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1、Tuberculosis,commonlyknownasTB(shortfortubercularbacillus),isaworldwidecontagious(传染性)andanoftensevereairbornediseasecausedbyvariousstrainsofmycobacteria(分支杆菌),usuallyMycobacteriumtuberculosis(结核分枝杆菌,MTBforshort);typicallyattacksthelungs,butcanalsoaffectsotherorgansofthebody.Theclassicsymptomsofacti
2、veTBarechroniccough,long-termlowdegradefever,nightsweats(盗汗),fatigue,lossofappetiteandweight;occasionalyhaemoptysis(咯血).latent(隐形,潜伏性)tuberculosisisthesecondmostcommoncauseofdeathfrominfectiousdisease(afterHIV);Roughlyone-thirdoftheworldspopulation(2billion)hasbeeninfectedwithMTB,withnewinfectionsoc
3、curringinabout1%ofthepopulationeachyear13.7millionchronicactivecases,8.8millionnewcases,and1.45millionassociateddeathscases,AnnualnumberofnewreportedTBcases.DatafromWHOThedistributionoftuberculosisisnotuniformacrosstheglobe:mostoftheinfectionoccurredindevelopingcountries,especiallyinChina,andIndia.i
4、scloselylinkedtothepoorpublichealthinthesecountries.Theincidenceoftuberculosishasdeclined dramatically overpastdecadesofyears.itsresurgence(复燃)inthe1980sduetotheriseofdrug-resistant(耐药的)strains,theemergenceofglobalHIVinfection,andthelackofappropriatehealthcare.TheresurgenceofTBhasdashedhopesofcomple
5、telyeliminatingTBfromthepopulationandresultedinthedeclarationofaglobalhealthemergencybytheWHO(in1993).MainlycausedbyM. tuberculosis, isamemberoftheMycobacterium tuberculosiscomplex(结核分枝杆菌复合群)referstoageneticallyrelatedgroupofMycobacteriumspeciesthatcancausetuberculosisinhumansorotherorganismsMycobac
6、teriumtuberculosiscomplex: Mycobacterium africanum(非洲型) Mycobacterium microti(田鼠型) Mycobacterium bovis (牛型) Mycobacterium tuberculosis (MTBforshort)mostcommonlyfoundinWestAfricancountriesopportunisticpathogenofthelaterstagesofHIVdiseasedrinkingnon-sterilisedmilkfrominfectedcowsPasteurization(巴氏消毒)ha
7、slargelyeliminateditsinfectionisarod-shaped(杆状),slow-growing,aerobic(需氧)bacterium,hasanunusual,waxy(蜡状的)coatingonitscellsurface(primarilyduetothepresenceofmycolicacid(分枝菌酸)),whichaccountsformanyofitsuniqueclinicalcharacteristics,suchasitsimperviousness(不通透性)toGramstaining,soitisclassifiedasanacid-fa
8、stbacillus(AFB,抗酸杆菌).ThemosteffectivetechniquesaretheZiehlNeelsen(尼氏染色)andrhodamineauraminestains(罗丹明-金安染色),ZiehlNeelsestainsdyeAFBsabrightredthatstandsoutclearlyagainstabluebackground.ThisisanacidfaststainofMTBwithZiehlNeelsestainsGrowslowly:dividesevery16to20hours,whichisanextremelyslowratecompare
9、dwithotherbacteria,whichusuallydivideinlessthananhourcanwithstandweakdisinfectants(消毒剂)andsurviveinadverseenvironmentforweeks,likethedryandcoldcircumstance,ortheacidic(酸性的)andthealkaline(碱性的)environment,buttheyaresensitivetotheultravioletlight(紫外线).firstdiscoveredin1882byRobertKoch.receivedtheNobelP
10、rizeinphysiologyormedicinein1905forthisdiscovery.Kochphenomenon(Koch现象)iswellknownasthedifferentresponsesofaanimalbetweentheprimaryinfectionandthereinfectionwithMTB.Primaryinfection:firmnodule,deepulcerformandpersist,untiltheanimalsdie.reinfection:localinduration,superficalulcer,healedquickly.Caused
