Topic Editors

Medicine Department, Ecosystemes Amazoniens et Pathologie Tropicale, EA 3593, Labex CEBA, University of French Guiana, Cayenne, France

Fungal Infections in Immunocompromised Hosts

Abstract submission deadline
closed (15 October 2021)
Manuscript submission deadline
closed (31 December 2021)
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23887

Topic Information

Dear Colleagues,

Despite significant progress being made due to the scaling up of antiretroviral therapy, advanced HIV disease remains a major public health problem worldwide. Late diagnosis and follow-up interruption ensure that a substantial number of persons have low CD4 counts and are thus at risk of developing opportunistic infections. Fungi are among the most frequent opportunistic pathogens and are a major cause of death. However, the magnitude of the problem has not yet been clearly measured, and the different ecosystems across the world lead to differences in the respective incidence of specific fungal pathogens. This may come as a surprise 40 years after the discovery of AIDS, but many regions across the world—often those with low resources—struggle to identify fungal pathogens. Knowledge of one’s regional epidemiology is, hence, essential to guide diagnosis and presumptive treatment while waiting for diagnostic confirmation. Furthermore, the use of immunosuppressive therapy has greatly expanded the number of persons at risk for invasive fungal pathogens. As for advanced HIV, the respective burden of different fungi is often still sketchy.

This Research Topic welcomes articles from different areas of the world describing the respective importance of the main invasive fungal infections in immunocompromised patients—cryptococcosis, histoplasmosis, pneumocystosis, talaromycosis, aspergillosis, invasive candidiasis, etc. The description of this diversity aims to improve our knowledge of the contrasted epidemiological contexts across the world and help improve care of patients in or coming from different regions.

Prof. Dr. Mathieu Nacher
Topic Editor

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Journal of Fungi
jof
4.7 4.9 2015 18.4 Days CHF 2600
Viruses
viruses
4.7 7.1 2009 13.8 Days CHF 2600
Microbiology Research
microbiolres
1.5 1.3 2010 16.6 Days CHF 1600

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Published Papers (10 papers)

