Emerging Fungal Infections: New Patients, New Patterns, and New Pathogens

: The landscape of clinical mycology is constantly changing. New therapies for malignant and autoimmune diseases have led to new risk factors for unusual mycoses. Invasive candidiasis is increasingly caused by non-albicans Candida spp., including C. auris, a multidrug-resistant yeast with the potential for nosocomial transmission that has rapidly spread globally. The use of mould-active antifungal prophylaxis in patients with cancer or transplantation has decreased the incidence of invasive fungal disease, but shifted the balance of mould disease in these patients to those from non-fumigatus Aspergillus species, Mucorales, and Scedosporium/Lomentospora spp. The agricultural application of triazole pesticides has driven an emergence of azole-resistant A. fumigatus in environmental and clinical isolates. The widespread use of topical antifungals with corticosteroids in India has resulted in Trichophyton mentagrophytes causing recalcitrant dermatophytosis. New dimorphic fungal pathogens have emerged, including Emergomyces, which cause disseminated mycoses globally, primarily in HIV infected patients, and Blastomyces helicus and B. percursus, causes of atypical blastomycosis in western parts of North America and in Africa, respectively. In North America, regions of geographic risk for coccidioidomycosis, histoplasmosis, and blastomycosis have expanded, possibly related to climate change. In Brazil, zoonotic sporotrichosis caused by Sporothrix brasiliensis has emerged as an important disease of felines and people.

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Post-Translational Modifications Drive Success and Failure of Fungal–Host Interactions

Journal of Fungi ◽

10.3390/jof7020124 ◽

2021 ◽

Vol 7 (2) ◽

pp. 124

Author(s):

Charmaine Retanal ◽

Brianna Ball ◽

Jennifer Geddes-McAlister

Keyword(s):

Fungal Pathogens ◽

Fungal Infections ◽

Treatment Options ◽

Global Scale ◽

Host Cells ◽

Candida Spp ◽

Post Translational Modifications ◽

Fungal Host ◽

Resistant Species

Post-translational modifications (PTMs) change the structure and function of proteins and regulate a diverse array of biological processes. Fungal pathogens rely on PTMs to modulate protein production and activity during infection, manipulate the host response, and ultimately, promote fungal survival. Given the high mortality rates of fungal infections on a global scale, along with the emergence of antifungal-resistant species, identifying new treatment options is critical. In this review, we focus on the role of PTMs (e.g., phosphorylation, acetylation, ubiquitination, glycosylation, and methylation) among the highly prevalent and medically relevant fungal pathogens, Candida spp., Aspergillus spp., and Cryptococcus spp. We explore the role of PTMs in fungal stress response and host adaptation, the use of PTMs to manipulate host cells and the immune system upon fungal invasion, and the importance of PTMs in conferring antifungal resistance. We also provide a critical view on the current knowledgebase, pose questions key to our understanding of the intricate roles of PTMs within fungal pathogens, and provide research opportunities to uncover new therapeutic strategies.

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Cross-Disciplinary Genomics Approaches to Studying Emerging Fungal Infections

Life ◽

10.3390/life10120315 ◽

2020 ◽

Vol 10 (12) ◽

pp. 315

Author(s):

Pria N. Ghosh ◽

Lola M. Brookes ◽

Hannah M. Edwards ◽

Matthew C. Fisher ◽

Phillip Jervis ◽

...

Keyword(s):

Fungal Pathogens ◽

Fungal Infections ◽

Large Population ◽

Wildlife Health ◽

Viral Pathogens ◽

Population Sizes ◽

Emerging Fungal Infections ◽

Near Future ◽

Supply Systems ◽

Made In

Emerging fungal pathogens pose a serious, global and growing threat to food supply systems, wild ecosystems, and human health. However, historic chronic underinvestment in their research has resulted in a limited understanding of their epidemiology relative to bacterial and viral pathogens. Therefore, the untargeted nature of genomics and, more widely, -omics approaches is particularly attractive in addressing the threats posed by and illuminating the biology of these pathogens. Typically, research into plant, human and wildlife mycoses have been largely separated, with limited dialogue between disciplines. However, many serious mycoses facing the world today have common traits irrespective of host species, such as plastic genomes; wide host ranges; large population sizes and an ability to persist outside the host. These commonalities mean that -omics approaches that have been productively applied in one sphere and may also provide important insights in others, where these approaches may have historically been underutilised. In this review, we consider the advances made with genomics approaches in the fields of plant pathology, human medicine and wildlife health and the progress made in linking genomes to other -omics datatypes and sets; we identify the current barriers to linking -omics approaches and how these are being underutilised in each field; and we consider how and which -omics methodologies it is most crucial to build capacity for in the near future.

