Problemas clínicos en Micología Médica: problema número 56 / Clinical problems in Medical Mycology: Problem number 56

We present the case of a twenty six year-old woman with rheumatoid arthritis, treated with certolizumab. She sought medical attention due to cough, fever and night sweats. X-ray exam showed a miliary pneumonia. She was treated for tuberculosis and 50days later she presented with aphasia. Magnetic nuclear resonance revealed brain lesions. Histoplasma capsulatum PCR test and urinary antigen were positive, so an antifungal treatment with voriconazole was started. Visual adverse effects forced to change the antifungal schedule in both the length of treatment and the antifungal drug. With this measure the patient progressed favorably. The test of urinary Histoplasma capsulatum antigen and PCR amplification were key to make a diagnosis and also for a follow-up.(AU)

Se presenta el caso de una paciente de 26años de edad, profesora de educación física. Nació y vive en Burzaco, conurbano sur de la Provincia de Buenos Aires, República Argentina. Debido a su trabajo había realizado diversos viajes y acampado en diferentes provincias de nuestro país (Misiones, Corrientes, San Juan y Mendoza). En el extranjero solo había visitado Orlando (EE.UU.). Desde hacía 10años padecía artritis reumatoide juvenil. Por esta patología recibió metotrexato 15mg/semana, prednisona 5mg/día e hidroxicloroquina 400mg/día durante 7años. Posteriormente le fue prescrito certolizumab 200mg cada dos semanas y, posteriormente, 400mg cada cuatro semanas. Tras dos años con esta medicación le fue suspendida por la aparición de tos seca, fiebre, astenia, adinamia y sudores nocturnos. Debido a estas manifestaciones se le realizó una radiografía de tórax (fig. 1) y se suspendió inmediatamente el tratamiento con el inmunomodulador (certolizumab).(AU)

[Changing Trends in Isolation Frequencies and Species of Clinical Fungal Strains: What Do the 12-years (2008-2019) Mycology Laboratory Data Tell About?] / Enfeksiyon Etkeni Mantarlarin Zamana Göre Siklik ve Tür Dagilimlarindaki Degisimler: 12 Yillik (2008-2019) Mikoloji Laboratuvari Verileri Ne Söylüyor?

The frequency and variety of infections caused by fungi are increasing. However, changes and intercenter and regional differences are observed in the distribution of fungal species over the years. It is important to update the epidemiological data in order to enable early and appropriate treatment. In this retrospective study, the number of fungi isolated from clinical samples, their distribution at the genus/ species level and the variations over the years in Hacettepe University hospital which is a regional center for patients at risk of fungal infection were investigated. For this purpose, laboratory records from 2008- 2019 were examined and 21813 fungal strains isolated from 19636 clinical samples were detected. When the first (2008-2013) and second (2014-2019) six-year periods were compared, a 2.5 fold increase was observed in the number of specimens yielding fungal growth (first period; n= 5620, second period; n= 14016). Fungi were most frequently isolated from urine (45.0%), lower respiratory tract (30.7%) and blood (6.8%) samples. Mould isolation rate in all samples increased significantly in the second six-year period (from 8.3% to 10.6%, p≤ 0.001). As expected, the most frequent yeast was Candida albicans (57.0%) and mould was Aspergillus fumigatus complex (50.4%). In the second six-year period, isolation of C.albicans (59.3% to 56.0%, p≤ 0.001) among yeasts and A.fumigatus complex (58.1% to 48.0%, p≤ 0.001) among moulds decreased significantly. In urine specimens, most common fungi were C.albicans (49.8%), Candida glabrata complex (15.6%), Candida tropicalis (8.9%) and Candida kefyr (7.5%). In lower respiratory tract specimens, the most common mould was A.fumigatus complex (51.2%), which has decreased from 63.7% in the first six years to 47.1% in the second period (p≤ 0.001). Over the same period, other Aspergillus species (from 25.5% to 34.1%, p= 0.002) and non-Aspergillus moulds (from 36.3% to 52.9%, p≤ 0.001) were increased. In blood samples, C.albicans (44.4%), Candida parapsilosis complex (21.5%) and C.glabrata complex (13.0%) were the most frequent species. In the second six-year period, the frequency of C.albicans decreased from 47.3% to 42.2% (p= 0.059) and the frequency of C.glabrata complex increased from 9.5% to 15.5% (p≤ 0.001) when compared to the first period. For the sterile specimens other than blood, the most common species were C.albicans (37.8%), C.glabrata complex (9.1%) and C.parapsilosis complex (4.7%). However, the number of fungal isolates and the distribution of the species showed great variation over the years. In our center, a substantial increase in the number of fungal strains isolated from the clinical specimens were observed over a 12-years period. In addition and similar to previously published reports, the increase of strains belonging to species with decreased antifungal susceptibility and/or species with unknown susceptibility were detected. The use of local data is required in order to implement early and appropriate antifungal treatment because of inter-center and regional differences observed in epidemiological trends regarding the distributions of fungal genera and species. Surveillance studies to be conducted with the participation of large and sufficient numbers of centers in our country, as we have done for our center, will also contribute to approaches regarding the management of fungal infections by revealing the epidemiological data in a comprehensive manner.

