CRYPTOCOCCUS NEOFORMANS

Dr.T.V.Rao MD

DR.T.V.RAO MD

CRYPTOCOCCOSIS
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.

CRYPTOCOCCUS NEOFORMANS
A Capsulated yeast A true yeast.. A sporadic disease in the past. Most common infection in AIDS patients.
DR.T.V.RAO MD

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.
DR.T.V.RAO MD 4

AS SEEN IN INDIA INK PREPARATION

DR.T.V.RAO MD

CULTURING
CSF -Culturing on Sabouraud's agar, and incubated at 37 0 c for up to 3 weeks Cultures appear as Creamy, white, yellow Brown colored Simple urease test helps in confirming the isolate.

DR.T.V.RAO MD

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.
DR.T.V.RAO MD 7

CRYPTOCOCCUS NEOFORMANS
Cryptococus neoformans
var grubii var gatti var enoformans

(now C.gatti)

SEROTYPES - CRYPTOCOCCUS NEOFORMANS

Serotype

A 80% clinical cases

B tropical, subtropical S. California, Hawaii, Brazil, Australia, SE Asia C rare D Europe Denmark, Germany, Italy, France, Switzerland

PIGEONS AND RED RIVER GUM TRESS HARBORS THE CRYPTOCOCCUS IN NATURE

DR.T.V.RAO MD

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LIFE CYCLE OF C.NEOFROMANS

DR.T.V.RAO MD

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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.

DR.T.V.RAO MD

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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.
DR.T.V.RAO MD 13

PATHOGENESIS
Can manifest with involvement of ,Skin,
mucosa,organs,Bones,and as Disseminated form.

Can mimic like Tuberculosis ,

DR.T.V.RAO MD 14

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
DR.T.V.RAO MD 18

IDENTIFICATION OF C.ALBICANS
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.

DR.T.V.RAO MD

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1MICROSCOPIC MORPHOLOGY OF C. NEOFORMANS SHOWING ENCAPSULATED BUDDING, YEAST CELLS. NO PSEUDO HYPHAE ARE PRODUCED . 0

C. NEOFORMANS ON SABOURAUD'S

DEXTROSE AGAR C. neoformans on Sabouraud's dextrose agar showing typical dark cream coloured, smooth, moist, shining and mucoid colonies.
DR.T.V.RAO MD

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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
DR.T.V.RAO MD 22

PREVENTION
Fluconazole prophylaxis

Active immunizationcryptococcal GXM-tetanus toxoid conjugate vaccine- in animal models, no human trials
Monoclonal antibodies- would require repeated injections

Avoid high risk environments

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

 Created by Dr.T.V.Rao MD for Medical and Paramedical students in Developing World

Email

doctortvrao@gmail.com

DR.T.V.RAO MD

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