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Fungal infections in neonates

10.1093/med/9780198755388.003.0035 ◽

2017 ◽

Author(s):

Adilia Warris

Keyword(s):

Invasive Candidiasis ◽

Neonatal Intensive Care ◽

Fungal Infections ◽

Invasive Fungal Disease ◽

Antifungal Prophylaxis ◽

Extremely Low Birth Weight ◽

Neonatal Intensive Care Units ◽

Low Birth Weight Infants ◽

Optimal Dosing ◽

Neurodevelopmental Impairment

Fungal infections in the neonatal population are caused predominantly by Candida species and invasive fungal disease mainly affects extremely low birth weight infants. The vast majority of Candida infections are due to C. albicans and C. parapsilosis, while the more fluconazole-resistant Candida species are only sporadically observed. Invasive candidiasis typically occurs during the first month of life and presents with non-specific signs of sepsis. Despite antifungal treatment, 20% of neonates developing invasive candidiasis die and neurodevelopmental impairment occurs in nearly 60% of survivors. Antifungal prophylaxis reduces the incidence in neonatal intensive care units with high rates of invasive candidiasis (>10%). Amphotericin B, fluconazole, micafungin, and caspofungin can be used to treat neonatal candidiasis, although optimal dosing for fluconazole and the two echinocandins has not yet been established.

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COVID-19-Associated Candidiasis (CAC): An Underestimated Complication in the Absence of Immunological Predispositions?

Journal of Fungi ◽

10.3390/jof6040211 ◽

2020 ◽

Vol 6 (4) ◽

pp. 211 ◽

Cited By ~ 5

Author(s):

Amir Arastehfar ◽

Agostinho Carvalho ◽

M. Hong Nguyen ◽

Mohammad Taghi Hedayati ◽

Mihai G. Netea ◽

...

Keyword(s):

Fungal Infections ◽

Antibiotic Use ◽

Multidrug Resistant ◽

Molecular Techniques ◽

Antifungal Drugs ◽

Diagnostic Tools ◽

Candida Spp ◽

Comparative Performance ◽

Number Of Patients ◽

Clinical Awareness

The recent global pandemic of COVID-19 has predisposed a relatively high number of patients to acute respiratory distress syndrome (ARDS), which carries a risk of developing super-infections. Candida species are major constituents of the human mycobiome and the main cause of invasive fungal infections, with a high mortality rate. Invasive yeast infections (IYIs) are increasingly recognized as s complication of severe COVID-19. Despite the marked immune dysregulation in COVID-19, no prominent defects have been reported in immune cells that are critically required for immunity to Candida. This suggests that relevant clinical factors, including prolonged ICU stays, central venous catheters, and broad-spectrum antibiotic use, may be key factors causing COVID-19 patients to develop IYIs. Although data on the comparative performance of diagnostic tools are often lacking in COVID-19 patients, a combination of serological and molecular techniques may present a promising option for the identification of IYIs. Clinical awareness and screening are needed, as IYIs are difficult to diagnose, particularly in the setting of severe COVID-19. Echinocandins and azoles are the primary antifungal used to treat IYIs, yet the therapeutic failures exerted by multidrug-resistant Candida spp. such as C. auris and C. glabrata call for the development of new antifungal drugs with novel mechanisms of action.

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Antimicrobial resistance among fungi from patients with urinary tract infections in Ojo, Lagos, Nigeria

GSC Biological and Pharmaceutical Sciences ◽

10.30574/gscbps.2021.14.3.0082 ◽

2021 ◽

Vol 14 (03) ◽

pp. 254-264

Author(s):

Dauphin Dighitoghi Moro ◽

Oluwole Moses David

Keyword(s):

Urinary Tract ◽

Amphotericin B ◽

Urinary Tract Infections ◽

Fungal Pathogens ◽

Fungal Infections ◽

Antifungal Susceptibility ◽

Candida Spp ◽

Fungal Isolates ◽

Vaginal Swabs ◽

Tract Infections

The incidence of fungal urinary tract infections has risen gradually and has thus constituted a public health challenge. The aim of this study was to determine the prevalence of urinary tract infections by fungi in two health centres in Ojo, Lagos. A total of 200 patients attending the health centers constituting 160 males’ urines and 40 females’ vaginal swabs were recruited for this study. Midstream urine samples and vaginal swabs were aseptically collected and processed using standard mycological techniques. Fungal isolates were identified based on cultural characteristics, lactophenol blue stain, chlamydospore formation, colony colour on CHROM agar Candida medium and API yeast identification. Antifungal susceptibility testing of the isolates was performed by using the Broth dilution and Kirby-Bauer disk diffusion methods using two of the most commonly used antifungal agents. A total of 122 fungal isolates, of which 68 (55.7%) were Candida spp. and 54(44.3%) Aspergillus spp. were recovered. The Candida spp. included 64 (52.5%) C. albicans and 4(3.3%) C. glabrata while Aspergillus spp. included A. flavus, 20(16.4%), A. fumigatus, 24 (19.8%) and A niger, 10(8.2%). The most common fungal pathogens in the urinary tracts of the subjects were Candida albicans and Aspergillus fumigatus. Both C. albicans and A. fumigatus were highly susceptible to both fluconazole and amphotericin B in dimethyl sulphoxide and water (90-100%). Similarly, all Aspergillus spp. were susceptible to both antifungals except A. flavus which showed a slight resistance (10-15%), which appears to be emerging. Both fluconazole and amphotericin B still show high chances of therapeutic efficacy against fungal infections of the urinary tracts.

