新型隐球菌颅内感染101例临床特点及诊断

目的总结新型隐球菌颅内感染的临床特点及临床诊断。方法用临床病例分析统计方法,对101例确诊的新型隐球菌脑膜炎或脑炎患者的发病规律和临床特点进行归纳、分析。结果101例患者中95例(94.1%)为亚急性或慢性起病,85.0%以上的患者有头痛、发热,72例(71.3%)患者出现呕吐,另外意识障碍、精神异常、发作性抽搐、视力、听力损害也较常见。97例脑脊液涂片发现隐球菌;2例多次涂片阴性,隐球菌培养阳性;1例经脑实质穿刺活检病理确诊;1例小脑囊肿术后病理确诊。大部分病例确诊前被误诊为其他疾病。结论新型隐球菌颅内感染大多数以亚急性或慢性起病,临床表现、脑脊液常规、生化检查及头颅影像学检查均缺乏特异性。脑脊液或脑组织病原学检查发现隐球菌为诊断的金标准。     

Treatment of acute cryptococcal disease

Successful treatment outcome for cryptococcal disease has been available since the introduction of the polyene antifungal, amphotericin B. Over the past 15 - 20 years, treatment of acute cryptococcal disease has dramatically improved. Several therapeutic strategies have been introduced which improve overall outcome of therapy and help decrease the duration of treatment. Not surprisingly, most data now exists on the treatment of AIDS-associated cryptococcal disease, especially cryptococcal meningitis. Currently, amphotericin B with or without flucytosine is regarded as the best initial therapy for patients with meningitis or more severe illness, although, the azoles and other formulations of amphotericin B can considered in other situations. The choice of treatment for cryptococcal disease depends on both the anatomic sites of involvement and the host’s immune status, all of which will be addressed in this article.     

43例获得性免疫缺陷综合征合并隐球菌脑膜炎临床特点分析

目的：了解获得性免疫缺陷综合征(AIDS)合并隐球菌脑膜炎的临床特点、治疗及转归。方法观察大理州人民医院感染病科收治的43例 AIDS 合并隐球菌脑膜炎的临床特点、治疗及转归。结果发热38例,头痛43例,恶心呕吐16例,昏迷16例,抽搐12例,视觉障碍 8例,嗜睡22例,精神异常6例,脑膜刺激征41例、皮疹5例。不同程度存在 AIDS 相关表现。CD4<100个/μl,占88.4%(38/43)。脑脊液压力升高,白细胞升高,蛋白质升高,葡萄糖降低,病死率53.5%(23/43),且静脉吸毒感染者病死率高于异性性传播感染者(P <0.01),及时抗真菌治疗及适时高效抗逆转录病毒治疗(HAART)有效。结论 AIDS 并隐球菌脑膜炎患者临床表现复杂,无特异性,合并症多,病情重,病死率高,早期诊断,及时抗真菌治疗,适时 HAART 治疗是决定患者预后的主要因素,可降低病死率,提高生活质量,延长生命。     

非艾滋病相关隐球菌脑膜炎的预后因素分析

目的 探讨影响非艾滋病(AIDS)相关隐球菌脑膜炎(隐脑)的预后因素.方法 收集复旦大学附属华山医院感染科11年(1997至2007年)间收治的154例非MDS相关隐脑病例,并随访1年,分析影响其病死率的危险因素.结果 随访1年中,全因病死率为28.7%(41/143,11例失访),归因病死率为19.6%(28/143).单因素分析结果 显示,与全因病死率增加显著相关的因素包括年龄≥60岁、血液恶性肿瘤、实体恶性肿瘤、发病至确诊时间>4个月、病程中出现意识障碍(昏迷、癫痫发作、脑疝),以及行脑脊液脑室外引流或分流术等.与全因病死率减少显著相关的因素包括初始治疗方案中含有两性霉素B者、初始治疗方案中含有氟胞嘧啶者,以及两性霉素B鞘内注射者.Cox多元回归分析结果 显示,与全因病死独立相关的因素包括年龄≥60岁、发病至确诊时间>4个月、昏迷、脑疝,以及初始治疗方案不含两性霉素B者;与归因病死独立相关的因素包括发病至确诊时间>4个月、脑疝以及初始治疗方案不含两性霉索B者.结论 非AIDS相关隐脑患者中年龄≥60岁、意识障碍、发病至确诊时间>4个月者预后不佳,应用两性霉素B的初始治疗对预后改善起着关键性作用.     

