Bronchial aspirate obtained during bronchoscopy yields increased fungal load compared to bronchoalveolar lavage fluid in patients at risk of invasive aspergillosis and Pneumocystis pneumonia.

Bronchoalveolar lavage fluid (BALF) is a standard respiratory sample for diagnosing invasive fungal diseases like Pneumocystis pneumonia (PCP) and invasive pulmonary aspergillosis (IPA). However, procedural variations exist across medical centers and wards. This study aimed to compare the diagnostic potential of BALF and bronchial aspirate (BA) obtained during bronchoscopy in 173 patients suspected of fungal infections. A prospective observational study was conducted from April 2020 to November 2021. BALF and BA were collected during bronchoscopy and subjected to direct examination, fungal culture, Aspergillus fumigatus qPCR (AfqPCR), and Pneumocystis jirovecii qPCR (PjqPCR). Galactomannan detection was performed on BALF. Patients were classified based on established European Organization for Research and Treatment of Cancer (EORTC) criteria. Out of 173 patients, 75 tested positive for at least one test in BA or BALF. For Aspergillus, proportion of positive AfqPCR (14.5% vs. 9.2%; P < 0.0001) and fungal loads (Cq of 31.3 vs. 32.8; P = 0.0018) were significantly higher in BA compared to BALF. For Pneumocystis, fungal loads by PjqPCR was also higher in BA compared to BALF (Cq of 34.2 vs. 35.7; P = 0.003). BA only detected A. fumigatus and P. jirovecii in 12 (42.9%) and 8 (19.5%) patients, respectively. BA obtained during a BAL procedure can be a suitable sample type for increased detection of P. jirovecii and A. fumigatus by qPCR. The use of BA in diagnostic algorithms requires further investigation in prospective studies.

Bronchoalveolar lavage fluid (BALF) vs. bronchial aspirate (BA) for fungal diagnosis in 173 patients suspected of invasive fungal infection: BA showed higher fungal loads than in BALF by qPCR for the detection of Aspergillus fumigatus and Pneumocystis jirovecii.

Invasive pulmonary aspergillosis real-world outcomes: Clinical features and risk factors associated with increased mortality.

Invasive pulmonary aspergillosis (IPA) is a severe fungal infection that primarily affects immunocompromised patients and is associated with high mortality. Contemporary clinical characteristics of IPA and "real-world" estimates and predictors of associated mortality are inadequate. TriNetX, a global research network, was queried to identify adult patients with IPA diagnoses based on the ICD-10 code B44.0. We performed a propensity score-matched analysis comparing clinical characteristics among patients who survived versus non-survivors at 1 year. We identified 4371 patients with IPA. We found neoplasms, solid organ transplant recipients, hematologic malignancies, and aplastic anemia as the most predominant risk factors. The overall 1-year mortality was 32% for IPA. 1-year mortality was highest for patients with COVID-19 in the ICU, followed by those with acute myeloid leukemia and aplastic anemia (54%, 50%, and 39%, respectively). After propensity score matching, severe sepsis, pleural effusion, and candidiasis were mortality contributors within a year after diagnosis. Liver injury, systemic glucocorticoid exposure over the previous 6 months, lower lymphocyte and CD4 counts, elevated ferritin, LDH, thrombocytopenia, anemia, or elevated glycosylated hemoglobin (HbA1c) were independent predictors of mortality at 1 year. Voriconazole was the most common treatment (67%). The annual incidence of IPA was 0.001%, increasing to 0.02% among critically ill patients in the ICU. IPA continues to have a very high mortality. We encourage prospective studies to validate and refine the identified clinical markers linked to increased mortality.

Invasive pulmonary aspergillosis (IPA) is common among immunocompromised patients. Analyzing a global research network, we found 32% of patients with IPA died a year after diagnosis. We identified the primary underlying conditions, contributors, and predictors of mortality.

Grading of Anatomopathological Disparity in the Cases of Invasive Pulmonary Aspergillosis in wild avian species as recorded in Pigeons (Columba livia), Peafowls (Pavo cristatus), and Griffon Vultures (Gyps fulvus).

