Coreceptor utilization and primary cell tropism by HIV-1 subtype C strains.

Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2011.Human immunodeficiency virus type 1 (HIV-1) isolates can be differentiated based on their ability to use particular coreceptors – R5 viruses use CCR5, X4 viruses use CXCR4 and R5X4 (dual tropic) viruses use both CCR5 and CXCR4. It is widely reported that HIV-1 subtype C (HIV-1C) has a unique viral coreceptor evolution pattern in that a complete switch from the predominant CCR5 (R5) to CXCR4 (X4) phenotype is less common for this subtype compared to other subtypes. However, dual tropic HIV-1C isolates have occasionally been described. Furthermore, it has been reported that certain highly active antiretroviral drugs (HAART) may select for X4 viral variants. Therefore, this thesis study was undertaken to better understand the functional and genotypic characteristics of dual tropic HIV-1C isolates, and to characterize drug resistance and coreceptor usage patterns in HAART-naïve versus HAART-failing HIV-1C infected patients. Thirty-five functional HIV-1 env clones derived from seven dual tropic HIV-1C strains were generated and their coreceptor usage characterized in transformed cell lines. All 35 env clones efficiently infected transformed cells expressing CXCR4. Twenty of 35 clones (57%) also utilized the CCR5 receptor. No R5-only clones were detected. Functional coreceptor usage data was correlated to env gene sequence data. The ability of the HIV-1C env clones to facilitate infection of primary lymphocytes and monocyte-derived macrophages was next investigated. The majority of clones characterized as X4 or R5X4 on cell lines used either CXCR4 alone or CXCR4 and CCR5, respectively, in primary cells. A few viruses displayed comparable CCR5 and CXCR4 usage and clones from one virus preferred CCR5 usage in macrophages. Thus in a few cases coreceptor phenotyping in transformed cell lines does not predict usage in primary cells. Genetic determinants for coreceptor usage in primary cells require further investigation. Finally the patterns of drug resistance mutations were studied and coreceptor usage among 45 HAART-naïve and 45 HAART-failing HIV-1C infected patients analyzed. Ninety-five percent of HAART-failing patients had viruses with at least one drug resistance mutation. Thymidine analog resistance mutations (TAMs) were present in 55% of patients. HAART-failing patients had significantly higher prevalence (59%) of X4/R5X4-utilizing viruses compared to HAART-naïve patients (30%) (p<0.02) using the Trofile Co-receptor Tropism Assay while 41% of HAART-failing patients used CCR5 and 70% of HAART-naïve patients used CCR5. Functional results correlated with predictive algorithm methods. This study enhances our understanding of HIV-1 pathogenesis and the results have important implications for the use of coreceptor antagonists for the clinical management of HIV-1C infection

Exploring the diverse perspectives of the disciplinary methods aimed at modifying problem behaviours in young children in selected areas in Pietermaritzburg.

Master of Social Science in Psychology. University of KwaZulu-Natal, 2015.Racial diversity shapes the way individuals perceive the concept of discipline, from the meaning they attach to it, to the different disciplinary methods they apply, to the role they assume in the disciplinary process. Described as a form of love, respect and guidance, discipline encompasses the teaching of values and behaviours. Young children are encouraged to know the rules and boundaries within the home and schooling facilities, making them mindful of the behaviours that are expected of them. In South Africa, the modern child is labelled as technologically more advanced, eager to do more, see more and learn more, and therefore needs constant stimulation. Notwithstanding the impact of race and culture in nurturing a child, technology currently also plays a role, with the study results revealing that the majority of participants denied children luxuries as a method of modifying problem behaviours. Parents and educators approached discipline in various ways, implementing methods familiar to them. The research results revealed that several participants supported the occasional smack on the bottom, arguing that the intent and attitude of a light smack or tap is very different from physical abuse, and demonstrates love and guidance. Many of the participants interviewed were in favour of maintaining corporal punishment within the home environment. Further positive disciplinary methods used included time-out, rewards and praise, a change in tone of voice, and the denying of luxuries. The participants held very negative views on the use of demerits, with a number of participants choosing not to do so. Participants described demerits as demoralising and de-motivating, and claimed that it created a sense of unfairness on the part of learners. The parents, crèche facilitators and Grade R educators interviewed highlighted problems that included a lack of parental involvement in homework, recreational activities, and most importantly, discipline. Emphasis was also placed on establishing a more positive, healthy educator-learner relationship. The recommendations of the study included creating greater awareness through the means of support networks and workshops for parents and educators. These could establish a forum to share information and provide support when dealing with problem behaviours, language barriers and discipline

