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Monograph On

Dematiaceous fungi

A guide for description of dematiaceous fungi fungi of

medical importance, diseases caused by them, diagnosis and treatment

By

Mohamed Refai and Heidy Abo El-Yazid

Department of Microbiology, Faculty of Veterinary Medicine, Cairo University

2014

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Preface

The first time I saw cultures of dematiaceous fungi was in the laboratory of Prof. Seeliger in Bonn,

1962, when I attended a practical course on moulds for one week. Then I handled myself several

cultures of black fungi, as contaminants in Mycology Laboratory of Prof. Rieth, 1963-1964, in

Hamburg. When I visited Prof. DE Varies in Baarn, 1963. I was fascinated by the tremendous

number of moulds in the Centraalbureau voor Schimmelcultures, Baarn, Netherlands. On the

other hand, I was proud, that El-Sheikh Mahgoub, a Colleague from Sundan, wrote an

internationally well-known book on mycetoma. I have never seen cases of dematiaceous

fungal infections in Egypt, therefore, I was very happy, when I saw the collection of

mycetoma cases reported in Egypt by the eminent Egyptian Mycologist, Prof. Dr Mohamed

Taha, Zagazig University.

To all these prominent mycologists I dedicate this monograph.

Prof. Dr. Mohamed Refai, 1.5.2014

Heinz Seeliger Heinz Rieth Gerard de Vries,

El-Sheikh Mahgoub Mohamed Taha

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Contents 1. Introduction 4 2. 30. The genus Rhinocladiella 83

2. Description of dematiaceous

fungi

6 2. 31. The genus Scedosporium 86

2. 1. The genus Alternaria 6 2. 32. The genus Scytalidium 89

2.2. The genus Aurobasidium 11 2.33. The genus Stachybotrys 91

2.3. The genus Bipolaris 16 2. 34. The genus Stemphylium 93

2.4. The genus Cladosporium 20 2.35. The genus Ulocladium 94

2.5. The genus Cladophialophora 24 2. 36. The genus Wangiella 96

2.6. The genus Cheatomium 28 2. 37. The genus Xylohypha 98

2.7. The genus Coniothyrium 31 3. Diseases caused by dematiacaeous fungi

99

2.8.The genusParaconiothyrium 32 3. 1. Phaeohyphomycosis 99

2.9. The genus Curvularia 33 3.1.1. Skin infections 99

2.10. The genus Epicoccum 36 3.1.2. Nail infections 103

2.11. The genus Exophiala 38 3.1.3. Eye infections 103

2.12. The genus Drechslera 44 3.1.4. Respiratory phaeohyphomycosis 106

2.13. The genus Exserohilum 45 3.1.5. Central nervous system infection 108 2.14. The genus Fonseceae 47 3.1.6. Disseminated pheohyphomycosis 111 2.15. The genus Hortaea 51 3.2. Chromomycosis 115 2.16. The genus Lasiodiplodia 53 3.3. Mycetoma 118 2.17. The genus Lecythophora 54 4. Dematiaceous fungi in Egypt 120

2.18. The genus Leptosphaeria 56 5. Mycotoxicoses 122

2.19. The genus Madurella 58 5.1. Alternariosis 122

2.20. The genus Myrothecium 61 5.2. Facial eczema (Pithomycotoxicosis) 122

2.21. The genus Nattrassia 62 5.3. Stachybotryotoxicosis 124

2.22.The genus Ochroconis 64

2.23. The genus Phialemonium 67 6. Laboratory diagnosis 125

2.24. The genus Phialophora 69

2. 25. The genus Phoma 73 7. Treatment 126

2.26. The genus Pithomyces 75 Pyrenochaeta2. 27. The genus 76 8. Contamination and deterioration by

dematiaceous fungi 127

2.28. The genus Pythium 79

2. 29. The genus Ramichloridium 81 9. References

133

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1. Introduction The dematiaceous fungi are usually defined as those that have melanin or melanin-like

pigment in the wall of the hyphae and/or spores and can cause a variety of infections in humans known as phaeohyphomycosis (phaeo is Greek for "dark"). Over 100 species and 60 genera of dematiaceous, or pigmented fungi have been implicated in human diseases. The vast majority are filamentous fungi or moulds, though a few yeast species are also important pathogens. Though they represent a very heterogeneous group of fungi, the distinguishing characteristic common to all these various species is the presence of melanin in their cell walls, which imparts the dark colour to their conidia or spores and hyphae. The colonies are typically brown to black in colour as well. Dematiaceous fungi are generally found in soil or associated with plants and distributed worldwide. Those causing the specific conditions of mycetoma and chromoblastomycosis are primarily found in tropical regions. Exposure is thought to be from inhalation or minor trauma, which may not even be noticed by the patient.

The taxonomy and nomenclature of dematiaceous fungi undergo constant revision and

are controversial. Thus, a single organism may be identified by a variety of names in

the recent and historical literature, a circumstance that contributes to confusion for

clinicians and for all but the most dedicated mycologists. This monograph does not

attempt to deal definitively with the difficult questions of mycological classification

and nomenclature of dematiaceous fungi, but alternative names or appropriate

synonyms will be given in each case. Identification of these fungi is based mostly

upon morphology. Important structures include annellides (Phaeoannellomyces,

Exophiala), phialides (Phialophora, Wangiella), adelophialides (Phialemonium

without collarettes, Lecythophora with collarettes), differentiation of conidiophores

(Cladosporium) and conidial hilum, septation and germination (Bipolaris, Drechslera,

Exserohilum).

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A variety of infectious syndromes are attributed to dematiaceous fungi Two unique conditions, mycetoma and chromoblastomycosis, are caused by a small number of species and are usually seen in tropical regions.

Mycetoma is commonly associated with chronic swelling and draining sinus tracts, usually of the lower extremities. It can be debilitating and difficult to treat.

Chromoblastomycosis often presents with verrucous lesions that may occur anywhere on the body, but usually on the lower extremities. This is a chronic, slowly progressive subcutaneous mycosis. Minor trauma typically precedes the lesions. Initially, nodular lesions are present, which may progress over years to form large, verrucous plaques.

Phaeohyphomycosis is a term that encompasses many clinical syndromes due to a wide variety of fungi. Conditions include superficial infections such as keratitisand subcutaneous nodules, allergic diseases, and invasive infections such as brain abscess and disseminated disease.

Relatively little is known regarding the pathogenic mechanisms by which many of these fungi cause disease, particularly in immunocompetent individuals. One of the likely candidate virulence factors is the presence of melanin in the cell wall, which is common to all dematiaceous fungi. There are several mechanisms proposed by which melanin may act as a virulence factor :

It is thought to confer a protective advantage by scavenging free radicals and hypochlorite that are produced by phagocytic cells in their oxidative burst that would normally kill most organisms.

Melanin may bind to hydrolytic enzymes, thereby preventing their action on the plasma membrane.

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2. Description of dematiaceous fungi of medical importance

2. 1. The genus Alternaria

The genus Alternaria currently contains around 300 species. Alternaria is a wide-spread dematiaceous fungus commonly isolated from plants, soil, food, and indoor air environment.. At least 20% of agricultural spoilage is caused by Alternaria species; most severe losses may reach up to 80% of yield. Many human health disorders can be caused by these fungi, which grow on skin and mucous membranes, including on the eyeballs and within the respiratory tract. Allergies are common, but serious infections are rare, except in people with compromised immune systems. Species of Alternaria are often prolific producers of a variety of toxic compounds. The terms alternariosis and alternariatoxicosis are used for disorders in humans and animals caused by a fungus in this genus.

2.1.1. Alternaria alternata (Fr.) Keissl. (1912) Synonyms: Alternaria tenuis Nees 1917 Macrosporium fasciculatum Cooke & Ellis (1817), Torula alternata Fr. (1832), Alternaria fasciculata Jones & Grout (1897), Alternaria rugosa McAlpine (1896)

Morphology Alternaria species grow rapidly producing flat, downy to woolly colonies, covered by grayish, short, aerial hyphae. The surface is greyish white at the beginning which later darkens and becomes greenish black or olive brown with a light border. Microscopically, the fungus develops septate, brown hyphae. Conidiophores are also septate and brown in colour, occasionally producing a zigzag appearance. They bear simple or branched large conidia, which have both transverse and longitudinal septations (muriform conidia). They are dark in colour, elongated and found in chains. The conidia may be observed singly or in acropetal chains and may produce germ tubes. They are ovoid to obclavate, darkly pigmented, muriform, smooth or roughened. The end of the conidium nearest the conidiophore is round while it tapers towards the apex.

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The species can be divided into three groups according to the number of conidia on the conidiophore:

Noncatenatae with single conidia;

Brevicatenatae with short chains containing three to five conidia;

Longicatenatae with long chains containing 10 spores or more.

Alternaria alternata belongs to the last group.

The microscopic differences between Alternaria species are not significant, and the character of every species varied depending on the conditions of growth. So, the identification of species is very difficult.

Alternaria alternata

A. tenuissima

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A. infectoria

A. triticina

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Pathogenicity :

Alternaria spp. have emerged as opportunistic pathogens particularly in patients with immunosuppression, such as the bone marrow transplant patients They are one of the causative agents of phaeohyphomycosis. Cases of onychomycosis, sinusitis, ulcerated cutaneous infections, and keratitis, as well as visceral infections and osteomyelitis due to Alternaria have been reported. In immunocompetent patients, Alternaria colonizes the paranasal sinuses, leading to chronic hypertrophic sinusitis. In immunocompromised patients the colonization may end up with development of invasive disease. It is among the causative agents of otitis media in agricultural field workers.

1. Allergy

Alternaria is a major aeroallergen in many parts of the world. Sensitivity to Alternaria has been increasingly recognized as a risk factor for the development and persistence of asthma, asthma severity, and potentially fatal asthma exacerbations. Cases with IgE-mediated sensitivity to Alternaria who developed an acute, life-threatening asthma attack were reported. Alternaria alternata is one of the most important fungi that can cause asthma and rhinitis. Not only the intact spores can produce and transfer the allergens, the fragmented hyphae and spores also can transfer the allergens. In the United State, almost 3.6% of the population are sensitive to Alternaria alternata in the skin test. So, the asthma caused by Alternaria alternata is a big problem to human.

2. alternarioses

The published literature contains 210 reported cases of human alternarioses between 1933 and the present day. The most frequent clinical manifestations are :

I. Cutaneous and subcutaneous infections (74.3%). The most important risk factors for cutaneous and subcutaneous infections are solid organ transplantation and Cushing's syndrome,

II. Oculomycosis (9.5%). Exposure to soil and garbage is common in all cases of oculomycosis, with corticotherapy being a risk factor in 50% of these cases.

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III. Invasive and non-invasive rhinosinusitis (8.1%). The most important risk factors for rhinosinusitis are bone marrow transplants.

IV. Immunosuppression is frequently associated with cutaneous and subcutaneous infections and rhinosinusitis.

V. Previous contact with soil and/or trauma to the nails is associated with most cases of onychomycosis.

.

Recently reported cases: 1. Cutaneous alternariosis with chronic granulomatous disease (6)

2. Cutaneous infection with Alternaria triticina in a bilateral lung transplant recipient.7

3. Alternaria alternata infection associated osteomyelitis of maxilla: a rare disease entity.8

4. Corneal transplant infection due to Alternaria alternata: A Case Report.9

5. Deep cutaneous mycosis due to Alternaria infectoria after liver transplantation: successful treatment with fluconazole.10

6. Alternaria alternata invasive fungal infection in a patient with Fanconi's anemia after an unrelated bone marrow transplant.11

7. The importance of genus Alternaria in mycotoxins production and human diseases12

8. Exposure to Alternaria alternata in US homes is associated with asthma symptoms14

9. Phaeohyphomycosis caused by Alternaria infectoria in a renal transplant recipient15

10. Phaeohyphomycoses, Emerging Opportunistic Diseases in Animals16

11. Alternaria infectoria brain abscess in a child with chronic granulomatous disease.17

12. Fungal meningoencephalitis caused by Alternaria: a clinical case.18

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2.2. The genus Aurobasidium

The genus Aureobasidium includes 14 species and one variety. Among these, Aureobasidium pullulans is the only well-known species. Aureobasidum pullulans is a black yeast-like species that is particularly known for its biotechnological significance as a producer of the biodegradable extracellular polysaccharide (EPS) pullulan (poly-α-1,6-maltotriose). This component is a promising biomaterial, and is currently used among others for the packaging of food and drugs. Its biotechnological potential is also seen in the production of a variety of hydrolytic enzymes.

2.2.1. Aureobasidium pullulans (de Bary) G. Arnaud, 1918

Synonyms: Dematium pullulans de Bary 1884) Pullularia pullulans (de Bary) Berkhout (1923) Anthostomella pullulans (de Bary) F.T. Benn (1928) Hormonema pullulans (de Bary) Lagerb. & Melin (1932) Aureobasidium pullulans (De Bary)., Ribaldi & Corte (1957) Phymatotrichum baccarum Oudem (1900) Dematoidium nigrescens Stautz (1931) Perfect stage: Guignardia pullulans

Colonies are fast growing, smooth, covered with slimy masses of conidia, cream or pink to brown or black. Hyphae are hyaline and septate, frequently becoming dark-brown with age and undergoing holothallic transformation to form chains of 1- to 2-celled, thick-walled, darkly pigmented arthroconidia commonly called chlamydoconidia. Conidia are hyaline to sub-hyaline hyphae. Conidia are hyaline, smooth-walled, single-celled, ellipsoidal but of variable shape and size (8-12 x 4-6 um).

Different colonial morphologies of Aurobasidium pullulans

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A. pullulans yeast colonies yeast cells mould phase Mycelium

Aurobasidium pullulans varieties31:

Four varieties of the species A. pullulans with somewhat different ecology are recognised:

1. Aurobasidium pullulans var. pullulans from slightly osmotic substrates and

the phyllosphere;

2. Aurobasidium pullulans var. melanogenum from watery habitats;

3. Aurobasidium pullulans var. subglaciale from glacial habitats; and

4. Aurobasidium pullulans var. namibiae, which was described on the basis of only

one strain isolated from dolomitic marble in Namibia.

1. A. pullulans var. pullulans (Viala & Boyer 1891), Synonyms: Dematium pullulans de Bary 1884 Aureobasidium pullulans (de Bary) Arn. var. aubasidani Yurlova in Yurlova & de Hoog 1997 Candida malicola D.S. Clark & R.H. Wallace 1955 Dematoidium nigrescens Stautz 1931

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2. A. pullulans var. melanogenum Hermanides-Nijhof (1977), Synonyms: Torula schoenii Roukhelman 1937 Pullularia fermentans Wynne & Gott var. schoenii (Roukhelman) Wynne & Gott 1956

3. A. pullulans var. subglaciale Zalar, de Hoog & Gunde-Cimerman (2008)

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4. A. pullulans var. namibiae Zalar, de Hoog & Gunde-Cimerman (2008)

Pathogenecity

Aureobasidium pullulans is capable of causing a variety of diseases in humans. The fungus is most often found in damp places either inside the home or in the environment. Chronic human exposure via humidifiers or air conditioners can lead to hypersensitivity pneumonitis (extrinsic allergic alveolitis) or "humidifier lung". This condition is characterized acutely by dyspnoea, cough, fever, chest infiltrates, and acute inflammatory reaction. The condition can also be chronic, and lymphocyte-mediated. The chronic condition is characterized radiographically by reticulonodular infiltrates in the lung, with apical sparing. It is a rare cause of disease and is more likely to occur in immunosuppressed patients.

The list of signs and symptoms mentioned in various sources

for Aureobasidium pullulans exposure includes the following symptoms: Pneumonia Asthma Dermatitis Keratitis Respiratory system irritation

Digestive symptoms Respiratory symptoms Skin symptoms Urinary symptoms Allergy symptoms Sinusitis Peritonitis Skin infection Fungal infection Hypersensitivity pneumonia

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Cases recently reported 1. Grain dust originating from organic and conventional farming as a potential source of

biological agents causing respiratory diseases in farmers.32

2. Aureobasidium pullulans infection in a patient with chronic lymphocytic leukemia33

3. Multiple rare opportunistic and pathogenic fungi in persistent foot skin infection34

4. Aureobasidium pullulans keratitis35

5. Outbreak of hypersensitivity pneumonitis in an industrial setting36

6. Extended fungal skin infection due to Aureobasidium pullulans.37

7. Sauna takers disease in Indoor Allergens: Assessing and Controlling Adverse Health Effects.38

8. Association between sensitization to Aureobasidium pullulans (Pullularia sp) and severity of asthma39

9. Humidifier lung and humidifier fever.40

10. Disseminated nosocomial fungal infection byAureobasidium pullulans var. melanigenum: a case Report.41

11. Cutaneous infection of a porcupine (Erethizon dorsatum) by Aureobasidium pullulans.42

12. Outbreak of Aureobasidium species. Lower respiratory tract Infections caused by re

use of single‐use stopcocks during bronchoscopy43

13. Identification and possible disease mechanisms of an under-recognized fungus, Aureobasidium pullulans44

14. Hypersensitivity pneumonitis secondary to residential exposure to Aureobasidium pullulans in 2 siblings45

15. Aureobasidium pullulans infection: Fungemia in an infant and a review of human cases.46.

16. Catheter-related septicemia due to Aureobasidium pullulans.47

17. Fungi and allergic lower respiratory tract diseases48

18. Subcutaneous mycosis and fungemia by Aureobasidium pullulans: a rare pathogenic fungus in a post allogeneic BM transplant patient49

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2. 3. The genus Bipolaris

Bipolaris is a large genus of dematiaceous hyphomycetes with more than 100 species, most of them being saprobes in soil and pathogens of plants, while some of the saprobic species are potentially able to infect humans and animals. The typical morphological features of Bipolaris species include rapidly growing dark colonies, geniculate conidiophores with sympodial conidiogenesis, and large conidia with transverse distosepta, usually without a protuberant hilum (a basal scar indicating the point of attachment in the conidiogenous cell) and with bipolar germination.

Colonies on potato dextrose agar at 25°C are initially white, soon becoming gray to black with a black reverse. Rapid growth. Texture is woolly to cottony. Hyphae are septate and dark. Conidiophores may be up to 150 µm in length, are sympodial, geniculate, simple or branched, bearing conidia through pores or openings (poroconidia). Conidia have 2 to 5 transverse distosepta or pseudosepta (septa that do not extend to the cell wall with cells inclosed within sacs) and 3 to 6 cells. They measure approximately 14-40 x 6-11 µm. A flattened hilum or point of attachment is seen on the basal cell. Conidia germinate from both poles (bipolar).

Clinically relevant Bipolaris species are B. australiensis, B. hawaiiensis, B. spicifera, and, to a lesser extent, B. papendorfii. These fungi are able to infect both immunocompetent and immunosuppressed patients, mainly in tropical and subtropical areas.

