第二十二章 致病性真菌（Chapter 22 pathogenic fungi）

第二十二章致病性真菌（Chapter22pathogenicfungi)

Chapter22pathogenicfungi

Thefungicanbedividedintoshallowinfectionfungi,deepinfectionfungiandpathogenicfungi.

Thefirstshallowinfectionoffungi

Surfaceinfectionoffungi

Suchfungiaremainlyfoundinthesurfaceofhumanskinandhair.Itrarelycauseshostcellreactionbecauseitdoesnotcontacttissuecells.ThiskindoffungusinourcountrymainlyhastheinfectionofMalasseziafurfur,cancausetheskinsurfacetoappearthetinea,suchasperspirationspot,commonlyknownassweatspot.Thisfungusislipid.Therewerereportsfrom92percentofnormalhumanscalp,torso,face,limbsandotherparts.Theinducingfactorishightemperaturesweat.Becausethebacteriacanproducedicarboxylicacidthatinhibitsmelanocytes,thelocalpigmentofpsoriasisisdecreased.Thefungushascoarse,branched,myceliaandclumpsofyeastlikecells.TheskinofthepatientwithWoodlampuvwavelength365nmirradiationorscrapeofscaly,canemitgoldfluorescence,whichcanhelpdiagnose.

Psoriasisfungus

Thefungusthatcausesshallowskininfectionsismostlydermatophytes.Skinringwormfungihaveaddictedtothecharacteristicsofkeratin,theinfringementofpartsareconfinedtothediversificationofskin,hairandfinger(toe),andpathologicalchangesisafungalproliferationanditsmetabolitesresponsecausedbystimulationofthehost.Skintinea,especiallyhandtineaisthemostcommonlyseenfungaldiseaseinhumans.Theskinistricho-phyton,EpidermophytonandMicrosporum.

Thebiologicalcharactersdermatophytebacteriacangrowonthesand-preservingmediumandformfilamentouscolony.Accordingtothecolonymorphology,colorandthelargeconidiaproducedbythespore,theskincanbepreliminarilyidentified.

Thecolonyoftineaisgrey,red,orangeorbrown,withavillous,powderedorwaxysurface.Themicrosporesofthin,slender,thinwalls,andsmallconidiumofgrapeorpearareseenbelow.Myceliumhasspirallyshaped,racquet,deerhornandnodules.

Thedermatophyteoftheepidermiswaswhitegooseandfeather,andlaterturnedtoyellow-greenpowder.Underthemirror,thereareovoidorcoarse-likethinwall,largeconidiaandracquetmycelium,andthickmembranoussporescanbeseenintheoldculture.

Themicrosporophytecolonyisgray,orangeortan,andthevilligraduallychangetopowder.Underthemicroscope,thereisalarge,Clostridiumspinospore,andtheovoidoftheovoidislongattheendofthebranchofthehypha.Myceliumhasnodules,combsandrackets.

Pathogenicityakindofskintineafunguscancauselesionsindifferentparts,thesamesitelesionscanalsobecausedbydifferentskinringwormbacteria.3kindsofringwormfungus

canviolateskin,causethehandtinea,tinea,psoriasis,miajock,etc.Tineaandepidermisoftheepidermiscaninfringeonthefingers,causingtineatoloseitslusterandthickening.Inaddition,thetrichomycosisandmicrosporescanalsoinfringehair,causingtinea,tineaandtinea.

Accordingtoourcountryin1998skinringwormfungiisolatedfrompatientswithredhairversicolorbacterium(T.rubrum)forthemost,accountingfor56%ofthesuperficialfungalculturepositive,followedbypurplehairversicolorbacterium(T.violaceum),whiskersversicolorbacterium(T.mentagrophyte)andflocculentskinringwormfungi(E.floccosum)etc.,themaincauseonychomycosis,tineamanusandringwormofthebody.TineahasbeenpopularinmanypartsofChina,causingsufferingandlifelongregret.Spreadthroughcontactorhaircuttingtools.Withimprovedliving,improvedculturalknowledgeandextensiveuseofgriffins,tineaisalreadyrare.Butinrecentyears,thepetdog,thecat’sdependents,theheadofthechildhaslookedupagain.Theinfectionwasdividedintothreetypes:psoriasis,tineaandtinea.Theringwormismainlycausedbyt.s.choenleinii.Tineatineaisoftencausedbypurpletineaandtineatinea(t.t.onsurans),whichisbrittleandbrittle,leavingablackroot,whichisknownasblacktinea.Psoriasisismainlycausedbytherust-coloredmicrosporefungus(m.f.errugineum).Tineaismorecommoninadolescents,morementhanwomen,andrarelyinadults.

