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The Fungi of Medical The Fungi of Medical ImportanceImportance

Chapter 22

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Fungi as infectious agentsFungi as infectious agents

►molds & yeasts are widely distributed in air, molds & yeasts are widely distributed in air, dust, fomites & normal floradust, fomites & normal flora

► humans are humans are relatively resistantrelatively resistant► fungi are fungi are relatively nonpathogenicrelatively nonpathogenic► of the 100,000 fungal species, only 300 of the 100,000 fungal species, only 300

have been linked to disease in animalshave been linked to disease in animals► fungi are the most common plant pathogensfungi are the most common plant pathogens► human mycoses are caused by both human mycoses are caused by both true true

pathogenspathogens and and opportunistic pathogensopportunistic pathogens

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Mycoses Mycoses (general statements on)(general statements on)

►Most fungal pathogens do not require a host Most fungal pathogens do not require a host to complete their life cycles and infections to complete their life cycles and infections are not communicableare not communicable

►Dermaphytes & Dermaphytes & Candida spCandida sp naturally inhabit naturally inhabit human body & are transmissiblehuman body & are transmissible

►Dermaphytoses most prevalent fungal Dermaphytoses most prevalent fungal infectioninfection

►Most cases go undiagnosed or misdiagnosedMost cases go undiagnosed or misdiagnosed► Infections can be systemic, subcutaneous, Infections can be systemic, subcutaneous,

cutaneous or superficialcutaneous or superficial

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Levels of invasionLevels of invasion

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► immunity to fungal infections consist of immunity to fungal infections consist of nonspecific barriers, inflammation & cell nonspecific barriers, inflammation & cell mediated defensesmediated defenses

► diagnosis & identification require microscopic diagnosis & identification require microscopic examination of stained specimens, culturing in examination of stained specimens, culturing in selective & enriched media & specific selective & enriched media & specific biochemical & serological testsbiochemical & serological tests

► control with Antifungals such as amphotericin control with Antifungals such as amphotericin B, flucytosine, azoles & nystatinB, flucytosine, azoles & nystatin

MycosesMycoses

Antifungal TherapiesAntifungal Therapies►Mycoses are among the most difficult diseases to Mycoses are among the most difficult diseases to

healheal Fungi can often resist the oxidative damage of T cells Fungi can often resist the oxidative damage of T cells

during cell-mediated immune responsesduring cell-mediated immune responses Fungi are biochemically similar to human cells and Fungi are biochemically similar to human cells and

antifungal drugs can harm human tissuesantifungal drugs can harm human tissues

►Fungi have ergosterol in their membranes rather Fungi have ergosterol in their membranes rather than cholesterol and it is often a target for than cholesterol and it is often a target for antifungal treatmentantifungal treatment Side effects can still result, especially with long-term Side effects can still result, especially with long-term

useuse

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Systemic mycoses caused by Systemic mycoses caused by true pathogenstrue pathogens

► Thermal dimorphismThermal dimorphism► Restricted to certain endemic regions of the Restricted to certain endemic regions of the

worldworld► Soil is normal habitatSoil is normal habitat► Infection by inhalation of spores Infection by inhalation of spores Pulmonary Pulmonary

infectionsinfections Histoplasma capsulatumHistoplasma capsulatum Coccidioides immitisCoccidioides immitis Blastomyces dermatitidisBlastomyces dermatitidis ParacoccidioidomycosisParacoccidioidomycosis brasiliensisbrasiliensis

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Thermal Dimorphism

25 degrees - Hyphal state………………..37 degrees – Yeast state

Thermal dimorphism is a property of true fungal pathogens but is uncommon for opportunistic pathogens

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Distribution of True Fungal Distribution of True Fungal PathogensPathogens

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Histoplasma Histoplasma capsulatumcapsulatum

► causes histoplasmosiscauses histoplasmosis► typically dimorphictypically dimorphic► distributed worldwide, most prevalent in distributed worldwide, most prevalent in

eastern & central regions of USeastern & central regions of US► grow in moist soil high in nitrogen content grow in moist soil high in nitrogen content

