Résumé exécutif.<p>Introduction.<p>La tuberculose est une maladie infectieuse qui constitue un fardeau pour la société et en ce sens qu’elle est responsable d’un important taux de mortalité spécifique, surtout dans les pays en développement. Malgré les grands progrès en termes de méthodes de diagnostic, de prévention et de traitement, près de 9 millions de nouveaux cas apparaissent chaque année au niveau mondial et les 30% se trouvent en Afrique. On estime que la tuberculose est responsable de près de 2 millions de morts par an, principalement parmi les populations les plus pauvres. Pourtant, la maladie peut être guérie à l’aide des médicaments dont le coût est inférieur à 18 USD par patient. <p>Pour faire face à ce problème lié à la tuberculose, l’OMS a recommandé vers 1994 l’application de la stratégie « Directly Observed Treatment Short-course, (DOTS) ». Cette stratégie, constituée de 5 points clés, n’a donné que des résultats partiels. Par conséquent, les experts de l’OMS ont conçu et ont publié une autre stratégie appelée « Halte à la Tuberculose » en 2006. Cette nouvelle stratégie, allant au delà des 5 principaux points de la stratégie DOTS, fait appel à toutes les structures sanitaires publiques et privées et à tous les acteurs de santé, y compris la communauté, pour participer au dépistage et à la prise en charge des tuberculeux.<p>A Madagascar, la lutte contre cette maladie est coordonnée par l’équipe du Programme national de lutte contre la tuberculose (PNT). Ce programme est fonctionnel depuis 1991 et applique les stratégies recommandées par l’OMS. Par ailleurs, il a conçu un manuel destiné aux prestataires de soins et aux différents responsables du niveau opérationnel. Le PNT s’est fixé comme principaux objectifs d’améliorer le système de dépistage et d’atteindre un taux de guérison de 85%. En 2006, 15 ans après la mise en œuvre du programme, le taux de notification des nouveaux cas de tuberculose à frottis positif (TPM+) était de 81 pour 100.000 habitants par an et la proportion de réussite au traitement pour ce dernier groupe de tuberculeux était encore de 78%. La létalité et le taux d’échec au traitement à Madagascar est relativement bas. La relativement faible proportion de réussite, inférieure à l’objectif, est avant tout liée au taux d’abandon élevé. Depuis 2006, le PNT a adopté le système décentralisé dans la prise en charge des malades. <p>Généralement, un tuberculeux a un parcours long et ardu à effectuer à partir de l’apparition des premiers signes d’imprégnation tuberculeuse jusqu’à la guérison. Ce parcours est à la fois d’ordre géographique et thérapeutique. Bien que les malades présentent des signes cliniques quasiment identiques, demandant un schéma thérapeutique standard, ils vivent dans des contextes différents. Et chaque contexte a un effet spécifique sur l’adhésion au traitement. Pourtant, ces contextes sont rarement considérés dans les stratégies conçues au niveau national et international. Soulignons que Madagascar est un vaste pays de 590.000 km² ayant des contextes (contexte géographique, contexte culturel, nombre de formations sanitaires, etc.) très variables d’une région à l’autre et d’un district à l’autre. L’application des directives sans tenir compte ces différents contextes locaux pourrait être à l’origine de la non réussite su système de suivi des malades et donc du contrôle de la tuberculose. Inversement, les districts et les centres de diagnostic et de traitement (CDT) qui adaptent les directives selon leurs contextes et/ou qui prennent des initiatives répondant aux contextes des malades, ont plus de chance de réussir le contrôle de la tuberculose.<p>Objectifs.<p>D’une manière spécifique, la présente thèse vise à :<p>-\ / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

PhD (Health Sciences) / Department of Advanced Nursing Science

MSc (Statistics) / Department of Statistics

Tuberculosis (TB) is an infectious and fatal disease that ranks as the second leading killer worldwide. It is caused by Mycobacterium tuberculosis (Mtb) which is an obligate intracellular parasite that colonizes the alveolar macrophages of the immune system. The major health concern associated with TB is its co-infection with HIV and the development of strains with multi-drug resistance. The elimination of TB has been hindered due to the lack of understanding of the survival strategies used by this pathogen. Thus, research towards discovering new effective antibacterial drugs is necessary and a group of Mtb kinase enzymes were targeted in this study because these enzymes are crucial for metabolism, pathogenesis and, hence, the survival of Mtb. Kinases are a group of structurally distinct and diverse proteins that catalyze the transfer of the phosphate group from high energy donor molecules such as ATP (or GTP) to a substrate. The phosphorylation of proteins modifies the activity of specific proteins which is subsequently used to control complex cellular processes within Mtb. The starting point of this research targeted eight specific Mtb kinases namely; Nucleoside diphosphokinase, Homoserine kinase, Acetate kinase, Glycerol kinase, Thiamine monophosphate kinase, Ribokinase, Aspartokinase and Shikimate kinase. The aim of this project was to subclone the gene sequences for these eight recombinant Mtb kinases and express them in Escherichia coli, to purify the proteins and determine their activity. In the effort to find new lead compounds, the final stage of this study focused on the basic screening of the TB kinases against an extract prepared from Pelargonium sidoides, a medicinal plant, to identify any inhibitory effects. Although this traditional medicinal plant has been broadly researched and extensively used to treat TB, there is still a lack of understanding of this plant’s scientific curative effect. Various molecular and biochemical methods were used to achieve the aims of this project. The putative gene sequence was obtained from the annotated genome of H37Rv, deposited at NCBI as NC_000962.2. The genes encoding the kinases were successfully PCR-amplified from genomic DNA, cloned into an expression vector in-frame with a C- or N-terminal 6-histidine-tag and expressed in E. coli BL21 (DE3). The purification of the protein