosis infection in Ukraine." Open Medicine 5, no. 1 (February 1, 2010): 30–35. http://dx.doi.org/10.2478/s11536-009-0114-6.

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AbstractThe goal of this research was detection of the drug-resistance level of Mycobacterium tuberculosis infection in the Odesa region of Southwest Ukraine, investigation of the level of mutation in katG and rpoB genes for M. tuberculosis with polymerase chain reaction (PCR), and spread of these mutations in different groups of patients with tuberculosis. An extremely high level of primary and acquired resistance of M. tuberculosis to first-line antituberculosis drugs has been found in the Southwest region of Ukraine. The PCR method has proved to have high sensitivity in the detection of mutations in katG and rpoB genes. The data showed significant spreading of M. tuberculosis strains with mutations in katG and rpoB genes in penitentiaries and an increased level of these mutations during tuberculosis treatment. The presence of mutations in rpoB and katG genes was associated with a more severe course of tuberculosis, increased risk of treatment default, persistence of positive smears on microscopy at discharge, and poor closing of tuberculous cavities. Extremely high level of mutations in the rpoB and katG genes of M. tuberculosis was observed in Beijing family strains. Our findings support the capability of the PCR method to detect M. tuberculosis that is resistant to drugs such as isoniazid and rifampicin.
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Allué-Guardia, Anna, Rajagopalan Saranathan, John Chan, and Jordi B. Torrelles. "Mycobacteriophages as Potential Therapeutic Agents against Drug-Resistant Tuberculosis." International Journal of Molecular Sciences 22, no. 2 (January 13, 2021): 735. http://dx.doi.org/10.3390/ijms22020735.

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The current emergence of multi-, extensively-, extremely-, and total-drug resistant strains of Mycobacterium tuberculosis poses a major health, social, and economic threat, and stresses the need to develop new therapeutic strategies. The notion of phage therapy against bacteria has been around for more than a century and, although its implementation was abandoned after the introduction of drugs, it is now making a comeback and gaining renewed interest in Western medicine as an alternative to treat drug-resistant pathogens. Mycobacteriophages are genetically diverse viruses that specifically infect mycobacterial hosts, including members of the M. tuberculosis complex. This review describes general features of mycobacteriophages and their mechanisms of killing M. tuberculosis, as well as their advantages and limitations as therapeutic and prophylactic agents against drug-resistant M. tuberculosis strains. This review also discusses the role of human lung micro-environments in shaping the availability of mycobacteriophage receptors on the M. tuberculosis cell envelope surface, the risk of potential development of bacterial resistance to mycobacteriophages, and the interactions with the mammalian host immune system. Finally, it summarizes the knowledge gaps and defines key questions to be addressed regarding the clinical application of phage therapy for the treatment of drug-resistant tuberculosis.
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Mumena, David Kajoba, Geoffrey Kwenda, Caroline Wangari Ngugi, and Andrew Kimanga Nyerere. "Drug-Resistant Tuberculosis Types and Their Treatment Regimens Using First-Line, Second-Line Injectable, Third-Line, Fluoroquinolones, Aminoglycosides, Cyclic Polypeptides, Novel and Repurposed Anti-Tuberculosis Drugs." Journal of Biomedical Research & Environmental Sciences 3, no. 8 (September 2022): 988–93. http://dx.doi.org/10.37871/jbres1542.

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Drug-Resistant Tuberculosis (DR-TB) causes high mortality and morbidity rates globally. DR-TB and COVID-19 pandemic are posing a major risk to global public health and economic security, and are jeopardizing efforts in the control, prevention and elimination of TB globally. Mycobacterium tuberculosis (MTB) has continued to evolve resistance to anti-TB drugs. Different types of DR-TB have been defined and they include; mono drug-resistant TB, Multi Drug-Resistant TB (MDR-TB), poly drug-resistant TB, pre-Extensively Drug-Resistant TB (pre-XDR TB), Extensively Drug-Resistant TB (XDR-TB), Extremely Drug-Resistant TB (XXDR-TB), and Totally Drug-Resistant TB (TDR-TB). DR-TB is caused by several factors which include: non-adherence, poor compliance, low efficacy anti-TB drugs, delayed diagnosis, interrupted supply, stock-outs, inadequate infection control, HIV co-infection, spontaneous mutations, and chromosomal replication errors. Global TB targets have gone off-track and years of progress reversed due to DR-TB and the COVID-19 pandemic. Treatment failure, death and costs incurred are higher among patients suffering from DR-TB than among those with susceptible TB. For this reason, susceptible TB needs to be diagnosed quickly and treated effectively to prevent its progression to DR-TB. Treatment for susceptible TB requires the use of first-line anti-TB drugs; rifampicin, isoniazid, pyrazinamide, and ethambutol. While DR-TB is treated using the second- and third-line anti-TB drugs. Effective treatment of TB is dependent on: prompt and accurate diagnosis of TB and recognition of drug-resistance; adherence to treatment; robust contact tracing and prophylactic treatment of TB contacts; and screening for TB infection in high-risk groups.
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Shen, Xin, Guo-miao Shen, Jie Wu, Xiao-hong Gui, Xia Li, Jian Mei, Kathryn DeRiemer, and Qian Gao. "Association between embB Codon 306 Mutations and Drug Resistance in Mycobacterium tuberculosis." Antimicrobial Agents and Chemotherapy 51, no. 7 (April 16, 2007): 2618–20. http://dx.doi.org/10.1128/aac.01516-06.

