Allergic bronchopulmonary mycosis due to Schizophyllum commune in a patient with chronic hepatitis B.

INTRODUCTION: Schizophyllum commune (S. commune) is an opportunistic pathogenic fungus and can cause infection of the respiratory system in immunocompromised hosts. Allergic bronchopulmonary mycosis (ABPM) is the major disease caused by S. commune. However, identification of S. commune using routine mycological diagnostic methods is difficult. It is easy to make mistakes in diagnosis and treatment, resulting in deterioration of the disease. We report the first case of ABPM due to S. commune in a Chinese patient with chronic hepatitis B. CASE PRESENTATION: The patient presented cough, sputum and dyspnea for six months. The pathogen was missed during routine laboratory workup. We performed bronchoscopy examination and bronchoalveolar lavage. S. commune was identified by metagenomic next-generation sequencing (mNGS) of bronchial alveolar lavage fluid (BALF). Hence, the patient was immediately treated with 200 mg voriconazole twice daily (intravenous infusion) and 20 mg prednisone once a day (oral therapy), along with oral entecavir for hepatitis B. There was no recurrence of infection after the medication was discontinued. CONCLUSIONS: S. commune infection should be considered in the diagnosis of patients with refractory cough, sputum and dyspnea, especially in immunocompromised individuals. The mNGS technique is an effective supplementary technique for the diagnosis of S. commune infection, enabling precise clinical decision-making and appropriate treatment. Most patients have good prognosis with a combination of proper antifungal therapy and hormonal therapy.

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.

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

Diagnostic performance of serum galactomannan and ß-D-glucan for invasive aspergillosis in suspected patients: A meta-analysis.

BACKGROUND: Serum galactomannan (GM) and ß-D-glucan (BG) are known markers of invasive aspergillosis (IA). The aim of this meta-analysis was to evaluate the efficiency of serum GM and BG as diagnostic markers of symptomatic IA infection and compare the performance of the combined tests with that of either test individually. METHODS: A literature search was carried out using PubMed, Web of Science, and EMBASE databases to include relevant studies published in English up to May 2023. The quality assessment was performed using Review Manager 5.3 software. A bivariate model was applied to pool diagnostic parameters using Stata 14.0 software. We used Cochrane I2 index to assess heterogeneity and identify the potential source of heterogeneity by meta-regression. Paired t tests were used to compare the value of GM and BG for IA diagnosis when used in combination or alone. RESULTS: Sixteen studies were eligible for inclusion in the meta-analysis. For proven or probable IA, serum GM and BG yielded a pooled sensitivity of 0.53 (95% CI 0.40-0.66) vs 0.72 (95% CI 0.61-0.81) and a pooled specificity of 0.94 (95% CI 0.91-0.97) vs 0.82 (95% CI 0.73-0.88). The area under the curve (AUC) of ROC was 0.90 (95% CI 0.87-0.92) vs 0.83 (95% CI 0.80-0.86) for all studies. The pooled sensitivity and specificity for IA diagnosis by combined GM and BG assays (GM/BG) were 0.84 (95% CI 0.69-0.86) and 0.76 (95% CI 0.69-0.81), respectively. The sensitivity of the combined GM/BG test to diagnose IA was higher than of the GM or BG test alone. CONCLUSION: Serum GM and BG tests had a relatively high accuracy for IA diagnosis in suspected patients. The diagnostic accuracy of both assays is comparable, and the diagnostic sensitivity is further improved by the combined detection of the 2 markers.

Acute Invasive Pulmonary Aspergillosis: Clinical Presentation and Treatment.

Among all clinical manifestations of pulmonary aspergillosis, invasive pulmonary aspergillosis (IPA) is the most acute presentation. IPA is caused by Aspergillus hyphae invading the pulmonary tissue, causing either tracheobronchitis and/or bronchopneumonia. The degree of fungal invasion into the respiratory tissue can be seen as a spectrum, going from colonization to deep tissue penetration with angio-invasion, and largely depends on the host's immune status. Patients with prolonged, severe neutropenia and patients with graft-versus-host disease are at particularly high risk. However, IPA also occurs in other groups of immunocompromised and nonimmunocompromised patients, like solid organ transplant recipients or critically ill patients with severe viral disease. While a diagnosis of proven IPA is challenging and often warranted by safety and feasibility, physicians must rely on a combination of clinical, radiological, and mycological features to assess the likelihood for the presence of IPA. Triazoles are the first-choice regimen, and the choice of the drug should be made on an individual basis. Adjunctive therapy such as immunomodulatory treatment should also be taken into account. Despite an improving and evolving diagnostic and therapeutic armamentarium, the burden and mortality of IPA still remains high. This review aims to give a comprehensive and didactic overview of the current knowledge and best practices regarding the epidemiology, clinical presentation, diagnosis, and treatment of acute IPA.

