Cryptococcus
Cryptococcus is a genus of fungi that exists globally in soil and on trees, primarily responsible for a serious infection known as cryptococcosis. The infection typically occurs through the inhalation of airborne spores, which can be found in contaminated soil, especially around the feces of wild birds, or from certain types of trees. The two main species causing disease in humans are Cryptococcus neoformans and Cryptococcus gattii, with neoformans being more prevalent in immunocompromised individuals. Cryptococcus infections can range from asymptomatic colonization to severe conditions such as meningitis, particularly affecting the central nervous system.
Symptoms may include cough, chest pain, fever, and neurological issues like headache and altered mental status. Diagnosis often involves specific tests on blood or cerebrospinal fluid to detect the fungus, and imaging studies may help identify the infection's extent. Treatment generally includes a combination of antifungal medications, with the specific regimen tailored to the patient's immune status. While cryptococcosis can be treated effectively, especially in immunocompromised patients, complications can arise, emphasizing the importance of timely medical intervention.
Cryptococcus
- TRANSMISSION ROUTE: Inhalation
Definition
Cryptococcus is a type of fungus found worldwide in soil and areas on and around trees. Cryptococcus causes cryptococcosis, an invasive mycosis in humans.
Natural Habitat and Features
A Cryptococcus infection, or cryptococcosis, is typically caused by the inhalation of fungal spores from contaminated soil. Neoformans and gattii are the two main forms of cryptococcosis that are transmitted to humans. Neoformans is the most common species found in the United States and comes from the aged feces of wild birds, such as pigeons. The feces become dry, and, once disrupted, they produce spores that are released into the air.
Gattii, which is typically found in tropical and subtropical climates, has also been identified in Canada and the United States. Gattii is not associated with bird feces but with the bark, leaves, and plant debris of eucalyptus trees and gum trees.
Cryptococcus cells are round or oval-shaped and are surrounded by a polysaccharide capsule comprising mannose, xylose, and glucuronic acid. During sexual reproduction of the Cryptococcus cell, two fungal cells fuse and develop threadlike extensions called hyphae. Neoformans and gattii are considered to be two distinct species. Each species has five serotypes based on the antigenic specificity of the capsular polysaccharide. Neoformans include serotypes A, D, and AD. Gattii includes serotypes B and C. Serotype A causes most cryptococcal infections in immunocompromised persons.
C. neoformans is an encapsulated yeast that grows at 98° Fahrenheit (37° Celsius). Its identification is based on its microscopic appearance: smooth, convex, and yellow or tan colonies on solid media at 68° to 98° F (20° to 37° C).
Pathogenicity and Clinical Significance
Cryptococcal infection response mainly depends on the infected person’s immune status before infection and the involved sites. Responses include harmless colonization of the airway and asymptomatic infections to meningitis and disseminated disease. This organism’s primary transmission is respiratory, but not directly from human to human. C. neoformans can also develop in nonhuman animals.
Once the fungal elements have been inhaled, the yeast spores deposit themselves in the pulmonary alveoli. They must survive the neutral to alkaline pH (acidity) and physiologic concentrations of carbon dioxide before they can be phagocytized by alveolar macrophages. Both neoformans and gattii, once inhaled, may cause pneumonia-like symptoms, including shortness of breath, cough, chest pain, and fever. A chest X-ray may reveal focal or diffuse infiltrates and a nodule or mass.
The mode of entry for Cryptococcus is through the lungs; however, the central nervous system is the main site of clinical involvement. Cryptococcal meningitis and meningoencephalitis are the most common and most serious forms of cryptococcal disease affecting the central nervous system. These forms can be fatal if not treated appropriately; death can occur from two weeks to years following the onset of symptoms. Headache, altered mental status, confusion, lethargy, obtundation (decreased alertness), seizures, and coma are the most common symptoms. Other organ involvement sites for infection are the skin, prostate, bones, eyes, heart (as myocarditis), liver (as hepatitis), and adrenals.
Neoformans typically infects immunocompromised persons, yet it has also infected persons who are not immunocompromised. At high risk of developing cryptococcus are persons who have human immunodeficiency virus infection and other immunocompromised persons, including those undergoing organ transplantation and persons receiving corticosteroid treatment. The incubation period for neoformans is unknown.
Gattii rarely infects immunocompromised persons; it usually infects persons with healthy immune systems. Persons infected with this type of Cryptococcus may begin to exhibit symptoms two to fourteen months following exposure. Persons infected with gattii respond much slower to treatment than those infected with neoformans, thereby increasing the risk of developing significant central nervous system sequela.
Cryptococcal-encapsulated yeast cells can be visualized using an India ink preparation on cerebral spinal fluid. In addition, blood, urine, tissue, and sputum can also be examined microscopically for the presence of Cryptococcus. A rapid cryptococcal antigen test can also be done using blood or cerebral spinal fluid. To definitively determine the infection type, the organism must be cultured, which requires special testing at state health department laboratories or at the Centers for Disease Control and Prevention. Computed tomography scans and magnetic resonance imaging studies may help distinguish cryptococcal infections from other symptomologies.
Drug Susceptibility
Meningeal and other serious cryptococcal infections can have a rapid onset of symptoms, so the administration of the appropriate antibiotic “cocktail” is critical. Amphotericin B, in combination with oral flucytosine or fluconazole, is the first-line drug therapy for cryptococcosis. This combination penetrates the blood-brain barrier more effectively. Amphotericin B has a rapid onset of action, leading to faster clinical improvement. For persons with renal impairment, liposomal amphotericin B is used (this type of amphotericin has sparing renal function properties). Ketoconazole or itraconazole should not be used in the initial treatment of cryptococcosis because they do not adequately penetrate the blood-brain barrier.
Cryptococcosis includes varying degrees of treatment regimens following initial drug therapy. These regimens depend on immune system involvement. An immunocompromised person with a human immunodeficiency virus (HIV) infection will begin initial aggressive treatment with the therapeutic goal of controlling the acute cryptococcal infection, followed by lifelong suppression therapy. The therapeutic goal for persons with cryptococcosis but who are not HIV-positive is permanent cure, with no chronic suppressive therapy.
When systemic therapy becomes refractory, intrathecal or intraventricular amphotericin B may be required. Therapy is considered successful only after cerebral spinal fluid cultures are negative, and the infected person has had significant clinical improvement.
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