Background: Globally, there are 10 million new cases of tuberculosis (TB) disease annually and 95% of cases occur in low- and middle-income countries (LMIC). More than 1 billion people use tobacco, and 80% of tobacco users reside in LMIC. Smoking approximately doubles the risk of TB disease and is associated with excess mortality during TB treatment. We aimed to estimate the proportion of annual incident TB cases and TB mortality attributable to tobacco smoking in high burden TB countries. Methods: To estimate population attributable fractions (PAF), we obtained country specific estimates of TB incidence and TB mortality rates from the WHO 2015 Global TB Report. Country specific smoking prevalence was estimated from WHO 2015 tobacco surveillance reports and the Tobacco Atlas. Risk ratios for the effect of smoking on TB incidence and TB mortality were obtained from previously published meta-analyses. Country specific PAF of smoking for TB disease were age and sex adjusted. Results: In high burden countries during 2014, an estimated 4.5 million adults developed TB disease and 163,000 people died from TB. An estimated 740 million adult smokers lived in those high burden countries in 2014. We estimated that tobacco smoking was attributable for 17.7% (95% confidence interval [CI] 8.6-21.9%) of TB cases and 15.0% (95% CI 1.9-31.6%) of TB mortality. Of the high burden countries, Russia had the highest proportion of smoking attributable TB disease (31.8%, 95% CI 16.0-37.8%) and death (28.1%, 95% CI 3.8-51.3%). India had the greatest absolute number of TB cases (233,000) and TB deaths (7,400) attributable to smoking. Men (30.5%, 95% CI 14.9%-36.9%) had a greater proportion of TB cases attributable to smoking than women (4.7%, 95% CI 1.9%-6.2%). Conclusion: In high-burden TB countries, nearly one-sixth of all TB cases and TB deaths were attributable to smoking. Our findings highlight the need for tobacco control in high TB burden regions and specifically among patients with TB. Reaching key populations and integrating smoking cessation efforts into TB programs will be essential to achieve global TB control goals.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the leading causes of death globally, especially in low and middle-income countries. TB is primarily a curable disease, with chemotherapy predicated on a combination of four drugs. The increase in multiple forms of drug-resistant TB is a major cause for concern, underpinning the importance of a continuous pipeline of new anti-TB agents. Drug repositioning - that is, the optimization of existing drugs for new therapeutic indications - has shown promise in expanding the therapeutic options for TB chemotherapy. Fusidic acid (FA), a natural product-derived antibiotic, has modest in vitro antimycobacterial activity. Through a multi-disciplinary approach combining aspects of chemistry and biology, this study investigated the pharmacological and physicochemical properties of FA that might be exploited for optimization of FA as a lead compound for TB drug discovery. FA is a weak carboxylic acid, and it was hypothesised that the carboxylic acid moiety limits its permeation of the complex mycobacterial cell wall. Therefore, this study aimed to identify novel FA analogues with improved permeation properties and designed to act as potential prodrugs. By modifying the C-3 hydroxyl and the carboxylic acid moiety, alkyl and aminoquinoline derivatives were covalently fused to FA through ester and amide coupling reactions to generate hybrids and/or potential prodrugs.

No description available.

