Aspergillosis In Patients Research Articles

P262 Clinico- microbiological profile of post-COVID pulmonary fungal infections encountered during the second wave of COVID-19 pandemic at a tertiary care teaching hospital in the Himalayas

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM ObjectiveThe study aims to generate preliminary data about post-COVID pulmonary fungal infections in the Himalayas and analyze patients’ micro-radio-clinical profiles and outcomes.MethodologyWe conducted a retrospective study at a tertiary care teaching hospital in the Himalayas to generate preliminary post-COVID pulmonary fungal infection data. Sputum, Endotracheal Tube (ET), and Bronchoalveolar lavage (BAL) samples of patients sent to the Mycology laboratory were subjected to KOH mount and aerobic inoculation on Sabouraud dextrose agar plates at 37°C. The patients’ symptoms, diagnosis, clinical-radiological profile, and outcome were collected from the hospital database.ResultsAmong n = 16 cases of post-COVID pulmonary fungal infections aged 53 +/- 13.38 years, n = 7 (43.75%) had Pulmonary Aspergillosis (n = 5 A. fumigatus, n = 1 A. flavus, n = 1 A. niger), n = 5 (31.25%) had Pulmonary Mucormycosis (Rhizopus arrhizus), and n = 4 (25%) had mixed infection. In 2 of 4 mixed infection patients, R. arrhizus was identified on KOH microscopy and A. fumigatus on SDA Agar. Both A. fumigatus and R. arrhizus were identified on KOH Microscopy of the third patient, while only A. fumigatus was cultivated on his SDA Agar. Aspergillus flavus and R. arrhizus were isolated simultaneously from the sample of the last patient, but only R. arrhizus was identified on KOH Microscopy.Clinical symptoms were similar among Pulmonary Aspergillosis and Mucormycosis patients, but hemoptysis was reported only among Pulmonary Aspergillosis patients. Pre-existing co-morbid end-organ damage, AKI, CKD, CLD, COPD, and CAD was more common among Pulmonary Mucormycosis patients and rare among Pulmonary Aspergillosis patients. Treatment requirements and clinical outcomes of patients infected with either mold were similar. The clinical profile of mixed infection patients was notably different from the others. All the patients were males, none complained of chest pain or expectoration, and none had a history of PTB, AKI, CKD, CLD, COPD, or CAD. Only 2 (50%) mixed infection patients needed supplemental high flow oxygen, unlike all (100%) patients diagnosed with single mold infection. None of the mixed infection patients required steroids. Moreover, none of the mixed infection patients died, unlike 60% mortality in cases of single-species infections.On radiological investigation, n = 6 had typical thick-walled cavitary lesions with air-fluid levels and multiple centrilobular nodules giving a tree in bud appearance, of which n = 4 had bilateral lung involvement, and n = 2 had only one lung involved. n = 1 patient had a well-circumscribed lung abscess.ConclusionCOVID patients from the Himalayas had a higher prevalence of invasive pulmonary fungal infections, probably due to the dense surrounding vegetation. The immuno-compromised state following COVID-19 infection/treatment might be responsible for the progression of regular exposure to invasive pulmonary infection.

P059 The overexpression of efflux pump gene cdr1B resulting in voriconazole- and isavuconazole- resistance in Aspergillus fumigatus recovered from a patient with chronic pulmonary aspergillosis in China