was complex, but various different methods and techniques were explored to obtain sufficient amounts of protein. The functional characterization of the kinases involved an HPLC enzyme assay that showed that the recombinant kinases were active. These enzymes were then screened against the potential inhibitory compounds in P. sidoides using enzyme assays to generate dose-response curves. This allowed an effective comparison not only of the Mtb kinases’ activity under normal conditions but also the kinases’ activity in the presence of a potential inhibitor. Overall, the inhibition of the enzymes required the presence of higher concentrations of the P. sidoides extract. However, the SK enzyme results presented a significantly higher inhibition and the lowest IC50 value, in comparison to the other kinases, which makes this kinase an attractive potential drug target against TB. In summation, cloning and purification of SK was successful, resulting in a concentration of 2030 μg/ml of purified enzyme and its activity analysis demonstrated enzyme functionality. This activity was reduced to zero in the presence of 1 x 102 mg/ml dilution of P. sidoides plant extract. This research conducted has extended the quality of information available in this field of study. These interesting results, proposing and identifying SK as a suitable potential target can be a starting point to significantly contribute and progress in this field of research, with the eventual goal of developing a drug to combat this fatal disease. / Life Sciences / M. Sc. (Life Sciences)

Tuberculosis (TB) is an infectious and fatal disease that ranks as the second leading killer worldwide. It is caused by Mycobacterium tuberculosis (Mtb) which is an obligate intracellular parasite that colonizes the alveolar macrophages of the immune system. The major health concern associated with TB is its co-infection with HIV and the development of strains with multi-drug resistance. The elimination of TB has been hindered due to the lack of understanding of the survival strategies used by this pathogen. Thus, research towards discovering new effective antibacterial drugs is necessary and a group of Mtb kinase enzymes were targeted in this study because these enzymes are crucial for metabolism, pathogenesis and, hence, the survival of Mtb. Kinases are a group of structurally distinct and diverse proteins that catalyze the transfer of the phosphate group from high energy donor molecules such as ATP (or GTP) to a substrate. The phosphorylation of proteins modifies the activity of specific proteins which is subsequently used to control complex cellular processes within Mtb. The starting point of this research targeted eight specific Mtb kinases namely; Nucleoside diphosphokinase, Homoserine kinase, Acetate kinase, Glycerol kinase, Thiamine monophosphate kinase, Ribokinase, Aspartokinase and Shikimate kinase. The aim of this project was to subclone the gene sequences for these eight recombinant Mtb kinases and express them in Escherichia coli, to purify the proteins and determine their activity. In the effort to find new lead compounds, the final stage of this study focused on the basic screening of the TB kinases against an extract prepared from Pelargonium sidoides, a medicinal plant, to identify any inhibitory effects. Although this traditional medicinal plant has been broadly researched and extensively used to treat TB, there is still a lack of understanding of this plant’s scientific curative effect. Various molecular and biochemical methods were used to achieve the aims of this project. The putative gene sequence was obtained from the annotated genome of H37Rv, deposited at NCBI as NC_000962.2. The genes encoding the kinases were successfully PCR-amplified from genomic DNA, cloned into an expression vector in-frame with a C- or N-terminal 6-histidine-tag and expressed in E. coli BL21 (DE3). The purification of the protein was complex, but various different methods and techniques were explored to obtain sufficient amounts of protein. The functional characterization of the kinases involved an HPLC enzyme assay that showed that the recombinant kinases were active. These enzymes were then screened against the potential inhibitory compounds in P. sidoides using enzyme assays to generate dose-response curves. This allowed an effective comparison not only of the Mtb kinases’ activity under normal conditions but also the kinases’ activity in the presence of a potential inhibitor. Overall, the inhibition of the enzymes required the presence of higher concentrations of the P. sidoides extract. However, the SK enzyme results presented a significantly higher inhibition and the lowest IC50 value, in comparison to the other kinases, which makes this kinase an attractive potential drug target against TB. In summation, cloning and purification of SK was successful, resulting in a concentration of 2030 μg/ml of purified enzyme and its activity analysis demonstrated enzyme functionality. This activity was reduced to zero in the presence of 1 x 102 mg/ml dilution of P. sidoides plant extract. This research conducted has extended the quality of information available in this field of study. These interesting results, proposing and identifying SK as a suitable potential target can be a starting point to significantly contribute and progress in this field of research, with the eventual goal of developing a drug to combat this fatal disease. / Life Sciences / M. Sc. (Life Sciences)