11、bythedelayedhypersensitivityandimmunityinTBdisease.Itisprimarilyanairborne(空气传播的)disease,thebacteriaarespreadfrompersontopersonintinymicroscopicdroplets(微滴)throughtheairwhenpeoplewhohaveanactiveTBinfectionexpelfluidsintotheair.Theprobabilityoftransmissionfromonepersontoanotherdependsuponseveralfacto
12、rs,includingthe(1)numberofinfectiousdropletsexpelledbythecarrier,(2)theeffectivenessofventilation(通风),thedurationofexposure,(3)thevirulence(毒力)oftheM. tuberculosisstrain(4)thelevelofimmunityintheuninfectedpersonDropletnucleicontainingtuberclebacilliareinhaled,enterthelungs,andtraveltothealveoli.Tube
13、rclebacillimultiplyinthealveoli.macrophagessecretedseriesofcytokine(细胞因子,IL-1,IL-6andTNF)torecruitlymphocytesmoremacrophages.Themacrophagesaggregatedwithlymphocytesformagranuloma,thatkeepsthebacillicontainedandundercontrol(LTBI).Iftheimmunesystemcannotkeepthetuberclebacilliundercontrol,thebacillibeg
14、intomultiplyrapidly(TBdisease).Thisprocesscanoccurindifferentareasinthebody,suchasthelungs,kidneys,brain,orbone.Asmallnumberoftuberclebacillienterthebloodstreamandspreadthroughoutthebody.Thetuberclebacillimayreachanypartofthebody.CD4+TCD8+TTh0Th1:细胞免疫:细胞免疫, 增增强巨噬细胞吞噬功能强巨噬细胞吞噬功能IL-12Th2:辅助体液免疫辅助体液免疫I
15、L-4APCTc(CTL):细胞毒作用):细胞毒作用分化:分化:AgAgCell-mediatedimmunityprovidespartialprotectionforthehost,whilethehumoralimmunityhasdodefinedprotectionrole.delayedhypersensitivityisrelatedtothetuberkulinskintestandKochpheneomonen.Exudation(渗出),proliferation(增生)andcaseousnecrosis(干酪样坏死)arethebasicpathologicalchan
16、gesoftuberculosisonetypeofthepathologicalchangewasdominantdependingonthecoursethedisease.existsimultaneouslyandcantransformreciprocally.asawhole,thediseasemayfluctuatebetweenperiodsofexacerbationandremission exudation: observedduringtheinitialorexacerbation(恶化)stage Proliferation:typicallydisplayedi
17、ntuberculargranuloma;recoverystage,signofintactcellmediatedimmunityCaseous necrosis:appearsinconditionsofpresenceoflargenumberofhypertoxicbacilliandofhypersensitivitycombinedwithweakimmunity tubercular Granuloma(结核性肉芽肿):Areusuallysmall(3weekswithorwithoutsputumproduction),occasionally,itmaybeproduct
18、ivewithblood-tinged(血色)sputumHaemoptysis(咯血)canbeslight,moderateormassive.inveryrarecases,theinfectionmayerodeintothepulmonaryartery,resultinginmassivebleedingChestpainUsuallyduetotheextensionofinflammationtotheparietalpleura,Dyspnea(呼吸困难)Uncommon,whenitpresent,indicatedextensivesevereparenchymal(实质
19、)disease,tracheobronchialobstruction(气管支气管阻塞)orlargeamountofpleuraleffusion(胸腔积液).physicalSigns(self-study)Thephysicalsignswerenonspecificanddependentonthequalityandextentofthelesion.Smallextentofdisease:oftennoabnormalsigninthechestExtensiveexudativeandcaesationnecrosis:signsoflungconsolidation:rei
20、nforcementintactilefremitus(触觉震颤),dullpercusssionnotes(叩诊浊音),bronchialbreathingsoundsandfinerales(水泡音).Bigcavity:tympaniticresonnance(鼓音)andamphoricresonance(空瓮音)onpercussion.Extensivefibrosis:trachealdeviationtowardstotheaffectedside,chestwallcollapsedoftheaffectedside,dullpercussionnote,Endobronch
