Fungi ! - Hilary Supplies
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Fungi ! Alan Postlethwaite BSc (Hons) Podiatry, DipBMec, FPSPract 29 November 2015 1
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Transcript of Fungi ! - Hilary Supplies
Fungi!
AlanPostlethwaiteBSc(Hons)Podiatry,DipBMec,FPSPract
29November2015
1
Agenda
• ClassificaJonoffungalinfecJons• Structureoffungi• FungalorganismsandinfecJon• Someavailabletreatments• Newboysontheblock• Yourrole!
2
Howmany?
• Approx.1,500,000species• Lessthan100pathogenictoman• Whichdoweusuallycomeacross?
3
Howmany?
• Approx.1,500,000species• Lessthan100pathogenictoman• Whichdoweusuallycomeacross?
– TineaPedis– Onychomycosis
4
Howmany?
• Approx.1,500,000species• Lessthan100pathogenictoman• Whichdoweusuallycomeacross?
– TineaPedis– Onychomycosis
(Dermatophytes)
5
Whatarethese?
6
1 2 3
4 5 6
TheDiversityofFungi:Fromtrufflestotoenailstoterminaldiseases
RelaBonshipswithHumans:thegood,thebad,andtheugly• • AnJbioJcsderivedfromfungi(penicillin,cepaholosporin)• Gastronomy
– Wine,beer;bread;soysauce,truffles• EcologicalRole:decomposingorganicma\er;• Indispensableinnutrientcyclingandexchange• Biocontrol-entomopathogenicfungi• OtherenzymaJcprocesses,e.g.cellulasesfromTrichoderma
areusedin"biostoning"ofdenimfabricstogiverisetothesoc,whitenedfabric--stone-washeddenim
• Detrimentaltothefoodchain(plantpathogens)• HumanandassociateddomesJcanimaldiseases• ProduceToxins• Onychomycosis;UsJlagoMaydisandbluecorn
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ThePathogenicFungi
FungalinfecJonsclassifiedonthedegreeofJssueinvolvementandmodeofentryintothehost:• Superficial-localizedtotheskin,thehair,andthenails.• Subcutaneous-infecJonconfinedtothedermis,subcutaneous
Jssueoradjacentstructures.• Systemic-deepinfecJonsoftheinternalorgans.PrimaryandOpportunisJc• Requirethehost(hostdependent;PneumocysJs,Microsporidia,
C.albicans)• Terminateinhost(Aspergillus,Histoplasma)
8
Howdowegetinfected?
FungalnailinfecJonhasli\letodowithpersonalcleanliness.• Canbeassimpleas
– bangingatoeorfinger;– trimmingnailstooclosely;– wearingJghtshoes.
AllenoughtoweakenthenailandexposetheunderlyingnailbedtoinfecJon.• ToenailsaremostvulnerabletoinfecJon,
– (spendmuchoftheirdaydark,warmandmoist)
9
Whatisthebiggestproblemforus?
• PaJentcompliance!• Why??• IttakesJmeandrepeJJvetreatment• Nailgrowthrate?• Halluxfullyinfected?
10
Increasedrisk
• Agingisacommonriskfactorfornailfungusforseveralreasons,including:
– DiminishedbloodcirculaJon– Moreyearsofexposuretofungi– Nailsmaygrowmoreslowlyandthickenwithage,makingthemmoresuscepJbletoinfecJon
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Otherfactors
• Perspiringheavily• Workinginahumidormoistenvironment• WearingsocksandshoesthathindervenJlaJonanddon'tabsorbperspiraJon
• Walkingbarefootindamppublicplaces,suchasswimmingpools,gymsandshowerrooms
• PresenceofTineaPedis(Athlete’sfoot)• Havingaminorskinornailinjury,adamagednail,oranotherinfecJon
• Havingdiabetes,circulaJonproblemsoraweakenedimmunesystem
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Fungi
MYCOLOGICALLY
CLINICALLY
FILAMENTOUSFUNGI/MOULDS
YEASTS YEAST-LIKEFUNGI
DIMORPHICFUNGI
MOULDS
YEASTS DERMATOPHYTES
TRICHOPHYTON
MICROSPORUM
EPIDERMOPHYTON13
BasicBiologyofFilamentousFungi(moulds)
• ThecellwallcomprisesofchiJn.• MainbodyoftheplantistheThallus–produceshyphae–formsmycelium.
• ReproducebyformaJonofspores.• Producemicroormacroconidiaasexually.
