醫(yī)學(xué)微生物學(xué)資料：真菌各論

1、2022/9/161Pathogenic fungi2022/9/162Type of mycosisCausative fungal agentsMycosis Superficial Malassezia speciesHortaea werneckiiTrichosporon speciesPiedraia hortaePityriasis versicolorTinea nigraWhite piedraBlack piedraCutaneous Microsporum species, trichophyton species, and epidermophyton floccosu

2、mCandida albicans and other candida speciesDermatophytosis Candidiasis of skin, mucosa, or nailsSubcutaneous Sporothrix schenckiiPhialophora verrucosa, Fonsecaea pedrosoil,Pseudallescheria boydii, Madurella mycetomatisExophiala, bipolaris, exserohilum, and othersSporotrichosis Chromoblastomycosis My

3、cetomaPhaeohyphomycosis Endemic（primary,systemic） Coccidioides immitis, C posadasiiHistoplasma capsulatumBlastomyces dermatitidisParacoccidioides brasiliensis Coccidioidomycosis Histoplasmosis BlastomycosisParacoccidioidomycosis Opportunistic Candida albicans and other candida speciesCryptococcus ne

4、oformans？Aspergillus fumigatus and other aspergillus spiecesSpices of rhizopus, absidia, mucor, and other zygomycetesPenicillium marneffei Systemic candidiasisCryptococcosis Aspergillosis Mucormycosis (zygomycosis)Penicilliosis The major mycoses and causative fungi2022/9/163Dermatophytes Sporothrix

5、andother subcutaneous fungi2022/9/164Case study and questions Darrell, a 24-year-old medical student, he recently purchases Delbert (a bulldog puppy) from a local backyard breeder. Darrel has taken to giving Delbert frequent smooches on his muzzle, after approximately 3 months of proud puppy ownersh

6、ip and smooching and his upper lip was beginning to swell. Over a 1-week period, his upper lip became swollen and inflamed, and small pustular areas became apparent among the sparse hairs of this moustache. Similar changes were also becoming apparent on Delberts muzzle. This concerned Darrell, so he

7、 promptly took Delbert to the vet. The vet took one look at the pair, wrote a prescription for Delbert, and told Darrell that he should make a visit to the dermatologist.2022/9/165Questions What was the likely cause of Darrel/Delberts afflictionHow would you go about making a diagnosis?How would you

8、 go about treating this infection?Who gave what to whom?2022/9/166Dermatophytes Microsporum TrichophytonEpidermophyton2022/9/167Trichophyton species 毛癬菌屬Large, smooth, thin wall, septate, pencil-shapedMorphology 25， sabourauds agar2022/9/168Microsporum species 小孢子菌屬Thick wall, spindle shape, multice

9、llular2022/9/169Epidermophyton floccosum 表皮癬菌屬Bifurcated hyphae with multiple, smooth, club shaped macroconidia (2-4 cells)2022/9/1610Epidemiology2022/9/1611Reservoir: human, animal, or soil Transmission: contact with intact or detached skin or hair. Epidemiology2022/9/1612 Fatty acids Susceptibilit

10、y Balance between fungal growth and skin desquamation Poor inflammatory response chronic infection Hyphae : eg. EndothrixPathogenesis2022/9/1613 Delayed hypersensitivity responses CMI(cell-mediated immunity) responses T-lymphocytes defects :chronic ,wide spread Trichophyton.rubrumImmunity2022/9/1614

11、Dermatophyte diseases（manifestations）2022/9/1615Dermatophyte infection of scalp (ringworm)Scalp lesions: annular marginationScrapings taken from the edge of the scalp lesion in KOHCulture : hyphae, macroconidia, and microconidia are present are present. The macroconidia are characteristic of Trichop

12、hyton Tinea capitis (scalp)2022/9/1616Tinea pedis (feet)2022/9/1617Tinea corporis (the body)Tinea unguium (nails)2022/9/1618Tinea barbae (bearded area)Tinea cruris (jock itch)2022/9/1619Diagnosis Microscopic examination Culture KOH Woods lamp Ultraviolet lamp2022/9/1620Treatment and prevention Topic

