The purpose of this study was to analyse the tracking systems used to identify patients with tuberculosis who missed a clinic appointment at primary health care facilities in Waterberg District. A quantitative descriptive correlation design was used to determine if there was an association between the tracking systems used and the defaulter rates. Data was collected using a questionnaire with nurses from 46 primary health care facilities, defaulter rates were accessed from the ETR.Net and the two sets of data were correlated. The results showed that the blue folder yielded the lowest mean defaulter rate while the green card yielded the highest mean defaulter rate. Nurses were unaware of the true defaulter rate in their facilities as they underestimated these rates. They therefore did not implement relevant intervention strategies to recall patients or find ways to improve the tracking systems used to reduce the defaulter rate in their health facilities. / Health Studies / M. A. (Health Studies)

The purpose of this study was to explore factors related to poor adherence to TB treatment in Keetmanshoop municipal area in Namibia. A qualitative, exploratory design was used to explore basic information about the study. Participants were using purposive sampling technique. The researcher-implemented triangulation, based on three different categories of participants, namely Field Promoters (preferred). DOT supporters (more preferred), and TB patients (most preferred). Participants were chosen in a ratio of preference. 1:2:3 respectively. The transcripts and audio tapes from interviews were analysed using the thematic content analysis. Five main themes emerged. In order of descending prominence, these themes included: factors leading to lack of adherence to TB treatment, support to enhance adherence to treatment, existing behaviours determining adherence, suggestions to promote adherence to treatment and practices to promote adherence to treatment. / Health Studies / M.A. (Public Health)

In this thesis, a mathematical model for HIV and TB co-infection with TB treatment among populations of Ethiopia is developed and analyzed. The TB model includes an age of infection. We compute the basic reproduction numbers RTB and RH for TB and HIV respectively, and the overall repro- duction number R for the system. We find that if R < 1 and R > 1; then the disease-free and the endemic equilibria are locally asymptotically stable, respectively. Otherwise these equilibria are unstable. The TB-only endemic equilibrium is locally asymptotically stable if RTB > 1, and RH < 1. How- ever, the symmetric condition, RTB < 1 and RH > 1, does not necessarily guarantee the stability of the HIV-only equilibrium, but it is possible that TB can coexist with HIV when RH > 1: As a result, we assess the impact of TB treatment on the prevalence of TB and HIV co-infection. To derive and formulate the nonlinear differential equations models for HIV and TB co-infection that accounts for treatment, we formulate and analyze the HIV only sub models, the TB-only sub models and the full models of HIV and TB combined. The TB-only sub model includes both ODEs and PDEs in order to describe the variable infectiousness and e ect of TB treatment during the infectious period. To analyse and solve the three models, we construct robust methods, namely the numerical nonstandard definite difference methods (NSFDMs). Moreover, we improve the order of convergence of these methods in their applications to solve the model of HIV and TB co-infection with TB treatment at the population level in Ethiopia. The methods developed in this thesis work and show convergence, especially for individuals with small tolerance either to the disease free or the endemic equilibria for first order mixed ODE and PDE as we observed in our models. / Mathematical Sciences / Ph. D. (Applied Mathematics)

The purpose of this study was to explore and describe the personal experiences of enrolled nurses while caring for patients infected with multidrug-resistant tuberculosis (MDR-TB) in an urban tuberculosis hospital in KwaZulu-Natal province, South Africa. Generic qualitative research was conducted with a sample of purposively selected enrolled nurses who cared for MDR-TB patients. Data was collected through in-depth individual interviews and analysed using Colaizzi’s (1978) method of data analysis. The research findings revealed six major themes: the working context, fear of contracting the disease, problems that have an impact on the quality of nursing care, nurses' perceptions of the patients, support structures and nurses' expressed needs. The findings of this study indicate that the nurses work in a challenging environment and need to be supported, as they experience more negative than positive feelings while caring for these patients. / Health Studies / (M.A. (Health Studies))

