The University of Pretoria (UP) is at the forefront of the global search for new malaria treatments through the work of Professor Lyn-Marié Birkholtz, whose group in the University’s Department of Biochemistry, Genetics and Microbiology (BGM) is investigating innovative ways to tackle antimalarial resistance by delivering a much-needed understanding of the biology of malaria parasites.

Antimicrobial resistance (AMR) is a major public health concern that also has significant implications for the treatment of malaria. AMR occurs when organisms such as bacteria, viruses, fungi and parasites evolve to survive exposure to medicines that are designed to kill them. This makes treatments less effective or even useless. The malaria parasite Plasmodium falciparum causes the deadliest form of the disease; antimalarial resistance occurs when the parasite adapts to survive treatment, resulting in prolonged illness, higher disease transmission and increased mortality.

Every year, World AMR Awareness Week is observed from 18 to 24 November to promote responsible medicine use across human, animal and environmental health. This World Health Organization-led campaign calls for global action to prevent drug-resistant infections, including that of malaria, which threaten decades of medical progress.

Artemisinin, the miracle antimalarial

Modern malaria treatment changed in the 1970s when Chinese scientist Professor Tu Youyou, inspired by ancient Chinese medicine texts, isolated artemisinin from the plant Artemisia annua (qinghao). Her discovery revolutionised malaria therapy and earned her the 2015 Nobel Prize in Physiology or Medicine.

Artemisinin’s fast action against P. falciparum led to artemisinin-based combination therapies (ACTs), which pair artemisinin with a longer-acting partner drug. This dual approach ensures rapid parasite clearance while reducing the risk of resistance. Since their introduction in the early 2000s, ACTs have saved millions of lives and remain the cornerstone of malaria treatment.

ACTs combine two drugs with different mechanisms: artemisinin rapidly reduces the number of parasites in the bloodstream, while the partner drug kills any remaining ones. When the parasite begins to tolerate either drugs, treatment weakens, leading to slower recovery, possible treatment failure and greater transmission.

Over time, resistant strains of malaria parasites developed in multiple geographic regions and affected different populations. Artemisinin partial resistance, where artemisinin works more slowly, is a serious treatment failure. This first appeared in Southeast Asia more than 15 years ago, leading to widespread treatment failures. More recently, ACT resistance was confirmed in parts of eastern Africa, including Rwanda, Uganda, Eritrea and Tanzania. Genetic studies show these are independent emergences, meaning resistance evolved locally rather than spreading from Asia.  

Given that 95% of global malaria cases and 97% of malaria deaths occur in Africa, the threat cannot be overstated. Most deaths are among children under five, the group most vulnerable to treatment failure. If ACTs stop working, the consequences for already stretched health systems would be devastating, including rising cases, more deaths and lost progress towards malaria elimination.

Urgent, coordinated action is crucial. Priorities include strengthening surveillance to detect resistance early; promoting rational use of antimalarials; investing in new drug discovery; integrating control measures; and closing funding gaps that threaten progress.

Drug discovery expertise at UP

Prof Birkholtz’s BGM group is pinpointing weak spots that new antimalarial entities could target. The group forms part of the Grand Challenges African Drug Discovery Accelerator (GC ADDA) to deliver interventions for malaria as a serious concern in Africa. The mentorship of Prof Birkholtz – Department of Science, Technology and Innovation/National Research Foundation SARChI chair in Sustainable Malaria Control at the UP Institute for Sustainable Malaria Control (UP ISMC) – has developed a new generation of researchers, each with their own niche within the antimalarial drug discovery space.

Two members of the group, Dr Dina Coertzen and Dr Mariette van der Watt, are members of the GC ADDA, and exemplify Africa-led innovation in the global fight against malaria and AMR.

“Understanding parasite-specific systems can lead to the identification of new ‘targets’ to guide the development of innovative treatment strategies,” Dr Coertzen says.

Dr Van der Watt is focusing on transmission-stage biology and drug discovery, aiming to identify compounds that treat malaria symptoms and prevent transmission.

UP’s transdisciplinary approach is demonstrated by Dr Phanankosi Moyo of the Department of Plant and Soil Sciences, who is exploring the medicinal potential of plants to address both AMR and malaria.

“I aim to discover novel plant-derived antimalarial agents that act on both the disease-causing and transmission stages of the parasite,” he says. “This dual approach seeks not only to treat malaria but to reduce its spread within communities.”

Dr Jandeli Niemand studies membrane transport proteins that help the parasite survive and resist drugs.

“These proteins are important drug targets because they regulate the uptake and efflux of nutrients, waste products and therapeutic compounds, thereby directly affecting drug efficacy,” she explains.

Another intervention that UP is involved in relates more specifically to leadership training in the SADC region. Since 2022, the UP ISMC, Gordon Institute of Business Science and other stakeholders have been running a malaria leadership, management and governance course for national malaria control programme managers and officers from eight SADC countries – Angola, Botswana, Eswatini, Mozambique, Namibia, South Africa, Zambia and Zimbabwe. Malawi was added to the mix in 2025. The one-year course is presented simultaneously in English and Portuguese.

A call to action

World AMR Awareness Week reminds us that resistance anywhere is a threat everywhere. Everyone – from researchers and health workers to policymakers and the public – has a role to play in safeguarding lifesaving medicines. We must promote accurate diagnosis, discourage incomplete treatments, support surveillance and research, and advocate for sustained investment in malaria control and drug discovery.

The fight against malaria AMR is not only about protecting medicines, but protecting lives, health systems and decades of global progress. Losing ACTs would be a public health catastrophe. Protecting them means protecting Africa’s progress towards a malaria-free future.