隐球菌性脑膜炎诊断与治疗进展

80年代以前,在发达国家新型隐球菌感染罕见,其主要发生在细胞介导的免疫功能不全的患者,如淋巴瘤或接受糖皮质激素及免疫抑制剂治疗的患者。然而,自从80年代初期发现艾滋病以来,隐球菌已成为HIV/AIDS患者的主要发病和死亡原因。在美国有5％～10％的AIDS患者感染隐球菌,该真菌也是脑膜炎最常见的原因之一。在我国由于糖皮     

艾滋病合并隐球菌脑膜炎18例临床分析

目的　提高对艾滋病 (AIDS)合并隐球菌脑膜炎的认识。方法　对赤道几内亚巴塔地区医院 18例AIDS合并隐球菌脑膜炎患者进行临床综合分析。结果　 18例AIDS合并隐球菌脑膜炎患者的临床主要表现为 :发热、剧烈头痛、极度乏力、肢体痛、脑膜刺激征及消瘦与脱水等。脑脊液 (CSF)培养均为新型隐球菌生长 ;涂片及隐球菌多糖荚膜抗原 (ELISA法 )检测的阳性率分别为 77 8% (14/ 18) ,94 4% (17/ 18)。结论　隐球菌脑膜炎为AIDS常见机会性感染及主要致死病因之一。     

AIDS并发新生隐球菌脑膜炎临床分析

目的通过对42例合并新生隐球菌脑膜炎的艾滋病（AIDS）病人随访与临床分析,探讨该病的临床特征和预后,提高对该病的再认识。方法阶段性回顾总结合并新生隐球菌脑膜炎的AIDS病人的临床资料和实验室资料,分析AIDS合并新生隐球菌脑膜炎病人的临床特征和预后。结果 42例AIDS病人合并新生隐球菌脑膜炎,发病率为3.54%（42/1188）,病死率21.43%。大多数病人合并多种机会性感染。结论 AIDS病人并发新生隐球菌脑膜炎临床表现多样,预后不佳。病原学检查是诊断新生隐球菌脑膜炎的主要依据,给予抗真菌药物是必要的治疗措施。     

人类免疫缺陷病毒阴性老年人新型隐球菌感染的危险因素

目的探讨人类免疫缺陷病毒(HIV)阴性老年人新型隐球菌感染的危险因素。方法回顾性分析259例HIV阴性老年新型隐球菌感染患者,应用Logistic回归分析新型隐球菌感染不同组织的危险因素。结果新型隐球菌性脑膜炎156例,肺炎132例,其中48例同时患有隐球菌性脑膜炎和肺炎,其他隐球菌感染患者19例。新型隐球菌脑膜炎组与新型隐球菌肺炎组之间呈相似的年龄和性别分布,基础疾病及潜在危险因素在两组中比例无显著差异。免疫抑制剂、肝硬化失代偿期和自身免疫病为新型隐球菌性脑膜炎的危险因素;免疫抑制剂、肝硬化失代偿期、糖尿病及自身免疫性疾病为新型隐球菌性肺炎的独立危险因素;免疫抑制剂及外伤为新型隐球菌皮肤感染的独立危险因素。结论免疫抑制剂、肝硬化失代偿期、自身免疫病、糖尿病及外伤为HIV阴性老年人侵袭性新型隐球菌病的危险因素。     

人获得性免疫缺陷综合症合并新型隐球菌脑膜炎1例

新型隐球菌性脑膜炎是由新型隐球菌(Cryptococcus neoformans)直接侵犯中枢神经系统引起的颅内感染,是临床最常见的深部真菌病之一.隐球菌属于条件致病菌,主要经呼吸道传播,在肺部仅引起轻度的炎症.艾滋病患者由于感染人类免疫缺陷病毒(HIV)因而引起严重的免疫抑制性临床综合征,造成患者由于机体免疫功能严重缺陷而经常并发各种致命性的机会性感染,其中并发隐球菌脑膜炎也较为常见,而临床上国内病例资料报告不多见. 由于HIV感染合并隐球菌性脑膜炎的临床表现复杂、疗程长、疗效差、复发率高,是目前临床治疗的难点之一.本研究旨在探讨5-氟胞嘧啶+两性霉素B治疗隐球菌性脑膜炎的可行性.现报告成功治疗1例人免疫缺陷性病毒(HIV)感染合并隐球菌脑膜炎患者.     

