Cryptococcus is a fungus that is found in the soil throughout the world. Because Cryptococcus is common in the environment, most people probably breathe in small amounts of microscopic, airborne spores every day. Sometimes these spores cause symptoms of a respiratory infection, but other times there are no symptoms at all. In healthy people, the fungus usually does not cause serious illness because the immune system can fight off the infection. However, in people with weakened immune systems, the fungus can stay hidden in the body and later reactivate, spreading to other parts of the body and causing serious disease.

An infection with the fungus Cryptococcus is known as cryptococcosis, and it is a serious opportunistic infection among people with advanced HIV/AIDS. Cryptococcosis is not contagious, meaning it cannot spread from person-to-person. Cryptococcal meningitis specifically occurs after Cryptococcus has spread from the lungs to the brain.

Worldwide, approximately 1 million new cases of cryptococcal meningitis occur each year. Most of these cases are opportunistic infections that occur among people with HIV/AIDS. Although the widespread availability of antiretroviral therapy (ART) in developed countries has helped reduce cryptococcal infections in these areas, it is still a major problem in developing countries where access to healthcare is limited. Throughout much of sub-Saharan Africa, for example, Cryptococcus is now the most common cause of meningitis. Cryptococcal meningitis is one of the leading causes of death in HIV/AIDS patients; in sub-Saharan Africa, it may kill more people each year than tuberculosis.

There are several ways to diagnose a cryptococcal infection. Traditional methods include using a microscope to observe Cryptococcus cells in a specimen from a patient, or growing Cryptococcus from a patient specimen on a special culture plate. Both microscopy and culture are accurate methods to detect Cryptococcus, but they are not very sensitive, meaning that in a small number of cases, these methods may not detect the fungus even if it is present in the body, leading to a missed diagnosis.

Cryptococcal antigen is a substance produced by the fungus Cryptococcus. Antigen tests can also be used to diagnose cryptococcal infection, and antigen can be detected in the body even before a patient has any symptoms of the infection. Tests that detect cryptococcal antigen (latex agglutination and enzyme immunoassay) are both sensitive and accurate, but are not always available in many parts of the world.

A new antigen detection test, called the Lateral Flow Assay (LFA), is a rapid dipstick test. This test is:

• Simple and quick: The results of the LFA are available in 10 minutes, and the test can be performed without the use of complicated laboratory equipment. Cryptococcal antigen is detectable in cerebrospinal fluid (the fluid surrounding the brain and spinal cord) and serum (a component of blood) even before meningitis symptoms develop.
• Effective: The test is sensitive, accurate (>95%), and highly predictive of who is at risk for developing cryptococcal meningitis.
• Affordable: At a cost of approximately $2 per test, the LFA is cheaper than the other methods used to diagnose cryptococcosis.

Treatment for cryptococcal infection lasts for several months and usually consists of three phases: induction, consolidation, and maintenance. Induction is given to rapidly clear the organism from the body. Consolidation is given to ensure that the infection is completely eradicated, and maintenance is given to prevent the infection from recurring.

There are several antifungal medications that can treat cryptococcal infection. Amphotericin B is an intravenous medication that is given only in hospitals because it requires close monitoring for side effects. Flucytosine and fluconazole are oral medications that a patient can take at home. Fluconazole is available in some areas of the world free of cost to governments through the Diflucan Partnership Program (Pfizer).

More information on the treatment of cryptococcal infection, including treatment for cryptococcal antigenemia as well as meningitis, can be found in the following documents:

• World Health Organization guidelines for the Diagnosis, Prevention, and Management of Cryptococcal Disease in HIV-Infected Adults, Adolescents, and Children
• South African Guidelines for the Prevention, Diagnosis, and Management of Cryptococcal Meningitis and Disseminated Cryptococcosis in HIV-infected patients
• Infectious Diseases Society of America Clinical Practice Guidelines for the Management of Cryptococcal Disease

It is not possible to prevent the initial infection with Cryptococcus because the fungal spores are common in the environment. However, cryptococcal infection can be detected and treated before it develops into life-threatening meningitis. Cryptococcal antigen can be detected in the blood weeks to months before the patient develops symptoms of disease. Patients who are found to have cryptococcal antigen in their body are much more likely to develop meningitis than those who do not, so the presence of cryptococcal antigen is highly predictive of the development of cryptococcosis. In addition, HIV-infected patients with low CD4 counts are more likely to test positive for cryptococcal antigen than patients with higher CD4 counts. Patients with low CD4 counts can be tested for cryptococcal antigen in their blood, and patients who test positive for the antigen can then be treated with antifungal medication (fluconazole) to prevent the infection from developing into meningitis.