Term Applied to Conditions in Which Fungi

8/14/2019 Term Applied to Conditions in Which Fungi

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MycosesTerm applied to conditions in which fungi passthe resistance barriers of the human or animalbody and establish infections.

Classification is based on:Site of infection

Route of acquisition

Type of Virulence Exhibited


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Mycoses are classified according to tissue levels/site of infection:

Superficial mycoses- limited to the outermost layers ofthe skin and hair.

Cutaneous mycoses - extend deeper into the epidermis,as well as invasive hair and nail diseases.

Subcutaneous mycoses - involve the dermis,subcutaneous tissues, muscle, and fascia

Systemic mycoses due to primary pathogens- originateprimarily in the lungs and may spread to many organsystems.

Systemic mycoses due to opportunistic pathogens -infections of patients with immune deficiencies whowould otherwise not be infected


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MycosesSuperficialCutaneousSubcutaneousSystemicOpportunistic


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According to Route of Acquisition:

ExogenousEndogenous

According to Type of Virulence Exhibited:

Primary pathogens

Opportunistic pathogens


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Superficial Mycoses

Pityriasis versicolor--pigmented lesions on torso(Malassezia globosa, M. restricta, M. furfur)

Tinea nigra -gray to black macular lesions often onpalms or sole [Phaeoannelloyces werneckii]

Black piedra-dark gritty deposits (small firm black

nodule) on hair shaft (Piedraia hortai)White piedra-soft, friable, whitish to beige granules /

nodules along distal ends of hair shaft (Trichosporonbeigelli)

All are diagnosed by microscopy and are easilytreated by topical preparations.


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Cutaneous InfectionsInfections of skin and its appendages (nails, hair); 20 species of dermatophytes causeringworm.


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Cutaneous MycosesTypes: a) Dermatophytoses b)

Dermatomycoses

Dermatophytoses:Epidermophyton nails and skin

Microsporum hair and skin

Trichophyton hair, skin and nails

Dermatomycoses:Candida spp.


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Cutaneous MycosesTinea Pedis (Athletes foot)

Most prevalent of all dermatophytoses

Occurs as a chronic infection of the toe webs(becomes macerated and peels, then cracks appear)

Tinea Unguium (Onychomycosis)

Nail infection which may follow prolonged tineapedis

Nails become yellow, brittle, thickened and crumbly


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Cutaneous MycosesTinea cruris (jock itch)Occurs in the groin area and usually involve

males and present as dry, itchy lesions thatoften start on the scrotum and spread to the

groin

Tinea manusRingworm of the hands or finger

Dry scaly lesions may involve one or bothhands, single fingers or two or more fingers


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Cutaneous MycosesTinea corporisDermatophytosis of the glabrous skin

commonly gives rise to the annular lesions ofringworm, with a clearing scaly center

surrounded by a red advancing border that maybe dry or vesicular

The dermatophyte grows only within dead,keratinized tissue, but fungal metabolites,

enzymes and antigens diffuse through theviable layers of the epidermis to causeerythema


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Ringworm skin infection: Tinea corporisSource: Microbiology Perspectives, 1999


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Candida albicans infection of the nails.Source: Microbiology Perspectives, 1999.


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Cutaneous MycosesTinea capitisTinea capitis is a disease caused by superficial

fungal infection of the skin of the scalp,eyebrows, and eyelashes, with a propensity for

attacking hair shafts and follicles.The disease is considered to be a form of

superficial mycosis or dermatophytosis.

Several synonyms are used, including ringworm

of the scalp and tinea tonsurans.


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Subcutaneous mycosesSubcutaneous infections fungi that cause this type of

mycoses usually reside in soil or on vegetation; they enter theskin or subcutaneous tissue by traumatic inoculation withcontaminated material;

In general lesions become granulomatous but usually confinedsubcutaneously

Infection occurs by implantation of spores or mycelialfragments into a skin wound.

Can spread to lymph vessels.


