Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment (original) (raw)
Fig 7
Impact of starting allele frequency on OXA-R allele change.
(A) Monte Carlo simulation over 1,500 generations using strong selection (selection coefficient (s) = 0.1) on a population size (N) of 65,000 with a starting allele frequency (p(R)) of 0.15 for standing variation or 1/(2N) for new mutation. These simulations underestimate time to fixation for true de novo mutation, because we do not account for the waiting time for resistance to appear which is dependant on the rate of drug resistance mutations and Ne [3]. The starting frequency of 0.15 corresponds to the frequencies of OXA-resistance alleles observed in Kenya. (B) Change in frequency of resistant parasites (i.e. homozygotes for OXA-R alleles) from standing variation under a range of selection coefficients. The dashed lines correspond to the two thresholds (10% and 20%) at which treatment efficacy would be compromised. The numbers at the dashed lines correspond to the parasite generations needed to cross these thresholds. These predictions are deterministic, because we expect minimal stochastic variation when starting resistance allele frequencies are high.