A Repertoire of Clinical Non-Dermatophytes Moulds

Humans are constantly exposed to micromycetes, especially filamentous fungi that are ubiquitous in the environment. In the presence of risk factors, mostly related to an alteration of immunity, the non-dermatophyte fungi can then become opportunistic pathogens, causing superficial, deep or disseminated infections. With new molecular tools applied to medical mycology and revisions in taxonomy, the number of fungi described in humans is rising. Some rare species are emerging, and others more frequent are increasing. The aim of this review is to (i) inventory the filamentous fungi found in humans and (ii) provide details on the anatomical sites where they have been identified and the semiology of infections. Among the 239,890 fungi taxa and corresponding synonyms, if any, retrieved from the Mycobank and NCBI Taxonomy databases, we were able to identify 565 moulds in humans. These filamentous fungi were identified in one or more anatomical sites. From a clinical point of view, this review allows us to realize that some uncommon fungi isolated in non-sterile sites may be involved in invasive infections. It may present a first step in the understanding of the pathogenicity of filamentous fungi and the interpretation of the results obtained with the new molecular diagnostic tools.


Introduction
It is estimated that there are between 1.5 and 5 million fungal species on Earth, and about 100,000 species are currently described [1,2]. Of these species, only a few hundred have the capacity to infect humans [3]. Humans are constantly exposed to potential fungal pathogens, as they are part of their normal flora and that of soil, water and air [3]. Moulds are a part of the vast kingdom of fungi alongside yeasts, mushrooms, polypores, plant parasitic rusts and smuts, microsporidia and Pneumocystis. Filamentous fungi are ubiquitous in the environment and can lead to opportunistic diseases presenting as superficial, invasive or disseminated infections. The number of described species is constantly increasing, probably due to the popularisation of DNA-based diagnostic tools, which now allow the distinction between close taxa and the identification of fungi, even in small quantities [1,4]. The taxonomy of fungi is also in constant evolution with the "one fungus, one name" nomenclature and integrative taxonomy approach combining genomics, morphology and ecology [1,5]. In recent years, epidemiological changes in invasive fungal diseases have been observed, new risk factors have emerged, and the number of patients at risk of developing these infections is also increasing [6,7]. Medical mycology is, therefore, a constantly evolving dynamic. Aspergillus, Penicillium, mucorales and dematiaceous fungi are the main filamentous fungi taxa involved in human diseases. Current reviews mainly focused on these taxa [3,8,9]. However, other, rarer species of moulds can emerge in specific infection 2 of 69 sites, such as Paecilomyces variotii or Purpureocillium lilacinum in sino-pulmonary fungal infections, and should not be overlooked [10].
In this review, we offer an overview, as of 16 June 2020, of the filamentous fungi identified in humans by culture and nucleotide analyses associated or not with histopathology. We also provide information on the organs where these micromycetes are isolated and on the semiology of the infections. We have chosen to divide our review into two approaches. First, we describe the taxa of interest and indicate their preferred site of infection. We then described which filamentous fungi were involved at each major anatomical site.

Systematic Literature Review and Database Creation
First, all fungi names and synonyms were collected on both Mycobank (https:// www.mycobank.org/, accessed on 15 November 2019) and NCBI Taxonomy (https:// www.ncbi.nlm.nih.gov/taxonomy, accessed on 15 November 2019) that represent the state of the art of taxonomy of microfungi, updated on 15 November 2019. From Mycobank, the downloaded fungi taxon names and synonyms were provided in the worksheet https://www.MycoBank.org/images/MBList.zip accessed on 15 November 2019. From NCBI Taxonomy, the query used was Fungi[subtree] AND species[rank] AND specified [prop]. Python script using the Biopython package [11] was also implemented to fetch synonyms from NCBI Taxonomy. We have aggregated and deduplicated these two fungi name listings in order to obtain a single list of 239,890 fungi taxa and corresponding synonyms, if any ( Figure 1). For each fungus name in the list, we used a Python script and Biopython package [11] to query PubMed to find bibliographic references that mention the fungi name or its synonyms associated with the term "human" in the article title (TI), abstract (AB), author-supplied keywords (Other Term (OT)) or the Medical Subject Headings' (MeSH) terms. The syntax of the queries was dynamically built using this pattern (fungi_name_or_synonyms [

