TB Nurse Case Management Albuquerque, New Mexico
July 22-23, 2008
Tuberculosis in Children Jeffrey R. Starke, MD
July 22, 2008
TUBERCULOSIS INTUBERCULOSIS IN CHILDRENCHILDREN
Jeffrey R. Starke, M.D.Jeffrey R. Starke, M.D. Professor and Vice Chairman of PediatricsProfessor and Vice Chairman of Pediatrics
Baylor College of MedicineBaylor College of Medicine Houston, Texas USAHouston, Texas USA
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Tuberculosis is a socialTuberculosis is a social disease with medicaldisease with medical implications.implications.
A Difficult CaseA Difficult Case A 7 yo HIV + girl has cough, abdominal pain, cervicalA 7 yo HIV + girl has cough, abdominal pain, cervical
and axillary adenopathy, bilateral rales and a largeand axillary adenopathy, bilateral rales and a large liver. A 10 day course of clarithromycin did notliver. A 10 day course of clarithromycin did not improve her symptoms. Her CD4 count was 291/20%,improve her symptoms. Her CD4 count was 291/20%, her hemoglobin was 8.9, but other labs were WNL.her hemoglobin was 8.9, but other labs were WNL. After several weeks, her cough improved, she wasAfter several weeks, her cough improved, she was sweating a lot but did not have fever or weight loss.sweating a lot but did not have fever or weight loss. Her adult cousin had pulmonary tuberculosis 2Her adult cousin had pulmonary tuberculosis 2--33 years ago [household contact].years ago [household contact].
Does she have tuberculosis?Does she have tuberculosis?
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i i i i i l i i i i i i i i
i i i l
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25 - 49 50 - 99 100 - 300
0 - 9 10 - 24
300 or more No estimate
Rate per 100 000
Estimated TB incidence rates, 2000
The boundaries and names shown and the des gnat ons used on this map do not mply the express on of any opinion whatsoever on the part of the World Health Organizat on concerning the egal status of any country, territory, c ty or area or of ts authorit es, or concerning the del m tat on of ts front ers or boundaries. Dotted l nes on maps represent approx mate border l nes for which there may not yet be ful agreement.
Global Tuberculos s Control. WHO Report 2002. WHO/CDS/TB/2002.295
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EPIDEMIOLOGY OF TUBERCULOSIS INEPIDEMIOLOGY OF TUBERCULOSIS IN THE WORLDTHE WORLD –– WHO ESTIMATESWHO ESTIMATES
9.2 million incident cases in 20069.2 million incident cases in 2006 4.1 million of these cases were sputum4.1 million of these cases were sputum AFB smear positiveAFB smear positive 14.4 million prevalent cases14.4 million prevalent cases 0.7 million HIV0.7 million HIV--infected persons withinfected persons with new onset TB in 2006new onset TB in 2006 0.5 million new cases of multidrug0.5 million new cases of multidrug--resistant TB in 2006resistant TB in 2006 1.7 million deaths a/w TB in 20061.7 million deaths a/w TB in 2006
EPIDEMIOLOGY OF CHILDHOODEPIDEMIOLOGY OF CHILDHOOD TUBERCULOSIS IN SELECTED 22 HIGHTUBERCULOSIS IN SELECTED 22 HIGH--
BURDEN COUNTRIESBURDEN COUNTRIES ChildhoodChildhood Case RateCase Rate
CountryCountry CasesCases % Total Cases% Total Cases ChildrenChildren TotalTotal Afghanistan 17.540 25.3 1Afghanistan 17.540 25.3 189 32489 324 Brazil 23,520 20.7Brazil 23,520 20.7 47 6647 66 China 86,978 5.3China 86,978 5.3 27 12927 129 Pakistan 61,905 25.3Pakistan 61,905 25.3 103 172103 172 South Africa 35,449 16.1South Africa 35,449 16.1 237 501237 501 Zimbabwe 12,267 16.1Zimbabwe 12,267 16.1 221 603221 603 Range 2.7Range 2.7-25.3 1525.3 15-237 66237 66-603603 Total 659,397 9.6Total 659,397 9.6
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TRANSITIONS IN TUBERCULOSISTRANSITIONS IN TUBERCULOSIS
Cured
Treated
Diagnosed
Susceptible
Exposed
Infected
Diseased
Sick
TIME TABLE OF CHILDHOODTIME TABLE OF CHILDHOOD TUBERCULOSISTUBERCULOSIS
Site of DiseaseSite of Disease Time to DevelopTime to Develop Miliary andMiliary and meningealmeningeal 11--9 months9 months Primary pulmonary 2Primary pulmonary 2--12 months12 months Lymph node [cervical] 2Lymph node [cervical] 2--12 months12 months Pleural effusionPleural effusion 33--9 months9 months SkeletalSkeletal 6 months6 months –– 2 years2 years RenalRenal 11--5 years5 years
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ARE CHILDREN WITHARE CHILDREN WITH TUBERCULOSISTUBERCULOSIS
EVER CONTAGIOUS?EVER CONTAGIOUS?
