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SYSTEMIC MYCOSIS. III MBBS. Systemic Mycosis. Fungal infection of internal organs. Primarily involve the respiratory system. Infection occurs by inhalation of air- borne conidia. More than 95% are self limiting & asymptomatic. Rest are symptomatic & disseminate by hematogenous route.

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Systemic mycosis

SYSTEMIC MYCOSIS

III MBBS

Dr Ekta, Microbiology, GMCA


Systemic mycosis1
Systemic Mycosis

  • Fungal infection of internal organs.

  • Primarily involve the respiratory system.

  • Infection occurs by inhalation of air- borne conidia.

  • More than 95% are self limiting & asymptomatic.

  • Rest are symptomatic & disseminate by hematogenous route.

Dr Ekta, Microbiology, GMCA


Systemic mycosis2
Systemic Mycosis

  • Caused by dimorphic fungi which infect healthy & immunocompetent individuals.

  • Other systemic infections found in immunocompromised patients are called as opportunistic mycotic infections.

  • Includes :

    Histoplasma capsulatum

    Blastomyces dermatitidis

    Coccidioides immitis

    Paracoccidioides brasiliensis

Dr Ekta, Microbiology, GMCA


Histoplasmosis
HISTOPLASMOSIS

  • Intracellular infection of the RES caused by Histoplasma capsulatum. Endemic in parts of USA

  • Also called Darling’s disease; 1st described by Samuel Darling.

    “histio” within histiocytes

    “plasma” resembled plasmodium.

  • Present in soil, rotting areas and in feces of chicken, bats & other birds. (high N2 content)

Dr Ekta, Microbiology, GMCA


Pathogenesis pathology
Pathogenesis & Pathology

Inhalation of conidia or mycelial fragments

Converted into yeast in alveolar macrophages

Localized granulomatous inflammation

Granuloma with or assist in

without caseation dissemination to RES

  • Involves all phagocytic cells of RES, cytoplasm being studded with fungal cells.

Dr Ekta, Microbiology, GMCA


Clinical features
Clinical features

  • Resembles TB – mainly asymptomatic

  • Clinical types –

  • Pulmonary

  • Cutaneous & mucocutaneous

  • Disseminated histoplasmosis – commonly seen in children below 2 yrs & adolescents

    - individuals with HIV are at a greater risk.

Dr Ekta, Microbiology, GMCA


Laboratory diagnosis
Laboratory Diagnosis

Specimen – sputum, BM, LNs, scrapings from lesions, biopsy & peripheral blood.

Direct Examination

  • Blood smear – Giemsa or Wright stains.

    - small, oval yeast like cells, 2-4µ within mononuclear or polymorphonuclear cells, narrow neck budding.

  • Fluorescent Ab technique.

Dr Ekta, Microbiology, GMCA


Fungal culture
Fungal Culture

  • SDA , BHI at 25° & 37°C.

  • LPCB - White cottony mycelia with large (8-20µ) thick walled, spherical spores with tubercles or finger

    like projections –

    Tuberculate

    Macroconidia.

Dr Ekta, Microbiology, GMCA


Immunodiagnosis
Immunodiagnosis

  • Histoplasmin skin test – I.D. test with 0.1 ml histoplasmin Ag – DTH response.

  • Serological tests – LPA

    * titer of 1:32 or higher or 4-fold increase in titer of Abs is significant.

Dr Ekta, Microbiology, GMCA


Treatment prophylaxis
Treatment & Prophylaxis

  • Amphotericin B – disseminated & other severe forms.

  • Oral Itraconazole

  • Regular cleaning of farm buildings, chicken houses for prevention.

Dr Ekta, Microbiology, GMCA


Blastomycosis
BLASTOMYCOSIS

  • Also called as Gilchrist’s disease or Chicagodisease due to its endemicity in N.America (N.American blastomycosis)

  • Caused by Inhalation of the spores of Blastomyces dermatitidis

  • Causes suppurative & granulomatous infection

Dr Ekta, Microbiology, GMCA


Clinical features1
Clinical features

  • 1° infection resembles TB or histoplasmosis.

  • Clinical types:

  • Pulmonary

  • Cutaneous – commonest form, hence the name “dermatitidis”.

    - seen over exposed parts like face, neck & hands.

  • Disseminated type – form multiple abscesses in different parts like bone, genitourinary system, breast etc

Dr Ekta, Microbiology, GMCA


Laboratory diagnosis1
Laboratory Diagnosis

Specimen – sputum, BAL, biopsy or pus

from abscesses, urine.