The purpose of this study was to establish empirical evidence on risk factors influencing drug-resistant tuberculosis (DR-TB) in Swaziland. Globally factors have been identified and specific programmatic interventions were implemented to counter the emergence of DR-TB, but the case still remains with Swaziland. The research question was “What are the risk factors influencing the epidemiology of DR-TB patients enrolled for treatment at the National Tuberculosis Referral Hospital? The research objectives were to investigate factors that influence the emergence of DR-TB in Swaziland, to establish the relationship between DR-TB and HIV and to develop a poster that will exhibit the findings on the study on risk factors influencing the epidemiology of DR-TB. A mixed method was used. A qualitative study of participants using the in-depth one on one interview with a grand tour question “ What are the risk factors that resulted in you having DR-TB” and probing questions. The quantitative retrospective part was utilised to review medical records. Convenience sampling was utilised to recruit participants using an interview guide to collect data and random sampling for the quantitative aspect using a checklist to collect data. Risk factors influencing the development of DR-TB were identified to be previous treatment with anti-tuberculosis drugs, human immunodeficiency virus (HIV). The findings showed that the prevalence of HIV in DR-TB was 61% for HIV positive and 39% for negative and the quantitative data showed 77% HIV positive and 23% negative to HIV. Lack of education for patients and their families on precautionary measures to take when caring for a family member, and what to do in cases of developing side effects. This study concludes that both the need to ensure that bacteriologically confirmed patients are initiated to treatment, adhere to their treatment and complete treatment and due to the number of direct cases being infected with DR-TB ensuring that infection control strategies are put in place at work and at home settings / Health Studies / M.A. (Public Health)

This study has been concerned with the design and synthesis of A TP analogues with the potential to act as inhibitors of glutamine synthetase - a novel target for therapeutic intervention in the treatment of tuberculosis. Using a structural -analogy approach, various 3-indolylalkanoic acid, benzimidazole and pyrazolo[3,4-dJpyrimidine derivatives have been prepared and characterized. Alkylation of the heterocyclic bases using 4-(bromomethyl)-2,2-dimethyl-1 ,3-d ioxolane, 2-(bromomethoxy)ethyl acetate and 2-(chloroethoxy)ethanol in the presence of either NaH or BulOK afforded the corresponding N-alkylated derivatives of benzimidazole and 4-aminopyrazolo[3,4-dJpyrimidine (4-APP). Similar reactions with 3-indo lylalkanoic esters resulted in O-alkyl cleavage with the formation of new esters. Alkylation of benzimidazole with allyl bromide, 4-bromobutene and 2-methylbut-2-ene has also been shown to afford the corresponding l-alkenylbenzimidazoles in moderate to excellent yield (43-96%). Subsequent oxidation of these products using CTAP, gave the dihydroxy derivatives in poor to good yields (26-77%). Phosphorylation of various hydroxy derivatives of benzimidazole and 4-APP has been achieved using diethyl chlorophosphate to afford the corresponding monophosphate and 1,2-diphosphate esters. Glycosylation of each of the heterocyclic bases has been successfully achieved using 1,2,3,4,6-penta-O-acetyl-D-glucopyranose and SnCl4 in acetonitri le, while methanolysis of the resulting tetraacetates, using methanolic NaOMe, afforded the hydroxy derivatives in good yield (50-70%). Various 1- and 2-dimensional NMR spectroscopic methods (e.g., IH, 13C, lip, COSY, HSQC and HMBC) have been used to confirm the structures of the synthesized A IP analogues. The application of NMR prediction programmes has been explored, permitting assessment of their agreement with the experimental data and confirmation of assigned structures. High-resolution electron impact (EI) mass spectrometric data have been used to explore the mass fragmentation pathways exhibited by selected derivatives, and certain common fragmentations have been identified. Molecular modelling of selected products as potential glutamine synthetase ligands has been performed on the Accelrys Cerius2 platform, and interactive receptor-ligand docking studies have been conducted using the Ligand-Fit module. These studies have revealed possible hydrogen-boding interactions between the selected analogues and various amino acid residues in the glutamine synthetase active site.

