Content area
Full text
Received Mar 19, 2018; Revised Apr 22, 2018; Accepted May 8, 2018
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
Cryptococcosis is a fungal infection that occurs worldwide. Despite the predominant result of opportunistic infections of immunocompromised patients, the incidence of infections among immunocompetent individuals is increasing [1–4]. Recently, studies have shown that cryptococcosis is a neglected tropical disease, although it is not recognized as such by the World Health Organization [5, 6]. Some factors that contributed to this conclusion included high mortality rates in treated patients (ranging from 20 to 60%) that can reach 100% in untreated patients [6].
Despite the importance of this disease, the treatment of cryptococcosis is limited to the antifungals fluconazole and amphotericin B, which are used alone or in combination with 5-flucytosine [7]. The primary etiological agents of cryptococcosis are species of the complexes Cryptococcus neoformans and C. gattii [8], which respond differently to the treatment established for meningoencephalitis [9]. C. gattii is not only more clinically aggressive but also more difficult to control. Species of the C. gattii complex can compromise immunocompetent individuals and cause severe diseases of the central nervous system, such as meningitis, encephalitis, and meningoencephalitis [9]. In addition, lesions and long-term sequelae more commonly result from infections caused by species of the C. gattii complex than those caused by species of the C. neoformans complex [10]. Despite this disparity in symptoms, studies on possible new antifungals are primarily aimed at C. neoformans [11].
Species of the C. gattii complex have some attributes that can hinder antifungal therapy, such as heteroresistance to fluconazole [12]. In these cases, the treatment is limited to amphotericin B, which, although efficient, is highly toxic [13]. Another factor that can hinder antifungal therapies is the polysaccharide capsule, which, particularly for C. gattii, helps fungi escape the immune system [14] and decreases their susceptibility to antifungal agents [15]. In addition, the ability to form biofilms on host cells or medical devices, which is also promoted by the capsule, is a major factor associated with the high resistance of Cryptococcus spp. to antifungal drugs and host defense...