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2.3.1. Bipolaris spicifera (Bainier) Subram., (1971) Synonyms: Brachycladium spiciferum Bainier, (1908) Brachysporium spiciferum (Bainier) Corbetta, (1963) Curvularia spicifera (Bainier) Boedijn, (1909) Dendryphion spiciferum (Bainier) Sacc. & Traverso,(1910) Drechslera spicifera (Bainier) Arx, (1970) Helminthosporium spiciferum (Bainier) Nicot, (1953)

Bipolaris spicifera

2.3.2. Bipolaris australiensis Tsuda & Ueyama (1981)

Synonyms: Drechslera australiensis M.B. Ellis,(1971) Drechslera australiensis (Bugnic.) Subram. & B.L. Jain, (1966) Helminthosporium australiense Bugnic., (1956)

Bipolaris australiensis

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2.3.3. Bipolaris hawaiiensis (M.B. Ellis) Uchida & Aragaki (1979) Synonyms: Helminthosporium hawaiiense Bugnic., (1955) disseminated disease and C. boppii, C. emmonsii and C. saturnica causing cutaneous infections.92

Bipolaris hawaiiensis

Pathogenicity:

Bipolaris is one of the causative agents of phaeohyphomycosis. Bipolaris can infect both immunocompetent and immunocompromised host. Bipolaris may be also pathogenic to certain plant species, particularly to Graminiae and also to animals, such as the dog. It may cause nasal mycotic granuloma in the cattle. Bipolaris may also be isolated as a laboratory contaminant.

Diseases caused by Bipolaris:

Skin Infections Nose Infections General Body Infections If Bipolaris gets into the bloodstream it can lead to endocarditis. Respiratory infections are a potential source of entry into the bloodstream. Peritonitis is a huge potential problem from this mold. The most common reaction to Bipolaris is skin infections. It affects the skin through

open wounds. The mold spores attack the wound, making it impossible to cure with antibiotics.

Bipolaris is also linked to severe immune disorders. The toxins that are released from this mold put continual stress on the immune system making it difficult to fight off illness.

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Recently reported cases:

1. Emerging agents of Phaeohyphomycosis: pathogenic species of Bipolaris and Exserohilum.19

2. Phaeohyphomycosis caused by the fungal genera Bipolaris and Exserohilum. A report of 9 cases and review of the literature.20

3. Onset of an outbreak of Bipolaris hawaiiensis fungal endophthalmitis after intravitreal injections of triamcinolone.21

4. Fatal Bipolaris spicifera infection in an immunosuppressed child22 5. Fungal endophthalmitis associated with compounded products.23 6. An outbreak of fungal endophthalmitis after intravitreal injection of compounded

combined bevacizumab and triamcinolone.24 7. Corneal abscess caused by Bipolaris spicifera.25 8. Bipolaris hawaiiensis as etiologic agent of allergic bronchopulmonary mycosis: first

case in a paediatric patient.26 9. Cerebral phaeohyphomycosis caused by Bipolaris spicifera after heart

transplantation.27 10. Cerebral and renal phaeohyphomycosis in a dog infected with Bipolarisspecies.28 11. Fatal fungal endarteritis caused by Bipolaris spicifera following replacement of the

aortic valve29 12. A set of 104 isolates from human clinical samples from the United States, revealed

that the most common anatomical sites where isolates were recovered were the nasal region (30.7%), skin (19.2%), lungs (14.4%), and eyes .(12.5%).30

2.4. The genus Cladosporium

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The genus Cladosporium was established in 1816 by Link. Due to the very brief, imprecise circumscription of the genus Cladosporium in the past, numerous superficially similar pigmented, holoblastic hyphomycetes with amero- to phragmosporous conidia formed in acropetal chains have been placed in Cladosporium, which made this genus very heterogeneous and polyphyletic. A recently published checklist contains data for 772 Cladosporium names, i.e., valid, invalid, legitimate and illegitimate species and varieties.50 Reasons for this vast number of taxa probably reside in the imprecise, wide circumscription of this genus in literature, the strong morphological variability of most species, and the occurrence of some species on a wide range of substrates.

Based on re-assessments of morphological features and molecular data, human pathogenic species were separated from the genus and are now known to be species of Cladophialophora, which differ in their morphology (conidiophores lacking or semi-macronematous, hila not coronate, less pigmented) and physiology (inability to liquefy gelatin). A monographic revision of the hyphomycete genus Cladosporium was published by Bensch et al. (2012)51. Based on morphological and molecular characteristics, only 169 species were recognized. All other names previousl;y given to Cladosporium species were considered as synonyms.

Cladosporium Link, 1832. Synonyms: Sporocladium Chev., 1826. Heterosporium Klotzsch, 1832,

Heterosporium Klotzsch ex Cooke, 1877. Myxocladium Corda, 1837. Didymotrichum Bonord., 1851. Acrosporella Riedl & Ershad, 1977

Type species: C. herbarum (Pers.: Fr.) Link (Clements & Shear 1931). Teleomorph: Davidiella Crous & U. Braun, 2003

Morphology: The colony is compact, olive-black, has well-defined darker margin and the surface is covered with short brown-green aerial mycelium. The reverse of the colony is black. Most of the Cladosporium spp. do not grow at temperatures above 35°C . Microscopically, the fungus produces chains of branching

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conidia by acropetalous (distal) budding. The length of the chains and conidial size differ with individual species. The dark spores are 1- or 2-celled and occur in long, branching chains that arise from a dark conidiophore. The youngest spore is at the top of the chain. The slightest movement will disrupt the chains, making microscope mounts of the whole structure nearly impossible. The best way to recognize the genus is by the prominent scars on the spores where the adjacent ones were attached.The most important Cladosporium species are: 2.4.1. Cladosporium herbarum (Pers.: Fr.) Link, 1832. Synonyms: 1. Acladium heterosporum Wallr., (1833) 2. Cladosporium alnicola Corda, (1837) 3. Cladosporium caricicola Corda, (1837) 4. Cladosporium condylonema Pass., (1889) 5. Cladosporium entoxylinum Corda, (1837) 6. Cladosporium epimyces Cooke, (1882) 7. Cladosporium fasciculatum Corda, (1837) 8. Cladosporium fuligineum Bonord., (1864) 9. Cladosporium graminum Corda, (1837) 10. Cladosporium nodulosum Corda, (1837) 11. Cladosporium tomentosum Corda, (1837) 12. Cladosporium typharum Desm., (1834) 13. Dematium epiphyllum Pers., (1801) 14. Dematium fuscum Pers., (1822) 15. Dematium gramineum Pers.(1822) 16. Helminthosporium acuum P. Karst., (1892) 17. Helminthosporium compactum P. Karst., (1892) 18. Helminthosporium flexuosum Corda, (1837) 19. Helminthosporium herbarum Schwein., (1832) 20. Helminthosporium phyllophilum P. Karst. (1884) 21. Helminthosporium vesiculosum Thüm.,(1877) 22. Helmisporium acuum P. Karst. (1892) 23. Helmisporium compactum P. Karst. (1892) 24. Helmisporium flexuosum Corda (1837) 25. Helmisporium herbarum Schwein. (1832) 26. Heterosporium caulicola Ellis & Everh., (1894) 27. Heterosporium cladasparioides Ellis & Everh. (1894) 28. Heterosporium cladosporioides Ellis & Everh., (1894) 29. Heterosporium cytisi Ranoj., (1910)

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C. herbarum (Mycobank) C. cladosporioides C. sphaerospermum

2.4.2. Cladosporium cladosporioides (Fresen.) G.A. de Vries, 1952. Synonyms:

1. Penicillium cladosporioides Fresen., (1850) 2. Hormodendrum cladosporioides (Fresen.) (1880) 3. Cladosporium hypophyllum Fuckel, (1870) 4. Monilia humicola Oudem., (1902)

2.4.3. Cladosporium sphaerospermum Penz., 1882. Synonyms: Torula lichenopsis Höhn., (1927)

Significabce of Cladosporium

Species of Cladosporium are cosmopolitan in distribution and commonly encountered on all kinds of plant, fungal and other debris, are frequently isolated from soil, food, paint, textiles and other organic matters.

Some species of this genus are plant pathogenic, i.e., they are causal agents of leaf spots and other lesions, or they occur as hyperparasites on other fungi.

Some species have a medical relevance in clinical laboratories and may cause allergic lung mycoses.

Cladosporium species have also been known to colonize and ruin crops or food, as on frozen meat.

Cladosporium species also produce compounds associated with the characteristic mould smell.

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One species of Cladosporium are used to produce enzymes which are used in the manufacturing of pharmaceuticals. Most classically, these enzymes transform certain steroid compounds into progesterone, a hormone used in birth control.

Pathogenicity Cladosporium species are causative agents of:

Skin lesions: Cladosporium carrionii is considered as an agent of chromoblastomycosis which is a subcutaneous infection characterized by verrucous lesions and the formation of brown, sclerotic fission cells, which look like copper pennies, in tissues.

Keratitis: wide variety of corneal infections, irritations and inflammations],

Onychomycosis

Sinusitis: an inflammation of the paranasal sinuses which may be associated with viral respiratory infections and seasonal allergic problems or hay fever

pulmonary infections

Brain abscesses: Cladophialophora bantiana is the most common and dangerous neurotropic fungus which causes brain abscess. The infection which is caused due to this fungus is risky, not only to the patient due to the poor prognosis, but also to the clinician because of the difficulty in its management as well as to the laboratory personnel who handle it

Cases recently reported:

1. Microfungal contaminants on mobile phones of health services vocational school students in marmaris52

2. Harmful biological agents at museum workposts.53 3. Some chronic rhinosinusitis patients have elevated populations of fungi in their

sinuses.54 4. Fungi and allergic lower respiratory tract diseases55 5. Phaeohyphomycotic dermatitis in a giant panda (Ailuropoda melanoleuca) caused

by Cladosporium cladosporioides.56 6. The occurrence of molds in patients with chronic sinusitis.57 7. Unusual causes of fungal rhinosinusitis: a study from a tertiary care centre in South

India.58 8. Differences in fungi present in induced sputum samples from asthma patients and

non-atopic controls: a community based case control study59 9. Allergic bronchopulmonary mycosis due to fungi other than Aspergillus: a global

overview.60 10. Acute meningitis caused by Cladosporium sphaerospermum61 11. Keratitis-associated fungi form biofilms with reduced antifungal drug susceptibility.62 12. Cutaneous and systemic pathogenicity of a clinical isolate of

Cladosporium sphaerospermum in a murine model.63

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2.5. The genus Cladophialophora Cladophialophora is a genus of black yeast-like fungi comprising a number of clinically highly significant species in addition to environmental taxa. The genus has previously been characterized by branched chains of ellipsoidal to fusiform conidia. However, this character was shown to have evolved several times independently in the order Chaetothyriales. On the basis of a multigene phylogeny (nucLSU, nucSSU, RPB1), most of the species of Cladophialophora (including its generic type C. carrionii) belong to a monophyletic group comprising two main clades (carrionii- and bantiana-clades). The genus includes species causing chromoblastomycosis and other skin infections, as well as disseminated and cerebral infections, often in immunocompetent individuals. The genus has been expanded to encompass several other clinically significant species, including the neurotropic fungi C. bantiana and C. modesta causing brain infections, C. devriesii and C. arxii causing disseminated disease and C. boppii, C. emmonsii and C. saturnica causing cutaneous infections.92 Pathogenicity Cladophialophora spp. cause phaeohyphomycosis, chromoblastomycosis and mycetoma:

Cladophialophora bantiana: causes cerebral phaehyphomycosis in the form of brain abscesses, for which the clinical course is usually fatal. It may also cause skin lesions.

Cladophialophora boppii: causes chromoblastomycosis

Cladophialophora carrioinii : causes chromoblastomycosis

Cladophialophora devriesii: to causes disseminated phaehyphomycosis.

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Description of important Cladophialophora species 2.5.1. Cladophialophora bantiana de Hoog, Kwon-Chung & McGinnis, (1995) Synonyms: Torula bantiana Sacc., in Saccardo, (1912) Cladosporium bantianum (Sacc.) Borelli, (1960) Xylohypha bantiana (Sacc.) McGinnis, Borelli, Padhye & Ajello, (1986) Cladosporium trichoides Emmons Binford, Thompson & Gorham, (1952) Cladosporium bantianum (Sacc.) Borelli, (1960) Cladosporium trichoides var. chlamydosporum Kwon-Chung, (1978)

In culture, the colony is black with a velvety texture or dark grey in colour, depending on the type of agar medium it is grown on. It grows slowly under temperatures ranging from 14-42 °C with optimal growth around 30 °C. It can be distinguished from other species of the genus Cladophialophora by the presence of urease activity. Microscopically, the fungus produces predominantly hyphal growth both in vivo and in vitro, that consists of dark coloured largely unbranched, wavy chains of conidia, individually 5–10 µm in length. The dark colour is due to the presence of the dark pigment melanin.

Cladophialophora bantiana

26

2.5.2. Cladophialophora carrionii de Hoog, Kwon-Chung & McGinnis, (1995) Synonyms: Cladosporium carrionii Trejos (1954) Cladophialophora ajelloi Borelli (1980)

Colonies are slow growing, reaching 3-4 cm in diameter after one month, with a compact suede-like to downy surface and are olivaceous-black in color. Microscopically, the fungus produces ascending to erect, olivaceous-green, apically branched, elongate conidiophores producing branched acropetal chains of smooth-walled conidia. Conidia are pale olivaceous, smooth-walled or slightly verrucose, limoniform to fusiform, 1.5-3.0 x 2.0-7.0 µm in size. Bulbous phialides with large collarettes and minute, hyaline conidia are occasionally formed on nutritionally poor media. Maximum growth temperature 35-37C.

Cladophialophora carrionii

2.5.3. Cladophialophora modesta McGinnis, de Hoog & Haase (1999) 2.5.4. Cladophialophora devriesii (Padhye et Ajello) de Hoog et al., 1995 Synonyms: Cladosporium devriesii Padhye & Ajello, (1984)

2.5.5. Cladophialophora arxii Tintelnot et al., (1995)

27

2.5.6.Cladophialophora boppii (Borelli) de Hoog, Kwon-Chung & McGinnis, ((1995) Synonym: Taeniolella boppii Borelli, (1983))

Cladophialophora devriesii Cladophialophora modesta Cladophialophora arxii Cladophialophora boppii

Recently reported cases 1. Cladophialophora bantiana brain abscess: A case with long survival in metropolitan

France64 2. Phaeohyphomycosis caused by Cladophialophora bantiana.65 3. Canine eumycetoma caused by Cladophialophora bantiana in a Maltese: case report

and literature review.66 4. Cladophialophora (Xylohypha) bantiana--an unusual cause of septic arthritis67 5. Brain abscess caused by Cladophialophora bantiana in China68 6. Cutaneous phaeohyphomycosis due to Cladophialophora bantiana69 7. Cerebral phaeohyphomycosis due to Cladophialophora bantiana in a Huacaya

alpaca (Vicugna pacos).70 8. Cerebellar Cladophialophora bantiana infection in a patient with marginal zone

lymphoma treated with immunochemotherapy including rituximab71 9. Cladophialophora bantiana brain abscess in an immunocompetent patient72 10. Focal pulmonary granuloma caused by Cladophialophora bantiana in a domestic

short haired cat.73 11. Disseminated Cladophialophora bantiana infection in an idiopathic thrombocytopenic

purpura patient: a case report.74 12. Necrotizing pyogranulomatous meningoencephalitis with intralesional fungal hyphae,

consistent with Cladophialophora bantiana75 13. Cutaneous phaeohyphomycosis caused by Cladophialophora bantiana in a scar after

treatment with intralesional corticosteroid injections76 14. Chromoblastomycosis caused by Cladophialophora carrionii in a child from India78

28

15. A fatal case of prostatic abscess in a post-renal transplant recipient caused by Cladophialophora carrionii.77

16. Corneal chromoblastomycosis caused by Cladophialophora carrionii after cataract surgery80

17. Cladophialophora carrionii: an aetiological agent of cutaneous chromoblastomycosis from a non-endemic area, North India81

18. Sub-cutaneous phaeohyphomycosis caused by Cladophialophora devriesii in a United Kingdom resident82

19. Femoral osteomyelitis due to Cladophialophora arxii in a patient with chronic granulomatous disease83

20. Systemic mycosis caused by a new Cladophialophora species84 21. Subcutaneous phaeohyphomycosis caused by Cladophialophora boppii85 22. Toenail infection by Cladophialophora boppii.86 23. Pulmonary Cladophialophora boppii infection in a lung transplant recipient: case

report and literature review87 24. Cladophialophora (Xylohypha) bantiana--an unusual cause of septic arthritis.89 25. Fatal cerebral abscess caused by Cladophialophora bantiana.91

2. 6. The genus Cheatomium

The genus Chaetomium contains about 95 species. Chaetomium spp. are contaminants but they are also encountered as causative agents of infections in humans. A few cases of fatal deep infections due to Chaetomium atrobrunneum have been reported in the immunocompromised host. Other clinical syndromes include brain abscess, peritonitis, and onychomycosis.

Morphology Colonies are rapidly growing, cottony and white in colour initially. Mature colonies become grey to olive in colour. From the reverse, the colour is tan to red or brown to black. Microscopically. the fungus shows septate hyphae, perithecia, asci and ascospores. Perithecia are large, dark brown to black in color, fragile, globose to flask shaped and have filamentous, hair-like, brown to black appendages (setae) on their surface. Perithecia have ostioles (small rounded openings) and contain clavate to cylindrical asci, which rapidly dissolve to release one-celled, olive brown in color, and lemon shaped ascospores, which are 4 to 8 in number.

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2.6.1. Chaetomium globosum Kunze (1829) Synonym: Chaetomium kunzeanum Zopf (1881) Chaetomium affine Corda (1840) Chaetomium setosum Bainier (1887) Chaetomium barbatum Traaen (1914) Chaetomium subterraneum Swift & Povah (1929) Chaetomium japonicum Saito & Okasaki

Chaetomium globosum

2.6.2. Chaetomium brasiliense Bat. & Pontual,1948

Bat. & Pontual1948. Chaetomium hamatumSynonyms: Chaetomium repandum Bat. & Pontual, 1948 Chaetomium velutinum L.M, 1949. Chaetomium alboarenulum Ames, 1963 Chaetomium congoense Ames, 1963 Chaetomium leucophora Ames, 1963 Chaetomium perpulchrum Ames, 1963

31

Pathogenicity : Chaetomium spp. are among the fungi causing infections wholly referred to as phaeohyphomycosis. Fatal deep mycoses due to Chaetomium atrobrunneum have been reported in an immunocompromised host. Brain abscess, peritonitis, cutaneous lesions, and onychomycosis may also develop due to Chaetomium spp. Recently reported cases:

1. A case report of a mixed Chaetomium globosum/Trichophyton mentagrophytes onychomycosis.178

2. Fungal keratitis caused by Chaetomium atrobrunneum.179 3. Phaeohyphomycosis and onychomycosis due to Chaetomium spp., including the first

report of Chaetomium brasiliense infection.180 4. Non-dermatophyte moulds as skin and nail foot mycosis agents: Phoma

herbarum, Chaetomium globosum and Microascus cinereus.181 5. Onychomycosis due to ascomycete Chaetomium globosum: a case report.182 6. Clavispora lusitaniae and Chaetomium atrobrunneum as rare agents of

cutaneous infection.183 7. Three isolations of Chaetomium globosum from erythematous epilation of canine

skin.184 8. Onychomycosis by Chaetomium spp.185 9. Chromoblastomycosis caused by Chaetomium funicola: a case report from Western

Panama.186 10. Invasive chaetomium infection in two immunocompromised pediatric patients.187

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2. 7. The genus Coniothyrium

2.7.1. Coniothyrium fuckelii Sacc., (1878) Synonyms: Clisosporium fuckelii (Sacc.) Kuntze, (1898) Microsphaeropsis fuckelii (Sacc.) Boerema, (2003) Paraconiothyrium fuckelii (Sacc.) Verkley & Gruyter (2012)

Significance: Coniothyrium fuckelii was reported as a cause of liver infection and Coniothyrium species was reported as a cause of phaeohyphomycosis :

1. Liver infection caused by Coniothyrium fuckelii in a patient . 278 2. Phaeohyphomycosis caused by Coniothyrium279

.

