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Fungal Infections in Immunocompromised Hosts
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Fungal Infections in Immunocompromised Hosts

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

Deadline for manuscript submissions: closed (31 October 2018) | Viewed by 103233

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Dimitrios P. Kontoyiannis

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Guest Editor
Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: fungal pathogenesis; clinical mycology; resistance; fungal diagnostics; experimental antifungals; mold infections; infections in cancer patients; infectious diseases; medical mycology
Special Issues, Collections and Topics in MDPI journals
Prof. Monica Slavin

E-Mail Website
Guest Editor
Department of Infectious Diseases and Infection Prevention, Peter MacCallum Cancer Centre, Melbourne, Australia
Interests: invasive fungal disease; antifungal treatment and prophylaxis; infection in the immunocompromised host

Special Issue Information

Dear Colleagues,

First convened in 1980, the International Immunocompromised Host Society (ICHS) symposium is the premier, international, multi-disciplinary forum for scientific and clinical exchange to improve understanding and management of infections in the immunocompromised host. Since its inception, mycology has been a key theme throughout the bi-annual meetings. The recent meeting in June 2018, in Athens, Greece, similarly, had a cutting edge mycology program delivered by leading international experts addressing current and future innovations in mycology.

Worldwide deaths from Candida, Aspergillus, Pneumocystis and Cryptococcus infections are estimated to exceed 1.4 million annually with individual patient mortality rates in excess of 30%. Invasive fungal diseases (IFDs) are occurring in expanding populations at risk, such as those with liver disease and receiving novel treatments, such as biologics and small molecule protein kinase inhibitors, providing insight into fungal pathogenesis. Outbreaks occurring in healthcare or after natural disasters are increasingly identified requiring specialized investigation. The emerging global problem of antifungal resistance has prompted an increasing focus on antifungal drug discovery, as well as optimizing PK/PD of antifungals, and on fungal biofilms, which may select resistance. Approaches such as harnessing the mycobiome and immunotherapy may offer new options for managing IFD.

The development and integration of improved diagnostic tests for IFD including MALDI-TOF, nucleic acid and biomarker detection and immunogenetic assays offers promise for implementing more precise individual risk profiles and early intervention to prevent or treat IFD. At a population level these tests offer important antifungal stewardship tools to support the judicious use of antifungals. In this unique supplement we have compiled several state of the art topics that are based on lectures delivered by eminent mycology experts during the 37th ICHS meeting. We hope that the esteemed audience of Journal of Fungi will enjoy and appreciate the ever evolving and complex field of fungal infections in vulnerable hosts.

Sincerely,
Prof. Dimitrios P. Kontoyiannis
Prof. Monica Slavin
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Candida
  • Aspergillus
  • Cryptococcucus
  • endemic fungii
  • resistance
  • fungal diagnostics
  • fungal epidemiology
  • fungal pharmacology
  • antifungal agents
  • immunocompromised host

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Related Special Issue

Published Papers (12 papers)

