Search Results (99)

Aspergillus can cause a spectrum of diseases depending on the immune status and predisposing conditions. Invasive pulmonary aspergillosis (IPA) is classically seen in patients with severe immunocompromise, such as patients with hematologic malignancies, transplant recipients, and chronic corticosteroid use at high doses. Recently, IPA cases in patients without these classic risk factors, including those associated with severe respiratory viral infections, chronic obstructive pulmonary disease, liver failure, and critical illness, are being increasingly recognized. Delayed recognition and missed diagnoses contribute to increased mortality in these patient populations. Maintaining a high index of suspicion and implementation of systematic screening protocols in high-risk patients may help reduce missed or delayed diagnoses and improve patient outcomes. This review describes the pathophysiology, incidence, risk factors, outcomes, and diagnostic and treatment considerations in IPA in patients with emerging risk factors. Full article

Background/Objectives: Chronic pulmonary aspergillosis (CPA) is a debilitating condition often affecting immunocompetent patients with underlying structural lung diseases, particularly pulmonary tuberculosis. This study investigates single nucleotide variants (SNVs) in immunogenetic-related genes among a Brazilian cohort with CPA. Methods: Twelve patients with confirmed CPA, based on ESCMID/ERS criteria, were sequenced using custom multigenic panel sequencing. Variants were annotated, classified using ACMG guidelines, and analyzed for potential impact on protein interactions and immune pathways. Results: A set of SNVs in CX3CR1, IL12B, IL4R, PTX3, CCR5, and IFNG genes were classified as variants of uncertain significance (VUS), but protein–protein interaction analysis suggests a potential role in immune evasion and dysfunction. Conclusions: This is the first study to apply a custom multigenic panel for CPA susceptibility in a Brazilian cohort, contributing to future functional and clinical studies in fungal immunogenetics. Full article

Background: A significant complication among post-tuberculosis patients is chronic pulmonary aspergillosis (CPA), with prevalence and outcomes varying by region. This study aimed to explore the epidemiology, clinical characteristics, and microbiological profiles of 219 post-tuberculosis patients with persistent respiratory symptoms and lung cavities in Indonesia. Methods: The patients were divided into CPA (n = 144) and non-CPA (n = 75) groups. This cross-sectional study diagnosed CPA in post-tuberculosis patients using ERS/ESCMID criteria, integrating clinical, radiological, and fungal assessments. Serological tests for Aspergillus-specific IgG were conducted using immunochromatographic (ICT) and ELISA on serum samples. Sputum specimens were used in parallel for fungal culture, and radiological evaluations (e.g., chest X-rays or CT scans) were performed to identify typical CPA features such as cavitation and fibrosis. Results: Persistent cough was significantly more common in CPA patients (83.3%, p = 0.015), highlighting its role as a clinical indicator for CPA. Radiological infiltrates were found in 165 patients (75.3%); critical diagnostic markers of CPA were cavitation and pericavitary fibrosis. Aspergillus-specific IgG testing demonstrated high diagnostic utility, with positivity rates of 69.4% for ICT and 63.2% for ELISA among CPA patients. Among those with infiltrates, a positive Aspergillus culture was not more common (p > 0.05), whereas Aspergillus IgG was more often raised (p = 0.037), as was a positive ICT (p = 0.021). Regional analysis revealed a higher CPA burden in Region 1 (75%) compared to Region 2 (56%, p = 0.003), with Aspergillus fumigatus and Aspergillus niger predominating in Region 1. Conclusions: These findings highlight the importance of comprehensive approaches and region-specific CPA management strategies in Indonesia. Full article

A subgroup of patients with chronic pulmonary aspergillosis (CPA) exhibits elevated serum total immunoglobulin E (IgE) levels, similar to allergic bronchopulmonary aspergillosis; however, the underlying mechanisms remain unclear. This study aimed to clarify the underlying pathophysiology of the CPA subgroup with high serum total IgE levels. In this study, we prospectively collected CPA cases treated at our hospital between January and July 2022 and measured serum cytokine levels along with clinical data. We compared 34 healthy controls (HCs) and 51 patients with CPA and found significantly elevated levels of inflammatory cytokines and tissue repair and destruction-related cytokines in CPA. Among the 51 patients with CPA, 10 had total IgE levels of >500 IU/mL, whereas the remaining 41 did not. The IgE-high group exhibited significantly increased eosinophil counts and elevated levels of type 2 cytokines and pro-inflammatory cytokines. Based on these findings, patients with CPA exhibited an enhanced inflammatory response in terms of cytokines compared with HCs. In particular, the CPA subgroup with high total IgE levels may have an underlying enhancement of type 2 inflammation. Our study provides insights into the potential novel pathomechanisms of CPA and may contribute to the development of new treatment strategies. Full article

