Aspergillus Species In Patients Research Articles

Radiological Diagnosis of Pulmonary Aspergillosis.

Imaging plays an important role in the various forms of Aspergillus-related pulmonary disease. Depending on the immune status of the patient, three forms are described with distinct imaging characteristics: invasive aspergillosis affecting severely immunocompromised patients, chronic pulmonary aspergillosis affecting less severely immunocompromised patients but suffering from a pre-existing structural lung disease, and allergic bronchopulmonary aspergillosis related to respiratory exposure to Aspergillus species in patients with asthma and cystic fibrosis. Computed tomography (CT) has been demonstrated more sensitive and specific than chest radiographs and its use has largely contributed to the diagnosis, follow-up, and evaluation of treatment in each condition. In the last few decades, CT has also been described in the specific context of cystic fibrosis. In this particular clinical setting, magnetic resonance imaging and the recent developments in artificial intelligence have shown promising results.

Rapid Diagnosis of Invasive Fungal Infections Caused by Candida and Aspergillus Species in Patients Admitted to Intensive Care Unit of a Tertiary Care Hospital

Rapid Diagnosis of Invasive Fungal Infections Caused by Candida and Aspergillus Species in Patients Admitted to Intensive Care Unit of a Tertiary Care Hospital

COVID-19-associated pulmonary aspergillosis (CAPA) in Iranian patients admitted with severe COVID-19 pneumonia.

PurposeBacterial or virus co-infections with SARS-CoV-2 have been reported in many studies; however, the knowledge on Aspergillus co-infection among patients with COVID-19 was limited. This study was conducted to identify and isolate fungal agents and to evaluate the prevalence of pulmonary aspergillosis (CAPA) as well as antifungal susceptibility patterns of Aspergillus species in patients with COVID-19 admitted to Shahid Beheshti Hospital, Kashan, Iran.MethodsThe study involved 119 patients with severe COVID-19 pneumonia referred to the Shahid Beheshti Hospital, Kashan, Iran. A total of 17 Aspergillus spp. that were isolated from COVID-19 patients suspected of CAPA were enrolled in the study. CAPA was defined using ECMM/ISHAM consensus criteria. The PCR amplification of the β-tubulin gene was used to identify the species. The antifungal activities of fluconazole, itraconazole, voriconazole, amphotericin B against Aspergillus spp. were evaluated according to the Clinical and Laboratory Standards Institute manual (M38-A3).ResultsFrom the 119 patients with severe COVID-19 pneumonia, CAPA was confirmed in 17 cases (14.3%). Of these, 12 (70.6%) were males and 5 (29.4%) were females; the mean age at presentation was 73.8 years (range: 45–88 years; median = 77; IQR = 18). Aspergillus fumigatus (9/17; 52.9%), Aspergillus flavus (5/17; 29.4%), Aspergillus oryzae (3/17, 17.6%), were identified as etiologic agents of CAPA, using the molecular techniques. Voriconazole and amphotericin B showed more activity against all isolates. Moreover, the MIC of fluconazole, itraconazole varied with the tested isolates. For 3 clinical isolates of A. fumigatus, 2 isolate of A. flavus and 3 A. oryzae, the MIC of fluconazole and itraconazole were ≥ 16 µg/mL.ConclusionsWe observed a high incidence (14.3%) of probable aspergillosis in 119 patients with COVID-19, which might indicate the risk for developing IPA in COVID-19 patients. When comparing patients with and without CAPA regarding baseline characteristics, CAPA patients were older (p =0 .024), had received more frequent systemic corticosteroids (p = 0.024), and had a higher mortality rate (p = 0.018). The outcome of CAPA is usually poor, thus emphasis shall be given to screening and/or prophylaxis in COVID-19 patients with any risk of developing CAPA.

Allergic Diseases Caused by Aspergillus Species in Patients with Cystic Fibrosis.

Aspergillus spp. are spore forming molds; a subset of which are clinically relevant to humans and can cause significant morbidity and mortality. A. fumigatus causes chronic infection in patients with chronic lung disease such as asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). In patients with CF, A. fumigatus infection can lead to allergic disease, such as allergic bronchopulmonary aspergillosis (ABPA) which is associated with high rates of hospitalizations for acute exacerbations and lower lung function. ABPA results from TH2 immune response to Aspergillus antigens produced during hyphal growth, marked by high levels of IgE and eosinophil activation. Clinically, patients with ABPA experience difficulty breathing; exacerbations of disease and are at high risk for bronchiectasis and lung fibrosis. Oral corticosteroids are used to manage aspects of the inflammatory response and antifungal agents are used to reduce fungal burden and lower the exposure to fungal antigens. As the appreciation for the severity of fungal infections has grown, new therapies have emerged that aim to improve treatment and outcomes for patients with CF.

