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1
Vittor, Amy Yomiko. "Deforestation and malaria associations between vegetation, vector ecology and malaria epidemiology in the Peruvian Amazon /." Available to US Hopkins community, 2003. http://wwwlib.umi.com/dissertations/dlnow/3080786.
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2
Nsengimana, Ferdinand. "Comparison of Malaria Control Interventions in Southern Africa." ScholarWorks, 2018. https://scholarworks.waldenu.edu/dissertations/5918.
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There is lack of evidence on which of the two highly recommended malaria prevention methods, insecticide treated bednets and indoor residual spraying, is more effective than the other. There is also limited peer reviewed literature that compares the characteristics of people who use the two malaria prevention methods. Based on the Health Belief Model, the research questions tested whether there is any relationship between the use of mosquito bednet or the use of indoor residual spraying and contracting malaria, and whether there is any relationship between sociodemographic and socioeconomic factors and the use of malaria prevention methods. Using a quantitative research design, secondary data from the 2011 Angola malaria indicator survey were analyzed. Chi-square for association, logistic regression, and multinomial logistic regression tests were used. There was no statistically significant association between the use of mosquito bednet and having malaria. However, the use of indoor residual spraying significantly reduced the likelihood of getting malaria. There was also a statistically significant association between place of residence, wealth index, level of education, and number of household members and using mosquito bednet and between wealth index and using indoor residual spraying. In conclusion, the malaria prevention programs should focus on indoor residual spraying. It is recommended that all households in southern Africa malaria prone areas should be regularly sprayed. The findings of this study contribute to positive social change in the sense that by using more effective malaria prevention method, individuals will be able to function normally on daily basis, save on expenses related to employment loses or treatment and care of the sick, as well as loss of life and improve own economic status.
3
Boakye-Agyeman, Felix. "Quantifying the Quality of Antimalarial Drugs in Ghana." ScholarWorks, 2017. https://scholarworks.waldenu.edu/dissertations/4502.
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Malaria is still an epidemic in many parts of the world-about 220 million people are still infected with malaria worldwide and about 700 thousand people die from this disease per year. Most of the drugs used to treat malaria work well if they are used as required and they contain the right amounts of the active ingredient; however, it is estimated that more than 10% of drugs traded worldwide are counterfeits including 38% to 53% of antimalarial tablets produced in China and India. Due to the lack of data covering the extent of counterfeit antimalarial drugs in Ghana, the purpose of this quantitative study was to determine the percentage of counterfeit antimalarial drugs sold in Ghana by assessing the amounts of the 2 most common antimalarial drugs, artemether (ATMT) and lumefantrine (LMFT) in drugs sold in Ghana retail outlets. These drugs were purchased from retail outlets in Ghana and analyses at the Mayo Clinic Pharmacology core lab (Rochester, MN). The quality of the drugs were characterized by comparing the actual amount of ATMT & LMFT in each tablet to the expected amount. Using explanatory theory along with dose response-response occupancy theory, the researcher addressed quantitative solutions to questions related to the percentage and distribution of counterfeit ATMT and LMFT tablets. The results revealed that overall 20% of the drugs are counterfeit; this is not dependent on the location or kind of outlet but rather depends on whether the tablets were imported or locally manufactured and whether the tablets had a pedigree scratch panel. This study provides a better understanding of how much antimalarial medication is counterfeit in Ghana, which will aid interventions to minimize the adverse effects of counterfeit antimalarial medication in Ghana
4
Kisavi-Atatah, Catherine. "Perspectives of Women in Nairobi Kenya Toward Malaria Control." ScholarWorks, 2011. https://scholarworks.waldenu.edu/dissertations/1155.
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Malaria infection has been and continues to be a serious public health concern that has mystified many in the public health care industry. One area in Sub Saharan Africa that continues to feel the devastating effects of malaria is in Nairobi, Kenya. This qualitative research study explored the attitudes of women in Nairobi, Kenya and how they view intervention measures already introduced by public health care experts in fighting malaria. The phenomenological research approach used purposeful sampling to recruit 16 women from Nairobi, Kenya to participate in semi-structured, open-ended interviews. The ecological systems theory was used as a lens of analysis to help illuminate the views of women on already-introduced malaria intervention measures in Nairobi, Kenya. Nvivo 10 helped manage data and the interpretative phenomenological analysis was used to analyze data and identify themes and subthemes through coding. The findings from this study indicate that (a) there is a disconnect within the systems, especially between public health officials and ordinary citizens, and (b) ordinary citizens felt that intervention measures already introduced have not been effectively implemented. The recommendations derived from the study will improve relationships between public health officials and ordinary citizens in order to effectively implement malaria control measures already introduced. This study will benefit public health officials, ordinary citizens in Nairobi, and other health care providers all over the world. This study contributes to social positive change by providing greater insight on already-introduced mosquito intervention measures.
5
Zinyengere, David Takudzwa. "Household Determinants of Malaria in Mutasa District of Zimbabwe." ScholarWorks, 2018. https://scholarworks.waldenu.edu/dissertations/5597.
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Malaria is a vector borne, acute febrile illness, caused by Plasmodium parasites. Malaria impacts the medical and socioeconomic development programs of affected communities, as it diverts both individual and national resources into managing the disease burden. The purpose of this study was to explore and evaluate household determinants of malaria in Mutasa District, Zimbabwe. The precede-proceed theoretical model guided the study. Secondary data from Demographic Health Survey and District Health Management Information System, and current data from household determinant questionnaires, were used to evaluate the influence and significance of identified household determinants. Multiple logistic regression models were used to examine the association between malaria prevalence and the identified household determinant factors. The study result showed the existence of household determinant factors that affected the prevalence of malaria in Mutasa District. The presence of livestock animals within a 50-meter radius of the household, ownership of animal drawn carts and low socioeconomic status significantly increased malaria risk, while availability of drinking water within a 50-meter radius of the household, significantly reduced malaria risk. Other variables, although not statistically significant, had varied levels of malaria infection risk. The study results may contribute to positive social change by providing an insight into innovative strategies that enhance existing interventions. The study results may also provide opportunities for upgrading malaria intervention policies and sustainable community participation, thus enhancing malaria elimination efforts
6
Marijani, Theresia. "Modelling drug resistance in malaria." Thesis, Stellenbosch : University of Stellenbosch, 2009. http://hdl.handle.net/10019.1/4063.
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Derjew, Emebet T. "Knowledge of Malaria Infection and Treatment-Seeking Behavior Among Tanzanian Pregnant Women." ScholarWorks, 2017. https://scholarworks.waldenu.edu/dissertations/4052.
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Despite the availability of effective drugs to prevent malaria during pregnancy using intermittent preventive treatment with Sulfadoxine-Pyrimethamine or Fansidar and insecticide bed net, use of these methods are still little used in Sub-Saharan Africa, including Tanzania. As a result, many pregnant women are at risk of malaria consequences such as maternal anemia and low birth weight babies, which increase the rate of infant mortality. Data from the Demographic Health Survey for Tanzania HIV/AIDs and the Malaria Indicator Survey 2011-2012 were used in a cross-sectional design guided by the health belief model. Logistic regression examined the association between (a) preventive treatment-seeking behavior and (b) SES, malaria media exposure, knowledge of malaria signs and symptoms, perceived seriousness of malaria, and knowledge of malaria preventive measures. After controlling for transportation, family responsibility, and age, significant associations (p < 0.05) were found between SES, malaria media exposure, knowledge of malaria signs and symptom, perceived seriousness of malaria, knowledge of malaria preventive measures, and treatment-seeking behavior. This study contributes to positive social change by helping design and implement policies and programs to improve the knowledge of Tanzanian pregnant women about the risk of malaria infection and the benefits of preventive treatments. Interventions to reduce malaria infection during pregnancy will reduce the associated morbidity and mortality of both mothers and infants; as a result, families and communities will be healthier and prevent unnecessary medical cost of malaria.
8
Grills, Ardath White. "The complexity of Plasmodium falciparum infections in children in western Kenya /." Download the dissertation in PDF, 2006. http://www.lrc.usuhs.mil/dissertations/pdf/Grills2006.pdf.
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Nakakawa, Juliet. "Modelling malaria and sickle cell gene." Thesis, Stellenbosch : Stellenbosch University, 2011. http://hdl.handle.net/10019.1/17989.
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Thesis (MSc)--Stellenbosch University, 2012.<br>ENGLISH ABSTRACT: The high sickle cell gene frequency has been hypothesised to be related to the protective
advantage against malaria disease among heterozygous individuals. In this thesis, we
study the interaction between the dynamics of malaria and sickle cell gene. The main aim
is to investigate the impact of malaria treatment on the frequency of sickle cell gene. For
this, we develop a mathematical model that describes the interactions between malaria
and sickle cell gene under malaria treatment. The model includes both homozygous for
the normal gene (AA) and heterozygous for sickle cell gene (AS) and assumes that AS
individuals are not treated since they do not show clinical symptoms. We first analyse
the model without malaria treatment, using singular perturbation techniques, basing on
the fact that epidemiological and demographical dynamics occur on two different time
scales (fast and slow dynamics). Our analysis on the fast time scale shows that high
sickle cell gene frequency leads to high endemic levels for longer duration of parasitemia
among heterozygous individuals. However, if the duration of parasitemia is reduced then
high sickle cell gene frequency is associated with low endemic levels. We also note that
on the slow time scale, the invasion ability of sickle cell gene is dependent on the malaria
epidemiological parameters. The invasion coefficient given as the difference in the weighted
death rates of AA and AS individuals is used as a measure to determine the establishment
of sickle cell gene in the population. Results show that, the gene may establish itself if the
weighted death rate of AA individuals is greater than that of AS individuals otherwise it
fails. We note that, high mortality of AA individuals leads to establishment of sickle cell
gene in the population. Then we analysed the model with treatment, our results indicate
that the frequency of sickle cell gene decreases with an increase in the recovery rate of AA
individuals. We thus conclude that eradication of malaria disease will lead to a reduction
in sickle cell gene frequency.<br>AFRIKAANSE OPSOMMING: Daar word veronderstel dat die hoë sekelsel geenfrekwensie onder heterosigotiese individue
verwant is aan die beskermende voordeel teen malaria siekte. In hierdie verhandeling
ondersoek ons die wisselwerking tussen die dinamika van malaria en die sekelsel geen. Die
hoofdoel is om die invloed van malaria behandeling op die frekwensie van die sekelsel geen
te ondersoek. Hiervoor het ons ‘n wiskundige model ontwikkel, wat die wisselwerking
tussen die dinamika van malaria en die sekelsel geen met malaria behandeling, beskryf.
Die model sluit beide homosigotiese vir die normale geen (AA) en heterosigotiese vir die
sekelsel geen (AS) in, en neem aan dat AS individue nie behandel is nie omdat hulle nie
die eerste kliniese simptome getoon het nie. Ons ontleed eers die model sonder malaria
behandeling, deur gebruik te maak van enkelvoudige pertubasie tegnieke, wat gegrond is
op die feit dat epidemiologiese en demografiese dinamika plaasvind op twee verskillende
tydskale (vinnige en stadige dinamika). Ons ontleding op die vinnige tydskaal dui dat
hoë sekelsel geenfrekwensie onder heterosigotiese individue lei tot hoë endemiese vlakke
vir ‘n langer duur van parasitemie. Nietemin, as die duur van parasitemie afneem, dan
word hoë sekelsel geenfrekwensie verbind met lae endemiese vlakke. Ons neem ook waar
dat op die stadige skaal die indringingsvermoë van die sekelsel afhanklik is van malaria
se epidemiologiese parameters. Die indringingskoëffisiënt wat bereken word as die verskil
van die geweegde sterftekoerse van AA en AS individue, word gebruik as ‘n maatstaf om
die vestiging van die sekelsel geen in die bevolking te bepaal. Resultate toon dat die geen
homself kan vestig as die geweegde sterftekoers van AA individue groter is as di e van die AS
individue, andersins misluk dit. Ons let op dat hoë mortaliteit van AA individue lei tot die
vestiging van die sekelsel geen in die bevolking. Daarna het ons die model wat behandeling
insluit ge-analiseer en ons resultate toon dat die frekwensie van die sekelsel geen afneem
met ‘n toename in die herstelkoers van AA individue. Ons kom dus tot die gevolgtrekking
dat die uitwissing van malaria siekte sal lei tot die afname in sekelsel geenfrekwensie.
10
Quenneh, Taiyee Nelson. "Insecticide Treated Nets as an Effective Malaria Control Strategy in Liberia." ScholarWorks, 2016. https://scholarworks.waldenu.edu/dissertations/2012.
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Malaria is a vector-borne disease that presents the most persistent and serious public health burden in Liberia. Numerous studies have examined the relationship between ITN use and malaria prevalence. However, little research has explored the effectiveness of ITNs in controlling malaria among children in postwar Liberia. The aim of this study was to examine the association between ITN ownership, parental economic status, ITN installation support, and malaria prevalence among children. This was a quantitative cross-sectional study guided by the health belief model. The study used secondary data from the 2011 Liberia Malaria Indicator Survey. Chi-square for association and Logistic regression were used to analyze the data. The results revealed a significant association between parental education and malaria prevalence. There was also a significant association between parental economic status and malaria prevalence. However, there was no significant association between ITN ownership and malaria prevalence after controlling for parental education and ownership of structure. These findings may foster social change by helping public health authorities in Liberia integrate ITN use with other strategies like mosquito larvae elimination and indoor/outdoor insecticide spraying as part of a comprehensive approach to malaria control. Additionally, massive awareness and economic capacity building should be undertaken to empower malaria endemic communities with the understanding that malaria can be rapidly reduced with other robust strategies in combination with ITN use. These strategies, if implemented, may effectively control malaria prevalence among children and the emotional and financial burdens endure by their families.
11
Azunie, Naomi Chuiwo. "An Integrated Approach to Malaria Prevention and Control in Rural Cameroon." ScholarWorks, 2017. https://scholarworks.waldenu.edu/dissertations/3971.
