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Aspergillus Infection
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Aspergillus Infection

A special issue of Journal of Fungi (ISSN 2309-608X).

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 28670

Special Issue Editor

Prof. Dr. Nikolai Klimko

E-Mail Website
Guest Editor
Department of Clinical Mycology, Allergy and Immunology in I.Mechnikov North Western State Medical University, Saint Petersburg, Russia
Interests: antifungal pharmacology; clinical mycology; fungal epidemiology; fungal resistance; immunocompromised host

Special Issue Information

Dear Colleagues,

In recent years, Aspergillus infection has ceased to be a rare disease. Recent global estimates found 3,000,000 cases of chronic pulmonary aspergillosis, and ~250,000 cases of invasive aspergillosis occurring annually. An increase in the prevalence of chronic pulmonary aspergillosis is associated with an increase in the number of patients with tuberculosis and other chronic lung diseases. Late diagnosis and inadequate treatment of chronic pulmonary aspergillosis lead to the development of irreversible respiratory failure and high mortality.

Invasive aspergillosis is occurring in expanding populations of immunocompromised patients, among which new risk groups have been identified, for example, severe patients with influenza in ICU. The advent of new diagnostics and new antifungals has significantly reduced mortality from invasive aspergillosis in hematological patients, but mortality in other immunocompromised patients remains unacceptably high. The emerging problem of Aspergillus spp. antifungal resistance requires the development of new drugs, as well as optimizing the PK/PD of antifungals. I hope this Special Issue of the Journal of Fungi allows us to take a fresh look at the changing landscape of Aspergillus infection.

Prof. Dr. Nikolai Klimko
Guest Editor

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Keywords

  • Aspergillus
  • antifungal agents
  • chronic pulmonary aspergillosis
  • fungal diagnostics
  • fungal epidemiology
  • fungal resistance
  • invasive aspergillosis
  • immunocompromised host

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Published Papers (7 papers)

