Avaliação de indivíduos com infecção subclínica por Leishmania braziliensis do ponto de vista clínico e imunológico após 13 anos de acompanhamento

Abstract

Introduction: Cutaneous leishmaniasis (CL), caused by Leishmania braziliensis, is characterized by an intense inflammatory response and the development of skin ulcers. In endemic areas, exposed individuals may develop subclinical infection (SC), effectively controlling the parasite without presenting clinical symptoms. Understanding the immunological mechanisms involved in this response is crucial for improving diagnostic and preventive strategies against CL. Objectives: To evaluate, after 13 years, the clinical and immunological responses of household contacts of CL patients who were previously identified as subclinically infected, comparing them to individuals with active CL, endemic normals (EN), and healthy controls (HC). This study aimed to identify immunological markers associated with protection in these individuals.Materials and Methods: This was a prospective cohort study conducted in Corte de Pedra, Bahia, Brazil, involving 308 household contacts followed since 2010. Levels of IFN-γ, TNF, IL-1β, IL-6, and Granzyme B were measured in whole blood cultures stimulated with soluble Leishmania antigen from 18 SC individuals. Cytokine quantification and antibody detection were performed using enzyme linked immunosorbent assay (ELISA). Statistical analyses included the Kruskal-Wallis test, Mann-Whitney U test, and Spearman’s correlation. Results: During the follow-up period, 57 individuals developed CL. The 18 SC individuals maintained IFN-γ production after 13 years, although at lower levels compared to active CL patients. TNF, IL-1β, IL-6, and Granzyme B production was also lower in SC individuals compared to CL but higher than in EN and HC. No direct correlation was observed between delayed-type hypersensitivity (DTH) and IFN-γ levels; however, 77.8% of DTH-positive individuals exhibited detectable IFN-γ. Conclusion: SC individuals exhibited a lower inflammatory response, which may contribute to the absence of disease manifestation. Although a linear correlation between DTH positivity and IFN-γ production was not observed, frequency analysis revealed a significant association between these variables. This indicates that IFN-γ is frequently produced in DTH positive individuals but can also be produced independently of DTH responses in some cases.