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Malaria is a life-threatening parasitic disease spread to humans through bites of an infected mosquito. In rural Cameroon, malaria is one of the major causes of morbidity and mortality. Several studies have examined the use of various malaria preventive tools; however, there is insufficient literature available on use of an integrated approach to prevent and control malaria in rural Cameroon. The aim of this study was to provide information necessary for bridging the gap in understanding the proper use of insecticide treated nets (ITNs) and antimalarial drugs and the roles of education and socioeconomic status in malaria prevention and control efforts in rural Cameroon. This quantitative cross-sectional study was guided by the socioecological framework. Secondary data from the 2011 Cameroon Demographic and Health Survey (sample size of 216) was used in this study. The Chi-Square, binary logistic, and multinomial logistic regressions were used to analyze the data. The result revealed that there was a significant association (p < 0.05) between proper use of ITNs and malaria prevalence among children under 5 years old, education and proper use of antimalarial drugs, and socioeconomic status and health seeking behavior. There was also a significant association between healthcare preference and malaria treatment outcomes among children under 5 and pregnant women. These findings may contribute to social change by helping public health officials in Cameron to continue to prioritize local needs and enforce the proper use of available malaria tools in rural communities through an integrated approach to prevent and control malaria in rural Cameroon, especially for children under 5 years old and pregnant women, which would lead to improved quality of life.
12
Dada, John Olusegun. "Composite Risk Behaviors that Enhance the Transmission of Malaria in Pregnancy." ScholarWorks, 2017. https://scholarworks.waldenu.edu/dissertations/3872.
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Malaria causes high morbidity and mortality, especially among the most vulnerable populations, including pregnant women. Malaria in pregnancy (MiP) can be prevented by compliance with the 3 core measures: sleeping under insecticide-treated nets (ITNs), 3 doses of sulfadoxine-pyrimethamine as intermittent preventive treatment (IPTp-SP), and effective case management of malaria and anemia. The purpose of this cross-sectional household survey was to examine the composite risk behaviors that enhance the transmission of MiP. Stratified and multistage sampling methods were used to select a sample of 300 pregnant women in Abuja, Nigeria. Bivariate and multivariate analysis were conducted. According to study findings, participants' mean age was 28.6 years, many (117 or 68.0% of the participants) used an ITN the night before the survey, and some (113 or 38.0%) had used SP for IPTp. Many participants (183 or 61.0%) were of high malaria risk status (MRS). The predictors of MRS were knowledge, OR 3.282, 95% CI [1.091, 9.873], p=0.03; number of pregnancy, OR=5.589, 95% CI [1.465, 21.316], p=0.01; attendance at antenatal clinic, OR= 3.777, 95% CI [1.119, 12.746], p=0.03; level of education, OR=0.050, 95 CI [0.013, 0.197], p=0.000; perceived barriers of ITN, OR=0.308, 95% CI [0.165, 0.575], p=0.000; and perceived benefits of SP for IPTp, OR=3.156, 95% CI [1.879, 5.301], p=0.000 . Perceived seriousness, perceived severity of malaria, age, and religion were not significantly related to MRS. This study leads to positive social change by providing information for policy makers to review MiP-related policies and programs to ensure quality messages, providers, and products are accessible and affordable across rural and urban settings where the target population live and work.
13
Brisson, Michael Paul. "U.S. Army Enlisted Soldiers' Adherence to Prescribed Malaria Chemoprophylaxis in Afghanistan." ScholarWorks, 2015. https://scholarworks.waldenu.edu/dissertations/1456.
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Over the past 13 years, the United States Army has been engaged in armed conflict within Afghanistan. Unfortunately, the United States Army has been forced to evacuate soldiers from the battlefield because of malaria, a parasitic disease that is endemic in Afghanistan. Even though the U.S. Army has adopted an effective chemoprophylaxis protocol, soldiers' adherence to their prescribed medication has been historically low. This research addressed a gap in literature regarding the adherence rates of U.S. Army enlisted soldiers to their prescribed oral malaria chemoprophylaxis. In addition, this research investigated self-reported reasons for soldiers' nonadherence to this medication. The study employed an experimental, correlational research design to aid in understanding the relationship between adherence to malaria chemoprophylaxis and age, gender, military rank, education level, and previous deployment experience. Ninety-four active-duty U.S. Army personnel deployed to Afghanistan participated in the study. The frequency distribution of responses to the 8-questions Morisky Medication Adherence Scale were presented and indicated that for almost all of the questions, the percentage of participants who answered yes was larger than the percentage who answered no, indicating low levels of adherence among the study participants. The findings indicated that age, gender, and perception of risk all significantly contributed to the models predicting medication adherence. With the scientific and medical advances of the 20th and 21st centuries, few if any military personnel should contract malaria. These findings contribute to a greater awareness of medication adherence, which directly supports positive social change within the Armed Forces of the United States.
14
Ugwu, Gabriel Ugwuja. "Family Predictive Factors of Rural Malaria Prevalence in Nsukka, Eastern Nigeria." ScholarWorks, 2019. https://scholarworks.waldenu.edu/dissertations/7764.
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Children in early childhood are still suffering from burdens of malaria-related morbidity and mortality. There have been insufficient studies on how family-level factors may predict the prevalence of malaria (PoM), and negatively impact the control of malaria in rural areas, especially among children. In this study, potential family factors were explored to address the challenges associated with the increase in PoM among the children in rural areas of Nsukka. Socioecological framework guided this study at the interpersonal level. The quantitative cross-sectional study used secondary data from Demographic and Health Surveys (DHS) of 2015 in Nsukka rural communities. Data were analyzed using chi-square analysis and multinomial logistic regression. The result showed a statistically significant relationship (P<0.05) between the age group susceptibility among children. There were statistically significant relationships between the family’s ownership of land for agricultural use, the family’s choice of a treatment facility and socioeconomic status. The couple’s extent of effective communication and whether the children in early childhood slept under the mosquito net showed statistically significant results. Positive social change implications depicted organizational level benefit that may help UNICEF and WHO by recruiting representatives in the distribution of preventive, control and treatment of malaria to the rural areas. Empowerment of women in the household to attend to their children during an emergency and standard housing policy initiative such as Family in Children (FIC) address both individual and societal levels, respectively.
15
Udjombala, Hilka Tuyenikelao. "Malaria in Namibia : a community study." Thesis, Stellenbosch : Stellenbosch University, 2001. http://hdl.handle.net/10019.1/52329.
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Thesis (Mcur)--Stellenbosch University, 2001.<br>ENGLISH ABSTRACT: The researcher has identified several problems in the North West Health
Directorate community of Namibia regarding malaria and malaria related deaths.
Against this background the study was undertaken to:
• Identify the attitude(s) of the community towards malaria.
• Determine the community's knowledge of malaria.
• Determine the prevention strategies the community employed to guard
against malaria.
• Make recommendations.
Methodological triangulation was used to obtain data and the findings reflected
the following:
• Lack of knowledge about malaria, its causes, management and prevention
due to lack of adequate health information.
• Socio-cultural factors have an influence on the community's knowledge of
malaria, their attitudes towards malaria and on strategies employed by the
community to prevent malaria.
Recommendations included provision of proper and adequate health information
to the community by health workers, increasing community participation in order
to enhance attitude change and co-ordination and collaboration between
traditional healers and the Ministry of Health and Social Services.
Keywords: malaria I community I prevention I knowledge I attitudes<br>AFRIKAANSE OPSOMMING: Die navorser het verskeie probleme rakende malaria en malaria verwante
sterftes in die gemeenskap van die Noordwes Gesondheidsdirektoraat van
Namibië geïdentifiseer. Teen hierdie agtergrond is die studie gedoen om:
• Die houding van die gemeenskap teenoor malaria te identifiseer.
• Die gemeenskap se kennis omtrent malaria te bepaal.
• Die voorkomende strategieë wat die gemeenskap toepas om malaria te
voorkom te bepaal.
• Aanbevelings te maak.
Metodologiese triangulasie is gebruik om data te verkry en die bevindinge het die
volgende gereflekteer:
• Gebrek aan kennis aangaande malaria, die oorsake, hantering en
voorkoming van malaria as gevolg van 'n gebrek aan voldoende
gesondheidsinligting.
• Sosio-kulturele faktore beïnvloed die gemeenskap se kennis van malaria,
hul houding teenoor malaria en die strategieë wat hul toepas om malaria
te voorkom.
Aanbevelings sluit in die voorsiening van korrekte en voldoende
gesondheidsinligting aan die gemeenskap deur gesondheidswerkers, verhoging
van gemeenskapsdeelname om houdingsveranderinge teweeg te bring asook
om die koërdinasie en samewerking tussen tradisionele helers in die Ministerie
van Gesondheid en Welsyn te verbeter.
Sleutelwoorde: malaria I gemeenskap I voorkoming I kennis I houding.
16
Udenweze, Ifeanyi Livinus. "Impact of Socioeconomic Status and Health-Seeking Behavior on Malaria in Pregnancy." ScholarWorks, 2019. https://scholarworks.waldenu.edu/dissertations/7438.
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Malaria in pregnancy remains a public health challenge in Nigeria despite the fund appropriation for malaria control. The health challenges of malaria in pregnancy vary with populations and there is limited knowledge on the impact of the socioeconomic status and health-seeking behavior on malaria in pregnancy in Nigeria. The objective of this cross-sectional quantitative survey was to examine whether socioeconomic status and health-seeking behavior predict malaria in pregnancy in Nigeria using the social cognitive theoretical model. The data from a 2015 Nigeria Malaria Indicator Survey was used in this study. Data were analyzed using chi-square, binary, and multivariate logistics regression analyses. The study demonstrated that socioeconomic status (wealth index/income [Poorest: OR 2.709, 95% CI 1.869-3.928, p 0.000; Poorer: OR 1.791, 95% CI 1.256-2.555, p 0.00] and no education: OR 2.868, 95% CI 1.761-4.671, p 0.000) made significant contributions in predicting malaria in pregnancy. The research results also showed that socioeconomic status is a predictor of health-seeking behavior (wealth index/income [Poorest: OR 0.414, 95% CI 0.244-0.705, p 0.001], no education: OR 0.329, 95% CI 0.174-0.622, p 0.001 and primary education: OR 0.348, 95% CI 0.191-0.636, p 0.001). Additionally, the study findings showed that malaria in pregnancy determined the choice of formal health-seeking behavior by pregnant women (malaria in pregnancy: OR 0.551, 95% CI 0.469-0.648, p 0.000). The results of this research might guide Nigeria's Ministry of Health to develop approaches on women empowerment that would focus on socioeconomic status and health-seeking behavior of women such as programs to improve women's education and income generation.
17
Davies, Marcella. "Women's Perceptions of Malaria in the Western Rural Areas of Sierra Leone." ScholarWorks, 2018. https://scholarworks.waldenu.edu/dissertations/5618.
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Malaria is one of the leading causes of death for children and women in Sierra Leone. The purpose of this qualitative study was to explore and understand the lived experiences of women from the rural areas of Sierra Leone regarding malaria. A purposive sample of Krio women from the western rural area, aged 21-55 years, spoke English, and had taken care of someone with malaria described their perceptions and lived experiences with the disease in face-to-face interviews. The research questions were based on the health belief model and focused on knowledge, beliefs, and perceptions about malaria prevention and treatment. Interpretative phenomenological analysis was used to identify themes through coding. The findings indicated that (a) lack of doctors, medicines, and medical supplies at government clinics discourages malaria victims from visiting those clinics; (b) the use of traditional herbs is prevalent because of their effectiveness, affordability, easy access, and lack of side effects; (c) women were not aware of recommended comprehensive malaria control measures, which include the continuous use of durable insecticide nets, residual spraying, case management, and artemisinin-based therapy. The results also show that (a) pregnant women should not take prescribed medications to prevent or treat malaria because they harm the fetus, and (b) traditional herbs may be taken with Western medicines to treat severe malaria. Recommendations include: that the government evaluate the efficiency and effectiveness of its current malaria programs in local clinics, and that future studies be undertaken to identify antimalarial properties in commonly accepted local herbs. Changes in policies and practices relating to the prevention and treatment of malaria will serve as building blocks for positive social change to reduce the malaria incidence rate in Sierra Leone.
18
Bazirutwabo, Bonaventure. "Impact of Social Support on Malaria Management by Burundian Community Health Workers." ScholarWorks, 2018. https://scholarworks.waldenu.edu/dissertations/5162.
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Malaria is the main cause of mortality for children under the age of 5 in Burundi. The access to malaria diagnostics and treatment is hampered not only because of logistical issues, but also due to the lack of qualified human resources and their inequitable distribution across the country. To mitigate the lack of human resources for health, the government of Burundi, along with its partners, shifted some tasks to community health workers (CHWs) to cover unmet healthcare needs for selected diseases such as malaria, diarrhea, and pneumonia. The purpose of this study was to determine whether the social support provided to CHWs had an impact on morbidity due to malaria for children under the age of 5. The social networks and social support theoretical framework was used to explore the type of social support received by CHWs and its impact on the number of children treated. The 88 CHWs who participated in this cross sectional survey, were randomly selected from a pool of 719 CHWs who were part of a pilot project that was implemented in the districts of Gahombo, Gashoho, and Mabayi, from 2011 to 2014. The study findings showed mixed results with a positive correlation between the instrumental support received and the number of children under the age of 5 treated. However, a statistically significant correlation was not established between the emotional, informational, and appraisal support received and the number of children under the age of 5 treated. The positive social change implications of the study include providing evidence to build and enhance human resource capacity for improving the health of children living in Burundi, an under-resourced country, through the development of a support package that can be offered to CHWs to help them perform their duties in a more effective way.
19
Wesolowski, Amy. "Quantifying Human Movement Patterns for Public Health." Research Showcase @ CMU, 2014. http://repository.cmu.edu/dissertations/329.
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Human travel affects important processes in public health and infectious disease dynamics. Refined spatial and temporal data are needed to accurately model how the dynamics of human travel contribute to epidemiological patterns of disease as well as access to healthcare resources. Here, I address a number of key issues related to modeling human mobility patterns and applications for understanding the spatial spread of infectious diseases and geographic access to public health resources. Using large sources of behavioral data anonymously collected from mobile phones within two African countries, I first analyze the utility of these data to quantify human mobility patterns as well as the usefulness of common modeling frameworks. Then I compare these data to two more common sources of human travel data: the national census and a comprehensive travel survey. Next, I use these data to assess the impact of human travel on the movement of malaria parasites. The final component of my thesis focuses on the utility of this data source to generally understand the role of geographic isolation on travel patterns to better understand the disparity between areas with various levels of access to public resources and the uptake of preventative healthcare such as immunizations and antenatal care.
20
Kongkasuriyachai, Darin. "Understanding malaria transmission targeted disruption of a sexual stage gene, PFS16 /." Available to US Hopkins community, 2003. http://wwwlib.umi.com/dissertations/dlnow/3080700.
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Oreyomi, Olabosipo O. "Barriers to Utilization of Malaria Preventive Measures in Rural Nigeria Among Pregnant Women." ScholarWorks, 2019. https://scholarworks.waldenu.edu/dissertations/6468.
