Fungal Diseases: An Overview

Fungal Diseases Overview

• Fungal diseases are explored in the context of body defense, immunity, and infection (311-112).
• Lakkhana Kanhayuwa Wingfield is a professor in the Department of Microbiology, Faculty of Science at Prince of Songkla University.

Fungi Characteristics

• Fungi degrade organic matter.
• They exist as heterotrophs.
• They serve as sources for new drugs and food.
• Some cause plant or human diseases.
• Opportunistic fungal pathogens can cause disease in compromised hosts.

Fungal Classification

• Saprobes obtain nutrients from decaying organic matter.
• Symbionts live in symbiosis with other organisms.
• Commensals live in the gut.
• Some Fusarium species are pathogenic in tissue.

Closer Look at Fungi

• Fungi are eukaryotic organisms.
• The rigid cell wall contains chitin and glucan.
• The cell membrane contains ergosterol.
• Multicellular fungi include molds and mushrooms, which consist of masses of mycelia.
• Yeasts are unicellular fungi.

Cytoplasmic Components of Fungi

• Plasma membrane consists of a phospholipid bilayer with associated transmembrane proteins.
• Ergosterol within serves as a target for fungicides and antifungal drugs.
• Anchors some enzymes.
• Chitin synthase and glucan synthase are integral membrane proteins.
• Relays signals from the external environment to cells interior through signal transduction.

Morphology of Fungi

• Molds are filamentous fungi that are multicellular.
• Hyphae are tubular structures.
• Mycelium is a mat-like structure of hyphae.

Types and Colors of Hyphae

• Septate hyphae, such as those found in Penicillium and Aspergillus, have cross-walls.
• Non-septate hyphae, such as those found in Rhizopus and Mucor, lack cross-walls.
• Hyaline hyphae, as found in Penicillium and Aspergillus, are clear or transparent.
• Dematiaceous fungi produce melanin pigment

Macroscopic Appearance of Fungi

• Surface textures can be woolly, cottony, velvety, or granular.
• Colors can include gray, gray-white, gray-green, purple-brown, dark brown, black, yellow, orange, olive green, and pink-gray.
• Reverse sides can be black, yellow, red, or brown.
• Diffusible pigments may also be present.

Morphology of Yeasts

• Yeasts are unicellular.
• Yeasts form round, pasty, or mucoid colonies.
• Yeasts reproduce by budding or fission.
• Mother cells produce daughter cells.

Pseudohyphae and True Hyphae

• Pseudohyphae appear as chains of successively budding yeast cells that remain attached.
• True hyphae develop from a germ tube emerging from a spore or yeast cell.
• Candida albicans can produce true hyphae.

Dimorphic Fungi

• Exist in both yeast and mold forms.
• Temperature triggers the shift between phases (heat shock response).
• Dimorphism is reversible and linked to virulence.
• True fungal pathogens cause systemic infections.

Reproductive Systems

• Asexual reproduction involves mitosis.
• Asexual spores include:
  • Sporangiospores (Rhizopus and Mucor spp.)
  • Conidia (Aspergillus spp., Penicillium spp., and dermatophytes)
  • Arthroconidia
  • Blastospores
  • Chlamydospores

Spores of Dermatophytic Fungi

• Trichophyton spp. have pencil-shaped spores.
• Microsporum spp. have spindle-shaped spores.
• Epidermophyton spp. have club-shaped spores.

Role of Fungi in Diseases

• Mycotic diseases often occur in very sick patients with a compromised immune system or hospitalization.
• Fungal infections can develop in one or more organ systems, either superficially (outer layers of skin) or deeply (heart, central nervous system, or abdominal viscera).
• Development of fungal infection depends on the host's immune status, opportunity for interaction between host and fungus, and the infectious dose.

Clinical Recognition of Fungal Infections

• Prompt diagnosis is crucial.
• Essential steps include clinical suspicion through history and physical examination, searching for cutaneous/mucosal lesions, inspecting implanted devices, conducting ophthalmologic examinations, diagnostic imaging studies, and procuring specimens for lab diagnosis.

Classification of Human Mycoses

• Categorized by which structures fungi colonize or invade:
  • Superficial mycoses affect the keratinized outer layers of skin, hair, and nails.
  • Cutaneous mycoses affect the deeper layers of the epidermis, including hair and nails.
  • Subcutaneous mycoses affect the dermis, subcutaneous tissues, muscle, and fascia.
  • Systemic mycoses include endemic and opportunistic mycoses.

Superficial Mycoses

• Infections of the skin and hair surface which elicit little or no host immune response.
• Often asymptomatic and are of cosmetic importance.
• Examples include Pityriasis versicolor and tinea, such as Tinea nigra, White piedra, and Black piedra.

Pityriasis Versicolor

• Is caused by the lipophilic yeast Malassezia furfur.
• Lab diagnosis involves skin scraping of infected areas and microscopic examination with 10% KOH.
• Culturing can be done using synthetic media with olive oil.

Superficial Mycoses (cont.)

• Clinical syndromes may include irregular, discolored, raised patches with fine scales on the arms, chest, shoulders, face, and neck.
• Fragmented hyphae and yeast cells of Malassezia furfur can be observed microscopically.

Tinea Nigra

• Clinical syndromes include solitary, irregular, pigmented macules on palms or soles, and is not contagious.
• Organism involved is Hortaea werneckii.

