Objectives By the end of this lecture the student must be: - PowerPoint Presentation

Slide1

Objectives

By the end of this lecture the student must be:

Identify

the

Characters

of

Fungi

describe

the chemical tests for this genus

C) Differentiate between different

sps

.

D) List and match the symptoms, diagnosis and treatment for different

sps

.

Slide2

Medical Mycology

Myco

= Fungi

Ology = ScienceMycology is the science deals with fungiMycoses = Fungal infectionDermatophytosis - "ringworm" disease of the nails, hair, and/or stratum corneum of the skin caused by fungi called dermatophytes Dermatomycosis  - more general name for any skin disease caused by a fungus

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What is the FUNGUS?

Eukaryotic

→

a true nucleus Do not contain chlorophyllOrganoheterotrophicCannot photosynthesize their own foodLive either as saprophytes or parasitesHave chitin cell wallsProduce filamentous structuresReproduce by spores (sexual & asexual)Are aerobic life forms

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What are

Actinomyces

?

True Bacteria (Prokaryotic)Similar to fungi (fungi-like bacteria) WHY?Clinical infection resembles mycosesGrow on mycotic mediaGrow slowly >48 hGross colonies resemble fungi(rough, heaped, short aerial filaments)Resemble mycelia microscopically, with branched mycelia in tissue and smears

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Fungi vs. Bacteria

Fungi

Bacteria

EukaryotesProkaryotesNucleus*ChitinPeptidoglycanCell WallHeterotrophs

Auto- or

Heterotrophs

Nutrition

Sexually & asexually

 Binary fission

Reproduction

Aspergillus

E. coli

Example

Chitin is not found in any other microorganisms

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Slide6

Types of fungi

Multicellular

:

Molds- filamentousPenicillium, AspergillusUnicellular: YeastsCandida, CryptococcusDimorphic FungiDermatophytes, Histoplasma6

Slide7

YEAST

Facultative Anaerobes

Fermentation=ethanol and CO

2Non-filamentous unicellular fungiSpherical or oval

Reproduction by

Fission

or

budding

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DIMORPHIC FUNGI

Growth as a mold or as a yeast

Most pathogenic fungi are dimorphic fungi

At 37o C yeast-like

At 25o

C mold-like

Can also occur with changes in CO

2

Fungi grow differently in tissue vs nature/culture; often dictated by temp

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Slide9

Basic structure of fungi

Hyphae

Main body of most fungi is made up of fine,

Cylindrical, branching threads called hyphaeTubular cell wall filled with cytoplasm & organelles Most hyphae are 2-10 m diameterMyceliaWhen formed of many cells, cellular units connect together (intertwining) to form long filamentousAerial mycelium

Part projects above the surface of medium

Vegetative mycelium

Part penetrate into medium and absorb food

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Basic structure of fungi

Septa

—regular cross-walls formed in hyphae

Septate: Hyphae with septa - orAseptate or coenocytic: Lacking septa except to delimit reproductive structures & aging hyphaePrimary septa: Formed as a process of hyphal extension & generally have a septal pore, which allows for cytoplasmic & organelle movementSecondary or adventitious septa are imperforate, formed to wall off ageing parts of the mycelium

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Reproduction

Propagate via

formation of spores

Sexual and asexual sporesThe shape and type of spores areDifferent from one type of fungi to anotherImportant in the classification & identification of different species of fungi11

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Asexual spore

Conidiospore

Multiple (chains) or single spores formed at the end of an aerial hypha

Not enclosed by a SACAspergillus spp.Penicillium sppConidiophore: filament that forms Conidospore12

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ConidioSpores

Arthrospores

Cells in

hyphae develop thick wall & separate by disarticulationCoccidioides-  genus of dimorphic AscomyceteBlastosporesThickened wallBud from the parent cellCandida, Cryptococcus

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Chlamydospores

Spore contained within hypha

Rounded & Thick cell wall

ChlamydophoresAerial hypha with chlamydosporese.g. Candida albicans14

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Sporangiospore

Spore

contained in a sporangium at the end of a

sporangoiphoreSporangium: A sac or cell containing spores produced asexuallySproangiophore- aerial hypha with sporangiumRhizopus spp