21、ialtuberculosis:localwheeze.1.Allergic(过敏性的)symptoms:Tuberculousrheumatism(结核性关节炎)(Poncetsdisease蓬,塞氏病):isanimmunoligacalreactionofM.tuberculosiswithresultantreactivepolyarthritis(反应性多关节炎)follicularkeratoconjunctivitis(滤泡性角结膜炎)2.Unresponsive(无反应性)/Cryptic(隐匿性)TB(self-study)Seeninpatientswithextremei
22、mmunesuppression.persistenthighfeverofunknownorigin,bonemarrowsuppression(骨髓抑制)orleukemoidreaction(类白血病反应).respiratorysymptomsandchestX-rayabnormaityareusuallyabsent.oftenmisdiagnosedassepsis,leukemia,andotherconectivetissuedisease.Confirmationbybiopsy(granulomasand/or acid-fastbacilldemonstrated)of
23、liverorbonemarrowAccordingtotheChineseMedialAssociation(CMA,1999),tuberculosisisclassifiedas5types:PrimarypulmonaryTB(原发性肺结核)Blood-bornedissemination(miliarytuberculosis)(血源播散性肺结核,粟粒性肺结核)Post-primarypulmonaryTB(reactivationtuberculosisorsecondarytuberculosis)(继发性肺结核)tuberculouspleurisy(结核性胸膜炎)extrap
24、ulmonarytuberculosis(肺外结核)referstotheinfectionofapreviouslyuninfected(tuberculin-negative)individual. mostcommoninchildrenlessthan5yeasoldIncludeprimarycomplex(原发综合征)andintrathoraciclymphatictuberculosis(胸内淋巴结结核)Usuallyasymptomatic.Clinicaldiseasesmaybepresentifthereisahypersensitivityreactionorprog
25、ressiveinfection:nonspecificpneumonia,Bronchialobstruction(Segmentalatelectasis,肺不张)PleuraleffusionMostcanrecovercompletelywithoutsequela(后遗症),howeversomeofthemmaydevelopactive(reactive)tuberculosisafteraperiodofquiescence(静止)Primarycomplexthecombinationofaprimarylesionandregionallymphnodesisreferre
26、dtoastheprimarycomplex Mediastinallymphadenopathy(淋巴结病)Insomecases,isolatedoccurwithoutanyvisibleChangeinthepulmonaryparenchyma.ChestradiographyPrimarypulmonaryTBanditstransformation (1)primarycomplex,inmostcases,ithealsspontaneously.(2)DirectextensionprogressivepulmonaryTB.(3)Spreadtothepleuratuber
27、culouspleurisyandpleuraleffusion.(4)Blood-bornespreadCausedbyblood-bornedisseminationwhichcanoccurredinprimaryandpost-primarypulmonaryTBincludingacute,sub-acute,andchronicAcute:Occurringchieflyininfantsandadolescent,especiallyinthepeoplewithimpairedimmunefunctionSeveretoxemiasymptoms(毒血症状)ifnottreat
28、edtimelyorproperly,theprognosisispoor,assomepatientsmaysufferfromthecomorbidity(共存病)ofmeningitis.TheclassicalappearancesonchestX-rayareoffine12mmlesionsuniforminsize,densityanddistributionresemblingmilletseedsdistributedthroughoutthelungfields.Theonsetofareusuallyinsidious,withoutstrikingclinicalsym
29、ptoms.patientsusuallyhavearelativecompetentimmunity.radiographicfindingsareextensivemilliaryornodular(结节状的)shadowofvariablesize,densityanddistribution,mostfrequentlyinthebilateralupperandmiddlezonesofthelung.freshexudation,obsolete(陈旧的)indurationandcalcifiednodulesmayexistsimultaneously.referstoinfe
30、ctioninapersonwhohasbeensensitisedbyearlierexposure.exogenous(外源性,newinfection)orendogenous(内源性,reactivationofadormantprimarylesion)thelesionusuallypresentwithvarietyradiographiccharacteristicsandmostcommonlyoccurredinapicalorposteriorsegmentsoftheupperlobesandthesuperiorsegmentsofthelowerlobes.some
31、patientsaresputumsmear-positiveandinfectious.classificationbasedonpathologyandchestradiography1infiltrativepulmonarytuberculosis(浸润性肺结核)2cavitarypulmonarytuberculosis(空洞型)3tuberculoma(结核球)4Caseouspneumonia(干酪性肺炎)5Chronicfibrocaseoustuberculosiswithcavitation(慢性纤维空性肺结核)mostcommontypeOccursbyinfection