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Review

21 pages, 286 KiB  
Review
Invasive Aspergillosis in Pediatric Leukemia Patients: Prevention and Treatment
by Savvas Papachristou, Elias Iosifidis and Emmanuel Roilides
J. Fungi 2019, 5(1), 14; https://doi.org/10.3390/jof5010014 - 11 Feb 2019
Cited by 14 | Viewed by 4653
Abstract
The purpose of this article is to review and update the strategies for prevention and treatment of invasive aspergillosis (IA) in pediatric patients with leukemia and in patients with hematopoietic stem cell transplantation. The major risk factors associated with IA will be described [...] Read more.
The purpose of this article is to review and update the strategies for prevention and treatment of invasive aspergillosis (IA) in pediatric patients with leukemia and in patients with hematopoietic stem cell transplantation. The major risk factors associated with IA will be described since their recognition constitutes the first step of prevention. The latter is further analyzed into chemoprophylaxis and non-pharmacologic approaches. Triazoles are the mainstay of anti-fungal prophylaxis while the other measures revolve around reducing exposure to mold spores. Three levels of treatment have been identified: (a) empiric, (b) pre-emptive, and (c) targeted treatment. Empiric is initiated in febrile neutropenic patients and uses mainly caspofungin and liposomal amphotericin B (LAMB). Pre-emptive is a diagnostic driven approach attempting to reduce unnecessary use of anti-fungals. Treatment targeted at proven or probable IA is age-dependent, with voriconazole and LAMB being the cornerstones in >2yrs and <2yrs age groups, respectively. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
9 pages, 249 KiB  
Review
Invasive Candidiasis in Infants and Children: Recent Advances in Epidemiology, Diagnosis, and Treatment
by Thomas J. Walsh, Aspasia Katragkou, Tempe Chen, Christine M. Salvatore and Emmanuel Roilides
J. Fungi 2019, 5(1), 11; https://doi.org/10.3390/jof5010011 - 24 Jan 2019
Cited by 47 | Viewed by 7273
Abstract
This paper reviews recent advances in three selected areas of pediatric invasive candidiasis: epidemiology, diagnosis, and treatment. Although the epidemiological trends of pediatric invasive candidiasis illustrate a declining incidence, this infection still carries a heavy burden of mortality and morbidity that warrants a [...] Read more.
This paper reviews recent advances in three selected areas of pediatric invasive candidiasis: epidemiology, diagnosis, and treatment. Although the epidemiological trends of pediatric invasive candidiasis illustrate a declining incidence, this infection still carries a heavy burden of mortality and morbidity that warrants a high index of clinical suspicion, the need for rapid diagnostic systems, and the early initiation of antifungal therapy. The development of non-culture-based technologies, such as the T2Candida system and (1→3)-β-d-glucan detection assay, offers the potential for early laboratory detection of candidemia and CNS candidiasis, respectively. Among the complications of disseminated candidiasis in infants and children, hematogenous disseminated Candida meningoencephalitis (HCME) is an important cause of neurological morbidity. Detection of (1→3)-β-d-glucan in cerebrospinal fluid serves as an early diagnostic indicator and an important biomarker of therapeutic response. The recently reported pharmacokinetic data of liposomal amphotericin B in children demonstrate dose–exposure relationships similar to those in adults. The recently completed randomized clinical trial of micafungin versus deoxycholate amphotericin B in the treatment of neonatal candidemia provides further safety data for an echinocandin in this clinical setting. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
10 pages, 259 KiB  
Review
New Concepts in Diagnostics for Invasive Mycoses: Non-Culture-Based Methodologies
by Thomas F. Patterson and J. Peter Donnelly
J. Fungi 2019, 5(1), 9; https://doi.org/10.3390/jof5010009 - 17 Jan 2019
Cited by 55 | Viewed by 8272
Abstract
Non-culture-based diagnostics have been developed to help establish an early diagnosis of invasive fungal infection. Studies have shown that these tests can significantly impact the diagnosis of infection in high risk patients. Aspergillus galactomannan EIA testing is well-recognized as an important adjunct to [...] Read more.
Non-culture-based diagnostics have been developed to help establish an early diagnosis of invasive fungal infection. Studies have shown that these tests can significantly impact the diagnosis of infection in high risk patients. Aspergillus galactomannan EIA testing is well-recognized as an important adjunct to the diagnosis of invasive aspergillosis and can be detected in serum, bronchoalveolar lavage and other fluids. Galactomannan testing used along with PCR testing has been shown to be effective when integrated into care paths for high risk patients for both diagnoses and as a surrogate marker for outcome when used in serial testing. Beta-d-glucan assays are non-specific for several fungal genera including Aspergillus and Candida and in high risk patients have been an important tool to augment the diagnosis. Lateral flow technology using monoclonal antibodies to Aspergillus are available that allow rapid testing of clinical samples. While standard PCR for Candida remains investigational, T2 magnetic resonance allows for the rapid diagnosis of Candida species from blood cultures. Aspergillus PCR has been extensively validated with standardized approaches established for these methods and will be included in the diagnostic criteria in the revised European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC-MSG) definitions. Finally, these non-culture-based tests can be used in combination to significantly increase the detection of invasive mycoses with the ultimate aim of establishing an early diagnosis of infection. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
23 pages, 1408 KiB  
Review
Sporotrichosis In Immunocompromised Hosts
by Flavio Queiroz-Telles, Renata Buccheri and Gil Benard
J. Fungi 2019, 5(1), 8; https://doi.org/10.3390/jof5010008 - 11 Jan 2019
Cited by 75 | Viewed by 8551
Abstract
Sporotrichosis is a global implantation or subcutaneous mycosis caused by several members of the genus Sporothrix, a thermo-dimorphic fungus. This disease may also depict an endemic profile, especially in tropical to subtropical zones around the world. Interestingly, sporotrichosis is an anthropozoonotic disease [...] Read more.
