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INTRODUCTION
Cryptococcus form acute, subacute, chronic pulmonary and systemic
fungal infection – Cryptococcosis
CAUSATIVE AGENT:
Cryptococcus neoformans
[Link] var neoformans
[Link] var gatti
[Link] var grubi
Cryptococcus albidus
Cryptococcus laurentii
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GENERAL FEATURES
Encapsulated yeast
Ubiquitous in nature
Rapidly identified by India ink & by its urease activity.
Not thermally dimorphic
Otherwise known as Filobasidiella neoformans.
Some times capsule free mutant strains were also isolated and identified by
Mason Fontana stain
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EPIDEMIOLOGY
World wide, found in feces of starlings, pigeon, turkey and other avian.
Under this condition capsules are dehydrated to form a thin protective layer
around the organism.
When it is inhaled – rehydrated to form a wide refractile capsule and
multiply.
SEROTYPE
[Link] var neoformans – D, A & D
[Link] var gattii -B&C
[Link] var grubi -A
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PREDISPOSING FACTORS
Hodgkin's disease,
Leucosis,
treatment with corticosteroids,
*T cell deficiency (AIDS).
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MECHANISM OF PATHOGENICITY
The key virulence determinant – capsule primarily made up of
glucuronoxylomannan.
Aspargine and creatinine serves as nitrogen source for Cryptococci in brain
Disseminated infection mainly seen in patients with AIDS
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Pigeon
Starling Turkey
Cryptococci -
capsule dehydrated
Alveolar macrophages capsules rehydrated Phagocytosis
Multiply
Bones Kidney Liver Skin CNS
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CLINICAL DIAGNOSIS
Incubation period – 14 to 25 days
CLINICAL MANIFESTATION
Pulmonary
Central nervous system
Cutaneous
Osseous
Occular and
Other forms
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PULMONARY CRYPTOCOCCOSIS
Portal entry for cerebrospinal or generalized cryptococcosis
Asymptomatic / may cause self limiting pneumonia with sensitization in
patients with normal immune response
In some cases patients develop non productive cough, pleuritic pain &
weight loss.
resolve
Primary infection
invasive / chronic pulmonary infection leads to
risk for dissemination to CNS
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CENTRAL NERVOUS SYSTEM INFECTION
Dissemination to brain & meninges meningitis,
meningoencephalitis / cryptococcoma
MENINGITIS
Symptoms develop over a week or month
Severe head ache, fever, nausea, vomitting, papilledema, nuchal rigidity,
slurred speech, confusion, paralysis , finally coma occurs.
Patient with acute onset die immediately.
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MENINGOENCEPHALITIS
Occurs due to invasion of Cryptococcus to cerebral cortex, brain stem and
cerebellum.
SYMPTOMS
Cerebral edema, hydrocephalus.
Coma & death with in short time
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CRYPTOCOCCOMA
Rarely occurs
Characterized by localized solid tumor like mass found in cerebral hemisphere /
cerebellum & rarely in spinal cord.
SYMPTOMS
Head ache, Drowsiness
Nausea, Vomitting
Mental change, Double vision
Unsteadiness, Paralysis
coma
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CUTANEOUS INFECTION
Primary skin infection ulcerative lesion / cellulitis
Seen mainly in patients with AIDS
Lesions resolve spontaneously or treatment with antifungals
Untreated primary infection leads to secondary cutaneous infection
On patients with AIDS lesions found on head neck as papules, nodules.
Anal ulceration also occurs
Moniter carefully for dissemination to CNS
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OSSEOUS CRYPTOCOCCOSIS
Osseous infection – 10%
Associated with pain (dull pain on movement) and swelling
Occasionally arthritis
Mainly involve cranial and vertebral bones
Lesions are lytic without periosteal proliferation
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OCCULAR CRYPTOCOCCOSIS
Occurs due to dissemination
Increased intracranial pressure leads to
Papilledema
Optic atrophy
Other signs are uncommon
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OTHER INFECTIONS
Endocarditis
Occasionally pyelonephritis
Prostritis
Localized oesophagial lesion
Hepatitis
Sinusitis and
Adrenal cortical lesion
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LAB DIAGNOSIS
SPECIMEN
# CSF # Biopsy tissue
# Sputum # Bronchial washing
# Pus # Blood
# Urine
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DIRECT EXAMINATION
Wet mount
10% potassium hydroxide – ovoid budding yeast cells
India ink preparation
Organisms surrounded by wide refractile gelatinous capsule
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CULTURE
SDA - cream colored, smooth, mucoid yeast like colonies.
Cornmeal agar - budding yeast like cells, no pseudohyphae.
+ Tween 80
Niger seed agar - dark brown colonies due to absorption of brown
pigment from media.
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BIOCHEMICALS
BIOCHEMICALS FERMENTATION ASSIMILATION
Glucose - +
Sucrose - +
Lactose - nil
Galactose - +
Maltose - +
Trehalose - +
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DISTINGUSHING FEATURESOF [Link] FROM NON
PATHOGENIC SPECIES
Growth at 37.c, while non pathogens do not grow
Assimilate nitrate, while non pathogens cannot
Hydrolyze urea
[Link] pathogenic to mice
On CDBT media
[Link] var neoformans – bright red colonies
[Link] var grubi - no pigments
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SEROLOGY
Detection of capsular polysaccharide antigen in CSF by
Latex agglutination test
CIEP – method of choice for diagnosing cryptococcal meningitis (100%
positive in AIDS patient)
In non AIDS patient it is less sensitive (60%)
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ANIMAL INOCULATION
Specimen is injected intraperitonially to mouse or rat
After 2 to 4 wks an autopsy shows gelatinous mass in visceral cavity, spleen
involvement.
In more virulent stain infection of lung & brain occurs
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TREATMENT
Amphotericin B – alone nephrotoxic
Amphotericin B with Flucytosine - toxicity penetration
Miconazole - for cutaneous infection
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