Common Fungi Causing Ent Diseases

Microbial World 

Prokaryotes: 1. Bacteria 2. Archae



Eukaryotes 1. 2. 3. 4.

Algae Fungi Protozoa Parasites

Fungi  Features:  Cell wall: Chitin  Cell membrane:

 Ergosterol  Zymosterol  Aerobic/ facultatively anaerobic  Mostly microscopic  Moisture essential for growth

Types of Fungi  Yeasts:  Single celled  Reproduction: Budding

 Molds:  Long filaments (hyphae)  Form mycelium  Septate/ Non septate

 Dimorphic

Importance  Biologic recycling of organic matter  Preparation of foods:     

Beer Cheese Bread Wine Mushrooms

 Economic impact: Plant diseases  Source of biologically active compounds: •Hallucinogens •Adrenergic alkaloids •Vitamins •Mutagens

•Carcinogens •Antibiotics •Immunosuppressive agents •Potential anticancer substances

Groups 1. Zygomycetes:   

Bread moulds (Rhizopus) Food spoilage organisms Rhizomucor

1. Basidiomycetes:   

Common mushrooms Cryptococcus Malassezia

3. Ascomycetes:       

Aspergillus Histoplasma Coccidioides Candida Pneumocystis Sporothrix Dermatophytes

4. Deuteromycetes (Fungi Imperfectii):  

Medically & economically imp fungi Penicillin producing

Types of Fungal Diseases 1. Fungal allergies 2. Mycotoxicoses 3. Mycoses

Fungal Allergies  Strong hypersensitivity reactions against:  Fungal spores  Fungal components

 Do not require:  Growth  Viability

 Depending upon the site of deposition of

allergens:     

Rhinitis Sinusitis Bronchial asthma Alveolitis Generalized pneumonitis

Mycotoxicoses  Mycetismus  Mycotoxins:  Amatoxins  Phallotoxins  Aflatoxin  Ochratoxin  Sporidesmin  Zearalenone  Sterigmatocystin

 Target organ:

Liver

Mycoses  Actual growth of a fungus on a human

or animal host  Establishment of mycoses depends upon:  Host defenses  Size of innoculum  Route of exposure  Virulence of the fungus

Clinical Classification of Mycotic Infections  Superficial:  Pityriasis versicolor  Tinea nigra

 Cutaneous:  Candidiasis  Dermatophytosis

 Subcutaneous:  Rhinosporidiosis  Rhinoentomophthoromycosis

 Systemic:      

Histoplasmosis Paracoccidioidomycosis Candidiasis Cryptococcosis Aspergillosis Mucormycosis

Specimen Collection, Handling & Transport  Sample Collection:  Primary criterion for diagnosis of mycotic infections  Transportation & processing done ASAP

 Tissue from site of active disease- ideal  Most common specimens:        

Respiratory secretions Hair Skin Nail Tissue Blood Bone marrow CSF

Respiratory Specimen  Viscous material (Tracheal aspirate):  Cotton Swab  Specimen digested with trypsin & concentrated

 Sputum:  Deep cough early in the morning  Nebulizer to induce sputum

 Collected into a sterile screw top

container  Media:

 Non selective  Media with antibiotics

 KOH preparation

Mucin Collection  Nasal decongestant spray  Flush with 20ml N/S  Forceful exhalation through nose  Return collected in sterile pan

 Skin:  70% isopropyl alcohol before sampling  Scraped from outer edge of a surface lesion

 Blood:  Transport medium required

 Exudates/ Pus:  Sterile sealed container

Diagnosis  Direct microscopic examination  Culture  Serology

Direct Microscopic Examination  Wet preparations:  KOH mount  India Ink  Calcofluor white

 Histologic stains:  Periodic- Acid Schiff (PAS ) stain  Grocott- Gomori methenamine silver nitrate (GMS) stain  H&E stain  Giemsa stain  Masson- Fontana stain

Culture  Culture Media:  Saboraud’s Dextrose Agar  SDA with antibiotics  Brain Heart Infusion (BHI) agar enriched with blood & antibiotics

 Incubation:  Temp: 25-30°C (37°C for dimorphic fungi)  Duration: 4-6 weeks

Candida  Candida: Part of normal flora of skin, mucus

membranes & GIT  Candidiasis: Most common systemic mycoses  Pathogenic strains:    

C. C. C. C.

albicans tropicalis glabrata krusei

 Clinical Classification of Candidiasis:  Cutaneous & Mucosal candidiasis:

 Thrush  Stomatitis  Esophagitis  Systemic Candidiasis  Esophagitis  Chronic Mucocutaneous Candidiasis

 Predisposing factors:  Cutaneous & mucosal candidiasis:  Physiologic:  Pregnancy Old age Infancy Traumatic Hematologic: AIDS DM Iatrogenic: Antibiotics Steroids

