傳染病學課件：獲得性免疫缺陷綜合征（英文版）

AcquiredImmuneDeficiencysyndrome(AIDS)

2023/11/152023/11/15InitialReportsJune5,1981:5casesofPCPingaymenfromUCLA(MMWR)July3,1981:26additionalcasesDec10,1981:3NEJMpapersdescribecasesGottliebMSNEJM2001;344:1788-91DefinitionAIDSisafatalchronicinfectiousdiseasecausedbytheHumanImmunodeficiencyVirus(HIV),transmittedmainlythroughsexualcontactsandbodyfluids,characterizedpathologicallybyselectivedepletionofhelperT(CD4+)lymphocytesandimpairmentofcell-mediatedimmunity,andclinicallybysevereopportunisticinfectionsandmalignancies.

2023/11/15

Classification:HIV-1andHIV-2,belongtofamilyRetroviridae,subfamilyLentivirus,andwerediscoveredin1983and1985,respectively.

Etiology2023/11/152023/11/15ThereplicationcycleofHIV

2023/11/152023/11/15吸附↓脫衣殼↓逆轉(zhuǎn)錄↓環(huán)化↓前病毒,整合↓轉(zhuǎn)錄,翻譯↓核心顆粒裝配↓出芽HIV動態(tài)感染過程2023/11/15HIVgenomeNinegenes,3structuregenes,3regulatorygenesand3unknownfunctiongenes.(l)GAG(groupantigen)geneencodesmaincoreproteinp24;(2)pol(polymerase)geneencodesreversetranscriptase;(3)ENVgeneencodessurfaceproteinsgp120andgp41.2023/11/15Tropism:Highaffinityoftheviralgp120envelopeproteinfortheCD4molecule(receptor),whichisnormallyonthesurfaceofhelperTlymphocytes,10%-20%ofbloodmonocytesandmacrophages,5%ofBcells,neuroglia,neuronsofcentralnervoussystem,LangerhanscellsinskinandcolorectalepithelialcellsarealsoknowtoexpresssmallamountsofCD4ontheirsurfaces.2023/11/15OtherEarlyDevelopments1982:Term“AIDS”coinedFirstcasesinwomenreportedFirsttransfusionandverticallytransmittedcasesreported1983:IsolationofaretrovirusfromapatientwithAIDSbyMontagnier’sgroup1984:DetectionofHTLV-IIIinptswithandatriskforAIDS(Gallo)SepkowitzKNEJM2001;344:1764-722023/11/15Source:NationalAIDScasesurveillancedata,CDCMonthsafterOIdiagnosis0.20.40.60.81.001981-1987Proportionsurviving1030405060200OtherEarlyDevelopments1985:FDAapprovesfirstcommercialHIVantibodytest1986:NIHestablishestheAIDSClinicalTrialsGroup1987:AZT=firstantiretroviralapprovedbyFDA2023/11/15EpidemiologyFirstcaserepotedinmid-1981fromUSA；80，000，000Infectedpersonallovertheworld；Over24,800,000AIDSpatientsdied；NewlyIncreased50,000,000peryear,16000patientseveryday,11caseseveryminute.Africa>America>Asia>Europe；Atleast1,000,000infectedpersoninChina.2023/11/15EstimatednumberofpeoplenewlyinfectedwithHIVglobally,1990–2007

2023/11/15HIVepidemicinChina

Sincethefirstcasewasreportedinmid-1981fromU.S.A.,over150nationsintheworldreportedAIDS.AIDSwasfirstreportedinBeijing,China,in1985.SincethentheHIVepidemichasbecomemorevisibleinChina.Thecasesreportedareincreasingeveryyearandhavespreadthroughoutthecountry.

2023/11/15FourphasesoftheHIVepidemicinChinaFirstphase(1985–1988)wasmarkedbyasmallnumberofAIDScasesincoastalcities.

Secondphase(1989–1993)identificationofHIVinfectionin146drugusersinsouthwesternYunnanProvince.

