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Medical Mycology in Developing Countries: The Neglected and Forgotten Mycoses
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Medical Mycology in Developing Countries: The Neglected and Forgotten Mycoses

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 (10 January 2024) | Viewed by 9204

Special Issue Editors

Dr. Susana Frases

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Guest Editor
Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Cidade Universitária, Ilha do Fundão, Rio de Janeiro 21941-902, CEP, Brazil
Interests: mycology; fungal pathogens; biophysics
Dr. Rodrigo Almeida-Paes

E-Mail Website
Guest Editor
Laboratory of Mycology, Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz. Foundation (FIOCRUZ), Rio de Janeiro 21040-360, RJ, Brazil
Interests: mycosis; molecular diagnosis; serology; fungal identification; new antifungal drugs; therapy; translational medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neglected in recent years, rare mycoses in underdeveloped or developing countries need attention from physicians, health systems, and society. Since notification is not mandatory, there are not even international programs for prevention or control, much less accurate data on incidence and prevalence.

In this Special Issue, we will compile the latest advances and medical challenges in epidemiology, diagnosis, and treatment of neglected mycoses that affect developing countries, such as chromoblastomycosis, lobomycosis, paracoccidioidomycosis, candidiasis by antifungal-resistant species, and mycetoma.

Dr. Susana Frases
Dr. Rodrigo Almeida-Paes
Guest Editors

Manuscript Submission Information

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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

  • chromoblastomycosis
  • lobomycosis
  • paracoccidioidomycosis
  • Candida haemulonii
  • mycetoma
 

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Published Papers (5 papers)

