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.     

隐球菌性脑炎患者颗粒酶B、颗粒溶素、穿孔素的表达及临床意义

目的研究颗粒酶B（grmazymeB,GrB）、颗粒溶素（granulysin,GNLY）及穿孔素（pefforin,又称pore-formingpro—tein,PFP）三种免疫效应分子在隐球菌性脑膜炎（cryptococcalmeningitis）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（peripheral blood monotmclearcells,PBMC）,其次用免疫印迹（western blot）的方法检测其中的GrB、GNLY、及PFP的蛋白含量,用实时荧光定量（RVQ）-PCR方法测定其中GrB、GNLY、及PFP的mRNA含量。并分析隐球菌性脑膜炎患者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、PFP蛋白含量和mRNA均明显降低,而GrB无明显变化。隐球菌性脑膜炎患者中GNLY蛋白表达水平与血清IgG、IFN-γ水平成正相关（r=0．477,P〈0．05;r=0．534,P〈0．05）,与IL-10水平成负相关（r=-0．505,P〈0．05）。结论GNLY、PFP）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。     

The Optic Nerve Compartment Syndrome in Cryptococcus-Induced Visual Loss

Abstract

Visual loss in cryptococcal meningitis has been postulated to be due to papilloedema and/or optic neuritis. A 28-year-old human immunodeficiency virus (HIV)-positive female presented with visual loss, swollen optic discs, and elevated intracranial pressure due to cryptococcal meningitis. Computerised tomographic cisternography and T2-weighted magnetic resonance imaging showed occlusion of the peri-optic subarachnoid space and its reopening after serial lumbar punctures. Presumably lowering of the intracranial pressure resulted in equalisation of pressure across the pressure gradient created by the fungal block. This case supports a third mechanism of visual loss in cryptococcal meningitis, namely, an optic nerve compartment syndrome, that seems more plausible as the principal mechanism.     

胶体金免疫层析法和乳胶凝集试验检测隐球菌荚膜多糖抗原对艾滋病继发隐球菌感染的诊断价值

目的 探讨胶体金免疫层析法(LFA)和乳胶凝集试验(LA)检测隐球菌荚膜多糖抗原对艾滋病患者继发隐球菌感染的诊断价值及治疗观察的临床意义.方法 采用LFA和LA对艾滋病患者继发隐球菌感染治疗前后的脑脊液标本和血清标本行隐球菌荚膜多糖抗原检测,并与脑脊液墨汁染色和真菌培养进行比较,评价其诊断的灵敏度和特异度.同时动态观察治疗期间隐球菌荚膜多糖抗原滴度的变化,和LFA的干扰因素.结果 LFA和LA对脑脊液标本隐球菌检测的敏感度分别为97.73%和95.45%,血清标本的敏感度也分别为97.73%、95.45%;对脑脊液标本的特异性分别为95.83%、95.83%,对血清标本的特异性分别为89.39%和87.12%.艾滋病继发隐球菌感染患者脑脊液标本中的隐球菌荚膜多糖抗原滴度随着患者病情的好转而逐渐下降,治疗前后脑脊液和血清中荚膜抗原滴度差异均有统计学意义(t=6.309,P<0.001;t=6.814,P<0.001).结论 LFA与LA适用于隐球菌脑膜脑炎患者的快速诊断;脑脊液隐球菌多糖荚膜抗原的动态监测对艾滋病患者继发隐球菌感染的疗效观察具有重要的参考价值.     

