{"doi":"10.1371/journal.pcbi.1013865","title":"The role of the spleen in red blood cell loss caused by malaria: A mathematical model","abstract":"<jats:p>\n                    The human spleen significantly influences red blood cell (RBC) dynamics due to its ability to retain and/or remove RBCs from peripheral blood circulation. This filtering can mediate a range of malaria disease manifestations, depending on the physiological properties of the spleen. Data collected from patients undergoing splenectomy in Papua, Indonesia, revealed that in asymptomatic infections the spleen harboured substantially more infected RBCs than were circulating in the peripheral blood and that the spleen is also congested with uninfected RBCs. We hypothesise that two conditions hold for the spleen to retain such a high proportion of infected and uninfected RBCs: (i) the retention rate of uninfected RBCs is significantly higher than in uninfected patients; and (ii) phagocytosing macrophages cannot clear all of the infected RBCs from the spleen. In this paper, we present a mathematical model of RBC dynamics that includes, for the first time, the spleen as a compartment capable of retaining large numbers of infected and uninfected RBCs in\n                    <jats:italic>Plasmodium falciparum</jats:italic>\n                    and\n                    <jats:italic>P. vivax</jats:italic>\n                    infections. By calibrating the model to the Papuan data, we demonstrate that the spleen plays a significant role in removing not only infected RBCs but also uninfected RBCs. Uninfected RBC retention in the spleen, attributable to malaria, is substantially higher than circulating RBC loss due to parasitisation, for infections by both\n                    <jats:italic>Plasmodium</jats:italic>\n                    species. In chronic infections, the ratio of circulating uninfected RBCs lost to splenic retention per circulating uninfected RBC lost to parasitisation is 17:1 for\n                    <jats:italic>P. falciparum</jats:italic>\n                    and 82:1 for\n                    <jats:italic>P. vivax</jats:italic>\n                    . These ratios are larger than previously published estimates for acute clinical infections.\n                  </jats:p>","journal":"PLOS Computational Biology","year":2026,"id":644638,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":4,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1678045,"name":"Saber Dini","orcid":null,"position":1,"is_corresponding":false},{"id":668003,"name":"Steven Kho","orcid":"0000-0003-0926-8049","position":2,"is_corresponding":false},{"id":269825,"name":"Bridget E. Barber","orcid":"0000-0003-1066-7960","position":3,"is_corresponding":false},{"id":1678046,"name":"Pierre A. Buffet","orcid":null,"position":4,"is_corresponding":false},{"id":998396,"name":"Megha Rajasekhar","orcid":"0000-0003-0665-6919","position":5,"is_corresponding":false},{"id":236386,"name":"David J. Price","orcid":"0000-0003-0076-3123","position":6,"is_corresponding":false},{"id":269823,"name":"Nicholas M. Anstey","orcid":"0000-0002-2192-0506","position":7,"is_corresponding":false},{"id":316985,"name":"J. A. 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We hypothesise that two conditions hold for the spleen to retain such a high proportion of infected and uninfected RBCs: (i) the retention rate of uninfected RBCs is significantly higher than in uninfected patients; and (ii) phagocytosing macrophages cannot clear all of the infected RBCs from the spleen. In this paper, we present a mathematical model of RBC dynamics that includes, for the first time, the spleen as a compartment capable of retaining large numbers of infected and uninfected RBCs in\n                    <jats:italic>Plasmodium falciparum</jats:italic>\n                    and\n                    <jats:italic>P. vivax</jats:italic>\n                    infections. By calibrating the model to the Papuan data, we demonstrate that the spleen plays a significant role in removing not only infected RBCs but also uninfected RBCs. Uninfected RBC retention in the spleen, attributable to malaria, is substantially higher than circulating RBC loss due to parasitisation, for infections by both\n                    <jats:italic>Plasmodium</jats:italic>\n                    species. In chronic infections, the ratio of circulating uninfected RBCs lost to splenic retention per circulating uninfected RBC lost to parasitisation is 17:1 for\n                    <jats:italic>P. falciparum</jats:italic>\n                    and 82:1 for\n                    <jats:italic>P. vivax</jats:italic>\n                    . These ratios are larger than previously published estimates for acute clinical infections.\n                  </jats:p>","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41525406","pmcid":"PMC12810929","openalex_id":"https://openalex.org/W7123353683","authors":[],"funders":[{"funder_name":"National Health and Medical Research Council","grant_id":"1196068","title":"Optimising treatment and prevention strategies to accelerate malaria elimination"},{"funder_name":"National Health and Medical Research Council","grant_id":"2024622","title":null},{"funder_name":"National Health and Medical Research Council","grant_id":"2018654","title":null},{"funder_name":"National Health and Medical Research Council","grant_id":"2025376","title":null},{"funder_name":"National Health and Medical Research Council","grant_id":"2019153","title":null},{"funder_name":"National Health and Medical Research Council","grant_id":"2016792","title":null},{"funder_name":"National Health and Medical Research Council","grant_id":"1037304","title":"Tropical Disease - immunity, pathogenesis and vaccine development: global translation"},{"funder_name":"Agence Nationale de la Recherche","grant_id":"ANR-24-CE17-2900-01","title":null}],"total_grants":8,"fwci":40.0919,"citation_percentile":0.9973658,"influential_citations":0,"citation_trend":[{"year":2026,"count":4}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1013865&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1013865&type=printable","host_type":"publisher"},{"url":"https://dx.plos.org/10.1371/journal.pcbi.1013865","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pcbi.1013865","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41525406","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12810929/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12810929","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12810929?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1101/2025.05.08.25327032","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/41525406/","host_type":""},{"url":"https://ora.ox.ac.uk/objects/uuid:8c6a1f0f-3e5d-4019-b83d-e6f17f17b20a","host_type":""}],"fields_of_study":["Malaria Research and Control","Blood properties and coagulation","Hematological disorders and diagnostics","0303 health sciences","03 medical and health sciences","Erythrocytes","Spleen","Humans","Malaria","Models, Biological","Malaria, Falciparum","Malaria, Vivax","Plasmodium falciparum","Animals","Indonesia","Plasmodium vivax"],"mesh_terms":["Animals","Erythrocytes","Humans","Indonesia","Malaria","Models, Biological","Plasmodium falciparum","Plasmodium vivax","Spleen","Splenectomy","Malaria, Falciparum","Malaria, Vivax","Computational Biology"],"keywords":["Spleen","Red blood cell","Plasmodium falciparum","Malaria","Splenectomy","Peripheral blood","Asymptomatic","Blood cell","Erythrocytes","Malaria, Vivax","Humans","Computational Biology","Models, Biological","Research Article"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-09T01:43:55.658983Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}