Evaluation of interleukin-8 levels in the diagnosis of invasive pulmonary aspergillosis in patients with haematological malignancies.

This study aimed to determine the level of interleukin (IL)-8 in diagnosing of invasive pulmonary aspergillosis (IPA). We conducted this study with 50 controls and 25 IPA patients with haematological malignancies. Demographic data, haematological diagnoses, chemotherapy regimen, galactomannan level, fungal culture, and computed tomography findings of the patients were evaluated prospectively. IL-8 levels were studied with the ELISA method. The mean age of patients in the case group was 60.84 ± 15.38 years, while that of the controls was 58.38 ± 16.64 years. Of the patients, 2/25 were classified as having 'proven', 13/25 as 'probable', and 10/25 as 'possible' invasive aspergillosis (IA). Serum IL-8 levels were found to be significantly higher in the case group compared to the controls. There was a negative correlation between serum IL-8 levels and neutrophil counts and a positive correlation with the duration of neutropenia. A significant cutoff value for serum IL-8 parameter in detecting IPA disease was obtained as ≥274 ng/l; sensitivity was 72%; specificity was 64%; PPV was 50%; and NPV was 82%. In the subgroup analysis, there was no significant difference in serum IL-8 levels between the case group and the patients in the neutropenic control group, while a significant difference was found in with the patients in the non-neutropenic control group. Serum IL-8 levels in neutropenic patients who develop IPA are not adequate in terms of both the diagnosis of the disease and predicting mortality. New, easily applicable methods with high sensitivity and specificity in diagnosing IPA are still needed.

Although a significant cutoff value for serum interleukin (IL)-8 was found in the diagnosis of IPA, there was no statistical difference in serum IL-8 when subgroup analysis was performed with neutropenic control patients. Therefore, serum IL-8 is not a successful marker in diagnosing neutropenic patients with IPA.

Prospective and systematic screening for invasive aspergillosis in the ICU during the COVID-19 pandemic, a proof of principle for future pandemics.

The diagnostic performance of a prospective, systematic screening strategy for COVID-19 associated pulmonary aspergillosis (CAPA) during the COVID-19 pandemic was investigated. Patients with COVID-19 admitted to the ICU were screened for CAPA twice weekly by collection of tracheal aspirate (TA) for Aspergillus culture and PCR. Subsequently, bronchoalveolar lavage (BAL) sampling was performed in patients with positive screening results and clinical suspicion of infection. Patient data were collected from April 2020-February 2022. Patients were classified according to 2020 ECMM/ISHAM consensus criteria. In total, 126/370 (34%) patients were positive in screening and CAPA frequency was 52/370 (14%) (including 13 patients negative in screening). CAPA was confirmed in 32/43 (74%) screening positive patients who underwent BAL sampling. ICU mortality was 62% in patients with positive screening and confirmed CAPA, and 31% in CAPA cases who were screening negative. The sensitivity, specificity, positive and negative predictive value (PPV & NPV) of screening for CAPA were 0.71, 0.73, 0.27, and 0.95, respectively. The PPV was higher if screening was culture positive compared to PCR positive only, 0.42 and 0.12 respectively. CAPA was confirmed in 74% of screening positive patients, and culture of TA had a better diagnostic performance than PCR. Positive screening along with clinical manifestations appeared to be a good indication for BAL sampling since diagnosis of CAPA was confirmed in most of these patients. Prospective, systematic screening allowed to quickly gain insight into the epidemiology of fungal superinfections during the pandemic and could be applicable for future pandemics.

Prognostic factors and outcomes of invasive pulmonary aspergillosis, a retrospective hospital-based study.