Manual Database Incrementation
In the MS Access database (MS Access 2013 TM, Microsoft), each of the 7428 fungi had a record from a page linked to the PubMed-relevant references. For each PubMed reference, an analysis of the title and/or abstract and/or whole paper was performed manually to ensure that it was isolated from humans. This process was time-consuming. Only

Fungal Location by Focusing on the Predominant Genus
In total, 6913 articles/PMIDs were included. This bibliographical research identified 565 fungal species of 192 genera, which had been reported at least once in humans. The list of theses taxa is detailed in Table 1, with their former and current scientific name, if applicable. Briefly, there were 204 dematiaceous fungi, 81 Aspergillus spp., 25 Penicillium spp., 35 Fusarium spp., 45 mucorales, 14 of to the Scedosporium/Lomentospora complex, and 161 to other mould species distributed in 103 genera. The results obtained for each of these taxa will be presented below. Regarding the publications reporting the isolation of these micromycetes at all anatomical sites (a publication can be counted multiple times due to the possible report of multiple anatomical sites in the same publication), the leading genus was Aspergillus (total: 4401). The Fumigati and Flavi sections were the most recorded into this genus (total: 2671 and 865, respectively). In second place come the dematiaceous fungi (total: 1976), followed by the Scedosporium/Lomentospora complex (total: 1222), mucorales (total: 1089) and Fusarium (total: 713). Penicillium was rarely reported in human infections (total: 163).

Aspergillus
Aspergillus species were the most frequent moulds isolated in human clinical samples. In this repertoire, the 81 Aspergillus species identified at least once in humans belong to 14 sections of the 20 described [19], as follows: Aspergillus, Candidi, Circumdati, Clavati, Cremei, Flavi, Flavipedes, Fumigati, Nidulantes, Nigri, Polypaecilum, Restricti, Terrei and Usti. As reported in the literature, the filamentous fungus mostly isolated from humans is Aspergillus fumigatus [20], followed by Aspergillus flavus, Aspergillus niger and Aspergillus terreus. The lung and respiratory tracts were the most common anatomical sites of infection, with a total of 1180 publications for A. fumigatus, 174 for A. flavus, 102 for A. niger and 81 publications for A. terreus. These fungi are indeed ubiquitous in the environment and are transmitted by the airways [21]. The results will be approached in terms of the Aspergillus section to rule out potential misidentifications related to morphological identification [4]. The anatomical site in the second position and concerning all the sections was the skin system. Cutaneous aspergillosis can be primary and can affect immunocompetent patients or can be secondary in cases of disseminated infection, predominantly in immunosuppressed patients [22][23][24]. The Nigri section has a tropism for the auditory system, with 79 publications, which has already been noted in the literature [25]. Regarding the clinical presentations involving the central nervous system or heart, the Fumigati section was predominantly represented (194 and 118 publications, respectively). The Fumigati, Flavi and Nigri sections had a predominantly ocular involvement, with 140, 93, and 36 publications, respectively.

Fusarium
The genus Fusarium includes at least 200 species, grouped into about ten phylogenetic species complexes [15,16,26]. In this review of the literature, only eight species complexes were found to have been isolated from humans: F. chlamydosporum species complex (FCSC), F. dimerum species complex (FDSC), F. incarnatum-F. equiseti species complex (FIESC), F. oxysporum species complex (FOSC), F. sambucinum species complex (FSAMSC), F. solani species complex (FSSC), F. fujikuroi species complex (FFSC) and Gibberella fujikuroi species complex (GFSC). Interestingly, looking at the Fusarium genus as a whole, three anatomical sites stand out: the ocular system (190 publications), the cutaneous system (233 publications) and systemic involvement (134 publications). This is consistent with the data in the literature reporting superficial cases, mainly keratitis and onychomycosis in immunocompromised or immunocompromised patients and disseminated infections in immunocompromised patients [27][28][29][30]. Species belonging to the FSSC are predominantly represented, which has previously been shown to be the most virulent Fusarium species complex in animal models [31].

