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Diagnosis of Invasive Fungal Diseases

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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 (30 September 2024) | Viewed by 10146

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Dr. Dong-Gun Lee

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Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
Interests: diagnosis and management of infectious complications in immunocompromised patients, especially invasive fungal diseases; prevention of infectious diseases in procedures such as post-transplantation vaccination
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Dear Colleagues,

Invasive fungal diseases are on the rise. The biggest reason for this is that the number of patients with a reduced immune function, such as patients with acute leukemia or undergoing transplantation, is increasing, and they suffer from invasive fungal diseases as opportunistic infections while surviving for a long time. Another reason is that in the past, diagnosis was only possible with extremely limited methods such as culture tests, and the yield of this test method was low, so diagnoses were not performed properly or promptly. New diagnostic methods such as PCR, MALDI-TOF, and lateral flow devices were developed, and methods that can use specimens other than blood—for example, bronchoalveolar lavage, urinalysis, etc.—are being tested. In addition, by applying these methods clinically, fungal diseases can be better understood and treated early. In addition, a kit that can not only diagnose fungal diseases but can also check antifungal resistance at the same time as diagnosis is being developed. The development and application of this new diagnostic method will lead to the early detection of invasive fungal diseases, which will lead to the early initiation of appropriate antifungal drugs, thereby improving patients’ outcomes.

This Special Issue introduces methods that were recently developed or are being developed for diagnosing invasive fungal diseases and shares the experiences of each hospital and center that have applied these methods clinically.

Dr. Dong-Gun Lee
Guest Editor

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Keywords

invasive fungal diseases
new diagnostic methods
antifungal resistance
PCR
rapid kit

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Published Papers (8 papers)

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14 pages, 21265 KiB

Open AccessArticle

Label-Free Optical Transmission Tomography for Direct Mycological Examination and Monitoring of Intracellular Dynamics

by Eliott Teston, Marc Sautour, Léa Boulnois, Nicolas Augey, Abdellah Dighab, Christophe Guillet, Dea Garcia-Hermoso, Fanny Lanternier, Marie-Elisabeth Bougnoux, Frédéric Dalle, Louise Basmaciyan, Mathieu Blot, Pierre-Emmanuel Charles, Jean-Pierre Quenot, Bianca Podac, Catherine Neuwirth, Claude Boccara, Martine Boccara, Olivier Thouvenin and Thomas Maldiney

J. Fungi 2024, 10(11), 741; https://doi.org/10.3390/jof10110741 - 26 Oct 2024

Viewed by 674

Abstract

Live-cell imaging generally requires pretreatment with fluorophores to either monitor cellular functions or the dynamics of intracellular processes and structures. We have recently introduced full-field optical coherence tomography for the label-free live-cell imaging of fungi with potential clinical applications for the diagnosis of invasive fungal mold infections. While both the spatial resolution and technical set up of this technology are more likely designed for the histopathological analysis of tissue biopsies, there is to our knowledge no previous work reporting the use of a light interference-based optical technique for direct mycological examination and monitoring of intracellular processes. We describe the first application of dynamic full-field optical transmission tomography (D-FF-OTT) to achieve both high-resolution and live-cell imaging of fungi. First, D-FF-OTT allowed for the precise examination and identification of several elementary structures within a selection of fungal species commonly known to be responsible for invasive fungal infections such as Candida albicans, Aspergillus fumigatus, or Rhizopus arrhizus. Furthermore, D-FF-OTT revealed the intracellular trafficking of organelles and vesicles related to metabolic processes of living fungi, thus opening new perspectives in fast fungal infection diagnostics. Full article

(This article belongs to the Special Issue Diagnosis of Invasive Fungal Diseases)

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9 pages, 804 KiB

Open AccessArticle

Three-Month Mortality in Nonhaematological Patients with Chronic Pulmonary Aspergillosis: Differences between Subtypes

by Pablo González García, Julia Fernández-Navarro, Mónica Bru-Arca, Elisa Álvarez-Artero, Pablo Solís, María Pía Roiz Mesones, Juan Luis Muñoz Bellido, María Antonia García Castro, Moncef Belhassen-García and Javier Pardo Lledías

