Y1 Progress report | Dina Coertzen

Development of Molecular Tools for Surveillance of Malaria Transmission Reservoirs

In my current role as a full-time lecturer in the Department of Biochemistry, Genetics, and Microbiology at the University of Pretoria, my research is integrated within the UP Institute for Sustainable Malaria Control (UP ISMC), a flagship transdisciplinary research institute at UP, renowned for driving excellence in community-based transdisciplinary research.

The institute's strategic goals are directly aligned with national and international malaria elimination guidelines through collaboration with academic, NGO and governmental stakeholders. The community engagement and transdisciplinary needs of the FAR-Leaf II project are therefore seamlessly aligned with UP ISMC's research priorities. These project outcomes, in line with UP ISMC, are fully aligned with the UP Thrive 2038 plan, which has prioritised transdisciplinarity, collaboration, and partnership to address complex societal challenges and ensure institutional impact and meaningful partnerships. Consequently, the funding from FAR-Leaf II has played a crucial role in helping me establish myself as an early-career researcher in line with the strategic goals within the UP ISMC and my host institute, UP.

My previous research background and publication track record focused on pre-clinical antimalarial drug discovery, with a particular interest in blocking the transmissible stages of the malaria parasite, Plasmodium falciparum, in infected individuals. Blocking parasite transmission between humans and mosquitoes has been identified as a promising control strategy to drive malaria elimination. However, through my interaction with the ISMC, we identified a research gap: a lack of a comprehensive understanding of malaria transmission dynamics in sub-Saharan Africa. This lack of understanding could pose a significant challenge to the successful implementation of antimalarial drugs with transmission-blocking activity.

The main challenge in sub-Saharan Africa is the lack of robust, reliable methods to distinguish between the developmental stages of P. falciparum parasites in infected humans, thereby preventing routine investigation of transmission dynamics. Current diagnostic methods only detect the presence of parasites but cannot distinguish between the pathogenic (asexual) and transmissible (sexual gametocyte) stages. This requires obtaining cell components that require either immediate and direct analysis or highly specific sample storage and handling conditions. This, combined with further downstream sample processing, is technically difficult and time-consuming, and may lead to poor results or sample loss.

Therefore, in this project, we aim to develop a robust, reproducible molecular detection tool to survey the transmissible gametocyte stages of P. falciparum parasites in field-collected whole-blood samples from patients. In developing this method, I have repurposed a diagnostic kit for COVID-19 testing, using whole-blood collection tubes that preserve sample integrity. The advantage of this kit is that it will eliminate the inefficient, time-consuming sample processing required to achieve highly specific, quantitative results.

This project has two aspects: A laboratory aspect to optimise the detection method, and a clinical aspect to translate the method for investigating transmission dynamics in the field. The transdisciplinary and community engagement outcomes of this project, initiated through collaboration with the UP ISMC, are evidenced through the diverse range of expertise brought together.

It entails incorporating my expertise in growing the required transmissible (gametocyte) parasite stages in the laboratory to develop a quantifiable diagnostic method (Department of Biochemistry, Genetics and Microbiology). The project's feasibility is supported by established resources and infrastructure, including a P. falciparum cell culture facility with ethical approval, SOPs, and protocols for producing both the pathogenic and transmissible stages of the parasite. Subsequently, this method can be applied to patient sampling in the field, in collaboration with researchers with expertise in public health (School of Public Health Systems and Public Health) and stakeholders, to facilitate and support clinical sample collection through the UP ISMC research community.

Furthermore, through the UP ISMC, I have also been provided access to research mentorship and supervisory capacity (Dr Taneshka Kruger). To date, the laboratory aspect has been completed, and a manuscript is in preparation. The second clinical aspect, with all its ethical approval, is set to commence in July 2026. I have enrolled one MSc student to share and disseminate project knowledge, established new collaborations within the FAR-Leaf health cluster and the University of Pretoria, and disseminated my knowledge at a key malaria research conference.

Through the successful implementation of this project, we will, for the first time, generate new knowledge about the previously unknown in-patient transmission reservoir of parasites, responsible for sustaining malaria transmission within the Vhembe district in Limpopo, South Africa. This information will inform future diagnostic, prophylactic, and treatment guidelines and guide the implementation of novel transmission-blocking strategies to aid overall malaria elimination. The generated data will be used to develop models that can be translated to other endemic regions and to inform cross-border malaria control programs in sub-Saharan Africa. Through this project's interaction with the UP ISMC, the project outcomes are strategically aligned with national and international malaria control and eradication priorities.

However, the method being developed in this project has caveats: the RT-qPCR method used is expensive and requires trained technicians and specialised equipment. Although this method is novel in repurposing a kit to avoid difficult sample processing, the technical processing requirements, the need for a clinical setting, and the need for a phlebotomist for sampling make it unsustainable for detecting transmission forms across sub-Saharan Africa. Therefore, the long-term implementation of a surveillance system to monitor parasite transmission dynamics would involve incorporating the transmissible-stage markers validated in this study into a non-invasive, rapid antigen-based diagnostic test.

Apart from contributing to national malaria eradication programs, the successful outcomes of this fellowship, through its leadership training, will enable me to establish myself as an independent early-career researcher within the next five years. Through the outcomes of this project, I aim to secure additional funding to build a long-term, sustainable academic research platform to investigate malaria transmission dynamics in sub-Saharan Africa.

Developing novel detection methods and obtaining geospatial data to inform transmission dynamics are critical to the development and implementation of transmission-blocking strategies and chemotherapeutics and may be the most efficient way to ultimately eradicate malaria in Africa. This would be a cross-border regional platform collaborating with national and international stakeholders. Through current networks with national and international NGOs and stakeholders (Goodbye Malaria, RollbackMalaria, South African Malaria Elimination Consortium (SAMEC), South African Medical Research Council, National Department of Health (NDoH), Elimination8 (E8), and the National Institute for Communicable Diseases (NICD)).

Annual report submitted by Dr Dina Coertzen

(summarised for publication by Heidi Sonnekus for the FAR-LeaF Programme)