{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T19:36:57Z","timestamp":1794339417323,"version":"4.9.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-98154-1","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T08:48:53Z","timestamp":1745484533000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Host biomarkers and parasite biomass are associated with severe malaria in Mozambican children: a case\u2013control study"],"prefix":"10.1038","volume":"15","author":[{"given":"Rosauro","family":"Varo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Sitoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lola","family":"Madrid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Aide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inocencia","family":"Cuamba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An\u00e9lsio","family":"Cossa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenjerai","family":"Jairoce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Barrios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Marti\u00e1\u00f1ez-Vendrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00faria","family":"Balanza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pau","family":"Cister\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Ouchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lloren\u00e7","family":"Quint\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie M.","family":"Crowley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himanshu","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C.","family":"Kain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Mayor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quique","family":"Bassat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"98154_CR1","unstructured":"World malaria report 2023. (Geneva, 2023)."},{"issue":"Suppl 1","key":"98154_CR2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/tmi.12313_2","volume":"19","author":"WHO","year":"2014","unstructured":"WHO. Severe malaria. Trop. Med. Int. Health 19(Suppl 1), 7\u2013131. https:\/\/doi.org\/10.1111\/tmi.12313_2 (2014).","journal-title":"Trop. Med. Int. Health"},{"key":"98154_CR3","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/415673a","volume":"415","author":"LH Miller","year":"2002","unstructured":"Miller, L. H., Baruch, D. I., Marsh, K. & Doumbo, O. K. The pathogenic basis of malaria. Nature 415, 673\u2013679. https:\/\/doi.org\/10.1038\/415673a (2002).","journal-title":"Nature"},{"key":"98154_CR4","doi-asserted-by":"publisher","first-page":"211ps218","DOI":"10.1126\/scitranslmed.3007432","volume":"5","author":"AJ Cunnington","year":"2013","unstructured":"Cunnington, A. J., Walther, M. & Riley, E. M. Piecing together the puzzle of severe malaria. Sci. Transl. Med. 5, 211ps218. https:\/\/doi.org\/10.1126\/scitranslmed.3007432 (2013).","journal-title":"Sci. Transl. Med."},{"key":"98154_CR5","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.trstmh.2004.11.014","volume":"99","author":"V Desakorn","year":"2005","unstructured":"Desakorn, V. et al. Stage-dependent production and release of histidine-rich protein 2 by Plasmodium falciparum. Trans. Roy. Soc. Trop. Med. Hyg. 99, 517\u2013524. https:\/\/doi.org\/10.1016\/j.trstmh.2004.11.014 (2005).","journal-title":"Trans. Roy. Soc. Trop. Med. Hyg."},{"key":"98154_CR6","doi-asserted-by":"publisher","first-page":"e204","DOI":"10.1371\/journal.pmed.0020204","volume":"2","author":"AM Dondorp","year":"2005","unstructured":"Dondorp, A. M. et al. Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. PLoS Med. 2, e204. https:\/\/doi.org\/10.1371\/journal.pmed.0020204 (2005).","journal-title":"PLoS Med."