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BasicBiologyofYeasts
• Unicellular• Reproduceby‘budding’.• CandidaAlbicans(oropharangeal/gastrointesJnalcommensal)–causescandidiasis,thrush
• Note:Dimorphicfungicangrowasmycelialfungiorassinglecellyeasttype.
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SourcesofFungalinfecBon
• Animals–Zoophilicfungi– E.g.microsporumcanis(catanddogringworm)
• Soil–Geophilicfungi• Humans–Anthropophilicfungi
– Spreadviainfectedsurfacesandcommoninthecommunity
• Dermatophytesmayoriginatefromanyofthesesources
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Fungi
• FungiareeukaryoJcorganisms(cellswithorganelles&acellwall)
• Fungiarethemajordecomposersoforganicma\ere.gcellulose
• Fungicauseabout70%ofallthemajorcropdiseases
• Thediversemetabolicpathwaysoffungigeneratemanycommercialproductssuchasethanol,organicacids,enzymes,anJbioJcsBUTsomeextremelypotenttoxinsthataffecthumanandanimalhealthe.gaflatoxins
• WiththeadventoftransplantsurgeryandtheincreaseinimmunosuppressivecondiJons,includingAIDS,fungiareemergingasasignificantgroupoflife-threateninghumanpathogens
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FungalStructure
• FungiareeukaryotesthatobtainfoodbyabsorpJon.• AbsorpJvenutriJonmeansthatfungiexcretehydrolyJcenzymestobreak-downcomplexorganicmoleculesintosimpleonesthatcanbeabsorbed.
• Fungimaybeunicellular(yeasts)ormulJcellular(most).• AllfungireproducebyasexualmechanismsBUTmostcanreproducebysexualprocessesaswell
• Fungiaredispersedbymeansofsporesofalmostinfinitevariety,producedbyeitheranasexualorasexualprocess
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FungalStructure
• Somespeciesoffungiconsistofsinglecells(yeasts)• Mostspecies,however,consistofmulJplethread-like
cellscalledhyphae.• Thehyphaeareorganisedintoanetworkoffibres
calledamycelium(i.e.themouldthatbecomesapparentondecayingfood)
• FungihaveacellwallconsisJngofthepolysaccharidechiBn.
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Hyphae
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FungalStructure
• Likehumancells,fungalcellscontainanucleus,endoplasmicreJculum,mitochondria,andotherorganelles.
• BUTmostfungalcellspossessarigidcellwallcontainingpolysaccharidessuchaschiJnandglucan,whichdifferfromhuman&bacterialcellwalls.
• Theplasmamembranediffersfromthehumaninthetypeofsterolpresent– Ergosterol,insteadofcholesterol,istheprimarycomponentofthecellmembraneinfungi.
– TheprimaryfuncJonofergosterolsistomodulatemembranefluidityandiniJategrowthandincreasethesize
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FungalSpores
• Manykindsoffungiproduceseed-likestructuresduringreproducJonthatarealsocalledspores.
• Thesporesofalargenumberofimportantfungiarelessthan5µmaerodynamicdiameter-hencecanenterthelungs.
• Theyalsomaycontainsignificantamountsofmycotoxins(secondarymetabolitesproducedbymicrofungi)
• DiseasesassociatedwithinhalaJonoffungalsporesincludetoxicpneumoniJs,hypersensiJvitypneumoniJs,tremors,chronicfaJguesyndrome,kidneyfailure,andcancer.
• InBritain>20mouldsareknowntocauseallergicreacJonsincludinghayfever&rhiniJs
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Fungalvshumancells
• UniquecellwallusingchiJnasthemainstructuralpolymer
• Cellmembranecontainsuniquefungalsterols• Someuniquecytoplasmicmembraneenzymesinsomespecies
• NB:thesemayallbetargetedbyan6-fungaltherapies
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FungalBy-Products
• Fungiproduceawiderangeofsecondarymetabolites-theyplaynoroleinthenormal,basicmetabolicpathwaysusedforgrowthandenergyproducJon,etc.
• SomeofthesesecondarymetaboliteshaveanJbioJcproperJes.
• Othersarepotenttoxinsthataredangerouswheneatenbyhumansorotheranimalse.g.aflatoxins
• Othersincludepigmentsinsertedintothefungalwallsorreleasedintothesurroundingenvironment,orflavour&odourcomponentsoftoadstools.
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Aspergillusfumigatus
CausesAspergillosisviafungalsporesinhaledfromdecomposingorganicma\er(A)Typicalsporingheadsofthefungusinlaboratoryculture.