Chronic Pulmonary Aspergillosis: Notes for a Clinician in a Resource-Limited Setting Where There Is No Mycologist.

Chronic pulmonary aspergillosis (CPA) is a spectrum of several progressive disease manifestations caused by Aspergillus species in patients with underlying structural lung diseases. Duration of symptoms longer than three months distinguishes CPA from acute and subacute invasive pulmonary aspergillosis. CPA affects over 3 million individuals worldwide. Its diagnostic approach requires a thorough Clinical, Radiological, Immunological and Mycological (CRIM) assessment. The diagnosis of CPA requires (1) demonstration of one or more cavities with or without a fungal ball present or nodules on chest imaging, (2) direct evidence of Aspergillus infection or an immunological response to Aspergillus species and (3) exclusion of alternative diagnoses, although CPA and mycobacterial disease can be synchronous. Aspergillus antibody is elevated in over 90% of patients and is the cornerstone for CPA diagnosis. Long-term oral antifungal therapy improves quality of life, arrests haemoptysis and prevents disease progression. Itraconazole and voriconazole are alternative first-line agents; voriconazole is preferred for patients with contra-indications to itraconazole and in those with severe disease (including large aspergilloma). In patients co-infected with tuberculosis (TB), it is not possible to treat TB with rifampicin and concurrently administer azoles, because of profound drug interactions. In those with pan-azole resistance or intolerance or progressive disease while on oral triazoles, short-term courses of intravenous liposomal amphotericin B or micafungin is used. Surgery benefits patients with well-circumscribed simple aspergillomas and should be offered earlier in low-resource settings.

Absolute Eosinophil Count was Significantly Associated with Serum (1,3)-β-D-Glucan in Patients with Invasive Fungal Infections.

Measurement of serum (1,3)-β-D-glucan has emerged as an important diagnostic strategy for invasive fungal infections (IFI). Previous studies suggested that the eosinophil count would be related with the value of serum (1,3)-β-D-glucan. 572 blood samples obtained from 126 patients at the First Affiliated Hospital of Zhengzhou University were analyzed. The unsuitable samples were excluded according to the patient selection. In our study, we found that in the 572 cumulative results, the absolute eosinophil count was significantly associated with the value of (1,3)-β-D-glucan (r = 0.57; 95% confidence interval (CI) 0.51 - 0.63) but not with total leukocyte, neutrophils, lymphocytes, monocytes, and basophils. Then, we found that there were 126 patients with invasive fungal infections, 109 patients with candidiasis and 17 patients with aspergillosis. In the 109 patients who had candidiasis, absolute eosinophil count was significantly associated with the value of (1,3)-β-D-glucan (r = 0.59; 95% CI 0.53 - 0.65). Similarly, in the 17 patients who had aspergillosis, the absolute eosinophil count was significantly associated with the value of (1,3)-β-D-glucan (r = 0.65; 95% CI 0.51 - 0.75). Meanwhile, similar findings in different types of Candida species or Aspergillus species in patients were found except in Candida glabrata infection. As a routine and broadly used test, serial absolute eosinophil count is related with IFI, and it could be used to evaluate the progress of IFI.

Radiological abnormalities associated with Aspergillus colonization in a cystic fibrosis population

To determine if sputum colonization with Aspergillus species in patients with cystic fibrosis (PWCF) correlates with radiological abnormalities and/or a reduction in pulmonary function (FEV1). We prospectively evaluated 32 PWCF utilizing high resolution computed tomography (HRCT) of the thorax and pulmonary function testing (PFT). The cohort was assessed as two groups: Aspergillus positive (n=16) and Aspergillus negative (n=16) based on sputum culture for Aspergillus species. A modified Bhalla scoring system was applied to each HRCT scan by two blinded radiologists. Aspergillus positive patients had more severe and significant bronchiectasis compared to those Aspergillus negative (p<0.05). This was most marked in the right upper and lower lobes (RUL, RLL). Total Bhalla score was clinically significant in both groups and approached statistical significance between groups (p=0.063). No difference in pulmonary function between the groups was detected. PWCF colonized by Aspergillus species have greater radiological abnormalities undetectable by PFTs. Early radiological evaluation of Aspergillus colonized PWCF is therefore warranted.

