A Multidisciplinary Approach to Fungal Infections: One-Year Experiences of a Center of Expertise in Mycology

Invasive fungal diseases (IFDs) often represent complicated infections in complex patient populations. The Center of Expertise in Mycology Radboudumc/CWZ (EMRC) organizes a biweekly multidisciplinary mycology meeting to discuss patients with severe fungal infections and to provide comprehensive advice regarding diagnosis and treatment. Here, we describe the patient population discussed at these meetings during a one-year period with regards to their past medical history, diagnosis, microbiological and other diagnostic test results and antifungal therapy. The majority of patients discussed were adults (83.1%), 62.5% of whom suffered from pulmonary infections or signs/symptoms, 10.9% from otorhinolaryngeal infections and/or oesophagitis, 9.4% from systemic infections and 9.4% from central nervous system infections. Among children, 53.8% had pulmonary infections or signs/symptoms, 23.1% systemic fungal infections and 23.1% other, miscellaneous fungal infections. 52.5% of adult patients with pulmonary infections/symptoms fulfilled diagnostic criteria for chronic pulmonary aspergillosis (CPA). Culture or polymerase chain reaction (PCR) demonstrated fungal pathogens in 81.8% of patients, most commonly Aspergillus. A multidisciplinary mycology meeting can be a useful addition to the care for patients with (I)FDs and can potentially aid in identifying healthcare and research needs regarding the field of fungal infections. The majority of patients discussed at the multidisciplinary meetings suffered from pulmonary infections, predominantly CPA.

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SOD5 is the Prototype of a New Class of Cu-only Superoxide Dismutases

Acta Crystallographica Section A Foundations and Advances ◽

10.1107/s2053273314091906 ◽

2014 ◽

Vol 70 (a1) ◽

pp. C809-C809

Author(s):

Ahmad Galaleldeen ◽

Julie Gleason ◽

Diane Cabelli ◽

John Hart ◽

Valeria Culotta

Keyword(s):

Fungal Pathogens ◽

Fungal Infections ◽

Superoxide Dismutases ◽

X Ray Diffraction ◽

Mucosal Surfaces ◽

Copper Site ◽

Zinc Binding Site ◽

Life Threatening ◽

Copper Zinc ◽

Systemic Infections

Superoxide dismutases (SODs) are antioxidant enzymes that catalyze the dismutation of superoxide into molecular oxygen and hydrogen peroxide. Candida albicans is a polymorphic fungus that causes the majority of fungal infections in humans. In the immunocompetent population, colonization of C. albicans can result in acute infections of the mucosal surfaces both in the oral and genital cavities, however, immunocompromised individuals encounter life-threatening systemic infections. Several factors contribute to the pathogenesis of C. albicans including the expression of SOD5; a postulated copper-zinc SOD. SOD5 enables C. albicans to evade the immune response of the host, namely the oxidative burst. In the absence of SOD5, reactive oxygen species (ROS) accumulate and C. albicans exhibit a severe loss in viability. Our studies sought to examine the crystal structure of SOD5. The protein was overexpressed in E. coli and due to its insolubility; it was denatured, refolded, and further purified. Following protein purification, a sedimentation velocity experiment was performed and the data revealed that SOD5 is a monomeric protein in solution. The structure was then determined using single crystal X-ray diffraction. The structure of SOD5 confirms that it is a prototype of monomeric SODs possessing a copper-only active site and lacking a zinc binding site. In addition, this protein was devoid of the electrostatic loop that typically characterizes all SOD1s. The SOD5 copper site is solvent accessible, cupped in an electrostatic architecture that could serve in superoxide guidance. SOD5-like proteins are widespread among fungal pathogens and appear adapted for the metal and oxidative challenges at the host-pathogen interface.