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PMObjectivesTriazole resistance in the pathogenic Aspergillus fumigatus has been increasing worldwide, posing a growing therapeutic challenge. To date, triazole resistance in clinical isolates of A. fumigatus causing pulmonary aspergillosis has been mainly attributed to the mutations in the cyp51A gene or its promoter, followed by mutations in cyp51B and hmg1 gene encoding 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. From chronic pulmonary aspergillosis (CPA) patient, we isolated a strain of A. fumigatus (BMU10672) with resistance to voriconazole (VRC) and isavuconazole (ISZ), which was caused by overexpression of efflux pump Cdr1B.MethodsAntifungal susceptibility testing of the isolate of A. fumigatus BMU10672 was performed using the broth microdilution method (CLSI M38-A3), E-test and disk diffusion method. The promoter region and open reading frame of the cyp51A, cyp51B, and hmg1 gene were amplified and sequenced. Then, the expression levels of cyp51A, cyp51B, and efflux pump gene cdr1B with or without being exposed to VRC or ISZ were quantified using real-time PCR, compared with triazole-susceptible A. fumigatus Af293. And the function of efflux pump Cdr1B was tested by efflux pump substrate (Nile red) accumulation assay and efflux pump inhibitor (FK520) assay.ResultsThe minimum inhibitory concentration (MIC) of itraconazole (ITC), VRC, posaconazole (POS), ISZ and amphotericin B (AMB), and the minimal effective concentration (MEC) of caspofungin (CAS) against A. fumigatus BMU10672 was 1 μg/ml, 2 μg/mL, 0.5 μg/mL, 2 μg/mL, 1 μg/mL and 0.125 μg/mL, respectively. The results of E-test and disk diffusion assay were consistent with those of the broth microdilution method (Figs. 1a and b). Together, these results indicate that A. fumigatus BMU10672 is resistant to VRC and ISZ, while being susceptible to ITC, POS, AMB, and CAS. Sequencing of the cyp51A, cyp51B and hmg1 gene of A. fumigatus BMU10672 were all intact. The basal and VRC- or ISZ- induced expression levels of efflux pumps gene cdr1B in A. fumigatus BMU10672 were all higher (> 4-fold) than those in triazole-susceptible A. fumigatus Af293. However, no differences in basal and VRC- or ISZ- induced expression levels of cyp51A gene and cyp51B gene were observed between A. fumigatus BMU10672 and Af293. The efflux pump substrate Nile red accumulation assay showed the A. fumigatus BMU10672 accumulated less Nile red than Af293, confirming that Cdr1B was active at exporting Nile red, while efflux pumps inhibitor FK520 can increase the accumulation of the Nile red in A. fumigatus BMU10672 (Fig. 1c). Inhibition of efflux pumps activity by inhibitor FK520 resulted in a MIC reduction of 4-fold in VRC and ISZ MICs, and 2-fold in ITC and POS, against A. fumigatus BMU10672 (Figs. 1a and b).ConclusionOverexpression of efflux pumps gene cdr1B resulting in VRC- and ISZ- resistance in the clinical isolate of A. fumigatus BMU10672.

P291 Aspergillosis: another force to reckon with during COVID-19 times

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectives Aspergillus is a ubiquitous fungus in the Indian environment. Spores are constantly circulating in hospital and community environments alike. Infections like COVID-19 which affect not only innate immune system but also lead to local immune-compromization especially in the respiratory system make the patient vulnerable to infections like Aspergillosis. Hereby, we present the prevalence of Aspergillus infection in a tertiary care center over a period of 1 year with special reference to co-infections with COVID-19 as Aspergillosis or mixed infection (Aspergillosis and Mucormycosis).Material and MethodsAll the samples which were submitted to Mycology laboratory during the time period of 1 year from January 2021 to December 2021 were included in the study. The samples were processed as per the standard mycological techniques for direct examination and culture. Those patients which had direct KOH mount positive for septate hyphae and grew Aspergillus on culture were included for the purpose of this study. Records of Aspergillosis patients who were positive for COVID-19 too were assessed to look for significant associating factors.ResultsOut of a total of 6863 samples, 66 samples came out to be positive for Aspergillus sp. Out of which, 55 were identified phenotypically as A. flavus, 3 A. fumigatus, 2 A. terreus and 1 was A. niger. In five of the strains, species could not be identified even phenotypically and were reported as Aspergillus sp. Maximum isolates (43) were from nasal and paranasal sinuses (sinus discharge, nasal tissue, nasal polyp, nasal muck, nasal crust, maxillary meatus etc) 16 were pulmonary samples (sputum, tracheal aspirate, bronchoalveolar lavage, pleural fluid, lung tissue), two were corneal scrapings, two samples were dental tissue and palatal necrosed material and two were nail samples. One sample was from a patient with ear discharge. A total of 15 patients had COVID-19 infection at the time of diagnosis or within 3 months prior. In all, 12 patients had co-infections of Aspergillus and Mucormycetes (9 being COVID positive too), and 2 patients had co-infection of Aspergillus and Candida. Records of COVID-19 patients revealed that all 12 patients with co-infection of Aspergillus and Mucormycetes were treated as per guidelines for Mucormycetes infection. Out of other three, two were confirmed CAPA as per the criteria. One patient was treated for COVID-19 infection only.ConclusionMucormycosis was another infection during COVID-19 times, which was like a huge wave, sweeping all attention. Rather Aspergillus infections got shadowed by mucormycosis despite the fact that during COVID-19 times, as many as 15% of cases were found to be positive for Aspergillosis in COVID-19 positive patients, especially in ICU areas. In the times to come, it is speculated that sequelae of Aspergillus infections may be seen among COVID-19 patients. Emerging drug resistance among Aspergilli can worsen the situation further.