},{"key":"98154_CR7","doi-asserted-by":"publisher","first-page":"e35985","DOI":"10.1371\/journal.pone.0035985","volume":"7","author":"MP Rubach","year":"2012","unstructured":"Rubach, M. P. et al. Plasma Plasmodium falciparum histidine-rich protein-2 concentrations are associated with malaria severity and mortality in Tanzanian children. PLoS ONE 7, e35985. https:\/\/doi.org\/10.1371\/journal.pone.0035985 (2012).","journal-title":"PLoS ONE"},{"key":"98154_CR8","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1093\/infdis\/jis371","volume":"206","author":"KB Seydel","year":"2012","unstructured":"Seydel, K. B. et al. Plasma concentrations of parasite histidine-rich protein 2 distinguish between retinopathy-positive and retinopathy-negative cerebral malaria in Malawian children. J. Infect. Dis. 206, 309\u2013318. https:\/\/doi.org\/10.1093\/infdis\/jis371 (2012).","journal-title":"J. Infect. Dis."},{"key":"98154_CR9","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1093\/infdis\/jit500","volume":"209","author":"SM Kariuki","year":"2014","unstructured":"Kariuki, S. M. et al. Value of Plasmodium falciparum histidine-rich protein 2 level and malaria retinopathy in distinguishing cerebral malaria from other acute encephalopathies in Kenyan children. J. Infect. Dis. 209, 600\u2013609. https:\/\/doi.org\/10.1093\/infdis\/jit500 (2014).","journal-title":"J. Infect. Dis."},{"key":"98154_CR10","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1093\/cid\/cix592","volume":"65","author":"R Boyce","year":"2017","unstructured":"Boyce, R. et al. Use of a dual-antigen rapid diagnostic test to screen children for severe Plasmodium falciparum malaria in a high-transmission, resource-limited setting. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 65, 1509\u20131515. https:\/\/doi.org\/10.1093\/cid\/cix592 (2017).","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"98154_CR11","doi-asserted-by":"publisher","first-page":"ofx151","DOI":"10.1093\/ofid\/ofx151","volume":"4","author":"GS Park","year":"2017","unstructured":"Park, G. S. et al. Plasmodium falciparum histidine-rich protein-2 plasma concentrations are higher in retinopathy-negative cerebral malaria than in severe malarial anemia. Open Forum Infect. Dis. 4, ofx151. https:\/\/doi.org\/10.1093\/ofid\/ofx151 (2017).","journal-title":"Open Forum Infect. Dis."},{"key":"98154_CR12","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1093\/infdis\/jis675","volume":"207","author":"IC Hendriksen","year":"2013","unstructured":"Hendriksen, I. C. et al. Defining falciparum-malaria-attributable severe febrile illness in moderate-to-high transmission settings on the basis of plasma PfHRP2 concentration. J. Infect. Dis. 207, 351\u2013361. https:\/\/doi.org\/10.1093\/infdis\/jis675 (2013).","journal-title":"J. Infect. Dis."},{"key":"98154_CR13","doi-asserted-by":"publisher","first-page":"e1001297","DOI":"10.1371\/journal.pmed.1001297","volume":"9","author":"IC Hendriksen","year":"2012","unstructured":"Hendriksen, I. C. et al. Diagnosing severe falciparum malaria in parasitaemic African children: A prospective evaluation of plasma PfHRP2 measurement. PLoS Med. 9, e1001297. https:\/\/doi.org\/10.1371\/journal.pmed.1001297 (2012).","journal-title":"PLoS Med."},{"key":"98154_CR14","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1093\/cid\/cis590","volume":"55","author":"IC Hendriksen","year":"2012","unstructured":"Hendriksen, I. C. et al. Diagnosis, clinical presentation, and in-hospital mortality of severe malaria in HIV-coinfected children and adults in Mozambique. