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Identification of immune correlates of natural protection against tuberculosis in a population with a high incidence of latent infectionGolakai, Hawa Jande 03 1900 (has links)
Thesis (MScMed)--Stellenbosch University, 2008. / ENGLISH ABSTRACT: Setting
This study was conducted in the Tygerberg area of Cape Town in South Africa.
Background
A third of the world’s population is latently infected with Mycobacterium tuberculosis,
and correlates of protection against progression to active disease urgently need to be
identified to facilitate the development of an effective vaccine against the disease. The
production of IFN-γ is recognised as an immune correlate of protection from tuberculosis,
but other immune regulators have been implicated in playing a significant role in
protective immunity. The aims of this project were three-fold: (i) to identify promising
TB vaccine candidates by screening a panel of novel MTB antigens, by stimulating whole
blood cultures in vitro with the novel proteins and quantifying the level of IFN-γ
production, (ii) to identify other cytokines and chemokines that may be immune
correlates of protection using the Luminex fluorescent bead-based technique and (iii) to
compare the performance of the two techniques.
Methods
Antigen Screening study
Whole blood of 57 adult and adolescent participants defined as latently infected
individuals was stimulated with a panel of 78 novel TB-specific, DosR- or RD1-encoded
antigens. The 7-day culture supernatants were used in IFN-γ ELISA to quantify the level
of IFN-γ production. Luminex Assay study
Whole blood culture supernatants of 15 HIV negative, TST positive adults were used in
the Luminex LINCO 21-plex cytokine assay. This was done to determine which of 21
cytokines, that may be LTBI-associated cytokines, were produced after stimulation with 9
TB-specific recombinant antigens, and to quantify their level of expression.
Results
In the antigen screening study, it was found the majority of the 78 proteins tested were
able to induce a positive IFN-γ response. The classic TB antigens were used as controls,
and the frequency of responses was highest after stimulation with ESAT-6 and
TesatCFP10 (80 – 85% of responders). Ten latency antigens elicited an IFN-γ response in
19 – 45% of participants, and five reactivation antigens stimulated a positive reaction in
15 – 48% of responders. The category of antigens that elicited the most frequent and
highest responses overall was the resuscitation-promoting factors (Rpf). Over 30% of
participants responded to all 5 Rpfs, and the level of responses were equally divided in
the low and moderate-to-high levels, with an additional 5% of responses in the high
(>1000pg/ml) range.
In the Luminex study, the positive stimulant TesatCFP10 consistently induced expression
of most cytokines. In addition latency antigens Rv1733c, Rv0569 and Rv2029c also
induced moderate-to-high level cytokine expression. A Th1-biased cytokine profile was
observed, with the preferential expression of pro-inflammatory and cell-mediated
cytokines like IFN-γ, TNF-α, IP-10, MIP1-α and G-CSF being produced. Th2 cytokines
IL-4, IL-5, IL-13 and eotaxin were very poorly expressed or were not expressed at
detectable levels. A very strong induction of IL-6, IL-8 and MCP-1 was observed, but this cytokine/chemokine association suggested contamination of the recombinant antigens
with bacterial endotoxins.
