Understanding antimalarial kill profiles and their influence on the development of drug resistance

About the Project

Malaria persists as a global health issue with the recent WHO malaria report 263 million cases and 597 thousand deaths (WHO, 2024). The extensive benefits of recent vaccine roll outs are yet to be realised. This means that prevention of malaria relies predominantly on vector control strategies whilst treatment is ultimately dependent the antimalarial compounds currently available. As the malaria parasite has been capable of developing resistance to every antimalarial that has ever been introduced, understanding parasite killing mechanisms, the timeliness of compound kill profiles and their interaction with resistance development may offer valuable insights into parasite death mechanisms and targeting strategies.

This project aims to evaluate antimalarial kill profiles and broaden our understanding of how and when the parasite dies in response to drug treatment and how these mechanisms interact with resistance development. With collaborators in Kenya, there is also the opportunity to work on recent field isolates with varying resistance profiles.

The project will include in vitro culture of Plasmodium falciparum asexual stages, the use of plaque assays, flow cytometry and confocal microscopy with the aim to evaluate:

1. The Kill profile of a broad range of antimalarials
2. The time course of programme cell death characteristics
3. How the parasite kill timeline interacts with resistance development

Supervisors

Dr Holly Matthews

Dr Rachael Magwaza