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Research

11 pages, 258 KiB  
Article
Guideline Adherence and Outcomes of Patients with Candidemia in Brazil
by Jordana Machado Araujo, João Nóbrega de Almeida Junior, Marcello Mihailenko Chaves Magri, Silvia Figueiredo Costa and Thaís Guimarães
J. Fungi 2024, 10(4), 282; https://doi.org/10.3390/jof10040282 - 12 Apr 2024
Viewed by 1112
Abstract
Candidemia is a significant cause of mortality among hospitalized patients, both worldwide and in Brazil. Prompt and appropriate treatment are essential to mitigate mortality, and clinical practice guidelines aim to optimize patient care based on the best scientific evidence. This study aims to [...] Read more.
Candidemia is a significant cause of mortality among hospitalized patients, both worldwide and in Brazil. Prompt and appropriate treatment are essential to mitigate mortality, and clinical practice guidelines aim to optimize patient care based on the best scientific evidence. This study aims to examine the management of candidemia, assessing adherence to the guidelines of the Brazilian Society of Infectious Diseases in a single center located at São Paulo, Brazil. All adult patients hospitalized from 2016 to 2018 who presented one positive blood culture for Candida spp. were included. Electronic medical records were retrospectively reviewed to collect information relevant to the treatment for candidemia, in order to assess the adherence to the Brazilian guideline for the management of candidemia in relation to nine defined outcomes, and we correlated those findings with 30-day mortality by using uni- and multivariate analyses. A total of 115 patients were included; 68 patients (59.1%) were male, with a mean age of 55 years. C. albicans, C. tropicalis and C. glabrata were the most prevalent species. In total, 80 patients (69.5%) received antifungal treatment. The adherence to Brazilian guideline recommendations was determined as described in the following: initial treatment with echinocandin in 48 (60%); step-down to fluconazole in 21 (26.2%); collection of first control blood culture in 43 (58.9%); collection of second control blood culture, if the first one had been positive, in 14 (73.6%); treatment for 14 days after the first negative blood culture in 53 (65.4%); central venous catheter (CVC) removal in 66 (82.5%); CVC removal if the first control blood culture had been positive in 17 (89.4%); performance of a transthoracic echocardiogram in 51 (63.7%) and performance of a fundoscopy in 59 (73.7%). Univariate analysis showed that CVC removal and initial echinocandin therapy were more prevalent in the surviving group, but with no statistically significant difference. On the other hand, step-down to fluconazole demonstrated higher survival rate in the multivariate analysis OR 0.15 (95% CI 0.03–0.8); p = 0.02. The analysis of these nine recommendations demonstrates that it is necessary to improve adherence to specific recommendations and also disseminate strategies of the initial use of echinocandin as the drug of choice and addressing length of treatment and follow-up and complementary exams. Our study provides reassurance that the step-down to fluconazole is safe and may be recommended, if the preexisting conditions are present. Full article
(This article belongs to the Special Issue Medical Mycology in Developing Countries: The Neglected and Forgotten Mycoses)
15 pages, 1328 KiB  
Article
First Report of the Emerging Pathogen Kodamaea ohmeri in Honduras
by Bryan Ortiz, Roque López, Carlos Muñoz, Kateryn Aguilar, Fernando Pérez, Isis Laínez-Arteaga, Fernando Chávez, Celeste Galindo, Luis Rivera, Manuel G. Ballesteros-Monrreal, Pablo Méndez-Pfeiffer, Dora Valencia and Gustavo Fontecha
J. Fungi 2024, 10(3), 186; https://doi.org/10.3390/jof10030186 - 28 Feb 2024
Cited by 1 | Viewed by 2291
Abstract
Kodamaea ohmeri is an environmental yeast considered a rare emerging pathogen. In clinical settings, the correct identification of this yeast is relevant because some isolates are associated with resistance to antifungals. There is a lack of available data regarding the geographical distribution, virulence, [...] Read more.
Kodamaea ohmeri is an environmental yeast considered a rare emerging pathogen. In clinical settings, the correct identification of this yeast is relevant because some isolates are associated with resistance to antifungals. There is a lack of available data regarding the geographical distribution, virulence, and drug resistance profile of K. ohmeri. To contribute to the knowledge of this yeast, this study aimed to describe in depth three isolates of K. ohmeri associated with fungemia in Honduras. The identification of the isolates was carried out by sequencing the ribosomal ITS region. In addition, the susceptibility profile to antifungals was determined, and some properties associated with virulence were evaluated (exoenzyme production, biofilm formation, cell adhesion, and invasion). The isolates showed strong protease, phospholipase, and hemolysin activity, in addition to being biofilm producers. Adherence and invasion capacity were evident in the HeLa and Raw 264.7 cell lines, respectively. This study expands the understanding of the underlying biological traits associated with virulence in K. ohmeri, and it is the first report of the detection and identification of K. ohmeri in Honduras as a cause of human infection. Full article
(This article belongs to the Special Issue Medical Mycology in Developing Countries: The Neglected and Forgotten Mycoses)
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18 pages, 6566 KiB  
Article
Comparative Analysis of Capsular and Secreted Polysaccharides Produced by Rhodotorula mucilaginosa and Cryptococcus neoformans
by Gustavo Dornelles, Glauber R. de S. Araújo, Marcus Rodrigues, Vinicius Alves, Rodrigo Almeida-Paes and Susana Frases
J. Fungi 2023, 9(11), 1124; https://doi.org/10.3390/jof9111124 - 20 Nov 2023
Viewed by 1752
Abstract
Fungal infections are a global public health challenge, especially among immunocompromised patients. Basidiomycetous yeasts, such as Rhodotorula mucilaginosa, have emerged as opportunistic pathogens, but have received less attention than Cryptococcus neoformans. This study aimed to characterize the polysaccharides of R. mucilaginosa [...] Read more.
