主要致病性真菌

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1第一页，共八十一页。浅部感染真菌外表感染真菌皮肤癣真菌皮下组织真菌感染2第二页，共八十一页。3第三页，共八十一页。外表感染真菌位置：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响统称：角层癣菌 代表：秕糠马拉癣菌(Malassezia furfur)病症：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第四页，共八十一页。Malassezia furfurTinea versicolor on skin

2、surface (sweat stain)The lesions are small hypopigmented or hyperpigmented maculesMost common site : back, underarm, upper arm, chest, neck Most common in adolescent and young adult males Associated with increased sweating5第五页，共八十一页。Pityriasis versicolor showing hyperpigmented lesions in a Caucasian

3、 and hyphopigmented lesions in an Australian Aborigine6第六页，共八十一页。Culture of Malassezia furfur on Dixons agar (contains glycerol mono-oleate)7第七页，共八十一页。Piedraia hortae (何德毛结节菌)It usually affected the scalp hairThe nodules are darker in color, harder, and more firmly attached to the hairsBlack Piedra8

4、第八页，共八十一页。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第九页，共八十一页。Fungal otitis externaFungal infection of the external auditory canalCaused by several species of Aspergillus (most often A.niger), but Candida albicans is also capable of infecting

5、 this siteThe major symptoms are itching and feeling of fullness in ear10第十页，共八十一页。11第十一页，共八十一页。皮肤癣真菌引起皮浅薄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第十二页，共八十一页。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第十三页，共八

6、十一页。14第十四页，共八十一页。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

7、 matting. 15第十五页，共八十一页。手足癣治疗原那么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第十六页，共八十一页。Tinea Unguiumusually caused by Trichophyton sp17第十七页，共八十一页。甲癣治疗原那么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第十八页，共八十一页。Tinea Corporis:caused by M. canis, following contact with infectious kittens 19第十九页，共八十一页。 T

8、inea Cruris (Jock itch):Infection of the groin, mainly seen in men20第二十页，共八十一页。Tinea Capitis (scalp ringworm)Tinea favosa发内孢子21第二十一页，共八十一页。Tinea Capitis (scalp ringworm)Tinea alba发外孢子22第二十二页，共八十一页。Tinea Capitis (scalp ringworm)脓癣23第二十三页，共八十一页。头癣治疗原那么剪发洗发搽药服药消毒24第二十四页，共八十一页。Candidiasis of skin, mucou

9、s membranes and nails Predisposing factorsInfancy, pregnancy, old ageDisorders of immune function, e.g., leukemia, corticosteroid therapyChemotherapy, e.g., immunosuppressive, antibioticEndocrine disease, e.g., diabetes mellitusCarcinoma25第二十五页，共八十一页。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第二十六页，共八十一页

10、。Cutaneous candidiasis : including Interdigital candidiasis, diaper candidiasis, paronychia and onychomycosisVulvovaginal candidiasis and balanitisInterdigital candidiasis Candidia onychomycosis and paronychia 27第二十七页，共八十一页。Oropharyngeal candidiasis : including thrush, glossitis, stomatitis and angu

11、lar cheilitisOral thrush28第二十八页，共八十一页。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第二十九页，共八十一页。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第三十页，共八十一页。ChromomycosisInfections occur in exposed are

12、as, skin lesions become dark, so called chromomycosisRepresentive species: Cladosporium carrianii, Fonsecaea pedrosoi, etc.Are saprophytic fungi, usually enters the body by trauma31第三十一页，共八十一页。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第三十二页，共八十一页。ChromomycosisChronic verrucous chromoblastomycosis of the

13、hand due to Cladophialophora carrionii 33第三十三页，共八十一页。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 ac

14、tinomycete filaments known as grains34第三十四页，共八十一页。EumycetomaDark grainsMadurella mycetomatisLeptosphaeria senegalensisExophiala jeanselmeiPale grainsFusarium sp.Acremonium sp.Scedosporium apiospermum ActinomycetomaWhite-yellow grainsActinomadura maduraeNocardia brasiliensisYellow-brown grainsStrepto

15、myces somaliensisRed-pink grainsActinomycetoma pellettieri35第三十五页，共八十一页。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第三十六页，共八十一页。Characteristics of systemic dimorphic mycosesAre uncommon, ofte

16、n occurs in endemic areas Most infections are asymptomatic or self-limitingin immune-compromised hosts, infections are often fatalThe pattern of infection are similarRoute of acquisition is inhalation Pulmonary infectionDisseminated infection (Blood, Bone marrow, Brain and CSF, Joint)37第三十七页，共八十一页。C

17、occidioidomycosisCoccidiodes 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 sph

18、erules.ConidiaSpherules38第三十八页，共八十一页。Coccidioidomycosis:Encounter: Mycelium found in dry, dusty soil. Contact by inhalation of arthroconidiaSpread: Most commonly an asymptomatic self limited pulmonary disease, but may spread via the blood to skin, soft tissues, bones, joints and meninges.Immune Resp

19、onse: 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 & IgA39第三十九页，共八十一页。1. Ethnicity: Filipinos, African Americans,

20、Native Americans at higher risk2.Age: Extremes more susceptible3.Sex: Males more susceptible4.Pregnancy: 3rd trimester5.ImmunosuppressionF. Diagnosis1.Exam: Suppurative or granulomatous inflammation2.Histopathology: spherules or endospores seen in sputum, exudates or tissue3.Culture: danger, highly