BACKGROUND: On World TB Day 2016, CDC reported an increase in number of US tuberculosis (TB) cases in 2015, the first time in 23 years. TB is the largest cause of mortality from any bacterial disease worldwide, with 95% of cases and deaths in low and middle-income countries, where it remains endemic. The recent increase in US TB cases highlights the fact that TB is a global issue, thus requiring a global effort to achieve elimination, with particular focus on active TB and Latent TB Infection (LTBI) identification and treatment among populations at high risk. The refugee population requires particular attention, considering TB disproportionately afflicts refugees and there are more refugees worldwide today than in the past 20 years. Georgia is among the top 10 US states for refugee arrivals, with majority resettling in DeKalb County, approximately 90% in 2010. There is a lack of data on TB rates among these populations and effects of implementation of the 2007 expanded CDC Technical Instructions on imported TB and LTBI reactivation. OBJECTIVES: (1) Estimate and compare TB disease incidence rates among refugee, other foreign-born, and US-born populations in DeKalb County from 2004 to 2015 (2) Determine refugee TB case contribution to total DeKalb County TB case burden (3) Examine possible trends in number of cases diagnosed ≤ 6 months of US entry, among refugee and other foreign-born persons screened overseas before and after implementation of 2007 expanded CDC Technical Instructions. METHODS: Retrospective study on all new TB cases diagnosed in DeKalb County during 2004-2015. Due to the lack of data on refugee population estimates along with the dynamic nature of this population, three different annual incidence rates were calculated for refugees and other FB. Participant characteristics were compared using chi-square tests and univariate analyses to identify significant differences between groups. Logistic regression was used to model change in number of TB diagnoses ≤ 6 months of US entry against implementation status (pre vs. post) and immigration status (refugee vs. other-FB). RESULTS: From 2004 to 2015, a total of 898 active TB cases were diagnosed in DeKalb County; 569 total foreign-born (144 refugees and 425 other foreign-born) and 329 US-born. Age, race/ethnicity, TB verification type, HIV status, and previous TB diagnosis were found to have significant differences between groups (p < 0.05). Throughout the study period, the highest TB incidence rate was among refugees followed by other FB, and drastically lower rates among US-born. There were significantly more diagnoses ≤ 6 months of US entry among post vs pre-implementation, OR: 2.784 (95% CI: 1.683 – 4.606). Refugee vs. other-FB, OR: 5.103 (95% CI: 3.085 – 8.442). Majority of cases with prior B1 classification (83.6%) were diagnosed ≤ 6 of US entry, which is considered to be possible imported TB, While (90.9%) persons with Class B2, although few, were diagnosed ≤ 6 months of US entry, which suggests possible LTBI reactivation. DISCUSSION: Although TB cases and rates have decreased in DeKalb County over the years, particularly among US-born persons, the foreign-born population remains disproportionately afflicted, with majority of county disease burden, over 70% in 2015. Refugee TB rates in DeKalb County are more comparable to rates in high TB incidence low and middle-income countries rather than US rates. Imported TB and LTBI activation may be major factors involved in the stagnation of progression towards TB elimination. Efforts need to refocus on LTBI identification and treatment to tackle the global issue of TB.

Thesis (MPH)--University of Limpopo, 2010. / INTRODUCTION: Sub-optimal adherence to prescribed medications is documented as a major cause of drug resistance in tuberculosis (TB). Directly observed treatment – short course (DOTS) remains the WHO gold standard for improving adherence. Concerns with DOT as the single solution have been raised and a range of adherence strategies are increasingly being recommended. RESEARCH QUESTION: Can the SIMpill electronic reminder system increase medication adherence amongst TB patients? METHODOLOGY: A cohort of TB patients in the Frances Baard District (Northern Cape) was recruited to the project. Each patient was given their TB medication in a special SIMpill container that uses cellular phone technology to remind those patients who forget to take their medication on time. Each time the container is opened an SMS is sent to a computer server. If the container is not opened at the prescribed time the SIMpill computer sends a reminder SMS to the patient. The data collected on the computer server was analysed to show which patients opened the medication container within the agreed tolerance time, which required to be reminded by SMS, and which failed to take their medication. After the treatment programme, patients were taken through a structured questionnaire to find out their views on the functioning and user acceptability of the SIMpill system. RESULTS: 65 patients completed the SIMpill project and were subsequently interviewed. 97% of patients felt the SMS reminders helped them take their medication. The aggregated data from the SIMpill computer server showed adherence levels averaged 83% with no SMS reminders, rising to 92% if SMS reminders needed to be sent. CONCLUSION: Poor adherence is a problem in long-term therapy programmes such as those required for TB treatment. Using the SIMpill system with a cohort of 65 patients, adherence increased from 83% to 92% if SMS reminders needed to be sent by the SIMpill system

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.

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

Using a multiple stage age of infection model, we derive an expression for the basic reproduction number, Ro. We apply this method to find Ro in analogous treatment models. We find, in the model without treatment, Ro depends only on the mean infective period, and not on the infective distribution. In treatment models, Ro depends on the mean infective and mean treatment period, as well as the distribution of the infective period, but not on the distribution of the treatment period. With an explicit formula for Ro and the final size relation, we provide a practical alternative to evaluating the effect of treatment and other control measures. We compare our models to previous models of SARS and TB.

