Dissertations / Theses: 'Multidrug resistant tuberculosis (MDR-TB)'

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Adebanjo, Omotayo David. "Knowledge, attittudes and practices of healthcare workers about prevention and control of multidrug-resistant tuberculosis at Botsabelo Hospital Maseru, Lesotho." Thesis, University of Limpopo ( Medunsa Campus), 2011. http://hdl.handle.net/10386/423.

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Thesis (MPH)--University of Limpopo, 2011.
Background: Tuberculosis is one of the major public health problems in Lesotho. With the occurrence of multi-drug resistant tuberculosis, little is known about the views of health care workers on this disease. The aim of this study was to investigate the knowledge, attitudes, and practices of healthcare professionals about prevention and control of MDR-TB at Botsabelo hospital, situated in Maseru, Lesotho. Methods: This study was conducted by means of a semi-structured, anonymous, and self-administered questionnaire that was sent to health care workers. Returned questionnaires were collected through designated boxes stationed at selected places at the study site from 23rd September to 13th October 2010. The investigator and his assistants collected the returned questionnaires on the 15th October 2010. Results: The results of this study indicate that, overall, less than half (47.3%) of respondents had good level of knowledge about MDR-TB; but the overwhelming majority of them held negative attitude towards patients with MDR-TB. Further analysis showed that the level of knowledge did not affect the attitude towards patients suffering from MDR-TB but it influenced their practices. Having good level of knowledge about MDR-TB was associated with good practices such as the use of protective masks and MDR-TB guidelines and involvement in educating patients about MDR-TB. Moreover, the findings of this study showed also that the attitude of respondents towards patients suffering from MDR-TB did not influence their practices. Conclusion: In conclusion, less than half of respondents had good level of knowledge about MDR-TB, but over 85.5% of them held negative attitude towards patients suffering from MDR-TB. Although the level of knowledge about MDR-TB was found not to have influenced the attitude of respondents towards patients suffering from MDR-TB; and that xi their attitude did not influence practices, good level of knowledge was positively associated with safer practices such as using protective masks, educating patients on MDR-TB, and referring to the MDR-TB guidelines manual. An educational remedial intervention is recommended.

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Akçakir, Yasemin. "Correlates of treatment outcomes of multidrug-resistant tuberculosis (MDR-TB): a systematic review and meta-analysis." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86914.

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Background: Multi-drug resistant tuberculosis (MDR-TB) is a major threat to global tuberculosis control. While observational studies have reported outcomes of MDR-TB treatment, there have been no randomized controlled trials for MDR-TB treatment outcomes. We did a systematic review and meta-analysis to examine individual and study-level factors associated with treatment outcomes for MDR-TB in the observational studies.
Method: We searched MEDLINE, EMBASE, BIOSIS, Web of Science from 1970 to July 2008, for publications in any language that described at least one treatment outcome among at least 25 patients with microbiologically proven MDR-TB. Data were extracted and where missing, principle investigators were contacted for more information. Rates of treatment outcomes were pooled using random effects. Subgroup analyses and meta-regression models were used to explore sources of heterogeneity.
Results: After screening 2187 titles and abstracts, 265 articles were identified for retrieval and full-text review, and of these, 72 articles met the inclusion criteria and were included in the meta-analysis. Data analysis was performed using the 64 unique cohorts reported by the 72 articles. The cohorts were quite heterogeneous in characteristics and outcomes. The mean size of the cohorts was 124 patients (range 25 to 1011). The mean age of participants in the cohorts was 39 years with females accounting for about one third. The median length of treatment was 18 months, and the average number of drugs in the regimen was five. The overall pooled rates of cumulative success (successful patients who did not relapse) was 50%, of cumulative failure (failure plus relapse) was 17%, of death was 13% and of default was 18%. These pooled outcome rates, however, must be interpreted with caution because of heterogeneity across studies. Subgroup and meta-regression analyses helped identify several factors associated with improved outcomes. Factors significantly associated with increased treatment success are treatment duration longer than 20 months, use of more than three sensitive drugs, individualized regimen, use of fluoroquinolones, or use of second-line agents in general. Factors that were significantly associated with high treatment mortality were high prevalence of HIV co-infection and use of three or fewer drugs. Low default rate was most strongly associated with shorter treatments and directly observed therapy. Use of second-line drugs was significantly associated with higher default rate. Considerable heterogeneity remained even within subgroups.
Conclusion: Outcomes of MDR-TB appear to vary considerably across studies and populations. The heterogeneity among studies poses a challenge in interpreting the results of this meta-analysis for clinical care, underscoring the need for future research to clarify optimal treatment of MDR-TB.
Contexte : La tuberculose multi-résistante (TB-MR) est une menace importante pour le contrôle de la tuberculose dans le monde. Tandis que les études d'observation ont rapporté des résultats de traitements de TB-MR, il n'y a eu aucune étude randomisée. Nous avons fait une revue systématique de la littérature et une méta-analyse afin d'examiner les facteurs liés aux résultats de traitement pour TB-MR, au niveau de l'individu et de l'étude, dans les études d'observation.
Méthode : Nous avons cherché à l'aide de MEDLINE, EMBASE, BIOS, et Web of Science, les publications dans toutes les langues qui décrivent au moins un résultat de traitement parmi au moins 25 patients atteints de TB-MR microbiologiquement prouvée, de 1970 à juillet 2008. Les données ont été extraites et les taux de résultats de traitement ont été mis en commun en utilisant le modèle d'effet au hasard random effect. Des analyses de sous-groupes et des modèles de méta régression ont été employés pour explorer les sources d'hétérogénéité.
Résultats : Après avoir répertorié2187 titres et résumés d'articles, 265 articles ont été identifiés et sélectionnées afin de récupérer le texte intégral pour les réviser; 72 de ces articles ont répondu aux critères d'inclusion et ont été inclus dans la méta analyse. L'analyse de données a été exécutée en utilisant les 64 cohortes uniques rapportées par les 72 articles. Les cohortes étaient hétérogènes dans leurs caractéristiques et leurs résultats. La taille moyenne des cohortes était de 124 patients (25 à 1011). L'âge moyen des participants était de 39 ans et les femmes représentaient environ le tiers des participants. La longueur médiane du traitement était de 18 mois et les patients recevaient en moyenne cinq médicaments différents. Le taux global de succès cumulatif (patients guéris qui n'ont pas fait de rechute) était de 50%, d'échec cumulatif (échec plus rechute), 17%, de mort, 13% et d'abandon de traitement, 18%. Toutefois, ces taux doivent être interprétés avec prudence en raison de l'hétérogénéité à travers des études. Avec des analyses de sous-groupes et de méta régression plusieurs facteurs associées à succès de traitement ont été identifier, comme - durée de traitement plus que 20 mois, utilisation de 3 médicaments ou plus, traitement individualise, ou l'utilisation de médicaments de secondes lignes. Facteurs associe avec la mortalité étaient haut prévalence de VIH et utilisation de 3 médicaments ou moins. Un taux élevé de non-adherence etait associe avec traitement plus longue, auto administration de médicaments, et l'utilisation de médicaments de seconde ligne. Une importante hétérogénéité est demeurée même dans les sous-groupes.
Conclusion : Les résultats de TB-MR semblent varier considérablement selon les études et les populations. L'hétérogénéité parmi les études pose un défi dans l'interprétation des résultats de cette méta analyse, soulignant le besoin d'autre recherche afin d'évaluer le traitement optimal pour TB-MR.

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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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Souza, Márcia Alves de. "Avaliação do desempenho da PCR Multiplex alelo específico para detecção de genes de Mycobacterium tuberculosis associados à resistência a Rifampicina e Isoniazida, a partir de amostra clínica." Universidade Federal do Amazonas, 2013. http://tede.ufam.edu.br/handle/tede/2565.

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Made available in DSpace on 2015-04-11T13:54:24Z (GMT). No. of bitstreams: 1 Marcia Alves de Souza.pdf: 1923965 bytes, checksum: 3ad1484efad384495579203b0e85259c (MD5) Previous issue date: 2013-05-30
FAPEAM - Fundação de Amparo à Pesquisa do Estado do Amazonas
A Tuberculose (TB) é uma doença infecciosa causada pelo complexo Mycobacterium tuberculosis, sendo considerada um grave problema de saúde pública mundial. Atualmente, isolados de M. tuberculosis resistentes a pelo menos um medicamento utilizado no tratamento da TB tem sido documentados em todos os países. De acordo com a Organização Mundial de Saúde (OMS) a TB multirresistente (TBMR) é definida quando, isolados de M. tuberculosis de pacientes apresentam resistência a pelo menos Isoniazida e Rifampicina, os dois fármacos fundamentais no tratamento da TB. A resistência à Rifampicina tem sido associada às mutações gênicas no bacilo, no gene rpoB (referentes aos códons 531, 526 e 516). Para a Isoniazida, as mutações associadas à resistência têm sido relatadas nos genes katG, inhA, ahpC e kasA, sendo que a mutação no gene katG, referente ao códon 315, tem sido a mais citada para resistência a este fármaco. Neste contexto, métodos moleculares têm sido propostos pra detecção de mutações gênicas, em isolados de M. tuberculosis, que possam estar associadas à resistência aos fármacos. O presente estudo avaliou o desempenho da PCR multiplex alelo específico (PCR-MAS), diretamente em 86 amostras de escarro de pacientes com TB pulmonar multibacilares (n=42) e paucibacilares (n=44) da Policlínica Cardoso Fonte. A PCR-MAS teve como alvos: os genes katG ,inhA e rpoB. A concordância entre a PCR-MAS e o Método de Redução de Nitrato foi avaliada utilizando o teste kappa e a associação entre as mutações gênicas e a resistência fenotípica aos fármacos foi realizada pelo teste exato de Fisher. A análise de concordância, pelo teste kappa, foi realizada entre as PCR-MAS a partir de amostra de escarro e de isolados de M. tuberculosis. A PCR-MAS apresentou fraca concordância com o Método de Redução de Nitrato, pois de 18 amostras resistentes à Isoniazida, apenas em 4 (22,2%) foram detectadas as mutações para o gene katG ou inhA. No entanto, a avaliação da sensibilidade fenotípica à Rifampicina, apresentou boa concordância com a PCR-MAS (kappa = 0,7237), quando as amostras foram de pacientes de TB pulmonar multibacilar. Além disso, houve associação da presença de mutações no gene rpoB com resistência fenotípica à Rifampicina (p = 0.0014). Em relação a concordância entre as PCR-MAS, de amostras de escarro e seus respectivos isolados de M. tuberculosis, o desempenho foi excelente quando testados em amostras de pacientes com TB pulmonar multibacilar, para detecção de mutações no gene rpoB (kappa = 0,7742). Portanto, os resultados obtidos com a PCR-MAS, a partir de amostras de escarros, foram satisfatórios e poderão ser utilizados para monitorar e pesquisar as mutações associada à resistência à Rifampicina em pacientes de TB multibacilar na rede básica de saúde, pois é um teste rápido, reprodutível e de menor custo.

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Tinzi, Siphokuhle. "Exploration of experiences of patients with the adverse-drug effects of multidrug-resistant tuberculosis treatment in a primary health care facility in the Western Cape." University of the Western Cape, 2017. http://hdl.handle.net/11394/5660.

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Magister Curationis - MCur
Multidrug resistant TB (MDR-TB) is a form of TB caused by bacteria (germs) that are resistant to the usual drugs that are used to treat "normal" TB. The duration of treatment for MDR-TB is a maximum of 22 months. People with MDR-TB are treated in specialized tertiary hospitals and in out-patient clinics in the PHC facilities. The treatment includes a six months injectable phase with a wide range of TB drugs. The adverse effects of MDR-TB drugs are among the worst side effects ever reported by patients. The aim of the current study was to explore the experiences of adverse effects of MDR-TB treatment amongst patients in a primary health care facility in the Western Cape. An explorative qualitative study design was used to explore the experiences of patient with the adverse effects of MDR-TB treatment in a primary health care facility in the Western Cape. In depth interviews were conducted with 12 MDR-TB patients. Data analysis was done by using the Tesch's method of content analysis. The study revealed that participating MDR-TB patients experienced various emotional, financial, physical and social challenges. Participants explained that the experience of being on MDR-TB treatment is emotionally draining; the pain and discomfort of the adverse effect of treatment makes a person to feel anxious and depressed. Financially they depended on social grants because they had to stop working after starting treatment. They could not function well physically because of the toxic nature of the adverse effects of treatment; which resulted in fatigue, dizziness and burning sensation on the feet and hands. They were faced with a lot of stigma from the community and even family members because of their illness. The study also revealed that in spite of the challenges and obstacles the participants were all motivated to complete their treatment and get cured. It is recommended that more support structures be made available for patients who are being treated for MDRT-TB such as; psychotherapy, social support and counselling on health education. Provision needs to be made for patients who are receiving daily injection; for it to be given in their homes. Health care providers treating MDR-TB patients need to do home visits together with MDR-TB adherence counsellors, to monitor the physical wellbeing of patients at home. This will also provide patients with the platform to discuss their health concerns in a more accommodative and relaxed environment. New drug regimen with fewer tablets and less treatment duration is needed for MDR-TB.

