Malaria is a deadly disease that causes around 250 million cases and more than 600,000 deaths worldwide each year. The disease is caused by the Plasmodium parasite, the deadliest and most widespread parasite on the African continent. P. falciparum is a single-celled parasite that evolves rapidly, making it difficult to develop durable and effective diagnostics, drugs, and vaccines against the disease. Malaria parasites indeed present great genetic diversity and people are frequently infected with several different parasite strains. In some parts of Africa, up to 80% of people infected with malaria carry several genetically distinct parasite strains.
The study results in an updated Atlas of malaria cells,
the “Malaria Cell Atlas”
which will allow scientists around the world to implement better surveillance of parasites and disease, but perhaps also to identify new ways of blocking the development of the parasite, in particular thanks to new drugs or vaccines capable of prevent transmission. Research using single-cell RNA sequencing provides detailed information on the life stages of this parasite as it matures from an asexual to a sexual state, necessary for transmission. from parasite to mosquitoes.
Malaria parasites are found either in an asexual or sexually developed form in the human host. Asexual replication in humans causes malaria symptoms, but to be transmitted, parasites must develop into a male or female reproductive cell or gametocyte. This sexual commitment and development are controlled by transcription factors, proteins that regulate gene activity. Mature sexual forms of the parasite circulate in the bloodstream until they are absorbed by mosquitoes. Here,
- researchers manage to precisely monitor gene expression levels and identify those involved in each step of the process;
- the approach applied to parasites from blood samples taken from 4 people naturally infected with malaria in Mali makes it possible to confirm these results with high resolution;
- the comparison of laboratory data with these data on natural infection also allowed scientists to identify types of parasitic cells never before observed, in laboratory strains, which on the one hand shows the importance of real-world data but also confirms the rapid evolution of the parasite;
- genes of interest are thus identified, which overexpressed in certain strains during the stages of sexual development are involved in the survival of the parasite and therefore in the development of the disease.
The next step will be to assess the impact of these genes on transmission. Jesse Rop, one of the lead authors, comments on these advances: “This is the first time that the stages of sexual development of malaria parasites in laboratory and natural strains have been mapped, allowing us to gain deeper insight into the biology present in natural strains – which do not “is not observed in laboratory strains, providing us with invaluable understanding of how malaria develops and spreads.”
“ Malaria constitutes a huge global health burden, affecting millions of people each year, and attempts to control and treat the disease are quickly defeated by the parasite. Better understanding the life cycle of the parasite, the genes involved and the factors that control them is essential for ongoing malaria research. Our research highlights key points in the parasite’s sexual development, which, if targeted in future drug development, could break the transmission cycle and help minimize spread.”