 Systemic Candidiasis: Immunosuppression Surgery Steroids Malignancies Cytoxic drugs

Morphology  Dimorphism:    

Yeast cells True hyphae Pseudohyphae Germ tubes

 Microscopy:  Spherical/ ellipsoidal budding yeasts  Size: 3-6 μm  Cornmeal agar: Chlamydiospores

 Culture:       

Species cannot be differenciated Within 24-48hrs Raised Cream coloured Opaque 1-2mm Hyphae penetrating the agar medium

Aspergillus  Ubiquitous molds  Numerous species  Approx 20 cause human infection  Pathogenic species:  A. fumigatus  A. flavus: Nose & PNS  A. niger: systemic disease in immunocompromised

 Clinical diseases:  Otomycosis  Fungal rhinosinusitis

Morphology  Microscopy:  Conidiophores  Expand into large vesicles at the end  Covered with phialides

 Culture:  Powdery  Pigmented  A. fumigatus: Gray, green A. flavus: Yellow- green A. niger: Black

Aspergillus niger & flavus

Mucormycosis  Phycomycosis,    

zygomycosis Molds Class: Zygomycetes Order: Mucorales Fungi:  Ubiquitous  Thermotolerant  Saprophytes

 At risk patients:  Acidosis  Leukemia  Immunocompromise

 Etiologic agents:  Rhizopus oryzae  R. rhizopodiformis  Absidia corymbifera  R. pusillus  Rhizomucor spss.  Mucor spss.

 Clinical manifestations:  Rhinocerebral mucormycosis  Thoracic mucormycosis  Cutaneous infections

Morphology  Microscopy:  Broad  Sparsely septate hyphae (10μm)  Twisted & ribbonlike  Branching at rt. angles

 Culture:  Rapid growth  Abundant, cottony aerial mycelia

Paracoccidioidomycosis  C/A: Paracoccidioides brasiliensis  Chronic granulomatous disease:  Mucous membranes  Skin  Respiratory system

 Most cases from Brazil  Invade mucous memb of mouth→ teeth fall

out  White plaques in buccal mucosa  Histologically: Captain’s wheel

Cryptococcosis  C. neoformans  Distinctive yeast  Diseases:  Meningitis  Pulmonary disease

 Found in pigeon & chicken droppings  Diagnosis:  India ink test  Latex agglutination test for cryptococcal antigen

India Ink staining of CSF

 Polyenes  Azoles  Imidazoles  Triazoles

 Echinocandin

s  Allylamines  Flucytosine  Griseofulvin

Polyenes  Eg.:  Amphotericin B  Nystatin

 MOA:  Bind to sterols of eukaryotic cell memb→ leakage of cell contents

 Amphotericin B:    

Active against all fungi Leishmania Given parenterally Poor CSF penetration

 ADRs:     

Fever Rigor Nephrotoxicity Hyperkalemia Headache

Azoles  Inhibit cyt p450 14α-demethylase

→inhibit fungal cell wall synthesis  Active against:  Candida  Dermatophytes  Aspergillus

 Imidazole:  Topical: Clotrimazole  Systemic: Ketoconazole

 Triazoles:  Fluconazole: Inactive against invasive moulds  Itraconazole: Inactive against zygomycetes

Echinocandins  Capsofungin  Inhibit cell wall glucan synthesis

→cell wall lysis  Active against:  Candida  Aspergillus

 Inactive against:  Other moulds  Cryptococcus

Allylamines  Terbinafine  Reduce ergosterol synthesis  Active against dermatophytes  Uses:  Skin dermatophyte infection  Nail dermatophyte infection

 Flucytoscine:  Incorporates into fungal mRNA instead of uracil

→ disruption to protein & DNA synthesis  Activity:  Cryptococcus  Candida

 Resistance: Common  ADRs:  Bone marrow toxicity  Hepatotoxicity

 Griseofulvin:  MOA unclear  Use: Nail infections

Mycotic Diseases of the External Ear    

Otomycosis Dermatophytosis Chromoblastomycosis Sporotrichosis

Otomycosis

 Defn: Superficial, diffuse, fungal

infection of the ear canal  Predisposing condition usually present

 Aetiological agents:  Aspergillus: (Tropical & Subtropical regions)  Niger Flavus Fumigatus

 Candida: (Temperate regions) Albicans Parapsilosis Tropicalis

 Penicillium  Rhizopus  Mixed

Epidemiology  Environment:  Warm  Humid

 Children less commonly affected  Not contagious  Predisposing factors:  Seborrhic dermatitis  Psoriasis  Prolonged use of:  Topical antibiotics Topical corticosteroids

