Abstract
Cryptococcal disease remains a significant source of global morbidity and mortality for people living with HIV, especially in resource-limited settings. The recently updated estimate of cryptococcal disease revealed a global incidence of 223,100 cases annually with 73% of these cases being diagnosed in sub-Saharan Africa. Furthermore, 75% of the estimated 181,100 deaths associated with cryptococcal disease occur in sub-Saharan Africa. Point-of-care diagnostic assays have revolutionised the diagnosis of this deadly opportunistic infection. The theory of asymptomatic cryptococcal antigenaemia as a forerunner to symptomatic meningitis and death has been conclusively proven. Thus, cryptococcal antigenaemia screening coupled with pre-emptive antifungal therapy has been demonstrated as a cost-effective strategy with survival benefits and has been incorporated into HIV national guidelines in several countries. However, this is yet to be implemented in a number of other high HIV burden countries. Flucytosine-based combination therapy during the induction phase is associated with improved survival, faster cerebrospinal fluid sterilisation and fewer relapses. Flucytosine, however, is unavailable in many parts of the world. Studies are ongoing on the efficacy of shorter regimens of amphotericin B. Early diagnosis, proactive antifungal therapy with concurrent management of raised intracranial pressure creates the potential to markedly reduce mortality associated with this disease.
Highlights
The pathogenic encapsulated yeasts in the genus Cryptococcus remains one of the most important opportunistic fungal pathogens worldwide [1]
Lipid formulations of amphotericin B can be used in place of conventional amphotericin B and are less nephrotoxic, not more effective. They are preferred for cryptococcal meningitis in patients who are immunosuppressed through organ transplantation, who do not tolerate conventional amphotericin B well
Recent data from a phase II randomized controlled non-inferiority trial from Tanzania showed that single dose 10 mg/kg of liposomal amphotericin B is well-tolerated with a non-inferior early fungicidal activity (EFA) compared to 14-day courses of 3 mg/kg liposomal amphotericin B in the treatment of HIV-associated cryptococcal meningitis [59]
Summary
The pathogenic encapsulated yeasts in the genus Cryptococcus remains one of the most important opportunistic fungal pathogens worldwide [1]. Cryptococcosis is associated with very high morbidity and mortality both in immunocompetent and immunocompromised patients [2]. Cryptococcus neoformans, which predominantly affects immunocompromised patients, and Cryptococcus gattii, which can infect both immunocompetent and immunocompromised individuals, are the two major. J. Fungi 2017, 3, 67 environment [3]. Disseminated Cryptococcus neoformans infection is largely seen in individuals with advanced HIV infection (CD4 < 200 cells/μL); it is an AIDS defining disease accounting for up 15% of AIDS-related death globally and even higher (20–50%) in resource limited settings [4,5,6,7]
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