The Need for Privatization of Jharkhand State Electricity Board – An Organizational Study

The paper explores the pros and cons of privatization in electrical utilities in India. The study of Jharkhand State Electricity Board examines whether a need for privatization exists and determine to what extent the organization is prepared for implementation privatization. The results suggest that there is a need to privatize the organization, as it is weak in three aspects of operations, finance and human resource. The results also suggest that there are many factors internal and external to the organization, which affect the implementation of privatization. Hence a well-planned strategic slow paced privatization is needed

Embedding Undergraduate Research through Industry-Based Projects: Student Experiences

Traditionally, formal training in research methodology begins in postgraduate programmes; however, potential exists to embed high-impact research skills during the undergraduate programme to develop learning by inquiry, promote critical thinking and engaged scholarship. Identifying factors that affect students’ research engagement can provide important practical implications to effectively encourage and facilitate undergraduate research opportunities. This exploratory qualitative study investigates the undergraduate student experience of the research process embedded in collaborative industry-based projects, through focus-group discussions. Using predefined domains from the interview guide, key themes emerging from the focus group discussions included a process-orientated approach to research, knowledge synthesis through data collection and handling, data collection experience, and students’ experience of a collaborative and deep approach to learning. Key enablers of the research engagement included funding for undergraduate research and transfer of research skills into higher levels of study whilst key barriers were limited foundational research knowledge and the impact of emergency situations. Other emergent themes included knowledge transfer through early initiation of research in the undergraduate programme. Institutional and programmatic engagement is required to support undergraduate students with the rigours of becoming knowledge co-constructors for their graduate destination or continuation of postgraduate studies

Displacement & domesticity since 1945 : refugees, migrants and expats making homes : following the EAHN's sixth thematic conference (Brussels, 27-28 march 2019)

In the recent history of globalisation and mass human displacement, the practical and epistemological tools of architecture play a role in revealing the multi-faceted relationship between migration and home. The goal of the European Architectural History Network's sixth thematic conference was to illuminate and critically reflect on the conceptual role and socio-material expressions of domesticity employed in response to displacement in contemporary history, beginning with the year 1945. Many of the papers reflected a deep interest in the processes involved in thinking, building and preserving home as well as the growing importance of interdisciplinary and cross-cultural collaborations. Inspired by this, we seek to prompt ways, especially from within the architectural discipline and community, to conceive of alternative epistemological and heuristic frameworks for integrating interdisciplinary knowledge

Emerging Carbapenem-Resistant Enterobacter cloacae Producing OXA-48-, VIM-and IMP-Type-β-Lactamases in Eastern Cape Hospitals in South Africa

Abstract Introduction: Enterobacter cloacae strains have been isolated from Eastern Cape hospitalised patients. Methodology: We have molecularly characterised blaOXA-48-, blaIMP-and blaVIM-expressing E. cloacae isolates demonstrating resistance to carbapenems from five hospitals by multilocus sequence typing. Organism identification and antimicrobial susceptibility testing was done using automated systems and the isolates were screened for carbapenemases using either conventional or real-time PCR and then typed using multilocus sequence typing. Further characterisation of IMPtype-producing E. cloacae isolates, an unusual occurrence in South Africa, was performed by pulsedfield gel electrophoresis. Results and Conclusion: Twenty-five E. cloacae isolates from 24 patients were investigated. Eighteen (72%) isolates harboured either one of the following genes: blaIMP, blaVIM or blaOXA-48. Multilocus sequence typing data and pulsed-field gel electrophoresis showed that several strains from the same geographical region and hospitals were genetically related