32、throughtheairwaysSite:Upperpartofthelungs(subclavicularorapicalregion).Outcom:healing;progressiveenlargementofthelesionwithliquefactionnecrosis,cavitation;andbronchogenicspread;breakthroughthepleuratocausepneumothorax(气胸)orpyopneumothorax(脓气胸);transformationintochronicfibrocaseoustuberculosiswithcav
33、itation.appearasawelldefinedroundedmasstypicallylocatedintheupperlobes.Theyareusuallysingleandmeasureup2-5cmindiameter.Smallsatellitelesionsareseeninmostcases.AndthearehelpfulindistinguishingtuberculosisfrompulmonarytumorstuberculomacavitarypulmonarytuberculosisCavitiesformwhennecrosisliquefiedandth
34、esemi-liquidnecroticmaterialisdischargedintothebronchialtreefromwhereitisusuallycoughedup.,usuallyoccurringintheupperlungorapexwithvarietyforms,Caseouspneumoniarapidseriousprogressionoftuberculosis.occursinpeoplewhoareimmunosuppressedandcannotcontroltheinfection.Grossly,onelobeoranentirelungmaybeaff
35、ected.TheinvolvedtissueisconsolidatedDiffusepatchyshadowsandgroundglassappearance.Chronicfibro-cavitarypulmonarytuberculosisarecurringseveresecondaryProlongedcourse,recurrentdeteriorationresultedinmarkeddestructionofthelungwithnecrosisandfibrosis,Itischaracterizedby:Multiplethickenedcavitieswithvari
36、ablesizeaccompaniedwithsignificantfibrosisresultinginelevatedhilumoflungandthechangeofdroopingwillow(垂柳)likelung-markinganddislocationofthelungtissue.Theupperlunghasmorelesionsandolderlesionsthanthelowerlung.Significance:Becauseofthemarkeddestructionofthelungthesputumisofteninfective(calledopentuber
37、culosis(开放性肺结核).Laboratorytestsandexaminations1.microbiologicalexamination(微生物学检查)2.radiologicalexamination(影像学检查)3Immunologicaltests(免疫学检查)4Fiberopticbronchoscopy(纤维支气管镜)MicrobiologicalexaminationIncludingmycobacteriasmear(涂片)andculture(培养)Directmicroscopyofsputumsmearisthemostimportantfirststep.Ap
38、ositivesmearissufficientforthepresumptivediagnosisofTBTheprobabilityofdetectingacid-fastbacilliisproportionaltothebacillaryburdeninthesputum(typicallypositivewhen500010000organismsarepresent).ThemosteffectivetechniquesaretheZiehlNeelsenstainPositiveZiehlNeelsenstainMycobacteriaweredyedabrightredthat
39、standsoutclearlyagainstthebluebackgroundFordiagnosticpurposes,atleastthreeconsecutivesputumspecimensareneeded,eachcollectedin8-to24-hourintervals,withatleastonebeinganearlymorningspecimen.Ifpossible.TherearefourspecimencollectionmethodsforpulmonaryTBdisease:CoughingInducedsputumBronchoscopyGastricas
40、pirationCoughingisthemostcommonlyusedmethodofsputumcollection,Forpatientsunabletocoughupsputum,inducedcoughingupmaybeusedbyinhalationofhypertonicsaline(高渗盐水)(3%5%)oralternativesamplecollectedfrombronchoalveolarlavage(支气管肺泡灌洗),and/ortransbronchialbiopsy(活检)withbronchoscopy。SpecimenCollectionMicrobiol
41、ogicalexamination(self-study)Whenacid-fastbacilliareseeninasmear,theyarecounted.Thereisasystemforreportingthenumberofacid-fastbacillithatareseenatacertainmagnification.Accordingtothenumberofacid-fastbacilliseen,thesmearsareclassifiedas4+,3+,2+,or1+.Thegreaterthenumber,themoreinfectiousthepatientdefi
