{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T12:55:32Z","timestamp":1772801732311,"version":"3.50.1"},"reference-count":27,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["302571\/2015-9"],"award-info":[{"award-number":["302571\/2015-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: Visceral leishmaniasis (VL) is a life-threatening protozoan disease prevalent in tropical and subtropical regions and a frequent coinfection among people living with HIV. Early identification of patients at high risk of death may reduce case-fatality. This study evaluated the post-test prognostic value of C-reactive protein (CRP) and interleukin-6 (IL-6) as biomarkers of mortality in VL. Methods: A retrospective hospital-based cohort of 101 VL patients was analyzed. CRP and IL-6 concentrations at admission were correlated with clinical findings, the Kala-Cal\u00ae prognostic score, and in-hospital mortality. Results: Eight patients died, most presenting with hemorrhagic manifestations. At admission, 87.1% of patients had both biomarkers above the predefined cut-offs. CRP and IL-6 levels were markedly elevated in patients with hemorrhage or fatal outcomes. The AUC was 0.85 for CRP and 0.87 for IL-6, with no significant difference between markers. Optimal prognostic cut-offs were 150 mg\/L for CRP and 90 pg\/mL for IL-6. Conclusions: In this sample, CRP and IL-6 showed good prognostic performance in VL. In patients with low initial clinical risk, positive biomarker results substantially increased the probability of death. When combined with Kala-Cal\u00ae, these markers may improve risk stratification and guide referral decisions.<\/jats:p>","DOI":"10.3390\/pathogens15030259","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T14:06:56Z","timestamp":1772460416000},"page":"259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of Systemic Inflammation as a Tool for Estimating the Risk of Death by Visceral Leishmaniasis"],"prefix":"10.3390","volume":"15","author":[{"given":"Ingridi de Souza","family":"Sene","sequence":"first","affiliation":[{"name":"LAPAC\u2014Patologia Cir\u00fargica e Molecular and Mestrado em Ci\u00eancias e Sa\u00fade, Centro de Ci\u00eancias das Sa\u00fade, Universidade Federal do Piau\u00ed, Teresina 64049-550, Brazil"},{"name":"Laboratory of Genomic Surveillance and Molecular Biology (LVGBM)\u2014Oswaldo Cruz Foundation-Piau\u00ed, Teresina 64049-550, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3109-7899","authenticated-orcid":false,"given":"Vladimir Costa","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Genomic Surveillance and Molecular Biology (LVGBM)\u2014Oswaldo Cruz Foundation-Piau\u00ed, Teresina 64049-550, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5978-1241","authenticated-orcid":false,"given":"D\u00e9bora Cavalcante","family":"Br\u00e1s","sequence":"additional","affiliation":[{"name":"Laboratory of Genomic Surveillance and Molecular Biology (LVGBM)\u2014Oswaldo Cruz Foundation-Piau\u00ed, Teresina 64049-550, Brazil"},{"name":"N\u00facleo de Tecnologia Farmac\u00eautica, Universidade Federal do Piau\u00ed, Teresina 64049-550, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7115-7978","authenticated-orcid":false,"given":"Dorcas Lamounier","family":"Costa","sequence":"additional","affiliation":[{"name":"LAPAC\u2014Patologia Cir\u00fargica e Molecular and Mestrado em Ci\u00eancias e Sa\u00fade, Centro de Ci\u00eancias das Sa\u00fade, Universidade Federal do Piau\u00ed, Teresina 64049-550, Brazil"},{"name":"Centro de Intelig\u00eancia em Agravos Tropicais Emergentes e Negligenciados (CIATEN) and Departamento Materno Infantil, Centro de Ci\u00eancias das Sa\u00fade, Universidade Federal do Piau\u00ed, Teresina 64049-550, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4584-8588","authenticated-orcid":false,"given":"Gabriel Reis","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Centro de Intelig\u00eancia em Agravos Tropicais Emergentes e Negligenciados (CIATEN) and Tropical Diseases Department of Microbiology, Infectious Disease and Immunology, Faculty of Medicine, University of Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7302-2006","authenticated-orcid":false,"given":"Carlos