主要致病性真菌

1、主要致病性真菌淺部真菌感染致病性真菌感染和條件致病性真菌感染深部真菌感染致病性真菌感染和條件致病性真菌感染1第一頁(yè)，共八十一頁(yè)。淺部感染真菌外表感染真菌皮膚癬真菌皮下組織真菌感染2第二頁(yè)，共八十一頁(yè)。3第三頁(yè)，共八十一頁(yè)。外表感染真菌位置：寄居于人體皮膚和毛干的最表層。因不接觸組織細(xì)胞，很少引起宿主細(xì)胞反響統(tǒng)稱：角層癬菌 代表：秕糠馬拉癬菌(Malassezia furfur)病癥：由于此菌能產(chǎn)生對(duì)黑色素細(xì)胞有抑制作用的二羧酸，使花斑癬局部色素減退，如汗?jié)n斑點(diǎn)，俗稱汗斑。誘發(fā)因素為高溫多汗4第四頁(yè)，共八十一頁(yè)。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第五頁(yè)，共八十一頁(yè)。Pityriasis versicolor showing hyperpigmented lesions in a Caucasian

3、 and hyphopigmented lesions in an Australian Aborigine6第六頁(yè)，共八十一頁(yè)。Culture of Malassezia furfur on Dixons agar (contains glycerol mono-oleate)7第七頁(yè)，共八十一頁(yè)。Piedraia hortae (何德毛結(jié)節(jié)菌)It usually affected the scalp hairThe nodules are darker in color, harder, and more firmly attached to the hairsBlack Piedra8

4、第八頁(yè)，共八十一頁(yè)。Piedraia hortae forms a hard superficial pigmented nodule around the hair shaft (在毛干上形成硬的黑色結(jié)節(jié)，如沙粒狀)9第九頁(yè)，共八十一頁(yè)。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第十頁(yè)，共八十一頁(yè)。11第十一頁(yè)，共八十一頁(yè)。皮膚癬真菌引起皮淺薄部感染皮膚癬是人類最多見的真菌病統(tǒng)稱：皮膚癬菌，大約40多個(gè)種，分屬于3個(gè)屬嗜角質(zhì)蛋白，37不能生長(zhǎng)，侵犯部位：角化的表皮，毛發(fā)，指趾甲病理變化：由真菌增殖及代謝產(chǎn)物刺激宿 主引起12第十二頁(yè)，共八十一頁(yè)。致病性 指趾甲 皮膚 毛發(fā)毛癬菌屬 + + +表皮癬菌屬 + + -小孢子癬菌屬 - + + 一種皮膚癬菌可在不同部位引起病變相同部位的病變也可由不同的皮膚癬菌引起13第十三頁(yè)，共八

6、十一頁(yè)。14第十四頁(yè)，共八十一頁(yè)。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第十五頁(yè)，共八十一頁(yè)。手足癬治療原那么水皰型溫和搽劑和霜?jiǎng)┙腔^度型先角質(zhì)剝脫劑，再用抗真菌霜?jiǎng)┙n糜爛型粉劑收干，抗繼發(fā)感染，再溫和抗真菌16第十六頁(yè)，共八十一頁(yè)。Tinea Unguiumusually caused by Trichophyton sp17第十七頁(yè)，共八十一頁(yè)。甲癬治療原那么局部治療甲涂劑系統(tǒng)治療伊曲康唑，特比萘芬等聯(lián)合治療配合拔甲或削甲治療18第十八頁(yè)，共八十一頁(yè)。Tinea Corporis:caused by M. canis, following contact with infectious kittens 19第十九頁(yè)，共八十一頁(yè)。 T

8、inea Cruris (Jock itch):Infection of the groin, mainly seen in men20第二十頁(yè)，共八十一頁(yè)。Tinea Capitis (scalp ringworm)Tinea favosa發(fā)內(nèi)孢子21第二十一頁(yè)，共八十一頁(yè)。Tinea Capitis (scalp ringworm)Tinea alba發(fā)外孢子22第二十二頁(yè)，共八十一頁(yè)。Tinea Capitis (scalp ringworm)膿癬23第二十三頁(yè)，共八十一頁(yè)。頭癬治療原那么剪發(fā)洗發(fā)搽藥服藥消毒24第二十四頁(yè)，共八十一頁(yè)。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第二十五頁(yè)，共八十一頁(yè)。念珠菌性間擦疹好發(fā)部位：腋窩、乳房下、腹股溝、會(huì)陰，多見于嬰兒及肥胖者。26第二十六頁(yè)，共八十一頁(yè)

10、。Cutaneous candidiasis : including Interdigital candidiasis, diaper candidiasis, paronychia and onychomycosisVulvovaginal candidiasis and balanitisInterdigital candidiasis Candidia onychomycosis and paronychia 27第二十七頁(yè)，共八十一頁(yè)。Oropharyngeal candidiasis : including thrush, glossitis, stomatitis and angu

