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A BRT Corridor Through Stockholm’s Inner-city : Assessing the Operational Impacts of a BRT Corridor Along Bus Line 4 Using Microscopic SimulationCARON MALUCELLI, FRANCISCO January 2020 (has links)
Bus Rapid Transit (BRT) corridors and systems have emerged in the past three decades as affordablesolutions of medium capacity public transport services to highly urbanized areas, especially in LatinAmerica and Asia. In Stockholm, trunk bus lines have gained priority over mixed traffic over the yearsthrough exclusive bus lanes, signal priority, and reliability control, for example, but no complete BRTsolution has been implemented yet. Among the inner-city trunk lines, Line 4 is the most demanded witharound 70,000 passengers boarding the service daily. This thesis proposes, then, to assess theoperational impacts that BRT solutions as segregate median lanes, stations with off-board farecollection and platform level boarding and alighting through all bus doors, full signal priority andheadway control strategy, would have in bus Line 4, using a microscopic simulation approach. Twoscenarios were simulated, and the results compared to the existing conditions (Base Scenario).Scenario 1 considered a 5-minute headway service and Scenario 2, 3-minute headways. Overall, theproposed scenarios reduce travel times by 37.6-49.1%, increase average operational speeds (includingdwell times) by 60.4-96.6%, decrease dwell times by 57.9-65.6%, decrease delays by 18.4-36%,decrease vehicle occupancy rates by 3.5-44.9% and improve the Coefficient of Variation of theheadways from 0.83-0.85 in the Base Scenario to 0.1 in Scenario 1 and 0.2 in Scenario 2. As a resultof the reduction in travel times, a BRT service would need 13 buses to operate a 5-minute headwayand 21 buses for a 3-minute headway, against 27 vehicles that are used currently for a 4 to 6-minuteheadway during peak hour.
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Diffusion in nanopores recorded by microscopic measuring techniquesChmelik, C., Freude, D., Haase, J., Hwang, S., Kärger, J., Valiullin, R. 05 March 2020 (has links)
The poster presents two measuring techniques which, by their very nature, can be focused on,
exclusively, microscopic dimensions, including the interior of the individual particles (crystallites) of
the material under study. Correspondingly, they are referred to as “microscopic measuring techniques”.
The examples presented refer, in particular, to the potentials of these techniques for investigating mass
transfer in complex systems.
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Numerical Methods for the Microscopic Cardiac Electrophysiology ModelFokoué, Diane 26 September 2022 (has links)
The electrical activity of the heart is a well studied process. Mathematical modeling and computer simulations are used to study the cardiac electrical activity: several mathematical models exist, among them the microscopic model, which is based on the explicit representation of individual cells. The cardiac tissue is viewed as two separate domains: the intra-cellular and extra-cellular domains, Ωᵢ and Ωₑ, respectively, separated by cellular membranes Γ. The microscopic model consists of a set of Poisson equations, one for each sub-domain, Ωᵢ and Ωₑ, coupled on interfaces Γ with nonlinear transmission conditions involving a system of ODEs. The unusual transmission conditions on Γ make the model challenging to solve numerically.
In this thesis, we first focus on the dimensional analysis of the microscopic model. We then reformulate the problem on the interface Γ using a Steklov-Poincaré operator. We discretize the model in space using finite element methods. We prove the existence of a semi-discrete solution using a reformulation of the model as an ODE system on the interface Γ. We derive stability and error estimates for the finite element method. Afterwards, we consider five numerical schemes including the Godunov splitting method, two implicit methods, (Backward Euler (BE) and second order Backward Differentiation Formula (BDF2)), and two semi-implicit methods (Forward Backward Euler (FBE), and second order Semi-implicit Backward Differentiation Formula (SBDF2)). A convergence analysis of the implicit and semi-implicit methods is performed and the results are compared with manufactured solutions that we have proposed. Numerical results are presented to compare the stability, accuracy and efficiency of the methods. CPU times needed to solve the problem over a single cell using FBE, SBDF2 and Godunov splitting methods are reported. The results show that FBE and Godunov splitting methods achieve better numerical accuracy and efficiency than implicit and SBDF2 schemes, for a given computational time.
Finally, we solve the model using FBE and Domain Decomposition Method (DDM) for two cells connected to each other by a gap junction. We investigate the influence of the space discretization and we explore the differences between a conforming and nonconforming mesh on Γ. We compare the solutions obtained with both FBE and DDM methods. The results show that both methods give the same solution. Therefore, the DDM is capable of providing an accurate solution with a minimal number of sub-domain iterations.