¾¾ Difficult to answer in the communityDifficult to answer in the community
¾¾ OrphanagesOrphanages –– caretaker with TB led tocaretaker with TB led to transmission; a child with TB did nottransmission; a child with TB did not
¾¾ SchoolsSchools –– only 2 reportedonly 2 reported ““epidemicsepidemics”” causedcaused by children <13 years oldby children <13 years old
¾¾ ChildrenChildren’’s Hospitalss Hospitals –– rare case reports ofrare case reports oftransmission, all with special circumstances,transmission, all with special circumstances,none has been patientnone has been patient -- toto -- patientpatient
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FEATURES OF CONTAGIOFEATURES OF CONTAGI USOUS PEDIATRIC TUBERCULOSISPEDIATRIC TUBERCULOSIS
¾¾Cavitary lung lesionCavitary lung lesion
¾¾ Sputum productionSputum production
¾¾ Positive acidPositive acid--fast stain of sputum smearfast stain of sputum smear
¾¾BronchoscopyBronchoscopy
¾¾Draining lesions or surgical drainage ofDraining lesions or surgical drainage ofan abscessan abscess
DIAGNOSIS OF TUBERCULOSISDIAGNOSIS OF TUBERCULOSIS
All existing diagnostic tests for TB inAll existing diagnostic tests for TB in children have significant shortcomingschildren have significant shortcomings Most tests are not available in settingsMost tests are not available in settings where the vast majority of TB cases arewhere the vast majority of TB cases are diagnoseddiagnosed The utility of most tests is furtherThe utility of most tests is further diminished in children with immunediminished in children with immune compromise [especially HIV infection]compromise [especially HIV infection]
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DIAGNOSTIC TESTS FOR CHILDHOODDIAGNOSTIC TESTS FOR CHILDHOOD TUBERCULOSISTUBERCULOSIS
The sensitivity and specificity of theThe sensitivity and specificity of the available tests are inherent in the testsavailable tests are inherent in the tests However, the positive and negativeHowever, the positive and negative predictive values are inherent in thepredictive values are inherent in the population on whom the tests are usedpopulation on whom the tests are used Therefore, all tests are more accurate whenTherefore, all tests are more accurate when used on children with a high index ofused on children with a high index of suspicion [epidemiologysuspicion [epidemiology –– HISTORY OFHISTORY OF RECENT CONTACT TO A TB CASERECENT CONTACT TO A TB CASE -- oror suspicious symptoms]suspicious symptoms]
Sensitivity = Specificity = 95%
90% prevalence 1% prevalence PPV= 99% (1% false+) PPV=15% (85% false+)
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MANTOUX TUBERCULIN SKIMANTOUX TUBERCULIN SKINN TESTTEST
¾¾ uses 5 TU [2 TU if R23] of purifieduses 5 TU [2 TU if R23] of purifiedprotein derivativeprotein derivative
¾¾ interpret in 48interpret in 48 –– 72 hours72 hours
¾¾ record size ofrecord size of indurationinduration in mmin mm
¾¾ if it makes a reaction at >72 hrs, itif it makes a reaction at >72 hrs, itcounts!counts!
