学术讨论—主要致病性真菌.ppt

主要(zhyo)致病性真菌浅部真菌(zhnjn)感染（致病性真菌(zhnjn)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 1第一页，共八十一页。浅部感染浅部感染(gnrn)(gnrn)真菌真菌n n表面感染真菌(zhnjn)(zhnjn)n皮肤癣真菌皮肤癣真菌n皮下组织真菌感染2 2第二页，共八十一页。3 3第三页，共八十一页。表面感染表面感染(gnrn)(gnrn)真菌真菌n n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n n统称：角层癣菌 n n代表(dibio)(dibio)：秕糠马拉癣菌(Malassezia furfur)n n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。n n诱发因素为高温多汗4 4第四页，共八十一页。Malassezia furfurn nTinea versicolor on skin surface(sweat stain)n nThelesionsaresmallhypopigmentedorhyperpigmentedmaculesn nMostcommonsite:back,underarm,upper arm,chest,neck n nMost common in adolescent and young adult males n nAssociated with increased sweating5 5第五页，共八十一页。PityriasisversicolorshowinghyperpigmentedlesionsinaCaucasianandhyphopigmentedlesionsinanAustralianAborigine6 6第六页，共八十一页。Culture of Malassezia furfur on Dixons agar(contains glycerol mono-oleate)7 7第七页，共八十一页。Piedraia hortae(何德毛结节何德毛结节(ji ji)(ji ji)菌菌)n nIt usually affected the scalp hairn nThe nodules are darker in color,harder,and more firmly attached to the hairsn nBlack Piedra8 8第八页，共八十一页。Piedraia hortaeformsahardsuperficialpigmentednodulearoundthehairshaft(在毛干上形成(xngchng)硬的黑色结节，如沙粒状)9 9第九页，共八十一页。Fungal otitis externan nFungal infection of the external auditory canaln nCaused by several species of Aspergillus(most often A.niger),but Candida albicans is also capable of infecting this siten nThe major symptoms are itching and feeling of fullness in ear1010第十页，共八十一页。1111第十一页，共八十一页。皮肤癣真菌皮肤癣真菌(zhnjn)(zhnjn)n n引起皮肤浅部感染n n皮肤癣是人类最多见的真菌病n n统称：皮肤癣菌，大约40多个种，分属于3个属n n嗜角质蛋白，37不能生长，侵犯(qnfn)(qnfn)部位：角化的表皮，毛发，指（趾）甲n n病理变化：由真菌增殖及代谢产物刺激宿 主引起1212第十二页，共八十一页。致病性 指（趾）甲指（趾）甲 皮肤皮肤(p f)(p f)毛发毛发毛癣菌属毛癣菌属 +表皮癣菌属表皮癣菌属 +-+-小孢子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(bngbin)相同部位的病变也可由不同的皮肤癣菌引起1313第十三页，共八十一页。1414第十四页，共八十一页。TineapediscausedbyT.rubrum.Sub-clinicalinfection(left)showingmildmacerationunderthelittletoeandmoresevereinfection(right)showingextensivemacerationofalltoewebspacesTineaistransmittedviathefeetbydesquamatedskinscalesinsubstrateslikecarpetandmatting.1515第十五页，共八十一页。手足癣治疗(zhlio)(zhlio)原则n n水疱型温和搽剂和霜剂水疱型温和搽剂和霜剂n n角化过度角化过度(gud)(gud)型先角质剥脱剂，再用抗型先角质剥脱剂，再用抗真菌霜剂真菌霜剂n n浸渍糜烂型粉剂收干，抗继发感染，浸渍糜烂型粉剂收干，抗继发感染，再温和抗真菌再温和抗真菌1616第十六页，共八十一页。Tinea Unguiumnusually caused by Trichophyton sp1717第十七页，共八十一页。甲癣治疗(zhlio)(zhlio)原则n n局部治疗甲涂剂局部治疗甲涂剂n n系统系统(xtng)(xtng)治疗伊曲康唑，特比萘芬等治疗伊曲康唑，特比萘芬等n n联合治疗配合拔甲或削甲治疗联合治疗配合拔甲或削甲治疗1818第十八页，共八十一页。Tinea Corporis:caused by caused by M.canisM.canis,following contact with infectious kittensfollowing contact with infectious kittens 1919第十九页，共八十一页。Tinea Cruris(Jock itch):Infection of the groin,mainly seen in menInfection of the groin,mainly seen in men2020第二十页，共八十一页。Tinea Capitis(scalp ringworm)Tinea favosa发内孢子发内孢子2121第二十一页，共八十一页。Tinea Capitis(scalp ringworm)Tinea alba发外孢子发外孢子2222第二十二页，共八十一页。Tinea Capitis(scalp ringworm)脓脓癣癣2323第二十三页，共八十一页。头癣(tu xun)(tu xun)治疗原则n n剪发剪发(jin f)(jin f)n n洗发洗发n n搽药搽药n n服药服药n n消毒消毒2424第二十四页，共八十一页。Candidiasis of skin,mucous membranes and nailsn n Predisposing factorsInfancy,pregnancy,old ageDisorders of immune function,e.g.,leukemia,corticosteroid therapyChemotherapy,e.g.,immunosuppressive,antibioticEndocrine disease,e.g.,diabetes mellitusCarcinoma2525第二十五页，共八十一页。念珠菌性间擦疹念珠菌性间擦疹好发部位：腋窝、乳房好发部位：腋窝、乳房(rfng)下、下、腹股沟、会阴，多见于婴儿腹股沟、会阴，多见于婴儿及肥胖者。及肥胖者。2626第二十六页，共八十一页。