Conclusion
In this study of latently infected individuals, the pattern of response observed for both
assays is largely a Th1-biased expression profile. The whole blood ELISA method is a
well-established assay for quantifying IFN-γ in culture supernatants, and has proven to be
effective here. This study has demonstrated, in humans with LTBI, immune recognition
of these novel MTB-specific antigens as illustrated by the positive IFN-γ levels induced
after stimulation. The multiplex technology is also a very versatile and sensitive assay,
capable of detecting multiple analytes simultaneously in one sample. The multiplex has
been valuable here in identifying some antigens as potential vaccine candidates, and a
subset of cytokines as potential immune mediators and prognostic indicators in TB
infection. / AFRIKAANSE OPSOMMING: Studie-area Hierdie studie was gedoen in die Tygerberg area van Kaapstad in Suid-Afrika. Agtergrond ‘n Derde van die wêreld se bevolking is latent geïnfekteer met Mycobacterium tuberculosis en korrelate van beskerming teen die siekte moet geïdentifiseer word om die ontwikkeling van ‘n effektiewe enstof te fasiliteer. Die produksie van IFN-γ is welbekend as ‘n immuunkorrelaat van beskerming teen tuberkulose (TB), maar ander immuunreguleerders speel ook ‘n belangrike rol in beskermende immuniteit. Die doelwitte van hierdie projek was drievoudig: (i) om belowende TB-entstof kandidate te identifiseer deur die sifting van ‘n paneel van nuwe MTB antigene mbv die in vitro stimulasie van volbloed kulture, ii) om ander sitokiene en chemokiene as immuunkorrelate van beskerming te identifiseer deur van die Luminex fluorescent bead-based tegniek gebruik te maak, en (iii) om die twee tegnieke te vergelyk op grond van hul prestasie as prognostiese of siftings metodes in latente infeksie. Metodes Antigeen siftings studie Volbloed van 57 volwasse en adolessente deelnemers, geïdentifiseer as latent geïnfekteerde individue, was gestimuleer met ‘n paneel van 78 nuwe TB-spesifieke DosR- or R-gekodeerde antigene. Die 7-dae kultuur supernatante was gebruik in ‘n IFN-γ ELISA om die hoeveelheid IFN-γ produksie the kwantifiseer. Luminex assay studie Volbloed kultuur supernatante van 15 HIV negatiewe, TST positiewe volwassenes was gebruik in die Luminex LINCO 21-plex cytokine assay. Dit was gedoen om die tipes en hoeveelheid ander LTBI-geassosieerde sitokienes te identifiseer wat geproduseer word na stimulasie met 9 TB-spesifieke rekombinante antigene. Resultate In die antigeen siftings studie is gevind dat die meerderheid van die 78 getoetste proteïene ‘n positiewe IFN-γ reaksie kon induseer. Vir die kontroles was die frekwensie van reaksies die hoogste na stimulasie met ESAT-6 en TesatCFP-10 (80 – 85% van reageerders). Tien latensie antigene was gereeld herken deur 19 – 45% van deelnemers en vyf reaktiverings-antigene het ‘n positiewe reaksie in 15 – 48% van reageerders gestimuleer. Die kategorie van antigene wat die meeste en hoogste response veroorsaak het, was die resusitasie-promoterende faktors (Rpf). Meer as 30% van deelnemers het op al 5 Rpfs gereageer en die vlak van reaksies was gelyk verdeel in die lae en matig-tot-hoog vlakke, met ‘n addisionele 5% van reaksies in die hoë (>1000pg/ml) reeks. In die Luminex studie het die positiewe stimulant TesatCFP-10 konsekwent die positiewe uitdrukking van die meeste sitokiene geïnduseer. Saam met dit het die latente antigene Rv1733c, Rv0569 en Rv2029c ook matige-toe-hoë vlakke van sitokien uitdrukking geïnduseer. ‘n Th1-gebaseerde sitokien profiel was waargeneem, met die begunstigde uitdrukking van pro-inflammatoriese en sel-gemedieerde sitokiene soos IFN-γ, TNF-α, IP-10, MIP1-α en G-CSF. Th2 sitokiene IL-4, IL-5, IL- 13 en eotaksien was of baie sleg uitgedruk of onder naspeurbare vlakke uitgedruk. ‘n Baie sterk induksie van IL-6, IL-8 en MCP-1 was waargeneem, maar hierdie
sitokiene/chemokiene assosiasie stel moontlik kontaminasie van die rekombinante
antigene met bakteriële endotoksiene voor.
Samevatting
Die reaksiepatroon wat in hierdie studie tussen die twee toetse waargeneem is, was
grootliks ‘n Th1-gebaseerde uitdrukkingsprofiel vir latente infeksie met TB. Die
volbloed ELISA metode is a betroubare gevestigde toets vir die kwantifisering van
IFN-γ in kultuur supernatante, wat ook in hierdie studie bewys is om effektief te wees.