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Sexual spores

Sexual spores - exhibit fusion of nuclei

Ascospore

Formed in sac-like cell (ascus)Often 8 spores formedAscomycetesBasidiospore Produced on a specialized club-shaped structure (basidium)BasidiomycetesZygospore Thick-walled spore formed during sexual reproductionZygomycetes/ Mucor and Rhizopus

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Classification of Fungi

Comprised of 

over 100,000 species

Classified into 4 orders according to the presence or absence of sexual reproductive cycle and the nature of sexual sporesOrders of FungiMyceliumReproduction

Zygomycetes

Non-

septate

Sexual

Ascomycetes

Septate

Sexual

Basidomycetes

Septate

Sexual

Deutromycetes

(Fungi

imperfecti)

Septate

No sexual

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ZYGOMYCETES

Phylum Zygomycota/Sexual/Non-septate

Lower fungi

< 1000 speciesProduce zygospore, or sporangiosporesInclude the common bread molds and other fungi that cause food spoilage Mucor and Rhizopus are most familiar example18

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Ascomycetes

Phylum Ascomycota, Septate/Sexual/Higher fungi

Certain yeasts & some fungi that causes plant disease

Contains more than 30,000 species of unicellular and multi-cellular fungiProduce sexual spores (ascospores)Produce asexual exospores (conidia)Unicellular e.g. Saccharomyces, CandidaMulticellular e.g. Penicillum, Asperigullus, Claviceps, Dermatophytes, Sporothrix schenckii, Histoplasma

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Basidomycetes

Phylum Basidiomycota/Septate/Sexual

Higher Fungi-Over 30,000 different species

Sexual spores borne on clublike stalks (basidia)Mushrooms (Agaricus bisporus, Agaricus campestris) are the most familiar membersAmong Basidiomycota, only Malassezia & Cryptococcus are frequent human pathogens20

Slide21

Septate mycelium:

Deutromycetes

:

Fungi imperfectiSexual life cycle is either unknown or absentReproduce by various types of asexual spores including buddingHave an abundant mycelium at times while at other times they grow as yeast-like cellsIncludes majority of pathogenic to man & animalResemble Ascomycetes in morphologyExamples: Trichophyton, Epidermophyton, Microsporon, Candida, Cryptococcus, Histoplasma21

Slide22

Fungal cell wall composition

Consists of

 80% of polysaccharidesPolysaccharide fibrils provide rigidity/integrity of wall 20% of the wall consists of ProteinsStructural components (Fibrous)Chitin microfibrils Polymers of ß (1-4)-linked N-

acetylglucosamine

Chitosan

(in

Zygomycota

only)

De-acetylated chitin

ß-linked

glucans

Polymers

of

β-1,3-linked glucose residues with short β

-

1,6-linked

side

chains

22

Slide23

Fungal cell wall composition

Matrix components

(Gel-like components) Structural polymers are contained in gel-like matrixMannoproteins Glycoproteins (form matrix throughout wall) (1,3) glucan

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Structure of cell membrane

Semi-permeable

Phospholipid

bilayer Involved in uptake of nutrientsAnchorage for enzymes/proteins, e.g., chitin synthase, glucan synthase, etc.Signal transductionDiffers in that it contains ERGOSTEROL

Site of action for certain antifungal drugs

Human cell doesn't contain

ergosterol

Human cell contains

cholesterol

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Medical Effect of Fungi

I.