Patients with hematological malignancies (HMs) are at higher risk of severe COVID-19 and secondary infections, which further complicate their outcomes. This study evaluated the impact of secondary infections (SIs) on mortality in hospitalized HM patients with SARS-CoV-2 infection and identified risk factors associated with SIs. We included 217 patients with HMs and COVID-19 admitted to a tertiary hospital in Rome, from April 2020 to September 2022. SIs occurred in 44.2% of patients, with bloodstream infections (42.7%) and respiratory infections (30.5%) being most frequent; among the latter, COVID-19-associated pulmonary aspergillosis (CAPA) was observed in 41.4% of cases. Viral reactivations, predominantly CMV, occurred in 9.2% of patients. The overall mortality rate was 29%, with higher mortality observed in patients with SIs (47.4% vs. 14.7%, p < 0.01). Risk factors for SIs included severe COVID-19 (OR = 2.957, p < 0.05) and prolonged hospitalization (OR = 1.095, p < 0.001). Severe COVID-19 (OR = 8.229, p < 0.001), intensive care unit (ICU) admission (OR = 15.232, p < 0.001), chronic steroid therapy (OR = 2.803, p < 0.05), SIs (OR = 2.892, p < 0.05), and viral reactivation (OR = 6.269, p < 0.01) were independent predictors of mortality. SIs and viral reactivations are common in patients with HMs and SARS-CoV-2 infection and significantly increase mortality, highlighting the need for timely management and preventive strategies in this vulnerable population. Full article

Objectives: Chronic pulmonary aspergillosis (CPA) is a fungal lung infection characterised by the slowly progressing destruction of the lung parenchyma and has four main subtypes. The objective of this work was to evaluate the epidemiology of CPA in our area and evaluate the involvement of the different subtypes in mortality. Methods: This was a descriptive longitudinal retrospective study developed in three tertiary hospitals in Spain. Among all patients admitted with a pulmonary aspergillosis diagnosis, we selected those who fulfilled the criteria for chronic aspergillosis according to the criteria of Denning, excluding those with a haematological disorder. Results: Among 409 inpatients recorded as having a pulmonary aspergillosis infection, only 76 (18.5%) fulfilled the criteria for CPA, with an estimated incidence of 0.67 cases/100,000 inhabitants/year. The subtypes detected were subacute invasive aspergillosis (SAIA) in 33 (43.4%) patients, simple aspergilloma (SA) in 25 (32.9%) patients, cavitary chronic aspergillosis (CCPA) in 13 (17.1%) patients, and chronic fibrosis (CFPA) in five (6.5%) patients. The overall three-month mortality rate was 23%, which was higher in SAIA patients. The predictors of early mortality were age > 65 years (OR 3.0 CI 95 1.0–9.5 p = 0.043) and the SAIA subtype vs. other subtypes (OR 3.1 CI 95 1.0–9.5 p = 0.042). Conclusions: The incidence rate estimated was inferior to that previously reported. The three-month mortality in patients with CPA was high, with older age and the SAIA subtype being the variable independent predictors of a worse prognosis. Full article

