主要致病性真菌医学知识专题宣讲课件.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,主要致病性真菌医学知识专题宣讲,*,主要致病性真菌医学知识专题宣讲,浅部感染真菌,表面感染真菌,皮肤癣真菌,皮下组织真菌感染,2,主要致病性真菌医学知识专题宣讲,3,主要致病性真菌医学知识专题宣讲,表面感染真菌,位置：寄居于人体皮肤和毛干的最表层。因不接触组织细胞，很少引起宿主细胞反应,统称：角层癣菌,代表：秕糠马拉癣菌,(,Malassezia,furfur),症状：,由于此菌能产生对黑色素细胞有抑制作用的二羧酸，使花斑癣局部色素减退，如汗渍斑点，俗称汗斑。,诱发因素为高温多汗,4,主要致病性真菌医学知识专题宣讲,Malassezia,furfur,Tinea versicolor on skin surface(sweat stain),The lesions are small hypopigmented or hyperpigmented macules,Most common site:,back,underarm,upper arm,chest,neck,Most common in adolescent and young adult males,Associated with increased sweating,5,主要致病性真菌医学知识专题宣讲,Pityriasis versicolor showing hyperpigmented lesions in a,Caucasian and hyphopigmented lesions in an Australian Aborigine,6,主要致病性真菌医学知识专题宣讲,Culture of,Malassezia furfur,on Dixons agar,(contains glycerol mono-oleate),7,主要致病性真菌医学知识专题宣讲,Piedraia hortae,(,何德毛结节菌,),It usually affected the scalp hair,The nodules are darker in color,harder,and more firmly attached to the hairs,Black Piedra,8,主要致病性真菌医学知识专题宣讲,Piedraia hortae,forms a hard superficial pigmented nodule around the hair shaft,(,在毛干上形成硬的黑色结节，如沙粒状,),9,主要致病性真菌医学知识专题宣讲,Fungal otitis externa,Fungal infection of the external auditory canal,Caused by several species of,Aspergillus,(most often,A.niger,),but,Candida albicans,is also capable of infecting this site,The major symptoms are itching and feeling of fullness in ear,10,主要致病性真菌医学知识专题宣讲,11,主要致病性真菌医学知识专题宣讲,皮肤癣真菌,引起皮肤浅部感染,皮肤癣是人类最多见的真菌病,统称：皮肤癣菌，大约,40,多个种，分属于,3,个属,嗜角质蛋白，,37,不能生长,，,侵犯部位：角化的表皮，毛发，指（趾）甲,病理变化：由真菌增殖及代谢产物刺激宿 主引起,12,主要致病性真菌医学知识专题宣讲,致病性,指（趾）甲 皮肤 毛发,毛癣菌属 +,表皮癣菌属 +-,小孢子癣菌属 -+,+,一种皮肤癣菌可在不同部位引起病变,相同部位的病变也可由不同的皮肤癣菌引起,13,主要致病性真菌医学知识专题宣讲,14,主要致病性真菌医学知识专题宣讲,Tinea pedis caused by,T.rubrum,.Sub-clinical infection(left)showing mild maceration under the little toe and more severe infection(,right,)showing extensive maceration of all toe web spaces,Tinea is transmitted via the feet by desquamated skin scales in substrates like carpet and matting.,15,主要致病性真菌医学知识专题宣讲,手足癣治疗原则,水疱型温和搽剂和霜剂,角化过度型先角质剥脱剂，再用抗真菌霜剂,浸渍糜烂型粉剂收干，抗继发感染，再温和抗真菌,16,主要致病性真菌医学知识专题宣讲,Tinea Unguium,usually caused by,Trichophyton,sp,17,主要致病性真菌医学知识专题宣讲,甲癣治疗原则,局部治疗甲涂剂,系统治疗伊曲康唑，特比萘芬等,联合治疗配合拔甲或削甲治疗,18,主要致病性真菌医学知识专题宣讲,Tinea Corporis:,caused by,M.canis,following contact with infectious kittens,19,主要致病性真菌医学知识专题宣讲,Tinea Cruris(Jock itch):,Infection of the groin,mainly seen in men,20,主要致病性真菌医学知识专题宣讲,Tinea Capitis(scalp ringworm),Tinea favosa,发内孢子,21,主要致病性真菌医学知识专题宣讲,Tinea Capitis(scalp ringworm),Tinea alba,发外孢子,22,主要致病性真菌医学知识专题宣讲,Tinea Capitis(scalp ringworm),脓癣,23,主要致病性真菌医学知识专题宣讲,头癣治疗原则,剪发,洗发,搽药,服药,消毒,24,主要致病性真菌医学知识专题宣讲,Candidiasis of skin,mucous,membranes and nails,Predisposing factors,Infancy,pregnancy,old age,Disorders of immune function,e.g.,leukemia,corticosteroid therapy,Chemotherapy,e.g.,immunosuppressive,antibiotic,Endocrine disease,e.g.,diabetes mellitus,Carcinoma,25,主要致病性真菌医学知识专题宣讲,念珠菌性间擦疹,好发部位：腋窝、乳房下、,腹股沟、会阴，多见于婴儿,及肥胖者。