Thesis (MBA)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Childhood tuberculosis is an infectious disease that can cause serious illness and mortality in especially young children. Following contact with an infectious adult tuberculosis case, the disease is easily preventable through preventive isoniazid treatment, yet very few exposed and at-risk children currently access this healthcare service in most high-burden settings. Previous research pointed out the multifactorial and complex nature of the barriers to accessing preventive care. Specifically, the lack of a formalised recording and reporting tool, such as the universally used tuberculosis treatment registers, possibly contribute to the operational barriers of preventive care delivery to these children. The purpose of this research was to evaluate the cost-effectiveness of an isoniazid preventive treatment register tool used at community level. The study utilised previously reported data from the study population and other high-burden settings to construct a decision analysis model that included varying probabilities of isoniazid preventive treatment across three high risk age groups (<1 year of age, 1 – 2 years of age, 3 – 5 years of age), coupled with disease probabilities and associated treatment costs. The scenarios simulated included 1) the routine isoniazid preventive treatment service (3% started on treatment, 17% identified as eligible); and 2) an isoniazid preventive treatment service supported by a recording register (15% (adherent to six months of treatment) and 38% (started on IPT treatment)). In addition, two hypothetical simulations were included for 76% and 100% isoniazid preventive treatment uptake; these hypothetical simulations required additional community based healthcare worker resources in addition to the register tool. The observations from the literature indicated that more children were identified (24(17%) vs. 54(38%)) and started (4(3%, base case) vs. 54) on isoniazid preventive treatment following the implementation of the register. As expected, the mean number of tuberculosis cases prevented, increased as the proportion of eligible children that received isoniazid preventive treatment, improved; the change in the number of cases prevented per simulation showed incremental improvements which were all significantly better (p<0.01) than the base case.. The incremental cost-effectiveness ratios incurred savings for each of the scenarios simulated since the mean costs for each of the simulations were significantly less (p<0.01) than the costs associated with the base case. The current evidence suggests that the proposed isoniazid preventive treatment register tool is a cost-effective alternative to the current standard of care in place at community level for at-risk children exposed to tuberculosis. It is therefore recommended that the tool be used incrementally on a bigger scale, until such time that sufficient evidence has been generated to support widespread implementation.

Thesis (MScMedSc)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Anti-tuberculosis drugs target specific essential cellular processes and structural components. The first line drug, rifampicin (RIF) is a RNA polymerase inhibitor which targets the β-subunit and subsequently inhibits the initiation of transcription. Previous proteomic and transcriptomic analyses have shown that exposure to RIF for 24hrs significantly increased the abundance of proteins involved in energy metabolism in clinical isolates. No studies have been done to describe the transcriptional responses to RIF in an in vitro RIF resistant M. tuberculosis isolate. Application of in vitro mutants is novel since it will exclude most of the confounding factors which may be present in clinical isolates obtained from patients where the bacterium may have been incubated for several weeks or even years. This study aimed to determine the effect of prolonged exposure to RIF and the effect of the rpoB Ser531Leu mutation on the expression of energy metabolism genes, sigma factors and a regulator in RIF mono-resistant in vitro mutants with different levels of RIF resistance (minimum inhibitory concentration (MIC): 40μg/ml and 70μg/ml). RIF mono-resistant in vitro mutants were generated from a pan susceptible Beijing cluster 208 progenitor using the Luria Delbruck assay. In vitro RIF mono-resistant mutants harbouring