Toll样受体对临床常见侵袭性真菌识别作用的研究进展

近年来,由于免疫受损患者的增加,真菌病的发病率日益增高,一些严重的侵袭性真菌病如不及时诊治可迅速致死,如念珠菌病、烟曲霉病、马内菲青霉病、隐球菌病等。固有免疫是机体抗感染的第一道防线,机体抵抗入侵病原真菌的第一步就是通过病原识别受体（Pathogen Recognition Receptors,PRR）对其进行识别以启动固有免疫。TLRs（Toll-like receptors）是抗感染免疫中最重要的PRR之一。目前固有免疫在侵袭性真菌发病过程中的重要作用日益受到重视,TLRs作为固有免疫阶段的主要受体,了解其对侵袭性真菌的识别作用将有助于深入理解固有免疫在抗真菌感染免疫中的作用,对认识临床真菌病的发病机制具有重要意义。现将近几年研究情况综述如下。     

ICU常见机会性真菌感染CSCD

重症监护室(ICU)收治的患者多数都有免疫功能受损,是真菌感染的易感人群,这类人群发生真菌感染后病情严重,预后较差。ICU常见的机会性真菌感染有念珠菌、曲霉菌、隐球菌、马尔尼菲蓝状菌和组织胞浆菌等,主要与艾滋病、器官移植、恶性肿瘤、使用皮质类固醇激素和免疫抑制剂等因素相关,这些真菌感染临床症状常无特异性,容易被忽视而延误诊治。因此,熟悉ICU常见真菌感染的诊治原则,确保早期诊断和及时治疗,是降低真菌感染发生率和死亡率的关键。     

肺部真菌感染CT诊断进展

正近年来,随着器官移植、艾滋病等免疫功能低下患者的逐年增多,肺部真菌感染也呈上升趋势,死亡率较高。及时诊断及适当抗真菌治疗是降低死亡率的关键,而CT对于早期诊断肺真菌病至关重要。目前国内缺乏与病原真菌相关的CT诊断系统介绍,本文就此作一综述,以期提高各类肺真菌病的鉴别诊断水平,更好指导临床。     

ICU常见机会性真菌感染

重症监护室(ICU)收治的患者多数都有免疫功能受损,是真菌感染的易感人群,这类人群发生真菌感染后病情严重,预后较差。ICU常见的机会性真菌感染有念珠菌、曲霉菌、隐球菌、马尔尼菲蓝状菌和组织胞浆菌等,主要与艾滋病、器官移植、恶性肿瘤、使用皮质类固醇激素和免疫抑制剂等因素相关,这些真菌感染临床症状常无特异性,容易被忽视而延误诊治。因此,熟悉ICU常见真菌感染的诊治原则,确保早期诊断和及时治疗,是降低真菌感染发生率和死亡率的关键。     

侵袭性曲霉病的临床诊断评价

近20年来随着肿瘤大剂量化疗、造血干细胞和实体器官移植的发展,机会性真菌感染发病率逐年增加,其中侵袭性曲霉病是肿瘤和移植患者死亡的重要原因。尽管不断有新的抗真菌药物问世,侵袭性曲霉病总体治愈率仅为50％左右^[1]。主要原因是早期诊断困难,导致抗真菌治疗的延误。2002年欧洲癌症-侵袭性真菌感染治疗研究协作组和美国国立变态反应和感染病研究院真菌病研究组（EORTC／MSG）提出根据宿主因素、临床特征、真菌学证据及组织病理,将侵袭性真菌病的诊断分为3级,即确诊、拟诊和疑诊,为临床研究和流行病学研究制定出规范的诊断标准^[2]。     

