In the decades preceding the AIDS epidemic, the reported incidence of cryptococcal infection saw a dramatic increase (Fraser et al 1979). This increase was seen with other mycotic infections as well and was attributed to increasing numbers of persons with immunosuppressive conditions, migration of susceptible persons into hyperendemic areas, and aging of the population (Fraser et al 1979). With the advent of the AIDS epidemic in the 1980s, the incidence of cryptococcal infection, in particular cryptococcal meningitis, increased even more (Kovacs et al 1985; Eng 1986; Minamoto and Rosenberg 1997). Between 5% and 15% of untreated patients with AIDS in certain areas of the world will develop C neoformans disease during the course of their illness (Taelman et al 1991; Currie and Casadevall 1994). However, following the introduction of highly active antiretroviral therapeutic regimens, the incidence of cryptococcal meningitis has declined significantly in the HIV-infected population in western countries (Sacktor et al 2001). However, this has not been a universal experience. For instance, in China, cryptococcal meningitis is the most common opportunistic infection in AIDS and is a significant cause of mortality (Wang and Carm 2001). Cryptococcal meningitis may herald AIDS and occur in individuals not otherwise suspected to be HIV infected (Berger et al 1987; Giberson and Kalyan-Raman 1987). An epidemiological study from inpatient databases of 18 states in the United States identified 30,840 hospitalizations coded for cryptococcal meningitis (Pyrgos et al 2013). Only 21.6% of these cases occurred in HIV-uninfected persons.
Not unexpectedly, cryptococcal meningitis also occurs with increased frequency in a variety of other immunosuppressive conditions. For instance, it is a significant cause of morbidity and mortality in organ transplant recipients. In a study from the University of Pittsburgh, a major organ transplant center, the incidence of cryptococcal meningitis among transplant recipients was 0.5% (28/5521) (Wu et al 2002). The greatest risk for development was among heart transplant recipients at 2.1% (8/372); however, the greatest mortality with the disease was in liver transplant recipients (Wu et al 2002). Sarcoidosis (Ross and Katz 2002) and idiopathic CD4 lymphopenia (Sancesario et al 2011) are other risk factors for cryptococcal meningitis. Cryptococcal meningitis has been reported in a multiple sclerosis patient on natalizumab (Valenzuela et al 2014).
Individuals without any recognized immunological deficiency continue to account for a substantial proportion of CNS cryptococcosis. In one study, immunocompetent persons comprised 43.5% of all the cases (Lui 2006). In comparison to the immunocompromised group, immunocompetent individuals had a higher incidence of cryptococcal meningitis, lower rates of fungemia, and lower mortality (Lui 2006).