Understanding Cryptococcus Neoformans : Features, Causes and Treatment

Understanding Cryptococcus Neoformans : Features, Causes and Treatment

An infection called cryptococcosis, which is more frequently seen in immunosuppressed people but is uncommon in healthy people, is brought on by the invasive fungus known as Cryptococcus.

An infection called cryptococcosis, which is more frequently seen in immunosuppressed people but is uncommon in healthy people, is brought on by the invasive fungus known as Cryptococcus. Two species of Cryptococcus commonly associated with human infections are Cryptococcus neoformans and Cryptococcus gutti. This organism is widely distributed in certain regions of the world. The most typical exposure types, however, involve a history of exposure to dirt and bird droppings.


Cryptococcus species are fungal pathogens that are morphologically encapsulated yeasts. Immunosuppression is the primary mechanism responsible for cryptococcal disease. Illnesses such as AIDS, diabetes, chronic liver disease, Cryptococcal illness is frequently linked to patients undergoing organ transplantation, chronic kidney failure, and long-term steroid use.


Each year, there are about 625,000 documented deaths due to cryptococcosis, which is estimated to cause about 1 million cases worldwide. In the United States, the incidence of cryptococcosis is estimated at approximately 0.4 to 1.3 cases per 100,000 population and 2 to 7 cases per 100,000 in AIDS patients, with a case fatality rate of approximately 12%.

The incidence of cryptococcal infections has decreased dramatically over the past two decades due to advances in antiretroviral therapy. Cryptococcus neoformans is usually associated with infections in immunocompromised patients, whereas Cryptococcus gattii is associated with infections in immunocompromised patients.


Cryptococcus fungi are commonly found in soil contaminated with bird droppings, decaying wood, and tree cavities. The fungal capsule contains the polysaccharides glucuronoxylomannan and glucuronyl arabinogalactan, which are the main factors contributing to pathogen virulence. Infection usually occurs by breathing in spores from the environment.

Initial infections are usually asymptomatic and are contained in healthy individuals. Spread of the disease from the original site of infection occurs by hematogenous spread in immunocompromised patients. Another mechanism by which infection occurs is that when a patient becomes immunocompromised, the organism reactivates at the original site of infection years later.


They are facultative intracellular organisms. Cryptococcus fungi exist in asexual (yeast) and sexual (telemorph) forms. When cultured on various agar media, it forms colonies of white slime. The two predominant species of Cryptococcus are distinguished by their growth characteristics on canavanine glycine bromothymol blue agar.

Histological identification can be done by Methenamine silver staining for the yeast type, Musicalmine staining for the yeast and capsular types, and Fontana-Masson staining for melanin in yeast.

History and Physical

Cryptococcus neoformans and Cryptococcus gattii are both spread by inhalation and cause similar diseases. Meningoencephalitis is the most frequent clinical manifestation of infection, despite the fact that the lungs are the most common site of pathogen entry into the body.

Clinical features of cryptococcal meningitis usually appear within 1 to 2 weeks and include fever, malaise, headache, stiff neck, photophobia, nausea, and vomiting. The disease rarely leads to coma or death. The literature reports that symptoms such as coughing, shortness of breath, and rash are rare.

Physical examination findings may reveal focal neuropathy indicative of increased intracranial pressure and increased diastolic pressure.


Patients with central nervous system symptoms are evaluated with a brain radiograph to rule out the presence of elevated CSF pressure. Analysis, culture and staining of cerebrospinal fluid and immunodiagnostic testing of cerebrospinal fluid are the main diagnostic tests performed to diagnose cryptococcal meningitis. Analysis of body fluids usually shows low white blood cell count, low glucose, and elevated protein, but may be normal in about 25-30% of cases.

Infected liquid cultures will show off-white colonies in about 3-7 days. Ink staining aids in rapid identification of organisms. Detection of cryptococcal antigens by immunodiagnostic testing of serum and cerebrospinal fluid provides a definitive diagnosis of infection.

