into the retro-orbital plexus per week is still burdensome, and should be replaced in the near future by a model harbouring a hematopoietic stem cell line capable of producing human erythroblasts/cytes [52], with the advantage of producing reticulocytes to also support P. vivax [53]. The main advantages of the NSG-IV model are that it offers extremely high reproducibility of both huRBC grafting and parasite survival, a rapidly rising parasitemia that reaches high levels, for long durations, and it does not need preliminary adaptation of parasite strains to the mouse. In addition, by modulating the quantity of huRBC administered, the final parasitemia can be adjusted to the needs of each experiment over a range of 1–40% for several weeks, or months, in a stable, controlled, and flexible fashion. Despite the improved behaviour and morphology of the parasites, there is still a residual inflammatory response that needs to be addressed in order to optimise this model further. Supporting Information Figure S1 Effect of inosine on the IV-NSG model. Using the suboptimal dose of 400 ml of huRBC, which leads to a decrease in chimerism possibly due to inflammation as described in Figure 6, we show that the addition of inosine at a dose of 250 mg/kg per day IP (blue line) significantly improves the survival of P. falciparum in NSG mice compared to untreated controls (red line). Panel A: differences in chimerism; Panel B: differences in parasitemia on logarithmic scale; Panel C: differences in parasitemia on arithmetic scale. Statistical analysis using the non parametric Wicoxon ranking test of data from 3 mice (inosine) and 4 mice (controls) infected by UPA strain showing: from day 0–15 an absence of detectable effect (n = 15: Z = 21.43; P = 0,152), from day 15–29, a significant difference (n = 10: Z = 22,57; P = 0,0101), from day 27–67, a significant References 1. 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