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Vallie, Razia. "Assessing and comparing the effectiveness of treatment for multidrug resistant tuberculosis between specialized TB hospital in-patient and general outpatient clinic settings within the Western Cape Province, South Africa." University of the Western Cape, 2016. http://hdl.handle.net/11394/5600.

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Magister Public Health - MPH
Background: Multidrug resistant tuberculosis (MDR TB) is a growing threat globally. The large increase in the incidence and prevalence of MDR TB in South Africa in recent years has impacted on the way in which MDR TB is managed within the health services. It became logistically difficult to manage MDR TB by treating all patients as in-patients in a specialized tuberculosis (TB) hospital. The clinics, which are run by nurses and/or general medical officers, are then required to manage this more complex form of TB, with limited resources, less experience and assumingly with less MDR TB knowledge. Of particular concern is that shifting of the patient management from specialized TB hospitals to Primary Health Care clinics which might worsen the already poor MDR TB treatment outcomes. There has been minimal assessment of the management of MDR TB at clinic level and hence the comparison of treatment outcomes for those patients initiated on treatment in clinics compared to in-patients in specialized TB hospitals is urgently needed. Aim: To compare the treatment outcomes and the effectiveness of medication regimens provided to MDR TB patients initiated on treatment in specialized TB hospitals as inpatients, to that of MDR TB patients initiated on treatment as outpatients at community clinics within the Western Cape Province, South Africa. Methodology Study Design: A retrospective cohort study was undertaken, as the length of treatment for a MDR TB patient can be for 24 months or longer and this study was based on treatment outcome data. Study Population and sample: The study population was uncomplicated MDR TB patients initiated on treatment in hospitals and clinics from January 2010 to December 2012. The sample comprised of 568 participants that were laboratory confirmed to have MDR TB and had the outcomes of their treatment recorded in an electronic database or a paper register. Data Collection: The researcher collected MDR TB information from standardized MDR TB registers as well as an electronic MDR TB database. Analysis: Data was analyzed comparing the exposed (clinic initiated) and unexposed (hospital initiated) cohorts incidence of 4 key treatment outcomes, namely: successfully treated, failed treatment, died and defaulted treatment. Bivariate analysis (relative and absolute) was done to determine the cumulative incidence ratio and cumulative incidence difference and multivariate logistic regression analysis for the adjusted odds ratio to control for confounders and effect modifiers. Ethics: Permission to conduct this research was obtained from the relevant authorities. The confidentiality of the participants as per the Department of Health policy and in adherence to general ethical guidelines was strictly maintained. The study proposal received ethical clearance and approval from the University of the Western Cape Research Committee. Results: All participants within this study received the appropriate treatment as per the MDR TB guidelines. The incidence rate for the main outcomes of this study indicated that successfully treated for the clinic initiated participants was 41% and 31% for the hospital initiated participants. ‘Defaulted’ treatment was 39% and 41%, ‘failed’ treatment 7% and 13% and ‘died’ was 14% and 16%, respectively. The clinic initiated participants appeared to have better treatment outcomes on bivariate analysis, however on multivariate analysis, there was no difference in the treatment outcomes of the clinic initiated participants compared to the hospital initiated participants, and therefore the clinic initiated treatment is seen as effective. The time to treatment initiation for clinic and hospital initiated participants is excessively long for both cohorts, with a median of 29 days, and 37 days respectively. The key findings of note in the multivariate analysis is that the Human Immunodeficiency Virus positive (HIV+) participants provided with antiretrovirals therapy (ART) were, based on adjusted cumulative incidence ratios, 6.6 times more likely to have a successfully treated outcome (95% CI 1.48-29.84), and were 0.2 times less likely to die (95% CI 0.08-0.53). Having a previous cured history of TB and no previous history of TB were 2.9 times more likely to have a successfully treated outcome (95% CI 1.48-5.56) and were 0.1 times (0.04-0.38) less likely to fail treatment. An interesting finding was that participants living in the rural districts were 2.6 times more likely to die. Conclusion: Clinic initiated treatment for uncomplicated MDR TB is as effective as hospital initiated treatment. Also, those provided with ART and those without previous TB or who had a previous bout of TB cured, had better outcomes. Main Recommendations: The Western Cape health department should continue with the decentralization of MDR TB services to the clinics and could safely consider expanding the decentralization to include uncomplicated Preextensively drug-resistant TB and Extensively drug-resistant TB patients. Offering ART to HIV+ patients should be mandatory. The delays in the time to treatment initiation of MDR TB need to be further investigated.

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Azores, Molovon Jr Pasagui. "Possible Risk Factors for Multidrug-Resistant Tuberculosis Infection in the Philippines." ScholarWorks, 2017. https://scholarworks.waldenu.edu/dissertations/3551.

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Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is a leading cause of morbidity and mortality in the Philippines. The purpose of this study was to gain knowledge about the relationship between potential risk factors and MDR-TB. Risk factors (the independent variables) for MDR-TB (the dependent variable) include previous TB treatment, infection with HIV, exposure to patients with drug-susceptible TB/MDR-TB, delays in diagnosis and treatment, employment status, smoking, imprisonment, alcohol abuse, and poor compliance with TB treatment regimens. The study was based on the epidemiological approach to causal inference work. A case-control study design was used wherein a quantitative method was applied in data analysis to assess the strength of the pre-identified possible risk factor(s) association to MDR-TB infection. Data were collected using survey questionnaires that were administered to patients (N = 172) from health centers in Leyte, San Mateo Rizal, and San Lazaro. Hypotheses were tested using chi-square analysis, Fisher's exact test, and an odd ratio. Drug-susceptible TB respondents who smoked on a daily basis were three times more likely (95% CI 1.021-13.341, OR 3.69) to develop an MDR-TB infection than were other respondents. Respondents who did not comply with the anti-TB treatment regimen were nine times more likely (95% CI 2.104-43.059, OR 9.519) to develop an MDR-TB infection than other respondents. Health care providers may be able to use study findings to develop programs to help drug-susceptible TB patients stop smoking and better comply with treatment regimens designed to prevent MDR-TB infection, resulting, potentially, in improved public health outcomes for patients.

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Visser, Hanri. "Mechanisms of resistance to new generation anti-TB drugs." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/96863.

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Thesis (MScMedSc)--Stellenbosch University, 2015.
ENGLISH ABSTRACT: Drug resistance in Mycobacterium tuberculosis is an increasing global problem. Drug resistance is mostly caused by single nucleotide polymorphisms (SNPs) within the bacterial genome. This observed increase in global incidence of drug resistant tuberculosis (TB) has sparked the search for new anti-TB drugs and the repurposing of drugs that are currently used against other organisms or species of mycobacteria. One such repurposed drug, clofazimine (CFZ), is currently used for the treatment of leprosy, caused by Mycobacterium leprae. The mechanism of action of CFZ is not clear, but it is hypothesized that CFZ is reduced by a mycobacterial type II NADH oxidoreductase (NDH-2). The reduction of CFZ drives the production of reactive oxygen species (ROS) which is toxic to the pathogen. The aim of this study was to elucidate the mechanism of CFZ resistance. Towards this aim, spontaneous in vitro CFZ resistant mutants were selected, characterized and whole genome was used identify SNPs which may cause CFZ resistance. Mutations were identified in a transcriptional regulator encoded by Rv0678, fatty-acid-AMP ligase, or FadD28 (Rv2941) and glycerol kinase or GlpK (Rv3696c). Mutations in Rv0678 have previously been shown to play a role in both CFZ resistance and bedaquiline (BDQ) cross-resistance, while no link has been found between CFZ resistance and mutations in fadD28 and glpK. The novel, non-synonymous SNP identified in Rv0678 resulted in the replacement of an alanine residue with threonine at codon 84, which is located in the DNA binding domain. Virtual modelling of the mutated Rv0678 protein showed that the A84T mutation may influence DNA binding, possibly due to its proximity to the DNA binding domain. This mutation caused a change in hydrophobicity, which may influence binding to DNA. Previous studies showed that mutations in Rv0678 resulted in the upregulation of mmpL5, a putative efflux pump. However, the mechanism whereby CFZ resistance occurs via increased abundance of this efflux pump in the cell wall is not clear and needs further investigation. The cross-resistance between CFZ and BDQ, caused by mutations in Rv0678, is of concern and may influence the planning of anti-TB drug regimens for the future. The roles of the other two mutations identified in this study in CFZ resistance is also not clear and requires further investigation. Finally, the findings of this study support the role of Rv0678 in CFZ resistance thereby suggesting that this gene could be useful as a diagnostic marker to test for CFZ resistance in clinical isolates.
AFRIKAANSE OPSOMMING: Middelweerstandigheid in Mycobacterium tuberculosis is 'n wêreldwye toenemende probleem. Middelweerstandigheid word meestal veroorsaak deur enkel nukleotied polimorfismes (SNPs) in die bakteriële genoom. Hierdie toename in middelweerstandige tuberkulose (TB) het gelei tot die soektog na nuwe anti-TB-middels en die alternatiewe aanwending van middels wat tans teen ander organismes of spesies van mikobakterieë gebruik word. Een so 'n alternatiewe middel, clofazimine (CFZ), word tans gebruik vir die behandeling van melaatsheid wat veroorsaak word deur Mycobacterium leprae. CFZ se meganisme van werking is nie duidelik nie, maar dit word vermoed dat CFZ gereduseer word deur 'n mikobakteriële tipe II NADH oksidoreduktase (NDH-2). Die reduksie van CFZ dryf die produksie van reaktiewe suurstof spesies wat giftig is vir die patogeen. Die doel van hierdie studie was om die meganisme van CFZ weerstandigheid te ondersoek. Om hierdie doel te bereik was spontane in vitro CFZ weerstandige mutante gekies, gekarakteriseer en heel genoom volgorde bepaling is gebruik om SNPs te identifiseer wat CFZ weerstandigheid veroorsaak. Mutasies in Rv0678, 'n transkripsie reguleerder, vetsuur-AMP ligase, of FadD28 (Rv2941) en gliserol kinase of GlpK (Rv3696c) geïdentifiseer. Dit is al voorheen gevind dat mutasies in Rv0678 ‘n rol speel in beide CFZ weerstandigheid en bedaquiline (BDQ) kruis-weerstandigheid, terwyl geen verband gevind is tussen CFZ weerstandigheid en mutasies in fadD28 en glpK nie. Die nuwe, nie-sinonieme SNP, geïdentifiseer in Rv0678 het gelei to die vervanging van 'n alanien aminosuur met treonien by kodon 84, wat geleë is in die DNS bindings domein. Virtuele modellering van die gemuteerde Rv0678 proteïen het getoon dat die A84T mutasie DNS binding moontlik kan beïnvloed, as gevolg van sy nabyheid aan die DNS bindings domein. Hierdie mutasie veroorsaak 'n verandering in die hidrofobiese natuur, wat DNS binding kan beïnvloed. Vorige studies het getoon dat mutasies in Rv0678 lei tot die opregulering van mmpL5, 'n waarskynlike uitvloei pomp. Die meganisme waardeur CFZ weerstandigheid veroorsaak, deur ‘n groot aantal van hierdie uitvloei pompe in die selwand, is nie duidelik nie en moet verder ondersoek word. Die kruis-weerstandigheid tussen CFZ en BDQ, wat veroorsaak word deur mutasies in Rv0678, is van belang en kan die beplanning van anti-TB middel behandeling vir die toekoms beïnvloed. Die rolle van die ander twee mutasies, wat in hierdie studie geïdentifiseer is, in CFZ weerstandigheid is ook nie duidelik nie en vereis verdere ondersoek. Ten slotte, die bevindinge van hierdie studie steun die rol van Rv0678 in CFZ weerstandigheid en dit dui daarop dat hierdie geen gebruik kan word as 'n diagnostiese merker om vir CFZ weerstandigheid te toets in kliniese isolate.

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Franco, Marília Masello Junqueira. "Genotipagem e pesquisa de resistência fenotípica e genética à rifampicina e isoniazida em linhagens de Mycobacterium bovis isoladas de linfonodos de bovinos de abatedouro na região centro-oeste do estado de São Paulo." Botucatu, 2016. http://hdl.handle.net/11449/143102.