新型隐球菌性脑膜炎与结核性脑膜炎的诊断与鉴别诊断

目的 总结分析新型隐球菌性脑膜炎(CNM)与结核性脑膜炎(TBM)的临床特点,以提高CNM与TBM诊断与鉴别诊断水平。方法 搜集2016年1月至2017年12月成都市公共卫生临床医疗中心收治的CNM患者32例(CNM组)及同期收治的TBM患者171例(TBM组),对两组患者的一般资料(年龄、性别、生活区域、是否并发免疫功能低下)、临床症状(头痛、发热、呕吐、呼吸道症状、抽搐、脑膜刺激征及病理征)、脑脊液(CSF)实验室检查指标(CSF压力、细胞数、淋巴细胞百分比、蛋白、葡萄糖)、头颅CT检查(正常、脑水肿、脑积液、脑实质结节样改变、多发软化灶)情况进行对比分析。结果 TBM组患者年龄为(39.23±12.77)岁,高于CNM组患者[(28.71±11.29)岁],差异有统计学意义(t=4.35,P=0.000);TBM组患者呼吸道症状、抽搐、头颅CT检查提示脑实质结节样改变及多发软化灶发生率分别为94.74%(162/171)、35.09%(60/171)、41.52%(71/171)、38.01%(65/171),均明显高于CNM组患者[分别为34.38%(11/32)、15.62%(5/32)、6.25%(2/32)、9.38%(3/32)],差异均有统计学意义(χ ²值分别为73.26、4.69、13.07、8.68,P值分别为0.000、0.030、0.000、0.003);CNM组患者免疫功能低下(包括并发HIV感染、尿糖病,接受器官移植,长期口服糖皮质激素或免疫抑制剂等)和头颅CT检查提示脑水肿改变发生率分别为34.38%(11/32)、46.88%(15/32),均高于TBM组患者[分别为18.13%(31/171)、25.15%(43/171)],差异均有统计学意义(χ ²值分别为4.34、6.24,P值分别为0.037、0.013);CSF实验室检查中,TBM组患者CSF细胞数[中位数(M)(四分位数;Q₁,Q₃)]、蛋白[M(Q₁,Q₃)]、葡萄糖含量分别为208.00(178.00,240.00)×10 ⁶/L、1058.00(940.00,1204.00)mg/L、(1.77±0.79)mmol/L,均明显高于CNM组患者[分别为64.50(51.00,81.00)×10 ⁶/L、764.00(608.00,894.50)mg/L、(0.25±0.17)mmol/L],差异均有统计学意义(Z=-76.77,P=0.000;Z=-6.83,P=0.000;t=10.82,P=0.000);CNM组患者CSF压力为[(273.42±71.58)mm H₂O(1mm H₂O=0.098kPa)],明显高于TBM组患者[(214.22±88.38)mm H₂O],差异有统计学意义(t=3.57,P=0.000)。结论 CNM患者并发免疫功能低下和头颅CT提示脑水肿改变的比率高于TBM患者,而在呼吸道及抽搐症状的发生、头颅CT提示脑实质结节样改变、多发软化灶等发生的比率均低于TBM患者。     

腰大池和脑室外引流术在艾滋病合并隐球菌性脑膜炎患者颅内高压治疗中的应用

目的探讨腰大池和脑室外引流术对获得性免疫缺陷综合征(亦称艾滋病)合并隐球菌性脑膜炎患者颅内高压的治疗效果。方法共138例隐球菌性脑膜炎合并颅内高压患者[人类免疫缺陷病毒(HIV)阳性36例、HIV阴性102例],抗隐球菌治疗的同时,76例行腰大池引流术、改良腰大池引流术或脑室外引流术(HIV阳性17例、HIV阴性59例),62例行腰椎穿刺鞘内给药(HIV阳性19例、HIV阴性43例),比较引流组与鞘内给药组以及两组HIV阳性亚组与HIV阴性亚组患者引流管留置时间、脑脊液隐球菌培养转阴时间、并发症情况,并进行疗效评价。结果引流组患者治疗1周内颅内高压症状即明显改善。首次引流管置管中位时间30(17,35)d,其中HIV阳性者与HIV阴性者差异无统计学意义[28(15,32)d对30(18,35)d;U=-1.459,P=0.144]。引流组脑脊液隐球菌培养转阴中位时间41(26,58)d,其中HIV阳性者与HIV阴性者差异无统计学意义[46(28,66)d对36(21,45)d;U=-1.608,P=0.108];鞘内给药组脑脊液隐球菌培养转阴中位时间42(32,65)d,其中HIV阳性者与HIV阴性者差异无统计学意义[52(38,68)d对39(30,62)d;U=-0.401,P=0.688];而引流组与鞘内给药组差异有统计学意义(U=-2.117,P=0.034)。引流组治疗总有效率为86.84%(66/76),其中HIV阳性者与HIV阴性者差异无统计学意义[14/17对89.83%(53/59);χ~2=0.172,P=0.678];鞘内给药组为72.58%(45/62),其中HIV阳性者与HIV阴性者差异无统计学意义[8/19对86.05%(37/43);χ~2=0.023,P=0.880];而引流组与鞘内给药组差异有统计学意义(χ~2=4.413,P=0.036)。结论早期采用腰大池或脑室外引流术治疗艾滋病合并隐球菌性脑膜炎患者能够有效控制颅内高压、缩短有症状病程、提高临床疗效。     