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2.8. The genus Paraconiothyrium 2.8.1. Paraconiothyrium cyclothyrioides Verkley (2004)

Significance:

Paraconiothyrium cyclothyrioides was reported as a cause of Cutaneous

Phaeohyphomycosis:

1. Cutaneous phaeohyphomycosis caused by Paraconiothyrium cyclothyrioides. 280

2. Triple cutaneous mycosis (Cunninghamella bertholletiae, Phomopsis spp. and Paraconiothyrium spp.) in an immonucompromised patient: a Martinican case report281

.

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2.9. The genus Curvularia The genus Curvularia contains several species, most of them are facultative pathogens of plants, and cereals in tropical or subtropical areas, while the remaining few are found in temperate zones. Curvularia may cause infections in both humans and animals.

Morphology Curvularia produces rapidly growing, woolly colonies on potato dextrose agar at 25°C. From the front, the color of the colony is white to pinkish gray initially and turns to olive brown or black as the colony matures. From the reverse, it is dark brown to black. Curvularia produces septate, brown hyphae, brown conidiophores, which are simple or branched and are bent at the points where the conidia originate. The conidia are straight or pyriform, brown, multiseptate with transverse septa, and have dark basal protuberant hila. The central cell is typically darker and enlarged compared to the end cellsin and usually gives the conidium a curved appearance. The number of the septa in the conidia, the shape of the conidia (straight or curved), the colour of the conidia (dark vs pale brown), existence of dark median septum, and the prominence of geniculate growth pattern are the major microscopic features that help in differentiation ofCurvularia spp. among each other. For instance, the conidia of Curvularia lunata have 3 septa and 4 cells, while those of Curvularia geniculate mostly have 4 septa and 5 cells.

Curvularia can be easily distinguished from Bipolaris and Drechslera spp. since the conidia are non-distoseptate, that is, septate from edge to edge of the conidial wall. The teleomorphic state of the type species Curvularia lunata is Cochliobolus lunatus.

34

2.9.1. Curvularia lunata (Wakker) Boedijn, 127 (1933)

Synonyms: Acrothecium lunatum Wakker, (1898)]

Helminthosporium curvulum Sacc., (1916)

Helmisporium curvulum Sacc. (1916)

Curvularia lunata.

Pathogenicity C. lunata is the most commonly encountered species. Importantly, the infections may develop in patients with intact immune system. However, similar to several other fungal genera, Curvularia has recently emerged also as an opportunistic pathogen that infects immunocompromised hosts

Curvularia spp. are among the causative agents of:

1. phaeohyphomycosis, 2. wound infections, 3. mycetoma, 4. onychomycosis, 5. keratitis, 6. allergic sinusitis, 7. cerebral abscess, 8. cerebritis, 9. pneumonia, 10. allergic bronchopulmonary disease, 11. endocarditis, 12. dialysis-associated peritonitis, and 13. disseminated infections may develop due to Curvularia spp.

35

Recently reported cases

1. Curvularia infections: case reports and a review of the spectrum of disease along

with therapeutic options.93

2. Curvularia dermatomycosis in a jersey heifer: a case report94

3. Curvularia lunata: A rare cause of black-grain eumycetoma95

4. Curvularia abscess of the brainstem.96

5. Subcutaneous phaeohyphomycosis due to Curvularia lunata in a renal transplant

patient97

6. Curvularia brain abscess.98

7. Curvularia endophthalmitis following open globe injuries99

8. Cutaneous Curvularia infection of the forearm.100

9. Curvularia lunata endophthalmitis. 1101

10. Curvularia keratomycosis in a dog.102

11. Eosinophilic fungal rhinosinusitis due to the unusual pathogen Curvularia

inaequalis. 103

12. Human Curvularia infections: Report of five cases and review of the

literature.104

13. Fatal cerebral phaeohyphomycosis due to Curvularia lunata in an

immunocompetent patient105

36

2.10. The genus Epicoccum Epicoccum is a dematiaceous mould widely distributed and commonly isolated from air, soil and foodstuff. It is found also in some animals and textiles. It is the common causative agent of leaf spots of various plants. There are no documented cases of Epicoccum infection in humans or animals. Epicoccum is occasionally isolated from clinical samples. However, Epicoccum has not been documented as a pathogen and these isolates are considered as contaminants. The genus Epicoccum contains a single species, Epicoccum purpurascens.

Morphology Epicoccum grows rapidly and produces woolly to cottony or felty colonies on potato dextrose agar at 25°C. The colonies are yellow to orange, orange to red or pink initially and become greenish brown to black by aging. Epicoccum may produce a diffusable pigment which turns the colour of the inoculated medium to yellow, orange, red or brown. Black dots (100-2000 µm in diameter) may be observed macroscopically on the colony surface. These are the tufts of hyphae which have conidiophores on their surface. These tufts of hyphae are cushion-shaped and nonconvoluted and are called sporodochia. Microscopically, the fungus develops septate, short and yellow to brown in color hyphae. The conidiophores that originate on hyphae form clusters, branch repeatedly and are visible as dense masses and give rise to conidia, which are round, non-septate, and pale in color. Mature conidia are rough, verrucose to warty, and brown to black in color. They contain multiple transverse and vertical septa and have a funnel-shaped base and attachment scar that is formed from aggregated conidiophores on the sporodochium. 2.10.1. Epicoccum purpurascens Ehrenb., Sylvae (1818) Synonyms: Epicoccum versicolor var. purpurascens Rabenh. (1844) Epicoccum nigrum Link (1816) Epicoccum neglectum Desm. (1842) Epicoccum granulatum Penz. (1882) Thyrococcum humicola R.E. Buchanan (1911) Epicoccum oryzae S. Ito & Iwadare, (1934) Toruloidea tobaica Szilvinyi (1936) Epicoccum mezzettii Goid. (1937

37

2.10.2. Epicoccum nigrum Link (1916)

Synonyms: Epicoccum vulgare Corda (1837) Epicoccum versicolor Rabenh (1844) Epicoccum versicolor var. nigrum (Link) Rabenh (1844 Epicoccum purpurascens Ehrenb. (1818) Epicoccum neglectum Desm (1842) Epicoccum granulatum Penz. (1882) Thyrococcum humicola R.E. Buchanan (1911) Epicoccum oryzae S. Ito & Iwadare (1934) Toruloidea tobaica Szilvinyi (1936) Epicoccum mezzettii Goid. (1937)

Culture of Epicoccum nigrum.

Pathogenicity

Epicoccum is a cause of:

1. Upper and lower respiratory tract disease. 2. Phaeohyphomycosis, 3. skin disease, 4. allergic fungal sinusitis. 5. Hypersensitivity pneumonitis

38

Recently reported cases:

1. Effect of proteolytic activity of Epicoccum purpurascens major allergen, Epi p1 in allergic inflammation.386

2. Identification of Epicoccum purpurascens allergens by two-dimensional immunoblotting and mass spectrometry.387

3. Biosynthesis of silver nanoparticles by the endophytic fungus Epicoccum nigrum and

their activity against pathogenic fungi.388

.

2.11. The genus Exophiala

Exophiala is a genus that consists of more than 30 species. Traditionally,

these fungi are considered dematiaceous dimorphic fungi, due to their phenotypic characteristics at the beginning of colony formation as “black

yeasts, and when the cultures mature, brown hyphae are formed which bear conidiogenous cells referred to as annellides, a typical characteristic of this

genus of fungi.

Exophiala species are differentiated from Phialophora and Wangiella by the formation of annelides rather than phialides.

Members of the genus Exophiala are difficult to classify and identify. Several species have marked phenetic characteristics, such as the large conidiophores

of E. spinifera, or the thermotolerance and absence of nitrite assimilation in E.

dermatitidis. The majority of species, however, are morphologically variable,

due to their passage through complicated life cycles where diagnostic features are variably expressed and, conversely, very similar microscopic structures

can be expressed in phylogenetically remote species. In recent years diagnostic approaches have been supplemented by molecular tools,

particularly sequence data of the rRNA internal transcribed spacer (ITS)

regions.

Colonies are initially smooth, greenish-grey to black, mucoid and yeast-like, becoming raised and developing tufts of aerial mycelium with age, often

becoming dome-shaped and suede-like in texture. Reverse is olivaceous-black. Numerous ellipsoidal, yeast-like, budding cells are usually present,

especially in young cultures. Scattered amongst these yeast-like cells are larger, inflated, subglobose to broadly ellipsoidal cells (germinating cells)

39

which give rise to short torulose hyphae that gradually change into unswollen

hyphae. Conidia are formed on lateral pegs either arising apically or laterally at right or acute angles from essentially undifferentiated hyphae or from strongly

inflated detached conidia. Conidiogenous pegs are 1-3 µm long, slightly tapering and imperceptibly annellate. Conidia are hyaline, smooth, thin-walled,

broadly ellipsoidal, 3.2-4.4 x 1.2-2.2 µm, and with inconspicuous basal scars. Cultures grow at 37C but not at 40C.

The followings are the main Exophiala species:

2.11.1. Exophiala jeanselmei (Langeron) McGinnis & A.A. Padhye (1977)

Synonyms: Torula jeanselmei Langeron, (1928)

Pullularia jeanselmei (Langeron) Dodge, (1935) Phialophora jeanselmei (Langeron) Emmons (1945) Exophiala jeanselmei var. jeanselmei (1977)

2.11.2. Exophiala spinifera (H.S. Nielsen & Conant) McGinnis (1977)

Synonyms: Phialophora spinifera (1968)

Rhinocladiella spinifera (H.S. Nielsen & Conant) de Hoog, (1977)

41

Exophiala spinifera

2.11.3. Exophiala dermatitidis (Kano) de Hoog (1977) Synonyms: Hormiscium dermatitidis Kano (1934) Fonsecaea dermatitidis (Kano) Carrion (1950) Hormodendrum dermatitidis(Kano) Conant (1954) Phialophora dermatitidis (Kano) C.W.Emmons (1963) Wangiella dermatitidis (Kano) McGinnis (1977)

2.11.4. Exophiala pisciphila McGinnis & Ajello (1974) Synonymm: Aureobasidium salmonis (J.W. Carmich.) Borelli (1969)

41

2.11.5. Exophiala salmonis Carmich. (1966) Synonyms: Aureobasidium salmonis (J.W. Carmich.) Borelli (1969)

Exophiala salmonis on the blood agar

42

2.11.6. Exophiala hongkongensis Woo, Ngan, Tsang, Ling, Chan, Leung,

Yuen, Lau (2013)

2.11.7. Exophiala xenobiotica de Hoog, J.S. Zeng, Harrak & Deanna A. Sutton (2006))

Pathogenicity

Exophiala species are causative agents of :

1. mycetoma (especially for E. jeanselmei)

2. localized cutaneous infections

3. subcutaneous cysts,

4. endocarditis

5. keratitis

6. cerebral and disseminated infections.

7. Phaeohyphomycosis

8. mycetoma

43

Recently reported cases:

1. Clinical spectrum of exophiala infections and a novel Exophiala species, Exophiala hongkongensis122

2. Massive contamination of Exophiala dermatitidis and E. phaeomuriformis in railway stations in subtropical Turkey123

3. Exophiala dermatitidis endocarditis on native aortic valve in a postrenal transplant patient and review of literature on E. dermatitidis infections.124

4. Pulmonary infection caused by Exophiala dermatitidis in a patient with multiple myeloma: A case report and a review of the literature.125

5. Exophiala xenobiotica aerocystitis in a Queensland grouper Epinephelus lanceolatus

(Bloch)126

6. Exophiala jeanselmei keratitis: case report and review of literature.127

7. A case of phaeohyphomycosis caused by Exophiala oligosperma successfully treated with local hyperthermia.128

8. A case of phaeohyphomycosis of the face caused by Exophiala oligosperma in an immunocompromised host.129

9. Eumycetoma of the foot caused by Exophiala jeanselmei in a Guinean woman.130

10. Subcutaneous phaeohyphomycosis caused by Exophiala equina, with susceptibility to eight antifungal drugs.131

11. An unusual case of eumycetoma caused by Exophiala jeanselmei after a sea urchin injury.132

12. Cutaneous and mucosal phaeohyphomycosis caused by Exophiala spinifera in a pregnant patient: case report and literature review133

13. Chronic disfiguring facial lesions in an immunocompetent patient due to Exophiala spinifera: a case report and review of literature.134

14. A case of Exophiala spinifera infection in Southern Brazil: Molecular identification and antifungal susceptibility.135

15. Cutaneous phaeohyphomycosis caused by Exophiala spinifera in a patient with systemic lupus erythematosus.136

16. Subcutaneous phaeohyphomycosis due to Exophiala spinifera in an immunocompromised host.137

17. Exophiala spinifera as a cause of cutaneous phaeohyphomycosis: case study and review of the literature.138

18. Development of IgG antibodies to Exophiala dermatitidis is associated with inflammatory responses in patients with cystic fibrosis.139

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2.12. The genus Drechslera

Drechslera is a cosmopolitan dematiaceous fungus primarily isolated from plants and soil. The Drechslera or Helminthosporium species are imperfect filamentous fungi belonging to the class Deuteromycetes. The genus includes a dozen of phytopathogenic species causing crop diseases grouped under the term helminthosporiose.

The colonies are dark brown to black. The brown geneculate conidiophores are simple or branched and produce small, brown multicellular conidia in a sympodial mode. These isolated conidia are cylindrical or ellipsoidal, with

2.12.1. Drechslera biseptata (Sacc. & Roum.) M.J. Richardson & E.M. Fraser, (1968) Synonyms: Helminthosporium biseptatum Sacc. & Roum. (1881) Brachysporium biseptatum (Sacc. & Roum.) Sacc., (1886) Marielliottia biseptata (Sacc. & Roum.) Shoemaker (1999) Helminthosporium biforme Mason & Hughes, (1948) Drechslera biforme (Mason & Hughes) Subram. & B.L. Jain (1966)

Pathogenicity

McGinnis et. al. (1986)106 have reviewed the Drechslera isolates from human and animal disease and concluded that all pathogenic species are today considered as members of the genera Bipolaris and Exserohilum. However, Drechslera biseptata has recently been reported from a brain abscess.

45

2.13. The genus Exserohilum

The genus is characterized by its conidia, which are ellipsoidal, distoseptate, and have a protruding and truncate hilum. The genus Exserohilum may be differentiated from the closely related genera Bipolaris and Drechslera by forming conidia with a strongly protruding truncate hilum (i.e. exserted hilum). The hilum is defined as "a scar on a conidium at the point of attachment to the conidiophore". In Drechslera species, the hilum does not protrude whereas in Bipolaris species the hilum protrudes only slightly.

2.13.1. Exserohilum rostratum (Drechsler) K.J. Leonard & Suggs (1974) Synonyms: Helminthosporium rostratum Drechsler (1923) Bipolaris rostrata (Drechsler) Shoemaker (1959) Drechslera rostrata (Drechsler) M.J. Richardson & E.M. Fraser (1968) Luttrellia rostrata (Drechsler) Gornostai, Vodorosli, Griby (1978) Helminthosporium halodes Drechsler (1923)

Morphology Exserohilum rostratum grows rapidly on potato dextrose agar and produces woolly colonies that are pale initially but quickly become dark gray, to bluish-black to brownish-black with a black reverse. Hyphae are septate and brown. Conidiophores are long, septate, simple (non-branched), geniculate, and become paler near the apex. Conidia are various shades of brown and may range from less than 80 to greater than 100 µ in length, may be straight to distinctly curved, and contain 1 to over 12 septa. The feature all species share is a strongly protruding hilum from the basal cell. Conidia may be slow to form in culture.

46

Three species of Exserohilum have been recognized as human pathogens: Exserohilum rostratum, E. longirostratum and E. mcginnisii. Pathogenecity The infections reported to be caused by Exserohilum species are:

1. sinusitis 2. skin infections 3. cerebral abscesses 4. keratitis 5. osteomyelitis 6. prosthetic valve endocarditis 7. disseminated infection

Cases recently reported:

1. Exserohilum and the compounding pharmacy: pushing the envelope of virulence.188 2. Insights into fungal pathogenesis from the iatrogenic epidemic

of Exserohilum rostratum fungal meningitis.189 3. Rapid identification of antifungal compounds against Exserohilum rostratum using

high throughput drug repurposing screens.190 4. Mycotic keratitis caused by concurrent infections of Exserohilum mcginnisii and

Candida parapsilosis.191 5. Fungal disease following contaminated steroid injections: Exserohilum is ready for

its close-up.192 6. Exserohilum infections associated with contaminated steroid injections: a

clinicopathologic review of 40 cases.193 7. Real-world experience in the midst of an Exserohilum meningitis outbreak.194 8. Galactomannan testing for early diagnosis of Exserohilum rostratum infection.195 9. Real-time treatment guidelines: considerations during the Exserohilum rostratum

outbreak in the United States.196 10. Iatrogenic Exserohilum infection of the central nervous system: mycological

identification and histopathological findings.197

11. Exserohilum infection in an immunocompromised neonate.198 12. Keratomycosis caused by Exserohilum rostratum.199

47

2.14. The genus Fonseceae

The genus Fonsecaea is defined morphologically by the presence of indistinct melanised conidiophores with blunt, scattered denticles bearing conidia singly or in short chains that eventually become branched. de Hoog et al. (2004)107 revised the genus on the basis of ribosomal DNA internal transcribed spacer (ITS) sequence data recognising two species; F. pedrosoi and F. monophora. The previously described species F. compacta was found to be a morphological variant of F. pedrosoi. Morphologically, F. pedrosoi and F. monophora are very similar and can best be distinguished by genetic analysis.

According to AFLP fingerprinting, Fonsecaea isolates clustered in 5 groups corresponding with F. pedrosoi, F. monophora, and F. nubica: the latter 2 species each comprised 2 groups, and F. pedrosoi appeared to be of monophyletic origin (Najafzadeh et al., 2011)108

Colonies are slow growing, flat to heaped and folded, suede-like to downy, olivaceous to black with black reverse. Conidiogenous cells pale olivaceous, arranged in loosely branched systems, with prominent denticles. Conidia pale olivaceous, clavate to ellipsoidal, in short chains, subhyaline, smooth and thin-walled, 3.5-5 x 1.5-2 µm. F. monophora on average has slightly longer conidial chains and slightly shorter denticles than F. pedrosoi. All strains grow at 37C but not at 40C.