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ABSTRACT embB306 mutants were detected in both ethambutol (EMB)-resistant and EMB-susceptible strains of Mycobacterium tuberculosis. Multidrug-resistant (MDR) strains had a higher proportion of embB306 mutants than non-MDR strains (odds ratio, 6.78; P < 0.001). The embB306 locus is a candidate marker for rapid detection of MDR and extremely drug resistant tuberculosis.
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Pecho-Silva, Samuel, Ana Claudia Navarro-Solsol, Vicky Panduro-Correa, Jorge L. Maguina, Ali A. Rabaan, Luis Rene Quiroz-Ramirez, Kovy Arteaga-Livias, and Alfonso J. Rodriguez-Morales. "The first successful cochlear implant in Latin America after severe aminoglycoside-induced ototoxicity in a Peruvian patient cured of extensively drug-resistant tuberculosis." Revista del Cuerpo Médico Hospital Nacional Almanzor Aguinaga Asenjo 15, no. 4 (February 8, 2023): 622–25. http://dx.doi.org/10.35434/rcmhnaaa.2022.154.1501.

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Introduction: Multidrug-resistant tuberculosis is a significant public health problem for which drugs are used with many adverse effects. Among the devastating consequences of these diseases, there is a wide variation in the incidence of ototoxicity and hearing loss in patients with multidrug-resistant and extremely resistant tuberculosis. Cochlear implants may be indicated in patients with unilateral/severe bilateral hearing loss with no benefit from conventional hearing aids, but their use in patients with tuberculosis is rare. Case report: We present the first case of a right unilateral cochlear implant performed on a 34-year-old Peruvian patient who presented profound sensorineural hearing loss of cochlear origin. Conclusion: Cochlear implant surgery is an essential milestone in the treatment of patients with auditory sequelae of tuberculosis treatment. Close monitoring of possible complications of tuberculosis treatment should be strengthened in countries with a high incidence of multidrug-resistant and extremely resistant tuberculosis.
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Yadav, Snehlata, and Balasubramanian Narasimhan. "New Insights in Design and Development of Antitubercular Drugs." Current Bioactive Compounds 16, no. 1 (February 20, 2020): 13–23. http://dx.doi.org/10.2174/1573407215666190409153756.

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Background: Tuberculosis, an infectious disease caused mainly by the Mycobacterium tuberculosis accounts for the highest number of deaths worldwide. Despite curing millions, the currently used drug regimens are bounded by various limitations such as long course of therapy, emergence of resistance and permanent tissue damage. The treatment of multidrug-resistant and extremely drugresistant tuberculosis is a challenging task due to its reliance on second-line drugs which are less potent and more toxic than those used in the clinical management of drug-susceptible tuberculosis. Therefore, the major challenges in the upcoming years are to overcome the emergence of increased number of multidrug-resistant as well as extensively drug-resistant strains and the ineptness of the current treatment regimens against latent tuberculosis. Bedaquiline and Delamanid are the only new anti-TB drugs that have been currently approved since more than 40 years after discovery of isoniazid. Bedaquiline is the first diarylquinoline derivative that has showed resilient culture conversion at 24 weeks in phase IIb trials. Methods: Extensive literature search on the topic was undergone using a focused question. Results: Fifty-eight research articles from journals of repute are included in the review. The vaccine and peptide-based conjugates are recent developments against Mycobacterium for selective and specific targeting to the desired tissues. Conclusion: In this review, we have focused on the different classes of chemical as well as plant based compounds as potent antitubercular agents against multidrug-resistant tuberculosis strains. This review falls light on the importance of research been undergoing in different parts of the world to combat the ever increasing problem of mycobacterial resistance and the various treatment options available for the treatment of tuberculosis.
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Shaji, Jessy, and Mahmood Shaikh. "DRUG-RESISTANT TUBERCULOSIS: RECENT APPROACH IN POLYMER BASED NANOMEDICINE." International Journal of Pharmacy and Pharmaceutical Sciences 8, no. 10 (August 12, 2016): 1. http://dx.doi.org/10.22159/ijpps.2016v8i10.11295.