Penicillium
The genus Penicillium is ubiquitous in the environment and is rarely involved in human infections. When found in superficial and aerial samples, they are often considered contaminants. In this literature review, only 163 publications reporting the isolation of these hyaline hyphomycetes in humans were found. One species has emerged since the 1990s and mainly affects humans with acquired immunodeficiency syndrome (AIDS): Talaromyces marneffei [32,33], and this is the predominant species within the genus Penicillium representing 54% of the publications (89/164). The members of the genus Penicillium are mostly reported in three anatomical sites: the pulmonary sphere (48 publications), the cutaneous system (23 publications) and systemic involvement (36 publications).

Mucorales
The order of the mucorales (previously Zygomyces) includes the hyaline pauciseptated filamentous fungi group, comprising 13 genera: Mucor, Lichtheimia, Rhizomucor, Rhizopus, Absidia, Syncephalastrum, Cunninghamella, Apophysomyces, Mycocladus, Saksenaea, Actinomucor, Thamnostylum and Thermomucor. All of these are implicated in human infections [34]. In this literature review, Rhizopus was the genus mostly involved in human infections, with Rhizopus oryzae (121 publications) (plus its synonym and current appellation Rhizopus arrhizus (53 publications)) leading the way, followed by Rhizopus microsporus (90 publications). Mucorales can be classified according to the primary route of infection: airborne, direct contact with contaminated devices or by trauma [34,35]. Here, we compare the number of publications reporting isolation in the skin system versus the respiratory system, including from the oto-rhino-laryngological sphere and pulmonary sphere: The genera Apophysomyces (54 versus 26 publications, respectively), Mucor (40 versus 18 publications, respectively) and Saksenaea (45 versus eight publications, respectively) are mostly isolated from the skin system and therefore transmitted by contact; the genera Cunninghamella (12 versus 52 publications, respectively), Rhizopus (75 versus 134 publications, respectively) and Rhizomucor (8 versus 31 publications, respectively) are mostly isolated from the otorhino-laryngological sphere and pulmonary system and are, therefore, airborne; finally, Lichtheimia (77 versus 74 publications, respectively) had a less obvious tropism for one or the other of these two systems. The cutaneous or respiratory tropism can be explained by the differences found in the sporangia of these genera [35]. In fact, the wet spores of the Mucor, Apophysomyces and Saksenaea species are probably not primarily dispersed by the air and transmitted by trauma [35,36]. On the contrary, the sporangiospores of Rhizopus and Rhizomucor species are small (less than 4 µm in diameter), dry and therefore easily airborne [37,38]. This morphological hypothesis does not explain everything because, similar to Mucor, Lichteimia have wet spores and yet they are equivalently reported in the lung and skin in this review.

Dematiaceous moulds
Dematiaceous fungi are also known as "black fungi" due to the predominance of melanin in their cell walls, which likely acts as a virulence factor. These darkly pigmented fungi are found on the soil surface, where they live as saprophytes but also sometimes as parasites of plants [39]. This review has highlighted 204 dematiaceous fungi species isolated from humans, belonging to 19 genera: Alternaria, Exophiala, Cladophialophora, Scopulariopsis, Curvularia, Phialemoniopsis, Phialemonium, Exserohilum, Microascus, Bipolaris, Chaetomium, Cladosporium, Ochroconis, Phaeoacremonium, Rhinocladiella, Fonsecaea, Phialophora, Phoma and Madurella. The genus Exophiala is the most represented. Contamination most often takes place through infection of a wound by a telluric strain or during a transcutaneous traumatism by means of a plant [40]. This explains the predominantly cutaneous location found in this review (1043 publications). Among the cutaneous affections, melanised fungi are responsible for chromoblastomycosis, which mainly affect individuals performing soilrelated tasks [41], phaeohyphomycosis [42] and eumycotic myetoma [43]. Two synonyms species stand out for their tropism for the central nervous system, Cladiophialophora bantiana and Cladosporium trichoides, for which 51 publications and 30 publications, respectively, were found in this location.