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A Real-Time Computer Vision Based Framework For Urban Traffic Safety Assessment and Driver Behavior Modeling Using Virtual Traffic LanesAbdelhalim, Awad Tarig 07 October 2021 (has links)
Vehicle recognition and trajectory tracking plays an integral role in many aspects of Intelligent Transportation Systems (ITS) applications; from behavioral modeling and car-following analyses to congestion prevention, crash prediction, dynamic signal timing, and active traffic management. This dissertation aims to improve the tasks of multi-object detection and tracking (MOT) as it pertains to urban traffic by utilizing the domain knowledge of traffic flow then utilize this improvement for applications in real-time traffic performance assessment, safety evaluation, and driver behavior modeling. First, the author proposes an ad-hoc framework for real-time turn count and trajectory reconstruction for vehicles passing through urban intersections. This framework introduces the concept of virtual traffic lanes representing the eight standard National Electrical Manufacturers Association (NEMA) movements within an intersection as spatio-temporal clusters utilized for movement classification and vehicle re-identification. The proposed framework runs as an additional layer to any multi-object tracker with minimal additional computation. The results obtained for a case study and on the AI City benchmark dataset indicate the high ability of the proposed framework in obtaining reliable turn count, speed estimates, and efficiently resolving the vehicle identity switches which occur within the intersection due to detection errors and occlusion. The author then proposes the utilization of the high accuracy and granularity trajectories obtained from video inference to develop a real-time safety-based driver behavior model, which managed to effectively capture the observed driving behavior in the site of study. Finally, the developed model was implemented as an external driver model in VISSIM and managed to reproduce the observed behavior and safety conflicts in simulation, providing an effective decision-support tool to identify appropriate safety interventions that would mitigate those conflicts. The work presented in this dissertation provides an efficient end-to-end framework and blueprint for trajectory extraction from road-side traffic video data, driver behavior modeling, and their applications for real-time traffic performance and safety assessment, as well as improved modeling of safety interventions via microscopic simulation. / Doctor of Philosophy / Traffic crashes are one of the leading causes of death in the world, averaging over 3,000 deaths per day according to the World Health Organization. In the United States alone, there are around 40,000 traffic fatalities annually. Approximately, 21.5% of all traffic fatalities occur due to intersection-related crashes. Intelligent Transportation Systems (ITS) is a field of traffic engineering that aims to transform traffic systems to make safer, more coordinated, and 'smarter' use of transport networks. Vehicle recognition and trajectory tracking, the process of identifying a specific vehicle's movement through time and space, plays an integral role in many aspects of ITS applications; from understanding how people drive and modeling that behavior, to congestion prevention, on-board crash avoidance systems, adaptive signal timing, and active traffic management. This dissertation aims to bridge the gaps in the application of ITS, computer vision, and traffic flow theory and create tools that will aid in evaluating and proactively addressing traffic safety concerns at urban intersections. The author presents an efficient, real-time framework for extracting reliable vehicle trajectories from roadside cameras, then proposes a safety-based driving behavior model that succeeds in capturing the observed driving behavior. This work is concluded by implementing this model in simulation software to replicate the existing safety concerns for an area of study, allowing practitioners to accurately model the existing safety conflicts and evaluate the different operation and safety interventions that would best mitigate them to proactively prevent crashes.
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Optimal Evacuation Plans for Network Flows over Time Considering CongestionChamberlayne, Edward Pye 24 June 2011 (has links)
This dissertation seeks to advance the modeling of network flows over time for the purposes of improving evacuation planning. The devastation created by Hurricanes Katrina and Rita along the Gulf Coast of the United States in 2005 have recently emphasized the need to improve evacuation modeling and planning. The lessons learned from these events, and similar past emergencies, have highlighted the problem of congestion on the interstate and freeways during an evacuation. The intent of this research is to develop evacuation demand management strategies that can reduce congestion, delay, and ultimately save lives during regional evacuations. The primary focus of this research will concern short-notice evacuations, such as hurricane evacuations, conducted by automobiles. Additionally, this dissertation addresses some traffic flow and optimization deficiencies concerning the modeling of congested network flows.