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Orientador: Antonio Carlos Paes
Resumo: A tuberculose causada por Mycobacterium bovis (bTB) é uma zoonose de distribuição mundial com ampla gama de hospedeiros. Nos países onde a bTB é prevalente, 10 a 20% dos casos de tuberculose humana são causados por M. bovis. São escassos em todo o mundo estudos que investigam a resistência à isoniazida (INH) e rifampicina (RMP) em linhagens de M. bovis de origem bovina, reservatórios silvestres, e em casos humanos de tuberculose. Foi investigada a diversidade genotípica de 67 linhagens de M. bovis isoladas de bovinos de abatedouro, obtidas de 100 linfonodos com lesão caseosa, pelas técnicas de Spoligotyping e MIRU-VNTR, bem como foi determinado o perfil fenotípico de resistência à INH e RMP pela técnica de REMA, e pesquisadas possíveis bases genéticas para resistência aos antimicrobianos. Dentre os isolados, 11 (16%) foram classificados como MDR-TB, 8 (12%) resistentes à INH e 2 (3%) resistentes à RMP. A pesquisa pelo GenoType MTBDRplus ver. 2.0 não acusou a presença de mutações em nenhum dos isolados fenotipicamente resistentes. Foram identificados 16 spoligotipos entre as linhagens. A subfamília BOV_1 predominou com 52 (77,6%) isolados, com os SIT 481, 482, 594, 665, 691, 698, 1021, 1667, 1852, 2141 e dois isolados sem shared type. A BOV_2 foi identificada em 8 (11,9%) isolados, com o SIT 683. Os SIT 982, 1851 e 1853 foram agrupados na família BOV. Dois isolados não foram classificados em família ou subfamília. A análise de MIRU-VNTR com painel de 12 MIRUs, identificou 31 i... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Tuberculosis caused by Mycobacterium bovis (bTB) is a zoonosis of worldwide distribution with broad host range. In countries where bTB is prevalent, 10-20% of the human cases of tuberculosis are caused by M. bovis. All over the world there are few studies investigating the resistance to isoniazid (INH) and rifampicin (RMP) in M. bovis strains from cattle, wild reservoirs, and human cases of tuberculosis. The genotypic diversity of 67 M. bovis strains obtained out of 100 lymph nodes with caseous lesions from slaughtered animals was investigated by Spoligotyping and MIRU-VNTR techniques, as well as the assessment of their phenotypic profile of resistance to INH and RMP by REMA method and the search of possible genetic basis for antimicrobial resistance. Among the obtained isolates, 11 (16%) were classified as MDR-TB, 8 (12%) INH-resistant and 2 (3%) RMP-resistant. The use of GenoType MTBDRplus ver. 2.0 did not pointed the presence of genetic mutations in any of the phenotypically resistant isolates. Sixteen different spoligotype patterns were identified. The BOV_1 subfamily predominated with 52 (77.6%) isolates, with SITs 481, 482, 594, 665, 691, 698, 1021, 1667, 1852, 2141 and two isolates without a given SIT. BOV_2 was identified in 8 (11.9%) isolates, within SIT 683. The SITs 982, 1851 and 1853 were grouped in BOV family. Two isolates were not classified in family or subfamily. The MIRU-VNTR analysis using the 12 classical MIRUs, identified a cluster of 31 isolates belonging... (Complete abstract click electronic access below)
Doutor

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Pule, Caroline. "Defining the role of efflux pump inhibitors on anti-TB drugs in Rifampicin resistant clinical Mycobacterium Tuberculosis isolates." Thesis, Stellenbosch : Stellenbosch University, 2014. http://hdl.handle.net/10019.1/86758.

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Thesis (MScMedSc)--Stellenbosch University, 2014.
ENGLISH ABSTRACT: Central dogma suggests that mutations in target genes is the primary cause of resistance to first and second-line anti-TB drugs in Mycobacterium tuberculosis. However, it was previously reported that approximately 5% of Rifampicin mono-resistant clinical M. tuberculosis did not harbor mutations in the rpoB gene. The present study hypothesized that active efflux plays a contributory role in the level of intrinsic resistance to different anti-TB drugs (Isoniazid, Ethionamide, Pyrazinamide, Ethambutol, Ofloxacin, Moxifloxacin, Ciprofloxacin, Streptomycin, Amikacin and Capreomycin in RIF mono-resistant clinical M. tuberculosis isolates with a rpoB531 (Ser-Leu) mutation. This study aimed to define the role of Efflux pump inhibitors (verapamil, carbonylcyanide m-chlorophenylhydrazone and reserpine) in enhancing the susceptibility to different anti-TB drugs in the RIF mono-resistant clinical isolates. The isolates were characterized by determining the level of intrinsic resistance to structurally related/unrelated anti-TB drugs; determining the effect of EPIs on the level of intrinsic resistance in the isolates and comparing the synergistic properties of the combination of EPIs and anti-TB drugs. To achieve this, genetic characterization was done by PCR and DNA sequencing. Phenotyping was done by the MGIT 960 system EpiCenter software to determine the MICs of the different anti-TB drugs and the effect of verapamil and carbonylcyanide m-chlorophenylhydrazone on determined MICs. Due to inability to test reserpine in a MGIT, a different technique (broth microdilution) was used for the reserpine experiment. Additionally; fractional inhibitory concentrations (FIC) indices were calculated for each of these drugs. The FIC assess the anti-TB drugs/inhibitor interactions. STATISTICA Software: version 11 was used for statistical analysis. Results revealed that the RIF mono-resistant isolates were sensitive at the critical concentrations of all 10 drugs tested, with the exception of Pyrazinamide. This could be explained by the technical challenges of phenotypic Pyrazinamide testing. A significant growth inhibitory effect was observed between the combination of EPI and anti-TB drug exposure in vitro. This suggests that verapamil, carbonylcyanide m-chlorophenylhydrazone and reserpine play a significant role in restoring the susceptibility (decrease in intrinsic resistance level) of the RIF mono-resistant isolates to all anti-TB drugs under investigation. Additionally, a synergistic effect was observed by the combination treatment of the anti-TB drugs with the different EPIs. Based on these findings, we proposed a model suggesting that efflux pumps are activated by the presence of anti-TB drugs. The activated pumps extrude multiple or specific anti-TB drugs out of the cell, this in turn decrease the intracellular drug concentration, thereby causing resistance to various anti-TB drugs. In contrast, the addition of EPIs inhibits efflux pump activity, leading to an increase in the intracellular drug concentration and ultimate cell death. This is the first study to investigate the effect of different efflux pumps inhibitors on the level of intrinsic resistance to a broad spectrum of anti-TB drugs in drug resistant M. tuberculosis clinical isolates from different genetic backgrounds. The findings are of clinical significance as the combination of treatment with EPI and anti-TB drugs or use of EPIs as adjunctives could improve MDR-TB therapy outcome.
AFRIKAANSE OPSOMMING: Sentrale dogma beweer dat mutasies in teiken gene die primêre oorsaak van die weerstandheid teen anti-TB-middels in Mycobacterium tuberculosis is. Vorige studies het getoon dat ongeveer 5% van Rifampisien enkelweerstandige kliniese M. tuberculosis isolate nie ‘n mutasie in die rpoB geen het nie. Die hipotese van die huidige studie was dat aktiewe pompe 'n bydraende rol speel in die vlak van intrinsieke weerstandheid teen 10 verskillende anti-TB-middels (Isoniasied, Ethionamied, Pyrazinamied, Ethambutol, Ofloxacin, Moxifloxacin, Siprofloksasien, Streptomisien, Amikasien and Capreomycin) in RIF enkelweerstandige kliniese M . tuberculosis isolate met 'n rpoB531 (Ser-Leu) mutasie. Die doel van hierdie studie was om die rol van uitpomp inhibeerders (verapamil, carbonylcyanide m-chlorophenylhydrazone en reserpien) te definieer in die verbetering van die werking vir verskillende anti-TB-middels in die RIF enkelweerstandige kliniese isolate. Die doelstellings van die studie was om die vlak van intrinsieke weerstandigheid teen struktureel verwante/onverwante anti-tuberkulose middels asook die effek van die EPIs op die vlak van intrinsieke weerstand in die isolate is bepaal. Verder is sinergistiese eienskappe van die kombinasie van EPIs en anti-TB-middels ondersoek. Hierdie doelstellings is bereik deur genetiese karakterisering deur PKR en DNS volgorde bepaling. Fenotipering is gedoen deur gebruik te maak van MGIT 960 EpiCenter sagteware om die Minimum Inhibisie Konsentrasie (MIC) van die verskillende anti-TB-middels en die effek van verapamil en carbonylcyanide m-chlorophenylhydrazone op die MIC te bepaal. Reserpien kan nie in die MGIT sisteem getoets word nie, and daarom is 'n ander tegniek (mikro-verdunning) is gebruik om die effek van reserpien te toets. Fraksionele inhiberende konsentrasies (FIC) is bereken vir elk van hierdie middels die anti-TB-middels / inhibeerder interaksies te bepaal. STATISTICA v11 sagteware is gebruik vir alle statistiese analises. Resultate van hierdie studie toon dat die RIF enkelweerstandige isolate sensitief is teen kritieke konsentrasies van al die middels, met die uitsondering van Pyrazinamied. Weerstandigheid van Pyrazinamied kan wees as gevolg van welbekende tegniese probleme met die standaard fenotipiese pyrazinamied toets. ‘n Beduidende groei inhiberende effek is waargeneem tussen die kombinasie van EPI en anti-TB middel blootstelling in vitro. Dit dui daarop dat verapamil, CCCP en reserpine 'n belangrike rol speel in die herstel van die sensitiwiteit (afname in intrinsieke weerstand vlak) van die RIF enkelweerstandige isolate aan alle anti-TB-middels wat ondersoek is. Daarbenewens is 'n sinergistiese effek waargeneem deur die kombinasie van die verskillende anti-TB-middels en die verskillende EPIs. Op grond van hierdie bevindinge het ons ‘n model voorgestel wat toon dat uitvloei pompe geaktiveer word deur die teenwoordigheid van anti-TB-middels en die geaktiveerde pompe dan verskeie of spesifieke anti-TB-middels uit die sel pomp. Dus verminder die intrasellulêre konsentrasie van die middel en veroorsaak daardeur weerstandigheid teen verskeie anti-TB-middels. Die byvoeging van EPIs inhibeer uitvloei pompe se werking en lei tot 'n toename in die intrasellulêre konsentrasie van die middels en uiteindelik die dood van die selle. Hierdie is die eerste studie wat die effek van verskillende uitvloei pompe inhibeerders op die vlak van intrinsieke weerstand teen 'n breë spektrum van anti-TB-middels in die middel-weerstandige kliniese isolate ondersoek. Die bevindinge kan van belangrike kliniese belang wees aangesien die kombinasie van behandeling met EPI en anti-TB-middels die uitkoms MDR-TB terapie kan verbeter.

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Isaboke, James N. "Risk Factors for Tuberculosis and Multidrug-Resistant Tuberculosis Complications among Foreign-Born Persons in Houston, Texas." ScholarWorks, 2016. https://scholarworks.waldenu.edu/dissertations/1897.

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Tuberculosis (TB) is a leading public health problem across the world. For various reasons, TB and multidrug-resistant tuberculosis (MDR-TB) have increased. Clarification on TB/HIV co-infection and homelessness as risk factors for TB and MDR-TB is required to inform policy interventions to reduce TB-related morbidity, mortality, and healthcare costs. In this quantitative study, data from the Houston Health Department (N = 341) were analyzed to explore the relationship between TB and MDR-TB outcomes and TB/HIV co-infection and type of housing/homelessness. Foreign-born persons are disproportionately affected in the United States. The socio-ecological model provided a theoretical framework for the investigation. Multiple and logistic regression analyses were conducted to investigate the relationships between variables, controlling for age and gender. Results indicate that HIV infected persons were more likely than non-infected persons to contract TB, and homeless persons were more likely than non-homeless persons to contract TB/MDR-TB, suggesting that high TB/HIV co-infection rates increase prevalence of TB and MDR-TB while improvements in housing reduce prevalence of TB and MDR-TB. However, no significant associations between variables were found. The odds ratio, Exp(B) = 0.000, p -?¥ 0.90, 95% Cl [0.000, with no upper bound values] was observed for both independent variables. Regular screening for TB/HIV co-infection among persons with high TB and MDR-TB risk profiles is recommended. Further investigation is required. Inclusion of more covariates could further elucidate more evidence of an association between variables. Study findings may support interventions to reduce TB-related morbidity, leading to positive social change.

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Willemse, Danicke. "Regulation of efflux in rifampicin resistant mutants of Mycobacterium tuberculosis." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/79820.

