DEDUCING THE EFFECT OF OXYGEN ON PLASMODIUM FALCIPARUM INTRAERYTHROCYTIC DEVELOPMENT

Abstract

Plasmodium (P.) falciparum, the causative agent of malaria, undergoes cytoadhesion within different tissues of the body during its development within erythrocytes, which have differing oxygen (O2) concentrations. The mechanisms by which the parasite withstands this O2 variation are not fully understood, and a greater understanding of the in vivo effects of this variation may provide further insights into malaria pathogenesis. We conducted growth studies to better understand P. falciparum growth in 1% O2 (within the range observed in deep-tissue sites) and 13% O2 (within the range observed in venous blood). We collected data on parasitemia, the parasite multiplication rate (PMR), and the stages of parasite development within erythrocytes at the midpoint of the asexual life cycle across three cycles. We then mathematically modeled the long-term in vitro and in vivo dynamics of parasite growth in response to differences in O2 concentrations. Our results show that parasites grown in 1% O2 exhibit higher parasitemia and PMR than those grown at 13% O2. Furthermore, developmental-stage data suggest that the intraerythrocytic cycle length is longer in parasites grown in 13% O2. Outputs from our mathematical model incorporating these differences in parasite growth show peak parasite quantities during simulated infections occur earlier in 1% O2 compared to 13% O2. These findings highlight the need to better understand the progression of malaria infection throughout the body, particularly for Plasmodium species that cytoadhere in tissues with varying O2 concentrations, to leverage this biological process in therapeutic development.