Prevalence and resistance gene mutations of multi-drug resistant and extensively drug resistant mycobacterium tuberculosis in the Eastern Cape
- Authors: Hayes, Cindy
- Date: 2014
- Subjects: Multidrug-resistant tuberculosis -- South Africa -- Eastern Cape , Mycobacterium tuberculosis -- South Africa -- Eastern Cape , Microbial mutation
- Language: English
- Type: Thesis , Masters , MTech
- Identifier: vital:10125 , http://hdl.handle.net/10948/d1020374
- Description: The emergence and spread of multi-drug resistant (MDR-TB) and extensively drugresistant tuberculosis (XDR-TB) are a major medical and public problem threatening the global health. The objectives of this study were to (i) determine the prevalence of MDR-TB and XDR-TB in the Eastern Cape; (ii) analyze patterns of gene mutations in MDR-TB and (iii) identify gene mutations associated with resistance to second line injectable drugs in XDR-TB isolates. A total of 1520 routine sputum specimens sequentially received within a period of 12 months i.e. February 2012 to February 2013 from all MDR-TB and XDR-TB patients treated by Hospitals and clinics in the Eastern Cape were included in this study, of which 1004 had interpretable results. Samples were analyzed with the Genotype MTBDRplus VER 2.0 assay kit (Hain Lifescience) for detection of resistance to Rifampicin and Isoniazid while solid and liquid culture drug susceptibility tests were used for ethambutol, streptomycin, ethionamide, ofloxacin, capreomycin and amikacin. PCR and sequence analysis of short regions of target genes gyrA, (encode subunit of DNA topoisomerase gyrase), rrs (16S rRNA) and tlyA (encodes a 2’-O-methyltransferase) were performed on 20 XDR-TB isolates. MTBDRplus kit results and drug susceptibility tests identified 462 MDR-TB, 284 pre-XDR and 258 XDR-TB isolates from 267 clinics and 25 hospitals in the Eastern Cape. There was a high frequency of resistance to streptomycin, ethionamide, amikacin, ofloxacin and capreomycin. Mutation patterns indicated differences between the health districts as well as differences between the facilities within the health districts. The most common mutation patterns observed were: (i) ΔWT3, ΔWT4, MUT1 [D516V+del515] (rpoB), ΔWT, MUT1 [S315T1] (katG), ΔWT1 [C15T] (inhA) [39 MDR, 204 XDR-TB and 214 pre XDR-TB isolates], (ii) ΔWT8, MUT3 [L533P+S531L] (rpoB), ΔWT, MUT1 [S315T1] [145 MDR, 18 pre-XDR and 3 XDR-TB solates] and (iii) ΔWT3, WT4 [D516Y+del515] (rpoB), ΔWT, MUT1 [S315T1] (katG) [75 MDR, 1 pre-XDR and 7 XDR-TB isolates]. Mutations in inhA promoter regions were strongly associated with XDR-TB isolates. Two thirds (66.6 percent (669/1004) of the isolates had inhA mutations present with 25.4 percent (170/669) found among the MDR isolates, 39.2 percent (262/669) among the pre-XDR isolates and 35.4 percent (237/669) among the XDR-TB isolates, which implies that these resistant isolates are being spread by transmission within the community and circulating in the province. There was good correlation between XDR-TB drug susceptibility test results and sequence analyses of the gyrA and rrs genes. The majority of XDR-TB isolates contained mutations at positions C269T (6/20) and 1401G (18/20) in gyrA and rrs genes respectively. Sequence analysis of short regions of gyrA and rrs genes may be useful for detection of fluoroquinolone and amikacin/ kanamycin resistance in XDR-TB isolates but the tlyA gene is not a sensitive genetic marker for capreomycin resistance. This study highlighted the urgent need for the development of rapid diagnostics for XDR-TB and raised serious concerns regarding ineffective patientmanagement resulting in ongoing transmission of extremely resistant strains of XDRTB in the Eastern Cape suggesting that the Eastern Cape could be fast becoming the epicenter for the development of Totally Drug-resistant Tuberculosis (TDR-TB) in South Africa.