Direct Examination

  • Wet mount – KOH, CFW : double contoured, thick walled,

    multinucleate giant

    yeast cells with

    broad base budding

    daughter cells.

Dr Ekta, Microbiology, GMCA


Fungal culture1
Fungal Culture

  • Very slow growth – 2 to 4 weeks.

  • Tissue & cultures at 37°C shows budding yeast cells.

  • At 25°C - fine, branched septate hypha with conidia measuring 2-10µ located on short terminal or lateral branches.

Dr Ekta, Microbiology, GMCA


Diagnosis
Diagnosis

  • Immunodiffusion precipitation bands.

  • EIA / RIA

  • Skin test using blastomycin

    Treatment & Prophylaxis

  • Initial phase - Oral Ketoconazole & Itraconazole

  • Life threatening infections - AMB

Dr Ekta, Microbiology, GMCA


Coccidioidomycosis
COCCIDIOIDOMYCOSIS

  • Infection of the respiratory system caused by Coccidioides immitis.

  • Most virulent of all the fungal pathogens but not contagious.

  • More prevalent in western hemisphere.

  • Fungus present in soil & in rodents.

  • Infection occurs by

    - inhalation of arthroconidia or

    - reactivation of latent infection in immunocompromised patients.

Dr Ekta, Microbiology, GMCA


Clinical features2
Clinical features

  • Many develop influenza like fever – Valley fever or Desert Rheumatism

  • < 1% develop chronic progression disseminated disease –

    - skin (commonest) : granuloma, cold abscess.

    - osteomyelitis & synovitis

    - CNS (meningitis)

Dr Ekta, Microbiology, GMCA


Laboratory diagnosis2
Laboratory Diagnosis

Specimen – sputum, gastric contents, CSF,

exudate or pus.

Direct Examination

  • Presence of doubly refractile thick walled globular spherules

    (30-60µ in dia)

    filled with endospores

  • Tissue – HE, PAS & GMS

Dr Ekta, Microbiology, GMCA


Fungal culture2
Fungal Culture

  • Different from other dimorphic fungi – grows as mold at 25° & 37°C under standard conditions.

  • Growth in 3 - 5 days at 25°C

  • LPCB of culture shows branching septate hypha & chains of thick walled rectangular arthroconidia.

  • Arthroconidia are mature

    infectious propagules

    that develop from

    alternate cells on hypha.

Dr Ekta, Microbiology, GMCA


Immunodiagnosis1
Immunodiagnosis

  • Skin tests – I.D. inoculation of coccidioidin: positive is >5mm in 24-48 hours.

  • Serology – detection of Abs

    Treatment & Prophylaxis

  • Rapidly progressive disease – AMB

  • Chronic, mild to moderate - azoles

Dr Ekta, Microbiology, GMCA


Paracoccidioidomycosis
PARACOCCIDIOIDOMYCOSIS

  • Acute or chronic, granulomatous infection

  • primarily of lungs &

  • disseminates to skin, mucosa, LNs & other internal organs.

  • Caused by Paracoccidioides brasiliensis.

  • Confined to S.America (S.American blastomycosis).

Dr Ekta, Microbiology, GMCA


Laboratory diagnosis3
Laboratory Diagnosis

Specimen – sputum, BAL, pus & crusts from granulomatous lesions, biopsy

Direct Examination

Wet mount - KOH, CFW

- round refractile yeast

cells 2-10 to 30µ

- single or chain of cells

Tissuestains – HE, GMS

Dr Ekta, Microbiology, GMCA


Fungal culture3
Fungal Culture

  • SDA, BHIA & BA incubated at 25° & 37°C.

  • At 25°C – colonies are white to tan in colour,with a yellowish-brown reverse

    LPCB - mycelia bearing conidia & numerous intercalary chlamydospores.

  • 37°C – off-white to cream,

    rough to pasty.

    LPCB- spherical mother cell

    surrounded by multiple

    thin-necked daughter cells:

    “Mariner’s wheel”

Dr Ekta, Microbiology, GMCA


Treatment prophylaxis1
Treatment & Prophylaxis

  • Long term therapy

  • Reviewed periodically as relapses are frequent

  • AMB combined with sulfonamides

  • Oral Itraconazole

Dr Ekta, Microbiology, GMCA


Candidiasis
CANDIDIASIS

  • Commonest fungal disease in humans

  • Affects mucosa, skin, nails & internal organs - superficial and deep infections

  • Caused by yeast- like fungi of genus candida.

