Fig 4. Effect of importation on artemisinin-resistance evolution in an MDA scenario with PfPR_2-10 = 2%.

The box-and-scatter plots show how long it takes for the allele frequency of 580Y to reach 0.25 in the simulation. Note that both the drug used in MDA (DHA-PPQ) and the first-line drug used to treat symptomatic P. falciparum malaria (AL) contain an artemisinin derivative, so selection on 580Y is occurring throughout the simulation. Five importation rates were considered (x-axis). The imported genotype has an equal 25% probability of being any of the four genotypes C580/580Y and piperaquine sensitive/resistant. One hundred simulations were run for each importation rate, each of the two population sizes, and each possibility of zero to four rounds of MDA (5000 simulations in all). One dot corresponds to one simulation and the boxes are interquartile ranges. With no or very low importation (0.001/day), there is little genetic variation in the population and the bottleneck period typically has no effect on selection. When importation of drug-resistance is common, it is likely that drug-resistant genotypes will be present during the bottlenecking process; in these scenarios, more rounds or MDA lead to smaller bottlenecks and smaller bottlenecks result in more rapid selection. Treatment coverage is 55% for individuals over the age of 5, and 60% for children <5, and there is no improvement of treatment coverage in the post-MDA period. Negative values are present in the top panel as high rates of importation can lead to >0.25 580Y allele frequency before the initiation of MDA. Note that the simulation is run for twenty years, so any points at the top of the graph simply mean twenty or more years.