27例隐球菌性脑膜炎患者的临床分析

目的探讨隐球菌性脑膜炎的临床特征,以提高该病的诊治水平及预后。 方法回顾性分析复旦大学附属华山医院收治的27例诊断为隐球菌性脑膜炎患者的临床资料。 结果88.89%（24例）隐球菌性脑膜炎患者以头痛为首发症状;脑脊液糖（1.81 ± 0.69 mmol/L）降低尤为显著;若并发颅神经损害,多累及视神经和听神经;头颅CT或MR可见脑缺血病灶（37.04%）及软脑膜不同程度强化灶（59.26%）;所有患者均有不同程度的颅内压增高,病原学脑脊液墨汁染色阳性患者22例（占81.48%）,隐球菌培养阳性患者20例（占74.07%）,荚膜多糖抗原检测（乳胶凝集试验）阳性占100%;两性霉素B（AmpB）联合5-氟胞嘧啶（5-FC）治愈好转率100%（17/17）,AmpB + 5-FC +氟康唑治疗的4例患者中好转3例。 结论隐球菌性脑膜炎早期误诊率较高,脑脊液墨汁染色、隐球菌乳胶凝集试验及培养有助于确诊;两性霉素B联合5-氟胞嘧啶仍是目前经典的抗真菌治疗方案,两性霉素B与伊曲康唑联合治疗方案有待大样本的临床验证;早期控制真菌及颅高压是改善预后关键,必要时可尽早外科干预。     

Sequestration of active Cryptococcus neoformans infection in the parathyroid gland despite prolonged therapy in a renal transplant recipient

Abstract: Disseminated cryptococcal infection occurs mainly in the immunocompromised host, particularly in those with impaired cellular immunity. The treatment outcome depends not only on the duration and choice of antifungal therapy, but also on the activity of the organism to persist in different parts of the body despite therapy. We present a case of persistence of cryptococcal infection in the parathyroid gland in a kidney transplant recipient. A 38-year-old male renal transplant recipient diagnosed to have disseminated cryptococcosis was treated with discontinuation of immunosuppression, amphotericin B, and flucytosine for 2 weeks, and fluconazole subsequently. Dialysis was initiated when graft function deteriorated after discontinuation of immunosuppression. The patient showed no clinical signs of active cryptococcal infection on fluconazole therapy. One year after the diagnosis of cryptococcosis, and still on fluconazole, he underwent parathyroidectomy, for severe secondary hyperparathyroidism. Surprisingly, active cryptococcal infection with necrotizing granulomatous inflammation was demonstrated in the parathyroid, despite being on therapy. This patient illustrates that persistence of fungal infection despite prolonged therapy can occur in unusual sites such as the parathyroid and may be a source for future recurrence and dissemination.     