,26,主要致病性真菌医学知识专题宣讲,Cutaneous candidiasis:including,Interdigital candidiasis,diaper candidiasis,paronychia and onychomycosis,Vulvovaginal candidiasis and balanitis,Interdigital candidiasis,C,andidia,onychomycosis and paronychia,27,主要致病性真菌医学知识专题宣讲,Oropharyngeal candidiasis,:,including thrush,glossitis,stomatitis and angular cheilitis,Oral thrush,28,主要致病性真菌医学知识专题宣讲,皮下组织真菌感染,主要有孢子丝菌和着色真菌,申克孢子丝菌,，,属腐生性真菌，常因外伤接触带菌的花草等引起感染。此菌可引起孢子丝菌下疳。此菌也可引起深部感染。是一种二相性真菌。,着色真菌感染发生在暴露部位，称着色真菌病。我国主要有卡氏枝孢霉和裴氏着色芽生菌,。,29,主要致病性真菌医学知识专题宣讲,Sporotrichosis,此菌可经微小损伤侵入皮肤，然后沿淋巴管分布，引起亚急性或慢性肉芽肿，使淋巴管形成链状硬结，称为孢子丝菌下疳。,30,主要致病性真菌医学知识专题宣讲,Chromomycosis,Infections occur in exposed areas,skin lesions become dark,so called chromomycosis,Representive species:,Cladosporium carrianii,Fonsecaea pedrosoi,etc.,Are,saprophytic fungi,usually enters the body by trauma,31,主要致病性真菌医学知识专题宣讲,经外伤侵入,丘疹,结节,结节融合成疣状或菜花状,斑痕形成影响淋巴回流,肢体象皮肿,32,主要致病性真菌医学知识专题宣讲,Chromomycosis,Chronic verrucous chromoblastomycosis of the hand due to,Cladophialophora carrionii33,主要致病性真菌医学知识专题宣讲,Mycetoma,足分枝菌病,是由多种放线菌或真菌引起的一种慢性化脓性肉芽肿性疾病，主要感染足部，以肿胀、窦道和颗粒为特征。,caused by fungi are called eumycetoma(40%),Actinomycetoma is caused by actinomycetes(60%),It is characterized by the formation of abscess,which contain large aggregates of fungal or actinomycete filaments known as grains,34,主要致病性真菌医学知识专题宣讲,Eumycetoma,Dark grains,Madurella mycetomatis,Leptosphaeria senegalensis,Exophiala jeanselmei,Pale grains,Fusarium,sp.,Acremonium,sp.,Scedosporium apiospermum,Actinomycetoma,White-yellow grains,Actinomadura madurae,Nocardia brasiliensis,Yellow-brown grains,Streptomyces somaliensis,Red-pink grains,Actinomycetoma pellettieri,35,主要致病性真菌医学知识专题宣讲,深部真菌感染,引起深部感染的真菌包括两大类：致病性真菌与条件致病性真菌,致病性真菌主要有组织胞浆菌、球孢子菌、副球孢子菌和芽生菌，这些真菌均属二相性。多见于美洲，我国极少见。它们侵袭深部组织和内脏以及全身，引起慢性肉芽肿样炎症、溃疡和坏死。,条件致病性真菌包括有：念珠菌、隐球菌、曲霉菌与毛霉菌、肺孢子菌等。,36,主要致病性真菌医学知识专题宣讲,Characteristics of systemic dimorphic mycoses,Are uncommon,often occurs in,endemic areas,Most infections are,asymptomatic,or self-limiting,in immune-compromised hosts,infections are often fatal,The pattern of infection are similar,Route of acquisition is inhalation,Pulmonary infection,Disseminated infection(,Blood,Bone marrow,Brain and CSF,Joint),37,主要致病性真菌医学知识专题宣讲,Coccidioidomycosis,Coccidiodes immitis,is considered to be the,most virulent,of fungal pathogens.,Restricted to hot,semi-arid areas of SW USA and Mexico.,Grows in the soil,but inhalation of a single spore can initiate infection.,In infected tissues,C.immitis,appears as a mixture of endospores and,spherules.,Conidia,Spherules,38,主要致病性真菌医学知识专题宣讲,Coccidioidomycosis,:,Encounter:,Mycelium found in dry,dusty soil.Contact by,inhalation,of,arthroconidia,Spread:,Most commonly an asymptomatic self limited pulmonary disease,but may spread via the blood to skin,soft tissues,bones,joints and,meninges,.,Immune Response:,T-cell mediated(Th-1),Evasion of Defenses:,Resistant to killing by phagocytes,-,protein rich,hydrophobic outer wall,-alkaline halo associated with,urease,E.Damage:,secreted,proteinases,break down collagen,elastin,hemoglobin,IgG,&,IgA,39,主要致病性真菌医学知识专题宣讲,1.Ethnicity:Filipinos,African