Browsing by Author "Benadof, Dona"

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    A prospective, multicenter study of invasive fungal disease caused by molds in children and adults in Chile
    (2025) Rabagliati, Ricardo; Benadof, Dona; Thompson, Luis; Garcia, Patricia; Gonzalez, Tamara; Vizcaya, Cecilia; Soto, Andres; Gutierrez, Catalina; Rodriguez, Lorena; Labraña, Yenis; Tapia, Cecilia; Zubieta, Marcela; Lasso, Martin; Gutierrez, Valentina; Contardo, Veronica; Castillo, Yocelyn; Ducasse, Karen; Calvo, Mario; Valenzuela, Romina; Santolaya, Maria; Chilean Invasive Mycosis Network
    Background: Invasive mold diseases (IMDs) are a severe complication of immunocompromised subjects and an emerging problem among severely ill, apparently immunocompetent patients. The aim of this study was to describe the epidemiological and clinical features of IMDs in Chile. Methods: Prospective study of IMD cases in children and adults from 11 reference hospitals in Chile from May 2019 to May 2021. Results: One hundred seventy-six cases were included, 135 in adults and 41 in children, with an overall incidence of 0.4/1,000 admissions. The median age was 10.5 years in children and 56.6 years in adults, with male gender predominance in adults (61.5% versus 41.5%, p = 0.03). Immunosuppression was the most common condition in both children and adults. However, cancer, neutropenia, and hematopoietic cell transplantation were significantly more frequent in the pediatric group. In contrast, diabetes, viral pneumonia, chronic kidney disease, and chronic obstructive pulmonary disease were significantly more frequent among adult patients. Regarding the diagnostic category, 30.1% of cases were proven, 55.7% probable and 14.2% possible. Aspergillosis was the most frequent IMD diagnosed in 75.5% of cases, followed by fusariosis in children and mucormycosis in adults. Viral pneumonia was associated in 40.3% of cases, mainly COVID-19, with aspergillosis in 87.3%. No triazole resistance was observed in Aspergillus spp.. Antifungals were prescribed in 97.2% of the patients: voriconazole 61.4%, liposomal amphotericin 20.5%, combination antifungals 11.1%, and others 6.4%. Overall survival was 68.7%, 61.4%, and 51.7% at 30, 90 and 180 days, respectively. Discussion: This is the most extensive study of IMDs in Chile, evidencing an incidence of 0.4 per 1,000 admissions, with aspergillosis being the most frequent infection. Nearly 40% of cases were associated with respiratory viruses, accounting for the impact of COVID-19. Despite almost all patients starting antifungal therapy, the survival rate was poor. It is advisable to start a surveillance program of IMDs in Chile and verify the absence of azole resistance of Aspergillus spp.
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    Deep immunophenotyping reveals biomarkers of multisystemic inflammatory syndrome in children in a Latin American cohort
    (2022) Rey, Emma; Espinosa, Yazmin; Astudillo, Camila; Jimena, Lina; Hormazábal, Juan; Noguera, Loreani; Cofré, Fernanda; Piñera, Cecilia; González, Ricardo; Bataszew, Alexander; Muñoz, Paula; Benadof, Dona; Álvarez, Patricia; Acevedo, Valeria; Vial, Pablo; Vial, Cecilia; Poli, Cecilia
    Background: Multisystemic inflammatory syndrome in children (MIS-C) is a life-threatening disease that occurs 2-5 weeks after severe acute respiratory syndrome coronavirus 2 exposure and is characterized by severe multisystemic inflammation. Early recognition of MIS-C is key to prognosis; therefore, establishing clinical and laboratory biomarkers that predict complications is urgently needed. Objective: We characterized the immune response and clinical features of patients with acute MIS-C and determined biomarkers of disease in a cohort of 42 Latin American patients. Methods: Immune characterization was performed using flow cytometry from peripheral mononuclear cells and severe acute respiratory syndrome coronavirus 2-specific humoral and cellular response was performed using flow cytometry, enzyme-linked immunospot, enzyme-linked immunosorbent assay, and neutralizing antibody assays. Results: MIS-C is characterized by robust T-cell activation and cytokine storm. We uncovered that while C-X-C motif chemokine ligand (CXCL) 9, IL-10, CXCL8, CXCL10, IL-6, and IL-18 are significantly elevated in patients with shock, while CCL5 was increased in milder disease. Monocyte dysregulation was specifically associated with KD-like MIS-C. Interestingly, MIS-C patients show a natural killer cell degranulation defect that is persistent after 6 months of disease presentation, suggesting it could underlie disease susceptibility. Most MIS-C had gastrointestinal involvement, and higher levels of neopterin were identified in their stools, potentially representing a biomarker of intestinal inflammation in MIS-C. Severe acute respiratory syndrome coronavirus 2-specific cellular response and neutralizing antibodies were identifiable in convalescent MIS-C patients, suggesting sustained immunity. Conclusion: Clinical characterization and comprehensive immunophenotyping of Chilean MIS-C cohort provide valuable insights in understanding immune dysregulation in MIS-C and identify relevant biomarkers of disease that could be used to predict severity and organ involvement.

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