Full textAbstract:
Malaria is a mosquito transmitted tropical disease that accounts for more cases and deaths in Nigeria than in any other country worldwide. Globally malaria accounts for 300,000 deaths among young children and pregnant women annually. The promotion of the use of insecticide treated nets (ITNs) to reduce pregnant women's contact with mosquitoes has been the focus of malaria prevention efforts in Nigeria. However, the use of ITNs during pregnancy has been inexplicably low in Nigeria. A quantitative cross-sectional study was conducted to examine barriers to the utilization of ITNs among pregnant women in rural Nigeria. The social ecological model was utilized to analyze secondary data from a 2015 survey conducted in Nigeria in which 4,834 pregnant women between 15 to 49 years of age participated. The relationship between the use of ITNs and the knowledge of ITNs, traditional medicine, education, and family income was examined using multiple logistic regression modeling. Results showed that there was a significant relationship between the knowledge of ITN (p = 0.000), family income (p = 0.000), education of pregnant women (p = 0.000) and the use of ITN among pregnant women in rural Nigeria. However, there was no relationship between the use of traditional medicine (p = >0.5), and the use of ITN, perhaps because most of the women surveyed did not respond to the question about use of traditional medicine. Results of the study have important implications for positive social changes among pregnant women in Nigeria. These findings will inform strategies to increase the uptake of ITNs during pregnancy in Nigeria, improving birth outcomes, increasing maternal and child survival, and decreasing the economic burden due to malaria morbidity and mortality in rural Nigeria.
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Martin, Andrea Blue. "Development and Modeling of Multi-scale Continuous High Gradient Magnetophoretic Separator for Malaria-infected Red Blood Cells." Research Showcase @ CMU, 2017. http://repository.cmu.edu/dissertations/913.
Full textAbstract:
According to the World Health Organization, nearly 3.2 billion people are at risk of malaria. The most deadliest form of human malaria is caused by the pathogen Plasmodium falciparum, which has claimed over 400,000 lives worldwide in 20151. Even when optimally treated with drug and donor blood therapies, severe malaria has a high mortality rate. The parasites target a patient’s red blood cells and convert them into paramagnetic units before eventually rupturing the host cell, further spreading the infection. Combination drug therapies using quinine and artemisinin derivatives are common but are either expensive or have associated toxicities from mis-dosing. Moreover, antimalarial drugs are becoming increasingly ineffective against the growing number of drug-resistant malaria strains. Combination drug and blood exchange therapies are often implemented to flush out malaria-infected red blood cells (iRBC) but consume a great quantity of donor blood, carry a high risk of transmitting other blood-borne diseases, and have no agreed upon advantage or disadvantage among clinicians. Due to the relative disadvantages of other treatment methods, small scale high gradient magnetic separation (HGMS) devices, used in a variety of biological applications, may be another treatment option to consider. mPharesis (“magnetic apheresis”) is a proposed low-cost, disposable magnetic blood filtration device which continually removes iRBCs from a patient’s whole blood by capitalizing on the iRBC’s unique magnetic properties. The proposed treatment-scale system will provide emergency care with parameters similar to continuous hemofiltration systems in terms of blood flow rates (up to approximately 500 mL min-1), vascular access, and treatment times (up to about 3 hours). A novel medium-scale high gradient magnetic separation device is detailed here. The device consists of a disposable photo-etched embedded wire array and acrylic layered housing on an external permanent magnet set. The magnetic force and flow field design were computationally optimized. In-vitro feasibility experiments were conducted at several flow rates and physiological hematocrits (Hct) using a blood mixture composed of healthy RBCs and a non-pathogenic paramagnetic blood analog called methemoglobin RBCs (metRBCs). The device was able to selectively remove paramagnetic RBCs without excessive loss of healthy RBCs. Simplified experiments were performed with 30% Hct with 20% metRBCs. At steady state, the concentration of metRBCs was reduced by 27.0±2.2% in a single pass at a flow rate of 77 μL min-1 as compared to 1.6±0.7% in control experiments without a magnet present. The experimental paramagnetic RBC removal rate was over 380 times greater than similar published HGMS devices. These successful results were applied to a theoretical transport model. The model was designed to compare the parasite removal and Hct level changes between combination drug and exchange transfusion (ET) therapy versus treatment-scale mPharesis-drug therapy. When the mPharesis flow rate was set to typical continuous dialysis rates, treatment times and donor blood volumes were reduced for all 10 cases. Calculated treatment times were all less than 60% of the reported ET-drug treatments, with times ranging from 47 to 71 minutes. The mPharesis-drug treatment was calculated to need between 4% and 53% less donor blood than the reported ET-drug treatments. Between 775 and 1772 mL of packed donor RBCs (3 to 6 units of whole blood) were estimated for the mPharesis-drug treatments, versus the average 5 to 20 units used during ET2. Treatment reference charts were generated to provide time and donor blood volume estimates for a range of patient sizes and disease severities. Based on the maximum flow rate of 500 mL min-1, a treatment-scale mPharesis system was estimated to be the size of three stacked briefcases, which is a feasible size for deployment in a clinical setting. Finally, the design, fabrication, and microscopic visualization of a simple, benchtop-fabricated continuous HGMS device was detailed. This proof-of-concept microfluidic device was implemented to test the effect of hematocrit and flow rate on the separation of mixtures of metRBCs (heat-treated and un-heated) and transparent ghost RBCs. An automated image processing protocol provided feasible cell concentration profiles for each flow and rheological condition with a 6.5 to 9.7% lower sum than manual counting for three samples. For the no magnet conditions, the average near-magnet concentration of paramagnetic RBCs at the outlet (within 10% of 130 μm channel height adjacent to the wire array) was between 1.3 and 2.4 times greater than the average of the rest of the flow field (degree of separation, DOS). The most effective separation was found to occur at the lowest flow rate 0.4 μL min-1 and with the 0.5% Hct metRBC sample with DOS=26. The addition of 30% ghost RBCs reduced the efficiency for all flow rates, with DOS=7.4 for best flow rate of 0.4 μL min-1. Heat treatment did not significantly affect separation with DOS=7.3, likely due to the low impact of the relatively low concentration of metRBCs (0.5%). The mesoscale fabrication and design process, clearance model, cell counting algorithm, and HGMS fabrication protocol and microscopy study described in this thesis provides a useful framework for future HGMS optimization and the further development of a clinical treatment system for severe malaria patients with often limited treatment options.
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Steury, Elinda. "Mobile Phone Short Message Service (SMS) to Improve Malaria Pharmacoadherence in Zambia." Doctoral diss., University of Central Florida, 2014. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/6362.
Full textAbstract:
Malaria significantly contributes to morbidity and mortality rates in Zambia. The currently accepted malaria treatment is artemisinin-based combination therapy (ACT); it is more than 97% effective when the regimen is strictly adhered to. However, the mean ACT adherence rate in sub-Saharan Africa is only approximately 38-48%. Poor pharmacoadherence remains a significant barrier to malaria control and elimination.
The purpose of this study was to determine if adherence rates to a six-dose ACT antimalarial treatment differ between patients in Zambia who received short message service (SMS) reminders and those who did not.
An experimental, randomized, controlled trial was conducted to collect data from a sample of 96 adult patients with malaria who presented to Fisenge Clinic in the Copperbelt Province of Zambia. Participants were randomly assigned to a control or intervention group. The intervention group received SMS messages to remind them to take their medication according to the regimen. An electronic pillbox was used to measure pharmacoadherence for both groups, and patients were classified as probably adherent or probably non-adherent.
Data were analyzed using Chi-square for association between the SMS intervention and pharmacoadherence, and logistic regression used for predictors of adherence. No significant association was found between SMS reminders and pharmacoadherence among malaria patients being treated with ACT when evaluated with respect to those who received the SMS reminders and those who did not (?2=0.19, df=1, p=0.67). Binary logistic regression indicated that there were no variables associated with adherence (p>0.05).
Findings from this study contribute to the research regarding the use of mobile phones to promote adherence. This is the first study of its kind using SMS directly to the patient for ACT adherence in sub-Saharan Africa known to the author. It is possible that the use of the electronic pillbox and/or the novelty of participating in a research study contributed to higher levels of adherence than previously found in this geographical area. While data suggested that there was no association between SMS and adherence, further research is needed to explore the value of this intervention.<br>Ph.D.<br>Doctorate<br>Nursing<br>Nursing<br>Nursing
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Marijani, Theresia. "Mathematical modelling on interaction between malaria parasites and the host immune system." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71711.
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Arori, Christopher Nyakundi. "Assessing the Influence of Socioeconomic Factors, Knowledge Level, Attitudes, and Practices on Malaria Prevention Among the Gusii People of Kenya." ScholarWorks, 2011. https://scholarworks.waldenu.edu/dissertations/961.
Full textAbstract:
Global morbidity and mortality associated with malaria is rampant, and most of the clinical malaria cases are found in sub Saharan Africa. Previous and current research show that malaria is both preventable and treatable and that socioeconomic variables have a profound influence on how persons in rural Africa respond to malaria infections and the associated preventive strategies. This study assessed two key research questions for malaria cases in the Gusii region of Kenya regarding: First, whether a community education program on malaria has an impact in changing malaria preventive behaviors; and, second, if a relationship exists between socioeconomic factors and participants' knowledge and associated behavioral change to control malaria cases. Participatory model and social cognitive theory were used in conjunction with a community intervention with pre-post-test approach. Ten trainees each interviewed 36 participants, for a total of 360 participants, using a structured questionnaire before and after providing a layperson health education program (LPHEP) related to malaria prevention. Repeated measures one-way ANOVA, Chi-square, and Cramer's V test were used for the test of significance. Results showed statistically significant differences between pre- and post-test scores on signs and symptoms of malaria. Participants were able to identify and stated > 2 signs and symptoms of malaria after exposure to the LPHEP. Implications for positive social change included evidence that a simple LPHEP can improve malaria knowledge level.
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Desrosiers, Matthew R. "Investigating the Mechanisms Underlying Enhanced Bioavailability of Artemisinin Delivered Orally as Dried Leaves of Artemisia annua." Digital WPI, 2020. https://digitalcommons.wpi.edu/etd-dissertations/611.
Full textAbstract:
Malaria, a disease caused by parasites of the Plasmodium genus, infects over 220 million people annually, resulting in over 400,000 deaths. Most of these deaths occur in Africa in children < 5 years of age. Artemisia annua L., an ancient Chinese medicinal herb, is known for its foremost phytochemical constituent, artemisinin (AN). Semisynthetic derivatives of AN form the primary component of artemisinin combination therapies (ACTs), the frontline treatment for malaria worldwide. However, ACTs have several drawbacks including cost and availability. Thus, cheaper, more readily available antimalarials are needed. Recent clinical data suggested dried leaves of A. annua (DLA) administered orally as a tea infusion may be as efficacious as ACTs despite a significantly lower AN dose delivered. In mice, AN plasma concentration was improved when administered as DLA compared to pure AN. I therefore hypothesized that phytochemicals within DLA enhanced the oral bioavailability of AN. To investigate this hypothesis, here I examined the effects of DLA on the underlying mechanisms that govern oral bioavailability. Using an in vitro human digestion model, I showed that AN solubility was greater when delivered as DLA, largely due to essential oil in the plant. Furthermore, AN intestinal permeability was enhanced in a Caco-2 cell model of the intestinal epithelium. Extracts, teas, and phytochemicals produced by Artemisia also inhibited the activity of CYP2B6 and CYP3A4, the enzymes responsible for first-pass AN metabolism in the liver. Additionally, AN tissue distribution was improved when delivered as DLA and AN accumulation in tissues was higher in female vs. male rats. Finally, I showed that DLA was a more efficacious anti-inflammatory than pure AN in rats, potentially due to enhanced AN bioavailability. Taken together, these results shed light on the mechanisms behind enhanced oral bioavailability afforded by DLA and demonstrate the potential for DLA to be used as a therapeutic for malaria and other diseases.
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Santos-Ciminera, Patricia Dantas Ciminera Patricia Dantas Santos Santos Patricia. "Molecular epidemiology of epidemic severe malaria caused by Plasmodium vivax in the state of Amazonas, Brazil /." Download the dissertation in PDF, 2005. http://www.lrc.usuhs.mil/dissertations/pdf/Santos2005.pdf.
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DeConti, Derrick K. "Systematic Analysis of Duplications and Deletions in the Malaria Parasite P. falciparum: A Dissertation." eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/869.
Full textAbstract:
Duplications and deletions are a major source of genomic variation. Duplications, specifically, have a significant impact on gene genesis and dosage, and the malaria parasite P. falciparum has developed resistance to a growing number of anti-malarial drugs via gene duplication. It also contains highly duplicated families of antigenically variable allelic genes. While specific genes and families have been studied, a comprehensive analysis of duplications and deletions within the reference genome and population has not been performed. We analyzed the extent of segmental duplications (SD) in the reference genome for P. falciparum, primarily by a whole genome self alignment. We discovered that while 5% of the genome identified as SD, the distribution within the genome was partition clustered, with the vast majority localized to the subtelomeres. Within the SDs, we found an overrepresentation of genes encoding antigenically diverse proteins exposed to the extracellular membrane, specifically the var, rifin, and stevor gene families. To examine variation of duplications and deletions within the parasite populations, we designed a novel computational methodology to identify copy number variants (CNVs) from high throughput sequencing, using a read depth based approach refined with discordant read pairs. After validating the program against in vitro lab cultures, we analyzed isolates from Senegal for initial tests into clinical isolates. We then expanded our search to a global sample of 610 strains from Africa and South East Asia, identifying 68 CNV regions. Geographically, genic CNV were found on average in less than 10% of the population, indicating that CNV are rare. However, CNVs at high frequency were almost exclusively duplications associated with known drug resistant CNVs. We also identified the novel biallelic duplication of the crt gene – containing both the chloroquine resistant and sensitive allele. The synthesis of our SD and CNV analysis indicates a CNV conservative P. falciparum genome except where drug and human immune pressure select for gene duplication.
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DeConti, Derrick K. "Systematic Analysis of Duplications and Deletions in the Malaria Parasite P. falciparum: A Dissertation." eScholarship@UMMS, 2015. https://escholarship.umassmed.edu/gsbs_diss/869.
