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The determination of post-exposure regrowth effects and the bactericidal activity of selected antimycobacterial agents against mycobacterium tuberculosisMasango, Refilwe Winstance January 2000 (has links)
Thesis (Msc. (Medical Sciences)) -- University of LImpopo, 2000 / Refer to document / Medical Research Council (MRC)
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Major spoligotype families of Mycobacterium tuberculosis strains isolated from tuberculosis patients in Port Elizabeth, Eastern Cape, South AfricaNqini, Babalwa J January 2012 (has links)
South Africa is burdened with tuberculosis (TB) which is aggravated by the concurrent epidemic of HIV as well as the emergence of drug resistance. In most developed countries molecular techniques have been used to look at the dynamics of the TB epidemic however, despite the prevalence that is high in sub-Saharan Africa, there is little data on strain types that are available in Port Elizabeth. This study aims to find the major clades of M. tuberculosis that are circulating in Port Elizabeth. Two hundred MDR-TB DNA samples were obtained from the National Health Laboratory Services TB laboratory in Port Elizabeth. Spoligotyping and MIRU-VNTR were used to genotype the strains. Two hundred strains were sent to the University of Stellenbosch for spoligotyping and 179 of those were typed. Spoligotype defined families were further typed by MIRU-VNTR typing, so as to further differentiate and assess clonal diversity within the spoligotype families. The Beijing family was the dominant family and the MANU family being the least dominant, with percentages of 71 percent and 0.5 percent respectively. A comparison of spoligotyping results with the international spoligotyping database (SITVIT2) showed a total of 15 shared international types. Forty four percent (44 percent) of the isolates that were typed by MIRU-VNTR showed similarities, suggesting epidemiological relatedness. Thirty eight percent of isolates from spoligotyping were from the same family, the Beijing family, with the same shared international type STI1, but when typed by 12 MIRU-VNTR they showed no epidemiological relatedness and 18 percent of the isolates showed no relatedness when typed by 12 MIRU-VNTR but spoligotyping showed that they were from the LAM family. Results from our study illustrate the effectiveness of MIRU-VNTR typing together with spoligotyping in epidemiological studies in the region of Port Elizabeth.
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An investigation into joint HIV and TB epidemics in South AfricaPretorius, Carel Diederik 12 1900 (has links)
Thesis (PhD (Physics))--Stellenbosch University, 2009. / ENGLISH ABSTRACT: This dissertation investigates certain key aspects of mathematical modeling of HIV and
TB epidemics in South Africa with particular emphasis on data from a single well-studied
community. Data collected over a period of 15 years (1994 to 2009) in Masiphumelele, a
township near Cape Town, South Africa are used to develop a community-level mathematical
model of the local HIV-TB epidemic. The population is divided into six compartments and
a system of di®erential equations is derived to describe the spread of the dual epidemic.
Our numerical results suggest that increased access to antiretroviral therapy (ART) could
decrease not only the HIV prevalence, but also the TB noti¯cation rate. We present a
modeling framework for studying the statistical properties of °uctuations in models of any
population of a similar size. Viewing the epidemic as a jump process, the method entails
an expansion of a master equation in a small parameter; in this case in inverse powers
of the square root of the population size. We derive two-time correlation functions to
study the correlation between di®erent types of active TB events, and show how a temporal
element could be added to the de¯nition of TB clusters, which are currently de¯ned solely
by DNA type. We add age structure to the HIV-TB model in order to investigate the
demographical impact of HIV-TB epidemics. Our analysis suggests that, contrary to general
belief, HIV-positive cases are not making a substantial contribution to the spread of TB in
Masiphumelele. We develop an age-structured model of the HIV-TB epidemic at a national
level in order to study the potential impact of a proposed universal test and treat program
for HIV on dual HIV-TB epidemics. Our simulations show that generalized ART could
signi¯cantly reduce the TB noti¯cation rate and the TB-related mortality rate in the short
term. The timescale of the impact of ART on HIV prevalence is likely to be longer. We
study the potential impact of more conventional control measures against HIV. Guidance
for possible future and/or additional interventions emerge naturally from the results. We
advocate a reduction in intergenerational sex, based on our ¯nding that 1.5-2.5 standard
