Introduction
The Cryptococcus species belong to the Basidiomycota phylum and Tremellaceae family. The four common species of Cryptococcus are Cryptococcus neoformans, Cryptococcus gattii, Cryptococcus albidus, and Cryptococcus laurentii. Cryptococcus neoformans is the most pathogenic type, which affects immunocompromised individuals, particularly patients with AIDS or HIV. It causes infection in the lungs, central nervous system, and other parts. It is treated with antifungal drugs.
What Is Cryptococcus Neoformans Species?
Cryptococcus neoformans is a fungus living in the environment. People get an infection by breathing the microscopic fungus from the environment. People with weak immune systems get affected easily, and the infection with cryptococcus neoformans is called cryptococcosis. The two varieties of Cryptococcus neoformans are Cryptococcus neoformans var. neoformans and Cryptococcus neoformans var. gattii. There are five serotypes such as A, B, C, D, and AD.
Where Do the Cryptococcus Neoformans Occur?
Cryptococcus neoformans species are commonly found in the environment as saprophytic large budding yeast. It is a yeast-like fungus frequently found in the soil, pigeon excreta, and bats excreta. The C.neoformans var. neoformans (serotypes A and D) are found in soil contaminated with bird droppings (old and dried), especially pigeons. The C.neoformans var. gattii (serotypes B and C) are found in decaying woods.
Morphology of Cryptococcus Neoformans
Cryptococcus neoformans is an encapsulated yeast that is surrounded by a capsule of around 30 micrometers thick. It is round or oval-shaped with 4 to 6 micrometers in diameter. The life cycle of cryptococcus neoformans occurs in two forms. The asexual method involves reproduction by budding. The sexual method includes the conjugation of two yeast cells, the formation of basidium, and repetitious budding.
How Does Cryptococcus Neoformans Spread?
The transmission of Cryptococcus neoformans occurs due to the inhalation of spores, which are dry, light-weight, and easy to aerosolize. The spores inhaled enters the lungs, and the infection begins. Cryptococcus neoformans will not spread from one person to the other. There is no evidence of transmission of infection from humans to animals.
Pathogenesis of Cryptococcus Neoformans
The incubation period is not known. In healthy individuals, the infection remains latent for a long period or causes mild pulmonary infections, which are cleared easily. A healthy immune response reduces the severity of infection in healthy individuals. Whereas in immunocompromised individuals, the infection spreads from the lungs to the central nervous system causing cryptococcal meningoencephalitis. Cryptococcus can cross the blood-brain barrier to reach the brain. It also spreads to the skin, bones, eyes, adrenals, and other organs. The different routes of infection to invade the central nervous system include
- Paracellular route.
- Transcellular route.
- “Trojan Horse” Route - Cryptococcus neoformans use the monocytes to migrate to the brain.
What Are the Virulence Factors of Cryptococcus Neoformans?
The factors enhancing the virulence of Cryptococcus neoformans are:
- Capsule - The outer polysaccharide capsule of the neoformans is the most important factor in enhancing the invasion of the organism into the immune system.
- Melanin Production - The organism can produce a black or brown colored pigment called melanin. It protects the organism from the environment and immune system and helps to disseminate from the lungs.
- Extracellular Enzymes - The neoformans organisms have enzymes such as laccases and phospholipase B in the cell wall, which help them to survive in the host environment.
- Cell Wall Changes and Adaptation to the Host - The ability of the organism to remodel the cell wall helps in evading the immune system of the host.
- Extracellular Vesicles - The organisms contain microvesicles in the extracellular space, which are also known as virulence bags. They help the organism cross the blood-brain barrier and enter the central nervous system.
What Are the Diseases Caused by Cryptococcus Neoformans?
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Central nervous system infections such as meningitis, meningoencephalitis, and cryptococcosis.
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Ocular cryptococcosis (very rare).
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Osteomyelitis (cryptococcosis of bone).
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Cutaneous cryptococcosis.
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Prostate infection (asymptomatic).
What Are the Clinical Features of Cryptococcus Neoformans Infection?
The clinical features or the symptoms depend on the affected body parts. The symptoms include the following:
Symptoms in Lungs
- Flu-like symptoms such as cough.
- Chest pain.
- Shortness of breath.
- Fever.
Symptoms in the Brain
- Headache.
- Neck pain or stiff neck.
- Fever.
- Nausea and vomiting.
- Behavioral changes.
- Confusion and hallucinations.
- Sensitivity to light.
How to Diagnose Cryptococcus Neoformans?
The diagnosis is difficult because the lesions caused by Cryptococcus neoformans are similar to many other diseases. An effective diagnosis requires serological testing and isolation of the fungus from the patient’s body or biopsy samples. For cases of meningitis, lumbar puncture is done to collect the cerebrospinal fluid (CSF) to conduct further inspection. The diagnostic procedures are as follows:
Specimen Preparation - Cerebrospinal fluid, blood, urine, and scrapings from the lesions are collected from the suspected individuals for examination. The CSF is centrifuged before the culture examination.
Staining and Microscopic Examination
Gram Staining - Cryptococcus neoformans cells appear as gram-positive round bodies or gram-negative lipoid bodies.
Negative Staining - India Ink is used to visualize the cerebrospinal fluid.
Mucicarmine Stain - It is the specific stain for the polysaccharides present in the cell walls of Cryptococcus neoformans.
Cultural Examination - Sabouraud dextrose agar (SDA) is used for the cultural examination. Cryptococcus neoformans colonies develop within a few days at room temperature. The colonies develop brown pigmentation.
Serological Examination
Antigen detection - This is a specific test to detect antigens of cryptococcus in cases of cryptococcal meningitis.
Antigen quantification - This test quantifies the antibodies produced against the antigen.
What Are the Treatments for Diseases Caused by Cryptococcus Neoformans?
Immunocompetent or healthy individuals do not require treatment. If infection or lesions are present in the lungs, patients are prescribed antifungal drugs such as Fluconazole and Itraconazole. These drugs are used for the treatment of infection. In cases of severe lung and central nervous system infections, a combination of Amphotericin B and Flucytosine is prescribed. Surgery is recommended in cases of cryptococcosis to remove fungal growth.
Conclusion
Infections caused by Cryptococcus neoformans can cause death without proper treatment. It is difficult to prevent this infection as it spreads through bird droppings. Immunocompromised individuals should avoid areas contaminated with bird droppings. One approach to prevent cryptococcal meningitis is targeted screening, where susceptible individuals are screened and treated.