Effect of volume of instillate on the diagnostic utility of bronchoalveolar lavage galactomannan in patients with suspected chronic pulmonary aspergillosis-A pilot study.

BACKGROUND: Bronchoalveolar lavage (BAL) galactomannan (GM) is commonly used to diagnose Aspergillus-related lung diseases. However, unlike serum GM, which is measured in undiluted blood, BAL-GM is estimated using variable aliquots and cumulative volume of instillates during bronchoscopy. OBJECTIVE: Since different studies have reported varying diagnostic accuracy and cut-offs for BAL-GM in CPA, we hypothesized that the total volume of instillate and 'order/label' of aliquots significantly affects the BAL-GM values, which was evaluated as part of this study. PATIENTS & METHODS: We obtained 250 BAL samples from 50 patients (five from each) with suspected chronic pulmonary aspergillosis. BAL fluid was collected after instilling sequential volumes of 40 mL of normal saline each for the first four labels and a fifth label was prepared by mixing 1 mL from each of the previous labels. The GM level of each label was measured by PLATELIA™ ASPERGILLUS Ag enzyme immunoassay. This study measured the discordance, level of agreement, diagnostic characteristics (sensitivity, specificity and AUROC) and best cut-offs for BAL-GM in the different aliquots of lavage fluid. RESULTS: The study population, classified into CPA (28%) and non-CPA (72%) groups, based on ERS/ESCMID criteria (excluding BAL-GM) were not different with respect to clinico-radiological characteristics. The discordance of BAL-GM positivity (using a cut-off of >1) between the serial labels for the same patient ranged between 10% and 22%, while the discordance between classification using BAL-GM positivity (using a cut-off of ≥1) and clinic-radio-microbiological classification ranged between 18% and 30%. The level of agreement for serial labels was at best fair (<0.6 for all except one 'label'). The AUROC for the serial samples ranged between 0.595 and 0.702, with the '40 mL and the 'mix' samples performing the best. The best BAL-GM cut-off also showed significant variation between serial labels of varying dilutions (Range:1.01 - 4.26). INTERPRETATION: This study highlights the variation in BAL-GM measured and the 'positivity' between different 'labels' of aliquots of BAL, with the first aliquot and the mixed sample showing the best performances for diagnosis of CPA. Future studies should attempt to 'standardise' the instilled volume for BAL-GM estimation to standardise the diagnostic yield.

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.

Comparison of different criteria of metagenomic next-generation sequencing for the diagnosis of invasive pulmonary aspergillosis in critically ill patients.

OBJECTIVE: To compare different criteria of Metagenomic Next-Generation Sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) for diagnosing invasive pulmonary aspergillosis (IPA). METHODS: We compared the diagnostic agreement and performances of six BALF mNGS-derived criteria (SDSMRN>1, SDSMRN≥3, SMRN≥10, SMRN≥50, RPM ratio≥10, and relative abundance of genus>30 %) in pneumonia patients. RESULTS: A total of 115 patients were analyzed, with 28 identified with IPA. Diagnostic agreement among the six mNGS-derived criteria was moderate, with a Cohen's kappa of 0.577(P < 0.001). mNGS-derived criteria had low sensitivity ranging from 21.4 % to 57.1 % and high specificity from 88 % to 92 %. The optimal threshold of SDSMRN, SMRN, RPM ratio, and relative abundance of genus for diagnosing IPA were 5, 0.25, 8, and 20 %, respectively. Although using the optimal threshold, the sensitivity of mNGS is lower than 50 %. CONCLUSIONS: All mNGS-derived criteria had low sensitivity for diagnosing IPA. A combination of mNGS and conventional mycological tests may be the best diagnostic strategy.