氟康唑治疗隐球菌脑膜炎24例临床分析

目的 探讨氟康唑单用或联合氟胞嘧啶治疗非AIDS相关隐球菌脑膜炎(隐脑)的临床特征、疗效及转归.方法 回顾性分析复旦大学附属华山医院1997年至2007年间24例非AIDS相关隐脑病例(初始治疗均为氟康唑单用或联合氟胞嘧啶),观察其临床特点、疗效及转归.采用算术平均数和中位数进行统计学分析.结果 氟康唑治疗中位剂量为400 mg/d,中位疗程为20.5 d.初始治疗2周时,部分应答4例,占16.7%.无应答20例,占83.3%,有效率为16.7%,无死亡病例.治疗10周时,部分应答8例,占33.3%,完全应答7例,占29.2%,无应答4例,占16.7%,有效率为62.5%,死亡5例,占20.8%.病程中22例因疗效不佳而加用或改用两性霉索B、两性霉素B脂质分散体或伊曲康唑等.随访1年,24例中有11例死亡,其中8例死于隐脑,3例死于其他疾病.结论 对于非AIDS相关隐脑,以氟康唑单用或联合氟胞嘧啶作为初始治疗者疗效不佳,大部分息者因治疗失败而需改用其他抗真菌药物治疗,提示该方案不适用于非AIDS相关隐脑的初始治疗.     

隐球菌性脑膜炎患者颗粒溶素的表达及其临床意义

目的研究颗粒溶素（granulysin,GNLY）免疫效应分子在隐球菌性脑膜炎（cryptococcal meningitis）外周血单个核细胞中的表达及其临床意义。方法首先用密度梯度离心法分离得到25例隐球菌性脑膜炎患者和30例健康人外周血单个核细胞（PBMC）,其次用免疫印迹的方法检测其中的GNLY蛋白含量,用实时荧光定量（RFQ）-PCR方法测定其中GNLY的mRNA含量。并分析隐球菌性脑膜炎患者GNLY蛋白含量与一些免疫指标的相关性。结果与健康对照组比较,隐球菌性脑膜炎患者PBMC中GNLY蛋白含量（相对定量为正常对照组的0.56倍）和mRNA（相对定量为正常对照组的0.6倍）均明显降低（P〈0.01）。隐球菌性脑膜炎患者中GNLY蛋白表达水平与血清IgG水平成正相关（r=0.477,P〈0.05）。结论GNLY可能参与隐球菌性脑膜炎的疾病进程,这为探讨隐球菌性脑膜炎的病情监控和有效治疗提供了新的线索。     

Identification of Cryptococcus antigen in human immunodeficiency virus‐positive Turkish patients by using the Dynamiker® lateral flow assay

Cryptococcus neoformans causes life‐threatening meningoencephalitis, particularly in human immunodeficiency virus (HIV)‐positive individuals with low CD4 levels (<100 cells/μL). Although the burden of cryptococcal meningoencephalitis (CM) in Turkey is low (0.13 cases per 100 000 persons), asymptomatic individuals at risk of cryptococcosis should be screened for antigenemia to prevent the disease and/or promote early CM diagnosis. A lateral flow assay (LFA) is used to detect Cryptococcus antigen (CrAg) in cerebrospinal fluid and serum. We determined Cryptococcus antigenemia prevalence in serum samples of HIV‐positive and HIV‐negative adult patients by using Dynamiker® CrAg‐LFA, a point‐of‐care dipstick test. Patients’ demographic data, CD4 count, HIV‐RNA levels and anti‐retroviral therapy status were recorded. CrAg was detected in 28 (11%) of 254 HIV‐positive patients screened but not in 100 HIV‐negative control individuals; a significant difference was observed in the CrAg‐LFA positivity rate between HIV‐positive and HIV‐negative groups (x² = 11.970; P < .05). In CrAg‐positive patients, the median CD4 level was 666 cells/μL (115‐1344 cells/μL), with a median viral load of 23 copies/mL (0‐3.69 × 10⁶ copies/mL). In HIV‐positive CrAg‐negative patients, the median CD4 level was 633 cells/μL (31‐2953 cells/μL) and the median viral load was 12 copies/mL (0‐1.95 × 10⁶ copies/mL; P > .05). Results indicate that HIV‐positive patients with both low (<200 cells/μL) and high (>200 cells/μL) CD4 counts should be screened for asymptomatic cryptococcal antigenemia. HIV‐associated asymptomatic cryptococcosis is not uncommon in Turkey, which warrants systematic screening. Updated strategies for CM prevention among HIV‐positive patients should be used even in non‐endemic countries.