Fungal infections are a global public health challenge, especially among immunocompromised patients. Basidiomycetous yeasts, such as Rhodotorula mucilaginosa, have emerged as opportunistic pathogens, but have received less attention than Cryptococcus neoformans. This study aimed to characterize the polysaccharides of R. mucilaginosa and compare them with those of C. neoformans, analyzing their clinical implications. Comprehensive physicochemical, mechanical, and ultrastructural analyses of polysaccharides from both species were performed, revealing correlations with virulence and pathogenicity. R. mucilaginosa cells are surrounded by a capsule smaller than that produced by C. neoformans, but with similar polysaccharides. Those polysaccharides are also secreted by R. mucilaginosa. Cross-reactivity with R. mucilaginosa was observed in a diagnostic C. neoformans antigen test, using both in vitro and in vivo samples, highlighting the need for more reliable tests. Some R. mucilaginosa strains exhibited virulence comparable to that of C. neoformans in an invertebrate experimental model (Tenebrio molitor). This study contributes to a deeper understanding of yeast pathogenicity and virulence, highlighting the need for more accurate diagnostic tests to improve the differential diagnosis of infections caused by basidiomycetous yeasts. Full article
(This article belongs to the Special Issue Medical Mycology in Developing Countries: The Neglected and Forgotten Mycoses)
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17 pages, 4912 KiB  
Article
Development of Echinocandin Resistance in Candida haemulonii: An Emergent, Widespread, and Opportunistic Fungal Pathogen
by Laura N. Silva, Lívia S. Ramos, Simone S. C. Oliveira, Lucas B. Magalhães, Jefferson Cypriano, Fernanda Abreu, Alexandre J. Macedo, Marta H. Branquinha and André L. S. Santos
J. Fungi 2023, 9(8), 859; https://doi.org/10.3390/jof9080859 - 18 Aug 2023
Cited by 3 | Viewed by 1531
Abstract
Echinocandins, used for the prevention and treatment of invasive fungal infections, have led to a rise in breakthrough infections caused by resistant Candida species. Among these species, those belonging to the Candida haemulonii complex are rare multidrug-resistant (MDR) yeasts that are frequently misidentified [...] Read more.
Echinocandins, used for the prevention and treatment of invasive fungal infections, have led to a rise in breakthrough infections caused by resistant Candida species. Among these species, those belonging to the Candida haemulonii complex are rare multidrug-resistant (MDR) yeasts that are frequently misidentified but have emerged as significant healthcare-associated pathogens causing invasive infections. The objectives of this study were to investigate the evolutionary pathways of echinocandin resistance in C. haemulonii by identifying mutations in the FKS1 gene and evaluating the impact of resistance on fitness. After subjecting a MDR clinical isolate of C. haemulonii (named Ch4) to direct selection using increasing caspofungin concentrations, we successfully obtained an isolate (designated Ch4′r) that exhibited a high level of resistance, with MIC values exceeding 16 mg/L for all tested echinocandin drugs (caspofungin, micafungin, and anidulafungin). Sequence analysis revealed a specific mutation in the resistant Ch4′r strain, leading to an arginine-histidine amino acid substitution (R1354H), occurring at the G4061A position of the HS2 region of the FKS1 gene. Compared to the wild-type strain, Ch4′r exhibited significantly reduced growth proliferation, biofilm formation capability, and phagocytosis ratio, indicating a decrease in fitness. Transmission electron microscopy analysis revealed alterations in cell wall components, with a notable increase in cell wall thickness. The resistant strain also exhibited higher amounts (2.5-fold) of chitin, a cell wall-located molecule, compared to the wild-type strain. Furthermore, the resistant strain demonstrated attenuated virulence in the Galleria mellonella larval model. The evolved strain Ch4′r maintained its resistance profile in vivo since the treatment with either caspofungin or micafungin did not improve larval survival or reduce the fungal load. Taken together, our findings suggest that the acquisition of pan-echinocandin resistance occurred rapidly after drug exposure and was associated with a significant fitness cost in C. haemulonii. This is particularly concerning as echinocandins are often the first-line treatment option for MDR Candida species. Full article
(This article belongs to the Special Issue Medical Mycology in Developing Countries: The Neglected and Forgotten Mycoses)
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15 pages, 1239 KiB  
Article
Repurposing Benzimidazoles against Causative Agents of Chromoblastomycosis: Albendazole Has Superior In Vitro Activity Than Mebendazole and Thiabendazole
by Rowena Alves Coelho, Maria Helena Galdino Figueiredo-Carvalho, Fernando Almeida-Silva, Vanessa Brito de Souza Rabello, Gabriela Rodrigues de Souza, Leandro Stefano Sangenito, Luna Sobrino Joffe, André Luis Souza dos Santos, Maria Cristina da Silva Lourenço, Marcio L. Rodrigues and Rodrigo Almeida-Paes
J. Fungi 2023, 9(7), 753; https://doi.org/10.3390/jof9070753 - 16 Jul 2023
Cited by 2 | Viewed by 1712
Abstract
Chromoblastomycosis (CBM) is a neglected human implantation mycosis caused by several dematiaceous fungal species. Currently available therapy is usually associated with physical methods, especially surgery, and with high refractoriness. Therefore, drug discovery for CBM is essential. Drug repositioning is a strategy used to [...] Read more.
Chromoblastomycosis (CBM) is a neglected human implantation mycosis caused by several dematiaceous fungal species. Currently available therapy is usually associated with physical methods, especially surgery, and with high refractoriness. Therefore, drug discovery for CBM is essential. Drug repositioning is a strategy used to facilitate the discovery of new treatments for several diseases. The aim of this study was to discover substances with antifungal activity against CBM agents from a collection of drugs previously approved for use in human diseases. A screening was performed with the NIH Clinical Collection against Fonsecaea pedrosoi. Ten substances, with clinical applicability in CBM, inhibited fungal growth by at least 60%. The minimum inhibitory concentration (MIC) of these substances was determined against other CBM agents, and the benzimidazoles albendazole, mebendazole and thiabendazole presented the lowest MIC values. The selectivity index, based on MIC and cytotoxicity of these substances, revealed albendazole to be more selective. To investigate a possible synergism of this benzimidazole with itraconazole and terbinafine, the chequerboard method was used. All interactions were classified as indifferent. Our current results suggest that benzimidazoles have repositioning potential against CBM agents. Albendazole seems to be the most promising, since it presented the highest selectivity against all dematiaceous fungi tested. Full article
(This article belongs to the Special Issue Medical Mycology in Developing Countries: The Neglected and Forgotten Mycoses)
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