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<p>Tuberculosis (TB) had been a leading chronic bacterial infection since decades. Current therapeutic management of Mycobacterium tuberculosis (MTB) is inadequate due to the lengthy course of treatment, drug-related side effects and ill-planned therapy, and these factors can lead to therapeutic failure and the emergence of drug-resistant TB. The Multi-drug-resistant (MDR) TB needs a lengthy course of treatment with second-line antitubercular drugs (ATDs) having higher side effects and cost. The misuse of second-line ATDs may result in extremely drug-resistant (XDR) strain which is very difficult to treat and require high doses of drugs resulting in more toxicity and side effects. This review highlights the need for novel drug delivery for the treatment of drug-susceptible and resistant TB. The characteristics of the nanoparticulate system in ATDs delivery and its approach in the MDR and XDR TB are discussed. The lung is the site of infection in pulmonary TB and the targeted drug delivery to the site of infection helps in achieving increased efficacy with less dose further reducing the side effects and toxicity. The symbiotic association of nanotechnology and pulmonary drug delivery give rise to an efficient inhalable polymer based nanoparticulate system containing ATDs for the better management of drug-susceptible and resistant TB. Various ATDs loaded polymer based nanocarrier systems like Alginate, PLGA, Chitosan and Gelatin nanocarriers are discussed in detail. Thus, this review highlights the current research in pulmonary drug delivery of polymer based ATDs nanomedicine and their importance in control of drug-resistant TB.</p>
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Velayati, A. A., P. Farnia, M. A. Merza, G. K. Zhavnerko, P. Tabarsi, L. P. Titov, J. Ghanavei, et al. "New insight into extremely drug-resistant tuberculosis: using atomic force microscopy." European Respiratory Journal 36, no. 6 (November 30, 2010): 1490–93. http://dx.doi.org/10.1183/09031936.00064510.

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Dissertations / Theses on the topic "EXtremely Drug Resistant Tuberculosis"

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Smith, Louise. "Resilience of the partners of long term hospitalised patients with multidrug-resistant (MDR) and extreme drug-resistant (XDR) tuberculosis (TB)." Thesis, Nelson Mandela Metropolitan University, 2013. http://hdl.handle.net/10948/d1020913.

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Patients diagnosed with Multidrug-resistant(MDR) and Extreme drug-resistant (XDR) tuberculosis (TB) have to be hospitalised for a period of six to twelve months, according to the MDR/XDR Policy Guidelines on the treatment of drug-resistant TB – until the patient recovers, and is no longer infectious. There are factors associated with both the patients’ and their partners’ (spouses) resistance to long-term hospitalisation. This has resulted in several acts of violence against the hospital property and members of the health-care team. However, there are a small number of partners who assist the health-care team – by ensuring compliance from the patients and providing their continued support to the patient – despite their own risk of being infected with MDR and XDR TB. This qualitative study was aimed at exploring and describing the resilience factors that have been observed amongst a small number of partners of patients with MDR and XDR TB at an in-patient treatment centre in Port Elizabeth. The research design was exploratory, descriptive and contextual in nature; and the researcher interviewed eight spouses or live-in partners of patientsfor this study, until data saturation was achieved. The data were collected through semi-structured interviews; and the data analysis was conducted, according to the eight steps proposed by Tesch model of data analysis (in Creswell, 1998).Guba’smodel of trustworthiness was used to assess the data collected during the interviews. The findings from this study will inform the health-care team on methods of how the support of the patients’ partners could be mobilised in the holistic treatment plan of MDR and XDR TB patients in an in-patient treatment centre.
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Seddon, James Alexander. "Drug-resistant tuberculosis in children." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2012. http://researchonline.lshtm.ac.uk/4646555/.

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The number of children globally who develop drug-resistant tuberculosis is unclear, in part due to diagnostic challenges and limited resistance testing, and in part because recording and reporting is not comprehensive. Large numbers of children, however, are exposed to drug resistant bacilli each year and it is clear that the very young and those immune-compromised are vulnerable to developing disease. Few studies have looked at the progression from exposure to infection or from infection to disease in the child contacts of adults with drug-resistant tuberculosis. It is uncertain which factors influence this progression and also whether any interventions can prevent it. Finally, few studies have analysed the presentation, treatment and outcome of children with disease. This thesis starts by reviewing what is published regarding drug-resistant tuberculosis in children. This includes systematic reviews of the management of children exposed to drug resistant tuberculosis as well as the management of those with multi drug-resistant tuberculosis disease. It reviews what is known regarding the second-line tuberculosis drugs in children and then clarifies the definitions that are used throughout the rest of the work. The thesis then systematically examines each of the stages from infection to disease with a series of inter-related studies. The first study attempts to quantify the burden of drug resistance in the context that the work is carried out. The following study investigates the risk factors for infection and prevalent disease in children exposed to a multi drug-resistant tuberculosis source case. This is followed by two studies which explore the transmission of drug-resistant bacilli from adults to children. The identification and referral patterns and obstacles to referral for exposed children are examined through operational studies that include qualitative and quantitative components. A descriptive cohort study assesses the toxicity and efficacy of a standardised preventive treatment regimen given to child contacts. The final part of the thesis includes a series of studies to investigate the treatment of drug resistant tuberculosis disease in children and the adverse effects of the second-line medications.
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Patel, Fadheela. "Development of a cost-effective drug sensitivity test for multi-drug resistant and extensively drug-resistant tuberculosis." Thesis, Cape Peninsula University of Technology, 2010. http://hdl.handle.net/20.500.11838/1496.