艾滋病合并真菌感染研究概述

真菌感染是艾滋病患者最常见、比重最大的机会性感染,是最重要致死原因之一。常见的机会性真菌感染包括：念珠菌病、卡氏肺孢子菌病、隐球菌病、马尔尼菲蓝状菌感染、组织胞浆菌病、球孢子菌病。本文介绍了机体的CD4⁺T淋巴细胞与机会性真菌感染关系以及常见的真菌感染的流行病学、发病机制、临床表现、诊断、治疗、预防等方面研究进展。提高临床医生对这类真菌感染系统全面的认识,有助于做到早期诊断、早期治疗,合理选择抗真菌药物,从而提高患者生存质量,延长生存时间。     

艾滋病合并马尔尼菲篮状菌病的研究进展

马尔尼菲篮状菌病是一种由马尔尼菲篮状菌引起的深部真菌病,易发于免疫功能缺陷和免疫功能障碍的人群。随着艾滋病患者的逐渐增多,马尔尼菲篮状菌的感染率也随之上升。该文从马尔尼菲篮状菌病的流行病学、临床表现、临床诊断和治疗综述了马尔尼菲篮状菌病的研究进展。     

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。     

抗真菌药物敏感性试验方法的新进展

真菌感染,尤其是免疫低下患者机会性真菌感染发病率的不断上升使真菌病的治疗面临着严峻的挑战,各种新的抗真菌药物纷纷涌现。临床实践中,人们需要规范快速、易于应用的药敏试验来指导用药和判断预后,抗真菌药物敏感性试验在真菌感染的治疗中起着重要作用。     

艾滋病患者侵袭性真菌感染的治疗

艾滋病患者由于严重免疫缺陷而易于并发各种机会感染和肿瘤。高效抗反转录病毒联合治疗(HAART)的出现明显改善了艾滋病患者的预后,提高了患者生存质量,随着HAART在临床的广泛使用,艾滋病患者出现各种机会感染包括侵袭性真菌感染的概率大大降低。然而,由于我国艾滋病患者明确诊断时大多处于疾病晚期,机体免疫功能极低;部分患者尽管接受了HAART,但是由于依从性、病毒耐药性等原因导致患者未能出现良好的应答反应,患者的免疫功能仍未能得到     

自身免疫性大疱病合并侵袭性肺曲霉病:3例报告

目的通过典型病例回顾探讨自身免疫性大疱病糖皮质激素治疗过程中合并肺曲霉病的诊断和治疗情况。方法报告3例自身免疫性大疱病合并侵袭性肺曲霉病病例。3例病例均行痰镜检、培养、抗原检测、胸部CT或者坏死组织病理检查。分离病原菌经形态学和分子生物学鉴定为烟曲霉、黄曲霉和刺孢裸胞壳。结果 3例病例证实为侵袭性肺曲霉病。进行以伏立康唑为主的综合治疗后均治愈。结论自身免疫性大疱病糖皮质激素治疗过程中应警惕肺曲霉病的发生。多种实验室检查可以帮助早期诊断,提高疗效。     

Aiming for a bull’s-eye: Targeting antifungals to fungi with dectin-decorated liposomes

Globally, there are several million individuals with life-threatening invasive fungal diseases such as candidiasis, aspergillosis, cryptococcosis, Pneumocystis pneumonia (PCP), and mucormycosis. The mortality rate for these diseases generally exceeds 40%. Annual medical costs to treat these invasive fungal diseases in the United States exceed several billion dollars. In addition to AIDS patients, the risks of invasive mycoses are increasingly found in immune-impaired individuals or in immunosuppressed patients following stem cell or organ transplant or implantation of medical devices. Current antifungal drug therapies are not meeting the challenge, because (1) at safe doses, they do not provide sufficient fungal clearance to prevent reemergence of infection; (2) most become toxic with extended use; (3) drug-resistant fungal isolates are emerging; and (4) only one new class of antifungal drugs has been approved for clinical use in the last 2 decades. DectiSomes represent a novel design of drug delivery to drastically increase drug efficacy. Antifungals packaged in liposomes are targeted specifically to where the pathogen is, through binding to the fungal cell walls or exopolysaccharide matrices using the carbohydrate recognition domains of pathogen receptors. Relative to untargeted liposomal drug, DectiSomes show order of magnitude increases in the binding to and killing of Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus in vitro and similarly improved efficacy in mouse models of pulmonary aspergillosis. DectiSomes have the potential to usher in a new antifungal drug treatment paradigm.     

