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Full-Text Articles in Medicine and Health Sciences
Genomics And Transcriptomics Approaches To Understanding Drug Resistance Mechanisms In The Malaria Parasite Plasmodium Falciparum, Justin Allan Gibbons
Genomics And Transcriptomics Approaches To Understanding Drug Resistance Mechanisms In The Malaria Parasite Plasmodium Falciparum, Justin Allan Gibbons
USF Tampa Graduate Theses and Dissertations
The malaria parasite Plasmodium falciparum is responsible for about 500,000 deaths a year and is evolving resistance to the front-line treatment of artemisinin-based combination therapy. Resistance is currently confined to South East Asia, however millions of lives will be at risk if resistance spreads to Africa. Understanding the mechanism of resistance to artemisinins would aid containment strategies to prevent the spread of artemisinin resistance. There is also an urgent need to accelerate drug discovery since drug resistance has already been documented to all existing antimalarials. Here, I report on our efforts to understand the function of the gene k13, the …
Synthesis, In Vitro Characterization And Applications Of Novel 8-Aminoquinoline Fluorescent Probes, Adonis Mcqueen
Synthesis, In Vitro Characterization And Applications Of Novel 8-Aminoquinoline Fluorescent Probes, Adonis Mcqueen
USF Tampa Graduate Theses and Dissertations
Malaria is a parasitic disease that is caused by the plasmodium parasite. Plasmodium infection has affected man for thousands of years. With advances in drug discovery over the past century, malaria has evolved to possess resistance to most mainline therapeutics. This war of drug discovery vs plasmodium evolution continues to be fought to this very day, with attempts to eradicate malaria worldwide. Frontline treatments such as chloroquine, artemisinin, and atovaquone/proguanil have all seen parasitic resistance in strains of P. vivax as well as P. falciparum. While plasmodium possesses resistance to most classes of anti-malarials, the 8-aminoquinoline (8-AQ) class has …
Antimalarial Exoerythrocytic Stage Drug Discovery And Resistance Studies, Lynn Dong Blake
Antimalarial Exoerythrocytic Stage Drug Discovery And Resistance Studies, Lynn Dong Blake
USF Tampa Graduate Theses and Dissertations
Malaria is a devastating global health issue that affects approximately 200 million people yearly and over half a million deaths are caused by this parasitic protozoan disease. Most commercially available drugs only target the blood stage form of the parasite, but the only way to ensure proper elimination is to treat the exoerythrocytic stages of the parasite development cycle. There is a demand for the discovery of new liver stage antimalarial compounds as there are only two current FDA approved drugs for the treatment of liver stage parasites, one of which fails to eliminate dormant forms and the other inducing …
Altered Intraerythrocytic Development Phenotypes Of Artemisinin-Resistant Plasmodium Falciparum Confer A Fitness Advantage, Amanda Hott
USF Tampa Graduate Theses and Dissertations
Resistance to artemisinin combination therapies (ACTs) has emerged in southeast Asia threatening the most widely used treatment against antimalarial-resistant Plasmodium falciparum worldwide. Artemisinin resistance has been associated with a reduced rate of parasite clearance following treatment with an ACT and is attributed to increased survival of ring-stage parasites. Single nucleotide polymorphisms (SNPs) in kelch gene (K13) has been associated with delayed in vivo clearance half-life of artemisinin-resistant P. falciparum and is the only known molecular marker of resistance. The absence of reliable in vitro phenotypes for artemisinin resistance has limited our understanding of the resistance mechanism(s) and fitness costs, therefore …
Mmv Malaria Box Activity Screening In Dormant Plasmodium Falciparum Phenotypes, Sandra Galusic
Mmv Malaria Box Activity Screening In Dormant Plasmodium Falciparum Phenotypes, Sandra Galusic
USF Tampa Graduate Theses and Dissertations
The causative agent of malignant tertian malaria, Plasmodium falciparum undergoes an arrested growth phenotype of its erythrocytic stage when under drug-stress. Recent artemisinin treatment failures seem to be indicative of such induction followed by recrudescence rather than actual therapeutic failure. Likewise, P. vivax hypnozoites are the prototypic dormants and the latent infections for which they are responsible prove most difficult to treat. Dihydroartemisinin, an artemisinin-derivative, can be used to exploit this mechanism by inducing a dormant state in ring-stage P. falciparum parasites and in turn, their recovery may be used as a screening period for compounds that inhibit or foster …
Immunological Characterization Of Duffy Binding Protein Of Plasmodium Vivax, Miriam Thankam George
Immunological Characterization Of Duffy Binding Protein Of Plasmodium Vivax, Miriam Thankam George
USF Tampa Graduate Theses and Dissertations
Plasmodium vivax Duffy binding protein (DBP) is an essential ligand for reticulocyte invasion making it a premier asexual blood stage vaccine candidate. However, strain-specific immunity due to DBPII allelic variation may complicate vaccine efficacy, suggesting that an effective DBPII vaccine needs to target immune responses to conserved epitopes that are potential targets of strain-transcending neutralizing immunity. Anti DBPII monoclonal antibodies, which were previously characterized by COS7 cell binding assay as inhibitory and non-inhibitory to DBPII-erythrocyte binding, were mapped to DBPII gene fragment libraries using phage display. Inhibitory mAb 3C9 binds to a conserved conformation-dependent epitope in subdomain 3 while non-inhibitory …
Pathogenic Mechanisms And Signaling Pathways In Plasmodium Falciparum, Jennifer L. Sedillo
Pathogenic Mechanisms And Signaling Pathways In Plasmodium Falciparum, Jennifer L. Sedillo
USF Tampa Graduate Theses and Dissertations
Plasmodium falciparum is a human intracellular parasite that is the causative agent of a deadly form of malaria. This species alone is responsible for 200 million cases of malaria annually resulting in over 1 million deaths worldwide. The excessive mortality due to P. falciparum infection is due to its ability to cause severe pathogenesis through hyperparasitemia and cytoadherence defined as the ability of infected red blood cells to adhere to host vasculature. Cytoadherence is mediated through the export of parasite proteins to the surface of the infected red blood cell (RBC). Exported proteins have been identified but the pathway for …