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Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2010
The World Health Organisation estimates that nine million people are infected with tuberculosis (TB) every year of which ninety-five percent live in developing countries. Africa has one of the highest incidences of TB in the world. but few of its countries are equipped to diagnose drug-resistant TB. This study aimed to develop a robust. yet simple and cost-effective assay. which would require minimal sophisticated instrumentation and specialised personnel that would make drug sensitivity screening for multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) accessible to resource-poor high-burden settings. A four-quadrant colorimetric agar plate method was developed which showed good specificity (97.3%-100%) and sensitivity (77.8%-100%) compared to the polymerase chain reaction (PCR) method used as gold standard. Agreement between the methods. using Simple Kappa Coefficients. ranged between very good and excellent. all with high statistical significance (P < 0.0001). The currently used BACTEC MGIT SIREN sensitivity assay coupled with the E-test® strip method. as routinely used in the TB reference laboratory. was compared and showed excellent comparison with the newlydeveloped plate method. for each antibiotic tested. as well as the resultant monoresistant, MDR- or XDR-TB diagnoses. Moreover. the new method was found to be extremely cost-effective. priced at half the cost of a peR assay. These four quadrant plates. with a colorimetric indicator and selected antibiotics. can be considered as an economic altemative or a complimentary method for laboratories wishing to reduce the cost and complexity for TB drug sensitivity testing. Routine diagnostic testing would thus be made more accessible and affordable to laboratories that are not presently diagnosing drug resistant TB. therefore enhancing case detection and treatment in the resource-poor settings hardest hit by this curable disease.
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Krüüner, Annika. "Drug-resistant Mycobacterium tuberculosis in Estonia /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-455-0/.

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Dubiniecki, Christine. "Drug resistant tuberculosis in Montreal 1992-1995." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33751.

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Objective. Since the 1980's the incidence of tuberculosis (TB) in Montreal has remained at 11 cases per 100,000. In order to improve TB prevention and control programs, we sought to identify predictors of tuberculosis drug-resistance and to describe the epidemiology of TB drug resistance on the island of Montreal.
Study design. Retrospective descriptive analysis Study population. All culture proven TB patients reported to the Montreal Regional Health Board aged 0--49 for 1992--1994 and 0--18 years for 1995.
Results. Drug resistant TB was found in 18.3% of culture-proven TB cases. The rate of INH resistance in our study cohort was 10.6%. Two percent of TB cases were found to have MDR-TB. Only 3 TB cases (0.9%) in our study cohort developed acquired drug resistance over the study period. Previous history of TB was associated with a 3.9 times greater risk of drug resistant TB.
Conclusions. Drug resistance is a significant problem in Montreal that continues to hinder TB treatment and control. Previous history of tuberculosis is a strong predictor of drug resistance. In addition, immigration from individual countries was not associated with an increase in the rate of drug resistance. Nonetheless, country-specific drug resistance rates may serve to predict the likelihood of drug resistant TB among the foreign-born in Canada.
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Ford, Christopher Burton. "The Evolution of Drug Resistant Mycobacterium Tuberculosis." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10596.

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Mycobacterium tuberculosis (Mtb) poses a global health catastrophe that has been compounded by the emergence of highly drug resistant Mtb strains. We used whole genome sequencing (WGS) to directly compare the accumulation of mutations in Mtb isolated from cynomolgus macaques with active, latent and early reactivation disease. Based on the distribution of single nucleotide polymorphisms (SNPs) observed, we calculated the mutation rates for these disease states. Our data suggest that during latency, Mtb acquires a similar number of chromosomal mutations as would be expected to emerge in a logarithmically growing culture over the same period of time despite reduced bacterial replication during latent infection. The pattern of polymorphisms suggests that the mutational burden in vivo is due to oxidative DNA damage. We next sought to determine why some strains of Mtb are preferentially associated with high-level drug resistance. We demonstrate that Mtb strains from the East Asian lineage acquire drug resistances in vitro more quickly than Mtb strains from the Euro-American lineage. Their higher drug resistance rate in vitro reflects a higher basal mutation. Moreover, the in vitro mutation rate correlates well with the bacterial mutation rate in humans as determined by whole genome sequencing of clinical isolates. Finally, using an agent-based model, we show that the observed differences in mutation rate predict a significantly higher probability of multi-drug resistance in patients infected with East Asian lineage strains of Mtb. Lastly, we sought to determine the mechanisms Mtb uses to proofread nascently polymerized DNA. Through fluctuation analysis of deletion mutants of two potential \(polIII\epsilon\) homologs, we demonstrate that neither is responsible for the maintenance of DNA replication fidelity. To explore the possibility that one of these homologs, Rv3711c, participates in an unknown redundant pathway, we used transposon capture and sequence (TraCS) to identify genes conditionally essential in an Rv3711c deletion mutant. Our analysis suggests that while Rv3711c does not participate in proofreading, it may act in an alternative novel DNA repair pathway. Taken together, our fluctuation analysis and TraCS data suggest that mycobacteria do not use canonical methods of proofreading to maintain genomic fidelity.
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Shean, Karen Penelope. "Extensively drug resistant tuberculosis in South Africa." Master's thesis, University of Cape Town, 2011. http://hdl.handle.net/11427/11620.