Hierdie studie het gedemonstreer dat die nuwe TB-spesifieke antigene effektief
positiewe IFN-γ response in mense met LTBI induseer. Die multipleks tegnologie is
ook ‘n baie veelsydige en sensitiewe toets, wat in staat is om veelvoudige analite
gelyktydig in een monster te kan opspoor. In hierdie studie was dit veral waardevol
in die identifisering van ander moontlike antigene as prognostiese kandidate en
sitokiene as immuunbemiddelaars in TB-infeksie.
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An integrated development approach for policing : the case of Operation Good - HopeDe Lange, Romeo 12 1900 (has links)
Thesis (MPA)--Stellenbosch University, 2000. / ENGLISH ABSTRACT: This study was embarked upon to identify an alternative approach to policing. It was
an attempt to investigate whether an integrated development approach will be more
successful in preventing crime and violence than heterogeneous police task teams and
operations. Operation Good - Hope in the Western Cape, a SAPS crime prevention
strategy to police the urban terror and related crimes (PAGAD and gang violence),
was the focus of the study.
Plurality of research methodology was introduced to compile data. The data collected
was analysed in relation to the topic and the objective of the study and to the research
hypothesis.
Based on the data analysis the following are the main research findings:
• a working relationship existed between various SAPS components within
Operation Good - Hope, but was not properly managed and coordinated;
• Operation Good - Hope did not allowed for external collaboration with
relevant stakeholders and showed no sense of partnership;
• Operation Good - Hope did not police the social crime problems; and
• Operation Good - Hope was not shaped by a clear analysis and cohesive
strategy.
The findings of the study gave rise to the following recommendations:
• That a local - based strategy for crime prevention be develop and lead by local
government to normalise crime and violence; • That a provincial framework be developed for an integrated development
approach to police and stabalise serious violent crimes;
• That crime prevention solutions must be based on factors that causes crime;
and
• A crime prevention strategy be designed and implemented.
Finally, the study indicates that provincial crime prevention strategies should be
supplementive to local - based crime prevention strategies, to simultaneously
stabalise and normalise crime and violence. / AFRIKAANSE OPSOMMING: Die studie is onderneem om 'n alternatiewe benadering tot polisieëring te identifiseer.
Dit is ook 'n poging om uit te vind of 'n geïntegreerde ontwikkelingsbenadring meer
suksesvol is as hetrogene polisie taakspanne en operasies met die bekamping van
misdaad en geweld. Operasie Goeie - Hoop in die Wes - Kaap, 'n SAPD
misdaadvoorkoming strategie om stedelike terreur en verwante misdade (PAGAD en
bende geweld) te polisieer, was die fokus van die studie.
Data was ingesamel deur middel van 'n pluraliteit van navorsingsmetodologie. Die
ingesamelde data was geanaliseer in verhouding tot die tema, doelwitte van die studie
en met die navorsingshipotese.
Gebaseer op die data analise, is die volgende die hoof bevindinge van die studie:
• Daar was samewerking tussen verskillende SAPD komponente betrokke by
Operasie Goeie - Hoop, maar dit was nie deeglik bestuur en gekoordineer nie;
• Operasie Goeie - Hoop het nie voorsiening gemaak vir eksterne samewerking
en vennootskap met relevante rolspelers nie;
• Operasie Goeie - Hoop het nie die sosiale - misdaad probleme gepolisieër nie;
en
• Operasie Goeie - Hoop was nie bestuur deur 'n deeglike analise en deur 'n
samehangende strategie nie. Die studie het tot die volgende aanbevelings gelei:
• Die ontwikkeling van 'n plaaslike - gebaseerde strategie vir
misdaadvoorkoming onder leiding van die plaaslike regering om misdaad en
geweld te normaliseer;
• Die ontwikkeling van 'n provinsiale raamwerk vir 'n geïntegreerde
ontwikkelingsbenadering tot polisieëring en om ernstige geweldsmisdade te
stabaliseer;
• Dat oplossings tot misdaadvoorkoming gebaseer moet wees op faktore wat
misdaad veroorsaak; en
• Dat 'n misdaadvoorkomingstrategie ontwerp en geïmplimenteer moet word.