Aspergillosis which is caused by Aspergillus fumigatus, a fungal pathogen, can vary from a localized infection to severe life-threatening invasive or disseminated systemic diseases in birds. The present study aimed to evaluate and grade the anatomopathological disparity in the cases of invasive pulmonary aspergillosis (IPA) in Columba livia (pigeons), Pavo cristatus (peafowls), and Gyps fulvus (Griffon vultures). Necropsy gross lesions varied from mere congestion of lungs in P. cristatus, congestion and large necrotizing masses surrounded by a zone of hyperemia (10 mm dia) in lungs of C. livia, and typically disseminated granuloma in the lungs, air sacs, and organs of other serous membranes in G. fulvus. Histopathology varied from extensive parenchymal necrosis amidst exuberant fungal invasion in P. cristatus, multifocal to focally extensive tissue necrosis with colonies of fungal hyphae surrounded by heterophils and lymphocytes in C. livia, as well as typical mycotic granuloma embedded in the lungs, air sacs, and thoracoabdominal serous membranes with angio-invasion in G. fulvus. Based on gross and histopathological findings, we diagnosed the cases as Acute Invasive Pulmonary Aspergillosis (AIPA) in peafowls and pigeons, as well as Chronic Invasive Pulmonary Aspergillosis (CIPA) in Griffon vultures. There is a paucity of case reports on aspergillosis in wild avian species, and this report strived to document the cases of IPA in peafowls, pigeons, and vultures. This is the first report of its kind which evaluated anatomopathological disparity of IPA in pigeons, peafowls, and vultures with a proposed anatomopathological grading system which would help to understand and investigate the nature of aspergillosis in different avian hosts.

Investigation of the value of precipitins in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients with a positive marker for Aspergillus species.

Although a high prevalence of COVID-19-associated pulmonary aspergillosis has been reported, it is still difficult to distinguish between colonization with Aspergillus fumigatus and infection. Concomitantly, similarities between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and hypersensitivity pneumonitis were suggested. The objective of this study was to investigate retrospectively if precipitin assays targeting A. fumigatus could have been useful in the management of SARS-CoV-2 patients hospitalized in an Intensive Care Unit (ICU) in 2020. SARS-CoV-2 ICU patients were screened for Aspergillus co-infection using biomarkers (galactomannan antigen, qPCR) and culture of respiratory samples (tracheal aspirates and bronchoalveolar lavage). For all these patients, clinical data, ICU characteristics and microbial results were collected. Electrosyneresis assays were performed using commercial A. fumigatus somatic and metabolic antigens. ELISA were performed using in-house A. fumigatus purified antigen and recombinant antigens.Our study population consisted of 65 predominantly male patients, with a median ICU stay of 22 days, and a global survival rate of 62%. Thirty-five patients had at least one positive marker for Aspergillus species detection. The number of arcs obtained by electrosyneresis using the somatic A. fumigatus antigen was significantly higher for these 35 SARS-CoV-2 ICU patients (P 0.01, Welch's t-test). Our study showed that SARS-CoV-2 ICU patients with a positive marker for Aspergillus species detection more often presented precipitins towards A. fumigatus. Serology assays could be an additional tool to assess the clinical relevance of the Aspergillus species in respiratory samples of SARS-CoV-2 ICU patients. LAY SUMMARY: This study showed retrospectively that precipitin assays, such as electrosyneresis, could be helpful to distinguish between colonization and infection with Aspergillus fumigatus during the management of severe acute respiratory syndrome Coronavirus-2 (SARS CoV-2) patients in an intensive care unit.

Usefulness of Sona Aspergillus Galactomannan LFA with digital readout as diagnostic and as screening tool of COVID-19 associated pulmonary aspergillosis in critically ill patients. Data from a multicenter prospective study performed in Argentina.