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Includes abstract.
Includes bibliographical references (leaves 161-168).
There are few data for treatment-related outcomes in patients with XDR tuberculosis in settings with high HIV prevalence. We reviewed the case records of 227 consecutively diagnosed South African patients with XDR-TB between 2002 and 2008, and analysed the records of another 115 patients, retrospectively, for adverse drug reactions (ADRs). It was found that a significant proportion of XDR-TB patients are HIV unrelated, and prognosis, regardless of HIV status, poor. Nevertheless, survival in HIV infected patients is better than previously reported, and treatment with HAART improves outcomes. The frequency of ADR’s with XDR-TB treatment regimens is high, often severe, and negatively impacts on culture conversion outcomes. These data have implications for the formulation of recommendations for control programmes in resource-poor settings.
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Al-Shammaa, Zaid. "Targeting Drug-Resistant Tuberculosis Using SMART Nanotechnology Approach." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1439310613.

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Stoffels, Karolien. "Contribution to the research on drug resistant Mycobacterium tuberculosis." Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209194.

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Tuberculosis (TB) is a potentially fatal contagious disease that can affect almost any part of the body but is mainly an infection of the lungs. It is caused by micro-organisms of the Mycobacterium tuberculosis complex. It is the second greatest killer worldwide due to a single infectious agent, after the Human Immunodeficiency Virus (HIV). Without treatment, fatality is 50% in immune competent persons. TB remains the leading cause of death among HIV positive persons, causing one fifth of the deaths. The World Health Organization estimates that one third of the world population is infected by this micro-organism but only 5 to 10% develop TB disease. Nevertheless, this enormous reservoir leads to around 1.4 millions deaths annually. Standard curative treatment lasts at least 6 months and includes 4 different drugs. Toxicity of the drugs leading to (severe) adverse events and the long duration of the daily administration challenges patient’s compliance. Subinhibitory concentration of the drugs (due to poor adherence) can induce resistance of the mycobacteria to the provided drugs. Unlike most bacteria where resistance is acquired by plasmids, drug resistance of mycobacteria is obtained by genomic mutations. “Multi drug-resistant tuberculosis (MDR-TB)” is strictly defined as TB resistant to specifically isoniazid and rifampicin, the two main first line drugs. “Extensively drug resistance (XDR)” is defined as MDR-TB with additional resistance to any of the fluoroquinolones (such as ofloxacin or moxifloxacin) and to at least one of three injectable second-line drugs (amikacin, capreomycin or kanamycin). The increase of MDR-TB represents an enormous challenge to Public Health globally. This research examined different aspects of tuberculosis resistance performed in the Belgian National Reference Center, a clinical laboratory setting.

First of all, a profound analysis of the MDR-TB situation in Belgium was conducted. It is the first retrospective population-based survey of MDR-TB in Belgium, covering a 15-year period (1994-2008). It comprises 174 patients representing more than 80% of the culture positive MDR-TB patients reported to the Belgian register, thus this study is considered of national relevance. It includes bacteriological and molecular data on the isolates as well as clinical aspects of the patients and treatment results. Considering only the patient’s first MDR-TB isolate, an increase over time was observed in the number of isolates resistant to a second-line drug as well as the total number of drugs each isolate was resistant to. XDR-TB was detected since 2002 and panresistant TB (resistant to every available antituberculosis drug) since 2009. Overall, a successful treatment outcome was obtained for 67.8% of the MDR-TB cases. Drug susceptibility testing (DST) of Mycobacterium tuberculosis to first line drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) in liquid culture medium has a turn around time of at least two weeks, after identification of the positive culture (obtained after 2 to 4 weeks) from the patient’s clinical isolate. In order to provide the clinician with valuable information about the isolated mycobacteria leading to patient adapted therapy before bacteriological DST results are available, resistance is predicted by detection of mutations in certain genes of the mycobacteria. It is common practice for rifampicin (rpoB gene) and isoniazid (katG gene and/or inhA promoter region). In this MDR-TB collection, rifampicin resistant related mutations were found in 97.1% (168/173) of the clinical isolates and isoniazid resistant related mutations in 94.1% (160/170). The pncA, embB and gyrA genes have been sequenced to identify possible mutations because of their possible involvement with resistance to pyrazinamide, ethambutol and the fluoroquinolones respectively. However, little is known about the resistance prediction value of the mutations in these genes.

