# Cryptococcus: History, Epidemiology and Immune Evasion
## 3 First Historical Aspects of _Cryptococcus_ spp.  
The discovery of the _C. gattii_ fungus was carried out after several attempts to classify other species of the same genus throughout the years. It started in 1894 in Germany, when the pathologist [PERSON] and the surgeon [PERSON] isolated a yeast similar to _Saccharomyces_ from a bone infection in a patient, calling it \"_Saccharomyces hominis_\". Later in the same year in Italy, [PERSON] isolated a similar yeast from peach juice ferment and named it _Saccharomyces neoformans_ because of its peculiar colony formation [3; 13]. In 1901, in France, [PERSON] would give new nomenclatures to these yeasts, as they did not form asospores, which are clusters of spores within a single mother cell called an ascus [14], and did not ferment carbohydrates, both hallmarks of _Saccharomyces_. Thus, the yeast discovered by [PERSON] was named _Cryptococcus hominis_ and that of [PERSON] was renamed _Cryptococcus neoformans_. It was only in 1950 that [PERSON] in the United States would recommend the definitive nomenclature for the species (_C. neoformans_), which would be adopted in later works [15]. In the same year, [PERSON] and authors, for the first time, described an antigenic feature of the fungus in three specific serotypes: A, B and C [16]; only in 1968, [PERSON] described a fourth serotype, D [3]. Decades later, based on agglutination reactions of the capsular constituents of the fungus, the complex of species of _Cryptococcus neoformans_ could be divided into serotypes A, D and hybrid AD, with serotype A corresponding to the _grubii_ variant, whereas _C. gattii_ has distinguishing serotypes B and C [17; 18]. In addition to this classification, the division can also be made from DNA polymorphisms found in these species. In this way, the species _C. neoformans_ of serotype A, known as _C. neoformans_ variant _grubii_, can be divided into molecular types VNI, VNII and VNB, the latter referring to a specific variant [19], and serotype D, known as _C. neoformans_ variant _neoformans_ with molecular type VNIIV and the hybrid of the two serotypes AD with molecular type VNIII [17]. _C. gattii_ has a B serotype with the most common variants VGI and VGII and C serotype with VGIII and VGIV [20]. Although the characterization studies were carried out at the beginning of the century and since then, this pathogen has been known to cause disease in humans [13], _C. neoformans_ became more important at the end of the 20 th century with the AIDS crisis, where it was responsible for a large part of the morbidity in these patients. Recent data show that about 181,000 deaths from cryptococcal meningitis are recorded annually [21]. _C. gattii_ infections are more frequent in tropical and subtropical regions and even though their incidence has increased globally over the last few decades, they do not comprise the highest incidence globally, with about 80% of cases being caused by _C. neoformans_. However, _C. gattii_ is responsible for more severe cases of the disease [3], with studies suggesting these cases may be underdiagnosed, either because the tests used rely on cryptococcal serum antigen, which is very hard to detect in cases of localized pulmonary cryptococcosis, or are unable to discriminate between different species of _Cryptococcus_[22; 23].