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.

Thesis (M.Cur) --University of Limpopo, 2011 / The aim of this study was to determine the factors that contribute to the increase in the number of tuberculosis (TB) patients in Mpumalanga Province, and to develop guidelines and recommendations to address the challenges of this health issue. The design of the study was qualitative phenomenological. The population consisted of all TB patients who were receiving treatment either at the intensive or the continuation phase. The sampling method was purposive and the sample size comprised 20 participants, of whom 10 were drawn from Shatale clinic at Bushbuckridge, and 10 from Mashishing clinic at Thabachweu municipalities in the Ehlanzeni district of Mpumalanga Province. The data was gathered by means of semi-structured interviews. Data analysis was performed, from which themes and categories were derived. This study revealed several factors that contributed to the increase in the number of TB patients at the study sites. The factors considered most important in this study were the general lack of knowledge of TB among participants, despite their various levels of education, poverty, overcrowding, poor ventilation in the shacks and Reconstruction and Development Program (RDP) houses, unemployment, lack of support while taking treatment, religious and ritual beliefs, and the influence of traditional healers who dispense herbal medicines with the dictum that participants have been possessed by evil spirits and witches. The majority of patients developed TB as a secondary opportunistic infection because of their HIV-positive status, and lack of capacity to practice personal hygiene and proper infection control. Guidelines, strategies and recommendations were formulated to address these public health challenges in the context nursing education, research, administration and practice

Thesis (MPH)--University of Limpopo (Medunsa Campus), 2011 / Background and aim: Smear-negative pulmonary tuberculosis (SNPTB) has become an increasingly important clinical and public health problem, especially in areas that are affected by the dual infection of TB and human immunodeficiency virus (HIV) (Mello et al, 2006; WHO, 2006; Harries et al, 1998). There are recommended guidelines for diagnosing SNPTB to reduce misdiagnosis in sub-Saharan Africa, but there is little information on whether these guidelines are followed correctly (Harries et al, 1998). The aim of this study was to investigate the clinical diagnosis of SNPTB in HIV-positive patients at Athlone Hospital in Botswana. Methods: This was a quantitative, descriptive study which used two sources of data and data collection methods: a 4 year retrospective records review and questionnaires for clinicians. All clinicians responsible for treating HIV-positive patients (n=8) were asked to complete a questionnaire on self-reported (1) compliance with the guidelines (2) use of other methods to diagnose SNPTB and (3) reasons for not complying with the guidelines. All records on SNPTB in HIV-positive patients from 2006 to 2009 (n=281) were reviewed to establish the compliance and use of other methods to exclude other respiratory infections. Results: The response rate for clinicians was 87.5% (7/8). All clinicians (100% [7/7]) reported (a) always complying with using chest x-rays (CXRs), but (b) only sometimes complying with using 3 sputum results. Most clinicians (a) considered the duration of cough before making a diagnosis of SNPTB (57.1% [4/7]), and (b) placed patients on a trial of broad spectrum antibiotics before starting PTB treatment (85.7% [6/7]). The main reasons for non-compliance were: the inability of patients to submit sputum (100% [7/7]), delays in the laboratory (71.43% [5/7]), and lack of feedback from Botswana National Tuberculosis Program (BNTP) (57.14% [4/7]). Only 2.1% (6/281) of the records showed that other methods were used to rule out other respiratory infections, and overall compliance with the recommended guidelines was only 13.5% (40/281). Conclusion: The compliance with the recommended guidelines in making a diagnosis of SNPTB was very poor in this study. The unavailability of user-friendly and fast diagnostic methods resulted in many cases being treated for SNPTB with inadequate investigations.