n nCutaneouscandidiasis:includingCutaneouscandidiasis:includingInterdigitalcandidiasisInterdigitalcandidiasis,diaper,diapercandidiasis,paronychiaandonychomycosiscandidiasis,paronychiaandonychomycosisn nVulvovaginalcandidiasisandbalanitisVulvovaginalcandidiasisandbalanitisInterdigital candidiasis Candidiaonychomycosisandparonychia2727第二十七页，共八十一页。n nOropharyngealcandidiasis:includingthrush,glossitis,stomatitisandangularcheilitisOralthrush2828第二十八页，共八十一页。皮下组织真菌皮下组织真菌(zhnjn)(zhnjn)感染感染n n主要有孢子丝菌和着色真菌n n申克孢子丝菌，属腐生性真菌，常因外伤接触带菌的花草(huco)(huco)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。n n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。2929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，引起亚急性或慢性慢性(mn xng)肉芽肿，使淋巴管形成链状硬结，称为孢子丝菌下肉芽肿，使淋巴管形成链状硬结，称为孢子丝菌下疳。疳。3030第三十页，共八十一页。n nChromomycosisn nInfections occur in exposed areas,skin lesions become dark,so called chromomycosisn nRepresentive species:Cladosporium carrianii,Fonsecaea pedrosoi,etc.n nAre saprophytic fungi,usually enters the body by trauma3131第三十一页，共八十一页。n n经外伤侵入n n丘疹n n结节n n结节融合成疣状或菜花状n n斑痕形成影响淋巴回流(hu li)(hu li)n n肢体象皮肿3232第三十二页，共八十一页。ChromomycosisChronicverrucouschromoblastomycosisofthehandduetoCladophialophora carrionii3333第三十三页，共八十一页。Mycetoma 足分枝足分枝(fn zh)(fn zh)菌病菌病n n是由多种放线菌或真菌引起的一种是由多种放线菌或真菌引起的一种(y zhn)(y zhn)慢性化脓性肉芽肿性疾病，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。主要感染足部，以肿胀、窦道和颗粒为特征。n ncausedbyfungiarecalledeumycetoma(40%)n nActinomycetomaiscausedbyactinomycetes(60%)n nItischaracterizedbytheformationofabscess,whichcontainlargeaggregatesoffungaloractinomycetefilamentsknownasgrains3434第三十四页，共八十一页。n nEumycetoma Dark grainsDark grains Madurella Madurella mycetomatismycetomatis Leptosphaeria Leptosphaeria senegalensissenegalensis Exophiala jeanselmeiExophiala jeanselmei Pale grainsPale grains Fusarium Fusarium sp.sp.AcremoniumAcremonium sp.sp.Scedosporium Scedosporium apiospermum apiospermum n nActinomycetomaActinomycetomaWhite-yellow grainsWhite-yellow grains Actinomadura Actinomadura maduraemadurae Nocardia brasiliensisNocardia brasiliensisYellow-brown grainsYellow-brown grains Streptomyces Streptomyces somaliensissomaliensisRed-pink grainsRed-pink grains Actinomycetoma Actinomycetoma pellettieripellettieri3535第三十五页，共八十一页。深部真菌深部真菌(zhnjn)(zhnjn)感染感染 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(t men)(t men)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。3636第三十六页，共八十一页。Characteristics of systemic dimorphic mycosesn nAre uncommon,Are uncommon,often occurs in often occurs in endemic areasendemic areas n nMost infections are Most infections are asymptomaticasymptomatic or self-limiting or self-limitingn nin immune-compromised hosts,infections are often in immune-compromised hosts,infections are often fatalfataln nThe pattern of infection are similarThe pattern of infection are similar Route of acquisition is inhalation Route of acquisition is inhalation Pulmonary infectionPulmonary infection Disseminated infection(Disseminated infection(Blood,Bone marrow,Brain and CSF,Blood,Bone marrow,Brain and CSF,Joint)Joint)3737第三十七页，共八十一页。Coccidioidomycosisn nCoccidiodes immitis Coccidiodes immitis is considered is considered to be the to be the most virulentmost virulent of fungal of fungal pathogens.pathogens.n nRestricted to hot,semi-arid areas Restricted to hot,semi-arid areas of SW USA and Mexico.of SW USA and Mexico.n nGrows in the soil,but Grows in the soil,but inhalation of a single spore inhalation of a single spore can initiate infection.can initiate infection.In infected tissues,C.immitis appears as a mixture of endospores and spherules.ConidiaSpherules3838第三十八页，共八十一页。