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G6PD-deficient patients are resistant to Plasmodium falciparum malaria because their red blood cells (RBCs) have reduced levels of NADPH, leading to oxidative stress. This creates a hostile environment for the malaria parasite, which relies on RBCs for survival. The oxidative damage weakens infected RBCs, causing their premature destruction (hemolysis) before the parasite can complete its life cycle. This natural selection advantage explains the higher prevalence of G6PD deficiency in malaria-endemic regions.