Henrique Nery","family":"Costa","sequence":"additional","affiliation":[{"name":"LAPAC\u2014Patologia Cir\u00fargica e Molecular and Mestrado em Ci\u00eancias e Sa\u00fade, Centro de Ci\u00eancias das Sa\u00fade, Universidade Federal do Piau\u00ed, Teresina 64049-550, Brazil"},{"name":"Centro de Intelig\u00eancia em Agravos Tropicais Emergentes e Negligenciados (CIATEN) and Departamento de Medicina Comunit\u00e1ria, Centro de Ci\u00eancias das Sa\u00fade, Universidade Federal do Piau\u00ed, Teresina 64049-550, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e02851","DOI":"10.7554\/eLife.02851","article-title":"Global Distribution Maps of the Leishmaniases","volume":"3","author":"Pigott","year":"2014","journal-title":"Elife"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.4103\/0972-9062.184819","article-title":"Visceral Leishmaniasis Epidemiologic Evolution in Timeframes, Based on Demographic Changes and Scientific Achievements in Brazil","volume":"53","author":"Conti","year":"2016","journal-title":"J. Vector Borne Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Akuffo, H., Costa, C., van Griensven, J., Burza, S., Moreno, J., and Herrero, M. (2018). New Insights into Leishmaniasis in the Immunosuppressed. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006375"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1590\/0037-8682-0258-2016","article-title":"Predicting Death from Kala-Azar: Construction, Development, and Validation of a Score Set and Accompanying Software","volume":"49","author":"Costa","year":"2016","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Alvar, J., V\u00e9lez, I.D., Bern, C., Herrero, M., Desjeux, P., Cano, J., Jannin, J., and den Boer, M. (2012). Leishmaniasis Worldwide and Global Estimates of Its Incidence. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035671"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1590\/S0037-86822010000400010","article-title":"Is Severe Visceral Leishmaniasis a Systemic Inflammatory Response Syndrome? A Case Control Study","volume":"43","author":"Costa","year":"2010","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1179\/2047773213Y.0000000078","article-title":"Serum Cytokines Associated with Severity and Complications of Kala-Azar","volume":"107","author":"Costa","year":"2013","journal-title":"Pathog. Glob. Health"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"dos Santos, P.L., de Oliveira, F.A., Santos, M.L.B., Cunha, L.C.S., Lino, M.T.B., de Oliveira, M.F.S., Bomfim, M.O.M., Silva, A.M., de Moura, T.R., and de Jesus, A.R. (2016). The Severity of Visceral Leishmaniasis Correlates with Elevated Levels of Serum IL-6, IL-27 and SCD14. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004375"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Tong-Minh, K., Welten, I., Endeman, H., Hagenaars, T., Ramakers, C., Gommers, D., van Gorp, E., and van der Does, Y. (2021). Predicting Mortality in Adult Patients with Sepsis in the Emergency Department by Using Combinations of Biomarkers and Clinical Scoring Systems: A Systematic Review. BMC Emerg. Med., 21.","DOI":"10.1186\/s12873-021-00461-z"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5852","DOI":"10.1002\/jcb.27870","article-title":"The Diagnostic Accuracy of Procalcitonin and C-reactive Protein for Sepsis: A Systematic Review and Meta-analysis","volume":"120","author":"Tan","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0733-8651(03)00079-1","article-title":"C-Reactive Protein, Inflammation, and Coronary Risk","volume":"21","author":"Ridker","year":"2003","journal-title":"Cardiol. Clin."},{"key":"ref_12","unstructured":"Nehring, S.M., Goyal, A., and Patel, B.C. (2023). C Reactive Protein, StatPearls."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/ni.3153","article-title":"IL-6 as a Keystone Cytokine in Health and Disease","volume":"16","author":"Hunter","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Cota, G., Erber, A.C., Schernhammer, E., and Sim\u00f5es, T.C. (2021). Inequalities of Visceral Leishmaniasis Case-Fatality in Brazil: A Multilevel Modeling Considering Space, Time, Individual and Contextual Factors. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009567"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lindoso, J.A., Cota, G.F., da Cruz, A.M., Goto, H., Maia-Elkhoury, A.N.S., Romero, G.A.S., de Sousa-Gomes, M.L., Santos-Oliveira, J.R., and Rabello, A. (2014). Visceral Leishmaniasis and HIV Coinfection in Latin America. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0003136"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Veas, F. (2011). Acute Phase Proteins: Structure and Function Relationship. Acute Phase Proteins-Regulation and Functions of Acute Phase Proteins, InTech.","DOI":"10.5772\/756"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1172\/JCI200318921","article-title":"C-Reactive Protein: A Critical Update","volume":"111","author":"Pepys","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wilhelm, G., Mertowska, P., Mertowski, S., Przysucha, A., Stru\u017cyna, J., Grywalska, E., and Torres, K. (2023). The Crossroads of the Coagulation System and the Immune System: Interactions and Connections. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612563"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"a016295","DOI":"10.1101\/cshperspect.a016295","article-title":"IL-6 in Inflammation, Immunity, and Disease","volume":"6","author":"Tanaka","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s13071-024-06151-6","article-title":"The Spleen Is the Graveyard of CD4+ Cells in Patients with Immunological Failure of Visceral Leishmaniasis and AIDS","volume":"17","author":"Reinaldo","year":"2024","journal-title":"Parasit. Vectors"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S41","DOI":"10.1016\/j.htct.2023.10.006","article-title":"Association between Clinical Outcomes, Peripheral Blood and Cytomorphologic Features of Bone Marrow in Visceral Leishmaniasis","volume":"46","author":"Pinheiro","year":"2024","journal-title":"Hematol. Transfus. Cell Ther."},{"key":"ref_22","first-page":"371","article-title":"Haematological Investigations in Visceral Leishmaniasis","volume":"38","author":"Kager","year":"1986","journal-title":"Trop. Geogr. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e70014","DOI":"10.1111\/pim.70014","article-title":"Relationship Between Hepcidin, Iron Metabolism, Inflammation and Hypersplenism in Anaemia of Kala-Azar","volume":"47","author":"Freitas","year":"2025","journal-title":"Parasite Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1097\/SHK.0b013e3182a64682","article-title":"The Epidemiology of Acute Respiratory Distress Syndrome in Patients Presenting to the Emergency Department with Severe Sepsis","volume":"40","author":"Mikkelsen","year":"2013","journal-title":"Shock"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1097\/CCM.0000000000002321","article-title":"Serial Procalcitonin Predicts Mortality in Severe Sepsis Patients: Results From the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study","volume":"45","author":"Schuetz","year":"2017","journal-title":"Crit. Care Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lima, S.S., Braz, D.C., Silva, V.C., de Jesus Cardoso Farias Pereira, T., da Costa Ara\u00fajo Alves Carvalho, L.K., Costa, D.L., and Costa, C.H.N. (2025). Interleukin-8 Predicts Fatal Kala-Azar: A Case\u2013Control Study. Trop. Med. Infect. Dis., 10.","DOI":"10.20944\/preprints202507.2602.v1"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1017\/S0031182024001598","article-title":"Genome-Wide Association Study Analysis of Single Nucleotide Variants in L. infantum Associated with IL-6 Inflammatory Response in Visceral Leishmaniasis","volume":"152","author":"Carvalho","year":"2025","journal-title":"Parasitology"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/3\/259\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T09:46:17Z","timestamp":1772790377000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/3\/259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,28]]},"references-count":27,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["pathogens15030259"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15030259","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,28]]}}}