Treatment with CCR-4 antagonists has been shown to be protective against the development of invasive pulmonary aspergillosis in animal models. Herein, we present a case of fatal invasive pulmonary aspergillosis in a patient receiving Mogamulizumab. A 64-year-old man with refractory mycosis fungoides was found to have diffuse bilateral pulmonary nodules during a chest CT in June 2022. Bronchoalveolar lavage (BAL) fungal and bacterial cultures and galactomannan were negative, as well as serum beta-glucan and galactomannan. Histology showed a lymphoid infiltrate with a negative fungal stain, so a presumptive diagnosis of lymphoma infiltration was made, and the patient started the CCR-4 antagonist Mogamulizumab treatment in August 2022. He had no symptoms until November when he presented to the hematology clinic reporting dyspnea. He had neutrophilic leukocytosis (18.610 cells/µL), his c-reactive protein was 27 mg/dL, and his skin lesions from mycosis fungoides were just starting to improve. A CT scan showed large diffuse bilateral severely necrotic cavitated lesions with thick walls and apparently synchronous evolution. Beta-glucan was 31 pg/mL (wako method), while serum galactomannan 3.6. BAL was positive for Aspergillus fumigatus culture and galactomannan. Patient started voriconazole but, despite being in a stable condition, he suddenly died after two days. Discussion: Paradoxically, worsening of the chronic pulmonary aspergillosis has been reported after nivolumab treatment, and immune reconstitution syndromes are usually seen during neutrophil recovery after intensive chemotherapy. Our patient already presented indolent lung lesions from 5 months before and he remained completely asymptomatic until the aspergillosis diagnosis when he quickly passed away. Even if a progression of the lesions was expected in 5 months, this case had an atypical presentation. During the 5-month period, he had no pulmonary symptoms, and his c-reactive protein was negative. Furthermore, in the setting of the natural progression of subacute/chronic aspergillosis, a different radiological picture was expected with a less severe and probably asynchronous evolution. We think that the immune restoration associated with Mogamulizumab (also supported by the concurrent clinical response of the skin lesions) could have been detrimental in this case, exacerbating a catastrophic immune response or alternatively masquerading the clinical progression of aspergillosis. Clinicians should be aware of immune reconstitution syndromes possibly leading to fatal outcomes in immunocompromised patients starting CCR-4 antagonists. Full article

Background: We aim to investigate the characteristics of invasive pulmonary aspergillosis (IPA) in patients with HBV-related acute on chronic liver failure (HBV-ACLF). Methods: A total of 44 patients with probable IPA were selected as the case group, and another 88 patients without lung infections were chosen as the control group. Results: HBV-ACLF patients with probable IPA had more significant 90-day mortality (38.6% vs. 15.9%, p = 0.0022) than those without. The white blood cell (WBC) count was the independent factor attributed to the IPA development [odds ratio (OR) 1.468, p = 0.027]. Respiratory failure was associated with the mortality of HBV-ACLF patients with IPA [OR 26, p = 0.000]. Twenty-seven patients received voriconazole or voriconazole plus as an antifungal treatment. Plasma voriconazole concentration measurements were performed as therapeutic drug monitoring in 55.6% (15/27) of the patients. The drug concentrations exceeded the safe range with a reduced dosage. Conclusions: The WBC count might be used to monitor patients’ progress with HBV-ACLF and IPA. The presence of IPA increases the 90-day mortality of HBV-ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients, and voriconazole should be assessed by closely monitoring blood levels. Full article

In Indonesia, 2.4% of all new tuberculosis patients had multi-drug resistant disease (MDR-TB); an estimated 24,000 incidences. Historical case series of MDR-TB described a high frequency of cavitation and poor prognosis. The diagnosis of chronic pulmonary aspergillosis (CPA) relies on raised levels of Aspergillus IgG antibodies, and detectable Histoplasma IgG antibodies are suspicious for chronic pulmonary histoplasmosis (CPH). We investigated whether MDR-TB patients might have concurrent CPH or CPA. This was a cross-sectional study with 50 MDR-TB patients. ELISA was used to detect Histoplasma IgG antibodies and lateral flow assay was used to detect Aspergillus IgG/IgM antibodies. Several other possible disease determinants were assessed by multivariate analysis. Of the 50 MDR-TB patients, 14 (28%) and 16 (32%) had positive Histoplasma or Aspergillus serology; six patients (12%) had dual antibody reactivity. Radiological abnormalities in positive patients included diffuse or local infiltrates, nodules, consolidation, and apical cavities, consistent with CPH and CPA. Patients with detectable fungal antibodies tended to have worse disease, and 4 of 26 (15.3%) died in the first 5 months of dual infection (p = 0.11 compared with no deaths in those with only MDR-TB). The criteria for the diagnosis of CPH and CPA were fulfilled in those with moderately and far advanced disease (13 of 14 or 93%) and 12 of 16 (75%), respectively. Damp housing was the only determinant associated with Histoplasma antibodies (PR 2.01; 95%CI 0.56–7.19), while pets were associated with the Aspergillus antibody (PR 18.024; 95%CI 1.594–203.744). CPA or CPH are probably frequent in MDR-TB patients in Indonesia and may carry a worse prognosis. Full article

