zarqa private universitybiology 4223 – the fungi medical mycology prof. khaled h. abu-elteen
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Zarqa Private UniversityBiology Zarqa Private UniversityBiology 4223 – The Fungi4223 – The Fungi
Medical MycologyMedical Mycology
Prof. Khaled H. Abu-ElteenProf. Khaled H. Abu-Elteen
Zarqa Private UniversityBiology Zarqa Private UniversityBiology 4223 – The Fungi4223 – The Fungi
Fungal DiseasesFungal Diseases
Mycosis- fungal infectionMycosis- fungal infection < 100 cause human disease< 100 cause human disease Not highly contagiousNot highly contagious Humans acquire from natureHumans acquire from nature
Groups based on degree on tissue Groups based on degree on tissue involvement and mode of entryinvolvement and mode of entry
Cutaneous mycoses-Cutaneous mycoses-dermatophytesdermatophytes Epidermis, hair & nailsEpidermis, hair & nails Contagious-direct or indirect contactContagious-direct or indirect contact Secrete keratinase that degrades Secrete keratinase that degrades keratinkeratin
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Cutaneous MycosesCutaneous Mycoses Tinea( worm) capitis –blisters with scaly Tinea( worm) capitis –blisters with scaly
ringring Ringworm of the scalp Ringworm of the scalp
Spreads circularly forming bald spotsSpreads circularly forming bald spots Spread by contact with fomites , cats Spread by contact with fomites , cats
and dogsand dogs Tinea cruris-Tinea cruris- ringworm of groin ringworm of groin Tinea pedisTinea pedis - athlete's foot - athlete's foot
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Systemic MycosesSystemic Mycoses Dimorphic fungiDimorphic fungi
Yeast form is invasiveYeast form is invasive Can spread throughout bodyCan spread throughout body Usually caused by fungi in soilUsually caused by fungi in soil Inhalation of sporesInhalation of spores Begins in lungs and spread to rest of Begins in lungs and spread to rest of
bodybody Not contagious person to personNot contagious person to person
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IntroductionIntroduction
Obligate Parasitic Fungi Obligate Parasitic Fungi (dermatophytes)(dermatophytes): evolved to attack the : evolved to attack the outer surface of humansouter surface of humans
Facultative soil fungi:Facultative soil fungi: thermal thermal dimorphic saprobes, adaptations to dimorphic saprobes, adaptations to human bodyhuman body
Opportunistic saprobesOpportunistic saprobes: attack people : attack people with compromised immune systemswith compromised immune systems
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IntroductionIntroduction
Fungal InfectionsFungal Infections Superficial infections: involve Superficial infections: involve
outermost layers of skin and its outermost layers of skin and its appendages [ nails or hair] appendages [ nails or hair] ( Dermatophytosis)( Dermatophytosis)
Cutaneous infectionsCutaneous infections: involve deeper : involve deeper layers of skin causing allergic or layers of skin causing allergic or inflammatory responseinflammatory response
Subcutaneous infections: Subcutaneous infections: fungi with low fungi with low virulence, localized infection, or spread by virulence, localized infection, or spread by mycelial growthmycelial growth
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IntroductionIntroduction
Systemic infectionsSystemic infections: caused by : caused by true pathogenic fungi or true pathogenic fungi or opportunistic saprobesopportunistic saprobes
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MycosesMycoses: diseases cause : diseases cause by fungiby fungi
SuperficialSuperficial Cutaneous Cutaneous SubcutaneousSubcutaneous SystemicSystemic OpportunisticOpportunistic
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The SituationThe SituationFrequency
- most common fungal pathogen worldwide- 4th leading causes of nosocomial infections, 40% mortality- significant mortality and morbidity in low birth-weight infants- affects 75% women, 45% experience recurrence
> 10 million visits/year- classified as a STD by CDC
Immunocompromised- cancer and HIV-AIDs patientsC
- most commonly manifested in patients with leukemia or HIV-AIDs infections. Oral candidiasis is often a clue to acute primary infectionC
Public Concerns- increasing resistance to drug therapies due to antibiotics and antifungals
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FUNGALFUNGAL DISEASESDISEASES
Mycosis:Mycosis: Any fungal disease. Tend to be chronic Any fungal disease. Tend to be chronic
because fungi grow slowly. because fungi grow slowly.