P407 Standardization of PCR for the diagnosis of invasive aspergillosis and invasive mucormycosis from blood samples

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjectives(1) Standardization of PCR-based diagnosis of invasive aspergillosis and invasive mucormycosis in spiked blood samples. (2) Standardization of PCR-based diagnosis of invasive aspergillosis and invasive mucormycosis in proven cases. (3) Validation of the above-standardized protocol in patients with proven/probable invasive aspergillosis or mucormycosis.Materials and Methods: Blood samples were collected from healthy volunteers and patients with proven mucormycosis, proven invasive aspergillosis, and suspected invasive fungal infection. Standard strains of Mucorales and Aspergillus spp. were collected from the National Culture Collection of Pathogenic Fungi, PGIMER and DNA was extracted using a modified protocol of the fungal DNA extraction method by Lee and Taylor (1990). Mucor-specific primer (ZM13), described by Bialek R et al. (2005) was used for mucormycosis samples. Aspergillus specific primer pair was designed from mitochondrial DNA of A. fumigatus using Primer3 software. Genomic DNA was used to determine the optimum annealing temperature and concentration for ZM13 assay. DNA extracted from whole blood samples of healthy volunteers after spiking with a known quantity of A. fumigatus DNA and only genomic DNA was used separately to optimize annealing temperature and concentration of Aspergillus-specific primers. Similarly, whole blood, plasma, and serum samples from healthy volunteers were spiked with various concentrations of Rhizopus arrhizus and A. fumigatus DNA. DNA extracted from spiked samples was used to determine the analytical sensitivity of PCR assays. DNA extracted from blood samples of ten proven mucormycosis and five invasive aspergillosis patients were used to determine the optimum sample dilution factor and template volume for the assay. The final standardized protocols were validated using 28 proven/probable cases of invasive aspergillosis and invasive mucormycosis and thirty cases of suspected invasive fungal infection.ResultsThe optimum annealing temperature and primer concentrations for the assay were 54.3°C and 0.4μm respectively for ZM13 assay and 53°C and 0.45μm respectively for Aspergillus assay. The limit of detection was 0.06fg/μl for ZM13 assay and 0.08fg/μL for Aspergillus specific assay. For mucormycosis assay, the slope of the standard curve was −3.2687 and the percentage efficiency of the assay was 104% with 0.9936 as the coefficient of determination (R2). Likewise, the slope of the standard curve was −3.2695, the percentage efficiency of the assay 102%, and the coefficient of determination (R2) 0.9858 for aspergillosis assay. The best combination of template volume and sample dilution factor was 2.5 μl and 1000x in whole blood samples and, 2.5 μl and 100x in serum samples for mucormycosis assay. It was 1.0 μl and 10x in serum samples for Aspergillus specific assay. The sensitivity, specificity, positive predictive value, and negative predictive value of mucormycosis qPCR using serum samples were 79.3%, 86.4%, 65.7%, and 92.7% respectively. The assay had a positive likelihood ratio of 5.92 and a negative likelihood ratio of 0.24.ConclusionThe real-time PCR protocols standardized for the diagnosis of mucormycosis and invasive aspergillosis from blood samples showed promising results. However, the assay needs further validation in a larger study population.

Metabolomic profiling of exhaled breath condensate for the diagnosis of pulmonary aspergillosis.

ObjectiveThis study aims to ascertain the unique metabolic profile of exhaled breath condensate (EBC) samples in pulmonary aspergillosis (PA) patients, and explore their usefulness for the diagnosis of PA.MethodsA total of 133 patients were included in the study, including 66 PA patients (invasive pulmonary aspergillosis, n=3; chronic pulmonary aspergillosis, n=60; allergic bronchopulmonary aspergillosis, n=3) and controls (n=67). Ultra high-performance liquid chromatography coupled with high-resolution mass spectrometry(UHPLC-HRMS) was used to analyze EBC samples. Metabolic profiling of EBC samples that were collected from 22 CPA patients at various times during treatment (before treatment, <1 month, 1–2 months, 2–3 months, 3–6 months, and ≥6 months after treatment initiation) were performed using UHPLC-HRMS. Potential biomarkers were evaluated using cluster analysis, Venn diagram and receiver operating characteristic analysis (ROC).ResultsA total of 47 metabolites of potential interest were detected in the EBC samples. Further investigation showed that Asperpyrone C, Kotanin, Terphenyllin, Terrelumamide B, and Cyclotryprostatin D could be used as a diagnostic biomarker for PA. The classification between metabolic profiling of EBC samples from PA patients and controls was good with a sensitivity of 100%, specificity 89.6% for patients with PA, respectively. Venn diagram analysis of these biomarker candidates displayed three main types of compounds, which could be used for the further discrimination of aspergilloma and chronic cavitary PA. In addition, antifungal treatment had a limited influence on the value of the EBC results.ConclusionsThis metabolomic approach using UHPLC-HRMS could be used as a noninvasive method for the diagnosis of PA.