Made available in DSpace on 2011-05-04T12:36:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2009 / Introdução: Nas últimas duas décadas ampliou-se a demanda por serviços de maior complexidade tecnológica para o atendimento da tuberculose, especialmente em hospitais gerais e universitários. Em geral não há avaliação sistemática da magnitude da exposição local nas unidades hospitalares, apesar de ser considerada como doença ocupacional. Objetivo: Descrever e analisar o perfil epidemiológico da tuberculose-doença entre os pacientes atendidos no HUAP-UFF, e elaborar uma proposta de monitoramento da mensuração da doença. Métodos: Estudo descritivo e retrospectivo dos casos diagnosticados entre pacientes atendidos no HUAP-UFF no período de 2000 a 2006, construção de indicadores de morbidade e letalidade, e análise multivariada dos óbitos ocorridos entre os pacientes internados. Resultados: Foram diagnosticados 763 pacientes com tuberculose, 45,1 por cento no ambulatório, 11,1 por cento nas emergências e 43,8 por cento no setor de internação; 63,1 por cento eram do sexo masculino, com razão de 1,8 homens para cada mulher diagnosticada; a faixa etária mais atingida foi 30 a 59 anos. As formas clínicas pulmonares e extrapulmonares exclusivas foram predominantes, porém, entre os pacientes internados, verifica-se que as formas pulmonares positivas e negativas, associadas às extrapulmonares, e as pulmonares negativas exclusivas, foram mais frequentes. Nos pacientes que evoluíram para óbito a forma pulmonar foi também a mais encontrada. O tratamento foi iniciado em 41,9 por cento do total de casos e em 76 por cento dos pacientes internados. Entre os que iniciaram tratamento, 82,5 por cento utilizou o Esquema I. A presença de comorbidade foi mais prevalente entre os pacientes internados e os que evoluíram para óbito. O HUAP atua como uma referência não oficial de tuberculose para a sua região de abrangência. Conclusões: Os indicadores hospitalares e o perfil epidemiológico dos pacientes diagnosticados sugerem a necessidade de melhor organização da assistência à tuberculose na unidade e na sua região de referência e demonstraram a necessidade de definição rigorosa das medidas de biossegurança no hospital. / Background: Over the last decades the demand for higher complexity services for tuberculosis care has increased, especially in general and university hospitals. In these services, despite the fact that it is regarded as an occupational disease, often there is no systematic evaluation of the magnitude of the local exposure. Objective: To describe and analyze the epidemiological profile of tuberculosis-disease among the patients attended at HUAP, and to elaborate a monitoring proposal for measuring the disease. Methods: descriptive and retrospective study of the dignosed cases among patients attended at the HUAP-UFF for the 2000-2006 period, construction of morbidity and case-fatality and multivariate analysis of the deaths occurred among the admitted patients. Results: The tuberculosis diagnosis were made for 763 patients, 45.1% at the outpatient care, 11.1% at the emergency room and 43.8% at the admission sector; 63.1% were male, with male/female ratio of 1.8; the most affected age group was 30 to 69 years. Among the admitted patients it was observed that positive and negative pulmonary cases, associated to extra-pulmonary, and the exclusive negative pulmonary cases, were the most diagnosed. For the patients that evolved to death the pulmonary type was the most frequent as well. The treatment was started for 41.9% of the total cases and in 76% of the admitted patients. Among those who started treatment, 82.5% adopted the Scheme I. The presence of co-morbidity was more prevalent among the admitted patients and those who evolved to death. HUAP plays the role of an unofficial reference for tuberculosis in its region. Conclusions: The hospital indicators and the epidemiological profile of the diagnosed patients suggest the need for a better organization of tuberculosis care in the setting as well as its reference region and they show the need for a rigorous definition of the biosafety measures at the hospital.

Depuis janvier 2001, nous travaillons au Programme national de Lutte contre la tuberculose du Burkina Faso en tant que son coordonnateur. Nous avons jugé utile d’analyser la détection des cas de tuberculose et leurs résultats de traitement après quelques années de mise en œuvre de ce Programme. Le constat de la faiblesse de nos résultats et la recherche de solution de leur amélioration nous a conduits à mettre en œuvre une recherche sur la base de l’hypothèse suivante.<p><p>Hypothèse<p>Le présent travail repose sur l’hypothèse qu’une organisation de la lutte contre la tuberculose prenant en compte les préoccupations et les propositions des acteurs (tuberculeux, membres de leurs familles, professionnels de santé, guérisseurs traditionnels, et membres des comité de gestion des services de santé) peut contribuer à améliorer les résultats du programme National Tuberculose (Détection des cas ;Taux de succès au traitement) et (Meilleure adhésion des professionnels de santé, des patients et de leur proches aux stratégies de prise en charge des malades tuberculeux). <p><p>Éléments de méthodologie <p>Figure 1 :Schématisation de notre travail<p>Les travaux ont été réalisés au Burkina Faso. La pauvreté et les conditions de vies difficiles (logement, nutrition, climat chaux et sec) favorisent l’installation de la tuberculose.<p>Dans le cadre de l’analyse de base de la lutte antituberculeuse avant l’intervention nous avons réalisé deux études:<p>• Une enquête rétrospective dans six districts sur la période du 1er janvier au 31 décembre 2001. Cette étude visait à identifier les difficultés du système de santé à diagnostiquer et mettre sous traitement les malades atteints de tuberculose.<p>• Une étude rétrospective de cohortes. Elle a couvert la période 1995- 2003. Cette étude a porté sur le suivi du traitement des tuberculeux pendant 9 ans de mise en œuvre du Programme National de lutte contre la Tuberculose au Burkina Faso.<p>Dans le cadre de notre intervention nous avons réalisé quatre études :<p>• Une étude qualitative :vingt-huit groupes focalisés et 68 entrevues approfondies avec (des patients tuberculeux, des représentants de la communauté, des membres du comité de gestion du centre de santé, des guérisseurs traditionnels et des professionnels de la santé) pour savoir leurs perceptions de la stratégie de prise en charge des cas de tuberculose appliquée par le Programme National de lutte contre la Tuberculose.<p>• Trois études descriptives à visée analytique en vue d’évaluer les résultats de deux ans d’intervention (Les résultats de la décentralisation de la prise en charge des tuberculeux de l’hôpital de district vers le centre de santé périphérique. Les effets de l’intervention sur les étapes de la détection des cas de tuberculose. Et la contribution des guérisseurs traditionnels au contrôle de la tuberculose au Burkina Faso).