Splenic Tropism and Spleen‐Modulated Systemic Inflammation in Acute Plasmodium vivax Malaria
11 affiliations
- 1Menzies School of Health Research and Charles Darwin University Darwin Australia
- 2Papuan Health and Community Development Foundation Timika Indonesia
- 3Rumah Sakit Umum Daerah Kabupaten Mimika Timika Indonesia
- 4Exeins Health Initiative Jakarta Indonesia
- 5School of Mathematics and Statistics, University of Melbourne Melbourne Australia
- 6Eijkman Research Centre for Molecular Biology, BRIN National Research and Innovation Agency Cibinong West Java Indonesia
- 7Burnet Institute Melbourne Australia
- 8Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health University of Melbourne Melbourne Australia
- 9Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine University of Oxford Oxford UK
- 10UMR_S1134, BIGR, Inserm, Université de Paris Paris France
- 11Centre for Child Health, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada Yogyakarta Indonesia
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.
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BibTeX
@article{kho2026splenic,
title = {{Splenic Tropism and Spleen‐Modulated Systemic Inflammation in Acute Plasmodium vivax Malaria}},
author = {Steven Kho and Hasrini Rini and Noy N. Kambuaya and Syawal Satria and Freis Candrawati and Putu A. I. Shanti and King Alexander and Benediktus Andries and Aisah R. Amelia and Anjana Rai and Kim A. Piera and Agatha M. Puspitasari and Ristya Amalia and Pak Prayoga and Leo Leonardo and Maulina Hafidzah and Theo Situmorang and Dewi S. Margayani and Desandra A. Rahmayenti and Pengxing Cao and Enny Kenangalem and Leily Trianty and Damian Oyong and Julie A. Simpson and Rintis Noviyanti and Pierre A. Buffet and Jeanne R. Poespoprodjo and Nicholas M. Anstey},
journal = {American Journal of Hematology},
year = {2026},
month = sep,
doi = {10.1002/ajh.70498},
url = {https://doi.org/10.1002/ajh.70498},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Splenic Tropism and Spleen‐Modulated Systemic Inflammation in Acute Plasmodium vivax Malaria
AU - Steven Kho
AU - Hasrini Rini
AU - Noy N. Kambuaya
AU - Syawal Satria
AU - Freis Candrawati
AU - Putu A. I. Shanti
AU - King Alexander
AU - Benediktus Andries
AU - Aisah R. Amelia
AU - Anjana Rai
AU - Kim A. Piera
AU - Agatha M. Puspitasari
AU - Ristya Amalia
AU - Pak Prayoga
AU - Leo Leonardo
AU - Maulina Hafidzah
AU - Theo Situmorang
AU - Dewi S. Margayani
AU - Desandra A. Rahmayenti
AU - Pengxing Cao
AU - Enny Kenangalem
AU - Leily Trianty
AU - Damian Oyong
AU - Julie A. Simpson
AU - Rintis Noviyanti
AU - Pierre A. Buffet
AU - Jeanne R. Poespoprodjo
AU - Nicholas M. Anstey
PY - 2026
DA - 2026/09/10
JO - American Journal of Hematology
DO - 10.1002/ajh.70498
UR - https://doi.org/10.1002/ajh.70498
AB - 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.
SN - 0361-8609
SN - 1096-8652
ER -