Understanding how the parasite that causes malaria works, is an important piece of the puzzle in tackling the disease. There are five Plasmodium parasite species that cause malaria in humans. P. falciparum is the deadliest malaria parasite and the most prevalent on the African continent. All clinical symptoms of malaria are caused by the multiplication of malaria parasites in the red blood cells. The most common early symptoms of malaria are fever, headache and chills, while symptoms of severe malaria include fatigue, confusion, seizures, and difficulty breathing.
Key component found for malaria invasion
P. falciparum invades human red blood cells, but the precise details of the targets that the parasite binds to has not been known until recently. Although we knew that the malaria protein cysteinrich protective antigen (PfCyRPA) is essential for the invasion of red blood cells, its precise role in this process was not understood.
Findings by a multidisciplinary, collaborative research team from six institutions, led by Swiss TPH and the Institute for Glycomics in Australia, have provided new insights into how P. falciparum invades red blood cells. Published in Cell Reports, the study revealed that the parasite protein PfCyRPA binds specifically to a glycan structure containing sialic acid on the red blood cell surface – a key step in the invasion process. This discovery not only improves understanding of host-pathogen interactions but also supports the continued development of PfCyRPA as a potential blood-stage malaria vaccine component and as target for novel antimalarial drugs. As the emergence of drug resistance in malaria parasites is a threat to malaria control programmes, new antimalarial drugs are urgently needed.
Closing treatment gaps for the most vulnerable
Early diagnosis and treatment of malaria reduces disease, prevents deaths and contributes to reducing transmission. Malaria is a serious infection and always requires treatment with medicine. Several antimalarial treatments exist and doctors chose the appropriate therapy based on the type of malaria, drug resistance, weight or age of the patient and whether a person is pregnant. Artemisinin-based combination therapy medicines are the most effective treatment for P. falciparum malaria.
However, current antimalarials have not been developed specifically for infants weighing under 5 kg. There is no approved treatment available for them, and they are treated with tablets meant for children above 5 kg adjusted by weight. Yet, these tiny patients handle drugs differently due to the immaturity of their metabolising organs, which can lead to overdose and toxicity. To help fill this gap, Swiss TPH supported the CALINA study, which is led by Novartis with support from Medicines for Malaria Venture (MMV). The study evaluated a new formulation of Coartem® (artemether-lumefantrine) designed for babies weighing less than 5 kg in a clinical trial in several African countries. Swiss TPH was in charge of carrying out the study in the Democratic Republic of the Congo. Setting up study sites in challenging environments in low- and middle-income countries to test drugs for poverty-related diseases is something Swiss TPH has been doing for over 20 years in partnership with different organisations and countries.
The new formulation provides optimised dosing specifically tailored to the needs of these vulnerable patients. The results showed good efficacy and safety, with pharmacokinetic profiles suitable for this age and weight group. If approved, the treatment will close a significant treatment gap.
Swiss TPH's commitment to global malaria efforts
These two examples show how Swiss TPH is working along the entire value chain - from basic research on malaria parasites to the validation of new drugs in clinical research. We also work with partners to put new knowledge and tools into practice. For example, large-scale implementation studies in endemic countries provide critical evidence to support decision-makers worldwide in the fight against malaria.
In total, more than 200 researchers work on malaria at Swiss TPH. They are involved in the development of new diagnostics, treatments and vaccines as well as vector control strategies. As a WHO Collaborating Centre and a member of the Swiss Malaria Group, Swiss TPH plays a vital role in advancing innovative strategies for malaria elimination.