Molecular characterization of drug resistant Mycobacterium tuberculosis isolates from different regions in South Africa

Falmer, Alecia Angelique (Stellenbosch : Stellenbosch University, 2012-07-10)

Thesis (MScMedSc)--Stellenbosch University, 2008.

Thesis

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.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/21656
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