Mycotoxicoses:

Mould produces secondary metabolite (MYCOTOXINS) Highly toxic to humans Ingestion of toxic fungi or their metabolitesErgotism is caused by eating bread prepared from rye infected with Claviceps purpureaHistorically, several large scale outbreaks of madness in populations have been attributed to ergotismErgot are -adrenergic blockers inhibits response to adrenaline

vasoconstriction

necrosis



gangaren

Symptoms consisted of inflammation of infected tissue, followed by necrosis and gangrene

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Medical Effect of Fungi

Natural occurrence:

Food products contaminated with

AFLATOXINS include cereal (maize, rice & wheat), oilseeds (groundnut, soybean & cotton), spices (black pepper, coriander & zinger), tree nuts (almonds, and coconut) & milk Physical and chemical properties:Aflatoxins are potent toxic, carcinogenic, mutagenic, immunosuppressive agents, produced as secondary metabolites by Aspergillus flavus and A. parasiticus26

Slide27

Medical Effect of Fungi

II. Hypersensitivity Disease:

Fungal spores are

inhalated They can be an antigenic  elicit immune response  production of Ig or sensitized lymphocyteExample is hypersensitivity pneumonitis27

Slide28

Medical Effect of Fungi

III. Colonization and resultant disease:

They may attack:

Outermost layers of Skin, hair and/or mucous membrane  superficial mycosesEpidermis as well as nail and hair  cutaneous mycosesDermis, subcutaneous tissues, muscle and face  Subcutaneous mycoses The internal organs as the lungs, CNS, bones etc.

 systemic mycoses

Opportunistic

- cause infection only in the

immunocompromised

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Slide29

A.

Superfacial

mycosis

Tinea versicolor (Pityriasis versicolor)Tinea nigraThey are extremely superficial mycosesPrimary Manifestation is pigment change of the skinBoth are named for their respective skin manifestation29

Slide30

Tinea

versicolor

(Pityriasis versicolor)Causative agent: Malassezia globosaLess common-Malassezia furfurLipophilic Yeasts belongs to BasidomycotaNormal flora of skin and scalp  Superficial opportunistic pathogens of the skinAssociated with seborrheic dermatitis, dandruff (Pityriasis capitis) and atopic dermatitisPityriasis versicolor

is chronic superficial mycoses

Characterized by a blotchy discoloration of skin which may itch

With sunlight exposure the skin around patches will tan, but patches remains white

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Slide31

Pityriasis

versicolor

Chronic superficial mycosesCharacterized by hyperpigmented lesions Well-demarcated white, pink, or brownish lesions, often coalescing and covered with thin furfuraceous scalesThe colour varies according to;The normal pigmentation of the patientexposure of the area to sunlightthe severity of the disease.Lesions occur on the trunk, shoulders and arms,Rarely on the neck and faceFluoresce a pale greenish colour under Wood's ultra-violet light.31

Slide32

B. cutaneous Mycoses

Dermatophytes

attack keratinous structure of skin, hair and nail and cause the group of disease known as

Ringworms or TineaCandida can attack the skin, the mucous membranes and rarely the internal organsNon-dermatophyte moulds e.g. Hendrsonula toruloidea, Scytalidium hyalium, Scopulariopsis

brevicaulis

32

Slide33

i

.

Dermatophytes

Confined to the outer layers of skin, hair & nailsDo not invade living tissues Called dermatophytes (keratinophilic fungi) Produce extracellular keratinas  hydrolyze keratinUtilize keratin for their nutritionKeratin is the chief protein in skin, hair and nailThey caused dermatophycosis“Ringworm" or “Tinea"Dermatophycosis refers to the characteristic central clearing that often occurs in dermatophyte infections33

Slide34

I.

dermatophytes

Trichophyton

(19 species)Affect hair, skin & nailsInfect both children & adults EpidermophytonInfect skin, nails (rarely hair)Infect adults, rarely in children (ringworm)Epidermophyton

floccosum

Microsporum

(

13

species)

Affect

hair,

skin (rarely nails)

Frequently

in children, rarely in

adultsM. canis is the most common infect man

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Slide35

Ecology

and Mode of transmission

To determine the source of infection

AnthrophilicSome Dermatophytes affect man onlyPerson -to-person transmission through contaminated objects (comb, hat, etc.)T. rubrum and T. mentagrophytes Zoophilic Other affect animal mainly Direct transmission to humans by close contact with animalsM. canis and T. verrucosum

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Slide36

Ecology and Mode of transmission

Geophilic

Other live in soil and can affect man

Transmitted to humans by direct exposureM. gypseumEach geographic locality has its own dermatophytonT. violacium is the prevalent causative organism of Tinea capitis in EgyptM. audouini is prevalent cause in England36

