A biological model for the treatment of a genetic disorder that coevolved with infection. In this model, infection outcomes are assessed for the treatments of the host genetic disorder. Treatment 1, which has no effect on malaria, would leave patients with SCA highly susceptible to severe malaria and death. Treatment 2 with modest antiinfection activity that bypasses resistance, presents a strategy of choice. Treatment 3, which is potent against infection is expected to select resistant parasites given long-term treatment (of months to years) needed to treat the genetic disorder. Treatment 4 with antagonist interactions with antimalarial drugs are undesirable, whereas favorable drug interactions (treatment 5) combined with modest antiinfection activity as seen between HU and antimalarials (treatment 2), present the optimal path. This in conjunction with the improvement of the host genetic disorder (which in the case of SCA is through stimulation of hematopoiesis and reduction of vasculature inflammation) yields a safe long-term treatment that can be deployed in global health.