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 55, 1144\u20131153. https:\/\/doi.org\/10.1093\/cid\/cis590 (2012).","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"98154_CR15","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1128\/mBio.00217-19","volume":"10","author":"F Duffy","year":"2019","unstructured":"Duffy, F. et al. Meta-analysis of Plasmodium falciparum var signatures contributing to severe malaria in African children and Indian adults. MBio 10, 10\u20131128. https:\/\/doi.org\/10.1128\/mBio.00217-19 (2019).","journal-title":"MBio"},{"key":"98154_CR16","doi-asserted-by":"publisher","first-page":"2150456","DOI":"10.1080\/21505594.2022.2150456","volume":"14","author":"IS Walker","year":"2023","unstructured":"Walker, I. S. & Rogerson, S. J. Pathogenicity and virulence of malaria: Sticky problems and tricky solutions. Virulence 14, 2150456. https:\/\/doi.org\/10.1080\/21505594.2022.2150456 (2023).","journal-title":"Virulence"},{"key":"98154_CR17","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1186\/s12936-016-1624-8","volume":"15","author":"GM de Jong","year":"2016","unstructured":"de Jong, G. M., Slager, J. J., Verbon, A., van Hellemond, J. J. & van Genderen, P. J. Systematic review of the role of angiopoietin-1 and angiopoietin-2 in Plasmodium species infections: Biomarkers or therapeutic targets?. Malar. J. 15, 581. https:\/\/doi.org\/10.1186\/s12936-016-1624-8 (2016).","journal-title":"Malar. J."},{"key":"98154_CR18","doi-asserted-by":"publisher","first-page":"6832","DOI":"10.1038\/s41467-021-27215-6","volume":"12","author":"A Leligdowicz","year":"2021","unstructured":"Leligdowicz, A. et al. Risk-stratification of febrile African children at risk of sepsis using sTREM-1 as basis for a rapid triage test. Nat. Commun. 12, 6832. https:\/\/doi.org\/10.1038\/s41467-021-27215-6 (2021).","journal-title":"Nat. Commun."},{"key":"98154_CR19","doi-asserted-by":"publisher","first-page":"e4912","DOI":"10.1371\/journal.pone.0004912","volume":"4","author":"FE Lovegrove","year":"2009","unstructured":"Lovegrove, F. E. et al. Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children. PLoS ONE 4, e4912. https:\/\/doi.org\/10.1371\/journal.pone.0004912 (2009).","journal-title":"PLoS ONE"},{"key":"98154_CR20","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1186\/1475-2875-8-295","volume":"8","author":"AL Conroy","year":"2009","unstructured":"Conroy, A. L. et al. Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral) malaria from uncomplicated malaria. Malar. J. 8, 295. https:\/\/doi.org\/10.1186\/1475-2875-8-295 (2009).","journal-title":"Malar. J."},{"key":"98154_CR21","doi-asserted-by":"publisher","first-page":"e15291","DOI":"10.1371\/journal.pone.0015291","volume":"5","author":"AL Conroy","year":"2010","unstructured":"Conroy, A. L. et al. Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: A retrospective case-control study. PLoS ONE 5, e15291. https:\/\/doi.org\/10.1371\/journal.pone.0015291 (2010).","journal-title":"PLoS ONE"},{"key":"98154_CR22","doi-asserted-by":"publisher","first-page":"e17440","DOI":"10.1371\/journal.pone.0017440","volume":"6","author":"LK Erdman","year":"2011","unstructured":"Erdman, L. K. et al. Combinations of host biomarkers predict mortality among Ugandan children with severe malaria: A retrospective case-control study. PLoS ONE 6, e17440. https:\/\/doi.org\/10.1371\/journal.pone.0017440 (2011).","journal-title":"PLoS ONE"},{"key":"98154_CR23","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1097\/CCM.0b013e3182373157","volume":"40","author":"AL Conroy","year":"2012","unstructured":"Conroy, A. L. et al. Angiopoietin-2 levels are associated with retinopathy and predict mortality in Malawian children with cerebral malaria: A retrospective case-control study*. Crit. Care Med. 40, 952\u2013959. https:\/\/doi.org\/10.1097\/CCM.0b013e3182373157 (2012).","journal-title":"Crit. Care Med."},{"key":"98154_CR24","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1093\/infdis\/jiu156","volume":"210","author":"JB Weinberg","year":"2014","unstructured":"Weinberg, J. B. et al. Dimethylarginines: Endogenous inhibitors of nitric oxide synthesis in children with falciparum malaria. J. Infect. Dis. 210, 913\u2013922. https:\/\/doi.org\/10.1093\/infdis\/jiu156 (2014).","journal-title":"J. Infect. Dis."