2.14.1. Fonsecaea pedrosoi (Brumpt) Negroni (1936) Synonyms: Hormodendrum pedrosoi Brumpt, (1922) Acrotheca pedrosoi (Brumpt) Fonseca & Leão (1923) Trichosporum pedrosoi (Brumpt) Brumpt (1927) Trichosporum pedrosianum (Brumpt) M. Ota (1927) Gomphinaria pedrosoi (Brumpt) C.W. Dodge (1935) Hormodendroides pedrosoi (Brumpt) M. Moore & F.P. Almeida (1936) Phialophora pedrosoi (Brumpt) Redaelli & Cif: 592 (1941) Carrionia pedrosoi (Brumpt) Bric.-Irag (1942) Rhinocladiella pedrosoi (Brumpt) Schol-Schwarz (1968) Hormodendrum algeriense Montpell (1927) Hormodendrum rossicum Jacz. & Merlin (1929) Hormodendrum compactum Carrion (1935) Phialoconidiophora guggenheimia M. Moore & F.P. Almeida (1936) Fonsecaea compactum (Carrion) Carrion (1940) Fonsecaea pedrosoi var. communis Carrion (1940) Rhinocladiella compacta Carrion ex de Hoog, (1977)

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2.14.2. Fonsecaea compacta (Carrion) Carrion (1940) Synonyms: Hormodendrum compactum Carrion (1935) Phialoconidiophora compacta (Carrion) M. Moore & F.P. Almeida (1936) Fonsecaea compactum (Carrion) Carrion (1940) Phialophora compacta (Carrion) Redaelli & Cif., Granul (1942) Rhinocladiella compacta (Carrion) Schol-Schwarz (1968) [ Rhinocladiella compacta Carrion ex de Hoog (1977) Hormodendrum pedrosoi Brumpt, (1922) Hormodendrum algeriense Montpell (1927) Hormodendrum rossicum Jacz. & Merlin (1929) Phialoconidiophora guggenheimia M. Moore & F.P. Almeida (1936) Fonsecaea pedrosoi var. communis Carrion (1940)

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2.14.3. Fonsecaea monophora (M. Moore & F.P. Almeida) de Hoog, Vicente & D. Attili, (2004) Synonyms: Botrytoides monophora M. Moore & F.P. Almeida, (1936)

Pathogenicity Fonsecaea is one of the causative agents of:

1. Chromoblastomycosis presents with papules and verrucose cauliflower-like lesions most commonly on lower extremities.

2. Paranasal sinusitis. 3. Keratitis 4. Septic arthritis and osteomyelitis

5. Cerebral phaeohyphomycosis

Recently reported cases:

1. Fonsecaea nubica sp. nov, a new agent of human chromoblastomycosis revealed using molecular data.140

2. Chromoblastomycosis caused by Fonsecaea: clinicopathology, susceptibility and molecular identification of seven consecutive cases in southern China.141

3. Cerebral phaeohyphomycosis caused byFonsecaea monophora.142 4. Fonsecaea multimorphosa sp. nov, a new species ofChaetothyriales isolated from a

feline cerebral abscess.143 5. Fonsecaea pedrosoi: a rare etiology in fungal keratitis.144 6. Chromoblastomycosis mimicking tuberculosis verrucosa cutis: Look for copper

pennies145

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7. Fungal infections of the central nervous system in the immunocompetent host146 8. . Chromoblastomycosis in Australia: an historical perspective.147 9. Subcutaneous phaeohyphomycosis of the face presenting as

rhinoentomophthoramycosis.148 10. A. Revisiting the clinical and histopathological aspects of patients with

chromoblastomycosis from the Brazilian Amazon region.149 11. Chromoblastomycosis due to Fonsecaea pedrosoi and F. monophora in Cuba.150 12. Opportunistic Fonsecaea pedrosoi brain abscess in a patient with non-cirrhotic portal

fibrosis-induced hypersplenism--a novel association.151 13. Chromoblastomycosis caused by Fonsecaea: clinicopathology, susceptibility and

molecular identification of seven consecutive cases in Southern China.152 14. Chromoblastomycosis in Mainland China: a systematic review on clinical

characteristics153 15. Septic arthritis and osteomyelitis due to the chromoblastomycosis

agent Fonsecaea pedrosoi.154 16. Clinical, epidemiological and mycological report on 65 patients from the Eastern

Amazon region with chromoblastomycosis.155 17. A rare concomitant tubercular and Fonsecaea pedrosoi fungal infection of the skull

base.156 18. . A refractory case of chromoblastomycosis due to Fonsecaea monophora with

improvement by photodynamic therapy.157

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2.15. The genus Hortaea Hortaea werneckii is the only species of the genus. It is a dematiaceous yeast that inhabits the soil, particularly in tropical and subtropical climates. It is halophilic and has also been isolated from saltwater fish.

Hortaea werneckii is the causative agent of Tinea nigra. Tinea nigra is a superficial infection of stratum corneum. The infection is mostly acquired via direct inoculation of the fungus onto the skin due to contact with soil, wood, and decaying vegetation. The lesions of tinea nigra are usually located on palms but may occasionally involve other parts of the body, such as soles of the feet. These lesions are typically brown to black, flat, not scaly, and with irregular contours.

2.15.1.Hortaea werneckii (HORTA) Nishim. & Miyaji (1984)

Synonyms : Cladosporium werneckii HORTA 1921 Dematium werneckii DODGE 1935 Pullularia werneckii DE VRIES 1952 Exophiala werneckii (Horta) Arx, 180 (1970) Phaeoannellomyces werneckii (Horta) McGinnis & Schell (1979) Pullularia fermentans var. leaoi E.S. Wynne & Gott (1956)

The growth of H. werneckii in liquid media is often yeast-like, although it can switch to filamentous growth. The mechanism of the switch is not known. The cells appear brown because of melanin production.

The colonies of Hortaea werneckii grow slowly and are initially pale in color, moist, shiny, and yeast-like. In time, these colonies become velvety, olive black, and are covered with a thin layer of mycelium. From the reverse, the color is black.

Microscopicically, septate hyphae, (bicellular) yeast-like conidia, and chlamydospores are observed. The yeast-like conidia (2-5 x 5-10 µm) are the initial structures observed in the early phase of the colony development. These cells have a round end and a tapered and elongated annelidic neck part. They are hyaline initially and become pale olivaceous in time. Septate, thick-walled, and brown hyphae (up to 6 µm wide) are formed as the colony ages. The annelloconidia are formed at intercalary and lateral annellidic points along the hyphae.

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Hortaea werneckii yeast colonies and cells mould colonies mycelium

Recently reported cases:

1. Bilateral Tinea Nigra of palm: a rare case report from Eastern India.158 2. Tinea nigra in an unusual anatomic location159 3. Tinea nigra: successful treatment with topical butenafine160. 4. Spontaneous cure in a case of Tinea nigra.161 5. Tinea nigra and dermoscopy.162 6. Dermoscopy improves diagnosis of tinea nigra: a study of 50 cases.163 7. Study of the dermatoscopic pattern of tinea nigra: report of 6 cases.164 8. Tinea nigra palmaris: a clinical case in Argentina165 9. Tinea nigra by Hortaea werneckii, a report of 22 cases from Mexico.166 10. A case of tinea nigra palmaris in Okinawa,167 11. Tinea nigra: report of twelve cases in Venezuela.168 12. The mycological and molecular study of Hortaea werneckii isolated from blood and

splenic abscess.169 13. The first isolation of Hortaea werneckii from a household guinea pig.177

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2.16. The genus Lasiodiplodia

The genus Lasiodiplodia is a plant pathogen with a very wide host range. It causes rotting and dieback in most species it infects. It is a common post harvest fungus disease of citrus known as stem-end rot. On rare occasions it has been found to cause Fungal keratitis, lesions on nail and subcutaneous tissue. Colonies are grey to black, fluffy with abundant aerial mycelium; reverse black. Pycnidia are simple or compound, often aggregated, stromatic, ostiolate, up to 5 mm wide. Conidiophores are hyaline, simple, sometimes septate, rarely branched cylindrical, arising from the inner layers of cells lining the pycnidial cavity. Conidiogenous cells are hyaline, simple, cylindrical to subobpyriform, holoblastic, annellidic. Conidia are initially unicellular, hyaline, granulose, subovoid to ellipsoide-oblong, thick-walled, base truncate; mature conidia one-septate, cinnamon to fawn, often longitudinally striate, 20-30 x 10-15 µm. 2.16.1. Lasiodiplodia theobromae (Pat.) Griffon & Maubl (1909) Synonyms: Botryodiplodia theobromae Pat. (1892) Diplodia theobromae (Pat.) W. Nowell (1923) Lasiodiplodia tubericola Ellis & Everh. (1896) Lasiodiplodia nigra Appel & Laubert (1907)

Pathogenicity

Lasiodiplodia theobromae has been associated with mycotic keratitis, lesions on nail and subcutaneous tissue..

Recently reported cases:

1. Lasiodiplodia theobromae keratitis: a case report and review of literature.285

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2. Maxillary sinusitis caused by Lasiodiplodia theobromae.286 3. Lasiodiplodia theobromae pneumonia in a liver transplant recipient.287 4. Mycotic keratitis and endophthalmitis caused by unusual

fungi:Lasiodiplodia theobromae288

2.17. The genus Lecythophora

The genus Lecythophora contains 6 species, with two species of medical interest; L hoffmannii and L. mutabilis. Lecythophora spp are a filamentous fungus which is normally found as a commensal on rotting vegetation . Colonies are flat, smooth, moist, pink to orange, with regular and sharp margin; reverse pink. Hyphae are narrow, hyaline, producing conidia laterally from small collarettes directly on the hyphae, or from lateral cells which are sometimes arranged in dense groups; lateral cells flask-shaped or nearly cylindrical. Collarettes are unpigmented, about 1.5 µm wide. Conidia are hyaline, smooth and thin walled, broadly ellipsoidal to cylindrical or allantoid, 3.0-3.5 x 1.5-2.5 µm, produced in slimy heads.

2.17.1. Lecythophora mutabilis (Beyma) Gams & McGinnis(1983) Synonyms: Margarinomyces mutabilis J.F.H. Beyma (1944) Phialophora mutabilis (J.F.H. Beyma) Schol-Schwarz (197

2.17.2. Lecythophora hoffmannii (JBeyma) Gams & McGinnis (1983 Synonyms: Margarinomyces hoffmannii J.F.H. Beyma *1939) Phialophora hoffmannii (J.F.H. Beyma) Schol-Schwarz (1970) Sporotrichum foliicola Oudem (1902) Phialophora aurantiaca J.F.H. Beyma (1939) Aureobasidium foliicolum (Oudem.) G.M. Muell. (1964) Cephalosporium candidum var. arachnoides Sukapure & Thirum (1966)

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Pathogenecity

Lecythophora hoffmannii has been associated with cases of:

1. subcutaneous infections,

2. keratitis,

3. sinusitis,

4. peritonitis.

5. gluteal abscess;

Dogs are thought to become infected from ingesting or inhaling conidial spores

while foraging, through skin wounds or when eating small amphibians and

reptiles. In dogs, chronic diarrhea is usually reported as a symptom of

infection, although lymphadenopathy and osteomyelitis have been reported[5].

Cases recently reported:

1. Lecythophora hoffmannii isolated from a case of canine osteomyelitis in Japan.109 2. Scytalidium dimidiatum and Lecythophora hoffmannii: unusual causes of fungal

infections in a patient with AIDS110 3. Mixed infection caused by Lecythophora canina sp. nov. and Plectosphaerella

cucumerina in a German shepherd dog11 4. Recurrent Lecythophora mutabilis keratitis and endophthalmitis after deep anterior

lamellar keratoplasty112 5. Septic shock induced by Lecythophora mutabilis in a patient with mitochondrial

encephalomyopathy113 6. Lecythophora mutabilis prosthetic valve endocarditis in a diabetic patient.114

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2.18. The genus Leptosphaeria

Leptosphaeria is a dematiaceous filamentous fungus found in the soil. It has currently three defined species. Leptosphaeria species grows in its teleomorphic phase. Colonies of Leptosphaeria grow slowly. The texture is woolly and the front color is dark olive with a gray margin. The reverse color is dark olive to black and is again surroundered by a grayish margin. Microscopically, hyphae, cleistothecia, asci, and ascospores are observed. Cleistothecia are without ostioles, globose to subglobose, and black in color. They carry the asci inside. Asci are clavate to cylindrical and bitunicate. Each ascus carries 8 ascospores inside. Ascospores are 4- to 9-celled, hyaline or pigmented, fusoid to curved, and with a constriction at each septum. Leptosphaeria thompkinsii forms ascospores with 6 septa and pointed ends while ascospores of Leptospheria senegalensis have 4 septa and rounded ends.

2.18.1. Leptosphaeria coniothyrium (Fuckel) Sacc. (1875) Synonyms: Sphaeria coniothyrium Fuckel (1870) Melanomma coniothyrium (Fuckel) L. Holm (1957) Diapleella coniothyrium (Fuckel) M.E. Barr(1986)

1. Kalmusia coniothyrium (Fuckel) Huhndorf (1992)

2.

2.18.2. Leptosphaeria senegalensis Segretain, Baylet, Darasse & Camain (1959)

Synonyms: Leptosphaeria thompkinsii El-Ani (1966)

2.18.3. Leptosphaeria thompkinsii El-Ani (1966)

Colonies of Leptosphaeria spp.

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Microscopic features of Leptosphaeria spp.

Pathogenicity Leptosphaeria spp. are the among the causative agents of:

1. mycetoma and 2. phaeohyphomycosis.

Leptosphaeria senegalensis mycetoma is seen mostly in Central Africa. In cases with mycetoma, black and soft grains with pale centers are observed. These grains are irregular in shape and about 1 mm in diameter.

Recently reported cases:

1. Leptosphaeria Senegalensis Causing Mycetoma Pedis in Madras 283

2. Mycetoma in Yemen: clinicoepidemiologic and histopathologic study284

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2.19. The genus Madurella

Madurella is a dematiaceous filamentous fungus found in soil, particularly in tropical and subtropical areas of Africa, India, and South America. The genus Madurella has two species; Madurella mycetomatis and Madurella grisea.

2.19.1. Madurella mycetomatis (Laveran) Brumpt (1905) Synonyms: Streptothrix mycetomatis Laveran (1902) Madurella mycetomi (Laveran) Brumpt (1905) Madurella americana Gammel, (1927) Madurella ikedae Gammel (1927) Madurella ikedai Gammel (1927)

Colonies are slow growing, flat and leathery at first, white to yellow to yellowish-brown, becoming brownish, folded and heaped with age and the formation of aerial mycelia. A brown diffusable pigment is characteristically produced in primary cultures. Although most cultures are sterile, two types of conidiation have been observed, the first being flask-shaped phialides that bear rounded conidia, the second being simple or branched conidiophores bearing pyriform conidia (3-5 um) with truncated bases. The optimum temperature for growth of this mould is 37C.

59

2.19.2. Madurella grisea Mackinnon, Ferrada & Montemart (1949)

Colonies are slow growing, dark, leathery, folded with radial grooves and with a light brown to greyish surface mycelium. With age colonies become dark brown to reddish-brown and have a brownish-black reverse. Microscopically cultures are sterile although hyphae of two widths have been described, thin at 1 to 3 um in width or broad at 3 to 5 um in width. The optimum temperature of growth for M. grisea is 30C, it does not grow at 37C.

Pathogenicity Madurella is pathogenic for humans and causes infections. Madurella spp. are among the causative agents of human mycetoma.

Recently reported cases:

1. Mycetoma foot due to Madurella mycetomatis.227 2. Mycetoma caused by Madurella mycetomatis: a neglected infectious burden.228 3. Madurella mycetomatis infection following allogenic stem cell transplantation for

aplastic anemia.229 4. Eumycetoma by Madurella mycetomatis with 30 years of evolution: therapeutic

challenge.230 5. Clinical profile and management of craniocerebral Madurellamycetoma..231 6. Madurella mycetomatis as an agent of brain abscess: case report and review of

literature.232 7. Clinical profile and management of craniocerebral Madurella mycetoma.233 8. Mycetoma caused by Madurella mycetomatis: a completely neglected medico-social

dilemma.234

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9. Peripheral blood mononuclear cells of mycetoma patients react differently to Madurella mycetomatis antigens than healthy endemic controls235

10. Oral cavity eumycetoma: a rare and unusual condition.236 11. Madura foot237 12. A histopathological exploration of the Madurella mycetomatis grain.238 13. . A Rare Presentation of Concurrent Scedosporium apiospermum and Eumycetoma

in an Immunocompetent Host.239 14. In vitro antifungal activity of isavuconazole against Madurellamycetomatis.240 15. Mycetoma. Craniocerebral maduromycosis.241 16. Phylogenetic analysis of the complete mitochondrial genome of

Madurella mycetomatis confirms its taxonomic position within the order Sordariales.242

17. Eumycetoma243 18. Analysis of 18 Tunisian cases of mycetoma at the Sousse hospital (1974-2010)244 19. MRI findings in cranial eumycetoma.245 20. New species of Madurella, causative agents of black-grain mycetoma.246 21. Mycetomas diagnosed in Senegal from 2008 to 2010247 22. Madurella mycetomatis mycetoma treated successfully with oral posaconazole.248 23. A chronic, destructive mycetoma infection in a diabetic foot in Saudi Arabia.249 24. In vitro susceptibility of Madurella mycetomatis to posaconazole and terbinafine250 25. The safety and efficacy of itraconazole for the treatment of patients with eumycetoma

due to Madurella mycetomatis.251 26. Clinical and epidemiological features of mycetoma in Morocco252 27. Mycetoma in Tunisia: a 15-case series253 28. Bilateral mycetoma--a case report.254 29. Madurella mycetoma--a rare case with cranial extension.255

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2.20. The genus Myrothecium

This genus contains 8 species. The Myrothecium species are ubiquitous plant pathogens, but are also found on many substrates containing cellulose such as paper, cotton, textiles and plant debris. The Myrothecia have a significant industrial interest in the production of cellulase and are used as a biopesticide to control weeds and nematode population.

The fungus produces moist black or green colonies surrounded by a flaky white margin. The conidiophores, aggregated in superficial pads (sporodochia), bear cylindrical and densely grouped hyaline phialides. The unicellular and smooth conidia, fusiform or cylindrical, have a fan appendix Their moist colonies are black or green surrounded by a flaky white margin. The conidiophores, aggregated in superficial pads (sporodochia), bear cylindrical and densely grouped hyaline phialides. The unicellular and smooth conidia, fusiform or cylindrical, have a fan appendix.

2.20.1. Myrothecium verrucaria (Alb. & Schwein.) Ditmar, (1813)

Synonyms: Peziza verrucaria Alb. & Schwein., (1805) Gliocladium fimbriatum J.C. Gilman & E.V. Abbott, (1927) Metarhizium glutinosum S.A. Pope, Mycologia 36: 343 (1944)

Myrothecium verrucaria

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2.20.2. Myrothecium roridum Tode, (1790)

Synonyms: Dacrydium roridum (Tode) Link, (1809) Gliocladium nigrum Moreau & V. Moreau, (1941)

Myrothecium roridum

Pathogenecity

They have a pathogen capacity related to the production of mycotoxins (trichothecenes, Deoxytrichoverrins, etc.).

2.21. The genus Nattrassia

2.21.1. Nattrassia mangiferae (Syd. & P. Syd.) B. Sutton & Dyko (1989)

Synonyms: Dothiorella mangiferae Syd. & P. Syd (1916)

Fusicoccum mangiferae (Syd.&P.Syd.) Johnson, Slippers & Wingf. (2005)

Fusicoccum mangiferum (Syd.& P.Syd.) Johnson, Slippers & Wingf. (2005)

Fusicoccum mangiferae (Syd.& P.Syd.) Johnson, Slippers & Wingf., (2005)

Neofusicoccum mangiferae (Syd.& P.Syd.) Crous, Slippers & Phillips (2006)

Fusicoccum eucalypti Sousa da Câmara (1929)

Hendersonula cypria Nattrass (1937)

Exosporina fawcettii E.E. Wilson (1947)

Hendersonula agathidis H.E. Young (1948)

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Microscopic morphology of the Scytalidium dimidiatum synanamorph of Nattrassia mangiferae showing

chains of one- to two-celled, darkly pigmented arthroconidia.

Cultures are effuse, hairy, dark grey to blackish-brown, or white to greyish, with a cream-coloured to deep ochraceous-yellow colony reverse. Colourless (hyaline) Microscopically, the fungus shows chains of one- to two-celled, darkly pigmented arthroconidia, 3.5-5 x 6.5-12 µm, produced by the holothallic fragmentation of undifferentiated hyphae.