J. Fungi 2024, 10(10), 706; https://doi.org/10.3390/jof10100706 - 10 Oct 2024

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Abstract

Objectives: Chronic pulmonary aspergillosis (CPA) is a fungal lung infection characterised by the slowly progressing destruction of the lung parenchyma and has four main subtypes. The objective of this work was to evaluate the epidemiology of CPA in our area and evaluate the involvement of the different subtypes in mortality. Methods: This was a descriptive longitudinal retrospective study developed in three tertiary hospitals in Spain. Among all patients admitted with a pulmonary aspergillosis diagnosis, we selected those who fulfilled the criteria for chronic aspergillosis according to the criteria of Denning, excluding those with a haematological disorder. Results: Among 409 inpatients recorded as having a pulmonary aspergillosis infection, only 76 (18.5%) fulfilled the criteria for CPA, with an estimated incidence of 0.67 cases/100,000 inhabitants/year. The subtypes detected were subacute invasive aspergillosis (SAIA) in 33 (43.4%) patients, simple aspergilloma (SA) in 25 (32.9%) patients, cavitary chronic aspergillosis (CCPA) in 13 (17.1%) patients, and chronic fibrosis (CFPA) in five (6.5%) patients. The overall three-month mortality rate was 23%, which was higher in SAIA patients. The predictors of early mortality were age > 65 years (OR 3.0 CI 95 1.0–9.5 p = 0.043) and the SAIA subtype vs. other subtypes (OR 3.1 CI 95 1.0–9.5 p = 0.042). Conclusions: The incidence rate estimated was inferior to that previously reported. The three-month mortality in patients with CPA was high, with older age and the SAIA subtype being the variable independent predictors of a worse prognosis. Full article

(This article belongs to the Special Issue Diagnosis of Invasive Fungal Diseases)

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9 pages, 835 KiB

Open AccessCommunication

Diagnostic Value of Serum Biomarkers for Invasive Aspergillosis in Haematologic Patients

by Isabel Montesinos, Imane Saad Albichr, Elodie Collinge, Bénédicte Delaere, Te-Din Huang, Pierre Bogaerts, Corentin Deckers, Mai Hamouda, Patrick M. Honoré, Pierre Bulpa and Anne Sonet

J. Fungi 2024, 10(9), 661; https://doi.org/10.3390/jof10090661 - 20 Sep 2024

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Abstract

Background: Invasive aspergillosis (IA) is a significant cause of morbidity and mortality in patients with haematological malignancies. Accurate diagnosis of IA is challenging due to non-specific symptoms and the impact of antifungal prophylaxis on biomarker sensitivity. Methods: This retrospective study evaluated the diagnostic performance of three serum biomarkers: Aspergillus Galactomannan Ag VirClia Monotest^® (VirClia), Wako β-D-Glucan Test^® (Wako BDG), and MycoGENIE Real-Time PCR^® (MycoGENIE PCR). True positives were defined as patients with proven or probable IA (n = 14), with a positive Platelia Aspergillus Antigen^® (Platelia) serving as a mycological criterion. True negatives were identified as patients with a positive Platelia assay but classified as non-probable IA (n = 10) and outpatients who consistently tested negative with the Platelia test throughout the study period (n = 20). Results: Most patients diagnosed with proven or probable IA were acute myeloid leukaemia or myelodysplastic syndrome patients receiving mould-active antifungal prophylaxis or treatment (71%). VirClia demonstrated high sensitivity (100%) for detecting IA, with a specificity of 83%. Wako BDG and MycoGENIE PCR showed lower sensitivities for IA (57% and 64%, respectively). MycoGENIE PCR detected Aspergillus spp. and Mucorales in two patients. Conclusions: Accurate diagnosis of IA remains challenging, especially in patients who have received mould-active antifungal treatment. VirClia showed comparable performance to Platelia, suggesting its potential for routine use. However, Wako BDG and MycoGENIE PCR results were less favourable in our study cohort. Nevertheless, MycoGENIE PCR detected two probable co-infections with Aspergillus spp. and Mucorales. Full article