COVID-19-associated pulmonary aspergillosis (CAPA) incidence varies depending on the country. Serum galactomannan quantification is a promising diagnostic tool since samples are easy to obtain with low biosafety issues. A multicenter prospective study was performed to evaluate the CAPA incidence in Argentina and to assess the performance of the lateral flow assay with digital readout (Sona Aspergillus LFA) as a CAPA diagnostic and screening tool. The correlation between the values obtained with Sona Aspergillus LFA and Platelia® EIA was evaluated. In total, 578 serum samples were obtained from 185 critically ill COVID patients. CAPA screening was done weekly starting from the first week of ICU stay. Probable CAPA incidence in critically ill patients was 10.27% (19/185 patients when LFA was used as mycological criteria) and 9% (9/100 patients when EIA was used as mycological criteria). We found a very good correlation between the two evaluated galactomannan quantification methods (overall agreement of 92.16% with a Kappa statistic value of 0.721). CAPA diagnosis (>0.5 readouts in LFA) were done during the first week of ICU stay in 94.7% of the probable CAPA patients. The overall mortality was 36.21%. CAPA patients' mortality and length of ICU stay were not statistically different from for COVID (non-CAPA) patients (42.11 vs 33.13% and 29 vs 24 days, respectively). These indicators were lower than in other reports. LFA-IMMY with digital readout is a reliable tool for early diagnosis of CAPA using serum samples in critically ill COVID patients. It has a good agreement with Platelia® EIA. LAY SUMMARY: The incidence of COVID-associated pulmonary aspergillosis (CAPA) in critically-ill Argentinian patients was established (10.27%). Serum galactomannan quantification was useful as a screening tool for this mycosis. A good agreement between Platelia® EIA and Sona Aspergillus LFA is reported.

Detection of invasive pulmonary aspergillosis in mice using lung perfusion single-photon emission computed tomography with [99mTc]MAA.

There is an urgent need for development of better diagnostic strategies to improve outcomes in patients with invasive pulmonary aspergillosis (IPA). We hypothesized that lung perfusion single-photon emission computed tomography (SPECT) may be more sensitive and specific than computed tomography (CT) of the chest for detection of IPA because it is an angioinvasive pulmonary infection with characteristics that are different from those of bacterial pneumonia. We used SPECT with injection of technetium-99m-labeled macroaggregated albumin ([99mTc]MAA) to measure pulmonary perfusion in noninfected mice, mice with IPA, and mice with bacterial pneumonia. Histopathologic analysis was performed to evaluate the correlation between the perfusion defect and mould invasion. We also attempted to quantitatively evaluate the SPECT images to identify differences in decreased perfusion levels in affected areas in the mouse lung. Histopathologic analysis in the IPA mouse model showed a clear match between areas with a perfusion defect and the presence of mold, indicating that the location of the perfusion defect on a SPECT image reflects angioinvasion of the mould in the lungs. Some of these perfusion defects could be seen before appearance of the infiltrate of CT images. Quantitative analysis confirmed that perfusion in the affected areas was significantly decreased in the IPA model but not in the bacterial pneumonia model (P < .0001). This imaging method may be preferable to the alternative methods presently used to identify the presence of mold in a patient's lungs.

Chronic Invasive Pulmonary Aspergillosis in Two Cats with Diabetes Mellitus.

Human patients with diabetes mellitus are at increased risk of fungal infections. Diabetes mellitus has also been implicated as a predisposing factor in the establishment of fungal lung infections in cats. Two diabetic cats of different origins presented with severe acute respiratory conditions that resulted in their death. At necropsy examination there was friable, black material in the main bronchi that obstructed the bronchial lumina. Microscopical examination of the lungs revealed the presence of pneumonia, calcium oxalate crystals and a large quantity of fungal hyphae and conidial heads. Fungal infection was confirmed with Grocott's methenamine silver stain. The results of the mycology analysis were compatible with Aspergillus section Nigri.

Invasive aspergillosis in a putty-nosed monkey (Cercopithecus nictitans) with adrenocortical Cushing's syndrome.

BACKGROUND: An 18-year-old captive female putty-nosed-monkey (Cercopithecus nictitans) with a history of long-term infertility and hyperglucocorticism was euthanized because of perforating thoracic trauma induced by group members and subsequent development of neurological signs. METHODS: Complete necropsy and histopathological examination of formalin-fixed tissue samples was carried out. RESULTS: The monkey showed invasive pulmonary and cerebral infection with Aspergillus fumigatus together with adrenocortical neoplasia and signs of Cushing's syndrome, such as alopecia with atrophic skin changes, evidence for diabetes mellitus and marked immunosuppression. CONCLUSIONS: Spontaneous endocrinopathies are rarely described in non-human primates. Here we report the first case of spontaneous adrenocortical hyperglucocorticism predisposing to systemic aspergillosis in a putty-nosed monkey.