Case Of Aspergillosis Research Articles

A practical approach to investigating nosocomial acquisition of Aspergillus.

Invasive mould disease (IMD) has a high mortality in immunosuppressed patients. Invasive aspergillosis (IA) is the most common IMD. A guideline for preventing IA has been published jointly by the Centers for Diseases Control and Prevention, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation. Use of high-efficiency particulate air filters, adequate air exchange rates, sealing of patient rooms, and preventing exposure to moulds by nursing patients in areas away from construction sites are recommended by the guideline. However, there is limited information in relation to the actions to be undertaken by infection prevention and control teams in the event of one or more cases of nosocomial aspergillosis. In this review, we describe a systematic approach to aspergillosis by defining possible and probable nosocomial acquisition based on the number of days since hospital admission. We advocate an incremental response to the investigation of nosocomial aspergillosis in patients in protective isolation taking into account the number of cases and the likelihood of nosocomial origin. For single cases of nosocomial IA, we suggest that infection control investigations should focus on case surveillance and walk-through inspection escalating in a step-wise manner to enhanced case surveillance, verification of environmental controls, environmental monitoring, genotyping of clinical and environmental isolates, and review of antifungal prophylaxis for multiple cases and outbreaks. Where applicable, the construction site should be inspected with the aim to reduce the dispersal of conidia. Surveillance systems need to be strengthened to better understand the epidemiology of IA.

Aspergillus Contamination in Healthcare Facilities: An Ever-Present Issue—Prevention and Control Measures

Aspergillus spp. are ubiquitous fungi present in soil, organic debris, water, decaying vegetation and dust produced in renovation and/or building work. Several studies have shown the presence of aspergilli in various healthcare environments. Typically, thousands of fungal spores are inhaled every day, but if spore clearance fails (typically in immunocompromised patients), fungi can grow and invade lung tissue, causing invasive aspergillosis (IA) which is one of the most frequent infections in highly immunocompromised patients. Aspergillus fumigatus is the most common species involved; this species can be attributed to about 80% of the cases of aspergillosis. According to the WHO, Aspergillus fumigatus is one of four critical priority fungi. The first-line treatment of diseases caused by Aspergillus, in particular IA, is based on triazole antimycotics. Unfortunately, resistance to antimycotics is increasing, partly due to their widespread use in various areas, becoming a significant concern to clinicians who are charged with caring for patients at high risk of invasive mycoses. A recent WHO report emphasised the need for strategies to improve the response, and in particular strengthen laboratory capacity and surveillance, support investment in research and strengthen public health interventions for the prevention and control of fungal infections through a One Health approach.

A Case of Central Nervous System Aspergillosis Associated with Fungal Sphenoid Sinusitis Presenting with Bilateral Hemianopia and Diagnosed by Optic Pathway System Biopsy

A Case of Central Nervous System Aspergillosis Associated with Fungal Sphenoid Sinusitis Presenting with Bilateral Hemianopia and Diagnosed by Optic Pathway System Biopsy

Evaluation of environmental factors related to Aspergillus fumigatus azole resistance in the Netherlands

Emergence of azole-resistant Aspergillus fumigatus represents a concern for public health worldwide. Here we applied a spatial analysis to a large number of records on A. fumigatus azole resistance in the Netherlands to evaluate the relationship of a set of environmental factors with the emergence of resistant isolates and to identify the potential risk areas. A total of 1850 aspergillosis cases were included in the analysis: 1559 caused by wild-type (WT) and 291 by azole-resistant (RES) strains. High-resolution maps containing environmental variables (climate, crop cultivations) were used as layers for spatial analysis. QGIS software was used for transformation and calculation of layers, and visualizing maps, whereas MaxEnt software was used to perform spatial analysis. A separate distribution map for WT and RES was generated using each layer, then the ratio between RES and WT suitability was calculated, and a new map was generated showing the areas where suitability of RES was higher than WT (ratio > 1). Layers presenting areas with a ratio > 1 were then used for a further analysis including all these layers together to generate a final risk map, to identify the most contributing environmental variables, and to estimate the number of people potentially exposed to the risk. Results showed that the areas with the highest RES/WT ratio were associated with the following variables: legume cultivations ratio 1.5–2.7; fruit tree plantations, ratio 2.1; dump sites and artificial sites, ratio 2.3–2.7; spring minimum and mean temperatures, ratio 1.6–1.8. Areas with medium, high, and very high risk covered a surface of about 2330 km2 and people exposed were >319,000, with Zeeland and Noord-Holland being the provinces with the highest risk. All together these results suggest that azole-resistance emergence is a complex phenomenon depending on a multitude of environmental variables that are not yet been fully explored.

