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cryptococcus neoformans

Cryptococcus neoformans

Dr.T.V.Rao MD

Dr.T.V.Rao MD


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 neoformans3
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

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

  • 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.

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.

Cryptococcus neoformansSerotypes

Dr.T.V.Rao MD

serotypes cryptococcus neoformans
Serotypes - Cryptococcus neoformans


A – 80% clinical cases

B – tropical, subtropical – S. California, Hawaii, Brazil, Australia, SE Asia

C – rare

D – Europe – Denmark, Germany, Italy, France, Switzerland

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

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

Can manifest with involvement of ,Skin,

mucosa,organs,Bones,and as Disseminated form.

Can mimic like Tuberculosis,


Dr.T.V.Rao MD

clinical manifestations

- 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
clinical manifestations16

Sub acute meningitis or meningo-encephalitis

Headache, fever, cranial nerve palsies, lethargy, coma

Subacute (days)  months


Higher yeast burden

 incidence raised intracranial pressure

Often disseminated

Immune reconstitution disease

Clinical Manifestations
clinical manifestations17

Subacute meningitis or meningo-encephalitis

Headache, fever, cranial nerve palsies, lethargy, coma

Subacute (days)  months


Higher yeast burden

 incidence raised intracranial pressure

Often disseminated

Immune reconstitution disease

Clinical Manifestations
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,


Laboratory Diagnosis.

Dr.T.V.Rao MD

identification of c albicans
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

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
  • C. neoformans on Sabouraud's dextrose agar showing typical dark cream coloured, smooth, moist, shining and mucoid colonies.

Dr.T.V.Rao MD

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

  • 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

Lymphoproliferative disorders



Hyper IgM or IgE syndrome

Monoclonal antibodies (infliximab)


CD4 T-cell lymphoma (idiopathic)


Organ transplant

Peritoneal dialysis


20% without HIV have no underlying comorbidity


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

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Dr.T.V.Rao MD