¾¾ false negatives: 10false negatives: 10%% to 20%to 20% in diseasein disease
FACTOFACTORRS THAT CAUSE DECREASEDS THAT CAUSE DECREASED RESPONSE TO TUBERCULINRESPONSE TO TUBERCULIN
HostHost-rerelatlateedd InfecInfecttionionss, v, vaccineacciness Chronic disChronic diseease, mase, maalnutrlnutriitiontion ImmunosuppressivImmunosuppressivee disdiseaseseases (HIV,(HIV, malignancmalignancyy,, CVD)CVD) Drugs (corDrugs (cortiticosteroidscosteroids)) ExtremExtremes oes off age, sage, sttrressess OvOvererwwhhelmielming tuberng tubercculoulossisis
TuberculinTuberculin - relarelatedted ImproperImproper stostorage orrage or diludilutitionon Adsorption to glass oAdsorption to glass orr plplasticastic
AdminisAdministtraratitionon - rerelatlateedd ReadingReading - rerelalatteedd
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INDURATION SIZEINDURATION SIZE –– POSITIVEPOSITIVE TUBERCULITUBERCULIN SKIN SKINN TESTTEST
>> 10 mm10 mm>> 5 mm5 mm
¾¾ ForeignForeign--born from a HRborn from a HR¾¾ HIV coHIV co--ininffectionection countrcountryy¾¾ Immune cImmune coompromisempromise
¾¾ DrugDrug ––usersusers¾¾ Recent contact to TBRecent contact to TB
¾¾ Living in HR congregateLiving in HR congregate¾¾ SuspectSuspected diseaseed disease settingsetting
¾¾ Specific HR groupsSpecific HR groups ¾¾ Children < 4 yChildren < 4 yrrs old (AAP)s old (AAP)
> 15> 15 mmmm
No riskNo risk ffaaccttoorsrs PrevPrevious BCious BCG vG vaccination?accination?
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INTERACTION OF BCG VACCINESINTERACTION OF BCG VACCINES WITH THE TUBERCULIN SKIN TESTWITH THE TUBERCULIN SKIN TEST
¾¾ 50% of vaccinated infants do not react to a TST;50% of vaccinated infants do not react to a TST; most of the rest stop reacting within 5 yearsmost of the rest stop reacting within 5 years
¾¾ most nonmost non--infants who get one or more BCGinfants who get one or more BCG vaccinations will react to a TST (usually < 15vaccinations will react to a TST (usually < 15 mm), but effect wanes over 5mm), but effect wanes over 5 –– 10 years10 years
¾¾ outside infancy,outside infancy, ““positivepositive”” TST more likely toTST more likely to indicate infection withindicate infection with M. tuberculosisM. tuberculosis thanthan bebe residual from BCGresidual from BCG
TUBERCULINTUBERCULI SKIN TESTING OFN SKIN TESTING OF FOREIGNFOREIGN--BORN ADOPTEESBORN ADOPTEES
On one hand, most children have received aOn one hand, most children have received a BCG vaccine within the past year, whichBCG vaccine within the past year, which can cause reaction to a TSTcan cause reaction to a TST
On the other hand, many have lived inOn the other hand, many have lived in conditions conducive to transmission ofconditions conducive to transmission of M. tuberculosisM. tuberculosis …… and we canand we can’’t do ant do an investigationinvestigation
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TUBERCULINTUBERCULI SKIN TESTING OFN SKIN TESTING OF FOREIGNFOREIGN--BORN ADOPTEESBORN ADOPTEES
General GuidelinesGeneral Guidelines
