Abstract:
Population genetic diversity of Plasmodium falciparum antigenic loci is high
despite large bottlenecks in population size during the parasite life cycle. The prevalence
of genetically distinct haplotypes at these loci, while well characterized in humans, has
not been thoroughly compared between human and mosquito hosts. We assessed para-
site haplotype prevalence, diversity, and evenness using human and mosquito P. falciparum
infections collected from the same households during a 14-month longitudinal cohort study
using amplicon deep sequencing of two antigenic gene fragments (ama1 and csp). To a
prior set of infected humans (n = 1,175/2,813; 86.2% sequencing success) and mosquito
abdomens (n = 199/1,448; 95.5% sequencing success), we added sequences from infected
mosquito heads (n = 134/1,448; 98.5% sequencing success). The overall and sample-level
parasite populations were more diverse in mosquitoes than in humans. Additionally, hap-
lotype prevalences were more even in the P. falciparum human population than in the
mosquito population, consistent with balancing selection occurring at these loci in humans.
In contrast, we observed that infections in humans were more likely to harbor a dominant
haplotype than infections in mosquitoes, potentially due to removal of unfit strains by the
human immune system. Finally, within a given mosquito, there was little overlap in genetic
composition of abdomen and head infections, suggesting that infections may be cleared
from the abdomen during a mosquito’s lifespan. Taken together, our observations provide
evidence for the mosquito vector acting as a reservoir of sequence diversity in malaria
parasite populations.
IMPORTANCE Plasmodium falciparum is the deadliest human malaria parasite, and
infections consisting of concurrent, multiple strains are common in regions of high
endemicity. During transitions within and between the parasite’s mosquito and human
hosts, these strains are subject to population bottlenecks, and distinct parasite strains
may have differential fitness in the various environments encountered. These bottlenecks
and fitness differences may lead to differences in strain prevalence and diversity between
hosts. We investigated differences in genetic diversity and evenness between P. falciparum
parasites in human and mosquito hosts collected from the same households during a 14-
month longitudinal study in Kenya. Compared to human parasite populations and infec-
tions, P. falciparum parasites observed in mosquito populations and infections were more
diverse by multiple population genetic metrics. This suggests that the mosquito vector
acts as a reservoir of sequence diversity in malaria parasite populations.