Hacia el diagnóstico temprano de la candidiasis invasora en el paciente crítico

The management of invasive fungal infections in critically ill patients, from diagnosis to selection of the ther- apeutic protocol, is often a challenge. Early diagnosis and treatment are associated with a better prognosis, but apart from cases with positive cultures from blood or fluid/tissue biopsy, diagnosis is neither sensitive nor specific, and there is a need for specific markers in these diseases. Serodiagnostic assays such as mannan an-tigen, mannan antibodies, Candida albicans germ-tube antibodies or (1→3)-β-D-glucan detection, and mo-lecular techniques for the detection of fungal-specific DNA have been developed with promising results in critical care settings. One of the main features in diagnosis is the evaluation of risk factors for infection, which will identify patients in need of preemptive or empirical treatment. Clinical scores were built from those risk factors. The combination of prediction rules and non-culture microbiological tools could be currently be the key to improving the diagnosis and prognosis of invasive fungal infections in critically ill patients.     

The Ascomycetes MAT locus: its evolution, structure and regulation

Invasive fungal infections of the respiratory tract are a major cause of serious morbidity and mortality especially in immunocompromised patients due to neutropenia, corticosteroids, or hematologic malignancy. The role of imaging is very important in the management of patients with fungal infections and chest x-ray is still the most used exploration. Nevertheless, new approaches recommend the systematic use of computed tomography scan for early documentation of invasive fungal infection. Combination of clinical setting with recognition of radiological pattern is the best approach to pulmonary fungal diseases. The following is a review of the imaging features of different invasive fungal infections we can face in our daily practice.     

Radiology of invasive fungal infections of the respiratory tract

Invasive fungal infections of the respiratory tract are a major cause of serious morbidity and mortality especially in immunocompromised patients due to neutropenia, corticosteroids, or hematologic malignancy. The role of imaging is very important in the management of patients with fungal infections and chest x-ray is still the most used exploration. Nevertheless, new approaches recommend the systematic use of computed tomography scan for early documentation of invasive fungal infection. Combination of clinical setting with recognition of radiological pattern is the best approach to pulmonary fungal diseases. The following is a review of the imaging features of different invasive fungal infections we can face in our daily practice.     

院内深部真菌感染92例临床分析

目的探讨院内深部真菌感染的临床表现、感染相关因素及诊断治疗措施.方法对1993年1月至2002年12月间经微生物检查证实的92例院内深部真菌感染的病例临床资料进行回顾性分析.结果在92例患者中,肺部疾病26例,糖尿病19例,血液病及肿瘤19例,外科手术后13例,消化系统疾病6例,慢性肾脏病6例,风湿性疾病3例.主要感染真菌为白色念珠菌和酵母菌.感染相关因素:长时间应用广谱抗生素病人65例,应用糖皮质激素22例,应用免疫抑制剂18例,应用气管切开或气管内插管以及中心静脉留置导管17例,进行血液净化治疗的9例.治疗痊愈59例(64.1%),好转10例(10.9%),死亡23例(25%).结论白色念珠菌是院内深部真菌感染的主要致病菌株,有逐年增加趋势,病死率高.与长时间应用广谱抗生素及免疫抑制剂等有相关性.     

