肾移植术后隐球菌性脑膜炎的临床分析

目的 分析肾移植术后隐球菌性脑膜炎的临床特点,以期提高临床医生的诊治水平.方法 回顾性分析肾移植术后隐球菌性脑膜炎的临床表现、实验室检查和治疗预后.结果 4例患者中,男2例,女2例,全部为首次同种异体肾移植.所有患者均有发热和头痛症状,多表现为轻度头痛和低热.3例患者隐球菌涂片和培养均为阳性.所有患者分别给予两性霉素B脂质体、伏立康唑、5-氟胞嘧啶等抗真菌治疗,其中1例合并两性霉素B鞘内注射.经2～4个月治疗后,4例隐球菌涂片转阴,临床症状消失,均在我院随访,至今未复发.结论 肾移植术后隐球菌性脑膜炎首发症状隐匿,临床表现不典型,极易误诊漏诊.早期明确诊断、多科室协作、规范足量治疗是提高此病救治成功的关键.     

艾滋病合并新生隐球菌感染的研究进展

新生隐球菌感染是全世界艾滋病患者死亡的主要原因,尤其是在撒哈拉以南非洲地区发病率最高[1]。新生隐球菌除了容易感染HIV个体外,还易感染其他免疫功能低下的个体,如造血系统恶性肿瘤、器官移植后服用免疫抑制剂及免疫缺陷病患者。格特隐球菌主要侵犯免疫功能正常的个体,但也感染免疫功能低下患者如合并艾滋病毒的患者[2]。     

1982至2020年中国肾移植受者合并隐球菌病的系统分析

隐球菌病是威胁肾移植患者生命的严重感染性疾病,本文旨在报道我国肾移植患者合并隐球菌病(cryptococcosis in kidney transplant patients,C-KT)的情况.通过对208例患者的资料进行分析,发现隐球菌病平均发病时间为肾移植后(5.48±4.09)年,就诊时间为发病后(27.28±3...     

播散性隐球菌病1例

我们在临床工作中遇到1例播散性隐球菌病患者，现报道如下。     

55例社区获得性肺隐球菌病病例分析

本文旨在通过研究社区获得性肺隐球菌病的临床特点,提高医务人员对肺隐球菌病的认识,做到早期诊断和治疗.采用回顾性病例分析研究,统计2003年1月~2009年12月入住复旦大学附属中山医院的55例确诊及临床诊断为肺隐球菌病患者的临床资料.55例患者中,男性34例,女性21例;年龄17~75岁,平均(44.8±13.4)岁....     

新生隐球菌感染与细胞因子的相互关系

新生隐球菌是重要的条件致病真菌,可导致免疫抑制患者产生致命的新生隐球菌性脑膜炎;继而在脑部损伤部位有多种细胞因子的表达和炎症细胞的浸润,形成了一个细胞因子网络,介导一系列致病机制和防御机制的产生。为明确细胞因子与新生隐球菌在致病和防御过程中的相互作用,本文就新生隐球菌与细胞因子的关系进行综述。     

肝肾移植术后患者隐球菌感染的临床特征分析

目的研究肝、肾移植术后患者隐球菌感染的临床特征。方法选取2010年1月到2015年7月来浙江大学医学院附属第一医院就诊的肝、肾移植术后并确诊为隐球菌感染的患者,对其临床特征进行回顾性分析。结果研究周期内有23例患者符合入组要求,其中肾移植术后21例、肝移植术后2例。对23例患者进行分析,发现单纯隐球菌肺炎6例(占26.0%)、单纯隐球菌性脑膜炎6例(占26.0%)、隐球菌性脑膜炎合并隐球菌肺炎8例(占34.7%)、隐球菌败血症2例(占8.6%),皮肤隐球菌感染1例(占4.3%)。所有隐球菌肺炎均经肺穿刺病理确诊,临床表现以发热,咳嗽咳痰,气急症状居多。胸部CT表现为结节、空洞、肿块、渗出等。所有隐球菌脑膜炎患者中9例经脑脊液培养出新生隐球菌、7例脑脊液墨汁染色见隐球菌,其中3例培养及涂片均为阳性。临床表现以头痛、发热、呕吐症状居多,1例并发癫痫,1例并发意识障碍。所有患者分别给予氟康唑、两性霉素B、氟胞嘧啶针、伏立康唑等抗真菌治疗,其中3例隐球菌脑膜炎患者予两性霉素B鞘内注射。经1~6个月治疗后,总体预后情况良好(好转22例,死亡1例)。结论肝、肾移植术后患者因免疫抑制剂的长期使用,隐球菌感染值得重视,其临床症状不典型,易误诊及漏诊,通过对其主要症状及影像学特点判断,结合肺穿刺活检、脑脊液检查、血培养等检查手段,可明显提高隐球菌感染的检出率,从而做到早诊断,早治疗,降低病死率。     