(B)MicroscopicsecJonoflungJssue,stainedtoshowhyphaeofAspergillusinanairsac.Suchaballofhyphaegrowingsaprotrophicallyinthelungistermedanaspergilloma.
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It’snotallbad
YeastsandFungihavemanyuses.
26
Penicillin
• TheanJbacterialeffectofpenicillinwasdiscoveredbyAlexanderFlemingin1929.
• HenotedthatafungalcolonyhadgrownasacontaminantonanagarplatestreakedwiththebacteriumStaphylococcusaureus,andthatthebacterialcoloniesaroundthefungusweretransparent,becausetheircellswerelysing.
• FleminghaddevotedmuchofhiscareertofindingmethodsfortreaJngwoundinfecJons
• Heimmediatelyrecognisedtheimportanceofafungalmetabolitethatmightbeusedtocontrolbacteria.
• Thesubstancewasnamedpenicillin,becausethefungalcontaminantwasidenJfiedasPenicilliumnotatum
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• FlemingfoundthatitwaseffecJveagainstmanyGramposiJvebacteriainlaboratorycondiJons,andheevenusedcrudepreparaJonsofthissubstance,fromculturefiltrates,tocontroleyeinfecJons.
• However,hecouldnotpurifythiscompoundbecauseofitsinstability,anditwasnotunJltheperiodoftheSecondWorldWar(1939-1945)thattwootherBriJshscienJsts,FloreyandChain,workingintheUSA,managedtoproducetheanJbioJconanindustrialscaleforwidespreaduse.
• AllthreescienJstssharedtheNobelPrizeforthiswork,whichsavedliterallymillionsoflives.
• ItissJlla"frontline"anJbioJc,incommonuseforsomebacterialinfecJonsalthoughthedevelopmentofpenicillin-resistanceinseveralpathogenicbacterianowlimitsitseffecJveness
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FungalInfecJon
• Fungicancauseavarietyofdiseaseswith3majordivisions:allergies,toxicityreacJons,andfungalinfecJons.
• AllergicreacJonstofungiarecausedbysensiJvitytofungalproteinssuchasinhaledfungalspores.
• ToxicityreacJonsresultfromtheconsumpJonoffungaltoxinsincontaminatedfoodorpoisonousmushrooms.– FungalallergiesandtoxicreacJonsareimportantconcernsinagricultureand
otherindustrieswherefungalcontaminaJoniscommon.
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Mycoses
• 4groupsbasedontheJssueorbodysiteinvaded.Superficial-affectthehairshacandtheoutermost,nonlivinglayeroftheskine.gJneanigra(Exophialawerneckii)&piedra(Piedraiahortae)
• Cutaneous-involveinfecJonoftheskin,hair,andnailse.gdermatophyeandcandidainfecJons
• Subcutaneous-affecttheskinaswellasthemuscleandconnecJveJssueimmediatelybelowtheskine.gmycetoma
• Systemic-involvethebloodandinternalorganse.gblastomycosis
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Dermatophytosis
• Dermatophytosis(Jneaorringworm)ofthescalp,glabrousskin,andnailsiscausedbyacloselyrelatedgroupoffungiknownasdermatophytes– havetheabilitytouJlisekeraJnasanutrientsource,i.e.theyhaveaunique
enzymaJccapacity[keraJnase].
• Thediseaseprocessindermatophytosisisuniquefortworeasons:– nolivingJssueisinvadedthekeraJnisedstratumcorneumissimply
colonised.Presenceofthefungusanditsmetabolicproductsusuallyinducesanallergicandinflammatoryeczematousresponseinthehost.ThetypeandseverityofthehostresponseisocenrelatedtothespeciesandstrainofdermatophytecausingtheinfecJon.
– thedermatophytesaretheonlyfungithathaveevolvedadependencyonhumanoranimalinfecJonforthesurvivalanddisseminaJonoftheirspecies.
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Cutaneous
• 1.DermatophyteinfecJonsarecommoninfecJonsoftheskin,hair,andnails.Becauseofthecircularskinpatchesfoundinalldermatophytoses,theyareocenreferredtoasringworm,orJnea,infecJons.
• TheinfecJousfungibelongtooneofthreeGeni
– Trichophyton– Epidermophyton
– Microsporum
• Thesefungioriginatefrominfectedhumans,animals,orsoils.
• Transmissionisusuallyfrompersontopersonorfromanimaltoperson.
