{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T15:28:21Z","timestamp":1778858901929,"version":"3.51.4"},"reference-count":75,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Pesquisas\u2014CNPq","doi-asserted-by":"publisher","award":["475102\/2011-8"],"award-info":[{"award-number":["475102\/2011-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Kala-azar is a protracted disease caused by the protozoan Leishmania infantum (zoonotic) or L. donovani (anthroponotic), transmitted by sandflies. Patients present with fever, anemia, and hepatosplenomegaly, potentially progressing to hemorrhaging, secondary infections, and death. Its pathogenesis is linked to an exaggerated cytokine response. We studied 72 hospitalized patients, analyzing clinical data and outcomes in relation to L. infantum DNA loads in blood and bone marrow, and plasma concentrations of IL-1\u03b2, IL-6, IL-8, IL-10, IL-12, TNF-\u03b1, and TGF-\u03b2. Cytokine levels were found to be elevated. L. infantum kDNA loads in blood and bone marrow were strongly correlated and increased with disease duration. Higher parasite loads were observed in men, adults, and HIV-infected patients, and they were significantly associated with mortality. IL-6 was independently linked to sepsis. In multivariate analysis, IL-12 was the only cytokine inversely associated with blood parasite load. Parasite load, but not cytokine levels, correlated with disease severity, suggesting additional mechanisms drive progression. IL-12 appears to limit parasitemia, indicating a weak, persistent adaptive immune response that is ultimately overwhelmed by a progressive, inefficient, and inflammatory innate response.<\/jats:p>","DOI":"10.3390\/pathogens14070615","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T08:13:56Z","timestamp":1750407236000},"page":"615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immune\u2013Pathological Correlates of Disease Severity in New-World Kala-Azar: The Role of Parasite Load and Cytokine Profiles"],"prefix":"10.3390","volume":"14","author":[{"given":"Ingridi de Souza","family":"Sene","sequence":"first","affiliation":[{"name":"Laboratory of Leishmaniasis, Institute of Tropical Medicine Natan Portella, Teresina 64002-510, 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":"Laboratory of Leishmaniasis, Institute of Tropical Medicine Natan Portella, Teresina 64002-510, Brazil"},{"name":"Maternal and Child Department, Federal University of Piau\u00ed, Teresina 64049-550, Brazil"},{"name":"Intelligence Center for Emerging and Tropical Diseases (CIATEN), Teresina 64049-550, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele Alves","family":"Zacarias","sequence":"additional","affiliation":[{"name":"Laboratory of Leishmaniasis, Institute of Tropical Medicine Natan Portella, Teresina 64002-510, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jailthon Carlos","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Leishmaniasis, Institute of Tropical Medicine Natan Portella, Teresina 64002-510, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel Reis","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Intelligence Center for Emerging and Tropical Diseases (CIATEN), Teresina 64049-550, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela Rodrigues","family":"Andrade","sequence":"additional","affiliation":[{"name":"Integrated Laboratory of Microbiology and Immunoregulation, CPqGM-Fiocruz-Bahia, Salvador 40296-710, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge Clar\u00eancio de Sousa","family":"Andrade","sequence":"additional","affiliation":[{"name":"Integrated Laboratory of Microbiology and Immunoregulation, CPqGM-Fiocruz-Bahia, Salvador 40296-710, Brazil"}],"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":"Laboratory of Leishmaniasis, Institute of Tropical Medicine Natan Portella, Teresina 64002-510, Brazil"},{"name":"Intelligence Center for Emerging and Tropical Diseases (CIATEN), Teresina 64049-550, Brazil"},{"name":"Department of Community Medicine, Federal University of Piau\u00ed, Teresina 64049-550, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1093\/infdis\/162.6.1354","article-title":"Bacterial Infections in Patients with Visceral Leishmaniasis","volume":"162","author":"Andrade","year":"1990","journal-title":"J. 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