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Quantitative Multiplexed Detection of Common Pulmonary Fungal Pathogens by Labeled Primer Polymerase Chain Reaction

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2013-0592-oa ◽

2014 ◽

Vol 138 (11) ◽

pp. 1474-1480 ◽

Cited By ~ 8

Author(s):

Zhengming Gu ◽

Daelynn R. Buelow ◽

Ruta Petraitiene ◽

Vidmantas Petraitis ◽

Thomas J. Walsh ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Fungal Pathogens ◽

Bronchoalveolar Lavage Fluid ◽

Fungal Infections ◽

Lavage Fluid ◽

Quantitative Detection ◽

Target Sequence ◽

Chain Reaction ◽

Polymerase Chain ◽

Primer Polymerase Chain Reaction

Context Invasive fungal infections are an important cause of morbidity and mortality among immunocompromised patients. Objective To design and evaluate a multiplexed assay aimed at quantitative detection and differentiation of the 5 molds that are most commonly responsible for pulmonary infections. Design Using labeled primer polymerase chain reaction chemistry, an assay was designed to target the 5.8S and 28S ribosomal RNA genes of Aspergillus spp, Fusarium spp, Scedosporium spp, and members of the order Mucorales (Rhizopus oryzae, Rhizopus microsporus, Cunninghamella bertholletiae, Mucor circinelloides, Lichtheimia corymbifera, and Rhizomucor pusillus). This assay was split into 2 multiplexed reactions and was evaluated using both samples seeded with purified nucleic acid from 42 well-characterized clinical fungal isolates and 105 archived samples (47 blood [45%], 42 bronchoalveolar lavage fluid [40%], and 16 tissue [15%]) collected from rabbit models of invasive pulmonary fungal infections. Results Assay detection sensitivity was less than 25 copies of the target sequence per reaction for Aspergillus spp, 5 copies for Fusarium spp and Scedosporium spp, and 10 copies for the Mucorales. The assay showed quantitative linearity from 5 × 101 to 5 × 105 copies of target sequence per reaction. Sensitivities and specificities for bronchoalveolar lavage fluid, tissue, and blood samples were 0.86 and 0.99, 0.60 and 1.00, and 0.46 and 1.00, respectively. Conclusions Labeled primer polymerase chain reaction permits rapid, quantitative detection and differentiation of common agents of invasive fungal infection. The assay described herein shows promise for clinical implementation that may have a significant effect on the rapid diagnosis and treatment of patients' severe infections caused by these pulmonary fungal pathogens.

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Role for IL-1 Family Cytokines in Fungal Infections

Frontiers in Microbiology ◽

10.3389/fmicb.2021.633047 ◽

2021 ◽

Vol 12 ◽

Author(s):

James S. Griffiths ◽

Giorgio Camilli ◽

Natalia K. Kotowicz ◽

Jemima Ho ◽

Jonathan P. Richardson ◽

...

Keyword(s):

Fungal Pathogens ◽

Fungal Infections ◽

Systemic Disease ◽

Severe Disease ◽

Life Threatening ◽

Current Therapies ◽

Immunotherapy Target ◽

Systemic Infections ◽

Fungal Immunity ◽

Anti Fungal

Fungal pathogens kill approximately 1.5 million individuals per year and represent a severe disease burden worldwide. It is estimated over 150 million people have serious fungal disease such as recurrent mucosal infections or life-threatening systemic infections. Disease can ensue from commensal fungi or new infection and involves different fungal morphologies and the expression of virulence factors. Therefore, anti-fungal immunity is complex and requires coordination between multiple facets of the immune system. IL-1 family cytokines are associated with acute and chronic inflammation and are essential for the innate response to infection. Recent research indicates IL-1 cytokines play a key role mediating immunity against different fungal infections. During mucosal disease, IL-1R and IL-36R are required for neutrophil recruitment and protective Th17 responses, but function through different mechanisms. During systemic disease, IL-18 drives protective Th1 responses, while IL-33 promotes Th2 and suppresses Th1 immunity. The IL-1 family represents an attractive anti-fungal immunotherapy target. There is a need for novel anti-fungal therapeutics, as current therapies are ineffective, toxic and encounter resistance, and no anti-fungal vaccine exists. Furthering our understanding of the IL-1 family cytokines and their complex role during fungal infection may aid the development of novel therapies. As such, this review will discuss the role for IL-1 family cytokines in fungal infections.