The United Arab Emirates has very little data on the incidence or prevalence of fungal diseases. Using total and underlying disease risk populations and likely affected proportions, we have modelled the burden of fungal disease for the first time. The most prevalent serious fungal conditions are recurrent vulvovaginitis (~190,000 affected) and fungal asthma (~34,000 affected). Given the UAE’s low prevalence of HIV, we estimate an at-risk population of 204 with respect to serious fungal infections with cryptococcal meningitis estimated at 2 cases annually, 15 cases of Pneumocystis pneumonia (PCP) annually, and 20 cases of esophageal candidiasis in the HIV population. PCP incidence in non-HIV patients is estimated at 150 cases annually. Likewise, with the same low prevalence of tuberculosis in the country, we estimate a total chronic pulmonary aspergillosis prevalence of 1002 cases. The estimated annual incidence of invasive aspergillosis is 505 patients, based on local data on rates of malignancy, solid organ transplantation, and chronic obstructive pulmonary disease (5.9 per 100,000). Based on the 2022 annual report of the UAE’s national surveillance database, candidaemia annual incidence is 1090 (11.8/100,000), of which 49.2% occurs in intensive care. Fungal diseases affect ~228,695 (2.46%) of the population in the UAE. Full article

Chronic pulmonary aspergillosis (CPA) is a rare but significant complication of lung cancer surgery. Its effect on survival remains unclear. Our aim was to describe the outcomes of the patients who developed CPA following the surgery for non-small cell lung cancer (NSCLC), identify the risk factors associated with its development following lung resection, and evaluate its impact on survival. All the patients with a diagnosis of CPA and operated NSCLC were identified in the National Aspergillosis Centre (NAC) database (2009–2020). Additional patients were identified in the Northwest Clinical Outcomes Research Registry (2012–2019) database. A regression analysis was performed to examine potential links between CPA and long-term outcomes and also to identify the factors associated with the development of CPA. The primary outcomes were the development of CPA, 1-year and 5-year mortality, and overall survival. Thirty-two patients diagnosed with CPA after lung resection were identified in the NAC database, of which 11 were also contained within the NCORR database, with a prevalence of 0.2% (n = 11/4425). Post-operative CPA was associated with significantly lower survival on log-rank analysis (p = 0.020). Mortality at one year was 25.0% (n = 8) and 59.4% (n = 19) at five years after the CPA diagnosis. On univariable analysis, a lower mean percentage-predicted forced expiratory volume in 1 s, ischaemic heart disease, and chronic obstructive pulmonary disease were all significantly associated with CPA development. CPA is a rare complication following lung cancer surgery which has a significant impact on long-term survival. Its development may be associated with pre-existing cardiopulmonary comorbidities. Further research in larger cohorts is required to substantiate these findings. Full article

Neutrophil and (alveolar) macrophage immunity is considered crucial for eliminating Aspergillus fumigatus. Data derived from bronchoalveloar lavage (BAL) characterizing the human immuno-pulmonary response to Aspergillus fumigatus are non-existent. To obtain a comprehensive picture of the immune pathways involved in chronic pulmonary aspergillosis (CPA), we performed proteome analysis on AL of 9 CPA patients and 17 patients with interstitial lung disease (ILD). The dihydrorhodamine (DHR) test was also performed on BAL and blood neutrophils from CPA patients and compared to blood neutrophils from healthy controls (HCs). BAL from CPA patients primarily contained neutrophils, while ILD BAL was also characterized by a large fraction of lymphocytes; these differences likely reflecting the different immunological etiologies underlying the two disorders. BAL and blood neutrophils from CPA patients displayed the same oxidative burst capacity as HC blood neutrophils. Hence, immune evasion by Aspergillus involves other mechanisms than impaired neutrophil oxidative burst capacity per se. CPA BAL was enriched by proteins associated with innate immunity, as well as, more specifically, with neutrophil degranulation, Toll-like receptor 4 signaling, and neutrophil-mediated iron chelation. Our data provide the first comprehensive target organ-derived immune data on the human pulmonary immune response to Aspergillus fumigatus. Full article