the Ser531Leu rpoB mutation and which displayed different levels of RIF resistance were selected. To assess the effect of prolonged RIF exposure on the expression of candidate genes, the in vitro mutants were cultured in liquid media and exposed to RIF for 1, 7 and 14 days. High quality RNA was extracted from these cultures at each time point and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) was done on the selected candidate genes. The results indicate that limited expression of energy metabolism genes and sigma factors was observed after prolonged RIF exposure. In addition, the activity of the regulator (Rv1846c) was down-regulated in the presence of RIF explaining the up-regulated state of energy metabolism genes. To assess the effect of the rpoB Ser531Leu mutation on the candidate genes, RNA was extracted from the RIF unexposed culture at mid-log phase. RT-qPCR was done for each in vitro mutant in addition to the wild-type progenitor isolate. These results show that energy metabolism genes and sigma factors were significantly up-regulated in the RIF resistant mutantss harbouring an rpoB Ser531Leu mutation. This suggests that the mutation had a significant effect on the cellular energy cost due to the up-regulated state of the energy metabolism genes. In addition, an increase in the expression of sigma factors may be required to compensate for the rpoB mutation by enforcing the binding of the RNA polymerase and sigma factors to the promoter for transcription to be initiated. It is therefore important to assess these candidate genes for their potential as novel candidates for future drug design as this is an important aspect to influence tuberculosis control. / AFRIKAANSE OPSOMMING: Teen-tuberkulose middels teiken essensiële sellulêre prosesse en strukturele komponente. Die eerste linie teen-tuberkulose middel, rifampisien (RIF) is ʼn RNS polimerase inhibeerder wat die β-subeenheid teiken en daarna die inisiasie van transkripsie onderdruk. Vorige proteomiese en transkriptomiese analises het getoon dat blootstelling aan RIF vir 24 uur beduidende styging in sekere protiene wat verband hou met energie metabolisme in kliniese isolate veroorsaak. Die huidige studie poog om die effek van langdurige RIF blootstelling, asook die effek van die rpoB Ser531Leu mutasie op die uitdrukking van energie metabolisme gene, sigma faktore en reguleerders op RIF-enkel weerstandige in vitro mutante by verskillende vlakke van RIF weerstandigheid (Minimum Inhiberende Konsentrasie (MIK): 40μg/ml en 70μg/ml) te ondersoek. RIF-enkelweerstandige in vitro mutante isolate is gegenereer van ʼn sensitiewe Beijing 208 stamfamilielid deur die Luria Delbruck metode. In vitro RIF enkelweerstandige mutante met die rpoB Ser531Leu mutasie en verskillende vlakke van RIF weerstandigheid is geselekteer. Om die langdurige effek van RIF blootstelling op kandidaat geen uitdrukking te ondersoek, is in vitro mutante isolate gegroei in vloeibare medium en blootgestel aan RIF vir 1, 7 en 14 dae. Goeie kwaliteit RNS is geëkstraheer van hierdie kulture by elke tydpunt om Werklike-tyd Kwantitatiewe Polimerase Ketting Reaksie (RT-qPCR) op die kandidaat gene uit te voer. Die resultate toon dat ʼn beperkte aantal energie metabolisme en sigma faktor gene uitgedruk was na RIF blootstelling. Verder is die uitdrukking van die reguleerder (Rv1846c) af gereguleer in die teenwoordigheid van RIF en dit verduidelik die op gereguleerde energie metaboliese geen patroon. Om die effek van die rpoB Ser531Leu mutasie op die kandidaat gene te evalueer, is RNS geëkstraheer van ʼn weerstandige en RIF sensitiewe kultuur wat nie blootgestel was aan RIF nie. RT-qPCR is uit gevoer op elke in vitro mutante isolaat asook op ʼn sensitiewe isolaat sonder ʼn mutasie. Hierdie resultate toon dat energie metabolisme gene en sigma faktore beduidend opreguleer word in die isolate met ʼn rpoB Ser531Leu mutasie. Dit dui daarop dat die mutasie ʼn beduidende effek op die sellulêre energie koste het, omdat die energie metabolisme gene op gereguleer is. Verder kan ʼn toename in die uitdrukking van sigma faktore benodig word om die effek van die rpoB mutasie te oorkom deur binding van die RNS polimerase en die sigma faktore aan die promotor om transkripsie inisiasie te forseer. Dit is daarom belangrik om hierdie kandidaat gene verder te ondersoek vir toekomstige ontwikkeling van teenmiddels teen tuberkulose.