Invasive pulmonary aspergillosis in critically ill patients with pneumonia due to COVID-19, influenza, and community-acquired pneumonia: A prospective observational study.

Influenza A and SARS-CoV-2 are risk factors for invasive pulmonary aspergillosis. Both influenza-associated pulmonary aspergillosis and COVID-19-associated pulmonary aspergillosis result in high mortality and poor clinical outcomes. No prospective study has so far compared the features, treatment, and outcomes of influenza-associated pulmonary aspergillosis and COVID-19-associated pulmonary aspergillosis within a similar time frame. Therefore, this study aimed to determine the frequency, risk factors, and outcomes of invasive pulmonary aspergillosis in critically ill patients with influenza, COVID-19, and community-acquired pneumonia. This prospective study included adult patients with pneumonia and was conducted at The Aga Khan University Hospital in Karachi, Pakistan. Patients were divided into three groups, including community-acquired pneumonia, influenza pneumonia, and COVID-19 pneumonia. The data collected included information on demographic characteristics, comorbidities, clinical features, laboratory results, treatment, and outcomes. A total of 140 patients were included in this study. These included 35 (25%), 70 (50%), and 35 (25%) patients with community-acquired pneumonia, influenza pneumonia, and COVID-19 pneumonia, respectively. In addition, 20 (14.2%) patients were found to have invasive aspergillosis, of whom 10/35 (28.5%), 9/70 (12.8%), and 1/35 (2.8%) patients were in the COVID-19, influenza, and community-acquired pneumonia groups, respectively. Moreover, nine (90%) COVID-19-associated pulmonary aspergillosis patients required vasopressors, compared to three (33%) patients with influenza-associated pulmonary aspergillosis (P=0.020). In total, seven (70%) COVID-19-associated pulmonary aspergillosis patients required invasive mechanical ventilation compared to four (44%) influenza-associated pulmonary aspergillosis patients (P=0.37). The mean±SD length of hospital stay was highest in the COVID-19-associated pulmonary aspergillosis patients (18.3±7.28 days) compared to influenza-associated pulmonary aspergillosis patients (11.7±5.34 days) (P=0.036). The number of deaths in influenza-associated pulmonary aspergillosis and COVID-19-associated pulmonary aspergillosis patients was three (33.3%) and five (50%), respectively (P=0.526). A higher proportion of patients with COVID-19 developed invasive aspergillosis compared to those with influenza. Although the mortality rate in COVID-19-associated pulmonary aspergillosis was comparable to that in influenza-associated pulmonary aspergillosis patients, COVID-19-associated pulmonary aspergillosis patients had a significantly longer stay in the hospital.

P-138: Clinical profile and outcome of invasive aspergillosis in patients with myeloma: a single centre expereince from North India

P-138: Clinical profile and outcome of invasive aspergillosis in patients with myeloma: a single centre expereince from North India

Metagenomic next-generation sequencing for the diagnosis of pulmonary aspergillosis in non-neutropenic patients: a retrospective study.

