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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.