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15 pages, 310 KiB  
Review
When Viruses Meet Fungi: Tackling the Enemies in Hematology
by Alessandro Busca, Francesco Marchesi, Chiara Cattaneo, Enrico Maria Trecarichi, Mario Delia, Maria Ilaria Del Principe, Anna Candoni and Livio Pagano
J. Fungi 2022, 8(2), 184; https://doi.org/10.3390/jof8020184 - 13 Feb 2022
Viewed by 2696
Abstract
The association of invasive fungal infections (IFI) and viral infections has been described in patients with hematologic malignancies (HM), in particular in hematopoietic stem cell transplant recipients. Regrettably, the diagnosis is often challenging, making the treatment inappropriate in some circumstances. The present review [...] Read more.
The association of invasive fungal infections (IFI) and viral infections has been described in patients with hematologic malignancies (HM), in particular in hematopoietic stem cell transplant recipients. Regrettably, the diagnosis is often challenging, making the treatment inappropriate in some circumstances. The present review takes into consideration the viral infections commonly associated with IFI. Clinical presentation of IFI and viral infections, risk factors, and impact on the outcome of HM patients are discussed throughout the paper. Full article
(This article belongs to the Topic Fungal Infections in Immunocompromised Hosts)
23 pages, 787 KiB  
Review
Growth of Aspergillus fumigatus in Biofilms in Comparison to Candida albicans
by Eefje Subroto, Jacq van Neer, Ivan Valdes and Hans de Cock
J. Fungi 2022, 8(1), 48; https://doi.org/10.3390/jof8010048 - 04 Jan 2022
Cited by 6 | Viewed by 2447
Abstract
Biofilm formation during infections with the opportunistic pathogen Aspergillus fumigatus can be very problematic in clinical settings, since it provides the fungal cells with a protective environment. Resistance against drug treatments, immune recognition as well as adaptation to the host environment allows fungal [...] Read more.
Biofilm formation during infections with the opportunistic pathogen Aspergillus fumigatus can be very problematic in clinical settings, since it provides the fungal cells with a protective environment. Resistance against drug treatments, immune recognition as well as adaptation to the host environment allows fungal survival in the host. The exact molecular mechanisms behind most processes in the formation of biofilms are unclear. In general, the formation of biofilms can be categorized roughly in a few stages; adhesion, conidial germination and development of hyphae, biofilm maturation and cell dispersion. Fungi in biofilms can adapt to the in-host environment. These adaptations can occur on a level of phenotypic plasticity via gene regulation. However, also more substantial genetic changes of the genome can result in increased resistance and adaptation in the host, enhancing the survival chances of fungi in biofilms. Most research has focused on the development of biofilms. However, to tackle developing microbial resistance and adaptation in biofilms, more insight in mechanisms behind genetic adaptations is required to predict which defense mechanisms can be expected. This can be helpful in the development of novel and more targeted antifungal treatments to combat fungal infections. Full article
(This article belongs to the Topic Fungal Infections in Immunocompromised Hosts)
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16 pages, 2132 KiB  
Article
Evaluation of 2-[18F]-Fluorodeoxysorbitol PET Imaging in Preclinical Models of Aspergillus Infection
by Jianhao Lai, Swati Shah, Rekeya Knight, Neysha Martinez-Orengo, Reema Patel, Amelia Mitchell, Zeping Wang, Falguni Basuli, Alvaro A. Ordonez, Sanjay K. Jain and Dima A. Hammoud
J. Fungi 2022, 8(1), 25; https://doi.org/10.3390/jof8010025 - 28 Dec 2021
Cited by 7 | Viewed by 1829
Abstract
Despite increasing associated mortality and morbidity, the diagnosis of fungal infections, especially with Aspergillus fumigatus (A. fumigatus), remains challenging. Based on known ability of Aspergillus species to utilize sorbitol, we evaluated 2-[18F]-fluorodeoxysorbitol (FDS), a recently described Enterobacterales imaging ligand, [...] Read more.
Despite increasing associated mortality and morbidity, the diagnosis of fungal infections, especially with Aspergillus fumigatus (A. fumigatus), remains challenging. Based on known ability of Aspergillus species to utilize sorbitol, we evaluated 2-[18F]-fluorodeoxysorbitol (FDS), a recently described Enterobacterales imaging ligand, in animal models of A. fumigatus infection, in comparison with 2-[18F]-fluorodeoxyglucose (FDG). In vitro assays showed slightly higher 3H-sorbitol uptake by live compared with heat-killed A. fumigatus. However, this was 10.6-fold lower than E. coli uptake. FDS positron emission tomography (PET) imaging of A. fumigatus pneumonia showed low uptake in infected lungs compared with FDG (0.290 ± 0.030 vs. 8.416 ± 0.964 %ID/mL). This uptake was higher than controls (0.098 ± 0.008 %ID/mL) and minimally higher than lung inflammation (0.167 ± 0.007 %ID/mL). In the myositis models, FDS uptake was highest in live E. coli infections. Uptake was low in A. fumigatus myositis model and only slightly higher in live compared with the heat-killed side. In conclusion, we found low uptake of 3H-sorbitol and FDS by A. fumigatus cultures and infection models compared with E. coli, likely due to the need for induction of sorbitol dehydrogenase by sorbitol. Our findings do not support FDS as an Aspergillus imaging agent. At this point, FDS remains more selective for imaging Gram-negative Enterobacterales. Full article
