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Cryptococci are the causative agents of cryptococcosis
Last reviewed: 06.07.2025
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Cryptococcosis (synonyms: torulosis, European blastomycosis, Busse-Buschke disease) is a subacute or chronic disseminated mycosis observed in individuals with severe immunodeficiency.
The causative agent is the opportunistic yeast-like fungus Cryptococcus neoformans (perfect form - Fibbasidielia neoformans). Among the fungi of the genus Cryptococcus, only two species are pathogenic for humans and cause cryptococcosis - C. neoformans (the main causative agent) and C. laurentii (sporadic diseases).
Morphology of cryptococci
The fungus has the form of round, less often oval yeast cells measuring 6-13 µm, sometimes up to 20 µm, which are surrounded by a capsule, the size of which can reach 5-7 µm, and sometimes exceeds the diameter of the vegetative cell. The capsule consists of an acidic polysaccharide, its size is directly dependent on the virulence of the strain. Invasive forms are represented by yeast cells surrounded by a large capsule, giving them significant dimensions (up to 25 µm).
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Cultural properties of cryptococci
Cryptococcus is unpretentious, grows well on conventional media (Sabouraud, wort-agar, MPA), the optimal is a slightly acidic or slightly alkaline reaction of the medium. C. neoformans grows equally well both at 25 °C and at 37 °C, while saprophytic cryptococci are not able to reproduce at 37 ° C. Forms typical shiny juicy colonies, mediated by the presence of a polysaccharide capsule. On Sabouraud agar, it can form shiny creamy-brown colonies.
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Biochemical activity of cryptococci
Low.
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Antigenic structure of cryptococci
According to capsular polysaccharide antigens, 4 serovars are distinguished: A, B, C and D. Among the pathogens, serovars A and D predominate. Serovars B and C cause sporadic lesions in the tropics and subtropics.
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Ecological niche of cryptococci
Cryptococci are widespread in nature, most often they are isolated from people, animals, pigeon droppings, soil, various fruits, berries, vegetables, leaves.
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Sustainability in the environment
Quite high; sensitive to temperature effects.
Antibiotic sensitivity
Sensitive to amphotericin B and fluconazole.
Sensitivity to antiseptics and disinfectants
Sensitive to the action of commonly used antiseptics and disinfectants.
Pathogenicity factors of cryptococci
A capsule that protects the pathogen from the action of phagocytes and humoral defense factors, non-specifically activating T-suppressors and inducing the cleavage of complement components and serum opsonins. The pathogen does not form toxins. The enzyme phenoloxidase secreted by the fungus is considered a possible pathogenicity factor.
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Pathogenesis of cryptococcosis
Cryptococci form a primary inflammatory focus in the lungs with the involvement of regional lymph nodes. In most cases, the process ends with spontaneous recovery. Dissemination of the fungus from the primary focus in the lungs is possible. The inflammatory response varies depending on the patient's immune status. The risk group for dissemination is formed by lipids with impaired T-lymphocyte function. Cytotoxic reactions play a major role in the elimination of the pathogen.
Cellular immunity
Antibodies and complement do not provide resistance of the organism against the pathogen. The presence of antibodies to fungal antigens in patients with negative DTH is a bad prognostic sign. As a rule, the patient has cellular immunodeficiency.
Epidemiology of cryptococcosis
The source of infection is soil. The cryptococcus fungus has been isolated from soil, nests and pigeon droppings, fruit juices, milk, and butter. The mechanism of transmission is aerogenic, the route of transmission is airborne dust. From the soil, where the fungus is small in size (2-3 μm) due to lack of moisture, it enters the lungs with dust. Primary lesions are localized in the lungs, although the possibility of the fungus penetrating the skin and mucous membranes cannot be ruled out. The susceptibility of the population is low and depends on the state of cellular immunity. Diseases are sporadic, and most of the cases are men. Group diseases associated with inhalation of infected dust while working in old buildings contaminated with pigeon droppings have been described. The patient is not contagious to others. The main conditions predisposing to the development of the disease are AIDS, leukemia, Hodgkin's disease, metabolic disorders, and conditions after organ transplantation.
Symptoms of cryptococcosis
The main symptoms of cryptococcosis are meningeal lesions (up to 80% of cryptococcal meningitis in AIDS patients).
Primary cryptococcosis is often asymptomatic or its manifestations are minor and do not require medical care. Cases of detection of primary forms are extremely rare. Primary skin lesions are observed much less often. The main clinically diagnosed form of the disease is cryptococcal meningitis. The lesions are characterized by slow development and the absence of specific signs in the initial stage. Intermittent headaches, the intensity of which increases, dizziness, visual impairment, increased excitability are typical. In the dynamics of the disease, weeks or months after the onset, disturbances of consciousness are observed. The clinical picture includes typical signs of meningitis - high body temperature and stiff neck. Epileptoid seizures, optic disc edema and symptoms of cranial nerve damage are possible. More than 50% of patients have residual neurological disorders.
Laboratory diagnostics of cryptococcosis
The materials for the study include sputum, pus, ulcer scrapings, cerebrospinal fluid, urine, bones, and tissue biopsies.
In native preparations, the pathogen, surrounded by a yellowish mucous capsule, has the appearance of round or ovoid cells measuring 2x5-10x20 μm. Fungi are easily detected in wet smears of cerebrospinal fluid stained with India ink. The capsule is detected in India ink or Buri-Gins stained preparations. Histological preparations for detection of C. neoformans are stained with mucicarmine.
To isolate a pure culture, the material to be studied is inoculated onto sugar agar, Sabouraud medium, beer wort with the addition of antibiotics. The inoculations are incubated at 37 °C, colonies are formed in 2-3 weeks. On dense media, colonies are formed from whitish-yellowish to dark brown in color, with a creamy consistency; on carrot-potato agar, the colonies of the fungus are dark brown or brown in color. Identification of C. neoformans is carried out taking into account the formation of urease on Christiansen medium and the inability to assimilate lactose and inorganic nitrogen, virulence, and growth at 37 °C.
The bioassay is performed on mice that are infected intraperitoneally with blood, urine sediment or exudate from the patient. After 2-4 weeks, the animals are killed, dissected and the homogenate of the liver, spleen and brain is isolated on media with antibiotics. The isolated fungal cultures are identified by cultural, morphological and enzymatic properties.
In the serum of patients, agglutinins, precipitins, complement-fixing antibodies are detected in low titers and inconstantly. Antibody titers in the RSC rarely make up 1:16 and, as an exception, 1:40. The appearance of antibodies and an increase in their titer serve as a favorable prognostic sign. The detection of a circulating antigen in the latex agglutination reaction has absolute diagnostic significance, with titers of the reaction sometimes making up 1:1280 or more.