Malaria is a deadly disease transmitted by the female Anopheles mosquito in many tropical and subtropical regions. This disease kills more 500 000 people annually, yet these deaths can be prevented if malaria is diagnosed timeously and treated effectively. Despite many initiatives to fight this disease, the incidence of malaria remains high in the Mutale Municipality in the Limpopo Province where the majority of malaria cases have been diagnosed over the past decade. This study aimed to explore the current status of health education for the prevention and control of malaria in primary schools in the Ha-Makuya Village, Vhembe District in the Mutale Municipality. The possible existence of educational strategies in place to promote malaria awareness in schools was investigated. It was assumed that strategies such as collaboration between the Departments of Health and Education on health education, and policy provision on the topic could lead to children learning about malaria prevention and control, and in turn, inform their parents, leading to the broader community practicing preventive measures, leading to the reduction and eventual elimination of malaria in endemic areas. A qualitative research approach was employed in this study, informed by the interprevist paradigm, using a case study. Data was collected through interviews with relevant stakeholders in this matter, such as principals, teachers, nurses and a district official, in order to gain an understanding of their views on and perception of this disease, and to gauge their knowledge on practices to promote malaria awareness through health education. Existing policies were also analysed to examine possible content on this matter. It was found that even though some of the stakeholders’ knowledge on malaria-related issues was lacking, their attitude towards prevention strategies was positive. It was further found that, even though some effort was being made to work together, collaboration between the stakeholders was at best tenuous. Policy was also found to be lacking on provisions for the successful implementation of health education programmes for the prevention and control of malaria in schools. Recommendations to address these issues were made to the Departments of Health and Education, principals, teachers, policy-makers, as well as for further study. / Dissertation (MEd)--University of Pretoria, 2017. / Early Childhood Education / MEd / Unrestricted

Malaria claims millions of lives annually. This global killer causes approximately 2.7 million annual deaths worldwide; addressing this problem has become more and more crucial. Due to pathogen evolution no efficient vaccine for treatment of malaria currently exists. As infection has developed as a field of study, it became ever more clear that infections could only be understood within the context of the host-pathogen community. This project aims to predict possible drug targets based on host-pathogen interactions rather than just protein-protein interactions within a single organism. Similar to Lee et al. (2008) pathogen-host interaction predictions are based on orthology, these interactions are then analysed to identify potential drug targets. This could potentially aid researchers in their continuous battle against malaria and the larger scale battle against pathogen evolution. To predict in vitro host-pathogen interactions DISCOVERY uses an ortholog clustering method called ORTHOMCL. ORTHOMCL is very suitable for ortholog clustering of malaria data for two reasons. Firstly, it is capable of distinguishing between recent paralogs and ancient paralogs, which enables the inclusion of recent paralogs together with orthologs. Secondly, ORTHOMCL was initially developed for the use of malaria data. Identification of in vitro interactions is followed by scoring methods to determine the possible in vivo interactions that might occur between the Plasmodium parasite and the human and mosquito hosts. Scoring measures and weights were applied to 5 different factors to calculate a final score. These final scores allow user input to define the preferred stringency when viewing possible interactions with a single protein. These different factors are sequence similarity, PEXEL/VTS motif presence, microarray expression, metabolic map sharing and sub-cellular locations boundaries. DISCOVERY’S results and results from two other (Dyer et al. and Lee et al.) in silico prediction methods were compared with Vignali et al’s experimental interactions which are based on a yeast two-hybrid approach. Similar to results shown by Doolittle and Gomez these comparisons had poor results. The next step was to compare the in silico results with each other. Dyer et al’s and Lee et al‘s results compared poorly with each other. Although DISCOVERY did not compare well with Dyer et al’s results, comparisons with Lee et al. showed more promise. Poor comparisons with Dyer et al. may be due to their unique approach to predict in vitro host-pathogen interactions. This project identified the lack of enough valid and reliable experimental data to evaluate in silico prediction methods as a definite challenge for host-pathogen interaction predictors. Although this is a major problem, DISCOVERY improved on older prediction methods with the use of a more applicable ortholog clustering technique and the use of more assessment methods during in vivo interaction predictions. DISCOVERY also used scoring methods rather than exclusion methods during the identification of in vivo interactions. This allows a user to specify a threshold of sensitivity when viewing interactions. The true potential of host-pathogen interaction predictions would only be realized when the gap between predictions and evaluation data is bridged. / Dissertation (MSc)--University of Pretoria, 2010. / Biochemistry / unrestricted

