Splenic Tropism and Spleen‐Modulated Systemic Inflammation in Acute Plasmodium vivax Malaria

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Abstract
In chronic Plasmodium vivax (Pv) infection, the spleen accounts for over 98% of total‐body parasite biomass. Whether splenic tropism also occurs in acute infection and how the spleen influences pathogenesis have not been systematically explored. In Papua, Indonesia, we compared clinical and hematology data in 24 spleen‐intact and 25 previously splenectomized patients with acute uncomplicated vivax malaria. Plasma levels of Pv lactate dehydrogenase (PvLDH) and markers of intravascular haemolysis, inflammation, endothelial activation and neutrophil activation were measured by ELISA. Circulating parasitaemia was four times higher in splenectomized compared to spleen‐intact patients but total‐body Pv biomass (PvLDH) was three times lower in patients without a spleen. Parasite staging and greater organ‐specific symptoms suggest parasite redistribution in the absence of a spleen. Linear regression modeling adjusting for circulating parasitaemia, age, sex and fever duration demonstrated an 8.1‐fold higher PvLDH concentration in spleen‐intact patients, indicating a splenic biomass accounting for 89% of total‐body parasites. Giemsa‐based splenic histology in an untreated patient splenectomized during acute vivax malaria revealed a spleen‐to‐blood biomass ratio of 10.7. In spleen‐intact patients, splenic biomass correlated strongly with markers of disease intensity, endothelial activation and systemic inflammation, whereas circulating parasitaemia correlated weakly or not at all. Compared to spleen‐intact patients, cell‐free hemoglobin, endothelial activation and systemic inflammation were higher in splenectomized patients while inflammasome‐dependent responses were lower. In conclusion, Pv is predominantly an infection of the spleen in acute clinical vivax malaria. While the size of this hidden population correlates with disease intensity, the spleen likely modulates inflammatory pathways and heme‐associated pathology.
Funding Information
  • National Health and Medical Research Council (2019153)
  • National Health and Medical Research Council (2025376)
  • National Health and Medical Research Council (1037304)
  • National Health and Medical Research Council (1135820)
  • National Health and Medical Research Council (2042554)
  • Wellcome Trust (099875)
  • Department of Foreign Affairs and Trade, Australian Government

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