MALARIA: Parasite sexual development finally deciphered and mapped

Malaria is a deadly disease, causing approximately 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 reliable and effective diagnostics, drugs, and vaccines against this disease. Malaria parasites do have a great deal of genetic diversity, and people are often infected with several different strains of the parasite. In some parts of Africa, up to 80% of people infected with malaria carry several genetically distinct strains of the parasite.

Studying The result was an updated Atlas of Malaria Cells,

“Malaria Cell Atlas”

which will allow scientists around the world to improve surveillance of parasites and disease, but perhaps also identify new ways to block parasite development, particularly through new drugs or vaccines that can prevent transmission. Studies using single-cell RNA sequencing provide detailed information about the life stages of this parasite as it transitions from an asexual state to the sexual state required for transmission from the parasite to mosquitoes.

Malaria parasites occur in the human host in either asexual or sexual form. Asexual reproduction in humans causes symptoms of malaria, but the parasites must develop into a male or female reproductive cell or gametocyte to be transmitted. This sexual activity and development is controlled by transcription factors, proteins that regulate the activity of genes. Mature sexual forms of the parasite circulate in the bloodstream until they are ingested by mosquitoes. Here,

• researchers are able to accurately track gene expression levels and identify participants at each stage of the process;
• an approach applied to parasites from blood samples taken from 4 individuals naturally infected with malaria in Mali allows confirmation of these results at high resolution;
• Comparing laboratory data with these natural infection data also allowed scientists to identify never-before-observed types of parasitic cells in laboratory strains, which on the one hand shows the importance of real-world data, but also confirms the rapid evolution of the parasite. ;
• in this way, genes of interest are identified whose overexpression in certain strains at sexual stages is involved in the survival of the parasite and, consequently, in the development of the disease.

The next step will be to evaluate the influence of these genes on transmission. Jesse Rop, one of the lead authors, comments on these achievements: “This is the first time that the sexual development stages of malaria parasites in laboratory and natural strains have been mapped, allowing us to gain greater insight into the biology present in natural strains that is not seen in laboratory strains, providing us with invaluable insight into how malaria develops and spreads.”

” Malaria poses a huge global health burden, affecting millions of people every year, and attempts to control and treat the disease are quickly being overwhelmed by the parasite. A better understanding of the parasite’s life cycle, the genes involved, and the factors that control them has important implications for ongoing malaria research. Our study identifies key points in the parasite’s sexual development that, if targeted in future drug development, could break the transmission cycle and help minimize spread.”