隐球菌荚膜抗原胶体金免疫层析法在非HIV患者隐球菌脑膜炎诊断中的价值

目的探讨隐球菌荚膜抗原胶体金免疫层析法在非HIV患者隐球菌脑膜炎中的诊断价值。方法回顾性分析2013-2018年复旦大学附属华山医院3627例疑似中枢神经系统感染的住院患者的临床资料,收集符合隐球菌脑膜炎初诊的患者214例,分析各检验结果对隐球菌脑膜炎的诊断价值。结果隐球菌脑膜炎患者多数表现为脑脊液糖和氯化物水平显著下降,蛋白含量增高,白细胞增多且以单核细胞为主,脑脊液真菌镜检和培养的阳性率分别为75.23%和78.04%,脑脊液隐球菌胶体金免疫层析法检测阳性率高达100%。隐球菌脑膜炎患者随治疗时间的推移,脑脊液和血的隐球菌荚膜抗原滴度逐渐下降。结论胶体金免疫层析法适用于非HIV患者隐球菌脑膜炎的快速诊断,灵敏度高、特异性强,对隐球菌肺炎的患者能提前筛查是否有中枢神经系统感染,对荚膜抗原的动态监测有助于隐球菌病治疗疗效的观察。     

Sensitivity and specificity of an index for the diagnosis of TB meningitis in patients in an urban teaching hospital in Malawi

Tuberculous (TB) meningitis is difficult to diagnose and has a high mortality rate, particularly when presentation is delayed. A diagnostic index developed in Vietnam, an area of low-HIV seroprevalence, has been proposed as a means to differentiate TB meningitis from acute bacterial meningitis using clinical and laboratory features. We applied this index over a 4-month period to adults presenting with meningitis to an urban teaching hospital in Malawi, where HIV seroprevalence is 70% among medical inpatients. Eighty-five consecutive eligible patients were studied. Nine had TB meningitis, 64 bacterial meningitis and 12 cryptococcal meningitis. The sensitivity of the diagnostic index for predicting TB meningitis was 78%, with a specificity of 43%, too low to be used in the diagnosis of TB meningitis in this setting. This finding is likely to be generalizable to other southern African countries with similarly high-HIV seroprevalences.     

A multicentre, randomized, double-blind, placebo-controlled trial of primary cryptococcal meningitis prophylaxis in HIV-infected patients with severe immune deficiency

OBJECTIVES: To assess the efficacy and survival benefit of low-dose fluconazole (400 mg weekly) for primary prophylaxis for cryptococcal meningitis in patients with advanced HIV infection. METHODS: A prospective multicentre, randomized, double-blind, placebo-controlled study was carried out in HIV-infected patients with CD4 counts <100 cells/microL. RESULTS: Of 90 patients enrolled, 44 received fluconazole and 46 received placebo. The baseline characteristics were similar in the two groups. On an intent-to-treat basis, 10 cases of cryptococcal meningitis developed, three (6.8%) in the fluconazole group and seven (15.2%) in the placebo group. Patients in the placebo group were more likely to develop cryptococcal meningitis than those in the fluconazole group [hazard ratio=2.23; 95% confidence interval (CI): 0.58-8.63; P=0.245]. The survival benefit of fluconazole was greater than that of the placebo. The number of deaths per 10 000 person-days was 2.7 for the fluconazole group (2/7342) and 11.7 for the placebo group (9/7713) (rate difference=9; 95% CI: 0.4-17.5; P=0.046). Based on survival analysis, patients in the placebo group were 4.3 times more likely to die than those in the fluconazole group (95% CI: 0.9-19.8; P=0.065). CONCLUSION: Fluconazole 400 mg once weekly for primary prophylaxis for cryptococcal meningitis in Thailand should be considered in HIV-infected patients, as our study suggested a survival benefit. However, a larger study should be conducted to confirm our findings.     

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.