Central nervous system (CNS) lesions, especially invasive fungal diseases (IFDs), in immunocompromised patients pose a great challenge in diagnosis and treatment. We report the case of a 48-year-old man with acute myeloid leukaemia and probable pulmonary aspergillosis, who developed hyposthenia of the left upper limb, after achieving leukaemia remission and while on voriconazole. Magnetic resonance imaging (MRI) showed oedematous CNS lesions with a haemorrhagic component in the right hemisphere with lepto-meningitis. After 2 weeks of antibiotics and amphotericin-B, brain biopsy revealed chronic inflammation with abscess and necrosis, while cultures were negative. Clinical recovery was attained, he was discharged on isavuconazole and allogeneic transplant was postponed, introducing azacitidine as a maintenance therapy. After initial improvement, MRI worsened; brain biopsy was repeated, showing similar histology; and 16S metagenomics sequencing analysis was positive (Veilonella, Pseudomonas). Despite 1 month of meropenem, MRI did not improve. The computer tomography and PET scan excluded extra-cranial infectious–inflammatory sites, and auto-immune genesis (sarcoidosis, histiocytosis, CNS vasculitis) was deemed unlikely due to the histological findings and unilateral lesions. We hypothesised possible IFD with peri-lesion inflammation and methyl-prednisolone was successfully introduced. Steroid tapering is ongoing and isavuconazole discontinuation is planned with close follow-up. In conclusion, the management of CNS complications in immunocompromised patients needs an interdisciplinary approach. Full article

Aspergillosis is a fungal infection caused by various species of Aspergillus, most notably A. fumigatus. This fungus causes a spectrum of diseases, including allergic bronchopulmonary aspergillosis, aspergilloma, chronic pulmonary aspergillosis, and invasive aspergillosis. The clinical manifestations and severity of aspergillosis can vary depending on individual immune status and the specific species of Aspergillus involved. The recognition of Aspergillus involves pathogen-associated molecular patterns (PAMPs) such as glucan, galactomannan, mannose, and conidial surface proteins. These are recognized by the pathogen recognition receptors present on immune cells such as Toll-like receptors (TLR-1,2,3,4, etc.) and C-type lectins (Dectin-1 and Dectin-2). We discuss the roles of cytokines and pathogen recognition in aspergillosis from both the perspective of human and experimental infection. Several cytokines and chemokines have been implicated in the immune response to Aspergillus infection, including interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), CCR4, CCR17, and other interleukins. For example, allergic bronchopulmonary aspergillosis (ABPA) is characterized by Th2 and Th9 cell-type immunity and involves interleukin (IL)-4, IL-5, IL-13, and IL-10. In contrast, it has been observed that invasive aspergillosis involves Th1 and Th17 cell-type immunity via IFN-γ, IL-1, IL-6, and IL-17. These cytokines activate various immune cells and stimulate the production of other immune molecules, such as antimicrobial peptides and reactive oxygen species, which aid in the clearance of the fungal pathogen. Moreover, they help to initiate and coordinate the immune response, recruit immune cells to the site of infection, and promote clearance of the fungus. Insight into the host response from both human and animal studies may aid in understanding the immune response in aspergillosis, possibly leading to harnessing the power of cytokines or cytokine (receptor) antagonists and transforming them into precise immunotherapeutic strategies. This could advance personalized medicine. Full article

This study reports a peculiar case of systemic candidiasis infection associated with pulmonary aspergillosis in an apparently immunocompetent alpaca. A captive 7-year-old female alpaca exhibited respiratory symptoms, underwent treatment with benzylpenicillin and dexamethasone, and succumbed to the infection 40 days later. During the post-mortem examination, subcutaneous emphysema, widespread pneumonia with multiple suppurative foci, scattered necro-suppurative lesions throughout the renal and hepatic parenchyma were evident. Histopathological analysis of the collected tissues revealed multifocal mild lymphoplasmacytic chronic interstitial nephritis, necro-suppurative pneumonia with the presence of fungal hyphae, multifocal foci of mineralization, and fibrosis in the liver. Fungal cultures confirmed the growth of Aspergillus fumigatus from the lungs, and Candida albicans from the liver, kidney, and heart. The only recognizable risk factor for candidiasis and pulmonary aspergillosis in this case was prior corticosteroid and antibiotic therapy. Nevertheless, it is crucial to consider systemic candidosis and pulmonary aspergillosis as potential differential diagnoses in respiratory infections among camelids. Prolonged treatment with glucocorticoids and antibiotics should be avoided as it could represent a risk factor for the onset of pathologies caused by opportunistic fungi such as Candida spp. and Aspergillus spp. Full article