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Fungal Infection in Lung Transplantation

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0041-1729173 ◽

2021 ◽

Vol 42 (03) ◽

pp. 471-482

Author(s):

Cassie C. Kennedy ◽

Kelly M. Pennington ◽

Elena Beam ◽

Raymund R. Razonable

Keyword(s):

Fungal Infection ◽

Fungal Pathogens ◽

Lung Transplant ◽

Fungal Infections ◽

Treatment Strategies ◽

Invasive Fungal Infections ◽

Molecular Diagnostic ◽

Candida Spp ◽

Diagnostic Strategies ◽

Culture Techniques

AbstractInvasive fungal infections threaten lung transplant outcomes with high associated morbidity and mortality. Pharmacologic prophylaxis may be key to prevent posttransplant invasive fungal infections, but cost, adverse effects, and absorption issues are barriers to effective prophylaxis. Trends in fungal infection diagnostic strategies utilize molecular diagnostic methodologies to complement traditional histopathology and culture techniques. While lung transplant recipients are susceptible to a variety of fungal pathogens, Candida spp. and Aspergillus spp. infections remain the most common. With emerging resistant organisms and multiple novel antifungal agents in the research pipeline, it is likely that treatment strategies will continue to evolve.

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Influence of antifungal prophylaxis on the occurrence of fungal infections in patients undergoing allogeneic transplantation

Srpski medicinski casopis Lekarske komore ◽

10.5937/smclk2-32279 ◽

2021 ◽

Vol 2 (2) ◽

pp. 92-98

Author(s):

Jelena Cakić ◽

Irena Đunić

Keyword(s):

Fungal Infections ◽

Lymphoblastic Leukemia ◽

Oral Candidiasis ◽

Invasive Pulmonary Aspergillosis ◽

Allogeneic Transplantation ◽

Hematologic Malignancies ◽

Antifungal Prophylaxis ◽

Candida Spp ◽

Medical Histories ◽

The Impact

Introduction: Patients with hematologic malignancies, such as acute myeloid leukemia and acute lymphoblastic leukemia (AML/ALL), myelodysplastic syndrome (MDS), and those undergoing allergenic stem cell transplantation (alloSCT) are at the highest risk of invasive fungal infections (IFI). The most common causative agents are Candida spp. and Aspergillus spp. Among the strategies for preventing IFIs is the adequate implementation of antifungal prophylaxis recommended by the NCCN (National Comprehensive Cancer Network). Aim: The aim of the study was to analyze the occurrence of IFIs in these patients, as well as to analyze the impact and importance of timely antifungal prophylaxis with regards to the development of these infections. Materials and methods: The retrospective study included 42 patients, of the average age of 35 years, who underwent the allo-SCT program, between 2017 to 2019, and received antifungal prophylaxis at the Clinic for Hematology of the Clinical Center of Serbia (CCS). Based on information obtained from medical histories, databases were formed. Statistical analysis included descriptive statistical methods that were performed in the SPSS program. Results: Nineteen (45.2%) patients presented with the clinical manifestation of oral candidiasis. Invasive pulmonary aspergillosis developed in only 3 (7.1%) patients. There was a statistically significant association between clinically manifest aspergillosis (7.1%) and the presence of antigens (Galactomannan) in these patients (p <0.001). There was also a statistically significant association between clinically manifest aspergillosis and graft weakness: 2 (66.6%) vs. 1 (33.3%), (p = 0.016). Conclusion: The use of adequate antifungal prophylaxis significantly reduces the incidence of IFIs in patients undergoing the allo-SCT program, and this contributes to the reduction of morbidity and mortality.

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Invasive Fungal Infection in Febrile Patients with Hematologic Malignancies Undergoing Chemotherapy in Iran

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190211163245 ◽

2019 ◽

Vol 19 (3) ◽

pp. 302-307 ◽

Cited By ~ 1

Author(s):

Saba Sheikhbahaei ◽

Alireza Mohammadi ◽

Roya Sherkat ◽

Alireza Emami Naeini ◽

Majid Yaran ◽

...

