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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2025-06-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Ingridi de Souza Sene |
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| description | 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. |
| format | Article |
| id | doaj-art-2ae297590a874209b0e16c04e3cd2127 |
| institution | Kabale University |
| issn | 2076-0817 |
| language | English |
| publishDate | 2025-06-01 |
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| series | Pathogens |
| spelling | doaj-art-2ae297590a874209b0e16c04e3cd21272025-08-20T03:32:27ZengMDPI AGPathogens2076-08172025-06-0114761510.3390/pathogens14070615Immune–Pathological Correlates of Disease Severity in New-World Kala-Azar: The Role of Parasite Load and Cytokine ProfilesIngridi de Souza Sene0Dorcas Lamounier Costa1Daniele Alves Zacarias2Jailthon Carlos dos Santos3Gabriel Reis Ferreira4Daniela Rodrigues Andrade5Jorge Clarêncio de Sousa Andrade6Carlos Henrique Nery Costa7Laboratory of Leishmaniasis, Institute of Tropical Medicine Natan Portella, Teresina 64002-510, BrazilLaboratory of Leishmaniasis, Institute of Tropical Medicine Natan Portella, Teresina 64002-510, BrazilLaboratory of Leishmaniasis, Institute of Tropical Medicine Natan Portella, Teresina 64002-510, BrazilLaboratory of Leishmaniasis, Institute of Tropical Medicine Natan Portella, Teresina 64002-510, BrazilIntelligence Center for Emerging and Tropical Diseases (CIATEN), Teresina 64049-550, BrazilIntegrated Laboratory of Microbiology and Immunoregulation, CPqGM-Fiocruz-Bahia, Salvador 40296-710, BrazilIntegrated Laboratory of Microbiology and Immunoregulation, CPqGM-Fiocruz-Bahia, Salvador 40296-710, BrazilLaboratory of Leishmaniasis, Institute of Tropical Medicine Natan Portella, Teresina 64002-510, BrazilKala-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.https://www.mdpi.com/2076-0817/14/7/615visceral leishmaniasis<i>Leishmania infantum</i>hemorrhagesepsisHIV-coinfectionmortality |
| spellingShingle | 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 Immune–Pathological Correlates of Disease Severity in New-World Kala-Azar: The Role of Parasite Load and Cytokine Profiles Pathogens visceral leishmaniasis <i>Leishmania infantum</i> hemorrhage sepsis HIV-coinfection mortality |
| title | Immune–Pathological Correlates of Disease Severity in New-World Kala-Azar: The Role of Parasite Load and Cytokine Profiles |
| title_full | Immune–Pathological Correlates of Disease Severity in New-World Kala-Azar: The Role of Parasite Load and Cytokine Profiles |
| title_fullStr | Immune–Pathological Correlates of Disease Severity in New-World Kala-Azar: The Role of Parasite Load and Cytokine Profiles |
| title_full_unstemmed | Immune–Pathological Correlates of Disease Severity in New-World Kala-Azar: The Role of Parasite Load and Cytokine Profiles |
| title_short | Immune–Pathological Correlates of Disease Severity in New-World Kala-Azar: The Role of Parasite Load and Cytokine Profiles |
| title_sort | immune pathological correlates of disease severity in new world kala azar the role of parasite load and cytokine profiles |
| topic | visceral leishmaniasis <i>Leishmania infantum</i> hemorrhage sepsis HIV-coinfection mortality |
| url | https://www.mdpi.com/2076-0817/14/7/615 |
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