播散性隐球菌病1例及其实验研究

目的 播散性隐球菌病1例临床及实验研究.方法 患者男,72岁,红皮病1年2个月,口服醋酸泼尼松治疗,双下肢出现结节、溃烂6个月.皮损组织病理、皮损组织真菌培养、尿素酶试验、PCR扩增测序比对明确诊断,同时做胸部及脑部CT.结果 皮损组织病理显示为感染肉芽肿改变,可见大量圆形和椭圆形酵母细胞.皮损组织真菌培养可见酵母样菌落生长,菌株尿素酶试验阳性,ITS区测序比对鉴定为新生隐球菌grubii变种.血清隐球菌荚膜多糖抗原乳胶凝集试验阳性(++++).胸部CT显示左下肺后基底段空洞性病灶.依据临床及实验室检查确诊为由新生隐球菌grubii变种引起的 播散性隐球菌病.给予患者静滴氟康唑400 mg/d治疗2周,之后改口服300 mg/d治疗,3个月后结节性皮损全部消退,胸片显示左肺陈旧性病变,血清隐球菌荚膜多糖抗原乳胶凝集试验阳性(++).治疗15个月后,血清隐球菌荚膜多糖抗原乳胶凝集试验仍阳性(++).结论 对该病例的临床和实验室研究为临床明确诊断和治疗提供了依据,确定菌种需要进行分子生物学研究.     

播散性隐球菌病1例并文献复习CSCD

目的报道1例播散性隐球菌病(disseminated cryptococcosis)及相关文献复习。方法回顾性分析1例播散性隐球菌病例,检索外文生物医学期刊整合系统、CHKD期刊全文数据库等近20a国内外报道的病例,结合文献复习总结播散性隐球菌病的临床特点。结果患者女,16岁,因"咳嗽、发热10余天"入院,既往有"特发性血小板减少性紫癜"并长期口服激素治疗。经腰椎穿刺术及血培养等确诊为播散性隐球菌病,抗真菌治疗后症状好转。数据库共检索148例播散性隐球菌病,免疫功能正常宿主59例,男95例,女53例,年龄2~77岁,儿童47例,死亡41例。结论播散性隐球菌病病死亡率高,应争取早期诊断和治疗,提高治愈率,减少致残率。     

肺隐球菌病的CT表现

肺隐球菌病（pulmonary cryptococcosis,PC）是一种较少见的肺部真菌病,由隐球菌感染而引起的一种亚急性或慢性的肺部真菌病。近年来肺隐球菌感染有增加的趋势,而临床表现及影像表现无特异性,常常容易误诊,为了提高对本病的认识,现收集2001年1月～2009年12月经病理证实的11例肺隐球菌病的CT及临床资料,以提高对肺部病灶的鉴别诊断能力。     

50例隐球菌血症的临床与预后分析

目的探讨不同免疫状态人群隐球菌血症的临床特点。方法对浙江大学医学院附属第一医院（2002年12月至2014年3月）50例隐球菌血症的临床资料进行回顾性分析,根据患者自身免疫情况分成免疫缺陷组（41例）和免疫健全组（9例）,对研究病例的性别、发病年龄、临床表现、实验室检查、抗真菌药物及疗效进行分析。结果 50例隐球菌血症中男性30例,女性20例,年龄15~83岁,平均（49±17.0）岁;43例有不同程度发热表现,性别、年龄、平均住院时间、临床表现、白细胞、中性粒细胞比例、C反应蛋白、尿素氮等在两组中差异无统计学意义,免疫缺陷组患者合并隐球菌性脑膜炎、同时合并隐球菌性脑膜炎及肺隐球菌病的病例高于免疫健全组。住院期间死亡10例,病情恶化13例,好转27例。结论隐球菌血症的临床表现不典型,免疫缺陷组较免疫健全组易引起隐球菌血症,免疫缺陷组更易合并隐球菌性脑膜炎及肺隐球菌病,隐球菌血症的预后差。     

肺隐球菌病12例临床分析

目的 提高对隐球菌病的认识.方法 对确诊为肺隐球菌病的12例病例的临床资料进行回顾性分析.结果 12例病例中,男性8例,女性4例,年龄31～68岁,平均年龄(51.8±12.6)岁,6例伴有基础疾病,但无1例有鸟类接触史;有临床症状者10例,其中咳嗽8例,咯痰3例,胸痛4例,发热2例,有体征者仅2例;胸部影像表现为:1...     

