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MEDICALLY IMPORTANT FUNGI

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MEDICALLY IMPORTANT FUNGI DR. BREIDA BOYLE INTRODUCTION Fungi are a diverse group of sacrophytic and parasitic eukaryotic organisms Kingdom: Mycota Of 100,000 fungal ... – PowerPoint PPT presentation

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Title: MEDICALLY IMPORTANT FUNGI


1
MEDICALLY IMPORTANT FUNGI
  • DR. BREIDA BOYLE

2
INTRODUCTION
  • Fungi are a diverse group of sacrophytic and
    parasitic eukaryotic organisms
  • Kingdom Mycota
  • Of 100,000 fungal species only 100 have
    pathogenic potential for humans, only a few
    account for clinically important infections
  • Mycoses Human Fungal Diseases
  • Fungal spores may be important as human
    allergenic agents

3
INTRODUCTION
  • MYCOSES
  • CUTANEOUS limited to the dermis
  • SUBCUTANEOUS when infection penetrates
    significantly beneath the skin
  • SYSTEMIC when the infection is deep within the
    body or disseminated to internal organs

4
PATHOGENIC FUNGI
TRUE PATHOGENS
OPPORTUNISTIC PATHOGENS
5
TRUE PATHOGENS
Cutaneous infective agents
Subcutaneous infective agents
Actinomadura madurae Cladosporium Madurella
grisea Phialophora Sporothrix schenckii
Epidermophyton species Microsporum
species Trichophyton species
Systemic infective agents
Blastomyces dermatitidis Coccidioides
immitis Histoplasma capsulatum Paracoccidioides
brasiliensis
6
OPPORTUNISTIC PATHOGENS
Absidia corymbifera Aspergillus fumigatus Candida
albicans Crytococcus neoformans Pneumocystis
carinii Rhizomucor pusillus Rhizopus oryzae
(R.arrhizus)
7
CLASSIFICATION OF FUNGI
  • Depends on
  • Characteristic Structures
  • Habitats
  • Modes of Growth
  • Modes of Reproduction

8
Cell Wall and Membrane
  • Composed mainly of chitin rather than
    peptidoglycan (bacteria)-so unaffected by
    antibiotics
  • Chitin consists of a polymer of
    N-acetylglucosamine
  • Fungal Membrane contains ergosterol rather than
    cholesterol found in mammalian cells, use in
    antifungal agents such as amphotericin which
    binds to ergosterol?pores that disrupts membrane
    function ?cell death

9
Cell Membrane
  • The imidazole antifungal drugs
    ( clotrimazole, ketoconazole, miconazole) and the
    triazole antifungal agents (fluconazole ,
    itraconazole) interact with the C-14
    a-demethylase to block demethylation of lansterol
    to ergosterol, vital component of cell membrane
    and disruption of its synthesis results in death

10
HABITAT
  • All fungi are heterotrophs ( their require some
    form of organic carbon for growth)
  • They depend on transport of soluble nutrients
    across their cell membrane
  • To do this they secrete degradative enzymes (
    proteases etc) into their immediate environment,
    therefore they live on dead organic material
  • So Natural Habitat is soil or water containing
    decaying organic matter

11
MODES OF FUNGAL GROWTH
UNICELLULAR YEASTS
FILAMENTOUS MOLDS
However there are some dimorphic fungi ( they
switch between these Two forms depending on
their environment)
12
Filamentous (mold-like) Fungi
  • Thallus (vegetitive body) mass of threads with
    many branches resembling cotton ball
  • Mass mycelium
  • Threads hyphae, tubular cells that in some fungi
    are divided into segments septate whereas in
    other fungi the hyphae are uninterrupted by
    crosswalls-nonseptate
  • Grow by branching and tip elongation

13
YEAST like FUNGI
  • These fungi exist as populations of single ,
    unconnected , spheroid cells, not unlike many
    bacteria, although they are sometimes 10 times
    larger than a typical bacterial cell
  • Yeasts reproduce by budding
  • Some fungal species particularly those that cause
    systemic infection exist as dimorphic fungi

14
REPRODUCTION
15
SPORULATION
  • The principle way in which fungi reproduce and
    spread within the environment
  • Fungal spores are metabolically dormant,
    protected cells, released by the mycelium in
    enormous numbers
  • Borne by the air or water to new sites , where
    they germinate and establish new colonies
  • Spores can be generate sexually or asexually

16
ASEXUAL SPORULATION
(MITOSIS)
Colour of a particular fungus seen on bread,
culture plate is due to the Conidia, easly
airborne and disseminated
17
SEXUAL SPORULATION
meiosis
Relatively rare compared to asexual sporulation,
and spore shape often Used as a method of
identification
18
CUTANEOUS MYCOSES -DERMATOPHYTOSES
  • EPIDEMIOLOGY
  • Three genera-Trichophyton, Epidermophyton,
    Microsporum
  • Anthropophilic-reside on the human skin
  • Zoophilic-reside on the skin of domestic and farm
    animals
  • Geophilic-reside in the soil
  • Transmission from humans or animals is by
    infected skin scales