Mycoses are classified into the following categories:Mycoses are classified into the following categories:
I. Systemic mycoses: Fungal infections deep within the I. Systemic mycoses: Fungal infections deep within the
body. Can affect a number if tissues and organs.body. Can affect a number if tissues and organs.
Usually caused by fungi that live in the soil and are Usually caused by fungi that live in the soil and are
inhaled. Not contagious.inhaled. Not contagious.
Examples:Examples:
Histoplasmosis (Histoplasmosis (Histoplasma capsulatumHistoplasma capsulatum): ):
Initial infection in lungs. Later spreads Initial infection in lungs. Later spreads
through blood to most organs.through blood to most organs.
Coccidiomycosis (Coccidiomycosis (Coccidioides immitesCoccidioides immites): ):
Resembles tuberculosis.Resembles tuberculosis.
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Systemic Mycosis: HistoplasmosisSystemic Mycosis: Histoplasmosis
Disseminated Histoplasma capsulatum, lung infection.
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FUNGALFUNGAL DISEASES (Continued)DISEASES (Continued)
II. Cutaneous mycoses: Fungal infections of the skin, II. Cutaneous mycoses: Fungal infections of the skin,
hair, and nails. hair, and nails. Secrete keratinase, an enzyme that degrades Secrete keratinase, an enzyme that degrades
keratin.keratin. Infection is transmitted by direct contact or contact Infection is transmitted by direct contact or contact
with infected hair (hair salon) or cells (nail files, with infected hair (hair salon) or cells (nail files,
shower floors).shower floors). Examples:Examples:
Ringworm (Ringworm (Tinea capitisTinea capitis and and T. corporisT. corporis)) Athlete’s foot (Athlete’s foot (Tinea pedisTinea pedis)) Jock itch (Jock itch (Tinea crurisTinea cruris))
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Opportunistic Infection by Opportunistic Infection by Candida Candida albicansalbicans in an AIDS Patient in an AIDS Patient
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Severe nail infection with Trichophyton rubrum ina 37-year-old male AIDS patient.
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Disseminated Histoplasma capsulatum, skin infection.
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Cutaneous MycosisCutaneous Mycosis
Ringworm skin infection: Tinea corporis
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Cutaneous MycosisCutaneous Mycosis
Candida albicans infection of the nails.
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FUNGALFUNGAL DISEASES (Continued)DISEASES (Continued)
III. Subcutaneous mycoses: Fungal infections beneath III. Subcutaneous mycoses: Fungal infections beneath
the skin. the skin. Caused by saprophytic fungi that live in soil or on Caused by saprophytic fungi that live in soil or on
vegetation. vegetation. Infection occurs by implantation of spores or Infection occurs by implantation of spores or
mycelial fragments into a skin wound. mycelial fragments into a skin wound. Can spread to lymph vessels. Can spread to lymph vessels.
IV. Superficial mycoses: Infections of hair shafts andIV. Superficial mycoses: Infections of hair shafts and
superficial epidermal cells. Prevalent in tropical superficial epidermal cells. Prevalent in tropical
climatesclimates..