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Thesis (MScMedSc)--Stellenbosch University, 2013.
ENGLISH ABSTRACT: Multidrug resistant tuberculosis (MDR-TB), defined as having resistance to at least the first-line drugs, isoniazid and rifampicin (RIF), is a global health problem. Mutations in the rpoB gene, encoding the β-subunit of RNA polymerase, are implicated in RIF resistance - with the S531L and H526Y mutations occurring most frequently. The level of RIF resistance varies for strains with identical rpoB mutations, which suggests that other factors play a role in RIF resistance. Efflux has been implicated in determining the intrinsic level of RIF resistance. Increased expression of the multidrug efflux pump, Rv1258c, following RIF exposure was observed in some Mycobacterium tuberculosis MDR clinical isolates and H37Rv RIF mono-resistant mutants, but not others. The factors influencing the induction of Rv1258c are poorly understood. The aim of this study was to investigate the effects of rpoB mutations on expression of Rv1258c and whiB7, a transcriptional regulator of Rv1258c, in M. tuberculosis H37Rv in vitro generated RIF resistant mutants, in the absence and presence of RIF. The promoter region of M. tuberculosis H37Rv Rv1258c was cloned into a position upstream of a lacZ gene (encoding β-galactosidase) in multi-copy episomal and integrating vectors. Vector functioning and the effect of rpoB mutations on Rv1258c promoter activity were initially investigated in the non-pathogenic related species, Mycobacterium smegmatis mc2155 rpoB mutants and subsequently in M. tuberculosis by doing β-galactosidase assays. qRT-PCR was done to investigate the effects of rpoB mutations on native Rv1258c and whiB7 gene expression. Episomal and integrating vectors were functional and the integrating vector system was used for subsequent β-galactosidase assays in M. tuberculosis. Rv1258c promoter activity in the S531L mutant was approximately 1.5 times less and in the H526Y mutant 1.5 times higher than that of the wild-type in M. smegmatis. Similarly, Rv1258c promoter activity in the S531L mutant was approximately half and in the H526Y mutant approximately double that of the wild-type in M. tuberculosis. A similar trend in Rv1258c and whiB7 expression to those observed using β-galactosidase assays were observed when investigating the native Rv1258c and whiB7 gene transcript levels compared to the wild-type using qRT-PCR, although differences were not significant. Exposure of the M. smegmatis and M. tuberculosis rpoB mutants to sub-inhibitory levels of RIF did not affect Rv1258c promoter activity. Mutations in rpoB had a marginal effect on Rv1258c and whiB7 transcript levels, but showed the same trend as that seen for Rv1258c promoter activity. It remains to be determined whether these differences are biologically significant. When considering efflux pumps as new targets for treatment, possible differences in efflux pumps expression due to different rpoB mutations should be considered.
AFRIKAANSE OPSOMMING: Multi-middel weerstandige tuberkulose (MDR-TB) word gedefinieer as weerstandigheid tot ten minste rifampisien (RIF) en isoniasied, wat deel van die eerstelyn anti-tuberkulose behandeling vorm. Mutasies in die rpoB geen, wat die β-subeenheid van die RNA polimerase enkodeer, word geassosieer met RIF weerstandigheid. S531L en H526Y rpoB mutasies kom die algemeenste voor. RIF weerstandigheids vlakke verskil egter tussen isolate met identiese rpoB mutasies, wat impliseer dat ander faktore ook 'n rol in RIF weerstandigheid speel. 'n Toename in transkripsie van die Rv1258c geen, wat 'n multi-middel effluks pomp enkodeer, is waargeneem met blootstelling aan RIF, slegs in sommige M. tuberculosis H37Rv RIF mono-weerstandige mutante and MDR kliniese isolate, maar nie in ander nie. Die faktore wat die induksie van die Rv1258c effluks pomp beïnvloed is nie goed nagevors nie. Die studie ondersoek die effek van die rpoB mutasies op die uitdrukking van die Rv1258c en whiB7,'n transkripsionele regulator van Rv1258c, gene in M. tuberculosis H37Rv in vitro gegenereerde RIF weerstandige mutante, in die teenwoordigheid en afwesigheid van RIF. Die promotor area van die M. tuberculosis H37Rv Rv1258c geen is in 'n posisie stroomop van 'n lacZ geen, wat vir β-galaktosidase enkodeer, in multi-kopie episomale en integreerende vektors ingekloneer. Die funksionaliteit van die vektor en effek van rpoB mutasies op Rv1258c promotor aktiwiteit is ondersoek in die naverwante nie-patogeniese spesies, M. smegmatis en daarna in M. tuberculosis deur β-galaktosidase essais te doen. qRT-PCR is gedoen om die effek van rpoB mutasies op die vlak van transkripsie van die natuurlike Rv1258c geen en die whiB7 geen te bestudeer. Beide die episomale en integreerende vektors was funksioneel en daar is besluit om die integreerende vektor vir daaropeenvolgende β-galaktosidase essais in M. tuberculosis te gebruik. Rv1258c promotor aktiwiteit van die S531L mutant was ongeveer 1.5 keer minder as en die van die H526Y mutant 1.5 keer hoër as die van die ongemuteerde bakterië in M. smegmatis. Soortgelyk was die Rv1258c promoter aktiwiteit van die S531L mutant ongeveer die helfde van en die van H526Y mutant ongeveer dubbel die van die ongemuteerde bakterië in M. tuberculosis 'n Soortgelyke neiging in die vlakke van Rv1258c en whiB7 transkripte van die natuurlike geen is gedurende qRT-PCR waargeneem alhoewel die verskille nie beduidend was nie. Blootstelling aan sub-inhibitoriese konsentrasies van RIF het geen effek op Rv1258c uitdrukking in die M. smegmatis of M. tuberculosis rpoB mutante gehad nie. Die rpoB mutasies het net 'n effense effek op Rv1258c en whiB7 transkrip vlakke in M. tuberculosis rpoB mutante, maar transkrip vlakke het 'n soortgelyke neiging as die Rv1258c promoter aktiwiteit getoon. Of die waargenome verskille biologies betekenisvol is, moet nog bepaal word. Indien effluks pompe as teikens vir bahandeling gebruik sou word, moet in ag geneem word dat effluks pompe moontlik verskillend uitgedruk word in verskillende rpoB mutante.
The DST/NRF Centre of Excellence in Biomedical Tuberculosis Research, Stellenbosch University
DAAD-NRF in Country Scholarship and Ernst and Ethel Eriksen Trust
Harry Crossley Foundation

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Matlola, Nthane Martha. "The in vitro anti-mycobacterial activities of the novel tetramethylpiperidyl-substituted phenazines, B4121 and B4128." Thesis, University of Pretoria, 1999. http://hdl.handle.net/2263/24462.

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The intra- and extracellular activities of 2 novel tetramethylpiperidine (TMP)-substituted phenazines, B4121 and B4128 against Mycobacterium tuberculosis H37R (ATCC 27294) were determined and compared with those of clofazimine (B663). Clofazimine, together with B4121 and B4128, were also tested for their activities against drug-resistant strains of M.tuberculosis. Both B4121 and B4128 were significantly more active than clofazimine against M.tuberculosis, including multidrug-resistant clinical strains of this microbial pathogen, demonstrating a lack of cross resistance between the riminophenazines and standard anti-tuberculous drugs. Using M.tuberculosis-infected monocyte-derived macrophages both B4121 and B4128 were found to possess intracellular activity, which was superior to that of both clofazimine and rifampicin. The relationship between anti mycobacterial action of the TMP-subsitituted phenazines and clofazimine and the effects of these agents on microbial PLA2 activity, cation (K+, Ca2+) fluxes and energy metabolism (ATP) was also investigated. PLA2 and cation fluxes were measured by radiometric procedures, while microbial ATP was assayed using a luciferin/luciferase chemiluminescence method. All 3 riminophenazines, particularly B4128 caused dose-related enhancement of microbial PLA2 activity, which was associated with inhibition of K+-influx and enhancement of uptake of Ca2+. The results of kinetics studies demonstrated that riminophenazine-mediated enhancement of PLA2 activity and inhibition of K+ uptake in mycobacteria are rapidly-occurring and probably related events that precede, by several minutes, any detectable effects on microbial ATP concentrations and uptake of Ca2+. Inclusion of the extracellular and intracellular Ca2+-chelating agents EGTA and BAPTA, respectively, individually or in combination, did not prevent the effects of the riminophenazines on mycobacterial PLA2 (enhancement) or K+ transport (inhibition), whereas α-tocopherol, which neutralizes PLA2 primary hydrolysis products, antagonized the inhibitory effects of the riminophenazines on microbial K+ uptake. These results demonstrated that the riminophenazine-mediated enhancement of PLA2 is a Ca2+-independent event. The involvement of PLA2 in the antimicrobial activity of the riminophenazines was supported by the observation that added, exogenous Iysophosphotidylcholine (a primary hydrolysis product of PLA2 action on membrane phospholipids) also inhibited K+ transport and growth of mycobacteria. Enhancement of endogenous PLA2 as a mechanism of riminophenazine-mediated disruption of cation transport and antimycobacterial activity was further investigated using the conventional calcium-mobilizing stimuli, calcium ionophore A23187 and thapsigargin. Both agents, but A23187 in particular caused in dose-related enhancement of microbial PLA2 activity, which was associated with inhibition of K+ influx and growth. Influx of Ca2+ into A23187- and thapsigargin-treated mycobacteria was observed using both radiometric and FURA-2-based spectrofluorimetric procedures. Exposure of the mycobacteria to these agents resulted in an immediate increase in uptake of Ca2+, which implies that enhancement of PLA2 activity in calcium-mobilizing stimuli-treated mycobacteria is Ca2+ dependent. In conclusion, the TMP-substituted phenazines possess anti mycobacterial properties which are superior to those of clofazimine, particularly against intraphagocytic M.tuberculosis. The superior anti mycobacterial properties of these agents is paralleled by their potentiating effects on microbial PLA2 and consequent inhibitory action on uptake of K+, particularly in the case of B4128. Mycobacterial PLA2 and K+ transporters may therefore represent novel targets for antimicrobial chemotherapy.
Thesis (DPhil (Medical Immunology))--University of Pretoria, 2007.
Immunology
unrestricted

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Ngwane, Andile Happyboy. "Elucidation of the mode of action of a furanone based antituberculosis compound." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71976.

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Thesis (PhD)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: The prevalence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis has been increasing to alarming levels globally. This has been exacerbated by tuberculosis (TB) co-infection with HIV where the epidemic is endemic. South Africa as a developing country is hit hard by TB and efforts to develop TB drugs that are compatible with anti-retroviral medication and also effective against MDR/XDR, could help shorten the treatment duration of the current TB treatment regimens. This thesis presents the identification and characterisation of a novel furanone based compound (F1082) and its derivatives as leads for anti-TB drug development. Furanones are generally known for an array of biological activities ranging from antibacterial, antifungal and antitumor. F1082 has an aromatic benzene structure and was identified from screening synthetic compounds against M. tuberculosis. It is potent against M. tuberculosis at minimum inhibitory concentration (MIC) of 8 μg/ml. It is selective for mycobacteria since it did not inhibit the growth of Gram-positive and Gram-negative bacteria at concentrations five times the MIC for M. tuberculosis. F1082 is generally bacteriostatic around MIC concentrations in its effects against M. tuberculosis however; it may be bactericidal at higher concentrations. It is as effective against MDR, XDR and clinical isolates of M. tuberculosis at the same concentration as the M. tuberculosis H37Rv reference strain. This suggests that F1082 may have a different mechanism of action compared to current TB drugs. It has been shown to have no antagonistic effect with the first-line anti-TB drugs and it has been shown to synergize with rifampicin by reducing the MIC of rifampicin. A drawback of F1082 is that it is cytotoxic to human cell lines, but this is presently being addressed through the synthesis of analogues that have shown improved activity and less cytotoxicity. The synthesis of more than 40 analogues has led to identification of 4 compounds that have more than five times higher activity and more than 100 times less cytotoxicity against human cell-lines. Microarray analyses have identified possible metabolic pathway/s in M. tuberculosis that is/are affected by F1082. One subset of genes which showed the most prominent alteration encodes the siderophores, which are involved with iron homeostasis in the M. tuberculosis bacillus. Of these genes, 7 were of interest (mbtB, mbtC, mbtD, mbtE, mbtF, mbtH and bfrB) as they all fall in the same cluster and are involved in iron acquisition. Due to the involvement of iron we also show that F1082 generates oxidative stress that is metal (iron) dependent. From the results we conclude that F1082 is a promising antituberculosis lead compound with unique target properties and also specificity against mycobacteria.
AFRIKAANSE OPSOMMING: Die voorkoms van veelvuldige middelweerstandige M.tuberculosis (MDR) en uiters middelweerstandige M.tuberculosis (XDR) is besig om toe te neem teen ‘n kommerwekkende tempo wêreldwyd. Hierdie situasie word vererger met die ko-infektering van M.tuberculosis en HIV. Suid- Afrika, as ontwikkelende land, word sleg benadeel met tuberkulose siekte. Antituberkulose middels wat kan saamwerk met bestaande antiretrovirale middels en ook effektief is teen MDR en XDR stamme, kan alles meewerk om die behandelingstyd van tuberkulose te verkort. In hierdie tesis identifiseer en karakteriseer ons ‘n furanoon-gebaseerde verbinding (F1082) en derivate daarvan as voorloper-middels vir anti-tuberkulose middelontwikkeling. Furanone is algemeen bekend vir ‘n verskeidenheid van biologiese aktiwiteite insluitende antibakteriële-, antifungale- en antitumor aktiwiteite. F1082 bevat ‘n aromatiese benseenstruktuur en is oorspronklik geïdentifiseer gedurende die skandering van sintetiese middels teen M.tuberculosis. Dit het ‘n sterk werking teen M.tuberculosis met ‘n minimum inhibitoriese konsentrasie (MIC) van 8ug/ml. Dit is baie selektief vir mikobakterieë aangesien dit nie gram-positiewe of gram-negatiewe bakterieë teen 5 maal die MIC, soos vir M.tuberculosis, geïnhibeer het nie. F1082 is bevind om, by laer konsentrasies, bakteriostaties te wees in sy aktiwiteit teen M.tuberculosis maar by hoër konsentrasies word ‘n meer bakteriosidiese effek waargeneem. F1082 is effektief teen MDR, XDR en kliniese isolate van M.tuberculosis en teen dieselfde konsentrasie soos vir die M. tuberculosis H37Rv verwysingstam waargeneem is. Dit impliseer dat F1082 dalk ‘n alternatiewe meganisme van werking het in vergelyking met die van die huidige TB teenmiddels. F1082 toon geen antagonistiese werking in kombinasie met die voorste anti- TB middels nie, maar toon wel sinergistiese werking in kombinasie met rifampisien. F1082 toon nog sitotoksiese aktiwiteit teenoor menslike sellyne, maar die sintese van derivate van F1082 toon tot dusvêr groter anti-TB aktiwiteit en verminderde sitotoksisiteit. Die sintese van meer as 40 homoloë het gelei tot die identifisering van vier verbindings met vyf keer hoër anti-TB aktiwiteit en honderd keer verminderde sitotoksisiteit teen menslike sellyne as F1082 self. “Microarray” ontledings het ‘n aantal metabolise paaie geïdentifiseer waar F1082 ‘n effek kan uitoefen. Een stel gene wat die mees uitstaande effek toon kodeer vir siderofore wat betrokke is by yster homeostase in M.tuberculosis. Van hierdie gene was daar sewe van belang omdat hulle in dieselfde groep voorkom en almal betrokke is by ysteropname (mbtB, mbtC, mbtD, mbtE, mbtF, mbtH, bfrB). Weens die rol wat F1082 in ysterhomeostase speel, toon ons ook dat F1082 intrasellulêre oksidatiewe stres bevorder wat yster afhanklik is. Al ons resultate dui daarop dat F1082 ‘n belowende ant-TB voorloper verbinding is met spesifisiteit teen M.tb en unieke teikeneienskappe in M. tuberculosis.

