Schematic of the IRS experiment design. (A) Initial transmission events and migrant genomes in a local population (blue circle) are sourced from a global pool of genes (red square). Mutation of new genes and the death of existing genes in the global pool occur at the same rate as in the local population (see Methods). The value of the migration rate is inferred from an empirical dataset for a high transmission region in Ghana (see Methods). Individual infections are tracked locally. We also track events of transmission, mutation of genes, recombination within and between genomes, and acquisition and loss of specific immune memory in hosts. (B) Each simulation follows three stages (after a burn-in period): a pre-IRS period during which the transmission in the local population reaches a stable state; an IRS period of 2, 5, or 10 years reducing transmission, and a post-IRS period when transmission rates go back to pre-IRS levels. (C) Three levels of transmission intensity (biting rates) are explored in the experiments (pre-/post-IRS, low: 44 bites per host per year; medium: 110 bites/h/y; high: 221 bites/h/y). (D) The two regimes (with and without NFDS) are ensured to be comparable by specifying the average duration of infection as a function of the number of previous infections in G with a curve fitted to the points generated under S. The expression for the duration of infection under S is given here, and its explanation can be found in the methods (2.2).