Pathogenecity: Nattrassia mangiferae is a recognised agent of:

1. onychomycosis 2. Dermatomycosis 3. Keratitis 4. Cerebral phaeohyphomycosis 5. Disseminated infection 6. endophthalmitis.

Recently reported cases

1. A case of sinusitis caused by nattrassia mangiferae in iran328 2. Nattrassia mangiferae keratitis after laser in situ keratomileusis329 3. An uncommon agent of onychomycosis.330 4. Dermatomycoses caused by Nattrassia mangiferae in Sao Paulo, Brazil. 331 5. Nattrassia mangiferae causing fungal keratitis.332 6. Onychomycosis in São Paulo, Brazil.333 7. First case of cerebral phaeohyphomycosis caused by Nattrassia mangiferae in

Iran.334 8. Nattrassia mangiferae keratitis after laser in situ keratomileusis.335 9. Disseminated infection with Nattrassia mangiferae in an immunosuppressed

patient.336 10. Case report. Nattrassia mangiferae endophthalmitis.337

11. Post-traumatic fatal Nattrassia mangiferae orbital infection.338

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2.22.The genus Ochroconis The genus Ochroconis lacks a known sexual state and thus belongs to the Fungi Imperfecti. It is generally classified as a dematiaceous (dark-walled) fungus. It contains the following species:

2.22.1. Ochroconis gallopava (W.B. Cooke) de Hoog (1983)

Synonyms: Diplorhinotrichum gallopavum W.B. Cooke (1964)

Dactylaria gallopava (W.B. Cooke) G.C. Bhatt & W.B. Kendr. (1968)

Dactylaria constricta var. gallopava (W.B. Cooke) Salkin & Dixon, (1987)

Colonies are smooth to suede-like, dry, flat, tobacco-brown to brownish-black with a dark brown diffusible pigment. Hyphae are brown with relatively thick walls. Conidiophores are mostly cylindrical to acicular, sometimes poorly differentiated, bearing a few conidia at the tip. Conidia are two-celled, subhyaline to pale brown, smooth-walled to verrucose, cylindrical to clavate, constricted at the septum, 11-18 x 2.5-4.5 µm in size, with the apical cell wider than the basal cell. A remnant of a denticle may also be seen at the conidial base. Optimum growth at 35C, tolerant to 40C.

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2.22.2. Ochroconis anomala

2.22.3. Ochroconis constricta Synonyms: Dactylaria constricta var. constricta Heterosporium terrestre .

Scolecobasidium constrictum 2.22.4. Ochroconis humicola Synonyms: Scolecobasidium humicola

O. constricta O. humicola

Health significance

1. Epidemic fatal encephalitis in fowls, turkeys, and poults

2. In human, Ochroconis gallopava’s most common targets are respiratory

system and central nervous system and also affects skin, joints, muscles,

liver, spleen, thyroid, and other parts of the body.

3. Ochroconis gallopava cause phaeohyphomycosis which is a tissue infection

forming scab-like black colored lesions in affected organs including

skin, acute or chronic inflammation, microabscess, fibrosis, granuloma, and

necrosis as well.

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Economic significanc215

Ochroconis anomala is in 2012. It was isolated from the black stains that appeared on the walls of Lascaux Cave in France. The species was discovered along with a closely related O. lascauxensis. The species are regarded as a threat to the prehistoric paintings of the cave. The fungus was honoured as one of the "Top 10 New Species" discovered in 2012 selected by the International Institute for Species Explorationat Arizona State University among more than 140 nominated species. The uniqueness is its recent emergence and serious threat to the cave painting. The selection was declared on 22 May 2013.

An example of the cave painting in the Lascaux Cave

Recently reported cases:

1. Disseminated Ochroconis gallopava infection in a heart transplant patient. 200 2. Ochroconis gallopava infection in a patient with chronic granulomatous disease: case

report and review of the literature.201 3. First report of subcutaneous phaeohyphomycosis caused

byOchroconis tshawytschae in an immunocompetent patient. 202 4. Ochroconis gallopava: a dematiaceous mold causing infections in transplant

recipients. 203 5. Ochroconis gallopava peritonitis in a cardiac transplant patient on continuous

ambulatory peritoneal dialysis.204 6. Ochroconis calidifluminalis, a sibling of the neurotropic pathogen O. gallopava,

isolated from hot spring.205 7. Transplant-associated Ochroconis gallopava infections. 206 8. Epidemiology of central nervous system mycoses. 207 9. Pathogenicity of Ochroconis gallopava isolated from hot springs in Japan and a

review of published reports. 208 10. Fatal systemic phaeohyphomycosis caused by Ochroconis gallopavum in a dog

(Canis familaris).209

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11. Rapid identification of Ochroconis gallopava by a loop-mediated isothermal amplification (LAMP) method. 210

12. Pemphigus patient with pulmonary fungal infection caused byOchroconis gallopava: the first case report in China211

13. Infections due to dematiaceous fungi in organ transplant recipients: case report and review. 212

14. Phaeohyphomycosis caused by Dactylaria (human dactylariosis): report of a case with review of the literature. 213

15. Subcutaneous abscesses caused by Ochroconis gallopavum214 16. Two new species of the genus Ochroconis, O. lascauxensis and O. anomala isolated

from black stains in Lascaux Cave, France.215

2.23. The genus Phialemonium

The genus was created to accommodate taxa intermediate to Acremonium and Phialophora. It contains several species, of which 2 species have health significance, namely P. curvatum and P. obovatum. This genus is characterized by its abundance of adelophialides and few discrete phialides with no signs of collarettes. 2.23.1. Phialemonium curvatum W. Gams & W.B. Cooke (1983) Synonym: Phialemoniopsis curvata H. Perdomo, D. García, Gené, Cano & Guarro (2013)

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2.23.2. Phialemonium obovatum W. Gams & McGinnis (1983)

Pathogenecity

1. Arthritis

2. Endocarditis

3. Endophthalmitis

4. Subcutaneous infection

5. Infection in patients undergoing hemodialysis.

6. Infection of the lower spine

7. respiratory system

Recently reported cases: 1. Phialemonium infection complicating chronic suppurative otitis media.339

2. Phialemonium obovatum keratitis after penetration injury of the cornea.340 3. Phialemonium curvatum fungaemia in an immunocompromised patient: case report.341 4. Phialemonium curvatum infection after phacoemulsification: a case report.342 5. Molecular and phenotypic characterization of Phialemonium and Lecythophora isolates

from clinical samples.343 6. Infections due to Phialemonium species: case report and review.344 7. Pulmonary Phialemonium curvatum phaeohyphomycosis in a standard poodle dog.345 8. Lung infection due to opportunistic fungus, Phialemonium obovatum, in a bone marrow

transplant recipient: an emerging infection with fungemia and Crohn disease-like involvement of the gastrointestinal tract.346

9. Fatal endocarditis in a neonate caused by the dematiaceous fungus Phialemonium obovatum: case report and review of the literature.347

10. Phialemonium curvatum infection after bone marrow transplantation.348 11. Disseminated infection with Phialemonium obovatum in a German shepherd dog.349 12. Osteolytic phaeohyphomycosis caused by Phialemonium obovatum350

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2.24. The genus Phialophora

The genus Phialophora contains more than 40 species, most are saprophytes commonly found in soil or on decaying wood. Morphological features, such as the shape of the collaretes, organization of the phialides, existence of chlamydospores, and biochemical features, such as the assimilation of melibiose help in differentiation of the species from each other. However, the following species have been documented as causing either chromoblastomycosis or phaeohyphomycosis :

1. Phialophora americana 2. Phialophora bubakii 3. Phialophora europaea 4. Phialophora parasitica 5. Phialophora reptans 6. Phialophora repens 7. Phialophora richardsiae 8. Phialophora verrucosa

Morphology

Colonies of Phialophora grow moderately slowly and attain a diameter of 2 3 cm following an incubation of 7 days at 25°C. The texture is wooly to velvety and may be heaped and granular in some strains. From the front, the color is initially white and later becomes dark grey-green, brown or black. From the reverse, it is iron grey to black. Microscopically, members of the genus Phialophora produce clusters of single-celled conidia in basipetal succession from characteristic flask-shaped or cylindrical phialides which have distinctive collarettes. Conidia are hyaline to olivaceous brown, smooth-walled, ovoid to cylindrical or allantoid, and usually aggregate in slimy heads at the apices of the phialides, which may be solitary, or in a brush-like arrangement.

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2.24.1. Phialophora verrucosa Medlar (1915) Synonyms: Phialophora calyciformis G. Sm. (1962) Cadophora richardsiae Nannf (1934) Cadophora brunnescens R.W. Davidson (1935) Phialophora richardsiae (Nannf.) Conant (1937) Cadophora richardsiae Nannf (1934) Cadophora brunnescens R.W. Davidson (1935) Phialophora calyciformis G. Sm (1962) Pleurostomophora richardsiae (Nannf.) Mostert, Gams & Crous, (2004)

P. verrucosa.

2.24.2. Phialophora richardsiae (Nannf.) Conant (1937) Synonyms: Cadophora richardsiae Nannf. (1934) Pleurostomophora richardsiae (Nannf.) Mostert, Gams & Crous, (2004) Cadophora brunnescens R.W. Davidson (1935) Phialophora calyciformis G. Sm (1962)

Phialophora verrucosa

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2.24.3. Phialophora parasitica Ajello, Georg & C.J.K. Wang (1974) Synonym: Haeoacremonium parasiticum (Ajello, Georg & Wang) W. Gams, Crous & Wingf.(1996)

Phialophora parasitica

2.24.4. Phialophora repens (Davidson) Conant (1935) Synonyms: Cadophora repens Davidson, (1935) Pleurostomophora repens (Davidson) Mostert, Gams & Crous (2004)

Phialophora repens

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2.24.5. Phialophora europaea de Hoog, Mayser & Haase, (2000) Synonym: Cyphellophora europaea (de Hoog, Mayser & Haase) Réblová & Unter., (2013)

Phialophora europaea

Pathogenicity

Phialophora species cause the following clinical forms: 1. cutaneous infections, 2. nail infections 3. subcutaneous cysts, 4. keratitis, 5. endocarditis, 6. arthritis, 7. osteomyelitis, 8. cerebral infection, 9. fatal hemorrhage, and 10. disseminated infection. Phialophora europaea has been isolated from cutaneous and

nail infections in North-western Europe

Recently reported cases: 1. Phialophora verrucosa as a cause of deep infection following total knee arthroplasty.

216 2. Generalized chromomycosis caused by Phialophoraverrucosa. 217 3. Generalized subcutaneous phaeohyphomycosis caused by Phialophora verrucosa:

report of a case and review of literature.218 4. Recalcitrant primary subcutaneous phaeohyphomycosis due to

Phialophora verrucosa.219 5. In vitro activities of nine antifungal drugs against 81Phialophora and Cyphellophora

isolates. 220 6. Endophthalmitis caused by Phialophora verrucosa: a case report and literature

review of Phialophora ocular infections. 221

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7. Endophthalmitis caused by Phialophora verrucosa and Streptococcus intermedius: a case report. 222

8. Chromoblastomycosis Caused by Phialophora richardsiae.223 9. Chronic fistula of the forefoot in a Moroccan man: bone chromomycosis due

to Phialophora verrucosa.224

10. Subcutaneous phaeohyphomycosis (mycotic cyst.225

11. A new species, Phialophora europaea, causing superficial infections in humans.226

2. 25. The genus Phoma

Phoma is a dematiaceous filamentous fungus that inhabits the soil and plant material. Phoma species are cosmopolitan in nature and are common plant.pathogens. Phoma species may rarely cause infections in humans. The genus Phoma contains several species. Colour of the colony, morphology of the conidia, existence and structure of chlamydospores help in differentiation of the species from each other.

2.25.1. Phoma herbarum Westend.,(1852)

Synonyms: Phoma oleracea Sacc., (1880)] Aposphaeria violacea Bertel, (1904) Phoma pigmentivora Massee,(1911) Phoma hibernica Grimes, M. O'Connor & Cummins, (1932) Phoma lignicola Rennerf (1937) Pyrenochaeta mali M.A. Sm., (1963)

Morphology Phoma develops rapidly growing flat, spreading, powdery to velvety, and often largely submerged colonies in the medium. Colonies are initially white and later become olive grey in colour with an occasional tint of pink. The reverse is dark brown to black. Some species (particularly, Phoma cruris-hominis and Phoma herbarum) produce a reddish-purple to yellowish-brown diffusable pigment which is readily visible from the reverse. Microscopically, the fungus develops septate, hyaline to brown hyphae, round to pyriform large pycnidia, have one to several openings (ostioles) on their surface from which the conidia are released outside. Conidia are unicellular, hyaline, and oval-shaped. Each conidium typically has two oil droplets inside.

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Some Phoma species produce brown chlamydospores that are arranged singly or in chains. These chlamydospores may be unicellular or multicellular as in Alternaria.

Colonies of phoma species Pycnidia of Phoma.

Pathogenicity Phoma species may cause:

1. cutaneous, 2. subcutaneous, 3. corneal or 4. systemic.

Recently reported cases:

1. Screening of different species of Phoma for the synthesis of silver nanoparticles351 2. Unusual mould infection in the human stratum corneum.352 3. Subcutaneous phaeohyphomycosis caused by Phoma cruris-hominis in renal

transplant patient.353 4. Subcutaneous abscess caused by Phoma sp. resembling Pyrenochaeta rameroi.

Uniques fungal infection occuring in immunosuppressed recipient of renal allograft.354

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2.26. The genus Pithomyces

The genus Pithomyces contains 15 species commonly found on litter and soil, however, one species, Pithomyces chartarum is often involved with facial eczema of sheep.

2.26.1. Pithomyces chartarum (Berk. & M.A. Curtis) M.B. Ellis (1960) Synonyms: Sporidesmium chartarum Berk. & M.A. Curtis (1874) Piricauda chartarum (Berk. & M.A. Curtis) R.T. Moore (1959) Sporidesmium bakeri Syd. & P. Syd. (1914)

Colonies are fast growing, dark grey to black, suede-like to downy and produce darkly pigmented, multicellular conidia (phragmo- or dictyoconidia) formed on small peg-like branches of the vegetative hyphae. Conidia are broadly elliptical, pyriform, oblong, and commonly echinulate or verrucose. Spores (conidia) produced at the apex of short side branches of the vegetative filaments, dark brown, 2- to several-celled. When the spores are released they retain a small portion of the cell that produced them. The spores of P. chartarum, the most commonly isolated species, have both longitudinal and transverse walls.

Pathogenecity

Pithomyces chartarum occurs worldwide but is a problem predominantly where farm animals are intensively grazed, especially in New Zealand. The spores of the fungus release the mycotoxin sporidesmin in the gastrointestinal tract,

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causing a blockage in the bile ducts that leads to injury of the liver. Bile, chlorophyll and other waste products consequently build up in the bloodstream causing photo sensitivity of the skin especially that exposed to direct sunlight. This in turn causes severe skin irritation that the animal attempts to relieve by rubbing its head against available objects, resulting in peeling of the skin.

Recently reported cases:

1. Mycotoxicoses of ruminants and horses355

2. The effect of zinc oxide and elemental zinc boluses on the concentrations of Zn in

serum and faeces, and on providing protection from natural Pithomyces chartarum

challenge in sheep.356

3. First case of pithomycotoxicosis (facial eczema) in the Netherlands358

4. Pithomycotoxicosis (facial eczema) in ruminants in the Azores, Portugal.359

5. Putative sporidesmin toxicity in an Eastern Grey kangaroo (Macropus giganteus).360

2. 27. The genus Pyrenochaeta Pyrenochaeta is a filamentous fungus that inhabits the soil and plant debris, particularly in tropical climates. The genus Pyrenochaeta contains four active species;

1. Pyrenochaeta romeroi. 2. Pyrenochaeta keratinophila 3. Pyrenochaeta mackinnonii, 4. Pyrenochaeta unguis-hominis,

Many isolates previously identified as Madurella grisea have been reidentified as Pyrenochaeta romeroi,

some authorities believe that Pyrenochaeta romeroi should be classified in the genus Phoma.

Morphology Colonies grow moderately rapidly. They are flat and woolly to cottony; the color is white initially and becomes olivaceous green to olivaceous gray; everse is dark. Microscopically, there are septate, hyaline to subhyaline

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hyphae, pycnidia, and conidia. Pycnidia are globose to flask-shaped, ostiolate, brown to black and have setae. Phialides arise from the inner lining of the pycnidia. Conidia (2-4 x 1-2 µm) are one-celled, oval to cylindrical, hyaline, and straight or slightly curved

2.27.1. Pyrenochaeta romeroi Borelli (1959) Synonym: Medicopsis romeroi (Borelli) Gruyter, Verkley & Crous (2012)

Colony of Pyrenochaeta romeroi Pycnidium ellipsoidal to bacilliform conidia

2.27.2. Pyrenochaeta keratinophila Verkley, C. Ferrer & Gené (2009)266

Pyrenochaeta keratinophila pycnidium mycelium conidia

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Pathogenicity

1. Pyrenochaeta romeroi has been isolated from cases with mycetoma. The grains are soft, irregular, and black with a subhyaline center.

