Etiology and Ecology
The primary causative agent of the infection is Cryptococcus neoformans. There are two main varieties: var. neoformans, which is globally distributed, and var. gattii, which predominates in warm climate regions. Sporadic cases can be caused by C. albidus and C. laurentii. The sexual (teleomorph) state of the fungus is called Filobasidiella neoformans and is capable of forming hyphae with basidiospores.
In nature, these fungi inhabit soil, air, grass, and food products. An important reservoir is bird droppings, especially pigeon guano. The variety var. gattii has a specific ecological niche: it is associated with soil beneath flowering eucalyptus trees.
The primary route of transmission is airborne (inhalation of dust containing the pathogen). Contact transmission (through damaged skin) and alimentary transmission are less common.
Morphology and Virulence Factors
In the human body (within tissues and macrophages), cryptococci appear as large, round cells ranging from 3 to 25 µm in diameter with a single small bud. Their defining feature is a massive polysaccharide capsule composed of glucuronoxylomannan. It appears as a clear halo surrounding the cell and serves as the primary virulence factor by effectively inhibiting phagocytosis. Occasionally, a reduced mycelium can be detected in tissues.
When cultured in vitro (on artificial media), the cells are smaller, measuring 4–8 µm. They retain their capsule, reproduce by narrow-base budding, and can form both pseudomycelium and true mycelium.
In addition to the capsule, an important virulence factor is the enzyme phenoloxidase, which is a unique biochemical marker found exclusively in cryptococci.
Clinical Presentation and Immunity
Host defense against cryptococci relies primarily on cell-mediated immunity. A negative delayed-type hypersensitivity (DTH) skin test reaction to fungal antigens indicates profound cellular immunodeficiency and carries an extremely poor prognosis. The disease rarely occurs in immunocompetent individuals.
The infection is often asymptomatic or presents with vague symptoms, but high-risk patients develop severe manifestations:
- Cryptococcal meningitis: develops slowly (though the course is more acute in AIDS). It manifests with fever, severe headache, nuchal rigidity, dizziness, visual disturbances, and agitation.
- Pulmonary involvement: accompanied by low-grade fever, night sweats, and a cough with mucous sputum.
- Skin lesions: characterized by the appearance of papules and ulcers with raised borders.
In the absence of an adequate immune response, generalized dissemination of the fungus throughout the body occurs.
Microbiological Diagnostics
Laboratory specimens include cerebrospinal fluid (CSF), sputum, pus, urine, or scrapings from skin ulcers.
- Microscopic examination: A classic rapid diagnostic method for CSF sediment is India ink staining. Against the dark background of the ink, budding yeasts surrounded by an unstained clear capsule are clearly visible. Gram staining, Gram-Weigert stain, May-Grünwald-Giemsa stain, PAS reaction, and acridine orange fluorescent microscopy are also utilized.
- Culture method: Inoculation of specimens is performed on Sabouraud agar. Incubation is carried out at 37 °C for two weeks. Shiny, slightly elevated colonies with a characteristic mucoid (creamy) consistency develop.
- Serological testing: Used to detect specific fungal antigens in the patient's biological fluids.