},{"key":"98154_CR25","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/1471-2334-14-170","volume":"14","author":"AI Abdi","year":"2014","unstructured":"Abdi, A. I. et al. Plasmodium falciparum antigenic variation: relationships between widespread endothelial activation, parasite PfEMP1 expression and severe malaria. BMC Infect. Dis. 14, 170. https:\/\/doi.org\/10.1186\/1471-2334-14-170 (2014).","journal-title":"BMC Infect. Dis."},{"key":"98154_CR26","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1093\/infdis\/jit419","volume":"209","author":"CA Moxon","year":"2014","unstructured":"Moxon, C. A. et al. Persistent endothelial activation and inflammation after Plasmodium falciparum infection in Malawian children. J. Infect. Dis. 209, 610\u2013615. https:\/\/doi.org\/10.1093\/infdis\/jit419 (2014).","journal-title":"J. Infect. Dis."},{"key":"98154_CR27","doi-asserted-by":"publisher","first-page":"4674","DOI":"10.1128\/iai.05161-11","volume":"79","author":"JM Ong\u2019echa","year":"2011","unstructured":"Ong\u2019echa, J. M., Davenport, G. C., Vulule, J. M., Hittner, J. B. & Perkins, D. J. Identification of inflammatory biomarkers for pediatric malarial anemia severity using novel statistical methods. Infect. Immun. 79, 4674\u20134680. https:\/\/doi.org\/10.1128\/iai.05161-11 (2011).","journal-title":"Infect. Immun."},{"key":"98154_CR28","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1186\/1475-2875-11-181","volume":"11","author":"E Rovira-Vallbona","year":"2012","unstructured":"Rovira-Vallbona, E. et al. Low antibodies against Plasmodium falciparum and imbalanced pro-inflammatory cytokines are associated with severe malaria in Mozambican children: a case-control study. Malar. J. 11, 181. https:\/\/doi.org\/10.1186\/1475-2875-11-181 (2012).","journal-title":"Malar. J."},{"key":"98154_CR29","first-page":"9","volume":"6","author":"SL Oyegue-Liabagui","year":"2017","unstructured":"Oyegue-Liabagui, S. L. et al. Pro- and anti-inflammatory cytokines in children with malaria in Franceville, Gabon. Am. J. Clin. Exp. Immunol. 6, 9\u201320 (2017).","journal-title":"Am. J. Clin. Exp. Immunol."},{"key":"98154_CR30","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1111\/tmi.12787","volume":"21","author":"S Adukpo","year":"2016","unstructured":"Adukpo, S. et al. Triggering receptor expressed on myeloid cells 1 (TREM-1) and cytokine gene variants in complicated and uncomplicated malaria. Trop. Med. Int. Health 21, 1592\u20131601. https:\/\/doi.org\/10.1111\/tmi.12787 (2016).","journal-title":"Trop. Med. Int. Health"},{"key":"98154_CR31","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1093\/ofid\/ofw134","volume":"3","author":"AL Conroy","year":"2016","unstructured":"Conroy, A. L. et al. Host biomarkers are associated with response to therapy and long-term mortality in pediatric severe malaria. Open Forum Infect. Dis. 3, 134. https:\/\/doi.org\/10.1093\/ofid\/ofw134 (2016).","journal-title":"Open Forum Infect. Dis."},{"key":"98154_CR32","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/1475-2875-6-147","volume":"6","author":"HB Armah","year":"2007","unstructured":"Armah, H. B. et al. Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children. Malar. J. 6, 147. https:\/\/doi.org\/10.1186\/1475-2875-6-147 (2007).","journal-title":"Malar. J."},{"key":"98154_CR33","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1097\/inf.0000000000001382","volume":"36","author":"CR McDonald","year":"2017","unstructured":"McDonald, C. R. et al. Brain-derived neurotrophic factor is associated with disease severity and clinical outcome in Ugandan children admitted to hospital with severe malaria. Pediatr. Infect. Dis. J. 36, 146\u2013150. https:\/\/doi.org\/10.1097\/inf.0000000000001382 (2017).","journal-title":"Pediatr. Infect. Dis. J."