(bat and bird droppings)(bat and bird droppings)► Inhalation of organism produces primary Inhalation of organism produces primary

pulmonary infection that may progress to pulmonary infection that may progress to systemic involvement of a variety of organs & systemic involvement of a variety of organs & chronic lung diseasechronic lung disease

► amphotericin B, ketoconazoleamphotericin B, ketoconazole

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Histoplasma capsulatumHistoplasma capsulatum

Areas with large amounts of bird droppings are esp. dangerous

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Coccidioides immitisCoccidioides immitis

►causes coccidioidomycosiscauses coccidioidomycosis►dimorphicdimorphic► lives in alkaline soils in semiarid, hot lives in alkaline soils in semiarid, hot

climates & is endemic to southwestern climates & is endemic to southwestern USUS

►spores inhaled from dust leads to spores inhaled from dust leads to primary pulmonary infection which can primary pulmonary infection which can progress to system body-wide diseaseprogress to system body-wide disease

►amphotericin B treatmentamphotericin B treatment

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Coccidioides immitisCoccidioides immitis

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Coccidioides immitisCoccidioides immitis

Disseminated coccidiomycosis

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Blastomyces dermatitidisBlastomyces dermatitidis

► causes blastomycosiscauses blastomycosis► dimorphicdimorphic► free-living species distributed in soil of a large free-living species distributed in soil of a large

section of the midwestern and southeastern section of the midwestern and southeastern USUS

► inhaled spores convert to yeasts & multiply in inhaled spores convert to yeasts & multiply in lungslungs

► symptoms include cough & feversymptoms include cough & fever► chronic cutaneous, bone, & nervous system chronic cutaneous, bone, & nervous system

complicationscomplications► amphotericin Bamphotericin B

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Blastomyces dermatitidisBlastomyces dermatitidis

Hyphal state

Yeast state

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Blastomyces dermatitidisBlastomyces dermatitidis

Cutaneous blastomycosis

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ParacoccidioidomycosisParacoccidioidomycosis brasiliensisbrasiliensis

►Distributed in Central & South America Distributed in Central & South America ► Infections of the lung or skinInfections of the lung or skin►Most infections are self-limiting, Most infections are self-limiting,

systemic disease is not commonsystemic disease is not common►Ketoconazole, amphotericin B, sulfa Ketoconazole, amphotericin B, sulfa

drugsdrugs

Budding yeast

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Subcutaneous mycosesSubcutaneous mycoses

► Invade traumatized skin, rarely Invade traumatized skin, rarely become systemic but can cause become systemic but can cause destructive local lesionsdestructive local lesions lymphocutaneous sporotrichosislymphocutaneous sporotrichosis chromoblastomycosischromoblastomycosis mycetomamycetoma

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Sporothrix schenckiiSporothrix schenckii►sporotrichosis (rose-gardener’s disease)sporotrichosis (rose-gardener’s disease)►very common saprobic fungus that very common saprobic fungus that

decomposes plant matter in soil decomposes plant matter in soil ► infects appendages & lungsinfects appendages & lungs►Lymphocutaneous variety occurs when Lymphocutaneous variety occurs when

contaminated plant matter penetrates contaminated plant matter penetrates the skin & the pathogen forms a nodule, the skin & the pathogen forms a nodule, then spreads to nearby lymph nodesthen spreads to nearby lymph nodes

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lymphocutaneous lymphocutaneous sprotrichosissprotrichosis

Primary sore and series of secondary nodules along lymphatic chain in the arm

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mycetomamycetoma

►when soil microbes are accidentally when soil microbes are accidentally implanted into the skinimplanted into the skin

►progressive, tumorlike disease of the progressive, tumorlike disease of the hand or foot due to chronic fungal hand or foot due to chronic fungal infection; may lead to loss of body partinfection; may lead to loss of body part

►caused by caused by PseudallescheriaPseudallescheria or or MadurellaMadurella

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Cutaneous mycosesCutaneous mycoses