Full textAbstract:
Duplications and deletions are a major source of genomic variation. Duplications, specifically, have a significant impact on gene genesis and dosage, and the malaria parasite P. falciparum has developed resistance to a growing number of anti-malarial drugs via gene duplication. It also contains highly duplicated families of antigenically variable allelic genes. While specific genes and families have been studied, a comprehensive analysis of duplications and deletions within the reference genome and population has not been performed. We analyzed the extent of segmental duplications (SD) in the reference genome for P. falciparum, primarily by a whole genome self alignment. We discovered that while 5% of the genome identified as SD, the distribution within the genome was partition clustered, with the vast majority localized to the subtelomeres. Within the SDs, we found an overrepresentation of genes encoding antigenically diverse proteins exposed to the extracellular membrane, specifically the var, rifin, and stevor gene families. To examine variation of duplications and deletions within the parasite populations, we designed a novel computational methodology to identify copy number variants (CNVs) from high throughput sequencing, using a read depth based approach refined with discordant read pairs. After validating the program against in vitro lab cultures, we analyzed isolates from Senegal for initial tests into clinical isolates. We then expanded our search to a global sample of 610 strains from Africa and South East Asia, identifying 68 CNV regions. Geographically, genic CNV were found on average in less than 10% of the population, indicating that CNV are rare. However, CNVs at high frequency were almost exclusively duplications associated with known drug resistant CNVs. We also identified the novel biallelic duplication of the crt gene – containing both the chloroquine resistant and sensitive allele. The synthesis of our SD and CNV analysis indicates a CNV conservative P. falciparum genome except where drug and human immune pressure select for gene duplication.
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Gildenhuys, Johandie. "Interactions of quinoline antimalarial drugs with ferrihaem : structural and kinetic insights into the inhibition of malaria pigment formation." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/85621.
Full textAbstract:
Thesis (PhD)--Stellenbosch University, 2013.<br>ENGLISH ABSTRACT: The work in this dissertation provides structural and kinetic insight into the mechanism of
action of quinoline antimalarial drugs which may aid rational drug design. Quinoline
antimalarial drug-ferrihaem (Fe(III)PPIX) complexes were investigated. Single crystal Xray
diffraction (SCD) structures of the complexes formed between Fe(III)PPIX and the
quinoline methanol antimalarials quinine, quinidine and mefloquine have been determined,
and are the first observed structures of complexes formed between free Fe(III)PPIX and
quinoline antimalarial compounds. Quinine, quinidine and mefloquine are shown to have a
three-point binding mode to Fe(III)PPIX, which comprises direct coordination of the drug
to the Fe(III) centre through its benzylic alcohol functionality, π-stacking between the drug
and porphyrin aromatic systems, and intramolecular hydrogen bond formation between the
porphyrin propionate group and the protonated quinuclidine nitrogen atom of the drug in
the case of quinine and quinidine, and formation of an intramolecular hydrogen bonding
network in the case of mefloquine. Extended X-ray absorption fine structure spectroscopy
(EXAFS) was use to elucidate structural information of Fe(III)PPIX-drug complexes in
solution, and indicates that coordination persists in solution.
The protocol for lipid-mediated formation of β-haematin, where monopalmitic glycerol
was used as a model lipid, was successfully modified to incorporate antimalarial drugs into
the aqueous layer in order to investigate drug activity under biologically-relevant
conditions. Four compounds were chosen, namely chloroquine and amodiaquine, both 4-
aminoquinolines and quinine and quinidine. IC50 values for the inhibition of β-haematin
formation show good correlation with biological activities determined against a
chloroquine-sensitive Plasmodium falciparum strain. The lipid-water interface system was
further used to investigate the effects of quinine, quinidine chloroquine and amodiaquine
on the kinetics of β-haematin formation. The results led to the development of a kinetic
model based on the Avrami equation and the Langmuir isotherm. The data strongly support
a mechanism of antimalarial drug action by adsorption to the growing face of haemozoin,
with precipitation of Fe(III)PPIX at high drug concentrations accounting for decreased
yields. Adsorptions constants (log Kads) determined for each drug show a strong correlation
with biological activity. Finally, the first SCD structure of the μ-propionato dimer of
Fe(III)PPIX, the structural unit of haemozoin, has been determined as its DMSO solvate.
EXAFS suggests that this species is only formed upon nucleation, with the π-π dimer
species being favoured in solution.<br>AFRIKAANSE OPSOMMING: Die werk in die dissertasie verleen struktuur en kinetiese insig in the meganisme van
aktiwiteit vir kinolien antimalariamiddels wat kan bydra tot die ontwikkeling van nuwe
medisyne. Kinolien antimalariamiddel-ferriheem (Fe(III)PPIX) komplekse was ondersoek.
Navorsing is gedoen op die enkelkristal X-straaldiffraksie strukture van die komplekse
gevorm tussen Fe(III)PPIX en die kinolien metanol antimalaria middels kinien, kinidien en
mefloquine. Die strukture is die eerste komplekse wat waargeneem is tussen vrye
Fe(III)PPIX en kinolien antimalariamiddels. Kinien, kinidien en mefloquine het ʼn driepunt
bindingsvorm, direkte koördinasie met die Fe(III) deur die bensielalkohol groep, ʼn π-
stapel tussen die middel en die porfirien aromatiese sisteem, ʼn intramolekulêre
waterstofbinding tussen the porfirienpropionaat funksie en die geprotoneerde kinuklidien
stikstofatoom (kinien en kinidien) en ʼn netwerk van intramolekulêre waterstof bindings
(mefloquine) insluit. Uitgebreide X-straal absorpsie fyn struktuur spektroskopie (EXAFS)
is gebruik om inligting oor Fe(III)PPIX-middel komplekse in oplossing te verkry en het
aangedui dat die koördinasie in oplossing voorkom.
Deur gebruik te maak van monopalmitiengliserol as die lipid in the lipid-water interfase
sisteem, waar antimalariamiddels suksesvol in die buffer geïnkorporeer was, was die
middel se aktiwiteit onder biologiese kondisies geondersoek. Vier middels was gekies
naamlik, chloroquine en amodiaquine, albei 4-aminokinoliene en kinien en kinidien om die
IC50-waarde vir inhibisie van β-hematien vorming te bepaal. Die IC50 waardes het ʼn goeie
korrelasie met biologiese aktiwiteite teen die chloroquine-sensitiewe Plasmodium
falciparum stam gewys. Die lipid-water interfase-sisteem was ook gebruik om die effek
van kinien, kinidien, chloroquine en amodiaquine op die kineties effek op die vorming van
β-hematien te ondersoek. Die resultate het gelei to die ontwikkeling van die kinetiese
model gebaseer op die Avrami vergelyking en die Langmuir isoterm. Die data ondersteun
ʼn meganisme van middel aksie waar die middel teen die groeiende vlak van hemosoïen
kristal adsorbeer. Die neerslag van Fe(III)PPIX wat vorm by hoë konsentrasies, het gelei
tot laer opbrengste. Die adsorpsiekonstante (log Kads) bepaal vir elke middel, het goeie
korrelasie met biologiese aktiwiteit getoon. Enkelkristal X-straaldiffraksie strukture van μ-
propionatodimeer van Fe(III)PPIX, die struktuur eenheid van hemosoïen, was bepaal as ʼn
DMSO solvaat. EXAFS het aangedui dat die spesie slegs by kernvorming ontstaan en dat
die π-π dimeerspesie in oplossing voorkom.
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Alvarado, Stephenie M. "Identification of novel antimalarials from marine natural products for lead discovery." Master's thesis, University of Central Florida, 2010. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/4591.
Full textAbstract:
An estimated 500 million cases of malaria occur each year. The increasing prevalence of drug resistant strains of Plasmodium in most malaria endemic areas has significantly reduced the efficacy of current antimalarial drugs for prophylaxis and treatment of this disease. Therefore, discovery of new, inexpensive, and effective drugs are urgently needed to combat this disease. Marine biodiversity is an enormous source of novel chemical entities and has been barely investigated for antimalarial drug discovery. In an effort to discover novel therapeutics for malaria, we studied the antimalarial activities of a unique marine-derived peak fraction library provided by Harbor Branch Oceanographic Institute (HBOI). Within this unique library, we have screened 2,830 marine natural product (MNP) peak fractions through a medium throughput screening effort utilizing the SYBR Green-I fluorescence based assay, and have identified 253 fractions that exhibit antimalarial activity. From those inhibiting fractions we have identified twenty species of marine organisms that inhibit Plasmodium falciparum growth, from which thirty-five fractions were selected for further study. Among those thirty-five, eighty-three percent were also found to inhibit the chloroquine resistant strain of P. falciparum, Dd2. The most potent inhibitors were then screened for their cytotoxic properties using the MTT cell viability assay. Among the samples that exhibited potent inhibition of P. falciparum growth were fractions derived from a sponge of the genus Spongosorites sp.. This genus of sponge has been reported to contain the nortopsentin and topsentin class of bis-indole imidazole alkaloids. Nortopsentin A inhibited the parasite growth at the trophozoite stage with an IC[sub]50 value of 1.6micrometer]. This is the first report of antimalarial activity for this class of compound.<br>ID: 030423269; System requirements: World Wide Web browser and PDF reader.; Mode of access: World Wide Web.; Thesis (M.S.)--University of Central Florida, 2010.; Includes bibliographical references (p. 56-61).<br>M.S.<br>Masters<br>Burnett School of Biomedical Sciences<br>Medicine
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Ferreira, Katherine. "Understanding the Role of Plasmodium falciparum VAMP8 SNARE Homologue." Honors in the Major Thesis, University of Central Florida, 2013. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/1541.
Full textAbstract:
Malaria is one of the worlds most deadly infectious diseases and results in almost a million deaths each year, largely in children under the age of five in Sub-Saharan Africa. Outside Africa, malaria is responsible for a large number of cases in the Amazon rainforest of Brazil, Middle East, and in some areas of Asia [37]. According to the World Health Organization, there was an estimated 655, 000 deaths from malaria in 2012. Malaria is caused by a eukaryotic Apicomplexan parasite, Plasmodium, which has three distinct life cycles occurring in the midgut of the female Anopheles mosquito, the liver of the human host, and human erythrocytes. When the parasite infects the erythrocyte, some induced cell host modifications are made in order to accommodate growth. During its intra-erythrocytic life cycle, the malaria parasite traffics numerous proteins to a set of unique destinations within its own plasma membrane including the digestive vacuole, the apicoplast, rhoptries, and micronemes. Vesicular transport is an essential process in eukaryotic cells. This coordinated process is responsible for moving thousands of proteins between compartments within the cell. Essential to the targeting and fusion of protein transport vesicles in eukaryotes are SNAREs (soluble N-ethylmaleimide sensitive factor attachment protein receptors), a family of fusogenic proteins that are localized to distinct intracellular compartments [11]. Studies performed in our laboratory have identified 18 proteins putatively belonging to the PfSNARE family [2]. To date the exact role of PfSNAREs in the unique trafficking pathways of malaria is undetermined. Of particular interest to our study is PfVAMP8. In model eukaryotic organisms, VAMP8 containing vesicles deliver cargo to lysosomes and are involved in endocytosis. The food vacuole of the parasite is very similar to that of lysosomes and is essential to parasite survival. The study aims to identify the organelle(s) to which PfVAMP8 is localized and characterize membrane-association properties of this parasite’s R-SNARE protein. We believe that PfVAMP8 would localize to unique compartments in the parasite protein network flow. An in depth understanding of its mechanisms and localizations could be a key in developing novel anti-malarials. This study aims to identify the organelle(s) to which PfVAMP8 are localized, determine the trafficking determinants of this protein and determine this proteins’ expression and membrane association during the intra-erythrocytic stages of Plasmodium falciparum. Our immunofluorescence studies with known biological markers reveals that, PfVAMP8 passes through the endoplasmic reticulum, Golgi, and localizes to the food vacuole during trophozoite and schizont stage. Further characterization of the membrane association properties of the protein in this study reveals that PfVAMP8 is a soluble integral membrane protein with amphipathic characteristics.<br>B.S.<br>Bachelors<br>Burnett School of Biomedical Sciences<br>Molecular Biology and Microbiology
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Basson, Eldrian. "The prevalence of malaria in Mefloquine hydrochloride - mefliam ® users during the deployment of military forces in Burundi, East Africa." Thesis, Bloemfontein : Central University of Technology, Free State, 2007. http://hdl.handle.net/11462/87.
Full textAbstract:
Thesis (M. Tech.) - Central University of Technology, Free State, 2007<br>Malaria and the mosquito that induces the disease in humans have hounded the military for decades. Malaria represents one of the most important infectious disease threats to deployed military forces. Malaria in soldiers has a serious economic impact, both in terms of lost productivity and treatment cost for the state. A contingent of South African National Defence Force members has been deployed in Burundi since November 2001, as part of a peacekeeping mission. At the time of the study no information was available regarding the prevalence of malaria among military personnel during deployments in Burundi and East Africa.
In Africa, the saying is that malaria is the disease of poverty and a cause of poverty. To combat malaria, it is of vital importance that the recommended medication be taken exactly as prescribed and that the course is completed. However, one of the greatest challenges facing the African continent in the present fight against malaria is drug resistance. The discovery of Mefloquine and the subsequent development of suitable drugs, have been intimately associated with military imperatives, contingencies and requirements. Since World War II, the development of Chloroquine-resistant falciparum malaria has driven the search for new drugs. Mefloquine, developed by the Walter Reed Army Institute of Research in the United States, was first shown effective as a prophylaxis and treatment of resistant falciparum malaria in the 1970’s.
To obtain data, questionnaires were administered to SANDF soldiers deployed in Burundi, East Africa. The total size of the population under investigation was 336 with a final sample size of 111 respondents. The sample was selected by using simple random sampling. The questionnaire aimed to determine the perception of respondents regarding the malaria threat, their compliance with taking the medication, and their experiencing of possible side-effects which might occur due to the chemoprophylaxis and the prophylactic efficacy of Mefliam®.
The fact that, of the 111 people who used Mefliam®, only four presented with any malaria symptoms, is an indicator that Mefliam® is an effective option as an antimalarial drug to be used in East Africa and Burundi.
The results of this study will be used by the personnel of the South African National Defence Force (SANDF) and other military forces deployed in East Africa. It is envisaged that the results will be used by military policy- and decision-makers as a control programme and by others involved in the control of malaria. The findings and recommendations should also be of interest to anyone visiting the area.
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Valor, Cristhian. "3-Amino-2-Piperidinequinoline A Novel Natural Product-Inspiried Synthetic Compound with Antimalarial Activity." Honors in the Major Thesis, University of Central Florida, 2014. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/1652.