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Biosensors for Fungal Detection

Journal of Pure and Applied Microbiology ◽

10.22207/jpam.15.4.02 ◽

2021 ◽

Author(s):

Hamdi Nsairat ◽

Areej M. Jaber ◽

Mazen Al-Sulaibi

Keyword(s):

Molecular Diagnosis ◽

Diagnostic Tests ◽

Fungal Pathogens ◽

Pathogen Detection ◽

Drug Sensitivity ◽

Fungal Infections ◽

Pathogenic Fungi ◽

Chain Reactions ◽

Polymerase Chain Reactions ◽

Polymerase Chain

Due to the serious threat of invasive fungal infections, there is an emergent need for improved a sensitive and more accurate diagnostic tests for detection of systemic pathogenic fungi and plant health. Traditional fungal diagnosis can only be achieved at later growing phases. The complex and difficult immunodiagnostic is also widely employed. Enzyme-based immunoassays which lead to cross-interaction with different fungi still also obeyed. A polymerase chain reactions (PCRs)- based molecular diagnosis are does not enable precise identification of fungal pathogens, or the ability to test isolates for drug sensitivity. In the future, biosensing technologies and nanotechnological tools, will improve diagnosis of pathogenic fungi through a specific and sensitive pathogen detection. This report systematically reviews the most prominent biosensor trends for fungi detection.

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The Prevalence Onychomycosis in North Western Region of Rajasthan

International Healthcare Research Journal ◽

10.26440/ihrj/01_10/139 ◽

2018 ◽

Vol 1 (10) ◽

pp. 323-329

Author(s):

Ravindra Kumar ◽

Sanju Pannu ◽

Mukesh Kumar ◽

Om Prakash Yadav

Keyword(s):

Fungal Pathogens ◽

Fungal Infections ◽

Fungal Growth ◽

Morphological Identification ◽

Infection Prevalence ◽

Study Region ◽

Nail Diseases ◽

Accurate Treatment ◽

Microbiological Techniques ◽

One Year

NTRODUCTION: Onychomycosis is a fungal infection of nail caused by dermatophytes, yeast and mould. Onchomycosis infection continues to spread worldwide and found to persist everywhere. Onchomycosis infection prevalence is continuously increasing and the possible fungal pathogens are also increasing. All nail diseases are not fungal in origin hence laboratory investigations are needed to differentiate accurately between fungal infections and other conditions.AIM: to find out mycological profile & morphological identification of fungal agent in onchomycosis infection and their prevalence in a part of Rajasthan.MATERIALS AND METHOD: A total 50 samples of nail clipings were investigated in department of microbiology by using 20% KOH and culture tubes of Sabouraud’s Dextrose Agar (SDA) which were mixed with chloramphenicol and cycloheximide.RESULT: A total of 50 samples (18 male and 32 females) were tested in period of one year (January to December 2016). Among them 28(56%) samples showed fungal growth, the predominat fungual pathogen in present study were Tricophyton spp. 12 (42.86%) followed by yeasts 09 (32.14%) then molds 07(25%). Fungi commonly presented in the middle age, between 31-40 years of age, due to trauma at the work site and in women, due to their wet work.CONCLUSION: This study highlighted that Dermatophyte T.Rubrum as the main fungal pathogen which caused onychomycosis in the study region. As there are several fungi which cause the infection so it is necessary to perform culture for appropriate treatment So, it is imperative to diagnose it properly by using microbiological techniques and to treat it properly. For proper management of onychomycosis, diagnosis and accurate treatment play a key role in better outcome.

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Is it enough for COVID-19 screening test? Limitation of swab test and general characteristics of mild symptom patients

Science Progress ◽

10.1177/00368504211026152 ◽

2021 ◽

Vol 104 (2) ◽

pp. 003685042110261

Author(s):

Sungwoo Choi ◽

Hyo Jeong Choi ◽

Ho Jung Kim

Keyword(s):