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Three General Types of Subcutaneous

MycosesChromoblastomycosis

Mycetoma

Sporotrichosis

All caused by traumatic inoculation of theetiologic fungi into the subcutaneous tissue


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Chromoblastomycosis

Generally limited to the subcutaneous tissuewith no involvement of bone, tendon or muscles

Characterized by so called copper pennies(histological examination reveals muriform cellswith perpendicular septations)

Fonsecaea pedrosoi, Fonsecaea compacta

Mycetoma

Suppurative and granulomatous subcutaneous

mycosis which is destructive of contiguous bone,tendon and skeletal muscle

Characterized by draining sinus tracts fromwhich small visible pigmented grains or granules

are extruded (microcolonies of fungi)


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Types of MycetomaEumycotic MycetomaPseudallescheria boydii

Actinomycotic MycetomaNocardia brasiliensis


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Sporotrix schenckii is a thermallydimorphic fungus that lives on vegetation;

It is associated with a variety of plants

grasses, trees, sphagnum moss, rose bushes,and horticultural plants; causes sporotrichosis,a chronic granulomatous infectionGrows as mold at ambient temperaturesGrows in tissue as budding yeast at 35 37 C

Sporotrichosis


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Systemic or Deep

Mycoses1. Primary Mycoses

Coccidioides immitis, Histoplasmacapsulatum, Blastomyces dermatitidis, andParacoccidioides brasiliensis

2. Opportunistic Mycoses

Cryptococcus neoformans, Candida spp.,Aspergillus spp., Penicillium marneffei,Zygomycetes, Trichosporon beigelii, andFusarium spp.


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Systemic/Deep fungal infections are

uncommonNatural immunity is high; physiologic barriers include:1. Skin and mucus membranes

2. Tissue temperature fungi grow better at less than 37C(mesophiles)

3. Redox potential in vivo conditions too reducing for most fungi

Infection requires a large inoculum and isaffected by the resistance of the host

infection often occurs in endemic areasmost infections are asymptomatic or self-limiting

in immune-compromised hosts, infections are more often fatal(distinction between infection and disease)

P i S t i


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Primary SystemicMycosesMost cases are asymptomatic or clinically

mild infections occurring in normal patientsliving or traveling in endemic areas

Usually able to establish in normal host

Fungal pathogens include Coccidioidesimmitis, Histoplasma capsulatum,Blastomyces dermatitidis, andParacoccidioides brasiliensis


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Systemic fungal disease is most often associated with threeorganisms (in U.S.)

1. Coccidioides immitis

2. Histoplasma capsulatum

3. Blastomyces dermatitidis

Normally found in soil, these organisms infect via inhalation.


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Coccidioidomycosis Coccidiodes immitis is considered to

be the most virulent of fungalpathogens.

Restricted to hot, semi-arid areas ofSW USA and Mexico.

Grows in the soil, but inhalation of asingle spore can initiate infection

(self limited)

In infected tissues, C. immitisappears as a mixture of hyphae

and spherules.

Conidia

Spherules


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Coccidioidomycosis:Normally a

benign, sub-clinical upper respiratory infectionIn a small percentage of cases, organism disseminates fromthe lungs to a variety of organs, particularly the CNS,meninges, skin, soft tissues, and bone

In infected tissues, organism is seen as a mixture of spherules andendospores.
http://www.doctorfungus.org/mycoses/human/cocci/coccidioidomycosis.htmhttp://www.doctorfungus.org/mycoses/human/cocci/coccidioidomycosis.htm


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1. Race: Filipinos > African American> Caucasian

2. Age: Extremes more susceptible

3. Sex: Males more susceptible

4. Pregnancy

5. Immunosuppression Diagnosis1. Suppurative or granulatomas inflammation

2. Spherule or endospores seen on pathology

3. Culture of microorganisms

4. Complement fixation assay (in cerebrospinal fluid)

Risk factors for disseminated

coccidioidomycosis

Treatment

Amphotericin B, Fluconazole


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(also called cave disease)

Caused by the dimorphic fungus Histoplasma capsulatum

Tuberculated macroconidia, grown at 25CIntracellular yeast at 37C

Histoplasmosis is characterized by intracellular

growth of the pathogen in macrophages and agranulomatous reaction in tissue. Thesegranulomatous foci may reactivate and causedissemination of fungi to other tissues.