42、nitivediagnosisrequiresculture.Smear-negativesputumshouldalsobeculturedMTBgrowsslowlyandmaytakebetween4and6weekstoappearonsolidmedium.Fastergrowth(13weeks)occursinliquidmedium.DrugsensitivitytestingisalsoshouldbeperformedandareparticularlyimportantinthosewithaprevioushistoryofTB,treatmentfailureorch
43、ronicdiseaseMycobacteriacultureCultureremainsthegoldstandardforlaboratoryconfirmationofTBdisease,andgrowingbacteriaarerequiredtoperformdrug-susceptibilitytestingandgenotypingthechestradiographismportantfordiagnosisofpulmonaryTBdisease.Chestabnormalitiescansuggestthediagnosis.Aposterior-anteriorradio
44、graphofthechestisthestandardview,alateralviewmayberequiredoccasionaly.acomputerizedtomography(CT)scanmayprovideadditionalinformation:moredetailedimagesofpartsofthebodythatcannoteasilybeseenonastandardchestradiograph,usefulinfindingminororhiddenlesionsandindifferentiatingnoduleslesionsinthelung.Chest
45、Radiographradiographicabnormalitiesmayappearanywhereinthelungsandmaydifferinsize,shape,density.generally,theyareoftenseenintheapicalandposteriorsegmentsoftheupperlobeorinthesuperiorsegmentsofthelowerlobe.importantinjudgmentwhetherthelesionareactiveorquiescentTheradiographicappearancesofoldhealedtube
46、rculosisaredifferentfromthatoftheactivedisease.Infiltration,caseousnecrosisandcavityareconsideredasactiveTB.NOTE:1suggestivediagnosisforTBAbnormalitiesseenonchestradiographsmaybesuggestiveof,butareneverdiagnosticof,TBdisease.ChestRadiographTestforM. tuberculosis infectionCurrently,therearetwomethods
47、availableforthedetectionofMTBinfection:Mantouxtuberculinskintest(TST,结核菌素实验);Interferon-gammareleaseassays(IGRAs,-干扰素释放试验)IntheTSTtest,asubstancecalledpurifiedproteinderivative(PPD,纯蛋白衍生物),whichisderivedfromtuberculin,isinjectedundertheskin.TypicallyPPDproducesaT-cellmediateddelayed-typehypersensiti
48、vityreactionifthepersonhasbeeninfectedwithMTB.Ittakes2to8weeksforthehosttoestablishdelayedcell-mediatedhypersensitivityafterinitialinfectionwithMTBanddetectedbytheTST.AdministeringtheTSTTheTSTisperformedbyintradermal(皮内)injectionof0.1mlofPPDcontaining5tuberculinunitsintothevolarsurfaceoftheforearm.R
49、eadingtheTSTThereactiontotheTSTshouldbeassessed48to72hoursaftertheinjection,bymeasuringthediameterofinduration(硬结)(palpableraised,hardenedarea)acrosstheforearm(perpendiculartothelongaxis)inmillimeters.Ifthereisnoinduration,theresultshouldberecordedas0mm.Erythema(redness)shouldnotbemeasuredjudgemento
50、ftheTST PPDNegative -0-4mmPositive + 5 mmMild positivepositive + 10 mmModerate positivePositive + 20 mm (or bleb,水疱水疱)Significant positiveTSTisavaluabletool,butnotperfect.Severalfactorscanleadtofalse-positiveorfalsenegativeskintestreactionsTSTFalse-PositiveReactions:Infectionwithnontuberculousmycoba
51、cteriaBCGvaccinationTSTFalse-NegativeReactions:Concurrentviralinfection(e.g.,measles麻疹,mumps腮腺炎,chickenpox水痘,HIV);overwhelmingTBdiseaseChronicrenalfailureImmunosuppressivetherapy(corticosteroid)impropertestingtechniqueinterpretationoftheTSTitmayovercomeTSTsfalse-positivelimitationThesetestsmeasureth