中国大陆艾滋病合并隐球菌感染临床Meta分析

新生和格特隐球菌是临床重要的机会致病真菌,感染多发生于免疫功能受损的患者.在国外主要见于AIDS人群,如在非洲的AIDS人群中,隐球菌病的发病率高达30％,且有隐球菌病暴发流行的报道[1].在我国,隐球菌病呈散发性,多数仍为外观健康的人群[2].近年来,随着AIDS、移植和肿瘤患者的增多,隐球菌病的发病率也呈上升趋势.根据2009年卫生部公布的数据,估计中国大陆目前存活HIV感染者和AIDS患者约74万,2009年新发HIV感染者4.8万,部分地区疫情严重.为了解隐球菌感染在我国大陆地区AIDS人群中的发病情况,本研究统计有AIDS合并隐球菌感染以来公开报道的有关隐球菌感染病例,进行归纳、分析,以了解该病在我国的临床及流行病学特点.     

HIV合并隐球菌脑膜炎的诊断策略

目的探讨HIV合并隐球菌脑膜炎的诊断策略。方法选择2011年3月—2013年7月武汉某医院感染科HIV合并隐球菌脑膜炎患者31例,选取同期非隐球菌脑膜炎患者17例。分别采用乳胶凝集试验、脑脊液墨汁染色和脑脊液培养检测标本,比较各种方法对隐球菌脑膜炎的诊断价值,并检测隐球菌脑膜炎患者CD+4T淋巴细胞。结果乳胶凝集试验检测血清和脑脊液隐球菌抗原的敏感度最高,为96.8%,脑脊液培养检测隐球菌的诊断符合率最高,为93.8%,患者CD+4T淋巴细胞均≤100个/μl。结论对CD+4T淋巴细胞≤100个/μl的HIV人群开展血清隐球菌抗原筛查,阳性患者进一步做脑脊液墨汁染色和真菌培养确诊,有助于隐球菌脑膜炎的早期诊断。     

AIDS并发隐球菌脑膜炎的诊断和治疗

隐球菌脑膜炎是AIDS患者常见的中枢神经系统机会性感染,病死率高,易复发。早期诊断本病对提高治愈率、改善预后至关重要。本文对AIDS并发隐球菌脑膜炎的病因、病原学诊断和治疗等方面的进展进行综述。     

未接受HAART的HIV/AIDS患者血清隐球菌抗原阳性率调查

目的调查未接受高效抗反转录病毒治疗(highly active antiretroviral therapy,HAART)的HIV/AIDS患者血清隐球菌抗原的阳性率。方法回顾性调查我院感染科2012年1—9月住院的77例未接受HAART的HIV/AIDS患者外周血CD4+T淋巴细胞计数及血清隐球菌抗原阳性率,比较隐球菌抗原阳性患者与阴性患者的CD4+T淋巴细胞计数。结果 77例(男53例,女24例)中,血清隐球菌抗原阳性48例,阳性率为62.34%,阴性29例,阴性率为37.66%。其中,CD4+T淋巴细胞计数≤50个/mm3的患者血清隐球菌抗原阳性率为72.73%。血清隐球菌抗原阳性患者外周血CD4+T淋巴细胞计数显著低于阴性患者(P=0.022)。结论未接受HAART的外周血CD4+T淋巴细胞计数较低的HIV/AIDS患者血清隐球菌抗原阳性率高,血清隐球菌抗原阳性患者CD4+T淋巴细胞水平低于阴性患者(P<0.05)。     

3例AIDS患者合并隐球菌脑膜炎

在晚期艾滋病(AIDS)患者并发的机会性感染中,真菌(包括念珠菌、酵母菌、隐球菌、曲菌、组织胞浆菌等)感染所占比例较高。现将上海市公共卫生中心感染科收治确诊的3例AIDS合并隐球菌脑膜炎患者的临床特点分析报告如下。1一般资料3例AIDS合并隐球菌脑膜炎患者为2003年1月至2004年     

The radiology of pulmonary cryptococcosis in a tertiary medical center.

