Department of Chemistry / MSc (Chemistry) / Due to the increasing incidence of Plasmodium strains that are resistant to current frontline antimalarial drugs, malaria remains a global public health challenge. In recent years, the emergence of resistance to frontline antimalarial drugs including the more recently discovered artemisinin class drugs has become one of the greatest challenges of controlling malaria incidence and mortality. There is, therefore, an urgent need to develop novel targets and antimalarial drugs that are effective against drug-resistant malarial parasites. Recent studies have demonstrated that calcium dependent protein kinases (CDPKs) regulate a variety of biological processes in the malaria parasite Plasmodium falciparum and that CDPK4 is important for parasite development. The gene disruption of CDPK4 in Plasmodium berghei, which results in major defects in sexual differentiation of the parasite has highlighted the importance of CDPK4 in Plasmodium biology and suggests that it may be used as a target for therapeutic drugs. PfCDPK4 is expressed in the gamete/gametocyte stage, and this could make PfCDPK4 an essential target for malaria drug discovery. The structure of PfCDPK4 was used as a template in the discovery of malaria drug leads and in designing chemical compounds or inhibitors that will show anti-parasitic activity against the target molecule. The model structure of PfCDPK4 was generated through homology modelling, and model structure validation confirmed that the model structure of PfCDPK4 is of stereochemical quality. The molecular modelling approach of in silico screening was utilized in this research, wherein a large library of chemical compounds, some natural chemical compounds, and clinically approved kinase inhibitors were screened against the target molecule PfCDPK4. In silico screening of the Bio-Focus library against PfCDPK4 resulted in twenty-six compounds being identified; in vitro single screening at a concentration of 5 μM confirmed that three compounds exhibit moderate antimalarial activity against the NF54 strain of Plasmodium falciparum, with the percentage inhibition ranging between 42% and 47%.

MSc Applied Mathematics) / Department of Mathematics and Applied Mathematics / See the attached abstract below

MENVSC (Geography) / Department of Geography and Geo-Information Sciences / Semi-arid regions of Africa are prone to epidemics of malaria. Epidemic malaria occurs along the geographical margins of endemic regions, when the equilibrium between the human, parasite and mosquito vector populations are occasionally disturbed by changes in one or more meteorological factors and a sharp but temporary increase in disease incidence results. Monthly rainfall and temperature data from the South African Weather Service and malaria incidence data from Department of Health were used to determine the influence of meteorological variables on malaria transmission in Limpopo from 1998-2014. Meteorological influences on malaria transmission were analyzed using time series analysis techniques. Climate suitability for malaria transmission was determined using MARA distribution model. There are three distinct modes of rainfall variability over Limpopo which can be associated with land falling tropical cyclones, cloud bands and intensity of the Botswana upper high. ENSO and ENSO-Modoki explains about 58% of this variability. Malaria epidemics were identified using a standardized index, where cases greater than two standard deviations from the mean are identified as epidemics. Significant positive correlations between meteorological variables and monthly malaria incidence is observed at least one month lag time, except for rainfall which shows positive correlation at three months lag time. Malaria transmission appears to be strongly influenced by minimum temperature and relative humidity (R = 0.52, p<0.001). A SARIMA (2, 1, 2) (1, 0, 0)12 model fitted with only malaria cases has prediction performance of about 53%. Warm SSTs of the SWIO and Benguela Niño region west of Angola are the dominant predictors of malaria epidemics in Limpopo in the absence of La Niña. Warm SSTs over the equatorial Atlantic and Benguela Niño region results in the relaxation of the St. Helena high thus shifting the rainy weather to south-east Africa. La Niña have been linked with increased malaria cases in south-east Africa. During El Niño when rain bearing systems have migrated east of Madagascar ridging of the St. Helena high may produce conducive conditions for malaria transmission. Anomalously warmer and moist winters preceding the malaria transmission season are likely to allow for high mosquito survival and the availability of the breeding sites thus high population in the beginning of the transmission season hence resulting in increased epidemics. / NRF

MPH / Department of Public Health / Background: Malaria is a public health issue killing more than 435 000 people in Sub Saharan Africa. In South Africa, malaria is endemic in 3 provinces namely: Limpopo, Mpumalanga and Kwazulu Natal. Limpopo Province contributes more cases than the other provinces in the country. Purpose: The purpose of the study was to assess community knowledge and prevention practices of malaria at Masisi village, in Mutale Municipality, Vhembe District. The study was conducted at Mutale municipality, Vhembe District. Methodology: A quantitative cross-sectional descriptive approach was used. Data was collected using a questionnaire with open and close ended questions. The targeted population was made up of males and females between the ages of 18 to 75. Validity and reliability have been ensured in the study and the results for reliability were 0.85. Pretesting was done in 5 household at Sanari village which is near Masisi village as they share the same characteristics. A sample of 152 participants was selected from the target population by means of systematic sampling and then select them randomly. Questionnaires were used to collect data. There after Data were analyzed using SPSS version 24.0. The analyzed data were presented in tables, graphs, and in percentages. Results: The findings revealed that majority of the participants 103(67.8%) have secondary education, and most of them, 103(67.8%) are unemployed. The study revealed that about 77% have knowledge regarding malaria transmission. About 130(85.5%) indicated that malaria is caused by a mosquito bite. About 57(38.51%) indicated that they use mosquito coils and nets in their household. Conclusion: Malaria still poses a threat to the lives of people living in malaria endemic areas. Community members at Masisi village have better insight regarding malaria transmission, causes and signs and symptoms. Although the community shows a better understanding of the prevention method they still has to put this into practice in order to eliminate malaria in the area. Health workers are doing a great job in educating the community regarding malaria related issues. / NRF

PhD (Geography) / Department of Geography and Geo-Information Sciences / Malaria is a climate-change concatenated biological hazard that may, like any other natural hazard, can lead to a disaster if there is a failure in handling emergencies or risks. A holistic solution for malaria mitigation can be provided when indigenous knowledge is complemented with scientific knowledge. Malaria remains a challenge in South Africa and Limpopo province is the highest burdened malaria-endemic region. Specifically, Vhembe District is the highest burdened followed by Mopani District (Raman et al., 2016). This research sought to mitigate malaria transmissions in Mopani District through the integration of indigenous and scientific knowledge. The study was carried out in Mopani District of South Africa and 4 municipalities were involved. These are Ba-Phalaborwa, Greater Tzaneen, Greater Letaba, and Maruleng. A pragmatism philosophy was adopted hence the study took a mixed approach (sequential multiphase design). Data was collected from 381 selected participants through in-depth interviews, a survey and a focus group discussion. Participants for the in-depth interviews were obtained through snowballing and selected randomly for the survey, while for the focus group discussion purposive sampling was used. The study applied constructivist grounded theory to analyze qualitative data and to generate theory. Statistical Package for Social Sciences version 23.0 was used for quantitative data. Based on empirical findings, it was concluded that temperature and rainfall among other various factors exacerbate malaria transmission in the study area. Results of the study also show that people in Mopani District predict the malaria season onset by forecasting rainfall using various indigenous knowledge based indicators. The rainfall indicators mentioned by participants in the study were used in the developed early warning system. An Early warning system is an essential tool that builds the capacities of communities so that they can reduce their vulnerability to hazards or disasters. In the design of the system, Apache Cordova, JDK 1.8, Node JS, and XAMPP software were used. The study recommends malaria management and control key stakeholders to adopt the developed early warning system as a further mitigation strategy to the problem of malaria transmission in Mopani District. / NRF