Four-month-old infant with chronic granulomatous disease and invasive aspergillosis with bone involvement

Chronic granulomatous disease is the inborn error of immunity with the highest frequency of invasive aspergillosis. In this context, invasive aspergillosis is frequent in adolescence, with rare cases before one year of age. We present a case of chronic granulomatous disease and invasive aspergillosis in a four-month-old infant. The patient was a male infant living in jail with his hypothyroid mother. He presented with a tumor in the left axillary region when he was four months old, and the chest X-ray suggested rib fractures. The patient was hospitalized on suspicion of child abuse. The chest computed tomography scan showed axillary abscess, rib osteolysis, pneumonia, and pulmonary nodules. He was treated with broad-spectrum antibiotics, and then he was discharged. Four months later, he was readmitted with fever and extension of the purulent abscess to the left scapular region; a computed tomography scan showed worsening images. Aspergillus fumigatus was isolated from the abscess pus, leading to an invasive aspergillosis diagnosis. The patient was treated with voriconazole for 28 days, and then he was discharged. The chronic granulomatous disease was diagnosed by the dihydrorhodamine test. The mutated gene causing the inborn error of immunity was CYBB with the variant c.80_83del/Y; the mother was the carrier (c.80_83del/WT). At 12 months of age, the patient was readmitted for invasive aspergillosis, refractory to treatment, and died. This exceptional case teaches us how environmental conditions determine exposure to infectious agents in chronic granulomatous disease patients. Also, it illustrates that invasive aspergillosis can develope in infants with this pathology and should be treated aggressively.

Successful treatment of invasive Aspergillus rhinosinusitis and orbital aspergillosis with oral isavuconazole in a patient with contraindications to conventional first- and second-line therapy

Abstract Objectives Acute invasive fungal rhinosinusitis represents a severe, life-threatening condition that necessitates prompt diagnosis and intervention. In this case report, we discuss the use of isavuconazole, a novel, broad-spectrum triazole antifungal, approved for use in Canada in 2019 (Government of Canada. Summary Basis of Decision – Cresemba – Health Canada. Summary Basis of Decision. 2019. Accessed 6 June 2024. https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00424#:~:text=Summary%20Basis%20of%20Decision%20(SBD)%20for%20Cresemba&text=Summary%20Basis%20of%20Decision%20(SBD)%20documents%20provide%20information%20related%20to,original%20authorization%20of%20a%20product) that can be considered an alternative to voriconazole. Methods We present the case of a 78-year-old man with a unique case of invasive Aspergillus rhinosinusitis and orbital aspergillosis. He was admitted for urgent left maxillary antrostomy, left anterior and posterior ethmoidectomy, and left transorbital resection of lesion tissue with orbital decompression. His treatment course was complicated by a contraindication to voriconazole because of prolonged QTc interval and inability to tolerate IV amphotericin B. Key findings The patient was treated with a 14-week course of isavuconazole as an alternative to voriconazole. At 3 months, there was no clinical evidence for infection, and the patient was sent for a computed tomography (CT) of the head and sinus to assess for evidence of active infection or bone destruction, which showed significant improvement in paranasal sinus inflammation and soft tissue infiltration. At his 6-month follow-up, his CT head showed regression in inflammatory change, with no deterioration in his sinusitis, and no further antifungal treatment was required. Conclusions Given the novelty of isavuconazole, there has been limited experience with its use in the setting of rhinosinusitis and orbital invasive aspergillosis. This case highlights isavuconazole as a reasonable alternative to voriconazole and other triazoles in patients that are intolerant or have contraindications related to QTc prolongation.