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Jikijela, Olwethu. "Clinical characteristics and treatment outcomes of multi-drug resistant tuberculosis patients attending a hospital in Buffalo City Metropolitan Municipality, Eastern Cape." University of the Western Cape, 2018. http://hdl.handle.net/11394/6423.

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Magister Public Health - MPH (Public Health)
The presence of highly effective medicines has made very little impact in reducing deaths as a result of tuberculosis (TB), a curable condition but when managed inappropriately, may result in Drug Resistant TB. TB accounts for about one in four deaths that occur in HIV positive people and HIV has been found to be a risk factor for complex unfavorable outcomes in MDR TB patients and a very strong predictor for death and default. The relationship between diabetes and TB has also been explored, with some authors identifying diabetes as a risk factor for TB, and with related poor clinical outcomes in both conditions when they co-exist. Exploring the clinical characteristics and treatment outcomes of MDR TB patients in the presence of these risk factors could present an opportunity to provide better care through increased case-detection activities, improved clinical management and better access to care for all these conditions. The aim of the study was to describe the clinical characteristics and treatment outcomes of MDR TB patients initiated on treatment at Nkqubela and Fort Grey Hospitals.

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Morales, Miranda Helen Elizabeth. "Influencia de la depresion´sobre la adherencia al tratamiento en pacientes TB-MDR de la Red Almenara de Essalud - Lima , Año 2015." Bachelor's thesis, Universidad Ricardo Palma, 2015. http://cybertesis.urp.edu.pe/handle/urp/351.

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INTRODUCCIÓN: Se efectuó un estudio sobre la depresión y su asociación con la adherencia al tratamiento de fármacos antituberculosos en pacientes con Tuberculosis Multidrogorresistente (TB-MDR) que asisten al Programa de Control de Tuberculosis (PCT) de la Red Asistencial Almenara de EsSalud- Lima. OBJETIVO: Determinar si la depresión influye en la adherencia al tratamiento en los pacientes multidrogorresistentes (TB-MDR) de la Red Asistencial Almenara en EsSalud- Lima, año 2015. PACIENTES Y MÉTODOS: El presente estudio analítico transversal prospectivo se desarrolló con una población de 81 pacientes con TB-MDR. Para la medición del nivel de depresión se utilizó el Test de depresión de Zung; mientras que para la medición de la adherencia al tratamiento antituberculoso se utilizó el Test de Morisky- Green y la revisión de las Fichas de control de tratamiento antituberculoso de cada paciente. El análisis de los resultados se realizó mediante la Prueba de la Exacta de Fisher para lo cual se consideró un intervalo de confianza de 95% (p<0.05). RESULTADOS: Los pacientes que no presentan depresión tienen el 82.14% de adherencia al tratamiento, además los que presentan depresión leve tienen 76.67% de adherencia al tratamiento. Mientras que los pacientes con depresión moderada presentan 17.65%.Es decir, se encuentra una asociación estadísticamente significativa entre la Depresión y la adherencia al tratamiento (p<0.05) CONCLUSIONES: Según los resultados del el estudio la depresión se asocia a la mala adherencia al tratamiento antituberculoso en los pacientes con tuberculosis multidrogorresistente (TB-MDR).

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Firfirey, Nousheena. "Occupational adaptation : the experiences of adult patients with MDR- TB who undergo long- term hospitalisation." University of the Western Cape, 2011. http://hdl.handle.net/11394/5300.

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Magister Scientiae (Occupational Therapy) - MSc(OT)
TB is a multi- faceted public health problem spurred on by the biological progression of the disease as well as the social issues associated with it. The treatment of TB is however primarily driven by the medical model where the focus is on the disease and not on a holistic view of the patient. Occupational therapy is a profession concerned with the use of occupation in the promotion of health and well being through the facilitation of the process of occupational adaptation. There is however a paucity of literature pertaining to the role that occupational therapy could play within the TB context. The aim of this study was to explore how adults with MDR- TB who undergo long-term hospitalisation at a hospital in the Western Cape experience occupational adaptation. The objectives of the study were to explore how the participants perceive their occupational identity, to explore the meaning and purpose the participants assign to their occupational engagement and to explore the how the participants perceive their occupational competence. The interpretive research paradigm employing a phenomenological qualitative research approach was utilized in this study. Purposive sampling was used to select four participants based on specific selection criteria. The data gathering methods utilized included diaries, semistructured interviews, participant observation and a focus group. Photographs taken by the researcher for the purpose of participant observation were used to elicit a rich, in depth response from the participants during the focus group discussion. All data was analysed through thematic content analysis. The study findings highlighted that the participants viewed themselves as occupational beings and that they valued the role that occupational engagement played in facilitating their occupational competence and ultimately their ability to adapt to long- term hospitalisation. The environmental demands and constraints that they experienced however infringed their engagement in meaningful occupation and hampered their ability to achieve occupational competence. It was recommended that the hospital adopt an integrative intervention approach to the management of MDR- TB patients that include principles of psychosocial rehabilitation and occupational enrichment to address occupational risk factors and institutionalisation.

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Tsuro, Urgent. "Modelling the impact of risk factors affecting TB treatment." Thesis, University of Fort Hare, 2013. http://hdl.handle.net/10353/d1019782.

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The Tuberculosis infection rate has been generally escalating due to poor health conditions in the Gweru district of Zimbabwe. The study therefore seeks to identify the risk factors that affect TB treatment in the Gweru district. A cross sectional study was carried out in which a questionnaire was employed for data collection on 113 respondents. A binary logistic regression model was employed for data analysis. A total of 98 TB patients were interviewed: [50 respondents (44.0%) had Multi-drug resistant Tuberculosis and 63 respondents (56.0%) had general Tuberculosis). Before being enrolled into the study, an informed consent form was given to each of the participants. The data was then put into excel and later transferred to SPSS for analysis. Out of the 14 potential risk factors of TB treatment, only 6 variables (side effects, gender, alcohol use, HIV status, smoking during the treatment period and having been pre-exposed to TB drugs) were statistically significant in their association with treatment failure.

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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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Nhokwara, Primrose Tinashe. "Factors that influence the utilisation of ototoxicity monitoring services for patients on treatment for drug-resistant tuberculosis." Master's thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/15683.

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Multi-drug resistance is increasingly becoming a challenge to tuberculosis control programmes globally. Treatment of multi-drug resistance tuberculosis (MDR-TB) includes aminoglycoside antibiotics which are known to cause hearing loss. Ototoxicity monitoring services are often provided to patients undergoing treatment for MDR-TB for early detection of ototoxic hearing loss to facilitate alerting the patients and relevant medical staff about the presence and progression of any hearing loss. Previously, models of managing patients with MDR-TB required mandatory hospitalization for at least 6 months. This made it relatively easy to monitor the hearing status of patients during their stay in the hospital. However, with recent introduction of policy guidelines that support management of patients with MDR-TB on an outpatients basis, ototoxicity monitoring for these patients will need to be reorganized to align with the new policy guidelines. The extent of the uptake of these services when patients are accessing them as outpatients is however, unknown. This study therefore aimed to describe the patterns of utilisation and explore the barriers and factors that facilitate the use of ototoxicity monitoring services when provided on an outpatient basis in the Cape Town Metropolitan area, Western Cape, South Africa.

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Firfirey, Nousheena. "The evaluation of the integrated client-centred intervention programme (ICIP) for clients with MDR-TB at DP Marais Hospital in the Western Cape." University of Western Cape, 2020. http://hdl.handle.net/11394/7687.

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Philosophiae Doctor - PhD
Although TB is a curable communicable disease, poor adherence to TB treatment is a major barrier to TB control in South Africa as it increases the risks of morbidity, mortality and drug resistance at individual and community level. As a result, multi-drug-resistant TB (MDR-TB) has become a serious public health issue. Underpinning this study was the assumption that a client-centred approach to treatment of MDR-TB clients, with a hospital programme which adopts an integrated multidisciplinary approach that is client-centred and is not purely biomedically driven, would improve treatment outcomes of MDR-TB clients.

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Greeff, Wildine Marion. "Ototoxicity Monitoring using Automated Extended High-Frequency Audiometry and the Sensitive Range of Ototoxicity in Patients with MDR-TB." Master's thesis, Faculty of Health Sciences, 2021. http://hdl.handle.net/11427/32696.

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Background: Disabling hearing loss is a global burden. This burden is worsened by the emergence of multi-drug resistant tuberculosis (MDR-TB). Some of the medications used to treat MDR-TB are damaging to the cochlea and auditory nerve (ototoxic) and can lead to permanent hearing loss and/or balance disorders. Ototoxicity monitoring aims to reduce this burden by preventing or minimising the damage caused by ototoxic treatment as it can progress and worsen speech perception difficulties. However, the proposed test battery for ototoxicity monitoring is lengthy and demands active participation which is not ideal for ill patients (such as those on MDR-TB treatment). The Sensitive Range of Ototoxicity (SRO) technique is recommended to shorten the test time. The SRO consists of seven consecutive relatively high frequencies determined from the highest frequency the participant responded to. The SRO technique is time efficient. Although the SRO technique provides the prospect of a shortened test battery, there is still a global lack of audiologists. Automated audiometry is a vital application for testing especially when audiologists are not available to physically do the test. Automated audiometry has been previously validated. Clinically, automated audiometry is objective and allows for standardisation. Even though automated audiometry helps improve access to monitoring more patients, patient preference is an important factor when using automated audiometry to ensure patient-centred care is not compromised. Aims and Objectives: This study aimed to investigate the specificity and sensitivity of the SRO technique with automated audiometry compared to the gold standard (manual audiometry). This comparison was made by firstly, determining the testing time efficiency and the correlation of thresholds obtained with the different test methods and, secondly, testing the diagnostic value of automated audiometry using the SRO technique. The incidence of an ototoxicity-induced hearing loss was described by determining the time interval between starting ototoxic MDR-TB treatment and the onset of a significant threshold shift (STS) according to ASHA's criteria. Lastly, the test method preference of the participants with MDR-TB was described and compared using a short exit survey. Study Design: A prospective repeated-measures study design was used. Participants were chosen based on a risk factor (i.e. exposure to ototoxic medication) for an outcome of interest (i.e. the presence or absence of an STS). With a repeated measures study, multiple tests using different test methods can be compared with the same sample. Participants: Twenty-seven in-patients at Brooklyn Chest Hospital and DP Marais TB Hospital with normal hearing and on MDR-TB medication were included in the study. Their age range was from 19 to 51 years old with an average age of 33 years old. Non-probability convenience sampling was used as it was cost-effective, reduced data collection time and was relatively easy to execute. Data collection materials and procedures: The procedure for data collection included weekly follow-up testing for a maximum of four weeks. The test battery was as follows: an auditory symptom questionnaire, otoscopy examination, and manual and automated audiometry using the SRO technique with a fifteen-minute break in between. Participants were tested with the KUDUwave ™ in a non-sound treated room. The frequency range was determined with the SRO technique. If an STS was obtained, the patient was discharged from the study after completing an exit survey. Statistics: Analysis included descriptive statistics and inferential statistics. A Bonferroni corrected p-value (initially p ≤ 0.05) was used. Manual and automated audiometry thresholds were compared using the Pearson's Correlation Coefficient test. Manual and automated audiometry testing time and threshold means were compared using paired sample's t-tests. The diagnostic value of automated audiometry with the SRO technique was assessed with Receiver Operating Characteristics (ROC) Curves. Results: Manual audiometry was statistically more time-efficient compared to automated audiometry by an average of one minute and ten seconds (t (94) = -5.44; p< 0.003). There was a strong positive correlation for both left and right ears between the thresholds' obtained from manual and automated audiometry at 8kHz to 16 kHz (df> 28 = r > 0.70, p< 0.003). Automated audiometry was found to be a fair diagnostic test (area under the curve was 0.75; p= 0.002). Also, the ROC curve revealed that automated audiometry had a sensitivity of 61% and specificity of 90% when compared to manual audiometry (gold standard). Only participants that started data collection within 31 days after starting their MDR-TB treatment were included in the analysis of determining the incidence of an ototoxicity-induced hearing loss (n= 24 ears). This study found that 41.67% of ears (n= 10) had an ototoxicity-induced hearing loss. A box and whisker plot revealed that data was skewed to the right (i.e. more variation in data between the median and the maximum values) and that the median number of days for an ototoxicity-induced hearing loss to appear was 33 days. Secondly, 55.55% of participants (n=15 out of 27) reported auditory symptoms before data collection commencement. Aural fullness was the most reported symptom (n= eight out of 15). Ten out of 15 (66.66%) participants that reported auditory symptoms obtained an ototoxicity-induced hearing loss. Lastly, most participants (i.e. 13 out of 19; 68.42%) that completed the exit survey had no preference between manual or automated audiometry. The common rationale among these participants was “No difference noted.” Conclusion: This research study has revealed that manual audiometry was more time-efficient compared to automated audiometry in patients with MDR-TB. Also, automated audiometry was a fair diagnostic test. It may aid in reducing the disproportionate audiologist to patient ratio, especially in a developing country. However, manual audiometry (with the SRO technique) is more clinically appropriate in patients that are difficult-to-test. Secondly, audiometric settings can be changed to accommodate testing frequencies in 1/6 octaves so that the SRO technique can be clinically adopted. An ototoxicity-induced hearing loss seems to appear 33 days after ototoxic MDR-TB treatment commencement. Aural fullness was a commonly reported symptom among participants with MDRTB. Aural fullness is omnipresent in peripheral auditory pathologies. Therefore, auditory symptoms reported by patients' needs a comprehensive audiological investigation. Lastly, more research is needed on how patients (and clinicians) experience the advances in technology innovation especially in audiology where technology innovation is continuously evolving.

