Fig 1. Schematic showing the relationship between prevalence and drug-resistance pre- and post-MDA, and three small-population example scenarios showing the effects of MDA on parasite population size and probability of elimination.

The three scenario plots summarize 100 simulations under three rounds of MDA by showing the deciles (10th percentile to 90th percentile) of the simulation outcomes, with the non-extinct trajectories labelled by their decile. The y-axis shows the number of parasite-positive individuals including those that are not detectable by microscopy; x-axis shows five years. Simulated trajectories that reach extinction/elimination (<5 parasite-positive individuals) end in a black square and are not continued. In the orange box, the first decile is not shown as the number of parasite-positive individuals was <5 prior to the MDA. All examples include importation of drug-resistance of approximately two artemisinin-resistant genotypes per year. Elimination occurs for ~70% of simulations in the scenarios shown, and for ~80% of scenarios the number of parasite-positive individuals stays below 20 for at least three years. These example scenarios are chosen as boundary examples; in all three, probability of elimination increases with an extra round of MDA, lower importation rates of drug-resistance, lower pre-MDA prevalence, higher treatment coverage, or improved treatment coverage (ITC) post-MDA. The top-right panel shows the change in the parasite population profile from pre- to post-MDA. The box widths and heights show the inter-quartile range for the number of parasite-positive individuals (any level of parasitaemia) and the frequency of 580Y alleles, respectively, with colors matching the three example scenarios. The way that resistance risk is introduced into MDA scenarios is that the parasite population is pushed into this graph’s upper-left corner, the resistance bottleneck. In the example simulations corresponding to the colored boxes, the parasite population sizes drop to the single digits or low double digits, but 580Y allele frequencies are unpredictable and can potentially be high, making the future path of drug resistance highly unpredictable.