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Research

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18 pages, 349 KiB  
Article
Trends on Aspergillus Epidemiology—Perspectives from a National Reference Laboratory Surveillance Program
by Raquel Sabino, Paulo Gonçalves, Aryse Martins Melo, Daniela Simões, Mariana Oliveira, Mariana Francisco, Carla Viegas, Dinah Carvalho, Carlos Martins, Teresa Ferreira, Cristina Toscano, Helena Simões and Cristina Veríssimo
J. Fungi 2021, 7(1), 28; https://doi.org/10.3390/jof7010028 - 6 Jan 2021
Cited by 18 | Viewed by 3618
Abstract
Identification of Aspergillus to species level is important since sibling species may display variable susceptibilities to multiple antifungal drugs and also because correct identification contributes to improve the knowledge of epidemiological studies. Two retrospective laboratory studies were conducted on Aspergillus surveillance at the [...] Read more.
Identification of Aspergillus to species level is important since sibling species may display variable susceptibilities to multiple antifungal drugs and also because correct identification contributes to improve the knowledge of epidemiological studies. Two retrospective laboratory studies were conducted on Aspergillus surveillance at the Portuguese National Mycology Reference Laboratory. The first, covering the period 2017–2018, aimed to study the molecular epidemiology of 256 Aspergillus isolates obtained from patients with respiratory, subcutaneous, or systemic infections and from environmental samples. The second, using our entire collection of clinical and environmental A. fumigatus isolates (N = 337), collected between 2012 and 2019, aimed to determine the frequency of azole-resistant A. fumigatus isolates. Aspergillus fumigatus sensu stricto was the most frequent species in both clinical and environmental samples. Overall, and considering all Aspergillus sections identified, a high frequency of cryptic species was detected, based on beta-tubulin or calmodulin sequencing (37% in clinical and 51% in environmental isolates). Regarding all Fumigati isolates recovered from 2012–2019, the frequency of cryptic species was 5.3% (18/337), with the identification of A. felis (complex), A. lentulus, A. udagawae, A. hiratsukae, and A. oerlinghauensis. To determine the frequency of azole resistance of A. fumigatus, isolates were screened for azole resistance using azole-agars, and 53 possible resistant isolates were tested by the CLSI microdilution reference method. Nine A. fumigatus sensu stricto and six Fumigati cryptic isolates showed high minimal inhibitory concentrations to itraconazole, voriconazole, and/or posaconazole. Real-time PCR to detect cyp51A mutations and sequencing of cyp51A gene and its promoter were performed. The overall frequency of resistance to azoles in A. fumigatus sensu stricto was 3.0%. With this retrospective analysis, we were able to detect one azole-resistant G54R mutant A. fumigatus environmental isolate, collected in 2015. The TR34/L98H mutation, linked to environmental transmission route of azole resistance, was the most frequently detected mutation (N = 4; 1.4%). Our findings underline the demand for correct identification and susceptibility testing of Aspergillus isolates. Full article
(This article belongs to the Special Issue Aspergillus Infection)
8 pages, 236 KiB  
Communication
Drug-Resistant Aspergillus flavus Is Highly Prevalent in the Environment of Vietnam: A New Challenge for the Management of Aspergillosis?
by Tra My N. Duong, Phuong Tuyen Nguyen, Thanh Van Le, Huong Lan P. Nguyen, Bich Ngoc T. Nguyen, Bich Phuong T. Nguyen, Thu Anh Nguyen, Sharon C.-A. Chen, Vanessa R. Barrs, Catriona L. Halliday, Tania C. Sorrell, Jeremy N. Day and Justin Beardsley
J. Fungi 2020, 6(4), 296; https://doi.org/10.3390/jof6040296 - 18 Nov 2020
Cited by 18 | Viewed by 3140
Abstract
The burden of aspergillosis, especially Chronic Pulmonary Aspergillosis, is increasingly recognized, and the increasing presence of azole-resistant environmental Aspergillus fumigatus has been highlighted as a health risk. However, a sizable minority of aspergillosis is caused by Aspergillus flavus, which is assumed to [...] Read more.
The burden of aspergillosis, especially Chronic Pulmonary Aspergillosis, is increasingly recognized, and the increasing presence of azole-resistant environmental Aspergillus fumigatus has been highlighted as a health risk. However, a sizable minority of aspergillosis is caused by Aspergillus flavus, which is assumed to be sensitive to azoles but is infrequently included in surveillance. We conducted environmental sampling at 150 locations in a rural province of southern Vietnam. A. flavus isolates were identified morphologically, their identity was confirmed by sequencing of the beta-tubulin gene, and then they were tested for susceptibility to azoles and amphotericin B according to EUCAST methodologies. We found that over 85% of A. flavus isolates were resistant to at least one azole, and half of them were resistant to itraconazole. This unexpectedly high prevalence of resistance demands further investigation to determine whether it is linked to agricultural azole use, as has been described for A. fumigatus. Clinical correlation is required, so that guidelines can be adjusted to take this information into account. Full article
(This article belongs to the Special Issue Aspergillus Infection)
17 pages, 1406 KiB  
Article
Outcomes of Antifungal Prophylaxis in High-Risk Haematological Patients (AML under Intensive Chemotherapy): The SAPHIR Prospective Multicentre Study
by Jean-Pierre Gangneux, Christophe Padoin, Mauricette Michallet, Emeline Saillio, Alexandra Kumichel, Régis Peffault de La Tour, Patrice Ceballos, Thomas Gastinne and Arnaud Pigneux
J. Fungi 2020, 6(4), 281; https://doi.org/10.3390/jof6040281 - 12 Nov 2020
Cited by 3 | Viewed by 2584
Abstract
Antifungal prophylaxis (AFP) is recommended by international guidelines for patients with acute myeloid leukaemia (AML) undergoing induction chemotherapy and allogeneic hematopoietic cell transplantation. Nonetheless, treatment of breakthrough fungal infections remains challenging. This observational, prospective, multicentre, non-comparative study of patients undergoing myelosuppressive and intensive [...] Read more.