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Giyose, Patela. "Strategies used to implement the national guidelines on preventing and early management of multi-drug resistant tuberculosis (MDR-TB) at the buffalo city municipality clinics in East London Eastern Cape province." Thesis, University of Fort Hare, 2013. http://hdl.handle.net/10353/1297.

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The purpose of the study was to explore and describe the strategies used by nurses to implement the national treatment guidelines to prevent, detect and manage multi-drug resistant tuberculosis (MDR-TB) patients. Tuberculosis remains one of the leading infectious diseases and the major cause of death worldwide with estimates of 9.2 million new TB cases in 2008 and 1.7 deaths including 200 000 in clients co-infected with HIV. South Africa is currently ranked 3rd among the 22 high TB burden countries in the world. The HIV/AIDS epidemic contributes significantly to the upward trend in TB morbidity and it is estimated that more than 50% of TB patients are also HIV positive (South African Department of Health 2009:10). The current rate of tuberculosis infections as a result of new infections as well as re-infections of patients is of concern to the disease control and policy making bodies of South Africa. Questions regarding the effectiveness of tuberculosis policies and programmes emerge at all times (Luhulima, Netshandama and Davhana-Maselesele, 2008: 36). Patients with multidrug-resistant (MDR) tuberculosis (TB) are at high risk of treatment failure. It is anticipated that early identification of MDR-TB and appropriate treatment will improve patient outcome and disease control. This study intends to explore the effectiveness of health systems in the prompt identification and management of MDR patients. This study was conducted using a qualitative, explorative and descriptive design. A purposive sample of clinics and professional nurses was selected, and voluntary participation was ensured. The data was collected through individual interviews which were audio taped and then transcribed verbatim. Findings revealed that MDR-TB guidelines were available at the clinics. The professional nurses implemented the guidelines to prevent, detect and manage multi-drug resistant tuberculosis, by screening and testing symptomatic high risk groups, contact tracing and monitoring, providing initial counselling and education to patients and family, preparing patients for admission when indicated and coordinating referrals to the centralised MDR-TB unit. However, there were notable constraints with regards to the management of MDR-TB patients and the overall TB programme. These included MDR-TB specific training, staff shortages, dysfunctional community DOT programme, shortage of beds at the MDR-TB treatment centres, and patient factors like defaulting, migration for various reasons, alcoholism. All these constraints call for intensified strategic management at both policy and facility level. It is also necessary that all policies related to patient management need extensive scientific study to monitor and evaluate their effectiveness. More research studies are required on policy analysis and utilization.

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Ngema, Xolani Terrance. "Metallic nanoparticles with polymeric shell: A multifunctional platform for application to biosensor." University of the Western Cape, 2018. http://hdl.handle.net/11394/6330.

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Philosophiae Doctor - PhD (Chemistry)
Tuberculosis (TB) is an airborne disease caused by Mycobacterium tuberculosis (MTB) that usually affects the lungs leading to severe coughing, fever and chest pains. It was estimated that over 9.6 million people worldwide developed TB and 1.5 million died from the infectious disease of which 12 % were co-infected with human immunodeficiency virus (HIV) in the year 2015. In 2016 the statistics increased to a total of 1.7 million people reportedly died from TB with an estimated 10.4 million new cases of TB diagnosed worldwide. The development of the efficient point-of-care systems that are ultra-sensitive, cheap and readily available is essential in order to address and control the spread of the tuberculosis (TB) disease and multidrugresistant tuberculosis.

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Rifat, Mahfuza. "Multidrug resistant tuberculosis (MDR-TB) in community setting of Bangladesh." Thesis, 2015. http://hdl.handle.net/1959.13/1312209.

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Research Doctorate - Doctor of Philosophy (PhD)
Background: Bangladesh is one of the high burden countries for tuberculosis (TB) as well as for multi-drug resistant tuberculosis (MDR-TB). Research projects presented in this thesis addressed the following areas: risk factors for development of MDR-TB; factors related to previous tuberculosis treatment of MDR-TB patients; delays in treatment of drug sensitive tuberculosis patients; and the health system delay in the treatment of MDR-TB patients, in Bangladesh. Method: This thesis by publication consists of four papers. A case control study of 250 MDR-TB patients as cases and 750 drug sensitive TB patients as controls was conducted to determine the risk factors of MDR-TB in Bangladesh. A total 293 patients of the same dataset, who had history of previous tuberculosis treatment, were included in the second study to identify the factors related to previous tuberculosis treatment. MDR-TB patients who were diagnosed using the rapid diagnostic tests (n=207), were included in our fourth study, to determine the health system delay in MDR-TB treatment. We had conducted another cross sectional study (n=7280) to determine the delay in drug sensitive TB patient which has also been included in this thesis. Key findings: Our first study suggests that previous tuberculosis treatment is the major contributing factor to MDR-TB (OR 716.6, 95% CI 282.1-1820.8). Other factors found to be associated with MDR-TB are age group “18-25” (OR 1.8, CI 1.1-2.9) and “26-45” (OR 1.7, CI 1.1-2.7), compared to the age-group “ >45 years”; patient’s education up to secondary level (OR 1.9, CI 1.32.8), as opposed to the “no education” group; service and business as occupation (OR 2.9, CI 1.3-6.4; OR 3.7, CI 1.6-8.7, respectively); smoking history (OR 1.6, CI 0.99-2.5); and type 2 diabetes (OR 2.6 CI 1.5-4.3). Incomplete treatment (4.3; 95% CI 1.7-10.6), hospitalization for tuberculosis treatment (OR 16.9; CI 1.8-156.2), and adverse reaction (OR 8.2; 95% CI 3.2-20.7), are the factors related to previous tuberculosis treatment most likely to result in MDR-TB. Drug sensitive TB patients, who are seeking care from informal practitioners access care more promptly, but experience prolonged delay in initiating treatment, compared to those visiting qualified practitioners (p<0.05). Health system delay (time between visiting a provider and start of treatment) of MDR-TB patient was associated with the visit to private practitioners for first consultation, compared to visiting a DOTS centre (mean difference (days): 37.7; 95%; CI 15.0-60.4.1; p 0.003). Introduction of rapid diagnostic methods for MDR-TB has reduced the diagnosis time although some degree of delay was present in treatment initiation (median 5 and 10 days, respectively). Conclusion and recommendation: National Tuberculosis programmes should address identified risk factors in MDR-TB control strategy including previous tuberculosis treatment. Socio-demographic groups such as specific age-groups and people with some levels of education, who were associated with development of MDR-TB, could be addressed by the national TB control programme, through effective communication approach in preventing drug resistance. The integration of MDR-TB control activities with diabetes and tobacco control; engaging the private practitioners in MDR-TB control; and continued involvement of informal practitioners for early referral for diagnosis and treatment of TB, are needed in Bangladesh.

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Njaramba, Peter. "Managing multidrug-resistant tuberculosis in hospitalized patients at Sizwe Tropical Diseases Hospital: A five year review of treatment outcomes." Thesis, 2006. http://hdl.handle.net/10539/1436.

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Student number:0312412A Faculty of Health Sciences School of Public Health
Management of multidrug-resistant tuberculosis (MDR-TB) is more expensive, lengthy and is associated with less favourable outcomes and more adverse reactions than management of susceptible tuberculosis. The aim of this study was to review the management and treatment outcomes of registered MDR-TB patients hospitalized at Sizwe hospital during a five-year period. A cross-sectional study with both descriptive and analytic features was done on 237 MDR-TB patients hospitalized from the beginning of June 1998 to the end of May 2003. Data were analysed using SPSS version 12 Software. Main outcome measures were interim treatment outcomes at the end of hospitalization period. These outcomes comprised culture conversion rates, time to culture conversion, transfer out, interruption, and death rates. Multiple logistic regression analysis was performed to determine risk factors for poor treatment outcomes. These poor outcomes were defined as treatment interruption, failure and mortality rates. The burden of institutional care for MDR-TB patients in this setting was found to involve high numbers of MDR-TB patients for whom the allocated hospital beds were insufficient. Patients with primary MDR-TB, who had no history of nonadherence to treatment, were paradoxically more likely to be hospitalized shortly after diagnosis. Acquired MDR-TB patients were mostly managed as outpatients immediately after diagnosis only to be hospitalized later due to persistent nonadherence or disease severity. Overall, acquired MDR-TB patients were hospitalized in larger numbers than those with primary disease. This reflects the higher prevalence of acquired MDR-TB compared to primary MDR-TB. Page v Abstract Culture turnaround time was on average 19 days. The overall culture conversion rate of the hospitalized patients was low at 41.9 percent. This low culture conversion rate resulted in protracted hospitalization periods and high interim mortality rates. The mean duration of hospitalization, 3.52 months, correlated favourably with the time interval to the first culture conversion of 2.96 months. Hospitalization did not guarantee the expected adherence to treatment. Surgical interventions were done belatedly with resultant high mortality outcomes. The main reasons given by patients for refusing hospital treatment were visiting traditional healers, solving socioeconomic problems and attending to family matters. A large percentage of hospitalized patients were co-infected with HIV. HIV care and support was incomplete as antiretroviral drugs were not available at the hospital. Among the main findings of the study was the powerful influence HIV status had on poor hospitalization outcomes. Recommendations arising from the study include the need to provide ARVs at the Sizwe hospital. Admission and discharge guidelines aimed at ensuring adequate beds are reserved for deserving patients should be formulated. Continuing education for service providers must be encouraged and rewarded. Infection control procedures at both community and health institution level ought to be vigorously promoted. Patients known to be hopelessly non-adherent should at least be partially hospitalized in the interest of public health.

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Ramtahal, Melissa Afton. "Spread of multi drug resistant tuberculosis (MDR) including extensively drug resistant turberculosis (XDR TB), in rural KwaZulu-Natal." Thesis, 2011. http://hdl.handle.net/10413/6294.

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Mycobacterium tuberculosis (MTB) is an airborne pathogen that is easily transmitted from person to person. An intact immune system prevents the organism from causing disease in most individuals. In South Africa, the prevalence of human immunodeficiency virus (HIV) has reached astronomical levels and is now fuelling the tuberculosis (TB) epidemic. Drug resistant MTB strains combined with a weakened host immune system is a lethal combination. Multi-drug resistant (MDR) including extensively drug resistant (XDR) tuberculosis is on the increase, with Tugela Ferry in KwaZulu-Natal South Africa, reporting the largest cluster of XDR cases in the world. It is unknown whether a single clone of the drug resistant strain is circulating in this area or whether there are multiple strains at play. Using 2 complementary genotyping methods, we showed that the MDR strains present are the result of clonal spread associated with the F28 family, as well as de novo resistance which manifests as unique patterns. The XDR epidemic in Tugela Ferry is the result of clonal spread of a strain belonging to the F15/LAM4/KZN family.
Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2011.