Pseudallescheria/Scedosporium Species Complex (PSC)
Among the PSC, six genera were represented: Allescheria, Lomentospora, Monosporium, Petriellidium, Pseudallescheria and Scedosporium. These fungi are ubiquitous in the environment and can be found in soil, compost and polluted water [44]. Regarding current nomenclature and taxonomy, the Pseudallescheria/Scedosporium species complex includes the three major species isolated from humans: Scedosporium apiospermum, Scedosporium boydii, and Lomentospora prolificans, and four distinct species, namely Scedosporium aurantiacum (29 publications), Scedosporium dehoogii (2 publications), Scedosporium inflatum (86 publications) and Scedosporium minutisporum (1 publication) [45]. By grouping the publications concerning the main species and their synonyms, we find 468 publications reporting the isolation of Scedosporium apiospermum, 275 publications reporting the isolation of Scedosporium boydii and 261 publications concerning the isolation of Lomentospora prolificans in humans. In regard to locations, S. boydii and S. apiospermum are found in all anatomical sites, with a greater prevalence in the pulmonary sphere (72 and 94 publications, respectively) and the cutaneous system (79 and 110 publications, respectively). Scedosporium prolificans is mainly found in the pulmonary sphere (56 publications) and in systemic infections (52 publications).

Fungal Location by Focusing on the Anatomical Site
Within the 19 anatomical sites, the semiology of infection was detailed for the six major categories of fungi involved in human pathologies ( Table 2).      Regarding systemic localisation (comprising fungaemia, aortitis, vasculitis, lymph node infection and bone marrow infection), there is a large majority of fungaemias. The genus Aspergillus was predominantly isolated from blood samples, with Aspergillus fumigatus and Aspergillus flavus predominating (Figure 2). It should be noted that the genus Fusarium was in second place with Fusarium solani. Aspergillus is rarely isolated from blood cultures and is usually in the case of infective endocarditis. This predominance of Aspergillus detection in systemic infections is explained by the use of new detection tools, including PCR.

Central Nervous System
Three genera are mostly represented in central nervous system infections: Aspergillus, dematiaceous fungi and Pseudallescheria/Scedosporium species complex (Figure 3). The majority of infections occur as brain abscesses or meningitis. Figure 2 highlights several species of dematiaceous fungi. Exserohilum rostratum has been involved in iatrogenic meningitis outbreaks secondary to the use of contaminated injectable corticosteroids [46][47][48][49][50][51]. Cladophialophora bantiana is a dematiaceous mould that may infect immunocompetent patients (mainly farmers or residents of agricultural regions), whose reservoirs and modes

Central Nervous System
Three genera are mostly represented in central nervous system infections: Aspergillus, dematiaceous fungi and Pseudallescheria/Scedosporium species complex (Figure 3). The majority of infections occur as brain abscesses or meningitis. Figure 2 highlights several species of dematiaceous fungi. Exserohilum rostratum has been involved in iatrogenic meningitis outbreaks secondary to the use of contaminated injectable corticosteroids [46][47][48][49][50][51].
Cladophialophora bantiana is a dematiaceous mould that may infect immunocompetent patients (mainly farmers or residents of agricultural regions), whose reservoirs and modes of transmission are still poorly known [52]. Its neurotropism is highlighted by 51 publications concerning the CNS among a total of 84 in this review. Its synonym, Cladosporium trichoides, causes brain abscesses for which we have recovered 30 publications. Both are responsible for 81 publications reporting CNS involvement.

Ocular System
All categories of fungi can cause ocular damage. Indeed, as filamentous fungi are ubiquitous in the environment, this type of infection is frequently observed during inju ries with plants. The genera Aspergillus with Aspergillus fumigatus, Aspergillus flavus, As

Auditory System
The genus Aspergillus is predominantly isolated from the auditory system, with As pergillus niger in the lead, a member of the Nigri section known for its tropism for the auditory meatus [25]. Aspergillus flavus and Aspergillus fumigatus come in second place ( Figure 5). These fungi are responsible for fungal otomycosis in the majority of cases [53] Interestingly, 29 publications reported the identification of Pseudallescheria/Scedosporium complex in the auditory system, including 18 reporting otomycosis. Scedosporium apiosper mum was predominant, with ten publications reporting otomycosis, including two cases of malignant otitis externa [54,55] and one otitis complicated with temporomandibular arthritis [56]. Other species stand out in Figure 4, such as Absidia corymbifera, of which five publications report the involvement in otomycosis, including one case of malignant otitis externa [57] and a few cases of Penicillium otomycosis (six publications).