Clinical Manifestations  C/C:  Aural fullness  Pruritis  Discharge

 Otoscopy:  Debris  Erythematous/ oedematous ear

canal  A. niger: (Blotting paper)  Mat of fungus  Black sporing heads

 Chronic infection:  Eczematoid change  Lichenification

Diagnosis

 Clinical  Microscopic

examination  Culture

Management  Removal of debris  Cleaning  Antifungal agents:  Local application  Gauze packs  Mercurochrome & boric acid

Mycotic diseases of the nose and nasal passages  Entomophthoramycosis  Rhinosporidiosis

Entomophthoramycosis  Definition:

   

Chronic localised subcutaneous fungal infection that originates from nasal mucosa and spreads painlessly to the adjacent subcutaneous tissue of the face Rare Seen in healthy individuals Severe facial disfigurement C/A: Conidiobolus coronatus

Management  Oral antifungal drugs  Treatment continued 1mnth after

lesions have disappeared  Surgical resection:  Hastens spread of infection

Rhinosporidiosis  Definition:  Uncommon granulomatous infection that affects nasal mucosa, ocular conjunctiva & other mucosa

 Etiology:  Rhinosporidium seeberi  Fungi: controversial  18S small subunit ribosomal DNA: Mesomycetozoa

 In tissues:  Thick walled sporangium like structures  Endospores

Epidemiology  Geographical distribution:  South India  Sri Lanka  East Africa  Central & South America

 Natural habitat:  Stagnant pools of fresh water

 M>F  Age:15-40yrs

Clinical Features  Nasal obstruction  Rhinoscopy:  Pink/ Red/ Purple  Papular/ Nodular  Smooth surfaced  Papillomatous/ Proliferative

 Diagnosis:  HPE:  Large sporangia filled with spores  Thick wall  Operculum

Rhinosporidiosis

 Management:  Surgical excision  Cauterization

 Outcomes &

Complications:  Recurrence

Mycotic Diseases of Paranasal Sinuses Classification (Based on HPE & C/F): 1. Invasive Sinusitis: 1. Active Invasive 2. Chronic Invasive 3. Chronic granulomatous invasive or paranasal granuloma

2. Noninvasive Sinusitis 3. Allergic Fungal Sinusitis

Invasive Fungal Sinusitis  Diagnosis:  Evidence of sinusitis:  Radiographic Nasal endoscopy

 Fungal hyphae: HPE

Etiological Agents  Acute fulminant:  Rhizopus spss.  R. arrhizus

 Absidia spss.  Rhizomucor spss.  Aspergillus spss. A. flavus A. fumigatus

 Fusarium spss.  S. apiospermum

 Chronic invasive:     

Alternaria spss. Aspergillus spss. Bipolaris spss. Curvularia spss. Exserohilum spss.

 Granulomatous

invasive:  A. flavus

Epidemiology    

Worldwide Adults Immunocompromised children Risk factors:        

Prolonged neutropenia Metabolic acidosis Hematological malignancies Haematopoetic stem cell transplant recipients Diabetics Corticosteroid therapy Deferoxamine treatment HIV infection

Clinical Features  Acute Invasive: Immunocompromised Unilateral facial swelling Unilateral headache Nasal obstruction/ pain Serosanguinous nasal discharge  Necrotic black lesions on:     

 Hard palate  Nasal turbinate

     

Periorbital/ perinasal swelling Destruction of facial tissue Ptosis Proptosis Ophthalmoplegia Loss of vision

 Chronic invasive:      

Nasal obstruction Chronic sinusitis Thick nasal polyposis Thick purulent mucus Orbital apex syndrome Cavernous sinus thrombosis

 Chronic granulomatous:    

Nasal obstruction Unilateral facial discomfort Enlarging mass Proptosis

Diagnosis  CT Scan:  Acute invasive: Multiple sinuses Unilateral No air fluid level Thickening of sinus lining  Bone destruction    

 Chronic invasive:  Hyperdense mass  Sinus wall erosion

 Chronic

granulomatous:  Opacification of sinuses  Erosion

 MRI:  Cavernous sinus  Cerebral

 Local biopsy:  HPE  Direct microscopy:  KOH mount

 Culture

Management  Control of underlying host disorders  Removal of necrotic & infected tissue  Effective antifungal therapy

Noninvasive Fungal Sinusitis  Fungal ball:  Dense mass of fungal hyphae

 Aetiological agent:  Aspergillus fumigatus  Other Aspergillus spss  S. apiospermum  Alternaria

 Epidemiology:  Older age group  F>M

Clinical Features  Asymptomatic  Nasal obstruction  Purulent nasal    

discharge Cacosmia Facial pain Unilateral symptoms Unusual symptoms:      

