Within-host competition and drug resistance in the human malaria parasite Plasmodium falciparum

Infections with the malaria parasite Plasmodium falciparum typically comprise multiple strains, especially in high-transmission areas where infectious mosquito bites occur frequently. However, little is known about the dynamics of mixed-strain infections, particularly whether strains sharing a host compete or grow independently. Competition between drug-sensitive and drug-resistant strains, if it occurs, could be a crucial determinant of the spread of resistance. We analyzed 1,341 P. falciparum infections in children from Angola, Ghana, and Tanzania and found compelling evidence for competition in mixed-strain infections: overall parasite density did not increase with additional strains, and densities of individual strains (chloroquine-sensitive and chloroquine-resistant) were reduced in the presence of competitors. We also found that chloroquine-resistant strains exhibited low densities compared to chloroquine-sensitive strains (in the absence of chloroquine), which may underlie observ...