acase@tulane.edu / 1 / Taylor Foreman

The increase of multi-drug resistant and extensively drug resistant tuberculosis (TB) cases makes it urgent to develop a new generation of TB drugs to counter resistance and shorten treatment. Structural biology, which allows us to “visualize” macromolecules, is now playing a key role in drug discovery. In this work, a structure-based approach was applied to the study of the mode of action of current TB chemotherapies, the identification of potential therapeutic targets, and the design of new inhibitors against TB. Knowledge of the precise mechanisms of action of current TB chemotherapies will provide insights into designing new drugs that can overcome drug-resistant TB cases. Structural biology combined with biochemical and genetic approaches was used to elucidate the mechanisms of actions of isoniazid, ethionamide and prothionamide. The active forms of these anti-TB prodrugs were identified by protein crystallography and the target-inhibitor interactions were revealed by the complex structures. Although these drugs are activated through two completely different routes, they all inhibit InhA, an essential enzyme in mycolic acid biosynthesis, by modification of the enzyme cofactor NAD, which unveils a novel paradigm of drug action. Isoniazid, ethionamide and prothionamide all target InhA, which validates the enzyme as a superb drug target. A structure-based approach was adopted to design new inhibitors targeting InhA, using triclosan as the scaffold. Guided by the InhA-inhibitor complex structures, two groups of triclosan analogs were identified with dramatically increased inhibitory activity against InhA. Structural biology has also provided fundamental knowledge of two potential therapeutic targets, Mtb β-lactamase (BlaC) and fatty-acyl-CoA thioesterase (FcoT). Mtb β-lactamase has been proposed to be the most significant reason for mycobacterial resistance to β-lactam antibiotics. The determination of Mtb BlaC structure not only demonstrates the mechanism of drug resistance but also provides a solid base for the design of new β-lactamase inhibitors that could be used with β-lactam antibiotics as a new regimen to treat tuberculosis. The crystal structure of FcoT provided crucial information in identification of the function of this previously hypothetical protein. The characterization of FcoT revealed an important pathway that is critical for Mtb’s survival in host macrophages.

El presente tema de tesis pretende realizar un análisis costo efectividad entre la Técnica Reacción en Cadena de la Polimerasa y la Prueba de Sensibilidad y Resistencia para el diagnóstico de tuberculosis multidrogorresistente , este análisis busca la mejor relación entre beneficios y costos para alcanzar la forma más eficaz de realizar la vigilancia epidemiológica de la tuberculosis multidrogorresistente, tomando en cuenta que los consecuentes diagnósticos tardíos generan multidrogorresistencia y que el costo individual por paciente multidrogorresistente asciende aproximadamente a 7000 Bs. 1 Las pruebas de sensibilidad a los fármacos antituberculosos son imprescindibles y recomendadas para la vigilancia epidemiológica de la resistencia, debida generalmente a malos tratamientos o mala supervisión de los mismos en grupos de alto riesgo difíciles de manejar y controlar (reclusos, enfermos con VIH). La sensibilidad a los fármacos esenciales se investiga en todo enfermo nuevo, en fracasos de tratamiento y en recaídas. La prueba de sensibilidad y resistencia es una técnica que tiene buena sensibilidad (70-90%) pero el aislamiento de las micobacterias por cultivo es entorpecido por su lento crecimiento, la demora hace poco útil este tipo de estudios con carácter asistencial ya que los resultados se obtienen en 6 semanas, se pueden obtener excelentes resultados si se mantienen estrictamente las normas de control de calidad. pero el neumólogo siempre recibe una imagen vieja de la situación, de tal manera que en casos en los que se requiera una toma de decisiones rápidas para instaurar una terapéutica efectiva su valor es muy limitado.

La Tuberculosis en la actualidad es considerada un problema de Salud Pública en todo el mundo, lo que se evidencia en las altas tasas de morbilidad y mortalidad. El objetivo del trabajo es determinar el Perfil epidemiológico y clínico de pacientes con Tuberculosis en la Microred Cono Norte - Tacna 2012. Es un estudio descriptivo, retrospectivo de corte transversal; que tomo como muestra 117 pacientes de la Estrategia Sanitaria Nacional de Prevención y Control de la Tuberculosis de enero a octubre del 2012; resultado de un muestreo probabilístico estratificado. Para la selección de datos se utilizó como técnica la revisión documental de historias clínicas mediante una ficha de captación de información. Los resultados obtenidos resaltantes; el sexo masculino (53,8%), grupo etáreo adulto joven (53,8%), ocupación estudiantes (29,9%), cicatriz de Vacuna BCG (86,3%), forma Tuberculosis Pulmonar (74,4%), condición de ingreso caso nuevo (87,2%), hábito al tabaco, alcohol o drogas (41,0%), contacto tuberculosis (40,2%), estado nutricional normal (52,1%) y método de diagnóstico el examen bacteriológico (62,4%).

