[Truncated abstract] Iron is essential to most biological systems. Under pathological conditions affecting the iron metabolic pathway, iron can be deposited in the tissue in various forms. The work presented in this thesis has exploited the relationship between the magnetic and the chemical properties of tissue iron deposits to further understanding of two major pathologies, the haemoglobinopathies termed thalassaemias and the malaria parasite Plasmodium falciparum, both amongst the most common health concerns in tropical countries. The iron-specific magnetic susceptibilities ¿Fe for spleen tissue samples from 7 transfusion dependent ß-thalassaemia (ß-thal) patients and 11 non-transfusion dependent ß-thalassaemia/Haemoglobin E (ß/E) patients were measured at 37°C. Both groups of patients were iron loaded with no significant difference in the distribution of spleen iron concentrations between the two groups. There was a significant difference between the mean ¿Fe of the spleen tissue from each group. The ß/E patients had a higher mean (± standard deviation) spleen ¿Fe (1.55 ± 0.23 × 10-6 m3.kgFe -1) than the ß-thal patients (1.16 ± 0.25 × 10-6 m3.kgFe -1). Correlations were observed between ¿Fe of the spleen tissue and the fraction of magnetic hyperfine split sextet in the 57Fe Mössbauer spectra of the tissues at 78 K (Spearman rank order correlation ¿ = -0.54, p = 0.03) and between ¿Fe of the spleen tissue and the fraction of doublet in the spectra at 5 K (¿ = 0.58, p = 0.02) indicating that ¿Fe of the spleen tissue is related to the chemical speciation of the iron 2 deposits in the tissue. The biological variability of the iron-specific magnetic susceptibility of the tissue iron examined would contribute a random uncertainty of 19% to magnetic susceptibility based non-invasive measurements of tissue iron concentration. ... Magnetic susceptibility measurements were also performed on malaria parasitised red blood cells. In vitro cultures of P. falciparum were magnetically enriched up to 61-fold using high field gradient magnetic separation columns, and the magnetic susceptibility of cell contents was directly measured. Forms of haem iron were quantified spectroscopically. Further fractionations were performed such that, by controlling the fluid velocity through the column, cells with more than a critical amount of paramagnetic 3 iron were preferentially extracted. A chloroquine-sensitive (CQS) laboratory strain of parasites converted approximately 60% of host cell haem iron to haemozoin and this product was the primary source of the increase in cell magnetic susceptibility. The volumetric magnetic susceptibility of the magnetically enriched cells was found to be 0.15 ± 0.03 × 10-7 relative to the suspension medium, accounting for the enrichment of mature parasites. Comparisons of fractionation samples of two pairs of CQS and chloroquine resistant (CQR) strains showed enrichment of mature parasites was significantly greater in the CQS than the CQR strains. The results suggest the possibility of using magnetic separation columns in identifying CQR strains of P. falciparum, potentially in a diagnostic or research setting. The study also underlines the need to identify and quantify the forms of iron in CQR and CQS parasite strains as the fate of haem iron will have implications in understanding the mechanisms of chloroquine resistance.

