Cryptococcosis is a life-threatening fungal infection caused by the Cryptococcus neoformans/Cryptococcus gattii species complex. Most cases are recorded in patients suffering from HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome). However, this infection also occurs in non-HIV patients with a proportion of 10-30% of all cases. The study aimed at the clinical and molecular characterization of non-HIV patients diagnosed with cryptococcosis at the Tropical Medicine Foundation (FMT-HVD) from July 2016 to June 2019. Medical records of respective patients were analyzed to describe the course of cryptococcosis in non-HIV patients. In addition, multi-locus sequence typing (MLST) was applied to identify the sequence types of the isolated Cryptococcus strains, to perform phylogenetic analysis, and to evaluate the isolates' genetic relationship to global reference strains. Antifungal susceptibility profiles to amphotericin B, fluconazole, and itraconazole were assessed by broth microdilution. From a total of 7 patients, 4 were female, the age range varied between 10 and 53 years (median of 36.3 years). Cryptococcal meningitis was the common clinical manifestation (100%). The period between onset of symptoms and confirmed diagnosis ranged from 15 to 730 days (mean value of 172.9 days), and the observed mortality was 57.1%. Of note, comorbidities of the assessed cryptococcosis patients comprised hypertension, diabetes mellitus, and intestinal tuberculosis. Genotyping applying PCR-RFLP of the URA5 gene identified all clinical isolates as C. gattii genotype VGII. Using MLST, it was possible to discriminate the sequence types ST20 (n = 4), ST5 (n = 3), and the newly identified sequence type ST560 (n = 1). The antifungals amphotericin B, fluconazole, and itraconazole showed satisfactory inhibitory activity (microdilution test) against all C. gattii VGII strains.

中文翻译：

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巴西北部亚马孙州非 HIV 患者的隐球菌脑膜炎

隐球菌病是由新型隐球菌/加蒂隐球菌复合体引起的危及生命的真菌感染。大多数病例记录在患有 HIV/AIDS（人类免疫缺陷病毒/获得性免疫缺陷综合征）的患者中。然而，这种感染也发生在非 HIV 患者中，占所有病例的 10-30%。该研究旨在对 2016 年 7 月至 2019 年 6 月在热带医学基金会 (FMT-HVD) 诊断为隐球菌病的非 HIV 患者进行临床和分子表征。分析各个患者的病历以描述非 HIV 患者的隐球菌病病程。艾滋病患者。此外，应用多位点序列分型（MLST）来鉴定分离的隐球菌菌株的序列类型，进行系统发育分析，并评估分离株的 与全球参考菌株的遗传关系。通过肉汤微量稀释评估了对两性霉素 B、氟康唑和伊曲康唑的抗真菌敏感性。共有 7 名患者，其中 4 名为女性，年龄范围在 10 至 53 岁之间（中位数为 36.3 岁）。隐球菌性脑膜炎是常见的临床表现（100%）。从出现症状到确诊的间隔时间为 15 至 730 天（平均值为 172.9 天），观察到的死亡率为 57.1%。值得注意的是，评估的隐球菌病患者的合并症包括高血压、糖尿病和肠结核。应用 URA5 基因的 PCR-RFLP 的基因分型将所有临床分离株鉴定为 C. gattii 基因型 VGII。使用 MLST，可以区分序列类型 ST20 (n = 4)、ST5 (n = 3)、和新识别的序列类型 ST560 (n = 1)。抗真菌剂两性霉素 B、氟康唑和伊曲康唑对所有 C. gattii VGII 菌株均显示出令人满意的抑制活性（微量稀释试验）。