Malaria control and elimination in areas characterized by high transmission present a significant challenge to global health. A large fraction of the population across all ages in such areas harbor the malaria parasite Plasmodium falciparum, often without clinical manifestations, providing a vast reservoir of infection to sustain continued transmission to mosquito vectors. Our longitudinal research addresses changes in P. falciparum prevalence and diversity in response to a large-scale IRS intervention implemented across Bongo District, Ghana between 2013-2015. Parasite diversity was examined from the perspective of the highly recombinant multigene family known as var, which encodes for the major variant surface antigen of the P. falciparum blood stage of infection. High throughput sequencing data show that despite a significant reduction in parasite prevalence post IRS, the asymptomatic reservoir retained enormous var diversity. The challenge in hyperendemic malaria regions remains identifying the long-term funding sources required to sustain malaria control interventions to reduce this immense P. falciparum diversity to a break point.