Objective: Invasive pulmonary aspergillosis (IPA) affects immunocompromised hosts and is associated with higher risks of respiratory failure and mortality. However, the clinical outcomes of different IPA types have not been identified. Methods: Between September 2002 and May 2021, we retrospectively enrolled patients with IPA in Taichung Veterans General Hospital, Taiwan. Cases were classified as possible IPA, probable IPA, proven IPA, and putative IPA according to EORTC/MSGERC criteria and the AspICU algorithm. Risk factors of respiratory failure, kidney failure, and mortality were analyzed by logistic regression. A total of 3-year survival was assessed by the Kaplan-Meier method with log-rank test for post-hoc comparisons. Results: We included 125 IPA patients (50: possible IPA, 47: probable IPA, 11: proven IPA, and 17: putative IPA). Comorbidities of liver cirrhosis and solid organ malignancy were risk factors for respiratory failure; diabetes mellitus and post-liver or kidney transplantation were related to kidney failure. Higher galactomannan (GM) test optical density index (ODI) in either serum or bronchoalveolar lavage fluid was associated with dismal outcomes. Probable IPA and putative IPA had lower 3-year respiratory failure-free survival compared to possible IPA. Probable IPA and putative IPA exhibited lower 3-year renal failure-free survival in comparison to possible IPA and proven IPA. Putative IPA had the lowest 3-year overall survival rates among the four IPA groups. Conclusion: Patients with putative IPA had higher mortality rates than the possible, probable, or proven IPA groups. Therefore, a prompt diagnosis and timely treatment are warranted for patients with putative IPA.

Baseline chest computed tomography for diagnosis of invasive aspergillosis in patients with acute myeloid leukaemia treated with intensive chemotherapy: A retrospective single-centre cohort study.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a relatively common infection in patients with acute myeloid leukaemia (AML), and is associated with high mortality rates. Optimising early detection is key to reduce the burden of IPA in this population. In this retrospective cohort study, we evaluated the added value of baseline chest CT before start of classical induction chemotherapy. METHODS: Adult patients receiving first-line intensive chemotherapy for AML were included if a baseline chest CT scan was available (±7 days). Data were collected from the electronic health record. IPA was classified using the EORTC/MSGERC 2020 consensus definitions. RESULTS: Between 2015 and 2019, 99 patients were included. During first-line treatment, 29/99 (30%) patients developed a probable IPA. Baseline chest CT was abnormal in 61/99 (62%) and 14/61 (23%) patients had typical radiological signs for IPA. An abnormal scan showed a trend towards higher risk for IPA (hazard ratio (HR): 2.12; 95% CI 0.95-4.84). Ground glass opacities were a strong predictor for developing IPA (HR 3.35: 95% CI 1.61-7.00). No probable/proven IPA was diagnosed at baseline; however, a bronchoalveolar lavage (BAL) at baseline was only performed in seven patients. Twelve-week mortality was higher in patients with IPA (7/26, 27% vs. 5/59, 8%; p = .024). CONCLUSION: Baseline chest CT scan could be an asset in the early diagnosis of IPA and contribute to risk estimation for IPA. In patients with an abnormal baseline CT, performing a BAL should be considered more frequently, and not only in patients with radiological findings typical for IPA.

Impact of posaconazole prophylaxis and antifungal treatment on BAL GM performance in hematology malignancy patients with febrile neutropenia: a real life experience.

BACKGROUND: Diagnostic accuracy of galactomannan measurements is highly variable depending on the study population, diagnostic procedures, and treatment procedures. We aimed to evaluate the effect of posaconazole prophylaxis and empiric antifungal treatment upon diagnostic accuracy of GM measurements in bronchoalveolar lavage (BAL), bronchial lavage (BL), and serum in hematological malignancy population. METHODS: Patients hospitalized in a single tertiary care center with hematologic malignancies undergoing fiberoptic bronchoscopy (FOB) with a preliminary diagnosis of IPA were retrospectively included. RESULTS: In all the study population (n = 327), AUC for BAL, BL, and serum GM were as follows: 0.731 [0.666-0.790], 0.869 [0.816-0.912], and 0.610 [0.540-0.676] with BL samples having the best diagnostic value. GM measurements in patients under posaconazole prophylaxis (n = 114) showed similar diagnostic performance. While specificity was similar between patients with and without posaconazole prophylaxis, sensitivity of GM measurements was lower in patients with prophylaxis. Analyses with patient classified according to antifungal treatment at the time of FOB procedure (n = 166) showed a decreased diagnostic accuracy in serum GM and BAL GM measurements related with the duration of treatment. However, BAL, BL, and serum GM measurements presented similar sensitivity and specificity in higher cut-off values in longer durations of antifungal treatment. CONCLUSION: Our study shows that posaconazole prophylaxis and active short-term (3 days) antifungal treatment do not significantly affect overall diagnostic performance of GM measurements in bronchoalveolar lavage and bronchial lavage samples. However, using different cut-off values for patients receiving active treatment might be suggested to increase sensitivity.

Invasive pulmonary aspergillosis following human metapneumovirus infection in solid-organ transplant recipients: Another virus to add to the list.