1.1. Assess for symptoms of tuberculosis diseaseAssess for symptoms of tuberculosis disease ––prolonged (>2 wk) cough, weight loss, feversprolonged (>2 wk) cough, weight loss, fevers
2.2. Note a BCG scar and/or immunization recordsNote a BCG scar and/or immunization records
3.3. Place and read a 5 TU TST withoutPlace and read a 5 TU TST without ““controlscontrols””
4.4. Delay or repeat the TST if the child is significantlyDelay or repeat the TST if the child is significantlymalnourishedmalnourished
5.5. ““PositivePositive”” TST reaction is 10mm, though this willTST reaction is 10mm, though this will result in some overtreatment due to recent BCGresult in some overtreatment due to recent BCG vaccinationvaccination
6.6. Treat LTBI with isoniazid unlessTreat LTBI with isoniazid unless specificspecific evidence ofevidence of INHINH--resistance is uncoveredresistance is uncovered
InterferonInterferon γγ teststests
oo MTB specific antigens:MTB specific antigens: GeneGen s in region of difference (RD1) on MTB genomees in region of difference (RD1) on MTB genome Culture filtrate protein 10 (CFPCulture filtrate protein 10 (CFP-10)10) Early secretory antigen target 6 (ESATEarly secretory antigen target 6 (ESAT-6)6)
oo Identifies LTBI &/or diseaseIdentifies LTBI &/or disease oo Does not cross react with BGC vaccine orDoes not cross react with BGC vaccine or
most other mycobacteriamost other mycobacteria oo Requires:Requires:
single medical visitsingle medical visit blood collectionblood collection laboratory equipment and personnellaboratory equipment and personnel
oo Results in 24Results in 24--48 hrs48 hrs
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Commercial TestsCommercial Tests QuantiFEROQuan NtiFERON-TB GoldTB Gold
Company: Cellestis,Company: Cellestis, AustraliaAustralia
US FDA approvedUS FDA approved Available in some areas ofAvailable in some areas of
USUS InIn-Tube improvementTube improvement
oo Method:Method: ¾¾Whole bloodWhole blood ¾¾ Incubated with MTBIncubated with MTB
antigensantigens (ESAT(ESAT-6 & CFP6 & CFP-10)10)
¾¾TT-Cells produce INFCells produce INF- γγ ¾¾Supernate removedSupernate removed ¾¾ INFINF- γγ measured bymeasured by
ELISA readerELISA reader
TT-Spot.Spot.TBTB or ELISPOTor ELISPOT Company: OxfordCompany: Oxford
Immunotec, UKImmunotec, UK FDA reviewingFDA reviewing Available in Europe &Available in Europe &
CanadaCanada oo Method:Method: ¾¾TT-cellscells ¾¾ Incubated with MTBIncubated with MTB
antigensantigens (ESAT(ESAT-6 & CFP6 & CFP-10)10)
¾¾TT-Cells produce INFCells produce INF- γγ ¾¾ IFNIFN- γγ binds to antibodybinds to antibody
in wellsin wells ¾¾Spots develop and areSpots develop and are
counted manually or bycounted manually or by readerreader
Release AssaysComparison of Tuberculin Skin Test and Interferon-٢
OneOneTwoTwoPatient visits requiredPatient visits required NoNoYesYesBoostingBoosting
NoNoNoNoDistinguish between TB infectionDistinguish between TB infection and TB diseaseand TB disease
9090-100%100%7070-95%95%Estimated specificity, TB inEstimated specificity, TB in immunocompetent adultsimmunocompetent adults
7575-95%95%7575-90%90%Estimated sensitivity, TB inEstimated sensitivity, TB in immunocompetent adultsimmunocompetent adults