13、al tolnaftate, or axoles usually sufficient. Systemic griseofulvin, azoles : refractory cases. Keratolytic agents No specific preventive measures available2022/9/1621Other superficial mycoses Pityriasis (tinea) versicolor: caused by Malassezia.furfur Tinea nigra caused by Hortaea.werneckii Piedra: c

14、aused by Trichosporon cutaneum or Piedraia hortae 2022/9/1622 Subcutaneous fungi Sporothrix schenckiiSporotrichosisFonsecaeaPhialophoraCladosporium ChromoblastomycosisMycetomaActinomycetes nocardia 2022/9/1623Case study and questions Two healthy construction laborers were seen by a dermatologist dev

15、eloping painless bilateral ulcerative lesions along the lymphatics of their forearms. On examination, both patients are afebrile. The dermatologist noted regional lymphadenopathy, and the lesions extended up the lymphatics as tender erythematous nodules, some of the patients revealed that these lesi

16、ons began to appear 2 to 3 weeks after the two laborers had demolished an attic that they got splinters from carrying salvaged wood from the rafters. They also commented that a lot of dust was raised during the salvage.2022/9/1624Questions What was the most likely diagnosis, and how should the diagn

17、osis have been confirmed?What generalizations can you make about subcutaneous mycotic infections?What are the therapeutic strategies used in the various subcutaneous mycoses2022/9/1625Sporothrix schenckii2022/9/1626Sporothrix schenckii:Yeast ：typically cigar-shaped Mold2022/9/1627Epidemiology（ Sporo

18、trichosis） Traumatic inoculation with contaminated material. Ubiquitous, particularly in hay, moss, soil or on decaying vegetation, Occupational disease of gardeners and farmers.2022/9/1628In the spring of 1988 : in the United statesHistory outbreaks of Sporotrichosis 2000-2003: Busselton-Margaret R

19、iver region of Western Australia2022/9/1629PathogenesisConidia / yeast bind to extracellular matrix.Melanin production resistance to oxidative killing.Infection spreads along lymphatic drainage routes2022/9/1630Immunity CMI： cell mediated immunityAntibody Manifestations 2022/9/1631Sporotrichosis cla

20、ssic skin lesions of sporotrichosis nodules along the lymphatic vessels.2022/9/1632Lymphatic involvementSporotrichosis2022/9/1633DiagnosisDefinitive diagnosis depends on culture of infected pus or tissue.Identification requires demonstration of the typical conidia and of dimorphism. 2022/9/1634 Pota

21、ssium iodide : for cutaneous fungi Amphotericin or itraconazole: for progressive disease. Itraconzole： for all but cutaneous sporotrichosis Eradication of the environmental reservoir of S.schenckii is not usually practicalTreatment and preventions 2022/9/1635皮膚癬菌、孢子絲菌及其它皮下真菌皮膚癬菌侵犯人的皮膚、毛發(fā)和指（趾）甲，導(dǎo)致淺部感

22、染，引起各種癬病毛癬菌屬、表皮癬菌屬、小孢子癬菌屬直接顯微鏡檢查， 鏡檢陰性者進(jìn)行培養(yǎng)治療： 托萘酯、丙烯胺、咪唑類2022/9/1636申克孢子絲菌自然腐生菌，雙相真菌，引起孢子絲菌病分布廣泛：干草、苔蘚、土壤或植物常見于園丁、農(nóng)夫等外傷后接觸被污染的土壤等感染細(xì)胞免疫為主臨床表現(xiàn)： 常見于手( 可見皮膚丘疹、潰瘍、膿包、皮損沿淋巴管分布)診斷： 根據(jù)臨床表現(xiàn)、病史、培養(yǎng)結(jié)果治療： 飽和碘化鉀溶液口服，兩性霉素B、伊曲康唑2022/9/1637 Opportunistic fungi Candida Aspergillus2022/9/1638Candia, Aspergillus, and

