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Mycobacterium Tuberculosis Infections

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Mycobacterium Tuberculosis Infections MycobacteriumMycobacterium tuberculosistuberculosis infectionsinfections KarinKarin Nielsen,Nielsen, MD,MD, MPHMPH PediatricPediatric InfectiousInfectious DiseasesDiseases UCLAUCLA MattelMattel ChildrenChildren’’ss HospitalHospital RegardingRegarding tuberculosistuberculosis TheThe worldworld tuberculosistuberculosis refersrefers to:to: 1.1. MM TBTB complexcomplex 2.2. WhatWhat anan individualindividual withwith aa ++ PPDPPD hashas 3.3. ExposureExposure toto TBTB 4.4. DiseaseDisease 5.5. Exposure,Exposure, latencylatency andand diseasedisease TuberculosisTuberculosis CommunicableCommunicable diseasedisease causedcaused byby MycobacteriumMycobacterium tuberculosistuberculosis,, oror thethe acidacid--fastfast tubercletubercle bacillus.bacillus. TBTB inin HistoryHistory IdentifiedIdentified inin StoneStone AgeAge skeletonsskeletons PrevalentPrevalent inin AncientAncient EgyptEgypt UpriseUprise inin thethe MiddleMiddle AgesAges afterafter thethe BlackBlack death.death. DiseaseDisease ofof poverty,poverty, crowding,crowding, war,war, famine,famine, displacement,displacement, insalubriousinsalubrious lifelife && workwork Abreugraphy or chest photofluorography (mass miniature radiography) is a photo-fluorography for mass TB screening using miniature (50 to 100 mm) photograph of the screen of a x-ray fluoroscopy first developed in 1936 by Dr. Manoel Dias de Abreu, Brazil. January 4- National Abreugraphy Day in Brazil 2012 1/3 of the world’s population has been infected with TB 2012 Countries with 80% of TB cases worldwide Deaths in adults due to infectious diseases in developing countries EpidemiologyEpidemiology InIn thethe midmid--1980s,1980s, aa resurgenceresurgence ofof TBTB occurredoccurred inin thethe US.US. SinceSince 1993,1993, TBTB ratesrates havehave beenbeen decliningdeclining inin thethe U.S.U.S. However:However: – TB cases continue to be reported in every state. – Drug-resistant TB continues to be reported in nearly all states. – An estimated 10 to 15 million are infected with M tb in the US. – With no intervention, 10% will develop TB throughout their lifetime. 25%25% ofof newlynewly diagnoseddiagnosed casescases areare foreignforeign--born.born. TBTB CaseCase Rates,Rates, UnitedUnited States,States, 20102010 D.C. < 3.5 (year 2000 target) 3.6 - 5.6 > 5.6 (national average) Rate: cases per 100,000 TB incidence coefficient per state, Brazil 2008 Overall incidence: 20.6/ 100,000 Porto Alegre EpidemiologyEpidemiology HigherHigher riskrisk groupsgroups forfor TB:TB: – First generation immigrants from high risk countries. – Native Americans – Alaskan natives – Homeless individuals – Individuals in correctional facilities – Patients with diabetes mellitus, lymphoma, immunosuppression – Patients with prolonged or high dose use of steroids. – Individuals from urban/ low income areas. Jamer RM, et al. NEJM 2002; 347:1860-6. ReportedReported TBTB CasesCases byby Race/EthnicityRace/Ethnicity UnitedUnited States,States, 20052005 Hispanic White, non-Hispanic (21%) (25%) American Indian/ Alaska Native (1%) Black, non-Hispanic Asian/Pacific Islander (30%) (22%) Percentage of TB Cases Among Foreign-born Persons 19922010 1999 >50% 25%-49% <25% TransmissionTransmission andand PathogenesisPathogenesis MechanismMechanism ofof transmission:transmission: PrimarilyPrimarily byby dropletdroplet nucleinuclei expelledexpelled byby someonesomeone withwith infectiousinfectious TB.TB. DropletsDroplets withwith bacillibacilli areare inhaledinhaled andand reachreach alveoli,alveoli, beingbeing ingestedingested byby macrophages.macrophages. BacilliBacilli maymay spreadspread viavia thethe bloodstream.bloodstream. InIn mostmost cases,cases, developmentdevelopment ofof diseasedisease isis containedcontained byby thethe immuneimmune system.system. AboutAbout 10%10% ofof infectedinfected personspersons willwill developdevelop disease;disease; riskrisk inverselyinversely proportionalproportional toto immuneimmune function.function. BackgroundBackground Majority of TB cases are pulmonary in all age groups. Children have more extra-pulmonary disease than adults. May occur at any anatomical site or be disseminated Exposure: Hx of contact; - skin test, CXR and PE Latent Tuberculous Infection (LTBI): + skin test, +/ - CXR, - PE Infected individuals with no TB disease are asymptomatic, and non-infectious. Disease: Symptoms, signs and radiological abnormalities are apparent. Distinction between infection and disease in children is unclear. ProbabilityProbability TBTB WillWill BeBe TransmittedTransmitted • Infectiousness of person with TB • Environment in which exposure occurred • Duration of exposure • Virulence of the organism TransmissionTransmission OnlyOnly adultsadults andand