White Piedra

• Clinical syndromes involves affecting the hair of the groin and axillae.
• Surrounds the hair shaft, forming white-to-brown masses that are easily removed.
• Caused by Trichosporon

Black Piedra

• Clinical syndromes present as small, dark nodules on the hair shaft, often asymptomatic and involving the scalp.
• Caused by piedraia hortae

Cutaneous Mycoses

• Characterized by infections of the keratinized layer of skin, hair, and nails.
• Host response may be elicited and become symptomatic, with itching, scaling, broken hairs, and ring-like patches of thickened and discolored skin.

Diagnosing Cutaneous Mycoses

• Diagnosis includes using a Wood lamp, where a +ve fluorescence indicates infection.
• Direct microscopy of skin/nail scrapings or hair samples is performed with a KOH mount.
• Isolation of the fungi is done in culture.

Subcutaneous Mycoses

• Less common
• Infections occur deeper in skin layers, even the cornea, muscle, and connective tissue.
• Access gained by traumatic inoculation, leading to abscess formation, non-healing ulcers, and draining sinus tracts.
• Can also lead to tissue destruction and epitheliomatous hyperplasia.
• Infections remain localized to the subepidermal tissue with rare dissemination.

Sporotrichosis

• Caused by Sporothrix schenckii.
• Morphology can be dimorphic.
• Is ubiquitous in soil and decaying vegetation.
• Mold form colonies have a wrinkled surface and produces conidia in "daisy petal" form.
• Yeast form appears as spheric, oval, or elongated yeast-like cells.

Transmission and Diagnosis

• Epidemiology involves zoonotic transmission through armadillo hunters and infected cats.
• Clinical syndromes include Lymphangitic sporotrichosis with lymphatic nodules and painless subcutaneous nodules along lymphatic drainage.
• Can be diagnosed using tissue samples to find yeast buds.
• Oral potassium iodine in a saturated solution or Intraconazole are adequate treatments

Chromoblastomycosis

• Subcutaneous mycosis caused by pigmented (dematiaceous) fungi like Fonsecaea, Cladosporium, and Exophiala.
• Chestnut brown muriform cells (sclerotic bodies).
• Epidemics are in warm climate and commonly effects feet when lacking proper footwear
• Infections include multiple, large, warty, cauliflower-like growths.

Eumycotic Mycetoma

• Subcutaneous mycosis characterized by the formation of multiple granulomas and abscesses containing fungal hyphae (granules or grains).
• Abscesses lead to the extrusion of granules.
• Etiologic agents include true fungi like Phaeoacremonium spp., Madurella spp., Curvularia spp., Fusarium spp., Exophiala spp., and Scedosporium spp.
• Common in tropical areas with low rainfall and gains infections through traumatic implantation.

Systemic Mycoses (Endemic)

• Infections caused by dimorphic fungal pathogens and confined to geographic regions.
• Primary infection in the lung disseminates to other organs/tissues.
• Cause infections in healthy individuals.
• Organisms include Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis, Paracoccidioides brasiliensis and penicillium marneffei

Histoplasmosis

• Caused by Histoplasma capsulatum.
• Clinical syndromes range from mild, asymptomatic forms to severe forms with fever, chills, headache, muscle aches, dry cough, and chest discomfort.
• Lab diagnosis includes cultures of body fluids/tissues, urine tests, blood tests, microscopic examination, and chest X-rays.
• Acquired from environments with bird or bat droppings.

Penicilliosis Marneffei

• Causes by Talaromyces marneffei.
• Clinical syndromes include fever, anemia, weight loss, and molluscum contagiosum-like skin lesions on the face and trunk.
• Occurs primarily in HIV-infected individuals in Thailand and southern China.

Systemic Mycoses (Opportunistic)

• Caused by fungi that are human commensals or found in the environment.
• Exhibiting low virulence, causes infection in immunocompromised individuals except Cryptococcus neoformans and C. Gattii who are higher virulence
• Common opportunistic fungi include Candida spp., Cryptococcus neoformans, Aspergillus spp., and Pneumocystis jirovecii.

Candidiasis

• Caused by Candida albicans, which is normal flora of oropharynx, GI, and the female genital tract.
• Superficial candidiasis=Thrush.

Thrush Lab Diagnosis

• Lab diagnosis involves cultures and microscopic observations of Clue cells with coccobacilli
• Microscopy can be performed on vaginal samples or through Hyphae

Pneumocystis pneumonia

• Opportunistic mycosis that generally causes asymptomatic infection.
• When symptomatic, clinical results are Pneumonia
• Diagnosis can be determined by staining the cell wall in Gomori staining methods

###Opportunistic Mycoses

• Cryptococcosis is fungi acquired in Yeast-like manner
• Cryptococcosis acquired as pulmonary infection and CNS.infection
• Lab tests will diagnose in CSF by taking Sputum
• Detection of Cryptococcus requires antigen

Aspergillis

Opportunistic infection from hyperventilation that becomes invasive

• Symptoms include pulmonary and disseminate disease
• Diagnosis from blood test and biopsies
• morphology looks for branch like stems
• caused by Conida growth in cultured tissue environment

Fungi and their mycotoxins

• Mycotoxins are frequently found in food.
• Aflatoxin, produced by Aspergillus species, affects the liver
• Ochratoxin, produced by Aspergillus and Penicillium affects the kidneys
• Patulin, produced by Penicillium patulum affects the neurotoxins
• Trichothecene is produced by Fasarium
• Zearalenone produced by Fusarium

Other types of common fungi side effects

• Common to cause diarrhea, nausea, and fatigue
• High water content mushrooms can be cooked to be edible