32
Species Natural habitat Incidence Epidermophyton floccosum Humans Common Trichophyton rubrum Humans Very Common Trichophyton interdigitale Humans Very Common Trichophyton tonsurans Humans Common Trichophyton violaceum Humans Less Common Trichophyton concentricum Humans Rare* Trichophyton schoenleinii Humans Rare* Trichophyton soudanense Humans Rare* Microsporum audouinii Humans Less Common* Microsporum ferrugineum Humans Less Common* Trichophyton mentagrophytes Mice, rodents Common
Trichophyton equinum Horses Rare
Trichophyton erinacei Hedgehogs Rare* Trichophyton verrucosum Cattle Rare
Microsporum canis Cats Common
Microsporum gypseum Soil Common
Microsporum nanum Soil/Pigs Rare
Microsporum cookei Soil Rare
*Geographicallyrestricted.
DermatophytesaccordingtoMycologyOnline(2015)h\p://www.mycology.adelaide.edu.au/Mycoses/Cutaneous/Dermatophytosis/
33
DermatophyteInfecJon
• DermatophyteinfecJonsarerestrictedtothedeadJssuesoftheskinanditsappendages(suchasnailsorhair).
• Minortrauma,prolongedorrepeatedcontactwithliquid,andpoorskinhygienepromoteinfecJonsbythesefungi.
• Moisture,warmth,andperspiraJoncoupledwithpaJentproperJessuchasspecificskinchemistryandgeneJcpredisposiJonincreasethechancesofdevelopingadermatophyteinfecJon.
• Tineapedis(athlete'sfoot)ocenoccursbetweenthetoes
• Usually,theinfecJonbeginswithitchingandthedevelopmentofsmallfluid-filledblisters.
• Themoistskinpeelsandcracks,allowingsecondarybacterialinfecJonstodevelop.Peeling,cracking,pain,anditchingcharacterisechronicinfecJon.
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TineaPedis
www2.provlab.ab.ca
www.dartmouth.edu
www.latrobe.edu.au35
2.CandidalInfecJon
• Theseyeastsarenormalinhabitantsofthemucousmembranesofthenose,mouth,vagina,andanus.
• CandidaalbicanscancausesymptomsanddiseaseifthelocalcondiJonsorthehost'sweakenedimmunesystemallowittoovergrow.
• SuscepJbilitytoCandidainfecJonsisincreasedwhentheskinisweakenedbyinjury,burns,orprolongedexposuretowetenvironments.
• Warm,moistcondiJons,asfoundinthefoldsofskininandaroundthearmpits,groin,breasts,inbetweentoesetc
• RarelyCandidainvadesdeeperJssuesaswellastheblood,causinglife-threateningsystemiccandidiasis-morecommoninimmunocompromised
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CandidaInfecJonofwebofskinbetweenthefingers
37
Footwear&humidity
• ThewearingoffootwearisthemajorcontributortofootinfecJons.
• PlantarsurfaceoffootsuppliedbyalargenumberofeccrinesweatglandswhichincreaseexcreJoninwarmcondiJons.
• Occlusivefootwearcreatesawarmenvironment,prevenJngevaporaJonandthushydraJngthefoot.
• Leydenetal(1987)demonstratedthisbyhydraJngthenaturallydryregionoftheforearm.Within24hoursthenormalbacterialpopulaJonhadincreasedfrom103to106organisms/cmsquared.AlargeincreasewasinthepathogenStaphylococcus
• Acer7daysofhydraJontheresultsdisplayedatriplingofthe24hourbacterialdensity,includingpredominanceofDiptheroids.TheauthorsstatedthispopulaJoncloselyresemblesthatwhichisfoundonthefoot.
38
NormalSkinFlora
• Marshalletal(1986)believethatsomedifferencesmustexistbetweenfootfloraandotherskinsites.Thedifferencesarea\ributedtoanatomicalvariaJonsalreadymenJonedplusthewearingofocclusivefootwear.TheauthorsinvesJgatedthreesites.
• 1.sole• 2.dorsum
• 3.4thtoeclec• TheirresultsdisplayedMicrococciandCoryneformasthemostnumerous.Staphylococci
wereweredominantonthesoleanddorsumwithCornyeformdominantinthe4thtoeclec.
• Pelczaretal(1992)listStaphylococcusepidermis&aureus,Propionibacteriumacnes,Diptheroids,Pityosporumspp.andCandidaspp.asthenormalskinflora.
39
TreatmentopJons?
• MedicaJon– TopicalsoluJons/lacquers– Tablets
• Chemicalnailremoval• Surgery• Laser/lighttherapy• HolisJc
40
Howdotreatmentswork?