11、lar cheilitisOral thrush28第二十八頁(yè)，共八十一頁(yè)。皮下組織真菌感染主要有孢子絲菌和著色真菌申克孢子絲菌，屬腐生性真菌，常因外傷接觸帶菌的花草等引起感染。此菌可引起孢子絲菌下疳。此菌也可引起深部感染。是一種二相性真菌。著色真菌感染發(fā)生在暴露部位，稱著色真菌病。我國(guó)主要有卡氏枝孢霉和裴氏著色芽生菌。29第二十九頁(yè)，共八十一頁(yè)。Sporotrichosis此菌可經(jīng)微小損傷侵入皮膚，然后沿淋巴管分布，引起亞急性或慢性肉芽腫，使淋巴管形成鏈狀硬結(jié)，稱為孢子絲菌下疳。30第三十頁(yè)，共八十一頁(yè)。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第三十一頁(yè)，共八十一頁(yè)。經(jīng)外傷侵入丘疹結(jié)節(jié)結(jié)節(jié)融合成疣狀或菜花狀斑痕形成影響淋巴回流肢體象皮腫32第三十二頁(yè)，共八十一頁(yè)。ChromomycosisChronic verrucous chromoblastomycosis of the

13、hand due to Cladophialophora carrionii 33第三十三頁(yè)，共八十一頁(yè)。Mycetoma 足分枝菌病是由多種放線菌或真菌引起的一種慢性化膿性肉芽腫性疾病，主要感染足部，以腫脹、竇道和顆粒為特征。 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第三十四頁(yè)，共八十一頁(yè)。EumycetomaDark grainsMadurella mycetomatisLeptosphaeria senegalensisExophiala jeanselmeiPale grainsFusarium sp.Acremonium sp.Scedosporium apiospermum ActinomycetomaWhite-yellow grainsActinomadura maduraeNocardia brasiliensisYellow-brown grainsStrepto

15、myces somaliensisRed-pink grainsActinomycetoma pellettieri35第三十五頁(yè)，共八十一頁(yè)。深部真菌感染引起深部感染的真菌包括兩大類：致病性真菌與條件致病性真菌致病性真菌主要有組織胞漿菌、球孢子菌、副球孢子菌和芽生菌，這些真菌均屬二相性。多見于美洲，我國(guó)極少見。它們侵襲深部組織和內(nèi)臟以及全身，引起慢性肉芽腫樣炎癥、潰瘍和壞死。條件致病性真菌包括有：念珠菌、隱球菌、曲霉菌與毛霉菌、肺孢子菌等。36第三十六頁(yè)，共八十一頁(yè)。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第三十七頁(yè)，共八十一頁(yè)。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第三十八頁(yè)，共八十一頁(yè)。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第三十九頁(yè)，共八十一頁(yè)。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第四十頁(yè)，共八十一頁(yè)。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第四十一頁(yè)，共八十一頁(yè)。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第四十二頁(yè)，共八十一頁(yè)。 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第四十三頁(yè)，共八十一頁(yè)。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第四十四頁(yè)，共八十一頁(yè)。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第四十五頁(yè)，共八十一頁(yè)。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第四十六頁(yè)，共八十一頁(yè)。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第四十七頁(yè)，共八十一頁(yè)。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第四十八頁(yè)，共八十一頁(yè)。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第四十九頁(yè)，共八十一頁(yè)。白假絲酵母菌(Candida albicans) 形態(tài)：圓形或卵圓形單細(xì)胞真菌，革蘭陽性繁殖：出芽繁殖，形成假菌絲，在組織易形成芽生孢子培養(yǎng)：普通瓊脂、血瓊脂與沙保培養(yǎng)基 需氧。室溫或 37甚至42生長(zhǎng)良好 菌落灰白色或奶油色，外表光滑，帶有濃厚的酵母氣味。 有大量向下生長(zhǎng)的營(yíng)養(yǎng)假菌絲，呈類酵母型。 在玉米粉培養(yǎng)基上可長(zhǎng)出厚膜孢子屬于假絲酵母菌屬，俗稱白念，為酵母型真菌，是條件致病菌 可引起皮膚、黏膜和內(nèi)臟的急性或慢性炎癥，即念珠菌病，是最常見的深部感染真菌病，口腔念珠菌病是艾滋病患者最先出現(xiàn)的繼發(fā)性

38、感染。生物學(xué)特性50第五十頁(yè)，共八十一頁(yè)。假菌絲和厚膜孢子51第五十一頁(yè)，共八十一頁(yè)。Systemic involvementUrinary tract infectionPulmonary candidiasis Endocarditis MeningitisCandidaemia(septicaemia) Infancy, old age, pregnancy, prolong antibiotic, HIV/AIDS, diabetes 52第五十二頁(yè)，共八十一頁(yè)。微生物檢查： 1、直接鏡檢：同時(shí)見出芽的念珠菌與假菌絲 2、別離培養(yǎng)與鑒定：假菌絲，芽生孢子 芽管形成試驗(yàn)/厚膜孢子形成試驗(yàn)

