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Due to Microascaceae and Thermoascaceae Species Invasive fungal infections due to Microascaceae and Thermoascaceae species Mihai Mareș Laboratory of Antimicrobial© by author Chemotherapy University “Ion Ionescu de la Brad” Iași - Romania ESCMID Online Lecture Library © by author ESCMID Online Lecture Library We are not living in a world with fungi, but in a world of fungi… Invasive Fungal Infections – A Multifaceted Challenge New aspects: Nosocomial Emerging pathogens © infectionsby author Risk patients Biofilms on ESCMID Online Lecture Library indwelling devices The main players Invasive candidiasis© by authorInvasive aspergilosis • average incidence: 2.9 cases per 100.000 in • average incidence: 2.3 cases per general population; 466 cases per 100.000 100.000 in general population; in neonates • attributable mortality: global 58% , • attributable mortality:ESCMID 49% Online Lecture• allogeneic-bone Library marrow Gudlaugsson, CID 2003 transplantation 86.7% Lin CID 2001 Emerging fungal pathogens Zygomycetes Scedosporium Paecilomyces © byAlternaria author Fusarium Scopulariopsis ESCMIDTrichosporon Online Lecture Library Emerging fungal pathogens © by author ESCMID Online Lecture Library Chair: Prof. Oliver Cornely Chair: Prof. George Petrikkos Emerging fungal pathogens belonging to Microascaceae and Thermoascaceae • Taxonomic overview • Clinical findings • Treatment options © by author ESCMID Online Lecture Library © by author Taxonomic overview ESCMID Online Lecture Library Taxonomic overview Microascaceae Meiosporic genera: • Microascus • Pseudallescheria • Petriella Mitosporic genera: • Scopulariopsis (asexual relatives of Microascus) • Scedosporium (asexual relatives of Pseudalescheria and Petriella) © by author ESCMID Online Lecture Library Taxonomic overview © by author ESCMID Online Lecture Library Issakainen 2009 Taxonomic overview © by author ESCMID Online Lecture Library Issakainen 2009 Taxonomic overview New trends in Pseudalescheria taxonomy • The former single species – Pseudallescheria boydii has become P. boydii complex or P. boydii© sensuby author lato. • P. boydii complex comprise: P. angusta, P. boydii sensu stricto, P. desertorum, P. ellipsoidea, P. fusoidea, P. minutispora, ScedosporiumESCMID apiospermum Online, S. Lecture aurantiacum Library, and S. dehoogii. Zeng et al. 2007, Med Mycol. Gilgado et al. 2009, Med Mycol. Taxonomic overview New trends in Pseudalescheria taxonomy © by author • P. boydii and S. apiospermum, traditionally considered as the teleomorph and anamorph of the same species, belong to two different species.ESCMID Online Lecture Library Gilgado et al. 2008, JCM Taxonomic overview © by author ESCMID Online Lecture Library Gilgado et al. 2009, Med Mycol. Taxonomic overview • Scedosporium prolificans is not related to P. boydii complex, but to Petriella genus. • This species is homogenous from genetic point of view and is encountered only in its asexual stage. © by author Issakainen et al. 1999, Mycol Res. Gilgado et al. 2008, JCM ESCMID Online Lecture Library Ecology • Pseudallescheria and Scedosporium species prefer human impacted environments such as agricultural and garden soil, sewage, polluted ponds and sediments (outdoor pathogens) • Hydrocarbon-contaminated soil was reported as a source of these fungi • P. boydii was isolated from brackish and salty water, oceanic estuaria, marine soil • These species are more abundant in soils containing high levels of ammonium and humic compounds • The proportion of S. dehoogii increases with the degree of human impact, whereas S. apiospermum is more abundant in agricultural soils, parks and© playgrounds by author than in industrial area. • S. prolificans can be a nosocomial pathogen in some hospitals (air-borne, catheter-related) ESCMID Online Lecture Library Taxonomic overview Thermoascaceae Meiosporic genera: • Thermoascus Mitosporic genera: • Paecilomyces (asexual relatives of Thermoascus) © by author ESCMID Online Lecture Library Taxonomic overview Thermoascaceae Most important species • Thermoascus crustaceus (Paecilomyces crustaceus) • Thermoascus taitungiacus (Paecilomyces taitungiacus) • Paecilomyces variotii • Paecilomyces lilacinus • Paecilomyces marquandii • Paecilomyces viridis • Paecilomyces javanicus © by author ESCMID Online Lecture Library Taxonomic overview Thermoascaceae • Paecilomyces variotii and its thermophilic relatives belong to the order Eurotiales (Trichocomaceae) • Mesophilic species related to Paecilomyces farinosus are in the order Hypocreales© by author ( Clavicipitaceae and Hypocreaceae). Luangsa et al. 2004, Mycologia ESCMID Online Lecture Library Ecology • Saprobic species commonly isolated from soil and a wide range of substrata, such as plants, animals, food products, air and indoor environment, and also from insects. • Two