Complete Plasmodium falciparum infection cycle model

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SUMMARY A variety of novel malaria control strategies are being developed to target the parasites within the human or mosquito vector, or as they transition from vector-to-host or hos-to-vector. Most of these approaches are being studied and evaluated by using laboratory-based in vitro and rodent models in the context of malaria transmission dynamics, because to date there is no experimentally easy and affordable human Plasmodium falciparum malaria transmission model. Furthermore, the small number of in vitro-cultured P. falciparum strains capable of infecting mosquitoes represent another obstacle in the study of mosquito stages of P. falciparum infection. To maintain gametocytogenesis and mosquito infectivity, asexually grown P. falciparum cultures should either be maintained at low passage number or should be passaged through infection cycles in the mosquito vector, but these strategies also require a malaria transmission model comprising the entire human infection cycle. We have recently advanced the development of an existing humanized mouse model to enable the complete P. falciparum infection cycle, from gametocyte to gametocyte. Here we will further this achievement into a standardized, affordable and accessible human malaria infection model, thereby closing a critical gap in malaria transmission studies. In aim 1 we will explore the utility of the humanized mouse-based P. falciparum transmission model with various malaria vector species and P. falciparum isolates. In aim 2 we will investigate the utility of the humanized mouse-based P. falciparum transmission model to maintain P. falciparum gametocyte infectiousness under laboratory conditions.