<p>• Nous avons fait une analyse de situation deux ans après la fin de l’intervention pour voir ce qu’il reste du processus et des résultats dans les districts d’intervention et aussi ce qui se passait dans les districts témoins.<p><p>Principaux résultats de ces études :<p>Avant intervention<p>• La première étude dans le cadre de l’analyse de base de la lutte antituberculeuse au Burkina Faso a montré que le niveau de dépistage des cas de tuberculose pulmonaire à microscopie positive est faible, du fait de la déperdition des cas dans chacune des étapes qui conduisent au diagnostic de la tuberculose. Le dépistage est dépendant de l’efficacité opérationnelle des personnels des services de santé, ainsi que du recourt au CDT (centre de diagnostic et de traitement de la tuberculose) par les patients suspects référés.<p>• La deuxième étude a analysé neuf ans de suivi des tuberculeux par le programme national de lutte contre la tuberculose et a trouvé que le taux de négativation des examens de crachats de contrôle du deuxième mois de traitement a baissé de façon régulière depuis 1997. Cela pourrait être du à certaines caractéristiques des patients telles que des affections associées ou surtout à un traitement incorrect (irrégularité dans la prise des médicaments, doses insuffisantes, apparition de résistances ?)<p><p>Les résultats de l’intervention<p>• L’intervention a commencé par l’étude de l’accessibilité et de l’adhésion au traitement de la tuberculose. Elle révèle que les patients tuberculeux expérimentent trois groupes interdépendants de difficultés pour terminer avec succès leur traitement (difficultés pour arriver au centre de santé, difficultés pour aller régulièrement au centre de traitement, difficultés à l’intérieur du centre de santé). Ces difficultés sont compliquées par des facteurs d’accessibilité géographique, de pauvreté et de genre.<p>La mise en œuvre pendant deux ans du paquet d’activités défini de façon consensuel par les acteurs (Patients tuberculeux, professionnels de santé, guérisseurs traditionnels, membres de la communauté) a apporté plusieurs résultats :<p>• Pendant les premiers ateliers qui réunissaient les représentants des malades, des professionnels de santé et des guérisseurs traditionnels, les échanges étaient quasiment impossibles. Les malades ne voulaient pas s’exprimer devant les professionnels de santé, les guérisseurs traditionnels se méfiaient des professionnels de santé et ceux-ci monopolisaient la parole comme s'ils étaient les détenteurs de tout le savoir. A partir du quatrième atelier, les échanges sont devenus vraiment interactifs et chaque type de participant disait vraiment ce qu’il pensait et abordait tous les sujets de la réunion sans se faire d’auto censure). <p>• L’identification des tousseurs et des tousseurs chroniques parmi les patients adultes de la consultation générale s’est améliorée (respectivement de 10,6% à 14% et de 1,1% à 1,8%). La référence des patients suspects de tuberculose vers le laboratoire pour les examens de crachats s’est aussi améliorée (de 66% à 78,3%). Cependant notre étude a mis en exergue un problème important et à résoudre qui est la faible accessibilité du laboratoire pour les patients suspects de tuberculose). <p>• En milieu rural plus de 46% des patients suspects ont opté pour la collecte de crachats sur place plutôt que de se rendre au laboratoire de l’hôpital pour les examens de crachats. La détection des cas de tuberculose a augmenté de (14 cas pour 100.000 habitants à 15) dans les districts témoins contre une augmentation de (14 cas pour 100.000 habitants à 26) pour les districts d’intervention. Nous n’avons pas noté de différence significative entre les taux de succès de traitement en comparant les districts d’intervention avec les districts témoins. <p>• Les associations des guérisseurs traditionnels ont identifié 248 patients suspects de tuberculose dont 44 (17,74%) ont été confirmés positifs. Ils ont ramené 87 malades absents au traitement. Justifiant ainsi de l’utilité de leur implication).<p><p>Nous avons fait une sortie de collecte de données et d’analyse de la situation dans les districts sites d’intervention en août 2008, soit plus de deux ans après la fin de l’intervention pour savoir ce qu’il en restait :<p><p>• La décentralisation de la prise en charge des cas de tuberculose de l’hôpital de district vers les centres de santé périphériques est reprise dans les plans d’action des districts concernés. <p>• Nous avons constaté que les outils de gestions des cas (fiche et carte de traitement du CSPS du tuberculeux, bulletin d’examen de crachats, fiche de rapport d’activités tuberculose du CSPS, registre transitoire de la tuberculose du CSPS) sont toujours là et utilisés par les professionnels de santé. <p>• Les associations d’anciens malades sont encore là. Elles tiennent leurs réunions périodiques même si elles sont irrégulières. <p>• Les associations de guérisseurs traditionnels mènent encore des activités de référence de patients suspects de tuberculose aux centres de santé dans le district de Gorom. <p>• La supervision croisée ne se fait plus entre les trois districts d’intervention. Elle a été jugée difficile à organiser par insuffisance de ressources humaines et matérielles selon les médecins chefs de district. <p>• Au Burkina Faso les directions régionales de la santé et les districts ont une certaine autonomie pour le choix des activités à inclure dans les plans d’action annuels. Dès 2006 les districts témoins ont planifié les activités suivantes (décentralisation de la collecte des crachats et du traitement des tuberculeux, implication des associations à base communautaire, utilisation des outils de gestion de la tuberculose dans les centres de santé périphériques. Ils ont aussi utilisé le module de formations des professionnels de santé de l’intervention dès 2006). La détection des cas de tuberculose était de 26 cas pour 100.000 habitants dans les districts sites de l’intervention contre 15 cas pour 100.000 habitants pour les témoins en fin de l’intervention. Deux ans environ après l’intervention, la détection est devenue 24,5 cas pour 100.000 habitants dans les districts d’intervention contre 23,9 cas pour 100.000 habitants dans les districts témoins pour une moyenne nationale de 20,5 cas. Le taux de succès au traitement était de 75% dans les districts témoins et de 74,3% dans les districts d’intervention pour une moyenne nationale de 72,8%.