<p>The aim of this qualitative study was to explore experiences of malaria and attitudes to malaria prevention among nurses from Tanzania. Eleven nurses from three hospitals in northern Tanzania were interviewed. The analysis resulted in following categories: <em>The m</em><em>alaria situation was so severe at that time, Being both nurse and parent, Hindrances in the battle, Sharing knowledge </em>and<em> There is a change. </em>Ten out of eleven nurses had had malaria and all of them had been treated with anti-malarial drugs and many of them still had malaria regularly. They remembered times when the malaria situation was worse and the disease killed many more people. Having children resulted in constant worry. Being a nurse had advantages because they lived close to the hospitals so they could initiate early treatment and because they could afford to take preventive measures. Hindrances in the battle against malaria were other people’s lack of knowledge, poverty and difficulty to change lifestyle and environmental conditions. They were proud to be nurses and knowledge was their strength. There were geographical differences in how much hope they had for the future. The nurses in Zanzibar were the most optimistic. The nurses supported the governmental actions against malaria.</p> / <p>Syftet med denna kvalitativa studie var att undersöka vilka upplevelser sjuksköterskor från Tanzania hade av malaria och deras attityder till malariaförebyggande åtgärder. Elva sjuksköterskor från tre sjukhus i norra Tanzania intervjuades. Analysen resulterade i följande kategorier: <em>Malariasituationen var så allvarlig på den tiden, Att vara sjuksköterska och förälder, Hinder i kampen, Att dela kunskap </em>och<em> Det har blivit en förändring.</em> Tio av de elva sjuksköterskorna hade haft malaria och alla hade fått malariabehandling och flera av dem hade fortfarande malaria regelbundet. De hade minnen från när malariasituationen var värre och många fler människor dog av sjukdomen. Att vara förälder innebar konstant oro. Att vara sjuksköterska hade fördelar eftersom de bodde nära sjukhusen och därför kunde inleda snabb behandling och för att de hade råd att genomföra förebyggande åtgärder. Hinder i kampen mot malaria var andra människors okunskap, fattigdom och svårigheter att förändra livsstil. De var stolta över att vara sjuksköterskor och kunskap var deras styrka. Det fanns geografiska skillnader när det gällde deras framtidstro. Sjuksköterskorna på Zanzibar var de mest hoppfulla. Sjuksköterskorna stödde de statliga insatserna mot malaria.</p>

No description available.

The aim of this qualitative study was to explore experiences of malaria and attitudes to malaria prevention among nurses from Tanzania. Eleven nurses from three hospitals in northern Tanzania were interviewed. The analysis resulted in following categories: The malaria situation was so severe at that time, Being both nurse and parent, Hindrances in the battle, Sharing knowledge and There is a change. Ten out of eleven nurses had had malaria and all of them had been treated with anti-malarial drugs and many of them still had malaria regularly. They remembered times when the malaria situation was worse and the disease killed many more people. Having children resulted in constant worry. Being a nurse had advantages because they lived close to the hospitals so they could initiate early treatment and because they could afford to take preventive measures. Hindrances in the battle against malaria were other people’s lack of knowledge, poverty and difficulty to change lifestyle and environmental conditions. They were proud to be nurses and knowledge was their strength. There were geographical differences in how much hope they had for the future. The nurses in Zanzibar were the most optimistic. The nurses supported the governmental actions against malaria. / Syftet med denna kvalitativa studie var att undersöka vilka upplevelser sjuksköterskor från Tanzania hade av malaria och deras attityder till malariaförebyggande åtgärder. Elva sjuksköterskor från tre sjukhus i norra Tanzania intervjuades. Analysen resulterade i följande kategorier: Malariasituationen var så allvarlig på den tiden, Att vara sjuksköterska och förälder, Hinder i kampen, Att dela kunskap och Det har blivit en förändring. Tio av de elva sjuksköterskorna hade haft malaria och alla hade fått malariabehandling och flera av dem hade fortfarande malaria regelbundet. De hade minnen från när malariasituationen var värre och många fler människor dog av sjukdomen. Att vara förälder innebar konstant oro. Att vara sjuksköterska hade fördelar eftersom de bodde nära sjukhusen och därför kunde inleda snabb behandling och för att de hade råd att genomföra förebyggande åtgärder. Hinder i kampen mot malaria var andra människors okunskap, fattigdom och svårigheter att förändra livsstil. De var stolta över att vara sjuksköterskor och kunskap var deras styrka. Det fanns geografiska skillnader när det gällde deras framtidstro. Sjuksköterskorna på Zanzibar var de mest hoppfulla. Sjuksköterskorna stödde de statliga insatserna mot malaria.