Sporotrichosis is a global implantation or subcutaneous mycosis caused by several members of the genus Sporothrix, a thermo-dimorphic fungus. This disease may also depict an endemic profile, especially in tropical to subtropical zones around the world. Interestingly, sporotrichosis is an anthropozoonotic disease that may be transmitted to humans by plants or by animals, especially cats. It may be associated with rather isolated or clustered cases but also with outbreaks in different periods and geographic regions. Usually, sporotrichosis affects immunocompetent hosts, presenting a chronic to subacute evolution course. Less frequently, sporotrichosis may be acquired by inhalation, leading to disseminated clinical forms. Both modes of infection may occur in immunocompromised patients, especially associated with human immunodeficiency virus (HIV) infection, but also diabetes mellitus, chronic alcoholism, steroids, anti-TNF treatment, hematologic cancer and transplanted patients. Similar to other endemic mycoses caused by dimorphic fungi, sporotrichosis in immunocompromised hosts may be associated with rather more severe clinical courses, larger fungal burden and longer periods of systemic antifungal therapy. A prolonged outbreak of cat-transmitted sporotrichosis is in progress in Brazil and potentially crossing the border to neighboring countries. This huge outbreak involves thousands of human and cats, including immunocompromised subjects affected by HIV and FIV (feline immunodeficiency virus), respectively. We reviewed the main epidemiologic, clinical, diagnostic and therapeutic aspects of sporotrichosis in immunocompromised hosts. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
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16 pages, 1151 KiB  
Review
A Moldy Application of MALDI: MALDI-ToF Mass Spectrometry for Fungal Identification
by Robin Patel
J. Fungi 2019, 5(1), 4; https://doi.org/10.3390/jof5010004 - 3 Jan 2019
Cited by 134 | Viewed by 15828
Abstract
As a result of its being inexpensive, easy to perform, fast and accurate, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF MS) is quickly becoming the standard means of bacterial identification from cultures in clinical microbiology laboratories. Its adoption for routine identification of [...] Read more.
As a result of its being inexpensive, easy to perform, fast and accurate, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF MS) is quickly becoming the standard means of bacterial identification from cultures in clinical microbiology laboratories. Its adoption for routine identification of yeasts and even dimorphic and filamentous fungi in cultures, while slower, is now being realized, with many of the same benefits as have been recognized on the bacterial side. In this review, the use of MALDI-ToF MS for identification of yeasts, and dimorphic and filamentous fungi grown in culture will be reviewed, with strengths and limitations addressed. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
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11 pages, 2061 KiB  
Review
Paracoccidioidomycosis in Immunocompromised Patients: A Literature Review
by João N. De Almeida Jr., Paula M. Peçanha-Pietrobom and Arnaldo L. Colombo
J. Fungi 2019, 5(1), 2; https://doi.org/10.3390/jof5010002 - 26 Dec 2018
Cited by 39 | Viewed by 6755
Abstract
Paracoccidioidomycosis (PCM) is an endemic mycosis found in Latin America that causes systemic disease mostly in immunocompetent hosts. A small percentage of PCM occurs in immunocompromised patients where low clinical suspicion of the infection, late diagnosis, and uncertainties about its management are factors [...] Read more.
Paracoccidioidomycosis (PCM) is an endemic mycosis found in Latin America that causes systemic disease mostly in immunocompetent hosts. A small percentage of PCM occurs in immunocompromised patients where low clinical suspicion of the infection, late diagnosis, and uncertainties about its management are factors that negatively impact their outcomes. We conducted a literature review searching reports on PCM associated to HIV, cancer, maligned hemopathies, solid organ transplantation, and immunotherapies, in order to check for peculiarities in terms of natural history and challenges in the clinical management of PCM in this population. HIV patients with PCM usually had low T CD4+ cell counts, pulmonary and lymph nodes involvement, and a poorer prognosis (≈50% mortality). Most of the patients with PCM and cancer had carcinoma of the respiratory tract. Among maligned hemopathies, PCM was more often related to lymphoma. In general, PCM prognosis in patients with malignant diseases was related to the cancer stage. PCM in transplant recipients was mostly associated with the late phase of kidney transplantation, with a high mortality rate (44%). Despite being uncommon, reactivation of latent PCM may take place in the setting of immunocompromised patients exhibiting clinical particularities and it carries higher mortality rates than normal hosts. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
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18 pages, 1947 KiB  
Review
Development and Applications of Prognostic Risk Models in the Management of Invasive Mold Disease
by Marta Stanzani and Russell E. Lewis
J. Fungi 2018, 4(4), 141; https://doi.org/10.3390/jof4040141 - 19 Dec 2018
Cited by 7 | Viewed by 3977
Abstract
Prognostic models or risk scores are frequently used to aid individualize risk assessment for diseases with multiple, complex risk factors and diagnostic challenges. However, relatively little attention has been paid to the development of risk models for invasive mold diseases encountered in patients [...] Read more.
Prognostic models or risk scores are frequently used to aid individualize risk assessment for diseases with multiple, complex risk factors and diagnostic challenges. However, relatively little attention has been paid to the development of risk models for invasive mold diseases encountered in patients with hematological malignancies, despite a large body of epidemiological research. Herein we review recent studies that have described the development of prognostic models for mold disease, summarize our experience with the development and clinical use of one such model (BOSCORE), and discuss the potential impact of prognostic risk scores for individualized therapy, diagnostic and antifungal stewardship, as well as clinical and epidemiological research. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
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Figure 1