This study aimed to obtain further in-depth information on the value of metagenomic next-generation sequencing (mNGS) for diagnosing pulmonary aspergillosis in non-neutropenic patients. We did a retrospective study, in which 33 non-neutropenic patients were included, of which 12 were patients with pulmonary aspergillosis and 21 were diagnosed with non-pulmonary aspergillosis. Fungi and all other co-pathogens in bronchoalveolar lavage fluid (BALF) (27 cases), blood (6 cases), and/or pleural fluid (1 case) samples were analyzed using mNGS. One of the patients submitted both BALF and blood samples. We analyzed the clinical characteristics, laboratory tests, and radiologic features of pulmonary aspergillosis patients and compared the diagnostic accuracy, including sensitivity, specificity, positive predictive value, and negative predictive value of mNGS with conventional etiological methods and serum (1,3)-β-D-glucan. We also explored the efficacy of mNGS in detecting mixed infections and co-pathogens. We further reviewed modifications of antimicrobial therapy for patients with pulmonary aspergillosis according to the mNGS results. Finally, we compared the detection of Aspergillus in BALF and blood samples from three patients using mNGS. In non-neutropenic patients, immunocompromised conditions of non-pulmonary aspergillosis were far less prevalent than in patients with pulmonary aspergillosis. More patients with pulmonary aspergillosis received long-term systemic corticosteroids (50% vs. 14.3%, p < 0.05). Additionally, mNGS managed to reach a sensitivity of 91.7% for diagnosing pulmonary aspergillosis, which was significantly higher than that of conventional etiological methods (33.3%) and serum (1,3)-β-D-glucan (33.3%). In addition, mNGS showed superior performance in discovering co-pathogens (84.6%) of pulmonary aspergillosis; bacteria, bacteria-fungi, and bacteria-PJP-virus were most commonly observed in non-neutropenic patients. Moreover, mNGS results can help guide effective treatments. According to the mNGS results, antimicrobial therapy was altered in 91.7% of patients with pulmonary aspergillosis. The diagnosis of Aspergillus detected in blood samples, which can be used as a supplement to BALF samples, seemed to show a higher specificity than that in BALF samples. mNGS is a useful and effective method for the diagnosis of pulmonary aspergillosis in non-neutropenic patients, detection of co-pathogens, and adjustment of antimicrobial treatment.

Biologic drugs in treating allergic bronchopulmonary aspergillosis in patients with cystic fibrosis: a systematic review.

Aspergillus fumigatus is a common saprophytic fungus causing allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (CF). The recommended first-line treatment for ABPA is oral steroids, followed by antifungal therapy. However, both treatments are not free from adverse effects; thus, efforts are being made to identify new drugs showing the same effectiveness but with fewer or no side-effects. Therein, biologic drugs have been significantly implemented in clinical practice in treating ABPA in patients with CF. To systematically review the available literature, providing evidence for the administration of biologic drugs as a new potential treatment of ABPA in both the paediatric and adult populations with CF. A systematic review of the literature published between January 2007 and July 2021 was performed, using a protocol registered with the International Prospective Register of Systematic Reviews (PROSPERO CRD42021270932). A total of 21 studies focusing on the use of biologics in treating ABPA in CF patients was included. We highlighted a paucity of data providing evidence for biologic drug use in ABPA. Scientific evidence is insufficient to support firm conclusions and randomised clinical trials are urgently required to investigate the efficacy and safety of biologics for ABPA in CF patients.

MAVS Expression in Alveolar Macrophages Is Essential for Host Resistance against Aspergillus fumigatus.

Our recent data demonstrate a critical role of the RIG-I-like receptor family in regulating antifungal immunity against Aspergillus fumigatus in a murine model. However, the importance of this pathway in humans and the cell types that use this innate immune receptor family to detect A. fumigatus remain unresolved. In this study, using patients who underwent hematopoietic stem cell transplantation, we demonstrate that a polymorphism in human MAVS present in the donor genome was associated with the incidence of invasive pulmonary aspergillosis. Moreover, in a separate cohort of confirmed invasive pulmonary aspergillosis patients, polymorphisms in the IFIH1 gene alter the inflammatory response, including IFN-responsive chemokines. Returning to our murine model, we now demonstrate that CD11c+ Siglec F+ alveolar macrophages require Mavs expression to maintain host resistance against A. fumigatus. Our data support the role of MAVS signaling in mediating antifungal immunity in both mice and humans at least in part through the role of MAVS-dependent signaling in alveolar macrophages.

Existing tests vs. novel non-invasive assays for detection of invasive aspergillosis in patients with respiratory diseases.

Background:Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-β-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-based Aspergillus assays.Methods:Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM and Aspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed.Results:The entire cohort included 3530 admissions (proven/probable IPA = 66, no IPA = 3464) and the subcohort included 127 admissions (proven/probable IPA = 38, no IPA = 89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) (χ2 = 19.83, P < 0.001), serum BDG (≥70 pg/mL: 33% [31/95]) (χ2 = 24.65, P < 0.001), and fungal culture (33% [84/253]) (χ2 = 29.38, P < 0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher's exact P = 1.000) to and slightly lower specificity (87% [77/89]) (χ2 = 5.52, P = 0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812–0.953]) and BAL GM (0.901 [0.824–0.977]) (P = 0.734). Sputum LFD had similar specificity (91% [81/89]) (χ2 = 0.89, P = 0.345) to and lower sensitivity (63% [24/38]) (χ2 = 4.14, P = 0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) (χ2 = 6.95, P = 0.008), BDG (χ2 = 10.43, P = 0.001), and fungal culture (χ2 = 12.70, P < 0.001).Conclusions:Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test.