},{"key":"98154_CR34","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1093\/infdis\/jiad561","volume":"229","author":"I Mufumba","year":"2024","unstructured":"Mufumba, I. et al. sTREM-1: A biomarker of mortality in severe malaria impacted by acute kidney injury. J. Infect. Dis. 229, 936\u2013946. https:\/\/doi.org\/10.1093\/infdis\/jiad561 (2024).","journal-title":"J. Infect. Dis."},{"key":"98154_CR35","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s13054-015-0773-4","volume":"19","author":"AL Conroy","year":"2015","unstructured":"Conroy, A. L. et al. Prospective validation of pediatric disease severity scores to predict mortality in Ugandan children presenting with malaria and non-malaria febrile illness. Crit. Care (London, England) 19, 47. https:\/\/doi.org\/10.1186\/s13054-015-0773-4 (2015).","journal-title":"Crit. Care (London, England)"},{"key":"98154_CR36","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.1086\/648409","volume":"200","author":"R Helbok","year":"2009","unstructured":"Helbok, R. et al. The Lambarene organ dysfunction score (LODS) is a simple clinical predictor of fatal malaria in African children. J. Infect. Dis. 200, 1834\u20131841. https:\/\/doi.org\/10.1086\/648409 (2009).","journal-title":"J. Infect. Dis."},{"key":"98154_CR37","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1093\/ije\/dyt148","volume":"42","author":"C Sacoor","year":"2013","unstructured":"Sacoor, C. et al. Profile: Manhica health research centre (Manhica HDSS). Int. J. Epidemiol. 42, 1309\u20131318. https:\/\/doi.org\/10.1093\/ije\/dyt148 (2013).","journal-title":"Int. J. Epidemiol."},{"key":"98154_CR38","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/1475-2875-7-36","volume":"7","author":"C Guinovart","year":"2008","unstructured":"Guinovart, C. et al. Malaria in rural Mozambique. Part I: Children attending the outpatient clinic. Malar. J. 7, 36. https:\/\/doi.org\/10.1186\/1475-2875-7-36 (2008).","journal-title":"Malar. J."},{"key":"98154_CR39","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/1475-2875-7-37","volume":"7","author":"Q Bassat","year":"2008","unstructured":"Bassat, Q. et al. Malaria in rural Mozambique. Part II: Children admitted to hospital. Malar. J. 7, 37. https:\/\/doi.org\/10.1186\/1475-2875-7-37 (2008).","journal-title":"Malar. J."},{"key":"98154_CR40","doi-asserted-by":"publisher","first-page":"e873","DOI":"10.1016\/s2214-109x(22)00125-5","volume":"10","author":"C Guinovart","year":"2022","unstructured":"Guinovart, C. et al. The epidemiology of severe malaria at Manhi\u00e7a district hospital, Mozambique: A retrospective analysis of 20 years of malaria admissions surveillance data. Lancet Glob. Health 10, e873\u2013e881. https:\/\/doi.org\/10.1016\/s2214-109x(22)00125-5 (2022).","journal-title":"Lancet Glob. Health"},{"key":"98154_CR41","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1093\/cid\/ciz419","volume":"70","author":"M Richard-Greenblatt","year":"2020","unstructured":"Richard-Greenblatt, M. et al. Prognostic accuracy of soluble triggering receptor expressed on myeloid cells (sTREM-1)-based algorithms in febrile adults presenting to Tanzanian outpatient clinics. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 70, 1304\u20131312. https:\/\/doi.org\/10.1093\/cid\/ciz419 (2020).","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"98154_CR42","unstructured":"Malaria, P. N. d. C. d. (ed Ministry of Health) (Maputo, 2011)."