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- W4313373309 abstract "Abstract Despite important advances in malaria control, the disease is still a major public health issue in sub-Saharan Africa. Recent reports indicate over 400,000 deaths annually. Parasite resistance to known antimalarial drugs delays control and elimination. Dual oxidase 1 (Duox1), a member of the NADPH oxidase enzyme family, generates hydrogen peroxide that is used by its partner enzyme lactoperoxidase to generate antimicrobial hypothiocyanite. Malaria parasites are susceptible to hypothiocyanite in vitro. Duox1 is required for the generation of hypothiocyanite in vivo. We hypothesized that malaria parasites are susceptible to the Duox1-mediated antimicrobial system in vivo. Duox1-deficient and wild-type, Duox1-expressing mice were infected with Plasmodium berghei by either intravenous injection of sporozoites or exposure to infected mosquitos. The results indicate that Duox1-deficient mice either infected with intravenous injection of P. berghei sporozoites (p<0.004) or by exposure to P. berghei-infected mosquito bites (p<0.002), have significantly higher blood parasite density at peak parasitemia compared to wild-type mice. Survival data indicated that Duox1-deficient mice are more susceptible to P. berghei infection than control animals (p<0.03 for intravenous infection, p<0.02 for exposure to mosquito bites). Histopathological analysis of brain tissues revealed a slightly higher number of indices of cerebral pathology including cerebrovascular infected red blood cells and hemozoin accumulation, hemostasis, and hemorrhage. Overall, these data propose a novel role of Duox1 in delaying the onset of parasitemia and clinical outcomes in malaria infection." @default.
- W4313373309 created "2023-01-06" @default.
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- W4313373309 date "2020-05-01" @default.
- W4313373309 modified "2023-09-27" @default.
- W4313373309 title "Role of Dual Oxidase 1 in severe malaria" @default.
- W4313373309 doi "https://doi.org/10.4049/jimmunol.204.supp.227.12" @default.
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