Cryptococcus neoformans

Dr. Mazen ZAYLAA

2023-2024
 Mention the morphology of the organism

 Explain the pathogenesis and the clinical significance of the previous

organism

 Explain the lab diagnosis of Cryptococcus neoformans

 Outline the prevention and treatment of this disease

General Characteristics of fungi
■ Nonmotile eukaryotes with a chitinous cell wall that take the form of yeasts,
hyphal molds, or dimorphic fungi.

■ Cause an array of diseases including skin, lung, opportunistic, and systemic

infections.

■ Fungi can cause endemic infections as well as localized infections (ie,

superficial, cutaneous, or subcutaneous). Some fungi are opportunistic
pathogens that cause disease in immunocompromised hosts.

■ Grow on Sabouraud agar, which is selective for fungi due to its low pH,
which inhibits growth of most bacteria.

■ Cell membrane contains ergosterol and cell wall is composed of chitin.

General Characteristics of fungi
Cryptococcosis
 Cryptococcosis is a systemic mycosis caused by the encapsulated, yeastlike
fungi C. neoformans and C. gattii.

 C. neoformans is worldwide in distribution and is found as a ubiquitous

saprophyte of soil, especially that which is enriched with pigeon droppings.

 C. neoformans includes capsular serotypes A and D.

Morphology
 Microscopically, C. neoformans and C. gattii are spheric to oval, encapsulated,
yeastlike organisms, 2 to 20 μm in diameter.

 Has thick polysaccharide capsule.

 Replication is by budding from a relatively narrow base. Single buds are usually
formed, but multiple buds and chains of budding cells are sometimes present.

 Germ tubes, hyphae, and pseudohyphae are usually absent in clinical material.

 In tissue and on staining with India ink, the cells are variable in size, spheric,
oval, or elliptic, and are surrounded by optically clear, smoothly contoured,
spheric zones or “halos” that represent the extracellular polysaccharide capsule
Epidemiology

 Cryptococcosis is usually acquired by inhaling aerosolized

of C. neoformans and C. gattii from the environment.

 Subsequent dissemination from the lungs, usually to the

CNS, produces clinical disease in susceptible individuals.

 Primary cutaneous cryptococcosis may occur after

transcutaneous inoculation but is rare.

 Although both C. neoformans and C. gattii are pathogenic

for immunocompetent individuals

 C. neoformans is most often encountered as an

opportunistic pathogen. It is the most common cause of
fungal meningitis and tends to occur in those patients with
defective cellular immunity.

 Whereas C. neoformans are found worldwide in

association with soil contaminated with avian Excreta

 Bird (especially pigeon) droppings.

Clinical Syndromes

 C. neoformans is a major opportunistic pathogen of patients with AIDS.

Those individuals with CD4+ lymphocyte counts of less than 100/mm3
(usually <200/mm3) are at high risk for CNS and disseminated
cryptococcosis.

 Cryptococcosis may present as a pneumonic process or, more commonly, as

a CNS infection secondary to hematogenous and lymphatic spread from a
primary pulmonary focus.

 Less often, a more widely disseminated infection may be seen with

cutaneous, mucocutaneous, osseous, and visceral forms of the disease.

 Pulmonary cryptococcosis is variable in presentation, from an

asymptomatic process to a more fulminant bilateral pneumonia.
Clinical Syndromes

C. neoformans infection in the lungs can

cause a pneumonia-like illness. The
symptoms are often similar to those of
many other illnesses, and can include:

 Cough
 Shortness of breath
 Chest pain
 Fever
Clinical Syndromes

 C. neoformans is highly neurotropic, and the most common form of disease

is cerebromeningeal. The course of disease is variable and may be quite
chronic; however, it is inevitably fatal if untreated.

 Clinical presentation is that of fever, headache, meningismus, visual

disturbances, abnormal mental status, and seizures.

 The clinical picture is highly dependent on the patient’s immune status

and tends to be dramatically severe in AIDS patients and other severely
compromised patients treated with steroids or other immunosuppressive
agents.

 Other manifestations of disseminated cryptococcosis include skin lesions,

ocular infections, osseous lesions and prostatic involvement, which may be
an asymptomatic reservoir of infection.
Clinical Syndromes

Cryptococcal meningitis is an infection caused

by the fungus Cryptococcus after it spreads
from the lungs to the brain. The symptoms of
cryptococcal meningitis include:

• Headache
• Fever
• Neck pain
• Nausea and vomiting
• Sensitivity to light
• Confusion or changes in behavior
Diagnosis mucicramine[red] or methanamine silver stains
soap bubble lesion in gray matter of brain

 The diagnosis of infection caused by C. neoformans and C. gattii may be made by

culture of blood, cerebrospinal fluid (CSF), or other clinical material.

 Microscopic examination of CSF may reveal the characteristic encapsulated budding

yeast cells. The cells of C. neoformans, when present in CSF or other clinical
material, may be visualized with Gram stain, as well as with India ink.

 Culture of clinical material on routine mycologic media will produce mucoid

colonies composed of round, encapsulated, budding yeast cells that are urease-
positive within 3 to 5 days.

 Most commonly, however, the diagnosis of cryptococcal meningitis is made by

direct detection of the capsular polysaccharide antigen in serum or CSF
latex agglutination

 Polymerase chain reaction (PCR

Treatment

 All patients should receive amphotericin B plus flucytosine acutely for 2 weeks
(induction therapy), followed by an 8-week consolidation with either oral
fluconazole (preferred)

 AIDS patients generally require lifelong maintenance therapy with either

fluconazole

 Treatment of these patients should be followed both clinically and mycologically.

 Mycologic follow-up requires repeat lumbar puncture to be performed

(1) at the end of the 2-week induction therapy to ensure sterilization of the CSF,
(2) at the end of the consolidation therapy,
(3) whenever indicated by a change in clinical status during follow-up.
CSF Abnormalities Associated with Meningitis