Ten slotte toon die studie aan dat 'n provinsiale misdaadvoorkomingstrategie
ondersteunend moet wees tot 'n plaaslike - gebaseerde misdaadvoorkomingstrategie,
om te gelyke tyd misdaad en geweld te stabaliseer en te normaliseer.
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Misdaadvoorkoming in Elsiesrivier : 'n gevallestudieRademeyer, Ignatius M. 12 1900 (has links)
Thesis (MPA)--Stellenbosch University, 2000. / ENGLISH ABSTRACT: The researcher focuses on the contributions made by community involvement, including
community policing and crime prevention strategies, on the prevention of attempted
murder in Elsies River, a gang ridden area.
A theoretical overview of community policing and crime prevention is provided. The
combination of crime prevention strategies, community involvement and role players to
prevent the contribution caused that give rise to crime, receive attention.
Against this background the applicability of social crime prevention - internationally
tested policing strategies included - is discussed in order to review the act of attempted
murder. Furthemore, the application of the solutions presented at ground level receive
attention and reasons are offered for the successful implementation of the Elsies River
Community- Police Crime Prevention Action Plan in 1998. The reality is compared to the
theory and conclusions are drawn concerning the handling of the problem.
Gang activities in Elsies River and the impact thereof on the reporting of attempted
murder is summarised. The Elsies River Community- Police Crime Prevention Action Plan
which was implemented between April and June 1998, is discussed and the influence
thereof on the reporting of attempted murder is analysed statistically.
In conclusion the findings of the research are enunciated and recommendations are
made to the successful prevention of crime. / AFRIKAANSE OPSOMMING: In hierdie werkstuk word die voorkoming van poging tot moord in Elsiesrivier, 'n
bendegeteisterde gebied, deur middel van gemeenskapsbetrokkenheid,
gemeenskapspolisiëring ingesluit, en misdaadvoorkomingstrategieë ondersoek.
'n Teoretiese oorsig van gemeenskapspolisiëring en misdaadvoorkoming word gegee.
Die kombinering van misdaadvoorkomingstrategieë, gemeenskapsbetrokkenheid en die
betrokkenheid van rolspelers om die aanleidende faktore wat tot misdaad lei te
voorkom, geniet aandag.
Teen hierdie agtergrond word die toepaslikheid van sosiale misdaadvoorkoming, waarby
ingesluit internasionaal getoetste polisiëringstrategieë, bespreek om die voorkoms van
poging tot moord aan te spreek. Voorts geniet die toepassing van die voorgestelde
oplossings op grondvlak aandag en redes word aangevoer waarom die implementering
van die Elsiesrivier Gemeenskap- Polisie Misdaadvoorkomingsaksieplan in 1998 so
suksesvol was. Die praktyk word met die teorie vergelyk en gevolgtrekkings word
gemaak rakende die hantering van die probleem.
Bendebedrywighede in Elsiesrivier en die impak daarvan op die aanmelding van poging
tot moord word oorsigtelik behandel. Die Elsiesrivier Gemeenskap- Polisie
Misdaadvoorkomingsaksieplan wat gedurende April tot Junie 1998 geïmplementeer was,
word bespreek - die invloed wat dié strategie op die aanmelding van poging tot moord
gehad het, word statisties ontleed.
Ten slotte word die bevindings van die navorsing weergegee en aanbevelings word
gemaak om misdaad suksesvol te voorkom.
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An evaluation of the cost-effectiveness of the introduction of an isoniazid prophylaxis treatment (IPT) register for tuberculosis contact management in children less than five years of age in a high-burden community healthcare clinic (CHC) setting in the Western Cape, South AfricaVan Soelen, Nelda 12 1900 (has links)
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.