Americans,Native Americans at higher risk,2.Age:Extremes more susceptible,3.Sex:Males more susceptible,4.Pregnancy:3,rd,trimester,5.Immunosuppression,F.Diagnosis,1.Exam:Suppurative or,granulomatous,inflammation,2.Histopathology:spherules or endospores seen in sputum,exudates or tissue,3.Culturedanger,highly infectious!,4.Serology:Complement fixation assay(in cerebrospinal fluid),particle agglutination assay,G.Treatment,Amphotericin,B followed by an,azole,E.Risk Factors,Coccidioidomycosis,:,40,主要致病性真菌医学知识专题宣讲,Histoplasmosis,(also called,cave disease,),Caused by the dimorphic fungus,Histoplasma capsulatum,Tuberculated macroconidia,grown at 25C,Intracellular yeast at 37C,Histoplasmosis is characterized by intracellular growth of the pathogen in macrophages and a granulomatous reaction in tissue.These granulomatous foci may reactivate and cause dissemination of fungi to other tissues.,41,主要致病性真菌医学知识专题宣讲,Histoplasmosis,A.,Encounter,.,H.capsulatum,grows in soil,especially soil contaminated by guano.Inhalation of conidia from the environment is source of infection.This is more likely in endemic areas.In U.S.these include the Atlantic Ocean to N.Dakota(500,000 cases/year in U.S.),except New England&Florida.Most cases occur in Ohio Valley and Mississippi Valley),42,主要致病性真菌医学知识专题宣讲,More Histoplasmosis,90%of cases are asymptomatic,but in rare cases flu like respiratory symptoms occur,Disseminated,histoplasmosis,occurs in 1:200 cases and is diagnosed frequently in patients with AIDS living in the central U.S.,In these cases,the organism spreads,via blood,from the lung to involve bone marrow,adrenal glands,heart valves and CNS,4.Spread can also be associated with underlying lung disease(e.g.,emphysema).,B.Spread,C.Immune Response,Cell-mediated responses are of primary importance,Activated macrophage can kill yeast cells,D.Evasion of Defenses,Survival in macrophages elevates pH of,phagosomes,Yeast cells absorb iron(,siderophore,)and calcium from host,Alteration of cell surface,43,主要致病性真菌医学知识专题宣讲,Histoplasmosis,Direct histology and culture of blood or bone marrow,Serological testing for antibody and,histoplama,antigen in blood and urine.,E.Diagnosis,D.Damage,Lung-bronchial obstruction and inflammatory,sequelae,Disseminated,histoplasmosis-fulminant,disease that may result in toxic shock,CNS-fatal if untreated.,44,主要致病性真菌医学知识专题宣讲,Even More Histoplasmosis,F.Treatment,Amphotericin,still mainstay of therapy vs.disseminated and severe pulmonary,histoplasmosis,.,Ketoconasole,or,itraconasole,is effective as therapy for self-limited disease(used in AIDS).,Ocular Histoplasmosis,A small fraction of individuals form scar tissue in the retina many years after the original histoplasmosis infection.Live organisms cannot be recovered from these specimens.The scarring can obscure the macula and lead to loss of central vision.The first signs are small“histo spots”.Advanced disease is treated with laser photocoagulation to limit the proliferation of blood