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Disseminated Histoplasma capsulatum, lung infection.Source: Microbiology Perspectives, 1999.


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1. Usually, acute benign respiratorydisease

2. Rarely, progressive, chronic ordisseminated disease

3. Endemic area in U.S. -AtlanticOcean to N. Dakota (500,000cases/year in U.S.), except NewEngland & Florida. Most cases inOhio Valley and Mississippi Valley)

H. capsulatum grows in soil,especially soil contaminatedby guano (can be culturedfrom soil).


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More Histoplasmosis

1.Disseminated histoplasmosis is diagnosed frequently inpatients with AIDS living in the central U.S.

2.It is often the initial manifestation of immunodeficiency.3.In these cases, the organism spreads via blood from the

lung to involve bone marrow, liver, spleen, or skin (see

calcified granulomas).4.Spread can also be associated with underlying lung disease(e.g., emphysema).

Diagnosis

Histology and culture Skin test for histoplasmin [the major hyphal antigen] is not

useful, because most people are positive in endemic area.

In HIV-infected patients with disseminated histoplasmosis,histo. antigen detection in serum and urine is at least 50%,and 90% sensitive, respectively.

0% of histoplasmosis cases are clinically insignificant


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Even More Histoplasmosis

Cell-mediated responses are of primary importance Phagocytic activity of macrophage is considered an important component

of resistance to drugs. Activated macrophage can kill yeast

Therapy

Amphotericin still mainstay of therapy vs. disseminatedhistoplasmosis.

Ketoconasole or itraconasole is effective as therapy for self-limited disease (used in AIDS).

Ocular Histoplasmosis

A small fraction of individuals form scartissue in the retina many years after theoriginal histoplasmosis infection. Thisscarring can obscure the macula and leadto loss of central vision. The first signsare small histo spots. Advanceddisease is treated with laserphotocoagulation to limit the proliferation

Immune response
http://www.nei.nih.gov/health/histoplasmosis/index.asphttp://www.nei.nih.gov/health/histoplasmosis/index.asp


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Blastomycosis Granulomatous mycotic

infection that predominantlyinvolves lungs and skin; but canspread to other organs. Mostprevalent in males 40-60 yearsof age and children.

Blastomyces dermatitidis

Organism probably originates in the

soil (but cant be cultured fromsoil in endemic areas) andinfection ensues by inhalation ofspores.
http://www.doctorfungus.org/mycoses/human/blasto/blastomycosis.htmhttp://www.doctorfungus.org/mycoses/human/blasto/blastomycosis.htm


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Blastomycosis

Most cases are in southern, central, and southeastern USA.

The pulmonary infection is either self -limited or progressive.

Dissemination often occurs to the skin and to the bone - 80% ofpatients have large skin lesions; a large number also havegranulomatous pulmonary lesions.

Clinical findings

Direct examination in tissue

Isolation (yeast-extract-phosphate agar)

Mold to yeast at 37C

Diagnosis


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Therapy

Amphotericin B is the drug of choice for rapidly

progressive blastomycosisKetoconazole for less severe cases

Immune response

1. Alveolar macrophage provide a modest first line of defense.2. PMNs (stimulated) also kill Blastomyces cells (by oxidative

mechanisms).

3. Conidia are more sensitive to killing by PMNs because yeastare too big.

4. Cell-mediated immunity of great importance

O t i ti M


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Opportunistic Mycoses

Opportunistic mycoses are fungal infections that do notnormally cause disease in healthy people, but do cause disease

in people with weakened immune defenses(immunocompromised people). Weakened immune functionmay occur due to inherited immunodeficiency diseases, drugsthat suppress the immune system (cancer chemotherapy,corticosteroids, drugs to prevent organ transplant rejection),radiation therapy, infections (e.g., HIV), cancer, diabetes,

advanced age and malnutrition.