2. Pyrenochaeta unguis-hominis has been isolated from the infected nails of some cases.

Recently reported cases:

1. Pyrenochaeta keratinophila sp. nov., isolated from an ocular infection in Spain.266

2. Subcutaneous phaeohyphomycotic cyst caused by Pyrenochaeta romeroi.267

3. Molecular diagnosis and therapeutic experience of

subcutaneous Pyrenochaeta romeroi infection: a case report and review of the

literature.268 4. Draft Genome Sequence of Dematiaceous Coelomycete Pyrenochaeta sp. Strain UM

256, Isolated from Skin Scraping269

5. Phaeohyphomycosis caused by Pyrenochaeta romeroi mimicking a plantar wart in a

kidney transplant recipient.270

6. Pyrenochaeta romeroi: a causative agent of phaeohyphomycotic cyst.271

7. Subcutaneous phaeohyphomycotic cyst caused by Pyrenochaeta romeroi.272

8. Isolation, identification and susceptibility of Pyrenochaetaromeroi in a case of

eumycetoma of the foot in the UK.273

9. New pyrenochaeta species causing keratitis274

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2.28. The genus Pythium

Pythium spp. are plant pathogens that produce motile oospores. Organisms of

this genus are sometimes called aquatic fungi, but they really are not

considered to be true fungi. The genus Pythium contains over 120

morphological species with a unique degree of ecological specialization that

include important plant pathogens, parasites of a diversity of organisms in

aerial and water environments and saprophytes that subsist on dead organic

material. Pythium species are often studied as part of medical mycology due

to their ability to produce a chronic granulomatous process in which one sees

hyphal structures. The disease is sometimes called "swamp cancer" due to its

association with water exposure. In animals they cause cutaneous lesions in

cats and dogs, in horses rhere may be bone involvement. Pythyum insidiosum

is the agent of swamp cancer of horses and phythiosis in man. Pythium, like

others in the family Pythiaceae, are usually characterized by their production

of coenocytic hyphae, hyphae without septations. Oogonia generally contain a

single oospore. Antheridia contain an elongated and club-shaped antheridium

2.28.1. Pythium insidiosum De Cock, L. Mend., A.A. Padhye, Ajello & Kaufman (1987)

Synonym: Hyphomyces destruens C.H. Bridges & C.W. Emmons (1961)

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Pathogenecity:

Pythyum insidiosum causes the followings:

1. Vascular pythiosis

2. Cutaneous pythiosis

3. gastrointestinal pythiosis

4. keratitis

Recently reported cases: 1. In vitro susceptibility of zoospores and hyphae of Pythium insidiosum to

antifungals.361

2. Photodynamic Therapy in Pythium insidiosum - An In Vitro Study of the Correlation of Sensitizer Localization and Cell Death.362

3. Vascular pythiosis in a thalassemic patient presenting as bilateral leg ulcers.363 4. Cutaneous pythiosis in two dogs from Wisconsin, USA.364 5. Evaluation for the clinical diagnosis of Pythium insidiosum using a single-tube nested

PCR.365 6. Canine gastrointestinal pythiosis treatment by combined antifungal and

immunotherapy and review of published studies.366 7. Long-term follow-up after successful treatment of Pythium insidiosum keratitis in

Israel.367 8. Pathology of nasal infection caused by Conidiobolus lamprauges

and Pythium insidiosum in sheep.368 9. Iron chelation therapy as a treatment for Pythium insidiosum in an animal model.369 10. Pythiosis of the digestive tract in sheep.370 11. [Pythium insidiosum ocular infection].371 12. Outbreak of Pythium keratitis during rainy season: a case series.372 13. Treatment of pythiosis in equine limbs using intravenous regional perfusion of

amphotericin B.373 14. Treatment of intestinal pythiosis in a dog with a combination of marginal excision,

chemotherapy, and immunotherapy.374 15. Equine pythiosis: report in crossed bred (Criole Venezuelan) horses.375 16. Dual infection with Pythium insidiosum and Blastomyces dermatitidis in a dog.376

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2. 29. The genus Ramichloridium

Ramichloridium contains about 25 species that are usually associated with forest litter and rotting wood, however the genus contains one species of medical interest : Ramichloridium schulzeri .The remaining species of medical importance were considered as synonyms of Rhinocladiella as in:

1. Ramichloridium cerophilum: synonym of Rhinocladiella aquaspersa 1. Ramichloridium mackenziei synonym of Rhinocladiella mackenziei 2. Ramichloridium obovoidea: synonym of R. mackenziei 3. Ramichloridium obovoiedum: synonym of R. mackenziei

Colonies grow moderately rapidly, consisting of a compact, flat, submerged, pale orange, locally with some powdery, brownish aerial mycelium; reverse pink to orange. Conidiophores are erect, straight, unbranched, thick-walled, reddish-brown, up to 250 µm high, gradually becoming paler towards the apex, of variable length, elongating sympodially during conidiogenesis, with scattered, pimple-shaped conidium bearing denticles which have unpigmented scars. Conidia are subhyaline, smooth-walled or slightly rough-walled, ellipsoidal, obovoidal or fusiform, 6.5-10.0 x 3-4 µm, usually with an acuminate base and unpigmented scars.

2.29.1. Ramichloridium schulzeri (Sacc.) de Hoog (1977)

Synonyms: Chloridium schulzerii (Sacc.) Sacc. (1884) Psilobotrys schulzerii Sacc. (1884) (1884) Psilobotrys schulzeri Sacc. (1884) Chloridium schulzeri (Sacc.) Sacc (1886) Rhinocladiella schulzeri (Sacc.) Matsush. (1975) Acrotheca acuta Grove, (1916) Rhinotrichum multisporum Doguet, (1952) Myrmecridium schulzeri (Sacc.) Arzanlou, W. Gams & Crous, (2007)

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Pathogenecity

Ramichloridium schulzeri is one of the causes of phaeohyphomycosis.

Recently reported cases:

1. Aspiration cytology of brain abscess from a fatal case of cerebral phaeohyphomycosis due to Ramichloridium mackenziei.275 2. Cerebral phaeohyphomycosis caused by Ramichloridium mackenziei in the Eastern Province of Saudi Arabia.276 3. Successful therapy of cerebral phaeohyphomycosis due to Ramichloridium mackenziei with the new triazole posaconazole.

277

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2. 30. The genus Rhinocladiella

Rhinocladiella is a cosmopolitan fungus which can be found in soil,

herbaceous substrates, and decaying wood. The genus

Rhinocladiella comprises 8 species, 3 of which are accepted

namely, Rhinocladiella aquaspersa, Rhinocladiella atrovirens and

Rhinocladiella mackenziei , while the remaining five species have been

obsolete and have been only considered by experts as synonyms for a few

species under Fonsecaea and Exophiala genera.

1. Rhinocladiella aquaspersa 2. Rhinocladiella atrovirens 3. Rhinocladiella mackenziei

4. Rhinocladiella compactum

a synonym of Fonsecaea compacta 5. Rhinocladiella mansonii

a synonym of Exophiala castellanii 6. Rhinocladiella pedrosoi

a synonym of Fonsecaea pedrosoi 7. Rhinocladiella schulzeri

a synonym of Ramichloridium schulzeri 8. Rhinocladiella spinifera

a synonym of Exophiala spinifera

2.30.1. Rhinocladiella aquaspersa (Borelli) Schell, McGinnis & Borelli (1983) Synonym: Acrotheca aquaspersa Borelli (1972)

Colonies are slow growing, velvety, dark green to black in colour. Microscopically, septate hyphae, black, thin-walled, slightly roughened hyphae. Conidiophore are poorly differentiated with__ branched, thick-walled, brown intercalary conidiogenous cells, cylindrical in the apical part of __ conidiophore. Conidia are hyaline having thin, ellipsoidal walls. __

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2.30.2. Rhinocladiella mackenziei (Campb. & Al-Hedaithy) Arzanlou & Crous (2007) Synonym: Ramichloridium mackenziei C.K. Campb. & Al-Hedaithy (1993)

2.30.3. Rhinocladiella atrovirens Nannf., (1934)

Melanchlenus eumetabolus Calandron (1953]

Melanchlenus cumetabolus Calandron (1953)

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Health significance: Rhinocladiella species are causative agents of Chromoblastomycosis.

Recently reported cases:

1. Chromoblastomycosis caused by Rhinocladiella aquaspersa.256

2. The first case of phaeohyphomycosis caused by Rhinocladiella basitona in an

immunocompetent child in China.257

3. Cerebral phaeohyphomycosis due to Rhinocladiellamackenziei (formerly

Ramichloridium mackenziei): case presentation and literature review.258

4. Rhinocladiella mackenziei as an emerging cause of cerebral phaeohyphomycosis in

Pakistan: a case series259

5. Co-existence of cerebral infection with Rhinocladiellamackenziei and primary central

nervous system lymphoma in a HIV-negative patient.260

6. Cerebral phaeohyphomycosis caused by Rhinocladiella mackenziei in a woman

native to Afghanistan.261

7. First autochthonous case of Rhinocladiella mackenziei cerebral abscess outside the

Middle East.262

8. Cerebral phaeohyphomycosis due to Rhinocladiellamackenziei (formerly

Ramichloridium mackenziei): a taxonomic update and review of the literature.263

9. In vitro activities of antifungal drugs against Rhinocladiellamackenziei, an agent of

fatal brain infection.264

10. Cerebral Phaeohyphomycosis Caused by Rhinocladiella mackenziei in a Woman

Native to Afghanistan.265

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2. 31. The genus Scedosporium The genus Scedosporium contains two species:

1. Scedosporium apiospermum 2. Scedosporium prolificans.

Pseudallescheria boydii is the telemorph of Scedosporium apiospermum. No sexual form (telemorph) is known for Scedosporium prolificans. 2.31.1. Scedosporium apiospermum (Sacc. ) Castell. & Chalm (1919) Synonyms: Monosporium apiospermum Sacc.(1911) Aleurisma apiospermum (Sacc.) Maire, (1921) Actinomyces albus Tarozzi (1909) Monosporium sclerotiale Pepere (1914) Dendrostilbella boydii Shear, (1922) Glenospora clapieri Catanei, (1927) Acremonium suis Bakai, Bolezni Svinei, Kiev: 198 (1967) Polycytella hominis C.K. Campb. (1987)

Scedosporium apiospermum

2.31.2. Scedosporium prolificans (Hennebert & B.G.Desai) E.Guého & de Hoog (1991) Synonyms: Scedosporium inflatum Malloch & Salkin (1984) Lomentospora prolificans Hennebert & B.G. Desai (1974)

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scedosporium prolificans

Morphology Colonies of Scedosporium prolificans grow rapidly at 25°C and mature within 5 days. The texture is cottony and moist (yeast-like) initially which later becomes flat with fine, short, mycelial tufts. From the front, the color is light gray to black and becomes dark gray to black as the colony matures. The reverse is gray to black. Septate hyaline hyphae, conidiogenous cells (annelides), and conidia are visualized. Annelides (conidiogenous cells) may arise directly from hyphae or are formed at the tips of the conidiophores. These annelides are flask-shaped and have a swollen base part and an elongated neck. Conidia (2-5 x 3-13 µm) are unicellular, oval-shaped, olive to brown, and have a slightly narrowed, truncated base. They are formed in clusters at the apices of the annelides. In addition, some isolates may produce round, thick-walled conidia which arise directly from the hyphae. Colonies of Scedosporium prolificans are darker compared to those of Scedosporium apiospermum. The inflated conidiogenous cells (annelides) and slightly wider conidia of Scedosporium prolificans, and the inability of Scedosporium prolificans to assimilate ribitol, xylitol, and L-arabinitol also help in differentiation of the two species. Besides, unlike Scedosporium apiospermum, Scedosporium prolificans does not convert to a sexual form. Differentiation of these two species has been achievable also by PCR assay and hybridization probes Pathogenicity Scedosporium prolificans is an emerging opportunistic fungal pathogen that causes :

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1. Subcutaneous infections, 2. Osteomyelitis, and arthritis 3. Disseminated phaeohyphomycosis 4. Pneumonia 5. Meningoencephalitis 6. Endocarditis 7. Ocular infections (keratouveitis)

Recently reported cases:

1. Battery of rockets "Scedosporium apiospermum" in mycotic keratitis289 2. ESCMID and ECMM joint guidelines on diagnosis and management of

hyalohyphomycosis: Fusarium spp.,Scedosporium spp. and others.290 3. Impact of Scedosporium apiospermum complex seroprevalence in patients with

cystic fibrosis.291 4. Matrix-assisted laser desorption ionization-time of flight mass spectrometry for fast

and accurate identification of Pseudallescheria/Scedosporium species.292 5. Infective endocarditis and meningitis due to Scedosporium prolificans in a renal

transplant recipient.293 6. Scedosporium prolificans immunomes against human salivary immunoglobulin A294 7. Successful prevention of scedosporiosis after lung transplantation in a cystic fibrosis

patient by combined local and systemic triazole therapy.295 8. Locally extensive angio-invasive Scedosporium prolificans infection following

resection for squamous cell lung carcinoma.296 9. Scedosporium apiospermum brain abscesses in an immunocompetent man with

silicosis297 10. Management of Scedosporium apiospermum in a pre- and post-lung transplant

patient with cystic fibrosis.298 11. Diabetic foot ulcer due to scedosporium apiospermum299 12. White grain mycetoma caused by Scedosporium apiospermum in North India: a case

report.300 13. Scedosporium apiospermum: An unreported cause of fungal sporotrichoid-like

lymphocutaneous infection in Australia and review of the literature301 14. . Nebulized voriconazole in infections with Scedosporium apiospermum - Case report

and review of the literature.302 15. Sporotrichoid eruption in a patient after lung

transplantation.Scedosporium apiospermum fungal thrombophlebitis and sporotrichoid nodules303

16. Scedosporium aurantiacum brain abscess after near-drowning in a survivor of a tsunami in Japan.304

17. Fungal keratitis caused by Scedosporium apiospermum: first report from Turkey305. 18. Scedosporium prolificans endogenous endophthalmitis.306

19. infection caused by Scedosporium apiospermum in immune-compromised patients. Report of two cases.307

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2. 32. The genus Scytalidium

Scytalidium is a genus that has a widespread distribution and contains 18

species. Scytalidium dimidiatum causes onychomycosis in tea leaf pluckers

2.32.1. Scytalidium dimidiatum (Penz.) B. Sutton & Dyko (1989) Synonyms: Torula dimidiata Penz., Michelia (1882) Fusicoccum dimidiatum (Penz.) D.F. Farr (2005) Neoscytalidium dimidiatum (Penz.) Crous & Slippers(2006 Hendersonula toruloidea Nattrass (1933)

Pathogenecity Scytalidium dimidiatum causes

1. onychomycosis 2. Subcutaneous infection 3. keratitis. 4. Cerebral phaeohyphomycosis 5. Disseminated fungal infection

Recently reported cases:

1. Scytalidium and scytalidiosis: what's new in 2012?308 2. Subcutaneous infection spread by Scytalidium (Neoscytalidium) dimidiatum309 3. . Successful eradication of Scytalidium dimidiatum-induced ungual and cutaneous

infection with voriconazole.310 4. . Epidemiological aspects of patients with ungual and cutaneous lesions caused

by Scytalidium spp.311 5. Intermittent posaconazole regimen to treat superficial

Scytalidium dimidiatum infection.312

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6. Nattrassia mangiferae causing fungal keratitis.313 7. . In vitro activity of fluconazole, itraconazole, voriconazole and terbinafine against

fungi causing onychomycosis.314 8. . Genotyping and in vitro antifungal susceptibility of

Neoscytalidium dimidiatum isolates from different origins. 315 9. Invasive Scytalidium dimidiatum infection in an immunocompetent adult.316 10. Invasive infection in a young immunocompetent soldier caused

by Scytalidium dimidiatum317 11. Cerebral phaeohyphomycosis caused by Scytalidium dimidiatum: a case report from

India.318 12. Disseminated fungal infection in a renal transplant recipient involving Macrophomina

phaseolina and Scytalidium dimidiatum: case report and review of taxonomic changes among medically important members of the Botryosphaeriaceae.319

13. [Non-dermatophytic moulds: onychomycosis in four patients infected with the human immunodeficiency virus320

14. In vitro susceptibility of isolates of Scytalidium spp. from superficial lesions against posaconazole321

15. In vitro activity of amphotericin B, itraconazole, voriconazole, posaconazole, caspofungin and terbinafine against Scytalidium dimidiatum and clinical isolates.322

16. . Onychomycosis by Scytalidium dimidiatum in green tea leaf pluckers: report of two cases.323

17. In vitro activity of voriconazole against dermatophytes, Scopulariopsis brevicaulis and other opportunistic fungi as agents of onychomycosis324

18. . Onychomycosis by Scytalidium dimidiatum: report of two cases in Santa Catarina, Brazil.325

19. Fusicoccum arbuti sp. nov. causing cankers on pacific madrone in western North America with notes on Fusicoccum dimidiatum, the correct name for Scytalidium dimidiatum and Nattrassia mangiferae.326

20. Scedosporium prolificans fungaemia in a patient with acute lymphoblastic leukaemia327

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2.33. The genus Stachybotrys

The genus Stachybotrys has a widespread distribution, and contains about 50

species. The name comes from the Greek words "stakhus" (ear of grain, stalk,

stick; σταχυς) or "stachy" (progeny) and "botrus" (cluster or bunch as in

grapes, trusses; βότρυς).The most infamous species, S. chartarum and S.

chlorohalonata are frequently associated with poor indoor air quality that arises

after fungal growth on water-damaged building materials.

Stachybotrys produces cottony, rapidly growing colonies which are white initially and turn to black by aging. Microscopically, the fungus develops septate hyphae, which appear hyaline initially and become darkly pigmented with age. The conidiophores which may be simple or branched, bear phialides at their apices. They are hyaline or pigmented, cylindrical in shape, and have swollen upper portions. They form clusters of 3 to 10. The conidia (4.5 x 9 µm) are oval, hyaline or pigmented, 1-celled, and in clusters

Stachybotrys produces trichothecene mycotoxins known as satratoxins. These toxins may lead to pathological changes in animal and human tissues.

2.33.1. Stachybotrys chartarum (Ehrenb.) S. Hughes (1958)

Synonyms: Stilbospora chartarum Ehrenb. (1818) Oidium chartarum (Ehrenb.) Link (1824) Oospora chartarum (Ehrenb.) Wallr., (1833) Stachybotrys atra Corda, (1837) Sporocybe lobulata Berk (1841) Synsporium biguttatum Preuss, (1849) Stachybotrys alternans Bonord., (1851) Stachybotrys atra var. brevicaulis Verona, (1839) Stachybotrys atra f. lobulata Verona, (1839) Stachybotrys atra var. brevicaule Verona (1939) Stachybotrys lobulata var. angustispora Moreau & V. Moreau (1841)

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Pathogenecity:

1. Hypersensitivity pneumonitis 2. Rhinitis 3. Allergy 4. Irritation to various areas including the eyes, mucous membranes of the mouth, nose

and throat, 5. Vomiting, and bleeding in the lungs and nose

Recently reported cases:

1. Stachybotrys eucylindrospora isolated from foreign material following a traumatic eye injury.377

2. TLR9-dependent IL-23/IL-17 is required for the generation of Stachybotrys chartarum-induced hypersensitivity pneumonitis.378

3. Allergen of the month--Stachybotrys chartarum379 4. Satratoxin-G from the black mold Stachybotrys chartarum induces rhinitis and

apoptosis of olfactory sensory neurons in the nasal airways of rhesus monkeys.380 5. Recurrence of Stachybotrys chartarum during mycological and toxicological study of

bioaerosols collected in a dairy cattle shed.381 6. Stachybotrys chartarum-induced hypersensitivity pneumonitis is TLR9 dependent.382 7. Stachybotrys chartarum: Current knowledge of its role in disease. 383 8. Quantification of siderophore and hemolysin from Stachybotrys chartarum strains,

including a strain isolated from the lung of a child with pulmonary hemorrhage and hemosiderosis.384

9. Initial characterization of the hemolysin stachylysin from Stachybotrys chartarum.385

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2. 34. The genus Stemphylium

Stemphylium is a dematiaceous filamentous fungus that is widely distributed on decaying vegetation and in the soil. It is commonly considered as a contaminant. The only well-known species included in the genus is Stemphylium macrosporoideum.

Morphology Colonies of Stemphylium grow rapidly, they are velvety to cottony in texture, gray, brown, or brownish-black in colour. Reverse is black. Microscopically, the fungus develops septate hyphae, which are pale brown to brown in colour. Conidiophores are black, may be simple or branched, bear a number of vesicular swellings or nodes. Conidiogenous cells are terminally located and percurrent (the proliferation which grows through the tip of the conidiogenous cell). Conidia (12-20 x 15-30 µm) are solitary, light brown to black in color, and rough- or smooth-walled. They are oblong or subspherical, rounded at the tips and have transverse and vertical septations (=muriform conidia) with a typical constriction at the central septum. They have thickened scars at their base 2.34.1.Stemphylium macrosporoideum (Berk.) Sacc., (1881) Synonyms: Epochnium macrosporoideum Berk., (1838) Acrospeira macrosporoidea (Berk.) Wiltshire, (1838) Hyphelia castaneae Wallr., (1833) Hyphelia castanea Wallr., (1833)

Pathogenicity

1. Some people may experience hay fever or asthma. Produces similar allergens that are associated with Alternaria.

2. Rare cases reported of phaeohyphomycotic sinusitis.

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2.35. The genus Ulocladium

Ulocladium is a dematiaceous filamentous fungus that inhabits the soil and decaying herbaceous plants. It is widely distributed in nature and may be isolated from paper, textiles, and wood as well. Ulocladium is commonly considered as a contaminant. It may very rarely cause human disease. Species of this genus contain both plant pathogens and food spoilage agents. Other species contain enzymes that are biological control agents. Some members of the genus can invade homes and are a sign of moisture because the mold requires water to thrive. They can cause plant diseases or hay fever and more serious infections in immuno-suppressed individuals.