Terbinafine(Lamisil)• Interfereswithcellmembranes.• Stopsfungifromproducingergosterol,anessenJalcomponentoffungalcellmembranes.
• Thisdisruptsthecellmembraneandcausesholestoappear.EssenJalconsJtuentsofthefungalcellsleakout.ThiskillsthefungiandclearsuptheinfecJon.
41
Similarproducts
• Caneston(clotrimazole)• CanestonOral&Duocream(clotrimazole,flucoazole)
• Daktarin(micanazole)• Diflucan(fluconazole)• Nizoralcream(ketoconazole)
42
Differenttopicalapproach
• MYKORED(Salicylicacid/BenzoicAcid)• ChangedpHlevelInhibitsmycelialgrowth• ChangesstructuralorganizaJonofthemyceliumatvariouslevels(wall,mitochondria,vacuoleandnucleus)
• Fungalfilamentsappearemptyincreasinguptakeofacid
• Alcoholbasedriesenvironment
43
Whennottotreat
• Pregnancy• Breastfeeding• DecreasedkidneyfuncJon.• DecreasedliverfuncJon.• Psoriasis.• Peoplewithalong-termautoimmunediseaseaffecJngconnecJveJssue,calledsystemiclupuserythematosus(SLE).
• Children(somemedicineisnotlicensedforusewithchildren).
44
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50
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51
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52
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53
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• PhotodynamicAnJmicrobialTherapy.• UsesPACTNailFungusGel• AcJvatedbyexposuretolightfromthePACTMEDlightdevice.
• Canonbury£2995+VAT• +gel(£24.99+VAT)
54
Evidence?
• ExperimentalinvesJgaJonshavedemonstratedconclusivelythatbothdermatomycetesandyeastscanbeeffecJvelykilledbyphotodynamicacJon
• (andGram-posiJveandGram-negaJvebacteriaandfungi)
• onlyaverysmallnumberofinvivoanimalandhumantrialshavebeenpublished.
55
PACTtreatmentprotocol
• Heavyde-bridementofeachaffectednail• 10minutegelapplicaJonofeachaffectednail• 9.5minutelightapplicaJonofeachaffectednail• Frequency:3completetreatmentsareneededwithin2-3weeks
56
Laser
57
ConsideraJons:CapitalcostChargetopaJentsEvidenceEaseofuse(LLLT)
USAcosts$10-14,000UK?
Lowlevellasertherapybecomingmoreaccessiblee.g.Omega
CLEARANAIL–ControlledMicroPenetraJon(CMP)
58
Algeos £1999+VAT
UsedinconjuncJonwithliquidTerbinafinee.g.Lamisil1%ATspray
Surgery
• Totalnailavulsion• Doesitremovethefungalspores?• Phenolisethenailmatrix?• ApplyanJ-fungalagentpostsurgery?• Li\leevidenceoneffecJveness• Extrememethod!
59
HolisJctherapy
• AppleCidervinegarsoak• TeaTreeOil• OreganoOilextract• Others????
60
HolisJccures–EarthClinic.comMostPopularToenailFungusRemedies:
AppleCiderVinegar36DisBlledVinegar17TeaTreeOil14Ted'sRemedies14Listerine10HydrogenPeroxide10Iodine8CoconutOil8Vicks7Garlic7
OreganoOil7Bleach6LemongrassEssenBalOil5SeaSalt3Mouthwash3UrineTherapy3CastorOil3DietaryChanges3Cayenne3
61
Tothinkabout…..
• InfecJonsofthefootmustbetreatedquicklyandefficientlytopreventseriouscomplicaJonsfromoccurring,especiallyifthehost'simmunesystemiscompromised.
• ThenormalfloraoftheskinhastheabilitytoestablishinfecJonofthefootifthebarrieroftheskinisbroken.
• BecausethefootisexposeddirectlytosurfaceswhenambulaJngthisbarriercaneasilybedisruptedallowingtheentryofpathogens.
62
Andyou??
• Youhavearoletoplay• NHSPodiatrydonottreatfungalinfecJons• GP’sarereluctanttoprescribe• Yourprofessionalapproachcanhelp-easily!• Advise,demonstrate,treat
– Whichtreatment?– Isitfungal?GP–sample(getjar1st)
63
Summary
• Fungalsporesareallaroundus• PaJentscanmoreeasilybeinfectedthantreated• Widerangeoftreatments
– Cost– Time– Compliance– Compromised
64
TheEnd
• Itisuptoyouhowfaryouwanttogo
• YoucanhelppaJentsandyoucanimproveyourprofession
• QuesJons!
65