There is increasing recognition that respiratory viral infections such as influenza, respiratory syncytial virus, parainfluenza virus, adenovirus, and SARS-CoV-2 can promote the development of invasive fungal pulmonary coinfections, particularly invasive aspergillosis, both in immunocompetent and immunocompromised patients. To date, there are no case reports exploring the role of human metapneumovirus as a risk factor for fungal coinfection. Below, we describe the case of a 63-year-old woman who received a kidney transplant and developed invasive pulmonary aspergillosis after a human metapneumovirus infection and discuss the possible phenomena that could favor this association.

Performance of mNGS in bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in non-neutropenic patients.

The diagnosis of invasive pulmonary aspergillosis (IPA) diseases in non-neutropenic patients remains challenging. It is essential to develop optimal non-invasive or minimally invasive detection methods for the rapid and reliable diagnosis of IPA. Metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) can be a valuable tool for identifying the microorganism. Our study aims to evaluate the performance of mNGS in BALF in suspected IPA patients and compare it with other detection tests, including serum/BALF galactomannan antigen (GM) and traditional microbiological tests (BALF fungal culture and smear and lung biopsy histopathology). Ninety-four patients with suspicion of IPA were finally enrolled in our study. Thirty-nine patients were diagnosed with IPA, and 55 patients were non-IPA. There was significance between the IPA and non-IPA groups, such as BALF GM (P < 0.001), history of glucocorticoid use (P = 0.004), and pulmonary comorbidities (P = 0.002), as well as no significance of the other demographic data including age, sex, BMI, history of cigarette, blood GM assay, T-SPOT.TB, and NEUT#/LYMPH#. The sensitivity of the BALF mNGS was 92.31%, which was higher than that of the traditional tests or the GM assays. The specificity of BALF mNGS was 92.73%, which was relatively similar to that of the traditional tests. The AUC of BALF mNGS was 0.925, which presented an excellent performance compared with other traditional tests or GM assays. Our study demonstrated the important role of BALF detection by the mNGS platform for pathogen identification in IPA patients with non-neutropenic states, which may provide an optimal way to diagnose suspected IPA disease.

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.

The Utility of Galactomannan and Polymerase Chain Reaction Assays in Bronchoalveolar Lavage for Diagnosis of Chronic Pulmonary Aspergillosis.

The diagnosis of chronic pulmonary aspergillosis (CPA) is established by combined clinic-radio-microbiological criteria. Out of the different microbiological criteria, a positive serology for Aspergillus-specific IgG levels is the cornerstone of diagnosis. Alternatively, other microbiological evidence are sometimes sought viz., positive Aspergillus antigen (broncho-alveolar lavage fluid, i.e., BALF galactomannan ≥ 1.0), histopathological demonstration of the fungi following lung biopsy or resection, demonstration of hyaline septate hyphae in direct microscopy resembling Aspergillus spp. or its growth on a respiratory specimen. However, the exact roles of BALF- GM and the newer BALF-PCR have not been confirmed by studies till date. This study enrolled 210 patients with suspected CPA. Of the participants, 88 patients met the criteria for CPA, whereas 122 patients had an alternative diagnosis. The sensitivity-specificity of AsperGenius® PCR and "in-house" PCR were 52.27(36.69-67.54) %-33.78 (23.19-45.72) % and 36.36 (22.41-52.23) %-39.19 (28.04-51.23) % respectively. The sensitivity/specificity of BALF (> 1.0) and serum galactomannan (> 1.0) were 46.55% (33.34-60.13)/64.08% (54.03-73.3) and 29.82% (22.05-37.6)/86.84% (81.1-92.59) respectively. The optimal cut-off values for BALF-Galactomannan and serum galactomannan in diagnosing CPA were found to be 0.69 (sensitivity: 64%; specificity: 53%) and 0.458 (sensitivity: 67%; specificity: 64%) respectively. This results of this study suggests that Aspergillus PCR from BAL may not be a good "rule-in" test for diagnosing CPA. While the performances of GM in BAL and serum may be better than PCR, it should be best used in conjunction with other clinical, radiological, and other microbiological characteristics.

Diagnostic Utility of Galactomannan Enzyme Immunoassay in Invasive Aspergillosis in Pediatric patients with Hematological Malignancy.