Using a multiple stage age of infection model, we derive an expression for the basic reproduction number, Ro. We apply this method to find Ro in analogous treatment models. We find, in the model without treatment, Ro depends only on the mean infective period, and not on the infective distribution. In treatment models, Ro depends on the mean infective and mean treatment period, as well as the distribution of the infective period, but not on the distribution of the treatment period. With an explicit formula for Ro and the final size relation, we provide a practical alternative to evaluating the effect of treatment and other control measures. We compare our models to previous models of SARS and TB.

South Africa is one of the high burden countries for TB in Sub Sahara in Africa with Mpumalanga as one of the provinces with a high burden of disease. Data available on tuberculosis in Msukaligwa indicate the following: Cure Rate 40%; Smear conversion at the end of intensive phase 35% and Defaulter Rate 27.5%. The problem of TB is made worse by the twin epidemic of HIV, with a prevalence of 38.9% in our district -the highest among the 3 districts in the province. Retreatment TB carries the risk of developing TB drug resistance with severe consequences for the patient and the population. Understanding the characteristics of these patients will help in designing interventions to prevent the problem, promote a high cure rate for patients with TB in our health care system and reduce to minimum the burden of re-treatment pulmonary TB on our health care facilities and community. One critical precondition for Retreatment TB is non adherence to TB treatment. Factors responsible for non adherence could be classified as individual patient factors; Co-morbid conditions; Health system; treatment related and Community factors. The outcomes of Retreatment TB could be, cure, and death and failure of treatment leading to drug resistance. The Setting of this study is the 58-bedded TB hospital in Ermelo. The Aim of the study was to describe the occurrence, characteristics and management outcome of Retreatment Pulmonary Tuberculosis in patients in the Ermelo TB hospital. The specific Objectives were to describe the socio-demographic, behavioural and clinical factors related to recurrence of the TB in patients; to determine the contribution of non adherence to treatment on recurrence of TB in the study population; to identify the prevalence of resistance to TB medication among patients with Retreatment TB ; to identify treatment outcomes in patients who have been followed up for the duration of Retreatment TB and finally to make recommendations to the Department of Health, Mpumalanga towards minimizing Retreatment TB and improving the overall TB programme. The Study design is cross sectional and descriptive; the study population comprised of patients admitted with TB at Ermelo TB hospital aged 15 years and older between 1 January 2005 and 31 December 2007.No specific probability sampling was applied in the selection of the patients. Data Collection involved visits to the TB hospital during the period and extracting the relevant information from the patient medical records and the TB register using a predesigned data collection form. Data analysis was done by the statistician from the Centre for Statistical Consultation, University of Stellenbosch. Being a descriptive study, the data analysis expresses the prevalence of various factors associated with retreatment TB. This study met the Ethical approval of the University of Stellenbosch as well as the Research Ethics Committee of the Department of Health & Social Services, Mpumalanga. Findings All the three hundred and eighty eight patient records with retreatment TB forming 19.6% of TB patients admitted between 2005 and 2007 were reviewed. The distributions of the patients were: males 66%; mean age of 41.4 years; females 34%; mean age 35.3 years. They were mostly unemployed; primary education 93%; unmarried 43% and married 34%.Retreatment TB was diagnosed with sputum smear microscopy in 71% with bacilli load of 3+ in 45%.The sources of referral to TB hospital were: public hospital 71 %; private doctors 2%. 74% of the patients have had TB 1-3 years before the episode under study. Retreatment TB categories were: after treatment completed 69%; default 19%; after cure 8% and treatment failure 4%. 98% of patients tested had +ve HIV status; the median CD4 cell count was 106 cells/µl at the time of retreatment; very few (5%) were on ART. Drug resistance to primary TB drugs was as follows: Rifampicin 16%; Isoniazid 29%; Ethambutol 19% and Streptomycin 23%. The treatment outcomes for those whom data were available were: successful 49.1%, death 23.8%; treatment default 22.9%. MDR-TB complicated 3.3% of the patients. Conclusion: Majority of the retreatment TB patients were males with an average age of 41years and unemployed. More than two thirds of the patient had completed TB treatment previously and default on treatment accounted for less than one quarter of retreatment categories. The process of care was better in terms of diagnosis of TB with sputum smear. Improvement in the documentation of key factors like smoking, alcohol, drug use among patients and co-morbidity as well as counselling and testing for HIV and provision of ARTs is required. Treatment outcomes with regards to successful outcome need to be monitored and improved upon.