寄生蟲malaria 2013

1、MalariaParasites/Plasmodium（瘧原蟲）,CongHuaDepartmentofParasitology,AccordingtotheWHOreport,malariakillsonechildevery30seconds.,Morethan90%casesareinsub-saharanAfrica.,Mortalityduetomalariacaseisestimatedtobeover1milliondeatheachyear.,Malariaisbyfartheworldsmostimportanttropicalparasiticdisease.,WorldD

2、istributionofMalaria,WhatisMalaria?,Malaria-badair,瘴氣打擺子，冷熱病,Studyonmalaria,CharlesL.A.Laveran1907,RonaldRoss1902,Tuyouyou2011,FourspeciesofhumanPlasmodiumprotozoa:,Plasmodiumvivax（間日瘧原蟲）P.malariae（三日瘧原蟲）P.ovale（卵形瘧原蟲）P.falciparum（惡性瘧原蟲）,MorphologyandLifecycle,Twohosts:humanandmosquitoes,FromMosquit

3、oestoHuman,感染階段子孢子(sporozoite),A.Inhuman,Exo-erythrocyticstage（紅外期）inliverErythrocyticstage(紅內(nèi)期）inRBCs,1.EE(exo-erythrocyticstage紅外期),P.v.6-8days;P.f.5-7.,Site:liver肝臟,Theinfectiveform:Sporozoite(子孢子）,Asmall,spindle-shapedcellwithasinglenucleus,whichdevelopedinmosquito,andisintroducedintomanbythebit

4、eofaninfectedmosquito.,Tachysporozoite(速發(fā)型子孢子)TS.,Thosedevelopingintomerozoite(裂殖子)andundergoesEEschizogonyimmediatelyaftertheyentertheliver.,Bradysporozoite(遲發(fā)型子孢子)BSorHypnozoites(休眠子).,Theywillremainintheliverwithoutfurtherdevelopmentinalatentperiod.,TSorBSschizogony（裂體增殖）schizont(裂殖體)merozoite(裂殖

5、子)ruptureoflivercellmerozoiteintotheblood.,EE(exo-erythrocyticstage紅外期),merozoites(裂殖子),Morphology,schizontmaturein6-14days,theliberationmerozoites（裂殖子）enterthebloodstream.,exo-erythrocyticschizont(裂殖體）inliver.,2.ES(erythrocyticstage紅內(nèi)期),Merozoites（裂殖子）,Trophozoites（滋養(yǎng)體）,Schizontes（裂殖體）,Gametocytes（

6、配子體）,Erythrocyticstage(紅內(nèi)期),Threestages:A.Trophozoitestage(滋養(yǎng)體期)B.Schizontstage(裂殖體期)C.Gametocytesstage(配子體期),Inredbloodcell-importantfordiagnosisandpathogenic,A.Trophozoite,Nucleus,Bluecytoplasm,vacuole,（1）Theringform(環(huán)狀體）-smalltrophozoite,smalltrophozoite,WrightorGiemsastainnucleusinredCytoplasmin

7、blueAsingleredchromatindotwithlightbluecytoplasmjustlikearing.,RBCcellenlargedPseudopodiaMalarialpigment(瘧色素）Schffnersdots(薛氏小點(diǎn))appear,Pseudopodiacytoplasma,Nucleus,Malarialpigment,Schffnersdots,（2）LargetrophozoitesLatetrophozoite(大滋養(yǎng)體）,Schizonts（裂殖體）(1)Immatureschizont未成熟裂殖體,Nucleusbegintodivide.Ma

8、lariapigmentbeginstoconcentrateinamass.,Nucleus,cytoplasm,Nucleus,(2)Matureschizonts成熟裂殖體,Nucleusdividedinto12-24CytoplasmdivideMerozoites(裂殖子)fromMalarialpigmentclumped,Merozoites,Malarialpigment,Matureschizonts成熟裂殖體,Plasmodiumvivax:SchizontsSmearsfrompatients.,C.Gametocytes(配子體）,Fig.28and29:Mature