OBJECTIVE: This study aims to determine the diagnostic utility of galactomannan enzyme immunoassay (GM EIA) in invasive aspergillosis (IA) in children with hematological malignancy (high risk population) in terms of sensitivity, specificity, negative predictive value (NPV) and positive predictive values (PPV) at various cut offs while validating the revised EORTC/MSG 2019 criteria in order to obtain the best cut-off. MATERIAL AND METHODS: For 100 pediatric patients, serum and respiratory samples were collected. Clinical, mycological workup (potassium-hydroxide mount, fungal culture) and GM EIA was done to classify proven, probable, and possible IA as per EORTC-MSG guidelines,2019. Sensitivity, specificity, PPV and NPV were calculated of GM indices at cut-off 0.5, 0.7 and 1, and validated with revised EORTC -MSG, 2019. RESULTS: Of 100 patients enrolled, 75 were diagnosed with ALL, 14 with AML, two with Hodgkin's, three had non-Hodgkin lymphoma, and six had undifferentiated leukemia. With routine mycological findings, 51 were classified as probable IA, 11 as possible IA, and 38 as no IA. Aspergillus flavus was the most prevalent on culture (56.9%, 29/51) followed by A. fumigatus (29%, 15/51) A. niger (7.8%, 4/51), A. terreus (3.9%, 2/51) and A. nidulans (2%, 1/51). GM EIA demonstrated sensitivity 82.3%, specificity 97.4%, PPV 98.1%, and NPV 77.1% at cut-off 0.67 when comparing probable/possible IA v/s no IA groups. The GM EIA had the best sensitivity (82.4%), specificity (81.8%), PPV (95.5%), and NPV (50%) at cut off 0.78 when the probable IA group was compared to the possible IA. Seven patients succumbed of whom 5 had GMI ≥ 2. CONCLUSION: This study deduces the optimal cut-off for serum GM EIA to be 0.67 obtained by ROC analysis when comparing possible and probable IA versus no IA and reinforces the definition of probable category of EORTC-MSG criteria, 2019. At 0.5 ODI the sensitivity (87.1%) and NPV (80.5%) are high, thus making it the most suitable cut-off for detecting true positive and ruling out IA respectively, in pediatric patients with hematological malignancy. GM EIA when performed adjunctive to clinico-radiological findings can prove to be screening, diagnostic and prognostic test for IA in pediatric hematological malignancy patients.

Diagnostic efficacy of metagenomic next generation sequencing in bronchoalveolar lavage fluid for proven invasive pulmonary aspergillosis.

Objective: To assess the diagnostic efficacy of metagenomic next generation sequencing (mNGS) for proven invasive pulmonary aspergillosis (IPA). Methods: A total of 190 patients including 53 patients who had been diagnosed with proven IPA were retrospectively analyzed. Using the pathological results of tissue biopsy specimens as gold standard, we ploted the receiver operating characteristic (ROC) curve to determine the optimal cut-off value of mNGS species-specific read number (SSRN) of Aspergillus in bronchoalveolar lavage fluid (BALF)for IPA. Furthermore, we evaluated optimal cut-off value of mNGS SSRN in different populations. Results: The optimal cut-off value of Aspergillus mNGS SSRN in BALF for IPA diagnosis was 2.5 for the whole suspected IPA population, and 1 and 4.5 for immunocompromised and diabetic patients, respectively. The accuracy of mNGS was 80.5%, 73.7% and 85.3% for the whole population, immunocompromised and diabetic patients, respectively. Conclusions: The mNGS in BALF has a high diagnostic efficacy for proven IPA, superioring to Aspergillus culture in sputum and BALF and GM test in blood and BALF. However, the cut-off value of SSRN should be adjusted when in different population.

Case report: nanopore targeted sequencing in the diagnosis of invasive pulmonary Aspergillus infection in a patient with acute promyelocytic leukemia.

Invasive pulmonary aspergillosis (IPA) is an infectious disease with a high mortality rate due to diagnostic difficulties associated with the lack of a typical clinical presentation and the inadequacy of the available laboratory testing methods. Nanopore targeted sequencing (NTS) is an alternative method of broad-based pathogen discovery, associated with rapid turnaround and high accuracy. This case report presents a patient with IPA and acute promyelocytic leukemia, diagnosed using the NTS method, which detected Aspergillus flavus in the patient's blood and pleural fluid. The patient was treated effectively with antifungal therapy. Early diagnosis of IPA improved long-term patient prognosis and quality of life.

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.