deviation in the age di®erence between sexual partners is necessary to create and sustain
a major HIV epidemic. A simulation framework is developed to help quantify variance
in age-structured epidemic models. The expansion technique is generalized to derive a
Fokker-Planck equation. Directions for future work, particularly in terms of developing
methods to model °uctuations and validate mixing assumptions in epidemiological models,
are identi¯ed. / AFRIKAANSE OPSOMMING: Hierdie proefskrif ondersoek aspekte van die wiskundige modelering van HIV en TB epi-
demies in Suid Afrika en fokus ook op 'n spesi¯eke gemeenskap. Data wat oor 'n periode
van 15 jaar ingesamel is (1994 tot 2009) in Masiphumelele, 'n woonbuurt naby Kaapstad,
Suid Afrika word gebruik om 'n wiskundige model te skep wat HIV-TB in die gemeen-
skap modeleer. Die populasie word in ses kompartemente verdeel en 'n stel di®erensiaal
vergelykings word afgelei om die verspreiding van di¶e epidemies te ondersoek. Ons nu-
meriese resultate toon aan dat verhoogde toegang tot antiretrovirale behandeling (ARB)
die potensiaal het om HIV prevalensie die TB koers beduidend te laat daal. Ons ontwikkel
'n raamwerk waarmee die statistiese eienskappe van °uktuasies ondersoek kan word in enige
populasie van dieselfde grootte. Die metode ontwikkel 'n meester vergelyking vir die on-
derliggende geboorte-dood stogastiese proses en brei dit uit in terme van 'n klein parameter;
in di¶e geval in inverse magte van die vierkantswortel van die populasie grootte. Die twee-tyd
korrelasie funksies word afgelei, en word gebruik om die korrelasie tussen verskillende tipes
van TB episodes te bestudeer, asook om te wys hoe 'n tydselement aan die de¯nisie van TB
groeperings gegee kan word. Di¶e word tans slegs d.m.v DNA tipe geklassi¯seer. Ouderdom-
struktuur word aan die model toegevoeg om die demogra¯ese impak van HIV-TB epidemies
te bestudeer. Ons analise toon aan dat, anders as wat algemeen aanvaar word, maak HIV-
positiewe gevalle nie 'n groot bydrae tot die verspreiding van TB in Masiphumelele nie. Ons
ontwikkel 'n ouderdom-gestruktureerde model van HIV-TB op nasionale vlak en gebruik die
model om die potensiÄele impak van 'n universele toets- en behandel strategie op die HIV-TB
epidemies te ondersoek. Ons simulasies toon aan dat algemene ARB waarskynlik 'n groot
impak op die TB aanmeldings koers asook die TB-verwante mortaliteits koers kan h^e binne
'n relatiewe kort tydperk. Die impak op HIV prevalensie sal eers oor 'n veel langer periode
duidelik word. Ons ondersoek ook die moontlikheid van meer konvensionele beheermaa-
treels. Ons ontmoedig tussengenerasie seksuale omgang, gegrond op ons bevinding dat 'n
standaard afwyking van 1.5-2.5 in die ouderdoms verskil tussen seksuele vennote, nodig is om
'n HIV epidemie van stapel te stuur en te onderhou. Ons ontwikkel 'n simulasie raamwerk
om variansie in ouderdomgestruktureerde modelle te benader. Die uitbreidingstegniek word
veralgemeen om 'n Fokker-Planck vergelyking af te lei. Ons identi¯seer probleme in die on-
twikkeling van metodes om interaksie patrone en °uktuasies te modeleer in epidemiologiese
modelle as opgawe vir toekomstige werk.
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A longitudinal study of migration and it relation to AIDS/TB mortality in rural South AfricaAfolabi, Sulaimon Atolagbe January 2017 (has links)
A thesis submitted to the Faculty of Humanities, University of Witwatersrand, Johannesburg, South Africa in fulfilment of the requirements of the Degree of Doctor of Philosophy in the field of Demography and Population Studies. / Background: In exploring the relationship between migration and HIV/AIDS, a
focus of earlier studies was on the role of the mobile population in the
geographical spread of the disease. There has been a shift in this perception and
the focus now is on the implications of being a migrant. A body of literature
has developed on the risk of migrants contracting HIV, but only a few studies
have examined the AIDS/TB mortality risk as a consequence of migration, with
the results showing that migrants have higher chance of dying of AIDS/TB
compared to their non-migrant counterparts. However, these studies mainly
looked at the impact of migration on mortality due to AIDS/TB and did not
make provision for the presence of other causes of death. Therefore, this study
is geared towards investigating migration as it relates to death caused by
AIDS/TB, longitudinally, and in the presence of other causes such as non
communicable diseases, other infectious diseases, and external causes of death,
in rural South Africa. Specifically, the study addressed the following questions:
(i) What is the risk of dying from AIDS/TB among migrants in rural South
Africa in the presence of other causes of death? (ii) How does this relationship
compare with the relationship between migration and other causes of death? (3)
What are possible predictors of the relationship between migration and
AIDS/TB in the presence of other causes of death?