An overview of antimicrobial resistance surveillance among healthcare-associated pathogens in South Africa

Healthcare-associated infections are a serious public health concern resulting in morbidity and mortality particularly in developing countries. The lack of information from Africa, the increasing rates of antimicrobial resistance and the emergence of new resistance mechanisms intensifies this concern warranting the need for vigorous standardised surveillance platforms that produce reliable and accurate data which can be used for addressing these concerns. The implementation of national treatment guidelines, policies, antimicrobial stewardship programmes and infection prevention and control practices within healthcare institutions require a platform from which it can draw information and direct its approach. In this review, the importance of standardised surveillance systems, the challenges faced in the application of a surveillance system and the condition (existence and nonexistence) of such systems in African countries is discussed. This review also reports on some South African data

Drug resistance and viral tropism in HIV-1 subtype C-infected patients in KwaZulu-Natal, South Africa: implications for future treatment options

Article approval pendingDrug resistance poses a significant challenge for the successful application of highly active antiretroviral therapy (HAART) globally. Furthermore, emergence of HIV-1 isolates that preferentially use CXCR4 as a coreceptor for cell entry, either as a consequence of natural viral evolution or HAART use, may compromise the efficacy of CCR5 antagonists as alternative antiviral therapy

Molecular characterisation of Acinetobacter baumannii isolates from bloodstream infections in a tertiary-level hospital in South Africa

Acinetobacter baumannii is an opportunistic pathogen and causes various infections in patients. This study aimed to describe the clinical, epidemiological and molecular characteristics of A. baumannii isolated from BCs in patients at a tertiary-level hospital in South Africa. Ninety-six isolates from bloodstream infections were collected. Clinical characteristics of patients were recorded from patient files. Organism identification and AST was performed using automated systems. PCR screening for the mcr-1 to mcr-5 genes was done. To infer genetic relatedness, a dendrogram was constructed using MALDI-TOF MS. All colistin-resistant isolates (n = 9) were selected for WGS. The patients were divided into three groups, infants (<1 year; n = 54), paediatrics (1–18 years; n = 6) and adults (≥19 years; n = 36) with a median age of 13 days, 1 and 41 years respectively. Of the 96 A. baumannii bacteraemia cases, 96.9% (93/96) were healthcare-associated. The crude mortality rate at 30 days was 52.2% (48/92). The majority of the isolates were multidrug-resistant (MDR). All isolates were PCR-negative for the mcr-1 to mcr-5 genes. The majority of the isolates belonged to cluster 1 (62/96) according to the MALDI-TOF MS dendrogram. Colistin resistance was confirmed in nine A. baumannii isolates (9.4%). The colistin-resistant isolates belonged to sequence type (ST) 1 (5/6) and ST2 (1/6). The majority of ST1 isolates showed low SNP diversity (≤4 SNPs). All the colistin-resistant isolates were resistant to carbapenems, exhibited an XDR phenotype and harboured the blaOXA−23 gene. The blaNDM gene was only detected in ST1 colistin-resistant isolates (n = 5). The lpsB gene was detected in all colistinresistant isolates as well as various efflux pump genes belonging to the RND, the MFS and the SMR families. The lipooligosaccharide OCL1 was detected in all colistin-resistant ST1 and ST2 isolates and the capsular polysaccharide KL3 and KL17 were detected in ST2 and ST1 respectively. This study demonstrated a 9.4% prevalence of colistin-resistant ST1 and ST2 A. baumannii in BC isolates. The detection of the lpsB gene indicates a potential threat and requires close prospective monitoring.National Health Laboratory Service (NHLS) Research Trust.https://www.frontiersin.org/journals/microbiologydm2022BiochemistryForestry and Agricultural Biotechnology Institute (FABI)GeneticsMicrobiology and Plant Patholog