Page 77 - University of Pretoria RESEARCH REVIEW 2018

Finding new ways to fight malaria Lyn-Marie Birkholtz, Department of Biochemistry, Genetics and Microbiology,
SARChI Chair in Sustainable Malaria Control, and UP ISMC
Malaria is a global public health problem. In a report released by the World Health Organization in November 2018, it was stated that 219 million cases of malaria were reported in 2017, with an estimated 435 000 deaths, mostly occurring in children younger than five years old.
Malaria is preventable and treatable, but control, management and the prospect of eliminating the disease is impeded
by the complexity of host-vector- parasite-environmental interactions. Over the past 70 years, controlling and eliminating malaria has been based on two strategies; namely, controlling the Plasmodium parasite, and controlling Anopheles mosquitoes.
Professor Lyn-Marie Birkholtz, the incumbent of the SARChI Chair in Sustainable Malaria Control and key member of the UP ISMC, is focussing her research on understanding the complex biology of malaria parasites to discover the ‘Achilles heels’ that can be targeted by novel antimalarials. Published in Scientific Reports in 2018, Birkholtz and her team showed
that asexually proliferating malaria parasites use unique mechanisms for cell cycle control. Her research team has developed a novel system to halt malaria parasites at a specific point in their cell cycle in a controlled fashion. This provides a valuable framework for investigating drugs targeting cell cycle regulation in malaria parasites, similar to anticancer drugs.
Beyond targeting proliferating malaria parasites, the team identifies drugs that can block transmission of
malaria parasites between humans
and mosquitoes. Potential novel therapeutics, including a next- generation Plasmodium PI4K inhibitor, UCT943, were shown to have the potential to form part of a single- exposure radical cure and prophylaxis (SERCaP) to treat, prevent and block the transmission of malaria (published in Antimicrobial Agents and Chemotherapy). Other drug discovery studies, published in Bioorganic and Medicinal Chemistry Letters, include testing 10 artemisinin derivatives. Currently, malaria is treated with artemisinin-based combination therapies (ACT), but resistance to ACT has recently been reported. Of the 10 derivatives, artemisone and artemiside inhibited asexual and gametocyte stages of the Plasmodium falciparum parasite, showing potential for malaria treatment.
This ability to block malaria transmission prompted a study to determine the prevalence of human genotypes that are susceptible to haemolysis as a potential side effect of transmission-blocking drug treatment. Based on the findings, published
in the Malaria Journal in 2018, such deficiencies are rare in South African human populations, supporting the use of particularly primaquine as
an adjunct tool to support malaria elimination strategies in South Africa.
The newly established Community of Practice (CoP) on Malaria Elimination, led by Professor Birkholtz, is an NRF initiative that came into effect in 2018 as a vehicle to implement integrated trans- and multidisciplinary solutions to the disease. The CoP incorporates the current expertise of five SARChI Chairs to focus on intervention strategies for malaria elimination, including the discovery of novel drug leads used with optimised delivery systems against both the malaria parasite and mosquito vectors.
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