主要致病性真菌.ppt

1、1,主要致病性真菌,浅部真菌感染（致病性真菌感染和 条件致病性真菌感染） 深部真菌感染（致病性真菌感染和 条件致病性真菌感染）,2,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,3,4,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,5,Malassezia furfur,Tinea versicolor on skin surface (sweat

2、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,6,Pityriasis versicolor showing hyperpigmented lesions in a Caucasian and hyphopigmented l

3、esions in an Australian Aborigine,7,Culture of Malassezia furfur on Dixons agar (contains glycerol mono-oleate),8,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,9,Piedraia hortae forms a hard sup

4、erficial pigmented nodule around the hair shaft (在毛干上形成硬的黑色结节，如沙粒状),10,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 f

5、eeling of fullness in ear,11,12,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,13,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,14,15,Tinea pedis caused by T. rubrum. Sub-clinical infection (left)

6、 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.,16,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,17,T

7、inea Unguium,usually caused by Trichophyton sp,18,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,19,Tinea Corporis:caused by M. canis, following contact with infectious kittens,20,Tinea Cruris (Jock itch):Infection of the groin, mainly seen in men,21,Tinea Capitis (scalp ringworm),Tinea favosa,发内孢子,22,

8、Tinea Capitis (scalp ringworm),Tinea alba,发外孢子,23,Tinea Capitis (scalp ringworm),脓癣,24,头癣治疗原则,剪发 洗发 搽药 服药 消毒,25,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., im

9、munosuppressive, antibiotic Endocrine disease, e.g., diabetes mellitus Carcinoma,26,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。,27,Cutaneous candidiasis : including Interdigital candidiasis, diaper candidiasis, paronychia and onychomycosis Vulvovaginal candidiasis and balanitis,Interdigital candidiasis,

10、Candidia onychomycosis and paronychia,28,Oropharyngeal candidiasis : including thrush, glossitis, stomatitis and angular cheilitis,Oral thrush,29,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。,30,Sporotrichosis,此菌可经微小损伤侵

11、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。,31,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,32,经外伤侵入 丘疹 结节 结节融合成疣状或菜

12、花状 斑痕形成影响淋巴回流 肢体象皮肿,33,Chromomycosis,Chronic verrucous chromoblastomycosis of the hand due to Cladophialophora carrionii,34,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 b

13、y the formation of abscess, which contain large aggregates of fungal or actinomycete filaments known as grains,35,Eumycetoma Dark grains Madurella mycetomatis Leptosphaeria senegalensis Exophiala jeanselmei Pale grains Fusarium sp. Acremonium sp. Scedosporium apiospermum,Actinomycetoma White-yellow

14、grains Actinomadura madurae Nocardia brasiliensis Yellow-brown grains Streptomyces somaliensis Red-pink grains Actinomycetoma pellettieri,36,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。,37,C

15、haracteristics 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

16、infection (Blood, Bone marrow, Brain and CSF, Joint),38,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 t

17、issues, C. immitis appears as a mixture of endospores and spherules.,Conidia,Spherules,39,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 ski

18、n, 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 but

19、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 37o in vitro.,47,Blastomycosis,Encounter: Most cases are in so

20、uthern, 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 lesi

21、ons. 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 infiltra

22、tes. Diagnosis: based on clinical findings and microscopic detection of organisms in tissue specimens,48,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 defens

23、e. 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,49,Opportunistic fungal infections,Opportunistic mycoses are fungal infections that do n

24、ot 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 p

25、revent 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,50,白假丝酵母菌(Candida albicans),形态：圆形或卵圆形单细

26、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,51,假菌丝和厚膜孢子,52,Systemic involvement,Urinary tract infection Pulmonary

27、candidiasis Endocarditis Meningitis Candidaemia(septicaemia) Infancy, old age, pregnancy, prolong antibiotic, HIV/AIDS, diabetes,53,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,54,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

28、 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，2537 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,55,56,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,57,微生

29、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,58,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,59,Aspergillus,Aspergillus is a filamentous, cosmopolitan and ubiquitous fungus found in nature. It is commonly isolated from soil, plant debris, and indo

30、or air environment. It is the second most commonly recovered fungus in opportunistic mycoses following Candida.,60,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 another.,61,62,Aspergi

31、llus flavus,Aspergillus niger,Aspergillus fumigatus,63,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）,64,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 i

32、solated species, followed by Aspergillus flavus and Aspergillus niger.,65,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）,66,Pathogenicity and Clinical Significance,全身性曲霉病 多发生在某些重症疾病晚期 原发病灶主要在肺 常由败血症引起全身性感染 生前很难得到确诊,67,Pathogenicity and Clinic

33、al Significance,黄曲霉毒素与恶性肿瘤，尤其是肝癌的发生密切相关,68,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.,69,Culture : In SDA with antibioti

34、cs at 25 and 37c 有隔菌丝和分生孢子头.,70,Pneumocystis carinii Pneumonia,71,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

35、 to reflect its tendency to infect the lungs.,72,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. 19

36、82 - AIDS and Pneumocystis carinii association.,73,PCP: ClassificationFungus 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, t

37、hought to be a Protozoan. Now believed to be a fungus, probably related to Saccharomyces.,74,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成孢子成熟孢子囊内含8个孢子 致病性 艾滋病患者最常见的并发症和主要的致死原因 微生物学检查 采集痰液，染色镜检，若发现滋养体或孢子囊可确诊 防治 本菌对多种抗真菌药物不敏感，用药首选复方新诺明,75,X-ray of Pneumocystis jirovecii pneumonia,There is increased opacification (whiteness) in the lower lungs on both sides, cha