Diagnostic Efficacy of Aspergillus Galactomannan Lateral Flow Assay in Patients with Hematological Malignancies: A Prospective Multicenter Study.

BACKGROUND: A rapid and reliable diagnostic test is needed to reduce mortality through early diagnosis of invasive aspergillosis (IA) in patients with hematological malignancies. OBJECTIVE: To evaluate the efficacy of serum and bronchoalveolar lavage (BAL) Aspergillus galactomannan lateral flow assay (GM-LFA) in IA diagnosis and determine the correlation of GM-LFA with GM enzyme immunoassay (GM-EIA) in patients with hematological malignancies. METHODS: In this prospective multicenter study, we used serum and BAL fluid samples from patients with hematological malignancies and suspected IA and performed GM-LFA and GM-EIA. According to the EORTC/MSGERC criteria, patients were grouped as proven (n = 6), probable (n = 22), possible IA (n = 55), or no IA (n = 88). The performance of serum GM-LFA at 0.5 optical density index (ODI) and area under the curve (AUC) were calculated. Spearman's correlation analysis and kappa statistics were performed to determine the agreement between the tests. RESULTS: GM-LFA showed an AUC of 0.832 in proven/probable IA (sensitivity [SEN], specificity [SPE], negative predictive value [NPV], and diagnostic accuracy were 75%, 100%, 92.6%, and 93.9%, respectively, at a 0.5 ODI) versus that in no IA. A moderate positive correlation was noted between the GM-LFA and GM-EIA scores (p = 0.01). The observed agreement between the tests at 0.5 ODI was almost perfect (p < 0.001). After excluding patients who received mold-active antifungal prophylaxis or treatment, the SEN, SPE, NPV, and diagnostic accuracy for proven/probable IA were 76.2%, 100%, 93.3%, and 94.5%, respectively. CONCLUSIONS: Serum GM-LFA demonstrated high discriminatory power and good diagnostic performance for IA in patients with hematological malignancies.

Invasive Pulmonary Aspergillosis After Sars-CoV-2 Infection as Limitation of Contemporary Transplantology: A Case Report.

Invasive fungal infections are uncommon in pediatric heart transplant recipients. Risk and mortality are highest in the first 6 months post-transplant, especially in patients with previous surgery and those requiring mechanical support. There is a possibility that prior SARS-CoV-2 infection may cause a more severe course of pulmonary aspergillosis, especially in immunosuppressed individuals. This report describes a female patient, eight years of age, who was admitted to the pediatric cardiac surgery department with symptoms of end-stage heart failure in urgent need of mechanical circulatory support (MCS). A left ventricular assist device (LVAD) was implanted as a bridge to transplantation. During over a year on the waiting list, LVAD was replaced twice due to the presence of fibrin on the inlet valve. While staying in the ward, the patient underwent SARS-CoV-2 infection. An orthotopic heart transplant was successfully performed after 372 days of MCS with LVAD. One month after transplantation, the girl developed severe pulmonary aspergillosis complicated by sudden cardiac arrest and implantation of venovenous extracorporeal membrane oxygenation (VV ECMO) used for 25 days. Unfortunately, a few days after weaning from VV ECMO, the patient died due to intracerebral bleeding.

A Pathology-based Case Series of Influenza- and COVID-19-associated Pulmonary Aspergillosis: The Proof Is in the Tissue.

Rationale: Invasive pulmonary aspergillosis has emerged as a frequent coinfection in severe coronavirus disease (COVID-19), similarly to influenza, yet the clinical invasiveness is more debated. Objectives: We investigated the invasive nature of pulmonary aspergillosis in histology specimens of influenza and COVID-19 ICU fatalities in a tertiary care center. Methods: In this monocentric, descriptive, retrospective case series, we included adult ICU patients with PCR-proven influenza/COVID-19 respiratory failure who underwent postmortem examination and/or tracheobronchial biopsy during ICU admission from September 2009 until June 2021. Diagnosis of probable/proven viral-associated pulmonary aspergillosis (VAPA) was made based on the Intensive Care Medicine influenza-associated pulmonary aspergillosis and the European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) COVID-19-associated pulmonary aspergillosis consensus criteria. All respiratory tissues were independently reviewed by two experienced pathologists. Measurements and Main Results: In the 44 patients of the autopsy-verified cohort, 6 proven influenza-associated and 6 proven COVID-19-associated pulmonary aspergillosis diagnoses were identified. Fungal disease was identified as a missed diagnosis upon autopsy in 8% of proven cases (n = 1/12), yet it was most frequently found as confirmation of a probable antemortem diagnosis (n = 11/21, 52%) despite receiving antifungal treatment. Bronchoalveolar lavage galactomannan testing showed the highest sensitivity for VAPA diagnosis. Among both viral entities, an impeded fungal growth was the predominant histologic pattern of pulmonary aspergillosis. Fungal tracheobronchitis was histologically indistinguishable in influenza (n = 3) and COVID-19 (n = 3) cases, yet macroscopically more extensive at bronchoscopy in influenza setting. Conclusions: A proven invasive pulmonary aspergillosis diagnosis was found regularly and with a similar histological pattern in influenza and in COVID-19 ICU case fatalities. Our findings highlight an important need for VAPA awareness, with an emphasis on mycological bronchoscopic work-up.

