Introduction to Medical Mycology

Medical mycology is the study of mycoses of man and their etiologic agents. Mycoses are the diseases caused by fungi. Of the several thousands of species of fungi that are known, less than 300 are pathogenic to man. fungal invasion of human tissue was recognized in the early 1800s before the science of bacteriology was developed.

What is a Fungus ? Kingdom fungi Eukaryotic – a true nucleus , heterotrophic, do not contain chlorophyll Produce filamentous structures (hyphae) Produce spores (sexual & asexual reproduction) Saprophytic ( on dead tissue).Parasitic (on living organism). All fungi required organic source of Carbon associated with decaying matter

Cell wall consist of chitin and B-glucan ,both are polysaccharide which is the site of action of some antifungal drugs. Cell membrane consist of ergosterol rather than cholesterol like bacterial cell membrane Ergosterol is the site of action of antifungal drugs e.g, Amphotericin B & Azole group. Most fungi are obligatory aerobes , others are facultative anaerobes.

Morphology of Fungi 1. Filamentous fungi (molds) is long branching filaments. Mass of filaments called mycelium, septate or non-septate (Coenocytic) 2. Yeasts , round or oval bodies which reproduce by the formation of buds known as blastospores. 3. Yeast-like fungi , this form of undetached budding yeast-cells which present the appearance of broad septate hyphae (pseudohyphae) e.g, candida.

4-Thermally Dimorphic Fungi These are fungi which exhibit a filamentous mycelial morphology (saprophytic phase) when grown at room temperature 27oC, but have a typical yeast morphology (parasitic phase) inside the body and when grown at 37oC in the laboratory (e.g. Histoplasmosis).

Dimorphic nature of true fungal pathogens Figure 22.2

Fungal classification Four groups of true fungi Ascomycota Basidiomycota Zygomycota This classification based on their method of sexual reproduction. Mitosporic Fungi (Fungi imperfecti)…have no sexual reproduction….most medical important fungi are included here.

Sexual spores exhibit fusion of nuclei. Ascospore - spore formed in a sac-like cell known as an ascus. Often eight (8) spores formed. (Ascomycetes) Basidiospore - sexual spore produced on a specialized club-shaped structure, called a basidium. (Basidiomycetes) Zygospore - a thick-walled spore formed during sexual reproduction (Phycomycetes)

Asexual Spores Chlamydospore – formed within hyphae , thick-walled .e.g, Candida albicans Sporangiospore –hundred formed within a sac (sporangium) at the end of an aerial hyphae .e.g,Rhizopus spp. , Mucor spp. Conidiospore Multiple (chains) or single spores formed at the end of an aerial hyphae (not enclosed within a sac) e.g, Aspergillus spp. , Penicillum

Blastospore is a bud coming off the parent cell e Blastospore is a bud coming off the parent cell e.g, Candida albicans Arthrospore is formed by breaking up of fungal mycelia e.g, Trichosporon Conidia , asexual spore formed at the top of hyphal branch, two types , micro & macroconidia e.g, Dermatophytes

Miscellanous terms: Conidiophore - a specialized branch of hypha on which conidia are developed. Dematiaceous - pigmented, dark in color, usually gray to black Sterigmata - a specialized structure that arises from a basidium and supports basidiospores

Pseudohyphae - a chain of elongated budding cells that have failed to detach (not true hyphae). Rhizoids - root-like structures. Sporangiophore - a special aerial hypha or stalk bearing a sporangium. Sporangium - a sac or cell containing spores produced asexually.

MYCOTIC DISEASES (Four Types) Hypersensitivity Allergy Mycotoxicosis Production of toxin Mycetismus (mushroom poisoning) Pre-formed toxin Infection

Epidemiology Normal habitat is the environment except candida albicans is part of normal human flora. Most mycotic agents are soil saprophytes. Mycotic diseases are not contagious except in few cases as in superfacial mycoses. Establishment of infection depends on inoculum size , resistance of the host rather than virulence of fungus.

Topographic Grouping of Fungi most often used Superficial - Confined to the outer most layers of the skin and hair. No host cellular or inflammatory response.T he disease is recognized purely on cosmetic basis. Cutaneous - in the keratin of the skin, nails, and hair. These organisms prefer non-living cornified layers. The disease is called a dermatophytosis or dermatomycosis. Host response is patchy scaling or eczema eruptions.

Topographic Grouping of Fungi: (continued) Subcutaneous - Involve the deeper layers of skin and often muscle tissue. Man is an accidental host following inoculation of fungal spores via some form of trauma. This type of infection is often identified by the presence of a characteristic tissue reaction or granule. Systemic - Attack the deep tissues and organ systems; often creating symptoms that resemble other diseases.

Categories of systemic disease: Those caused by truly pathogenic fungi with the ability to cause disease in the normal human host when the inoculum is of sufficient size (Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis, Paracoccidioides braziliensis). Those caused by opportunistic fungi, low virulence organisms, which require the patient's defenses to be lowered before the infection is established (Aspergillus spp. Candida albicans, Cryptococcus neoformans).

Diagnosis 1. Wet Mount (KOH) 2. Skin test (dermal hypersensitivity) 3 Diagnosis 1. Wet Mount (KOH) 2. Skin test (dermal hypersensitivity) 3. Serology (Latex agglutination , Complement fixation ….)in systemic infection 4. Fluorescent antibody 5. Biopsy and histopathology(pyogenic , granulomatous ,or necrotic) 6. Culture (Sabouraud dextrose agar) 7. DNA probes

THERAPY All eukaryotic cells contain sterols (mammalian cells contain cholesterol & fungal cell membrane contain ergosterol). So fungi are biochemically similar to the human host. Therefore it is difficult to develop chemotherapeutic agents that will destroy the invading fungus without harming the patient. This fact is a real problem .

Antifungal drugs 1-Allylamines 2-Azoles This inhibit sequalene epoxidase which is required for ergosterol synthesis e.g, Terbinafine (lamasil) , used orally and topically. 2-Azoles Inhibit the enzyme which is necessary to convert lanosterol to ergosterol.this include :Imidazole derivative include Econazole , Ketoconazole , Clotrimazole. Used topically.

3-Polyenes derivatives This include Amphotericin B & Nystatin Triazole derivatives, this include Fluconazole , Itraconazole . Used orally. Thiazoles derivative 3-Polyenes derivatives This include Amphotericin B & Nystatin

Amphotericin B AMB has a greater avidity for ergeosterol than for the cholesterol in the human cell. Used for systemic mycosis , I.V in drip infusion & need long term administration. Side effect include thrombophlebitis , nephrotoxicity , fever , chills , anemia.

4- Echinocandin Used for localized & systemic fungal infection( in immunocompromised pt) . It inhibits the synthesis of glucan in the cell wall via the enzyme 1,3 –Beta glucan synthetase. It administered by injection because it is poorly absorped orally. 5- Others, this include Tolnaftate which is similar to action of allylamines. Used topically.

Griseofulvin Slow reacting drugs used for skin , nail , and hair infection (keratin). It accumulates in stratum corneum and prevent hyphal penetration through these layers. Benzoic acid , combined with keratolytic agents e.g, whitefield ointment. Flucytosine or 5-flurocytosine interfere with RNA synthesis.

Sexual spores

End of Introduction