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The capacity building programme for youth at risk in the Western Cape: A community-based alternative for rehabilitation and reintegraton.Palmer, Michele January 2004 (has links)
There is a growing sense of apathy and lack of focus amongst the youth, which contributes to the threat of social integration. Constructive alternatives are therefore needed to curb gangsterism, drug abuse and other criminal activities among youth at risk. It has become imperative to challenge the present situation in which crime has become one of the most attractive options facing our youth. Through a programme of contructive engagement, a substantial difference can be made in their rehabilitation and ultimately their active participation in building a safer society. A strong emphasis should be placed on the development and implementation of effective restorative justice principles, alternative sentencing and community-based rehabilitation programmes, particularly for young people in marginalised communities.
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The capacity building programme for youth at risk in the Western Cape: A community-based alternative for rehabilitation and reintegraton.Palmer, Michele January 2004 (has links)
There is a growing sense of apathy and lack of focus amongst the youth, which contributes to the threat of social integration. Constructive alternatives are therefore needed to curb gangsterism, drug abuse and other criminal activities among youth at risk. It has become imperative to challenge the present situation in which crime has become one of the most attractive options facing our youth. Through a programme of contructive engagement, a substantial difference can be made in their rehabilitation and ultimately their active participation in building a safer society. A strong emphasis should be placed on the development and implementation of effective restorative justice principles, alternative sentencing and community-based rehabilitation programmes, particularly for young people in marginalised communities.
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A study towards the implementation of a fire service operational structure in the Eden District Municipality areaVan Rooyen, Zanda January 2005 (has links)
The Eden District Municipality (EDM) is a local authority whose area of responsibility covers the Garden Route and also includes the Klein Karoo. The boundaries are from Storms River in the east, to Swellendam in the west and the Swartberg Mountains in the north. The EDM covers a very big area with seven big municipalities to consider and work with. Five of the municipalities, Langeberg, Mossel Bay, Knysna, George and Oudtshoorn have their own fire fighting services. The EDM fire fighting serves mainly the rural area. This is very costly due to the large distance required to travel to a fire, whereas the local municipalities are operating in their own towns. The new municipal boundaries include the rural areas, but the municipalities cannot service the rural areas because they do not as yet charge rates in the rural areas and therefore there is no revenue for the fire fighting service. They operate on the basis of verbal working agreements that make coordination of fire fighting very difficult. The fire fighting functions of the EDM as a category C municipality and the local municipalities as category B municipalities have been specified in the Municipal Structure Act. The allocation (division) of functions and powers relating to fire fighting service between the district municipality and local municipalities as determined by the Municipal Structure Act (Act 117 of 1998) has not been done. Due to the lack of invested capital, the resources are in a bad state. Some of the services have no capacity to attend to chemical fires or hazardous substance emergencies. Internationally, private fire fighting services can be contracted by government departments. These private fire fighting services are very large and the areas that they serve are extensive. These services have their own personnel structures functioning in an organisational structure that serves them well. These private services are very cost-effective and can therefore offer reasonable rates. Based on an investigation of various fire fighting services and different structures, the proposed structure for fire fighting in the EDM area will be a combination of structures. The diverse nature of the area will make the location of a sectoral structure and extension of its capacity difficult, and several factors that will impact on an new structure must be kept in mind. If all works well it will be relatively easy to achieve the five operations performance objectives envisaged for restructuring namely quality, speed, dependability, flexibility and cost.
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Immune regulation in children and adults in a community with a high incidence of tuberculosisAdams, Joanita Frances Ann 12 1900 (has links)
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.