Fungal infection in patients treated with Bruton tyrosine kinase inhibitor-from epidemiology to clinical outcome: a systematic review.

The Bruton tyrosine kinase inhibitor (BTKi) has emerged as a key treatment for B-cell lymphomas. Despite its efficacy in the treatment of malignancies, numerous cases of invasive fungal infections (IFI) have been reported in patients receiving ibrutinib, a first-generation BTKi. Cases of invasive aspergillosis have also been reported with acalabrutinib and zanubrutinib. The objective of this study was to provide an overview of the pathogens involved, the time of onset of infections and factors influencing survival. Data sources: PubMed, Embase and Web of Science databases were used, and the results were reported according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Case reports, case series, clinical trials and cohort studies were included. All reported cases of IFI in patients treated with BTKi were analysed. For case reports/case series, demographic, microbiological and outcome data were retrieved. Assessment of risk of bias: Given the significant heterogeneity in clinical trials/cohort studies, only epidemiological analysis was performed, without formal incidence analysis. Methods of data synthesis: Epidemiologic data were presented as descriptive statistics. In total, 25215 patients from 92 retrospective and prospective clinical trials/cohort studies and 211 patients from 115 case reports/case series were included. Among clinical trials/cohorts, 736 IFI were reported, including 234 candidiasis (31.8%), 227 aspergillosis (30.8%) and 124 Pneumocystis jirovecii pneumonia (PJP) (16.8%). Among the case reports/case series, 155 (73.5%) had chronic lymphocytic leukaemia, and 56 (26.5%) had other malignancies. The main IFI were aspergillosis (n=107, 50.7%), cryptococcosis (n=33, 15.6%), PJP (n=26, 12.3%) and mucormycosis (n=23, 10.9%). The median delay between the initiation of BTKi and IFI was 2.3, 4.0, 3.0 and 3.0 for aspergillosis, cryptococcosis, PJP and mucormycosis, respectively. The survival rate improved when BTKi was discontinued during infection. Targeted therapies in lymphocytic malignancies raised new issues concerning infectious complications. Monitoring IFI in patients receiving second- and third-generation BTKi is crucial for improving the management of these manifestations.

Invasive aspergillosis in an immunocompetent patient: A retrospective case report and review of the literature.

Invasive aspergillosis (IA) is rare in immunocompetent patients. We present the case of a 44-year-old female with IA invading the lungs, mediastinum, heart, and brain, with a disease duration of 11 years. The patient was initially diagnosed with lung aspergillosis that had invaded the mediastinum on October 8, 2008. Irregular uptake of itraconazole led to the aggravation of lung lesions. Echocardiography and enhanced magnetic resonance imaging revealed a large irregular mass in the left atrium and an enhanced 1-cm nodular lesion in the right frontal lobe respectively in 2016. The patient refused to undergo a biopsy of the cardiac mass. Oral itraconazole (200 mg, twice daily) was recommended for subsequent days. The intracranial lesion gradually enlarged, and a complete tumor resection of the right frontal lobe was performed on February 23, 2017. The patient`s condition was well controlled with oral voriconazole by the end of follow-up until April 11, 2019. We conducted a search across multiple databases, including PubMed, Web of Science, Scopus, and Science Direct. We aimed to identify cases of aspergillosis that simultaneously invaded the lungs, heart, and brain. The details of these cases are summarized. Fourteen cases with available data met the requirements, and the mortality rate of these 14 cases was 100%. IA can occur even in immunocompetent patients receiving antifungal therapy. Therefore, timely diagnosis and effective long-term antifungal treatments are crucial. Voriconazole is an effective antifungal drug that is used to treat cerebral aspergillosis.

A Rare Case of Aspergillosis of Cranial Bone Flap in an Immunocompromised Patient: A Case Report

A Rare Case of Aspergillosis of Cranial Bone Flap in an Immunocompromised Patient: A Case Report

Rare and risky: a unique case of concurrent chronic pulmonary aspergillosis and lemierre syndrome

AbstractLemierre Syndrome is a condition that appears to have been overlooked in recent decades in clinical practice, often resulting in death or long-lasting sequelae when left undetected and untreated. Typically, it occurs following an upper respiratory tract infection, often stemming from tonsillitis, leading to thrombosis of the internal jugular vein and subsequent multiple septic emboli. Here, we present a case a 46-year-old patient with the clinical presentation of pneumogenic sepsis. Remarkably, we were able to diagnose the simultaneous presence of chronic pulmonary aspergillosis and Lemierre syndrome.

