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Pediatric Fungal Infections: Diagnostic and Therapeutic Aspects
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Pediatric Fungal Infections: Diagnostic and Therapeutic Aspects

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 20122

Special Issue Editor

Dr. M. Teresa Martin-Gomez

E-Mail Website
Guest Editor
Medical Mycology Division, Microbiology Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
Interests: non-culture based diagnosis; antifungals; fungal pathology in special populations

Special Issue Information

Dear colleagues, 

Children are not just small versions of adults, and thus, the knowledge we have related to fungal-related pathology in adults does not translate directly into pediatric clinics. In fact, the management of pediatric fungal allergies and infections is hampered by the availability of limited sets of data, if any, regarding the real performance of diagnostic tools in children (particularly non-culture-based lab techniques), age-related limitations in the use of drugs to treat fungal-related pathology, or lack of robust knowledge on pharmacokinetics/pharmacodynamics of antifungals in pediatric populations of different age groups, among others. This Special Issue of the Journal of Fungi is intended to cover such aspects through original research, case reports illustrating situations of particular interest, or comprehensive literature reviews. Experiences on pediatric antifungal stewardship programs are also welcome.

Dr. M. Teresa Martin-Gomez
Guest Editor

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

  • epidemiology
  • Non-culture-based diagnosis
  • pediatric fungal infections
  • pediatric fungal allergies
  • antifungal treatment
  • therapeutic drug monitoring
  • mycology-related stewardship programs

Published Papers (6 papers)

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Research

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13 pages, 1306 KiB  
Article
Invasive Fusariosis in Pediatric Hematology/Oncology and Stem Cell Transplant Patients: A Report from the Israeli Society of Pediatric Hematology-Oncology
by Marganit Benish, Sarah Elitzur, Nira Arad-Cohen, Assaf Arie Barg, Miriam Ben-Harosh, Bella Bielorai, Salvador Fischer, Gil Gilad, Itzhak Levy, Hila Rosenfeld-Keidar, Yael Shachor-Meyouhas, Galia Soen-Grisaru, Sigal Weinreb, Ronit Nirel and Ronit Elhasid
J. Fungi 2022, 8(4), 387; https://0-doi-org.brum.beds.ac.uk/10.3390/jof8040387 - 11 Apr 2022
Cited by 6 | Viewed by 2210
Abstract
Invasive Fusarium species infections in immunocompromised patients occur predominantly in those with hematological malignancies. Survival rates of 20–40% were reported in adults, but data in children are limited. Our retrospective, nationwide multicenter study of invasive fusariosis in pediatric hematology/oncology and stem cell transplant [...] Read more.
Invasive Fusarium species infections in immunocompromised patients occur predominantly in those with hematological malignancies. Survival rates of 20–40% were reported in adults, but data in children are limited. Our retrospective, nationwide multicenter study of invasive fusariosis in pediatric hematology/oncology and stem cell transplant (SCT) patients identified twenty-two cases. Underlying conditions included hematological malignancies (n = 16; 73%), solid tumors (n = 2), and non-malignant hematological conditions (n = 4). Nineteen patients (86%) were neutropenic, nine (41%) were SCT recipients, and seven (32%) received corticosteroids. Sixteen