Method: This research project is part of a longitudinal study of the inhabitants
of the Agincourt sub-district, situated in the rural north-eastern part of South
Africa. The study utilises the Agincourt Health and Demographic Surveillance
System data spanning 12 years, starting from 1st January, 2000 to 31st
December, 2011. The main target group for the study is individuals aged 20 to
69 years at the date of analysis. The selected individuals are divided into the
following categories: (i) the return migrants who returned after spending a
period of time outside the study area; (ii) the in-migrants who moved into the
study location for the first time, and (iii) the permanent residents (non
migrants). A six month residence threshold period is used to distinguish
participants from ordinary visitors. The migration status categorical variable
was further expanded from three to five categories with in-migrant and return
migrant categories being split to accommodate short and long-term durations of
exposure. In the year 2000, the baseline year, a total of 25,621 individuals who
met the entry criteria were recruited into the study.
For data analysis, a Fine and Gray model is used, which is a variant of a Cox
proportional hazard model, to estimate the competing risk of dying among the
selected participants by sex. The causes of death (CoD) variable was
categorised into the following broad categories: “AIDS/TB”, “Non
Communicable Disease”, “External cause” and “Other infectious disease”, with
indeterminate causes coded as missing. The five categories of migration serve
as the independent variable, with permanent residence acting as the reference
group, while the broad Cause of Death categories are the main dependent
variables. Other dependent variables are: period, nationality, education and
socio-economic status.
Results: This first set of results aims to address the question on the risk of
AIDS/TB mortality among migrants in rural South Africa in the presence of
other causes of death. The findings are that male and female short-term return
migrants have significantly higher relative risk of dying of AIDS/TB death
when compared to their non-migrants counterparts with sub-hazard ratio (SHR)
of 4.87 (95% CI 4.17-5.72; P<0.001) and 5.44 (95% CI 4.64-6.38; P<0.001))
reported for both gender group respectively. For male and female long-term
return migrants, their SHR was 1.80 (95% CI 1.43-2.26; P<0.001) and 2.06
(95% CI 1.57-2.70; P<0.001) respectively. The results did not reveal significant
results for the in-migrants.
The second set of results aims to address the second research question, which
is, how does the relationship between migration and mortality caused by
AIDS/TB in rural South Africa in the context of other causes of death compare
with the relationship between migration and causes different from AIDS/TB.
The results show that Short-term return migrants have higher mortality than
non-migrants, whatever the four causes of mortality. For instance, the
competing risk of death due to AIDS/TB for short-term return migrants
compared to non-migrants showed a lower SHR for external cause of death,
namely 8.78 (95% CI 5.86-13.16; P<0.05) vis-à-vis non-migrants. This implies
that the difference in the relative risk of mortality between migrants and non
migrants is even higher for external causes than for AIDS/TB. The same is
applicable to the risk of death from other infectious diseases for females, which
has a SHR of 4.97 (95% CI 2.50-9.89; P<0.05) in the competing risk model.
The relative risk of death due to AIDS/TB for male is 4.87 (95% CI 4.14-5.72
P<0.001) while that of female is 5.44 (95% CI 4.64-6.38; P<0.001);
respectively.
With regards to the question on the possible predictors of the relationship
between migration and AIDS/TB in the presence of other causes of death, it is
shown that period is one of the predictors of the relationship between migration
and AIDS/TB mortality. And, it is relevant to the study participants who died
as a result of AIDS/TB, NCDs and other infectious diseases. In general, the risk
dwindles in the latter period when the antiretroviral drugs become available for
AIDS/TB. Nationality is also a determinant of the relationship and it is
applicable to those who lost their lives due AIDS/TB (female only), NCDs and
other infections (female). In all, the Mozambican nationals are less likely to die
in comparison with the South Africans. Educational status is a predictor and it
relevance cuts across virtually all the causes of death. The dominant pattern that
is revealed in this context is that the higher the level of education, the lower the
risk of death due to any of the causes. The predictive impact of SES can only be felt among the respondents whose death was due to AIDS/TB and NCDs
(female only).
