ABSTRACT Introduction Invasive aspergillosis (IA) represents one of the most frequent invasive fungal infections in paediatric patients with risk factors. An increase in cases of azole‐resistant IA has been reported in adult patients. The aim of this study is to present a series of 11 cases of paediatric patients with this pathology. Methods A retrospective descriptive study including paediatric patients with probable or proven azole‐resistant IA treated between January 2019 and June 2024 in four tertiary hospitals in Spain. Results Eleven cases are reported, all patients with risk factors for IA, mainly with haematopoietic stem cell transplantation (HCT) due to haematological malignancies and heart transplant in the early post‐transplant period. These patients represent 22% of all proven or probable paediatric IA cases ( n = 50) diagnosed in the study centres during the period. Five were previously receiving azole‐based antifungal prophylaxis. The most frequently isolated species was Aspergillus fumigatus . Despite receiving at least partially active antifungals plus adjunctive treatment therapy from diagnosis, attributable mortality was high (8/11 patients). Conclusion Azole‐resistant IA should be suspected in paediatric patients with risk factors, especially if they show poor clinical course or have received azole prophylaxis. The performance of invasive tests, as well as species identification and resistance testing, is essential to optimise treatment. In breakthrough IA it should be considered empirical treatment with an antifungal from a different class than the one used for prophylaxis, alone or in combination.
Mucosa-associated invariant T (MAIT) cells are innate-like MR1-restricted T cells broadly distributed in human tissues. MAIT cells adapt their antigen-specific response patterns depending on cytokine cues such as IL-12 or IL-18 in the microenvironment, shifting toward either IL-10+ or IL-17+ profiles. However, if such patterns are maintained in the context of inflammatory diseases is unknown. Here, we investigated MAIT cell functional plasticity in Crohn's disease (CD). Circulating MAIT cells in CD patients were impaired both in terms of numbers, and in terms of interferon gamma (IFN-gamma) and tumor necrosis factor (TNF) expression, and cytotoxic properties in response to MR1-presented antigen. However, the MAIT cell regulatory IL-10+ profile and the IL-17A+ profile were compromised only during active disease and relatively preserved during remission. Transcriptional analysis of intestinal T cells suggested that MAIT cells in CD displayed elevated GNLY and NKG7 expression, while transcripts associated with regulation and quiescence characterized MAIT cells in healthy donor control tissue. There were also distinct transcriptional signatures according to localization, where intra-epithelial MAIT cells exhibited a tissue resident regulatory profile, whereas those in the lamina propria showed signs of activation and recruitment. Finally, we assessed whether treatments for CD influenced MAIT cell functionality in vitro. Corticosteroids and upadacitinib inhibited MAIT cell activation, yet upadacitinib promoted increased GM-CSF and IL-17A expression in the context of combined antigen and IL-18 stimulation. These findings indicate that MAIT cell functional response patterns are influenced by CD disease stage, treatment, and tissue localization.
CD8+ tissue-resident memory T cells (TRM) in the upper respiratory tract (URT) limit viral replication after transmission and prevent spread to the lower respiratory tract (LRT), whereas LRT CD8+ TRM are important for limiting immunopathology in the lung and promoting efficient viral clearance. Although the presence of local respiratory antigen is thought to be required for CD8+ TRM development in the LRT but not the URT, the relationship between local antigen encounter and cytokine signaling that influences TRM differentiation in distinct niches of the respiratory tract remains unknown. Here, we show using murine models that while URT TRM generated in the presence or absence of local respiratory antigen are phenotypically, transcriptionally, and functionally similar throughout the respiratory tract, their developmental pathways are compartmentally distinct and characterized by a context-dependent compensatory relationship between antigen and cytokine signaling. In the absence of local antigen, URT CD8+ TRM formation required TGF-beta signaling, and notably, while both IL-15 and IL-33 were broadly dispensable in the URT, IL-33 was able to rescue LRT CD8+ TRM development in the absence of local antigen. Together, these findings highlight key differences for CD8+ TRM development in distinct areas of the respiratory tract, offering valuable insights into the development of mucosal cellular immunity following intranasal and parenteral vaccination.
ABSTRACT Background Haemophagocytic lymphohistiocytosis (HLH) is a life‐threatening hyperinflammatory syndrome that may occur in people living with HIV/AIDS (PLWHA), often triggered by opportunistic infections such as disseminated histoplasmosis (DH). The substantial overlap in clinical and laboratory features between HLH and DH complicates timely diagnosis. Objectives To describe HLH among PLWHA with DH and compare clinical, laboratory and outcome characteristics between patients with and without HLH . Patients/Methods A retrospective observational study was conducted at São José Hospital of Infectious Diseases, Fortaleza, Brazil, between March 2023 and June 2024. Hospitalised PLWHA with DH were evaluated for HLH based on the presence of ≥ 3 HLH‐2004 criteria and an H‐Score ≥ 169. Baseline clinical, laboratory and outcome parameters were compared between patients with and without HLH. Results Among 61 patients diagnosed with DH, 11 (18.0%) met the study criteria for HLH. Patients with HLH were more likely to present with hepatomegaly ( p = 0.036), haemoptysis ( p = 0.030) and lower platelet counts ( p = 0.029). In‐hospital mortality was significantly higher among patients with HLH (54.5% versus 18.0%; p = 0.019). These patients more frequently required renal replacement therapy ( p = 0.028) and intensive care unit admission ( p = 0.048). Kaplan–Meier analysis with log‐rank testing demonstrated significantly reduced in‐hospital survival among patients with HLH ( p = 0.015). Conclusions HLH represents a severe complication in PLWHA with DH and is associated with increased mortality and greater need for intensive care. Early recognition and use of adjunctive diagnostic tools may facilitate timely management and improve clinical outcomes.
ABSTRACT Background Black yeast‐like species of the order Chaetothyriales cause superficial to life‐threatening systemic infections. Comprehensive global epidemiology data remain limited. Objectives This study aimed to analyze the global epidemiology, spectrum of pathogens, clinical manifestations and outcomes of Chaetothyriales infections. Methods We systematically reviewed 712 cases reported between 1976 and 2025. Results The analysis revealed a steady increase in diagnosed cases, with Cladophialophora bantiana (21%), Exophiala dermatitidis (19%), and E. jeanselmei (15%) being the predominant causative agents; notably, the proportion of E. jeanselmei declined from 18%–28% in 1976–2015 to 7% in 2016–2025. Published cases were more frequent in tropical/subtropical regions; however, cases were reported from Africa. Although 42% of infections occurred in immunocompetent individuals, transplant recipients, diabetics, and those with CARD9 deficiency showed higher risk. Deep infections exhibited substantially greater mortality than cutaneous forms (47% vs. 7%; p < 0.001); particularly, central nervous system infections (58%) and disseminated disease (53%) were involved. Conclusions This study highlights a seemingly growing burden of Chaetothyriales infections, possibly partly due to better recognition, emphasizing the need for improved surveillance, diagnostics, and targeted prevention in high‐risk populations.