The most common infections are:

Candidiasis

AspergillosisCryptococcosisZygomycosisPhaeohyphomycosis

Pneumocystis carinii
http://www.doctorfungus.org/mycoses/human/candida/Candida_index.htmhttp://www.doctorfungus.org/mycoses/human/aspergillus/aspergillosis.htmhttp://www.doctorfungus.org/mycoses/human/crypto/Crypto_index.htmhttp://www.doctorfungus.org/mycoses/human/zygo/zygomycosis.htmhttp://www.doctorfungus.org/mycoses/human/candida/Candida_index.htmhttp://www.doctorfungus.org/mail/january2003.htmhttp://www.doctorfungus.org/mail/january2003.htmhttp://www.doctorfungus.org/mycoses/human/candida/Candida_index.htmhttp://www.doctorfungus.org/mycoses/human/zygo/zygomycosis.htmhttp://www.doctorfungus.org/mycoses/human/crypto/Crypto_index.htmhttp://www.doctorfungus.org/mycoses/human/aspergillus/aspergillosis.htmhttp://www.doctorfungus.org/mycoses/human/candida/Candida_index.htm


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Opportunistic MycosesCandidiasis protracted courses of broad spectrum antibiotics,

cytotoxic chemotherapy, corticosteroids and vascular catheters

Aspergillossis quantitative and functional defects incirculating neutrophils are key risk factors for development ofinvasive aspergillosis

Zygomycosis (rhiocerrebral syndrome) occus in diabetics withketoacidosis, neutropenia and corticosteroids

Cryptococcosis defective cellular immunity (associated withAIDS)

Phaeohyphomycosis immunocompromised

Hyalohyphomycosis neutropenic patients


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Opportunistic MycosesCandidiasis most common opportunistic fungal infection (Candida

albicans); involve the epidermal and mucosal surfaces including those of theoral cavity, pharynx, esophagus, intestines, urinary bladder and vagina

Aspergillossis usually involves the lungsand brains (may disseminate tothe kidneys, liver, heart and bones)

Zygomycosis (rhiocerrebral syndrome) causes invasive sinopulmonaryinfections (Rhizopus, Rhizomucor, Mucor spp.)

Cryptococcosis most typical opportunistic fungal infection which frequentlycauses pneumonia and/or meningitidis

Phaeohyphomycosis a life threatening infection of brown to blackpigmented fungi of cutaneous, superficial and deep mycoses esp. brain

Hyalohyphomycosis opportunistic fungal infection caused by a variety ofnormally saprophytic fungi with hyaline hyphal elements (Fusarium spp.)


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Cryptococcus neoformans

Primary infection in lungsCryptococcal meningitis is most common

disseminated manifestation

Can spread to skin, bone and prostate

Organism is ubiquitous andinfections occur worldwide

C. neoformans recovered inlarge amounts in pigeonpoopDoes not cause disease in

birds


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Diagnosis Lumbar puncture and

microscopic examination of

cerebrospinal fluid isdiagnostic.

(India ink staining)

Cyrptococcal antigens in CSFand serum.

Immune response

Phagocytosis by neutrophils is inhibited by the presence of acapsule.However, activated neutrophils have an increased capacity tophagocytize C. neoformans.

Cell mediated immunity primary defenseAbout 30% of cryptococcus infections occur in patients withlymphoma (CNS) Therapy

Amphotericin BFluconazole also effective


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AspergillosisGenus occurs worldwide and

contains hundreds of species.These species constitute the

most commonly found fungi inany environment

Major portal of entry is therespiratory tract.Disseminationcan occur from the lungs andinvolve other areas of the lung,the brain, GI tract, and kidney.CNS and nasal-orbital cavities canalso occur without lunginvolvement. Risk factors forinvasive disease are neutropenia

and high doses of adrenal


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Aspergillosis Aspergillosis is the most common fatal infection seen in patients with chronic granulomatous disease

of childhood.

Patients with this condition are unable to form toxic oxygen radicals after phagocytosis.

Progressive and disseminated disease can complicate neoplastic diseases, especially acute leukemia,bone marrow and organ transplantation (not necessarily AIDS).