Tuberculosis (TB) is a preventable and a treatable disease yet it is considered to be one of the most common infections seen in HIV. People who are infected with HIV are 20 times more likely to develop TB than those without HIV. Globally, there are nearly 40 million people living with HIV and at least one-third of them are infected with TB. Ontario accounts for the highest number of TB cases in Canada yet HIV-TB co-infection in Ontario is not well described. Despite the close relationship between TB and HIV and increasing efforts to fight both concurrently, TB continues to create economic and social burden in HIV infections. Our study estimates the prevalence of active and latent TB and identifies risk factors associated with TB in a cohort of individuals living with HIV in Ontario. Cases diagnosed with HIV during 2001 to 2009 were extracted from the Ontario HIV Treatment Network Cohort Study (OCS). Reviewing Mantoux test results, diagnoses and medication history, identified active and latent TB cases. Period prevalence was estimated by proportion with TB and multivariate analyses were performed to identify associated factors. One thousand two hundred and ninety-three cases (1293) met our selection criteria. Three hundred and eighty four (384; 29.7%) were 29 years or younger, 805 (62.3%) aged between 30 years and 50 years and 104 (8.0%) aged 50 years or older. One thousand and nine (1009; 78.0%) were males. Four hundred and sixty six (466; 36.0%) had at least one record of a Mantoux skin test. The prevalence of active TB was 76/1293 = 0.0587 or 5.87% (95% CI 4.6% to 7.0%) whereas the prevalence of latent TB varied from 5.26% (68/1293 = 0.0526) 95% (CI 4.0% - 6.5%) to 11.37% (53/466 = 0.1137) 95% CI (8.2% to 13.7%) depending on the methodology. In the multivariate analysis, factors associated with active TB were age and birthplace. Individuals 50 years and older were more likely to have active TB than individuals 30 years and younger (OR 4.3 CI (1.7-12.7), p <0.01). Individuals born in Africa were more likely to have active TB than Canadian born (OR 14; 95% CI (5.9 – 32.8) p < 0.001). Factors associated with latent TB were sex and birthplace. Females were more likely to have latent TB than males (OR 2.4; 95% CI (1.1 – 5.2) p < 0.05). Individuals born in Africa were more likely to have latent TB than Canadian born (OR 12.3; 95% CI (4.7 – 32.1) p < 0.001). TB remains a major problem in persons infected with HIV with rates disproportionally high among the foreign born population. Low rates of Mantoux tests in OCS present a missed opportunity for active TB prevention among individuals with HIV. To identify individuals with higher risk of having TB after HIV diagnosis, better screening tools to identify latent TB are needed. Consideration should be given to data capture systems that would ideally be linked between Public Health and HIV clinics. / UOIT