[Update on the diagnosis of parasitic and fungal infections]. / Actualités du diagnostic des infections parasitaires et fongiques.

The diagnosis of parasitic and fungal infections, historically based on the detection of these pathogens using direct diagnosis (macro/microscopic examination, culture) or serological methods, has considerably evolved in the last decades, especially with the development of molecular approaches and mass spectrometry. These techniques, as well as most analyses of parasitic and fungal serology, are mostly the preserve of Hospital University Centers Parasitology-Mycology laboratories. In 2016, the French association of medical parasitology and mycology teachers and hospital practitioners (Anofel) has provided a Catalogue of rare analyses, regularly updated and freely accessible on the Anofel website (https://anofel.net/). This tool, which hinges on 4 parts (parasitology, parasitic serology, mycology, and fungal serology), aims to provide information on all available analyses, and a list of hospital laboratories able to undertake them. It is complementary to the other reference works that were developed by our association, including the Guide of analyses and methods in parasitology and mycology, published in 2018, and the eANOFEL pictures and videos database, freely accessible online (http://www.eanofel.fr). In this article, we draw-up a state-of-the-art of the most specialized techniques available in the parasitology-mycology laboratories and presented in the Catalogue of rare analyses of the Anofel collegium, and their interest for the diagnosis of these infections.

Recent advances and novel approaches in laboratory-based diagnostic mycology.

The field of diagnostic mycology represents much more than culture and microscopy and is rapidly embracing novel techniques and strategies to help overcome the limitations of conventional approaches. Commercial molecular assays increase the applicability of PCR testing and may identify markers of antifungal resistance, which are of great clinical concern. Lateral flow assays simplify testing and turn-around time, with potential for point of care testing, while proximity ligation assays embrace the sensitivity of molecular testing with the specificity of antibody detection. The first evidence of patient risk stratification is being described and together with the era of next generation sequencing represents an exciting time in mycology.

A Festschrift in Honor of Meredith Blackwell.

The end of the 20th century and the beginning of the 21st will be remembered as the golden age of molecular systematics of Fungi. The development of the Polymerase Chain Reaction (PCR), automated sequencing, and explicit algorithms for inferring phylogenetic trees transformed fungal systematics into a hypothesis-testing discipline that would go on to serve as the foundation for comparative and evolutionary genomics. Many mycologists participated in this modernization of mycology and perhaps none more than Meredith Blackwell. She has played - and continues to play - a leadership role in transforming mycology into a modern science based on a robust understanding of organismal biology, development, testing and refinement of biologically meaningful hypotheses, and incorporation of emerging technologies to data collection and analysis. In this volume we recognize Meredith and her contributions to mycology with the publication of the first Festschrift issue in the 110 year history of Mycologia.

Comments on practice guidelines for the diagnosis and management of aspergillosis made by the IDSA in 2016.

We sought to review the most important updates in the treatment of aspergillosis after the publication of the clinical practice guidelines for the diagnosis and management of invasive aspergillosis (IA) by the Infectious Diseases Society of America. Our aim is to discuss some of the key aspects concerning the following topics: early initiation of antifungal therapy, antifungal agent of choice, follow-up of patients with IA, and breakthrough aspergillosis.

Remarkable Works and Cases in the History of Medical Mycology in Japan.

Several pathogenic fungi and cases related to Japanese medical mycologists were reviewed. Trichosporon inkin (as Sarcinomyces inkin) was reported as a pathogen of scrotal lesion by Oho in 1921, and Trichosporon asahii was isolated from generalized keratotic lesions in 1922 by Akagi in Japan. They were once included in Trichophyton beigelii, but then based on revision using DNA molecular technology, were returned to their original names.Microsporum ferrugineum was reported by Ota as a causative dermatophyte of tinea capitis in Japan and surrounding areas. It was once classified under the genus Trichophyton, but after the discovery of characteristic rough-walled macroconidia belonging to genus Microsporum, the fungus was again assigned to the original name.

Laura Frontali-my life with yeast.

The Author relates her life from University to recent years. It was dominated by the developing importance of yeast, from agent of industrial fermentations to eukaryotic model organism. In this frame she recalls family life , friends, teachers, collaborations.

Advances and challenges in logical modeling of cell cycle regulation: perspective for multi-scale, integrative yeast cell models.