Invasive Aspergillosis in a Patient With Diabetes Mellitus as the Only Risk Factor: Case Report and Literature Review.

Infection by Aspergillus covers a broad clinical spectrum, including invasive pulmonary aspergillosis (IPA) and its disseminated extrapulmonary form, invasive aspergillosis (IA). It typically occurs in severely immunocompromised hosts, but it sometimes affects the immunocompetent population, especially patients with acute diseases being treated at the intensive care unit (ICU) and less often those with chronic conditions. In this article, we report the case of a 50-year-old male, with diabetes mellitus (DM) as the only risk factor, treated for IPA and IA with cardiac and central nervous system (CNS) involvement at a high complexity institution in Cali-Colombia. Clinical presentation and radiological findings are unspecific and require a high level of suspicion. To confirm the case, histological or cytological of the fungus is required; histopathological examination of lung tissue is the gold standard, but it is difficult to perform due to respiratory compromise and high risk of bleeding, so bronchoscopy and bronchoalveolar lavage (BAL) plays an essential role in the diagnostic process. A diagnostic algorithm that includes risk assessment, symptoms, imaging findings, and isolation in cultures is essential to allow the diagnosis and initiation of treatment promptly, which includes a combination of surgery and antifungal medications for long periods, even life-long treatment.

Severe pediatric adenoviral pneumonia combined with invasive pulmonary aspergillosis.

BACKGROUND: This study aimed to analyze the clinical characteristics of severe pediatric adenoviral pneumonia combined with invasive pulmonary aspergillosis. METHODS: We retrospectively analyzed the clinical data of five children clinically diagnosed with severe adenoviral pneumonia combined with invasive pulmonary aspergillosis at Xiamen Children's Hospital. RESULTS: These five children included one boy and four girls, with ages of onset ranging from 8 months and 15 days to 2 years and 2 months. All of them had fever with a mean duration of 11-35 days and cough. Pulmonary imaging was performed, which revealed solid pulmonary opacification in all five children, pleural effusion in two children, and emphysema and multiple small cavity formations in one child. Multiple microbiological tests were performed on the 5 children, and adenovirus was positive in the alveolar lavage fluid for the first time, and aspergillus culture was positive in the second test. On tracheoscopy, the bronchial mucosa was seen to be congested and edematous or pale and eroded; white moss-like material was seen adhering to the tracheal wall or even blocking the airway. The five children were treated with a combination of two or more broad-spectrum antimicrobials, glucocorticoids, and gamma globulins and underwent bronchoscopy. Voriconazole was added in the treatment regimen after the diagnosis of aspergillosis (28-34 days of treatment). Four of the children were discharged in good condition with a mean total length of hospital stay of 17-47 days. The other child leave against medical advice. Follow-up 3-5 months after discharge showed that one child had been cured; two children had developed obliterative bronchiolitis; one child had developed bronchiectasis; and the remaining child who had been discharged spontaneously was not contactable via telephone. CONCLUSIONS: Immune disorders and antibiotic and steroid treatments for adenovirus infection are high-risk factors for secondary invasive pulmonary aspergillosis in children. Prolonged fever and cough are the main manifestations, but which lack specificity, and bronchoscopic mucosal-specific injury evaluation and alveolar lavage fluid culture are helpful in the diagnosis of aspergillosis. The long-term prognosis of severe pediatric adenoviral pneumonia combined with invasive pulmonary aspergillosis maybe poor.