adolescentsadolescents withwith TBTB areare contagious.contagious. NumberNumber ofof organismsorganisms inin sputumsputum isis criticalcritical forfor infectivity,infectivity, andand thethe frequencyfrequency ofof cough.cough. InfectivityInfectivity lastslasts aa fewfew weeksweeks afterafter thethe initiationinitiation ofof effectiveeffective therapy.therapy. WhenWhen 33 sequentialsequential sputumsputum smearssmears areare negative,negative, thethe patientpatient isis consideredconsidered nonnon--contagiouscontagious.. TBTB maymay rarelyrarely bebe transmittedtransmitted transplacentallytransplacentally toto thethe fetus.fetus. RegardingRegarding TBTB inin childrenchildren…… MiliaryMiliary TBTB oror TBTB meningitismeningitis willwill occuroccur 1.1.OnlyOnly afterafter aa periodperiod ofof LTBILTBI 2.2.OnlyOnly afterafter aa positivepositive PPDPPD 3.3.FollowingFollowing exposureexposure toto anan adultadult withwith activeactive TBTB beforebefore skinskin testtest reactivityreactivity 4.4.ByBy reactivationreactivation ofof primaryprimary pulmonarypulmonary TBTB inin youngyoung childrenchildren 5.5.OnlyOnly afterafter establishmentestablishment ofof GhonGhon’’ss complexcomplex BurdenBurden ofof TB/HIVTB/HIV inin womenwomen TB HIV 8.8 million new cases 2.6 million new cases 14 million prevalent 33 million prevalent 59% Asia 16% Asia 26% Africa 68% Africa Women Women – 3.2 million (36% of total) – 15.5 million (52% of total) – Deaths 0.32 million – Deaths 0.85 million Highest burden in reproductive age 15-45 years of age TB HIV WHO Global TB Report 2011, UNAIDS Global AIDS Report 2011, WHO 2009 Women and Health IncubationIncubation TuberculinTuberculin reactivityreactivity appearsappears 22 toto 1212 weeksweeks afterafter initialinitial infection.infection. MedianMedian isis 33 -- 44 weeks.weeks. ExposedExposed individualsindividuals byby definitiondefinition havehave nono findingsfindings ofof TB,TB, somesome maymay eventuallyeventually developdevelop disease.disease. TheThe riskrisk ofof developingdeveloping diseasedisease isis highesthighest duringduring 66 monthsmonths afterafter infectioninfection andand remainsremains highesthighest forfor 22 yearsyears.. InfantsInfants andand postpost--pubertalpubertal adolescentsadolescents atat highesthighest riskrisk ofof diseasedisease development.development. CongenitalCongenital TuberculosisTuberculosis,, MiliaryMiliary lunglung lesionslesions andand hepatosplenomegalyhepatosplenomegaly.. ClinicalClinical ManifestationsManifestations InIn childrenchildren && adolescents,adolescents, mostmost TBTB infectionsinfections areare asymptomaticasymptomatic whenwhen thethe TSTTST (tuberculin(tuberculin skinskin test)test) isis +.+. CXRCXR oftenoften doesdoes notnot demonstratedemonstrate 1ary1ary complexcomplex ofof infection.infection. MostMost immunocompetentimmunocompetent childrenchildren withwith 1ary1ary infectioninfection dodo notnot havehave rapidrapid progressionprogression ofof disease.disease. EarlyEarly findingsfindings (1(1 toto 66 mosmos afterafter infection):infection): – fever – weight loss – cough, night sweats, chills. ClinicalClinical EvolutionEvolution ofof PrimaryPrimary PulmonaryPulmonary TBTB DropletDroplet nucleinuclei causescauses parenchymalparenchymal lunglung disease.disease. ChildChild maymay havehave lowlow gradegrade fever,fever, mildmild cough.cough. RegionalRegional lymphlymph nodesnodes areare involved.involved. EnlargingEnlarging granulomasgranulomas causecause obstructionobstruction ofof bronchiolesbronchioles leadingleading toto hyperaerationhyperaeration.. CaseousCaseous materialmaterial spillsspills intointo airway,airway, atelectasisatelectasis ensues:ensues: fever,fever, weightweight loss,loss, nightnight sweats,sweats, FTTFTT ThereThere maymay bebe anan initialinitial responseresponse toto antibiotics.antibiotics. PrimaryPrimary PulmonaryPulmonary TB,TB, rightright upperupper lobe,lobe, w/w/ atelectasisatelectasis PrimaryPrimary PulmonaryPulmonary TB,TB, 22 yryr oldold ClinicalClinical ManifestationsManifestations PulmonaryPulmonary radiographicradiographic findings:findings: –– LymphadenopathyLymphadenopathy ((hilarhilar,, mediastinalmediastinal,, cervical)cervical) –– InvolvementInvolvement ofof aa segmentsegment oror lobe.lobe. –– AtelectasisAtelectasis oror infiltrates.infiltrates. –– PleuralPleural effusionseffusions –– CavitaryCavitary lesionslesions –– MiliaryMiliary diseasedisease MeningitisMeningitis isis anan earlyearly manifestationmanifestation ofof disease.disease. GhonGhon ComplexComplex Calcified focus of infection with an associated lymph node. Particularly common in children. Can retain viable bacteria and be source of reactivation. MycobacteriumMycobacterium tuberculosistuberculosis infectioninfection withwith paratrachealparatracheal lymphlymph nodes.nodes. PrimaryPrimary pulmonarypulmonary
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