Successful treatment of aspergillosis in a 63-years old female patient with a SIOOT protocol of oxygen-ozone autohemotherapy: A case report

BackgroundInfections caused by the Aspergillus genus are relatively uncommon and typically associated with hospitalization, while only a few cases are linked to environmental exposure to filamentous moulds. These infections can significantly impact pulmonary function, and antifungal therapy may further compromise lung physiology, especially if fungal nodules develop. Consequently, many cases of aspergillosis are not directly treated to avoid additional lung damage. In this case report, we explore a novel approach using ozone therapy to improve clinical outcomes in a patient with pulmonary aspergillosis. To our knowledge, no previous data on the use of this procedure in treating Aspergillus infections have been published in the scientific literature. Case presentationA 63-year-old Caucasian female physician presented with persistent cough, mild fever, mucous sputum, fatigue, and general discomfort. After extensive laboratory analyses, she was initially suspected of having a Mycobacterium tuberculosis infection but was later accurately diagnosed with Aspergillus fumigatus. Allergy tests, thyroid function assessments, total-body PET, and maxillofacial imaging did not yield any findings to suggest alternative diagnoses. Aside from mild neutropenia and a positive antinuclear antibody (ANA) test, which appeared to be laboratory artifacts, the patient showed no significant inflammatory biomarkers, thyroid dysfunction, or signs of allergy. Chest CT revealed Aspergillus nodules with only mild obstructive respiratory impairment, which did not worsen upon administration of salbutamol. Following a period of mild symptoms, her health declined in the summer of 2022, prompting her to pursue ozone therapy at a colleague’s recommendation. After twelve oxygen-ozone treatments, her symptoms—including mild fever, cough, discomfort, and fatigue—fully resolved, and a follow-up chest CT showed a reduction in the presence of Aspergillus. ConclusionOxygen-ozone therapy administered through autohemotherapy proved to be a promising treatment for nodular aspergillosis in the lung, highlighting the need for further exploration of the mechanisms behind this positive outcome. This report is particularly relevant for physicians trained in ozone therapy, as it requires specialized professional expertise. This is the first documented case showing a successful outcome of ozone therapy in treating nodular Aspergillus fumigatus lung infection with mild obstructive pulmonary impairment. The favourable results should encourage physicians to consider this therapeutic approach in the future.

ASPERGILLOSIS IN ARTIFICIALLY BREEDING BLACK SWANS (CYGNUS ATRATUS) IN DPR KOREA AND IDENTIFICATION OF CAUSE FUNGUS

Black swans (Cygnus atratus (Latham) 1790), which was native in Australia, were distributed all over the world and artificially reared. Aspergillosis is non-contagious fungal disease infected in some poultries and wild birds and the important agent are some of Aspergillus species. Infection by Aspergillus species results in respiratory disease in poultry and wild birds. The disease is generally caused by Aspergillus fumigatus and Aspergillus flavus. This study was proceeded to document the clinical signs and lesions of Aspergillosis in artificially breeding black swan in DPR Korea, isolate and identify the causative fungi from lesions. Black swans at Swan Breeding Center in Taedong County, South Pyongan Province, DPR Korea were investigated. The infected swans died suddenly after two or three days when they lost appetite and had symptoms of dyspnea, sudden retraction or deformity of their neck and abnormal walking. The infected black swans had white fecal diarrhea. The fungal hyphae were also observed in the eyes. Here, we confirmed the clinical cases of Aspergillosis in artificially breeding black swans in DPR Korea and A. flavus was isolated in Potato Dextrose Agar (PDA) and identified morphologically from fungi cultivated in Malt Extract Agar (MEA), Czapek Yeast Extract Agar (CYA) and Czapek Dox Agar (CZ). The morphological characteristics like colony colors were similar with the findings of who isolated Aspergillus flavus from maize and soil in Kenya. The microscopic characteristics of fungus isolated from aspergillosis lesions in Black swans were investigated. The morphologically identified fungus was confirmed as A. flavus by sequencing of PCR product of 600bp fragment with primers ITS1/ITS4 and Blast analysis.

