Malaria is a global killer, a disease that destroys human lives and the economies of countries in which it thrives.
According to the latest figures by the World Health Organization (WHO), there were 241 million cases of malaria in 2020, with an estimated 627 000 deaths.
Four African countries, namely Nigeria (31,9%), the Democratic Republic of the Congo (13,2%), Tanzania (4.1%) and Mozambique (3,8%), were responsible for half the malaria deaths worldwide.
Although deaths attributed to malaria have declined in recent decades thanks to wide-ranging humanitarian efforts, the toll the disease exacts is still extremely high.
New research by Dr Janine Aucamp, a postdoctoral fellow from the Centre of Excellence for Pharmaceutical Sciences (Pharmacen™) at the North-West University (NWU) hopes to address this. Aucamp received a Global Grand Challenges grant to assist in pursuing this goal.
The research is titled A 3D Clinostat-Based Bioreactor Model of Liver-Stage Plasmodium falciparum and its Applications in Parasite Biochemistry and Anti-Malarial Drug Discovery.
Aucamp explains: “Malaria is a life-threatening parasitic disease that begins in the human liver. Once a person has been bitten by an infected mosquito, the malaria parasites travel to the person’s liver via the bloodstream and enter the liver cells to mature into the blood-infecting stage. Once the parasites begin to infect and spread in the victim’s red blood cells, disease symptoms begin to develop, as does the risk of infecting other mosquitoes during their blood meals. Antimalarial treatments that are currently available mainly target the blood-infecting stage to manage symptoms. However, targeting the infection during the early liver stage will prevent both the onset and spread of the disease.”
There are five parasite species that can cause malaria in humans, and of these five, Plasmodium falciparum is deemed the deadliest.
“To date, producing an effective Plasmodium falciparum liver-stage model for drug screenings has been a challenging hurdle. This is due to this parasite’s fastidious nature and dependence on human liver morphology and biochemistry. The project therefore aims to develop a clinostat-based 3D liver-stage malaria model using a commercially available liver cell line. The clinostat-based technology uses rotation to simulate microgravity, allowing ‘floating’ cells to develop into clusters with biochemical and morphological characteristics strikingly similar to liver tissue. The resulting model will be used to screen new drugs for antimalarial activity and in parasite research to identify new drug targets,” says Aucamp.
According to her, advanced 3D cell culture systems are becoming increasingly popular in many research fields, as they present an opportunity to conduct research under physiologically relevant conditions without needing animal models or human challenge trials to do so.
“This is especially helpful in the drug research setting. Newly developed potential drugs must first pass preclinical screenings to qualify for clinical trials. Animal models are preferred during preclinical screening to both support the efficacy and assess the safety of the potential drug. However, the less physiologically relevant the screening model, the more likely is the failure of subsequent clinical trials. As of 30 March 2022, there are nearly 170 000 registered active treatment-related clinical trials. It is estimated that a mere 5 to 10% of promising preclinical studies successfully translate into clinical trial successes. This low success rate is not only a financial waste, it puts trial volunteers at risk and significantly delays the clinical introduction of new, effective and safe medicines. The delay is particularly detrimental to the management of serious infectious diseases, where pathogen drug resistance is slowly and accumulatively rendering current treatment options useless. Advanced cell cultures can provide both physiologically relevant simulations and, more importantly, simulations of human origin, thus eliminating potential animal-human interspecies differences affecting screening data,” Aucamp concludes.
A new weapon in the fight against malaria is about to be released in a battle where dedication and expertise still prevail.