21、infectious!4.Serology: Complement fixation assay (in cerebrospinal fluid), particle agglutination assay G. TreatmentAmphotericin B followed by an azoleE. Risk FactorsCoccidioidomycosis:40第四十页，共八十一页。Histoplasmosis (also called cave disease)Caused by the dimorphic fungus Histoplasma capsulatumTubercul

22、ated macroconidia, grown at 25CIntracellular yeast at 37CHistoplasmosis 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第四十一页，共八十一页。Histoplasmo

23、sisA. 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 & Flori

24、da. Most cases occur in Ohio Valley and Mississippi Valley)42第四十二页，共八十一页。 More Histoplasmosis90% of cases are asymptomatic, but in rare cases flu like respiratory symptoms occurDisseminated histoplasmosis occurs in 1:200 cases and is diagnosed frequently in patients with AIDS living in the central U

25、.S. In these cases, the organism spreads via blood from the lung to involve bone marrow, adrenal glands, heart valves and CNS4.Spread can also be associated with underlying lung disease (e.g., emphysema).B. SpreadC. Immune ResponseCell-mediated responses are of primary importanceActivated macrophage

26、 can kill yeast cellsD. Evasion of DefensesSurvival in macrophages elevates pH of phagosomesYeast cells absorb iron (siderophore) and calcium from hostAlteration of cell surface 43第四十三页，共八十一页。Histoplasmosis Direct histology and culture of blood or bone marrowSerological testing for antibody and hist

27、oplama antigen in blood and urine. E. DiagnosisD. DamageLung-bronchial obstruction and inflammatory sequelaeDisseminated histoplasmosis-fulminant disease that may result in toxic shockCNS-fatal if untreated.44第四十四页，共八十一页。Even More HistoplasmosisF. TreatmentAmphotericin still mainstay of therapy vs.

28、disseminated and severe pulmonary histoplasmosis. Ketoconasole or itraconasole is effective as therapy for self-limited disease (used in AIDS).Ocular HistoplasmosisA small fraction of individuals form scar tissue in the retina many years after the original histoplasmosis infection. Live organisms ca

29、nnot 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第四十五页，共八十一页。Blastomycosis Granulomatous mycoti

30、c 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 37o

31、 in vitro.46第四十六页，共八十一页。BlastomycosisEncounter: 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

32、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 infectionDamage: Consequence of the i

33、mmune response to the organismskin lesions, respiratory infiltrates.Diagnosis: based on clinical findings and microscopic detection of organisms in tissue specimens47第四十七页，共八十一页。Amphotericin B is the drug of choice for rapidly progressive blastomycosisItraconazole or Ketoconazole for less severe cas

34、esImmune response1. 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 importanceBlastomycosisTreatment48第四十八页，共八十一页。Opportunis

35、tic fungal infectionsOpportunistic 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 su

36、ppress 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 pneum

37、onia (PCP) Penicillosis marneffei49第四十九页，共八十一页。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，外表光滑，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

38、感染。生物学特性50第五十页，共八十一页。假菌丝和厚膜孢子51第五十一页，共八十一页。Systemic involvementUrinary tract infectionPulmonary candidiasis Endocarditis MeningitisCandidaemia(septicaemia) Infancy, old age, pregnancy, prolong antibiotic, HIV/AIDS, diabetes 52第五十二页，共八十一页。微生物检查： 1、直接镜检：同时见出芽的念珠菌与假菌丝 2、别离培养与鉴定：假菌丝，芽生孢子 芽管形成试验/厚膜孢子形成试验

39、 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第五十三页，共八十一页。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，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54第五十四页，共八十一页。55第五十五页，共八十一页。致病性外源性感染，肺

40、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，多数病症不明显，自愈；有的引起支气管肺炎；严重者呈爆发性感染并迅速死亡局部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第五十六页，共八十一页。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别离鉴定 尿素酶或酚氧化酶动物试验： 小鼠57第五十七页，共八十一页。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第五十八页，共八十一页。Asper

41、gillusAspergillus 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第五十九页，共八十一页。morphologyIt is a filamentous

42、fungiHyphae are septate and hyaline. Consisting of a Vesicle The morphology and color of the conidiophore vary from one species to another. 60第六十页，共八十一页。61第六十一页，共八十一页。Aspergillus flavusAspergillus nigerAspergillus fumigatus62第六十二页，共八十一页。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第六十三页，共八十一页。SpeciesThe genus Aspergi

43、llus 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第六十四页，共八十一页。Pathogenicity and Clinical

44、 Significance局限性肺曲霉病根底疾病致肺空洞存在 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第六十五页，共八十一页。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66第六十六页，共八十一页。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第六十七页，共八十一页。Laboratory diagnosisThe specimen like s

45、putum 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第六十八页，共八十一页。Culture : In SDA with antibiotics at 25 and 37c有隔菌丝和分生孢子头.69第六十九页，共八十一页。Pneumocystis carinii Pneumonia70第七

46、十页，共八十一页。PCP: Historical Features1909 - 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第七十一页，共八十一页。PC

47、P: Historical FeaturesNot 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第七十二页，共

48、八十一页。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, thought to be a Protozoan.Now believed to be a fungus, probably related to Saccharomyces.73第七十三页，共八十一页。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