Epidermal growth factor receptor signaling governs the host inflammatory response to invasive aspergillosis.

The epidermal growth factor receptor (EGFR) has been identified as an epithelial cell receptor for Mucorales fungi and Candida albicans. Blocking EGFR with small molecule inhibitors reduces disease severity in mouse models of mucormycosis and oropharyngeal candidiasis. In contrast, cases of invasive aspergillosis have been reported in cancer patients who were treated with EGFR inhibitors, suggesting that EGFR signaling may play a protective role in the host defense against this infection. Here, we analyzed transcriptomic data from the lungs of mice with invasive aspergillosis and found evidence that Aspergillus fumigatus infection activates multiple genes that are predicted to function in the EGFR signaling pathway. We also found that A. fumigatus infection activates EGFR in both a human small-airway epithelial (HSAE) cell line and in the lungs of immunosuppressed mice. EGFR signaling in HSAE cells is required for maximal endocytosis of A. fumigatus and for fungal-induced proinflammatory cytokine and chemokine production. In a corticosteroid immunosuppressed mouse model of invasive pulmonary aspergillosis, inhibition of EGFR with gefitinib decreased whole-lung cytokine and chemokine levels and reduced accumulation of phagocytes in the lung, leading to a decrease in fungal killing, an increase in pulmonary fungal burden, and accelerated mortality. Thus, EGFR signaling is required for pulmonary epithelial cells to orchestrate the host innate immune defense against invasive aspergillosis in immunosuppressed hosts.IMPORTANCEWhen A. fumigatus infects the lungs, it invades epithelial cells that line the airways. During this process, the fungus interacts with epithelial cell receptors. This interaction stimulates epithelial cells to endocytose the fungus. It also induces these cells to secrete proinflammatory cytokines and chemokines that recruit phagocytes to the site of infection where they can kill the fungus. Here, we show that in small-airway epithelial cells, the EGFR acts as a sensor for A. fumigatus that triggers the production of chemokines in response to fungal infection. In corticosteroid-immunosuppressed mice, blocking EGFR with the kinase inhibitor gefitinib reduces chemokine production in the lungs. This leads to decreased accumulation of neutrophils and dendritic cells in the lungs, reduced A. fumigatus killing, and increased mortality. These results provide a potential explanation as to why some cancer patients who are treated with EGFR inhibitors develop invasive aspergillosis.

Isavuconazole and Amphotericin B Synergic Antifungal Activity: In Vitro Evaluation on Pulmonary Aspergillosis Molds Isolates.

Background/Objectives. Pulmonary aspergillosis is a severe respiratory infection caused by Aspergillus spp., whose resistance profiles and invasive attitude complicate therapeutical strategies. Several aspergillosis cases emerged as superinfections during the SARS-CoV-2 pandemic when isavuconazole and amphotericin B became essential antifungal alternatives. The main purpose of the present study was to investigate a possible synergic activity between these molecules against Aspergillus spp. isolated from respiratory samples. Methods. The gradient test method detected isavuconazole and amphotericin B MIC values, prompting an arrangement of their combination into an R.P.M.I. agar medium. According to Liofilchem s.r.l. instructions, the FIC index was used to establish synergy, additivity, indifference, or antagonism. Results. Among 36 Aspergillus spp. isolates, only A. fumigatus strains showed both synergy and additivity episodes. A. niger reported the highest antagonism percentage, while A. terreus revealed several indifference episodes. Conclusions. Isavuconazole and amphotericin B remain fundamental therapeutical alternatives, including a possible synergic effect against A. fumigatus. On the basis of this species-related difference, further studies will be essential to investigate different antifungal drug combinations against filamentous fungi isolates.