Coccidioidomycosis:A.A.Encounter:Encounter:Mycelium found in dry,dusty soil.Contact by Mycelium found in dry,dusty soil.Contact by inhalationinhalation of of arthroconidiaarthroconidiaB.B.Spread:Spread:Most commonly an asymptomatic self limited pulmonary disease,Most commonly an asymptomatic self limited pulmonary disease,but may spread via the blood to skin,soft tissues,bones,joints and but may spread via the blood to skin,soft tissues,bones,joints and meninges.meninges.C.C.Immune Response:Immune Response:T-cell mediated(Th-1)T-cell mediated(Th-1)D.D.Evasion of Defenses:Evasion of Defenses:Resistant to killing by phagocytesResistant to killing by phagocytes-protein rich,hydrophobic outer wallprotein rich,hydrophobic outer wall-alkaline halo associated with urease-alkaline halo associated with urease E.E.Damage:Damage:secreted proteinases break down collagen,elastin hemoglobin,IgG&IgAsecreted proteinases break down collagen,elastin hemoglobin,IgG&IgA3939第三十九页，共八十一页。1.Ethnicity:Filipinos,African Americans,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 infectious!4.Serology:Complement fixation assay(in cerebrospinal fluid),particle agglutination assay G.Treatment1.Amphotericin B followed by an azoleE.Risk FactorsCoccidioidomycosis:4040第四十页，共八十一页。Histoplasmosis (also called(also called cave diseasecave disease)Caused by the dimorphic fungus Histoplasma capsulatumTuberculated 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.4141第四十一页，共八十一页。HistoplasmosisA.A.EncounterEncounter.H.capsulatumH.capsulatum grows in soil,especially soil grows in soil,especially soil contaminated by guano.contaminated by guano.Inhalation of conidia from the Inhalation of conidia from the environment is source of environment is source of infection.This is more likely in infection.This is more likely in endemic areas.In U.S.these endemic areas.In U.S.these include the Atlantic Ocean to N.include the Atlantic Ocean to N.Dakota(500,000 cases/year in Dakota(500,000 cases/year in U.S.),except New England&U.S.),except New England&Florida.Most cases occur in Florida.Most cases occur in Ohio Valley and Mississippi Ohio Valley and Mississippi Valley)Valley)4242第四十二页，共八十一页。More HistoplasmosisMore Histoplasmosis1.1.90%of cases are asymptomatic,but in rare cases flu like respiratory 90%of cases are asymptomatic,but in rare cases flu like respiratory symptoms occursymptoms occur2.2.Disseminated histoplasmosis occurs in 1:200 cases and is diagnosed frequently in Disseminated histoplasmosis occurs in 1:200 cases and is diagnosed frequently in patients with AIDS living in the central U.S.patients with AIDS living in the central U.S.3.3.In these cases,the organism spreads In these cases,the organism spreads via bloodvia blood from the lung to involve bone from the lung to involve bone marrow,adrenal glands,heart valves and CNSmarrow,adrenal glands,heart valves and CNS4.4.Spread can also be associated with underlying lung disease(e.g.,emphysema).Spread can also be associated with underlying lung disease(e.g.,emphysema).B.SpreadC.Immune Response1.Cell-mediated responses are of primary importance2.Activated macrophage can kill yeast cellsD.Evasion of Defenses1.Survival in macrophages elevates pH of phagosomes2.Yeast cells absorb iron(siderophore)and calcium from host3.Alteration of cell surface 4343第四十三页，共八十一页。