This study investigated factors influencing the quality of data for the Tuberculosis (TB) control programme in Oshakati District in Namibia. A quantitative, cross-sectional descriptive survey was conducted using 50 nurses who were sampled from five departments in Oshakati State Hospital. Data was collected by means of a self-administered questionnaire. The results indicated that the majority (90%) of the respondents agreed that TB training improved correct recording and reporting. Sixty percent of the respondents agreed that TB trainings influenced the rate of incomplete records in the unit, while 26% of the respondents disagreed with this statement. This indicates that TB trainings influence the quality of data reported in the TB programme as it influences correct recording and completeness of data at operational level. Participants’ knowledge on TB control guidelines, in particular the use of TB records to, used to capture the core TB indicators influenced the quality of data in the programme. The attitudes and practises of respondents affected implementation of TB guidelines hence, influencing the quality of data in the programme. The findings related to the influence of the quality of data in the TB programme and its effect to decision-making demonstrated a positive relationship (p=0.0023) between the attitudes of study participant on the use of data collected for decision-making. Knowledge, attitudes and practice are the main factors influencing the quality of data in the TB control programme in Oshakati District. / Health Studies / M.A. (Public Health)

Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

MPH / Department of Public Health / Background: TB and HIV/AIDS were identified as priority healthcare problems of current years worldwide. Notable concerns (2878) were raised in Vhembe District Municipality because of an increase in patients with TB, including re-treatment patients (Department of Health, 2017). Purpose: The main aim of the study was to investigate the factors associated with the increase of new TB infection among clients in Thulamela Municipality, South Africa. Methodology: A quantitative descriptive survey design was used to conduct this study. Census sampling or total population sampling technique was used to select the respondents who were patients seeking treatment for TB from the designated clinics within Thulamela. Self-administered questionnaire was used to collect data from respondents. Data were analyzed using statistical package for social sciences version 25.0. Results: out of a high proportion of the respondents 45 % (n=98) respondents were taking ARV treatment while 27% (n=58) were taking respiratory disease treatment at the time of TB diagnosis. Moreover, 59% (n=169) respondents reported being next to a coughing person before diagnosed with Tuberculosis. Conclusion and recommendations: The results discovered that most respondents stayed in the dusty area for more than three years. Educating the community about how staying and working in dusty areas contribute to TB infection may decrease the rate of infection. / NRF

BACKGROUND: The prevalence of tuberculosis (TB) has been rapidly on the ascendency in the recent years globally due to its co-infection with HIV/AIDS. TB case finding is one of the technical pillars of the Directly Observed Treatment Short course (DOTS) TB strategy and there has been advocacy for early TB case detection to be the new focus of TB control efforts. PURPOSE: The purpose of this non-experimental study was to assess the determinants of TB case finding among pulmonary TB patients registered for treatment in Makana Municipality METHOD: A quantitative, non-experimental, cross sectional descriptive study among PTB patients registered for treatment at the primary health care clinics in Makana Municipality was done. Data collection was by self-administered questionnaires while sampling was by systematic sampling of PTB patients at five systematically selected clinics. RESULTS: Patient–related delay contributed more to total delay, in this study sample, than health system-related delay. Health system delay was found to be significantly associated with poorer finances, passive smoking