Pulmonary cryptococcal infections occur in both immunocompetent and immunocompromised individuals, with a reported increased incidence of diffuse pulmonary disease in acquired immune deficiency syndrome (AIDS) patients. The authors observed no differences in the radiographic appearances of pulmonary cryptococcal disease between human immunodeficiency virus (HIV) patients and other immunocompromised individuals. Chest computed tomography (CT) contributes to a more comprehensive understanding of pulmonary cryptococcal infections.     

AIDS caused by HIV1 and HIV2 infection: are there clinical differences? Results of AIDS surveillance 1986–97 at Fann Hospital in Dakar,Senegal

OBJECTIVE: To compare the clinical manifestations observed in AIDS patients infected with HIV2 and HIV1 infection. METHODS: The medical records of AIDS patients hospitalized between January 1986 and July 1997 at the Department of Infectious Diseases of Fann Hospital, Dakar, were reviewed. RESULTS: 599 hospitalizations (76%) were HIV1 seropositive patients, 137 (17%) were HIV2 seropositive patients and 54 (7%) were patients serologically dually reactive to HIV1 and HIV2. There was no significant difference in medium CD4 lymphocyte count between patients with HIV1 and HIV2 infection. Chronic diarrhoea and diarrhoea caused by bacterial infections were more frequently observed in HIV2-infected individuals. Oral candidiasis and chronic fever were more often noted in patients with HIV1 infection. Bacterial and cryptococcal meningitis was only observed among patients with HIV1 infection. CONCLUSIONS: Certain clinical differences were observed comparing AIDS patients with HIV1 and those with HIV2 infection. As there is no clear physiopathological explanation for these differences, additional studies with larger numbers of AIDS patients are needed to determine whether these differences are real.     

HIV／AIDS首次住院患者机会感染特点及其与CD4之间的关系

目的探讨HIV／AIDS首次住院患者机会感染特点及其与CD4计数的关系。方法对123例首次住院HIV／AIDS患者进行回顾性分析,总结不同CD4水平患者机会感染发生情况。结果123例患者中共发生机会性感染101例（82．1％）。当CD4计数大于200个／ul时,感染率为40．7％（11／27）,100—200个／山时为85．7％（12／14）,50～100个／ul时为90．0％（18／20）,低于50个／山时为96．8％（60／62）。当CD4计数在100个／山以上时,以2个或以下部位感染为主,而低于100个／山时常发生2个或以上部位的感染。常见机会感染有肺孢菌肺炎、肺结核、消化道真菌感染、隐球菌性脑膜炎、弓形虫脑病、带状疱疹和败血症。结论HIV／AIDS首次住院患者机会感染发病率高,多种病原体和多部位感染常见,且随着CD4计数减少,机会感染的发病率、累及部位增加。     

Risk factors for cryptococcal meningitis in HIV-infected patients.

To identify the risk factors for cryptococcal meningitis in patients with HIV disease we conducted a nested case-control study of 37 incident cases of cryptococcal meningitis and 74 controls, identified from a cohort of more than 2000 HIV-infected patients. Conditional logistic regression was used to study demographic and AIDS-related variables in addition to fluconazole and steroid use. No difference in demographic variables, HIV risk factors, or stage of AIDS was detected between cases and controls. Exposure to fluconazole for more than 90 days reduced the risk of cryptococcal meningitis by 82% (OR=0.18; 95% CI=0.04-0.85; p=0.03). We did not find a difference in steroid use between cases and controls for either the length or amount of steroid exposure (p=0.41). No difference in survival during follow-up in the clinic was observed by the log-rank test (p=0.74). Among the cases, a cryptococcal antigen was positive in more than 97% of the CSF or blood samples. CSF and blood cultures were positive in 81 and 44% of the samples, respectively. We conclude that demographic factors did not affect the risk of cryptococcal meningitis in an inner city United States population. While fluconazole use has a protective effect, steroid use was not associated with an increased risk of cryptococcal meningitis in HIV-infected patients.     