- Full Text:
- Date Issued: 2014
- Authors: Hayes, Cindy
- Date: 2014
- Subjects: Multidrug-resistant tuberculosis -- South Africa -- Eastern Cape , Mycobacterium tuberculosis -- South Africa -- Eastern Cape , Microbial mutation
- Language: English
- Type: Thesis , Masters , MTech
- Identifier: vital:10125 , http://hdl.handle.net/10948/d1020374
- Description: The emergence and spread of multi-drug resistant (MDR-TB) and extensively drugresistant tuberculosis (XDR-TB) are a major medical and public problem threatening the global health. The objectives of this study were to (i) determine the prevalence of MDR-TB and XDR-TB in the Eastern Cape; (ii) analyze patterns of gene mutations in MDR-TB and (iii) identify gene mutations associated with resistance to second line injectable drugs in XDR-TB isolates. A total of 1520 routine sputum specimens sequentially received within a period of 12 months i.e. February 2012 to February 2013 from all MDR-TB and XDR-TB patients treated by Hospitals and clinics in the Eastern Cape were included in this study, of which 1004 had interpretable results. Samples were analyzed with the Genotype MTBDRplus VER 2.0 assay kit (Hain Lifescience) for detection of resistance to Rifampicin and Isoniazid while solid and liquid culture drug susceptibility tests were used for ethambutol, streptomycin, ethionamide, ofloxacin, capreomycin and amikacin. PCR and sequence analysis of short regions of target genes gyrA, (encode subunit of DNA topoisomerase gyrase), rrs (16S rRNA) and tlyA (encodes a 2’-O-methyltransferase) were performed on 20 XDR-TB isolates. MTBDRplus kit results and drug susceptibility tests identified 462 MDR-TB, 284 pre-XDR and 258 XDR-TB isolates from 267 clinics and 25 hospitals in the Eastern Cape. There was a high frequency of resistance to streptomycin, ethionamide, amikacin, ofloxacin and capreomycin. Mutation patterns indicated differences between the health districts as well as differences between the facilities within the health districts. The most common mutation patterns observed were: (i) ΔWT3, ΔWT4, MUT1 [D516V+del515] (rpoB), ΔWT, MUT1 [S315T1] (katG), ΔWT1 [C15T] (inhA) [39 MDR, 204 XDR-TB and 214 pre XDR-TB isolates], (ii) ΔWT8, MUT3 [L533P+S531L] (rpoB), ΔWT, MUT1 [S315T1] [145 MDR, 18 pre-XDR and 3 XDR-TB solates] and (iii) ΔWT3, WT4 [D516Y+del515] (rpoB), ΔWT, MUT1 [S315T1] (katG) [75 MDR, 1 pre-XDR and 7 XDR-TB isolates]. Mutations in inhA promoter regions were strongly associated with XDR-TB isolates. Two thirds (66.6 percent (669/1004) of the isolates had inhA mutations present with 25.4 percent (170/669) found among the MDR isolates, 39.2 percent (262/669) among the pre-XDR isolates and 35.4 percent (237/669) among the XDR-TB isolates, which implies that these resistant isolates are being spread by transmission within the community and circulating in the province. There was good correlation between XDR-TB drug susceptibility test results and sequence analyses of the gyrA and rrs genes. The majority of XDR-TB isolates contained mutations at positions C269T (6/20) and 1401G (18/20) in gyrA and rrs genes respectively. Sequence analysis of short regions of gyrA and rrs genes may be useful for detection of fluoroquinolone and amikacin/ kanamycin resistance in XDR-TB isolates but the tlyA gene is not a sensitive genetic marker for capreomycin resistance. This study highlighted the urgent need for the development of rapid diagnostics for XDR-TB and raised serious concerns regarding ineffective patientmanagement resulting in ongoing transmission of extremely resistant strains of XDRTB in the Eastern Cape suggesting that the Eastern Cape could be fast becoming the epicenter for the development of Totally Drug-resistant Tuberculosis (TDR-TB) in South Africa.
- Full Text:
- Date Issued: 2014
Perceptions of school managers regarding knowledge sharing practices in the FET (Grade 10-12) schools in the butterworth District
- Authors: Mkabile, Bulelwa
- Date: 2011
- Subjects: School principals -- Education (FET) -- Schools
- Language: English
- Type: Thesis , Masters , M Ed
- Identifier: vital:18440 , http://hdl.handle.net/11260/d1007249
- Description: Education reforms and the constant changes in the curriculum require school managers and educators to keep abreast of the changes and developments. In order to achieve quality education in this Information Age, there is a need to share knowledge, resources, and good practices and ensure twinning of schools. The purpose of this study was to explore perceptions, beliefs and experiences of school managers regarding knowledge sharing in schools. Qualitative methods were used to collect and analyse the data. In accordance with the qualitative approach, a phenomenological design was adopted. Data was gathered through interviews from a sample of six school managers of Further Education and Training (Grade 10 -12) schools. The findings of the study revealed that school managers perceive their role as important for the success of knowledge sharing in schools. They attribute the good performance in their schools to the educators‟ willingness to share knowledge. However, trust, good relations and respect determined the willingness to share and with whom to share knowledge in schools. School managers believe that availability of Information and Communication Technology (ICT) infrastructural resources could improve knowledge sharing practices in schools. Staff meetings, subject meetings, workshops and notice boards were identified as some of the strategies currently used for sharing knowledge. The support of the district officials and other education specialists has contributed in helping schools deal with education reforms. Communities of practice are recommended in order to improve and encourage the sharing of tacit and implicit knowledge in schools. Researchers believe that professional communities of practice enhance sharing and provide greater opportunities for knowledge creation. Policy developers, curriculum planners and district officials need to develop and adopt creative and innovative strategies to ensure effective distribution and sharing of knowledge and information among school managers and educators in schools.