(This article belongs to the Special Issue Diagnosis of Invasive Fungal Diseases)

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12 pages, 1555 KiB

Open AccessArticle

Invasive Pulmonary Aspergillosis in Patients with HBV-Related Acute on Chronic Liver Failure

by Man Yuan, Ning Han, Duoduo Lv, Wei Huang, Mengjie Zhou, Libo Yan and Hong Tang

J. Fungi 2024, 10(8), 571; https://doi.org/10.3390/jof10080571 - 14 Aug 2024

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Background: We aim to investigate the characteristics of invasive pulmonary aspergillosis (IPA) in patients with HBV-related acute on chronic liver failure (HBV-ACLF). Methods: A total of 44 patients with probable IPA were selected as the case group, and another 88 patients without lung infections were chosen as the control group. Results: HBV-ACLF patients with probable IPA had more significant 90-day mortality (38.6% vs. 15.9%, p = 0.0022) than those without. The white blood cell (WBC) count was the independent factor attributed to the IPA development [odds ratio (OR) 1.468, p = 0.027]. Respiratory failure was associated with the mortality of HBV-ACLF patients with IPA [OR 26, p = 0.000]. Twenty-seven patients received voriconazole or voriconazole plus as an antifungal treatment. Plasma voriconazole concentration measurements were performed as therapeutic drug monitoring in 55.6% (15/27) of the patients. The drug concentrations exceeded the safe range with a reduced dosage. Conclusions: The WBC count might be used to monitor patients’ progress with HBV-ACLF and IPA. The presence of IPA increases the 90-day mortality of HBV-ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients, and voriconazole should be assessed by closely monitoring blood levels. Full article

(This article belongs to the Special Issue Diagnosis of Invasive Fungal Diseases)

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14 pages, 920 KiB

Open AccessArticle

Prevalence of Cryptococcal Antigenemia and Lateral Flow Assay Accuracy in Severely Immunosuppressed AIDS Patients

by Adriana Carla Garcia Negri, Maína de Oliveira Nunes, Gláucia Moreira Espíndola Lima, James Venturini, Sandra Maria do Valle Leone de Oliveira, Márcia dos Santos Lazera, Lídia Raquel de Carvalho, Marilene Rodrigues Chang, Rosianne Assis de Sousa Tsujisaki, Adriana de Oliveira França, Rinaldo Poncio Mendes and Anamaria Mello Miranda Paniago

J. Fungi 2024, 10(7), 490; https://doi.org/10.3390/jof10070490 - 16 Jul 2024

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Abstract

This study aimed to estimate the prevalence of cryptococcal antigenemia detected by lateral flow assay (LFA) in AIDS patients and its accuracy in the diagnosis of cryptococcosis. Conducted at a university hospital in Brazil from March 2015 to July 2017, it included AIDS patients over 18 years old with a CD4+ count ≤ 200 cells/mm³. Cryptococcal antigen (CrAg) detection using LFA and latex agglutination (LA), along with blood and urine cultures, were performed. The reference standard was the identification of Cryptococcus spp. in clinical specimens through microbiological or histopathological examination. Among 230 patients, the prevalence of CrAg detected by LFA (CrAg LFA) was 13.0%. Factors associated with cryptococcal antigenemia included fever, vomiting, seizures, and a lack of antiretroviral therapy. The sensitivity and specificity of CrAg LFA were 83.9% and 98.0%, respectively. The positive predictive value (PPV) was 86.7%, the negative predictive value (NPV) was 97.5%, and overall accuracy was 96.1%. Cross-reactions were observed in patients with histoplasmosis and paracoccidioidmycosis, but not with aspergillosis or positive rheumatoid factor. The study concludes that the LFA is a useful tool for detecting cryptococcal antigenemia in severely immunocompromised AIDS patients due to its high NPV, specificity, and PPV. Full article

