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To counter the global threat caused by  Plasmodium falciparum  malaria, new drugs and vaccines are urgently needed. However, there are no practical animal models because  P. falciparum  infects human erythrocytes almost exclusively. Here we describe a reliable  falciparum  murine model of malaria by generating strains of  P. falciparum in vivo  that can infect immunodeficient mice engrafted with human erythrocytes. We infected NOD  scid/β2m−/−   mice engrafted with human erythrocytes with  P. falciparum  obtained from  in vitro  cultures. After apparent clearance, we obtained isolates of  P. falciparum  able to grow in peripheral blood of engrafted NOD  scid/β2m−/−   mice. Of the isolates obtained, we expanded  in vivo  and established the isolate  Pf 3D7 0087/N9  as a reference strain for model development.  Pf 3D7 0087/N9  caused productive persistent infections in 100% of engrafted mice infected intravenously. The infection caused a relative anemia due to selective elimination of human erythrocytes by a mechanism dependent on parasite density in peripheral blood. Using this model, we implemented and validated a reproducible assay of antimalarial activity useful for drug discovery. Thus, our results demonstrate that  P. falciparum  contains clones able to grow reproducibly in mice engrafted with human erythrocytes without the use of myeloablative methods.

A Murine Model of falciparum-Malaria by In Vivo Selection of Competent Strains in Non-Myelodepleted Mice Engrafted with Human Erythrocytes