9、PlasmodiumvivaxMacrogametocyte(female);Fig.30:Microgametocyte(male),Nucleus,Nucleus,Maturemacrogametocyte(female)間日瘧原蟲雌配子體,Ovalinshape;LightbluecytoplasmCompactchromatinEccentricinposition(核小致密在一邊）,Nucleus,Cytoplasm,Microgametocyte(Male)間日瘧原蟲雄配子體,OvalinshapeCytoplasminlightReddishbluecolorLoosenucle

10、usCentricinposition(核大疏松在中央),Nucleus,Cytoplasm,Erythrocyticstage紅內(nèi)期,惡性瘧原蟲Plasmodiumfalciparum,RingformTwonucleiOrTworing,Plasmodiumfalciparum:Gametocytes,Figs.27,28:Maturemacrogametocytes(female);Figs.29,30:Maturemicrogametocytes(male),B.InMosquito,Gametocytesstage（配子體期）Sporogony(asexualreproduction

11、)孢子增殖,Mosquitoes-Vector,2.Fromhumantomosquitoes,Malariapatient,Malegametes（雄配子）,Exflagellation(出絲）ofmalegametes,Ookinetes(動合子),Oocysts(卵囊),在胃彈性纖維膜下，蟲體變圓并分泌囊壁形成球形的卵囊(oocyst),Sporozoites（子孢子）,InfectivestageSpindle-shaped1015m1mInmosquitoesaliva,FinalHost,IntermediateHost,Keynotes,1.Intermediatehost:Hu

12、man2.Finalhost:Mosquito3.Infectivestage:Sporozoite（子孢子）4.Infectivemode:Mosquitobiteskinofhuman5.Parasiticposition:Liverandredbloodcells6.Transmittedstage:Gametocytes（配子體）7.Schizogoniccycleinredcells（紅內(nèi)期裂體增殖周期）:48hrs/P.v；36-48hrs/P.f,ClinicalManifestationandPathogenesis,Itincludestheperiodofthetime:1

13、)sporozoitereachtheliver2)exo-erythrocyticstageintheliver3)erythrocyticstageintheRBCamounttoalargenumber.P.v.8-31days;P.f.7-27days;P.o.16-18days;P.m.18-35days,1.Incubationperiod（潛伏期）:,2.Anparoxysmattack發(fā)作,Typicalattack:chill-fever-sweating,Thecoldstage(chill)30min-1hr,Thehotstage(fever)411-4hr,Sweat

14、ingstage1-2hr,Timingofattack:P.v.,P.o.48hP.m.72hP.f.36-48h,3.Recrudescence(再燃）,Malariaoccursagainaftermanyyears.DuetothesmallnumberofviableErythrocyticformsofparasite(殘存的少量紅內(nèi)期原蟲)developagain.Itoccursinfourspeciesofparasites.,4.Relapse(復(fù)發(fā)),Bradysporozoite(Hypnozoites)thathavenotbeentreatedadequatelyw

15、ithatissueschizonticide.RelapseonlyoccursinP.vivaxandP.ovale,(1)Destructionofparasitizedredbloodcell;(2)Autoimmunehemolysis(免疫溶血）;(3)Increasedphagocytosisbythereticuloendothelialsystem（吞噬作用）;(4)Defectivebonemarrowresponse,5.Anemia,（1）spleenhyperanemia（脾充血）(2)hyperplasia(multiplication）ofmacrophages（

16、單核吞噬細(xì)胞增生）（3）swallowmalarialpigment（吞噬大量瘧色素-脾切面顏色變黑）,6.Splenomegaly（脾腫大）,惡性瘧病人（巨脾）,Tropicalsplenomegalysyndrome.,惡性瘧病人脾臟,SpleenfromacaseofP.falciparuminfection.Thedepositionofmalarialpigmentmakesitalmostblackincolor.,fatalmalariacausedbyP.f.(smallvesselsareplugged)Cerebralmalaria（腦型瘧）;Blackwaterfever