Fever Cough Proptosis Epistaxis Diplopia Nasal polyp

Diagnosis  CT Scan:  Partial/ total opacification  Flocculent calcification

 Mucopurulent material:  HPE:  Dense matted fungal hyphae separate from but adjacent to the mucosa of sinus  No allergic mucin  No granulomatous reaction  No fungal invasion

 Management:  Surgical removal  No antifungal agents

 Outcomes & Complications:  Recurrence: Rare  Intracerebral bleed/ infarct  Invasive fungal sinusitis

Allergic Fungal Sinusitis Noninvasive

  Immunocompetent individuals  Chronic rhinosinusitis  Criteria for diagnosis:  Chronic rhinosinusitis (CT Scan)  Allergic mucin  Clusters of eosinophils  Eosinophillic byproducts

 Noninvasive fungal elements  Type I (IgE mediated)

hypersensitivity  Nasal polyposis

 Ponikau et al. (1999):  210 pts with chronic rhinosinusitis  Fungus in nasal mucus: 202 pts (96%)  Surgical treatment: 101  Allergic mucin: 97 (96%)  Fungal elements in HPE: 82 (81%)

 Conclusion:  AFS- Underdiagnosed disorder

 Aetiology:  Aspergillus  Dematiaceous environmental moulds:  Alternaria Bipolaris Cladosporium Curvularia Drechslera

 Epidemiology:  Young immunocompetent adults  Relapsing rhinosinusitis  Unresponsive to: Antibiotics Antihistamines Corticosteroids

 M=F  Atopic  Southern United States

Clinical Features       

h/o Chronic rhinosinusitis U/L nasal polyposis Thick yellow-green mucus Bone necrosis of thin walls of sinus Proptosis DNS to opposite side Pt with nasal polyposis responding only to oral corticosteroids

Diagnosis

 CT Scan:    

Serpiginous opacification of >1 sinus Mucosal thickening Bone erosion No tissue invasion

 Microscopic Examination of allergic mucin:  Eosinophils  Fungal elements

 Histologic examination to r/o invasion  Lab tests:    

Eosinophilia Total serum IgE Specific IgE against fungal Ags +ve skin prick tests

 Fungal cultures

AFS

Management  Surgical debridement  Adjunctive medical management:  Oral corticosteroids  Specific allergen immunotherapy  Nasal corticosteroids  Antihistamines  Antileukotrienes  Sinonasal saline lavage

 Systemic antifungals: not

effective

Mycotic Diseases of the Throat  Candidiasis  Histoplasmosis  Paracoccidioidomycosis  Blastomycosis  Coccidioidomycosis  Cryptococcosis

Candidiasis  Infections caused by organisms of

genus Candida  Etiological Agents:  C.  C.  C.  C.  C.

albicans glabrata krusei tropicalis parapsilosis

Epidemiology  C. albicans:  Commensal in the mouth of 40% ppl  No. ↑es with: Tobacco smoking Dentures

 Host factors:  General:

 Debilitated pts.:

Broad spectrum antibiotics Corticosteroids DM Severe nutritional deficiencies Immunosuppressive diseases eg AIDS

 Local:

 Trauma:

Unhygienic dentures Ill fitting dentures

 Tobacco smoking

Clinical Manifestation  Clinical forms:  Pseudomembranous  Erythematous (or atrophic)  Hyperplastic (or hypertrophic)

Pseudomembranous     

Pts using steroid inhalers Immunocompromised individuals Neonates Terminally ill pts Lesions:  Raised white  Surface of:  Tongue  Soft & hard palate  Buccal mucosa  Tonsils  Confluent plaques  Painless

 Throat involvement: Severe dysphagia  Pseudomembrane wiped off: Pseudomembranous

Candidiasis

Candidiasis

Erythematous  Associated with:  Broad spectrum antibiotic treatment  Chronic corticosteroid use  HIV

 Any part of oral mucosa  Lesions:  Flat  Red  Tongue: depappillated areas

Hyperplastic (Candida leukoplakia)  Lesions undergo malignant

transformation  Lesions:  Small, palpable, translucent white areas  Large, dense, opaque plaques, hard, rough

 Lesions cannot be removed  Site:  Inner surface of both cheeks  Tongue

Other Candidal Lesions  Chronic atrophic

candidiasis:     

Denture stomatitis Associated with oral prostheses Asymptomatic Soreness Cheilitis

 Laryngeal Candidiasis:    

Hoarseness Dysphagia Stridor Plaques on laryngeal mucosa

 Diagnosis:  Clinical  Microscopy  HPE  Culture

 Managemen

t:  Antifungals  Topical Systemic

Mycotic Colonization of Tracheo-oesophageal Voice  Biofilm formation Prostheses  Invasion of silastic  Causative agents:    

C. C. C. C.

albicans glabrata krusei tropicalis

 Results in:  Valve failure  Device replacement

 Local antifungal therapy:

inadequate  Metal coating of prostheses

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