Slide37

Tinea

corporis

Small lesions occurring anywhere on the bodyCausative agent: Trichophyton rubrum, T. mentagrophytes, M. canis, and  M. audouinii Live on the skin surface (opportunistic)Reservoir: Humans, soil & animals

Acquired by person-to-person transfer usually via direct skin contact

with

infected individual

Animal-to-human

transmission is

common

37

Slide38

Tinea

pedis

"athlete's foot"Infection of toe webs and soles of feetCausative agent: Trichophyton rubrum, T. mentagrophytes and Epidermophyton floccosumRequires warmth and moisture to survive and growCauses

scaling, flaking & itch of affected areas

Reservoirs:

Humans

Athlete's

foot is a communicable

disease

Transmission:

when

people who regularly wear shoes go 

barefoot in

a moist

environment38

Slide39

Tinea

capitis

Infection of the scalpCausative agent: Trichophyton and Microsporum invade the hair shaftTrichophyton  infection prevail in Central America to USA & in parts of Western EuropeMicrosporum infection are in South America, Southern & Central Europe, Africa & Middle EastReservoirs: Humans & animals (dogs, cats and cattle)

Transmitted

by humans,

animals or

objects that harbor

the fungus

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Slide40

Dermatophytes

Tinea

cruris - "jock itch" Infection of the groin, perineum or perianal areaTrichophyton rubrumSome other contributing fungi are Candida albicans, T. mentagrophytes and Epidermophyton floccosum.

Tinea

barbae

Ringworm

of the bearded areas of the face and

neck

 

Trichophyton

mentagrophytes

 and T. verrucosum

40

Slide41

Dermatophytes

Tinea unguium (onychomycosis)

Infection of nails

Common - Trichophyton rubrumLess common- T. interdigitale, Epidermophyton floccosum, T. violaceum, Microsporum gypseum, T. tonsurans, T. soudanenseReservoirs: Humans and rarely animals or soil

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Treatment of

Dermatophytes

All

are sensitive to grisofulvinTolfnatate available over the counter – TopicalTerbinifine (Lamisil) - oral, topical.  Ketoconazole seems to be most effective for tinea versicolor and other dermatophytes Itraconazole - oral Echinocandins (caspofungin)

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Lab diagnosis of

Dermatophytes

Specimen collection

Skin Scrapings, nail scrapings and epilated hairsDirect MicroscopySpecimens should be examined using 10% KOH and Parker ink or calcofluor white mountsCharacteristic hyphae can be seen 43

Slide44

Lab diagnosis of

Dermatophytes

Culture

Specimens should be inoculated onto Sabouraud's dextrose agar (General purpose)Selective – Mycosel agarGentamicin: inhibits normal bacterial floraCycloheximide: inhibits saprophytic fungicontaining cycloheximide and incubated at 250C for 4 weeksThe growth of any dermatophyte is significant44

Slide45

II. Candida

Yeast-like organism that lives as a commensal in oral mucosa,

throat, skin, scalp, vagina, fingers, nails, bronchi, lungs, or

intestine and vagina Opportunistic organismThe causative agent of candidiasisC. albicans, C. tropicalis & C. glabrataCandidiasis encompasses infections that range from superficial such as thrush and vaginitisRarely become systemic in immunocompromised patientsSepticaemia, endocarditis and meningitis

45

Slide46

Symptoms of Candida

albicans

Thrush

appears as creamy-white or bluish-white patches on the tongue - which is inflamed and sometimes-beefy red - and on the lining of the mouth, or in the throat. Diaper rash caused by candida is an inflammation of the skin, usually red and sometimes scaly. Vaginitis is characterized by a white or yellow discharge. Inflammation of the walls of vagina and of the vulva (external genital area) causes burning and itching.Infections of the fingernails and toenails appear as red, painful swelling around the nail. Later, pus may develop.