Less LikelyLess LikelyYesYesCrossCross-reactivity with NTMreactivity with NTM UnlikelyUnlikelyYesYesCrossCross-reactivity with BCGreactivity with BCG ESATESAT-6, CFP6, CFP-1010ManyMany -PPDPPDAntigens studiedAntigens studied
IFNIFN-٢٢ Release AssayRelease AssayTuberculinTuberculin Skin TestSkin Test
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Sensitivity and SpecificitySensitivity and Specificity
QuantiQuant FERONiFERON--TB GoldTB Gold Sensitivity* (95%CI)Sensitivity* (95%CI)
Mori (Mori (‘‘04)04) 89 (8289 (82-94)94) Ravn (Ravn (‘‘05)05) 85 (7285 (72-94)94) Kang (Kang (‘‘05)05) 80 (6780 (67-90)90) Pai (Pai (‘‘05)05) 75 (6475 (64-85)85)
Specificity+ (95%CI)Specificity+ (95%CI) Mori (Mori (‘‘04)04) 98 (9598 (95-99)99) Ravn (Ravn (‘‘05)05) 97 (8797 (87-100)100) Kang (Kang (‘‘05)05) 96 (9096 (90-99)99) Goletti (Goletti (’’05)05) 90 (6890 (68-99)99)
TT--Spot.Spot.TBTB or ELISPOTor ELISPOT Sensitivity* (95%CI)Sensitivity* (95%CI)
Lalvni (Lalvni (‘‘01a)01a) 96 (8596 (85-99)99) Lalvni (Lalvni (‘‘01b) 80 (6601b) 80 (66-90)90) Pathan (Pathan (‘‘01)01) 92 (7492 (74-99)99) Chapman (Chapman (‘‘02) 92 (8102) 92 (81-98)98) Liebeschuetz(Liebeschuetz(’’04) 83 (7504) 83 (75-89)89) Meier (Meier (‘‘05)05) 97 (9097 (90-100)100)
Specificity+ (95%CI)Specificity+ (95%CI) Lalvni (Lalvni (‘‘01a)01a) 91 (8091 (80-98)98) Pathan (Pathan (‘‘01)01) 100(89100(89-100)100) Meier (Meier (‘‘05)05) 92 (6292 (62-100)100)
Pai, Expert Rev Mol Diagn. 6(3):413-422 (2006)
*Sensitivity in pts with active TB, Cx = Gold standard +Specificity in healthy low risk patients without TB
InterferonInterferon γγ teststests ProblemsProblems
Variable sensitivity (75Variable sensitivity (75--97%) in active TB97%) in active TB diseasedisease Specificity reported high (95%) but no goldSpecificity reported high (95%) but no gold standard for LTBI and concordancestandard for LTBI and concordance estimates 60estimates 60--90% with TST and Interferon90% with TST and Interferon γγ teststests
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TT--CELL ASSAYS FOR TUBERCULOSIS INCELL ASSAYS FOR TUBERCULOSIS IN CHILDRENCHILDREN
More data available for TMore data available for T--SPOT.SPOT.TBTB Appear to be more specific for tuberculosisAppear to be more specific for tuberculosis infection, especially in low prevalenceinfection, especially in low prevalence conditionsconditions Sensitivity is a bigger issue, especially inSensitivity is a bigger issue, especially in high prevalence conditions [recent contact]high prevalence conditions [recent contact] Dynamics of tests are largely unknownDynamics of tests are largely unknown Results have been highly variable, andResults have been highly variable, and
indeterminate results are common withindeterminate results are common with QuantiFERONQuantiFERON--TB GoldTB Gold
TRANSITIONS IN TUBERCULOSISTRANSITIONS IN TUBERCULOSIS
Cured
Treated
Diagnosed
Susceptible
Exposed
Infected
*Diseased
Sick
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HOW IS TUBERCULOSIHOW IS TUBERCULOSIS DIAGNOSED?S DIAGNOSED?
