This document discusses Cryptococcosis, caused by the yeast Cryptococcus. It can cause pulmonary and systemic fungal infections. Cryptococcus forms a polysaccharide capsule which is its main virulence factor. It is found worldwide in bird droppings and can be inhaled, causing disease. Clinical manifestations include pulmonary infection, central nervous system infection like meningitis or meningoencephalitis, and cutaneous or disseminated infection. Diagnosis involves visualizing the encapsulated yeast using methods like India ink or culture on specific media. Treatment involves antifungal drugs like amphotericin B and flucytosine.

1. CRYPTOCCOCOSIS
DR. HANAA SHEIKH

2. INTRODUCTION
Cryptococcus form acute, subacute, chronic pulmonary and systemic
fungal infection – Cryptococcosis
CAUSATIVE AGENT:
 Cryptococcus neoformans
 C.neoformans var neoformans
 C.neoformans var gatti
 C.neoformans var grubi
 Cryptococcus albidus
 Cryptococcus laurentii

3. 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

4. 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
 C.neoformans var neoformans – D, A & D
 C.neoformans var gattii - B & C
 C.neoformans var grubi - A

5. PREDISPOSING FACTORS
 Hodgkin's disease,
 Leucosis,
 treatment with corticosteroids,
 *T cell deficiency (AIDS).

6. 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

7. Cryptococci -
capsule dehydrated
Starling
Pigeon
Turkey
capsules rehydrated
Alveolar macrophages Phagocytosis
Multiply
Bones CNS
Skin
Liver
Kidney

8. CLINICAL DIAGNOSIS
 Incubation period – 14 to 25 days
CLINICAL MANIFESTATION
 Pulmonary
 Central nervous system
 Cutaneous
 Osseous
 Occular and
 Other forms

9. 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

10. 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.

11. MENINGOENCEPHALITIS
 Occurs due to invasion of Cryptococcus to cerebral cortex, brain stem and
cerebellum.
SYMPTOMS
 Cerebral edema, hydrocephalus.
 Coma & death with in short time

12. 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

13. 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

14. 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

15. OCCULAR CRYPTOCOCCOSIS
 Occurs due to dissemination
 Increased intracranial pressure leads to
 Papilledema
 Optic atrophy
 Other signs are uncommon

16. OTHER INFECTIONS
 Endocarditis
 Occasionally pyelonephritis
 Prostritis
 Localized oesophagial lesion
 Hepatitis
 Sinusitis and
 Adrenal cortical lesion

17. LAB DIAGNOSIS
 SPECIMEN
# CSF # Biopsy tissue
# Sputum # Bronchial washing
# Pus # Blood
# Urine

18. DIRECT EXAMINATION
 Wet mount
10% potassium hydroxide – ovoid budding yeast cells
 India ink preparation
Organisms surrounded by wide refractile gelatinous capsule

19. 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.

20. BIOCHEMICALS
BIOCHEMICALS FERMENTATION ASSIMILATION
Glucose - +
Sucrose - +
Lactose - nil
Galactose - +
Maltose - +
Trehalose - +

21. DISTINGUSHING FEATURESOF Cr.neoformans FROM NON
PATHOGENIC SPECIES
 Growth at 37
.
c, while non pathogens do not grow
 Assimilate nitrate, while non pathogens cannot
 Hydrolyze urea
 Cr.neoformans pathogenic to mice
 On CDBT media
 Cr.neoformans var neoformans – bright red colonies
 Cr.neoformans var grubi - no pigments

22. 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%)

23. 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

24. TREATMENT
 Amphotericin B – alone nephrotoxic
 Amphotericin B with Flucytosine - toxicity penetration
 Miconazole - for cutaneous infection