},{"key":"98154_CR43","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1111\/j.1365-3156.2009.02326.x","volume":"14","author":"Q Bassat","year":"2009","unstructured":"Bassat, Q. et al. Severe malaria and concomitant bacteraemia in children admitted to a rural Mozambican hospital. Trop. Med. Int. Health 14, 1011\u20131019. https:\/\/doi.org\/10.1111\/j.1365-3156.2009.02326.x (2009).","journal-title":"Trop. Med. Int. Health"},{"key":"98154_CR44","unstructured":"WHO. Basic Laboratory Methods in Medical Parasitology. (1999)."},{"key":"98154_CR45","doi-asserted-by":"publisher","first-page":"599","DOI":"10.4269\/ajtmh.2001.65.599","volume":"65","author":"T Planche","year":"2001","unstructured":"Planche, T. et al. Comparison of methods for the rapid laboratory assessment of children with malaria. Am. J. Trop. Med. Hyg. 65, 599\u2013602. https:\/\/doi.org\/10.4269\/ajtmh.2001.65.599 (2001).","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"98154_CR46","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/S0166-6851(01)00379-6","volume":"118","author":"CC Hermsen","year":"2001","unstructured":"Hermsen, C. C. et al. Detection of Plasmodium falciparum malaria parasites in vivo by real-time quantitative PCR. Mol. Biochem. Parasitol. 118, 247\u2013251 (2001).","journal-title":"Mol. Biochem. Parasitol."},{"key":"98154_CR47","doi-asserted-by":"publisher","first-page":"358ra128","DOI":"10.1126\/scitranslmed.aaf6812","volume":"8","author":"SJ Higgins","year":"2016","unstructured":"Higgins, S. J. et al. Dysregulation of angiopoietin-1 plays a mechanistic role in the pathogenesis of cerebral malaria. Sci. Transl. Med. 8, 358ra128. https:\/\/doi.org\/10.1126\/scitranslmed.aaf6812 (2016).","journal-title":"Sci. Transl. Med."},{"key":"98154_CR48","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.ijid.2023.11.031","volume":"139","author":"R Varo","year":"2024","unstructured":"Varo, R. et al. Adjunctive rosiglitazone treatment for severe pediatric malaria: A randomized placebo-controlled trial in Mozambican children. Int. J. Infect. Dis. 139, 34\u201340. https:\/\/doi.org\/10.1016\/j.ijid.2023.11.031 (2024).","journal-title":"Int. J. Infect. Dis."},{"key":"98154_CR49","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1186\/s12936-015-0946-2","volume":"14","author":"MT Hawkes","year":"2015","unstructured":"Hawkes, M. T. et al. Inhaled nitric oxide as adjunctive therapy for severe malaria: A randomized controlled trial. Malar. J. 14, 421. https:\/\/doi.org\/10.1186\/s12936-015-0946-2 (2015).","journal-title":"Malar. J."},{"key":"98154_CR50","doi-asserted-by":"publisher","first-page":"5630","DOI":"10.1128\/iai.72.10.5630-5637.2004","volume":"72","author":"KE Lyke","year":"2004","unstructured":"Lyke, K. E. et al. Serum levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6, IL-8, IL-10, tumor necrosis factor alpha, and IL-12(p70) in Malian children with severe Plasmodium falciparum malaria and matched uncomplicated malaria or healthy controls. Infect. Immun. 72, 5630\u20135637. https:\/\/doi.org\/10.1128\/iai.72.10.5630-5637.2004 (2004).","journal-title":"Infect. Immun."},{"key":"98154_CR51","doi-asserted-by":"publisher","first-page":"e12438","DOI":"10.1111\/pim.12438","volume":"39","author":"E Shabani","year":"2017","unstructured":"Shabani, E. et al. Elevated cerebrospinal fluid tumour necrosis factor is associated with acute and long-term neurocognitive impairment in cerebral malaria. Parasite Immunol. 39, e12438. https:\/\/doi.org\/10.1111\/pim.12438 (2017).","journal-title":"Parasite Immunol."},{"key":"98154_CR52","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s12936-018-2195-7","volume":"17","author":"R Varo","year":"2018","unstructured":"Varo, R. et al. Adjunctive therapy for severe malaria: A review and critical appraisal. Malar. J. 17, 47. https:\/\/doi.org\/10.1186\/s12936-018-2195-7 (2018).","journal-title":"Malar. J."},{"key":"98154_CR53","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1038\/ni1411","volume":"7","author":"J Klesney-Tait","year":"2006","unstructured":"Klesney-Tait, J., Turnbull, I. R. & Colonna, M. The TREM receptor family and signal integration. Nat. Immunol. 