  • Candida albicans : commonest pathogenic species.

  • Normal flora of skin, GIT & female genital tract.

  • Commonest fungal infection in HIV+ve individuals

Dr Ekta, Microbiology, GMCA


Epidemiology
Epidemiology

  • Predisposing factors

  • Natural receptive states like infancy, old age, pregnancy.

  • Changes in local bacterial flora 2º to antibiotics.

  • Endocrine diseases like DM

  • Severe chronic underlying debilitated conditions

  • Malignancy

  • Drugs – steroids, immunosuppressants & chemotherapeutic agents.

  • Trauma, burns or injury.

Dr Ekta, Microbiology, GMCA


Pathogenesis pathology1
Pathogenesis & Pathology

  • Adhesion – entry into host as yeast cell

  • Local colonization & invasion into deeper tissues

  • Hyphal form - phospholipase at tip - invasion

    large size - resistant to

    phagocytosis

  • Biofilm formation around cells – facilitates survival of organisms.

Dr Ekta, Microbiology, GMCA


Clinical classification of candidiasis
Clinical Classification of Candidiasis

Dr Ekta, Microbiology, GMCA


Mucocutaneous manifestations
Mucocutaneous Manifestations

  • Oral candidiasis or oral thrush – commonest form: - Creamy white patches on tongue or buccal mucosa

    - 90% of AIDS pt.

  • Vaginitis

    - Young & middle – aged females, during active reproductive life.

    - Acidic discharge, itching & burning sensation

Dr Ekta, Microbiology, GMCA


Cutaneous manifestations
Cutaneous Manifestations

  • Intertriginous – skin folds

  • Paronychia – nail folds

  • Diaper dermatitis – in babies

    - maceration & wet diapers

    Systemic Candidiasis

  • Gastrointestinal candidiasis

    - follow oral antibiotic therapy

    - in leukemia & hematological malignancy: ulcerations, peritonitis

Dr Ekta, Microbiology, GMCA


Clinical forms of candidiasis in hiv patients
Clinical forms of Candidiasis in HIV patients

  • Asymptomatic oral carriage

  • Oropharyngeal thrush

  • Angular cheilitis

  • Leukoplakia

  • Oesophagitis

  • Laryngitis

  • Vulvovaginitis, balanitis

  • Acute atrophic erythema

  • Hematogenous dissemination

Dr Ekta, Microbiology, GMCA


Laboratory diagnosis4
Laboratory Diagnosis

  • Clinical specimens are collected depending on the site of involvement.

    Direct Examination

  • Wet mount – KOH

    - Yeast cells, 4-8

    with budding &

    pseudohyphae

  • Gram’s stain – gram

    +ve budding yeast cells

Dr Ekta, Microbiology, GMCA


Fungal culture4
Fungal Culture

  • SDA & other bacteriological media

  • Colonies appear in 2-3 days.

  • Creamy white, smooth & pasty.

    Identification ofspecies using

  • Tetrazolium reduction medium (TRM)

  • CHROM agar

Dr Ekta, Microbiology, GMCA


C.tropicalis

C.krusei

C.albicans

CHROM Agar

Dr Ekta, Microbiology, GMCA


Germ tube test
Germ tube test

  • Culture is treated with sheep or normal human serum.

  • Incubated at 370Cfor 2 to 4 hrs.

  • Wet mount : shows long tube – like projections extending from the yeast cells, called GERM TUBE.

  • Positive for - C. albicans

    - C. dubliniensis

    - C. tropicalis (sometimes)

  • Also known as Reynolds – braude phenomenon.

Dr Ekta, Microbiology, GMCA


CANDIDA – GERM TUBE

Dr Ekta, Microbiology, GMCA


Chlamydospore formation
Chlamydospore formation

  • Cornmeal agar or Rice starch agar

  • Incubated at 250c

  • Large, highly refractive, thick – walled chlamydospores after 2-3 days of incubation.

    Biochemical tests

  • Sugar fermentation

  • Sugar assimilation

Dr Ekta, Microbiology, GMCA


Treatment prophylaxis2
Treatment & Prophylaxis

  • Correct the underlying condition

  • Oral & Mucocutaneous – 1% Gentian violet

  • Resistant mucosal lesions – Nystatin

  • Vaginal candidiasis – oral fluconazole (single dose), suppositories & creams

  • Systemic lesions – AMB

  • Oral antifungals

Dr Ekta, Microbiology, GMCA


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