31例非获得性免疫缺陷综合征肺隐球菌病临床分析

目的通过研究非获得性免疫缺陷综合征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。方法回顾性分析2001年1月至2011年12月在南京医科大学附属杭州市第一人民医院确诊的31例非获得性免疫缺陷综合征肺隐球菌病患者的性别、年龄分布、职业情况、伴随的基础疾病、临床症状、实验室检查、影像学特征、治疗方案及预后等各方面特点。结果肺隐球菌病发病年龄有年轻化趋势,临床特点及影像学表现缺乏特异性,极易误诊及漏诊。治疗方法及药物少,病程长。结论肺隐球菌病虽然临床表现缺乏特异性,但从病例分析结果来看诊治该病仍有一定规律可循,亟需提高对本病的认识,遇到疑似病例应行血乳胶凝集试验及肺活检或手术病理予以明确,药物治疗需要足够疗程。     

浆细胞样树突状细胞在宿主抵御隐球菌肺部感染中的作用及机制研究进展

肺隐球菌病是由隐球菌感染引起的常见真菌病,由于症状的非特异性,临床上诊断较为困难。作为条件致病性真菌感染,肺隐球菌病的结局主要与宿主免疫力有关。目前肺隐球菌病免疫学发病机制研究主要局限在T细胞和巨噬细胞。近年研究表明,作为树突状细胞亚群之一的浆细胞样树突细胞,由于其激活后可以产生大量的I型干扰素并活化相关的T细胞,所以在机体抵抗病毒和细菌免疫中发挥着重要的作用。但是浆细胞样树突细胞在真菌病,尤其是在隐球菌病的发生发展中发挥的作用尚不明确。本文将介绍肺隐球菌病的临床表现、诊治及T细胞和巨噬细胞在肺隐球菌病中的免疫机制,并通过介绍肺隐球菌病和浆细胞样树突细胞及二者之间已有报道的联系,初步阐述浆细胞样树突细胞在肺隐球菌病免疫学发病机制中的相关作用。     

52例新型隐球菌脑膜炎临床分析

新型隐球菌脑膜炎（Cryptococal neoformans menimgitis）是新型隐球菌引起的隐球菌病（cryptocaccol）,约占新型隐球菌感染的77％～80％,其临床表现不典型,误诊率高,病死率高,早期诊断,合理联合使用抗真菌药物治疗是提高隐球菌脑膜炎治愈率,降低病死率的关键。现对浙江大学医学院附属第一医院感染科2000年1月至2007年11月收治的52例新型隐球菌脑膜炎临床资料作回顾性分析,报道如下。     

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。     

肺隐球菌病41例临床分析

目的总结分析41例肺隐球菌病患者的临床特点。方法回顾性分析我院(2003年1月～2006年10月)41例肺隐球菌病的临床、影像学表现,免疫学检查、病理及抗真菌治疗疗效。结果①41例肺隐球菌病,男28例,女13例,有基础疾病者18例,有临床症状者22例,影像学表现为结节肿块型27例,肺炎型8例,混合型6例。②有基础疾病的18例患者中有临床症状者15例;影像学表现为肺炎型8例,混合型4例,结节肿块型6例;并发隐球菌脑膜炎2例。无基础疾病患者23例,多无临床症状或临床症状较轻,多表现为结节肿块型(21例),无并发症,预后较好。③抗真菌药物治疗36例,治愈34例,好转2例(有效率100%)。都使用氟康唑治疗,疗程2周～2年不等。结论免疫功能正常的肺隐球菌病患者病变局限,多为结节肿块型,并发症少,预后好;免疫功能异常者多表现为肺炎型或混合型,易出现全身播散。肺隐球菌病单用氟康唑抗真菌治疗效果好,应为首选。     

不同免疫状态肺隐球菌病临床特点分析

目的总结国内不同免疫状态人群肺隐球菌病（Pulmonary cryptococcosis,PC）临床特点,以提高该病的临床诊治水平。方法回顾性分析1998～2009年上海多家教学医院的100例Pc患者临床资料。结果既往无基础疾病史者占46．00％。临床以咳嗽、咳痰、发热为主要首发症状。无症状者多见于非免疫受损患者。非免疫受损PC病灶以胸膜下分布为主（55．22％）,单肺累及占72．97％,病灶位于肺野局部者占59．46％,病灶形态以结节／肿块影为主（55．41％）;而免疫受损患者病灶表现多样化,分布广泛而随机。19例患者行经支气管镜肺活检（TBLB）,病理结果阳性14例（73．68％）。36例患者行经皮肺穿刺活检（PCNB）,病理阳性26例（72．22％）。结论既往无基础疾病不能排除Pc可能。非免疫受损Pc患者病灶多靠近胸膜,病变较局限,形态以结节／肿块影多见。免疫受损患者病灶表现多样化,分布广泛而随机。TBLB和PCNB诊断PC阳性率较高,且两者可互为补充。     