23、 other Opportunistic Fungi Organism Growth tissueCulture at 25Culture at 37 sourceinfectionCandidaYeast (hyphae)aYeast(hyphae)aYeastEndogenous Skin, mucous membranes, urinary, disseminate dAspergillus Hyphae (septate)MoldMoldEnvironment Lung, disseminated,Zygomycetes bHyphae (nonseptate)moldMold Env

24、ironment Rhinocerebral, lung, disseminated a Less common feature; pseudohyphae are produced as well b Such genera as Absidia, Mucor, and Rhizopus2022/9/1639 Candia albicans Candia tropicalis Candia glabrata Aspergillus flavus Aspergillus fumigatus Aspergillus nigerZygomycetesAbsidia Rhizopus Mucor 2

25、022/9/1640 Candida albicans：conidia , thick-walled chlamydoconidia and pseudohyphae （1000）Candida albicansMorphology 2022/9/1641Candida albican: germ tubes (incubated at 37) 2022/9/1642 Infections are from endogenous flora more frequently. C. albicans is a common cause of nosocomial infections. The

26、number of available Candida may be enhanced by the use of antibacterial agents. Epidemiology2022/9/1643Pathogenesis Shift from yeast to hyphae. Strong attachements to human epithelial cells.Hyphae also secrete proteinases and phospholipasesReceptors bind C3 in an antiopsonic manner.Antimicrobics and

27、 immunosuppression increase risk. Surface mannoproteins Hyphal wall protein (Hwp1) Mechanical disruptions 2022/9/1644Pathogenesis of Candida albicans infection Attachment and invasion Fibronectin Epithelial cell Fibronectin bindingProteinase activityHyphae ECM bindingInterstitial collagenECMBasement

28、 membrane2022/9/1645Invasiveness of Candida albicansBoth blastoconidia and mycelial elements are present, the mycelial elements spread over the surface and invade the cell cuticle.C. Albicans strain that produces a protease is seen producing cavity-like depressions in the cell surface.2022/9/1646Imm

29、unityPolymorphonuclear neutrophils (PMNs）Compromised CMI is associated with progressive infectionCandida mannan may down-regulate CMI Balance between TH1 and TH2 cytokines is necessary. 1 Cell mediated immunity 2 Humoral immunity Antimannan IgG activates complement.2022/9/1647Manifestations I Thrush

30、 鵝口瘡Candida albicans2022/9/1648II VaginitisClinically found in :Pregnant women,DM patients Those treated with high dose of estrogen Those with long time use of antibiotics2022/9/1649III C. Albicans skin infectionIV Others Chronic mucocutaneous candidiasisEsophagitis and intestinal candidiasis Urinar

31、y tract infectionsEndophthalmitisDiaper rash2022/9/1650Diagnosis KOH and Gram smears of superficial lesions: yeast and hyphae.Lung involvement requires bronchoalveolar lavage.Endocarditis may require arterial blood cultures. Immunodiagnostic procedures are promising but not routine and not yet pract

32、ical for clinical use. 2022/9/1651Diagnosis Formation of hyphae and chlamydoconidia Carbohydrate assimilation and fermentation Rapidly produce colonies resembling staphylococciCulture : Sabourauds agar, blood agarC.albicans produces germ tubes2022/9/1652Treatment Nystatin Fluconazole Azoles Amphoter

33、icin BFlucytosine Superficial lesions Persistent relapsing or disseminated candidiasisChronic muocutaneous candidiasisInvasive disease 2022/9/1653Other common Candida speciesC. tropicalis C. glabrata 2022/9/1654Aspergillus2022/9/1655Aspergillus fumigatusAppergillus flavus Aspergillus niger Aspergill

34、us terreusAspergillus nidulans Morphology 2022/9/1656Aspergillus Asexual conidium forming structure (characteristic)Histologic sections : branching, septate hyphae Aspirate mixed with KOHABC2022/9/1657EpidemiologyMode of infection: inhalationConidia may be spread by construction projectsHospital air

35、 and air ductsHeat-resistant conidia provide a good mechanism for dispersal.2022/9/1658PathogenesisConidia bind to fibrinogen and lamininSmall enough to readily reach the alveoli when inhaledExtracellular proteases may cause injury.Immunity Alveolar macrophages PMNs2022/9/1659Manifestations Allergic

