肺隐球菌病医学知识培训课件

1、肺隐球菌病医学知识肺隐球菌病医学知识病史介绍患者，女性，47岁主述：因“反复咳嗽伴胸痛1月”入院（B院）现病史：患者于2010.9.5无明显诱因出现咳嗽，少量白痰，伴右侧胸痛，阵发性钝痛，深吸气时明显，无放射痛，无发热，无呕吐、头痛，某A院行胸部CT示“右下肺炎”，予以莫西沙星静滴8天患者咳嗽、胸痛有所缓解，继续口服莫西沙星6天，2010.9.27复查CT无吸收。于2010.10.12就诊B院。既往：体健。否认性病冶游史。家中曾养宠物（鸽子、狗）。查体：T：37.9 ，浅表淋巴结不大，右下肺可及湿啰音。辅助检查： 血常规、肝肾功能、D-二聚体正常；ESR：65mm/h，CRP：48mg/L；血

2、气分析正常；HIV（-） PPD试验阴性；LA试验、G试验阴性（送至C院检测）肺隐球菌病医学知识2病史介绍患者，女性，47岁肺隐球菌病医学知识22010.9.6 A院CT2010.9.27 A院CT肺隐球菌病医学知识32010.9.6 A院CT2010.9.27 A院CT肺隐球病史介绍A院气管镜检查：镜下：未见明显异常；右下肺灌洗和刷检：未见恶性细胞、TB阴性。 肺隐球菌病医学知识4病史介绍A院气管镜检查：肺隐球菌病医学知识42010.10.12 B院CT引导下经皮肺穿刺病理结果确诊： 肺隐球菌病上皮样肉芽肿性病变；成堆隐球菌肺隐球菌病医学知识52010.10.12 B院CT引导下经皮肺穿刺病

3、理结果确诊几点疑问真菌病一般都是免疫功能低下的患者隐球菌如何侵袭到肺的LA试验阴性肺隐球菌病CT表现和肺炎一样肺隐球菌病医学知识6几点疑问真菌病一般都是免疫功能低下的患者肺隐球菌病医学知识6关于隐球菌带厚荚膜的酵母菌（乳胶凝集试验）腐生菌：土壤、鸽粪、霉烂蔬菜、水果等感染部位：中枢神经系统、皮肤、肺 感染途径：吸入呼吸道经血行播散到其它部位分型：17个种、18个变种（新生隐球菌及变种具有致病性）肺隐球菌病医学知识7关于隐球菌带厚荚膜的酵母菌（乳胶凝集Epidemiology IA multicentre retrospective study of pulmonary mycosis clin

4、ically proven from 1998 to 2007Totally 474 cases of pulmonary mycosis from 16 centers in10 cities. pulmonary aspergillosis(1 80 cases，379)pulmonary candidiasis(162 cases，342)pulmonary cryptococcosis(74 cases，156)pneumocystis cafinii pneumonia(23 cases，4.8) pulmonary mucormycosis(10 cases，21) 中华结核和呼吸

5、杂志，2011,34(2)肺隐球菌病医学知识8Epidemiology IA multicentre rEpidemiology II Meta-Analysis of Clinical Manifestations of Pulmonary Cryptococcosis in China Mainland69.7 % patients had no underlying diseases The common underlying diseases wereacquired immune deficiency syndrome( AIDS) diabetesmalignant tumor 中

6、国临床医学，2013,20（3）：351-354肺隐球菌病医学知识9Epidemiology II Meta-AnalysEpidemiology III Retrospective investigation of 151 pulmonary cryptococcosis non-HIV cases between 1977 and 2012 44.4% patients had no UDs. The common UDs were diabetes (32.1%) hematologic disease (22.6%)collagen disease (22.6%) Japanese S

7、ociety of Chemotherapy and The Japanese Association for Infectious Diseases .J Infect Chemother. 2014 Oct 29 肺隐球菌病医学知识10Epidemiology III RetrosEpidemiology IV219 patients with proven cryptococcosis at 20 hospitals in Taiwan, 1997-2010210 isolates were C. neoformans (95.9%); 9 isolates were C. gattii

8、 (4.1%). 15.4% did not have any underlying condition. HIV infection was the most common underlying condition (54/219, 24.6%). Among HIV-negative patients, liver diseases (HBV carrier or cirrhosis) were common (30.2%) Taiwan Infectious Diseases Study Network for Cryptococcosis. PLoS One. 2013 Apr 17;

9、8(4):e61921. 肺隐球菌病医学知识11Epidemiology IV219 patients wEpidemiology VClinical analysis of 76 patients pathologically diagnosed with pulmonary cryptococcosis. Of 76 patients (54 males and 22 females), 41 (53.95%) were immunocompetent and 35 out of the 41 were asymptomatic. Shanghai Pulmonary Hospital .