sections: Section Paecilomyces containing mostly thermotolerant to thermophilic taxa and Section Isarioidea containing mostly mesophilic species isolated from insects. • Some species can also grow above the body temperature of higher animals hence are potential human pathogens. • Some iatrogenic infections© by authorreported (an outbreak of 12 patients associated with the use of an contaminated antiseptic solution in an IC setting) ESCMID Online Lecture LibraryLuangsa et al. 2004, Nat. Sci. Orth et al. 1996, Ann Intern Med. Clinical findings The Microascaceae as human pathogens Pseudallescheria Eumycetoma • A cronic, granulomatous, subcutaneous infection which is most common in the hot, arid areas of the world, but occurring also in the temperate Europe and USA because of an important cold-resistance exhibited by P. boydii. • Characteristic symptoms include painless swelling of the limbs after a soil- contaminated splinter of wood penetrate in the foot or hand. • The lesions mainly remain local but may slowly spread to adjacent tissues, including bones © by author • From the lesions (sometimes striking and invalidating deformities) is excreted a pus containing visible granules which consist of densely packedESCMID cells of theOnline causative Lecture Library organism. emedicine.medscape.com Clinical findings The Microascaceae as human pathogens Pseudallescheria Other superficial infections • Skin infections other than mycetoma – painless subcutaneous nodules with serous contents, ulcerating or granulomatous masses, tinea-like interdigital maceration, papulo-bullous lesions • Eye infections – keratitis or even endophtalmitis after an injury of the eye surface with an contaminated foreign body (immunocompetent patients) or secondary to life-threatening, generalized infections through disemination (immunosupressed patients) • Ear infections – relatively benign© by authorand remain localized (chronic otitis) • Paranasal sinusitis – fungal ball (a spherule consisting of densely packed hyphae) due to P. boydii; rarely, the infection may gradually extendESCMID to the adjacentOnline Lecture bones and Library to the brain. Guarro et al. 2006 Issakainen 2009 Clinical findings The Microascaceae as human pathogens Pseudallescheria Infections of the lower respiratory tract • P. boydii usually is found as a colonizer of the lower airways • Colonization may proceed to the formation of a fungus ball – a compact spherule of densely packed hyphae measuring up to several centimeters • When special conditions occur (cystic fibrosis, long-term corticosteroid therapy), the fungus may spread in the lungs, thus leading to pneumonia. • P. boydii pneumonia is associated with a variety of symptoms including impaired respiratory functions and hemoptysis (half of cases were fatal) • In immunosuppressed patients, Pseudallescheria may disseminate from lungs to other organs (especially central nervous system) producing a disseminated infection with a poor prognosis. • For S. prolificans too, lungs are the© main by portalauthor of entry. • In patients with hematological malignancy or receiving immunosuppressive therapy, the fungus rapidly spread from lungs to virtually any organ, resulting in a fatal, disseminated infection • Rarely, relative ESCMIDbenign cases withOnline cough Lecture and fever occurLibrary (transient colonization) Issakainen 2009 Clinical findings The Microascaceae as human pathogens Pseudallescheria Infections of the central nervous system • P. boydii has a marked predilection for the nervous system, even in basically healthy person while for S. prolificans, the nervous system is merely an organ among the others which are affected during the typically generalized infections • Neural pseudallescheriasis often© starts by authorfrom near- drowning incidences of otherwise healthy people; other risk factors include general immunosuppression and various trauma, including surgicalESCMID Onlinetreatments Lecture ofLibrary Issakainen 2009 immunocompetent persons Gelabert-Gonzales 2010, Neurocirurgia Clinical findings The Microascaceae as human pathogens Pseudallescheria Infections of the central nervous system • Single or multiple brain abscesses are the most common phenomena during such infections • The symptoms are variable and include headache, facial paresis, neck stiffness, altered mental status, seizures, and infarcts. CSF typically has a high© count by author of white blood cells • Poor prognosis – the mortality rate is very high (80-90%) ESCMID Online Lecture Library Issakainen 2009 Caggiano 2011, Mycopathol. Clinical findings The Microascaceae as human pathogens Pseudallescheria Infections of the central nervous system • In S. prolificans infections, the involvement of the brain is just a part of the patient’s life-threatening situation. • Usually, the patient
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