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Laboratory diagnosis of candida

Specimen:

A scraping or swab of the affected area or blood (candidemia) is placed on a microscope slide

Microscopic examination A drop of 10% KOH solution is added to the specimen.KOH dissolves the skin cells, but leaves  Candida intact, permitting visualization of pseudohyphae and budding yeast cells typical of many Candida species.CultureSwab/blood is streaked on a culture SDA mediumThe culture is incubated at 37°C for several daysThe characteristics of colonies may allow initial diagnosis of organism causing disease symptom47

Slide48

Laboratory diagnosis of candida

A germ tube test

 is a diagnostic test in which a sample of fungal spores are suspended in serum and examined by microscopy for the detection of any germ tubes

It is particularly indicated for colonies of white or cream color on fungal culture, where a positive germ tube test is strongly indicative of Candida albicans48

Slide49

Treatment of candidacies

Oral drugs: Amphotericin B, fluconazole, and ketoconazole, are the drugs most commonly used to treat candidiasis

Topical administration of antifungal drugs such as clotrimazole, miconazole , tioconazole, and nystatin

The drug of choice is nystatin49

Slide50

c. Subcutaneous

Mycoses

Rare

Confined to subcutaneous tissue & rarely spread systemicallyConfined mainly to tropical regionsInclude heterogeneous group of soil fungal infections Introduced into the extremities by trauma/woundTend to be slow in onset and chronic in durationThe main subcutaneous fungal infections includeSporotrichosis, chromoblastomycosis, MYCETOMA, lobomycosis, rhinosporidiosis, subcutaneous zygomycosis, & subcutaneous phaeohyphomycosis

50

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C. Subcutaneous Mycoses

Sporotrichosis

caused by Sporothrix schenckiiThe fungus is saprophyte on dead plant materialDimorphic fungiColonies of media at 250C have delicate radiating forms that appear as white at first but turned black with prolonged incubationMicroscopic examination reveals branched hyphae with numerous conidia51

Slide52

Sporotrichosis

It was once common in Europe but cases are now rare

Most prevalent in Americas, South Africa & Australia

Infection usually follows and insect bite, thorn pricks or scratches from a fish spine. Certain occupation groups appear to have increased risk from infection These include florists, farm workers and others who handle hay and moss The most common symptom is an ulcerative lesion that may develop into lymphangitisTreated by saturated solution of KI and Amphotericin B52

Slide53

2.

Chromoblastomycosis

Chronic, localized, slowly progressive infection of the subcutaneous tissue caused by several species of dematiaceous fungiTissue proliferation occurs around the area of inoculation producing crusted, verrucose, wart-like lesionsCausative agentMost common: Cladophialophora carrionii & Fonsecaea pedrosoiLess common: Fonsecaea compactum, Phialophora verrucosa

53

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Chromoblastomycosis

Mode of Transmission

Traumatic implantation of fungal elements into skin

The infection occurs in tropical or subtropical climates, often in rural areas.TraetmentChromoblastomycosis treated by surgical removal and 5-flurocytosine 54

Slide55

Mycetoma

Also called

Maduromycosis or Madura footMadura foot referring to first case seen in Madura region of India which was in the foot of patient Syndrome involving cutaneous & subcutaneous tissues, fascia, and boneInfection focused in one area of the body (Foot)Distribution: World-wide but most common in bare-footed populations in tropical sub- or regionsCharacterized by draining sinuses, granules (vary in size, colour & degree of hardness) & tumefaction

55

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Mycetoma

Mode of transmission

Traumatic implantation of causative agent

Causative agent (50% bacteria & 50% fungi)Soil-inhabiting bacteria (actinomycotic mycetoma or actinomycosis)Actinomadura madurae, Actinomyces israelii and Nocardia brasiliensisSoil-inhabiting fungi (eumycetoma)Madurella mycetomatis & Madurella grisea56

Slide57

Treatment

Treatment for

eumycetoma

is less successful than for actinomycetomaEUMYCETOMAsurgical treatment is still usually requiredKetoconazole 400mg daily, itraconazole 300 mg daily & IV amphotericin B 50 mg dailyTherapy is suggested for 1-2 yearsFlucytosine, Topical nystatin & potassium iodideACTINOMYCOTIC MYCETOMA

