3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item The role of mutations in uncomplicated Plasmodium falciparum malaria and sulfadoxine pyrimethamine efficacy in Mpumalanga Province, South Africa.(2006-11-17T07:55:38Z) Mngomezulu, Nicros MagangeniThe antifolate combination of sulfadoxine and pyrimethamine (SP) is one of few remaining affordable drug combinations available for wide-scale treatment of uncomplicated Plasmodium falciparum malaria in Africa. In vivo studies of SP efficacy conducted during 1998, 2000 and 2002 at the Naas sentinel site in Mpumalanga province, South Africa, demonstrated a gradual non-significant increase in late treatment failure (LTF) and early treatment failure (ETF) resistance to SP, while gametocyte carriage increased significantly between 1998 and 2002 (p < 0.0001). This study aimed to determined and compare the frequency of dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) resistant haplotypes in P. falciparum parasites from patients treated with SP in three consecutive standardized in vivo therapeutic efficacy studies in Mpumalanga province, since implementation of SP as first line treatment in 1998, and to investigate associations between the presence of mutations and treatment outcomes after SP treatment. Four hundred-and-three samples were studied and 358 yielded polymerase chain reaction products. A novel high throughput sequence-specific oligonucleotide probe-based approach was used to examine the resistance status of the three in vivo P. falciparum populations. Screening for the presence of all known point mutations in dhfr and dhps genes revealed that only five dhfr and three dhps allelic haplotypes were present. In all the samples investigated, point mutations were identified only at codons 108, 51 and 59 of the dhfr gene and at codons 347 and 540 of the dhps gene. The prevalence of dhfr resistant haplotypes was 35.4% in 1998, 38.7% in 2000, and 41.0% in 2002, while the prevalence of dhps resistant haplotypes was 9.7% in 1998, 7.2% in 2000 and 41.6% in 2002, the latter representing a significant increase (p < 0.002). The prevalence in both dhfr and dhps gene resistant haplotypes were selected gradually during the three in vivo studies in Mpumalanga province. Infection with parasites having triple dhfr mutations and double dhps mutations, "the quintuple mutant", was associated with SP treatment failure (p < 0.001). Mutations at both dhfr and dhps loci may be important predictors of SP resistance in Mpumalanga province.Item Morphological variation in the metatarsal bones of selected recent and pre-pastoral humans from South Africa(2006-03-23) Zipfel, BernhardThe study of the human metatarsals reveals frequent morphological variations from the typical descriptions. Pathologies of these bones in contemporary humans are common, and it has been suggested that some of these may be associated with some of these variants. Within this context, it was not clear to what extent footwear and other environmental factors such as modern substrates have influenced metatarsal morphology. This study essentially consists of three parts. First a preliminary morphometric study of the first, second and fifth metatarsals, to demonstrate the broad patterns of discrimination between selected hominoidea, namely humans, gorillas, chimpanzees and orangutans. In addition, the SKX 5017 first metatarsal fossil thought to be of Paranthropus robustus was included. Second, a primary morphometric investigation into the patterns of morphological discrimination in the five metatarsals of selected humans from South Africa, namely Sotho, Zulu, European and pre-pastoral subgroups. The contemporary human subgroups are associated with modern lifestyles and the pre-pastoral individuals represent habitually unshod forager societies from the western and southern Cape, dated 9750 - 2000 B.P. Third, a non-metric investigation into the patterns of variation in epigenetic and pathological variants of the metatarsus of the four human subgroups. A suite of existing metrical data was utilized for the preliminary hominoid study, and a suite of metrical and non-metrical data was collected for the primary human study from appropriate skeletal collections. Univariate analysis of these iv samples revealed important, though simplistic trends in morphology. Subsequent multivariate analyses utilizing principal components and canonical variates analysis were undertaken. Multivariate analysis of the hominoid samples revealed large scale variation between the species. This discrimination was on the basis of genetics, locomotor function and geography. Multivariate analysis of the human metrical data revealed very subtle morphological discrimination within and between the subgroups. Most of this discrimination appears to be genetic, followed by a functional or life-style based discrimination suggesting a broad discrimination between recent humans and the habitually unshod pre-pastoral subgroup. The epigenetic traits reveal considerable variation within groups, with similar trends between them. All subgroups have an appreciable number of identifiable pathological changes, with the recent human subgroups having the most and the prepastoral subgroup the least. In all subgroups, the hallucal metatarsal displays by far the greatest frequency in osseous modification. The main conclusions of this study are: 1.) The general patterns of morphological discrimination between the metatarsals of the human subgroups are very subtle. The non-metric traits are very variable, but do not discriminate between any of the subgroups. 2.) Both recent and ancient human groups present with similar patterns of pathological changes, but the frequency is different, these changes are to a great extent influenced by lifestyle. Regardless of temporal context, no clear correlation between morphological variation and pathological changes could be found.Item West Africa versus the U.S on cotton subsidies: Why,how and what next?(2006-02-15) Heinisch, Elinor LynnThis study examines the convergence of events, internationally and domestically, in the last decade that led to Benin, Burkina Faso and Mali challenging U.S. cotton subsidies. It outlines the political and economic context in which West African and American cotton farmers compete. It explores how the West Africans have confronted U.S. policy, why their cause has generated sympathy and interest, whether they are likely to be successful, and the implications of their campaign. The paper draws from analyses of the financial impact of U.S. cotton subsidies, documents filed with the World Trade Organization (WTO), public statements, media coverage, materials from nongovernmental organizations, and interviews with involved parties. It identifies four actors driving this initiative: the cotton farmers, the producers’ unions, the states and the international financial institutions, and their tactics: using the WTO, having many spokespeople with common messages, having powerful allies and using the media.Item Vulnerability to climate variability in Botswana 1972-2002(2006-02-08) Babugura, Agnes ADue to increasing rapid environmental change, coupled with changes in social, economic and political conditions, vulnerability assessments have become increasingly important for understanding society’s capacity to deal with such changes. The aim of this research is to examine vulnerability of rural societies as well as the configuration of forces that shape their ability to cope and adapt to climate variability. The study compares two rural societies living in different climatic regions in Botswana. These are, the southwestern part, which has the driest climate and the northern part, which has the wettest climate.