52、ereleaseofIFN-fromsensitisedTcellsinresponsetoantigenssuchasearlysecretedantigenictarget(ESAT)-6(早期分泌抗原靶蛋白6)orculturefiltrateprotein(CFP)-10(培养滤液蛋白10)thatarespecifictotheMTBandarenotsharedwithBCGoropportunisticmycobacteria.Thegreaterspecificityofthesetests,combinedwiththeconvenienceofonebloodtest,as
53、opposedtotwovisitsforskintesting,suggeststhatIGRAswillreplacethetuberculinskintestinlow-incidence,high-incomecountries.interferon-gammareleaseassaysSomemolecularandimmunologicalmethodsareavailableforrapiddetectionoftuberculosis.SuchasthePCR(polymerasechainreaction)andserologicaltestofantibodytoMycob
54、acteriumtuberculosis.PCR:advantages:rapid,candistinguishmycobacteriafromotherstrainsofmycobacteria.disadvantages:expensive,specialtechnical(equipment&technician)arerequired.serologicaltestofantibodytoMycobacteriumtuberculosisadvantages:rapid,low-cost,availableamongdifferentregions.disadvantages:hasl
55、owsensitivityandspecificity.Molecular&ImmunologicalDetectionDiagnosticfiberopticbronchoscopywithtransbronchialbiopsyandbronchoalveolarlavageisaneffectivewaytoobtaindiagnosticmaterial.itisessentialinthediagnosisofendobronchialtuberculosis.FiberopticbronchoscopyDiagnosisofTuberculosisDiseaseAcompletem
56、edicalevaluationforTBdiseaseincludesthefollowing4components:1.Medicalhistoryandclinicalmanifestation2.Diagnosticcriteria:bacillary positive pulmonary tuberculosis(痰菌阳性肺结核) bacillary negative pulmonary tuberculosis (痰菌阴性肺结核)3.Judgementoftheactivities4.ClassificationandtherecordformatDiagnosisofTuberc
57、ulosisDiseaseMedicalHistory:historyofTBexposure,infectionordiseasepastTBtreatmentdemographic(人口统计学的)riskfactorsforTB:country of origin, age, ethnicity, occupation, or racial group underlyingmedicalconditions: HIV infection , diabetes, medication that affect the hosts immunitySymptomsandsignssymptoms
58、includingprolongedcoughof3ormoreweeks,chestpain,andhemoptysis.lowgraderemittentfever,chills,nightsweats,appetiteloss,weightloss,fatigue.Tuberculosisalsoshouldbesuspectedwhenapneumonia-likeillnesshaspersistedlongerthan3weeks,orwhenarespiratoryillnessinanotherwisehealthyindividualdoesnotrespondtoregul
59、arantibiotics.thephysicalsignsinpatientswithTBarenotspecific.Diagnosticalcriteria: bacillary positive pulmonary tuberculosis(痰菌阳性): sputumsmearand/orcultureispositivewithcorrespondingsymptomsandchestx-rayfindings. bacillary negative pulmonary tuberculosis(痰菌阴性) canbediagnosedwhenatleastaseriesof3spu
60、tumsmearmicoscopyandonesputumcultureareallnegativeThediagnosisshouldbebasedoncriteriaasfollows:1typicalclinicalsymptomsandchestradiographiccharacteriscsofTBdisease.2exclusionofothernon-tuberculouspulmonarydiseaseclinically.3astrongpositivePPDtest,and/orIGRAtest,accompaniedwithsignificantlyelevatedES
61、R(erythrocytesedimentationrate,红细胞沉降率)4responsetodiagnostictreatmentofTBclinically.5positiveinPCRandprobetest6Extrapulomnaryhistopathologicalevidence7MTBwasfoundinBALor8TBpathologicalchangesinbronchiorlungtissueHaving3criteriaamongthe1-6or1in7-8thisdiagnosiscanbeestablishedclinically.Judgingactiviti
62、esandtherecordingmode PatientswithactiveTBshouldreceiveanti-tuberculosistherapy.Basedonclinicalfeature,radiographicfindingsandsputumbacterialexamination.SignsofactiveTB:sputumbacterialpositive,exudation,cavity,caseousnecrosischangesinchestX-ray.Recordformshouldberecordedinproperordersandarebasedon1c