Penicillin, gentamicin & co-

trimoxazole

for 5 weeks

Followed by maintenance therapy with amoxicillin & co-

trimoxazole

57

Slide58

Systemic Mycoses

Invasive infections of the internal organs with the organism gaining entry by;

Lungs, GIT or through intravenous lines

They may be caused by: Primary (TRUE) pathogenic fungiOpportunistic fungi that are of marginal pathogenicity but can infect the immunocompromised host58

Slide59

I. Primary Pathogenic Fungi

Histoplasma capsulatum

(Histoplasmosis )

Blastomyces dermatidis (Blastomycosis )Coccidioides immitis (Coccidiomycosis)Paracoccidioides brasiliensis (paracoccidioidomycosis)Dimorphic fungi normally found in soilInfection occurs in previously healthy personsArises through the respiratory route (inhalation)59

Slide60

Histoplasmosis

Caused by dimorphic

Histoplasma capsulatum

H. capsulatum is endemic in many parts of the world including North and South AmericaIt is found in the soil and growth is enhanced by the presence of bird and bat excretaEnvironments containing such material are often implicated as sources of human infection 60

Slide61

Histoplasmosis

Lungs are the main site of infection but dissemination to liver, heart & CNS can occur.

Pulmonary infection can resemble symptoms seen in tuberculosis

Treatment:Amphotericin BKetoconazole and other new azoles 61

Slide62

II. Opportunistic Fungi

Patients usually have some serious immune or metabolic defect, or have undergone surgery

The diseases include aspergillosis, systemic

Candidiasis, cryptococcosis, Zygomycosis, Pneumocystis cariniiExceptionally, other fungi that are normally not pathogenic, such as Trichosporon, Fusarium or Penicillium, may cause systemic infections. 62

Slide63

Cryptococcosis

Systemic infection caused by encapsulated yeast -

Cryptococcus neoformans

Inhabits soil around pigeon roosts Host defense is CMIAffects both healthy & immunosuppressed individualsCommon infection of AIDS, cancer or diabeticPrimary infection in lungs via inhalationPulmonary infection leads to cough, fever & lung nodulesPolysaccharide capsule resists phagocytosisCryptococcal meningitis is most common disseminated manifestationCan spread to skin, bone and prostate

63

Slide64

Cryptococcosis

Lab. Diagnosis

Lumbar puncture and microscopic examination of cerebrospinal fluid is diagnostic

India Ink for CSF Culture on SDAWhite mucoid colonies within 48hoursCryptococcal antigenSerum and CSF are 99% sensitive in AIDSSerum is less sensitive in normal hostsTreatmentAmphotericin B and fluconazole

64

Slide65

Aspergillosis

Aspergillus

is found in soil, on plants & in decaying organic matter.

600 species, A. fumigatus is one of the most ubiquitous of the airborne saprophytic fungiA. fumigatus is the main causative agent of AspergillosisDiseases of the soil fungus called AspergillusMajor portal of entry is the respiratory tractVia inhalation of conidiaConidia are eliminated in immunocompetent host by innate immune mechanismFor people with weakened immune systems, breathing in conidia can lead to infection65

Slide66

Aspergillosis

Most commonly affects the sinuses or lungs

Symptoms of sinus infections include fever, headache, and sinus pain

Lung infections can cause fever and coughIn the immunosuppressed host, Aspergillus can disseminate throughout the body.TreatmentAmphotericin B and nystatinVoriconazole is currently the first-line treatment for invasive aspergillosis 66

Slide67

Candidiasis

In severely immunocompromised patients,

C. albicans

can proliferate and disseminate throughout the body.An infection in the bloodstream can affect the kidneys, heart, lungs, eyes, or other organs causing high fever, chills, anemia, and sometimes a rash or shock 67

Slide68

Symptoms of Candida

albicans

Candida can cause the following problems depending upon the organ infected:

in kidneys can cause blood in the urine in heart can cause murmurs & valve damage in the lungs can cause bloody sputumin the eyes can cause pain and blurred vision in the brain can cause seizures and acute changes in mental function or behavior68