scholarly journals Molecular Epidemiology of Aspergillus fumigatus in Chronic Pulmonary Aspergillosis Patients

2021 ◽  
Vol 7 (2) ◽  
pp. 152
Author(s):  
Mireille H. van der Torre ◽  
Hongwei Shen ◽  
Riina Rautemaa-Richardson ◽  
Malcolm D. Richardson ◽  
Lilyann Novak-Frazer
Keyword(s):  
Genetic Diversity ◽  
Cystic Fibrosis ◽  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Molecular Epidemiology ◽  
Epidemiological Studies ◽  
Concerted Effort ◽  
Pulmonary Aspergillosis ◽  
Molecular Genotyping ◽  
Chronic Pulmonary Aspergillosis

Molecular fungal genotyping techniques developed and employed for epidemiological studies have understandably concentrated on establishing the genetic diversity of Aspergillus fumigatus in invasive aspergillosis due to its severity, the urgency for treatment, and the need to demonstrate possible sources. Some early studies suggested that these strains were phenotypically, if not genotypically, different from others. However, with improved discrimination and evaluations, incorporating environmental as well as clinical isolates from other Aspergillus conditions (e.g., chronic pulmonary aspergillosis and cystic fibrosis), this premise is no longer upheld. Moreover, with the onset of increased global triazole resistance, there has been a concerted effort to incorporate resistance profiling into genotyping studies and the realisation that the wider population of non-immunocompromised aspergillosis patients are at risk. This review summarises the developments in molecular genotyping studies that incorporate resistance profiling with attention to chronic pulmonary aspergillosis and an example of our UK experience.

scholarly journals Aspergillus fumigatus and Aspergillus flavus-Specific IgG Cut-Offs for the Diagnosis of Chronic Pulmonary Aspergillosis in Pakistan

2020 ◽  
Vol 6 (4) ◽  
pp. 249
Author(s):  
Kauser Jabeen ◽  
Joveria Farooqi ◽  
Nousheen Iqbal ◽  
Khalid Wahab ◽  
Muhammad Irfan
Keyword(s):  
Aspergillus Fumigatus ◽  
Sensitivity And Specificity ◽  
Aspergillus Flavus ◽  
Diagnostic Algorithm ◽  
Pulmonary Aspergillosis ◽  
Significant Difference ◽  
Ethical Approval ◽  
Chronic Pulmonary Aspergillosis ◽  
Specific Igg ◽  
First Time

Despite a high burden of chronic pulmonary aspergillosis (CPA) in Pakistan, Aspergillus-specific IgG testing is currently not available. Establishing cut-offs for Aspergillus-specific IgG for CPA diagnosis is crucial due to geographical variation. In settings such as Pakistan, where non-Aspergillus fumigatus (mainly A. flavus) Aspergillus species account for the majority of CPA cases, there is a need to explore additional benefit of Aspergillus flavus-specific IgG detection along with A. fumigatus-specific IgG detection. This study was conducted at the Aga Khan University, Karachi, Pakistan after ethical approval. Serum for IgG detection were collected after informed consent from healthy controls (n = 21), diseased controls (patients with lung diseases, n = 18), and CPA patients (n = 21). A. fumigatus and A. flavus IgG were detected using Siemens immulite assay. The sensitivity and specificity of A. fumigatus-specific IgG were 80.95% and 82.05%, respectively at a cut-off of 20 mg/L. The sensitivity and specificity of A. flavus-specific IgG were 80.95% and 79.49% at a cut-off of 30 mg/L. We report, for the first time, performance of A. flavus-specific IgG for CPA diagnosis. Although there was no statistically significant difference between the performance of both antigens, it seems contextually relevant to include A. flavus IgG in the CPA diagnostic algorithm in regions with higher non-A. fumigatus CPA infections.

scholarly journals Emergence of Echinocandin Resistance Due to a Point Mutation in the fks1 Gene of Aspergillus fumigatus in a Patient with Chronic Pulmonary Aspergillosis

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Cristina Jiménez-Ortigosa ◽  
Caroline Moore ◽  
David W. Denning ◽  
David S. Perlin
Keyword(s):  
Aspergillus Fumigatus ◽  
Point Mutation ◽  
Hot Spot ◽  
Pulmonary Aspergillosis ◽  
Content Type ◽  
First Case ◽  
Chronic Pulmonary Aspergillosis ◽  
Echinocandin Resistance

