Cryptococcus neoformans, which is found worldwide as a soil organism and thought to be transmitted by inhalation, most often causes disease in patients with abnormal cell-mediated immunity, notably patients with human immunodeficiency virus (HIV) infection and solid organ transplant recipients, but the infection also occurs rarely in apparently immunocompetent persons. It is the most common systemic fungal infection in patients infected with HIV. It is estimated that over 1 million cases of invasive cryptococcal infection occur annually in patients with acquired immunodeficiency syndrome (AIDS) worldwide with more than 600 000 deaths each year. Most of these cases occur in resource-poor settings, especially in sub-Saharan Africa. With the advent of effective antiretroviral therapy (ART), cryptococcal infections have become much less common in the United States.

Two varieties of C. neoformans exist, distinguishable by serology: C. neoformans var. neoformans (serotypes A and D) and C. neoformans var. gattii (serotypes B and C). Virtually all HIV-associated infection is caused by C. neoformans var. neoformans. C. neoformans var. gattii is endemic in Australia and recent outbreaks of C. neoformans var. gattii infection have occurred in the Pacific northwestern parts of North America.

PRESENTATION AND DIAGNOSIS

The most common manifestation of cryptococcal infection is meningitis. Most patients develop insidious features of a subacute meningitis or meningoencephalitis, with fever, malaise, and headache, and are generally symptomatic for at least 2 to 4 weeks before presentation. In patients with a more subacute or chronic course, mental status changes such as forgetfulness and coma can also be seen. Classic meningeal symptoms and signs such as stiff neck and photophobia occur in only about one-quarter to one-third of all patients and generally are less likely to occur in HIV-positive patients. The typical pattern in the cerebrospinal fluid (CSF) is chronic meningitis with a lymphocytic pleocytosis.