The study is also the first study on the molecular epidemiology of MDR-TB in the country. DNA fingerprinting showed a large diversity of strains (67% of the patients were infected by a strain with a unique pattern) and further epidemiological examination revealed limited local transmission of MDR-TB in Belgium.

The second part investigated the pncA gene and its association with pyrazinamide resistance in MDR-TB isolates from Belgium and in vitro cultured spontaneous mutants. The genetic analysis showed that 98.3% (59/60) of the Belgian clinical MDR pyrazinamide resistant (PZAR) isolates present a mutation in the pncA gene. We found 1.7% (1/60) of the PZAR MDR-isolates encoding wild type pncA and flank. A total (PZAR and PZAS) of 41 different amino acid changes, 3 protein truncations and 5 frameshifts were observed including eight novel mutations: 8Asp>Ala, 13Phe>Leu, 64Tyr>Ser, 107Glu>stop, 143Ala>Pro, 172Leu>Arg and frameshifts starting in codon 55 and 82. Analysis of all observed mutations (i.e. in clinical isolates as well as spontaneous mutants) revealed that they are not always associated with drug resistance and that they are not scattered randomly throughout the gene, but occur rather at preferential sites such as in codons with amino acids associated with either iron or substrate binding and catalytic active sites. The frequency of in vitro mutagenesis to pyrazinamide at pH 6.0 was determined and found to be relatively high at 10-5 CFU/ml.

Finally, the in vitro activity of tobramycin and clarithromycin (with unclear efficacy against M. tuberculosis) was evaluated on 25 M. tuberculosis clinical isolates with various resistance profiles. The effect of the drugs administered together was examined for possible synergistic effect. The median minimum inhibitory concentration (MIC) of 8 µg/ml obtained for both drugs in this study is rather high but are beyond the concentrations obtained in lung tissues. This suggests that both drugs should be investigated further as potential adjuncts to the treatment of resistant TB when other alternatives have failed; in particularly through new drug delivery systems such as the Dry Power Inhaler which allows local drug deposition with high drug concentrations in the lungs but low toxicity due to limited systemic absorption. In addition, for 36% of the tested isolates a decrease of the MIC of clarithromycin by a single or twofold dilution was observed in the presence of a subinhibitory concentration of tobramycin and no antagonistic effect was seen for the remaining isolates.

This research illustrates different (laboratory) aspects in the fight against drug resistant TB, all using the Belgian TB collection: characterisation of the Belgian MDR-TB situation on bacteriological, molecular and epidemiological level; profound analysis of genomic mutations and their possible association with drug resistance; and investigation of synergistic activity of drugs with low efficacy against M. tuberculosis.


Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished

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Kwong, Tsz-ching, and 鄺芷晴. "The role of molecular diagnosis of drug resistant tuberculosis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2015. http://hdl.handle.net/10722/208588.

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Emerging multidrug-resistant tuberculosis (MDR-TB) is one of the most urgent global public health issues. Recent advances in molecular techniques should enable the development of different rapid detection tests for drug-resistant TB. Large-scale comparative studies on the diagnostic accuracy and turn-around-time (TAT) of these novel assays may promote their smooth implementation as routine tests for TB in diagnostic laboratories. In a pilot evaluation of 30 clinical isolates and 202 sputum specimens, diagnostic performance of a novel in-house assay for MTB identification (IS6110 qPCR) was compared to a commercial COBAS TaqMan MTB test (Roche Diagnostics). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of IS6110 qPCR were 100%, 94.6%, 85.2% and 100%, respectively, compared to 94.7%, 100%, 100% and 98.6% for COBAS TaqMan MTB. Large-scale validation using 2,350 sputum specimens revealed the optimal cut-off crossing point (Cp) value of IS6110 qPCR was 29.61 with 97.3% sensitivity and 98.3% specificity determined by receiver operating characteristics (ROC) curve analysis. The median TAT for IS6110 qPCR and COBAS TaqMan MTB test to the reporting of results was 0.9 and 1.2 days, respectively. Among the IS6110 qPCR-positive specimens in the large-scale validation, 287 samples were tested in-house by katG MAS-PCR and rpoB PCR sequencing assays and 159 samples were tested by GenoType® MTBDRplus assay (Hain LifeScience). The sensitivity and specificity of katG MAS-PCR for isoniazid (INH) resistance detection were 71.4% and 99.5%, respectively. The sensitivity and specificity of rpoB PCR sequencing for rifampicin (RIF) resistance detection were 100% and 99.6%, respectively. Commercial GenoType® MTBDRplus assay reached 100% sensitivity for both INH and RIF resistance detection at a specificity of 99.3% and 100%, respectively. The median TAT for the in-house assays and GenoType® MTBDRplus assay to the reporting of the results was 4.7 and 1.4 days, respectively. The findings from this study provide different implementation strategies for diagnostic test combinations. The most cost-effective drug-resistant TB diagnosis cascade was IS6110 qPCR followed by GenoType® MTBDRplus assay. The TAT for results is 2.3 days at a cost of US$49.7. Despite an additional cost of US$24.6, COBAS TaqMan MTB test should replace IS6110 qPCR in populations with high prevalence of IS6110-negative strains. The in-house katG MAS-PCR and rpoB PCR sequencing assays should be used in developing countries instead of the expensive GenoType® MTBDRplus assay. Subsequently, accurate diagnosis of drug-resistant tuberculosis can be achieved in 4.5 days with a reasonable reagent cost of US$9.3. In conclusion, excellent diagnostic accuracy and shorter TAT of the molecular diagnostic cascade for drug-resistant TB, in particular IS6110 qPCR, can serve to guide physicians in the prompt choice of chemotherapy. This leads to timely delivery of anti-TB treatments to patients and holds the promise of easing the MDR-TB burden.
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Microbiology
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Master of Philosophy
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Books on the topic "EXtremely Drug Resistant Tuberculosis"