In immunosuppressed hosts:

invasive pulmonary infection,usually with fever, cough, andchest pain. May disseminate toother organs, including brain,skin and bone. Inimmunocompetent hosts:

localized pulmonary infection inpersons with underlying lungdisease. Also causes allergicsinusitis and allergicbronchopulmonary disease.

Agent:Aspergillus fumigatus,A. flavus.
http://www.doctorfungus.org/mycoses/human/aspergillus/aspergillosis.htmhttp://www.doctorfungus.org/mycoses/human/aspergillus/aspergillosis.htm


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Candidiasis

C. albicans is a member of the indigenous microbial flora of humans.

1. Found in the gastrointestinal tract, upper respiratory tract, buccalcavity, and vaginal tract.2. Growth is normally suppressed by other microorganisms found in

these areas.3. Alterations of gastrointestinal flora by broad spectrum antibiotics or

mucosal injury can lead to gastrointestinal tract invasion.4. Skin and mucus membranes are normally an effective barrier but

damage by introduction of catheters or intravascular devices canpermit Candida to enter the bloodstream.

In vitro (25o C): mostlyyeast;

In vivo (37o C): Yeast,hyphae andpseudohyphae


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Candidiasis Vaginal candidiasis is the mostcommon clinical infection. Local

factors such as pH and glucoseconcentration (under hormonalcontrol) are of prime importance inthe occurrence of vaginal candidiasis.In mouth: normal saliva reducesadhesion (lactoferrin is also

protective).

Immune ResponseHyphae are too big for phagocytosis but are damaged by PMNsand by extracellular mechanisms (myeloperoxidase and b-glucuronidase). Cytokine activated lymphocytes can inhibitgrowth ofC. albicans. Resistance to invasive infection byCandida is mediated by phagocytes, complement and antibody,though cell-mediated immunity plays a major role. Patientswith defects in phagocytosis function and myeloperoxidase

deficiency are at risk for disseminated (even fatal) Candidiasis.


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Candidiasis

Risk factors for candidiasisPost-operative statusCytotoxic cancer

chemotherapyAntibiotic therapyBurnsDrug abuseGastrointestinal damage.

Cutaneous

Thrush


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Chronic mucocutaneous

candidiasisChronic mucocutaneouscandidiasis (CMC) is the labelgiven to a group ofoverlapping syndromes thathave in common a clinical

pattern of persistent, severe,and diffuse cutaneouscandidal infections. Theseinfections affect the skin,nails and mucousmembranes.Immunologic studies of patientswith CMC often reveal defectsrelated to cell-mediatedimmunity, but the defectsthemselves vary widely.


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Mucutaneous candidiasis:

response to fluconazole

Transfusion of a Candida-specific transfer factorhas been reported to be very successful

(remission for > 10 years) when combined withantifungal therapy. The availability of effectiveoral agents, especially the azole antimicotics, hasdramatically changed the life of patients livingwith CMC.


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Environmental species kill neutropenicpatients.

Zygomycosis. Zygomycosis due to Rhizopus, Rhizomucor, Absidia,Mucorspecies, or other members of the class of Zygomycetes, alsocauses invasive sinopulmonary infections. An especially life-threatening form of zygomycosis (also known as mucormycosis), isknown as the rhinocerebral syndrome, which occurs in diabetics withketoacidosis. In addition to diabetic ketoacidosis, neutropenia andcorticosteroids are other major risk factors for zygomycosis.

Phaeohyphomycosis. Phaeohyphomycosis is an infection by brownto black pigmented fungi of the cutaneous, superficial, and deeptissues, especially brain. These infections are uncommon, life-threatening, and occur in various immunocompromised states.

Hyalohyphomycosis. Hyalohyphomycosis is an opportunistic fungalinfection caused by any of a variety of normally saprophytic fungi

with hyaline hyphal elements. For example, Fusarium spp. infectneutropenic patients to cause pneumonia, fungemia, anddisseminated infection with cutaneous lesions.

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Term Applied to Conditions in Which Fungi