vessels.,45,主要致病性真菌医学知识专题宣讲,Blastomycosis,Granulomatous mycotic infection that predominantly involves lungs and skin;but can spread to other organs.Most prevalent in males 40-60 years of age and children.,Blastomyces dermatitidis,Dimorphic organism originates in the soil and infection ensues by inhalation of spores.Converts to yeast in animal hosts or at 37,o,in vitro.,46,主要致病性真菌医学知识专题宣讲,Blastomycosis,Encounter,:Most cases are in southern,central,and southeastern USA.Infection is by inhalation of spores.,Spread:,The pulmonary infection is either self-limited or progressive.Dissemination often occurs to the skin and to the bone-80%of patients have large skin lesions;a large number also have granulomatous pulmonary lesions.,Risk Factors:,Occupational contact with soil;owning a dog.Living in endemic area.,Evasion of Defenses:,Escapes phagocytosis by neutrophils and monocytes by shedding its surface antigen after infection,Damage:,Consequence of the immune response to the organismskin lesions,respiratory infiltrates.,Diagnosis:,based on clinical findings and microscopic detection of organisms in tissue specimens,47,主要致病性真菌医学知识专题宣讲,Amphotericin,B is the drug of choice for rapidly progressive,blastomycosis,Itraconazole,or,Ketoconazole,for less severe cases,Immune response,1.Alveolar macrophage provide a first line of defense.,2.T-cell stimulated PMNs kill,Blastomyces,cells by oxidative mechanisms.,Conidia are more sensitive to killing by,PMNs,because yeast are too big.,TH-1 response is of primary importance,Blastomycosis,Treatment,48,主要致病性真菌医学知识专题宣讲,Opportunistic fungal infections,Opportunistic mycoses are fungal infections that do not normally cause disease in healthy people,but do cause disease in people with weakened immune defenses(immunocompromised people).Weakened immune function may occur due to inherited immunodeficiency diseases,drugs that suppress the immune system(cancer chemotherapy,corticosteroids,drugs to prevent organ transplant rejection),radiation therapy,infections(e.g.,HIV),cancer,diabetes,advanced age and malnutrition.,The most common infections are:,Candidiasis,Cryptococcosis,Aspergillosis,Pneumocystis carinii pneumonia(PCP),Penicillosis marneffei,49,主要致病性真菌医学知识专题宣讲,白假丝酵母菌,(,Candida,albicans),形态：,圆形或卵圆形单细胞真菌，革兰阳性,繁殖：,出芽繁殖，形成假菌丝，在组织易形成芽生孢子,培养：,普通琼脂、血琼脂与沙保培养基,需氧。室温或 37甚至42生长良好,菌落灰白色或奶油色，表面光滑，带有浓厚的酵母气味。,有大量向下生长的营养,假菌丝,，呈类酵母型。,在玉米粉培养基上可长出,厚膜孢子,属于假丝酵母菌属，俗称白念，为酵母型真菌，是条件致病菌,可引起皮肤、黏膜和内脏的急性或慢性炎症，即念珠菌病，是最常见的深部感染真菌病，口腔念珠菌病是艾滋病患者最先出现的继发性感染。,生物学特性,50,主要致病性真菌医学知识专题宣讲,假菌丝和厚膜孢子,51,主要致病性真菌医学知识专题宣讲,Systemic involvement,Urinary tract infection,Pulmonary candidiasis,Endocarditis,Meningitis,Candidaemia(septicaemia),Infancy,old age,pregnancy,prolong antibiotic,HIV/AIDS,diabetes,52,主要致病性真菌医学知识专题宣讲,微生物检查：,1、直接镜检：同时见出芽的念珠菌与假菌丝,2、分离培养与鉴定：假菌丝，芽生孢子,芽管形成试验/厚膜孢子形成试验,3、白色念珠菌细胞壁甘露聚糖抗原/,ELISA,特异性高但敏感性低,4、,动物试验：小鼠,53,主要致病性真菌医学知识专题宣讲,Cryptococcus neoformans,属于隐球菌属，为酵母型真菌,传染源是鸽子，人因吸入鸽粪污染的空气而感染,主要引起肺和脑的急性、亚急性或慢性感染。,生物学特性,圆形，有肥厚,荚膜,（一般厚度是直径的两倍）,染色：一般染色法不易着色，墨汁负染，胞内有较大的反光颗粒。