Antifungal prophylaxis (AFP) is recommended by international guidelines for patients with acute myeloid leukaemia (AML) undergoing induction chemotherapy and allogeneic hematopoietic cell transplantation. Nonetheless, treatment of breakthrough fungal infections remains challenging. This observational, prospective, multicentre, non-comparative study of patients undergoing myelosuppressive and intensive chemotherapy for AML who are at high-risk of invasive fungal diseases (IFDs), describes AFP management and outcomes for 404 patients (65.6% newly diagnosed and 73.3% chemotherapy naïve). Ongoing chemotherapy started 1.0 ± 4.5 days before inclusion and represented induction therapy for 79% of participants. In 92.3% of patients, posaconazole was initially prescribed, and 8.2% of all patients underwent at least one treatment change after 17 ± 24 days, mainly due to medical conditions influencing AFP absorption (65%). The mean AFP period was 24 ± 32 days, 66.8% stopped their prophylaxis after the high-risk period and 31.2% switched to a non-prophylactic treatment (2/3 empirical, 1/3 pre-emptive/curative). Overall, 9/404 patients (2.2%) were diagnosed with probable or proven IFDs. During the follow-up, 94.3% showed no signs of infection. Altogether, 20 patients (5%) died, and three deaths (0.7%) were IFD-related. In conclusion, AFP was frequently prescribed and well tolerated by these AML patients, breakthrough infections incidence and IFD mortality were low and very few treatment changes were required. Full article
(This article belongs to the Special Issue Aspergillus Infection)
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9 pages, 2990 KiB  
Article
Clonal Expansion of Environmental Triazole Resistant Aspergillus fumigatus in Iran
by Fatemeh Ahangarkani, Hamid Badali, Kiana Abbasi, Mojtaba Nabili, Sadegh Khodavaisy, Theun de Groot and Jacques F. Meis
J. Fungi 2020, 6(4), 199; https://doi.org/10.3390/jof6040199 - 1 Oct 2020
Cited by 16 | Viewed by 2657
Abstract
Azole-resistance in Aspergillus fumigatus is a worldwide medical concern complicating the management of aspergillosis (IA). Herein, we report the clonal spread of environmental triazole resistant A. fumigatus isolates in Iran. In this study, 63 A. fumigatus isolates were collected from 300 compost samples [...] Read more.
Azole-resistance in Aspergillus fumigatus is a worldwide medical concern complicating the management of aspergillosis (IA). Herein, we report the clonal spread of environmental triazole resistant A. fumigatus isolates in Iran. In this study, 63 A. fumigatus isolates were collected from 300 compost samples plated on Sabouraud dextrose agar supplemented with itraconazole (ITR) and voriconazole (VOR). Forty-four isolates had the TR34/L98H mutation and three isolates a TR46/Y121F/T289A resistance mechanism, while two isolates harbored a M172V substitution in cyp51A. Fourteen azole resistant isolates had no mutations in cyp51A. We found that 41 out of 44 A. fumigatus strains with the TR34/L98H mutation, isolated from compost in 13 different Iranian cities, shared the same allele across all nine examined microsatellite loci. Clonal expansion of triazole resistant A. fumigatus in this study emphasizes the importance of establishing antifungal resistance surveillance studies to monitor clinical Aspergillus isolates in Iran, as well as screening for azole resistance in environmental A. fumigatus isolates. Full article
(This article belongs to the Special Issue Aspergillus Infection)
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13 pages, 417 KiB  
Article
High-Frequency Direct Detection of Triazole Resistance in Aspergillus fumigatus from Patients with Chronic Pulmonary Fungal Diseases in India
by Ashutosh Singh, Brijesh Sharma, Kaushal Kumar Mahto, Jacques F. Meis and Anuradha Chowdhary
J. Fungi 2020, 6(2), 67; https://doi.org/10.3390/jof6020067 - 20 May 2020
Cited by 34 | Viewed by 4322
Abstract
Aspergillosis due to azole-resistant Aspergillus fumigatus is a worldwide problem with major therapeutic implications. In patients with invasive aspergillosis, a low yield of fungal cultures results in underestimation of azole resistance. To detect azole resistance in A. fumigatus, we applied the AsperGenius [...] Read more.
Aspergillosis due to azole-resistant Aspergillus fumigatus is a worldwide problem with major therapeutic implications. In patients with invasive aspergillosis, a low yield of fungal cultures results in underestimation of azole resistance. To detect azole resistance in A. fumigatus, we applied the AsperGenius® Resistance multiplex real-time polymerase chain reaction (PCR) assay to detect TR34/L98H, and TR46/T289A/Y121F mutations and the AsperGenius® G54/M220 RUO PCR assay to detect G54/M220 mutations directly in bronchoalveolar lavage (BAL) samples of 160 patients with chronic respiratory diseases in Delhi, India. Only 23% of samples were culture-positive compared to 83% positivity by A. fumigatus species PCR highlighting concerns about the low yield of cultures. Notably, 25% of BAL samples (33/160 patients) had azole resistance-associated mutation by direct detection using PCR assay. Detection of resistance-associated mutations was found mainly in 59% and 43% patients with chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA), respectively. Overall, a G54 mutation, conferring itraconazole resistance, was the predominant finding in 87.5% and 67% of patients with CPA and ABPA, respectively. In culture-negative, PCR-positive samples, we detected azole-resistant mutations in 34% of BAL samples. Azole resistance in chronic Aspergillus diseases remains undiagnosed, warranting standardization of respiratory culture and inclusion of rapid techniques to detect resistance markers directly in respiratory samples. Full article
(This article belongs to the Special Issue Aspergillus Infection)
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Review

