Modeling malaria in humanized mice: opportunities and challenges.

About half of the world is at risk for developing malaria, which killed over 600,000 people in 2012 alone. The limited host range of the Plasmodium species that cause malaria in humans poses challenges for studying these parasites in experimentally tractable in vivo systems. To address this challenge, humanized mice have been constructed in which the tissue compartments relevant to the mammalian stages of plasmodial parasites are humanized. The development of human liver chimeric mice, human erythroid chimeric mice, and dually engrafted mice now allows for faithful replication of the entire Plasmodium falciparum life cycle. Although refinements to these models are still needed, humanized mice provide a promising small-animal model to study development of P. falciparum and, conceivably, other human malarial parasite species, and may also aid in drug and vaccine development.