Conclusion: With circular labour migration in South Africa showing no
evidence of declining and with the attendant mortality risks due to AIDS/TB
and other causes, and needs to be carefully considered - in policies aiming to
control mortality in South Africa. Disease-induced migration creates burdens
not only for the left-behind families in terms of their means of livelihood
through loss of remittances, but also for the burden on health care facilities in
the rural area. With short-term labour migrants being a high risk group, the
success of intervention programmes addressing the problem of HIV infection
and the resultant mortality implication, such as ‘treatment as prevention’
programmes, can only be guaranteed by recognising the risks incumbent on this
group of people and the influence of the larger communities. / XL2018
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Development of an intervention programme for the prevention of complications of tuberculosis during pregnancy and puerperium period, Limpopo Province, South AfricaNetshimbupfe - Mulondo, Seani Adrinah 18 September 2017 (has links)
PhD (Advanced Nursing Science) / Department of Advanced Nursing Science / See the attached abstract below
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Incidence of tuberculosis amongst HIV positive clients who received isoniazid preventive therapy (IPT)Okoli, Emmanuel Ikechukwu 02 1900 (has links)
The research objectives were to describe the age and gender of adult HIV positive clients on ART who received IPT; the incidence of tuberculosis among clients that received IPT and the defaulter rate among those that were commenced on IPT. Quantitative non-experimental descriptive retrospective cohort study was undertaken to ascertain the incidence of tuberculosis among adult HIV positive clients who received IPT. 104 clinic records of HIV positive adult clients accessing care at Isithebe Clinic, iLembe-South Africa who were commenced on IPT between 01 July 2010 and 30
November 2011 were analysed. The study found that 66 of 104 (63.5%) study respondents completed the course of IPT and the majority of those that defaulted were due to poor quality of care. Gender was statistically found to have played a role on whether a patient completes IPT. None of the study respondents that completed IPT was diagnosed with TB disease. / Health Studies / M.A. (Public Health)
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Modelling the effect of HIV on age-specific incidence of active TB disease : a comparison between Taiwan and Cape Town MetropoleWinkler, Dietrich Maximilian Albert 03 1900 (has links)
Thesis (MSc)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: See full text / AFRIKAANSE OPSOMMING: Sien volteks
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Tuberkulose in 'n geselekteerde gemeenskap in die Wes-Kaap : 'n gemeenskapsstudieVan der Walt, Stephanie 12 1900 (has links)
Thesis (MCur)--University of Stellenbosch, 2002. / ENGLISH ABSTRACT: The Minister of Health identified tuberculosis as a National Health priority since
the incidence of tuberculosis in South Africa is increasing. The researcher
practiced as a community health nurse for seven years and was actively
involved with the community. It was experienced that irrespective well qualified
nursing staff and accessible and available health services, there was an
increase in tuberculosis in the Western Cape.
A non-experimental, descriptive, explorative study was conducted in a selected
community in the Western Cape to address the research problem:
What are the knowledge, perceptions, attitudes and treatment practices of
tuberculosis patients; their resources for support; and community leaders?
Structured interviews were held with 50 patients randomly selected from patients
attending the health clinic. Focus interviews were held with community leaders
purposefully selected for the research. A modified Photovoice technique was
also applied to the patients where they had to draw a picture of their feelings
when diagnosed with tuberculosis and the impact of the disease on themselves
and their environment.
The findings revealed a lack of information, major stigmatization of the disease,
and many patients not adhering to their treatment regimes. Most of the patients
had a negative idea of tuberculosis indicating that it always causes death.
Community leaders were very committed to assist in combating the problems in
their community. The findings indicated that health staff can be of more help to
the patient although they were generally satisfied with the care they received.
Recommendations include that health promotion programmes should be
planned in co-operation with community members to ensure that programmes
are appropriate and address the real needs of the community. / AFRIKAANSE OPSOMMING: Die Minister van Gesondheid het tuberkulose as 'n Nasionale
Gesondheidsprioriteit geïdentifiseer aangesien daar 'n toename in die insidensie
van tuberkulose in Suid-Afrika is. Die navorser het vir sewe jaar as 'n
gemeenskapsverpleegkundige gepraktiseer en was aktief betrokke by die
gemeenskap. Die navorser het gevind dat daar 'n toename in tuberkulose in die
Wes-Kaap was ten spyte van goed gekwalifiseerde verpleegpersoneel asook
toeganklike en beskikbare gesondheidsdienste.