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FUNGALFUNGAL DISEASES (Continued)DISEASES (Continued)
Opportunistic mycoses: Caused by organisms that are Opportunistic mycoses: Caused by organisms that are
generally harmless unless individual has weakened generally harmless unless individual has weakened
defenses:defenses:
AIDS and cancer patientsAIDS and cancer patients Individuals treated with broad spectrum Individuals treated with broad spectrum
antibioticsantibiotics Very old or very young individuals Very old or very young individuals
(newborns).(newborns). Examples:Examples:
Aspergillosis: Inhalation of Aspergillosis: Inhalation of AspergillusAspergillus spores. spores. Yeast Infections or Candidiasis: Caused Yeast Infections or Candidiasis: Caused
mainly by mainly by Candida albicansCandida albicans. Part of normal . Part of normal
mouth, esophagus, and vaginal flora.mouth, esophagus, and vaginal flora.
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Cutaneous InfectionsCutaneous Infections
Dermatophytic hyphomycetesDermatophytic hyphomycetes 40 species40 species EpidermophytonEpidermophyton (2 species) (2 species) MicrosporumMicrosporum (17 species) (17 species) TrichophytonTrichophyton (24 species) (24 species) 50% of dermatophytes human 50% of dermatophytes human
specificspecific
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Cutaneous InfectionsCutaneous Infections
Cause common tinea (ringworm)Cause common tinea (ringworm) Grow only on humansGrow only on humans Reservoir not in soil or animalsReservoir not in soil or animals Reservoir in carpets and upholstery Reservoir in carpets and upholstery
for up to two yearsfor up to two years
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Cutaneous InfectionsCutaneous Infections
Trichophyton Trichophyton rubrumrubrum
Chronic Chronic infections of the infections of the toe nailstoe nails
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Tinea corporisTinea corporis
Subcutaneous mycoses Subcutaneous infections - over 35 Subcutaneous infections - over 35
species produce chronic inflammatory species produce chronic inflammatory disease of subcutaneous tissues and disease of subcutaneous tissues and lymphatics. e.g. sporotrichosis - lymphatics. e.g. sporotrichosis - ulcerated lesions at site of inoculation ulcerated lesions at site of inoculation followed by multiple nodules - caused by followed by multiple nodules - caused by a dimorphic fungus: a dimorphic fungus: Sporotrix schenckii.
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Cutaneous InfectionsCutaneous Infections
Microsporum canisMicrosporum canis Reservoir in catReservoir in cat May move to humans or dogsMay move to humans or dogs Dies out after one or two person-Dies out after one or two person-
person transfersperson transfers
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Cutaneous InfectionsCutaneous Infections
Disease processDisease process Fungus stimulates epithelial cells of Fungus stimulates epithelial cells of
skin to divide more frequentlyskin to divide more frequently Makes more keratin available to Makes more keratin available to
fungusfungus Some species race specific in Some species race specific in
humanshumans Some species body location specificSome species body location specific
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Cutaneous InfectionsCutaneous Infections
Candida albicans – candidiasis Candida albicans – candidiasis Normal component of gut mycotaNormal component of gut mycota Excessive wetness Excessive wetness overgrowth overgrowth
on skinon skin Vaginal candidiasis common in Vaginal candidiasis common in
pregnant womenpregnant women
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Biology of Biology of Candida Candida albicansalbicans
Commensal Pathogen
A thin-walled dimorphic fungus
MorphogenesisUnicellular yeast (harmeless)Filamentous (pathogenic)
Principal Cell Wall PolymersGluccanMannan
Strict aerobe, favors moist surfacesCommensally found in gut, genitals, and lungsBody Temp 37º C, neutral pH
Figure 1. Yeast in Oral ScrapingA sample of an oral scraping contains yeast cells and pseudohyphae(www.doctorfungus.org)
Rapid Multiplication & Spread
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Diseases by Diseases by C. albicansC. albicans
ThrushThrush
EsophagitisEsophagitis
Cutaneous CandidiasisCutaneous Candidiasis
Genital Yeast InfectionsGenital Yeast Infections
Deep CandidiasisDeep Candidiasis
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Figure 1. Angular chelitis
Figure 2. Oral Thrush, atrophic Figure 3. Oral Thrush, pseudomembranous
Oropharyngeal Thrush
* Pseudomembranous
* Atrophic
* Angular chelitis
Symptoms
Risk FactorsHIV
Treatment: topical antifungals
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Genital Yeast Candidiasis
Symptoms
Risk Factors- disruption of normal microbiota
Treatment- direct genital administration- tablets, suppositories, creams
Figure 1. Vaginal Yeast Culture
Figure 2. Plasma cell balanitis. A band-like infiltrate of plasma cells is in the dermis of the male penis.