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Crime as deterrent to sustainable tourism growth? : perspectives on the impact of crime on tourism in the Western CapeDalhousie, Landi 12 1900 (has links)
Thesis (MPhil)--Stellenbosch University, 2005. / ENGLISH ABSTRACT: This study analyses the impact of crime on sustainable tourism growth in the Western
Cape. It investigates tourists' perceptions of crime in the province and the role of the
media in creating or influencing these perceptions. This study also provides an
overview of the most important government initiatives and policies that have been
undertaken and implemented at local, provincial and national levels. These policies
are discussed and evaluated to determine whether it has in fact brought or encouraged
sustainable tourism growth in the Western Cape.
A survey, with a sample size of 25 respondents was undertaken during the period of
April to June 2005 and comprised 13 tour operators, eight tourism bureaus and four
travel agencies, which are all based in the Western Cape. The aim of the study was to
gain insight into the travel motivations and patterns of the thousands of tourists that
visit the province every year and their perceptions regarding crime, from the
viewpoint of these primary producers (i.e. the travel intermediaries) in the tourism
production system.
Crime does not only affect residents, but also has an impact on tourist behaviour and
deters visitors from visiting a country, as most tourists are risk-aversive and consider
such factors when deciding on a destination. Only a small number of tourists are
disappointed with the crime situation when visiting the Western Cape, but the
majority of tourists still regard it as a serious problem, and possible deterrent, of the
province. These perceptions do have a tendency to change more positively once
tourists have visited the area. Nevertheless, respondents feel obliged to warn tourists
against crime or give them advice about their safety and security.
The various levels of government are committed towards improving safety and
security in South Africa and numerous policies and initiatives have been developed
and implemented. However, most do not specifically focus on crimes against tourists.
Safety and security is considered as a prerequisite for a successful tourism industry,
thus both local residents and tourists should receive equal attention with regards to
safety and security from the government. However, many respondents are unaware of
the existence of the government's initiatives to combat crime, which raises doubts about the effectiveness of these initiatives, their implementation and their intended
benefits. The government should formulate comprehensive and constructive
provincial policies in order to address the potentially detrimental impacts of crime on
sustainable tourism growth in the Western Cape. / AFRIKAANSE OPSOMMING: Hierdie studie analiseer die impak van misdaad op volhoubare toerisme groei in die
Wes-Kaap. Dit ondersoek toeriste se persepsies van misdaad in die provinsie en die
rol van die media om hierdie persepsies te beinvloed. Die studie gee 'n oorsig oor die
belangrikste regeringsinisiatiewe en -beleide wat geimplimenteer is op plaaslike,
provinsiale and nasionale vlakke. Hierdie beleide word bespreek en geevalueer om
vas te stel of dit daadwerklik volhoubare toerisme groei in die Wes-Kaap
bewerkstellig en aanmoedig.
'n Opname met 'n steekproef van 25 respondente was onderneem gedurende April tot
Junie 2005. Die steekproef sluit in 13 toer operateurs, agt toerismeburo's en vier
reisagentskappe, almal gebasseer in die Wes-Kaap. Die doel van die studie was om
insig te kry oor die motivering en reispatrone van die toeriste wat jaarliks die
provinsie besoek, asook wat hul persepsies oor misdaad is soos waargeneem deur die
primere produsente (d.w. s. reisbemiddelaars) in die toerisme produksiesisteem.
Misdaad affekteer nie net inwoners nie, maar het ook 'n impak op toeriste se gedrag
en kan selfs toeriste weerhou daarvan om die land te besoek, want veiligheid en
sekuriteit is van die belangrikste oorwegingsfaktore wanneer daar besluit word om 'n
land te besoek. Slegs 'n paar toeriste is teleurgesteld met die misdaad situasie wanneer
hulle die Wes-Kaap besoek, maar die meerderheid beskou dit steeds as 'n ernstige
probleem, of selfs afskrikmiddel, in die provinsie. Hierdie persepsies is geneig om te
verander nadat die toeriste die area besoek het. Respondente beskou dit egter steeds as
hul plig om toeriste teen misdaad te waarsku.