Full textAbstract:
Malaria afflicts about 500 million people worldwide thus causing significant global economic toll. The drugs available to treat the disease are rapidly losing their efficacy because of widespread prevalence of drug resistant parasites. Thus there is an urgent need to discover novel malaria therapeutics. This research is focused on to study the properties of a novel naturallike synthetic scaffold and analyze its selectivity, and cellular mechanism of action in Plasmodium falciparum. We have identified a novel compound, 3-amino-2-piperidinequinoline (APQ), which we termed UCF401. APQ demonstrated IC[sub50] at submicromolar concentrations against Plasmodium falciparum using the SYBR Green-I fluorescence assay measuring cellular proliferation. This compound also demonstrated low cytotoxicity against the NIH3T3 and HEPG2 cells using MTS assays, showing an IC50 of 174 [micro]M and 125 [micro]M respectively, suggesting of excellent selectivity. We evaluated the compliance of APQ with Lipinski's parameters and determined the in vitro physicochemical profiles of the compound. Our results show that APQ is a Lipinski parameter compliant and has good physicochemical properties. The cellular mechanism of action of APQ was characterized through the assessment of the effects of the compound at different stages of the parasite's intraerythrocytic life cycle. This assay was done by treating a synchronized cell line with the compound at 5X the IC50 value and then imaging the cells at 12-hour intervals. We found that APQ arrests parasite development at the trophozoite stage. In addition we determined that APQ is parasitocidal after a 96 h exposure. These results demonstrate that APQ can be considered as a validated hit and/or early lead.<br>B.S.<br>Bachelors<br>Biomedical Sciences<br>Biomedical Sciences
35
Sullenberger, Catherine. "Identificatin sic] of physiological substrates of Plasmodium falciparum PfPK5, a CDK-like kinase." Honors in the Major Thesis, University of Central Florida, 2011. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/518.
Full textAbstract:
Malaria is one of the most devastating infectious diseases causing 1-3 million fatalities a year. The majority of these cases occur amongst children in developing countries. Malarial strains in these areas are exhibiting increasing resistance to canonical treatments proving the importance of new drug targets for anti-malarials. Identification of new drug targets is dependent upon a better understanding of the molecular biology of the parasitic agent of malaria, Plasmodium. The regulation of Plasmodium's complex life cycle is still not well understood. Elucidation of signaling pathways involved in Plasmodium cell cycle regulation will provide insights into how the parasite thrives in human cells. A subset of kinases, referred to as cyclin-dependent kinases (CDKs), are crucial regulators of eukaryotic cell cycle progression. In silico studies show high homology between mammalian CDK's and a group of CDK-like Plasmodium kinases including PfPK5 (Plasmodium falciparum protein kinase 5). Plasmodium homologues to CDK regulators, cyclins, have also been identified. Understanding the role of PfPK5 in cell cycle regulation would require analysis of subcellular localization and cell cycle-dependent expression. Immunofluorescence assays demonstrate that PfPK5 is localized in the nucleus. PfPK5's expression profile, as determined by western blotting, shows highest expression in the schizont stage, the stage when the atypical multiple nucleated form of the parasite is observed. Possible PfPK5 interacting partners were detected by performing an anti-PfPK5 immunoprecipitation assay. Additionally, a hemagglutinin (HA)-tagged PfPK5 construct was made to increase the sensitivity of immunoprecipitation assay and identification of PfPK5 interacting partners. The characterization of PfPK5 and its interacting partners may prove useful in identification of novel drug targets in the future.<br>B.S.<br>Bachelors<br>Medicine<br>Molecular Biology and Microbiology
36
Eichorn, Joseph. "Determining the current level of knowledge among healthcare providers and nurses concerning the signs, symptons, and diagnosis of malaria in the United States." Honors in the Major Thesis, University of Central Florida, 2010. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/1402.
Full textAbstract:
This item is only available in print in the UCF Libraries. If this is your Honors Thesis, you can help us make it available online for use by researchers around the world by following the instructions on the distribution consent form at http://library.ucf.edu/Systems/DigitalInitiatives/DigitalCollections/InternetDistributionConsentAgreementForm.pdf You may also contact the project coordinator, Kerri Bottorff, at kerri.bottorff@ucf.edu for more information.<br>Bachelors<br>Nursing<br>Nursing
37
Leussa, Nyango-Nkeh Adrienne. "Characterisation of small cyclic peptides with antilisterial and antimalarial activity." Thesis, Stellenbosch : Stellenbosch University, 2014. http://hdl.handle.net/10019.1/86161.
Full textAbstract:
Thesis (PhD)--Stellenbosch University, 2014.<br>ENGLISH ABSTRACT: Antimicrobial peptides (AMPs) are currently the most researched group of compounds for new
antimicrobial drugs especially with the rise in resistance to almost all available drugs by public
health relevant pathogens. In this study we set out to characterise small cyclic AMPs in terms of
their activity towards human pathogens Listeria monocytogenes, a food-borne pathogen causing
listeriosis and Plasmodium falciparum, a parasite that causes malaria respectively, each a threat
to public health.
One of the small cyclic peptide libraries examined is the tyrocidines (Trcs) and analogues, which
are cyclic decapeptides [cyclo-(D-Phe-Pro-(Phe/Trp)-D-Phe/DTrp)-Asn-Gln-(Tyr/Phe/Trp)-Val-
(Orn/Lys)-Leu] produced by the Gram-positive bacteria Bacillus aneurinolyticus as part of the
tyrothricin complex which is non-ribosomally synthesised during sporulation. Previous research
found that the six major Trcs were active against Listeria monocytogenes and Plasmodium
falciparum and it was found that the identity of the aromatic residues in the aromatic dipeptide
unit has an important role in activity. We set out to extend the qualitative structure to activity
relationship (QSAR) studies using more Trc analogues and small synthetic Arg- and Trp-rich
cyclic peptides (RW-peptides) in a bid to establish essential structural motifs and pre-requisites
for activity. Eight natural and three synthetic Trc analogues and fifteen RW-peptides were either
naturally or by chemical synthesis produced and characterised in terms of chemical character and
biological activity. The Trcs were significantly more active than RW peptides, although much
more haemolytic and thus toxic. Results indicated the relevance for hydrogen bonding with an
aromatic amino acid residue for selective activity towards the leucocin A resistant L.
monocytogenes B73-MR1. However, structural properties favouring a tighter membrane
interaction hindered the Trc mode of action (MOA). We determined that Gln6 and hydroxyl
group of Tyr7 may be involved in interaction with the putative target in L. monocytogenes. There
was also need for an amphipathic balance between hydrophobicity and size/steric parameters for
optimal activity. From our QSAR studies we predict as lead peptide for a future library of
antilisterial Trcs: cyclo(VOMe3LfPWfNQY). Furthermore, the antilisterial activity of the Trcs
was found to be predominantly lytic and salt tolerant while RW-peptides were non-lytic and
sensitive to Ca2+. We confirmed that Ca2+ enhanced Trc antilisterial activity with Ca2+ increasing
the Trc anti-metabolic activity, but conversely inducing a non-lytic mechanism of action. From model membrane studies, we propose that the calcium induced Trc non-lytic MOA could be due
to detrimental lipid demixing, presence of a Trc sensitive Ca2+-induced non-membrane target in
the prematurely calcium induced intracellular anaerobic form of Listeria monocytogenes, and/or
the Trc-Ca2+ complexes may inhibit key components such as membrane bound electron transport
system or bacterial dehydrogenases.
We confirmed, as previously found, that the Trcs have potent antimalarial activity that is
sequence specific and non-lytic. The RW-peptides had very weak activity, but our results again
indicated that more hydrophobic and haemolytic peptides tend to be more active, particularly the
RW-peptide containing the Trp analogue β-(benzothien-3-yl)-alanine (Bal). A novel finding was
that one of the more polar Trc C analogues, namely tryptocidine C (Tpc C), in contrast to Trc C
showed potent antimalarial activity indicating the specific sequence and the role of the Trp7 in
activity. From these results a proposed lead peptide for future research is
cyclo[VOLfP(Bal)fNQ(Bal)]. Furthermore, in our search for the Trc and Tpc C target(s) we
employed high resolution fluorescence microscopy. Results show that Trc led to disorganisation
of neutral lipid structures and chromatin halting growth in late trophozoite/early schizont stages.
This indicated that membrane structures containing neutral lipids, as well as chromatin may be
targeted by the Trcs. Another novel finding in our studies was that chloroquine (CQ) resistance
not only correlated with resistance to Trcs, but the Trcs and CQ were found to be antagonistic
towards each other’s activity. This indicated a shared target and we propose the food vacuole as
another of the Trc targets in P. falciparum.<br>AFRIKAANSE OPSOMMING: Antimikrobiese peptiede (AMPe) is tans die mees nagevorsde groep verbindings in die soeke na
nuwe antimikrobiese middels, veral weens 'n toenemende weerstandigheid van patogene in die
openbare gesondheidsektor teen alle beskikbare middels. Die doel van hierdie studie was om
klein, sikliese AMPe in terme van hul aktiwiteit teenoor twee menslike patogene wat 'n
bedreiging vir openbare gesondheid is, Listeria monocytogenes, 'n voedsel-oordraagbare
patogeen wat listeriose veroorsaak, asook Plasmodium falciparum, die parasiet verantwoordelik
vir malaria, te karakteriseer.
Een van die klein, sikliese peptiedbiblioteke wat ondersoek is, is die tyrocidines (Trcs) en analoë
(sikliese dekapeptiede [siklo-(D-Phe-Pro-(Phe/Trp)-D-Phe/DTrp)-Asn-Gln-(Tyr/Phe/Trp)-Val-
(Orn/Lys)-Leu]). Hierdie peptiede deur die Gram-positiewe bakterie Bacillus aneurinolyticus
word wat nie-ribosomaal gesintetiseer as deel van die tirotrisien kompleks word tydens
sporulasie. Vorige navorsing het gewys dat die ses hoof Trcs teen Listeria monocytogenes en
Plasmodium falciparum aktief is en dat die identiteit van die aromatiese residue in die aromatiese
dipeptiedeenheid 'n belangrike rol speel in die Trc-aktiwiteit. Ons het gepoog om die
kwalitatiewe struktuur-aktiwiteit-verwantskap (QSAR) studies uit te brei deur meer Trc analoë
en klein sintetiese Arg- en Trp-ryke sikliese peptiede (RW-peptiede) te gebruik en sodoende
essensiële struktuur-motiewe en voorvereistes vir aktiwiteit vas te stel. Agt natuurlike en drie
sintetiese Trc analoë, asook vyftien RW-peptiede is of deur natuurlike of chemiese sintese
geproduseer en gekarakteriseer in terme van chemiese karakter en biologiese aktiwiteit. Die Trcs
het beduidend meer aktiwiteit as RW-peptiede getoon, maar is ook meer hemolities en dus meer
toksies. Die resultate dui op die belang van waterstofbinding met 'n aromatiese aminosuurresidu
vir die selektiewe aktiwiteit teenoor die leucocin A weerstandige L. monocytogenes B73-MR1.
Strukturele eienskappe wat tot 'n sterker membraan-interaksie lei, verhinder egter die
werkingsmeganisme. Ons het vasgestel dat Gln en die hidroksielgroep van Tyr betrokke kan
wees in die interaksie met die vermeende teenmiddelteiken in L. monocytogenes. 'n Balans tussen
amfipatiese/hidrofobiese en grootte/steriese parameters is ook noodsaaklik vir optimale
aktiwiteit. Vanuit ons QSAR studies word die peptied siklo-(VOMe3LfPWfNQY) as die
voorloper vir 'n toekomstige peptiedbiblioteek van antilisteriale Trcs voorgestel. Verder is daar
gevind dat die antilisteriese aktiwiteit van die Trcs oorwegend lities en sout-verdraagsaam is, terwyl die RW-peptiede nie-lities en Ca2+ sensitief is. Ons het bevestig dat Ca2+ die Trc
antilisteriese aktiwiteit verbeter, deur die Trc se antimetaboliese aktiwiteit verhoog, maar
terselfdertyd 'n nie-litiese werkingsmeganisme induseer. Vanuit model-membraan studies word
voorgestel dat Trc se nie-litiese werkingsmeganisme, soos teweeggebring deur Ca2+, die gevolg
kan wees van nadelige lipied vermenging, die teenwoordigheid van 'n kalsium geïnduseerde Trcsensitiewe
nie-membraan teiken in 'n vervroegde kalsium geïnduseerde intrasellulêre anaerobiese
vorm van Listeria monocytogenes, en/of dat die Trc-Ca2+ komplekse belangrike komponente
soos ’n membraan-gebonde elektron transport sisteem of bakteriële dehidrogenases inhibeer.
Daar is ook bevestig, soos voorheen gevind, dat die Trcs kragtige, antimalaria aktiwiteit besit wat
volgorde-spesifiek en nie-lities is. Die RW-peptiede het swak aktiwiteit getoon, maar ons
resultate het weereens bewys dat peptiede wat meer hidrofobies en hemolities is, meer aktief is,
veral die RW-peptiede wat die Trp analoog β-(bensoteïen-3-iel)-alanien (Bal) bevat. 'n Nuwe
bevinding is dat een van die meer polêre Trc C analoë, genaamd triptosidien C (Tpc C), in
teenstelling met Trc C, sterk antimalaria aktiwiteit het, wat 'n aanduiding is van die spesifieke
volgorde en die rol van die Trp7 in aktiwiteit. Vanuit hierdie bevindinge word die peptied siklo-
(VOLfP(Bal)fNQ(Bal)) as 'n voorloper vir toekomstige navorsing aangedui.
Vir ons soeke na die Trc en Tpc C teiken(s), het ons hoë resolusie fluoressensie mikroskopie
aangewend. Resultate toon dat Trc tot die ontwrigting van 'n neutrale lipied strukture en
chromatien lei en sodoende groei beperk in die laat trofosoïet/vroeë skisont fases. Dit het
aangedui dat die membraanstrukture wat neutrale lipiede bevat, sowel as chromatien, deur die
Trcs geteiken word. 'n Verdere nuwe bevinding in hierdie studie was dat chloroquine (CQ)
weerstandigheid nie net korreleer met weerstandigheid teen Trcs nie, maar dat die Trcs en CQ
antagonisties optree teenoor mekaar se aktiwiteite. Dit dui op 'n gemeenskaplike teiken en die
kosvakuool as 'n addisionele Trc teiken in P. falciparum word voorgestel.
38
Joshua, Isaac B. "The impact of an intervention program for the treatment of malaria in children in Papua New Guinea." Curtin University of Technology, School of Pharmacy, 2003. http://espace.library.curtin.edu.au:80/R/?func=dbin-jump-full&object_id=13852.
