“…In particular, if a population decreases in size, as might be expected as transmission decreases during successive rounds of MDA, the chance that changes in allele frequencies are stochastic rather than deterministic increases: the genetic diversity overall decreases (e.g., Schistosoma mansoni: Coeli et al, 2013), but the fate of individual alleles is unpredictable, and some may increase due to genetic drift caused by population decline. Another challenge is that, prior to treatment, parasite populations can be quite large (i.e., they have a high effective population size; Blouin et al, 1995;Blouin et al, 1999;Zhou et al, 2013;Rodelsperger et al, 2014;Jan et al, 2016), which means they have ample genetic variation, so genetic variation contributing to a poor response phenotype may be present at different frequencies and at different loci in different parasite populations (e.g., Haemonchus contortus, Gilleard and Redman, 2016). Furthermore, once MDA begins, mating and recombination could create new combinations of alleles from different genes, which may also decrease response to ivermectin.…”