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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.

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

HISTOPLASMOSIS

Intracellular infection of the RES caused by


Histoplasma capsulatum. Endemic in parts of USA
Also called Darlings 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)
17/12/07

Dr Ekta, Microbiology, GMCA

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.
17/12/07

Dr Ekta, Microbiology, GMCA

Clinical features

1.
2.
3.

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.

17/12/07

Dr Ekta, Microbiology, GMCA

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, 2-4 within mononuclear
or polymorphonuclear cells, narrow neck budding.
Fluorescent Ab technique.

17/12/07

Dr Ekta, Microbiology, GMCA

Fungal Culture

SDA , BHI at 25 & 37C.


LPCB - White cottony mycelia with large (820) thick walled, spherical spores with
tubercles or finger
like projections
Tuberculate
Macroconidia.

17/12/07

Dr Ekta, Microbiology, GMCA

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.

17/12/07

Dr Ekta, Microbiology, GMCA

Treatment & Prophylaxis

Amphotericin B disseminated & other


severe forms.
Oral Itraconazole
Regular cleaning of farm buildings,
chicken houses for prevention.

17/12/07

Dr Ekta, Microbiology, GMCA

BLASTOMYCOSIS

Also called as Gilchrists disease or Chicago


disease due to its endemicity in N.America
(N.American blastomycosis)
Caused by Inhalation of the spores of
Blastomyces dermatitidis
Causes suppurative & granulomatous infection

17/12/07

Dr Ekta, Microbiology, GMCA

Clinical features

1.
2.

3.

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
17/12/07

Dr Ekta, Microbiology, GMCA

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.
17/12/07

Dr Ekta, Microbiology, GMCA

Fungal Culture

Very slow growth 2 to 4 weeks.


Tissue & cultures at 37C shows budding yeast
cells.
At 25C - fine, branched septate hypha with
conidia measuring 2-10 located on short
terminal or lateral branches.

17/12/07

Dr Ekta, Microbiology, GMCA

Diagnosis

Immunodiffusion precipitation bands.


EIA / RIA
Skin test using blastomycin

Treatment & Prophylaxis

Initial phase - Oral Ketoconazole &


Itraconazole
Life threatening infections - AMB

17/12/07

Dr Ekta, Microbiology, GMCA

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.

17/12/07

Dr Ekta, Microbiology, GMCA

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)
17/12/07

Dr Ekta, Microbiology, GMCA

Laboratory Diagnosis
Specimen sputum, gastric contents, CSF,
exudate or pus.

Direct Examination

Presence of doubly refractile thick walled


globular spherules
(30-60 in dia)
filled with endospores
Tissue HE, PAS & GMS
17/12/07

Dr Ekta, Microbiology, GMCA

Fungal Culture

Different from other dimorphic fungi grows as mold at 25 &


37C under standard conditions.
Growth in 3 - 5 days at 25C
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.

17/12/07

Dr Ekta, Microbiology, GMCA

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

17/12/07

Dr Ekta, Microbiology, GMCA

PARACOCCIDIOIDOMYCOSIS

1.
2.

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).
17/12/07

Dr Ekta, Microbiology, GMCA

Laboratory Diagnosis
Specimen sputum, BAL, pus & crusts from
granulomatous lesions, biopsy

Direct Examination

Wet mount - KOH, CFW


- round refractile yeast
cells 2-10 to 30
- single or chain of cells
Tissue stains HE, GMS

17/12/07

Dr Ekta, Microbiology, GMCA

Fungal Culture

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


At 25C colonies are white to tan in colour,with a
yellowish-brown reverse
LPCB - mycelia bearing conidia & numerous intercalary
chlamydospores.
37C off-white to cream,
rough to pasty.
LPCB- spherical mother cell
surrounded by multiple
thin-necked daughter cells:
Mariners wheel
17/12/07

Dr Ekta, Microbiology, GMCA

Treatment & Prophylaxis

Long term therapy


Reviewed periodically as relapses are
frequent
AMB combined with sulfonamides
Oral Itraconazole

17/12/07

Dr Ekta, Microbiology, GMCA

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

17/12/07

Dr Ekta, Microbiology, GMCA

Epidemiology

1.

2.
3.
4.
5.
6.

7.

Predisposing factors
Natural receptive states like infancy, old age,
pregnancy.
Changes in local bacterial flora 2 to antibiotics.
Endocrine diseases like DM
Severe chronic underlying debilitated conditions
Malignancy
Drugs steroids, immunosuppressants &
chemotherapeutic agents.
Trauma, burns or injury.

17/12/07

Dr Ekta, Microbiology, GMCA

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.

17/12/07

Dr Ekta, Microbiology, GMCA

Clinical Classification of Candidiasis

17/12/07

Dr Ekta, Microbiology, GMCA

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

17/12/07

Dr Ekta, Microbiology, GMCA

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
17/12/07

Dr Ekta, Microbiology, GMCA

Clinical forms of Candidiasis in


HIV patients

Asymptomatic oral carriage


Oropharyngeal thrush
Angular cheilitis
Leukoplakia
Oesophagitis
Laryngitis
Vulvovaginitis, balanitis
Acute atrophic erythema
Hematogenous dissemination

17/12/07

Dr Ekta, Microbiology, GMCA

Laboratory Diagnosis

Clinical specimens are collected depending on


the site of involvement.

Direct Examination

Wet mount KOH


- Yeast cells, 4-8
with budding &
pseudohyphae
Grams stain gram
+ve budding yeast cells

17/12/07

Dr Ekta, Microbiology, GMCA

Fungal Culture

SDA & other bacteriological


media
Colonies appear in 2-3 days.
Creamy white, smooth & pasty.

Identification of species

using
Tetrazolium reduction medium
(TRM)
CHROM agar

17/12/07

Dr Ekta, Microbiology, GMCA

C.tropicalis
C.tropicalis

C.krusei
C.krusei

C.albicans
C.albicans

CHROM
CHROMAgar
Agar
17/12/07

Dr Ekta, Microbiology, GMCA

Germ tube test

Culture is treated with sheep or normal human


serum.
Incubated at 370C for 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.
17/12/07

Dr Ekta, Microbiology, GMCA

CANDIDA
CANDIDAGERM
GERM TUBE
TUBE

17/12/07

Dr Ekta, Microbiology, GMCA

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

17/12/07

Dr Ekta, Microbiology, GMCA

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
17/12/07

Dr Ekta, Microbiology, GMCA

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