Risk factors and the value of microbiological examinations of COVID-19 associated pulmonary aspergillosis in critically ill patients in intensive care unit: the appropriate microbiological examinations are crucial for the timely diagnosis of CAPA.

Introduction: During the Omicron pandemic in China, a significant proportion of patients with Coronavirus Disease 2019 (COVID-19) associated pulmonary aspergillosis (CAPA) necessitated admission to intensive care unit (ICU) and experienced a high mortality. To explore the clinical risk factors and the application/indication of microbiological examinations of CAPA in ICU for timely diagnosis are very important. Methods: This prospective study included patients with COVID-19 admitted to ICU between December 1, 2022, and February 28, 2023. The clinical data of influenza-associated pulmonary aspergillosis (IAPA) patients from the past five consecutive influenza seasons (November 1, 2017, to March 31, 2022) were collected for comparison. The types of specimens and methods used for microbiological examinations were also recorded to explore the efficacy in early diagnosis. Results: Among 123 COVID-19 patients, 36 (29.3%) were diagnosed with probable CAPA. CAPA patients were more immunosuppressed, in more serious condition, required more advanced respiratory support and had more other organ comorbidities. Solid organ transplantation, APACHEII score ≥20 points, 5 points ≤SOFA score <10 points were independent risk factors for CAPA. Qualified lower respiratory tract specimens were obtained from all patients, and 84/123 (68.3%) patients underwent bronchoscopy to obtain bronchoalveolar lavage fluid (BALF) specimens. All patients' lower respiratory tract specimens underwent fungal smear and culture; 79/123 (64.2%) and 69/123 (56.1%) patients underwent BALF galactomannan (GM) and serum GM detection, respectively; metagenomic next-generation sequencing (mNGS) of the BALF was performed in 62/123 (50.4%) patients. BALF GM had the highest diagnostic sensitivity (84.9%), the area under the curve of the mNGS were the highest (0.812). Conclusion: The incidence of CAPA was extremely high in patients admitted to the ICU. CAPA diagnosis mainly depends on microbiological evidence owing to non-specific clinical manifestations, routine laboratory examinations, and CT findings. The bronchoscopy should be performed and the BALF should be obtained as soon as possible. BALF GM are the most suitable microbiological examinations for the diagnosis of CAPA. Due to the timely and accuracy result of mNGS, it could assist in early diagnosis and might be an option in critically ill CAPA patients.

Efficacy and safety of voriconazole in the treatment of invasive pulmonary aspergillosis in patients with liver failure: study protocol for a randomized controlled clinical trial.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a common clinical type of liver failure, and patients with acute-on-chronic liver failure are prone to fungal infections, especially the increasing incidence of invasive pulmonary aspergillosis (IPA). Voriconazole is recommended as the first-line antifungal agent in the treatment of invasive aspergillosis; however, no recommendation has been given for patients with severe liver cirrhosis (Child-Pugh C) and liver failure. This trial aims to examine the therapeutic effects and safety of voriconazole in the treatment of IPA in patients with liver failure. METHODS: This study is a non-double-blind randomized controlled trial. The 96 eligible acute-on-chronic liver failure patients complicated with invasive pulmonary aspergillosis will be randomly assigned to receive either the optimized voriconazole regimen or the recommended voriconazole regimen for patients with mild to moderate liver cirrhosis (Child-Pugh A and B), at a 1:1 ratio, with an 8-week follow-up period. The antifungal efficacy of voriconazole will be the primary outcome measure. Plasma voriconazole trough concentration, the laboratory examination (CRP, PCT, ESR, etc.), chest CT, adverse events, and mortality at week 4 and 8 will be the secondary outcome measures. DISCUSSION: This trial aims to demonstrate the efficacy and safety of voriconazole in the treatment of IPA in patients with liver failure, which is expected to provide a reference for scientific optimization of voriconazole regimens and a realistic basis for the standardized treatment of acute-on-chronic liver failure patients complicated with invasive pulmonary aspergillosis. TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Registry, ChiCTR2100048259. Registered on 5 July 2021.

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.

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.

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.

Fatal invasive pulmonary aspergillosis in non-immunocompromised host: A case report.

