Cryptococcosis

Definition

Cryptococcosis occurs most often in persons who are immunosuppressed, especially individuals who are infected with human immunodeficiency virus (HIV; see Chapter 358 ). Meningoencephalitis is the most common clinical manifestation, but the lungs and other organs can be involved as well.

Epidemiology

Before the widespread availability of antiretroviral therapy, cryptococcosis occurred in 5 to 10% of patients with acquired immunodeficiency syndrome (AIDS; Chapter 357 ), especially in patients whose CD4 counts were less than 50 cells/µL. Cryptococcosis is less commonly seen now in developed countries but remains very common in Africa, where it is estimated that the prevalence among HIV-infected patients is as high as 30%.

C. neoformans is seen worldwide. C. gattii is more restricted geographically, but its distribution has been increasing beyond Australia and Southeast Asia, where its ecologic niche is the eucalyptus tree, to Brazil, the Pacific Northwest, and other areas of North America. Other cryptococcal species rarely cause human disease.

In the non-AIDS population, cryptococcosis is a frequent opportunistic infection in patients who have received a solid organ transplant, have been treated with corticosteroids or other immunosuppressive therapies, or have underlying illnesses, such as malignancy, diabetes mellitus, renal failure, cirrhosis, or chronic pulmonary disease. Rare cases have been transmitted from infected solid organ donors to organ recipients. For some patients, the only risk factor appears to be older age, and approximately 20% of non-HIV patients who are infected with C. neoformans have no known underlying illness. By comparison, about 40 of cases of C. gattii are in apparently normal hosts.

Pathobiology

The organism is inhaled from the environment and initially causes pulmonary infection. The primary host defense at this stage is complement-dependent phagocytosis and killing by macrophages and neutrophils. Natural killer cells also have the ability to kill the organism. Ultimately, however, T-cell immunity is the most important host determinant in limiting the replication of C. neoformans . In most normal hosts, the infection remains localized to the lungs and does not cause symptomatic infection, but a few organisms likely exist as walled-off, subpleural granulomas in many individuals who have had pulmonary infection.

If the host becomes immunosuppressed, the organism can then reactivate and disseminate to other sites. C. neoformans is clearly neurotropic, and the primary disease manifestation is meningoencephalitis. However, dissemination to many organs is likely, especially in patients whose T-cell immunity is deficient.

Virulence factors for C. neoformans include the capsule, which requires opsonization for efficient phagocytosis, and the production of melanin, which enables the organism to resist intracellular killing. Both of these factors may help explain the virulence of the organism once it has reached the central nervous system (CNS). Antibody and complement levels are low in the brain, so phagocytosis of the organism is minimal. Brain tissue provides high concentrations of substrates, such as catecholamines, for the organism’s phenol oxidase enzyme systems that produce melanin, thereby aiding its survival.

Clinical Manifestations