AduAdulltsts –– MycobacterialMycobacterial--based diagnosbased diagnosisis pospositive sputum AFB smearitive sputum AFB smear -- 60%60% -- 75%75% pospositive sputum cultureitive sputum culture -- 90%90% pospositive tuberculin skin testitive tuberculin skin test -- 80% [HIV < 50%]80% [HIV < 50%]
ChChildreildrenn pospositive sputum or gastric AFB smearitive sputum or gastric AFB smear -- 10%10% pospositive sputum or gastric cultureitive sputum or gastric culture -- 10%10% -- 40%40% pospositive tuberculin skin testitive tuberculin skin test -- 50%50% -- 80%80%
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DIAGNOSIS OF TUBERCULOSISDIAGNOSIS OF TUBERCULOSIS
““The diagnosis of tubeThe diagnosis rculosis inof tuberculosis in children relies on careful and thoroughchildren relies on careful and thoroughassessment of all the evidence derivedassessment of all the evidence derived from a careful history, clinicalfrom a careful history, clinicalexamination and relevantexamination and relevant investigations, e.g. the tuberculin skininvestigations, e.g. the tuberculin skintest [TST], chest radiography [CXR] andtest [TST], chest radiography [CXR] and sputum smear microscopy.sputum smear microscopy.””
Stop TB Partnership Childhood TBStop TB Partnership Childhood TBSubgroupSubgroup
DIAGNOSIS OF TUBERCULOSISDIAGNOSIS OF TUBERCULOSIS
Even in developed countries, theEven in developed countries, the ““gold standardgold standard”” for the diagnosis offor the diagnosis of tuberculosis in children is the triad of:tuberculosis in children is the triad of:
1.1. a positive TSTa positive TST 2.2. an abnormal CXR and/or physicalan abnormal CXR and/or physical
examexam 3.3. a history of recent contact to ana history of recent contact to an
infectious adult case of TBinfectious adult case of TB
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OBTAINING CULTURE AND AFB SMEAROBTAINING CULTURE AND AFB SMEAR SAMPLES FROM CHILDRENSAMPLES FROM CHILDREN
Traditional method is gastricTraditional method is gastric aspiration, performed as an inpatienaspiration, performed as an inpatie tnt on 3 consecutive morningson 3 consecutive mornings –– expensive, invasiveexpensive, invasive Bronchioalveolar lavage has noBronchioalveolar lavage has no advantageadvantage Nasopharyngeal aspirationNasopharyngeal aspiration –– fewfew studiesstudies Other sitesOther sites –– yields usually 0%yields usually 0% -- 25%25% culture positive, <10% smear positiveculture positive, <10% smear positive
INDUCED SPUTUM COLLECTION ININDUCED SPUTUM COLLECTION IN CHILDRENCHILDREN
ZarZar et al. Lancet 2005; 365: 130.et al. Lancet 2005; 365: 130. Can be done inpatient or outpatientCan be done inpatient or outpatient Infection control precautions importantInfection control precautions important Salbutamol, followed by 15 minutes ofSalbutamol, followed by 15 minutes of 5% hypertonic saline solution5% hypertonic saline solution Sputum obtained via suction with aSputum obtained via suction with a nasopharyngeal catheternasopharyngeal catheter Yield: 30% to 40% culture positiveYield: 30% to 40% culture positive
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INTERPRETING CHILDRENINTERPRETING CHILDREN’’S CHESTS CHEST RADIOGRAPHS FOR TBRADIOGRAPHS FOR TB
Rarely available in highest prevalence areasRarely available in highest prevalence areas Marked interMarked inter-- and intraand intra-- observer variabilityobserver variability Reliable in expert hands and in the presenceReliable in expert hands and in the presenceof suspicious symptomsof suspicious symptoms Commonest picture is persistentCommonest picture is persistentopacification together with enlarged hilar oropacification together with enlarged hilar orsubcarinal lymph nodes [though nodes notsubcarinal lymph nodes [though nodes notalways discernable]always discernable] The xThe x--ray is usually sicker than the patient!ray is usually sicker than the patient!