In1998,623casesofsuperficialfungalinfectioninwuhanwerefoundtobe35.8%,followedby22.8percentoftinea,15.8%oftinea,10.2%ofpsoriasisand7.3percenttinea.

Fungalinfectionofsubcutaneoustissue

Thefungusthatcausessubcutaneoustissueinfectionmainlyhasshadingfungusandsporesilkfungus.Infectionsoftenoccurintheinvasivepartofthefungus.Infectioninitiallyoccursinthedermis,subcutaneoustissueorbone,graduallyexpandingandeventuallyreachingtheskintable.Infectionsaregenerallylimitedtolocalareasbutcanalsospreadslowlytosurroundingtissues.

Colouringfungusisthegeneraltermforsomefungithatarecloselyrelatedtothesymptomsofdisease.Infectionsoccurinexposedpartsofthebody,andthelesionsareblackenedandcalledchromomycosis.Inourcountry,wemainlyhavetheCladosporiumcarrianiiandthepigmentedgerm(fonse-ceeapedrosoi)•Therearethreetypesofconidiaofpigmentedfungi:thebranchtype:themyceliumendhastheconidiaofthespores,andtheendsofthestalkhavespores;Apextype:acircleofconidiaaroundtheendofthemyceliumorthetransverseseptumofmycelium.Theflowervasetype:inthemyceliumdivision,theconidiaoftheconidiaaregrownoutofthevases,andthesporesofthesmallconidiaaregrownatthemouthofthebottle.Therearethreetypesofsporesinthepigmentedbuds.Themainbranchtypeofthecaramellacarphorus,occasionallyseethevasetype.Thiskindoffungusgrowsslowlyonthesandalmedium,oftenforweeks.Thefungusisbrown,andthesurfacehasveryshortmycelium.Inthebody,theskinismainlyviolated.Theincubationperiodismorethanonemonth,theelderlymonthsorevenoneyear.Thecourseofillnesscanlastfordecades.Earlyskinlesionsoccurwithpapules,andpapulesareenlargedtoformnodulesandnodulesarefusedintoverrucaorcauliflower.Withthedevelopmentofthedisease,theoriginallesionscarhealedandthenewovenwasproducedinthesurroundingarea.Thedailyscarisextensiveandaffectstheflowofthelymph.Whenimmunefunctionislow,caninvadethecentralnerve,orthebloodlinespreads.

Sporesilkfungusisakindofsaprophyticfungus.Itiswidelyfoundinsoil,plantandwood.Itisoftencausedbyinjurytotheplants,plantsandthorns.Itismostcommoninagronomists.Themainpathogenofinfectionisthesporotrichumschenckii.Thisbacteriumcanbreakintotheskinbyminordamage,andthenspreadalongthelymphaticdistribution,causingsubacuteorchronicgranuloma,causingthelymphaticvesselstoformachain-likehardknot,whichiscalledthechancreofsporesilkfungus.Thebacteriacanalsoentertheintestinesorthroughtherespiratorytractintothelungs,andthenthemenstrualbloodcanspreadtootherorganscausingdeepinfection.ThediseasehasspreadwidelyinChinaandhasbeenfoundinmostpartsofthecountrysincethe1950s.Therearemorecasesinthenortheast,accountingfor70percentofthereportedcasesinthecountry.Shenkesporesisadiphasicfungus.37°Ctrainingwithintheorganizationorasyeastphase,visiblewithovoidcorpuscle(3^7xl~2microns),usuallylocatedinneutrophilsandmononuclearcells,accidentallysawamycelium.Sometimesintissuestherearestellatebodies,andeosinophilicsubstancesradiateintothesurroundingarea.Onthesandcovermediumatroomtemperatureorto37°Cfor35dseegrowth,namelytograystickydots,graduallyexpandedintoablack,browncorrugatedfilmcolony.Thevitreousgrowthoftheglassslideshowsthattheslenderconidiastalksprotrudefromthemycelium,andthestalkshaveclustersofpear-shapedmicrospores.OnbloodAGARcontainingcystine37°C,thengrowtypeyeastfungus,breedinginbuddingmanner.