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Sewpersadh, Mandira. "Differences between genotypic and phenotypic resistance in MDR-TB strains in South Africa." Thesis, 2013. http://hdl.handle.net/10539/12539.

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South Africa (SA) is burdened with one of the highest tuberculosis (TB) infection rates worldwide. The dual epidemic of HIV and MDR- and extensively drug-resistant (XDR) -TB outbreaks prompted the World Health Organisation to call for a new rapid molecular diagnostics tool(s). To curb the spread of drug-resistant TB, SA introduced genotypic Hain MTBDRplus line probe assays (Hain LPA) for the routine rapid diagnosis of MDR-TB. This study aimed to determine the frequency, geographic distribution and genetic basis for phenotypic and genotypic drug susceptibility testing (DST) discordant findings. The cultures used in this study were isolated during the period June 2007- July 2008 from Western Cape, Gauteng, KwaZulu-Natal, and Northern Cape. A total of 118 comparable MGIT and Hain LPA DST were obtained with 41 isolates verified to be discordant. The predominant families were the LAM, T, X and, S. Hain LPA failed to identify INH resistance (R) in 46.3% (19/41) of isolates with MIC‟s supporting the phenotypic resistance. Genotypic RIF-R was shown in 31.7% (13/41) of isolates which was not expressed phenotypically but interestingly the MIC‟s favour the LPA resistance. Sequencing analysis of the rpoB gene region identified new mutations; Leu458Pro, Leu436Pro, and Asp441Gly, associated with missing wildtypes. For INH, the katG and inhA gene regions were sequenced. Mutations at codon Gly213Val, Pro232Lys, Lys254Asn, and Ser259Asn were detected in katG and a variety found in inhA. These mutations have not been previously reported neither are they incorporated on the Hain LPA strips. Detailed knowledge of the frequency distribution of resistance-linked mutations and associated MICs in different regions of SA, could facilitate understanding of the limitations of current molecular tests and inform testing algorithms. These findings impact on the use of new molecular diagnostics as well as epidemiological monitoring of drug-resistant strains.

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Rigouts, L., N. Coeck, M. Gumusboga, Rijk W. B. de, K. J. Aung, M. A. Hossain, K. Fissette, et al. "Specific gyrA gene mutations predict poor treatment outcome in MDR-TB." 2015. http://hdl.handle.net/10454/17328.

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Yes
Mutations in the gyrase genes cause fluoroquinolone resistance in Mycobacterium tuberculosis. However, the predictive value of these markers for clinical outcomes in patients with MDR-TB is unknown to date. The objective of this study was to determine molecular markers and breakpoints predicting second-line treatment outcomes in M. tuberculosis patients treated with fourth-generation fluoroquinolones. We analysed treatment outcome data in relation to the gyrA and gyrB sequences and MICs of ofloxacin, gatifloxacin and moxifloxacin for pretreatment M. tuberculosis isolates from 181 MDR-TB patients in Bangladesh whose isolates were susceptible to injectable drugs. The gyrA 90Val, 94Gly and 94Ala mutations were most frequent, with the highest resistance levels for 94Gly mutants. Increased pretreatment resistance levels (>2 mg/L), related to specific mutations, were associated with lower cure percentages, with no cure in patients whose isolates were resistant to gatifloxacin at 4 mg/L. Any gyrA 94 mutation, except 94Ala, predicted a significantly lower proportion of cure compared with all other gyrA mutations taken together (all non-94 mutants + 94Ala) [OR = 4.3 (95% CI 1.4-13.0)]. The difference in treatment outcome was not explained by resistance to the other drugs. Our study suggests that gyrA mutations at position 94, other than Ala, predict high-level resistance to gatifloxacin and moxifloxacin, as well as poor treatment outcome, in MDR-TB patients in whom an injectable agent is still effective.

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30

Mpanyane, Disego Mmatau. "The detection of drug resistant mutations in mycobacterium tuberculosis strains using anyplex MTB/NTM/MDR-TB plus assay in Limpopo Province." Thesis, 2015. http://hdl.handle.net/10386/1635.

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Thesis (MSc. (Medical Sciences)) -- University of Limpopo, 2015
Introduction: Multidrug-resistant tuberculosis (MDR-TB) caused by resistance to at least rifampicin (RIF) and isoniazid (INH) drugs is a growing public health concern in South Africa. The detection of MDR-TB still relies on culture despite advancement in molecular diagnostic technology. Currently MTBDRplus and GeneXpert are the only available assays used in rapid diagnosis of MDR-TB using chromosomal mutations in drug target regions. Some strains are missed by these assays due to their limitation in mutational detection profile. Novel Seegene Anyplex assays simultaneously detect TB and resistance to RIF and INH using fifteen and six mutational probes, respectively within 3 hours. Limpopo Province has limited information on the circulating strains of TB. Aim: To determine drug-resistant Mycobacterium tuberculosis (M. tuberculosis) mutations using Anyplex™ MTB/NTM/MDR-TB real time assay and characterise the drug-resistant strains. Methods: We prospectively collected 204 clinical samples at Modimolle MDR-TB unit and retrospectively used 104 culture isolates from MRC laboratory in Pretoria. The MTBDRplus assay was used to screen for M. tuberculosis and drug resistant mutations to RIF and INH drugs. Anyplex™ MTB/NTM/MDR-TB assay was used for rapid detection of M. tuberculosis and drug resistance to RIF and INH within 3 hours. The discordance between phenotypic and genotypic assays was resolved by sequencing and the Anyplex™ resistant profiles were spoligotyped. Diagnostic data was collected from NHLS and MRC databases and analysed using the Microsoft excel and Epi Info version 3.5. Descriptive statistics (percentages and frequencies) were used to explain proportions. Results: The Anyplex™ MTB/NTM assay detected M. tuberculosis in 69/111(62%) and 100/104 (96%) of clinical and culture samples respectively. The sensitivities, specificity, PPV and NPV obtained for both RIF and INH resistance by Anyplex™ MDR-TB assay were 67%, 59%, 67%, 55% and 15%, 100%, 100% and 17%, respectively. Anyplex™ MTB/NTM/MDR-TB resolved 23/45 (51%) of discordant vi samples. Sequencing of remaining discordant isolates revealed L511P, L533P and D516Y mutations within rpoB gene. A novel R385W mutation within katG was also detected. Spoligotyping of Anyplex™ MDR-TB resistant clinical isolates revealed Euro American clade with 20% followed by 15% Manu2, 5% East African Indian, 5% H37Rv, 5% atypical and 50% were orphans. Conclusion: The novel Anyplex™ MTB/NTM/MDR-TB assay is a rapid and valid technique for detecting M. tuberculosis and most common mutations conferring resistance to RIF and INH. However further investigations are required, as the assay has a lower sensitivity as compared to already endorsed techniques.
National Research Foundation (NRF) and University of Limpopo TB Grant

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31

Odendaal, Ronel. "Epidemiological impact of HIV on second - line drug resistance in patients with multidrug resistant tuberculosis in high HIV prevalent settings in South Africa." Diss., 2014. http://hdl.handle.net/2263/43209.

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32

Salindri, Argita. "Diabetes Reduces the Rate of Sputum Culture Conversion in Patients with Newly Diagnosed Multidrug Resistant Tuberculosis." 2015. http://scholarworks.gsu.edu/iph_theses/421.

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Background: Risk factors for acquired multidrug resistant tuberculosis (MDR TB) are well described but risk factors of primary MDR TB is understudied. We aimed to 1) assess risk factors for primary MDR TB, including diabetes, and 2) determine if diabetes reduced the rate of sputum culture conversion in patients with primary MDR TB. Methods: From 2011-2014 we conducted a prospective cohort study at the National Center for TB and Lung Disease in Tbilisi, Georgia. Adult (≥35 years) patients with primary TB were eligible. MDR TB was defined as resistance to at least rifampicin and isoniazid. Patients with HbA1c ≥6.5% were defined to have diabetes. Polytomous regression was used to estimate the association of patient characteristics with drug resistance. Cox regression was used to compare the hazard rate of sputum culture conversion in patients with and without diabetes. Results: Among 318 patients, 268 had drug susceptibility test results. Among patients with DST results, 19.4% was primary MDR TB and 13.4% had diabetes. In adjusted analyses, diabetes (aOR 2.51 95%CI 1.00 – 6.31) and lower socioeconomic status (aOR 3.51 95%CI 1.56 – 8.20) were associated with primary MDR TB. Among patients with primary MDR TB, 44 (84.6%) converted sputum cultures to negative. The hazard rate of sputum culture conversion was lower among patients with diabetes (aHR 0.34 95%CI 0.13 – 0.87) and among smokers (aHR 0.16 95%CI 0.04 – 0.61). Conclusions: We found diabetes to be associated with an increased risk of primary MDR TB; both diabetes and smoking were associated with a decreased rate of sputum culture conversion.

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Mengistu, Kenea Wakjira. "Treatment outcomes of patients with MDR-TB and its determinants at referral hospitals in Ethiopia." Thesis, 2019. http://hdl.handle.net/10500/26003.

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Text in English
Aim: The aims of this study were to investigate the treatment outcomes of patients with MDRTB and its determinants at referral hospitals in Ethiopia. The study also aims to develop a conceptual model for enhancing treatment of patients with MDR-TB in Ethiopia. Design and methods: A concurrent mixed methods design with quantitative dominance was used to investigate treatment outcomes of patients with MDR-TB and its determinants. Results: A total of 136 (n=136) patients with MDR-TB participated in the study, 74 (54%) were male and 62 (46%) were female. Forty-one (31%) of the patients had some co-morbidity with MDR-TB at baseline, and 64% had body mass index less than 18.5kg/m2. Eight (6%) of the patients were diagnosed among household contacts. At 24 months, 76/110 (69%) of the patients had successfully completed treatment, but 30/110 (27%) were died of MDR-TB. Multivariable logistic regression revealed that the odds of unfavourable treatment outcomes were significantly higher among patients with low body mass index (BMI <18.5kg/m2) (AOR=2.734, 95% CI: 1.01-7.395; P<0.048); and those with some co-morbidity with MDR-TB at the baseline (AOR=4.260, 95%CI: 1.607-11.29; p<0.004). The majority of the patients were satisfied with the clinical care they received at hospitals. But as no doctor was exclusively dedicated for the MDR-TB centre, patients could not receive timely medical attention and this was especially the case with those with emergency medical conditions. The caring practice of caregivers at the hospitals was supportive and empathic but it was desperate and alienating at treatment follow up centres. Patients were dissatisfied with the quality and adequacy of the socio-economic support they got from the programme. Despite the high MDR-TB and HIV/AIDS co-infection rate, services for both diseases was not available under one roof. Conclusions: Low body mass index and the presence of any co-morbidity with MDR-TB at the baseline are independent predictors of death among patients with MDR-TB. Poor communication between patients and their caregivers and inadequate socio-economic support were found to determine patients’ perceived quality of care and patients’ satisfaction with care given for MDR-TB.
Health Studies
D. Litt et Phil. (Health Studies)

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Nigusso, Fikadu Tadesse. "Risk factors for multidrug-resistant tuberculosis in Addis Ababa, Ethiopia." Diss., 2012. http://hdl.handle.net/10500/10191.

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This quantitative, descriptive study investigated risk factors for MDR-TB in Addis Ababa, Ethiopia. A total of 439 medical records belonging to MDR-TB and non MDR-TB patients managed in public health centres from January 2008 to December 2011 were analysed. Data were transcribed from each TB patient‟s medical records using a specifically designed checklist. The findings revealed that male gender, previous history of TB treatment, poor treatment adherence, an outcome of failure after TB re-treatment, previous category of failure, pulmonary involvement of TB infection and HIV infection were associated with MDR-TB. The findings illustrate that efforts should be made to prioritise the development and implementation of effective MDR TB screening and treatment protocols for these high risk groups to improve treatment outcome and minimize the emergence of XDR TB.
Health Studies
M. Public Health

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35

Lempens, P., T. Decroo, K. J. M. Aung, M. A. Hossain, L. Rigouts, Conor J. Meehan, Deun A. Van, and Jong B. C. de. "Initial resistance to companion drugs should not be considered an exclusion criterion for the multidrug-resistant tuberculosis shorter treatment regimen." 2020. http://hdl.handle.net/10454/18043.

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We investigated whether companion drug resistance was associated with adverse outcome of the shorter MDR-TB regimen in Bangladesh, after adjusting for fluoroquinolone resistance. MDR/RR-TB patients registered for treatment with a standardized gatifloxacin-based shorter MDR-TB regimen were selected for the study. Drug resistance was determined using the proportion method, gatifloxacin and isoniazid minimum inhibitory concentration testing for selected isolates, and whole genome sequencing. Low-level and high-level fluoroquinolone resistance were the most important predictors of adverse outcomes, with pyrazinamide resistance having a significant yet lower impact. In patients with fluoroquinolone-/second-line injectable-susceptible TB, non-eligibility to the shorter MDR-TB regimen (initial resistance to either pyrazinamide, ethionamide, or ethambutol) was not associated with adverse outcome (aOR 1.01; 95%CI 0.4-2.8). Kanamycin resistance was uncommon (1.3%). Increasing levels of resistance to isoniazid predicted treatment failure, also in a subgroup of patients with high-level fluoroquinolone-resistant TB. Our results suggest that resistance to companion drugs of the shorter MDR-TB regimen, except kanamycin resistance, is of no clinical importance as long as fluoroquinolone susceptibility is preserved. Hence, contrary to current WHO guidelines, exclusions to the standard regimen are justified only in the case of fluoroquinolone, and possibly kanamycin resistance.
Damien Foundation Belgium for its financial and logistic support to run the project including its research activities. European Research Council (Starting Grant INTERRUPTB 311725).

