Dr.T.V.Rao MD

CRYPTOCOCCUS NEOFORMANS

DR.T.V.RAO MD 1

Chronic, subacute to acute pulmonary, systemic or

meningitic disease, initiated by the inhalation of the

fungus. Primary pulmonary infections have no

diagnostic symptoms and are usually subclinical. On

dissemination, the fungus usually shows a

predilection for the central nervous system, however

skin, bones and other visceral organs may also

become involved.

Distribution: World-wide.

Aetiological Agent: Cryptococcus neoformans.

CRYPTOCOCCOSIS

CRYPTOCOCCUS NEOFORMANS

• A Capsulated yeast

– A true yeast..

• A sporadic disease

in the past.

• Most common

infection in AIDS

patients.

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MORPHOLOGY • A true yeast

• Round 4 – 10 microns

• Surrounded by Mucopolysaccharide capsule.

• Thick in vivo

• Negative staining with India Ink and Nigrosin

• 60% of the infected prove positive by India Ink preparation on examination of CSF

• KoH preparations in Sputum and other tissues,

• PAS and Mucicaramine staining helps confirmation.

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AS SEEN IN INDIA INK PREPARATION

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CULTURING •CSF -Culturing on Sabouraud's

agar, and incubated at 370 c for

up to 3 weeks

•Cultures appear as Creamy,

white, yellow

Brown colored

Simple urease test helps in

confirming the isolate.

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CRYPTOCOCCUS NEOFORMANS

SEROTYPES

• A true yeast

• 4 serotypes - A,B,C,D

• A and D - C.neofromans var neoformans

• B and C - C.neoformans var gatti.

• Many infections are caused by

C.neofromans var neoformans.

Found in wild/Domesticated birds.

Pigeons carry C.neofromans,

Birds do not get infected.

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DR.T.V.RAO MD

CRYPTOCOCCUS NEOFORMANS

Cryptococus neoformans

var grubii

(now C.gatti)

var gatti var enoformans

Serotype

A – 80% clinical cases

B – tropical, subtropical – S.

California, Hawaii, Brazil,

Australia, SE Asia

C – rare

D – Europe – Denmark,

Germany, Italy, France,

Switzerland

SEROTYPES - CRYPTOCOCCUS

NEOFORMANS

PIGEONS AND RED RIVER GUM TRESS HARBORS

THE CRYPTOCOCCUS IN NATURE

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LIFE CYCLE OF C.NEOFROMANS

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PATHOGENESIS

• Enters through lungs - inhalation of Basidiospores of C neoformans

• Enters deep into lungs, Men acquires more infections, and women less infected.

• Self limiting in most cases,

• Pulmonary infections can occur.

• Present as discrete nodules - Cryptococcoma.

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PATHOGENESIS • Can infect normal humans

• Abnormalities of T lymphocyte function aggravates, the clinical manifestations.

• In AIDS 3- 20% develop Cryptococcosis.

• Present with Chronic meningitis , Meningo encephalitis

• Manifest with – head ache low grade fever,

• Visual abnormalities ,Coma – fatal

• Treatment reduces the morbidity and cure in non immune suppressed expected.

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PATHOGENESIS

• Can manifest with involvement of

,Skin,

mucosa,organs,Bones,and as

Disseminated form.

Can mimic like Tuberculosis,

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CLINICAL MANIFESTATIONS

Lung

- Portal of entry

- asymptomatic (1/3) life threatening pneumonia (ARDS)

- Endobronchial colonization underlying chronic lung disease

- Single pulmonary nodule

- Symptomatic – acute, sub acute

CLINICAL MANIFESTATIONS CNS

- Sub acute meningitis or meningo-encephalitis

- Headache, fever, cranial nerve palsies, lethargy, coma

- Subacute (days) months

HIV

- Higher yeast burden

- incidence raised intracranial pressure

- Often disseminated

- Immune reconstitution disease

CLINICAL MANIFESTATIONS

CNS

- Subacute meningitis or meningo-encephalitis

- Headache, fever, cranial nerve palsies, lethargy, coma

- Subacute (days) months

HIV

- Higher yeast burden

- incidence raised intracranial pressure

- Often disseminated

- Immune reconstitution disease

LABORATORY DIAGNOSIS. • CSF Microscopic observation under India Ink

preparation

• Direct microscopy - Gram staining

• Cultures on Sabouraud dextrose agar,

• Serological tests for detection of Capsular antigen

• CSF findings mimic like Tuberculosis

• IN CSF - latex test for detection of Antigen

• Blood cultures,

• ELISA

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• Mixed culture of C.

neoformans and C.

albicans on bird seed

agar (Guizotia seeds)

showing the distinctive

brown colonies of C.

neoformans, due to the

selective absorption of

pigment from the media,

compared to the white

colonies of C. albicans.

IDENTIFICATION OF C.ALBICANS

DR.T.V.RAO MD 19

1MICROSCOPIC MORPHOLOGY OF C. NEOFORMANS SHOWING

ENCAPSULATED BUDDING, YEAST CELLS. NO PSEUDO HYPHAE

ARE PRODUCED.

0

• C. neoformans on

Sabouraud's

dextrose agar

showing typical

dark cream

coloured, smooth,

moist, shining and

mucoid colonies.

C. NEOFORMANS ON SABOURAUD'S

DEXTROSE AGAR

DR.T.V.RAO MD 21

TREATMENT

• Immune competent - Fuconazole,Itraconazole

• Immune Deficient – Amphotericin B

Flu cytosine

AIDS patients are not totally cured , Relapses

are frequent with fatal outcome.

Rapid resistance with Fluconazole.

Avoid contact with Birds

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• Fluconazole prophylaxis

• Active immunization- cryptococcal GXM-tetanus toxoid conjugate vaccine- in animal models, no human trials

• Monoclonal antibodies- would require repeated injections

• Avoid high risk environments

PREVENTION

EPIDEMIOLOGY • HIV

• Lymphoproliferative disorders

• Sarcoidosis

• Corticosteroids

• Hyper IgM or IgE syndrome

• Monoclonal antibodies (infliximab)

• SLE

• CD4 T-cell lymphoma (idiopathic)

• Diabetes

• Organ transplant

• Peritoneal dialysis

• Cirrhosis

• 20% without HIV have no underlying comorbidity

DR.T.V.RAO MD 25

• Created by Dr.T.V.Rao MD for Medical and

Paramedical students in Developing World

• Email

• doctortvrao@gmail.com