This study investigated the effects of temperature and relative humidity (both controlled and natural) on the lifecyle and morphology of adults of members of the Anopheles gambiae complex in northern KwaZulu-Natal, South Africa. Laboratory investigations into the effects of simulated temperature and relative humidity regimes concentrated on seasonal differences in longevity, egg hatchability, reproductive potential and adult survivorship of An. arabiensis. Differences were found in the life table parameters when these mosquitoes were reared under conditions of seasonal temperature and relative humidity. During the cool season the lifespan and adult survivorship of mosquitoes were greater than those reared during the warm season. In summer, the egg hatchability and reproductive potential were greatest whereas in winter An. arabiensis underwent gonotrophic dissociation although these females were found to take blood meals readily. The influence of seasonal temperature and relative humidity on the body size of An. arabiensis was investigated, both in the laboratory and under field conditions. In both environments, these factors were found to significantly influence body size. In winter, there was a 13% increase in wing size compared to summer bred mosquitoes. A comparison of body size of An. arabiensis, An. merus and An. gambiae reared under laboratory conditions of seasonal temperature and relative humidity showed that the wing size of An. arabiensis was greater than that of An. merus and An. gambiae. The effect of temperature and relative humidity on morphological criteria used in species separation was also investigated. Seasonal differences in wing spot size were compared for An. arabiensis, An. merus and An. gambiae. From this investigation it was concluded that the pale and dark spots on the wing of Anopheles mosquitoes could not be used in species identification due to the large degree of inter-species overlap in the wing spot measurements. The measurement of the pale band at the junction of the 3rd and 4th tarsomere on the hind leg was also investigated for its use in species separation and were found to be useful within the An. gambiae complex. The implications of this study on the transmission and control of malaria are discussed with reference to the late season transmission during March to May that is characteristic of the region. / Thesis (Ph.D)-University of Natal, Pietermaritzburg, 1996.

Malaria is a devastating disease caused by one of the world's most pathogenic parasites, Plasmodium. Five species of Plasmodium infect humans: P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi. P. falciparum is the most pathogenic and causes the greatest numbers of deaths. To date, no licensed vaccine against malaria is available, although there are numerous vaccine candidates in various stages of development. Pca 96 is a 96 kDa Plasmodium chabaudi adami protein shown to have a protective property in mice challenged with P. chabaudi adami. Thus, a P. falciparum orthologue of Pca 96 may be useful in vaccine development. BLAST searches with the Pca 96 amino acid and nucleotide sequences revealed proteins with high sequence identity to Pca 96 including the hypothetical P. falciparum PFC0760c and P. yoelii yoelii PY05757 proteins. A peptide sequence FKLGSCYLYIINRNLKEI was found to be conserved in all homologues of Pca 96, including PFC0760c, PY05757 and in the sequences of proteins from 5 other Plasmodium species. Bioinformatic approaches were explored to attempt to find a possible role of the protein and the possible importance of the conserved sequence. The conserved sequence was predicted to be an alpha helix and to contain possible HLA-DRB1*1101 and HLA-DRB1*0401(Dr4Dw4) T-cell epitopes (GSCYLYIINRNLKEI) in addition to a possible H2-Kd T-cell epitope (CYLYIINRNL). Protein-protein interaction predictions revealed that PFC0760c was likely to interact with proteins involved with nucleic acid binding. PFC0760c was predicted to have a domain found in proteins involved in the structural maintenance of chromosomes, which may suggest the protein is involved in chromatid cohesion during mitotic chromosome condensation. PFC0760c was also predicted to be located in the nucleus by the sub cellular prediction program, SubLoc. Anti-peptide antibodies were raised against the conserved amino acid sequence and against a peptide specific for PY05757 (SDDDNRQIQDFE). Both antibodies detected native antigens with immunofluorescence microscopy. The fluorescent signal appeared throughout the parasite cytoplasm and as an intense signal in the parasite nucleus. These immunofluorescence data supports the predicted nuclear location of the protein. A 822 bp portion of PFC0760c gene was expressed as a maltose-binding protein fusion protein (Pf33-MBP). Pf33-MBP was expressed and purified. Reducing SDS-PAGE and western blotting analysis revealed the fusion protein to be expressed at low levels as four bands (79, 60, 45 and 37 kDa). The purified fusion protein was cleaved with Factor Xa. MBP and Pf33 were of similar molecular mass after cleavage. To attempt to obtain better expression and purification, the 822 bp insert from pTS822 was sub-cloned into pGEX4T1. A glutathione-S-transferase (GST)-fusion protein (Pf33-GST) was expressed. The level of expression was poor and therefore not pursued. To take the study further, potential proteins that interact with PFC0760c and Pf33 need to be identified. In addition, immunisation of mice with the protein and subsequent Plasmodium challenge needs to be performed to ascertain the protective potential of the protein. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2011.