[Comparison of the Results of Galactomannan and Beta Glucan Antigen Tests in the Suspicion of Invasive Pulmonary Aspergillosis]. / Invaziv Pulmoner Aspergilloz Süpheli Hastalarda Galaktomannan ve Beta Glukan Antijen Testlerinin Karsilastirilmasi.

Opportunistic fungal infections are an important cause of morbidity and mortality in immunocompromised patients. Invasive aspergillosis (IA) has an important place among these infections with ~ 250.000 cases annually. Reducing the mortality rate due to invasive aspergillosis is possible with early diagnosis and treatment of the disease. Because of the low sensitivity in microscopic examination, the time consuming of culture growth, and the difficulties in distinguishing colonization/infection, serological methods are frequently used in the diagnosis of invasive aspergillosis. The aim of this study was to determine the diagnostic performance of galactomannan and beta glucan tests for the diagnosis of invasive pulmonary aspergillosis (IPA). Sixty patients, followed up with the suspicion of invasive pulmonary aspergillosis in Gazi University Hospital were included in the study. The clinical classification of the patients was made according to the revised European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) criteria. A total of 10 patients were classified as probable invasive aspergillosis and 20 patients were classified as possible invasive fungal disease. Demographic data of the patients and various risk factors were recorded. One hundred and thirty serum and nine bronchoalveolar lavage (BAL) fluid samples were studied with Plateliaᵀᴹ Aspergillus Ag (Bio-Rad, France), Dynamiker Aspergillus Galactomannan and Dynamiker Fungus (1-3)-beta-D-Glucan (Dynamiker, China) kits. Sensitivity and specificity values were calculated according to U.S. Food and Drug Administration (FDA) approved Plateliaᵀᴹ Aspergillus Ag test. According to this study, the most important risk factors in the development of IPA were the use of steroids and immunomodulatory drugs. The sensitivity of the galactomannan test in the probable group was 77.8%, the specificity was 96.7%, the sensitivity of the beta glucan test was 61.1%, and the specificity was 92.6%. When these two tests were evaluated together, it was observed that the sensitivity in the probable group increased to 83.3% and the specificity decreased to 89.3%. The combined use of galactomannan and beta glucan tests increases the diagnostic sensitivity. Although the presence of prolonged neutropenia is an important risk factor for IA, the use of steroids and immunomodulatory drugs should be kept in mind in non-neutropenic patients.

Retrospective Multicenter Evaluation of the VirClia Galactomannan Antigen Assay for the Diagnosis of Pulmonary Aspergillosis with Bronchoalveolar Lavage Fluid Samples from Patients with Hematological Disease.

Galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid samples has become an essential tool to diagnose invasive pulmonary aspergillosis (IPA) and is part of diagnostic guidelines. Enzyme-linked immunosorbent assays (ELISAs) (enzyme immunoassays [EIAs]) are commonly used, but they have a long turnaround time. In this study, we evaluated the performance of an automated chemiluminescence immunoassay (CLIA) with BAL fluid samples. This was a multicenter retrospective study in the Netherlands and Belgium. BAL fluid samples were collected from patients with underlying hematological diseases with a suspected invasive fungal infection. Diagnosis of IPA was based on the 2020 European Organisation for Research and Treatment of Cancer (EORTC)/Mycoses Study Group Education and Research Consortium (MSGERC) consensus definitions. GM results were reported as optical density index (ODI) values. ODI cutoff values for positive results that were evaluated were 0.5, 0.8, and 1.0 for the EIA and 0.16, 0.18, and 0.20 for the CLIA. Probable IPA cases were compared with two control groups, one with no evidence of IPA and another with no IPA or possible IPA. Qualitative agreement was analyzed using Cohen's κ, and quantitative agreement was analyzed by Spearman's correlation. We analyzed 141 BAL fluid samples from 141 patients; 66 patients (47%) had probable IPA, and 56 cases remained probable IPA when the EIA GM result was excluded as a criterion, because they also had positive culture and/or duplicate positive PCR results. Sixty-three patients (45%) had possible IPA and 12 (8%) had no IPA. The sensitivity and specificity of the two tests were quite comparable, and the overall qualitative agreement between EIA and CLIA results was 81 to 89%. The correlation of the actual CLIA and EIA values was strong at 0.72 (95% confidence interval, 0.63 to 0.80). CLIA has similar performance, compared to the gold-standard EIA, with the benefits of faster turnaround because batching is not required. Therefore, CLIA can be used as an alternative GM assay for BAL fluid samples.