Figure 1. Persister-like cell types of Plasmodium spp.

A.The Plasmodium vivax hypnozoite. P. vivax sporozoites injected into the host by infected Anopheles mosquitoes rapidly infect hepatocytes. In the liver cells, the parasites undergo a proliferative stage, including substantial nuclear division without cell division to produce a schizont (schizogony). The schizont differentiates into merozoite forms that burst from hepatocytes and enter the bloodstream where they invade erythrocytes. Alternatively, some sporozoites will form hypnozoites that can persist in a growth-arrested state for weeks to many months before entering schizogony and completing the developmental cycle in the liver.

B. Artemisinin refractory dormant ring stages in P. falciparum

Exposure of synchronous ring stage P. falciparum parasites to dihydroartemisinin (DHA) induces cell-cycle arrest. These dormant ring stage forms are characterized morphologically by condensed chromatin and reduced cytoplasm. By contrast, pre-exposed ring stage forms have a relatively diffuse nucleus and large cytoplasmic area. Dormant ring stage parasites persist for several days before resuming normal growth. DHA-induced ring stage dormancy is observed in artemisinin-susceptible and artemisinin–resistant P. falciparum^{45, 47}. The top panel shows Giemsa stained parasites (purple) inside erythrocytes. The lower panel provides a representation of the upper panel in which key structures visible in light microscopy are visible. The diameter of the erythrocyte is 6 micrometers.

Figure 1aadapted from Ref. 158. Fig 1b courtesy of Dennis E. Kyle (University of Georgia, Athens, USA).