Auditory System
The genus Aspergillus is predominantly isolated from the auditory system, with Aspergillus niger in the lead, a member of the Nigri section known for its tropism for the auditory meatus [25]. Aspergillus flavus and Aspergillus fumigatus come in second place ( Figure 5). These fungi are responsible for fungal otomycosis in the majority of cases [53]. Interestingly, 29 publications reported the identification of Pseudallescheria/Scedosporium complex in the auditory system, including 18 reporting otomycosis. Scedosporium apiospermum was predominant, with ten publications reporting otomycosis, including two cases of malignant otitis externa [54,55] and one otitis complicated with temporomandibular arthritis [56]. Other species stand out in Figure 4, such as Absidia corymbifera, of which five publications report the involvement in otomycosis, including one case of malignant otitis externa [57] and a few cases of Penicillium otomycosis (six publications).

Oto-Rhino-Laryngeal System
It is not surprising that a majority of aspergillosis rhinosinusitis is recorded (282 publications) ( Figure 6). This anatomical site also includes rhino-orbital, rhino-facial and rhino-orbito-cerebral involvement, which explains the strong representation of mucorales (170 publications). Rhizopus oryzae (heterotypic synonym Rhizopus arrhizus) is largely in Figure 5. Wordcloud represents the species name isolated in the auditory system. The size of the name of each species is proportional to the number of times it occurs in the repertoire.

Oto-Rhino-Laryngeal System
It is not surprising that a majority of aspergillosis rhinosinusitis is recorded (282 publications) ( Figure 6). This anatomical site also includes rhino-orbital, rhino-facial and rhino-orbitocerebral involvement, which explains the strong representation of mucorales (170 publications). Rhizopus oryzae (heterotypic synonym Rhizopus arrhizus) is largely in the majority of the mucorales (38 publications), which is not surprising, given that it is the most common mucorale species worldwide [58]. Rhizopus oryzae is responsible for variable oto-rhinolaryngeal system infections, with a majority of rhino-orbito-cerebral infections (17 publications) followed by rhino-sinusitis (nine publications) and rhino-orbital involvement (seven publications). These rhino-orbito-cerebral lesions can also be caused by Aspergillus fumigatus (16 publications) and two other species of mucorales Rhizopus arrhizus (12 publications) and Apophysomyces elegans (11 publications). One fungus stands out, Conidiobolus coronatus, which is responsible for entomophthoromycosis and rhino-facial infections. C. coronatus is a widely distributed insect pathogenic fungus belonging to the class Zygomycetes and is rarely involved in human pathology. This mycosis is mainly tropical due to its tropism of plant detritus in very humid environments [59].
J. Fungi 2023, 9, x FOR PEER REVIEW 50 of 67 most common mucorale species worldwide [58]. Rhizopus oryzae is responsible for variable oto-rhino-laryngeal system infections, with a majority of rhino-orbito-cerebral infections (17 publications) followed by rhino-sinusitis (nine publications) and rhino-orbital involvement (seven publications). These rhino-orbito-cerebral lesions can also be caused by Aspergillus fumigatus (16 publications) and two other species of mucorales Rhizopus arrhizus (12 publications) and Apophysomyces elegans (11 publications). One fungus stands out, Conidiobolus coronatus, which is responsible for entomophthoromycosis and rhino-facial infections. C. coronatus is a widely distributed insect pathogenic fungus belonging to the class Zygomycetes and is rarely involved in human pathology. This mycosis is mainly tropical due to its tropism of plant detritus in very humid environments [59]. 3.2.6. Pulmonary System The respiratory system is the anatomical site most affected by fungal infections (4496 publications). It should be noted that no distinction was made between colonisation and allergic bronchopulmonary aspergillosis, which thus includes the respiratory isolation of Aspergillus species. Similar to Aspergilli, moulds are ubiquitous saprophytes in the envi-

Pulmonary System
The respiratory system is the anatomical site most affected by fungal infections (4496 publications). It should be noted that no distinction was made between colonisation and allergic bronchopulmonary aspergillosis, which thus includes the respiratory isolation of Aspergillus species. Similar to Aspergilli, moulds are ubiquitous saprophytes in the environment. Their dispersion in the air is possible by the production of volatile spores, which ensures their presence in both indoor and outdoor environments [60,61]. Human contamination thus mainly occurs by inhaling the airborne conidia, with the lungs being the first to be exposed. We, therefore, note a wide variety of moulds responsible for lung damage (Figure 7).