Morphology

Species of Ulocladium resemble those of genus Alternaria with which they were once included. But Ulocladium, unlike Alternaria, do not produce alternariols, tenuazonic acid, altersolanols, or macrosporin.

Colonies of Ulocladium grow moderately rapidly. At 25°C and on potato dextrose agar, the colonies are wooly to cottony. From the front and the reverse, the color is olive brown to black .Microscopically, the fungus develops septate brown hyphae, brown conidiophores, and conidia. Conidiophores are simple or branched, smooth, strongly geniculate (bent at the points where the conidia are produced, leading to a zigzag appearence; "bent knee") and bear the conidia. Conidia (13-30 x 6-19 µm) are brown to black, round to oval in shape, smooth or rough and verrucous. They are usually egg-shaped and have a narrower base compared to its apex. These conidia are typically muriform and have transverse and longitudinal septations. They are solitary (Ulocladium botrytis) or may form short chains (Ulocladium chartarum). When chains are produced, a tubular, short outgrowth is formed on the conidia at the point of secondary conidium formation The genus Ulocladium has two active species:

1. Ulocladium chartarum 2. Ulocladium botrytis

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2.35.1. Ulocladium chartarum (Preuss) E.G. Simmons (1967) Synonyms:Alternaria chartarum Preuss (1848) Sporidesmium polymorphum var. chartarum (Preuss) Cooke (1875) Alternaria stemphylioides Bliss (1944)

Ulocladium chartarum

2.35.2. Ulocladium botrytis Preuss (1851) Synonyms: Stemphylium botryosum var. ulocladium Sacc. (1886) Stemphylium botryosum var. botrytis (Preuss) Lindau, (1908) Alternaria botrytis (Preuss) Woudenberg & Crou (2013) Alternaria abietis Tengwall (1924)

Ulocladium botrytis

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Pathogenicity

Ulocladium spp. may cause phaeohyphomycosis and particularly subcutaneous infections.

Recently reported cases: 1. Identification of allergens homologous to Alt a 1 from Stemphylium botryosum

and Ulocladium botrytis.389 2. An unusual phaeoid fungi: Ulocladium, as a cause of chronic allergic fungal

sinusitis.390 3. Ulocladium atrum Keratitis.391

2. 36. The genus Wangiella

Wangiella is a dematiaceous, cosmopolitan fungus that inhabits the soil and plant material. Wangiella may cause various infections in humans.The genus Wangiella contains only one species, Wangiella dermatitidis, where multiple conidial forms were used for its classification in other genera such as:

annellides, giving it the key characteristic of the genus Exophiala.

phialides having collarettes, giving it the characteristic of species of Phialophora

yeast forms that are suggestive of the black yeast genus Phaeococcomyces.

The name Wangiella was based upon

the production of phialides without distinct collarettes

molecular data suggesting that the species dermatitidis is distinctive enough to merit its own genus.

Accordingly the following names are considered as synonyms: Exophiala dermatitidis ,Fonsecaea dermatitidis ,Hormiscium dermatitidis ,

Hormodendrum dermatitidis , Phialophora dermatitidis

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2.36.1. Wangiella dermatitidis (Kano) McGinnis 1977 Synonyms: Hormiscium dermatitidis Kano 1934 Exophiala dermatitidis KANO 1937 Fonsecaea dermatitidis (Kano) Carrion 1950 Hormodendrum dermatitidis(Kano) Conant 1954 Phialophora dermatitidis(Kano) C.W.Emmons 1963

Colonies are slow growing, initially black and yeast-like, becoming suede-like, olivaceous grey and mould-like with age. The initial yeast-like phase is characterized by unicellular, ovoid to elliptical, budding yeast-like cells. The yeast-like cells are hyaline and thin-walled when young and becoming darkly pigmented and thick-walled when mature. With the development of mycelium or the mould-like stage, flask-shaped to cylindrical phialides without distinctive collarettes are produced. Conidia are hyaline to pale brown, one-celled, round to obovoid, 2.0-4.0 x 2.5-6.0 um, smooth-walled and accumulate in slimy balls (glioconidia) at the apices of the phialides or down their sides.

Wangiella dermatitidis yeast development of mycelia

Wangiella dermatitidis is a pathogen of humans that causes a disease known as phaeohyphomycosis, mostly associated with dermatotropic forms of disease. It is being reported with increasing frequency as a systemic pathogen with a marked neurotropic tendency. Predisposing factors for the systemic forms include cystic fibrosis, lymphocytic leukemia, diabetes mellitus, bronchiectasis, rheumatoid arthritis and catheterization. Initiation of both the dermatotropic and systemic disease forms is attributed to the traumatic implantation of the fungus into tissue, although in some cases the route of infection is unknown and pulmonary entry has not been ruled out

98

Recently reported cases: 1. Comparative Genomic and Transcriptomic Analysis of Wangiella dermatitidis, a

Major Cause of Phaeohyphomycosis and a Model Black Yeast Human Pathogen.170 2. Adaptation of the black yeast Wangiella dermatitidis to ionizing radiation: molecular

and cellular mechanisms.171 3. RNA interference of WdFKS1 mRNA expression causes slowed growth, incomplete

septation and loss of cell wall integrity in yeast cells of the polymorphic, pathogenic fungus Wangiella (Exophiala) dermatitidis.172

4. Unusual presentation of onychomycosis caused by Exophiala(Wangiella) dermatitidis.173

5. . Exophiala (Wangiella) dermatitidis and cystic fibrosis - Prevalence and risk factors.174

6. The treatment of pulmonary Wangiella dermatitidis infection with oral voriconazole.175 7. Roles of the pH signaling transcription factor PacC

in Wangiella(Exophiala) dermatitidis.176

2. 37. The genus Xylohypha

Species in this genus

1. Xylohypha bantiana (obsolete) This obsolete species is a synonym of Cladophialophora bantiana

2. Xylohypha emmonsii (obsolete) This obsolete species is a synonym of Cladophialophora bantiana

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3. Diseases caused by dematiacaeous fungi

3. 1. Phaeohyphomycosis

Synonyms: Cerebral chromomycosis, chromoblastomycosis, chromomycosis, cladosporiosis, phaeomycotic cyst, phaeosporotrichosis, subcutaneous mycotic cyst

The term phaeohyphomycosis (from the Greek phaios, meaning dark or

darkish) was introduced by Ajello et al. in 1974 to designate infections by

phaeoid or pigmented filamentous fungi that contain melanin in their walls.

The fungus often occurs on the skin where it forms nodules and cysts but is

also capable of invading deeper tissues and even the brain. The fungal

infection usually results when a contaminated material such as a splinter or

plant matter enters the skin, usually through a cut. The dark pigmented fungi

occur mostly in tropical and subtropical areas and can be found in soil and

rotting vegetation.

3.1.1. Skin infections

Phaeohyphomycosis of the skin typically begins as a single red nodule, usually

on the extremities. In the immunocompetent person, an indolent, painless

expansion in the skin and subcutaneous tissue occurs and can occasionally

develop well-formed cysts. In immunosuppressed patients local progression

and extension can occur rapidly producing scaly, crusty skin lesions or ulcers.

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Tinea nigra

Lesions on the leg and foot caused by cutaneous Alternaria infectoria infection

1. Cutaneous Phaeohyphomycosis caused by Paraconiothyrium cyclothyrioides.280 2. Bipolaris cutaneous fungal infection of 3 weeks duration involving the lower extremity.393

3. Infiltrating plaques, with a verrucoid appearance, occupying the back of hands (a) and forearms caused by Alternaria alternata394

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Pheohyphomycetic cysts on the leg and finger

1. Skin of a dog with cutaneous infection due to Alternaria infectoria. 2. a poorly defined, raised, subcutaneous swelling on the bridge of the nose.

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Recently reported cases 1. Bilateral Tinea Nigra of palm: a rare case report from Eastern India.158 2. Tinea nigra in an unusual anatomic location159 3. Tinea nigra palmaris: a clinical case in Argentina165 4. Tinea nigra by Hortaea werneckii, a report of 22 cases from Mexico.166 5. A case of tinea nigra palmaris in Okinawa,167 6. Tinea nigra: report of twelve cases in Venezuela.168 7. Cutaneous Infection with Alternaria triticina in a Bilateral Lung Transplant Recipient.7 8. Cutaneous alternariosis with chronic granulomatous disease (6) 9. Cutaneous infection of a porcupine (Erethizon dorsatum) by Aureobasidium

pullulans.42 10. Cutaneous phaeohyphomycosis due to Cladophialophora bantiana69 11. Cutaneous phaeohyphomycosis caused by Cladophialophora bantiana in a scar after

treatment with intralesional corticosteroid injections76 12. Cladophialophora carrionii: an aetiological agent of cutaneous chromoblastomycosis

from a non-endemic area, North India81 13. Cutaneous phaeohyphomycosis caused by Paraconiothyrium cyclothyrioides. 280 14. Cutaneous Curvularia infection of the forearm.100 15. Cutaneous and mucosal phaeohyphomycosis caused by Exophialaspinifera in a

pregnant patient: case report and literature review133 16. Cutaneous phaeohyphomycosis caused by Exophiala spinifera in a patient with

systemic lupus erythematosus.136 17. Cutaneous pythiosis in two dogs from Wisconsin, USA.364 18. Subcutaneous mycosis and fungemia by Aureobasidium pullulans: a rare pathogenic

fungus in a post allogeneic BM transplant patient49 19. Sub-cutaneous phaeohyphomycosis caused by Cladophialophora devriesiiin a

United Kingdom resident82 20. Subcutaneous phaeohyphomycosis due to Curvularia lunata in a renal transplant

patient97 21. Subcutaneous phaeohyphomycosis caused by Exophiala equina, with susceptibility

to eight antifungal drugs.131 22. Subcutaneous phaeohyphomycosis due to Exophiala spinifera in an

immunocompromised host.137 23. Subcutaneous phaeohyphomycosis of the face presenting as

rhinoentomophthoramycosis.148 24. Subcutaneous abscesses caused by Ochroconis gallopavum214 25. Subcutaneous phaeohyphomycosis (mycotic cyst.224 26. Subcutaneous abscess caused by Phoma sp. resembling Pyrenochaeta rameroi.

Uniques fungal infection occuring in immunosuppressed recipient of renal allograft.354

27. Subcutaneous phaeohyphomycotic cyst caused by Pyrenochaeta romeroi.267 28. Pyrenochaeta romeroi: a causative agent of phaeohyphomycotic cyst.271 29. Subcutaneous infection spread by Scytalidium (Neoscytalidium) dimidiatum309

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3.1.2. Nail infections

1. Onychomycosis due to ascomycete Chaetomium globosum: a case report.182 2. Onychomycosis by Chaetomium spp.185

3. An uncommon agent of onychomycosis.

330

4. Onychomycosis in São Paulo, Brazil.333 5. . Onychomycosis by Scytalidium dimidiatum in green tea leaf pluckers: report of two

cases.323

6. . Onychomycosis by Scytalidium dimidiatum: report of two cases in Santa Catarina, Brazil.325

7. Unusual presentation of onychomycosis caused by Exophiala(Wangiella) dermatitidis.173

3.1.3. Eye infections

Dematiaceous fungi are a particularly significant cause of fungal keratitis in

tropical areas, and most cases are associated with trauma from fungus-

contaminated plant material. Clinical features typically include redness,

photophobia, and decreased visual acuity accompanied with a yellow-white

infiltrate typically limited to the central cornea.

114

Recently reported cases:

1. Aureobasidium pullulans keratitis35

2. Fungal endophthalmitis associated with compounded products.23 3. An outbreak of fungal endophthalmitis after intravitreal injection of compounded

combined bevacizumab and triamcinolone.24 4. Corneal abscess caused by Bipolaris spicifera.25 5. Corneal chromoblastomycosis caused by Cladophialophora carrionii after cataract

surgery80 6. Fungal keratitis caused by Chaetomium atrobrunneum.179 7. Curvularia lunata endophthalmitis. 1101 8. Exophiala jeanselmei keratitis: case report and review of literature.127 9. Mycotic keratitis caused by concurrent infections of Exserohilum mcginnisii and

Candida parapsilosis.191 10. Keratomycosis caused by Exserohilum rostratum.199 11. Lasiodiplodia theobromae keratitis: a case report and review of literature.285 12. [Mycotic keratitis and endophthalmitis caused by unusual

fungi:Lasiodiplodia theobromae].288 13. Nattrassia mangiferae keratitis after laser in situ keratomileusis329 14. Nattrassia mangiferae causing fungal keratitis.332

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15. Nattrassia mangiferae keratitis after laser in situ keratomileusis.335 16. Case report. Nattrassia mangiferae endophthalmitis.337 17. Phialemonium obovatum keratitis after penetration injury of the cornea.340 18. Endophthalmitis caused by Phialophora verrucosa: a case report and literature

review of Phialophora ocular infections. 220 19. Endophthalmitis caused by Phialophora verrucosa and Streptococcus intermedius: a

case report. 221 20. Pyrenochaeta keratinophila sp. nov., isolated from an ocular infection in Spain.266 21. Outbreak of Pythium keratitis during rainy season: a case series.372 22. Scedosporium prolificans endogenous endophthalmitis.306

Commonly isolated fungi 395

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3.1.4. Respiratory phaeohyphomycosis:

Sinusitis caused by dematiaceous fungi, especially species of Bipolaris, Exserohilum, Curvularia and Alternaria is increasingly being reported,

especially in patients with a history of allergic rhinitis or immunosuppression.

This is a fairly recent concept, similar in presentation to allergic

bronchopulmonary aspergillosis (ABPA), which is typically seen in patients

with asthma or cystic fibrosis. The most common fungi

are Bipolarisand Curvularia species. Therapy is primarily systemic steroids,

usually prednisone at 0.5 mg/kg/d for 2 weeks, followed by a slow taper over 2

to 3 months or longer, if necessary. Itraconazole has been used as a steroid

sparing agent, but its efficacy is not clear, and routine use of itraconazole is

not specifically recommended.

Non-allergic pulmonary disease with the black molds usually occurs in

immunocompromised patients and may be due to a wide variety of species

commonly found in the environment (including Bipolaris,

Ochroconis (Dactylaria), Fonsecaea, and Chaetomium species). However,

cases in immunocompetent patients may also be seen.[ It is extremely

important to perform proper identification of the black mold from nonsterile

sites like fluid from bronchoalveolar lavage (BAL). The growth

of Cladosporium, species even in lung transplant recipients, is unlikely to be

causing disease, but other black molds like Dactylariawould cause much more

concern about potentially invasive lung disease or dissemination.

Maxillary sinus mycetoma Pneumonia due to Pseudoallescheria boydii

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Recently reported cases:

1. Outbreak of hypersensitivity pneumonitis in an industrial setting36

2. Hypersensitivity pneumonitis secondary to residential exposure to Aureobasidium pullulans in 2 siblings45

3. Bipolaris hawaiiensis as etiologic agent of allergic bronchopulmonary mycosis: first case in a paediatric patient.26

4. Some chronic rhinosinusitis patients have elevated populations of fungi in their sinuses.54

5. Unusual causes of fungal rhinosinusitis: a study from a tertiary care centre in South India.58

6. Differences in fungi present in induced sputum samples from asthma patients and non-atopic controls: a community based case control study59

7. Allergic bronchopulmonary mycosis due to fungi other than Aspergillus: a global overview.60

8. Pulmonary Cladophialophora boppii infection in a lung transplant recipient: case report and literature review87

9. Pulmonary infection caused by Exophiala dermatitidis in a patient with multiple myeloma: A case report and a review of the literature.125

10. Maxillary sinusitis caused by Lasiodiplodia theobromae.286 11. Lasiodiplodia theobromae pneumonia in a liver transplant recipient.287 12. A case of sinusitis caused by nattrassia mangiferae in iran328 13. Pulmonary Phialemonium curvatum phaeohyphomycosis in a Standard Poodle

dog.345 14. Lung infection due to opportunistic fungus, Phialemonium obovatum, in a bone

marrow transplant recipient: an emerging infection with fungemia and Crohn disease-like involvement of the gastrointestinal tract.346

15. An unusual phaeoid fungi: Ulocladium, as a cause of chronic allergic fungal

sinusitis.390 16. The treatment of pulmonary Wangiella dermatitidis infection with oral voriconazole.175

118

3.1.5. Central nervous system infection

Although rare, CNS infection is one of the best-described and frequently fatal

syndromes produced by the dematiaceous molds. A retrospective analysis of

101 reported cases of CNS phaeohyphomycoses found that over half occurred

in immunocompetent patients, with Cladophialophora bantiana the most

common species isolated. Disease is also caused by Ramichloridium

mackenziei, Ochroconis gallopavum (Dactylaria gallopavum), Wangiella

dermatitidis, Bipolaris spicifera, B. hawaiiensis, and Chaetomium species.

CNS infection from dematiaceous molds typically presents with indolent

headache, low-grade fever, and development of focal neurological signs.

Often, it requires surgical intervention and the use of a combination of

antifungal agents for successful management.

MRI of the brain (TZ-weighted), showing Hematoxylin-eosin stain of brain tissue showing hyphae with a mass located in the region of occasional swollen walls and branching the posteriorright basal ganglia and posterior temporal lobe with surrounding edema.