Full textAbstract:
Malaria is more prevalent today and the death toll is on the increase annually. It is one of the leading causes of morbidity and mortality worldwide and most of these deaths are in the poorest regions of the world. About 500 million cases are reported annually with more than 2 million deaths, and most are children. It is the major killer in the tropics and a major public health problem in developing countries and Papua New Guinea (PNG) is no exception. Resistant strains have been reported. This may be enhanced by inappropriate human behaviour in the use of anti-malarial drugs. Human factors include inappropriate prescribing and patient behaviour in using anti-malarial drugs. Despite the establishment of the standard treatment guidelines for malaria in PNG, three out of every four patients have chloroquine-resistant falciparum malaria and malaria remains a major health problem. The aim of this study was to evaluate the influence of an education program on patients carers' understanding and effective use of anti-malarial drugs for the treatment of uncomplicated malaria in children in general health clinics in PNG. The trial design involved a pre-post intervention study with a control group. The study was undertaken in the National Capital District. Papua New Guinea using one Clinic as the intervention site and another as the control site. The two clinics were similar in characteristics as confirmed in the study by demographic data where there were no significant differences observed. The data collection took placed over the period February to April 2002. It included observation of drug provision at study sites and interviews of patient carers on the first day at the clinic and a follow up seven days later. Three questionnaires were developed to evaluate the process and outcomes of malaria drug treatment in the above health facilities.<br>Prescribing data were collected from prescriptions and patient carers' interviewed prior to the intervention program. Following the provision of drug information to patient carers. similar drug information and compliance questioning was undertaken. Differences in the pre-post elements of the study and in the control group over the study period were evaluated using Chi-Squared, Kruskal-Wallis, Fisher's Exact or Student's t-tests as appropriate. In excess of 100 patients in the pre- and in the post intervention phases were evaluated for their understanding and effective use of the anti-malarial drugs. In addition, 100 clients were in the control group at another clinic. Patients had attended the clinic up to 8 times in the previous year with a median of 2 visits. Amodiaquine, Fansidar, albendazole and paracetamol made up a total of 60% of the drugs prescribed. The use of medicines was strongly supported with 94.4% indicating no problems with the medication. Only 3% of patients received herbal or local remedies for malaria treatment. 1n patients 10 years or less or their carers, it was found, there was a significant improvement in the carers understanding of the medications. There was a statistically significant improvement in patient outcomes from 57.9% to 92.3% reported as cured following the intervention program. The study has also identified low levels of appropriate administration of antibiotic suspensions in children by patient carers.<br>For example, incorrect responses recorded for amoxycillin suspension were 80.8% (143). Septrim tablets 92% (23), Septrim suspension 86% (123), erythromycin suspension 100% (26), and chloramphenicol suspension 84.4% (38). In this study the face to face (one-to-one) education program was used to influence patient carers understanding and effective use of drugs. The intervention program involved advising, informing, encouraging, and counselling the patient carers verbally on the appropriate and effective use of medicines. The verbal message was reinforced by a suitable label typed in English and Pidgin-English where instructions were clear, simple and unambiguous. The label was then attached to the envelopes or containers containing the drugs. On feedback, the information on the understanding and effective use of drugs was re-emphasized to the carers to reinforce their understanding for future references. Results showed that the intervention program made an impact in improved patient carers understanding and effective use of drugs and children's health outcomes. In conclusion, it is evident that a patient intervention program designed to improve the dosages and frequency of administration of anti-malarial drugs in PNG had no statistically significant outcome. This may be because the current level of understanding was quite high (>70%) and the study experienced a ceiling effect. However, as shown in the results, the patient carers understanding on the appropriate and effective use of drugs was lower during the pre-intervention and control group.<br>When compared clinic-pre with clinic-post, there was a significant difference (P < 0.05) in the cured group and the improved cure rate increases from 57.9% to 92.3%. When compared control pre with control post groups, there was no significant difference (P > 0.05) in the cured group. Therefore, the study identified an improvement in patient outcomes with respect to malaria. Hence. the simple intervention program in influencing patient carers understanding of the appropriate and effective use of medications led to a marked improvement in patient outcomes.
39
Thiart, Hanlie. "Immunological and epidemiological investigations into avian malaria in the African penguin during rehabilitation and in breeding colonies." Thesis, Stellenbosch : University of Stellenbosch, 2005. http://hdl.handle.net/10019.1/16620.
Full textAbstract:
Thesis (MSc)--University of Stellenbosch, 2005.<br>ENGLISH ABSTRACT: The African penguin, which occurs along the south-eastern and south-western shores of
South-Africa and Namibia, has experienced a severe reduction in population numbers
due to guano and egg collection in the first half of the 19th century, and oil pollution in
the second half of the 19th century as a result of oil tankers rounding the Cape of Good
Hope. The population would have been reduced by a further 19% had it not been for
the rehabilitation of penguins at the South African National Council for the Conservation
of Coastal Birds (SANCCOB) facility. Although this has been very successful,
mortalities as a result of avian malaria infection have considerably reduced the
efficiency of rehabilitation. In an effort to assess the role of immunity against malaria in
combating the disease, an enzyme-linked immunosorbent assay (ELISA) for the
detection of antibody levels to avian malaria was developed. The ELISA was used to
detect antibody levels to avian malaria of penguins on entry and during rehabilitation
from October 2001 to January 2003.
The aim of this study was to continue the determination of antibody levels to avian
malaria of penguins entering the SANCCOB facility, in order to allow an evaluation of
the antibody levels to avian malaria for two full calendar years. This investigation was
combined with a polymerase chain reaction (PCR)-based method, capable of detecting
any Plasmodium species in penguin serum. These two methods were also used to
investigate avian malaria in several breeding colonies in order to assess the role avian
malaria may play in the survival of the African penguin in the wild.
Results indicated that the ability of penguins to produce anti-Plasmodium antibodies
was not influenced by oiling and that infection with malaria was not due to
recrudescence but rather due to infection via mosquitoes. This indicated a possible role
of the SANCCOB facility in exposing the penguins to avian malaria. However a large
number of penguins arrived at the facility previously infected with malaria, indicating that
malaria was present in the breeding colonies. Investigations in the breeding colonies
revealed extremely high avian malaria prevalence even though no sick birds or
mortalities were observed. This raised the question whether different types of malaria
are responsible for infection in the SANCCOB facility and breeding colonies.<br>AFRIKAANSE OPSOMMING: Die Afrika Pikkewyn kom langs die suid-oostelike en suid-westelike kus van Suid Afrika
en Namibië voor. In die afgelope eeu het hierdie spesie ‘n geweldige afname in
populasie getalle ondervind. Dit was hoofsaaklik die gevolg van die versameling van
guano en pikkewyneiers in die eerste helfte van die 19de eeu en oliebesoedeling in die
tweede helfde van die 19de eeu. Die “South African Foundation for Conservation of
Coastal Birds” (SANCCOB) is ‘n seevoëlreddings- en rehabilitasiesentrum vir siek,
beseerde en ge-oliede pikkewyne. Dit word geskat dat die Afrika Pikkewyn populasie
met ‘n verdere 19% sou afgeneem het as dit nie vir die rehabilitasie by die SANCCOB
sentrum was nie. Hierdie sentrum het egter aansienlike vrektes in die somer as gevolg
van voëlmalaria, wat sodoende die effektiwiteit van die rehabilitasie verlaag. In ‘n
poging om die rol van immuniteit teen malaria te bepaal is ‘n “enzyme-linked
immunosorbent assay” (ELISA) ontwikkel vir die bepaling van antiliggaam vlakke teen
malaria. Hierdie ELISA is gebruik vir die bepaling van die anti-Plasmodium antiliggaam
vlakke van die pikkewyne by aankoms en ten tye van rehabilitasie by SANCCOB vanaf
Oktober 2001 to Januarie 2003.
Die doel van hierdie studie was eerstens om hierdie ELISA bepalings voort te sit om
sodoende antiliggaam vlakke teen malaria oor twee kalender jare te kan evalueer.
Hierdie ondersoek was gekombineer met ‘n polimerase ketting reaksie (PCR) metode,
wat enige Plasmodium spesie in pikkewynserum sou kon opspoor. Hierdie twee
metodes is ook gebruik vir ondersoeke in sommige broeikolonies, met die doel om te
bepaal watter rol voëlmalaria in die oorlewing van die Afrika pikkewyn in die natuur
speel.
Resultate het getoon dat olie nie die vermoë van die pikkewyn beïnvloed om anti-
Plasmodium antiliggame te vervaardig nie en dat malaria infeksie hoofsaaklik deur
muskiete veroosaak word en nie deur heruitbraak van ‘n bestaande infeksie nie. Dit dui
egter daarop dat pikkewyne blootgestel word aan voëlmalaria by die SANCCOB
sentrum. Daar is ook gevind dat ‘n groot aantal pikkewyne met malaria infeksies by die
sentrum opgedaag het wat dui op die voorkoms van malaria in die broeikolonies.
Ondersoeke in die broeikolonies het ‘n besonder hoë voorkoms van malaria onthul.
Geen vrektes of siek pikkewyne is in die broeikolonies waargeneem nie, wat moontlik
kan beteken dat pikkewyne by SANCCOB met ‘n ander tipe malaria geïnfekteer word
as in die broeikolonies.
40
Yap, Jessica. "Identification of Plasmodium falciparum protein kinase substrates and interacting proteins." Honors in the Major Thesis, University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/644.
Full textAbstract:
Characterization of PfPKA and PfPK5 substrates, as well as the proteins they interact with, will help us to develop innovative therapies targeting binding sites.; Malaria is a devastating disease that results in almost one million deaths annually. Most of the victims are children under the age of five in Sub-Saharan Africa. Malaria parasite strains throughout developing countries are continually building resistance to available drugs. Current therapies such as mefloquine, chloroquine, as well as artemisinin are becoming less effective, and this underscores the urgency for therapeutics directed against novel drug targets. In order to identify new drug targets, the molecular biology of the malaria parasite Plasmodium needs to be elucidated. Plasmodium exhibits a unique cell cycle in which it undergoes multiple rounds of DNA synthesis and mitosis without cytokinesis. Thus, cell cycle regulatory proteins are likely to be promising pathogen-specific drug targets. It is expected that fluctuating activity of key proteins, such as protein kinases, play an essential role in regulating the noncanonical life cycle of Plasmodium. Consequently, malarial kinases are a prime target for therapy. One way to better understand the role of malarial kinases in Plasmodium cell cycle regulation is to identify putative protein kinase substrates and interacting proteins. Two malarial kinases that have been implicated in regulating malaria parasite cell cycle stages were investigated in this study: P. falciparum CDK-like Protein Kinase 5 (PfPK5) and cAMP-Dependent Protein Kinase A (PfPKA). A transgenic P. falciparum line was created for the expression of epitope-tagged PfPK5 for pull-down analysis. Phospho-substrate antibodies were used to identify physiological substrates of both PfPK5 and PfPKA. Immunoblotting with these antibodies identified several potential substrates. Identities of the PfPKA physiological substrates were determined from the global P. falciparum phosphoproteome dataset that has recently been generated in our laboratory.<br>B.S.<br>Bachelors<br>Burnett School of Biomedical Sciences<br>Molecular and Microbiology
41
Penkler, Gerald Patrick. "Construction and validation of a detailed kinetic model of glycolysis in asexual Plasmodium falciparum : a feasibility study." Thesis, Stellenbosch : University of Stellenbosch, 2009. http://hdl.handle.net/10019.1/2298.
Full textAbstract:
Thesis (MSc (Biochemistry))--University of Stellenbosch, 2009.<br>ENGLISH ABSTRACT:
In Africa alone, Plasmodium, the causative agent of malaria is estimated to kill
a child, under the age of five every thirty seconds140. The ability of the parasite
to rapidly attain resistance, has resulted in immunity of the parasite to all,
except one group of frontline drugs. The need to develop novel drugs, vaccines
and prevention strategies that are accessible and affordable for third world
countries is of the utmost importance to prevent needless human suffering and
death.
The glycolytic pathway is an attractive drug target since it is the principal
source of ATP for the parasite. Many of the glycolytic enzymes have been
studied and proposed as drug targets, but the importance of these enzymes
for the function of the pathway as a whole has not been considered. It is
known, from the frameworks of metabolic control analysis, that control of the
flux and metabolite concentration can be divided among the individual steps. Differential control analysis of Plasmodium and erythrocyte glycolysis may
reveal potential drug targets. These analyses require a detailed kinetic model
of Plasmodium glycolysis, and the feasibility of constructing and validating
such a model was the aim of this study.
In this work we determined the feasibility of constructing and validating a
detailed kinetic model for the Plasmodium falciparum glycolytic pathway.
Whether the construction and validation of this kinetic model was feasible
or not was decided on the basis of the ability to: i) culture and isolate
sufficient asexual parasites for enzymatic and steady state assays , ii) obtain
kinetic parameters such as Km and Vmax for each glycolytic enzyme, either
from literature or experimentally, iii) measure glycolytic fluxes, iv) determine
glycolytic intermediate concentrations, v) construct a kinetic model from the
kinetic parameters and vi) validate it with steady state glycolytic fluxes and
metabolite concentrations
Each of the above criteria were successfully addressed. In summary, the
kinetic parameters and glycolytic fluxes that were measured experimentally,
were used to construct and partially validate a detailed kinetic model,
respectively. Further validation of the model by means of steady state
metabolite concentrations was shown to be possible with the development of
a suitable protocol to measure the glycolytic intermediate concentrations.
The model presented in this work may play an important role in drug
target identification and improving the current understanding of host-parasite
interactions and glycolytic regulation.<br>AFRIKAANSE OPSOMMING:
Plasmodium, die parasiet wat malaria veroorsaak, is in Afrika alleen elke
dertig sekondes verantwoordelik vir die afsterwe van ’n kind jonger as vyf
jaar. Die parasiet se vermoë om vinnig weerstand op te bou het daartoe
gelei dat Plasmodium weerstandbiedend is teen byna alle nuwe teen-malaria
middels, behalwe vir ’n enkele toonaangewende groep. Die ontwikkeling van
nuwe malaria teen-middels is van uiterste belang om lyding te voorkom.
’n Goeie teiken vir teen-malaria middels is die glikolitiese padweg omdat die
metaboliese padweg essensieël is vir die produksie van ATP, die energiebron
van die parasiet. Desondanks die feit dat meeste van die glikolitiese ensieme al
goed bestudeer en as teiken voorgestel is, is dit steeds onduidelik hoe hierdie
ensieme saam funksioneer om die metaboliese weg, as geheel, tot stand te bring.