(This article belongs to the Topic Fungal Infections in Immunocompromised Hosts)
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8 pages, 729 KiB  
Article
A Simple Predictive Score to Distinguish between Disseminated Histoplasmosis and Tuberculosis in Patients with HIV
by Mathieu Nacher, Kinan Drak Alsibai, Loïc Epelboin, Philippe Abboud, Frédégonde About, Magalie Demar, Félix Djossou, Romain Blaizot, Maylis Douine, Nadia Sabbah, Nicolas Vignier, Leila Adriouch, Aude Lucarelli, Mathilde Boutrou, Pierre Couppié and Antoine Adenis
J. Fungi 2022, 8(1), 16; https://doi.org/10.3390/jof8010016 - 27 Dec 2021
Cited by 1 | Viewed by 2192
Abstract
Disseminated histoplasmosis is a common differential diagnosis of tuberculosis in disease-endemic areas. We aimed to find a predictive score to orient clinicians towards disseminated histoplasmosis or tuberculosis when facing a non-specific infectious syndrome in patients with advanced HIV disease. We reanalyzed data from [...] Read more.
Disseminated histoplasmosis is a common differential diagnosis of tuberculosis in disease-endemic areas. We aimed to find a predictive score to orient clinicians towards disseminated histoplasmosis or tuberculosis when facing a non-specific infectious syndrome in patients with advanced HIV disease. We reanalyzed data from a retrospective study in Cayenne Hospital between January 1997–December 2008 comparing disseminated histoplasmosis and tuberculosis: 100 confirmed disseminated histoplasmosis cases and 88 confirmed tuberculosis cases were included. A simple logit regression model was constructed to predict whether a case was tuberculosis or disseminated histoplasmosis. From this model, a score may be obtained, where the natural logarithm of the probability of disseminated histoplasmosis/tuberculosis = +3.917962 × WHO performance score (1 if >2, 0 if ≤2) −1.624642 × Pulmonary presentation (1 yes, 0 no) +2.245819 × Adenopathies > 2 cm (1 yes, 0 no) −0.015898 × CD4 count − 0.001851 × ASAT − 0.000871 × Neutrophil count − 0.000018 × Platelet count + 6.053793. The area under the curve was 98.55%. The sensitivity of the model to distinguish between disseminated histoplasmosis and tuberculosis was 95% (95% CI = 88.7–98.3%), and the specificity was 93% (95% CI = 85.7.3–97.4%). In conclusion, we here present a clinical-biological predictive score, using simple variables available on admission, that seemed to perform very well to discriminate disseminated histoplasmosis from tuberculosis in French Guiana in well characterized patients. Full article
(This article belongs to the Topic Fungal Infections in Immunocompromised Hosts)
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12 pages, 27491 KiB  
Article
Enhanced Virulence of Candida albicans by Staphylococcus aureus: Evidence in Clinical Bloodstream Infections and Infected Zebrafish Embryos
by Yen-Mu Wu, Po-Yen Huang, Yi-Chuan Cheng, Chih-Hua Lee, Meng-Chieh Hsu, Jang-Jih Lu and Shao-Hung Wang
J. Fungi 2021, 7(12), 1099; https://doi.org/10.3390/jof7121099 - 20 Dec 2021
Cited by 5 | Viewed by 2350
Abstract
Coinfection with Candida and Staphylococcus results in higher mortality in animal studies. However, the pathogenesis and interplay between C. albicans and S. aureus in bloodstream infections (BSIs) is unclear. This study determines the clinical features and outcomes of mixed C. albicans/S. [...] Read more.
Coinfection with Candida and Staphylococcus results in higher mortality in animal studies. However, the pathogenesis and interplay between C. albicans and S. aureus in bloodstream infections (BSIs) is unclear. This study determines the clinical features and outcomes of mixed C. albicans/S. aureus (CA/SA) BSIs and biofilm formation on pathogenesis during coinfection. Demographics and outcomes for mixed BSIs and monomicrobial candidemia were compared. Compared to 115 monomicrobial C. albicans BSIs, 22 patients with mixed CA/SA BSIs exhibited a significantly higher mortality rate and shorter survival time. In vitro and in vivo biofilm analysis showed that C. albicans accounted for the main biofilm architecture, and S. aureus increased its amount. Antibiotic tolerance in S. aureus, which adhered to Candida hyphae observed by scanning electron microscope, was demonstrated by the presence of wild-type C. albicans co-biofilm. Upregulation in exotoxin genes of S. aureus was evidenced by quantitative RT-PCR when a co-biofilm was formed with C. albicans. Mixed CA/SA BSIs result in a higher mortality rate in patients and in vivo surrogate models experiments. This study demonstrates that the virulence enhancement of C. albicans and S. aureus during co-biofilm formation contributes to the high mortality rate. Full article