ABSTRACT We have identified the first case of an fks1 hot spot 1 point mutation causing echinocandin resistance in a clinical Aspergillus fumigatus isolate recovered from a chronic pulmonary aspergillosis patient with an aspergilloma who first failed azole and polyene therapy and subsequently failed micafungin treatment.

scholarly journals Correlation between Triazole Treatment History and Susceptibility in Clinically Isolated Aspergillus fumigatus

2012 ◽  
Vol 56 (9) ◽  
pp. 4870-4875 ◽  
Author(s):  
Masato Tashiro ◽  
Koichi Izumikawa ◽  
Katsuji Hirano ◽  
Shotaro Ide ◽  
Tomo Mihara ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Acquired Resistance ◽  
Microsatellite Genotyping ◽  
Pulmonary Aspergillosis ◽  
Content Type ◽  
Positive Correlation ◽  
Treatment History ◽  
Oral Itraconazole ◽  
Chronic Pulmonary Aspergillosis ◽  
The Relationship

ABSTRACTThis is the first report of a detailed relationship between triazole treatment history and triazole MICs for 154Aspergillus fumigatusclinical isolates. The duration of itraconazole dosage increased as the itraconazole MIC increased, and a positive correlation was observed (r= 0.5700,P< 0.0001). The number of itraconazole-naïve isolates dramatically decreased as the itraconazole MIC increased, particularly for MICs exceeding 2 μg/ml (0.5 μg/ml versus 2 μg/ml,P= 0.03). We also examined the relationship between cumulative itraconazole usage and the MICs of other azoles. A positive correlation existed between itraconazole dosage period and posaconazole MIC (r= 0.5237,P< 0.0001). The number of itraconazole-naïve isolates also decreased as the posaconazole MIC increased, particularly for MICs exceeding 0.5 μg/ml (0.25 μg/ml versus 0.5 μg/ml,P= 0.004). Conversely, the correlation coefficient obtained from the scattergram of itraconazole usage and voriconazole MICs was small (r= −0.2627,P= 0.001). Susceptibility to three triazole agents did not change as the duration of voriconazole exposure changed. In addition, we carried out detailed analysis, including microsatellite genotyping, for isolates obtained from patients infected with azole-resistantA. fumigatus. We confirmed the presence of acquired resistance to itraconazole and posaconazole due to a G54 substitution in thecyp51Agene for a patient with chronic pulmonary aspergillosis after oral itraconazole therapy. We should consider the possible appearance of azole-resistantA. fumigatusif itraconazole is used for extended periods.

Diagnostic cut-off of Aspergillus fumigatus -specific IgG in the diagnosis of chronic pulmonary aspergillosis

Mycoses ◽  
2018 ◽  
Vol 61 (10) ◽  
pp. 770-776 ◽  
Author(s):  
Inderpaul Singh Sehgal ◽  
Hansraj Choudhary ◽  
Sahajal Dhooria ◽  
Ashutosh Nath Aggarwal ◽  
Mandeep Garg ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Pulmonary Aspergillosis ◽  
Chronic Pulmonary Aspergillosis ◽  
Specific Igg

High detection rate of azole-resistant Aspergillus fumigatus after treatment with azole antifungal drugs among patients with chronic pulmonary aspergillosis in a single hospital setting with low azole resistance

2020 ◽  
Author(s):  
Keita Takeda ◽  
Junko Suzuki ◽  
Akira Watanabe ◽  
Teppei Arai ◽  
Tomohiro Koiwa ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Antifungal Therapy ◽  
Detection Rate ◽  
Hospital Setting ◽  
Antifungal Drugs ◽  
High Rate ◽  
Therapy Failure ◽  
National Hospital ◽  
Pulmonary Aspergillosis ◽  
Chronic Pulmonary Aspergillosis