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National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (U.S.). Division of Tuberculosis Elimination. TB elimination: Treatment of drug-resistant tuberculosis. Atlanta, Ga.]: National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Division of Tuberculosis Elimination, 2012.

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Harvard Medical School. Program in Infectious Disease and Social Change. and Open Society Institute, eds. The global impact of drug-resistant tuberculosis. Boston, MA: Program in Infectious Disease and Social Change, Dept. of Social Medicine, Harvard Medical School, 1999.

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Nguy, Shui. Drug-resistant tuberculosis: Causes, diagnosis, and treatments. Edited by K'ung Zhou. Hauppauge NY: Nova Science Publishers, 2009.

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Crofton, John. Guidelines for the management of drug-resistant tuberculosis. Geneva: World Health Organization, 1997.

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Crofton, John Wenman. Guidelines for the management of drug-resistant tuberculosis. Geneva: World Health Organization, 1997.

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John, Crofton. Guidelines for the management of drug-resistant tuberculosis. Geneva: WHO, 1997.

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John, Crofton. Guidelines for the management of drug-resistant tuberculosis. Geneva: World Health Organization, 1997.

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Guidelines on the management of drug-resistant tuberculosis. [Geneva]: World Health Organization, 1997.

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N, Rom William, and Garay Stuart M, eds. Tuberculosis. Boston: Little, Brown, 1996.

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Michael, Rich, and World Health Organization, eds. Guidelines for the programmatic management of drug-resistant tuberculosis. Geneva: World Health Organization, 2006.

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Book chapters on the topic "EXtremely Drug Resistant Tuberculosis"

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Dheda, Keertan, Aliasgar Esmail, Anzaan Dippenaar, Robin Warren, Jennifer Furin, and Christoph Lange. "Drug-Resistant Tuberculosis." In Clinical Tuberculosis, 301–26. Sixth edition. | Boca Raton, FL : CRC Press/Taylor & Francis Group, 2020.: CRC Press, 2020. http://dx.doi.org/10.1201/9781351249980-16.

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Davies, Peter D. O. "Multi-Drug-Resistant Tuberculosis." In Tuberculosis, 809–37. Berlin, Heidelberg: Springer Berlin Heidelberg, 2004. http://dx.doi.org/10.1007/978-3-642-18937-1_46.

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Liang, Lili, Yun Ma, Xin liu, and Yamin Lv. "Drug-Resistant Tuberculosis." In Drug Resistance in Bacteria, Fungi, Malaria, and Cancer, 193–208. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-48683-3_8.

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Ahmad Khan, Faiz, Greg Fox, and Dick Menzies. "Drug-Resistant Tuberculosis." In Handbook of Antimicrobial Resistance, 1–20. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0667-3_13-1.

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Ahmad Khan, Faiz, Greg Fox, and Dick Menzies. "Drug-Resistant Tuberculosis." In Handbook of Antimicrobial Resistance, 263–86. New York, NY: Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4939-0694-9_13.

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Bachappanavar, Nikhil, and Sinosh Skariyachan. "Combinatorial Designing of Novel Lead Molecules Towards the Putative Drug Targets of Extreme Drug-Resistant Mycobacterium tuberculosis: A Future Insight for Molecular Medicine." In Essentials of Bioinformatics, Volume II, 233–81. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-18375-2_12.

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Johnson, Livette S., and Kent A. Sepkowitz. "Treatment of multi-drug-resistant tuberculosis." In Tuberculosis, 317–30. Boston, MA: Springer US, 1995. http://dx.doi.org/10.1007/978-1-4899-2869-6_13.

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Xiao, Heping, Shenjie Tang, Wei Sha, Qing Zhang, and Jin Zhao. "Drug-Resistant TB." In Handbook of Global Tuberculosis Control, 135–56. Boston, MA: Springer US, 2017. http://dx.doi.org/10.1007/978-1-4939-6667-7_10.

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Schluger, Neil W. "Extensively Drug-Resistant Tuberculosis." In Emerging Infections 8, 337–53. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555815592.ch17.

