Fig. 3. Evolution of multi-drug resistance under three drug deployment strategies.

Epidemiological scenario shown is 0.1% PfPR_2-10 and 40% treatment coverage. Each row shows the genotype frequency of triple or double resistance to a particular set of antimalarial drugs, with the most resistant genotypes shown in purple (top two rows) or dark red (bottom three rows). In the bottom two rows, medium red corresponds to triple-mutant double-resistance and light red corresponds to double-mutant double-resistance. Median line is shown (nearly always at 0.0) and interquartile ranges are shaded. No importation is allowed in these figures. The columns show three different treatment strategies. The outcome measures are the genotype frequency of the maximally-resistant genotype after 20 years (x₂₀), the time until the maximally-resistant genotype reaches 0.01 frequency in the population (T_.01), the total area under the frequency curve of the maximally-resistant genotype (AUC), and the total number of non-discounted treatment failures during the twenty years that a strategy is implemented (NTF). AUC is the most appropriate measure of total MDR risk, but median AUC = 0.0 for the majority of scenarios in this low-transmission setting. The interquartile ranges in the right-hand column suggest that adaptive cycling has the highest probability of driving maximally-resistant genotypes to high levels. In the first row after 20 years, the triple-resistant reached 0.001 genotype frequency in 32/100 simulations under an adaptive cycling strategy. Under MFT and 5-year cycling, the triple-resistant never rose above 0.001 frequency during the twenty years of the simulation.