肺隱球菌病醫(yī)學知識培訓課件

1、肺隱球菌病醫(yī)學知識肺隱球菌病醫(yī)學知識病史介紹患者，女性，47歲主述：因“反復咳嗽伴胸痛1月”入院（B院）現(xiàn)病史：患者于2010.9.5無明顯誘因出現(xiàn)咳嗽，少量白痰，伴右側胸痛，陣發(fā)性鈍痛，深吸氣時明顯，無放射痛，無發(fā)熱，無嘔吐、頭痛，某A院行胸部CT示“右下肺炎”，予以莫西沙星靜滴8天患者咳嗽、胸痛有所緩解，繼續(xù)口服莫西沙星6天，2010.9.27復查CT無吸收。于2010.10.12就診B院。既往：體健。否認性病冶游史。家中曾養(yǎng)寵物（鴿子、狗）。查體：T：37.9 ，淺表淋巴結不大，右下肺可及濕啰音。輔助檢查： 血常規(guī)、肝腎功能、D-二聚體正常；ESR：65mm/h，CRP：48mg/L；血

2、氣分析正常；HIV（-） PPD試驗陰性；LA試驗、G試驗陰性（送至C院檢測）肺隱球菌病醫(yī)學知識2病史介紹患者，女性，47歲肺隱球菌病醫(yī)學知識22010.9.6 A院CT2010.9.27 A院CT肺隱球菌病醫(yī)學知識32010.9.6 A院CT2010.9.27 A院CT肺隱球病史介紹A院氣管鏡檢查：鏡下：未見明顯異常；右下肺灌洗和刷檢：未見惡性細胞、TB陰性。 肺隱球菌病醫(yī)學知識4病史介紹A院氣管鏡檢查：肺隱球菌病醫(yī)學知識42010.10.12 B院CT引導下經皮肺穿刺病理結果確診： 肺隱球菌病上皮樣肉芽腫性病變；成堆隱球菌肺隱球菌病醫(yī)學知識52010.10.12 B院CT引導下經皮肺穿刺病

3、理結果確診幾點疑問真菌病一般都是免疫功能低下的患者隱球菌如何侵襲到肺的LA試驗陰性肺隱球菌病CT表現(xiàn)和肺炎一樣肺隱球菌病醫(yī)學知識6幾點疑問真菌病一般都是免疫功能低下的患者肺隱球菌病醫(yī)學知識6關于隱球菌帶厚莢膜的酵母菌（乳膠凝集試驗）腐生菌：土壤、鴿糞、霉爛蔬菜、水果等感染部位：中樞神經系統(tǒng)、皮膚、肺 感染途徑：吸入呼吸道經血行播散到其它部位分型：17個種、18個變種（新生隱球菌及變種具有致病性）肺隱球菌病醫(yī)學知識7關于隱球菌帶厚莢膜的酵母菌（乳膠凝集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) 中華結核和呼吸

5、雜志，2011,34(2)肺隱球菌病醫(yī)學知識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、國臨床醫(yī)學，2013,20（3）：351-354肺隱球菌病醫(yī)學知識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 肺隱球菌病醫(yī)學知識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. 肺隱球菌病醫(yī)學知識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. 肺隱球菌病醫(yī)學知識12Epidemiology VClinical analyssummaryapproximately half of patients had no underlying diseasesa significant number of patients were asymptomatic肺隱球菌病醫(yī)學知識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 肺隱球菌病醫(yī)學知識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肺隱球菌病醫(yī)學知識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. 肺隱球菌病醫(yī)學知識16Production Of the capsule ICA/肺隱球菌病醫(yī)學知識培訓課件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. 肺隱球菌病醫(yī)學知識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 肺隱球菌病醫(yī)學知識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.肺隱球菌病醫(yī)學知識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.肺隱球菌病醫(yī)學知識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 肺隱球菌病醫(yī)學知識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.肺隱球菌病醫(yī)學知識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肺隱球菌病醫(yī)學知識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. 肺隱球菌病醫(yī)學知識25Radiology II CT scan findinMy opinion iiMolecular/functional radiology肺隱球菌病醫(yī)學知識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