'n Nie-eksperimentele, beskrywende, verkennende studie is gedoen op 'n
geselekteerde gemeenskap in die Wes-Kaap om die navorsingsprobleem aan te
spreek:
Wat is die kennis, persepsies, houdings en behandelingspraktyke van
tuberkulosepasiënte, hulle ondersteuningsbronne en gemeenskapsleiers?
Gestruktureerde onderhoude is met 50 pasiënte gevoer wat ewekansig
geselekteer is uit pasiënte wat die kliniek besoek het. Fokusonderhoude is met
gemeenskapsleiers gevoer wat doelbewus geselekteer is. 'n Gemodifiseerde
photo voice tegniek is ook toegepas waar pasiënte 'n skets moes maak van hulle
gevoelens toe hulle die eerste keer met tuberkulose gediagnoseer is, asook die
impak wat die siekte op hulself en hulomgewing het.
Die bevindinge het gewys dat daar 'n gebrek aan kennis was, dat daar 'n
grootskaalse stigmatisering van die siekte was en dat baie pasiënte nie by hulle
behandelingsregimens hou nie. Die meeste van die pasiënte het 'n negatiewe
idee van tuberkulose en het aangedui dat dit altyd die dood veroorsaak.
Gemeenskapsleiers was baie hulpvaardig en alhoewel die meeste pasiënte
aangedui het dat hulle tevrede was met die sorg wat hulle ontvang het, was daar
tog aanduidings dat gesondheidspersoneel van meer hulp kan wees.
Aanbevelings sluit in dat gesondheidsbevorderingsprogramme in samewerking
met gemeenskapslede beplan moet word om te verseker dat die programme
toepaslik is en die werklike behoeftes van die gemeenskap aanspreek.
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Accuracy and completeness of notification of tuberculosis in two high incident communities in Cape Town, South AfricaDunbar, Rory 12 1900 (has links)
Thesis (MScMedSc)--Stellenbosch University, 2011. / ENGLISH ABSTRACT: Introduction: Tuberculosis (TB) treatment registers and laboratory records are essential recording
and reporting tools in TB control programmes. Reliable data are essential for any TB control
programme but under-registration of TB cases has been well documented internationally, due to
under-reporting of patients on treatment or failure to initiate treatment. The accuracy and
completeness of routinely collected data are seldom monitored.
Aim: This study used record linking to assess the accuracy and completeness of TB treatment
register data and the feasibility of estimating the completeness of bacteriological confirmed
pulmonary TB registration in two high incident communities in South Africa with capturerecapture
methods.
Methods: All cases of bacteriologically confirmed TB defined as 2 smear-positive results and/or at
least one culture-positive result were included. Record linking was performed between three data
sources: (1) TB treatment registers; and (2) all smear and culture results from (a) the nearest
central laboratory, and (b) the referral hospital laboratory. To estimate the completeness of TB
treatment recording three-source log-linear capture-recapture models were used, with internal
validity analysis.
Results: The TB treatment registers had 435 TB cases recorded of which 204 (47%) were
bacteriologically confirmed cases. An additional 39 cases that were recorded as nonbacteriological
cases in the TB treatment register, were reclassified as bacteriologically confirmed.
In addition, there were 63 bacteriologically confirmed cases identified from the laboratory
databases which were not recorded in the TB treatment register. The final total number of
bacteriologically confirmed TB cases across all 3 databases was 306, an increase of 50% over
what had initially been recorded in the TB treatment register. The log-linear capture-recapture
model estimated the number of bacteriologically confirmed TB cases not found in any of the data
sources at 20, resulting in a total number of bacteriologically confirmed TB cases of 326 (95% CI 314-355). The completeness of registration of bacteriologically confirmed pulmonary TB cases
was 79% after record linking and 75% after the capture-recapture estimate.