Thirdphase(1994–2000)HIVinfectionhadbeenreportedinall31provinces,regions,andmunicipalities.HIVinfectionhadbeenreportedinall31provinces,regions,andmunicipalities.Fourthphase(2001–)thesilencesurroundingHIVinChinawasbeginningtoend.2023/11/15Epidemiology

SourcesofinfectionpatientNon-symptomcarriers☆HIVexistsin∶BloodsalivasementearVaginaldischargesmilk

2023/11/15HIVinBodyFluidsSemen11,000VaginalFluid7,000Blood18,000AmnioticFluid4,000Saliva1AveragenumberofHIVparticlesin1mlofthesebodyfluidsRoutesofTransmissionofHIV

SexualContact: Male-to-male Male-to-femaleorviceversa Female-to-female BloodExposure: Injectingdruguse/needlesharing Occupationalexposure Transfusionofbloodproducts Perinatal: Transmissionfrommomtobaby BreastfeedingEpidemiology

Routesoftransmisson(1)Homosexualandheterosexualcontact;(2)Injectionviai.v.drugaddiction,bloodandbloodproducts;(3)Mothertochildperinataltransmission;(4)Healthcareworkersmaybeinfectedbyneedlestickorbybrokenskinoccasionally.2023/11/152023/11/15Epidemiology

Highriskgroups

Malehomosexuals,sexualprovisionincludingprostitution,i.v.drugaddictsandhemophiliacs

repeateduseserumproducts.

2023/11/15PathogenesisCD4+TlymphocyteandotherCD4+cellsarelargelydamagedbyHIVindirectandindirectway,andleadtodysfunctionanddeficiencyincell-mediatedimmuneresponse.2023/11/15Clinicalmanifestation

Incubationperiod∶2-10yearsAcuteHIVinfection

AsymptomaticHIVinfection

Persistentgeneralizedlymphadenopathy(PGL)

AIDS

2023/11/15Stage1-PrimaryShort,flu-likeillness-occursonetosixweeksafterinfectionnosymptomsatallInfectedpersoncaninfectotherpeople2023/11/15Stage2-AsymptomaticLastsforanaverageoftenyearsThisstageisfreefromsymptomsTheremaybeswollenglandsThelevelofHIVintheblooddropstoverylowlevelsHIVantibodiesaredetectableintheblood2023/11/15Stage3-SymptomaticThesymptomsaremildTheimmunesystemdeterioratesemergenceofopportunisticinfectionsandcancers2023/11/15Stage4-HIV

AIDSTheimmunesystemweakensTheillnessesbecomemoresevereleadingtoanAIDSdiagnosis2023/11/15ClinicalmanifestationAIDSconstitutionalsymptoms:Fever,malaise,anorexia,diarrhea,lossofbodyweightetc.alsoknownasAIDSrelatedcomplex(ARC).Centralnervoussystemsymptoms:Headache,epilepsy,progressivedementia,paraplegiaetc2023/11/15Severeopportunisticinfections:PneumocysticCariniiPneumonia(PCP),Cryptococcalmeningitis,pulmonarytuberculosis,Candidiasis,cryptosporidiosis,Histoplasmosis,etc2023/11/15Opportunisticmalignancies:Kaposisarcoma,non-Hodgkinlymphomaetc.Otherdisordersassociatedwithsevereimmunesuppression:Chroniclymphoidinterstitialpneumoniaetc.

2023/11/15Figure9-222023/11/15ClinicalManifestationsWastingsyndromeKaposi’ssarcoma2023/11/15Kaposi'ssarcomainapatientwithAIDS

2023/11/15ClinicalManifestationHerpeszosterMamilla2023/11/15Cryptozoitesporotrichosis2023/11/15Clinicalmanifestationinvarioussystems[1]1.RespiratorysystemPneumocysticCariniiPneumonia(PCP),Pneumocystisjiroveci(耶氏肺孢子菌)LungtuberculosisCytomegalovirusinfectionFungalpneumoniaKaposisarcoma2023/11/15Clinicalmanifestationinvarioussystems[2]2.DidestivesystemOralcavityandesophagitisOralcavityhairyleukoplakiaInfectiousdiarrheaCrissum,rectumherpesvirusinfectionHepaticlesion2023/11/15VariousorallesionsinHIV-infectedindividuals.A.Thrush

2023/11/15BariumswallowofapatientwithCandidaesophagitis.

2023/11/15Clinicalmanifestationinvarioussystems[3]3.Nervoussystemopportunisticinfections

Cryptococcalmeningitis,Etc.Opportunisticmaliganency

primarylymphomaHIVdireckinfection∶dementiasyndrome2023/11/15Centralnervoussystemtoxoplasmosis

Centralnervoussystemlymphoma

2023/11/15Clinicalmanifestationinvarioussystems[4]4.SkinmucousmembraneKaposi’ssarcomaMoniliainfectionherpespudendalis,

cauliflowerexcrescence2023/11/15Clinicalmanifestationinvarioussystems[5]5.OcularregionRetinitis(CMV)