Metaboliese kontrole analise het aangetoon dat die glikolitiese beheer verdeel is tussen die onderskeie glikolitiese ensieme, m.a.w. geen enkele ensiematiese
stap het volledige beheer oor die fluksie van die glikolitiese padweg nie. Die
afsonderlike analise en vergelyking van Plasmodium - en rooibloedselglikolise
met behulp van differensiële metaboliese kontrole analise sal moontlik gebruik
kan word om gasheervriendelike teikens vir nuwe middels aan te toon. So
’n analise benodig ’n omvattende kinetiese model van Plasmodium glikolise.
Derhalwe was die doel van hierdie studie om vas te stel hoe uitvoerbaar dit is
om ’n kinetiese model van Plasmodium glikolise te konstrueer en te valideer.
Die uitvoerbaarheid van die konstruksie en validering van die kinetiese
model was geasseseer op grond van die vermoë om: i) parasietkulture te
kweek en genoegsame parasiete, wat in die aseksuele fase is, te isoleer
sodat ensiembepalings en bestendige toestand-bepalings gedoen kan word, ii)
kinetiese parameters soos Km - en Vmax-waardes vir elke glikolitiese ensiem,
hetsy vanuit literatuur of eksperimentele werk, te verkry, iii) glikolitiese fluksie
te meet, iv) glikolitiese intermediaatkonsentrasies te bepaal, v) ’n kinetiese
model van die bepaalde kinetiese parameters op te stel en vi) die model te
valideer met glikolitiese flukswaardes en metaboliet- konsentrasies wat in die
bestendige toestand verkry is.
Elk van die bogenoemde kriteria was met sukses in hierdie studie aangespreek.
Ter opsomming, die eksperimenteel bepaalde kinetiese parameters
en glikolietiese flukswaardes was gebruik om onderskeidelik ’n gedetaileerde
kinetiese model te konstrueer en gedeeltelik te valideer. Daar was getoon
dat verdere validering van die model deur middel van bestendige toestand
metabolietkonsentrasies moontlik is met die ontwikkeling van ’n geskikte
protokol om glikolitiese intermediaatkonsentrasies te meet. Die model, soos
opgestel in hierdie studie, kan moontlik ’n belangrike rol speel om teikens vir
nuwe malaria teen-middels te identifiseer en om gasheer-parasiet interaksies en
glikolitiese regulering beter te verstaan.
42
DaSilva, Thiago Gaspar. "CHARACTERIZATION OF PROTEIN PRENYLTRANSFERASES AND PROTEIN PRENYLATION IN PLASMODIUM FALCIPARUM." Master's thesis, University of Central Florida, 2004. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/4401.
Full textAbstract:
Malaria kills at least one million people each year, mostly children - a death every 30 seconds. Almost one half of the world population is at risk from malaria. Antimalarial drugs are the only means for the treatment of about 500 million annual global malaria cases. Because of prevalent drug-resistance it is extremely urgent to identify new drug targets. Many proteins involved in eukaryotic signal transduction and cell cycle progression undergo post-translational lipid modification by a prenyl group. Protein prenyltransferases, which catalyze the post-translational prenyl modification, have been established as a target for anticancer therapy. Research done in our laboratory has demonstrated recently that prenyl modification of proteins could be a novel target for the development of antimalarial drugs.The goal of this study is to understand the molecular mechanism of protein prenylation in Plasmodium. The key to use of prenyltransferase inhibitors for the pharmacological intervention is a thorough understanding of the in vivo prenylation pathways in the malaria parasite. Knowledge of the physiological functions of the cellular protein substrates of malarial prenyltransferases is an important first step in the elucidation of the mechanism of antimalarial action of inhibitors of protein prenylation. The research described in this thesis revealed the evidence for the existence of farnesylated and geranylgeranylated malaria parasite proteins. The study shows that the dynamics of protein prenylation changes with the intraerythrocytic development cycle of the parasite. We detected that prenylated proteins in the 50 kDa range were mostly farnesylated and that the proteins in the 22-25 kDa range were mostly geranylgeranylated. The prenylation of P. falciparum proteins is inhibited by prenyltransferase inhibitors. We have also demonstrated unique features of protein prenylation in P. falciparum compared to the human host such as farnesylation of proteins are sensitive to inhibition by geranylgeranyltransferase inhibitors.. In-silico search of the malarial genome sequence identified potential protein prenyltransferase substrates. One of these substrates is a SNARE protein Ykt6 homologue. The malarial Ykt6 was recombinantly expressed and subjected to an in-vitro prenylation assay. We showed that the recombinant Ykt6 was indeed a substrate for the malarial prenyltransferase.<br>M.S.<br>Department of Molecular Biology and Microbiology<br>Health and Public Affairs<br>Molecular Biology and Microbiology
43
Fréville, Aline. "Identification et caractérisation des inhibiteurs de type 2 et 3 de la phosphatase de type 1 chez Plasmodium falciparum." Phd thesis, Université du Droit et de la Santé - Lille II, 2012. http://tel.archives-ouvertes.fr/tel-00868793.
Full textAbstract:
Le paludisme (ou malaria) est la parasitose la plus répandue à travers le monde (WHO, 2011).La moitié de la population mondiale est exposée à cette maladie causée par le protozoairePlasmodium. La résistance aux traitements qui se développe chez le parasite représente un véritableobstacle à la mise en place de programmes de lutte globale. Le développement de nouveauxprotocoles thérapeutiques plus efficaces ciblant les apicomplexes Plasmodium passe par uneamélioration de nos connaissances concernant la biologie fondamentale des parasites. Par ce biais,nous pourrons identifier de nouvelles cibles originales visant des mécanismes essentiels etspécifiques au développement du pathogène. Chez Plasmodium falciparum (l'espèce responsable dela forme la plus mortelle de malaria), la phase érythrocytaire qui se déroule chez son hôte humain estrelativement courte (48 heures). Le parasite y subit un grand nombre de changementsmorphologiques nécessitant une différentiation précise, spécifique et régulée au cours du temps.Parmi les éléments pouvant contrôler ces mécanismes, les phénomènes de phosphorylationréversibles semblent être des candidats de choix.Nous avons, dans un premier temps, entrepris la caractérisation de PfI2. Ce travail a permisd'identifier cette protéine comme étant un régulateur négatif de PfPP1 localisé au niveaunucléocytoplasmique et indispensable au développement érythrocytaire du parasite. Des étudesd'interaction in vitro et in vivo ont permis d'identifier un certain nombre de résidus impliqués dans lafixation et la fonction de PfI2. En nous basant sur ces résultats, nous avons entrepris une explorationplus précise des relations structure/fonction du complexe PfI2/PfPP1.Concernant l'identification de PfI3, nous avons récemment publiée dans le Journal ofBiological Chemistry (Frèville A. 2012) un travail montrant que chez le parasite, l'inhibiteur 3 estlocalisé au niveau nucléaire et est essentiel au développement asexuel du pathogène. Desexpériences d'interaction in vitro ont permis de montrer que PfI3 est capable de se fixer in vitro àPfPP1 et ce principalement via le motif primaire RVxF. Chez des levures déplétées de leur inhibiteur3, l'expression épisomique de PfI3 n'a pas permis de restaurer la croissance des cellules. Desexpériences in vitro d'activités phosphatase révèlent une action positive de PfI3 sur PfPP1. Cerésultat, inverse de celui que l'on observe chez ses homologues chez la levure ou l'humain met enévidence une fonction différente et spécifique de PfI3 et font de cette protéine un régulateurnucléaire potentiel de PfPP1 chez Plasmodium falciparum.L'ensemble de ce travail de thèse à permis d'identifier et de caractériser chez Plasmodiumfalciparum deux régulateurs potentiels de la phosphatase de type 1 mais également de mettre enévidence un certain nombre d'éléments spécifiques au fonctionnement et au développement duparasite faisant de ces protéines des cibles thérapeutiques intéressantes.
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Steenkamp, Daniel. "A review of "sustainability vision" as corporate strategy in Africa, in the context of the opportunities provided by the prevalence of malaria." Thesis, Stellenbosch : Stellenbosch University, 2009. http://hdl.handle.net/10019.1/70390.
Full textAbstract:
Thesis (MBA)--Stellenbosch University, 2009.<br>ENGLISH ABSTRACT: Companies are confronted with a global market that is becoming increasingly saturated.
With free trade agreements allowing more competition into the traditionally lucrative
Western markets and economic recessions impacting the spend-ability of these markets,
there is mounting pressure to consider other market opportunities. Statistics reveal that the
traditional bottom of the economic pyramid actually contains a potentially very profitable
market, with a purchasing power parity of $12.5 trillion. To address this market,
prospective companies will have to rethink conventional business strategies, moulded to
the specific target market requirements.
The gradual shift in focus to the bottom of the economic pyramid, also serves to
emphasise the need of sustainable development of impoverished communities. By raising
communities out of poverty, they are liberated to partake in trade, respond to opportunities
and experience growth in self esteem. Whilst aid organisations play an important role in
establishing this freedom, rethinking business processes could result in more sustainable
impact on communities.
This feeds into the concept of creating a sustainability vision, where the corporate vision
should readdress not only the product but also the markets they seIVe. It should direct the
company toward the solution of social and environmental problems and meet the unmet
needs at the bottom of the economic pyramid.
In the context of Africa's geographical, political or social milieu, it is evident that the
continent offers unique challenges for engaging in trade. There are various attempts to
address these, but Africa is still deemed one of the most difficult environments in which to
establish operations. Africa also offers unique opportunities though, for those companies
willing to rethink the conventional.
Two companies saw the opportunity in malaria, a disease associated with impoverished
communities. Africa has the perfect breeding ground for the P. fa/ciparum strain of malaria,
which is incidentally also the most lethal. The strain has developed resistance against
current medication, which makes it extremely difficult to cure and control. It is estimated
that malaria costs African governments up to $12 billion per year and results annually in a
penalty of 1.3% less economic growth per person than could be expected in the absence
of malaria.
The two companies, on different ends of the supply chain, have been reviewed in the light
of the defined sustainability vision principles and the context of their strategic operations.
Though not without critique, and admittedly still in the early phases of some of their
processes, they have demonstrated that the concept of a sustainability vision in the African context is viable and that it is feasible to create wealth whilst serving the poor.<br>AFRIKAANSE OPSOMMING: Maatskappye word voortdurend gekonfronteer met markte wat neig om versadig te word
as gevolg van vryhandelsooreenkomste wat kompetisie stimuleer en ekonomiese
resessies wat vrye kontantvloei - en gevolglik koopgewoontes - be·invloed. Daar is dus
groeiende druk om voorheen ongekarteerde markte te ondersoek. Kontra verwagting toon
nuwe statistieke dat die tradisionele basis van die ekonomiese piramide 'n potensieel baie
winsgewende mark inhou, met koopkrag van $12,5 triljoen. Om hierdie mark te betree,
word van maatskappye verlang om konvensionele besigheidstrategiee in heroorweging te
neem en dit te vorm na gelang van die spesifieke konteks van hul teikenmark.
Die stelselmatige skuif in fokus na die basis van die ekonomiese piramide het die
noodwendige gevolg om die belang van ontwikkeling in agtergeblewe gemeenskappe te
benadruk. Deur gemeenskappe te verlos uit die juk van armoede, word self-waarde
gestimuleer en hulle die geleenlheid gegun om deel te neem aan aktiewe handel, wat
ekonomiese groei tot gevolg he!. Welwillendheids-organisasies speel 'n belangrike rol in
die opsig, maar besighede het die potensiaal om 'n meer blywende ekonomiese impak te
maak.
In die lig hiervan, word die konsep van 'n volhoubare visie benadruk, waar dit gestel word
dat 'n maatskappy se visie beide die produk en die teikenmark in herwoorweging moet
neem. Dit moet die organisasie lei om sosiale- en omgewingsprobleme aan te spreek en
voorheen onvoorsiene behoeftes op die basis van die ekonomiese piramide te bevredig.
Teen die agtergrond van Afrika se geografiese, politieke en sosiale milieu, is dit duidelik
dat die kontinent unieke uitdagings bied vir voornemende handel. Verskeie pogings word
aangewend om dit die hoof te bied, maar Afrika word steeds gesien as een van die
moeilikste kontekste om besigheid in te doen. Afrika offer wel ook unieke geleenthede vir
maatskappye wat bereid is om hul konvensionele banderings in herwoorweging te neem.
Twee maatskappye het die geleentheid raakgesien in malaria, 'n siekte wat normaalweg
met agtergeblewe gemeenskappe geassosieer word. Afrika bied die perfekte teelaarde vir
die P.falciparum variant van malaria, wat toevallig ook die mees dodelike variant is. Die
malaria variant het weerstand opgebou teen tradisionele voorskrif-medikasie. met die
gevolg dat dit besonder moeilik is om te voorkom en te beheer. Gesaghebbende bronne
skat dat malaria Afrika-regerings tot $12 miljard per jaar kan kos, en jaarliks lei tot 1,3%
minder ekonomiese groei as wat verwag sou word in die afwesigheid daarvan.
Twee maatskappye is geevalueer in die lig van die ge'identifiseerde volhoubare visie
beginsels en die konteks van hul operasionele bedrywighede. Hoewel hulle benadering nie
sonder kritiek is nie, en sommige strategiee nog die toets van tyd moet deurstaan, stel
hulle goeie voorbeelde van die potensiaal om rykdom te skep, terwyl die gemeenskap in
nood ook gedien word. Dit benadruk die potensiaal vir 'n volhoubare visie, ook in die Afrika
konteks.
45
Taleli, Lebusetsa. "Synthesis of triazole-linked chloroquinoline derivatives as novel antimalarial agents." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/79827.
Full textAbstract:
Thesis (MSc)--Stellenbosch University, 2013.<br>Aminoquinolines are important class of drugs that have been used for malaria chemotherapy for
centuries. However, long-term exposure to these drugs leads to extensive spread of drug
resistance. As such, modified chloroquinoline derivatives are being studied as alternative
antimalarial agents with the possibility to overcome drug resistance associated with chloroquine
analogues.
