Infection with the yeast, Cryptococcus neoformans, is usually, although not always, a consequence of underlying immune compromise. Prior to the 1980s, infection was rare. Up to half of cases of cryptococcal disease were associated with lymphomas, and many other patients with cryptococcosis received corticosteroid therapy before the onset of the infection. Currently, the most common form of immunologic predisposition to cryptococcal infection is advanced infection with the human immunodeficiency virus (HIV) in patients with extremely low CD4+ lymphocyte counts. Since the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic, cryptococcosis has emerged as a major cause of morbidity and mortality in persons infected, affecting between 5% and 10% of all AIDS patients in the United States at the peak of the epidemic in the mid-1990s. With the use of potent antiretroviral therapy (ART) for the treatment of HIV infection and the widespread use of the azole antifungals, the incidence of invasive cryptococcosis in the HIV-infected population has declined but has not disappeared. Indeed, in resource-poor settings cryptococcal meningitis is the second most common opportunistic infection in AIDS (after tuberculosis) and a leading cause of mortality.

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.