<p><p>Conclusion générale<p>Pour finir on peut dire que les éléments du paquet d’activités qui sont restés deux ans après la fin de l’intervention méritent d’être repris, organisés et intégrés dans la démarche de prise en charge des malades tuberculeux dans le Programme National de Lutte contre la Tuberculose. <p>Ce qui a manqué le plus, deux ans après l’intervention c’est la supervision des acteurs par une équipe de santé technique compétente et à effectif suffisant.<p>La tuberculose est une maladie et la prise en charge des cas est une activité d’abord médicale. Les activités peuvent être renforcées et les résultats améliorés par une collaboration de divers acteurs autour de l’équipe de santé. Le registre de la tuberculose du centre de santé qui se situe à l’hôpital de district doit rester la pièce principale du processus de prise en charge des malades tuberculeux. C’est dans ce registre que toutes les données de tous les tuberculeux pris en charge dans le district doivent figurer. L’équipe médicale responsable de ce registre est responsable du devenir de tous les patients tuberculeux dans le district. La décentralisation de la prise en charge des cas de l’hôpital de district vers le centre de santé périphérique implique des devoirs de l’équipe médicale du CDT à l’endroit des prestataires de soins des CSPS. A ce titre l’équipe médicale du CDT doit superviser et aider les CSPS dans une mise en œuvre efficace des taches qui leurs sont confiées. <p>Les membres organisés de la communauté peuvent apporter beaucoup dans l’information de la population sur la tuberculose, à condition que les contenus des messages soient élaborés sur une base d’informations techniques médicales vraies. La visite à domicile et l’accompagnement des malades graves par les associations seront utiles quand ils seront faits dans une synergie et une complémentarité de l’équipe médicale responsable du registre de la tuberculose. L’identification de plus de patients suspects de tuberculose et leur orientation vers les centres de santé par les associations n’aura de résultats que quand il existera un dispositif efficace de réponse dans le centre de santé ( laboratoires équipés animés par des techniciens de laboratoires motivés, compétents, en nombre suffisant et régulièrement supervisés par des superviseurs eux même compétents) ;(prestataires de soins formés à l’écoute des patients, motivés et supervisés régulièrement par des superviseurs compétents).<p>Notre étude nous enseigne qu’il est utile de prendre le temps nécessaire d’avoir les propositions des acteurs pour élaborer des stratégies qui rencontreront le plus possible leur adhésion. Notre étude nous enseigne aussi que plus il y a d’acteurs plus nous devons mettre en place des efforts de suivi, de supervision et d’accompagnement. <p>Le renforcement du système de santé (agents de santé compétents, motivés, équipés, supervisés et en nombre suffisant) est nécessaire pour la pérennisation de toute initiative et résultats de santé.<p><p>Since January in 2001, I am the National Tuberculosis Programme Manager in Burkina Faso. I thought it would be helpful to analyze TB cases detection and the outcomes of their treatment after a few years of tuberculosis control. Because of low results and looking how to improve them we made a research with the following hypothesis.<p><p>Hypothesis<p>This research is based on the hypothesis that organizing tuberculosis control buy taking into consideration the concerns and the propositions of the stakeholders (TB patients, members of their family, health workers, traditional healers, and members of the health centre Management committee) we can contribute to improving the results of the National Tuberculosis Control Programme (TB cases detection, treatment success) and (good adherence of health workers ,TB patients and their relatives to the strategies of health care to tuberculosis patients). <p><p>Figure 1 :Our work plan<p>The research was conducted in Burkina Faso. Poverty and difficult living conditions (accommodation, nutrition, hot and dry climate) are favorable for the spread of tuberculosis<p>As part of the basic analysis of tuberculosis control before the intervention, we carried out two researches:<p>• A retrospective research in six districts between 1st January and 31st December 2001. This research was aimed at analyzing the health system capacity to diagnose and to put patients infected with tuberculosis on treatment.<p>• A retrospective study of groups. It covered the period 1995- 2003. This study bordered on monitoring the treatment during the 9 years of implementation of the National Tuberculosis Control Programme in Burkina Faso.<p><p>As part of our intervention we carried out four studies:<p>• A qualitative study :twenty eight focused groups and 68 detailed discussions sessions with (tuberculosis patients, representatives of the community, members of the Health Centre Management Committee, traditional healers and health professionals) to sample their views on the tuberculosis treatment strategy applied by the National Tuberculosis Control Programme.<p>• Three analytic and descriptive studies, to evaluate the results of the two years of intervention. (Results of decentralisation of tuberculosis care, from district hospital to peripheral health centre’s. The effects of the intervention on the stages of detection of tuberculosis cases. And the contribution of traditional healers to tuberculosis control in Burkina Faso).<p>• We also looked for what was remaining from the process and the results of the intervention two years after the end of the intervention in the intervention district and what was happing in the witness districts.<p><p>Principal results of these studies <p>Before intervention<p>• The first study into the basic analysis of tuberculosis control in Burkina Faso showed that there is a low rate of positive microscopic pulmonary tuberculosis, because of losses in cases in each of the stages leading to the diagnosis of tuberculosis. Cases detection is dependent on the operational efficiency of health services staff, as well as the using of the CDT (Tuberculosis diagnosis and treatment centre’s) by the suspected tuberculosis patients.