The spectrum of human immunodeficiency virus infection in patients with factor IX deficiency (Christmas disease)

Early reports suggested that hemophiliacs with factor IX deficiency (Christmas Disease) may be at less risk for developing the acquired immunodeficiency syndrome (AIDS) than patients with classic hemophilia. We evaluated 12 factor IX deficient patients for clinical and immunologic abnormalities related to infection with the human immunodeficiency virus (HIV). Antibody to HIV was not detected in these patients prior to 1982. By 1985, 66 percent (eight of 12) patients were seropositive. All three concentrates available commercially before 1985 were associated with seropositivity. Furthermore, seropositive hemophiliacs had received on average significantly more factor IX concentrate than seronegative hemophiliacs (27,825 +/- 17,976 (S.D.) versus 1,250 +/- 1,500 factor units/year, (p less than 0.02). Half of the seropositive individuals had generalized lymphadenopathy with splenomegaly. Two seropositive patients have developed AIDS, one with cryptococcal meningitis and another with a large cell immunoblastic lymphoma. Infection with HIV has occurred with high frequency in hemophiliacs who received unmodified factor IX concentrates.     

A Retrospective Study of AIDS-Associated Cryptomeningitis

Abstract Cryptococcal meningitis has emerged as a leading cause of infectious morbidity and mortality in patients with AIDS. A retrospective analysis of records of HIV-infected individuals registered in the Immunodeficiency Clinic of a tertiary care hospital and research institute was carried out. Records of 6900 HIV-infected individuals who were enrolled in the clinic between January 2002 and March 2011 were analyzed. Records of 6900 HIV-infected individuals were screened. Ninety-one were diagnosed with cryptococcal meningitis (1.32%). In 68 individuals cryptococcal meningitis was the presenting illness. Nine patients developed meningitis within 6 months of starting antiretroviral treatment (ART). Six patients were receiving ART for more than 6 months at the time of diagnosis. The remaining eight patients were not on ART at the time of development of meningitis. The mean baseline CD4 count of patients was 77.7±61 (range, 4-259, n=91) cells/mm(3). Seventy-four patients had a CD4 value of less than 100 at the time of diagnosis of cryptococcal meningitis. Eleven of these ninety-one patients had a relapse of cryptococcal meningitis while receiving a maintenance dose of fluconazole. During follow-up 37 died, two were lost to follow-up, while 52 patients were on regular ART. Mortality due to cryptococcal meningitis amounted to 0.54% (37/6900). There was no correlation between survival and duration of ART at the time of cryptomeningitis (Pearsons χ(2)=0.241, p=0.884). There was a significant difference in the CD4 counts of the HIV-infected individuals who died with cryptomeningitis and those who survived (Pearson's χ(2)=9.1, df=4, p=0.05). The frequency of cryptococcal meningitis was 1.32%. Cryptococcal meningitis leads to high mortality in HIV patients. Management of cryptococcal infection remains a key facet of AIDS care in India.     

隐球菌性脑膜炎26例临床分析

目的 总结隐球菌性脑膜炎的资料,提高对隐球菌性脑膜炎的认识。方法 回顾性总结近20年（1981年10月至2001年9月）隐球菌性脑膜炎的一般资料,诊断及治疗情况。结果 共26例患者,其中男12例,女14例,年龄5－62岁,平均35．6岁,有基础疾病者16例,其中系统红斑狼疮（SLE）9例,人类免疫缺陷病毒感染或艾滋病（HIV／AIDS）4例,其他疾病3例;有明确鸽子接触史者12例;误诊结核性脑膜炎者5例,狼疮脑病者6例;墨汁染色找到隐球菌者23例（23／26）,乳胶凝集试验抗原阳性20例（20／20）。颅内压明显增高＞300mm H2O者15例,脑室扩大行侧脑室引流者9例;12例给予两性霉素B（AmpB) 5氟胞嘧啶,6例又同时加氟康唑治疗,5例AmpB 氟康唑,1例单纯应用AmpB治疗。AmpB最大用量：AmpB10.05g 脂质体两性霉素B20g,平均用量2.6g;治愈17例,好转4例,死亡或自动出院5例。同时发现近5年隐球菌性脑膜炎病例数明显增多。结论 近年来,隐球菌性脑膜炎发病率明显增高,可能和免疫抑制剂和糖皮质激素的应用及HIV／AIDS增多有关,减少病死的关键在于提高早期诊断率,治疗仍首选AmpB加5氟胞嘧啶,侧脑室引流可减少AmpB的用量,提高治愈率,缩短疗程。     