patients (73%) had disseminated fusariosis, five had local infection, and one had isolated fungemia. Fifteen patients (68%) had skin involvement and eight (36%) had a bloodstream infection. Four patients (18%) presented with osteoarticular involvement and four with pulmonary involvement. Nineteen patients (86%) received combination antifungal therapy upfront and three (14%) received single-agent treatment. Ninety-day probability of survival was 77%: four of the five deaths were attributed to fusariosis, all in patients with relapsed/refractory acute leukemias. Ninety-day probability of survival for patients with relapsed/refractory underlying malignancy was 33% vs. 94% in others (p < 0.001). Survival rates in this largest pediatric population-based study were strikingly higher than those reported in adults, demonstrating that invasive fusariosis is a life-threatening but salvageable condition in immunosuppressed children. Full article
(This article belongs to the Special Issue Pediatric Fungal Infections: Diagnostic and Therapeutic Aspects)
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17 pages, 556 KiB  
Article
Voriconazole Use in Children: Therapeutic Drug Monitoring and Control of Inflammation as Key Points for Optimal Treatment
by José María Valle-T-Figueras, Berta Renedo Miró, Maria Isabel Benítez Carabante, Cristina Díaz-de-Heredia, Jaume Vima Bofarull, Natalia Mendoza-Palomar, Maria Teresa Martín-Gómez and Pere Soler-Palacín
J. Fungi 2021, 7(6), 456; https://0-doi-org.brum.beds.ac.uk/10.3390/jof7060456 - 07 Jun 2021
Cited by 9 | Viewed by 2855
Abstract
Voriconazole plasma concentrations (PC) are highly variable, particularly in children. Dose recommendations in 2–12-year-old patients changed in 2012. Little data on therapeutic drug monitoring (TDM) after these new recommendations are available. We aimed to evaluate voriconazole monitoring in children with invasive fungal infection [...] Read more.
Voriconazole plasma concentrations (PC) are highly variable, particularly in children. Dose recommendations in 2–12-year-old patients changed in 2012. Little data on therapeutic drug monitoring (TDM) after these new recommendations are available. We aimed to evaluate voriconazole monitoring in children with invasive fungal infection (IFI) after implementation of new dosages and its relationship with safety and effectiveness. A prospective, observational study, including children aged 2–12 years, was conducted. TDM was performed weekly and doses were changed according to an in-house protocol. Effectiveness, adverse events, and factors influencing PC were analysed. A total of 229 PC from 28 IFI episodes were obtained. New dosing led to a higher rate of adequate PC compared to previous studies; still, 35.8% were outside the therapeutic range. In patients aged < 8 years, doses to achieve therapeutic levels were higher than recommended. Severe hypoalbuminemia and markedly elevated C-reactive protein were related to inadequate PC. Therapeutic PC were associated with drug effectiveness and safety. Higher doses in younger patients and a dose adjustment protocol based on TDM should be considered. Voriconazole PC variability has decreased with current updated recommendations, but it remains high and is influenced by inflammatory status. Additional efforts to control inflammation in children with IFI should be encouraged. Full article
(This article belongs to the Special Issue Pediatric Fungal Infections: Diagnostic and Therapeutic Aspects)
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Review