RATIONALE: Invasive pulmonary aspergillosis (IPA) is an uncommon but life-threatening disease. The disease often occurs in immunocompromised patients or critically ill patients. Here, we reported that IPA occurred in a non-immunocompromised host. PATIENT CONCERNS: A 45-year-old man was admitted to the hospital for 1 week due to fever and cough. He was engaged in waste recycling and lived in a dark and humid environment for a long time. DIAGNOSIS: Invasive pulmonary aspergillosis. INTERVENTIONS: Next generation sequencing and pathological examination of alveolar lavage fluid indicated aspergillus infection. He received voriconazole infusion after admission. After 5 weeks of antifungal treatment, his condition improved significantly and discharged. OUTCOME: One week after discharge, his condition deteriorated again and returned to the hospital. Unfortunately, he died. LESSON: The immunocompetent adults can develop invasive pulmonary aspergillosis if they are exposed to high-risk environments. IPA in non-immunocompromised host should arouse the vigilance of clinicians.

Aspergillus coinfection in critically Ill patients with severe dengue.

In 2014-2015, a significant outbreak of dengue fever occurred in southern Taiwan, with a subsequent decline in dengue incidence. Despite this, there is emerging concern about virus-associated aspergillosis, yet limited research has explored coinfections involving dengue and aspergillosis. We conducted a retrospective study at a single center in Southern Taiwan, specifically focusing on dengue patients admitted to the intensive care unit during the period between July and November 2015. Among the 142 dengue patients studied, only 8.06 % (10/142) underwent serum galactomannan testing, with a single patient undergoing bronchoalveolar lavage (BAL) galactomannan assay. Out of those tested, 20 % (2/10) returned positive serum galactomannan results. Herein, we present two consecutive cases of coinfection involving dengue and pulmonary aspergillosis in immunocompetent patients.

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.

Microbiological diagnosis of pulmonary invasive aspergillosis in critically ill patients with severe SARS-CoV-2 pneumonia: a bronchoalveolar study.

BACKGROUND: Diagnosing COVID-19-associated pulmonary aspergillosis (CAPA) can be challenging since radiological and clinical criteria in the critically ill patient are nonspecific. Microbiological diagnostic support is therefore crucial. The aim of this study was to document the incidence of aspergillosis using bronchoalveolar lavage (BAL) as the diagnostic method and to determine the performance of the current mycological diagnostic tests most widely used for the diagnosis of CAPA, together with evaluation of the Asp lateral flow device (LFD). METHODS: Prospective cohort study conducted between March 2020 and June 2022. Inclusion criteria were critically ill patients admitted to the ICU with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation. Diagnostic bronchoscopy and BAL were performed at the beginning of invasive mechanical ventilation. The sensitivity, specificity, positive and negative predictive value (PPV and NPV), positive and negative likelihood ratio (LR + and LR-) of BAL culture, direct examination with calcofluor white stain, ELISA (Platelia) and LFD (AspLFD) for detection of galactomannan (GM) were evaluated. Aspergillus-qPCR was applied when discrepancies between diagnostic tests arose. RESULTS: Of the 244 critically ill patients with SARS-CoV-2 pneumonia admitted to the ICU, the majority (n = 200, 82%) required invasive mechanical ventilation. Diagnostic bronchoscopic procedures were performed in 160 patients (80%), who were enrolled in this study. The incidence of CAPA was 18.7% (n = 30). LFD-GM demonstrated a sensitivity of 84%, specificity of 99%, PPV 94%, NPV 97%, LR(+) of 84, and LR(-) of 0.16. At GM-ELISA indices of ≥ 0.5 and ≥ 1.0, sensitivity was 92% and 79%, specificity was 95% and 99%, PPV 76% and 91%, NPV 99% and 96%, LR(+) 18 and 79, and LR(-) 0.08 and 0.21, respectively. The optimal cut-off index from the ROC curve was 0.48, with sensitivity of 95% and specificity of 95%. CONCLUSIONS: Using a diagnostic strategy based on bronchoscopy and BAL, we documented a high incidence of pulmonary aspergillosis in patients with severe SARS-CoV-2 pneumonia. Asp-LFD showed moderate sensitivity and excellent specificity, with a high PPV, and could be used for rapid diagnosis of patients with suspected CAPA.

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.