22 pages, 1972 KiB  
Review
Understanding Pathogenesis and Care Challenges of Immune Reconstitution Inflammatory Syndrome in Fungal Infections
by Sarah Dellière, Romain Guery, Sophie Candon, Blandine Rammaert, Claire Aguilar, Fanny Lanternier, Lucienne Chatenoud and Olivier Lortholary
J. Fungi 2018, 4(4), 139; https://doi.org/10.3390/jof4040139 - 17 Dec 2018
Cited by 47 | Viewed by 6364
Abstract
Immune deficiency of diverse etiology, including human immunodeficiency virus (HIV), antineoplastic agents, immunosuppressive agents used in solid organ recipients, immunomodulatory therapy, and other biologics, all promote invasive fungal infections. Subsequent voluntary or unintended immune recovery may induce an exaggerated inflammatory response defining immune [...] Read more.
Immune deficiency of diverse etiology, including human immunodeficiency virus (HIV), antineoplastic agents, immunosuppressive agents used in solid organ recipients, immunomodulatory therapy, and other biologics, all promote invasive fungal infections. Subsequent voluntary or unintended immune recovery may induce an exaggerated inflammatory response defining immune reconstitution inflammatory syndrome (IRIS), which causes significant mortality and morbidity. Fungal-associated IRIS raises several diagnostic and management issues. Mostly studied with Cryptococcus, it has also been described with other major fungi implicated in human invasive fungal infections, such as Pneumocystis, Aspergillus, Candida, and Histoplasma. Furthermore, the understanding of IRIS pathogenesis remains in its infancy. This review summarizes current knowledge regarding the clinical characteristics of IRIS depending on fungal species and existing strategies to predict, prevent, and treat IRIS in this patient population, and tries to propose a common immunological background to fungal IRIS. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
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Figure 1