(This article belongs to the Topic Fungal Infections in Immunocompromised Hosts)
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10 pages, 522 KiB  
Article
Clinical and Epidemiological Profile of Patients with Invasive Aspergillosis from a Fourth Level Hospital in Bogota, Colombia: A Retrospective Study
by Ana Goyeneche-García, Juan Rodríguez-Oyuela, Guillermo Sánchez and Carolina Firacative
J. Fungi 2021, 7(12), 1092; https://doi.org/10.3390/jof7121092 - 18 Dec 2021
Cited by 5 | Viewed by 2336
Abstract
Invasive aspergillosis (IA) is a severe mycosis caused by Aspergillus species. The infection mainly affects immunocompromised patients with a significant clinical burden. This study aimed to determine the clinical and epidemiological characteristics of patients diagnosed with IA in a fourth level hospital in [...] Read more.
Invasive aspergillosis (IA) is a severe mycosis caused by Aspergillus species. The infection mainly affects immunocompromised patients with a significant clinical burden. This study aimed to determine the clinical and epidemiological characteristics of patients diagnosed with IA in a fourth level hospital in Colombia, as these data are scarce in the country. A retrospective, observational study, from a single center was conducted with 34 male and 32 female patients, between 1 month- and 90-year-old, diagnosed with proven (18.2%), probable (74.2%) and possible (7.6%) IA, during a 21-year period. The most frequent underlying conditions for IA were chemotherapy (39.4%) and corticosteroid use (34.8%). The lung was the most common affected organ (92.4%). Computed tomography (CT) imaging findings were mainly nodules (57.6%) and consolidation (31.8%). A low positive correlation was found between serum galactomannan and hospitalization length. Aspergillus fumigatus prevailed (73.3%) in sputum and bronchoalveolar lavage cultures. Most patients were hospitalized in general wards (63.6%) and treated with voriconazole (80.3%). Mortality rate was 15.2%. Common risk factors for IA were identified in the Colombian cohort, including medications and underlying diseases. However, their frequency differs from other countries, reinforcing the idea that local surveillance is essential and at-risk patients should be carefully monitored. Full article
(This article belongs to the Topic Fungal Infections in Immunocompromised Hosts)
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6 pages, 2403 KiB  
Case Report
First Report of an Invasive Infection by Cephalotrichum gorgonifer in a Neutropenic Patient with Hematological Malignancy under Chemotherapy
by Ana Álvarez-Uría, Pilar Escribano, Verónica Parra-Blanco, José Francisco Cano-Lira, Alberto Miguel Stchigel, Gillen Oarbeascoa, Patricia Muñoz and Jesús Guinea
J. Fungi 2021, 7(12), 1089; https://doi.org/10.3390/jof7121089 - 17 Dec 2021
Viewed by 2259
Abstract
The etiological agents of infrequent invasive fungal infections (IFI) are difficult to identify on the species level using classic morphological examination. We describe the first case of an IFI caused by Cephalotrichum gorgonifer in a neutropenic patient with a hematological malignancy and put [...] Read more.
The etiological agents of infrequent invasive fungal infections (IFI) are difficult to identify on the species level using classic morphological examination. We describe the first case of an IFI caused by Cephalotrichum gorgonifer in a neutropenic patient with a hematological malignancy and put it on the map as a new causative agent of IFI. Case report, microbiological findings and description of the etiological agent. A 60-year-old man was diagnosed with mantle cell lymphoma. A CT scan confirmed the presence of lung infiltrates located at the right upper lobe. Histological examination of one of the nodules showed a large number of narrow septate hyphae with acute-angle branching and irregular round cell morphology; vessels walls appeared infiltrated, proving an angioinvasive pulmonary IFI. Sample culture resulted positive and molecular identification proved the presence of Cephalotrichum gorgonifer. Voriconazole was used for 12 months and the patient did not report any complications or side effects. Complete remission of lymphoma was achieved later by the time chemotherapy, radiotherapy, and radioimmunotherapy consolidation were completed. We recommend the inclusion of Cephalotrichum gorgonifer in the list of opportunistic pathogens causing mycoses in neutropenic hematological patients with suspected mould-related IFI. Full article
(This article belongs to the Topic Fungal Infections in Immunocompromised Hosts)
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5 pages, 990 KiB  
Case Report
Malassezia restricta Pneumonia in Solid Organ Transplant Recipients: First Report of Two Cases
by Alessandra Mularoni, Elena Graziano, Alice Annalisa Medaglia, Barbara Buscemi, Taylor Eddens, Lavinia Martino, Daniele Di Carlo, Antonio Cascio, Pier Giulio Conaldi, Alessandro Bertani and Paolo Antonio Grossi