63、lassification2involvedsitesandextension3bacteria-negativeorpositiveinsputum: smear(-)/(+), or culture(-)/(+), or no sputum4historyoftreatment:initialtreatmentorretreatmentSecondary pulmonary tubeculosis of right upper lobe with sputum smear-positive for initial treatment. Themajorgoalsoftreatmentfor
64、TBdiseasearetoCuretheindividualpatient;Minimizeriskofdeathanddisability;andReducetransmissionofM.tuberculosistootherpersons.guidingprinciplesforeffectivetreatment:early,regular,full-course,adequate,combinationtreatment(早期,规律,全程,适量,联合)Treatmentshouldbecommencedimmediatelyinanypatientwhoissmearpositiv
65、e,orwhoissmear-negativebutwithtypicalchestX-raychangesandnoresponsetostandardantibiotics.Avarietyofhighlyeffectiveshort-courseregimensareavailable;choicedependsonlocalhealthresourcesandinfrastructure.Theyarebasedontheprincipleofaninitialintensivephase(强化治疗,whichrapidlyreducesthebacterialpopulation),
66、followedbyacontinuationphase(巩固治疗)todestroyanyremainingbacteria. Mostpatientscanbetreatedathome.Admissiontoahospitalunitwithappropriateisolationfacilitiesshouldbeconsideredwherethereisuncertaintyaboutthediagnosis,intoleranceofmedication,questionablecompliance,adversesocialconditionsorasignificantris
67、kofMDR-TB. First-linedrugsSecond-linedrugsEthambutol(EMB,E,乙胺丁醇)Amikacin(AM,丁胺卡那霉素/阿卡米星)Isoniazid(INH,H,异烟肼)Kanamycin(KM,卡那霉素)Pyrazinamide(PZA,Z,吡嗪酰胺)aminosalicylicacid(PAS,对氨基水杨酸)Rifampin(RFP,R,利福平)Capreomycin(C,卷曲霉素)Streptomycin(SM,S,链霉素)DrugregimensabbreviationmannerDrugregimensareabbreviatedinas
68、tandardmanner.Thedrugsarelistedusingtheirsingleletterabbreviations.Aprefix(前缀)denotesthenumberofmonthsthetreatmentshouldbegivenfor;asubscript(下标)denotesintermittentdosing(so3meansthreetimesaweek)andnosubscriptmeansdailydosing.thehigh-intensityphaseisgivenfirst,thenthecontinuationphase,thetwophasesdi
69、videdbyaslash.So,2HREZ/4HR3 meansisoniazid,rifampicin,ethambutol,pyrazinamidedailyfortwomonths,followedbyfourmonthsofisoniazidandrifampicingiventhreetimesaweek. TuberclebacillioccurinTBpatientsin4pools:1.metabolicallyactive(代谢活跃)extracellularpool2.relativelymetabolically(代谢相对活跃)inactiveintracellular
70、pool3.relativelymetabolicallyinactiveintracellularpoolwithabrupttransientgrowth.4.metabolicallyquiescent(代谢静止)poolBasedonthegrowthfeatherofMTB,regimenscanbegivendailyorintermittently.Rifapinandisoniazidarebactericide(杀菌的)forbothextracellularandintracellularpoolsTB.Streptomycinisbactericideagainstext
71、racellularwhilepyrazinamideisagainstintracellularorganisms. isthefirst-linemedicationinpreventionandtreatmentoftuberculosisasthemostefficientbactericideforTB,isbactericideforbothextracellularandintracellularpoolsTB.canpermeatetheblood-brainbarrier(血脑屏障)(tubercularmeningitis)Thestandarddoseofisoniazi
72、dinadultsis5mg/kg/day(max300mgdaily)forsixmonthssideeffects:Commonlyincluderash(皮疹),abnormalliverfunction(肝损害),hepatitis(肝炎),peripheralneuropathy(周围神经病变).VataminB6canbeusedtorelievetheperipheralneuropathy,butitwillalsoalleviatetheeffectofisoniazidforTBdisease. bactericidalforextracellularandintracel