Conclusions: The results presented in this thesis highlighted the concern regarding the accuracy
and completeness of routinely collected TB recording and reporting data. A high percentage of bacteriologically confirmed cases from both laboratories were not recorded in the TB treatment
registers. Capture-recapture can be useful, but not essential, for evaluation of TB control
programmes, also in resource-limited settings, but methodology and results should be carefully
assessed. The present study estimated the extent of the problem of underreporting of TB in South
Africa and identified challenges in the process. Interventions to reduce underreporting of TB are
urgently needed. / AFRIKAANSE OPSOMMING: Inleiding: Registers van tuberkulose (TB) behandeling en laboratoriumrekords is noodsaaklike
instrumente in die dokumentering van en verslagdoening oor TB beheerprogramme. Betroubare
data is onontbeerlik vir enige TB beheerprogram maar onderregistrasie van TB gevalle is
internasionaal goed gedokumenteer. Die akkuraatheid en volledigheid van roetine data word selde gemoniteer. Doel: Hierdie studie het rekordkoppeling gebruik om die akkuraatheid en volledigheid van data in
TB behandelingsregisters te ondersoek. Voorts is die uitvoerbaarheid van die vangshervangsmetodes
vir die beoordeling van die volledigheid van bakteriologies bevestigde
pulmonale TB registrasie in twee hoë-insidensie gemeenskappe ondersoek.
Metodes: Alle gevalle van bakteriologies bevestigde TB, gedefinieer as 2 smeer-positiewe
resultate en/of ten minste een kultuur-positiewe resultaat, is in die studie ingesluit.
Rekordkoppeling is onderneem tussen drie databronne: (1) TB behandelingsregisters; en (2) alle
smeer- en kultuurpositiewe resultate van (a) die naaste sentrale laboratorium, en (b) die
verwysende hospitaallaboratorium. Om die volledigheid van TB behandelingsrekords te ondersoek
is drie-bron log-lineêre vangs-hervangs modelle gebruik met interne geldigheidsontleding.
Resultate: Die TB registers het 435 aangetekende TB gevalle bevat waarvan 204 (47%)
bakteriologies bevestigde gevalle was. 'n Bykomende 39 gevalle wat as nie-bakteriologies
bevestigde gevalle aangeteken was in die TB register is hergeklassifiseer as bakteriologies
bevestig. Daar is ook 63 bakteriologies bevestigde gevalle geïdentifiseer vanuit die laboratorium
databasisse wat nie in die TB register aangeteken was nie. Die finale totale aantal bakteriologies
bevestigede TB gevalle oor al drie databasisse heen was 306, 'n toename van 50% in vergelyking
met wat aanvanklik in die TB register aangeteken was. Die log-lineêre vangs-hervangs model het
die aantal bakteriologies bevestigde gevalle wat nie in enige van die databronne gevind kon word
nie as 20 gevalle geskat, wat gelei het tot 'n totaal van 326 (95% VI 314-355) bakteriologies
bevestigde gevalle. Die volledigheid van registrasie van bakteriologies bevestigde TB gevalle was
79% na rekordkoppeling en 75% na die vangs-hervangs skatting.
Gevolgtrekkings: Die resultate wat in hierdie tesis voorgelê is beklemtoon die besorgdheid oor die
akkuraatheid en volledigheid van die aanmelding en optekening van roetine TB data. 'n Hoë persentasie van bakteriologies bevestigde gevalle van beide laboratoriums is nie in die TB register
opgeteken nie. Vangs-hervangs kan nuttig wees, maar nie noodsaaklik nie, in die evaluasie van TB
beheerprogramme, ook in hulpbron-arm omgewings, maar die metodologie moet omsigtig
beoordeel word. Die huidige studie het die omvang van die probleem van onderrapportering van
TB in Suid-Afrika beraam en uitdagings in die proses geïdentifiseer. Intervensies om
onderrapportering te verminder word dringend benodig.
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Pharmacogenetics of Arylamine N-acetyltransferase genes in South African populationsWerely, Cedric J. 12 1900 (has links)
Thesis (PhD)--Stellenbosch University, 2012. / Includes bibliography / ENGLISH ABSTRACT: Tuberculosis (TB) has been declared a global health emergency by the World Health Organisation, and consequently there is an urgency to develop improved methods of diagnosis and treatment. Despite the current TB epidemic, the disease can be treated effectively using isoniazid (INH) in combination with other antibiotics. However, INH is inactivated in the body by certain drug metabolising enzymes, which may reduce the efficacy of TB treatment. The activity of these drug metabolising enzymes, called NAT, are in turn reduced by nucleotide changes (SNPs) in the gene. These genetic variants (alleles) have been correlated with the rapid- (FA), intermediate- (IA), and slow acetylation (SA) enzymatic activity, and one is therefore able to investigate potential phenotypic effects via genotypic analyses.