<p>• The second study before intervention which analyzed nine years of tuberculosis control by the National Tuberculosis Control Programme, discovered that the rate of negativation at the 2 month follow- up sputum examination has fallen steadily since 1997. This could be due to certain characteristics of patients due to an incorrect treatment (irregularity in taking medicines, insufficient dosages, and appearance of resistance?).<p><p>Results of the Intervention <p>• The intervention began with a study of accessibility and adherence to treatment of tuberculosis. It reveals that Tuberculosis patients experiment with three interdependent groups of difficulties for a successful treatment (difficulty in arriving at health centre’s, difficulties in regularly visiting treatment centre’s, difficulties within the health centre). These difficulties are further compounded by geographical accessibility factors, poverty and gender. <p>The two years of implementation of the packet of activities collectively defined by stakeholders (Tuberculosis patients, health services providers, and community members) has yield a lot of results: <p>• During the earlier workshops which brought together representatives of the patients, health services providers and traditional healers, deliberations were almost impossible. Patients did not want to talk in front of health service providers, traditional healer’s mistrusted health services providers and the latter monopolised all discussions, as if they were the only repository of all knowledge. From the fourth workshop however, discussions became really interactive and each type of participant expressed his thought and tackled all topics at the meeting without any ill-feeling. <p>• Identification of coughers and chronic coughers among adult patients of general consultation improved (respectively from 10.6% to 14% and from 1.1% to 1.8%). Reference of suspected tuberculosis patients to laboratories for sputum smear examination also improved (from 66% to 78.3%). However, our study highlighted an important problem which needs immediate solution. This problem is the low utilization of laboratories by suspected tuberculosis patients. <p>• In the rural areas more than 46% of suspected patients opted for the collection of sputum samples on the spot instead of going to the hospital laboratory for the sputum smear examination. Detection of tuberculosis cases increased from (14 cases per 100 000 inhabitants to 15) in pilot districts and it increase from (14 cases per 100 000 inhabitants to 26) in intervention districts. There was no significant difference between the two successful treatment rates, when we compared the intervention districts with the pilot districts. <p>• Traditional healers associations identified 248 suspected tuberculosis patients, out of whom 44 (17. 74%) were confirmed positive. They brought 87 absentee patients for treatment, thereby justifying the usefulness of their involvement.<p>We made the analysis of the situation in the intervention districts in august 2008, two years after the end of the intervention in order to know what was remaining:<p>• The decentralization of taking care of TB cases from the district hospital to the peripheral health center was written in the concerned districts year planning.<p>• We have noticed that the tools of cases management (CSPS therapy form and card of the TB patients, expectorations exams bulletin, CSPS TB activities report form, transitory register of the CSPS TB) are still there and used by the health care providers of this level.<p>• Associations of TB patients still exist. They hold their periodic meeting even if it is not regular.<p>• Associations of traditional healers are still holding activities to send patients suspected of TB to health center in the district of Gorom.<p>• Crossed supervision is not more done between the three districts of intervention. It has been judged difficult to organize because of insufficient human resources and material according to the chief’s doctors of the district.<p>• At the end of the intervention detection of TB cases was of 26 cases for 100 000 inhabitants in the districts of intervention against 15 cases for 100 000 inhabitants for the witnesses. Almost two years after the intervention the detection became 24, 5 cases for 100 000 inhabitants in the intervention district against 23, 9 case for 100 000 inhabitants in the witness districts. The significant difference that was existing between witnesses and intervention districts disappeared two years after the intervention. <p><p>General conclusion<p>As conclusion we can say that elements of activities that remained two years after the end of intervention are good to be taken, organized and integrated in the National Tuberculosis Program approach of taking care of TB Patients.<p>What lacked the most, two years after the intervention is the supervision of the stakeholders’ by a competent health technical team.<p>TB is a disease and taking care of the cases is first a medical activity. Activities can be reinforced and the results improved by a collaboration of various stakeholders around the health team. TB register of the health center that is located at the district hospital must remain the key piece of the TB patients managing process. It is in this register that all the data of all the TB patients cared in the district must be. The medical team responsible of this register is responsible of the becoming of all the TB patients in the district. The decentralization of taking care of TB cases from the district hospital to the peripheral health centers implies duties of the CDT medical team towards CSPS’ health care providers. Because of that the CDT medical team must monitor and help CSPS in the efficient implementation of the tasks assigned to them.