This research explored several adaptations to tuberculosis among the Indian population of Saskatchewan from 1926 to 1965 in order to demonstrate that this was an era in which disease played an significant role in the lives of the Indians. A broad ecological model' allowed for a variety of interactions to be explored. Within this framework, the study examined: the epidemiology and ecology of tuberculosis in the Saskatchewan Indian population; the development of health services to the Indians and the role of health services in the ecology of disease in this population; and the individual Indians' hospitalization and tuberculosis experience.<P> The epidemic of tuberculosis among the Indians of Saskatchewan began in the early 1880s. Rapidly assuming epidemic proportions, the death rate from tuberculosis among the Qu'Appelle Indians peaked in 1886 at a rate of 9,000 per 100,000. The death rate declined gradually after 1890 through the acquisition of population resistance and the elimination of the non-resistant families. The acute phase of the tuberculosis epidemic, characterized by extra-pulmonary disease in which the majority of cases terminated in a few months, lasted about two decades. Between 1907 and 1926, with gradually improving living conditions, continued acquisition of population resistance, but without application of any specific anti-tuberculosis measures, the death rate fell to 800 per 100,000.<p> Tuberculosis was endemic in the Saskatchewan Indian population by the beginning of the 1930s. Once endemic, the decline of the tuberculosis death rate continued to the end of the 1940s, without application of any specific anti-tuberculosis measures. By the time that specific measures were introduced, the death rate had declined to 417 per 100,000 in 1949. With the introduction of BCG vaccination and antimicrobial drug treatment, by 1959 the death rate declined to 39 per 100,000.<p> By the early 1960s tuberculosis mortality was successfully controlled in Saskatchewan, although death rates remained 15 times higher among the Indians. Tuberculosis morbidity continued to be a problem into the 1980s. In 1984, the incidence of tuberculosis was 21 times greater among the Indians than the corresponding rate in the non-Indian population.<p> Various environmental and cultural factors contributed to the Indian population's experiences with tuberculosis. The most important factor was the absence of population immunity. In addition, concentration of the population on reserves, the occurrence of intercurrent epidemics, sudden and dramatic dietary change, and lifestyle factors such as housing, sanitation and personal hygiene all contributed to incredibly high tuberculosis mortality in this population. The effect of medical care on the epidemiology of tuberculosis in the Saskatchewan Indians was not even considered in the preliminary analysis of the epidemic, because throughout the first several decades of the epidemic, no organized health services existed for the Indians.<p> In Saskatchewan, before World War II, medical services to the Indians were characterized by occasional surveys, the employment of part-time physicians, and health education through the distribution of circulars to Indian agents on health-related issues. Organized anti-tuberculosis programs which were developed in the years following the Second World War, in a large part, account for the dramatic decrease in the tuberculosis death rate in the province through the decade of the 1950s.<p> In the late 1940s, and throughout the 1950s and 1960s, most active Indian tuberculosis cases diagnosed in Saskatchewan were hospitalized for treatment. At least 10% of the Indian population of Saskatchewan received Indian hospital or sanatorium treatment throughout the first decade that those services were available to them.<p> Interviews conducted with fourteen Indian individuals who had been hospitalized for tuberculosis treatment provided two dichotomous perspectives on tuberculosis. Several individuals feared tuberculosis because of their familiarity with it in their families and on their reserves, however, most said that they knew tuberculosis, but they did not fear it. In terms of their knowledge about tuberculosis from a biomedical perspective, most had some idea of its symptomology although its specific etiology was not known. Most of the people interviewed appeared to understand the infectious nature of tuberculosis, however, their concern for their families may have stemmed from observations that tuberculosis was "in" particular families, not necessarily because they thought they could "give" tuberculosis to them. In terms of a perspective on the treatment of tuberculosis, most of the individuals interviewed were aware that hospital treatment was necessary. Archival sources and government annual reports, indicated that many Indians took a very active role in attending to their health needs. None of the individuals who were interviewed refused to go to the sanatorium, except for one woman who ran away several times. Most, however, planned their escape time after time. This suggests that their stay in the sanatorium and hospital may not have been of their own volition.<p> The most common and recurring theme that emerged from the interviews about life in the sanatoria or Indian hospital revolved around the structured, regimented nature of the treatment. Several individuals remembered quite vividly seeing other patients confined in strait jackets and body casts and distinctly remembered how strict the staff was with children.<p> While they were hospitalized, all of the individuals who were interviewed knew several other people who were being treated at the same time who were also their contemporaries from their own or surrounding reserves. All of the individuals also made several lasting friendships with people that they met while in the sanatorium. In addition, all, except for one young boy, were visited frequently by their families and friends. This indicates that the Indian people interviewed were not "isolated" from their families and friends for the duration of their treatment. Hospitalization, for those interviewed, was not a traumatic event because they had an extensive social network which enabled them to cope with the experience. In addition, because of the poor living conditions on many Indian reserves, a trip to the sanatorium or Indian hospital was a relief for some. Indian children in the sanatorium and hospital were given new clothes, toys, and books, and in some cases an education; things they did not get at home. One woman chose to remain in the sanatorium after her treatment regimen ended so that she could complete her education, something she could not do back at home in the north. Only one individual suggested that the experience was instrumental in determining the direction his future took.<p> In demonstrating that this was an era in which disease played a major role in the lives of the Indians, the epidemiology of tuberculosis in this population illustrated the pervasive influence that tuberculosis had on demographic and biological aspects of the population. The history of health services illustrated the role of medical intervention in the ecology of tuberculosis in this population. As a probe for behaviourial adaptations to disease on the individual level, the interviews contributed a human dimension to the study. To complete the picture of the role of disease in the lives of the Indians, the examination of the final component in adaptation, behaviourial adaptation to disease at the cultural level, is recommended.