17、（黑水熱）;AcuterespiratorydistresssyndromeARDS（急性呼吸君迫綜合征);HighFever;Pulmonaryedema(肺水腫);Shock;Death,Malignantmalaria惡性瘧疾(兇險(xiǎn)性瘧疾),SectionofliverfromacaseofP.falciparuminfection,TheKupffercells(macrophages)areloadedwithblackpigment,whichismalarialpigment(haemozoin).,BrainfromacaseofP.falciparuminfection.,I

18、nthiscasedeathoccurredduetohaemorrhages(出血）andnecrosisintheCNS(cerebralmalaria).,SectionofbrainfromacaseofP.falciparuminfection.,Theinfectedcellsadheretotheendothelialliningofthebloodvessels.Insmallbloodvesselsthisleadstoocclusion（阻塞）andnecrosis.HandE.400.Enlargedby23.4.,Sametissuesobservedinpolariz

19、ed（偏振光）light.,Themalarialpigmentinsidetheredcellsshinesmakingiteasilyvisible.HandE.400.Enlargedby23.4,Immunology,NaturalImmunityAcquireImmunityPremunition（帶蟲免疫）,Keynotes,1.pathogenicstageanddiagnosticstage：erythrocyticstage2.exo-erythrocyticstage（紅外期）：relationtoincubationperiodandrelapse.3.erythrocy

20、ticstage（紅內(nèi)期）：relationtoparoxysmrecrudescenceanddiagnosis.4.Gametocytesstage（配子體期）：relationtotransmission.5.Developmentinmosquito:relationtotransmission.,Diagnosis,A.ClinicalsymptomsandhistoryB.Microscopicexaminationofblood.CollectionofBlood：P.v.6-8hourafterstroke.P.f.Initialtime:Ringform7-10daysfor

21、gametocytes,Method,1.ThinandThickBloodsmear（厚薄血膜法）,制片方法,GiemsaandWrightstaining,Theredbloodcellarecompletelylysedduringtheprocessofstaining,malarialparasitesarenoteasytorecognizedbutthenumberislarge.Theredcellsmorphologyismaintainedsothatthemarlariaareeasytorecognizebutthenumberissmall.,Thickbloodsm

22、ear,Thinbloodsmear,C.Othermethods:Immunologic/Biochemical/Moleculardiagnosis.,IFA,PCR,Treatment,1.Threeprinciples:,*Controlofclinicalsymptoms*Eradicationofgametocytes*Preventrelapse,2.Drugs:,1)Anti-erythrocyticstagedrugs（殺紅內(nèi)期藥）-控制瘧疾發(fā)作:quinine（奎寧）、chloroquine（氯喹）、artemisinin（青蒿素）、mefloquine(甲氟喹)andar

23、temether（蒿甲醚）。2)Anti-exoerythrocytic&gametecyte（殺紅外期和配子期藥）-抗復(fù)發(fā)和傳播:primaquine（伯喹）andpyrimethamine（乙胺嘧啶）。3)Anti-sporozoite（殺子孢子藥）-預(yù)防和抗復(fù)發(fā)治療:pyrimethamine(乙胺嘧啶),青篙素-凝聚著中國科學(xué)家的智慧,Epidemiology,Epidemiologyfactors,1.Infectivesource:Malariapatientandcarrier2.Transmitvector:Mosquitoes-Anopheles（按蚊屬）3.Susceptiblepeople,Prevention,1.Chemoprophylaxis化學(xué)預(yù)防(inJulyOctober),Start1weekbeforeentryintotheendemicareaandbecontinuedfor4weeksafterreturningfromanendemicarea.Drugs:Chloroquine(氯喹)/pyrimethamine(乙胺嘧