(This article belongs to the Special Issue Diagnosis of Invasive Fungal Diseases)

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14 pages, 4357 KiB

Open AccessArticle

Clinical Implementation of β-Tubulin Gene-Based Aspergillus Polymerase Chain Reaction for Enhanced Aspergillus Diagnosis in Patients with Hematologic Diseases: A Prospective Observational Study

by Raeseok Lee, Won-Bok Kim, Sung-Yeon Cho, Dukhee Nho, Chulmin Park, In Young Yoo, Yeon-Joon Park and Dong-Gun Lee

J. Fungi 2023, 9(12), 1192; https://doi.org/10.3390/jof9121192 - 13 Dec 2023

Cited by 1 | Viewed by 2097

Abstract

The β-tubulin (benA) gene is a promising target for the identification of Aspergillus species. Assessment of the clinical implementation and performance of benA gene-based Aspergillus polymerase chain reaction (PCR) remains warranted. In this study, we assessed the analytical performance of the BenA probe PCR in comparison with the Aspergenius kit. We prospectively collected bronchoalveolar lavage (BAL) fluid via diagnostic bronchoscopy from adult patients with hematologic diseases. BenA gene-based multiplex real-time PCR and sequential melting temperature analysis were performed to detect the azole resistance of Aspergillus fumigatus. In total, 76 BAL fluids in 75 patients suspicious of invasive pulmonary aspergillosis (IPA) were collected. Before the application of PCR, the prevalence of proven and probable IPA was 32.9%. However, after implementing the benA gene-based PCR, 15.8% (12 out of 76) of potential IPA cases were reclassified as probable IPA. The analytical performance of the BenA probe PCR in BAL samples was comparable to that of the Aspergenius kit. The diagnostic performance was as follows: sensitivity, 52.0%; specificity, 64.7%; positive predictive value, 41.9%; negative predictive value, 73.3%; positive likelihood ratio, 1.473; and negative likelihood ratio, 0.741. Moreover, benA gene-based Aspergillus PCR discriminated all major sections of Aspergillus, including cryptic species such as Aspergillus tubingensis. Sequential melting temperature analysis successfully detected 2 isolates (15.4%) of A. fumigatus carrying resistant mutations. BenA gene-based Aspergillus PCR with melting temperature analysis enhances diagnostic accuracy and detects not only cryptic species but also resistant mutations of A. fumigatus. It shows promise for clinical applications in the diagnosis of IPA. Full article

(This article belongs to the Special Issue Diagnosis of Invasive Fungal Diseases)

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6 pages, 1210 KiB

Open AccessCase Report

Atypical Presentation of Invasive Aspergillosis during Treatment with Mogamulizumab

by Paolo Pavone, Laura Arletti, Fiorella Ilariucci, Tommaso Albano, Deborah Lusetti, Romina Corsini, Francesco Merli and Sergio Mezzadri