Indiana University-Purdue University Indianapolis (IUPUI) / Artemisinin resistance was first observed in Southeast Asia (SEA) and could pose a threat to malaria treatment all over the world. Recently mutations in the propeller region of Pfkelch13 gene have been used as a genetic marker for resistance observed in SEA. We investigated the presence of mutations in the Pfkelch gene in children in Kampala, Uganda with severe malaria (SM) treated with intravenous quinine, or with asymptomatic P.falciparum infection (AP) treated with artemether-lumefantrine. We sequenced the Pfkelch gene (2178bp) in 157 children with SM and 49 children with AP infection. In children with SM and AP we identified 106 (60.8%) and 27 (55.1%) parasites with mutations upstream of the Pfkelch13 propeller region. The two most prevalent mutations were 142NN (26.1% in SM, 33% in AP) and K189T (16.5% in SM, 12.2% in AP). In SM, only a single infection had a mutation in the propeller region (A578S), while in AP, mutations in the propeller region included A578S (n=1) and S522C (n=1). In children with SM, parasites with 142NN insertion compared to 3D7 Pfkelch13 parasites had lower parasite density (p=0.02) and lower parasite biomass (p=0.03). Children with SM who either had 142NN or K189T mutation cleared parasites after quinine treatment faster than those with the 3D7 Pfkelch13 genotype (P<0.001 for both mutations compared to 3D7). In this cohort mutations, upstream of the Pfkelch13 propeller region were common. Future studies will assess the presence of Pfcrt and Pfmdr mutations in this cohort, and how these relate to the Pfkelch13 mutations and to parasite clearance.

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Transmission-blocking vaccines (TBVs) target Plasmodium parasite sexual stages, aiming to block further development of the parasite within the mosquito host. Plasmodium falciparum zygote/ookinete surface protein Pfs25 is one of the leading TBV candidate antigens and antibodies against Pfs25 have been shown to exhibit complete transmission-blocking activity in pre-clinical studies. Phase 1 human clinical trials have revealed that Pfs25 was a poor immunogen in humans in the formulations tested and high titers of anti-Pfs25 antibodies are required to achieve good transmission-blocking activity in the ex vivo standard membrane feeding assay which measures the functional activity of the antibodies induced. Work in this thesis describes the production of recombinant monomeric Pfs25 protein, Pfs25 based particulate vaccines (Pfs25-IMX313 nanoparticle, Pfs25-HBsAg VLP and Pfs25-Q&beta; VLP) and a Pfs25-Pfs28 multivalent protein vaccine in the Pichia pastoris protein expression system. These proteins were tested in mice using protein-in-adjuvant formulations and their immunogenicity was assessed. Pfs25-IMX313 nanoparticle induced significantly higher anti-Pfs25 antibodies than monomeric Pfs25 and the antibodies had higher avidity and transmission-blocking activity. All of the candidate vaccines generated, except for Pfs25-HBsAg VLP, were immunogenic. The Pfs25-IMX313 nanoparticle induced the highest antibody response in mice followed by the Pfs25-Pfs28 multivalent protein and Pfs25-Q&beta; VLP.

How parasites influence the population dynamics of their hosts depends on 1) theproportion of individuals that carry the infection in the population, 2) what type of individuals aremost susceptible to infection and 3) the fitness effects of infection. In this study I first investigate thefrequency of malaria strains transmitted in the African winter quarters or at the European breedinggrounds in collared flycatchers (Ficedula albicollis). I then zoom in on the relationship between avianmalaria infection status and condition, expression of sexually selected ornament and reproductiveperformance of male collared flycatchers. I found that female flycatchers are more likely to beinfected than males and that both sexes have a large bias towards infection with European strains ofmalaria. Infected male flycatchers have higher reproductive success and tend to have largerornaments but there was no detected relationship between malaria infection and male condition.This is the first example, that I am aware of, of a positive relationship between malaria infection andreproductive success.