Abstract The prevalence of azole-resistant Aspergillus fumigatus (ARAF) among chronic pulmonary aspergillosis (CPA) patients treated with azoles in Japan is unknown. The aim of this study was to determine the detection rate of ARAF in isolates from CPA patients who were treated with azoles for varying durations. The potential mechanism of acquiring resistance was examined by sequencing cyp51A and hmg1, two genes associated with ARAF. A. fumigatus isolates (n = 120) were collected from CPA patients (n = 104) between February 2012 and February 2019, at National Hospital Organization Tokyo National Hospital. The isolates were tested for susceptibility to the azole drugs itraconazole (ITCZ) and voriconazole (VRCZ). The detection rate of ARAF among all isolates was 8.3% (n = 10). Of the 10 resistant isolates, eight were ITCZ-resistant and five were VRCZ-resistant. Among 47 isolates obtained from 36 CPA patients who were treated with ITCZ (for an average of 256 days) and/or VRCZ (for an average of 29 days), the resistance rates were 17.0% and 10.6%, respectively. In addition, 46.2% of 13 isolates obtained from CPA patients with ongoing azole treatment at the time of antifungal therapy failure were resistant to azoles. Among the 10 ARAF isolates, a point mutation was detected in cyp51A in seven isolates and in hmg1 in two isolates. ARAF was detected at a high rate in CPA patients, particularly in those with ongoing long-term azole treatment, at the time of azole antifungal therapy failure.

scholarly journals Molecular epidemiology of airway colonisation by Aspergillus fumigatus in cystic fibrosis patients

2001 ◽  
Vol 50 (4) ◽  
pp. 367-374 ◽  
Author(s):  
BERNARD CIMON ◽  
FRANÇOISE SYMOENS ◽  
RACHID ZOUHAIR ◽  
DOMINIQUE CHABASSE ◽  
NICOLE NOLARD ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Aspergillus Fumigatus ◽  
Molecular Epidemiology

In vitro and in vivo characterization of two nonsporulating Aspergillus fumigatus clinical isolates from immunocompetent patients

2019 ◽  
Vol 58 (4) ◽  
pp. 543-551
Author(s):  
Zheng Zhang ◽  
Yuan Jiang ◽  
Jun Chen ◽  
Peiying Chen ◽  
Qingtao Kong ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Pathogenic Fungus ◽  
Antifungal Drugs ◽  
Causative Role ◽  
Immunocompromised Patients ◽  
Pulmonary Aspergillosis ◽  
Brla Gene

Abstract Aspergillus fumigatus is a pathogenic fungus responsible for invasive aspergillosis (IA). Typically, it can produce abundant conidia to survive and spread. The infection by A. fumigatus usually occurs in immunocompromised patients due to failed clearance of inhaled conidia. However, the incidence of aspergillosis in immunocompetent hosts has been increasing, the pathogenesis of which is still unknown. Our team previously obtained two clinical nonsporulating A. fumigatus isolates from non-immunocompromised patients, which only have the form of hyphae. This present study demonstrated the in vitro and in vivo characteristics of the two nonsporulating A. fumigatus isolates and verified that their conidiation defects are associated to abolished expression of the sporulation-related central regulatory pathway brlA gene. In addition, we confirmed the mutation site of brlA gene (c.657_660delTCCT) contributes to the nonsporulating phenotype in one clinical isolate. Plate assay showed that the two nonsporulating isolates have a similar resistance to antifungal drugs, cell wall disturbing substances, and oxidative stress compared with the wild-type reference Af293. Most important of all, we employed an immunocompetent mouse model to mimic the pathogenesis of pulmonary aspergillosis in non-immunocompromised patients. It revealed that the hyphae of two nonsporulating isolates and Af293 have similar virulence in immunocompetent hosts. Interestingly, the hyphae fragments of Af293 but not conidia are able to induce invasive aspergillosis in immunocompetent mice. In conclusion, our study indicate that the form of hyphae may play a dominant causative role in pulmonary aspergillosis of immunocompetent hosts rather than conidia.

scholarly journals Molecular Epidemiology of Aspergillus fumigatus: an In-Depth Genotypic Analysis of Isolates Involved in an Outbreak of Invasive Aspergillosis

2011 ◽  
Vol 49 (10) ◽  
pp. 3498-3503 ◽  
Author(s):  
J. Guinea ◽  
D. Garcia de Viedma ◽  
T. Pelaez ◽  
P. Escribano ◽  
P. Munoz ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Molecular Epidemiology ◽  
Genotypic Analysis
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