,出芽繁殖，不形成假菌丝（酵母型,菌落）,培养特性：沙保或血琼脂培养基，25,37,生化特性：分解尿素,荚膜多糖抗原：,AD,和,AD 5,个血清型，我国约70%属,A,型,54,主要致病性真菌医学知识专题宣讲,55,主要致病性真菌医学知识专题宣讲,致病性,外源性感染,，,肺是主要入侵途径，也属于人体正常菌群，引起条件性感染,原发感染通常在肺部，多数症状不明显，自愈；有的引起支气管肺炎；严重者呈暴发性感染并迅速死亡,部分患者经血行传播至中枢神经及其它组织，引起肉芽肿性炎症，主要导致慢性脑膜炎,致病物质：荚膜,56,主要致病性真菌医学知识专题宣讲,微生物学检查,负染色镜检,抗原检查：,检查患者血清和脑脊液中新隐荚膜抗原分离鉴定,尿素酶或酚氧化酶,动物试验：,小鼠,57,主要致病性真菌医学知识专题宣讲,曲霉,Aspergillus,烟曲霉 支气管哮喘或肺部感染,毛霉,Mucor,腐生菌 脑、肺、胃肠道,卡氏肺孢菌,Pneumocystis,carinii,免疫缺陷病人 肺炎,58,主要致病性真菌医学知识专题宣讲,Aspergillus,Aspergillus,is a filamentous,cosmopolitan and ubiquitous fungus found in nature.,It is commonly isolated from soil,plant debris,and indoor air environment.,It is the second most commonly recovered fungus in opportunistic mycoses following,Candida,.,59,主要致病性真菌医学知识专题宣讲,morphology,It is a filamentous fungi,Hyphae are septate and hyaline.,Consisting of a Vesicle,The morphology and color of the conidiophore vary from one species to another60,主要致病性真菌医学知识专题宣讲,61,主要致病性真菌医学知识专题宣讲,Aspergillus flavus,Aspergillus niger,Aspergillus,fumigatus,62,主要致病性真菌医学知识专题宣讲,足细胞分生孢子梗顶囊杆状小梗串状分生孢子（分生孢子头）,63,主要致病性真菌医学知识专题宣讲,Species,The genus,Aspergillus,includes over 185 species.,Around 20 species have so far been reported as causative agents of opportunistic infections in man.,Among these,Aspergillus fumigatus,is the most commonly isolated species,followed by,Aspergillus flavus,and,Aspergillus niger,.,64,主要致病性真菌医学知识专题宣讲,Pathogenicity and Clinical Significance,局限性肺曲霉病,基础疾病致肺空洞存在,曲霉在此生长，不侵犯组织不播散,曲霉肺炎,（免疫功能低下）,过敏性支气管肺曲霉病,（过敏体质）,65,主要致病性真菌医学知识专题宣讲,Pathogenicity and Clinical Significance,黄曲霉毒素与恶性肿瘤，尤其是肝癌的发生密切相关,67,主要致病性真菌医学知识专题宣讲,Laboratory diagnosis,The specimen like sputum biopsy,bronchalveolar lavage or transbronchial biopsy depending in the site involved.,Direct examination of septate hyphae by 10%KOH preparation.,血清学诊断或血清学试验检出曲霉细胞壁半乳糖甘露乳糖抗原,.,68,主要致病性真菌医学知识专题宣讲,Culture:In SDA with antibiotics at 25 and 37c,有隔菌丝和分生孢子头.,69,主要致病性真菌医学知识专题宣讲,Pneumocystis carinii,Pneumonia,70,主要致病性真菌医学知识专题宣讲,PCP:Historical Features,1909-First recognized in lungs of Guinea pigs by Chagas.,Similar to Trypanosoma cruzi,yet different.,These observations were confirmed by Carini soon after.,1912-Delanoes named it after its discoverer and to reflect its tendency to infect the lungs.,71,主要致病性真菌医学知识专题宣讲,PCP:Historical Features,Not initially believed to affect humans.,1951-Vanek described an interstitial pneumonia with,Pneumocystis carinii,organisms in a human.,1955-First reported in immunodeficiency.,1957-First associated with chemotherapy.,1982-AIDS and,Pneumocystis carinii,association.,72,主要致病性真菌医学知识专题宣讲,PCP:Classification,Fungus or Protozoan?,Shares both fungal and protozoan nucleic acids and structural features of each.,Does not grow in fungal cultures,and antifungal therapy is ineffective.,Found to respond to anti-parasitic therapy.,Initially,thought to be a Protozoan.,Now believed to be a fungus,probably related to,Saccharomyces,.,73,主要致病性真菌医学知识专题宣讲,卡氏肺孢菌,Pneumocystis,carinii,生物学性状,单细胞型，兼具原虫及酵母菌的特点，其发育过程如下：,孢子小滋养体大滋养体（二分裂、出芽或,接合生殖,）囊前期孢子囊囊内减数分裂形