Epidemiology of Aspergillosis in Cancer Patients in Taiwan.

PurposeThe incidence of aspergillosis is increasing, and the risk factors for infection include cancer, admission to the intensive care unit, chronic pulmonary diseases, immunocompromised status, and taking immunomodulatory drugs. There are limited data about the incidence of aspergillosis in patients with different types of cancer. The aim of our study was to survey the incidence of aspergillosis in different cancer types from 2006 to 2017.Patients and MethodsData were collected from the Taiwan Cancer Registry database and International Classification of Diseases, 9th, 10th Revision, and Clinical Modification codes for diagnosing aspergillosis. Patients with a history of aspergillosis before cancer were excluded, and the secondary outcome was the risk of mortality in cancer patients with and without aspergillosis after 1 year.ResultsAmong 951 cancer patients with a diagnosis of aspergillosis, there were 614 hematopoietic and reticuloendothelial system patients, 100 lung cancer patients, and 73 lymphoma cancer patients. The overall incidence rates of aspergillosis tended to increase significantly from 2006 to 2017 (from 3.50 to 13.37 per 10,000 person-years, p value: <0.0001). Regarding sex, the incidence rates of aspergillosis in males and females were 12.52 and 7.53 per 10,000 person-years, respectively. Patients with a diagnosis of aspergillosis had a 2.30-fold (95% CI: 2.14–2.48, p value: <0.0001) higher risk of mortality than those without aspergillosis.ConclusionThe incidence of aspergillosis was increased in cancer patients, and cancer patients with aspergillosis had a significantly higher risk of mortality than those without aspergillosis.

Disease burden and demographic characteristics of mucormycosis: A nationwide population-based study in Taiwan, 2006-2017.

Epidemiological knowledge of mucormycosis obtained from national population-based databases is scarce. This study aimed to depict the disease burden and demographics of mucormycosis in Taiwan by using the Taiwan National Health Insurance Research Database (NHIRD) and those of aspergillosis as a comparator. Data from patients with either mucormycosis or aspergillosis from 2006 to 2017 identified with the International Classification of Diseases (ICD) codes were extracted from the NHIRD. The incidence, demographics and clinical data of both diseases were analysed. A total of 204 patients with mucormycosis and 2270 patients with aspergillosis who were hospitalised and treated with mould-active antifungals between 2006 and 2017 were identified. The average annual incidence of aspergillosis (0.81 cases per 100,000 population [0.81/100,000]) was 11-fold higher than that of mucormycosis (0.07/100,000). A significant increase in incidence was observed for aspergillosis (from 0.48/100,000 in 2006 to 1.19/100,000 in 2017, p < .0001) but not for mucormycosis (from 0.04/100,000 in 2006 to 0.11/100,000 in 2017, p=.07). The major underlying disease identified was diabetes mellitus (60.8%) for mucormycosis and malignant neoplasms (45.9%) for aspergillosis. The all-cause 90-day mortality rate was similar between mucormycosis and aspergillosis patients (39% vs. 37%, p=.60). For mucormycosis patients, multivariate analysis revealed that posaconazole use was associated with lower in-hospital mortality (aOR 0.38; 95% CI 0.15-0.97; p=.04). Mucormycosis is an uncommon fungal disease in Taiwan, occurring mostly in diabetic patients. However, the incidence might be underestimated due to limited diagnostics. Continuous surveillance might aid in delineating the evolving features of mucormycosis.

How Has the Aspergillosis Case Fatality Rate Changed over the Last Two Decades in Spain?

(1) Background: Aspergillus produces high morbidity and mortality, especially in at-risk populations. In Spain, the evolution of mortality in recent years due to this fungus is not well established. The aim of this study was to estimate the case fatality rate of aspergillosis in inpatients from 1997 to 2017 in Spain. (2) Methodology: A retrospective descriptive study was conducted with records of inpatients admitted to the National Health System with a diagnosis of aspergillosis. (3) Principal findings: Of 32,960 aspergillosis inpatients, 24.5% of deaths were registered, and 71% of the patients who died were men. The percentage of deaths increased progressively with age. The case fatality rate progressively decreased over the period, from 25.4 and 27.8% in 1997–1998 to values of 20.6 and 20.8% in 2016 and 2017. Influenza and pneumonia occurrence/association significantly increased case fatality rates in all cases. (4) Conclusions: Our study shows that lethality significantly decreased in the last two decades despite the increase in cases. This highlights the fact that patients with solid and/or hematological cancer do not have a much higher mortality rate than the group of patients with pneumonia or influenza alone, these two factors being the ones that cause the highest CFRs. We also need studies that analyze the causes of mortality to decrease it and studies that evaluate the impact of COVID-19.