Screening Test ◽

Community Treatment ◽

Upper Respiratory Tract ◽

Test Results ◽

Rt Pcr ◽

Pcr Assay ◽

Positive Rate ◽

Upper Respiratory ◽

Polymerase Chain ◽

Discharge Criteria

The most common method for SARS-CoV-2 testing is throat or nasal swabbing by real-time reverse transcription polymerase chain reaction (RT-PCR) assay. In South Korea, drive-through swab test is used for screening system and community treatment centers (CTCs), which admit and treat confirmed COVID-19 patients with mild symptoms, are being used. This retrospective study was conducted on patients admitted to a CTC on March 6, 2020. A total of 313 patients were admitted. The nasal and throat swabs were collected from the upper respiratory tract, and a sputum test was performed to obtain lower respiratory samples. The positive rate of the first set of test, sputum test was higher than that of the swab test ( p = 0.011). In the second set of test, 1 week after the first ones, the rate of positive swab tests was relatively high ( p = 0.026). In the first set of test, 66 of 152 (43.4%) patients showed 24-h consecutive negative swab test results, when the sputum test results were considered together, that number fell to 29 patients (19.1%) ( p < 0.001). Also, in the second set of test, 63 of 164 (38.4%) patients met the discharge criteria only when the swab test was considered; that number fell to 30 (18.3%) when the sputum test results were also considered ( p < 0.001). Using the swab test alone is insufficient for screening test and discharge decision. Patients who may have positive result in the sputum test can be missed.

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PCR-detectable Candida DNA exists a short period in the blood of systemic candidiasis murine model

Open Life Sciences ◽

10.1515/biol-2020-0075 ◽

2020 ◽

Vol 15 (1) ◽

pp. 677-682

Author(s):

Zheng-Xin He ◽

Hui-Hai Zhao ◽

Fu-Kun Wang

Keyword(s):

Heat Shock ◽

Murine Model ◽

Fungal Pathogens ◽

Clinical Medicine ◽

Diagnostic Techniques ◽

Systemic Candidiasis ◽

Blood Samples ◽

Short Period ◽

Polymerase Chain ◽

Medicine Today

AbstractInvasive candidiasis is a major challenge to clinical medicine today. However, traditional fungal diagnostic techniques and empirical treatments have shown great limitations. Although efforts are necessarily needed in methodology standardization and multicenter validation, polymerase chain reaction (PCR) is a very promising assay in detecting fungal pathogens. Using a “heat-shock” DNA preparation method, a rapid and simple PCR protocol for quantification of the Candida albicans (C. albicans) ribosomal DNA was established. The PCR assay could detect Candida DNA as low as 10 CFU/mL in samples prepared by the heat-shock protocol, without any cross-reaction with DNA prepared from other Candida spp. and bacterial pathogens. For simulated blood samples, the PCR test sensitivity of whole blood samples was better than that of plasma and blood cells. In the systemic candidiasis murine model, detectable DNA was only observed within 24 h after C. albicans SC5314 injection, which is much shorter than that observed in the kidney.

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Seroprevalence of SARS-CoV-2 Antibodies Among Health Care Personnel at a Health Care System in Pakistan

Asia Pacific Journal of Public Health ◽

10.1177/10105395211011010 ◽

2021 ◽

pp. 101053952110110

Author(s):

Salma Abbas ◽

Aun Raza ◽

Ayesha Iftikhar ◽

Aamir Khan ◽

Shahzaib Khan ◽

...

Keyword(s):

Health Care ◽

Control Measures ◽

Health Care Personnel ◽

Test Results ◽

Antibody Testing ◽

Chain Reaction ◽

Past Infection ◽

Infection Control Measures ◽

History Of ◽

Polymerase Chain

Health care personnel (HCP) are at high risk for coronavirus disease-2019 acquisition. Serum antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) indicate past infection. Our institution offered SARS-CoV-2 antibody testing to HCP. We surveyed HCP with positive test results to explore past exposure to SARS-CoV-2, details of symptoms during the preceding 6 months, and a history of SARS-CoV-2 polymerase chain reaction testing. A total of 2162 HCP underwent antibody testing. Eight hundred fifty-seven (39.6%) employees tested positive and, of these, 820 (95.7%) participated in the survey. When adjusted for age, males had higher odds of testing positive for SARS-CoV-2 antibodies compared with females (OR = 1.68; 95% CI = 1.37-2.05; P = .00) and clinical staff had higher odds of SARS-CoV-2 seropositivity compared with nonclinical staff (OR = 1.273; 95% CI = 1.06-1.53; P = .01). Implementation of effective infection control measures is essential to protect HCP from coronavirus disease-2019.

