Fig. 1

Schematic of the life cycle of Plasmodium vivax and comparable sibling simian species, depicted to represent the unique biological features of these species in the life cycle of primate malaria species and the importance of clinical and experimental interventions. The figure represents neotropical NHP models of P. vivax or macaque NHP models of Plasmodium cynomolgi and other simian parasite species that serve as surrogates for P. vivax (reviewed in [18–20]). The purple and green icons indicate where natural events and experimental manipulations can take place. The green mosquito icons refer to the natural inoculation of sporozoites through biting and the purple mosquito icons refer to the natural biting and infection of Anopheles ssp. mosquitoes by drawing in gametocyte-infected blood. The green medical symbol and syringe denoting the inoculation of sporozoites into the human and NHP hosts, respectively, refer to the possibility of challenging these hosts after immunization with a vaccine candidate to determine if protection can be induced. The purple medical symbol and syringe denote the collection of blood for testing involving human and NHPs, respectively. The purple syringe also signifies the specific collection of blood containing gametocytes from NHPs to artificially feed and infect Anopheles mosquitoes for supporting experiments on host–parasite biology within the vector host, transmission blocking vaccines, and access of sporozoites for in vivo or in vitro infection experiments. The unique biological features of P. vivax and comparable species depicted are the hypnozoite, the preferential invasion of merozoites into reticulocytes, the production of caveolae vesicle complexes (CVCs), represented as a mottled appearance of the infected RBCs, and the early and rapid development and circulation of gametocytes. Red arrows refer to processes relating to features that are currently in need of special research emphasis, answering questions like: (1) What is the make-up of hypnozoites and how are they activated? (2) What are the similarities and differences in primary and relapsing liver-stage schizonts and is their biology with merosome release in the blood stream comparable to rodent Plasmodium species where these were discovered? [21] (3) Which critical factors are required for reticulocyte host cell selection, invasion, and growth in these cells? And (4) what factors determine the development and circulation of gametocytes, potentially permitting transmission from the early stages of a blood-stage infection? “Reprinted from [19], with permission from Elsevier”. The artwork was created by Nagib Haque