This dissertation is a compilation of three manuscripts. Chapters 3 and 4 examine modeling network flows over time with congestion. Chapter 3 demonstrates the effects of congestion on flows using a microscopic traffic simulation software package, INTEGRATION. The flow reductions from the simulation are consistent with those found in several empirical studies. The simulation allows for the examination of the various contributing factors to the flow reductions caused by congestion, including level of demand, roadway geometry and capacity, vehicle dynamics, traffic stream composition, and lane changing behavior. Chapter 4 addresses some of the modeling and implementation issues encountered in evacuation planning and presents an improved modeling framework that reduces network flows due to congestion. The framework uses a cell-based linear traffic flow model within a mixed integer linear program (MILP) to model network flows over time in order to produce sets of decisions for use within an evacuation plan. The traffic flow model is an improvement based upon the Cell Transmission Model (CTM) introduced in Daganzo (1994) and Daganzo (1995) by reducing network flows due to congestion. The flow reductions are calibrated according to the traffic simulation studies conducted in Chapter 3. The MILP is based upon the linear program developed in Ziliaskopoulos (2000); however, it eliminates the "traffic holding" phenomenon where it cannot be implemented realistically within a transportation network. This phenomenon is commonly found in mathematical programs used for dynamic traffic assignment where the traffic is unrealistically held back in order to determine an optimum solution. Lastly, we propose additional constraints for the MILP that improve the computational performance by over 90%. These constraints exploit the relation of the binary variables based on the network topology. Chapter 5 applies the improved modeling framework developed in Chapter 4 to implement a demand management strategy called group-level staging -- the practice of evacuating different groups of evacuees at different times in order to reduce the evacuation duration. This chapter evaluates the benefits of group-level staging, as compared to the current practice of simultaneous evacuation, and explores the behavior of the modeling framework under various objective functions. / Ph. D.
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General Aviation Demand Forecasting Models and a Microscopic North Atlantic Air Traffic Simulation ModelLi, Tao 06 January 2015 (has links)
This thesis is focused on two topics. The first topic is the General Aviation (GA) demand forecasting models. The contributions to this topic are three fold: 1) we calibrated an econometric model to investigate the impact of fuel price on the utilization rate of GA piston engine aircraft, 2) we adopted a logistic model to identify the relationship between fuel price and an aircraft's probability of staying active, and 3) we developed an econometric model to forecast the airport-level itinerant and local GA operations. Our calibration results are compared with those reported in literature. Demand forecasts are made with these models and compared with those prepared by the Federal Aviation Administration. The second topic is to model the air traffic in the Organized Track System (OTS) over the North Atlantic. We developed a discrete-time event model to simulate the air traffic that uses the OTS. We proposed four new operational procedures to improve the flight operations for the OTS. Two procedures aim to improve the OTS assignments in the OTS entry area, and the other two aim to benefit flights once they are inside the OTS. The four procedures are implemented with the simulation model and their benefits are analyzed. Several implementation issues are discussed and recommendations are given. / Ph. D.
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Automatic Detection and Characterization of Parasite Eggs by Image ProcessingOstergaard, Lindsey Eubank 26 August 2013 (has links)
The accurate identification of parasites allows for the quick diagnosis and treatment of infections. Current state-of-the-art identification techniques require a trained technician to examine prepared specimens by microscope or other molecular methods. In an effort to automate the process and better facilitate the field identification of parasites, approaches are developed to utilize LabVIEW and MATLAB, which are commercially available image processing software packages, for parasite egg identification. The goal of this project is to investigate different image processing techniques and descriptors for the detection and characterization of the following parasite eggs: Ascaris lumbricoides, Taenia sp., and Paragonimus westermani. One manual approach and four automated approaches are used to locate the parasite eggs and gather parasite characterization data. The manual approach uses manual measurements of the parasite eggs within the digital images. The four automated approaches are LabVIEW Vision Assistant scripts, MATLAB separation code, MATLAB cross-section grayscale analysis, and MATLAB edge signature analysis. Forty-four separate measurements were analyzed through the four different approaches. Two types of statistical tests, single factor global Analysis of Variance (ANOVA) test and Multiple Comparison tests, are used to demonstrate that parasite eggs can be differentiated. Thirty-six of the measurements proved to be statistically significant in the differentiation of at least two of the parasite egg types. Of the thirty-six measurements, seven proved to be statistically significant in the differentiation of all three parasite egg types. These results have shown that it is feasible to develop an automated parasite egg detection and identification algorithm through image processing. The automated image processing techniques have proven successful at differentiating parasite eggs from background material. This initial research will be the foundation for future software structure, image processing techniques, and measurements that should be used for automated parasite egg detection. / Master of Science
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Grade 10 physical science students' reasoning about basic chemical phenomena at submicroscopic levelNyanhi, Musekiwa Gift 10 1900 (has links)
The study investigated South African Grade 10 Physical science learners’ reasoning about basic chemical phenomena at sub-microscopic level. The study adopted a non-experimental, exploratory and descriptive method and was principally guided by the ex-post facto research design using a concurrent embedded strategy of mixed qualitative and qualitative approach. A total of 280 grade 10 physical science learners in their intact classes and six of their teachers participated in the study. The 280 physical science learners comprised of 100 students from two top performing schools, 100 learners from two middle performing schools and the last 80 learners were drawn from two poor performing schools in Gauteng Department of Education’s Tshwane North District.