<p>Members of organized community can bring a lot in the information of the population on TB, at the condition that the contents of messages are elaborated on a base of true technical medical information. Home visit and support to the patient seriously sick by the association will be useful when they will be done in a synergy and complementarily of the medical team responsible for the TB register. Identification of more patients suspected of TB and their orientation to health centers by the associations will only have results when there will be an efficient response in the health system (equipped laboratories animated by motivated, competent, and regularly monitored laboratories technicians by monitors who are also competent); (health care providers trained to listen to the patients, motivated and regularly monitored by competent monitors).<p>Our study teaches us how useful it is to take necessary time to have stakeholders’ proposals in order to elaborate strategies that will meet the most their adhesion. Our study teaches us also that the more there are players the more we must put in place follow up, monitoring and support efforts,<p>The building of a strong health system (competent, motivated, equipped, monitored health staffs) is necessary for the durability of all health initiative and results. / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

Tuberculosis (TB) has become a serious South African health problem because it is the most common opportunistic disease that leads to death in people with HIV/AIDS. Due to the airborne nature of the disease it can easily be spread to anyone including healthy people. A lack of compliance to treatment by TB patients explains why prevalence rates of the disease are high and why there is an emergence of drug resistant strains such as XDR-TB and MDR-TB. Information on existing knowledge, attitudes and perceptions regarding TB can provide a crucial foundation for the development of educational programmes and interventions aimed at reducing the further spread of the disease. This study aimed at understanding the knowledge, attitudes and perceptions towards TB and relating these to the current prevalence of HIV/AIDS. A face-to-face interview survey was conducted among adult Grahamstown East residents (n=1020). The Health Belief Model (Rosenstock et al., 1994) and Bandura’s (1986) Social Cognitive Theory formed the theoretical framework of the data collection and analysis. The data generated from the field work was first descriptively analysed providing frequency tables. Thereafter cross tabulations were calculated for relevant items using independent variables, namely gender, level of education, and experience of dealing with TB. The results of the study show that, in general, knowledge concerning TB was sufficient to provide a foundation for the adoption of healthier behaviours in the female respondents. Few of the respondents reported feeling personally susceptible although the majority of the respondents acknowledged the severity of the disease. The cues to action lacked the influence to persuade people to adopt positive health related behaviours. The perceived benefits of adopting preventative behaviour were not very influential in the adoption of healthier behavioural changes in the respondents. Disease stigma regarding the dual association of TB and HIV/AIDS was the main barrier for the adoption of healthier behavioural attitudes. Perceived self-efficacy in preventative behaviours was generally low in the less educated respondents. Recommendations regarding areas for future research and change interventions are provided.

Health economists, national decision-makers and global health specialists have been interested in calculating the cost of a disease for many years. Only more recently they started to generate more comprehensive frameworks and tools to estimate the full range of healthcare related costs of illness in a user’s perspective in resource-poor settings. There is now an ongoing trend to guide health policy, and identify the most effective ways to achieve universal health coverage. The user fee exemptions health financing schemes, which grounded the tuberculosis control strategy, have been designed to improve access to essential care for ill individuals with a low capacity to pay. After decades of functioning and substantial progress in tuberculosis detection rate and treatment success, this thesis analyses the extent of the coverage (financial and social protection) of two disease control programs in West Africa. Learning from the concept of the medical poverty trap (Whitehead, Dahlgren, et Evans 2001) and available framework related to the economic consequences of illness (McIntyre et al. 2006), a conceptual framework and a data collection tool have been developed to incorporate the direct, indirect and intangible costs and consequences of illness incurred by chronic patients. In several ways, we have sought to provide baseline for comprehensive analysis and standardized methodology to allow comparison across settings, and to contribute to the development of evidence-based knowledge.<p><p>To begin, filling a knowledge gap (Russell 2004), we have performed microeconomic research on the households’ costs-and-consequences-of-tuberculosis in Burkina Faso and Benin. The two case studies have been conducted both in rural and urban resource-poor settings between 2007 and 2009. This thesis provides new empirical findings on the remaining financial, social and ‘healthcare delivery related organizational’ barriers to access diagnosis and treatment services that are delivered free-of-charge to the population. The direct costs associated with illness incurred by the tuberculosis pulmonary smear-positive patients have constituted a severe economic burden for these households living in permanent budget constraints. Most of these people have spent catastrophic health expenditure to cure tuberculosis and, at the same time, have faced income loss caused by the care-seeking. To cope with the substantial direct and indirect costs of tuberculosis, the patients have shipped their families in impoverishing strategies to mobilize funds for health such as depleting savings, being indebted and even selling livestock and property. Damaging asset portfolios of the disease-affected households on the long run, the coping strategies result in a public health threat. In resource-poor settings, the lack of financial protection for health may impose inability to meet basic needs such as the