7, 1266\u20131273. https:\/\/doi.org\/10.1038\/ni1411 (2006).","journal-title":"Nat. Immunol."},{"key":"98154_CR54","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1186\/s12936-016-1378-3","volume":"15","author":"R Tahar","year":"2016","unstructured":"Tahar, R. et al. Plasma levels of eight different mediators and their potential as biomarkers of various clinical malaria conditions in African children. Malar. J. 15, 337. https:\/\/doi.org\/10.1186\/s12936-016-1378-3 (2016).","journal-title":"Malar. J."},{"key":"98154_CR55","doi-asserted-by":"publisher","first-page":"e0001553","DOI":"10.1371\/journal.pgph.0001553","volume":"3","author":"N Balanza","year":"2023","unstructured":"Balanza, N. et al. Prognostic accuracy of biomarkers of immune and endothelial activation in Mozambican children hospitalized with pneumonia. PLOS Glob. Public Health 3, e0001553. https:\/\/doi.org\/10.1371\/journal.pgph.0001553 (2023).","journal-title":"PLOS Glob. Public Health"},{"key":"98154_CR56","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1186\/s12936-015-0900-3","volume":"14","author":"I Sinha","year":"2015","unstructured":"Sinha, I., Ekapirat, N., Dondorp, A. M. & Woodrow, C. J. Use of a rapid test to assess plasma Plasmodium falciparum HRP2 and guide management of severe febrile illness. Malar. J. 14, 362. https:\/\/doi.org\/10.1186\/s12936-015-0900-3 (2015).","journal-title":"Malar. J."},{"key":"98154_CR57","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1186\/s12936-017-2061-z","volume":"16","author":"H Gupta","year":"2017","unstructured":"Gupta, H. et al. Molecular surveillance of pfhrp2 and pfhrp3 deletions in Plasmodium falciparum isolates from Mozambique. Malar. J. 16, 416. https:\/\/doi.org\/10.1186\/s12936-017-2061-z (2017).","journal-title":"Malar. J."},{"key":"98154_CR58","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1128\/jcm.00875-19","volume":"57","author":"MM Plucinski","year":"2019","unstructured":"Plucinski, M. M. et al. Assessing performance of HRP2 antigen detection for malaria diagnosis in Mozambique. J. Clin. Microbiol. 57, 10\u20131128. https:\/\/doi.org\/10.1128\/jcm.00875-19 (2019).","journal-title":"J. Clin. Microbiol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-98154-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-98154-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-98154-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T20:02:25Z","timestamp":1745870545000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-98154-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,24]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["98154"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-98154-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,24]]},"assertion":[{"value":"24 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This work was partially funded by the Departament d\u2019Universitats i Recerca de la Generalitat de Catalunya (AGAUR; 2021 SGR 01517). We also acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the \u201cCentro de Excelencia Severo Ochoa 2019\u20132023\u201d program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. This research is part of the ISGlobal\u2019s Program on the Molecular Mechanisms of Malaria which is partially supported by the Fundaci\u00f3n Ram\u00f3n Areces. CISM is supported by the Government of Mozambique and the Spanish Agency for International Development (AECID). NB is supported by an FPU predoctoral fellowship from the Spanish Ministry of Universities (FPU18\/04260). The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. The authors declare not having financial competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14262"}}