A variety of techniques such as latex agglutination, enzyme-linked immunosorbent assay (ELISA), and lateral flow assay can be used to confirm the diagnosis of Cryptococcal antigens.

Disseminated cryptococcal infection is defined by positive blood cultures or positive cultures from at least two different sites. Disseminated infections are often associated with HIV infection and other immunocompromised conditions.

Treatment / Management

Pharmacological treatment of cryptococcal infections depends on the site of infection and severity of symptoms. According to his 2010 IDSA guidelines, a non-immunosuppressed patient with mild to moderate symptoms with suspected pulmonary cryptococcal infection should be treated with fluconazole at her dose of 400 mg daily for 6 to 12 months. can do.

It is also the treatment recommendation for non-meningeal, non-pulmonary cryptococcosis in patients in whom CNS disease has been ruled out. Lumbar puncture should be considered in non immunocompromised patients to rule out asymptomatic CNS involvement, but guidelines suggest that in asymptomatic, immunocompetent patients without CNS symptoms he can avoid LP. said.

Treatments for central nervous system cryptococcosis and immunocompromised hosts include therapies that target fungal pathogens, reduce intracranial pressure, and improve the patient's immune status.

Antifungal therapies targeting Cryptococcus have induction, consolidation, and maintenance phases. Amphotericin B and flucytosine are recommended as antifungal therapy for use in the induction phase for a minimum duration of 2 weeks, and fluconazole for 8 weeks is the recommended drug during the intensification phase of treatment.

Drug selection is generally similar for HIV-positive patients, organ transplant patients, and patients with other diseases that cause immunosuppression.

 After 2 weeks of induction therapy, reassessment of the cerebrospinal fluid is recommended, and if cultures sputum culture and sensitivity remain positive, the duration of induction therapy can be further extended. and after the consolidation phase, the duration of the maintenance phase is usually one year. Maintenance therapy can be discontinued when patients achieve healthy immune status that clinically correlates with CD4 cell counts greater than 100 cells/microliter.

Monitoring and control of intracranial pressure play an important role in reducing mortality associated with cryptococcal meningitis. Lumbar puncture is the preferred option for managing intracranial pressure, and ventricular drainage or ventriculoperitoneal shunts are used in patients requiring frequent lumbar punctures.

Drugs commonly used in bacterial meningitis to reduce intracranial pressure, such as acetazolamide, mannitol, and dexamethasone, are not recommended for cryptococcal meningitis. Another important aspect of cryptococcosis management is to improve the patient's immune status. Antiretroviral therapy is recommended for 2–10 weeks after initiation of antifungal therapy in HIV-positive patients.

Late initiation of antiretroviral therapy has been associated with better survival than early initiation. In organ transplant patients, the recommended approach to improving immune status is the gradual reduction of immunosuppressive therapy while maintaining a balance with the risk of organ rejection.

Mortality associated with cryptococcal infections has fallen precipitously due to advances in antiretroviral therapy. Prognostic factors for disease associated with poor outcome include altered mental status and cerebrospinal fluid antigen titers >1.

1024 and white blood cell count in cerebrospinal fluid <20/microL.

Differential diagnosis

  • Acanthamoeba infection.
  • Basal cell carcinoma.
  • Histoplasmosis.
  • Lipoma.
  • Nolluscum contagiosum.
  • Pneumocystis jiroveci pneumonia (PJP).
  • Syphilis.
  • Toxoplasmosis.
  • Tuberculosis .

Enhancing Healthcare Team Outcomes


Prophylactic treatment for cryptococcal infection is recommended in HIV-positive patients with a CD4 count of fewer than 100 cells/microL. Fluconazole and Itraconazole are the recommended drugs for prophylaxis against cryptococcosis.

Current research

Efficacy of sertraline, an antidepressant as an adjunct therapy with fluconazole, is being studied in preventing cryptococcal infections in asymptomatic patients who test positive for cryptococcal antigen. A long-term prospective study is being performed to have a better understanding of the immunogenetic defects that might play a role in the pathogenesis of cryptococcal infections.