Abstract
Cryptococcosis is considered endemic in Amazonas state, occurring more frequently in individuals with AIDS, who are predominantly infected by Cryptococcus neoformans molecular type VNI. Infections by Cryptococcus gattii VGII predominate in immunocompetent hosts from the American continent and are associated with outbreaks in North America, particularly the subtypes VGIIa and VGIIb, which are also present in the Brazilian Amazon region. Despite few environmental studies, several aspects of the molecular epidemiology of this disease in Amazonas remain unclear, including the limited use of multilocus sequence typing (MLST) to evaluate the genetic population structure of clinical isolates, mainly C. neoformans. Therefore, we used MLST to identify the sequence types of 38 clinical isolates of C. neoformans VNI and C. gattii VGII and used phylogenetic analysis to evaluate their genetic relationship to global isolates. Records of 30 patients were analyzed to describe the current scenario of cryptococcosis in the region and their associations with the different subtypes. Broth microdilution was also performed to determine the susceptibility profile to the antifungals amphotericin B, fluconazole and itraconazole. MLST identified that patients with HIV (n = 26) were exclusively affected by VNI strains with ST93, and among the VGII strains (n = 4), three STs (ST5, ST172 and the new ST445) were identified. An in-hospital lethality of 54% was observed in the HIV group, and there were no significant differences in the clinical aspects of the disease between the HIV and non-HIV groups of patients. In addition, all isolates were susceptible to the antifungals tested. Therefore, in Amazonas state, VNI isolates are a genetically monotypic group, with ST93 being highly important in HIV individuals.
Highlights
Cryptococcosis is a systemic, cosmopolitan and primary opportunistic infection associated with human immunodeficiency virus (HIV), representing an important public health problem [1,2,3,4]
HIV infection was reported for 26 patients (87%), of which 17 (74%) presented CD4+ T-cell counts below 50 mm3/ml, and all were affected only by C. neoformans VNI
C. neoformans VNI strains from Amazonas are a genetically monotypic group that commonly presented as ST93, but further whole genome analysis should be performed to confirm this genetic homogeneity
Summary
Cryptococcosis is a systemic, cosmopolitan and primary opportunistic infection associated with human immunodeficiency virus (HIV), representing an important public health problem [1,2,3,4]. Both the pathogens Cryptococcus neoformans and Cryptococcus gattii constitute species complexes widely distributed in the environment, mainly associated with bird feces and wood debris [5,6,7,8,9]. Data from the literature and the Brazilian Ministry of Health revealed that approximately 7,000 cases of cryptococcal meningoencephalitis are diagnosed annually, mainly in the southeast region, of which 90% occur in patients with AIDS, whose death rate associated with cryptococcosis is approximately 35–40% [15,16]
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