A two-tier multiple-choice paper and pencil Test of Basic Chemistry Knowledge (TBCK) based on the three levels of chemical representation of matter was administered to the 280 physical science learners in their Grade 11 first term to collect both quantitative and qualitative data. In addition to the TBCK, focus group discussions (FGDs) with learners, teacher interviews and document analysis were used to triangulate data.
The results revealed that most Grade 10 learners find it easy to identify pure elements and the solid state but find it difficult to negotiate between the three levels (macroscopic, sub-microscopic and symbolic) of chemical representation of matter. It became clear that learners experienced more difficulties in the concepts of basic solutions, acidic solutions, concentration and ionic compounds in solution. It also became apparent that some learners could not tell differences between a diatomic element and a compound indicating conceptual problems when they reason at particle level, and as a result they could not identify a mixture of elements. The results also indicated that the concepts of pure compounds and mixtures of compounds were not easy to comprehend as most learners took a pure compound for a mixture of atoms and a mixture of compounds for a mixture of elements. It is therefore concluded that learners find it difficult negotiating the three levels of chemical representation of matter. However, it is not clear whether the misconceptions the learners showed could be completely attributable to the concepts involved or the nature of the sub-microscopic models that were used in the test as it was also revealed that most teachers were not using sub-microscopic representations during instruction to enable learners to think at particle level. Furthermore, justifications to the multiple-choice tasks revealed lack of understanding of basic chemical concepts as well as language problems amongst learners as they could not clearly express their reasoning. Based on the results, some recommendations to educators, chemistry curriculum planners, teacher education and the chemistry education research field are suggested. / Science and Technology Education / D. Phil. ((Philosophy in Mathematics, Science and Technology Education)
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Transmission dynamics and tuberculosis control among HIV/AIDS patientsHollm-Delgado, Maria-Graciela 11 1900 (has links)
Introduction: Les efforts globaux pour contrôler la tuberculose sont présentement restreints par la prévalence croissante du VIH/SIDA. Quoique les éclosions de la tuberculose multi résistante (TB-MDR) soient fréquemment rapportées parmi les populations atteintes du
SIDA, le lien entre VIH/SIDA et le développement de résistance n’est pas clair.
Objectifs: Cette recherche visait à : (1) développer une base de connaissances concernant les
facteurs associés à des éclosions de la TB-MDR parmi les patients atteints du VIH/SIDA; (2)
utiliser ce cadre de connaissances pour accroître des mesures préliminaires pour mieux
contrôler la tuberculose pulmonaire chez les patients atteints du VIH/SIDA; et (3) afin
d’améliorer l’application des ces mesures, affiner les techniques bactériologiques existantes
pour Mycobacterium tuberculosis.
Méthodologie: Quatre études ont été réalisées : (1) Une étude longitudinale pour
identifier les facteurs associés avec une éclosion de la TB-MDR parmi les patients atteints du
SIDA qui ont reçu le traitement directement supervisé de courte durée (DOTS) pour la
tuberculose pulmonaire au Lima et au Pérou entre 1999 et 2005; (2) Une étude transversale
pour décrire différentes étapes de l’histoire naturelle de la tuberculose, la prévalence et les
facteurs associés avec la mycobactérie qu’on retrouve dans les selles des patients atteints du
SIDA; (3) Un projet pilote pour développer des stratégies de dépistage pour la tuberculose
pulmonaire parmi les patients hospitalisés atteints du SIDA, en utilisant l’essaie Microscopic
Observation Drug Susceptibility (MODS); et (4) Une étude laboratoire pour identifier les
meilleures concentrations critiques pour détecter les souches MDR de M. tuberculosis en
utilisant l’essaie MODS.