Comparison and Temporal Trends of Three Groups with Cryptococcosis: HIV-Infected, Solid Organ Transplant, and HIV-Negative/Non-Transplant

Background

The Infectious Disease Society of America (IDSA) 2010 Clinical Practice Guidelines for the management of cryptococcosis outlined three key populations at risk of disease: (1) HIV-infected, (2) transplant recipient, and (3) HIV-negative/non-transplant. However, direct comparisons of management, severity and outcomes of these groups have not been conducted.

Methodology/Principal Findings

Annual changes in frequency of cryptococcosis diagnoses, cryptococcosis-attributable mortality and mortality were captured. Differences examined between severe and non-severe disease within the context of the three groups included: demographics, symptoms, microbiology, clinical management and treatment. An average of nearly 15 patients per year presented at Duke University Medical Center (DUMC) with cryptococcosis. Out of 207 study patients, 86 (42%) were HIV-positive, 42 (20%) were transplant recipients, and 79 (38%) were HIV-negative/non-transplant. HIV-infected individuals had profound CD4 lymphocytopenia and a majority had elevated intracranial pressure. Transplant recipients commonly (38%) had renal dysfunction. Nearly one-quarter (24%) had their immunosuppressive regimens stopped or changed. The HIV-negative/non-transplant population reported longer duration of symptoms than HIV-positive or transplant recipients and 28% (22/79) had liver insufficiency or underlying hematological malignancies. HIV-positive and HIV-negative/non-transplant patients accounted for 89% of severe disease cryptococcosis-attributable deaths and 86% of all-cause mortality.

Conclusions/Significance

In this single-center study, the frequency of cryptococcosis did not change in the last two decades, although the underlying case mix shifted (fewer HIV-positive cases, stable transplant cases, more cases with neither). Cryptococcosis had a relatively uniform and informed treatment strategy, but disease-attributable mortality was still common.     

Pleuropulmonary manifestations of hepatic amebiasis.

Pleuropulmonary manifestations of hepatic amebiasis occurred in 30 patients; 18 (60%) presented with at least 1 pulmonary complaint and 10 (33%) had multiple pulmonary symptoms. In 14 patients (47%), abnormalities were found on examination of the chest. In 16 chest roentgenograms (53%), there was at least 1 abnormality: right-sided pleural effusion (9 patients) and elevated right hemidiaphragm (8 patients) were the most common. All patients were treated with metronidazole (Flagyl) and had resolution of the amebic liver abscess and pulmonary disease. Pleuropulmonary disease is a common complication of amebic liver abscess. The clinical presentation and chest roentgenograms are virtually diagnostic and obviate the need for invasive procedures to confirm the diagnosis. Pleuropulmonary disease resolves with amebicidal treatment of the hepatic abscess.     

35例肺隐球菌病临床分析

目的提高肺隐球菌病早期诊断与治疗的水平。方法对浙江大学医院附属第一医院2006年9月至2009年9月收治的35例病理确诊为肺隐球菌病患者的性别、年龄分布、职业情况、基础疾病、诱因、临床表现、实验室检查、影像学特征、治疗方案及预后特点等进行回顾性分析。结果患者以中青年男性为主,多数患者有基础疾病或诱因,临床症状相对轻微,其中40%无症状,一般实验室检查,气管镜检查及病原学检查阳性率极低,影像学表现以单发或多发结节肿块影为主(共占65.7%),氟康唑治疗3～9个月一般均能治愈,但亦有17.6%迁延不愈或无效者。结论中青年患者,无发热性肺部感染性病变,症状轻微,血象正常,血沉正常,痰细菌学检查阴性,考虑肺隐球菌病可能,尽早取得组织病理学依据,治疗首选氟康唑,疗程3～9个月,手术病理明确并病灶切除者,术后仍需常规应用氟康唑治疗。     

Cavitary pneumonia in an AIDS patient with cryptococcosis

Pulmonary cryptococcosis is an unusual fungal infection that is most often found in AIDS or in organ transplant recipients. Although in immunocompromised patients, cryptococcal infection often causes pulmonary infections, the diagnosis of lung involvement is generally difficult. The presentation of pulmonary cryptoccosis in HIV-infected patients appears to be more acute and severe than in other immunocompromised patients, probably related with the severe immunosuppression. Diffuse infiltrates, mediastinal and hilar lymph nodes enlargement are the most common radiological findings in AIDS-associated pulmonary cryptococcosis. Cavitation is a rare form of and includes only 10% to 15% of all cases. Only a few case reports or studies with small number of patients of pulmonary cryptococcosis have been published over the past two decades. We report a case of an AIDS patient who developed cavitary pneumonia as the only clinical expression of cryptococcosis.     