19
PATHOLOGY
  • Dermatophytes use keratin as a source of
    nutrition
  • Therefore they infect skin, hair, nails
  • All 3 organisms infect attack skin, Microsporum
    does not infect nails and Epidermophyton does not
    infect hair, they not invade underlying
    non-keratinized tissues

20
CLINICAL SIGNIFICANCE
  • DERMATOPHYTOSES
  • Characterized by itching,scaling skin patches
    that can become inflamed and weeping
  • Infection in different sites may be due to
    different organisms but is given one name

21
Tinea pedis(Athletes foot)
  • Common organisms are Trichophyton rubrum ,
    Trichophyton mentagrophytes and Epidermophyton
    floccosum.
  • Initially between the toes spreads to nails,
    yellow and brittle
  • Secondary bacterial infection
  • Id Reaction

22
Tinea corporis( Ringworm)
  • Epidermophyton floccosum, Trichophyton,
    Microsporum
  • Advancing annular rings with scaly center
  • Periphery of ring area of active fungal growth,
    usually inflammed and vesiculated
  • Non-Hairy areas of trunks mostly

23
Tinea capitis( scalp ringworm)
  • Trichophyton and Microsporum
  • Depends on area
  • Small scaling patches to involvement of entire
    hair with hairloss
  • Microsporum infects hair shafts , Woods lamp

24
TINEA CRURIS/UNGUIUM
  • Epidermophyton , Trichophyton rubrum, simliar to
    ringworm but thighs and genitalia
  • Trichophyton rubrum, nails thickened discoloured
    and brittle
  • Treatment for months until all of the infected
    nail grows out and is trimmed off

25
Treatment
  • Samples to be sent for fungal staining and
    culture
  • Infected skin may be treated with topical
    application of antifungal agents miconazole and
    clotrimazole
  • Refractory lesions oral griseofulvin and
    itraconazole, terbinafine
  • Infections of hair and nails usually require
    systemic ( oral) therapy

26
SUBCUTANEOUS MYCOSES( dermis, subc tissues and
Bone)
  • Causative organisms reside in the soil and in
    decaying or live vegetation
  • Almost always acquired through traumatic
    lacerations or puncture wounds
  • Common among those who work with soil and
    vegetation and have little protective clothing
  • Not usually transmitted humans to humans
  • Usually confined to tropics and subtropics with
    exception of Sporotrichosis in USA

27
Sporotrichosis
  • Sporothrix schenckii-dimorphic fungus
  • Granauloma ulcer at a puncture skin usually a
    thorn prick and may produce secondary lesions
    along draining lymphatics
  • In most disease is self-limiting may exist in
    chronic form
  • Treatment oral itraconazole
  • Chromomycosis Phialophora or Cladosporium

28
Mycetoma
  • Madurella grisea, Actinomadura madura
  • Localized abscess usually on the feet, that
    discharge pus serum and blood
  • Has coloured grains( compact hyphae) black,
    white, red or yellow depending on organism

29
Eastern US
Males
Diagram of Systemis mycoses(dimorphic, yeast in
infective tissue)
30
Clinical significance
  • Simliar to Tb in that asymtomatic primary
    infection is seen whereas chronic pulmonary or
    disseminated infection rare
  • In the immunocompetent usually mild and self
    limiting
  • In the immunocompromised the same infections can
    be life threatening

31
Coccidiodomycosis
  • Coccidioides immitis
  • Most in arid areas of south-western US
  • In the soil forms arthrospores
  • Spores airborne , germinate in the lungs and
    produce sphercules filled with many endospores-
    new spherule
  • In disseminated cases lesions in the bone or CNS
    -meningitis

32
Histoplasmosis
  • Histoplasma capsulatum
  • In the soil conidia, germinate lungs into
    yeast-like cells
  • Becomes engulfed by macrophages and XX
  • Benign self-limiting or chronic, progressive ,
    fatal
  • Disseminated disease only fungus intracellular
    RES parasitism
  • Area Ohio and Mississippi River area
  • DX Culture or Exoantigen (immunodiffusion assay)

AIDS patients at particular risk Treatment
Amphotericin or Itraconazole
33
OPPORTUNISTIC PATHOGENS
Absidia corymbifera Aspergillus fumigatus Candida
albicans Crytococcus neoformans Pneumocystis
carinii Rhizomucor pusillus Rhizopus oryzae
(R.arrhizus)
34
OPPORTUNISTIC MYCOSES
  • Those that affect the immunocompromised but are
    rare in normal individual
  • Organ transplantation, post chemotherapy for
    cancer, immunodeficient due to Aids and
    congenital immunodeficiency states
  • Candida species most commonly occurring fungal
    pathogen in the ICU setting

35
CANDIDIASIS(candidiosis)
  • Candida albicans and other candida species which
    are normal flora in the mouth, skin , vagina and
    intestines
  • C.albicans is dimorphic
  • May occur as a results of overgrowth as
    suppression of bacteria by antibiotics
  • Manifestations depend on the site e.g. oral
    candidiasis and vaginal candidiasis and
    disseminated candidiasis in cancer patients, post
    GI surgery and ABs, systemic corticosteroids