Pan-azole resistance in clinical Aspergillus fumigatus isolates carrying TR34/L98H from birds and mammals in Belgium

Aspergillosis causes significant health risks to both birds and mammals. The outcome of these infections is often poor due to delayed diagnosis and treatment failure. We investigated 152 cases of aspergillosis from birds and mammals in Belgium. Most samples originated from the taxonomic orders Artiodactyla (40.1 %) and Columbiformes (19.7 %). Five isolates (3.3 %) showed phenotypical resistance against at least one medical azole. Three of these isolates were pan-azole resistant bearing the TR34/L98H mutation. The predominance of this resistance mutation supports an environmental route for exposure and resistance selection, highlighting the importance of the One Health concept.

Shift from Widespread to Tailored Antifungal Prophylaxis in Lymphoma Patients Treated with CD19 CAR T Cell Therapy: Results from a Large Retrospective Cohort

BackgroundPatients undergoing CD19 chimeric antigen receptor (CAR) T-cell therapy exhibit multiple immune deficits that may increase their susceptibility to infections. Invasive fungal infections (IFI) are life-threatening events in the setting of hematological diseases. However, there is ongoing debate regarding the optimal role and duration of antifungal prophylaxis in this specific patient population. ObjectivesThe objective of this study was to provide a comprehensive overview of the evolution of IFI prophylactic strategies over time and to assess IFI incidence rates in a cohort of patients with relapsed or refractory (R/R) lymphoma treated with CAR-T cell therapy. Study DesignSingle-center, retrospective study from a cohort of patients with R/R B-cell lymphoma treated with CD19 CAR-T cell therapy between April 2016 and March 2023. Group A (April 2016- August 2020) consisted of patients primarily treated with fluconazole, irrespective of their individual IFI risk profile. In Group B (September 2020- March 2023) antifungal prophylaxis was recommended only for high-risk patients. ResultsOverall, 330 patients were included. Antifungal prophylaxis was prescribed to 119/142 (84%) patients in Group A and 58/188 (31%) in Group B (p<0.001). Anti-mold azoles were prescribed to 8 (5.6%) patients in Group A and 21 (11.2%) patients in Group B. In Group A, 42 (29%) patients switched to another antifungal, 9 (21%) because of toxicity, with 6 cases of transaminitis and 3 cases of prolonged QTc. In Group B, 21 (11.2%) patients switched the antifungal drug, mainly from fluconazole or micafungin to a mold-active agent following revised guidelines. No difference was found in liver toxicity between the two groups at infusion, day 10, and day 30. No significant differences were observed between the groups. IFI following CAR T-cell therapy were rare, with one case of cryptococcal meningoencephalitis in group A (0.7%) and one case of invasive aspergillosis in group B (0.5%), both occurring in patients on micafungin prophylaxis. ConclusionIn this large single-center cohort of patients with R/R lymphoma treated with CAR T-cells, we show that individualized prophylaxis, alongside careful management of CAR T-cell related toxicities like CRS, was associated with a very low IFI rate, avoiding the risk of unnecessary toxicities, drug-drug interactions, and high costs.

Neglected Pulmonary Infection Caused by Exophiala dermatitidis Misidentified as Rhodotorula spp.

Exophiala dermatitidis is an emerging black fungus that causes pulmonary infections that may be underestimated by conventional culture methods. We encountered one case that initially appeared to be yeast and was misidentified as Rhodotorula spp. using a commercial identification kit. Thus, genetic identification and clinical background investigations were conducted on 46 strains of Rhodotorula spp. The sequences of the internal transcribed spacer and large-subunit RNA genes (D1/D2 regions) of 43 isolates, excluding two environmental isolates and one difficult-to-culture isolate, were determined and genetically identified. Notably, 22 isolates were identified as E. dermatitidis and misidentified as Rhodotorula spp. using the conventional method. Based on the exclusion criteria, the clinical information of 11 patients was retrospectively reviewed. Five cases (definite) had definite exacerbation of pulmonary infections due to E. dermatitidis, and six cases (possible) had undeniable infections. Of the 11 cases of pulmonary infection suggested to be caused by E. dermatitidis, comorbidities included two cases of chronic pulmonary aspergillosis (CPA), three cases of pulmonary non-tuberculous mycobacterial (NTM) infection and one case of pulmonary nocardiosis, suggesting a trend towards simultaneous detection of chronic pulmonary infections. Steroid and immunosuppressive drug use was observed in five cases, and β-D-glucan elevation was observed in three of five definite cases of pulmonary infections due to E. dermatitidis. The possibility of E. dermatitidis infection should be considered when Rhodotorula spp. are isolated from cultures of airway-derived specimens, and, in addition to CPA and NTM, identification of E. dermatitidis may be important in chronic pulmonary infections.