Molecular Detection of Invasive Aspergillosis in Hematologic Malignancies

Aspergillus species are the most frequent causes of invasive mold infections in immunocompromised patients, particularly those who underwent chemotherapy for hematologic malignancies. The aim of this study was to determine the incidence and efficiency of the PCR-enzyme linked immunosorbent assay method (PCR-ELISA) for early detection of Aspergillus species in patients with hematologic malignancies. From 2004 to 2006, 194 patients with hematologic malignancies (who received chemotherapy) were evaluated for invasive aspergillosis (IA) in Shiraz, southern Iran. Ethylenediaminetetraacetic acid anticoagulant whole blood samples were collected prospectively once a week and stored at -20 degrees C until examination. All collected blood samples were assayed for the presence of the bands on ethidium bromide stained gel and for hybridization. The female-to-male ratio was 61:133, the mean age of patients was 33.7 years, and mean of hospitalization period was 21.2 days. PCR-ELISA was positive in 14 (7.2%) patients who exhibited clinical and radiologic signs of IA. The etiologic agents were Aspergillus flavus (11 cases) and Aspergillus fumigatus (three cases). The mean time of positivity of PCR-ELISA in the blood before the appearance of clinical signs was 12.6 days. PCR was found to be the earliest indicator of IA preceding nonspecific clinical and radiologic findings. The sensitivity, specificity, positive, and negative predictive values of PCR-ELISA to detect DNA-specific for Aspergillus species in patients with proven and probable IA were 66%, 96%, 62.5%, and 97%, respectively. In case patients were treated with antifungal drugs, and the treatment was successful, fungal PCR assay became negative after 14 days and if the treatment failed, assay was positive until death. We demonstrated, in the present study, the incidence of IA in leukemic patients and the usefulness of molecular assay for early diagnosis and monitoring of the treatment of IA.

Current Molecular Diagnostic Approaches to Systemic Infections with Aspergillus Species in Patients with Hematological Malignancies

Within the recent years, novel molecular methods, especially PCR assays, have been developed to improve the diagnosis of invasive aspergillosis in patients with malignant hematological diseases being at high risk for this life-threatening infection. Early diagnosis and treatment are essential for adequate therapeutical management, which however, often remains difficult since most of the diagnostic tools used clinically at present either lack specificity or acceptable sensitivity. The clinical value, advantages and remaining problems of recently developed molecular approaches to detect the emerging fungal pathogen are reviewed.

Prediction of systemic fungal infection in allogeneic marrow recipients: impact of amphotericin prophylaxis in high-risk patients.

To identify risk factors that might predict for systemic fungal infections in marrow transplant recipients within the first 100 days and to assess the efficacy of low-dose amphotericin B used as prophylaxis for candidemia and infection with invasive Aspergillus species in patients at risk. A retrospective analysis of transplant outcomes for 331 allogeneic marrow recipients transplanted between 1983 and 1989 was performed to identify patients who might be at increased risk of fungal infection. Factors analyzed included disease, remission status, transplant regimen, graft-versus-host disease (GVHD) prophylaxis, duration of neutropenia, and development of GVHD. A trial of low-dose amphotericin (5 to 10 mg/d) begun on day +1 and continuing for 2 to 3 months posttransplant was begun in 1987 to evaluate its utility in reducing systemic mycoses. There were 18 episodes of candidemia and 18 systemic mycoses documented by blood or tissue culture or by biopsy. The initiation of high-dose (0.5 to 1 mg/kg/d) corticosteroids early as a component of GVHD prophylaxis in 1986 was identified as the most important risk factor for fungal infections, with a sixfold increase in infections as compared with the previous GVHD regimen (P < .0001); this was despite a significant decrease in the incidence of grade II to IV GVHD (7% v 43%; P = .0001). Low-dose amphotericin B initiated before the start of high-dose corticosteroid GVHD prophylaxis reduced the incidence of fungal infections from 30% to 9% (P = .01) without renal toxicity. Cyclosporine levels were lower in the patients who received amphotericin, leading to an increase in the rate of GVHD to 19% (P = .02). Controlling for GVHD prophylaxis, prolonged neutropenia (P = .00), and grade II to IV GVHD (P = .01) were also identified as risk factors for fungal infection. Amphotericin B can be used in low doses as prophylaxis for fungal infections early in the posttransplant course. However, cyclosporine doses need to be monitored to maintain target levels.