**2. Historical milestones for** *H. capsulatum* **and histoplasmosis**

The first description of the disease was made in December 1905 by the pathologist Samuel Taylor Darling, when examining smears of tissues and bone marrow from a young carpenter from Martinique, whose death was mistakenly attributed to acute miliary tuberculosis. Darling found an enormous number of small, oval, and round bodies, located in alveolar epithelial cells and in the plasma of the spleen and rib marrow, which he attributed to a parasite resembling to be closely related to Leishmania. He proposed the name *H. capsulatum*, because of the similarity of its halo with a capsule [21].

Only a few years later, in 1912, Henrique da Rocha Lima, inferring the mycotic nature of this pathogen, offered a correct depiction of the microorganism and recognized *H. capsulatum* as a fungus [22].

The first case diagnosed in humans with an acute disseminated form of histoplasmosis was that of a 6-year-old child who died in 1932 [23].

De Monbreun cultivated and described the fungus from blood cultures taken 2 days before death and from the spleen at autopsy, in 1934. Also, in 1939, a culture of *H. capsulatum* was isolated by the same De Monbreun from a case occurring in a dog. He noticed that primary isolated colonies contained both mycelial and yeast phases from the fungus and was able to convert the mycelial phase to the yeast-like one by inoculating susceptible animals. Ciferri and Radaelli managed to convert a strain of *H. capsulatum* to the yeast form by cultural methods, growing it on blood agar at 37°C [22].

In 1941, Zarafonetis and Lindberg prepared histoplasmin, which is a filtrate of a culture of *H. capsulatum*, in the mycelial phase [24]. On the African continent, histoplasmosis was first reported in 1942 by Duncan [25].

Four decades after it was first described, histoplasmosis was considered a rare, acute, and lethal disease, based on reported cases in the medical literature. Starting with 1945, this belief was contradicted by several investigators, arguing that, in fact, fatal cases were the exception rather than the rule, the infection occurring in certain areas of the USA, in an asymptomatic or benign form, rarely recognized clinically by physicians and being misdiagnosed as tuberculosis [26].

In 1945, Christie and Peterson were the first using histoplasmin in an epidemiological survey, which clearly demonstrated the correlation between pulmonary calcifications and histoplasmin sensitivity in tuberculin-negative persons [27].

Also in 1945, Palmer confirmed the existence of subclinical cases of histoplasmosis, which reacted positively to the histoplasmin skin test [28]. Only 1 year later, the same Palmer demonstrated that the highest frequency of histoplasmin reactors was discovered in the same area of the USA, where clinical cases of histoplasmosis had been repeatedly diagnosed [28].

Furcolow demonstrated in 1949 the development of asymptomatic, benign, pulmonary infiltrations, indistinguishable from tuberculosis, in a group of tuberculinnegative, histoplasmin-positive persons, using a series of chest radiographs over a three-year period [29].

In 1949, Emmons isolated macroconidia of *H. capsulatum* from soil samples, by examining saline suspension by direct microscopy and demonstrated that the fungus goes through a developmental saprophytic cycle in soil [30].

A first description as a new variant of Histoplasma was made by Vanbreuseghem in 1952, and, in honor of Professor Albert Dubois, who provided the isolates, the fungus was named *H. capsulatum* var. duboisii [31].

In 1969, Edwards and colleagues published the first map of histoplasmin skin reactivity in the USA, illustrating the endemicity of the disease primarily in the Ohio and Mississippi River valleys [32].

Kwon-Chung, in 1972, reported the observation of sexual reproduction of *H. capsulatum* [33] and, only a few months later, he stated that Emmonsiella capsulata is the teleomorph or sexual stage, resulting from the sexual compatibility + and – mating types of *H. capsulatum* (asexual stage or anamorph) [34].

In 2003, Hwang and his colleagues conducted the first large genomic study, which identified and compared genes that exhibit phase-specific patterns of expression in *H. capsulatum*, providing a more complete description of both the yeast and mycelial phases of the fungus [35].

Using the multilocus sequence typing (MLST) method, in 2003, Kasuga performed the first analysis across the global distribution of the Histoplasma species. He found intermixed isolates from the three variants of Histoplasma in multiple phylogenetic clades and refined the classification of the fungus by identifying eight phylogenetic clades of *H. capsulatum* [36].

*Epidemiology of Histoplasmosis DOI: http://dx.doi.org/10.5772/intechopen.110901*

In 2014, it was documented and reported transplacental transmission of *H. capsulatum* in a series of patients [37].

For the first time in the medical literature, cases of mixed infection with different mating types of Histoplasma were described in two patients living with HIV in 2019, in an endemic area of Brazil [38].

In 2022, *H. capsulatum* was first detected by molecular techniques in the soil and penguin excreta collected from the Antarctic Peninsula [39].

To guide research, development, and more robust public health actions, in October 2022 WHO developed the first fungal priority pathogens list (WHO FPPL) which included Histoplasma spp. in the high-priority group [40].