ToxoplasmosisofbrainchoroiditisKaposi’ssarcoma2023/11/15LaboratoryExamination[1]1.Routineexaminations:Anemia,leucocytopenia,proteinuria.2.Immunologicalexaminations:Tlymphocytopenia,especiallyCD4+Tlymphocytes(healthyTcelllevelsrangefrom500to1500),decreaseinCD4\CD8ratio,lessthan1(normal1.75-2.1).2023/11/15LaboratoryExamination[2]3.Serologicalfindings:Positiveanti-HIVbyELISAandWesternblot（anti-gp24,anti-gp120andanti-gp41,anti-gp64

andanti-gp31）.4.PlasmaHIVRNAAssays:RT-PCR,branchedDNA(bDNA)IsolationVirus2023/11/152023/11/15Diagnosis[1]CriteriaforadultAIDSpatients.１.Confirmedpatients⑴HIVinfectionEpidemiolgy,Anti-HIV(+),WB(+).2023/11/15⑵AIDSpatientsEpidemiologyandclinicalmanifestation.Anti-HIV(+),CD4number<0.2*109/Lor0.2-0.5*109/L，Variouspathogensleadingtoopportunisticinfectionsoropportunisticmalignancies.2023/11/152023/11/15周智Diagnosis[2]2.Suspectedpatients⑴Epidemiologyandclinicalmanifestation,butanti-HIV(-)；⑵ChildrenfromHIV(+)parents；⑶Bodyweightlossmorethan10％，chroniccoughordiarrhealastedmorethanonemonth，fevermorethanonemonth，generalizedlymphadenopathy.

⑷Epidemiology,noclearcilinicalmanifestations,CD4+lymphocytes<0.2×109/L,(5)opportunisticinfectionsandopportunisticmalignancies,needingtofollowanti-HIV。

2023/11/15Differentialdiagnosis

1.IdiopathicCD4+lymphocytopenia.2.SecondaryCD4+lymphocytopeniaaftercancertherapyorresultingfromautoimmunediseases.2023/11/15Treatment1.AntiretroviraltherapyWhenusedincombinations,thesemedicationsaretermedHighlyActiveAntiretroviralTherapy(HAART).HAARTcombinesthreeormoreanti-HIVmedicationsinadailyregimen,sometimesreferredtoasa"cocktail".

2023/11/15(1)Nucleosidereversetranscriptaseinhibitors(NRT1):Zidovudine(AZT,ZDV),Didanosine(ddI),Zalctabine(ddC),Lamivudine(3TC),Stavudine(d4T)andAbacavir(2)Non-nucleosidereversetranscriptaseinhibitors(NNRTI):Delavirdine,Nevirapine,Efavirenz.(3)Proteaseinhihitors(PI):Saquinavir,Ritonavir,IndinavirandNelfinavir.(4)

FusionInhibitors.2023/11/15

Therapeuticprinciple:CombinationRecommondedregimens:2NRTIs+1PIandsoon.Indications:patientswithCD4+lmyphocytecount<0.5~109/LorplasmaHIVRNAviralload>5,000-10,000copies/ml;patientswithAIDS.Sideeffectsanddrugresistance.2023/11/152.Treatmentofcomplications:

(1)PCP:Pentamidine4mg/kgimorivforl4days:sulfamethoxazole-trimethoprim(SMZ-TMP)#3bid.(2)Kaposisarcoma:AZT+interferon;bleomycin;vinblastine;adriamycin.(3)Cryptosporidiosisandhistoplasmosis:Spiramycin.(4)Cytomegalovirus(CMV)infection:Gancyclovir.(5)cryptococcalmeningitis:Fluconazole.2023/11/153.Supportiveandsymptomatictreatments:

(1)Bloodtransfusiontotreatanemia.

(2)Immunomodulation:RecombinantIL-2(inexperiment).2023/11/15

HIVOccupationalExposureReviewfacilitypolicyandreporttheincidentMedicalfollow-upisnecessarytodeterminetheexposureriskandcourseoftreatmentBaselineandfollow-upHIVtestingFourweekcourseofmedicationinitiatedonetotwohoursafterexposureLiverfunctionteststomonitormedicationtoleranceExposureprecautionspracticedPrevention

1.Isolationofpatientsandconcurrentdisinfection.2.Blockingroutesoftransmission:(1)Educationofthepublic.(2)banningofdrugaddictionandprostitution.

2023/11/15(3)Strictscreeningofbloodandbloodproducts.(4)Popularizedisposalsyringesandneedles.(5)SterilizationofmedicalinstrumentsandfacilitiesusedbyAIDSpatients.

2023/11/153.Protectionofsusceptibles:(1)RestrictthemarriagewithHIVcarriers.(2)Useofcondomsandavoidsexualperversion.(3)Vaccination:stillatexperimentalstage.2023/11/15Fourwaystoprot