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16 pages, 441 KiB  
Review
Unusual Inflammatory Tinea Infections: Majocchi’s Granuloma and Deep/Systemic Dermatophytosis
by Jade Castellanos, Andrea Guillén-Flórez, Adriana Valencia-Herrera, Mirna Toledo-Bahena, Erika Ramírez-Cortés, Sonia Toussaint-Caire, Carlos Mena-Cedillos, Marcela Salazar-García and Alexandro Bonifaz
J. Fungi 2021, 7(11), 929; https://0-doi-org.brum.beds.ac.uk/10.3390/jof7110929 - 31 Oct 2021
Cited by 5 | Viewed by 6591
Abstract
Purpose of review. Inflammatory tinea is an uncommon group of dermatophyte entities that predominantly cause fungal infection of the skin and hair. This review intends to present all of the available evidence regarding its epidemiology, etiopathogenesis, clinical features, and diagnostic methods as well [...] Read more.
Purpose of review. Inflammatory tinea is an uncommon group of dermatophyte entities that predominantly cause fungal infection of the skin and hair. This review intends to present all of the available evidence regarding its epidemiology, etiopathogenesis, clinical features, and diagnostic methods as well as treatments recommended for various inflammatory tinea infections. This article provides a review of Majocchi’s granuloma and dermatophytic or Hadida’s disease. Recent findings. The new phylogenetic classification of dermatophytes includes nine genera, and those that affect humans are Trichophyton, Microsporum, Epidermophyton, and Nannizzia. Furthermore, molecular advancements have revealed impaired antifungal immune responses caused by inflammatory tinea, which are detailed in this article. Summary. The common denominator in these pathologies is the presence of impaired immune responses and, consequently, an impaired inflammatory response by the host. It is necessary to be familiar with these immunological characteristics in order to use the appropriate diagnostic methods and to provide adequate treatment. Full article
(This article belongs to the Special Issue Pediatric Fungal Infections: Diagnostic and Therapeutic Aspects)
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16 pages, 2445 KiB  
Review
Histoplasmosis in Children; HIV/AIDS Not a Major Driver
by Bassey E. Ekeng, Kevin Edem, Ikechukwu Amamilo, Zachary Panos, David W. Denning and Rita O. Oladele
J. Fungi 2021, 7(7), 530; https://0-doi-org.brum.beds.ac.uk/10.3390/jof7070530 - 30 Jun 2021
Cited by 11 | Viewed by 3254
Abstract
The classification of histoplasmosis as an AIDS-defining illness has largely attributed its occurrence in people to the presence of HIV/AIDS especially in Africa. Prior to the advent of the HIV/AIDS epidemic, many cases of histoplasmosis were documented both in the pediatric and adult [...] Read more.
The classification of histoplasmosis as an AIDS-defining illness has largely attributed its occurrence in people to the presence of HIV/AIDS especially in Africa. Prior to the advent of the HIV/AIDS epidemic, many cases of histoplasmosis were documented both in the pediatric and adult population. Our review revealed 1461 reported cases of pediatric histoplasmosis globally in the last eight decades (1939–2021). North America (n = 1231) had the highest number of cases, followed by South America (n = 135), Africa (n = 65), Asia (n = 26) and Europe (n = 4). Histoplasmosis was much more common in the non-HIV pediatric population (n = 1418, 97.1%) compared to the HIV population. The non-HIV factors implicated were, childhood malignancies (n = 207), such as leukemias and lymphomas as well as their treatment, lung diseases (n = 7), environmental exposures and toxins (n = 224), autoimmune diseases (n = 12), organ transplants (n = 12), long-term steroid therapy (n = 3), the use of immunosuppressive drugs such as TNF-alpha inhibitors (n = 7) malnutrition (n = 12), histiocytosis (n = 3), hyperimmunoglobulin M and E syndromes (n = 15, 1.2%), pancytopaenias (n = 26), diabetes mellitus (n = 1) and T-cell deficiency (n = 21). Paediatricians should always consider or rule out a diagnosis of histoplasmosis in children presenting with symptoms suggestive of the above clinical conditions. Full article
(This article belongs to the Special Issue Pediatric Fungal Infections: Diagnostic and Therapeutic Aspects)
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Other