15 pages, 312 KiB  
Review
From the Clinical Mycology Laboratory: New Species and Changes in Fungal Taxonomy and Nomenclature
by Nathan P. Wiederhold and Connie F. C. Gibas
J. Fungi 2018, 4(4), 138; https://doi.org/10.3390/jof4040138 - 16 Dec 2018
Cited by 15 | Viewed by 7141
Abstract
Fungal taxonomy is the branch of mycology by which we classify and group fungi based on similarities or differences. Historically, this was done by morphologic characteristics and other phenotypic traits. However, with the advent of the molecular age in mycology, phylogenetic analysis based [...] Read more.
Fungal taxonomy is the branch of mycology by which we classify and group fungi based on similarities or differences. Historically, this was done by morphologic characteristics and other phenotypic traits. However, with the advent of the molecular age in mycology, phylogenetic analysis based on DNA sequences has replaced these classic means for grouping related species. This, along with the abandonment of the dual nomenclature system, has led to a marked increase in the number of new species and reclassification of known species. Although these evaluations and changes are necessary to move the field forward, there is concern among medical mycologists that the rapidity by which fungal nomenclature is changing could cause confusion in the clinical literature. Thus, there is a proposal to allow medical mycologists to adopt changes in taxonomy and nomenclature at a slower pace. In this review, changes in the taxonomy and nomenclature of medically relevant fungi will be discussed along with the impact this may have on clinicians and patient care. Specific examples of changes and current controversies will also be given. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
17 pages, 869 KiB  
Review
Immunomodulation as a Therapy for Aspergillus Infection: Current Status and Future Perspectives
by Chris D. Lauruschkat, Hermann Einsele and Juergen Loeffler
J. Fungi 2018, 4(4), 137; https://doi.org/10.3390/jof4040137 - 14 Dec 2018
Cited by 26 | Viewed by 6925
Abstract
Invasive aspergillosis (IA) is the most serious life-threatening infectious complication of intensive remission induction chemotherapy and allogeneic stem cell transplantation in patients with a variety of hematological malignancies. Aspergillus fumigatus is the most commonly isolated species from cases of IA. Despite the various [...] Read more.
Invasive aspergillosis (IA) is the most serious life-threatening infectious complication of intensive remission induction chemotherapy and allogeneic stem cell transplantation in patients with a variety of hematological malignancies. Aspergillus fumigatus is the most commonly isolated species from cases of IA. Despite the various improvements that have been made with preventative strategies and the development of antifungal drugs, there is an urgent need for new therapeutic approaches that focus on strategies to boost the host’s immune response, since immunological recovery is recognized as being the major determinant of the outcome of IA. Here, we aim to summarize current knowledge about a broad variety of immunotherapeutic approaches against IA, including therapies based on the transfer of distinct immune cell populations, and the administration of cytokines and antibodies. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
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22 pages, 307 KiB  
Review
Pre-Existing Liver Disease and Toxicity of Antifungals
by Nikolaos Spernovasilis and Diamantis P. Kofteridis
J. Fungi 2018, 4(4), 133; https://doi.org/10.3390/jof4040133 - 10 Dec 2018
Cited by 33 | Viewed by 19169
Abstract
Pre-existing liver disease in patients with invasive fungal infections further complicates their management. Altered pharmacokinetics and tolerance issues of antifungal drugs are important concerns. Adjustment of the dosage of antifungal agents in these cases can be challenging given that current evidence to guide [...] Read more.
Pre-existing liver disease in patients with invasive fungal infections further complicates their management. Altered pharmacokinetics and tolerance issues of antifungal drugs are important concerns. Adjustment of the dosage of antifungal agents in these cases can be challenging given that current evidence to guide decision-making is limited. This comprehensive review aims to evaluate the existing evidence related to antifungal treatment in individuals with liver dysfunction. This article also provides suggestions for dosage adjustment of antifungal drugs in patients with varying degrees of hepatic impairment, after accounting for established or emerging pharmacokinetic–pharmacodynamic relationships with regard to antifungal drug efficacy in vivo. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
13 pages, 272 KiB  
Review
Antifungal Resistance: Specific Focus on Multidrug Resistance in Candida auris and Secondary Azole Resistance in Aspergillus fumigatus
by Sevtap Arikan-Akdagli, Mahmoud Ghannoum and Jacques F. Meis
J. Fungi 2018, 4(4), 129; https://doi.org/10.3390/jof4040129 - 5 Dec 2018
Cited by 41 | Viewed by 6860
Abstract
Antifungal resistance is a topic of concern, particularly for specific fungal species and drugs. Among these are the multidrug-resistant Candida auris and azole-resistant Aspergillus fumigatus. While the knowledge on molecular mechanisms of resistance is now accumulating, further data are also available for [...] Read more.
Antifungal resistance is a topic of concern, particularly for specific fungal species and drugs. Among these are the multidrug-resistant Candida auris and azole-resistant Aspergillus fumigatus. While the knowledge on molecular mechanisms of resistance is now accumulating, further data are also available for the clinical implications and the extent of correlation of in vitro resistance to clinical outcomes. This review article summarizes the epidemiology of C. auris infections, animal models focusing on the activity of novel antifungal compounds in C. auris infections, virulence factors, and the mechanisms of antifungal resistance for this multi-resistant Candida species. Regarding A. fumigatus, the significance of azoles in the treatment of A. fumigatus infections, reference methods available for the detection of resistance in vitro, molecular mechanisms of secondary azole resistance, routes of acquisition, and clinical implications of in vitro resistance are covered to provide guidance for the current status of azole resistance in A. fumigatus. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
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