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Auld, Sara C., Neel R. Gandhi, and James C. M. Brust. "Drug-Resistant Tuberculosis and HIV." In HIV and Tuberculosis, 203–37. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-29108-2_10.

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Conference papers on the topic "EXtremely Drug Resistant Tuberculosis"

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ankale, Padmaraj, Girija Nair, Abhay Uppe, Aleena Mathew, and Ria shah. "Socioeconomic Conditions Contributing to Multi Drug Resistant (MDR) and Extremely Drug Resistant(XDR) Tuberculosis." In ERS International Congress 2017 abstracts. European Respiratory Society, 2017. http://dx.doi.org/10.1183/1393003.congress-2017.pa2727.

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Sung, Nacmoon, Jeong Su Cho, Ki-Hong Kim, Jong-Ki Kim, JinHee Jung, Hyungseok Kang, Seungkyu Park, and Sanghoon Jheon. "Inactivation Of Multidrug Resistant (MDR)- And Extremely Drug Resistant (XDR)-Mycobacterium Tuberculosis Strains By Using Photodynamic Therapy (PDT)." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a3170.

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Waghmare, Manoj, Ketaki Utpat, Unnati Desai, and Jyotsna Joshi. "Drug resistant tuberculosis at a drug resistant tuberculosis centre, India- Analysis of outcome." In ERS International Congress 2017 abstracts. European Respiratory Society, 2017. http://dx.doi.org/10.1183/1393003.congress-2017.pa2729.

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Artiom, Jucov, and Lesnic Evelina. "Social determinants of drug-susceptible and drug resistant tuberculosis." In ERS International Congress 2016 abstracts. European Respiratory Society, 2016. http://dx.doi.org/10.1183/13993003.congress-2016.pa2749.

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Carroll, Matthew W., M. S. Lee, T. S. Song, Ying Cai, J. S. Lee, Y. M. Lee, L. E. Via, et al. "Linezolid For Extensively Drug Resistant Pulmonary Tuberculosis." In American Thoracic Society 2011 International Conference, May 13-18, 2011 • Denver Colorado. American Thoracic Society, 2011. http://dx.doi.org/10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a1838.

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Hidayathillah, Ariska Putri, Chatarina Umbul W, and Hari Basuki N. "Index Predictive of Drug Resistant Tuberculosis (MDR-TB) on Tuberculosis Patients." In The 2nd International Symposium of Public Health. SCITEPRESS - Science and Technology Publications, 2017. http://dx.doi.org/10.5220/0007511902270231.

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Campos, Michael Ramírez, Diana C. Rodríguez, and Alvaro D. Orjuela-Cañón. "Molecular Compounds Proposal for Drug-Resistant Tuberculosis in the Drug Discovery Process." In 2023 IEEE Colombian Conference on Applications of Computational Intelligence (ColCACI). IEEE, 2023. http://dx.doi.org/10.1109/colcaci59285.2023.10225875.

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Chopra, Manu, C. D. S. Katoch, G. D. S. Madan, and Barun Chakrabarty. "Outcomes of directly observed treatment for drug resistant tuberculosis." In ERS International Congress 2016 abstracts. European Respiratory Society, 2016. http://dx.doi.org/10.1183/13993003.congress-2016.pa2687.

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Moodliar, R., V. Aksenova, M. V. G. Frias IV, J. van de Logt, S. Rossenu, E. Birmingham, C. Kambili, et al. "Bedaquiline for Multi Drug-Resistant, Including Extensively or Pre-Extensively Drug-Resistant, Pulmonary Mycobacterium Tuberculosis in Children." In American Thoracic Society 2020 International Conference, May 15-20, 2020 - Philadelphia, PA. American Thoracic Society, 2020. http://dx.doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a1050.

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Madhav, Bhumika, Aparna Iyer, and T. K. Jayalakshmi. "Side effect profile of 2ndline drugs in multi drug resistant (MDR) and extensively drug resistant (XDR) tuberculosis." In Annual Congress 2015. European Respiratory Society, 2015. http://dx.doi.org/10.1183/13993003.congress-2015.pa2708.

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Reports on the topic "EXtremely Drug Resistant Tuberculosis"

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Yusim, Karina, Bette T. M. Korber, Shihai Feng, and Chang-Shung Tung. Compensatory mutation in RpoC restores fitness to rifampicin-resistant multi-drug resistant Mycobacterium tuberculosis. Office of Scientific and Technical Information (OSTI), August 2012. http://dx.doi.org/10.2172/1049993.

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Lau, J., and B. Baker. Isothermal DNA Assay to Detect Drug-Resistant Tuberculosis for Point-of-Care Diagnostics. Office of Scientific and Technical Information (OSTI), August 2013. http://dx.doi.org/10.2172/1093910.

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Rapid tests for diagnosing drug resistant tuberculosis are accurate and may be cost effective. National Institute for Health Research, November 2015. http://dx.doi.org/10.3310/signal-000145.

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