Op verskeie vlakke van regering word daar voortdurend gestreef na veiligheid en
sekuriteit in Suid-Afrika te verbeter. Verskeie regeringsbeleide en inisiatiewe is al
ontwikkel en geimplimenteer, maar die meeste fokus nie spesifiek op misdaad teen
toeriste nie. Veiligheid en sekuriteit word beskou as 'n voorvereiste vir 'n suksesvolle
toerisme industrie, daarom moet beide inwoners en toeriste dieselfde aandag met
betrekking tot veiligheid en sekuriteit van die regering ontvang. Dis egter
kommerwekkend dat meeste van die respondente onbewus is van hierdie inisiatiewe
om misdaad te bekamp. Die regering moet fokus daarop om 'n omvattende en konstruktiewe provinsiale beleid te formuleer om sodoende die nadelige impak van
misdaad op volhoubare toerismegroei in die Wes-Kaap aan te spreek.
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The prevention of fetal alcohol spectrum disorders : an ecological approachDe Vries, Maria Magdalena 03 1900 (has links)
Thesis (M Social Work)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Fetal alcohol spectrum disorders (FASD) is caused by maternal drinking during pregnancy. Pre-natal drinking has a range of deleterious effects including physical, mental and behavioural consequences for the affected child. Although FASD is completely preventable, it is irreversible with consequences that last into adulthood. The range of effects of FASD forms a spectrum with fully developed FAS on the one end and no effects on the other end of the spectrum.
The Western Cape has one of the highest recorded rates of FAS in the world. This seriously affects almost all systems in society and strains the already overburdened educational-, health-, social- and judicial systems. For this reason preventing FASD is of the utmost importance and requires a comprehensive approach on multiple levels.
This study explores and describes FASD prevention services in the Bonnievale, Robertson, Ashton and Montagu-areas – a wine-producing area in the Western Cape. Available FASD prevention services on all levels of prevention, the focus-areas of the different prevention activities, collaboration and co-ordination between the role-players and obstacles in delivering prevention services, was examined. By adopting an ecological approach, FASD prevention services could be investigated on multiple levels.
This study used a combination of quantitative and qualitative research. An exploratory design and a purposive sampling method were used. Participants were interviewed individually and with the help of a semi-structured questionnaire.
The findings of the empirical investigation show that, although prevention efforts are applied on the universal, selective and indicated levels of prevention, a lack of formal prevention efforts that are actively pursued - especially on the level of indicated prevention - exists. This is aggravated by the absence of formal co-ordination of services and structured systems of referrals. NGO‟s and government departments are, as a result, not clear about their respective roles and responsibilities and women with the highest risk for having a child with FAS, therefore, fall through the cracks of the system. This happens partly because social workers are often perceived as the only agents for social change in the community. According to the ecological approach all levels (micro, meso and macro) of organizations in the social environment should work together for change by repeating prevention messages on the different levels and thereby reinforcing it. In the study area, however, most FAS prevention services were on the micro-level with few on the meso-level and virtually none on macro-level.
Participants identified a lack of co-ordination, unplanned families, a lack of resources, a lack of training and training material and low levels of education as obstacles in service delivery.
Recommendations resulting from the study indicate that FAS prevention will benefit from structured, formal programs on all levels of prevention. This will require non-government organizations and government departments to co-ordinate services and to develop a formal system of referral amongst the role-players. Training of personnel in clinics, NGO‟s, government departments and volunteers, as well as the development of training material targeted at people on different levels of education, should receive attention. It is, in conclusion, recommended that community organizations and structures such as churches, places of business, farmer‟s associations and liquor outlets are actively involved in the prevention of FASD. / AFRIKAANSE OPSOMMING: Fetale Alkohol Spektrum Afwykings (FASA) word veroorsaak deur alkoholgebruik tydens swangerskap. Alkoholgebruik tydens swangerskap het „n reeks skadelike effekte, insluitend fisiese, psigiese en gedragsafwykings in die geaffekteerde kind. Alhoewel FASA heeltemal voorkombaar is, is dit onomkeerbaar en duur die gevolge daarvan voort in volwassenheid. Die reeks effekte van FASA vorm „n spektrum met volledig ontwikkelde FAS aan die een kant en geen effekte nie aan die ander kant van die spektrum.