Opportunistic invasive mycoses in AIDS. An autopsy study of 211 cases.

The opportunistic mycoses are an important cause of morbidity-mortality among patients with severe immunosuppression provoked by HIV. We present a study of 211 serial autopsies of patients with HIV/AIDS infection carried out by our service in a period of 10 years, observing frequency of invasive mycoses of the 44.1%. Pneumocystis carinii infection was the most frequent (32%) with a prevalence of lung affection. Candidiasis follows it in order of frequency with 31.1%, predominantly the oropharyngeal manifestation. Systemic or cerebromeningeal cryptococcosis were serious and common disorder (29%). Diseminated histoplasmosis occurred in 9.6% and in three cases (3.2%) pulmonary aspergillosis was diagnosed as a postmortem discovery in cavity lesions. In our series, other less common HIV-associated were not identified.     

Pulmonary cryptococcosis: A rare but emerging disease

Pulmonary cryptococcosis occurs primarily in immunocompromised hosts as an isolated infection or as a precursor to disseminated disease. Recent studies indicate that patients with isolated pulmonary cryptococcosis may be asymptomatic or, if symptomatic, will often have very low serum cryptococcal antigen, distinguishing them from patients with disseminated disease. Amphotericin B plus flucytosine is the initial treatment for disseminated cryptococcosis or severe symptomatic pulmonary cryptococcosis, followed by fluconazole once symptoms have improved. Fluconazole is recommended for asymptomatic or mild disease. Targeted immunotherapies and vaccines are being studied and offer exciting new prevention and treatment strategies.     

The Eiken Latex test for detection of a cryptococcal antigen in cryptococcosis

A latex agglutination test for cryptococcal antigen, the Eiken Latex test (Eiken, Tokyo, Japan), was compared with a monoclonal antibody-based agglutination assay, Pastorex^® Cryptococcus (Diagnostics Pasteur, Marneur-la-Coquette, France). In a murine model of disseminated cryptococcosis, the kinetics of the antigen titers by the Eiken Latex were similar to those by the Pastorex^® Cryptococcus, but sensitivity was much higher. In HIV-negative patients with pulmonary cryptococcosis, a cryptococcal antigen was detected in 6 of 10 patients by the Eiken Latex test and in only 3 of those patients by the Pastorex^® Cryptococcus. The results indicate that the Eiken Latex is more sensitive for the detection of the cryptococcal antigen, even in non-disseminated cryptococcosis. The sensitivity and specificity of the Eiken Latex were examined using 195 sera from 25 patients with pulmonary cryptococcosis and 170 patients with non-cryptococcosis. The cutoff value of 1:8 showed a sensitivity of 76% (19/25) and a specificity of 98.9% (168/170).     

Survey of Cryptococcus neoformans in the respiratory tract of patients with bronchopulmonary disorders and in the air.

Cryptococcus neoformans was cultured from 9 (1%) of 835 clinical specimens examined from the respiratory tract of patients. These isolations came from 3 (0.4%) of the760 patients; 8 isolates were from sputum and one from urine. The fungus was not demonstrable in the air at a selected site during a 2-year study although other species of Cryptococcus, namely, C. albidus, C. ater, C. flavus, C. laurentii, C. magnus, C. terreus and C. uniguttulatus were isolated. The three C. neoformans positive patients were males, with pulmonary tuberculosis as the primary disease and history of repeated exposure to pigeon excreta in two. None of these patients manifested any overt signs and symptoms specificially attributable to cryptococcosis, nor did they receive any antifungal therapy. Repeated isolations of C. neoformans from sputum, a positive urine culture and demonstration of cryptococcal antibodies in a serum specimen, followed by negative cultures and serology, suggested that patient 1 had spontaneously recovered from an episode of benign, minimal pulmonary cryptococcosis. Patients 2 and 3 probably carried the fungus as a transient resident of the respiratory tract. The results suggest that C. neoformans is of uncommon occurrence in the respiratory tract of patients with bronchopulmonary disorders and that the isolation of the fungus from this site may not necessarily imply an etiologic relationship.