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Deep Candidiasis
Figure 1. Four forms of invasive candidiasis (www.doctorfungus.org)
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PathogenesisHost Recognition
Adhesins
EnzymesHydrolases: Phosphoplipases, Lipases, Proteinases
MorphogenesisYeast form to Filamentous hyphae/pseudohyphae
Phenotypic Switching
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Figure 1. skin equivalent before infection
Figure 2. Infection with pathogenic clinical isolate of C. albicans. After 48 h the yeast penetrates the skin equivalent and destroys the tissue
Figure 3. Infection with non-pathogenic C. albicans. This strain is not able to penetrate into the tissue and thus behaves as avirulent as shown in the mouse model of systemic infection.
Virulence assay of different C. albicans strains using the skin equivalent (AST 2000)
(Fraunhofer, 2002)
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MORPHOGENESIS
Figure 2. Morphogenic forms of Candida albicanshttp://cbr-rbc.nrc-cnrc.gc.ca/thomaslab/candida/caindex.html
Figure 1. Morphogenesis.Morphogenesis in C. albicans is a pivotal virulence factor that allowsrapid multiplication andsubsequent disseminationin host tissue.(www.kent.ac.uk)
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Subcutaneous InfectionsSubcutaneous Infections
Fungal ActivityFungal Activity Fungi normally saprobicFungi normally saprobic Introduced through woundsIntroduced through wounds Adapt to the human animal by Adapt to the human animal by
changes inchanges in morphologymorphology physiologyphysiology
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Subcutaneous InfectionsSubcutaneous Infections
ChromoblastosisChromoblastosis Common among barefoot peoples of Common among barefoot peoples of
the tropicsthe tropics Soil hyphomycete speciesSoil hyphomycete species Enters human by thorns or wood Enters human by thorns or wood
sliversslivers Fungus grows Fungus grows host cells respond host cells respond
by rapid cell division by rapid cell division wart-like wart-like growths on feet or legsgrowths on feet or legs
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Subcutaneous InfectionsSubcutaneous Infections
Mycotic MycetomaMycotic Mycetoma Disease of barefoot tropical peopleDisease of barefoot tropical people Entry: wound on footEntry: wound on foot Attacks Attacks various tissuesvarious tissues
Stimulates formation of tumorStimulates formation of tumor Compact fungal colonies form Compact fungal colonies form
within tumorwithin tumor
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Subcutaneous InfectionsSubcutaneous Infections
Skin ruptures Skin ruptures and some and some colonies extrudecolonies extrude
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Systemic MycosesSystemic Mycoses
IntroductionIntroduction Caused by . . . Caused by . . .