J. Fungi 2021, 7(12), 1057; https://doi.org/10.3390/jof7121057 - 10 Dec 2021
Cited by 1 | Viewed by 2048
Abstract
Emerging fungal infections are a major challenge in solid organ transplantation (SOT) and are associated with high morbidity and mortality. We report two cases of Malassezia restricta pneumonia in SOT recipients. Infections were diagnosed with molecular analysis and histology. Patients were treated with [...] Read more.
Emerging fungal infections are a major challenge in solid organ transplantation (SOT) and are associated with high morbidity and mortality. We report two cases of Malassezia restricta pneumonia in SOT recipients. Infections were diagnosed with molecular analysis and histology. Patients were treated with antifungal therapy and have fully recovered. Full article
(This article belongs to the Topic Fungal Infections in Immunocompromised Hosts)
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14 pages, 3592 KiB  
Article
MicroRNA-6498-5p Inhibits Nosema bombycis Proliferation by Downregulating BmPLPP2 in Bombyx mori
by Congwu Hu, Zhanqi Dong, Boyuan Deng, Qin Wu, Peng Chen, Cheng Lu and Minhui Pan
J. Fungi 2021, 7(12), 1051; https://doi.org/10.3390/jof7121051 - 08 Dec 2021
Cited by 7 | Viewed by 2075
Abstract
As microRNAs (miRNAs) are important expression regulators of coding RNA, it is important to characterize their role in the interaction between hosts and pathogens. To obtain a comprehensive understanding of the miRNA alternation in Bombyx mori (B. mori) infected with Nosema [...] Read more.
As microRNAs (miRNAs) are important expression regulators of coding RNA, it is important to characterize their role in the interaction between hosts and pathogens. To obtain a comprehensive understanding of the miRNA alternation in Bombyx mori (B. mori) infected with Nosema bombycis (N. bombycis), RNA sequencing and stem-loop qPCR were conducted to screen and identify the significantly differentially expressed miRNAs (DEmiRNAs). A total of 17 such miRNAs were identified in response to N. bombycis infection, among which miR6498-5p efficiently inhibited the proliferation of N. bombycis in BmE-SWU1 (BmE) cells by downregulating pyridoxal phosphate phosphatase 2 (BmPLPP2). In addition, a fluorescence in situ hybridization (FISH) assay showed that miR6498-5p was located in the cytoplasm of BmE cells, while it was not found in the schizonts of N. bombycis. Further investigation of the effect of BmPLPP2 on the proliferation of schizonts found that the positive factor BmPLPP2 could facilitate N. bombycis completing its life cycle in cells by overexpression and RNAi of BmPLPP2. Our findings offer multiple new insights into the role of miRNAs in the interaction between hosts and microsporidia. Full article
(This article belongs to the Topic Fungal Infections in Immunocompromised Hosts)
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9 pages, 410 KiB  
Article
Invasive Fungal Infections in Persons Living with HIV in an Amazonian Context: French Guiana, 2009–2019
by Laurène Cachera, Antoine Adenis, Basma Guarmit, Sébastien Rabier, Pierre Couppié, Felix Djossou, Loïc Epelboin, Alessia Melzani, Philippe Abboud, Denis Blanchet, Magalie Demar, Kinan Drak Alsibai and Mathieu Nacher
J. Fungi 2021, 7(6), 421; https://doi.org/10.3390/jof7060421 - 27 May 2021
Cited by 1 | Viewed by 1987
Abstract
Although the burden of histoplasmosis in patients with advanced HIV has been the focus of detailed estimations, knowledge about invasive fungal infections in patients living with HIV in an Amazonian context is somewhat scattered. Our goal was thus to adopt a broader view [...] Read more.
Although the burden of histoplasmosis in patients with advanced HIV has been the focus of detailed estimations, knowledge about invasive fungal infections in patients living with HIV in an Amazonian context is somewhat scattered. Our goal was thus to adopt a broader view integrating all invasive fungal infections diagnosed over a decade in French Guiana. All patients hospitalized at Cayenne hospital from 1 January 2009 to 31 December 2018 with a proven diagnosis of invasive fungal infection were included (N = 227). Histoplasmosis was the most common (48.2%), followed by Cryptococcus infection (26.3%), and pneumocystosis (12.5%). For cryptococcal infection, there was a discordance between the actual diagnosis of cryptococcal meningitis n = (26) and the isolated presence of antigen in the serum (n = 46). Among the latter when the information was available (n = 34), 21(65.6%) were treated with antifungals but not coded as cryptococcocosis. Most fungal infections were simultaneous to the discovery of HIV (38%) and were the AIDS-defining event (66%). The proportion of major invasive fungal infections appeared to remain stable over the course of the study, with a clear predominance of documented H. capsulatum infections. Until now, the focus of attention has been histoplasmosis, but such attention should not overshadow other less-studied invasive fungal infections. Full article
(This article belongs to the Topic Fungal Infections in Immunocompromised Hosts)
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