Cryptococcal immune reconstitution inflammatory syndrome: report of four cases in three patients and review of the literature

Immune reconstitution inflammatory syndromes (IRIS) in patients with AIDS are characterized by atypical manifestations of opportunistic pathogens in patients experiencing improvement in CD4 cell counts following receipt of highly active anti-retroviral therapy (HAART). We report four cases of IRIS due to Cryptococcus neoformans in three patients and review the literature of cryptococcal IRIS in AIDS (an additional 21 episodes). The IRIS presentation was lymphadenitis in all three patients; one patient also had meningeal IRIS. Combining our patients with the literature review revealed the following IRIS presentations: lymphadenitis (n=14), central nervous system (CNS) IRIS (n=10): meningitis in six and mass lesions in four, and pulmonary cavities (n=1). The median CD4 count of cases at the time of initial cryptococcal diagnosis and prior to the start of HAART was 25 cells/μl and the median HIV viral load was 439 053 copies/ml. At time of presentation of the IRIS, the median CD4 count had increased by 197 cells/μl. The median time from initial cryptococcal diagnosis and the start of HAART to the IRIS was 11 months (range 7 weeks to 3 years) and 7 months (range <2 weeks to 22 months), respectively. Patients with CNS IRIS tended to have shorter intervals from initiation of HAART to presentation compared to patients with lymphadenitis: median 3.5 months compared to 7 months. In 24 of 25 cases, the clinical manifestations of the IRIS resolved (range: days to months). Only four patients were given anti-inflammatory medications: corticosteroids in two and non-steroidal anti-inflammatory drugs in two, thus precluding assessment of efficacy. Patients with cryptococcal disease who initiate HAART are at risk for cryptococcal IRIS.     

348例HIV/AIDS病人血清隐球菌抗原筛查的结果分析

目的分析在艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人(简称HIV/AIDS病人)中,应用血清隐球菌抗原筛查隐球菌感染的结果,为开展相关研究提供依据。方法对2012年10月至2013年7月,在贵阳市第五人民医院住院的348例HIV/AIDS病人进行血清隐球菌抗原检查,同时检查病人的CD+4T淋巴细胞(简称CD4细胞)计数;对血清隐球菌抗原阳性病人进行血培养、脑脊液(CSF)隐球菌抗原检查、墨汁染色及培养。结果 348例病人中,男256例,女92例,年龄19~77岁,平均(40.50±13.05)岁。血清隐球菌抗原阳性34例,阳性率9.77%(34/348),CD4细胞计数为0~1097个/mm3,中位数56个/mm3。CD4细胞计数≤50个/mm3组146例,50个/mm3组202例。CD4细胞计数≤50个/mm3和50个/mm3组病人阳性例数分别为24例和10例,阳性率为16.44%(24/146)和4.95%(10/202),两组间差异有统计学意义(u=3.56,P0.01)。血清隐球菌抗原阳性病人血培养阳性3例,CSF隐球菌抗原阳性27例,墨汁染色阳性22例,CSF培养阳性15例;34例病人中最后确认隐球菌感染33例。所有诊断隐球菌感染的病人血清隐球菌抗原均为阳性。结论 HIV/AIDS病人血清隐球菌抗原阳性率高,血清隐球菌抗原筛查有助于及时诊断隐球菌病,特别是CD4细胞计数≤50个/mm3的病人,推荐普遍检查。