肺隐球菌病课件

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1、肺隐球菌病1肺隐球菌病（PC，pulmonary cryptococcosis）-从一个病例谈起肺隐球菌病2病史介绍患者，女性，47岁主述：主述：因“反复咳嗽伴胸痛1月”入院（B院）现病史：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：既往：体健。否认性病冶游史。家中曾养宠物（鸽子、狗）。查体：查体：T：37.9，浅表淋巴结不大，右下肺可及湿啰

2、音。辅助检查：辅助检查：血常规、肝肾功能、D-二聚体正常；ESR：65mm/h，CRP：48mg/L；血气分析正常；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32010.9.6 A院CT肺隐球菌病4病史介绍A A院气管镜检查：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52010.10.12 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6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7关于隐球菌 带厚荚膜

3、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8Epidemiology IA multicentre retrospective study of pulmonary mycosis clinically proven from 1998 to 2007Totally 474 cases of pulmonary mycosis from 16 centers in10 cities.pulmonary aspergillosis(1

4、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)中华结核和呼吸杂志，2011,34(2)肺隐球菌病9Epidemiology II Meta-Analysis of Clinical Manifestations of Pulmonary Cryptococcosis in China Mainland 69.7%

5、patients had no underlying diseases The common underlying diseases wereacquired immune deficiency syndrome(AIDS)diabetesmalignant tumor 中国临床医学，2013,20（3）：351-354肺隐球菌病10Epidemiology III Retrospective investigation of 151 pulmonary cryptococcosis non-HIV cases between 1977 and 2012 44.4%patients had n

6、o UDs.The common UDs were diabetes(32.1%)hematologic disease(22.6%)collagen disease(22.6%)Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.J Infect Chemother.2014 Oct 29 肺隐球菌病11Epidemiology IV 219 patients with proven cryptococcosis at 20 hospitals219 patients wi

7、th proven cryptococcosis at 20 hospitals in Taiwan,in Taiwan,1997-20101997-2010210 isolates were C.neoformans(95.9%);210 isolates were C.neoformans(95.9%);9 isolates were C.gattii(4.1%).9 isolates were C.gattii(4.1%).15.4%did not have any underlying condition.15.4%did not have any underlying conditi

8、on.HIV infection was the most common underlying condition(54/219,HIV infection was the most common underlying condition(54/219,24.6%).24.6%).Among HIV-negative patients,liver diseases(HBV carrier or Among HIV-negative patients,liver diseases(HBV carrier or cirrhosis)were common(30.2%)cirrhosis)were

9、common(30.2%)Taiwan Infectious Diseases Study Network for Cryptococcosis.PLoS One.2013 Apr 17;8(4):e61921.2013 Apr 17;8(4):e61921.肺隐球菌病12Epidemiology V Clinical analysis of 76 patients pathologically diagnosed with pulmonary cryptococcosis.Of 76 patients(54 males and 22 females),41(53.95%)were immun

10、ocompetent and 35 out of the 41 were asymptomatic.Shanghai Pulmonary Hospital.Eur Respir J.2012 Nov;40(5):1191-200.肺隐球菌病13summary approximately half of patients had no underlying diseases a significant number of patients were asymptomatic肺隐球菌病14pathogenesis The capsule is the most important virulenc

11、e factor of the fungal pathogen Cryptococcus neoformans.The structure Production Of the capsule adhesion of Cryptococcus neoformans to epithelial lung cells protective immune responses against cryptococcosis 肺隐球菌病15The structure of capsule This structure consists of highly hydrated polysaccharides,i

12、ncluding 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16Production Of the capsule ICA/CO2-sensing pathways.1 Regulation of capsule synthesis by carbon dioxide J Clin Invest，1985，76(2):508-516 2 Comparative tra

13、nscriptome 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17Production Of the capsule II cryptococcal polysaccharide synthesis is increased by cryptococcal polysaccharide synthesis is increased by

14、 limitation of ferric iron availability to the cell and limitation of ferric iron availability to the cell and by dissolved CO2,and the two effects are additiveby dissolved CO2,and the two effects are additive.Regulation of cryptococcal capsular polysaccharide by iron.Regulation of cryptococcal caps

15、ular polysaccharide by iron.J Infect Dis.J Infect Dis.1993 Jan;167(1):186-1993 Jan;167(1):186-90.90.肺隐球菌病18Production Of the capsule III capsule 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19Production Of the capsule

16、 IV based on the axial lengthening of PS molecules.Capsule of Cryptococcus neoformans grows by enlargement of polysaccharide molecules.Capsule of Cryptococcus neoformans grows by enlargement of polysaccharide molecules.Proc Natl Acad Sci U S A.2009 Jan 27;106(4):1228-33.PS，etc capsule?alveolar micro

