MEDICALLY IMPORTANT FUNGI

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MEDICALLY IMPORTANT FUNGI

• DR. BREIDA BOYLE

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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

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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

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PATHOGENIC FUNGI
TRUE PATHOGENS
OPPORTUNISTIC PATHOGENS
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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
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OPPORTUNISTIC PATHOGENS
Absidia corymbifera Aspergillus fumigatus Candida
albicans Crytococcus neoformans Pneumocystis
carinii Rhizomucor pusillus Rhizopus oryzae
(R.arrhizus)
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CLASSIFICATION OF FUNGI

• Depends on
• Characteristic Structures
• Habitats
• Modes of Growth
• Modes of Reproduction

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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

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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

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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

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MODES OF FUNGAL GROWTH
UNICELLULAR YEASTS
FILAMENTOUS MOLDS
However there are some dimorphic fungi ( they
switch between these Two forms depending on
their environment)
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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

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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

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REPRODUCTION
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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

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ASEXUAL SPORULATION
(MITOSIS)
Colour of a particular fungus seen on bread,
culture plate is due to the Conidia, easly
airborne and disseminated
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SEXUAL SPORULATION
meiosis
Relatively rare compared to asexual sporulation,
and spore shape often Used as a method of
identification
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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Eastern US
Males
Diagram of Systemis mycoses(dimorphic, yeast in
infective tissue)
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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

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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

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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
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OPPORTUNISTIC PATHOGENS
Absidia corymbifera Aspergillus fumigatus Candida
albicans Crytococcus neoformans Pneumocystis
carinii Rhizomucor pusillus Rhizopus oryzae
(R.arrhizus)
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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

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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

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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

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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

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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

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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

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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

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PNEUMOCYSTIS CARINIIPNEUMONIA

• 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

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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

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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

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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

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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

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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

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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

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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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