Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria

Recent initiatives to improve translation of findings from animal models to human disease have focussed on reproducibility but quantifying the relevance of animal models remains a challenge. Here we use comparative transcriptomics of blood to evaluate the systemic host response and its concordance between humans with different clinical manifestations of malaria and five commonly used mouse models. Plasmodium yoelii 17XL infection of mice most closely reproduces the profile of gene expression changes seen in the major human severe malaria syndromes, accompanied by high parasite biomass, severe anemia, hyperlactatemia, and cerebral microvascular pathology. However, there is also considerable discordance of changes in gene expression between species and across all models, indicating that the relevance of biological mechanisms of interest in each model should be assessed before conducting experiments. Our data will aid selection of appropriate models for translational malaria research, and the approach is generalizable to other disease models.

Effect of six bis-THTT derivatives in the control of parasitaemia in two rodent malaria species

Malaria is a life-threatening disease caused by parasites of the genus Plasmodium and is transmitted to humans by the bite of female mosquitoes of the genus Anopheles. WHO has reported 219 million cases of malaria and 435,000 deaths were estimated in 2017. The anti-malarial treatment more frequently used is based on Chloroquine, which has been used for several decades. This prolonged application has caused the parasite to develop resistance to the use of the mentioned drug, so it becomes necessary to search for new treatments. In addition, some tetrahydro-(2H)-1,3,5-thiadiazine-2-thione (THTT) derivatives have been previously studied as possible trypanosomicides, obtaining satisfactory results in the treatment to Trypanosoma cruzi; Trichomonas vaginalis and T. b. rhodesiense, although no studies against malaria have been reported. In the present work, six bis-THTT derivatives were evaluated as potential anti-malarial drugs (JH1, JH2, JH3, JH4, JH5, and JH6) with BALB/c mice, which were inoculated with Plasmodium berghei ANKA strain and Plasmodium yoelii 17XL strain. The percentages of parasitemia were determined for each tested compound, which was assessed daily on smears from tail blood, stained with Giemsa’s reagent and observed under light microscopy as evidence of cure. Our results showed that JH2 and JH4 presented effective parasitemia control similar to chloroquine in P. berghei. Besides, JH5 and JH6 exhibited better results than Chloroquine with P. yoelii infection. In summary, four of the six bis-THTT derivatives tested, could be considerate as potential new drugs to infection malaria rodent control. Immune response essays should be realized in order to confirm our preliminary results.