This research explored several adaptations to tuberculosis among the Indian population of Saskatchewan from 1926 to 1965 in order to demonstrate that this was an era in which disease played an significant role in the lives of the Indians. A broad ecological model' allowed for a variety of interactions to be explored. Within this framework, the study examined: the epidemiology and ecology of tuberculosis in the Saskatchewan Indian population; the development of health services to the Indians and the role of health services in the ecology of disease in this population; and the individual Indians' hospitalization and tuberculosis experience.<P> The epidemic of tuberculosis among the Indians of Saskatchewan began in the early 1880s. Rapidly assuming epidemic proportions, the death rate from tuberculosis among the Qu'Appelle Indians peaked in 1886 at a rate of 9,000 per 100,000. The death rate declined gradually after 1890 through the acquisition of population resistance and the elimination of the non-resistant families. The acute phase of the tuberculosis epidemic, characterized by extra-pulmonary disease in which the majority of cases terminated in a few months, lasted about two decades. Between 1907 and 1926, with gradually improving living conditions, continued acquisition of population resistance, but without application of any specific anti-tuberculosis measures, the death rate fell to 800 per 100,000.<p> Tuberculosis was endemic in the Saskatchewan Indian population by the beginning of the 1930s. Once endemic, the decline of the tuberculosis death rate continued to the end of the 1940s, without application of any specific anti-tuberculosis measures. By the time that specific measures were introduced, the death rate had declined to 417 per 100,000 in 1949. With the introduction of BCG vaccination and antimicrobial drug treatment, by 1959 the death rate declined to 39 per 100,000.<p> By the early 1960s tuberculosis mortality was successfully controlled in Saskatchewan, although death rates remained 15 times higher among the Indians. Tuberculosis morbidity continued to be a problem into the 1980s. In 1984, the incidence of tuberculosis was 21 times greater among the Indians than the corresponding rate in the non-Indian population.<p> Various environmental and cultural factors contributed to the Indian population's experiences with tuberculosis. The most important factor was the absence of population immunity. In addition, concentration of the population on reserves, the occurrence of intercurrent epidemics, sudden and dramatic dietary change, and lifestyle factors such as housing, sanitation and personal hygiene all contributed to incredibly high tuberculosis mortality in this population. The effect of medical care on the epidemiology of tuberculosis in the Saskatchewan Indians was not even considered in the preliminary analysis of the epidemic, because throughout the first several decades of the epidemic, no organized health services existed for the Indians.<p> In Saskatchewan, before World War II, medical services to the Indians were characterized by occasional surveys, the employment of part-time physicians, and health education through the distribution of circulars to Indian agents on health-related issues. Organized anti-tuberculosis programs which were developed in the years following the Second World War, in a large part, account for the dramatic decrease in the tuberculosis death rate in the province through the decade of the 1950s.<p> In the late 1940s, and throughout the 1950s and 1960s, most active Indian tuberculosis cases diagnosed in Saskatchewan were hospitalized for treatment. At least 10% of the Indian population of Saskatchewan received Indian hospital or sanatorium treatment throughout the first decade that those services were available to them.<p> Interviews conducted with fourteen Indian individuals who had been hospitalized for tuberculosis treatment provided two dichotomous perspectives on tuberculosis. Several individuals feared tuberculosis because of their familiarity with it in their families and on their reserves, however, most said that they knew tuberculosis, but they did not fear it. In terms of their knowledge about tuberculosis from a biomedical perspective, most had some idea of its symptomology although its specific etiology was not known. Most of the people interviewed appeared to understand the infectious nature of tuberculosis, however, their concern for their families may have stemmed from observations that tuberculosis was "in" particular families, not necessarily because they thought they could "give" tuberculosis to them. In terms of a perspective on the treatment of tuberculosis, most of the individuals interviewed were aware that hospital treatment was necessary. Archival sources and government annual reports, indicated that many Indians took a very active role in attending to their health needs. None of the individuals who were interviewed refused to go to the sanatorium, except for one woman who ran away several times. Most, however, planned their escape time after time. This suggests that their stay in the sanatorium and hospital may not have been of their own volition.<p> The most common and recurring theme that emerged from the interviews about life in the sanatoria or Indian hospital revolved around the structured, regimented nature of the treatment. Several individuals remembered quite vividly seeing other patients confined in strait jackets and body casts and distinctly remembered how strict the staff was with children.<p> While they were hospitalized, all of the individuals who were interviewed knew several other people who were being treated at the same time who were also their contemporaries from their own or surrounding reserves. All of the individuals also made several lasting friendships with people that they met while in the sanatorium. In addition, all, except for one young boy, were visited frequently by their families and friends. This indicates that the Indian people interviewed were not "isolated" from their families and friends for the duration of their treatment. Hospitalization, for those interviewed, was not a traumatic event because they had an extensive social network which enabled them to cope with the experience. In addition, because of the poor living conditions on many Indian reserves, a trip to the sanatorium or Indian hospital was a relief for some. Indian children in the sanatorium and hospital were given new clothes, toys, and books, and in some cases an education; things they did not get at home. One woman chose to remain in the sanatorium after her treatment regimen ended so that she could complete her education, something she could not do back at home in the north. Only one individual suggested that the experience was instrumental in determining the direction his future took.<p> In demonstrating that this was an era in which disease played a major role in the lives of the Indians, the epidemiology of tuberculosis in this population illustrated the pervasive influence that tuberculosis had on demographic and biological aspects of the population. The history of health services illustrated the role of medical intervention in the ecology of tuberculosis in this population. As a probe for behaviourial adaptations to disease on the individual level, the interviews contributed a human dimension to the study. To complete the picture of the role of disease in the lives of the Indians, the examination of the final component in adaptation, behaviourial adaptation to disease at the cultural level, is recommended.