17、environment 肺隐球菌病20adhesion to epithelial lung cells an adhesion-like interaction between MP on the fungal surface and the complementary receptor molecules on the epithelial cells.Front Cell Infect Microbiol.2014 Aug 19;4:106.肺隐球菌病21Phagocytosis defence Size of Cryptococcus neoformans.Dynamic change

18、s Dynamic changes in the morphology of Cryptococcus neoformans during murine pulmonary in the morphology of Cryptococcus neoformans during murine pulmonary infection.infection.GXM against alveolar macrophages(AM).Mechanisms of immune evasion in fungal pathogens.Mechanisms of immune evasion in fungal

19、 pathogens.1 1 Microbiology.Microbiology.2001 Aug;147(Pt 8):2355-2001 Aug;147(Pt 8):2355-65.65.2 2 Curr Opin Microbiol.Curr Opin Microbiol.2011 2011 Dec;14(6):668-75.Dec;14(6):668-75.肺隐球菌病22immune response SP-D increases susceptibility to C.neoformans infection by promoting C.neoformans-driven pulmo

20、nary IL-5 and eosinophil infiltration.Th1/Th2 cytokine imbalance.B cells provide a first line of defense during pulmonary B cells provide a first line of defense during pulmonary C.neoformans infection in miceC.neoformans infection in mice 1 1 Genet Mol Res.Genet Mol Res.2013 Nov 2013 Nov 18;12(4):5

21、733-42 18;12(4):5733-42 2 2 Infect Immun.2014 Feb;82(2):683-93 3 3 J Immunol.J Immunol.2012 Dec 2012 Dec 15;189(12):5820-30 15;189(12):5820-30 肺隐球菌病23My opinion i Change alveolar microenvironment Abrogation of IL-4 receptor-dependent alternatively activated macrophages is sufficient to confer resist

22、ance against pulmonary cryptococcosis despite an ongoing T(h)2 response.Int Immunol.2013 Aug;25(8):459-70.肺隐球菌病24Radiology I Peripherally distributed pulmonary nodules/masses were most commonly seen.Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.J Infect Chemot

23、her.2014 Oct 29 Radiological(computed tomography)findings showed predominantly peripheral 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

24、lump shadows;23.8%by flake-like infiltrated shadows，and 7.4%had diffuse mixed lesions Zhongshan Hospital.Chinese Journal of Clinical Medicine，2013肺隐球菌病25Radiology II CT scan findings of 29 immunocompetent and 43 immunocompromised CT scan findings of 29 immunocompetent and 43 immunocompromised patien

25、tspatients Pulmonary nodules/masses,either solitary or multiple,were the Pulmonary nodules/masses,either solitary or multiple,were the most common CT finding,present in 65(90.3%)of the 72 patientsmost common CT finding,present in 65(90.3%)of the 72 patients Cavitations within nodules/masses were mor

26、e commonly seen in Cavitations within nodules/masses were more commonly seen in immunocompromised patients,especially AIDS patientsimmunocompromised patients,especially AIDS patientsair bronchograms were more commonly seen in immunocompetent air bronchograms were more commonly seen in immunocompeten

27、t patientspatients Pulmonary cryptococcosis:comparison of CT findings in immunocompetent and immunocompromised Pulmonary cryptococcosis:comparison of CT findings in immunocompetent and immunocompromised patients.patients.Acta Radiol.2014 Apr 22.肺隐球菌病26My opinion ii Molecular/functional radiology肺隐球菌

28、病27current situation in diagnosis 43.42%(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 virus 26.2%（17/65）were confirmed by surge

29、ry 1 Shanghai Pulmonary Hospital.Eur Respir J.2012 Nov;40(5):1191-200.2 Clin Infect Dis.1994 Jan;18(1):119-20.3 南京军区总医院.中华结核和呼吸杂志，2014,37（10）：764-768肺隐球菌病28My opinion iii BALF-LAT Alveolar pucture fluid（CT guided transthoracic needle aspiration Biopsy）-LAT肺隐球菌病29Assessment and monitoring LAT EOS CT肺

30、隐球菌病30My opinion iv At present,there is not a suitable indicator for monitoring the disease肺隐球菌病31Guideline and consensusIDSA Clinical Infectious Disease，2010，50（3）：291-322ATS Am J Respir Cit CareMed，2011，183(1)：96-128隐球菌感染诊治专家共识 中国真菌学杂志 2010,5（2）：65-68肺真菌病诊断和治疗专家共识 中华结核和呼吸杂志 2007,30（11）：821-834肺隐球菌病32 Thanks Thanks