Immune–Pathological Correlates of Disease Severity in New-World Kala-Azar: The Role of Parasite Load and Cytokine Profiles

Immune–Pathological Correlates of Disease Severity in New-World Kala-Azar: The Role of Parasite Load and Cytokine Profiles

Kala-azar is a protracted disease caused by the protozoan <i>Leishmania infantum</i> (zoonotic) or <i>L. donovani</i> (anthroponotic), transmitted by sandflies. Patients present with fever, anemia, and hepatosplenomegaly, potentially progressing to hemorrhaging, secondary inf...

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Main Authors: Ingridi de Souza Sene, Dorcas Lamounier Costa, Daniele Alves Zacarias, Jailthon Carlos dos Santos, Gabriel Reis Ferreira, Daniela Rodrigues Andrade, Jorge Clarêncio de Sousa Andrade, Carlos Henrique Nery Costa
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Pathogens
Subjects:
visceral leishmaniasis
<i>Leishmania infantum</i>
hemorrhage
sepsis
HIV-coinfection
mortality
Online Access:https://www.mdpi.com/2076-0817/14/7/615
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Summary:Kala-azar is a protracted disease caused by the protozoan <i>Leishmania infantum</i> (zoonotic) or <i>L. donovani</i> (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 <i>L. infantum</i> DNA loads in blood and bone marrow, and plasma concentrations of IL-1β, IL-6, IL-8, IL-10, IL-12, TNF-α, and TGF-β. Cytokine levels were found to be elevated. <i>L. infantum</i> 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.
ISSN:2076-0817

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