rights to education, housing, food, social capital and access to primary healthcare. Special feature of our work lies in the breakdown of the information gathered. We have been able to demonstrate significant differences in the volume and nature of the amounts spent across the successive stages of the care-seeking pathway. Notably, pre-diagnosis spending has been proved critical both in the rural and urban contexts. Moreover, disaggregated cost data across income quintiles have highlighted inequities in relation to the direct costs and to the risk of incurring catastrophic health expenditure because of tuberculosis. As part of the case studies, the tuberculosis control strategies have failed to protect the most vulnerable care users from delayed diagnosis and treatment, from important spending even during treatment – including significant medical costs, and from hidden costs that might have been exacerbated by poor health systems. To such devastating situations, the tuberculosis patients have had to endure other difficulties; we mean intangible costs such as pain and suffering including stigmatization and social exclusion as a result of being ill or attending tuberculosis care facilities. The analysis of all the social and economic consequences for tuberculosis-affected households over the entire care-seeking pathway has been identified as an essential element of future cost-of-illness evaluations, as well as the need to conduct benefit incidence assessment to measure equity.<p><p>This work has allowed identifying a series of policy weaknesses related to the three dimensions of the universal health coverage for tuberculosis (healthcare services, population and financial protection coverage). The findings have highlighted a gap between the standard costs foreseen by the national programs and the costs in real life. This has suggested that the current strategies lack of patient-centered care, context-oriented approaches and systemic vision resulting in a quality issue in healthcare delivery system (e.g. hidden healthcare related costs). Besides, various adverse effects on households have been raised as potential consequences of illness; such as illness poverty trap, social stigma, possible exclusion from services and participation, and overburdened individuals. These effects have disclosed the lack of social protection at the country level and call for the inclusion of tuberculosis patients in national social schemes. A last policy gap refers to the lack of financial protection and remaining inequities with regards to catastrophic health expenditure still occurring under use fee exemptions strategies. Thereby, one year before 2015 – the deadline set for the Millennium Development Goals – it is a matter of priority for Benin and Burkina Faso and many other countries to tackle adverse effects of the remaining social, economic and health policy and system related barriers to tuberculosis control. These factors have led us to emphasize the need for countries to develop sustainable knowledge. <p><p>National decision-makers urgently need to document the failures and bottlenecks. Drawing on the findings, we have considered different ways to strengthen local capacity and generate bottom-up decision-making. To get there, we have shaped a decision framework intended to produce local evidence on the root causes of the lack of policy responsiveness, synthesize available evidence, develop data-driven policies, and translate them into actions.<p><p>Beyond this, we have demonstrated that controlling tuberculosis was much more complex than providing free services. The socio-economic context in which people affected by this disease live cannot be dissociated from health policy. The implications of microeconomic research on the households’ costs and responses to tuberculosis may have a larger scope than informing implementation and adaptation of national disease-specific strategies. They can be of great interest to support the definition of guiding principles for further research on social protection schemes, and to produce evidence-based targets and indicators for the reduction and the monitoring of economic burden of illness. In this thesis, we have build on prevailing debates in the field and formulated different assumptions and proposals to inform the WHO Global Strategy and Targets for Tuberculosis Prevention, Care and Control After 2015. For us, to reflect poor populations’ needs and experiences, global stakeholders should endorse bottom-up and systemic policy-making approaches towards sustainable people-centered health systems.<p><p>The findings of the thesis and the various global and national challenges that have emerged from case studies are crucial as the problems we have seen for tuberculosis in West Africa are not limited to this illness, and far outweigh the geographical context of developing countries.<p><p><p>Keywords: Catastrophic health expenditure, Coping strategies, Cost-of-illness studies, Direct, indirect and intangible costs, Evidence-based Public health, Financial and Social protection for health, Health Economics, Health Policy and Systems, Informed Decision-making, Knowledge translation, People-centered policy-making, Systemic approach, Universal Health Coverage<p> / Doctorat en Sciences de la santé publique / info:eu-repo/semantics/nonPublished

Introduction: Despite being one of the most preventable diseases, TB still remains a serious and largely neglected disease. Nurses as compared to the general population are at greater risk of acquiring nosocomial TB. This study was conducted to describe the perceptions of nurses on the underlying contributory factors that may lead to the spread of TB in the clinics treating TB patients. Methods: Quantitative, non – experimental, descriptive, exploratory and cross sectional design was used. A structured and pretested questionnaire was used. Findings: The key contributory factors identified were insufficient TB training for staff and lack of knowledge on the TB legislative framework and TB policy directives. Conclusion: The findings indicate the need for a comprehensive TB infection prevention and control policy, with associated standards for provision and practice. / Health Studies / M.A. (Public Health)