history, seeking care from multiple health providers, initially visiting a non- NTCP health provider, TB stigma , overcrowding in the household and having difficulty with breathing as an initial symptom (p<0.05). CONCLUSION: There was a significant delay in TB case finding among PTB patients in this local municipality and patient related determinants contributed more than health system related determinants to this delay. There is need for the municipal TB programme to embark on an aggressive health education programme to furnish the populace with accurate information about TB, improve their health seeking behaviour and help address the issue of stigma associated with TB. / Health Studies

Thesis (MScMedSc) -- Stellenbosch University, 1998. / Bibliography / ENGLISH ABSTRACT: There is a progressive maturation of the immune system from infancy to adulthood. The immature immune system in early life is characterised by impaired macrophage function and antigen presentation as well as a higher naIve to memory T cell ratio with subsequent diminished IFN-y production. Children with tuberculosis often present with lymphadenopathy, the complications thereof or with systemic spread of the organisms. Adults generally manifest with pronounced systemic effects (such as weight loss and high fever) and immunopathology (such as cavitation and fibrosis). We hypothesised that the immunopathology in adults may be due to enhanced cytokine production in comparison to children. The first aim of this study was therefore to measure cytokine responses in healthy children and adults. Cytokine responses in patients with tuberculosis will be examined in future studies. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood obtained from 9 healthy children and 9 healthy adults. The cells were cultured in serum-free medium, unstimulated or polyclonally stimulated with Phytohaemagglutinin (PHA). Supernatants were harvested after which IFN-y, IL-2, TNF-a., IL-4 and IL-IO production was determined by means of ELISA analysis. Ri'J"A was ~ubsequently extracted from the cells followed by RT-PCR analysis for the semiquantitative determination of mRNA levels of these cytokines. PBMC isolated from healthy children produced significantly less IFN-y protein than adults. Futhermore, IFN-y production in the adults seemed to be trimodally distributed. No significant differences could be found in the production of IL-2, TNF-a, IL-4 and IL-] O. Although children produced low levels of IFN-y protein, their IFN-y, TNF-a, IL-2, IL-4 and IL-IO mRNA levels were comparable to that of adults. Tuberculosis is a major cause of mortality and morbidity, particularly in the third world. Ravensmead and Uitsig, two adjacent suburbs in the Western Cape, have a tuberculosis incidence of> I 000/100000 population. Also, up to 90 % of the children in the Western Cape have been reported to be infested by intestinal parasites such as Ascaris lumbricoides and Trichurius trichl/ria. Infection with M tuberculosis indut:es a Th 1 Stellenbosch University http://scholar.sun.ac.za iv In:.,c response, while intestinal parasites elicit a Th2 immune response. Th2 dominance induced by intestinal parasite infestations could predispose individuals to an enhanced susceptibility to M. tuberculosis. The second aim of this study was to investigate serum IgE levels, surrogate markers for Th2 activation, in the community. The serum 19B levels were subsequently correlated to the tuberculosis incidence per enumerator sub-district (ESD), crowding, female literacy and socio-economic levels. Similarly, the tuberculosis incidence per ESD was correlated with the above mentioned parameters. A significant positive correlation was found between tuberculosis incidence and the serum 19E levels in the community. However, further studies are needed to determine if intestinal parasites are the main cause of the high 19B levels in the community and to dCh111ine if parasite loads or Th2 dominance are causally linked to the incidence of tuberculosis. Correlation between serum 19E levels and tuberculosis incidence with the other parameters were significant, except in the case of crowding. The third aim of this study was to measure serum IgE and specific 19E