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7 pages, 816 KiB  
Case Report
Invasive Fungal Infection Caused by Magnusiomyces capitatus in an Immunocompromised Pediatric Patient with Acute Lymphoblastic Leukemia in Mexico City: A Case Report
by Jossue Ortiz-Álvarez, Jesús Reséndiz-Sánchez, Margarita Juárez-Montiel, Juan Alfredo Hernández-García, Edwin Vázquez-Guerrero, César Hernández-Rodríguez and Lourdes Villa-Tanaca
J. Fungi 2022, 8(8), 851; https://0-doi-org.brum.beds.ac.uk/10.3390/jof8080851 - 15 Aug 2022
Cited by 1 | Viewed by 1996
Abstract
Magnusiomyces capitatus (also denominated “Geotrichum capitatum” and “the teleomorph stage of Saprochaete capitata”) mainly affects immunocompromised patients with hematological malignancies in rare cases of invasive fungal infections (IFIs). Few cases have been reported for pediatric patients with acute lymphoblastic leukemia [...] Read more.
Magnusiomyces capitatus (also denominated “Geotrichum capitatum” and “the teleomorph stage of Saprochaete capitata”) mainly affects immunocompromised patients with hematological malignancies in rare cases of invasive fungal infections (IFIs). Few cases have been reported for pediatric patients with acute lymphoblastic leukemia (ALL), in part because conventional diagnostic methods do not consistently detect M. capitatus in infections. The current contribution describes a systemic infection in a 15-year-old female diagnosed with ALL. She arrived at the Children’s Hospital of Mexico City with a fever and neutropenia and developed symptoms of septic shock 4 days later. M. capitatus ENCB-HI-834, the causal agent, was isolated from the patient’s blood, urine, bile, and peritoneal fluid samples. It was identified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and a phylogenetic reconstruction using internal transcribed spacer (ITS) and 28S ribosomal sequences. The phylogenetic sequence of M. capitatus ENCB-HI-834 clustered with other M. capitatus-type strains with a 100% identity. In vitro antifungal testing, conducted with the Sensititre YeastOne susceptibility system, found the following minimum inhibitory concentration (MIC) values (μg/mL): posaconazole 0.25, amphotericin B 1.0, fluconazole > 8.0, itraconazole 0.25, ketoconazole 0.5, 5-flucytosine ≤ 0.06, voriconazole 0.25, and caspofungin > 16.0. No clinical breakpoints have been defined for M. capitatus. This is the first clinical case reported in Mexico of an IFI caused by M. capitatus in a pediatric patient with ALL. It emphasizes the importance of close monitoring for a timely and accurate diagnosis of neutropenia-related IFIs to determine the proper treatment with antibiotics, antifungals, and chemotherapy for instance including children with ALL. Full article
(This article belongs to the Special Issue Pediatric Fungal Infections: Diagnostic and Therapeutic Aspects)
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8 pages, 1608 KiB  
Case Report
Influenza-Associated Disseminated Aspergillosis in a 9-Year-Old Girl Requiring ECMO Support
by Natalia Mendoza-Palomar, Susana Melendo-Pérez, Joan Balcells, Jaume Izquierdo-Blasco, Maria Teresa Martín-Gómez, Monica Velasco-Nuño, Jacques G. Rivière and Pere Soler-Palacin
J. Fungi 2021, 7(9), 726; https://0-doi-org.brum.beds.ac.uk/10.3390/jof7090726 - 05 Sep 2021
Cited by 4 | Viewed by 2246
Abstract
A previously healthy 9-year-old girl developed fulminant myocarditis due to severe influenza A infection complicated with methicillin-resistant Staphylococcus aureus pneumonia, requiring extracorporeal membrane oxygenation (ECMO) support. Twelve days after admission, Aspergillus fumigatus was isolated in tracheal aspirate, and 12 h later she suddenly [...] Read more.
A previously healthy 9-year-old girl developed fulminant myocarditis due to severe influenza A infection complicated with methicillin-resistant Staphylococcus aureus pneumonia, requiring extracorporeal membrane oxygenation (ECMO) support. Twelve days after admission, Aspergillus fumigatus was isolated in tracheal aspirate, and 12 h later she suddenly developed anisocoria. Computed tomography (CT) of the head showed fungal brain lesions. Urgent decompressive craniectomy with lesion drainage was performed; histopathology found hyphae in surgical samples, culture-positive for Aspergillus fumigatus (susceptible to azoles, echinocandins, and amphotericin B). Extension workup showed disseminated aspergillosis. After multiple surgeries and combined antifungal therapy (isavuconazole plus liposomal amphotericin B), her clinical course was favorable. Isavuconazole therapeutic drug monitoring was performed weekly. Extensive immunological study ruled out primary immunodeficiencies. Fluorine-18 fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) follow-up showed a gradual decrease in fungal lesions. Influenza-associated pulmonary aspergillosis is well-recognized in critically ill adult patients, but pediatric data are scant. Clinical features described in adults concur with those of our case. Isavuconazole, an off-label drug in children, was chosen because our patient had severe renal failure. To conclude, influenza-associated pulmonary aspergillosis is uncommon in children admitted to intensive care for severe influenza, but pediatricians should be highly aware of this condition to enable prompt diagnosis and treatment. Full article
(This article belongs to the Special Issue Pediatric Fungal Infections: Diagnostic and Therapeutic Aspects)
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