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ensures their presence in both indoor and outdoor environments [60,61]. Human contamination thus mainly occurs by inhaling the airborne conidia, with the lungs being the first to be exposed. We, therefore, note a wide variety of moulds responsible for lung damage (Figure 7).

Cardiac Involvement
Cardiac involvement was found among 13% (74/565) of the species described in this repertoire. These species belonged to the major taxa Aspergillus, Penicillium, Fusarium, mucorales, dematiaceous fungi and Scedosporium/Lomentospora complex, as well as the genera Acremonium sp, Arthrographis sp., Conidiobolus sp., Emericella sp., Engyodontium sp., Paecilomyces sp., Purpureocillium sp., Pythium sp., Rasamsonia sp., Thermothelomyces sp. and Trichoderma sp., with Aspergillus fumigatus being the most common species isolated ( Figure 8). These infections are, however, rare with species belonging to the genus Penicillium, including only three publications (one endocarditis due to Penicillium chrysogenum [62] and two pericarditis due to P. citrinum and P. rubens [63,64]) being reported. Cardiac involvement was mainly in the form of endocarditis, whether native (105 publications) or on a prosthetic valve or implanted equipment (96 publications). Interestingly, in native valve endocarditis, mitral involvement seems to be the most frequent (41 publications) ( Table 3). Pericarditis and myocarditis were described in 37 and 49 publications, respectively.   Figure 8. Wordcloud represents the species name isolated in the cardiac system. The size of the name of each species is proportional to the number of times it occurs in the repertoire.
J. Fungi 2023, 9, x FOR PEER REVIEW Figure 9. Wordcloud represents the species name isolated in the digestive system. Th name of each species is proportional to the number of times it occurs in the repertoire.

Liver Involvement
In terms of hepatic involvement (Figure 10), there is great variability in found, including abscesses, hepatitis, ascites and lesions secondary to hematog semination ( Table 2). The genus Aspergillus is mostly represented (41 publicatio predominance of Aspergillus fumigatus and Aspergillus flavus. Invasive bowel infections by Aspergillus and mucorales (14 and 9 publications, respectively) are mainly reported concomitantly with disseminated infection. Invasion of the gastrointestinal tract is rarely described individually [183].
Splenic involvement was, in the majority of cases, secondary to haematogenous dissemination of the pathogen, with the exception of three situations where splenic abscesses were described. One case of a splenic abscess caused by Aureobasidium pullulans in a patient with lymphoma [184] and one caused by Hortaea werneckii in a patient with acute myeloid leukaemia [185] were both diagnosed postmortem. The third case of splenic abscess caused by Paecilomyces variotii was described in a child with chronic granulomatous disease [186].

Liver Involvement
In terms of hepatic involvement (Figure 10), there is great variability in the forms found, including abscesses, hepatitis, ascites and lesions secondary to hematogenous dissemination ( Table 2). The genus Aspergillus is mostly represented (41 publications) with a predominance of Aspergillus fumigatus and Aspergillus flavus.

Liver Involvement
In terms of hepatic involvement (Figure 10), there is great variability in the forms found, including abscesses, hepatitis, ascites and lesions secondary to hematogenous dissemination ( Table 2). The genus Aspergillus is mostly represented (41 publications) with a predominance of Aspergillus fumigatus and Aspergillus flavus.

Urinary Tract
In terms of urinary tract involvement (Figure 11), the vast majority of infections are renal (185 publications), with a predominance of the genus Aspergillus (85 publications). These infections may be primary or secondary to the haematogenous dissemination of the fungus.

Endocrine Glands
Among the endocrine glands, the thyroid is the most frequently affected (66 publications/84). In the majority of cases, the disease is secondary to systemic dissemination of the pathogen, diagnosed postmortem [188]. In fact, infiltration of the thyroid with Asper- Figure 13. Wordcloud represents the species name isolated in the skin system. The size of the name of each species is proportional to the number of times it occurs in the repertoire.