Histoplasmosis 1.Direct histology and culture of blood or bone marrow2.Serological testing for antibody and histoplama antigen in blood and urine.E.DiagnosisD.Damage1.Lung-bronchial obstruction and inflammatory sequelae2.Disseminated histoplasmosis-fulminant disease that may result in toxic shock3.CNS-fatal if untreated.4444第四十四页，共八十一页。Even More HistoplasmosisF.TreatmentAmphotericin 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 HistoplasmosisA 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.4545第四十五页，共八十一页。Blastomycosis Granulomatous mycotic infection that Granulomatous mycotic infection that predominantly involves lungs and skin;but predominantly involves lungs and skin;but can spread to other organs.Most prevalent can spread to other organs.Most prevalent in males 40-60 years of age and children.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.4646第四十六页，共八十一页。Blastomycosisn nEncounterEncounter:Most cases are in southern,central,and southeastern USA.Infection is:Most cases are in southern,central,and southeastern USA.Infection is by inhalation of spores.by inhalation of spores.n nSpread:Spread:The pulmonary infection is either self-limited or progressive.Dissemination 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 often occurs to the skin and to the bone-80%of patients have large skin lesions;a large number also have granulomatous pulmonary lesions.number also have granulomatous pulmonary lesions.n nRisk Factors:Risk Factors:Occupational contact with soil;owning a dog.Living in endemic area.Occupational contact with soil;owning a dog.Living in endemic area.n nEvasion of Defenses:Evasion of Defenses:Escapes phagocytosis by neutrophils and Escapes phagocytosis by neutrophils and monocytes by shedding its surface antigen after infectionmonocytes by shedding its surface antigen after infectionn nDamage:Damage:Consequence of the immune response to the organismskin lesions,Consequence of the immune response to the organismskin lesions,respiratory infiltrates.respiratory infiltrates.n nDiagnosis:Diagnosis:based on clinical findings and microscopic detection of organisms in based on clinical findings and microscopic detection of organisms in tissue specimenstissue specimens4747第四十七页，共八十一页。1.1.Amphotericin B is the drug of choice for rapidly progressive blastomycosisAmphotericin B is the drug of choice for rapidly progressive blastomycosis2.2.Itraconazole or Ketoconazole for less severe casesItraconazole or Ketoconazole for less severe casesImmune response1.Alveolar macrophage provide a first line of defense.2.T-cell stimulated PMNs kill Blastomyces cells by oxidative mechanisms.3.Conidia are more sensitive to killing by PMNs because yeast are too big.4.TH-1 response is of primary importanceBlastomycosisTreatment4848第四十八页，共八十一页。Opportunistic fungal infectionsn nOpportunistic mycoses are fungal infections that do not normally cause Opportunistic mycoses are fungal infections that do not normally cause disease in healthy people,but do cause disease in people with weakened disease in healthy people,but do cause disease in people with weakened immune defenses(immunocompromised people).Weakened immune function immune defenses(immunocompromised people).Weakened immune function may occur due to inherited immunodeficiency diseases,drugs that suppress may occur due to inherited immunodeficiency diseases,drugs that suppress the immune system(cancer chemotherapy,corticosteroids,drugs to prevent the immune system(cancer chemotherapy,corticosteroids,drugs to prevent organ transplant rejection),radiation therapy,infections(e.g.,HIV),cance