Histoplasmosis is a worldwide distributed systemic mycosis that frequently affects people living with HIV/AIDS and other immunocompromised hosts. In Brazil, the incidence of histoplasmosis has been reported through the observation of clinical cases, micro-epidemics or through the conduct of epidemiological surveys using the skin test with histoplasmin. Histoplasmosis represents the third cause of death from systemic mycosis in Brazil. It was also observed that the region of Brazil most affected by the disease is the southeast region. In addition, the presence of H. capsulatum has already been reported in densely populated areas such as São Paulo and Rio de Janeiro.
Histoplasma spp. is an intracellular pathogen. The pathogenic cells or yeast morphotype produce factors that allow it to parasitize or invade phagocytic cells, which include macrophages, neutrophils and dendritic cells, and which in turn serve not only as host cells but also as vectors of dissemination. Recent studies have shown that different factors produced by Histoplasma spp. allow it to evade the innate immune system and facilitate its intracellular proliferation and subsequent dissemination.
Histoplasmosis has a high mortality rate in these patients if treatment with itraconazole or amphotericin B is unsuccessful. These drugs can have severe pharmacokinetic drug interactions and toxicity. This study will evaluate three drug collections provided free of charge by the Medicines for Malaria Venture (www.mmv.org), which contain, in total, 1,040 different substances with putative activity against infectious and neglected diseases, as well as their vectors. Importantly, these drugs have already been approved for human use. The pathogen box has 400 compounds with proposed action against tuberculosis, malaria, kinetoplastids, helminths, toxoplasmosis, dengue, cryptosporidiosis and some reference compounds. The pandemic response box has 400 drug-like molecules with proposed action against bacteria, viruses