The irrigation farming methods on the Makhathini Flats are thought to be responsible for recent increase in malaria cases in the Mamfene area of northern KwaZulu-Natal despite ongoing malaria control activities. Their coincidence with the period of intensive fanning is an interesting one. This study was therefore carried out to determine the relationship between larval habitats and adult mosquito population in malaria transmission using Geographic Information System (GIS). Four types of breeding sites were utilised by malaria vectors in Mamfene, viz; types 1, II, III and IV. Habitat type I was tap pools, type II was irrigation spillage in agricultural land, type III was spillage outside but adjacent to the agricultural land and type IV was depression pools located both in the Balamhlanga swamp and inland. The cumulative larval density in all habitats peaked in March 1995 (20/man-hr), with irrigation spillage (type III) recording the highest density index (33/man-hr) as compared to tap pools (type I) which recorded 32.8/man-hr while other waterbodies recorded I3 .4/man-hr (type II) and O.5/man-hr (type IV) respectively. Subsamples of both larvae and adults of An. gambiae group were identified by the Polymerase Chain Reaction (PCR) technique. Of the larvae identified, 94.1 % and 5.9% (n=289) were An. arabiensis and An. quadriannulatus respectively while in the adult component, the composition was 98.7% and 1.3% (n=303) for An. arabiensis and An. quadriannulatus respectively. This confirmed An. arabiensis as the dominant malaria vector in Mamfene area while the exophilic behaviour of An. quadriannulatus was portrayed. Of the An. gambiae group dissected for parity, 51 .5%) were found parous. This is an indication that the population was old and was able to maintain transmission locally despite ongoing vector control measures. The Global Positioning System (GPS) was used to position larval and adult mosquito sampling sites. The spatial distribution of adult mosquitoes from the breeding sites were plotted using GIS soft ware (Map Info ) and the distance between the breeding sites and study houses were measured using a utility distance tool. With the aid of GIS, the adult mosquito density in houses could be used as an indicator to locate the breeding sites in the vicinity. The importance of these findings in terms of application in cost-effective malaria control cannot be over-emphasized. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1995.

This study aimed at investigating the knowledge, perceptions and attitudes of both the community and traditional healers with regard to the diagnosis and treatment of malaria in KwaZulu Natal with special reference to Ndumu in the magisterial district of Ingwavuma. Ingwavuma is one of the two northern magisterial district of KwaZulu Natal Province which is regarded as the highest malaria risk district in South Africa as a whole. The area has a warm temperature, 27-32°C, which is favourable for the development of the Anopheles mosquito. The factors predisposing the community to malaria infections were the socio-economic status of the area which is characterised by poverty. unemployment, poor housing and illiteracy, cross border migration, drug resistance, the agricultural development and irrigation scheme. Efficient control measures like house spraying a residual insecticide to control malaria vector mosquitoes, passive surveillance and active case detection with definitive diagnosis and treatment in place to prevent and control the upsurge of the disease The objectives of the study were to ascertain the knowledge. attitudes and perceptions of traditional healers in regard to malaria diagnosis and treatment and that of the community in relation to malaria treatment and diagnosis by traditional healers. The ultimate objective was to identify possible forms of collaboration between the traditional and the modern health services. The study was conducted from sections 2 - 10 of Ndumu where the population was 13 047 and 1300 households. A random sample of 173 respondents from the community and 70 traditional healers were selected for interview. Qualitative and quantitative methodologies were used in order to collect numerical and descriptive information. Data was collected using semi- structured questions and two sets were made: for traditional healers and the community. The study showed that the community was well aware of the signs of malaria but their knowledge was not supported by definitive testing and diagnosis of the condition. It came out that there are forms of health services available at grass root levels for example. self - help. where an individual tried on his own to combat he offending symptoms of the disease, family support systems, where family members especially the elder member gave support and assisted during the times of ill-health, the use of traditional healers, the malaria control camp, clinics and the hospital. The community supported the idea of collaboration between healers and the malaria control team and expressed their willingness to attend the services of a trained healer. Traditional healers confirmed the fact that some community members utilize traditional healers services and also expressed their wish to see the two forms of health services working together to control malaria. / Thesis (M.Sc.)-University of Natal, Durban, 2000.

