Tropism of Plasmodium malariae for young red blood cells and the bone marrow

Fundamental aspects of the biology of the third most prevalent human malaria species Plasmodium malariae, including the basis for its capacity to establish chronic, low-density infections associated with debilitating quartan fevers, remain poorly characterized, hampering control efforts. Here, we combined ex vivo flowcytometric profiling of P. malariae isolates with infection studies in a recently developed humanized mouse model. We demonstrate a 5-fold higher tropism of P. malariae compared to P. falciparum for immature red blood cells, challenging a nearly century-old paradigm, and - for the first time - provide evidence for the parasite's capacity to home to and infect host bone marrow. Collectively, these findings reveal key life cycle features of this enigmatic and neglected human malaria parasite.