119

Brain; cat. Cross-sections of the rostral Myriads of oblong, septate, branching hyphae and cerebrum and meninges. Well- a few macrophage

demarcated areas of black discoloration and softening caused by C. bantiana.116

Recently reported cases:

1. Alternaria infectoria brain abscess in a child with chronic granulomatous disease.17

2. Fungal meningoencephalitis caused by Alternaria: a clinical case.18

3. Cerebral phaeohyphomycosis caused by Bipolaris spicifera after heart transplantation.27

4. Cerebral and renal phaeohyphomycosis in a dog infected with Bipolaris species.28

5. Acute meningitis caused by Cladosporium sphaerospermum61

6. Cladophialophora bantiana brain abscess: A case with long survival in metropolitan France64

7. Brain abscess caused by Cladophialophora bantiana in China68

8. Cerebral phaeohyphomycosis due to Cladophialophora bantiana in a Huacaya alpaca (Vicugna pacos).70

9. Cerebellar Cladophialophora bantiana infection in a patient with marginal zone lymphoma treated with immunochemotherapy including rituximab71

10. Cladophialophora bantiana brain abscess in an immunocompetent patient72

11. Necrotizing pyogranulomatous meningoencephalitis with intralesional fungal hyphae, consistent with Cladophialophora bantiana75

12. Cladophialophora bantiana brain abscess: A case with long survival in metropolitan France88

13. Brain abscess caused by Cladophialophora bantiana in China.90

111

14. Fatal cerebral abscess caused by Cladophialophora bantiana.92

15. Curvularia Abscess of the Brainstem.96

16. Curvularia brain abscess.98

17. Fatal cerebral phaeohyphomycosis due to Curvularia lunata in an immune-competent patient105

18. Cerebral phaeohyphomycosis caused byFonsecaea monophora.142

19. Fonsecaea multimorphosa sp. nov, a new species ofChaetothyriales isolated from a feline cerebral abscess.143

20. Fungal infections of the central nervous system in the immunocompetent host146

21. Madurella mycetomatis as an agent of brain abscess: case report and review of literature.232

22. Clinical profile and management of craniocerebral Madurella mycetoma.233

23. Mycetoma. Craniocerebral maduromycosis.241

24. Cerebral phaeohyphomycosis due to Rhinocladiella mackenziei (formerly Ramichloridium mackenziei): case presentation and literature review.258

25. Cerebral phaeohyphomycosis due to Rhinocladiella mackenziei(formerly Ramichloridium mackenziei): a taxonomic update and review of the literature263

26. Aspiration cytology of brain abscess from a fatal case of cerebral phaeohyphomycosis due to Ramichloridiummackenziei.275

27. Cerebral phaeohyphomycosis caused by Ramichloridiummackenziei in the Eastern Province of Saudi Arabia.

28. Cerebral phaeohyphomycosis due to Rhinocladiellamackenziei (formerly Ramichloridium mackenziei): case presentation and literature review.258

29. Rhinocladiella mackenziei as an emerging cause of cerebral phaeohyphomycosis in Pakistan: a case series259

30. Co-existence of cerebral infection with Rhinocladiellamackenziei and primary central nervous system lymphoma in a HIV-negative patient.260

31. Cerebral phaeohyphomycosis caused by Rhinocladiella mackenziei in a woman native to Afghanistan.261

32. First autochthonous case of Rhinocladiella mackenziei cerebral abscess outside the Middle East.262

33. Cerebral phaeohyphomycosis due to Rhinocladiellamackenziei (formerly Ramichloridium mackenziei): a taxonomic update and review of the literature.263

34. Cerebral phaeohyphomycosis caused by Rhinocladiella mackenziei in a woman native to Afghanistan.265

35. Scedosporium aurantiacum brain abscess after near-drowning in a survivor of a tsunami in Japan.304

36. Cerebral phaeohyphomycosis caused by Scytalidiumdimidiatum: a case report from India.318

. (

111

3.1.6. Disseminated pheohyphomycosis

This is the most uncommon manifestation of infection seen with dematiaceous

fungi. There are case reports of several different dematiaceous molds that

have caused disseminated disease, including Bipolaris species and Wangiella

dermatitidis. In a recent review, most patients were immunocompromised,

though occasional patients without known immunodeficiency or risk factors

developed disseminated disease as well, and infections have occurred with

contaminated devices or biological products. In contrast to most invasive mold

infections, blood cultures are positive in over half the cases of disseminated

phaeohyphomycosis -- this is likely related to adventitial yeast forms in tissue.

Systemic pheohyphomycosis (cerebral)117 Systemic pheohyphomycosis (pulmonary)117

Recently recorded cases:

1. Alternaria alternata invasive fungal infection in a patient with Fanconi's anemia after an unrelated bone marrow transplant.11

2. Disseminated nosocomial fungal infection by Aureobasidium pullulans var. melanigenum: a case Report.41

3. Aureobasidium pullulans infection: Fungemia in an infant and a review of human cases.46.

4. Catheter-related septicemia due to Aureobasidium pullulans.47

5. Disseminated Cladophialophora bantiana infection in an idiopathic thrombocytopenic purpura patient: a case report.74

112

6. Systemic mycosis caused by a new Cladophialophora species84

7. Invasive chaetomium infection in two immunocompromised pediatric patients.187

8. Disseminated infection with Nattrassia mangiferae in an immunosuppressed patient.336

9. Disseminated Ochroconis gallopava infection in a heart transplant patient. 200

10. Fatal systemic phaeohyphomycosis caused by Ochroconis gallopavum in a dog (Canis familaris).209

11. Disseminated infection with Phialemonium obovatum in a German shepherd dog.349

12. Phialophora verrucosa as a cause of deep infection following total knee arthroplasty. 215

13. Invasive infection in a young immunocompetent soldier caused by Scytalidium dimidiatum317

14. Disseminated fungal infection in a renal transplant recipient involving Macrophomina phaseolina and Scytalidiumdimidiatum: case report and review of taxonomic changes among medically important members of the Botryosphaeriaceae.319

15. Scedosporium prolificans fungaemia in a patient with acute lymphoblastic leukaemia327

113

Cases of disseminated pheohyphomycosis reported in the literature396

114

115

3.2. Chromomycosis: The term chromoblastomycosis was first used initially to describe cases of polymorphic fungal disease of the lower limbs presenting with nodules or verrucous plaques with hyperkeratosis and acanthosis of the affected epithelial tissues, which could develop into complications such as ulceration, lymphedema and squamous cell carcinoma. The term blastomycosis gives the impression that the cause of this disease is a yeast. As various species of moulds are involved as causes, the term chromomycosis seems to be reasonable. The causative agents generally have a cosmopolitan distribution, the illness is reported more frequently in countries with tropical and subtropical climates, especially among people living in rural areas, not wearing shoes and therefore in whom plant wounds or other contaminated materials are common and repetitive. The disease is very common in Mexico Cuba, Dominican Republic, Venezuela, Colombia and Ecuador, Australia and South Africa. Several dematiaceous fungi cause chromoblastomycosis. Fonsecaea pedrosoi is the most common causative organism, although disease is also caused by Cladosporium and Phialaphora species.

Most lesions are located in exposed areas, mainly in lower limbs. The initial lesion appears at the site of inoculation, and usually it is a small, elevated, erythematous, non-pruritic papule. Over time other lesions in the same area or in adjacent areas, with involvement of local lymph vessels appear, the lesions tend to hypertrophy, increased desquamation and skin a reddish color to gray is appreciated. There may be peripheral spread and/ or scarring in the center of the lesions, but more often, these grow and clump together looking like cauliflower and may ulcerate as the lesions located in areas exposed to trauma, are frequently associated with secondary bacterial infections causing purulent exudate of foul smell.

116

Multiple, scaly erythematous plaques, with ulcers and erosions on the left shin.79

Immages: Rubén López Martínez and Francisca Hernández Hernández Faculty of Medicine, UNAM

117

Chromomycosis118 Chromomycosis119

Recently reported cases 1. Cladophialophora carrionii: an aetiological agent of cutaneous chromoblastomycosis

from a non-endemic area, North India.81

2. Fonsecaea nubica sp. nov, a new agent of human chromoblastomycosis revealed using molecular data

3. Chromoblastomycosis caused by Fonsecaea: clinicopathology, susceptibility and molecular identification of seven consecutive cases in southern China.141

4. Chromoblastomycosis in Australia: an historical perspective.147 5. Revisiting the clinical and histopathological aspects of patients with

chromoblastomycosis from the Brazilian Amazon region149 6. Chromoblastomycosis due to Fonsecaea pedrosoi and F. monophora in Cuba.150 7. Chromoblastomycosis caused by Fonsecaea: clinicopathology, susceptibility and

molecular identification of seven consecutive cases in Southern China152 8. Chromoblastomycosis in Mainland China: a systematic review on clinical

characteristics153 9. Septic arthritis and osteomyelitis due to the chromoblastomycosis

agent Fonsecaea pedrosoi.154 10. Clinical, epidemiological and mycological report on 65 patients from the Eastern

Amazon region with chromoblastomycosis155 11. A refractory case of chromoblastomycosis due to Fonsecaea monophora with

improvement by photodynamic therapy.157 12. . Generalized chromomycosis caused by Phialophora verrucosa.217 13. Chromoblastomycosis Caused by Phialophora richardsiae.223 14. Chromoblastomycosis caused by Rhinocladiella aquaspersa.256

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3.3. Mycetoma Mycetoma (Madura foot) is a chronic infection characterized by the development of tumifactions and sinuses. The infection most often occurs in the feet but may appear on the hands or buttocks. The organism occasionally invades the body producing lesions in the brain, the meninges and other internal organs, including the bones. The disease occurs most frequently in tropical and subtropical zones. The numerous fungi that have been isolated from cases of maduromycosis belong to several genera. These fungi produce black granules in the lesions. The dematiaceous fungi causing this disease fall in the genera:Madurella, Phialophora , Curvularia , Pyrenochaeta, Leptosphaeria and others.

Mycetoma in a horse Mycetoma in man

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Madura Foot: A Tropical Foot Disease The Mycetoma Research Center

Waterloo, Ontario Podiatric Care - MYCETOMAWHO ,University of Khartoum

Recently reported cases

1. Eumycetoma of the foot caused by Exophiala jeanselmei in a Guinean woman.130

2. Curvularia lunata: A rare cause of black-grain eumycetoma94

3. An unusual case of eumycetoma caused by Exophiala jeanselmei after a sea urchin injury.132

4. Mycetoma foot due to Madurella mycetomatis.227

5. Mycetoma caused by Madurella mycetomatis: a neglected infectious burden.228

6. Madurella mycetomatis infection following allogenic stem cell transplantation for aplastic anemia229

7. Eumycetoma by Madurella mycetomatis with 30 years of evolution: therapeutic challenge230

8. Clinical profile and management of craniocerebral Madurellamycetoma.231

9. Clinical profile and management of craniocerebral Madurellamycetoma.233

10. Mycetoma caused by Madurella mycetomatis: a completely neglected medico-social dilemma.234

11. Peripheral blood mononuclear cells of mycetoma patients react differently to Madurella mycetomatis antigens than healthy endemic controls.235

12. Oral cavity eumycetoma: a rare and unusual condition236

13. Madura foot237

14. . A histopathological exploration of the Madurella mycetomatis grain.238

15. A Rare Presentation of Concurrent Scedosporium apiospermum and Madurella grisea Eumycetoma in an Immunocompetent Host. Case report239

16. . In vitro antifungal activity of isavuconazole against Madurellamycetomatis.240

17. Craniocerebral maduromycosis.241

18. Phylogenetic analysis of the complete mitochondrial genome of Madurella mycetomatis confirms its taxonomic position within the order Sordariales.242

19. Eumycetoma243

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20. Analysis of 18 Tunisian cases of mycetoma at the Sousse hospital (1974-2010)244

21. MRI findings in cranial eumycetoma245

22. New species of Madurella, causative agents of black-grain mycetoma.246

23. [Mycetomas diagnosed in Senegal from 2008 to 2010247

24. Madurella mycetomatis mycetoma treated successfully with oral posaconazole248

25. A chronic, destructive mycetoma infection in a diabetic foot in Saudi Arabia.249

26. In vitro susceptibility of Madurella mycetomatis to posaconazole and terbinafine.250

27. The safety and efficacy of itraconazole for the treatment of patients with eumycetoma due to Madurella mycetomatis.251

28. Clinical and epidemiological features of mycetoma in Morocco252

29. Mycetoma in Tunisia: a 15-case series253

30. Bilateral mycetoma--a case report.254

31. Madurella mycetoma--a rare case with cranial extension.255

32. Leptosphaeria Senegalensis Causing Mycetoma Pedis in Madras283

33. Mycetoma in Yemen: clinicoepidemiologic and histopathologic study284

4. Dematiaceous fungi in Egypt Although dematiaceous fungi have been isolated from the air of slaughter house398 as well as from poultry feeds399, maduromycosis was only reported by El Mofty et al. (1956) and El Zawahry (1967) and Abdei-Aal (1974)

400. Recently,

cases were published by Taha (2014)401

.

121

Collection of cases of mycetoma presented by Prof. Dr. M. Taha, Zagazig University, Egypt401

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5. Mycotoxicoses 5.1. Alternariosis

The principle Alternaria mycotoxins that have been shown to occur naturally are tenuazonic acid, alternariol monomethyl ether, alternariol, altenuene, and altertoxin I. Iso-altenuene and altertoxin II have not been found in crops to date. AAL-toxins are structurally related to fumonisins. Alternaria toxins exhibit both acute and chronic effects. The LD50 values for alternariol monomethyl ether, alternariol, altenuene, and altertoxin I in mice is reported as 400, 400, 50 and 200 mg/kg b. w. respectively. Those for tenuazonic acid are 162 and 115 mg/kg b.w. (i.v.) for male and female mice respectively.Alternaria toxins have been implicated in animal and in human health disorders. Cases of death in rabbits and poultry have been reported as a result of toxic action of Alternaria spp. found in the fodder and feed.

Tenuazonic acid has been most studied. Its principle mode of action appears to be the inhibition of protein synthesis by suppression of the release of newly formed proteins from the ribosomes into the supernatant fluid. It exhibits antitumor, antiviral and antibacterial activity.

Alternariol and alternariol monomethyl ether show foetotoxic and teratogenic effects in mice, including a synergistic effect when a combination of the toxins was administered. Most Alternaria mycotoxins exhibit considerable cytotoxic activity, including mammalian toxicity. The altertoxins are of a particular concern due to their mutagenic activity. Altertoxin III exhibits mutagenic activity that is approximately one tenth of that of aflatoxin B1, while altertoxins I and II show lower mutagenicity.

Pithomycotoxicosis)(Facial eczema . 2.5

Facial eczema is a disease caused by the toxin of Pithomyces chartarum that mainly affects ruminants such as cattle, sheep, deer, goats and South American camelids (alpaca, llamas). The fungus is a saprophytic mould which lives on any dead litter lying at the base of pastures. This mould is present in pastures all year round but only becomes a problem at certain times when

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high ground temperatures coincide with high humidity and moisture. Under these conditions the mould grows rapidly producing many new hyphae which produce clusters of spores, which spread by wind throughout the pasture.

The spores produce a toxin called sporidesmin. When grazing animals ingest spores from the pasture, the toxin is absorbed in the gut from the spores into the bloodstream and then transported to the liver. Here the toxin causes inflammation of the bile duct which eventually closes, not allowing bile to be excreted into the small intestine. The bile then seeps back into the liver and bloodstream. The damaged liver cannot rid the body of wastes and a breakdown product of chlorophyll accumulates in the tissues. This results in the animal becoming photosensitive, and it tends to seek shade away from direct sunlight. If exposed to sunlight this results in immediate and severe inflammation of the skin on exposed non pigmented parts of the body. From the time the animal ingests toxic levels of spores to the appearance of the first symptoms is usually about ten days. In cows the first signs are a drop in milk production immediately after grazing toxic pasture. Later cows become restless at milking time, seek shade and lick their udders as photosensitisation develops. Skin lesions appear on unpigmented skin, especially the escutcheon, inside the hind legs, the udder and teats, and the coronets.

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5.3. Stachybotryotoxicosis

In the late 1930s, stachybotryotoxicosis was reported in humans working

on farms in Russia. People who were affected are those who handled hay or

feed grain infested with Stachybotrys chartarum. Some of the individuals who

were infected had burned the straw or even slept on straw-filled mattresses

that had rampant growth of Stachybotrys chartarum. The infested straw can be

described as black in colour from growth of the fungus. Common symptoms in

humans that have stachybotryotoxicosis were rashes, especially in areas

subject to perspiration, dermatitis, pain and inflammation of the mucous

membranes of the mouth and throat, conjunctivitis, a burning sensation of the

eyes and nasal passages, tightness of the chest, cough, bloody rhinitis, fever,

headache, and fatigue.

The workers who were infected developed symptoms within two to three days

of exposure to the fungus. Some members of the Russian teams investigating

this disease rubbed the fungus onto their skin to determine its direct toxicity.

The fungus induced local and systemic symptoms similar to those observed in

naturally occurring cases.

S. chartarum produces a variety of macrocylic trichothecenes and

related trichoverroids: roridin E and L-2; satratoxins F, G, and H; isosatratoxins F, G, and H; verrucarins B and J; and the trichoverroids, trichoverrols A and B and trichoverrins A and B. The satratoxins are generally produced in greater amounts than the other trichothecenes, but all compounds are produced in low quantities.

Macrocyclic trichothecenes are highly toxic compounds with a potent ability to inhibit protein synthesis. Numerous studies have demonstrated the toxicity of toxins from S. chartarum on animals and animal and human cells. Satratoxin G was the most cytotoxic of eight trichothecenes tested on mammalian cells, even more toxic than the well known T-2 toxin associated with alimentary toxic aleukia. Other researchers have also reported the high toxicity of satratoxins compared to other trichothecenes. The LD50 in mice for satratoxins is ~1 mg/kg (32).

In addition, S. chartarum produces nine phenylspirodrimanes (spirolactones and spirolactams) and cyclosporin, which are potent

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immunosuppressive agents. It was suggested that the combination of trichothecenes and these immunosuppressive agents may be responsible for the observed high toxicity of this fungus. New biologically active compounds are still being discovered in cultures of S. chartarum, e.g. atranones A-G, dolabellane diterpenes and stachylysin, a hemolysin (compounds that lyse erythrocytes), and a hydroxamate siderophore. They suggest these compounds could be pathogenicity factors involved in pulmonary hemorrhage in infants exposed to S. chartarum.

6. Laboratory diagnosis Unlike other more common fungal infections, there are no simple diagnostic tests to identify these fungi, particularly to the species level. No routine serologic, antigen or polymerase chain reaction (PCR) methods are available, which is at least partly due to the tremendous diversity of these pathogens. However, studies have begun to examine the potential of identifying species within this diverse group of fungi using PCR of highly conserved regions of ribosomal DNA. Currently, the diagnosis of infection due to dematiaceous fungi relies on pathologic examination of clinical specimens and careful gross and microscopic examination of cultures.

In the case of mycetoma the presence of black mycotic granules or grains can establish the diagnosis of mycetoma due to dematiaceous fungi. Histologically, they appear to be composed of fungal cells surrounded by a dense extracellular matrix composed primarily of a melanin compound, which gives it a dark color.

Chromomycosis is characterized by the production of characteristic dark sclerotic bodies in tissue, which are thick walled with septae.

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Phaeohyphomycosis does not have such pathognomonic features, though the histologic appearance is often characterized by irregular hyphal elements and beaded, yeast-like forms.

7. Treatment

7.1. Tinea nigra: topical therapy (azoles or keratolytics) 7.2. Onychomycosis: Itraconazole and terbinafine are the most commonly used systemic agents, and may be combined with topical therapy for refractory cases. 7.3. Subcutaneous Lesions: Surgical excision alone has been successful in a number of cases, including in immunocompromised patients. Oral systemic therapy with an azole in conjunction with surgery is also frequently employed and has been used successfully, especially in immunocompromised patients. 7.4. Chromoblastomycosis: Cryotherapy, itraconazole, or the combination resulted in the largest number of cures. For small lesions, surgery alone may be effective. A variety of other treatments have also been successful, including ketoconazole, flucytosine, local heat therapy and amphotericin B. 7.5. Mycetoma: requires prolonged systemic antifungal therapy in addition to surgery using ketoconazole, itraconazole, voriconazole or posaconazole 7.6. Central Nervous System Infection: Combination of amphotericin B, flucytosine and itraconazole 7.7. Disseminated Infection: The mortality rate is >70%, despite aggressive antifungal therapy. There are no antifungal regimens associated with improved survival in disseminated infection, including multiple combination therapies. Amphotericin B may be useful for severe disease, though some species are resistant. Lipid formulations will likely play an important role for such infections, as reduced toxicity combined with the potential for increased

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8. Contamination and deterioration by dematiaceous fungi Dematiaceous fungi cause several plant diseases causing great losses in grains like corn and wheat, fruits like apples, oranges, banana etc, vegetables like tomato, onions, potato etc. They also contaminate and deteriorate woods, leather, papers, meat, cheese etc. It is out of the scope of this monograph to discuss this problem and the following pictures are only examples for the actions of dematiaceous fungi.

Bipolaris, Southern corn leaf blight and stalk rot (Bipolaris maydis )...

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Tan spot of wheat ,Pyrenophora tritici120 Cladosporium kernel rot of corn

Darkening lesions on tomato leaves, Stemphylium solani

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Cladosporium

Mouldy vegetables

131

Mouldy fruits

Mouldy nuts

131

Mouldy cheese

Mouldy meat

132

Mouldy bread

Mouldy books

Mouldy paints

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