10、Eur Respir J. 2012 Nov;40(5):1191-200. 肺隐球菌病医学知识12Epidemiology VClinical analyssummaryapproximately half of patients had no underlying diseasesa significant number of patients were asymptomatic肺隐球菌病医学知识13summaryapproximately half of ppathogenesis The capsule is the most important virulence factor of

11、 the fungal pathogen Cryptococcus neoformans. The structure Production Of the capsuleadhesion of Cryptococcus neoformans to epithelial lung cells protective immune responses against cryptococcosis 肺隐球菌病医学知识14pathogenesis The capsule is tThe structure of capsule This structure consists of highly hydr

12、ated polysaccharides, including glucuronoxylomannan (GXM)，葡萄糖醛酸木糖甘露聚糖galactoxylomannan (GalXM) ，半乳糖木糖甘露聚糖mannoproteins (MPs)，甘露糖蛋白，less than 1% of the capsular weight肺隐球菌病医学知识15The structure of capsule ThiProduction Of the capsule ICA/CO2-sensing pathways . 1 Regulation of capsule synthesis by carbo

13、n dioxide J Clin Invest， 1985， 76( 2) : 508-516 2 Comparative transcriptome analysis of the CO2 sensing pathway via differential expression of carbonic anhydrase in Cryptococcus neoformans.Genetics. 2010 Aug;185(4):1207-19. 肺隐球菌病医学知识16Production Of the capsule ICA/肺隐球菌病医学知识培训课件Production Of the caps

14、ule IIIcapsule enlargement in living C. neoformans cells was influenced by Ca(2+) in the culture medium. Eukaryot Cell. 2007 Aug;6(8):1400-10. 肺隐球菌病医学知识18Production Of the capsule IIIProduction Of the capsule IVbased on the axial lengthening of PS molecules. Capsule of Cryptococcus neoformans grows

15、by enlargement of polysaccharide molecules.Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1228-33. PS，etc capsule?alveolar microenvironment 肺隐球菌病医学知识19Production Of the capsule IVbadhesion to epithelial lung cells an adhesion-like interaction between MP on the fungal surface and the complementary rece

16、ptor molecules on the epithelial cells. Front Cell Infect Microbiol. 2014 Aug 19;4:106.肺隐球菌病医学知识20adhesion to epithelial lung cePhagocytosis defenceSize of Cryptococcus neoformans. Dynamic changes in the morphology of Cryptococcus neoformans during murine pulmonary infection. GXM against alveolar ma

17、crophages (AM) . Mechanisms of immune evasion in fungal pathogens. 1 Microbiology. 2001 Aug;147(Pt 8):2355-65. 2 Curr Opin Microbiol. 2011 Dec;14(6):668-75.肺隐球菌病医学知识21Phagocytosis defenceSize of Crimmune response SP-D increases susceptibility to C. neoformans infection by promoting C. neoformans-dri

18、ven pulmonary IL-5 and eosinophil infiltration. Th1/Th2 cytokine imbalance. B cells provide a first line of defense during pulmonary C. neoformans infection in mice 1 Genet Mol Res. 2013 Nov 18;12(4):5733-42 2 Infect Immun. 2014 Feb;82(2):683-93 3 J Immunol. 2012 Dec 15;189(12):5820-30 肺隐球菌病医学知识22im

19、mune response SP-D increasesMy opinion iChange alveolar microenvironment Abrogation of IL-4 receptor-dependent alternatively activated macrophages is sufficient to confer resistance against pulmonary cryptococcosis despite an ongoing T(h)2 response. Int Immunol. 2013 Aug;25(8):459-70.肺隐球菌病医学知识23My o

20、pinion iChange alveolar miRadiology IPeripherally distributed pulmonary nodules/masses were most commonly seen. Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases .J Infect Chemother. 2014 Oct 29 Radiological (computed tomography) findings showed predominantly peri

21、pheral findings (85.53%) including nodular masses (55.26%), pneumonic infiltrates (23.68%) and mixed type (21.05%). Shanghai Pulmonary Hospital .Eur Respir J. 2012 Nov;40(5):1191-200. 71.8 % patients were characterized by nodular lump shadows; 23.8 % by flake-like infiltrated shadows，and 7.4 % had d

22、iffuse mixed lesions Zhongshan Hospital .Chinese Journal of Clinical Medicine， 2013肺隐球菌病医学知识24Radiology IPeripherally distriRadiology II CT scan findings of 29 immunocompetent and 43 immunocompromised patients Pulmonary nodules/masses, either solitary or multiple, were the most common CT finding, pr

23、esent in 65 (90.3%) of the 72 patients Cavitations within nodules/masses were more commonly seen in immunocompromised patients, especially AIDS patientsair bronchograms were more commonly seen in immunocompetent patients Pulmonary cryptococcosis: comparison of CT findings in immunocompetent and immu

24、nocompromised patients. Acta Radiol. 2014 Apr 22. 肺隐球菌病医学知识25Radiology II CT scan findinMy opinion iiMolecular/functional radiology肺隐球菌病医学知识26My opinion iiMolecular/functiocurrent situation in diagnosis43.42% (33 / 76) were initially misdiagnosed, often as cancer by false-positive (18)FDG-PET Failure of the cryptococcal serum antigen test to detect primary pulmonary cryptococcosis in patients infected with human immunodeficiency virus26.2%（17/65）were con