► infections strictly confined to keratinized infections strictly confined to keratinized epidermis (skin, hair, nails) are called epidermis (skin, hair, nails) are called dermatophytoses-dermatophytoses- ringwormringworm

►39 species in the genera 39 species in the genera Trichophyton, Trichophyton, Microsporum, Epidermophyton Microsporum, Epidermophyton

►communicable among humans, animals, & communicable among humans, animals, & soilsoil

► infection facilitated by moist, chafed skininfection facilitated by moist, chafed skin

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► Ringworm of scalp (tinea capitis) affects scalp Ringworm of scalp (tinea capitis) affects scalp & hair-bearing regions of head; hair may be lost& hair-bearing regions of head; hair may be lost

► Ringworm of body (tinea corporis) occurs as Ringworm of body (tinea corporis) occurs as inflamed, red ring lesions anywhere on smooth inflamed, red ring lesions anywhere on smooth skinskin

► Ringworm of groin (tinea cruris) “jock itch” Ringworm of groin (tinea cruris) “jock itch” affects groin & scrotal regionsaffects groin & scrotal regions

► Ringworm or foot & hand (tinea pedis & tinea Ringworm or foot & hand (tinea pedis & tinea manuum) is spread by exposure to public manuum) is spread by exposure to public surfaces; occurs between digits & on soles. surfaces; occurs between digits & on soles. (Athlete’s foot)(Athlete’s foot)

► Ringworm of nails (tinea unguium) is a Ringworm of nails (tinea unguium) is a persistent colonization of the nails of the hands persistent colonization of the nails of the hands & feet that distorts the nail bed& feet that distorts the nail bed

26Ringworm

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Ringworm / Dermatophytosis

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Ringworm treatmentRingworm treatment

►ointments containing tolnaftate, ointments containing tolnaftate, miconazole or menthol & camphormiconazole or menthol & camphor

► lamisil or griscofulvin 1-2 yearslamisil or griscofulvin 1-2 years

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Superficial mycosesSuperficial mycoses►Tinea versicolor causes mild scaling, Tinea versicolor causes mild scaling,

mottling of skinmottling of skin►White piedra is whitish or colored White piedra is whitish or colored

masses on the long hairs of the bodymasses on the long hairs of the body►Black piedra causes dark, hard Black piedra causes dark, hard

concretions on scalp hairsconcretions on scalp hairs White & black piedraWhite & black piedra

► Transmission is often mediated by shared hair brushes or Transmission is often mediated by shared hair brushes or combscombs

► Several members of a family are usually infected at the same Several members of a family are usually infected at the same timetime

► Infected areas must often be shaved to remove the fungiInfected areas must often be shaved to remove the fungi

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Tinea versicolor

Black PiedraBlack Piedra

White PiedraWhite Piedra

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Opportunistic MycosesOpportunistic Mycoses

Table

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Candida albicansCandida albicans

►widespread yeastwidespread yeast► infections can be short-lived, infections can be short-lived,

superficial skin irritations to superficial skin irritations to overwhelming, fatal systemic diseasesoverwhelming, fatal systemic diseases

►budding cells of varying size that my budding cells of varying size that my form both elongate pseudohyphae & form both elongate pseudohyphae & true hyphaetrue hyphae

►forms off-white, pasty colony with a forms off-white, pasty colony with a yeasty odoryeasty odor

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Candida albicansCandida albicans

►Normal flora of oral cavity, genitalia, large Normal flora of oral cavity, genitalia, large intestine or skin of 20% of humansintestine or skin of 20% of humans

► Account for 80% of nosocomial fungal infectionsAccount for 80% of nosocomial fungal infections► Account for 30% of deaths from nosocomial Account for 30% of deaths from nosocomial

infectionsinfections► ThrushThrush – occurs as a thick, white, adherent – occurs as a thick, white, adherent

growth on the mucous membranes of mouth & growth on the mucous membranes of mouth & throatthroat

