Review and recent progress: the mathematical modeling of mixed species Plasmodium infections

Mathematical modeling serves numerous uses in biology, notably in the exploration of phenomena that are difficult to observe empirically. Here, I review recent progress in modeling the blood-stage dynamics of mixed-species Plasmodium infections, namely P. malariae-P. falciparum and P. vivax- P. falciparum mixed infections. Modeling reproduces features of such infections found in nature including the asymmetry of parasite blood-stage densities, inter-specific suppression, and parasite asexual-form recrudescence following long-standing sub-patency. Several findings which merit clinical attention are presented: the ability of P. malariae and P. vivax to reduce the peak parasitemia of co-infecting P. falciparum, and the potential recrudescence of a low-level P. falciparum infection following a P. malariae infection or P. vivax infection or relapse. The action of antimalarial drugs is discussed, highlighting some potential complications in treating mixed-species malaria infections. Most notably, if a mixed-species infection is misdiagnosed as a single-species P. vivax infection, treatment can lead to the dangerous appearance of "hidden" P. falciparum.