The Application of Laser Microdissection in Molecular Detection and Identification of Aspergillus fumigatus from Murine Model of Acute Invasive Pulmonary Aspergillosis

Invasive aspergillosis (IA) is a major concern in patients with severe immune deficiency. As antifungal susceptibility varies in different fungal pathogens, accurate and timely identification of species is becoming imperative for guidance of therapy and reducing high mortality rates in patients with IA. But, in fact, the diagnosis is challenging and new validated techniques are required for the detection and identification of clinically relevant isolates. The laser capture microdissection (LCM) system enables analysis of cytologically and/or phenotypically defined cell types from heterogeneous tissue and has been used in diagnosis and fungal species identification in pulmonary aspergillosis of white storks. To establish the experimental foundation for clinical application of the system, we microdissected and collected Blankophor-stained single hyphal strands from tissue cryosections of murine model of invasive pulmonary aspergillosis (IPA) with A. fumigatus by LCM, subsequently processed for DNA extraction, PCR sequencing, and species molecular identification. The sensitivity of LCM–PCR sequencing was 89 % (89/100), and the specificity was 100 %. Moreover, the positive predictive value and negative predictive value were 100 and 78.43 %, respectively. The result approved that the LCM-based methods had the potential for accurately diagnosis and rapidly identification fungal pathogens of IPA.     

血液系统肿瘤患者侵袭性肺部真菌感染的外科手术治疗

目的探讨怀疑肺部有侵袭性真菌感染(invasivefungalinfection,IFI)的血液恶性肿瘤患者行手术切除肺部病灶的安全性及有效性。方法分析2005年4月～2009年7月之间因血液系统肿瘤合并疑似侵袭性肺部真菌感染而接受肺切除术的10名患者,总结术后并发症及死亡率来探讨手术的有效性和安全性。结果手术均在全身麻醉下进行,5例为胸廓切开术,5例为胸腔镜下手术。3例为病灶楔形切除术,7例为肺叶切除术。术后组织病理:确诊真菌感染6例(60%),慢性细菌感染1例,3例未见明确病原菌。术后4例出现并发症:3例为轻度并发症(30%),其中2例气胸后自行吸收,1例局限性肺不张;1例严重并发症为血胸(10%)。术后30d死亡率为10%。术后真菌复发率为16%。随访至2009年8月31日,中位随访时间为3.8个月(0.7～31.1个月),4例(40%)死亡,但手术相关死亡率为0%。结论手术切除不仅有助于明确诊断而且还可以清除病灶、防止IFI复发和允许进一步的免疫抑制治疗,手术本身是安全的。     

La infección fúngica en el paciente pediátrico inmunodeprimido

In recent years, immunodeficiency condition has experienced a rise among children, who are at risk of invasive fungal infections (IFI) due to their health condition. Cancer, non-malignant hematological diseases, as primary immunodeficiencies, hematopoietic stem cell transplantation (HSCT), extreme prematurity, or critically ill condition in Pediatric Intensive Care Unit (PICU) are some immunosuppressive situations in children. The use of oncologic therapies, including immunotherapy and monoclonal antibodies, for the treatment of the aforementioned health conditions has led to an increase in morbidity and mortality rates of IFI in children.The underlying diseases and their management, comorbidities, the diagnostic tests used (both molecular and imaging), as well as the treatment used can be significantly different between adult patients and children admitted to PICU or with cancer. In pediatrics, the treatment of IFI is based primarily on pharmacokinetic studies performed in adults. In higher risk patients prophylaxis should be considered and, in the case of an IFI diagnosis, an antifungal treatment should be administered as early as possible, supported by the reversion of the immune dysfunction and surgery when appropriate.     

慢性阻塞性肺疾病合并糖尿病患者肺部真菌感染病原学及易感因素分析

目的探讨慢性阻塞性肺疾病(COPD)合并糖尿病患者肺部真菌感染的病原学及易感因素。方法对58例COPD合并糖尿病肺部真菌感染患者进行病原学及预后分析,并与无糖尿病的COPD真菌感染患者76例进行比较。结果 2组患者病原菌均以白色念珠菌占首位,研究组真菌发病率高于对照组,预后较对照组更差。抗生素、年龄、糖皮质激素和营养状态等因素对2组患者真菌感染的影响差异无统计学意义。结论白色念珠菌仍是COPD患者肺部真菌感染的主要致病菌。糖尿病增加COPD患者感染真菌的风险,并且加重病情,影响预后。