levels against Ascaris and common allergens on presentation of tuberculosis and again after completion of successful treatment. Significant declines in serum 19B and Ascaris specific 19B levels were observed after completion of tuberculosis treatment. This down regulation of IgE levels may be due to an up regulation of ThI responses in patients following successful treatment for tuberculosis. / AFRIKAANSE OPSOMMING: Die immuunsisteem matureer toenemend vanaf kinderjare tot en met volwassewording. Die onvolwasse immuunsisteem van jong kinders word gekenmerk deur verswakte makrofaag-funksionering en antigeenpresentering, sowe) as 'n verhoogde naiwe tot geheue T-sel verhouding met gevolglikc verminderde IFN-y produksie. Kinders met tuberkulose presenteer gewoonlik met Iimfadenopatie, komplikasies daarvan of met gedissemineerde siekte. Volwassenes presenteer met sistemiese gevolge (soos gewigsverlies en hoe koors) en immunopatologie (soos kavitasie en fibrose). Ons hipotese is dat die immunopatologie in volwassenes die gevolg is van 'n verhoogde sitokienproduksie in vergelyking met kinders. Die eerste doelwit van die studie was om sitokienproduksie in gesonde kinders en volwassenes te meet. Sitokienproduksie in tuberkulose pasiente sal in 'n opvolgstudie bepaal word. Perifere bloed mononukleere selle was geisoleer vanuit heel bloed verkry vanaf 9 gesonde kinders en 9 gesonde volwassenes. Die selle was gekweek, ongestimuleer of gestimuleer met Phytohaemagglutinien (PHA). Supernatante was geoes vir die bepaling van IFN-y, IL-2, IL-4, IL-I0 en TNF-a. produksie, deur gebruik te maak van ELISA analise. RNA was gevolglik vanaf die selle ge-ekstraheer vir die tru-transkriptase polimeerketting reaksie analise, waartydens sitokien mRNA vlakke op 'n semi-kwantitatiewe wyse bepaal was. Perifere bloed mononukleere selle geisoleer vanaf die kinders het minder IFN-y geproduseer as die van volwassenes. Hierdie verminderde produksie was hoogs betekenisvol. Dit wou voorkom asof die IFN-y produksie deur volwassenes trimodaal versprei was. Geen betekenisvolle verskille tussen kinders en volwassenes kon gevind word in die produksie van IL-2, IL-4, IL-IO en TNF-a nie. Alhoewel kinders minder IFN-y proteien geproduseer het, het hulle IFN-y, IL-2, IL-4, IL-JO en TNF-a mRNA produksie met vlakke van volwassenes ooreengestem. Tuberkulose speel 'n groat rol in morbiditeit en mortaliteit in veral die derde wereld. Ravensmead en Uitsig, twee aangrensende voorstede in die Wes-Kaap, het 'n tuberkulose voorkomssyfer van> 1 000/1 00000 populasie. Verder, is tot 90 % van die kinders in die Stellenbosch University http://scholar.sun.ac.za VI Wes-Kaap gei'nfesteer met intestinale parasiete soos Ascaris Ilimbricoides en Trichllrills trichllria. M. tuberculosis infeksie induseer 'n Thl immuunrespons, terwyl intestinale parasiete 'n Th2 immuunrespons uitlok. 'n Dominante Th2 respons mag moontlik individue predisponeer tot 'n verhoogde vatbaarheid vir M. tuberculosis. Gevolglik was die tweede doelwit van die studie om serum IgE vlakke as surrogaat merkers vir Th2 aktivering in die gemeenskap bestudeer. Die serum IgE vlakke was gevolglik gekorreleer met die tuberkulose voorkoms per opnemerssensusgebied (OSG), saamdringing, vroulike geletterdheid en sosio-ekonomiese vlakke. Die tuberkulose voorkoms per OSG, is op dieselfde wyse gekorreleer met die bogenoemde parameters. 'n Betekenisvolle positiewe korrelasie is gevind tussen tuberkulose voorkoms en serum IgE vlakke in die gemeenskap. Verdere stuciies is egter nodig om te bepaal of intestinale parasiete weI die oorsaak van die hoe IgE vlakke in die gemeenskap is en of parasiet ladings of Th2 dominansie oorsaaklik verbind kan word aan die tuberkulose voorkoms. Die derde doelwit van die studie was om serum 19E en spesifieke IgE vlakke teen Ascaris en algemene allergene te meet met presentering van tuberkulose en weer na voltooing van suksesvolle behandeling. 'n Betekenisvolle afname in serum 19E en Ascaris spesifieke 19E vlakke is waargeneem na vohooing van tuberkulose behandeling. Die afregulering van 19E vlakke kan moontlik toegeskryf word aan die opregulering van Th1 response in pasi"ente na voltooing van suksesvolle behandeling van tuberkulose.