39、 3、白色念珠菌細(xì)胞壁甘露聚糖抗原/ELISA 特異性高但敏感性低 4、動(dòng)物試驗(yàn)：小鼠53第五十三頁(yè)，共八十一頁(yè)。Cryptococcus neoformans屬于隱球菌屬，為酵母型真菌 傳染源是鴿子，人因吸入鴿糞污染的空氣而感染 主要引起肺和腦的急性、亞急性或慢性感染。生物學(xué)特性圓形，有肥厚莢膜一般厚度是直徑的兩倍 染色：一般染色法不易著色，墨汁負(fù)染，胞內(nèi)有較大的反光顆粒。出芽繁殖，不形成假菌絲酵母型菌落培養(yǎng)特性：沙?；蜓傊囵B(yǎng)基，2537生化特性：分解尿素莢膜多糖抗原：AD 和AD 5個(gè)血清型，我國(guó)約70%屬A型54第五十四頁(yè)，共八十一頁(yè)。55第五十五頁(yè)，共八十一頁(yè)。致病性外源性感染，肺

40、是主要入侵途徑，也屬于人體正常菌群，引起條件性感染原發(fā)感染通常在肺部，多數(shù)病癥不明顯，自愈；有的引起支氣管肺炎；嚴(yán)重者呈爆發(fā)性感染并迅速死亡局部患者經(jīng)血行傳播至中樞神經(jīng)及其它組織，引起肉芽腫性炎癥，主要導(dǎo)致慢性腦膜炎致病物質(zhì)：莢膜56第五十六頁(yè)，共八十一頁(yè)。微生物學(xué)檢查負(fù)染色鏡檢抗原檢查： 檢查患者血清和腦脊液中新隱莢膜抗原別離鑒定 尿素酶或酚氧化酶動(dòng)物試驗(yàn)： 小鼠57第五十七頁(yè)，共八十一頁(yè)。曲霉Aspergillus 煙曲霉 支氣管哮喘或肺部感染 毛霉Mucor 腐生菌 腦、肺、胃腸道卡氏肺孢菌Pneumocystis carinii 免疫缺陷病人 肺炎58第五十八頁(yè)，共八十一頁(yè)。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第五十九頁(yè)，共八十一頁(yè)。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第六十頁(yè)，共八十一頁(yè)。61第六十一頁(yè)，共八十一頁(yè)。Aspergillus flavusAspergillus nigerAspergillus fumigatus62第六十二頁(yè)，共八十一頁(yè)。足細(xì)胞分生孢子梗頂囊桿狀小梗串狀分生孢子分生孢子頭63第六十三頁(yè)，共八十一頁(yè)。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第六十四頁(yè)，共八十一頁(yè)。Pathogenicity and Clinical

44、 Significance局限性肺曲霉病根底疾病致肺空洞存在 曲霉在此生長(zhǎng)，不侵犯組織不播散曲霉肺炎免疫功能低下過敏性支氣管肺曲霉病過敏體質(zhì)65第六十五頁(yè)，共八十一頁(yè)。Pathogenicity and Clinical Significance全身性曲霉病多發(fā)生在某些重癥疾病晚期原發(fā)病灶主要在肺 常由敗血癥引起全身性感染生前很難得到確診66第六十六頁(yè)，共八十一頁(yè)。Pathogenicity and Clinical Significance黃曲霉毒素與惡性腫瘤，尤其是肝癌的發(fā)生密切相關(guān) 67第六十七頁(yè)，共八十一頁(yè)。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.血清學(xué)診斷或血清學(xué)試驗(yàn)檢出曲霉細(xì)胞壁半乳糖甘露乳糖抗原.68第六十八頁(yè)，共八十一頁(yè)。Culture : In SDA with antibiotics at 25 and 37c有隔菌絲和分生孢子頭.69第六十九頁(yè)，共八十一頁(yè)。Pneumocystis carinii Pneumonia70第七

46、十頁(yè)，共八十一頁(yè)。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第七十一頁(yè)，共八十一頁(yè)。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第七十二頁(yè)，共

48、八十一頁(yè)。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第七十三頁(yè)，共八十一頁(yè)?？ㄊ戏捂呔鶳neumocystis carinii 生物學(xué)性狀單細(xì)胞型，兼具原蟲及酵母菌的特點(diǎn)，其發(fā)育過程如下：孢子小滋養(yǎng)體大滋養(yǎng)體二分裂、出芽或接合生殖囊前期孢子囊