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21 pages, 1294 KiB  
Review
Novel Antifungal Agents and Their Activity against Aspergillus Species
by Roya Vahedi-Shahandashti and Cornelia Lass-Flörl
J. Fungi 2020, 6(4), 213; https://doi.org/10.3390/jof6040213 - 9 Oct 2020
Cited by 18 | Viewed by 7797
Abstract
There is a need for new antifungal agents, mainly due to increased incidence of invasive fungal infections (IFI), high frequency of associated morbidity and mortality and limitations of the current antifungal agents (e.g., toxicity, drug–drug interactions, and resistance). The clinically available antifungals for [...] Read more.
There is a need for new antifungal agents, mainly due to increased incidence of invasive fungal infections (IFI), high frequency of associated morbidity and mortality and limitations of the current antifungal agents (e.g., toxicity, drug–drug interactions, and resistance). The clinically available antifungals for IFI are restricted to four main classes: polyenes, flucytosine, triazoles, and echinocandins. Several antifungals are hampered by multiple resistance mechanisms being present in fungi. Consequently, novel antifungal agents with new targets and modified chemical structures are required to combat fungal infections. This review will describe novel antifungals, with a focus on the Aspergillus species. Full article
(This article belongs to the Special Issue Aspergillus Infection)
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Other

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11 pages, 25705 KiB  
Brief Report
Role of Voriconazole in the Management of Invasive Central Nervous System Aspergillosis: A Case Series from a Tertiary Care Centre in India
by Nitin Gupta, Parul Kodan, Ankit Mittal, Gagandeep Singh, George Netto, Prashant Ramteke, Sundeep Malla, Rohit Kumar, Tirlangi Praveen Kumar, Komal Singh, Anivita Aggarwal, Devashish Desai, Manish Soneja, Immaculata Xess and Naveet Wig
J. Fungi 2020, 6(3), 139; https://doi.org/10.3390/jof6030139 - 18 Aug 2020
Cited by 5 | Viewed by 3369
Abstract
Invasive central nervous system (CNS) aspergillosis is acquired by either hematogenous dissemination or direct spread from a sinus infection. We describe a series of nine patients with CNS aspergillosis from a tertiary care teaching institute in North India who were treated with voriconazole [...] Read more.
Invasive central nervous system (CNS) aspergillosis is acquired by either hematogenous dissemination or direct spread from a sinus infection. We describe a series of nine patients with CNS aspergillosis from a tertiary care teaching institute in North India who were treated with voriconazole alone or in combination with surgery. All patients who had clinical and radiological features consistent with fungal CNS infection, showed the presence of septate hyphae on histopathology/microscopy and were either culture positive for Aspergillus spp. or had serum galactomannan positivity were diagnosed as CNS aspergillosis. Clinical features, risk factors, diagnostic modalities, treatment details and outcome at last follow-up were recorded for all patients diagnosed with CNS aspergillosis. A total of nine patients were diagnosed with CNS aspergillosis. The median duration of presentation at our hospital was six months (IQR-2-9 months). Six patients had concomitant sinus involvement, while two patients had skull-base involvement as well. All patients were treated with voriconazole therapy, and three of these patients underwent surgery. All but one patient survived at the last follow-up (median duration was 14 months (IQR- 8-21.5). Two patients had complete resolution, and voriconazole was stopped at the last follow-up, and the rest of the patients were continued on voriconazole. Of the six patients who were continued on voriconazole, all but one had more than 50% radiological resolution on follow-up imaging. Invasive CNS aspergillosis is an important cause of CNS fungal infection that is often diagnosed late and requires long-term voriconazole-based therapy. Full article
(This article belongs to the Special Issue Aspergillus Infection)
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