Résultats : Étude 1 démontre qu’une épidémie de TB-MDR parmi les patients atteints du
SIDA qui ont reçu DOTS pour la tuberculose pulmonaire ait été causée par la superinfection
du clone de M. tuberculosis plutôt que le développement de la résistance secondaire. Bien que ce clone ait été plus commun parmi la cohorte de patients atteints du SIDA, il n’avait
aucune différence de risque pour superinfection entre les patients avec ou sans SIDA. Ces
résultats suggèrent qu’un autre facteur, possiblement associé à la diarrhée, peu contribuer à la
prévalence élevée de ce clone chez les patients atteints du SIDA. Étude 2 suggère que chez la
plupart des patients atteints du SIDA il a été retrouvé une mycobactérie dans leurs selles
alors qu’ils étaient en phase terminale au niveau de la tuberculose pulmonaire. Or, les
patients atteints du SIDA ayant été hospitalisés pendant les deux dernières années pour une
autre condition médicale sont moins à risque de se retrouver avec une mycobactérie dans
leurs selles. Étude 3 confirme que la tuberculose pulmonaire a été commune à tous les
patients hospitalisés atteints du SIDA, mais diagnostiquée incorrectement en utilisant les
critères cliniques présentement recommandés pour la tuberculose. Or, l’essaie MODS a
détecté pour la plupart de ces cas. De plus, MODS a été également efficace quand la méthode
a été dirigée aux patients soupçonnés d’avoir la tuberculose, à cause de leurs symptômes.
Étude 4 démontre les difficultés de détecter les souches de M. tuberculosis avec une faible
résistance contre ethambutol et streptomycine en utilisant l’essai MODS avec les
concentrations de drogue présentement recommandées pour un milieu de culture. Cependant,
l’utilité diagnostique de MODS peut être améliorée ; modifier les concentrations critiques et
utiliser deux plaques et non une, pour des tests réguliers.
Conclusion: Nos études soulèvent la nécessité d’améliorer le diagnostic et le traitement de la
tuberculose parmi les patients atteints du SIDA, en particulier ceux qui vivent dans des
régions avec moins de ressources. Par ailleurs, nos résultats font ressortir les effets indirects
que les soins de santé ont sur les patients infectés par le VIH et qu’ils peuvent avoir sur le
développement de la tuberculose. / Background: Global efforts to control tuberculosis are currently being hampered by a
continuing rise in the prevalence of HIV/AIDS. Although outbreaks of multidrug resistant
tuberculosis (MDR-TB) are commonly reported among AIDS populations, the link between
HIV/AIDS and the development of drug-resistance remains unclear.
Objectives: This thesis aimed to: (1) build a knowledge foundation regarding underlying
factors associated with outbreaks of MDR-TB among HIV/AIDS patients; (2) use this
knowledge framework to develop preliminary health measures for controlling pulmonary
tuberculosis among HIV/AIDS patients; and (3) in an effort to better implement these health
measures, refine existing culture-based diagnostics for Mycobacterium tuberculosis.
Methods: Four studies were conducted: (1) a longitudinal study to identify the underlying
factors associated with an epidemic of MDR-TB among AIDS patients receiving Directly-
Observed Therapy Short-course (DOTS) for pulmonary tuberculosis in Lima, Peru between
1999 and 2005; (2) a cross-sectional study to characterize the prevalence and factors
associated with gastrointestinal shedding with mycobacteria among AIDS patients at
different stages in the natural history of tuberculosis; (3) a pilot study to develop screening
strategies for pulmonary tuberculosis among hospitalized HIV/AIDS patients using the
Microscopic Observation Drug Susceptibility (MODS) assay; and (4) a laboratory-based
study to define the optimal critical concentrations needed for detecting drug resistance in M.
tuberculosis using MODS.
