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 observed declines of chloroquine resistance in many
countries following retirement of chloroquine as a first-line therapy. Our
observations support a key role for within-host competition in the
evolution of drug-resistant malaria. Malaria control and
resistance-management efforts in high-transmission regions may be
significantly aided, or hindered, by the effects of competition in
mixed-strain infections. Consideration of within-host dynamics may spur
development of novel strategies to minimize resistance while maximizing
the benefits of control measures. Bushman
DataThis folder includes all
data necessary to reproduce the reported findings. Some files overlap in
content but are formatted to facilitate analysis (R code at
github.com). Data include
parasitemia, genotype, age, location, year of sample collection,
microsatellite genotyping results, MOI frequencies, and certain controls
used to correct results for mixed-genotype infections.