Thesis ( MPH.) -- University of Limpopo, 2022 / Background Multidrug-resistant tuberculosis (MDR-TB) has recently resulted to be in an emergence state globally and this of constitute a big challenge for TB control and the goals of the World Health Organization’s End TB Strategy. Aminoglycosides (AG) were often used as part of treatment of life-threatening illnesses such as MDR-TB for decades, however their adverse effects are widely described and hearing loss is one of the major side effects. The risk factors for hearing loss in patients treated with AG include the dose and duration of AG, infection with human immunodeficiency virus (HIV), older age and persons exposed to a high level of noise while the damage can be total and permanent. Severe hearing impairment has been reported to occur among patients treated for MDR-TB with injectable drugs, especially among the elderly and patients infected with human immunodeficiency virus, however, Bedaquiline containing regimens have demonstrated improved outcomes over injectable containing regimens in the long-term treatment of MDR-TB. Methods The objective of the current study was to investigate the burden of hearing loss amongst MDR-TB patients on bedaquiline at Zithulele Hospital in Eastern Cape Province. Therefore, the current study followed a quantitative retrospective approach using simple random sampling to select MDR-TB patients treated with bedaquiline and having a baseline audiogram be the initiation of treatment. The data was captured in a Microsoft Excel spreadsheet and then transferred to Statistical Package for Social Sciences (SPSS) Version 20 for data analysis in which categorical variables were presented as percentages and frequencies, while continuous variables was presented as mean, median and standard deviation lastly, comparison of categorical variables was done using a Chi-Squared test, whereas continuous variables were compared using a t-test. P-value of <0.05 will be considered significant. Results The mean age for the participants was 39.2 years with standard deviation of 11.8 and there was no statistical significance difference between the age groups (p value = 0.178). There no was a statistical significance difference between the employment status (p value = 0.794), previous use of injectables (p value = 0.360) and type of hearing of loss (p value = 0.536). Majority of the MDR-TB patients on bedaquiline did not have hearing loss at 67% while those who had gradual hearing loss and sudden hearing loss were 26.8% and 6.2% respectively. There was no statistical significance difference between males and females in both the right and left ears, however, the right ear results appeared to be slightly worse than the left ear results. It was found that both males and females had a high frequency hearing loss in the left ears of 26.8% and 22.2% respectively as compared to the right ears with of 25.9% and 1.6% respectively. The was a statistical significance difference between the age groups in both ears for hearing loss at p-value <0.001. The overall prevalence of hearing loss was found to be 32.9% and hearing loss at 20dB or more loss at any frequency was low at 11.9% while hearing loss at 10B or more loss at any frequency was the highest at 32.9% followed by loss response at 3 consecutive frequencies at 26.2%. Hearing loss was increasing with increasing age from 8.3% in age group and age was significantly associated with hearing loss as older patients were 2.2 times more likely to have a hearing loss at a degree of 20dB and 4.4 times more likely to have a hearing loss at a degree of 10dB. Previous use of injectables was also significantly associated with hearing loss as patients who used injectables previously were 11.5 times more likely to have a hearing loss at degree of 10dB, 5.6 and 11.3 times more likely to have a hearing loss at loss response at 3 consecutive frequencies and overall hearing loss respectively. Conclusion South Africa has a high burden of drug-resistant tuberculosis (DRTB) and until recently, ototoxic aminoglycosides were predominant in treatment regimens. Drug resistant TB treatment with bedaquilines caused clinically and statistically significant deterioration of hearing loss in patients, most prominently at high frequencies. Although public health interventions to prevent hearing loss have been deemed cost effective and have meaningful individual and economic implications, hearing loss and its prevention consistently receive inadequate attention as a global public health priority. Despite the serious impacts of hearing loss, little is known regarding prevalence of ototoxic hearing loss after treatment for DR-TB. Therefore, when the use of injectable ototoxic medications is unavoidable, audiological ototoxicity monitoring is essential to optimise hearing-related outcomes.