隐球菌感染诊治专家共识

1简介 隐球菌属在真菌分类学上归人半知菌亚门、芽孢菌纲、隐球酵母目、隐球酵母科,引起人类感染的隐球菌主要是新生隐球菌和格特隐球菌。两种隐球菌的无性繁殖体均为无菌丝的单芽孢酵母样菌,在体外为无荚膜或仅有小荚膜,进入人体内后很快形成厚荚膜,有荚膜的隐球菌菌体直径明显增加,致病力明显增强。     

以皮下结节为首发表现的播散性隐球菌感染1例

报道1例系统性红斑狼疮合并干燥综合征患者出现以皮下结节为首发表现播散性隐球菌感染。患者,女,50岁,以双下肢皮下结节、头痛为主要症状,血培养、脑脊液培养出新生隐球菌,皮肤活检病理可见大量均一、透亮的小圆形菌体真菌孢子浸润,PAS(+)、六胺银(+)。诊断为播散性隐球菌感染。先后使用两性霉素B、氟康唑、两性霉素B脂质体、氟胞嘧啶治疗1个月后症状好转。     

Cryptococcosis in Colombian children and literature review

Cryptococcosis is reported in adults and is often acquired immune deficiency syndrome (AIDS)-associated; however, its frequency in children is low. Based on the National Survey on Cryptococcosis conducted in Colombia, an epidemiological and clinical analysis was performed on cases of the disease observed in children less than 16 years old between 1993-2010. We found 41 affected children (2.6% prevalence) from the 1,578 surveys received. The country mean annual incidence rate was 0.017 cases/100,000 children under 16 years, while in Norte de Santander the incidence rate was 0.122 cases/100,000 (p < 0.0001). The average age of infected children was 8.4 and 58.5% were male. In 46.3% of cases, a risk factor was not identified, while 24.4% had AIDS. The most frequent clinical manifestations were headache (78.1%), fever (68.8%), nausea and vomiting (65.6%), confusion (50%) and meningeal signs (37.5%). Meningitis was the most frequent clinical presentation (87.8%). Amphotericin B was given to 93.5% of patients as an initial treatment. Positive microbiological identification was accomplished by India ink (94.7%), latex in cerebrospinal fluid (100%) and culture (89.5%). Out of 34 isolates studied, Cryptococcus neoformans var. grubii (VNI 85.3%, VNII 8.8%) was isolated in 94.1% of cases and Cryptococcus gattii (VGII) was isolated in 5.9% of cases. These data are complemented by a literature review, which overall suggests that cryptococcosis in children is an unusual event worldwide.     

Cryptococcosis of the nasopharynx in mice and rats

Summary An attempt to infect the upper respiratory tract of mice and rats with various bacteria and fungi by intranasally instillation was performed. Cryptococcus neoformans was the only agent to invade the tissue. The infection was limited to the nasopharynx, a phenomenon which probably indicates the presence of a specific chemotaxis or receptor.Dedicated to Prof. W. Kaplan, DVM, MPH     

Effects of melanin upon susceptibility of Cryptococcus to antifungals

Melanin is a recognized virulence factor in Cryptococcus neoformans; several pathogenetic mechanisms have been suggested. We studied melanin as an antifungal resistance factor. The growth of laccase-active strains of C. neoformans and C. albidus in L-DOPA resulted in the production of black pigment. The formal minimal inhibitory concentrations (MICs) of amphotericin B and fluconazole were not changed by melanization. However, when we examined those wells which contained inhibited cells, we found live cells only in wells containing melanized C. neoformans. In contrast, melanization did not protect C. albidus from killing by amphotericin B. In an amphotericin B time-kill study of C. neoformans, significantly more melanized cells than non-melanized survived for the first few hours. Fluorescence microscopy and flow cytometry analyses showed that fewer melanized cells were stained with the fluorescent dye MitoRed. Incubation of MitoRed (the model) or amphotericin B with melanin extracted from C. neoformans decreased the free concentrations of these substances. Fluconazole, in contrast, was not removed from solution by melanin. This suggests that neoformans cryptococcal melanin deposited amphotericin B in the cell wall binds, reducing its effective concentrations.     