Sectioniiinfectionofthefungus

Deeporsystemicfungalinfectionisafungusthatcaninvadedeeptissueandinternalorgansandthroughoutthebody.Mostoftheinfectionsareexogenousandhighlypathogenic,whichcancausechronicgranulomatousinflammation,ulcerandnecrosis.Amongthem,itiscommontohavecryptococcaldisease.Otherareassuchashistiocyte,microspores,blastomycetes,andmicrosporesarefoundonlyincertainpartsoftheamericas,suchasnorthandSouthAmerica,andtheyarecalledlocalepidemics.Itisextremelyrareinourcountry,withonlyindividualcasesreported.

Cryptococcusneoformans

Cryptococcusneoformansarewidelydistributedinnature,andthemainsourceofinfectionispigeons,whichareabundantinpigeondroppings.Thepigeonitselfhastheabilitytoresistthebacteria.

Peopleareinfectedwiththeairthatiscontaminatedwithpigeondroppings,especiallytheimmunocompromised.Itmainlycausesacute,subacuteorchronicinfectionofthelungandbrain.Lunginfectioncanspreadtoskin,mucousmembrane,boneandviscera,soitisalsoaconditionpathogenicfungus.

Cryptococcusneoformansisacircularyeaststrain,whichhasacapsularcapsuleandishighlyrefractive.Thenormal

stainingmethodisnothardtodetect,soitiscalledcryptococcus.Intheblackbackground,thereisaroundoroval,bright,bright,andsmallreflectinggranuleswithalargenumberofsmallparticles.Fordouble-walledcells,theoutsourcinghasatransparentcapsule.Thecapsuleisonetothreetimeslargerthanthebacteria.Non-pathogeniccryptococcushasnocapsule.Inthetissue,cryptococcusislarge(5 20mum),whichisthenreduced(2~5mum).The

fungioftenhavebuds,butdonotproducepseudomycelium.

NewcryptococcusinsandandbloodAGARmedium,cangrowin25°Cand37°C,non-pathogeniccryptococcusin37°Ccannotgrow.Newborncryptococcusdevelopsyeaststrainafterseveraldays,thesurfaceissticky,frommilkywhitetoorange,finallybrown.Somecoloniescanbefluidizedandcanflow.Thebacteriacanbreakdownurea,whichisdifferentfrompseudo-yeast.ThecapsuleiscomposedofpolysaccharidesandisdividedintoAD4serotypesaccordingtoitsantigens.Fromclinicalisolates,about70%ofthespeciesinChinaaretypeA.

Pathogenicityneocryptococcusisanexogenousinfection.Thelungsarethemainmeansofinvasion.Mostcasesofpulmonarycryptococcalinfectionarenotobviousandcanbeself-healing.Somepatientsmaycausebronchialpneumonia.Severecasesoflungmassinfiltration,asuddeninfectionofhairinfection.Someofthepatientshavebeendisseminatedwiththecentralnervoussystemandothertissues.Maincausemeningealsubacuteandchronicinfections,suchasahospitalinNewYork,1982199110years,151casesofHIV/AIDSautopsymaterialsfound17casescomplicatedbycryptococcusinfection,including12casesofmeningitis(70.6%),followedbypneumoniaandlymph

nodephlogistic.

Miceweresusceptibletothenewborncryptococcus,injectingthebacteriumintothebrain,veinorabdominalcavity,andthemicediedwithin1to3weeks.Capsularpolysaccharideisanimportantpathogenicsubstance,whichinhibitsphagocytosis,inducesanimalimmunity,andweakensthebody’sresistance.Neonatalcryptococcushaslostthecapsuleafterexposuretoultravioletradiation,andthepathogenicabilityofthemicehasdisappeared.Oncethecapsuleproducesaresponse,thepathogenicityisrestored.

