寄生虫malaria 2013

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

2、istributionofMalaria,WhatisMalaria?,Malaria-badair,瘴气打摆子，冷热病,Studyonmalaria,CharlesL.A.Laveran1907,RonaldRoss1902,Tuyouyou2011,FourspeciesofhumanPlasmodiumprotozoa:,Plasmodiumvivax（间日疟原虫）P.malariae（三日疟原虫）P.ovale（卵形疟原虫）P.falciparum（恶性疟原虫）,MorphologyandLifecycle,Twohosts:humanandmosquitoes,FromMosquit

3、oestoHuman,感染阶段子孢子(sporozoite),A.Inhuman,Exo-erythrocyticstage（红外期）inliverErythrocyticstage(红内期）inRBCs,1.EE(exo-erythrocyticstage红外期),P.v.6-8days;P.f.5-7.,Site:liver肝脏,Theinfectiveform:Sporozoite(子孢子）,Asmall,spindle-shapedcellwithasinglenucleus,whichdevelopedinmosquito,andisintroducedintomanbythebit

4、eofaninfectedmosquito.,Tachysporozoite(速发型子孢子)TS.,Thosedevelopingintomerozoite(裂殖子)andundergoesEEschizogonyimmediatelyaftertheyentertheliver.,Bradysporozoite(迟发型子孢子)BSorHypnozoites(休眠子).,Theywillremainintheliverwithoutfurtherdevelopmentinalatentperiod.,TSorBSschizogony（裂体增殖）schizont(裂殖体)merozoite(裂殖

5、子)ruptureoflivercellmerozoiteintotheblood.,EE(exo-erythrocyticstage红外期),merozoites(裂殖子),Morphology,schizontmaturein6-14days,theliberationmerozoites（裂殖子）enterthebloodstream.,exo-erythrocyticschizont(裂殖体）inliver.,2.ES(erythrocyticstage红内期),Merozoites（裂殖子）,Trophozoites（滋养体）,Schizontes（裂殖体）,Gametocytes（

6、配子体）,Erythrocyticstage(红内期),Threestages:A.Trophozoitestage(滋养体期)B.Schizontstage(裂殖体期)C.Gametocytesstage(配子体期),Inredbloodcell-importantfordiagnosisandpathogenic,A.Trophozoite,Nucleus,Bluecytoplasm,vacuole,（1）Theringform(环状体）-smalltrophozoite,smalltrophozoite,WrightorGiemsastainnucleusinredCytoplasmin

7、blueAsingleredchromatindotwithlightbluecytoplasmjustlikearing.,RBCcellenlargedPseudopodiaMalarialpigment(疟色素）Schffnersdots(薛氏小点)appear,Pseudopodiacytoplasma,Nucleus,Malarialpigment,Schffnersdots,（2）LargetrophozoitesLatetrophozoite(大滋养体）,Schizonts（裂殖体）(1)Immatureschizont未成熟裂殖体,Nucleusbegintodivide.Ma

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

9、PlasmodiumvivaxMacrogametocyte(female);Fig.30:Microgametocyte(male),Nucleus,Nucleus,Maturemacrogametocyte(female)间日疟原虫雌配子体,Ovalinshape;LightbluecytoplasmCompactchromatinEccentricinposition(核小致密在一边）,Nucleus,Cytoplasm,Microgametocyte(Male)间日疟原虫雄配子体,OvalinshapeCytoplasminlightReddishbluecolorLoosenucle

10、usCentricinposition(核大疏松在中央),Nucleus,Cytoplasm,Erythrocyticstage红内期,恶性疟原虫Plasmodiumfalciparum,RingformTwonucleiOrTworing,Plasmodiumfalciparum:Gametocytes,Figs.27,28:Maturemacrogametocytes(female);Figs.29,30:Maturemicrogametocytes(male),B.InMosquito,Gametocytesstage（配子体期）Sporogony(asexualreproduction

11、)孢子增殖,Mosquitoes-Vector,2.Fromhumantomosquitoes,Malariapatient,Malegametes（雄配子）,Exflagellation(出丝）ofmalegametes,Ookinetes(动合子),Oocysts(卵囊),在胃弹性纤维膜下，虫体变圆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（配子体）7.Schizogoniccycleinredcells（红内期裂体增殖周期）: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（潜伏期）:,2.Anparoxysmattack发作,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(残存的少量红内期原虫)developagain.Itoccursinfourspeciesofparasites.,4.Relapse(复发),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、单核吞噬细胞增生）（3）swallowmalarialpigment（吞噬大量疟色素-脾切面颜色变黑）,6.Splenomegaly（脾肿大）,恶性疟病人（巨脾）,Tropicalsplenomegalysyndrome.,恶性疟病人脾脏,SpleenfromacaseofP.falciparuminfection.Thedepositionofmalarialpigmentmakesitalmostblackincolor.,fatalmalariacausedbyP.f.(smallvesselsareplugged)Cerebralmalaria（脑型疟）;Blackwaterfever

17、（黑水热）;AcuterespiratorydistresssyndromeARDS（急性呼吸君迫综合征);HighFever;Pulmonaryedema(肺水肿);Shock;Death,Malignantmalaria恶性疟疾(凶险性疟疾),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（带虫免疫）,Keynotes,1.pathogenicstageanddiagnosticstage：erythrocyticstage2.exo-erythrocyticstage（红外期）：relationtoincubationperiodandrelapse.3.erythrocy

20、ticstage（红内期）：relationtoparoxysmrecrudescenceanddiagnosis.4.Gametocytesstage（配子体期）：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（杀红内期药）-控制疟疾发作:quinine（奎宁）、chloroquine（氯喹）、artemisinin（青蒿素）、mefloquine(甲氟喹)andar

23、temether（蒿甲醚）。2)Anti-exoerythrocytic&gametecyte（杀红外期和配子期药）-抗复发和传播:primaquine（伯喹）andpyrimethamine（乙胺嘧啶）。3)Anti-sporozoite（杀子孢子药）-预防和抗复发治疗:pyrimethamine(乙胺嘧啶),青篙素-凝聚着中国科学家的智慧,Epidemiology,Epidemiologyfactors,1.Infectivesource:Malariapatientandcarrier2.Transmitvector:Mosquitoes-Anopheles（按蚊属）3.Susceptiblepeople,Prevention,1.Chemoprophylaxis化学预防(inJulyOctober),Start1weekbeforeentryintotheendemicareaandbecontinuedfor4weeksafterreturningfromanendemicarea.Drugs:Chloroquine(氯喹)/pyrimethamine(乙胺嘧