J. Fungi 2024, 10(8), 584; https://doi.org/10.3390/jof10080584 - 17 Aug 2024

Viewed by 843

Abstract

Treatment with CCR-4 antagonists has been shown to be protective against the development of invasive pulmonary aspergillosis in animal models. Herein, we present a case of fatal invasive pulmonary aspergillosis in a patient receiving Mogamulizumab. A 64-year-old man with refractory mycosis fungoides was found to have diffuse bilateral pulmonary nodules during a chest CT in June 2022. Bronchoalveolar lavage (BAL) fungal and bacterial cultures and galactomannan were negative, as well as serum beta-glucan and galactomannan. Histology showed a lymphoid infiltrate with a negative fungal stain, so a presumptive diagnosis of lymphoma infiltration was made, and the patient started the CCR-4 antagonist Mogamulizumab treatment in August 2022. He had no symptoms until November when he presented to the hematology clinic reporting dyspnea. He had neutrophilic leukocytosis (18.610 cells/µL), his c-reactive protein was 27 mg/dL, and his skin lesions from mycosis fungoides were just starting to improve. A CT scan showed large diffuse bilateral severely necrotic cavitated lesions with thick walls and apparently synchronous evolution. Beta-glucan was 31 pg/mL (wako method), while serum galactomannan 3.6. BAL was positive for Aspergillus fumigatus culture and galactomannan. Patient started voriconazole but, despite being in a stable condition, he suddenly died after two days. Discussion: Paradoxically, worsening of the chronic pulmonary aspergillosis has been reported after nivolumab treatment, and immune reconstitution syndromes are usually seen during neutrophil recovery after intensive chemotherapy. Our patient already presented indolent lung lesions from 5 months before and he remained completely asymptomatic until the aspergillosis diagnosis when he quickly passed away. Even if a progression of the lesions was expected in 5 months, this case had an atypical presentation. During the 5-month period, he had no pulmonary symptoms, and his c-reactive protein was negative. Furthermore, in the setting of the natural progression of subacute/chronic aspergillosis, a different radiological picture was expected with a less severe and probably asynchronous evolution. We think that the immune restoration associated with Mogamulizumab (also supported by the concurrent clinical response of the skin lesions) could have been detrimental in this case, exacerbating a catastrophic immune response or alternatively masquerading the clinical progression of aspergillosis. Clinicians should be aware of immune reconstitution syndromes possibly leading to fatal outcomes in immunocompromised patients starting CCR-4 antagonists. Full article

(This article belongs to the Special Issue Diagnosis of Invasive Fungal Diseases)

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10 pages, 4728 KiB

Open AccessCase Report

Clinical and Radiological Features of Pneumocystis jirovecii Pneumonia in Children: A Case Series

by Erica Ricci, Claudia Bartalucci, Chiara Russo, Marcello Mariani, Carolina Saffioti, Erika Massaccesi, Filomena Pierri, Giacomo Brisca, Andrea Moscatelli, Roberta Caorsi, Bianca Bruzzone, Maria Beatrice Damasio, Anna Marchese, Alessio Mesini and Elio Castagnola

J. Fungi 2024, 10(4), 276; https://doi.org/10.3390/jof10040276 - 9 Apr 2024

Cited by 1 | Viewed by 2080

Abstract

Background: Pneumocytis jirovecii pneumonia (PJP) has high mortality rates in immunocompromised children, even though routine prophylaxis has decreased in incidence. The aim of this case series is to present the radiological and clinical pathway of PJP in a pediatric population. Description of Cases: All PJP cases in non-HIV/AIDS patients diagnosed at Istituto Giannina Gaslini Pediatric Hospital in Genoa (Italy) from January 2012 until October 2022 were retrospectively evaluated. Nine cases were identified (median age: 8.3 years), and of these, 6/9 underwent prophylaxis with trimethoprim/sulfamethoxazole (TMP/SMX; five once-a-week schedules and one three times-a-week schedule), while 3/9 did not receive this. PJP was diagnosed by real-time PCR for P. jirovecii-DNA in respiratory specimens in 7/9 cases and two consecutive positive detections of β-d-glucan (BDG) in the serum in 2/9 cases. Most patients (6/8) had a CT scan with features suggestive of PJP, while one patient did not undergo a scan. All patients were treated with TMP/SMX after a median time from symptoms onset of 3 days. In 7/9 cases, empirical TMP/SMX treatment was initiated after clinical suspicion and radiological evidence and later confirmed by microbiological data. Clinical improvement with the resolution of respiratory failure and 30-day survival included 100% of the study population. Discussion: Due to the difficulty in obtaining biopsy specimens, PJP diagnosis is usually considered probable in most cases. Moreover, the severity of the clinical presentation often leads physicians to start TMP/SMX treatment empirically. BDG proved to be a useful tool for diagnosis, and CT showed good accuracy in identifying typical patterns. In our center, single-day/week prophylaxis was ineffective in high-risk patients; the three-day/week schedule would, therefore, seem preferable and, in any case, should be started promptly in all patients who have an indication of pneumonia. Full article

(This article belongs to the Special Issue Diagnosis of Invasive Fungal Diseases)

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