- Full Text:
- Date Issued: 2011
- Authors: Mkabile, Bulelwa
- Date: 2011
- Subjects: School principals -- Education (FET) -- Schools
- Language: English
- Type: Thesis , Masters , M Ed
- Identifier: vital:18440 , http://hdl.handle.net/11260/d1007249
- Description: Education reforms and the constant changes in the curriculum require school managers and educators to keep abreast of the changes and developments. In order to achieve quality education in this Information Age, there is a need to share knowledge, resources, and good practices and ensure twinning of schools. The purpose of this study was to explore perceptions, beliefs and experiences of school managers regarding knowledge sharing in schools. Qualitative methods were used to collect and analyse the data. In accordance with the qualitative approach, a phenomenological design was adopted. Data was gathered through interviews from a sample of six school managers of Further Education and Training (Grade 10 -12) schools. The findings of the study revealed that school managers perceive their role as important for the success of knowledge sharing in schools. They attribute the good performance in their schools to the educators‟ willingness to share knowledge. However, trust, good relations and respect determined the willingness to share and with whom to share knowledge in schools. School managers believe that availability of Information and Communication Technology (ICT) infrastructural resources could improve knowledge sharing practices in schools. Staff meetings, subject meetings, workshops and notice boards were identified as some of the strategies currently used for sharing knowledge. The support of the district officials and other education specialists has contributed in helping schools deal with education reforms. Communities of practice are recommended in order to improve and encourage the sharing of tacit and implicit knowledge in schools. Researchers believe that professional communities of practice enhance sharing and provide greater opportunities for knowledge creation. Policy developers, curriculum planners and district officials need to develop and adopt creative and innovative strategies to ensure effective distribution and sharing of knowledge and information among school managers and educators in schools.
- Full Text:
- Date Issued: 2011
An investigation into how Johnnic Communications can maximise its online presence and e-commerce potential
- Authors: Goko, Jethro
- Date: 2006
- Subjects: Electronic commerce -- South Africa -- Technological innovations , Internet advertising -- South Africa , Internet marketing -- South Africa
- Language: English
- Type: Thesis , Masters , MBA
- Identifier: vital:8578 , http://hdl.handle.net/10948/510 , Electronic commerce -- South Africa -- Technological innovations , Internet advertising -- South Africa , Internet marketing -- South Africa
- Description: The exponential growth of the Internet and other new technologies globally continues to re-shape the South African consumer and business landscapes. Media and entertainment group Johnnic Communications Limited has invested more than R1 billion in new technologies in the past 10 years alone. However, the company still has to realise the desired returns on this investment – a situation that is forcing management to review all its online activities. This research project sought to determine what the key success factors are for the local and international online media industry, with a view to recommending potentially viable Internet strategies that could turn around operations such as Johnnic Communications’ online offerings from being nice-to-have cost centres, into exciting and key profit-generating streams. The research found that while Internet offerings cannibalise the readership of printed newspapers in South Africa, new technologies also present media houses with the opportunity to tap into new and broader markets, and hence new revenue streams. To that extent, it concluded that continuing to invest in the Internet is an imperative for Johnnic Communications, rather than an option. In addition to recommending new digital strategies, the research also concludes that developing critical mass and having a clear online strategy are crucial factors towards the company making money out of new technologies.
- Full Text:
- Date Issued: 2006
- Authors: Goko, Jethro
- Date: 2006
- Subjects: Electronic commerce -- South Africa -- Technological innovations , Internet advertising -- South Africa , Internet marketing -- South Africa
- Language: English
- Type: Thesis , Masters , MBA
- Identifier: vital:8578 , http://hdl.handle.net/10948/510 , Electronic commerce -- South Africa -- Technological innovations , Internet advertising -- South Africa , Internet marketing -- South Africa
- Description: The exponential growth of the Internet and other new technologies globally continues to re-shape the South African consumer and business landscapes. Media and entertainment group Johnnic Communications Limited has invested more than R1 billion in new technologies in the past 10 years alone. However, the company still has to realise the desired returns on this investment – a situation that is forcing management to review all its online activities. This research project sought to determine what the key success factors are for the local and international online media industry, with a view to recommending potentially viable Internet strategies that could turn around operations such as Johnnic Communications’ online offerings from being nice-to-have cost centres, into exciting and key profit-generating streams. The research found that while Internet offerings cannibalise the readership of printed newspapers in South Africa, new technologies also present media houses with the opportunity to tap into new and broader markets, and hence new revenue streams. To that extent, it concluded that continuing to invest in the Internet is an imperative for Johnnic Communications, rather than an option. In addition to recommending new digital strategies, the research also concludes that developing critical mass and having a clear online strategy are crucial factors towards the company making money out of new technologies.
- Full Text:
- Date Issued: 2006
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