Keyword(s):

Blood Culture ◽

Antifungal Therapy ◽

Fungal Infections ◽

Hematologic Malignancy ◽

Hematologic Malignancies ◽

Fungal Species ◽

Antifungal Prophylaxis ◽

Invasive Fungal Infections ◽

Severe Neutropenia ◽

Candida Spp

Background: Patients with hematological malignancies undergoing cytotoxic chemotherapy are susceptible to develop invasive fungal infections particularly Aspergillus and Candida spp. Early detection of these infections is required to start immediate antifungal therapy and increase the survival of these patients. Method: Our study included consecutive patients of any age with hematologic malignancies who were hospitalized to receive chemotherapy and suffer from persistent fever (rectal temperature >38.5°C) for more than 5 days despite receiving broad-spectrum antibiotics. A whole blood sample was taken and sent for blood culture. PCR was also conducted for Aspergillus and Candida species. Results: One hundred and two patients were investigated according to the inclusion criteria. The most common hematologic malignancy was AML affecting 38 patients (37.2%). Six patients were diagnosed with invasive fungal infections (A. fumigatus n=3, C. albicans n=2, A. flavus n=1) by PCR (5.8%) while blood culture showed fungus only in 1 patient. Three more cases were known as probable IFI since they responded to antifungal therapy but the PCR result was negative for them. AML was the most prevalent malignancy in IFI patients (83.3%) and odds ratio for severing neutropenia was 21.5. Odds for each of the baseline characteristics of patients including gender, age>60, diabetes mellitus, previous IFI, history of using more than 3 antibiotics, antifungal prophylaxis, episodes of chemotherapy> 8 and chemotherapy regimen of daunarubicin+cytarabine were calculated. Conclusion: We found that multiplex real-time PCR assay is more accurate than blood culture in detecting fungal species and the results are prepared sooner. Among all factors, the only type of cancer (AML) and severe neutropenia, were found to be risk factors for the development of fungal infections in all hematologic cancer patients and previous IFI was a risk factor only AML patients.

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Opportunistic Fungal Infection

Chest Imaging ◽

10.1093/med/9780199858064.003.0037 ◽

2019 ◽

pp. 209-213

Author(s):

Sonia L. Betancourt

Keyword(s):

Fungal Infection ◽

Opportunistic Infection ◽

Fungal Pathogens ◽

Fungal Infections ◽

Hematologic Malignancy ◽

Solid Organ Transplantation ◽

Solid Organ ◽

Candida Spp ◽

Common Opportunistic Infection ◽

Cryptococcus Spp

Opportunistic fungal infections are caused by fungi that are nonpathogenic in the immunocompetent host, many of which are part of the normal upper respiratory tract flora. These organisms may cause pulmonary infection in immunocompromised hosts. Immunocompromised patients and patients with febrile neutropenia with opportunistic fungal infections may have normal chest radiographs. Thus, chest CT should be performed for further evaluation. Imaging abnormalities in this patient population should raise suspicion for opportunistic infection. Neutropenia is the single most important risk factor for Aspergillosis. Aspergillus is the most common opportunistic infection in patients with hematologic malignancy and bone marrow transplantation. Aspergillus spp., Candida spp., and Cryptococcus spp. are the most common fungal infections in patients with solid organ transplantation. Pneumocystis jirovecii is the most common fungal infection in patients AIDS with CD4 count s<200 cells/mm3. Cryptococcal pneumonia is also common in this population. There has been a recent increase in uncommon fungal pathogens causing invasive pulmonary disease.

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Prevalence and Therapeutic Challenges of Fungal Drug Resistance: Role for Plants in Drug Discovery

Antibiotics ◽

10.3390/antibiotics9040150 ◽

2020 ◽

Vol 9 (4) ◽

pp. 150 ◽

Cited By ~ 4

Author(s):

Lewis Marquez ◽

Cassandra L. Quave

Keyword(s):

United States ◽

Drug Resistance ◽

Fungal Pathogens ◽

Fungal Infections ◽

The United States ◽

Multidrug Resistant ◽

Modern Medicine ◽

Candida Auris ◽

Medical Ethnobotany ◽

Global Issue

Antimicrobial resistance is a global issue that threatens the effective practice of modern medicine and global health. The emergence of multidrug-resistant (MDR) fungal strains of Candida auris and azole-resistant Aspergillus fumigatus were highlighted in the Centers for Disease Control and Prevention’s (CDC) 2019 report, Antibiotic Resistance Threats in the United States. Conventional antifungals used to treat fungal infections are no longer as effective, leading to increased mortality. Compounding this issue, there are very few new antifungals currently in development. Plants from traditional medicine represent one possible research path to addressing the issue of MDR fungal pathogens. In this commentary piece, we discuss how medical ethnobotany—the study of how people use plants in medicine—can be used as a guide to identify plant species for the discovery and development of novel antifungal therapies.

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