Thesis Abstract

Recent advances in the treatment of malaria have significantly improved the management of this life-threatening disease. Malaria is caused by Plasmodium parasites and is transmitted through the bites of infected mosquitoes. The most common species that infect humans are Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi. The clinical manifestations of malaria include fever, chills, headache, and in severe cases, it can lead to organ failure and death. Historically, the treatment of malaria relied heavily on antimalarial drugs such as chloroquine, quinine, and artemisinin-based combination therapies (ACTs). However, the emergence of drug-resistant strains of Plasmodium, particularly P. falciparum, has posed a significant challenge to malaria control efforts. In response to this challenge, researchers have made substantial progress in developing new antimalarial drugs with novel mechanisms of action. One of the most promising new classes of antimalarial drugs is the KAE609 series, which target the parasite's sodium efflux pump PfATP4. These compounds have shown potent activity against drug-resistant strains of P. falciparum in preclinical studies and are currently undergoing clinical trials. Another novel drug target is the parasite's proteasome system, which plays a crucial role in protein degradation and homeostasis. Compounds that inhibit the proteasome have demonstrated efficacy against various stages of the parasite life cycle and hold promise as potential antimalarial agents. In addition to developing new drugs, researchers have also focused on improving the delivery mechanisms of existing antimalarials to enhance their efficacy and reduce the risk of drug resistance. Nanomedicine-based approaches, such as the use of nanoparticle formulations and drug conjugates, have shown potential in overcoming the limitations of conventional antimalarial drugs. These nanomedicine platforms can improve the pharmacokinetics and biodistribution of antimalarial drugs, allowing for lower doses and less frequent dosing regimens. Furthermore, advances in genetic engineering and genome editing technologies have enabled researchers to manipulate the genomes of both the malaria parasite and the mosquito vector. By modifying key genes involved in parasite transmission and drug resistance, scientists aim to develop genetically modified organisms that can interrupt the malaria transmission cycle and prevent the spread of drug-resistant strains. Overall, recent advances in the treatment of malaria offer new hope in the fight against this deadly disease. By harnessing the power of innovative drug discovery, nanotechnology, and genetic engineering, researchers are paving the way for more effective, targeted, and sustainable malaria control strategies.

Thesis Overview