Malignant course of invasive pulmonary aspergillosis in the new coronavirus infection COVID-19

Respiratory infections caused by fungal pathogens are the main cause of death in immunocompromised patients. During the COVID-19 pandemic, the registration of respiratory fungal pathology, especially pulmonary aspergillosis, has increased significantly.&#x0D; We present a histopathologically confirmed case of fatal invasive pulmonary aspergillosis complicating COVID-19. A 65-year-old patient with long-term diabetes backgrounded with a severe course of COVID-19 (the virus was identified ICD-10 code U07.1) described. During the illness bilateral polysegmental pneumonia of fungal-bacterial (Klebsiella pneumoniae) etiology with necrosis and sequestration of the affected tissue the lower lobe of the right lung with the formation of a fungal ball and the development of a right-sided pneumothorax was developed. In other parts of both lungs, focal destruction of the interalveolar septa was determined with the formation of small cavities filled with detritus and accumulations of segmented neutrophils, with the proliferation of fungal mycelium, positively stained in the PAS reaction. Fungal hyphae and conidial heads were also found in the lumens of individual bronchi and vessels with invasion of their walls. Long-term (more than one month) course of the disease, clinical and radiological dynamics, and detection of a forming connective tissue capsule along the periphery of the necrosis zone during microscopy testifies in favor of the subacute nature of the infection.&#x0D; The presented clinical case, as well as a review of current publications and meta-analyses on invasive pulmonary aspergillosis, point to diagnostic problems and poor outcomes of invasive pulmonary aspergillosis in patients with COVID-19.&#x0D; Pulmonary aspergillosis associated with COVID-19 is a serious and potentially life ― threatening complication in patients with severe COVID-19 receiving immunosuppressive treatment. Early diagnosis of fungal infections is crucial to ensure the survival of such patients. Targeted biopsy examination with microscopy and/or seeding of a lung biopsy allows not only to establish the diagnosis of aspergillosis, but also to determine the presence of tissue invasion.&#x0D; Further research should include approaches aimed at developing an effective diagnosis of fungal tissue invasion and respiratory tract damage, determining the patients immune status in order to conduct personalized immunotherapy.

Chronic pulmonary aspergillosis in patients with active pulmonary tuberculosis with persisting symptoms in Uganda.

The occurrence of chronic pulmonary aspergillosis (CPA) among drug sensitive pulmonary tuberculosis (PTB) patients on optimal therapy with persistent symptoms was investigated. We consecutively enrolled participants with PTB with persistent pulmonary symptoms after 2months of anti-TB treatment at Mulago Hospital, Kampala, Uganda, between July 2020 and June 2021. CPA was defined as a positive Aspergillus-specific IgG/IgM immunochromatographic test (ICT), a cavity with or without a fungal ball on chest X-ray (CXR), and compatible symptoms >3months. We enrolled 162 participants (median age 30years; IQR: 25-40), 97 (59.9%) were male, 48 (29.6%) were HIV-infected and 15 (9.3%) had prior PTB. Thirty-eight (23.4%) sputum samples grew A.niger and 13 (8.0%) A.fumigatus species complexes. Six (3.7%) participants had intracavitary fungal balls and 52 (32.1%) had cavities. Overall, 32 (19.8%) participants had CPA. CPA was associated with prior PTB (adjusted odds ratio [aOR]: 6.61, 95% CI: 1.85-23.9, p=.004), and far advanced CXR changes (aOR: 4.26, 95% CI: 1.72-10.52, p=.002). The Aspergillus IgG/IgM ICT was positive in 10 (31.3%) participants with CPA. Chronic pulmonary aspergillosis may cause persistent respiratory symptoms in up to one-fifth of patients after intensive treatment for PTB. The Aspergillus IgG/IgM ICT positivity rate was very low and may not be used alone for the diagnosis of CPA in Uganda.

Unravelling the Molecular Identification and Antifungal Susceptibility Profiles of Aspergillus spp. Isolated from Chronic Pulmonary Aspergillosis Patients in Jakarta, Indonesia: The Emergence of Cryptic Species.