The eukaryotic cell cycle is robustly designed, with interacting molecules organized within a definite topology that ensures temporal precision of its phase transitions. Its underlying dynamics are regulated by molecular switches, for which remarkable insights have been provided by genetic and molecular biology efforts. In a number of cases, this information has been made predictive, through computational models. These models have allowed for the identification of novel molecular mechanisms, later validated experimentally. Logical modeling represents one of the youngest approaches to address cell cycle regulation. We summarize the advances that this type of modeling has achieved to reproduce and predict cell cycle dynamics. Furthermore, we present the challenge that this type of modeling is now ready to tackle: its integration with intracellular networks, and its formalisms, to understand crosstalks underlying systems level properties, ultimate aim of multi-scale models. Specifically, we discuss and illustrate how such an integration may be realized, by integrating a minimal logical model of the cell cycle with a metabolic network.

[Antifungal medication: new substances, new experiences]. / Antimykotika ­ neue Substanzen, neue Erfahrungen.

The incidence of life threatening invasive fungal infections in patients with hematological malignancies during intensive chemotherapy or after hematopoetic stem cell transplantation, patients after solid organ transplantation, ICU patients and premature infants is rising. Mortality rates of invasive fungal infections, caused by Aspergillus species or mucormycetes, may reach 100%, in spite of considerable progress in diagnosis, antifungal prophylaxis and therapy. Comprehensive, profound knowledge of specific diagnostic and current treatment algorithms is essential to improve the prognosis of patients suffering from systemic fungal infections; this article encompasses recent developments in the field of antifungal treatment.

[Application of mass spectrometry in mycology]. / Aplicación de la espectrometría de masas en micología.

MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) mass spectrometry (MS) is becoming an essential tool in most microbiology laboratories. At present, by using a characteristic fungal profile obtained from whole cells or through simple extraction protocols, MALDI-TOF MS allows the identification of pathogenic fungi with a high performance potential. This methodology decreases the laboratory turnaround time, optimizing the detection of mycoses. This article describes the state-of-the-art of the use of MALDI-TOF MS for the detection of human clinical fungal pathogens in the laboratory and discusses the future applications of this technology, which will further improve routine mycological diagnosis.

Problemas clínicos en micología médica: problema número 49 / Clinical problems in medical mycology: problem number 49

The case of a 59-year-old female born in Buenos Aires (Argentina) is presented. She had been diagnosed with HIV in 2007 and received highly active antiretroviral therapy until 2011; she also suffered from diabetes type 2. She had received empirical treatment (pyrimethamine-clindamycin) for cerebral toxoplasmosis. Fifteen days later she suffered a drug-induced skin disorder and was treated in the Dermatology Service of the Hospital Muñiz with corticosteroids. After five weeks she was readmitted to the Infectious Disease Unit due to asthenia, weight loss, left hip pain and weakness in all four limbs. Septic arthritis and aseptic hip necrosis were ruled out. Blood cultures were positive for Staphylococcus aureus and Escherichia coli. The patient received intravenous antibiotics, but before being discharged Acinetobacter baumannii was isolated from blood, catheter and urine cultures, and a new series of antibiotics were prescribed. On the 3rd day she presented encephalic facies, changes of behaviour and disorientation, without nuchal rigidity, Kernig and Brudzinski signs or focal signs. An X-ray computed tomography did not show parenchymal lesions. A yeast identified as Candida albicans was isolated in a cerebrospinal fluid culture. The same yeast was recovered in a new cerebrospinal fluid sample. The isolate was susceptible to amphotericin B and susceptible dose dependent to fluconazole. The patient was treated with amphotericin B (0.7 mg/kg plus 800 mg fluconazole daily). Three weeks later, new cerebrospinal fluid cultures were negative. Unfortunately, the patient died soon afterwards (AU)

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[ISHAM-WG Symposium: Introduction of Medical Phycology, Retrospective Overview, and Prospective Aspect].

Protothecosis is an emerging infectious zoonotic disease caused by species of the genus Prototheca (Trebouxiophyceae, Chlorophyta), which are classified as achlorophyllous algae closely related to the green algal genus Chlorella. Prototheca lost the ability to photosynthesize and are widely distributed throughout the natural world in sewage, soil, lakes, and marshes. It is therefore necessary to build an interdisciplinary network connecting human medicine, veterinary medicine, microbiological taxonomy, clinical microbiology, and environmental microbiology to increase knowledge in this area. We have established the working group "Medical Phycology : Protothecosis and Chlorellosis" (approved on May 4, 2014) under the umbrella of the International Society for Human and Animal Mycology (ISHAM) to support all scientific aspects dealing with this topic. We report the current circumstances and future prospects of this working group for the group to become better known by scientists.