36、 aspergillosis Lung is the organ primarily involved Invasive aspergillosis Highly invasive, blood vessels involved 2022/9/1660Invasive Aspergillus 2022/9/1661Diseases associated with Aspergillus speciesDisease Etiologic agent Mycotoxicoses Ingestion of contaminated food productsHypersensitivity pneu

37、monitisAllergic bronchopulmonary diseaseSecondary colonizationFugal colonization of preexisting cavity (eg.pulmonary abscess) without invasion into contiguous tissuesSystemic disease Invasive disease involving many organs2022/9/1662Diagnosis Easy to isolate and identify. Direct aspirate or biopsy is

38、 required to distinguish colonization from invasion. Serodiagnosis is useful only for allergic disease. 2022/9/1663Treatment and prevention Amphotericin B, itraconazole, Voriconazole : recently used Surgery : removal of localized lesion (for invasive disease).2022/9/1664念珠菌、曲霉菌以及其他機會致病性真菌致病性念珠菌： 為機會

39、致病真菌，白假絲酵母菌最為常見白假絲酵母菌: 單細(xì)胞真菌，可形成假菌絲，常存在于正常人口腔、上呼吸道、陰道及腸道內(nèi)，當(dāng)機體免疫功能低下或菌群失調(diào)時可引起皮膚粘膜、內(nèi)臟和中樞神經(jīng)系統(tǒng)感染診斷要點： 直接鏡檢、分離培養(yǎng)。同時檢到出芽的酵母菌和假菌絲才具有診斷意義治療： 制菌酶素或唑類用于皮膚粘膜感染 兩性霉素B,氟胞嘧啶和唑類抗真菌藥用于侵襲性感染2022/9/1665致病性曲霉菌： 機會致病真菌，可引起曲霉病，大多在久病體弱、免疫力低下或菌群失調(diào)時發(fā)生。多數(shù)感染來自于孢子的吸入、肺和鼻竇最先受累； 還可見于外傷性植入如角膜感染臨床表現(xiàn)過敏性曲霉病侵襲性曲霉病診斷要點： 涂片鏡檢、培養(yǎng)、組織病理學(xué)

40、檢查、血清學(xué)試驗防治： 兩性霉素B、伊曲康唑、手術(shù)2022/9/1666Cryptococcus, Coccidioides, and other Systemic Fungal pathogens 2022/9/1667Features of systemic fungal pathogens organismgrowthCulture at 25Culture at 37tissuesourcePrimary disease Disseminated disease Cryptococcus neoformansEncapsulated yeastEncapsulated yeastEnc

41、apsulated yeastEnvironment worldwidePneumonia Chronic meningtitisHistoplasma capsulatumMold, tuberculate macroconidiaSmall yeastSmall intracellular yeast Environment,US midwestPneumonia, hilar adenopathyRES enlargementBlastomyces dermatitidisMold Yeast Environment US midwestPneumonia Skin and bone l

42、esionsCoccidioides immitis Mold , arthroconidia(spherules )Spherules Environment Sonoran desertValley feverPneumonia meningitis, skin boneParacoccidioides brasiliensisMold Yeast, multiple blastoconidiaEnvironment Latin AmericaPneumonia Mucocutaneous, RESRES: reticuloendothelial system (lymph nodes,

43、liver, spleen, bone marrow)2022/9/1668Cryptococcus : Crytococcus neoformansHistoplasma: Histoplasma capsulatumBlastomyces : blastomyces dermatitidsCoccidioides: Coccidioides immitisParracoccidioides brasiliensis 2022/9/1669Crytococcus neoformans2022/9/1670India ink preparation: Yeast ：4 to 6 m +large polysaccharide capsule 25m glucuronoxylomannan(GXM)Morphology 2022/9/1671Epidemiology Worldwide Reservoir : soil Infection route Infectious organisms infections often found in: Prolonged steroid therapy Organ transplantation Malignancy Sarcoidosis 2022/9/1672Pathogenesis Antiph