Figure 1

The evolution of anti-malarial drug resistance. The evolution of anti-malarial drug resistance is shown schematically in three steps: Top) Appearance involves de novo mutation and within-host selection by drugs (brown). Sensitive parasites (black) initially outnumber resistant mutants (red), but after treatment, the proportion of parasites that are resistant (blue) increases, and so too does the likelihood of transmitting a resistant parasite. Middle) Emergence involves sporadic appearance (red) and stochastic establishment. Establishment involves generating "progeny" (infected humans) and becoming common enough to avoid stochastic fadeout. In the generations after appearance, the number of progeny fluctuates. This was simulated as an evolving branching process and illustrated with vertical lines whose thickness corresponds to the number of progeny in that generation. In the figure, the last one successfully established, defined as a point when 100 "offspring" existed with positive fitness, and spread was considered virtually certain. Bottom) After emergence, the spread of resistance was simulated in simple epidemiological models. Starting from 100 individuals who carried resistant parasites, the time to failure (10%, dashed line) depended strongly on the human population size (H).