Thesis (MPhil (Communicable Diseases)) (Dept of Interdisciplinary Health Sciences. Community Health))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: Global control of the tuberculosis (TB) epidemic remains one of the greatest health challenges of the 21st century, despite the availability of effective treatment over the past 50 years. The rising incidence of transmitted (primary) drug resistant TB threatens the very fabric of conventional TB control efforts, which are already strained by a rampant human immunodeficiency virus (HIV) epidemic. Ongoing transmission of Mycobacterium tuberculosis is a key factor that sustains the TB epidemic in endemic areas such as the socio-economically deprived townships of Cape Town, South Africa. My research explores the disease context, or social terrain, of TB in this endemic setting. It is primarily concerned with how the social terrain of endemic TB may contribute to ongoing transmission and the potential that it holds for enhancing TB control efforts. Analyses of qualitative data from eight township research sites in and around Cape Town show that pragmatic and novel approaches are required to pierce through the enormity of TB as a political and economic problem. Broadening the current biomedical focus on treating individual patients, to include more holistic community-based interventions, can and should be developed. Data were collected as part of qualitative pre-intervention community surveys conducted in 2005 and 2006 for a public health intervention trial (ZAMSTAR) performed in Zambia and South Africa. Twenty-four communities were selected as research sites and this study draws on the survey data collected in the trial’s eight South African sites. Although the data were collected for the ZAMSTAR trial, the aims and analyses presented in this study - which seek to improve our understanding of how the social terrain is meaningful for TB control - remain independent of ZAMSTAR. Through a retrospective analysis of the South African data, I inductively present three distinctive ways in which the social terrain is meaningful for TB control. First, the interaction between social cohesion and social diversity may be an important variable that predicts community response to public health interventions aimed at reducing the prevalence of TB in these endemic areas. This is demonstrated by triangulating ZAMSTAR’S adaptation of a social systems model with further analysis of the research sites. Second, the study identifies a common discourse running through the sites that stigmatizes TB as both a dirty and HIV-related disease. It is argued that this may be significantly contributing to TB diagnostic delay and I call for more holistic approaches to TB control that can reduce perceived marginalization and TB-HIV stigma. Third, congregate settings emerge as noteworthy visible features of social terrain that clearly have the potential to facilitate TB transmission within communities. The pre-intervention surveys qualitatively described public spaces within each research site and the use thereof. Basic principles of TB transmission are applied to these descriptions, developing a novel method of mapping the relative transmission risk possibly posed. Innovative use of similar approaches could identify likely transmission “hot spots” that may serve as focal points for targeted interventions, such as adjustments that increase ventilation or encourage TB suspects to seek urgent medical diagnosis and treatment. / AFRIKAANSE OPSOMMING: Die beheer van tuberkulose (TB) bly steeds een van die grootste gesondheids uitdagings van die 21ste eeu, ten spyte van die beskikbaarheid van effektiewe behandeling vir die afgelope 50 jaar. Die stygende insidensie van oorgedraagde (primêre) middelweerstandige TB bedreig die wese van konvensionele TB kontrole programme, wat reeds gebuk gaan onder die oorweldigende impak van die menslike immuungebrek virus (MIV) epidemie. Ononderbroke oordrag van Mycobacterium tuberculosis is ‘n kardinale faktor wat die epidemie onderhou in areas soos die sosioekonomies agtergeblewe dele van Kaapstad, Suid-Afrika. My navorsing ondersoek sosiale terrein (konteks) van TB in hierdie hiperendemiese konteks. Dit is primêr gemoeid met die moontlike bydrae van die sosiale terrein tot voortgaande TB oordrag en die potensiaal wat dit mag inhou om TB kontrole te verbeter. Analise van kwalitatiewe data van agt agtergeblewe gemeenskappe in en om Kaapstad wys dat nuwe en pragmatiese benaderings benodig word om die volle omvang van TB as ‘n politieke en ekonomiese problem aan te spreek. Data is versamel as deel van kwalitatiewe pre-intervensie gemeenskapsopnames wat gedoen is gedurende 2005 en 2006 vir ‘n publieke gesondheid intervensie studie (ZAMSTAR) in Zambië en Suid-Afrika. Die studie sou poog om die TB prevalensie betekenisvol te verlaag in gemeenskappe wat erg geaffekteer word deur MIV. Vir navorsings doeleindes is vier-en-twintig gemeenskappe geselekteer, waaronder agt Suid-Afrikaanse gemeenskappe. My studie analiseer kwalitatiewe data wat versamel is in hierdie agt gemeenskappe, wat verskeie observasie en deelnemende tegnieke ingespan het. Die studie poog om algemene begrip te verbeter