Cryptic species of Aspergillus have rapidly increased in the last few decades. Chronic pulmonary aspergillosis (CPA) is a debilitating fungal infection frequently affecting patients with previous TB. The identification and antifungal susceptibility profiles of different species of Aspergillus are important to support the management of CPA. The aim of this study was to describe the molecular and susceptibility profiles of Aspergillus isolated from CPA patients. The species identity of isolates was determined by combined DNA analyses of internal transcribed space (ITS), partial β-tubulin genes, and part of the calmodulin gene. We revealed a high (27%) prevalence of cryptic species among previous tuberculosis patients with persistent symptoms. Twenty-nine (49%) patients met the criteria for diagnosis of CPA with 24% containing Aspergillus cryptic species. This is the first report of five cryptic Aspergillus species from clinical isolates in Indonesia: A. aculea tus, A. neoniger, A. brunneoviolacues, A. welwitschiae, and A. tubingensis. Significantly, there was decreased sensitivity against itraconazole in the CPA group (66% susceptible to itraconazole) compared to the non-CPA group (90% susceptible to itraconazole) (p = 0.003). The species-level characterisation of Aspergillus and its antifungal susceptibility tests demands greater attention to better the management of CPA patients.

Incidence of Chronic Pulmonary Aspergillosis in Patients with Suspected or Confirmed NTM and TB-A Population-Based Retrospective Cohort Study.

Chronic pulmonary aspergillosis (CPA) is a severe and underdiagnosed pulmonary fungal infection with a significant overlap in symptoms and imaging findings of mycobacterium tuberculosis (TB) and non-tuberculous mycobacterium (NTM). Infection with TB or NTM is a predisposing underlying condition for CPA in approximately one-third of patients. A previously published study from Uganda showed increased incidence and complication rate of CPA with respect to pre-existing radiographic cavitation in a post-treatment TB population. The aim of this study was to investigate the incidence of CPA in a low-endemic population of confirmed or suspected TB and NTM patients. We manually reviewed 172 patients referred on suspicion or for treatment of TB or NTM at the Department of Respiratory Medicine, Odense University Hospital during the period of 1 January 2018 to 31 December 2020. We found no CPA amongst TB patients as opposed to an incidence of 8.2% (n = 4) in NTM-infected patients. We identified possible investigatory differences in Aspergillus blood sample screening protocols depending on NTM or TB, initiated at the Department of Respiratory Medicine at Odense University Hospital. A focused screening and investigatory protocol in NTM patients with persisting or developing symptoms is warranted in relation to suspected CPA.

Prevalence of Chronic Pulmonary Aspergillosis in Patients Suspected of Chest Malignancy.

Chronic pulmonary aspergillosis (CPA) is a potentially life-threatening fungal lung infection, and recent research suggests CPA to be more common than previously considered. Although CPA mimics other lung diseases including pulmonary cancer, awareness of this disease entity is still sparse. This study aimed to investigate the prevalence of CPA in a population of patients under suspicion of having lung cancer. We conducted a retrospective cohort study of 1200 patients and manually collected individual health record data from previous cancer examinations, with retrospective CPA status assessment using international criteria. Among 992 included patients, 16 (1.6%) fulfilled diagnostic criteria for CPA retrospectively, of whom 15 were undiscovered at initial lung cancer examination. The prevalence of CPA in this study population was 50 times higher than the reported prevalence of the overall European population. Our findings indicate that CPA is often missed in patients suspected of malignancy in the chest. Therefore, CPA should be kept in mind as a significant differential diagnosis.

Routine Surveillance of Healthcare-Associated Infections Misses a Significant Proportion of Invasive Aspergillosis in Patients with Severe COVID-19.

Rates of invasive aspergillosis (IA) among COVID-19 ICU patients seem to reach over 30% in certain settings. At Vienna General Hospital (VGH), all rooms in COVID-19 ICUs were put under negative pressure as a protective measure, thus increasing the risk of exposure to environmental pathogens for patients. Even though all ICU patients are surveilled for healthcare-associated infections (HAI), there were concerns that the routine protocol might not be sufficient for IA detection. We reviewed the electronic patient charts of all patients with COVID-19 admitted to ICUs between 1 March 2020 and 31 July 2021 for fungal co- or superinfections, comparing four diagnostic algorithms based on different recommendations for the diagnosis of IA (according to EORTC/MSG, BM-AspICU, IAPA and CAPA) to our routine surveillance protocol. We found that out of 252 patients who were admitted to the ICU during the study period, 25 (9.9%) fulfilled the criteria of probable or possible IA of at least one algorithm. The IAPA definitions detected 25 and the CAPA definition 23 probable and 2 possible cases, out of which only 16 were classified as hospital-acquired IA by routine surveillance. In conclusion, adjustment of the routine protocol using a classification system especially designed for respiratory viral illness seems useful for the surveillance of IA in a highly vulnerable patient cohort.