CHEST RADIOGRAPH TECHNIQUE FORCHEST RADIOGRAPH TECHNIQUE FOR CHILDRENCHILDREN
Check for three important featuresCheck for three important features
1.1. RotationRotation –– can make mediastinum becan make mediastinum be widerwider
2.2. InspirationInspiration –– when inadequate, canwhen inadequate, can causecause ““mass effectmass effect”” of mediastinum,of mediastinum, hilumhilum
3.3. PenetrationPenetration –– difficult to interpret ifdifficult to interpret if xx--ray isray is ““too whitetoo white”” oror ““too blacktoo black””
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TUBERCULOSIS IN HIVTUBERCULOSIS IN HIV--INFECTED CHIINFECTED CHILDRENLDREN Clinical and Radiographic PresentationClinical and Radiographic Presentation
in childrenin children wwiith prth preseeservrveed immunocompetend immunocompetence, pce, presenresentatation ition issindistinguiindistinguisshhable fromable from HIVHIV-uninfecuninfecteted childrend children
mostmost commcommon son syymptoms remmptoms remaain malin malnutrinutrition,tion, fevfeveer, nighr, nightt sswweeaatts, lys, lymphadenopathmphadenopathyy and coughand cough
extrapulmonextrapulmonaarryy diseasedisease (meningiti(meningitis as and tubernd tubercculoulomma,a,abdominal) iabdominal) iss moremore comcommmonon
TB meningiTB meningititis hass has thethe sasame clinime clinical acal and CSF findind CSF findings as in HIngs as in HIVV-uninfecuninfectedted cchildren ehildren excexceptpt thathatt inintratracceerebrrebral maal massss lesionlesions ars aree more commmore commonon
cheschest radt radiiographograph findingfindings ares are tytypical, but morpical, but moree exextensivtensive ande and aa broader dibroader diffefferrential diential diagnosisagnosis
TUBERCULOSIS IN HIVTUBERCULOSIS IN HIV--INFECTED CHIINFECTED CHILDRENLDREN Diagnostic ConsiderationsDiagnostic Considerations
Diagnosis of TB remains aDiagnosis of TB remains a problem, even in the bestproblem, even in the best of centersof centers –– broader differential diagnosisbroader differential diagnosis
Culture yCulture yiields are about the selds are about the saame for HIVme for HIV--infectedinfected and HIVand HIV--uninfected children when controlled foruninfected children when controlled for extent of diseaseextent of disease
Tuberculin skin test is uTuberculin skin test is useful in immunocompetentseful in immunocompetent HIVHIV--infected children but uinfected children but usefulness diminished withsefulness diminished with wwoorsening immunocompromisersening immunocompromise Interferon release assaysInterferon release assays -- no data for HIVno data for HIV--infectedinfected childrenchildren
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NEEDED IMPROVEMENTS IN DIAGNOSIS OFNEEDED IMPROVEMENTS IN DIAGNOSIS OF CHILDHOOD TUBERCULOSISCHILDHOOD TUBERCULOSIS
Further characterize the TFurther characterize the T--cell assayscell assays Refine and validate clinical scoring systemsRefine and validate clinical scoring systems Study all tests in HIVStudy all tests in HIV--infected childreninfected children Make chest radiography more readilyMake chest radiography more readilyavailableavailable –– much more important role formuch more important role forchildren than for adultschildren than for adults Pediatricians must advocate for resourcesPediatricians must advocate for resources MOST IMPORTANTMOST IMPORTANT –– Design TB controlDesign TB control programs to link children with likely sourceprograms to link children with likely source casescases –– CONTACT TRACING!!!CONTACT TRACING!!!
