Thesis (MScMedSc)--Stellenbosch University, 2008. / ENGLISH ABSTRACT: Application of molecular fingerprinting highlights transmission as the driving force behind the
drug resistant epidemic in South Africa. Different strains dominate within different geographical
regions, which is a reflection of micro-epidemics of drug resistance in the different regions.
Cluster analysis shows that strains within the same strain family are different. The Beijing drug
resistant strain family is the most dominant strain family (31%) in the Western Cape and of
particular concern is the highly transmissible Beijing cluster 220 strain in the Western Cape
communities. This cluster is widespread in the region and was previously identified in a MDR
outbreak in a high school in Cape Town. Results suggest that the spread of Beijing drug resistant
cluster 220 in the community was due to a combination of acquisition of drug resistant markers
and transmission. This study also indicate that atypical Beijing can acquire drug resistance and
become fit amongst HIV infected individuals. This is contrary to believe that atypical Beijing
strains are not frequently associated with drug resistance and are attenuated. This implies that
HIV levels the playing field for all drug resistant strains.
Mechanisms leading to the evolution of MDR-TB and XDR-TB in a mine setting with a wellfunctioning
TB control program which exceeds the target for cure rates set by the WHO were
investigated. Despite the excellent control program, an alarming increase in the number of drug
resistant cases was observed in 2003 and subsequent years. Phylogenetic analysis shows
sequential acquisition of resistance to first and second-line anti-TB drugs leading to the
development of MDR and XDR-TB. Contact tracing indicate extensive transmission of drug
resistant TB in the shafts, hospital and place of residence. This study shows that despite exceeding the WHO cure rate target, it was not possible to control the spread and amplification
of drug resistance. In summary, as a top priority, future TB control plans need to address
diagnostic delay more vigorously. / AFRIKAANSE OPSOMMING: Molukulêre tegnieke toon transmissie as die hoofrede vir die toename in die anti-tuberkulose
middelweerstandigheid epidemie in Suid-Afrika. Die verskillende Mikobakterium tuberkulose
rasse wat domineer in verskillende areas is ‘n refleksie van middelweerstandige mikro-epidemies
in verskillende gebiede. Analise van identiese rasgroepe demonstreer dat ras families bestaan uit
verskillende rasse. Die Beijing middelweerstandige rasfamilie is die mees dominante familie in
die Wes-Kaap (31% van monsters van middelweerstandige families) en van spesifieke belang is
die hoogs oordraagbare Beijing 220 groep. Hierdie groep is die mees wydverspreide groep in die
studie area en was voorheen geïdentifiseer tydens ‘n meervoudige middelweerstandige
uitbreking in ‘n hoërskool in Kaapstad. Die resultate dui aan dat die Beijing middelweerstandige
groep 220 in die gemeenskap versprei as gevolg van ‘n kombinasie van middelweerstand
verwerwing en transmissie. Hierdie studie dui verder aan dat die atipiese Beijing ook
middelweerstandigheid kan verwerf en hoogs geskik is vir infeksie veral in MIV geïnfekteerde
individue. Hierdie data is in teenstelling met die algemene denke dat atipiese Beijing nie gereeld
geassosieer word met middelweerstandigheid nie en dat dit dikwels geattenueer is. Dit beteken
dat MIV die hoof faktor is wat alle middelweerstandige rasse kans gee om te versprei.
Hierdie studie het die meganisme wat lei tot die evolusie van middelweerstandigheid en “XDRTB”
in die myne ondersoek. Die myn besit ‘n goeie funksioneerde tuberkulose kontrole program
wat alreeds die Wêreld Gesondheids Organisasie se mikpunt vir tuberkulose genesing oortref.
Ten spyte van ‘n uitstekende tuberkulose kontrole program, is daar ‘n bekommerenswaardige
toename in die aantal middelweerstandige tuberkulose gevalle waargeneem in 2003 en in die daaropvolgende jare. Filogenetiese analise wys dat opeenvolgende verwerwing van
middelweerstandigheid teen eerste en tweede vlak anti-tuberkulose middels gelei het tot die
ontwikkeling van meervoudige middelweerstandigheid en “XDR-TB”. Die opsporing van
kontakpersone om transmissie te bewys dui aan dat transmissie van middelweerstandige
tuberkulose in die werk plek, hospitaal en woon plek plaasvind. Hierdie studie wys dat ongeag
die feit dat die Wêreld Gesondheids Organisasie se genesings verwagtinge oortref is, dit steeds
onmoontlik was om die verspreiding en amplifisering van middelweerstandigheid te beheer. ‘n
Top prioriteit vir tuberkulose kontrole planne in die toekoms behoort die vertraging van diagnose
sterk aan te spreek.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/21656 |
| Date | 10 July 2012 |
| Creators | Falmer, Alecia Angelique |
| Contributors | Victor, Tommie, Stellenbosch University. Faculty of Health Sciences. DST-NRF Centre of Excellence for Biomedical TB Research. |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | Unknown |
| Type | Thesis |
| Format | xiv, 108 p. : ill. |
| Rights | Stellenbosch University |
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