73、lularpoolsTB.themostpowerfuldruginthetreatmentofTB.Themostseriousadverseeffectisrelatedtorifampicinshepatotoxicity(肝毒性),gastroentericreaction(胃肠道反应)Thestandarddoseofrifapininadultsis8-10mg/kg/day(maxdose450-600mgdaily)forsixmonthsisanintenselyredsolid,andthesmallfractionwhichreachesbodyfluidsisknown
74、forimparting(给予)aharmlessred-orangecolortotheurine(andtoalesserextent,alsosweatandtears)ofusers,forafewhoursafteradose islargelybacteriostatic(抑菌的),butcanbebacteriocidalonactivelyreplicatingintracellulartuberculosis.usedincombinationwithotherdrugs.canpermeatetheblood-brainbarrierThestandarddoseinadu
75、ltsis1.5g/dayfor2monthstoreducethedurationoftreatmentrequired.Regimensnotcontainingpyrazinamidemustbetakenforninemonthsormore,.Sideeffect:jointpain(arthralgia,关节痛),hepatotoxicity,decreasingrenalexcretionofuricacid(hyperuricemia,高尿酸血症) bacteriostaticonly,Thestandarddoseinadultsis0.75-1.0g/daySideeffe
76、ct:opticneuritis(视神经炎) isbactericideagainstextracellularorganismsThestandarddoseinadultsis0.75g/daySideeffects:ototoxicity(耳毒性),nephrotoxicity(肾毒性) TreatmentforTBusesantibioticstokillthebacteria.Themostcommonlyusedthreeantibioticsarerifampicin,isoniazidandethambutol.TBrequiresmuchlongerperiodsoftrea
77、tment(around6to12months)tocompletelyeliminatemycobacteriaofthebody.TheeffectivenessoftherapyforpulmonaryTBmaybejudgedbyafurthersputumsmearat2monthsandat5months.Apositivesputumsmearat5monthsdefinestreatmentfailure isatuberculosiscontrolstrategyrecommendedbytheWHO,theaimistohelpensurepatientsadheretot
78、herapy.wherebyatrainedhealth-careworkeroranothertraineddesignatedpersonwatchesapatientswalloweachdoseofanti-TBdrugsanddocumentsit.DOTcanreducethedevelopmentofdrugresistance,treatmentfailure,orrelapse(复燃)aftertheendoftreatment. Drug-resistantTB(耐药结核):thepresenceofresistancetoanyfirst-lineagent.Multid
79、rug-resistant(MDR)TB(耐多药):resistancetoatleastrifampicinandisoniazid,withorwithoutotherdrugresistance.Extensivelydrug-resistant(XDR)TB(广泛耐多药):resistancetoatleastrifampicinandisoniazid,inadditiontoanyquinolone(喹诺酮类)andatleastonesecond-lineagent.Theprevalenceofdrug-resistantTBisrising.risksfactors:prio
80、rhistoryofTB,historyofinadequatetreatment,HIVinfectionrequiredprolongedtreatmentwithlesseffective,moretoxicandmoreexpensivetherapies.Mortalityrateishigh.Isoniazidrifampinethambutolchosedinpregnancybutisoniazedisthefirstchoice.Thepreventivetreatmentoflatenttuberculosisinfection(LTBI)isessentialtocont
81、rollingandeliminatingTBbyreducingtheriskthatTBinfectionwillprogresstodisease.Thereareseveraltreatmentregimensavailable,butthe9HIsoniazidfor9monthsiscommonlyused.themostestablishedTBvaccineisBCG(theCalmetteGurinbacillus),aliveattenuatedvaccine(减毒活疫苗)derivedfromM.bovis.BCGisnoteffectiveforglobalTBepid
82、emiccontrol.appearstobeeffectiveinpreventingdisseminateddiseaseinchildren.butitsefficacyinadultsisinconsistentandnewvaccinesareurgentlyneeded.itusuallytargetchildrenandotherhigh-riskindividuals.BCGisverysafewiththeoccasionalcomplicationoflocalabscess(脓肿)formation.Itshouldnotbeadministeredtothosewhoareimmunocompromised(e.g.byHIV)orpregnant.