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TREATMENT OF LTBI IN CHILDRENTREATMENT OF LTBI IN CHILDREN
¾¾ 9 months of isoniazid (dai9 months of isoniazid (da ly or twice weekly underily or twice weekly under DOT) is only accepted regimenDOT) is only accepted regimen
¾¾ INHINH--resistance or intoleranceresistance or intolerance –– rifampin for 6 monthsrifampin for 6 months
¾¾ MultidrugMultidrug--resistanceresistance –– consult an expertconsult an expert
¾¾ Use isoniazid unless there is documented exposure toUse isoniazid unless there is documented exposure to a specific case of druga specific case of drug--resistant TBresistant TB
PEARLS OF WISDOM FOR TREATINGPEARLS OF WISDOM FOR TREATING LTBI IN CHILDRENLTBI IN CHILDREN
Use INH suspension only in childrenUse INH suspension only in children ≤≤ 5 kg5 kg Compliance with 9 months of INH averages 50%Compliance with 9 months of INH averages 50% -- be vigilant and skepticalbe vigilant and skeptical Use DOPT for: recent contacts, infants, immuneUse DOPT for: recent contacts, infants, immune compromisedcompromised When children arenWhen children aren’’t tolerating INH, the problemt tolerating INH, the problem is more often with the parent than the childis more often with the parent than the child Route LFTs only for: other liver toxic drugs, liverRoute LFTs only for: other liver toxic drugs, liver disease, signs or symptoms of hepatitisdisease, signs or symptoms of hepatitis
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TREATING EXPOSED CHILDRENTREATING EXPOSED CHILDREN
Very high rate of infectionVery high rate of infection
Takes up to 3 months for the skin test to turnTakes up to 3 months for the skin test to turn positivepositive
U.S. studiesU.S. studies –– 10% to 20% of childhood TB10% to 20% of childhood TB cases can be prevented if children exposedcases can be prevented if children exposed in a household receive isoniazidin a household receive isoniazid
WHO standardsWHO standards –– children <5 years old in achildren <5 years old in a TB household should be treatedTB household should be treated
DIRECTLY OBSERVED THERAPYDIRECTLY OBSERVED THERAPY FOR TUBERCULOSISFOR TUBERCULOSIS
means a dispassionate 3rd party is actuallymeans a dispassionate 3rd party is actually present when medications are taken with everypresent when medications are taken with every dosedose
““standard of carestandard of care”” in U.S. for treatingin U.S. for treating tuberculosis diseasetuberculosis disease
desirable for high risk infectionsdesirable for high risk infections -- newborns andnewborns and infants, household contacts, HIVinfants, household contacts, HIV -- infected orinfected or immune compromisedimmune compromised
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TREATMENT OFTREATMENT OF TUBERCULOSIS DISEASE INTUBERCULOSIS DISEASE IN
CHILDRENCHILDREN PulmonaryPulmonary
INH, RIF for 6 months + PZA for first 2 monthsINH, RIF for 6 months + PZA for first 2 months Add ETH initially if risk of INH resistanceAdd ETH initially if risk of INH resistance Can be q.d. or twice weeklyCan be q.d. or twice weekly INHINH--resistant: RIF+PZA+ETH for 9 monthsresistant: RIF+PZA+ETH for 9 months MDRMDR -- depends on susceptibilitydepends on susceptibility -- at least 18 monthsat least 18 months
CNS, DisseminatedCNS, Disseminated usually start with 4 drugs (INH, RIF, PZA + ETH orusually start with 4 drugs (INH, RIF, PZA + ETH or STM)STM) usual lengthusual length: 9: 9--12 months12 months q.d. initially, may use twice weekly laterq.d. initially, may use twice weekly later
FOLLOWFOLLOW--UP EVALUATIONS FORUP EVALUATIONS FOR CHILDREN WITH TUBERCULOSISCHILDREN WITH TUBERCULOSIS
skin test stays positiveskin test stays positive ““foreverforever”” frequent chest xfrequent chest x--rays unnecessaryrays unnecessary -- at diagnosis, 1at diagnosis, 1--22 months, end of therapymonths, end of therapy follow growth & development closelyfollow growth & development closely adequate nutritionadequate nutrition routine liver enzyme monitoring not necessaryroutine liver enzyme monitoring not necessary routine vitamin Broutine vitamin B66 not necessary except breastnot necessary except breast--feeding, pregnant adolescents, poor dietfeeding, pregnant adolescents, poor diet
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