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COVID-19 and pregnancy – where are we now? A review

Journal of Perinatal Medicine ◽

10.1515/jpm-2020-0132 ◽

2020 ◽

Vol 48 (5) ◽

pp. 428-434 ◽

Cited By ~ 7

Author(s):

Aleksandra Rajewska ◽

Wioletta Mikołajek-Bedner ◽

Joanna Lebdowicz-Knul ◽

Małgorzata Sokołowska ◽

Sebastian Kwiatkowski ◽

...

Keyword(s):

Case Fatality ◽

Fetal Distress ◽

Delivery Mode ◽

Test Results ◽

Rt Pcr ◽

Third Trimester ◽

The Third ◽

Laboratory Test Results ◽

Protective Antibodies ◽

Polymerase Chain

AbstractThe new acute respiratory disease severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is highly contagious. It has caused many deaths, despite a relatively low general case fatality rate (CFR). The most common early manifestations of infection are fever, cough, fatigue and myalgia. The diagnosis is based on the exposure history, clinical manifestation, laboratory test results, chest computed tomography (CT) findings and a positive reverse transcription-polymerase chain reaction (RT-PCR) result for coronavirus disease 2019 (COVID-19). The effect of SARS-CoV-2 on pregnancy is not already clear. There is no evidence that pregnant women are more susceptible than the general population. In the third trimester, COVID-19 can cause premature rupture of membranes, premature labour and fetal distress. There are no data on complications of SARS-CoV-2 infection before the third trimester. COVID-19 infection is an indication for delivery if necessary to improve maternal oxygenation. Decision on delivery mode should be individualised. Vertical transmission of coronavirus from the pregnant woman to the fetus has not been proven. As the virus is absent in breast milk, the experts encourage breastfeeding for neonatal acquisition of protective antibodies.

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Production of Phytotoxic Metabolites by Botryosphaeriaceae in Naturally Infected and Artificially Inoculated Grapevines

Plants ◽

10.3390/plants10040802 ◽

2021 ◽

Vol 10 (4) ◽

pp. 802

Author(s):

Pierluigi Reveglia ◽

Regina Billones-Baaijens ◽

Jennifer Millera Millera Niem ◽

Marco Masi ◽

Alessio Cimmino ◽

...

Keyword(s):

Fungal Pathogens ◽

Protocatechuic Acid ◽

Physiological Factors ◽

Diplodia Seriata ◽

Grapevine Trunk Diseases ◽

Botryosphaeria Dieback ◽

Trunk Diseases ◽

One Year ◽

Pathogen Dna

Grapevine trunk diseases (GTDs) are considered a serious problem to viticulture worldwide. Several GTD fungal pathogens produce phytotoxic metabolites (PMs) that were hypothesized to migrate to the foliage where they cause distinct symptoms. The role of PMs in the expression of Botryosphaeria dieback (BD) symptoms in naturally infected and artificially inoculated wood using molecular and analytical chemistry techniques was investigated. Wood samples from field vines naturally infected with BD and one-year-old vines inoculated with Diplodia seriata, Spencermartinsia viticola and Dothiorella vidmadera were analysed by cultural isolations, quantitative PCR (qPCR) and targeted LC-MS/MS to detect three PMs: (R)-mellein, protocatechuic acid and spencertoxin. (R)-mellein was detected in symptomatic naturally infected wood and vines artificially inoculated with D. seriata but was absent in all non-symptomatic wood. The amount of (R)-mellein detected was correlated with the amount of pathogen DNA detected by qPCR. Protocatechuic acid and spencertoxin were absent in all inoculated wood samples. (R)-mellein may be produced by the pathogen during infection to break down the wood, however it was not translocated into other parts of the vine. The foliar symptoms previously reported in vineyards may be due to a combination of PMs produced and climatic and physiological factors that require further investigation.

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