Die Wes-Kaap het een van die hoogste aangetekende voorkomssyfers van FAS in die wêreld. Dit affekteer feitlik alle sisteme in die samelewing en plaas nog meer druk op die reeds oorlaaide opvoedkundige-, gesondheids-, maatskaplike- en regssisteme. Om hierdie rede is die voorkoming van FASA van uiterste belang en word „n omvattende benadering op veelvuldige vlakke vereis.
Hierdie studie ondersoek en beskryf FASA voorkomingsdienste in die Bonnievale-, Robertson-, Ashton- en Montagu-area – „n wynproduserende streek in die Wes-Kaap. Die beskikbaarheid van FASA voorkomingsdienste op alle vlakke van voorkoming, die fokus-areas van die verskillende voorkomingsaktiwiteite, samewerking en koördinering van dienste tussen die rolspelers, sowel as struikelblokke in voorkomingsdienste, is ondersoek. Deur die ekologiese benadering aan te neem, kon FASA voorkomingsdienste op veelvuldige vlakke ondersoek word.
Die studie kombineer kwantitatiewe en kwalitatiewe navorsing. Die ontwerp van die studie is verkennend en daar is „n doelbewuste steekproef gedoen. Indivuduele onderhoude met deelnemers is met behulp van semi-gestruktureeerde vraelyste gevoer.
Die bevindinge van die empiriese ondersoek toon dat, alhoewel voorkomingspogings aangewend word op die universele, selektiewe en indikatiewe voorkomingsvlakke, daar 'n gebrek bestaan aan formele voorkomingspogings wat aktief nagestreef word, veral op die indikatiewe vlak. Dit word vererger deur die afwesigheid van formele koördinering van dienste en gestruktureerde verwysingsisteme.
Nie-regeringsorganisasies en staatsdepartemente het gevolglik nie duidelikheid oor hul onderskeie rolle en verantwoordelikhede nie. Die gevolg hiervan is dat vroue met die hoogste risiko om geboorte te skenk aan kinders met FAS, deur die krake in die sisteem val. Dit geskied deels omdat maatskaplike werkers dikwels gesien word as die enigste agente vir maatskaplike verandering in die gemeenskap. Volgens die ekologiese benadering behoort alle vlakke (mikro, meso en makro) van organisasie in die sosiale omgewing saam te werk om verandering teweeg te bring deurdat voorkomingsboodskappe op die verskillende vlakke te herhaal en sodoende te versterk word. In die studie-area is die meeste voorkomingsdienste egter op mikro-vlak gelewer met min op meso-vlak en feilik geen op makro-vlak nie.
Deelnemers aan die studie het „n gebrek aan koördinasie van dienste, onbeplande gesinne, „n gebrek aan hulpbronne, „n gebrek aan opleiding en opleidingsmateriaal en lae vlakke van geletterdheid geïdentifiseer as struikelblokke in dienslewering.
Aanbevelings wat uit die studie voortvloei, dui aan dat FASA voorkomingsdienste sal baat vind by gestruktureerde, formele programme op alle vlakke van voorkoming. Dit sal vereis dat nie-regeringsorganisasies en staatdepartemente hul dienste koördineer en „n formele verwysingstelsel tussen die verskillende rolspelers ontwikkel. Opleiding van personeel in klinieke, NRO‟s, staatsdepartemente en vrywilligers, sowel as die ontwikkeling van opleidingsmateriaal wat persone op verskillende vlakke van opvoeding teiken, behoort aandag te geniet. Dit word laastens ook aanbeveel dat gemeenskapsorganisasies en strukture byvoorbeeld kerke, besighede, boere-verenigings en verkoopspunte vir alkohol, aktief betrek word by die voorkoming van FASA.
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