Endemicfungus

Thesefungiarebothdiphasicandsensitivetoenvironmentaltemperature.Generalinthebodyor37°Ctocultivateatypeofyeast,artificialcultivationintofilamentoustypeatroomtemperature.

ThecapsularHistoplasmacapsulatumspecimenwasexaminedunderanoilmicroscopetoseethattherewereroundorovalyeastcellsineithermonocytesorneutrophils(1^5mumindiameter).Inordertoreproduce,thereareuncoloredcapsularsamples.Atroomtemperatureatroomtemperatureonthesandpreservationmedium,itgrowsslowly,formingwhitecottonflocculatecolonies,graduallychangingfromyellowtobrown.Themicroscopicexaminationcanbeseenthatthereareelongatedmyceliumfilaments,andinthesideofthemyceliumoronthestalkofthespores,thereisaspecialcircularlargeconidium(8~15mum),thickwall,withspinousprocessesaroundit,arrangedlikegears,andthissporehasdiagnostic

value.

ThemicroscopyoftheCoccidioidesimmitesshowedthattherewerelarge,thicksquashspores(20~80mum)containingmanyendogenousspores(2~6mum)，andtheruptureofthethickwallwasproducedbyendospore.Growingrapidlyonthesandpreservationmedium,itbegantobeawhitecolony,andsoonbecameabrownandyellowcottonflocculatecolony.Thereisalotofjointsporesinthemirror.

BothBlastomycesdermatitidesand

paracocci-diodesbrasiliensisofBrazilshowedthatthecellswereyeastinthemirrorandwerepropagatedinbud.Thedifferenceisthatthedermatitisisonlyonebudpercell,andtherearemorethanonebudonthesporecell.

Sectioniii.Pathogenicfungi

Thepathogenicfungalinfectionismainlyendogenous,suchasCandidaandaspergillus.Thisfungusisnotverypathogenic,

Mostlyinthelongbecomeweak,lowimmunity,orinthedysbacteriosis,suchastumor,diabetes,organtransplantsandHIVpatients,long-termuseofbroad-spectrumantibiotics,radiotherapy,chemotherapyandotherprocesswiththistypeoffungalinfection.Itspathogenicityisweak,notpromptdiagnosiscanalsoendangerlife.

One,pseudoyeast

Pseudosilkyeast,commonlyknownasbacteria,causesacuteand

chronicinflammationoftheskin,mucosaandinternalorgans.Itcanbeprimary,butmostlysecondaryinfection,occursinimmunocompromisedpatients.OralcandidiasisisoftenthefirstsecondaryinfectioninAIDSpatients.ThepathogenicbacteriaincandidiomycesareC.albicans,C.tropicalis,C.parapsilokis,c.k.rusei,etc.Themostcommonuseispseudo-yeast.In1995,onespeciesofDublincandidiosis(C.dubliniensis)wasisolated.Candidayeastinfectionpathogensinnearly10yearschange,whiteCandidayeastinfectiongraduallyreduced,whiletheotherCandidayeastinfectiongraduallyincreased,especiallyinDublinCandidayeastinfection.Thisphenomenoniscalledtheepidemiologicaltransition(epidemeologicalshift).Mainlybecauseoffluconazole.Whitecandidiosisismoresensitivetofluconazolethanothercandidites.DublinFMSareeasytoproduceandthereforereplace.In1998,623casesofsuperficialfungalinfectioninwuhanwerereportedtoshowthatwhiteCandidayeastwasresponsiblefor4.2%,andotherpseudo-silkyeastaccountedfor26.2%.Amongthe371samples,114werewhitecandids,and208wereothercandidites,sothedetectionofothercandidsshouldbetakenseriously.

