Scientists have developed a novel way with genome sequences to study and better understand transmission, treat and ultimately eradicate Plasmodium vivax, the most widespread form of malaria.
P. vivax is the most widespread human malaria parasite, responsible for more than 8.5 million clinical malaria cases worldwide and threatening more than two billion people in 90 countries. Unlike Plasmodium falciparum, another species of malaria, P. vivax cannot be cultured in vitro and remains poorly understood and resilient to elimination efforts.
The researchers analyzed the parasite gene expression profiles from P. vivax malaria patients enrolled in a study to determine the effectiveness of chloroquine as a malaria treatment. Using a combination of genomic and bioinformatic approaches, they compared the parasite transcriptomes, or set of Ribonucleic acid (RNA) molecules, from different patient infections and analyzed how the parasites responded to chloroquine, a common antimalarial drug, according to the research, which was published in Nature Communications.
Authors show that most parasite mRNAs derive from trophozoites and that the asynchronicity of P. vivax infections is therefore unlikely to confound gene expression studies. Analyses of gametocyte genes reveal two distinct clusters of co-regulated genes, suggesting that male and female gametocytes are independently regulated.
"By analyzing the parasite mRNAs directly from infected patient blood samples, we were able to observe that not all infections contained the same proportion of the male and female parasites that are required for infecting mosquitoes and propagating the disease. This observation suggests that parasite transmission is more complex that we previously thought and, perhaps, that the parasite is able to modify its development to ensure optimal survival," said the senior author.
The researchers analyzed the gene expression changes induced by chloroquine treatment and demonstrated that this antimalarial drug, while efficiently eliminating P. vivax parasites, acts differently that it does on P. falciparum parasites. Authors show that chloroquine efficiently eliminates most P. vivax parasite stages but, in contrast to P. falciparum, does not affect trophozoites. "This emphasizes the biological differences between these two human malaria parasites and the importance to specifically study this important pathogen if we hope to eventually eliminate malaria worldwide," the senior author said.
Genome sequencing studies have provided unique insights on this neglected human parasite, but are limited to identifying biological differences encoded in the DNA sequence. However, gene expression studies, which could provide information on the regulation of the parasite life cycle and its response to drugs, have been challenging to implement for this pathogen due to the heterogeneous mixture of parasite stages present in every patient's infection.
Transcriptome analysis of malaria parasite
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