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36

Arjun, Sitha Devi. "Experiences of the mobile injection team for multi drug resistant-tuberculosis patients in Ugu District, KwaZulu-Natal." Thesis, 2015. http://hdl.handle.net/10500/21046.

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The purpose of the study was to investigate and describe the experiences of a mobile injection team for multi drug resistant-tuberculosis outpatients, and to design and recommend a mobile injection team guideline based on the experiences of the team members in Ugu District, KwaZulu-Natal and to indicate the support that the MIT require. Phenomenological research was conducted. Convenient census sampling was used as all the seven members of the Ugu District mobile injection team were included. The inclusion criteria was at least six months’ working experience with MDR-TB patients in a mobile injection team at Ugu District, be an enrolled nurse registered with the South African Nursing Council as an enrolled nurse and must have an annual practicing certificate, or be a TB assistant, be willing to participate in the study and be located at the decentralised and satellite site. Data were collected through individual in-depth interviews with the participants. Data were analysed using Giorgi’s method of data analysis. The research findings revealed four broad themes (the perceptions held by the team, challenges, available support and needs to promote the service) and 73 sub-themes. The findings of the study indicate that the MDR-TB outreach injection teams experience many challenges in the community and need to be supported by their management in order to provide quality care to the patients. This study contributes to the development of guidelines to assist the mobile injection teams to provide quality patient care and effective service delivery. Based on the findings, the recommendation is that an intervention study be performed to compare the utilisation of the mobile MDR-TB injection team after implementing the recommendations made and the guidelines developed in this study
Health Studies
D. Litt. et Phil. (Health Studies)

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37

Ngabonziza, J. C. S., Y. M. Habimana, T. Decroo, P. Migambi, A. Dushime, J. B. Mazarati, L. Rigouts, et al. "Reduction of diagnostic and treatment delays reduces rifampicin-resistant tuberculosis mortality in Rwanda." 2019. http://hdl.handle.net/10454/17785.

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SETTING: In 2005, in response to the increasing prevalence of rifampicin-resistant tuberculosis (RR-TB) and poor treatment outcomes, Rwanda initiated the programmatic management of RR-TB, including expanded access to systematic rifampicin drug susceptibility testing (DST) and standardised treatment.OBJECTIVE: To describe trends in diagnostic and treatment delays and estimate their effect on RR-TB mortality.DESIGN: Retrospective analysis of individual-level data including 748 (85.4%) of 876 patients diagnosed with RR-TB notified to the World Health Organization between 1 July 2005 and 31 December 2016 in Rwanda. Logistic regression was used to estimate the effect of diagnostic and therapeutic delays on RR-TB mortality.RESULTS: Between 2006 and 2016, the median diagnostic delay significantly decreased from 88 days to 1 day, and the therapeutic delay from 76 days to 3 days. Simultaneously, RR-TB mortality significantly decreased from 30.8% in 2006 to 6.9% in 2016. Total delay in starting multidrug-resistant TB (MDR-TB) treatment of more than 100 days was associated with more than two-fold higher odds for dying. When delays were long, empirical RR-TB treatment initiation was associated with a lower mortality.CONCLUSION: The reduction of diagnostic and treatment delays reduced RR-TB mortality. We anticipate that universal testing for RR-TB, short diagnostic and therapeutic delays and effective standardised MDR-TB treatment will further decrease RR-TB mortality in Rwanda.

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Likibi, Mupata Lelwi. "Profile of multi drug resistant tuberculosis (MDR-TB) patients at Sizwe Hospital: 2001-2002." Thesis, 2012. http://hdl.handle.net/10539/11419.

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M.P.H., Faculty of Health Sciences, University of the Witwatersrand, 2011
Background: In Gauteng Province, South Africa, Sizwe Tropical Hospital (STH) is the designated centre for the specialized management of MDR-TB. But during the period covered by this study (2001-2002), all cases of TB (MDR-TB and NMDR-TB) were treated at STH. This was not according to the prescript of the National guidelines. This study describes the socio-demographic, treatment profile and treatment outcomes of MDR-TB patients seen and treated at STH during 2001 and 2002. Method: This was a cross sectional study involving retrospective review of records at STH. 281 systematically-sampled MDR-TB patient records were included in this study. Descriptive statistics were used to summarize the socio-demographic and treatment history characteristics and these were further analyzed to evaluate their relationship with MDR-TB treatment outcomes using Chi squared test of association. Means were compared using simple t-test. Results: The patients were majority black, unemployed, and living in townships and informal settlements. Sputum tests alone or combined with x-ray were most commonly used to diagnose MDR-TB (98%) at referring facilities; and the majority of patients arrived at STH with a referral note (98%). The median duration of stay at STH was 56 weeks (IQR 21-89). The majority of patients had a successful treatment outcome (75%); and amongst those with unsuccessful outcomes, a significant number had died (17%). Factors associated with poor iv outcomes in terms of death, default, treatment failure and transfer out were age groups (1-9 and 30-39), race, employment status, place of residence, housing structure, referral systems (referral note and feedback procedures) and HIV status. Discussion: The patients in this study had socio-demographic characteristics that facilitate TB transmission. There is a commendable referral system but various methods used to confirm MDR-TB and unjustified long duration of treatment prior to referral. Although in general the majority of patients have successful treatment outcomes, the policy guidelines of the management of MDR-TB are not implemented fully, and several factors associated to poor outcome are related to the health service and referral system. Recommendation: Effective adherence to the policy guidelines by health care providers and patients is recommended to improve treatment outcomes.

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Kavallieratos, Angela. "Hearing function in adults with Multiple Drug Resistant-TB : a retrospective review." Thesis, 2012. http://hdl.handle.net/10539/11880.

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KwaZulu-Natal has been ranked as having the fourth highest incidence of transmitted Multiple Drug Resistant-Tuberculosis (MDR-TB) in sub-Saharan Africa. Substantial literature exists indicating the permanent damage that MDR-TB medication has on hearing abilities. The purpose of this study was to describe the hearing function of adults on long term MDR-TB treatment from Murchison Hospital MDR-TB unit in the Ugu District in rural KwaZulu-Natal. The primary aim of the study was to review the possible changes in hearing function in a group of adults on long-term treatment for MDR-TB. Secondly, the study aimed to estimate the number of adults who may present with changes following MDR-TB treatment and establish if relationships exist between the audiological findings and factors such as age and gender. The design of the study was a retrospective comparative data review of 68 patient records, all of which underwent audiological investigations from the start of MDR-TB treatment over a five-month period. The study made use of descriptive and inferential statistics to analyse the data. Specific inferential statistical analysis included analysis of covariance as well as regression analysis. Results from the study showed changes in hearing function in Distortion Product Otoacoustic Emissions (DPOAEs) and Pure Tone Audiometry (PTA) results at all five audiological sessions and across a range of frequencies. 84% of the total sample presented with overall refer readings for DPOAEs and 98.53% of the group of adults presented with criteria indicative of ototoxic hearing loss, specifically a bilateral mild-profound sloping SNHL on clinical PTA results. In the total sample of patient records reviewed in this study, all 68 records showed a change in hearing function, be that changes in DPOAE function and/or changes in PTA thresholds, following long-term treatment for MDR-TB. Variations in the effects of gender and ear difference were minimal and non-significant in all results. Similar presentation, to ototoxic hearing loss, of other degenerative conditions exists; however these conditions were accounted for as exclusion criteria in this study. Therefore the only remaining cause of possible hearing deficit was that of ototoxicity. The study provided valuable data regarding hearing function in a population of adults on long-term MDR-TB treatment in South Africa. Furthermore, the study has highlighted the need for the establishment of standardised audiological monitoring programmes sensitive to ototoxic hearing loss, within the South African context where the incidence of Tuberculosis (TB) and MDR-TB is reportedly high.

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Ramese, Nnyadzeni. "Identification and characterisation of compounds with antimycobacterial activity from stomatostemma monteiroae." Thesis, 2019. http://hdl.handle.net/10386/2973.

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Thesis (MSc. (Microbiology)) -- University of Limpopo, 2019
The emergence of drug resistance to the first line drugs complicates the treatment of tuberculosis (TB), especially in parts of sub-Saharan Africa where accessibility to quality health care is limited. The search for alternative medication has been the centre of research for years due to challenges posed by infectious organisms including drug resistance, lengthy treatment periods and lack of quality health care in developing countries. Stomatostemma monteiroae is used in traditional medicine to treat TB and related symptoms. The aim of this study was to isolate and characterise compounds with antimycobacterial activity from Stomatostemma monteiroae. The plant materials were collected from Ga-Madiga village in Limpopo province of South Africa. Different plant parts namely: leaves, twigs, roots, tuber and tuber-peels were separated, washed, dried and milled to a fine powder. Several solvents (n-hexane, dichloromethane, acetone and methanol) were used to extract the plant material using various extraction methods such as maceration, defatting, and extract enrichment procedure and phytochemical analysis was done using standard chemical tests and thin layer chromatography. The qualitative antioxidant activity was determined by the thin layer chromatography (TLC) based 2,2-diphenyl-1picrylhydrazyl (DPPH) free radical scavenging activity and quantitative antioxidant activity was determined using colorimetric DPPH free radical scavenging and ferric reducing power assay. Antimycobacterial activity of the extracts was assessed using bioautography and micro dilution method tested on Mycobacterium smegmatis (ATCC 1441), Mycobacterium tuberculosis (ATCC 25177) and M. tuberculosis H37Rv (ATCC 27294). The cytotoxic effects of the extracts were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on Vero monkey kidney cells. The compounds with antimycobacterial activity were isolated using bioassay-guided fractionation and purified using preparative thin layer chromatography and thereafter identified using NMR spectroscopy to elucidate the structure. Various phytochemical constituents were detected in different plant parts, with the leaves and twigs possessing more of the phytoconstituents analysed. The TLC profile of S. monteiroae indicated that more compounds are non-polar to intermediate in polarity. The antioxidant activity analysis on TLC plates indicated that all the plant parts have low antioxidant activity, this was also confirmed by xxii quantitative tests. The leaves of S. monteiroae had antimycobacterial activity when analysed using bioautography, while other plant parts had no active bands. The minimum inhibitory concentration values were much higher than the positive control rifampicin and the roots (0.31 mg/mL) followed by the leaves (0.83 mg/mL) had lower inhibitory concentrations when tested against M. smegmatis. The MIC values of extracts against TB causing strains varied greatly, the leaves and the roots had even higher MIC value. Toxicity analysis indicated that all plant parts were non-toxic towards Vero cells (LC50 > 0.02 mg/mL). Bioassay-guided fractionation enabled isolation of one antimycobacterial pure compound from the leaves extracts. The isolated compound was identified using NMR and was found to be a sitosterol derivative 8,9-dehydro-4-methyl-24-vinylobtusifoliol. This compound had a noteworthy activity against M. smegmatis. The present study validates the use of S. monteiroae in the treatment of TB related symptoms traditionally. Further studies are required to analyse the cytotoxic effects of the isolated compound and also testing the antimycobacterial activity of the isolated compound on TB causing pathogens.
National Research Foundation (NRF)

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41

August, Keith. "HIV/AIDS, migrant labour and the experience of God : a practical theological postfoundationalist approach." Thesis, 2010. http://hdl.handle.net/2263/26862.

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Migrant workers in the Deciduous Fruit Industry are part of the marginalised communities in South Africa. They are often voiceless in the communities they find themselves. They are historically displaced, often prone to xenophobia and very vulnerable in terms of HIV. Not only do they have a high infection rate but they also struggle in isolation to carry the burden of HIV and AIDS affection or infection. They will face double jeopardy when a partner becomes ill, in the homeland and they have to continue with employment. The main aim of this research was to reach a holistic understanding through interdisciplinary investigation. The important question that I aim to answer is; “What is the experience of God in the lives of persons affected or infected by HIV and AIDS.” I have looked at Postfoundationalism and the Seven Movements as proposed by Muller to present the research undertaken among migrant workers with HIV and AIDS. The Practical Theology, which I explore, develops out of a very specific praxis, HIV and AIDS. I have also made used of Transversal Rationality as a practical way of doing interdisciplinary work with the stories of my co-researchers affected with HIV AIDS as a case study. I understand that Christian belief has its own integrity, which is exclusive, but if valid, is vital to be able to incorporate the different dimensions of our modern practise to give it the maximum level of meaning and significance. I hope to demonstrate this possibility through my thesis.
Thesis (PhD)--University of Pretoria, 2010.
Practical Theology
unrestricted

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Dissertations / Theses on the topic 'Multidrug resistant tuberculosis (MDR-TB)'

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