van hoe die sosiale terrein betekenisvol kan wees in TB kontrole; dit is my eie werk en is totaal onafhanklik van die groter ZAMSTAR studie. Induktiewe retrospektiewe analise van data identifiseer drie voorbeelde wat illustreer hoe die sosiale terrein betekenisvol mag wees vir TB kontrole. Eerstens, die interaksie tusses sosiale kohesie en sosiale diversiteit mag ‘n belangrike verandelike wees wat gemeenskapsrespons tot publieke gesondheidsintervensies voorspel. Dit word geïllustreer deur die toepassing van ‘n sosiale sisteme model (soos aangepas deur ZAMSTAR) en analise van ander aanvullende data. Tweedens, identifiseer die studie ‘n gemeenskaplike diskoers in alle navorsings gemeenskappe wat TB stigmatiseer as beide ‘n vuil en MIV-verwante siekte. Dit word geargumenteer dat hierdie verskynsel moontlik betekenisvol bydra tot vertraging van TB diagnose en die nodigheid vir meer holistiese benaderings wat marginalisasie en TB-HIV stigma kan verminder word uitgewys. Derdens blyk dit dat openbare vergaderplekke ‘n belangrike deel van die sosiale terrein vorm en duidelik die potensiaal het om TB oordrag binne gemeenskappe te fasiliteer. Die pre-intervensie opnames het alle openbare vergaderplekke sorgvuldig beskryf en basiese beginsels van TB oordrag is gebruik om vergaderplekke geografies te kaart volgens die moontlike transmissie risiko wat dit mag inhou. Innoverende gebruik van GIS-gebasseerde benaderings, soortgelyk aan die metode wat gebruik is om potensiële “transmission hot spots” te kaart, mag bydra om intervensies beter te fokus, deur bv. verbeterde ventilasie te verskaf of mense met simptome van TB aan te moedig om dringend mediese hulp te soek.

Thesis (PhD (Biomedical Sciences. Molecular Biology and Human Genetics))--Stellenbosch University, 2008. / This series of studies includes both methodological analyses, aimed at furthering our understanding of, and improving the tools used in molecular epidemiology, and investigative projects which have used these tools to add to our knowledge of the M. tuberculosis epidemic. Using serial isolates from tuberculosis patients, we have investigated the evolutionary rate of the IS6110 RFLP pattern. In accordance with other studies, we determined a ½-life for this epidemiological marker of 10.69 years, confirming its appropriateness for this purpose. We also identified an initial, much higher apparent rate which we proposed was the result of pre-diagnostic evolution. In support of this, our investigations in the context of household transmission of M. tuberculosis revealed that IS6110-based evolution is closely associated with transmission of the organism, resulting in a strain population rate of change of 2.9% per annum. To accommodate evolution within estimates of transmission, we proposed that calculations incorporate the concept of Nearest Genetic Distance (cases most similar in RFLP pattern and most closely associated in time). We used this to create transmission chains which allowed for limited evolution of the IS6110 marker. As a result, in our study community, the estimated level of disease attributable to ongoing transmission was increased to between 73 and 88% depending on the Genetic Distance allowed. We identified the duration of a study as a further source of under-estimation of transmission. This results from the artefactual abridgement of transmission chains caused by the loss of cases at the temporal boundaries of a study. Using both real and simulated data, we showed that viewing a 12-year study through shorter window periods dramatically lowered estimates of transmission. This effect was negatively correlated with the size of a cluster. Various combinations of MIRU-VNTR loci have been proposed as an alternative epidemiological marker. Our investigations showed that, while this method yielded estimates of transmission similar to those of IS6110, there was discordance between the two markers in the epidemiological linking of cases as a result of their independent evolution. Attempting to compensate for this by allowing for evolution during transmission improved the performance of IS6110, but generally had a deleterious effect of that of MIRU-VNTR. However, this marker remains a valuable tool for higher phylogenetic analysis and we used it to demonstrate a correlation between sublineages of the Beijing clade and the regions in which they are found. We proposed that, either the host population had selected for a particular sublineage, or that specific sublineages had adapted to be more successful in particular human populations. We further explored the dynamics of the epidemic over a 12-year period in terms of the five predominant M. tuberculosis clades. We found that, while four of these clades remained relatively stable, the incidence of cases from the Beijing clade increased exponentially. This growth was attributed to drug-sensitive cases although drug-resistant Beijing cases also appeared to be more successful than their non-Beijing counterparts. Possible factors contributing to this clade’s success were a greater proportion of positive sputum smears and a lower rate of successful treatment.

PhD / Department of Public Health / See the attached abstract