36
CRYTOCOCCOSIS
  • Crytococcus neoformans, found worldwide
  • Especially found in soil containing bird(esp.
    pigeons) droppings
  • Characteristic thick capsule that surrounds
    budding yeast cell seen Indian Ink
  • Most common form is mild subclinical lung
    infection
  • In the immunocompromised often disseminates to
    the brain , meningitis often fatal
  • However half those with crytococcal meningitis
    have no obvious immune deficiency

37
ASPERGILLOSIS
  • Several species of genus Aspergillus, mostly
    Aspergillus fumigatus
  • Worldwide distribution, ubiquitous
  • Filamentous molds, produce large numbers of
    conidiospores
  • Reside in soil, decomposing organic matter and
    dust, associated outbreks with construction work
  • Disease presentation depends on immunologic
    status of patient

38
ASPERGILLOSIS
  • Acute Aspergillus infections
  • Most severe and often fatal form of aspergillosis
    is acute invasive infection of the
    lung?dissemination to brain etc
  • Less severe form gives rise to a fungus ball(
    aspergilloma) , a mass of hyphal tissue that
    forms in lung cavities derived from prior disease

39
Allergic Aspergillosis
  • Relatively rare, can arise from inhalation of
    spores, without sussequent extensive spore
    germination hyphal invasion
  • The allergic reaction results in bronchial
    constriction
  • Diagnosis by immunoelectrophoresis

40
MUCORMYCOSIS
  • Most often caused by Rhizopus oryzae and less
    often by other members of the Mucorales such as
    Absidia corymbifera, Rhizopus pus
  • Ubiquitous in nature, spores found in great
    abdunance on rotting fruit and old bread
  • Usually restricted to those with underlying
    conditions such as burns, leukaemia or diabetus
    mellitus
  • The most common form of the disease can be fatal
    within a week-Rhino cerebral Mucormycosis

41
PNEUMOCYSTIS CARINII PNEUMONIA
  • Caused by a unicellular eukaryote, Pneumocystis
    carinii
  • Before the use of immunosuppressive agents and
    the onset of the AIDS epidemic , PCP was a rare
    disease
  • It is one of the most common opportunisitic
    diseasesof individuals treated with HIV-1 and
    usually fatal if untreated
  • It does not contain ergosterol and has not been
    cultured

42
PCP
  • Various cellular forms encysted group of dormant
    cells and vegetitive form trophozoite
  • Ubiquitous
  • Activation of preexisting dormant cells in the
    lungs in immunodeficient persons
  • The encysted forms induce an inflammination of
    the alveoli-exudate which blocks gas exchange
  • Diagnosis by microscopic examination , by silver
    stain or fluorescence of bronchial washings or
    biopsy

43
LABORATORY IDENTIFICATION
  • Standard media Sabourauds agar, potato dextrose
    agar, low ph 5.0 , inhibits bacterial growth but
    allows fungal colonies to form
  • Cultures can be started from spores or hyphae
    fragments
  • Specimens blood, pus, CSF, sputum, tissue
    biopsies, skin scrapings , nail clippings
  • Identification by the morphology of conidia
    structures and carbonhydrate assimiliation tests

44
LABORATORY DIAGNOSIS OF FUNGAL INFECTION
  • Specimens
  • Depends on site of infection
  • Systemic -Blood culture( really only useful for
    yeast-low sensitivity) or
  • - antigen testing
    e.g.crytococcal
    and histoplamsosis antigen
  • Pneumonia Bronchoscopy washings or brushings for
    staining and fungal culture or bronchial biopsy

45
LABORATORY DIAGNOSIS OF FUNGAL INFECTIONS
  • Meningitis Cerebrospinal fluid for methylene
    blue staining and indian ink and crytococcal
    antigen and fungal culture
  • If Skin infection require skin scrapings
  • If nail infection require nail clippings
  • Galactomannan antigen testing for aspergillus
    infection

46
LABORATORY DIAGNOSIS FUNGAL INFECTIONS
  • Types of tests carried out
  • Fungal Staining methylene blue staining or wet
    prep using KOH to dissolve tissue material
  • Fungal culture on media that encourages fungal
    growth e.g. PDA
  • Antigen Testing i.e. to test for antigen present
    in the wall of fungus e.g crytococcal antigen,
    galactomannan used in serum and CSF samples
  • PCR not used on a routine basis on samples

47
MANAGEMENT OF FUNGAL INFECTIONS
  • Some such as superfical skin infections require
    topical therapy only with cream e.g.nystatin
    cream
  • Some require local therpy e.g. pessaries for
    vaginal candidasis
  • Some require oral therapy for skin and nail
    infections up to 1 year e.g. terbinafine
  • In the immunocompromised systemic therapy
    required e.g. , voriconazole,fluconazole i./v or
    amphotericin

48
MANAGEMENT OF FUNGAL INFECTIONS
  • Important to diagnose fungal infections early in
    the immunocompromised as there is a high
    mortality associated with infection
  • Empirical therapy often started in advance of
    laboratory diagnosis in these patients

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