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Malaria biology and disease pathogenesis: insights for new treatments

Abstract

Plasmodium falciparum malaria, an infectious disease caused by a parasitic protozoan, claims the lives of nearly a million children each year in Africa alone and is a top public health concern. Evidence is accumulating that resistance to artemisinin derivatives, the frontline therapy for the asexual blood stage of the infection, is developing in southeast Asia. Renewed initiatives to eliminate malaria will benefit from an expanded repertoire of antimalarials, including new drugs that kill circulating P. falciparum gametocytes, thereby preventing transmission. Our current understanding of the biology of asexual blood-stage parasites and gametocytes and the ability to culture them in vitro lends optimism that high-throughput screenings of large chemical libraries will produce a new generation of antimalarial drugs. There is also a need for new therapies to reduce the high mortality of severe malaria. An understanding of the pathophysiology of severe disease may identify rational targets for drugs that improve survival.

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Figure 1: Severe malaria in children.
Figure 2: Quinine and artemisinin discoveries led to the development of many synthetic antimalarial drugs.
Figure 3: Merozoite invasion of the erythrocyte involves five steps, including the movement of erythrocyte membrane past the junction to form the parasitophorous vacuole (PV).
Figure 4: Malaria infection disrupts nitric oxide metabolism and causes harmful endothelial activation.

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Acknowledgements

This review was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health. We thank S.K. Pierce, S. Desai and C. Pola for critical comments and figure design.

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Miller, L., Ackerman, H., Su, Xz. et al. Malaria biology and disease pathogenesis: insights for new treatments. Nat Med 19, 156–167 (2013). https://doi.org/10.1038/nm.3073

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