Cryptococcosis: From Discovering the Natural Reservoir of its Etiology to the Genetic Manipulation of Cryptococcus neoformans: Milestones in Cryptococcal Research by Intramural Investigators at NIAID

Abstract

Cryptococcosis is one of the most serious fungal infection encountered worldwide. The etiologic agent is Cryptococcus neoformans, an environmental yeast species which initiates the infection after inhalation of the organism by the host. Although C. neoformans can cause lesions in almost every organ, the most common clinical manifestation, as well as the most common cause of death, is meningoencephalitis, an infection of the brain. Untreated cryptococcal meningoencephalitis is fatal, and death can result in as little as two weeks from the onset of symptoms or the symptoms may last for up to 13 years before death [1]. Despite the most advanced medical treatment, the fatality rate for cryptococcosis is close to 25% [1]. While cryptococcosis sporadically occurs in normal populations without any underlying condition, the disease primarily affects immunocompromised individuals, especially those with T-lymphocyte depletion or dysfunction such as is the case with HIV-1 patients. In fact, cryptococcosis was designated as the AIDS-defining opportunistic infection, as the HIV-1 epidemic became widely known since the mid 1980s. Infections with C. neoformans have significantly declined in the developed world as a result of antiretroviral therapy that has reduced the reservoir of immunosuppressed HIV-1 infected patient. However, due to an explosion of AIDS-associated cryptococcosis cases in developing countries, the disease still causes 780,000 deaths in the world annually [2].