Thesis (MPH. (Epidemiology)) -- University of Limpopo, 2022 / Background: Tuberculosis (TB) is a fatal disease globally, if not managed well, with a million or more people dying by the disease annually in low and middle-income countries (LMIC). Around two billion people are thought to be asymptomatically (latently) infected with Mycobacterium tuberculosis, putting them at risk of acquiring active tuberculosis. Tests that identify immunoreactivity to mycobacterial antigens rather than live bacteria, as well as mathematical modelling, are used to estimate the prevalence of latent tuberculosis infection. According to reports, tuberculosis (TB) was the cause of 1.3 million fatalities among HIV-negative people in 2016, surpassing the global number of HIV/acquired immune deficiency syndrome (AIDS) deaths. In addition, TB was a factor in 374,000 HIV-related deaths. Despite the effectiveness of chemotherapy over the last seven decades, tuberculosis remains the world's leading infectious killer. In 2016, 10.4 million new cases were reported, a number that has remained constant since the dawn of the twenty-first century, confounding public health specialists tasked with designing and implementing measures to lessen the global burden of tuberculosis disease. As a result, the current study aims to look into the epidemiology of tuberculosis in Lesotho in order to help policymakers make decisions on TB control in the country. Methodology:. In the current investigation, a cross-sectional, retrospective descriptive study design was used, as well as a probability sampling strategy. The National TB-Database from the Ministry of Health in Lesotho was used as the source of data for this quantitative investigation, which was analyzed using STATA statistical software version 12 for Windows (STATA Corporation, College Station, Texas). A Chi-Squared test was used to compare categorical variables, while a t-test was used to examine continuous variables. A statistically significant P-value of 0.05 was used. Results: A total of 18 836 TB patient records were recovered, with 45 percent of the TB patients being females. The average age of the TB patients was 35.9 years, with a standard deviation of 12.7%, and the ages ranged from one year to 84 years. There vi was a statistically significant difference between the age groups (p value 0.001), with 33.1 percent of TB patents being in the age group 25–34 years, followed by 29 percent, 15.4 percent, 11.2 percent, and 5.5 percent in the age groups 35–44 years, 45–55 years, 15–24 years, and 55–64 years 65 years.. There has been a fluctuating treatment outcome of TB from 63.5% for cured patients in 2012 to 57.2% in 2013 and this rose to 60.4% in 2014 then eventually reached 76.7% in 2019. The TB treatment success rate in Lesotho also showed a similar trend as the cure rate. The overall TB death rates in the current study was found to be increasing on an annual basis from 7.4% in 2012 to 9.2% in 2018 then dropped to 8.5% in 2019. The TB patients who have not been evaluated for treatment outcomes have been decreasing annually from 4.4% in 2012 to 0.8% in 2019. The proportion of TB patients with known HIV status increased from 22.3% in 2015 to 90.5% in 2019 and similarly to the proportion of TB patients with HIV status positive increased from 15.1% in 2015 to 60.4% in 2019. The proportion of TB patients with HIV status positive increased with increasing age group all age groups. Conclusion: TB is still a concern in Lesotho, where treatment target goals have not yet been fulfilled, the findings of this study underline the importance of addressing the underlying socio-economic causes of TB. The most important goal in TB control is to detect 70% and cure at least 85% of sputum smear positive cases. If these goals are met, the prevalence, incidence, transmission, and medication resistance to tuberculosis (TB) could all decrease. Despite the National Tuberculosis Control Programme's attempts to enhance TB patients' access to treatment and adherence to therapy, the percentage of patients who have good treatment outcomes remains low. Despite having an 84 percent detection rate and using the DOTS technique, the available data did not identify the types of tuberculosis, therefore we were unable to forecast multidrug-resistant tuberculosis (MDR-TB).

The purpose of this study was to determine and compare the outcomes of tuberculosis (TB) treatment among Human Immunodeficiency Virus (HIV) co-infected TB patients, and identify factors associated with these outcomes. A quantitative cross-sectional analytic design was used. Patient level secondary data was collected and analysed for the study. A total of 575 TB patients, including 360 non-HIV infected, 169 HIV co-infected and 46 without a documented HIV status, were enrolled. The overall treatment success rate was 91.5%, and HIV co-infected TB patients had a high rate (11.8%) of unfavourable outcomes. The cure rate was significantly lower (10.1% versus 24.2%) and the death rate higher in HIV co-infected patients (8.3% versus 2.5%). Age and TB classification were significantly associated with treatment outcome. No association was found with starting ART, Cotrimoxazole prophylactic treatment or enrolment in HIV care, but 22% of HIV co-infected TB patients were taking ART when they developed TB disease / Health Studies / M.A. (Public Health)

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