We investigated these genetic changes in the NAT1 and NAT2 genes in individuals from the local Coloured community (SAC) since this group has one of the highest TB incidences in the country. NAT2 is primarily responsible for the inactivation of INH, whilst NAT1 metabolises para-aminosalicyclic acid (PAS) which is used in the treatment of drug resistant TB.
The NAT2 results indicated that the NAT2 alleles were not equally represented in three local ethnic groups studied, and subsequently the rapid, intermediate and slow acetylation activity reflected these differences. However, the relative frequency of these variants in the SAC and Caucasian groups were relatively low. These differences require further investigation to determine their overall relevance to the NAT2 activity differences between groups.
In the case of the NAT1 analysis we also observed differences in the relative frequency of various NAT1 alleles between Caucasian and SAC individuals. However, many of these NAT1 SNPs and alleles have not as yet been characterised, so effects of these variants are currently unknown. Interestingly, the NAT1*4 and NAT1*10 alleles were the most prevalent NAT1 alleles in both Caucasians and SAC. The NAT1*4 allele exhibits the rapid NAT1 activity, whilst the activity of the NAT1*10 allele is currently subject to ongoing debate. In this respect, the analysis of NAT1 continues to be a topic for ongoing research.
These results, observed for the NAT genes, underscore the importance of doing genetic analyses in local ethnic groups, since these differences may vary significantly between the groups. / AFRIKAANSE OPSOMMING: Tuberkulose (TB) is deur die Wêreldgesondheidsorganisasie (WGO) tot 'n globale gesondheidsnood verklaar en derhalwe is dit noodsaaklik dat nuwe, verbeterde diagnostiese metodes ontwikkel word, wat tot meer effektiewe behandeling kan lei. Ten spyte van die huidige TB-epidemie, kan die siekte doeltreffend behandel word deur middel van isoniasied (INH), in kombinasie te met ander antibiotika. INH kan egter geïnaktiveer word deur sekere ensieme in die liggaam, met die gevolg dat INH nie meer effektief is nie in die behandeling van TB. Die aktiwiteit van hierdie ensiem, die sogenaamde NAT2 (Arielamien N-asetieltransferase 2) ensiem, word op sy beurt beïnvloed deur sekere nukleotied veranderings (SNPs) in die geen. Hierdie genetiese veranderings gekorreleer met ensiemaktiwiteitsveranderings (geklassifiseer as vinnig (FA) Intermediêr (IA) en stadig (SA)), wat mens in staat stel om potensiële fenotipiese effekte te ondersoek deur middel van genotipiese analise.
Ons het hierdie genetiese veranderings ondersoek in die NAT1 en NAT2 gene in individue van die Kleurling-gemeenskap (SAC) omdat díe bevolkingsgroep die hoogste voorkoms van TB in die land het. NAT2 is primêr verantwoordelik vir die inaktivering van INH, terwyl NAT1 para-amienosalisilaat (PAS) inaktiveer, wat gebruik word in die behandeling van midel-weerstandige TB.
Die NAT2 resultate dui daarop dat die allele van die NAT2 geen nie eweredig verteenwoordig wasin die drie etniese groepe nie en derhalwe word die vinnige (FA), intermediêre (IA) en stadige (SA) ensiemaktiwiteite deur hierdie verskille weerspieël. Hoewel die teenwoordigheid van hierdie variante relatief laag was in die SAC en Koukasiër gemeenskappe, is verdere studies nodig om die omvang van hierdie verskille te bepaal ten onsigte van NAT2 aktiwiteit tussen groepe.
In die geval van die NAT1 analise het ons verskille waargeneem in die voorkoms van verskeie NAT1 allele tussen Koukasiese en SAC individue. Baie van hierdie NAT1 SNPs is egter nog nie gekarakteriseer nie, en derhalwe is die effek van hierdie NAT1 variante onbekend. Die NAT1*4 en NAT1*10 allele was die prominentste NAT1 alleel in beide Koukasiërs en SAC. Die NAT1*4 is betrokke by vinnige NAT1 aktiwiteit, terwyl die effek van die NAT1*10 alleel nog onderhewig is aan aktiefwe debat. In hierdie verband, is die studie van NAT1 steeds 'n onderwerp vir toekomstige navorsing.
Hierdie resultate, wat vir die NAT gene waargeneem is, beklemtoon die belangrikheid van verdere genetiese analises in plaaslike etniese groepe, aangesien hierdie verskille beduidend kan wees tussen die verskillende groepe.
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