The biology and pathogenesis of vivax malaria

• Published in: Trends in parasitology Vol. 40; no. 7; pp. 573 - 590
• Main Authors: Anstey, Nicholas M., Tham, Wai-Hong, Shanks, G. Dennis, Poespoprodjo, Jeanne R., Russell, Bruce M., Kho, Steven
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2024
• Subjects: biology; hidden biomass; life cycle; pathophysiology; Plasmodium vivax; spleen; Plasmodium vivax; hidden biomass; life cycle; biology; spleen; pathophysiology
• ISSN: 1471-4922; 1471-5007; 1471-5007
• DOI: 10.1016/j.pt.2024.04.015

Most asexual vivax parasites accumulate in the reticulocyte-rich spleen, replicating in an endosplenic life cycle. This reservoir contributes to systemic inflammation and anemia, and helps maintain chronic infections and transmission.Plasmodium vivax merozoites preferentially invade nascent reticulocytes over mature reticulocytes through newly identified invasion pathways.Humanized mice and hepatocyte culture systems are characterizing hypnozoite biology, and new approaches for anti-relapse therapy.Anemia is mostly from splenic retention of uninfected red cells; frequently recurring and chronic infections cause progressive anemia, malnutrition, and death, especially in young children.Endothelial cell activation, a predictor of impaired perfusion and death in falciparum malaria, is even more pronounced in acute vivax malaria, likely contributing to organ dysfunction in severe disease. Plasmodium vivax contributes significantly to global malaria morbidity. Key advances include the discovery of pathways facilitating invasion by P. vivax merozoites of nascent reticulocytes, crucial for vaccine development. Humanized mouse models and hepatocyte culture systems have enhanced understanding of hypnozoite biology. The spleen has emerged as a major reservoir for asexual vivax parasites, replicating in an endosplenic life cycle, and contributing to recurrent and chronic infections, systemic inflammation, and anemia. Splenic accumulation of uninfected red cells is the predominant cause of anemia. Recurring and chronic infections cause progressive anemia, malnutrition, and death in young children in high-transmission regions. Endothelial activation likely contributes to vivax-associated organ dysfunction. The many recent advances in vivax pathobiology should help guide new approaches to prevention and management. Plasmodium vivax contributes significantly to global malaria morbidity. Key advances include the discovery of pathways facilitating invasion by P. vivax merozoites of nascent reticulocytes, crucial for vaccine development. Humanized mouse models and hepatocyte culture systems have enhanced understanding of hypnozoite biology. The spleen has emerged as a major reservoir for asexual vivax parasites, replicating in an endosplenic life cycle, and contributing to recurrent and chronic infections, systemic inflammation, and anemia. Splenic accumulation of uninfected red cells is the predominant cause of anemia. Recurring and chronic infections cause progressive anemia, malnutrition, and death in young children in high-transmission regions. Endothelial activation likely contributes to vivax-associated organ dysfunction. The many recent advances in vivax pathobiology should help guide new approaches to prevention and management.