Specialized pathogensSpecialized pathogensDimorphicDimorphic
One form outside the hostOne form outside the hostAnother form inside the hostAnother form inside the host
Opportunistic saprobesOpportunistic saprobes
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Systemic MycosesSystemic Mycoses
Dimorphic Pathogen MycosesDimorphic Pathogen Mycoses HistoplasmosisHistoplasmosis
Histoplasma capsulatumHistoplasma capsulatumGrows on bird droppings, chicken Grows on bird droppings, chicken manure, bat guanomanure, bat guano
Conidia inhaled Conidia inhaled primary lung primary lung infection infection almost always fatal almost always fatal until recentlyuntil recently
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Systemic MycosesSystemic Mycoses
Histoplasma Histoplasma capsulatumcapsulatum
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Systemic MycosesSystemic Mycoses
CoddidioidomycosisCoddidioidomycosis Coccidioides immitisCoccidioides immitis Dry, saline soilsDry, saline soils Endemic to SW deserts of North Endemic to SW deserts of North
AmericaAmerica Valley feverValley fever Until recently – almost always fatalUntil recently – almost always fatal
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Systemic MycosesSystemic Mycoses
Infection, disease process, and Infection, disease process, and clinical symptoms similar to clinical symptoms similar to histoplasmosishistoplasmosis
Can be effectively treated with Can be effectively treated with fluconazolefluconazole
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Opportunistic Opportunistic Pathogens/DiseasePathogens/Disease
GeneralGeneral Pathogens all grow well at 37CPathogens all grow well at 37C None cause disease in well individualsNone cause disease in well individuals Require breakdown in resistance Require breakdown in resistance
systemsystem Complication of diabetes, AIDS, Complication of diabetes, AIDS,
advanced cancer, sequel to steroid or advanced cancer, sequel to steroid or antibiotic treatmentsantibiotic treatments
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Opportunistic Opportunistic Pathogens/DiseasePathogens/Disease
ZygomycosisZygomycosis Species of ZygomycotaSpecies of Zygomycota
Rhizopus, Mucor, RhizomucorRhizopus, Mucor, Rhizomucor Rhinocerebral mycosisRhinocerebral mycosis
Spores enter through sinusesSpores enter through sinuses Grows rapidly outward to the eyes Grows rapidly outward to the eyes
and inward towards the brainand inward towards the brain
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Opportunistic Opportunistic Pathogens/DiseasePathogens/Disease
AspergillosisAspergillosis AspergillusAspergillus sp. sp. Bronchiopulmonary aspergillosisBronchiopulmonary aspergillosis
Mucus within the bronchi Mucus within the bronchi severe severe allergic reactionallergic reaction
AspergillomaAspergilloma Forms a mycelia ball in lung cavity Forms a mycelia ball in lung cavity
formed from earlier TBformed from earlier TB
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Opportunistic Opportunistic Pathogens/DiseasePathogens/Disease
Surgical intervention often requiredSurgical intervention often required Invasive aspergillosisInvasive aspergillosis
Severely debilitatedSeverely debilitated Immunosuppressed (AIDS)Immunosuppressed (AIDS)
Almost always fatal until recentlyAlmost always fatal until recently
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AIDS and MycosesAIDS and Mycoses
AspergillosisAspergillosis Candidiases (Candidiasis seen in 2/3 Candidiases (Candidiasis seen in 2/3
of AIDS patientsof AIDS patients CryptococcosisCryptococcosis Zygomycosis Zygomycosis Esophogeal candidiasis and Esophogeal candidiasis and
cryptococcosis are strong indicators cryptococcosis are strong indicators of AIDSof AIDS
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PRIMARY ANTI-FUNGAL PRIMARY ANTI-FUNGAL AGENTSAGENTS
1.1. Polyene derivativesPolyene derivatives Amphotericin BAmphotericin B NystatinNystatin
2.2. AzolesAzoles KetoconazoleKetoconazole FluconazoleFluconazole ItraconazoleItraconazole VoriconazoleVoriconazole
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AzolesAzoles
There are a few rare There are a few rare serious side effects serious side effects from Itraconazole from Itraconazole and Fluconazoleand Fluconazole
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5-5-fluorocytosinefluorocytosine(5-FC)(5-FC)
Interferes With RNA Interferes With RNA SynthesisSynthesis
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MECHANISMS OF ACTIONMECHANISMS OF ACTION
PolyenesPolyenes
AzolesAzoles
GriseofulvinGriseofulvin
5 - FC5 - FC
Ergosterol in cell Ergosterol in cell membranemembrane
Interfere with Interfere with ergosterol synthesisergosterol synthesis
Forms a barrier to Forms a barrier to fungal growthfungal growth
Inhibits RNA Inhibits RNA synthesissynthesis