Results: Study 1 revealed that an epidemic of MDR-TB among AIDS patients receiving
DOTS for pulmonary tuberculosis was due to super-infection with a specific clone of M.
tuberculosis rather than the development of secondary drug-resistance. Although this
epidemic clone was more common among patients in the AIDS cohort, risk of superinfection
did not differ between AIDS and non-AIDS patients after adjusting for baseline risk of exposure, suggesting that another factor possibly associated with diarrhea may be
contributing to the strain’s high prevalence among AIDS patients. Study 2 showed that the
majority of AIDS patients in the later stages of pulmonary tuberculosis exhibited
gastrointestinal shedding with mycobacteria. Stool shedding was rare in the absence of
pulmonary tuberculosis. AIDS patients were also less likely to shed mycobacteria if they had
been hospitalized during the previous two years for another medical condition. Study 3
confirmed that pulmonary tuberculosis was common among hospitalized AIDS patients but
frequently misdiagnosed using currently recommended diagnostic algorithms. The MODS
assay detected most cases and was equally effective when targeted to patients clinically
suspicious for tuberculosis. Study 4 demonstrated that low grade drug resistance in M.
tuberculosis to ethambutol and streptomycin was difficult to detect with MODS using
currently recommended drug-concentration standards in broth. Its diagnostic utility could be
improved by modifying drug-concentration standards, and including two versus one critical
concentration well for standardized testing.
Conclusion: Our studies underscore the need to improve the diagnosis and treatment of
tuberculosis among AIDS patients living in resource-constrained settings, all in an effort to
prevent morbidity, mortality and the transmission of drug-resistant strains. They also
highlight the indirect effect that general health care among HIV-infected patients can have on
the development of tuberculosis.
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Transmission dynamics and tuberculosis control among HIV/AIDS patientsHollm-Delgado, Maria-Graciela 11 1900 (has links)
Introduction: Les efforts globaux pour contrôler la tuberculose sont présentement restreints par la prévalence croissante du VIH/SIDA. Quoique les éclosions de la tuberculose multi résistante (TB-MDR) soient fréquemment rapportées parmi les populations atteintes du
SIDA, le lien entre VIH/SIDA et le développement de résistance n’est pas clair.
Objectifs: Cette recherche visait à : (1) développer une base de connaissances concernant les
facteurs associés à des éclosions de la TB-MDR parmi les patients atteints du VIH/SIDA; (2)
utiliser ce cadre de connaissances pour accroître des mesures préliminaires pour mieux
contrôler la tuberculose pulmonaire chez les patients atteints du VIH/SIDA; et (3) afin
d’améliorer l’application des ces mesures, affiner les techniques bactériologiques existantes
pour Mycobacterium tuberculosis.
Méthodologie: Quatre études ont été réalisées : (1) Une étude longitudinale pour
identifier les facteurs associés avec une éclosion de la TB-MDR parmi les patients atteints du
SIDA qui ont reçu le traitement directement supervisé de courte durée (DOTS) pour la
tuberculose pulmonaire au Lima et au Pérou entre 1999 et 2005; (2) Une étude transversale
pour décrire différentes étapes de l’histoire naturelle de la tuberculose, la prévalence et les
facteurs associés avec la mycobactérie qu’on retrouve dans les selles des patients atteints du
SIDA; (3) Un projet pilote pour développer des stratégies de dépistage pour la tuberculose
pulmonaire parmi les patients hospitalisés atteints du SIDA, en utilisant l’essaie Microscopic
Observation Drug Susceptibility (MODS); et (4) Une étude laboratoire pour identifier les
meilleures concentrations critiques pour détecter les souches MDR de M. tuberculosis en
utilisant l’essaie MODS.
Résultats : Étude 1 démontre qu’une épidémie de TB-MDR parmi les patients atteints du
SIDA qui ont reçu DOTS pour la tuberculose pulmonaire ait été causée par la superinfection
du clone de M. tuberculosis plutôt que le développement de la résistance secondaire. Bien que ce clone ait été plus commun parmi la cohorte de patients atteints du SIDA, il n’avait
aucune différence de risque pour superinfection entre les patients avec ou sans SIDA. Ces
résultats suggèrent qu’un autre facteur, possiblement associé à la diarrhée, peu contribuer à la
prévalence élevée de ce clone chez les patients atteints du SIDA. Étude 2 suggère que chez la
plupart des patients atteints du SIDA il a été retrouvé une mycobactérie dans leurs selles
alors qu’ils étaient en phase terminale au niveau de la tuberculose pulmonaire. Or, les
patients atteints du SIDA ayant été hospitalisés pendant les deux dernières années pour une
autre condition médicale sont moins à risque de se retrouver avec une mycobactérie dans
leurs selles. Étude 3 confirme que la tuberculose pulmonaire a été commune à tous les
patients hospitalisés atteints du SIDA, mais diagnostiquée incorrectement en utilisant les
critères cliniques présentement recommandés pour la tuberculose. Or, l’essaie MODS a
détecté pour la plupart de ces cas. De plus, MODS a été également efficace quand la méthode
a été dirigée aux patients soupçonnés d’avoir la tuberculose, à cause de leurs symptômes.
