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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\u2010intact 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\u2010intact patients but total\u2010body Pv biomass (PvLDH) was three times lower in patients without a spleen. Parasite staging and greater organ\u2010specific 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\u2010fold higher PvLDH concentration in spleen\u2010intact patients, indicating a splenic biomass accounting for 89% of total\u2010body parasites. Giemsa\u2010based splenic histology in an untreated patient splenectomized during acute vivax malaria revealed a spleen\u2010to\u2010blood biomass ratio of 10.7. In spleen\u2010intact 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\u2010intact patients, cell\u2010free hemoglobin, endothelial activation and systemic inflammation were higher in splenectomized patients while inflammasome\u2010dependent 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\u2010associated pathology.\n                  <\/jats:p>","DOI":"10.1002\/ajh.70498","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:03:41Z","timestamp":1789099421000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Splenic Tropism and Spleen\u2010Modulated Systemic Inflammation in Acute\n                    <scp>\n                      <i>Plasmodium vivax<\/i>\n                    <\/scp>\n                    Malaria"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0926-8049","authenticated-orcid":false,"given":"Steven","family":"Kho","sequence":"first","affiliation":[{"name":"Menzies School of Health Research and Charles Darwin University  Darwin Australia"},{"name":"Papuan Health and Community Development Foundation  Timika Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasrini","family":"Rini","sequence":"additional","affiliation":[{"name":"Papuan Health and Community Development Foundation  Timika Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noy N.","family":"Kambuaya","sequence":"additional","affiliation":[{"name":"Papuan Health and Community Development Foundation  Timika Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syawal","family":"Satria","sequence":"additional","affiliation":[{"name":"Papuan Health and Community Development Foundation  Timika Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freis","family":"Candrawati","sequence":"additional","affiliation":[{"name":"Papuan Health and Community Development Foundation  Timika Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Putu A. 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