►Vulvovaginal yeast infection Vulvovaginal yeast infection – painful – painful inflammatory condition of the female genital inflammatory condition of the female genital region that causes ulceration & whitish region that causes ulceration & whitish dischargedischarge

►Cutaneous candidiasis Cutaneous candidiasis – occurs in chronically – occurs in chronically moist areas of skin and burn patientsmoist areas of skin and burn patients

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Candida Candida albicansalbicans

Thrush

Candidal diaper rash

Vaginitis

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Cryptococcus neoformansCryptococcus neoformans

►a widespread encapsulated yeast that a widespread encapsulated yeast that inhabits soils around pigeon roosts inhabits soils around pigeon roosts

►causes cryptococcosiscauses cryptococcosis►common infection of AIDS, cancer or common infection of AIDS, cancer or

diabetes patientsdiabetes patients► infection of lungs leads to cough, infection of lungs leads to cough,

fever, & lung nodulesfever, & lung nodules►dissemination to meninges & brain can dissemination to meninges & brain can

cause severe neurological disturbance cause severe neurological disturbance & death& death

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Cryptococcus neoformansCryptococcus neoformans

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Pneumocystis jiroveci Pneumocystis jiroveci (P.carinii)(P.carinii)

►a small, unicellular fungus that causes a small, unicellular fungus that causes pneumonia (PCP), the most prominent pneumonia (PCP), the most prominent opportunistic infection in AIDS patientsopportunistic infection in AIDS patients

►this pneumonia forms secretions in the this pneumonia forms secretions in the lungs that block breathing & can be lungs that block breathing & can be rapidly fatal if not controlled with rapidly fatal if not controlled with medicationmedication

►pentamidine & cotrimoxazolepentamidine & cotrimoxazole

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AspergillusAspergillus

►very common airborne soil fungusvery common airborne soil fungus►600 species, 8 involved in human 600 species, 8 involved in human

diseasedisease► inhalation of spores causes fungus inhalation of spores causes fungus

balls in lungs and invasive disease in balls in lungs and invasive disease in the eyes, heart, & brainthe eyes, heart, & brain

►amphotericin B & nystatinamphotericin B & nystatin

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AspergillusAspergillus

Conjunctival infection Brain abscesses (darkened areas)

Invasive eye infection

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zygomycosiszygomycosis

►Zygomycota are extremely abundant Zygomycota are extremely abundant saprobic fungi found in soil, water, saprobic fungi found in soil, water, organic debris, & foodorganic debris, & food

►Genera most often involved are Genera most often involved are Rhizopus, Absidia, & MucorRhizopus, Absidia, & Mucor

►usually harmless air contaminants usually harmless air contaminants invade the membranes of the nose, invade the membranes of the nose, eyes, heart, & brain of people with eyes, heart, & brain of people with diabetes, malnutrition with severe diabetes, malnutrition with severe consequencesconsequences

44Hyphae and spores of zygomycosis-causing fungus

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Fungal allergies & Fungal allergies & mycotoxicosesmycotoxicoses

• Fungal spores are common sources of atopic Fungal spores are common sources of atopic allergiesallergies

1.1. asthma, often occurring in seasonal episodesasthma, often occurring in seasonal episodes

2.2. farmer’s lung, a chronic & sometimes fatal allergy of agricultural farmer’s lung, a chronic & sometimes fatal allergy of agricultural workers exposed to moldy grassesworkers exposed to moldy grasses

3.3. teapicker’s lungteapicker’s lung

4.4. bagassosis, a condition caused by inhaling moldy dust from processed bagassosis, a condition caused by inhaling moldy dust from processed sugarcane debrissugarcane debris

5.5. bark stripper’s disease caused by inhaling spores from logsbark stripper’s disease caused by inhaling spores from logs

• Fungal toxins lead to mycotoxicosesFungal toxins lead to mycotoxicosesSome may be caused by eating poisonous or Some may be caused by eating poisonous or

hallucinogenic mushroomshallucinogenic mushrooms

Ergot poisoning Ergot poisoning can occur from ingestion of moldy can occur from ingestion of moldy graingrain