ThebiologicalcharacteristicsofthewhiteCandidayeastmicroorganismroundoroval(2x4mum).Gram-positivestainingandunevencoloring.Inthebud,thesporeiscalledspore.Thesporesareelongatedintobudsandarenotseparatedfromthemothertoformlongerfalsemycelium(figure22~3).Thesporeisconcentratedinthejointpartofthepseudohypha.Invariousclinicalspecimensandbiopsytissuespecimens,therewasalsoalargeamountofpseudomycelium,indicatingthatcandidiosiswasinactivestateandhaddiagnosticvalue.

ThewhiteCandideyeastcangrowwellinnormalagar-agar,bloodAGARandsandculturemedium.Aerobic.Oratroomtemperatureof37°Cincubation1~3dgrowcolony,colonyhoarorcreamcolor,smoothsurface,withastrongsmellofyeast.Foralittlelonger,thecolonyincreases.Mycelium,withalargenumberofvegetativepseudomycelium,intheformofyeast.Thickfilmsporescanbefoundonthecornmealmedium(FIG.22~3).Thesporesofbacilluswhiteyeastwereelongatedintopseudohyphaeandthickfilmsporestohelpidentify.ThisfeatureisalsofoundinrecentfindingsfromDublincandice.SimpledifferencemethodforwhiteCandidain42°Cgrewwell,andDublinCandidayeastgrowthpoorornot.AfurtheridentificationofwhitecandidiomycetesfromHIVinfectionandAIDSpatientswasshowntobe17percentinDublincandids.

Pathogenicityandimmunologicalpseudoyeastcaninvademultiplepartsofthebody,suchasmouthandvaginamucosa,skin,lung,intestine,kidneyandbrain.Weakenedbodyresistanceisthemainreasonfortheinvasionofpseudosilkyeast.Inrecentyears,antibacterialdrugs,hormonesandimmunosuppressantshavebeenwidelyusedinclinicalpractice,andyeastinfectionshaveincreased.Bloodculturepositivesecondonlytoescherichiacoliandstaphylococcusaureus.

1.TheskinmucousmembraneinfectionskinCandidayeastinfectionoccursintheskinfolds,suchasunderthearmpits,groin,breast,,perineumandaroundanusfinger(toe)betweenpartsofskinmoisture,easilyconfusedwitheczema.Mucosalinfectionhasthrush,oralerosion,vulvaandvaginitis,amongwhich,themostthrush.Thelesionofthrushissimilartothatofdiphtheria,exceptthatthesurfaceisexposedtothenecrotictissuebelow,whichcanbemisdiagnosedasdiphtheria.Thrushcanbeseeninthefrailfirstborninfant,especiallyintheartificialfeeding.Butitisraretoseethenormalbacterialfloraofthemouth.

Thrushisusuallylimitedtolocalandmildsymptoms,whichcanleadtodeathifitspreadstothegut.

Visceralinfectionhaspneumonia,bronchitis,esophagitis,enteritis,cystitisandpyelonephritis.Occasionallycancausesepsis.

Thecentralnervousinfectionmayhavemeningitis,meningititis,cerebralabscessandsoon.

Thepersonwhoisallergictothecandidiasisofcandidiasiscanbeallergictocandidiasis,andthesymptomsaresimilartopsoriasisandeczema.Patientscanperformsymptomssuchasasthma.

Second,theaspergillus

Aspergillus(Aspergillus)iswidelydistributedinnature,growingrapidlyandformingfilamentouscoloniesonthesand-preservingmedium.Beginwithavarietyofcolorsforwhitewiththeproductionofconidia.Themostcommoncauseofhumandiseaseisthea.f.umingatus,whichismainlycausedbyrespiratoryinvasion,whichcausesbronchialasthmaorlunginfection.Intheenlargedbronchusandsinuses,aspergillusembolusoraspergillusisformedinthelung,andalargenumberofaspergillusismultipliedintoclumpsofcellfragmentsofcellulose,mucusandinflammation.Atthispoint,theX-rayshowsthatthereisacavityinthelung,anditsdenseshadowcanbeshiftedwiththepositioninthecavity,whichcanbedistinguishedfromthenoduleandlungcancer.Severecasescanbedisseminatedtothebrain,heartmuscleandkidney.Someaspergilluscanproducetoxins,andthetoxinsofA.flavusarecloselyrelatedtotheoccurrenceofmalignanttumors,esp