Plasmodium falciparum and Plasmodium vivax account for most of the mortality and morbidity associated with malaria in humans. Research and control efforts have focused on infections caused by P. falciparum and P. vivax, but have neglected other malaria parasite species that infect humans. Additionally, many related malaria parasite species infect nonhuman primates (NHPs), and have the potential for transmission to humans. For malaria elimination, the varied and specific challenges of all of these Plasmodium species will need to be considered. Recent advances in molecular genetics and genomics have increased our knowledge of the prevalence and existing diversity of the human and NHP Plasmodium species. We are beginning to identify the extent of the reservoirs of each parasite species in humans and NHPs, revealing their origins as well as potential for adaptation in humans. Here, we focus on the red blood cell stage of human infection and the host cell tropism of each human Plasmodium species. Determinants of tropism are unique among malaria parasite species, presenting a complex challenge for malaria elimination.
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