Severe manifestations of malaria, including cerebral malaria (CM) and respiratory distress, result in approximately three million deaths annually worldwide. Currently, relatively little is known about severe disease pathogenesis. The development and outcome of severe malaria is determined by host-pathogen interactions, a complex interface of genetics and immune responses. Hypothetically, a spectrum of genetic susceptibility and resistance to severe disease exists within the host population, and malaria infection results in diverse host and parasite responses that impact disease outcome. The aim of this study was to identify differential host and parasite responses in a murine model of severe malaria, Plasmodium berghei ANKA (PbA), in CM-susceptible and CM-resistant mice; and to analyze host genetics in patients with severe disease due to Plasmodium falciparum. In vivo, expression microarray analysis showed that, in malaria target organs, differential responses were related to immune response – primarily interferon and complement pathways – and apoptosis. Histopathological examination of the brain confirmed an increased prevalence of apoptosis in CM-susceptible mice. Further examination of the role of complement in CM-susceptibility determined that early complement 5 (C5) activation conferred susceptibility to CM, and that C5 deficiency conferred resistance, which could be recapitulated by antibody blockade of activated C5 or its receptor in susceptible mice. Additionally, single nucleotide polymorphism (SNP) studies identified that complement receptor 1 SNPs were associated with disease severity in patients with P. falciparum malaria. PbA parasites displayed a unique transcriptional signature in each tissue examined (brain, liver, spleen and lung), showed differential gene expression between CM-resistant and susceptible hosts, and were most prominent in lung tissue. Closer examination of lung involvement in PbA infection revealed that PbA-infected C57BL/6 mice develop acute lung injury (ALI), defined by disruption of the alveolar-capillary membrane barrier. ALI susceptibility did not correlate with CM susceptibility, but was influenced by peripheral parasite burden and CD36-mediated parasite sequestration in the lung. PbA provides a clinically relevant experimental model for CM and ALI, through which important disease mechanisms can be identified and modulated. Ideally, the use of such models aids in the discovery of disease biomarkers and novel therapeutic strategies, which may be applied to human severe and cerebral malaria.

Severe manifestations of malaria, including cerebral malaria (CM) and respiratory distress, result in approximately three million deaths annually worldwide. Currently, relatively little is known about severe disease pathogenesis. The development and outcome of severe malaria is determined by host-pathogen interactions, a complex interface of genetics and immune responses. Hypothetically, a spectrum of genetic susceptibility and resistance to severe disease exists within the host population, and malaria infection results in diverse host and parasite responses that impact disease outcome. The aim of this study was to identify differential host and parasite responses in a murine model of severe malaria, Plasmodium berghei ANKA (PbA), in CM-susceptible and CM-resistant mice; and to analyze host genetics in patients with severe disease due to Plasmodium falciparum. In vivo, expression microarray analysis showed that, in malaria target organs, differential responses were related to immune response – primarily interferon and complement pathways – and apoptosis. Histopathological examination of the brain confirmed an increased prevalence of apoptosis in CM-susceptible mice. Further examination of the role of complement in CM-susceptibility determined that early complement 5 (C5) activation conferred susceptibility to CM, and that C5 deficiency conferred resistance, which could be recapitulated by antibody blockade of activated C5 or its receptor in susceptible mice. Additionally, single nucleotide polymorphism (SNP) studies identified that complement receptor 1 SNPs were associated with disease severity in patients with P. falciparum malaria. PbA parasites displayed a unique transcriptional signature in each tissue examined (brain, liver, spleen and lung), showed differential gene expression between CM-resistant and susceptible hosts, and were most prominent in lung tissue. Closer examination of lung involvement in PbA infection revealed that PbA-infected C57BL/6 mice develop acute lung injury (ALI), defined by disruption of the alveolar-capillary membrane barrier. ALI susceptibility did not correlate with CM susceptibility, but was influenced by peripheral parasite burden and CD36-mediated parasite sequestration in the lung. PbA provides a clinically relevant experimental model for CM and ALI, through which important disease mechanisms can be identified and modulated. Ideally, the use of such models aids in the discovery of disease biomarkers and novel therapeutic strategies, which may be applied to human severe and cerebral malaria.