Epidermal Growth Factor Receptor Signaling Governs the Host Inflammatory Response to Invasive Aspergillosis.

The epidermal growth factor receptor (EGFR) has been identified as an epithelial cell receptor for Mucorales fungi and Candida albicans. Blocking EGFR with small molecule inhibitors reduces disease severity in mouse models of mucormycosis and oropharyngeal candidiasis. In contrast, cases of invasive aspergillosis have been reported in cancer patients who were treated with EGFR inhibitors, suggesting that EGFR signaling may play a protective role in the host defense against this infection. Here, we analyzed transcriptomic data from the lungs of mice with invasive aspergillosis and found evidence that Aspergillus fumigatus infection activates multiple genes that are predicted to function in the EGFR signaling pathway. We also found that A. fumigatus infection activates EGFR in both a human small airway epithelial (HSAE) cell line and in the lungs of immunosuppressed mice. EGFR signaling in HSAE cells is required for maximal endocytosis of A. fumigatus and for fungal-induced proinflammatory cytokine and chemokine production. In a corticosteroid immunosuppressed mouse model of invasive pulmonary aspergillosis, inhibition of EGFR with gefitinib decreased whole lung chemokine levels and reduced accumulation of phagocytes in the lung, leading to a decrease in fungal killing, an increase in pulmonary fungal burden, and accelerated mortality. Thus, EGFR signaling is required for pulmonary epithelial cells to orchestrate the host innate immune defense against invasive aspergillosis in immunosuppressed hosts.

ANCA-negative Crescentric Pauci-immune Glomerulonephritis Associated with Allergic Bronchopulmonary Aspergillosis: A Rare Entity

We present an unusual case of a 23-year-old male presenting with dyspnea, anasarca, and high-colored urine and simultaneously diagnosed as a case of allergic bronchopulmonary Aspergillosis. On detailed investigations, his serologies for vasculitis turned out to be all negative. Renal biopsy revealed pauci-immune crescentic glomerulonephritis. This rare report explains that the underlying immunological response to Aspergillus antigen can be the cause for casual association between the two entities.

An immunocompetent lady with invasive aspergillosis presenting as disseminated lesions: a case report

BackgroundInvasive Aspergillosis is a fungal infection caused by Aspergillus species, typically posing life-threatening risks to immunocompromised individuals. While occurrences in immunocompetent hosts are rare, a recent case report documented fulminant pulmonary aspergillosis in an immunocompetent patient during autopsy. Here, we present a case of invasive aspergillosis in an immunocompetent woman, manifesting with disseminated lesions.Case presentationA 29-year-old Asian woman presented to our hospital in March 2022, reporting chest pain and shortness of breath persisting for two months. Upon examination, she appeared thin and unwell, with no notable abnormalities otherwise. Radiographic imaging revealed an ill-defined lesion in her left lung. Subsequent bronchoscopy and lavage were performed, followed by initiation of empirical antibiotic therapy. Lavage results were negative for gram staining, culture, and ZN staining for AFB, but revealed numerous septate hyphae on fungal smear. Histopathological examination indicated chronic granulomatous inflammation with septal fungal hyphae, indicative of aspergillosis. Subsequent culture confirmed Aspergillus species, prompting initiation of voriconazole therapy. Remarkably, the patient exhibited significant improvement, with weight gain and restored appetite observed within a short period. Within 2 months of treatment, her symptoms resolved, and she resumed near-normal daily activities.ConclusionThis case highlights the diagnosis of aspergillosis in an immunocompetent individual presenting with disseminated nodular lesions across the lungs, mediastinum, and abdomen. Clinicians should maintain a high index of suspicion for aspergillosis in cases of non-resolving pneumonia and disseminated nodular lesions, even in patients lacking traditional predisposing factors.