Cryptococcus neoformans varieties as agents of cryptococcosis in Brazil

The study of the clinical isolates of Cryptococcus neoformans from 83 Brazilian patients with disseminated cryptococcosis showed that 75 were C. neoformans var. neoformans and 8 were var. gattii. Twenty-seven isolates were serotyped; all 19 var. neoformans were serotype A and all 8 var. gattii were serotype B. The correlation of the varieties of C. neoformans with the presence or not of hosts predisposing conditions to the mycosis showed that: (1) cryptococcosis caused by gattii variety occurred in 7 (58.3%) of the 12 nonimmunosuppressed patients, and (2) cryptococcosis caused by neoformans variety occurred in 65 (98.5%) of the 66 AIDS patients and in all 5 patients with other immunosuppressive conditions. The comparison of the distribution of the gattii and neoformans varieties between the nonimmunosup-pressed and immunosuppressed patients showed a significant statistical difference (p < 0.01).     

Th1-Th2 cytokine kinetics in the bronchoalveolar lavage fluid of mice infected with Cryptococcus neoformans of different virulences

Th1 immune response plays an important role in protection against infection with Cryptococcus neoformans in mice. We investigated the effect of virulence of C. neoformans on cytokine production in the lung of a mouse model of pulmonary cryptococcosis. BALB/c mice were inoculated intratracheally with a high or low virulence strain of C. neoformans, followed by serial measurements of Th1 and Th2 cytokine concentrations in the bronchoalveolar lavage (BAL) fluid using appropriate enzyme-linked immunosorbent assay kits. The number of colony-forming units (CFU) increased with time, and all mice infected with the highly virulent strain were dead at 28 days after inoculation. In contrast, the number of microorganisms diminished with time in the mice infected with the low virulence strain during the 4-week study. The numbers of neutrophils and lymphocytes in the BAL fluid paralleled those of CFU. High neutrophil counts were observed in the BAL fluid of mice infected with the highly virulent strain, while lymphocyte counts were increased only in the later part of the study in mice infected with the high and low virulence strains. The concentrations of Th2 cytokine, interleukin (IL)-4 were significantly higher in mice infected with the highly virulent strain at days 14 and 21 of infection, whereas the level of Th1 cytokine, interferon-gamma, was significantly higher in the latter strain at days 7 and 14. Our results suggest that strain-specific difference in the organism's ability to induce (or evade) the host immune system contributes to the outcome of infection.     

Different Susceptibility of Three Clinically Isolated Strains of Cryptococcus neoformans to the Fungicidal Effects of Reactive Nitrogen and Oxygen Intermediates: Possible Relationships with Virulence

We investigated the susceptibility of three clinically isolated strains of Cryptococcus neoformans with different virulences to reactive nitrogen and oxygen intermediates (RNI and ROI, respectively), representing two important mediators of macrophage microbicidal activity. All mice infected with the highly virulent strain of C. neoformans, YC-11, died within 3 to 6 weeks because of rapid multiplication of the organism in the lungs and dissemination to the brain. In contrast, a weakly virulent strain, YC-13, was almost completely eradicated from the lungs and did not disseminate to the brain, leading to survival of all infected animals during the period of observation (15 weeks). The virulence of the third strain, YC-5, was intermediate between the other two strains. To examine the susceptibility of C. neoformans to the fungicidal effect of nitric oxide (NO) and superoxide anions (O₂-), the organisms were exposed to these oxidants, which were chemically generated in a cell-free system. Interestingly, the number of live YC-13 yeast cells was markedly reduced after exposure to NO and O₂^?. In contrast, YC-11 was almost completely resistant to the killing effect of these oxidants. YC-5 showed an intermediate susceptibility. Our results demonstrate that the resistance of C. neoformans to the fungicidal effects of RNI and ROI is related to virulence, and suggest that the resistance to nitrogen- and oxygen-derived oxidants may be one of the factors to determine the outcome of infection with C. neoformans.     

Recovery of Cryptococcus neoformans from the nasopharynx of AIDS patients

Nasopharyngeal swabbings, obtained from AIDS patients, were plated onto Niger seed agar containing antibiotics. Cryptococcus neoformans was isolated from 35 out of 84 patients (41.7%) diagnosed as primary cryptococcal cases before antifungal administration, and 8 out of 86 (9.3%) cryptococcosis patients on antifungal therapy. The fungus could not be isolated from any of 447 samples from 194 AIDS patients not diagnosed with cryptococcosis. These findings are novel in that the presence of C. neoformans in AIDS patients at this site has never been looked at previously. This revised version was published online in June 2006 with corrections to the Cover Date.     

老龄活体供肾研究新进展

本文主要从老龄供肾优缺点分析,老龄供肾特征性改变情况分析,老龄供肾移植后功能变化分析,老龄供肾必须遵循的法律与伦理标准,取肾原则及疗效评估等多层次阐述了国内外老龄供肾在肾移植手术中的新进展,同时对其发展瓶颈与前景进行了剖析。