Endocrine Glands
Among the endocrine glands, the thyroid is the most frequently affected (66 publications/84). In the majority of cases, the disease is secondary to systemic dissemination of the pathogen, diagnosed postmortem [188]. In fact, infiltration of the thyroid with Aspergillus organisms occurs in approximately 20% of autopsies in patients dying from a disseminated disease [189]. However, a few rare cases of primary thyroid infections have been reported with Aspergillus fumigatus: two cases of thyroid suppuration in lupus patients treated with corticosteroids [190,191], two cases described in HIV patients [192,193] and one case in a child with chronic granulomatous disease [194]. Scedosporium apiospermum was reported to cause multiple thyroid abscesses in a patient with cirrhosis and autoimmune haemolytic anaemia, presenting swelling in the neck [195].

Rarely Involved Anatomical Sites
Dental location: Endodontic infections were rarely found in this review and manifested themselves in the form of root involvement [196,197], granuloma [198,199] or gingival infections [200,201]. No species seemed to have a particular tropism for this sphere.
Genital sphere: Interestingly, the male genital sphere seems to be mostly affected, with 71.4% of the publications (15/21) reporting testicular, epididymal or glans involvement. Only three publications reported vaginitis [202][203][204], two reported labial involvement [190,205] and one tubo-ovarian abscess [206]. No species seemed to have a particular tropism for this sphere.
Breast: A majority of Aspergillus was isolated from this particular site. It should be noted that the Aspergillus glaucus and Aspergillus niger complexes have already been isolated from milk samples [207,208]. Interestingly, four publications reported fungal infections following breast implant surgery, a situation that is not well-known in this field, due to Aspergillus niger [209,210], Paecilomyces variotii [211] and Scedosporium apiospermum [212].
Placental infection: a single case of placental aspergillosis due to Aspergillus niger was found in this literature review [213].

Discussion
The aim of this study was to establish as exhaustive a catalogue as possible of filamentous fungi identified in humans by culture and molecular biology, whether or not they were associated with histopathological findings. We found 565 filamentous fungi identified in humans, for which we specified the organs where these fungi had been found and the semiology of the infections. This repertoire thus helps to understand the pathogenic potential of certain fungi and can also alert clinicians that the isolation of certain rare fungi, such as Trichoderma longibrachiatum (from stool specimens), can lead to disseminated infection. One of the limitations of this work, however, is the lack of distinction between colonisation and infection, mainly for fungi isolated from non-sterile sites (i.e., the cutaneous system, pulmonary system, digestive system and ENT sphere). Fungi isolated from sterile sites were considered infections (i.e., the heart, liver and ocular system and CNS). The use of new powerful molecular tools, such as pan-fungal PCR, metagenomic and next-generation sequencing, now means it is possible to detect pathogens even in samples containing extremely low levels of nucleic acids [214,215] and to diagnose mixed infections [216]. However, the application of these tools to medical mycology can lead to interpretation difficulties [217][218][219]. This problem is particularly encountered with filamentous fungi, which are ubiquitous in the environment and for which it is sometimes difficult to distinguish between colonisation, infection and environmental contamination. It is now necessary to go further in our work for each anatomical site in order to distinguish colonisations from infections, in order to help clinicians interpret positive results and to assist with the diagnostic management of patients. Similarly, we did not distinguish between diagnosis by molecular biology and macroscopic identification, although it has been shown that potential errors were found in macroscopic identifications, mostly between close species within a section or species complex [4]. More, even in molecular identification, it was pointed out that 20% of the sequences available in public databases are unreliable [220,221]. We have based our repertoire according to state of the art at the time of reported publications. Therefore, in Table 1, we have chosen to group species by sections, sharing morphological similarities, in order to bypass this limitation.
Finally, one of the limitations of this publication is its temporality. As explained in Section 2, only references present in PubMed before 16 June 2020 were taken into account in order to have the same PubMed content for all fungi species. However, medical mycology is dynamic, and new organisms constantly need to be accounted for by both clinicians and microbiology laboratories [222]. Moreover, with the COVID-19 pandemic, a new risk factor has emerged [223]. Publications reporting the detection of filamentous fungi in humans have multiplied, reporting, for example, the emergence of mucormycosis and COVID-19associated pulmonary aspergillosis throughout the world [224,225]. It will therefore be necessary to update this data regularly.

Institutional Review Board Statement:
The study did not require ethical approval.