In this study, 15 aminoquinoline derivatives that are linked by a 1,4-disubstituted 1,2,3-triazole
ring to an ethyl and propyl carbon spacer with a distal amine motif were designed and
synthesized as novel antimalarial agents using the Cu(I)-promoted Huisgen reaction. The
compounds have been synthesized from the 7-chloro-N-(prop-2-yn-1-yl)quinolin-4-amine alkyne
precursor and the azides of ethyl and propyl amino moieties using a 1,3-dipolar cycloadditioncoupling
in the presence of CuI catalyst to obtain moderate to good yields (53 – 85%). These
compounds have been characterized by the combination of NMR, ESI+ HRMS and IR
spectroscopic methods.
The antiplasmodial activity of the compounds was investigated in vitro against P. falciparum
strain NF54 using chloroquine as a reference drug together with a standard antimalarial drug
artesunate. Of the 15 novel chloroquinoline derivatives, 11 have demonstrated to possess
promising potency by way of the inhibition concentrations less than 250 nM with the lowest
being 28 nM. The observed activities have been ascribed to the overall modifications such as the
introduction of a triazole linker and changing of carbon chain length as these were the variables.
The compounds are accordingly under further biological investigations and only the chloroquine
sensitive results are reported in this work.
46
Carbonell, Abigail. "Identification of potential lead antimalarial compounds from marine microbial extracts." Honors in the Major Thesis, University of Central Florida, 2013. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/829.
Full textAbstract:
Malaria, caused by the parasite Plasmodium falciparum, has a long history as a global health threat. The vector-borne disease causes millions of deaths yearly, especially in developing countries with tropical climates that facilitate transmission. Compounding the problem is the emergence of drug-resistant strains due to overuse of outdated treatments. New compounds with antiplasmodial activity are needed to be developed as effective drugs against malaria. The hypothesis for this project is that marine microorganisms have a high likelihood of yielding novel antiplasmodial chemotypes because of their high diversity, which has not yet been explored for antimalarial development. In this project, microbes harvested and fermented by the Harbor Branch Oceanographic Institute in Fort Pierce, Florida were explored as sources for antiplasmodial natural products. Using a SYBR Green I fluorescence-based assay, 1,000 microbial extracts were screened for inhibition of the multidrug-resistant Plasmodium falciparum strain Dd2. Dose-response analysis was performed on 46 fractions from isolates whose extracts demonstrated greater-than or equal to] 70% inhibition of Dd2 at 1 micro]g/mL. To evaluate cytotoxicity, the MTS cell viability assay was used to calculate IC50 of extracts from active isolates in NIH/3T3 embryonic mouse fibroblasts. Several extracts demonstrated low IC50 in Dd2 and high IC50 in 3T3, suggesting that they contain potential lead antimalarial compounds. Extracts with high selectivity indices (potent plasmodial inhibition with low mammalian toxicity) have been prioritized for dereplication, with the goal of identifying novel active components that can be developed as antimalarial drugs.<br>B.S.<br>Bachelors<br>Burnett School of Biomedical Sciences<br>Molecular Biology and Microbiology
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Gnangnon, Bénédicte. "Caractérisation moléculaire et fonctionnelle de la pseudo-tyrosine kinase-like (pTKL) de plasmodium." Thesis, Lille 2, 2019. http://www.theses.fr/2019LIL2S003/document.
Full textAbstract:
Le paludisme, première endémie parasitaire mondiale ayant engendré près d’un demi-million de morts en 2017 (d’après l’OMS), est due à une infection par un parasite du genre Plasmodium. Cet apicomplexe infecte, au cours de son cycle de vie, un hôte définitif, un moustique femelle du genre Anopheles, et un hôte intermédiaire homéotherme (l’Homme pour au moins 6 espèces). Chez ce dernier, après une phase de développement hépatique, le parasite envahit puis lyse les érythrocytes. L’accroissement exponentiel de la parasitémie engendre les symptômes du paludisme et permet la production de formes sexuées (gamétocytes) qui seront transmises au vecteur arthropode, permettant ainsi la complétion du cycle de vie du parasite.Plasmodium a co-évolué avec ses hôtes et mis en place divers modes de régulation de l’expression de ses gènes. La phosphorylation est l’une des modifications post-traductionnelles majeures et rapides qu’il utilise pour répondre aux changements environnementaux auxquels il est confronté au cours de son cycle de vie. Nombre de ses kinases et phosphatases jouent un rôle essentiel dans l’invasion de cellules hôtes, la croissance et la division cellulaires, ainsi que la motilité de certains stades. En revanche, le rôle des cinq pseudokinases de Plasmodium dans son développement n’a jusqu’ici pas été exploré.Durant ma thèse, j’ai caractérisé l’unique pseudo-Tyrosine Kinase-like (pTKL) de Plasmodium et étudié son rôle au cours du cycle intra-érythrocytaire du parasite.L’annotation de la pTKL de P. falciparum (PfpTKL) m’a permis d’identifier différents domaines et motifs, et notamment un domaine SAM (Sterile Alpha Motif), deux motifs RVxF (connus pour leur capacité d’interaction avec la Protéine Phosphatase de type 1, PP1) et un pseudo-domaine kinase appartenant à la famille des Tyrosine Kinases-like (TKL). Nous avons montré que ce pseudo-domaine kinase est capable de lier l’ATP de manière cation-indépendante, mais est dépourvu d’activité enzymatique. Des études d’interaction in vitro couplées à l’utilisation de modèles hétérologues (Levure, ovocytes de Xénope) m’ont permis d’identifier deux protéines parasitaires partenaires de PfpTKL : le domaine SAM de PfpTKL interagit directement avec la pseudo-protéase PfSERA5 (SErine Repeat Antigen 5), alors que les deux régions de la protéine contenant les motifs RVxF de PfpTKL interagissent avec PfPP1c (phosphatase majeure de Plasmodium). De façon intéressante, le deuxième motif RVxF est directement impliqué dans l’interaction avec PP1c et serait capable de moduler l’activité de cette dernière de manière allostérique.La localisation de la pTKL de P. berghei (PbpTKL) a ensuite été étudiée par immunofluorescence et confirmée par des expériences de fractionnement cellulaire. Nous avons ainsi observé que PbpTKL est exportée dans l’érythrocyte infecté au stade trophozoïte, puis retenue dans le parasite et la vacuole parasitophore au stade schizonte. L’étude de l’interactome de PbpTKL par IP/MS au stade trophozoïte a montré que PbpTKL s’associe à diverses protéines impliquées dans l’organisation du cytosquelette de l’érythrocyte, ainsi que dans l’érythropoïèse et l’homéostasie cellulaire. Ces observations suggèrent que pTKL joue un rôle, direct ou via ses partenaires, à l’interface entre le parasite et sa cellule hôte.Enfin, afin d’approcher la fonction de pTKL chez le parasite, nous avons généré différentes lignées génétiquement modifiées. L’étude phénotypique des souches de P. berghei KO et iKD pour pTKL a montré qu’elle était dispensable pour la complétion du cycle intra-érythrocytaire, l’expression des gamétocytes ainsi que l’activation des gamétocytes mâles. Ces données suggèrent que pTKL est dispensable pour ces stades de développement ou que l’expression de gènes redondants compense son absence. Quoi qu’il en soit, il est important de poursuivre les recherches sur le rôle de cette protéine aux autres stades de développement du parasite, notamment du zygote aux stades hépatiques<br>Malaria is the first endemic parasitic disease in the world with nearly half million deaths in 2017 according to the WHO. This disease is the result of an infection by an agent belonging to the Plasmodium genus. This apicomplexan parasite infects two hosts over its complex life cycle: a definitive one – a mosquito belonging to the Anopheles genus – and a homoeothermic intermediate host. At least six Plasmodium species can infect humans. In its intermediate host, Plasmodium first replicates in hepatocytes before releasing erythrocyte-infectious stages in the bloodstream. Once there, parasites invade and replicate within erythrocytes, before lysing them to release other infectious stages. This triggers an exponential rise in the parasitemia, as well as malaria symptoms. Sexual stages, called gametocytes, are produced over this intra-erythrocytic cycle to be transmitted to the arthropod vector, thus allowing the completion of the parasite life cycle.Plasmodium co-evolved with its hosts and set up diverse gene expression regulation pathways accordingly. Phosphorylation is one of the major and fastest post-translational modifications used by the parasite to respond to environmental changes. Many of its kinases and phosphatases play key roles in host cell invasion, cellular growth and division, as well as motility of specific developmental stages. However, the role of the five pseudo-kinases expressed by Plasmodium has not been explored yet.During my PhD project, I have performed the characterization of the unique Plasmodium pseudo-Tyrosine Kinase-like (pTKL) and explored its role over the parasite intra-erythrocytic cycle.P. falciparum pTKL (PfpTKL) in silico annotation allowed the delineation of the protein domains. Notably, a SAM (Sterile Alpha Motif) domain, two RVxF motifs (known for their binding potential with the major protein phosphatase type 1, PP1) and a pseudo-kinase domain belonging to Tyrosine Kinase-like (TKL) family were found. This pseudo-kinase domain was found to be able to bind ATP in a cation-independent way although devoid of kinase activity. Two parasite protein partners of PfpTKL have been identified using in vitro protein-protein interaction studies together with heterologous models (yeast, Xenopus ovocytes). First, PfSERA5 (SErine Repeat Antigen 5) specifically and strongly interacts with PfpTKL SAM domain and second, PfPP1c binds the two RVxF-containing regions of PfpTKL. Interestingly, the second RVxF motif, which is located within the pseudo-kinase domain, directly binds PfPP1c and seems to be involved in the allosteric regulation of the phosphatase activity. The subcellular localization of P. berghei pTKL (PbpTKL) was studied by IFA as well as sequential lysis of erythrocytes followed by immunoprecipitation assays. PbpTKL was shown to be exported to the host cell cytosol at the trophozoite stage, but retained in the parasitophorous vacuole and the parasite cytosol at the schizont stage. Furthermore, our interactome analysis conducted at the trophozoite stage by IP/MS showed that PbpTKL binds many host cell proteins involved in erythrocyte cytoskeleton organization, as well as erythropoiesis and cell homeostasis. These data suggest that pTKL plays a role at the parasite/host interface, either directly or via its protein partners.Finally, in an attempt to understand the role of pTKL for the parasite development, we generated genetically modified P. berghei strains. The phenotypic study of PbpTKL KO and iKD strains did not show any difference between the defective parasites and the parental wild type ones during the intra-erythrocytic cycle, gametocyte expression and male gametocyte activation. These data suggest the dispensability of pTKL or the expression of redundant gene(s) with similar functions in these parasite stages. Whatever the explanation, it is still important to follow up this investigation in other parasite stages, from zygotes to hepatic stages
48
Chan, Jennie. "Dissecting the Role of a lncRNA and Involvement of Plasmodium Infections in the Innate Immune Response: A Dissertation." eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/777.
Full textAbstract:
The innate immune system is a multicomponent response governed by intricate mechanisms of induction, regulation and resolution to elicit antimicrobial defenses. In recent years, the complexity of eukaryotic transcriptomes has become the subject of intense scrutiny and curiosity. It has been established, that RNA polymerase II (RNAPII) transcribes hundreds to thousands of long noncoding RNAs (lncRNAs), often in a stimulus and cell-type specific manner. However, the functional significance of these transcripts has been particularly controversial. While the number of identified lncRNAs is growing, our understanding of how lncRNAs themselves regulate other genes is quite limited. In chapter 2, a novel lncRNA is identified, more specifically, a natural antisense transcript, that mediates the transcription of the pro-inflammatory cytokine IL-1α. Through loss-of-function studies, I report the necessity of this transcript in mediating IL-1α mRNA expression by affecting RNAPII binding to the IL-1α promoter after toll-like receptor signaling. For the first time, I show that IL-1α is regulated at the transcriptional level. As a second independent component of this thesis, we explore the role of the innate immune response after infection by the malaria-causing parasite, Plasmodium berghei ANKA (PbA), and how innate immune components are both beneficial and detrimental to the host depending on when and where inflammation is triggered during infection. We attempt to identify the “malarial toxin” responsible for aberrations in the immune response that is detrimental for disease outcomes and the innate signaling pathways that are involved. Many pathogens induce pathological inflammatory conditions that lead to irreparable homeostatic imbalances and become fatal to the host. Here, type I Interferon signaling is required to dampen parasite load during liver-stage infections, but leads to host mobidity if these pathways are activated in the erythrocytic phase of infection. Together, this thesis provides new insights on how components of the innate immune system are regulated, and how dysregulation of immunity can potentially lead to adverse effects during active infections.
49
Chan, Jennie. "Dissecting the Role of a lncRNA and Involvement of Plasmodium Infections in the Innate Immune Response: A Dissertation." eScholarship@UMMS, 2015. https://escholarship.umassmed.edu/gsbs_diss/777.
Full textAbstract:
The innate immune system is a multicomponent response governed by intricate mechanisms of induction, regulation and resolution to elicit antimicrobial defenses. In recent years, the complexity of eukaryotic transcriptomes has become the subject of intense scrutiny and curiosity. It has been established, that RNA polymerase II (RNAPII) transcribes hundreds to thousands of long noncoding RNAs (lncRNAs), often in a stimulus and cell-type specific manner. However, the functional significance of these transcripts has been particularly controversial. While the number of identified lncRNAs is growing, our understanding of how lncRNAs themselves regulate other genes is quite limited. In chapter 2, a novel lncRNA is identified, more specifically, a natural antisense transcript, that mediates the transcription of the pro-inflammatory cytokine IL-1α. Through loss-of-function studies, I report the necessity of this transcript in mediating IL-1α mRNA expression by affecting RNAPII binding to the IL-1α promoter after toll-like receptor signaling. For the first time, I show that IL-1α is regulated at the transcriptional level. As a second independent component of this thesis, we explore the role of the innate immune response after infection by the malaria-causing parasite, Plasmodium berghei ANKA (PbA), and how innate immune components are both beneficial and detrimental to the host depending on when and where inflammation is triggered during infection. We attempt to identify the “malarial toxin” responsible for aberrations in the immune response that is detrimental for disease outcomes and the innate signaling pathways that are involved. Many pathogens induce pathological inflammatory conditions that lead to irreparable homeostatic imbalances and become fatal to the host. Here, type I Interferon signaling is required to dampen parasite load during liver-stage infections, but leads to host mobidity if these pathways are activated in the erythrocytic phase of infection. Together, this thesis provides new insights on how components of the innate immune system are regulated, and how dysregulation of immunity can potentially lead to adverse effects during active infections.
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Vonlaufen-Voumard, Deolinda. "Maladie de Wegener : manifestations stomatologiques /." Genève : Médecine et hygiène, 2005. http://www.unige.ch/cyberdocuments/theses2005/Vonlaufen-VoumardD/these.pdf.
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