Étude 4 démontre les difficultés de détecter les souches de M. tuberculosis avec une faible
résistance contre ethambutol et streptomycine en utilisant l’essai MODS avec les
concentrations de drogue présentement recommandées pour un milieu de culture. Cependant,
l’utilité diagnostique de MODS peut être améliorée ; modifier les concentrations critiques et
utiliser deux plaques et non une, pour des tests réguliers.
Conclusion: Nos études soulèvent la nécessité d’améliorer le diagnostic et le traitement de la
tuberculose parmi les patients atteints du SIDA, en particulier ceux qui vivent dans des
régions avec moins de ressources. Par ailleurs, nos résultats font ressortir les effets indirects
que les soins de santé ont sur les patients infectés par le VIH et qu’ils peuvent avoir sur le
développement de la tuberculose. / Background: Global efforts to control tuberculosis are currently being hampered by a
continuing rise in the prevalence of HIV/AIDS. Although outbreaks of multidrug resistant
tuberculosis (MDR-TB) are commonly reported among AIDS populations, the link between
HIV/AIDS and the development of drug-resistance remains unclear.
Objectives: This thesis aimed to: (1) build a knowledge foundation regarding underlying
factors associated with outbreaks of MDR-TB among HIV/AIDS patients; (2) use this
knowledge framework to develop preliminary health measures for controlling pulmonary
tuberculosis among HIV/AIDS patients; and (3) in an effort to better implement these health
measures, refine existing culture-based diagnostics for Mycobacterium tuberculosis.
Methods: Four studies were conducted: (1) a longitudinal study to identify the underlying
factors associated with an epidemic of MDR-TB among AIDS patients receiving Directly-
Observed Therapy Short-course (DOTS) for pulmonary tuberculosis in Lima, Peru between
1999 and 2005; (2) a cross-sectional study to characterize the prevalence and factors
associated with gastrointestinal shedding with mycobacteria among AIDS patients at
different stages in the natural history of tuberculosis; (3) a pilot study to develop screening
strategies for pulmonary tuberculosis among hospitalized HIV/AIDS patients using the
Microscopic Observation Drug Susceptibility (MODS) assay; and (4) a laboratory-based
study to define the optimal critical concentrations needed for detecting drug resistance in M.
tuberculosis using MODS.
Results: Study 1 revealed that an epidemic of MDR-TB among AIDS patients receiving
DOTS for pulmonary tuberculosis was due to super-infection with a specific clone of M.
tuberculosis rather than the development of secondary drug-resistance. Although this
epidemic clone was more common among patients in the AIDS cohort, risk of superinfection
did not differ between AIDS and non-AIDS patients after adjusting for baseline risk of exposure, suggesting that another factor possibly associated with diarrhea may be
contributing to the strain’s high prevalence among AIDS patients. Study 2 showed that the
majority of AIDS patients in the later stages of pulmonary tuberculosis exhibited
gastrointestinal shedding with mycobacteria. Stool shedding was rare in the absence of
pulmonary tuberculosis. AIDS patients were also less likely to shed mycobacteria if they had
been hospitalized during the previous two years for another medical condition. Study 3
confirmed that pulmonary tuberculosis was common among hospitalized AIDS patients but
frequently misdiagnosed using currently recommended diagnostic algorithms. The MODS
assay detected most cases and was equally effective when targeted to patients clinically
suspicious for tuberculosis. Study 4 demonstrated that low grade drug resistance in M.
tuberculosis to ethambutol and streptomycin was difficult to detect with MODS using
currently recommended drug-concentration standards in broth. Its diagnostic utility could be
improved by modifying drug-concentration standards, and including two versus one critical
concentration well for standardized testing.
Conclusion: Our studies underscore the need to improve the diagnosis and treatment of
tuberculosis among AIDS patients living in resource-constrained settings, all in an effort to
prevent morbidity, mortality and the transmission of drug-resistant strains. They also
highlight the indirect effect that general health care among HIV-infected patients can have on
the development of tuberculosis.
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