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8/14/2019 Pediatric TB Presentation http://slidepdf.com/reader/full/pediatric-tb-presentation 1/63 0 Pediatric Tuberculosis Ann M. Loeffler, MD Pediatric TB Consultant Francis J. Curry National Tuberculosis Center
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Pediatric TB Presentation

May 30, 2018

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Page 1: Pediatric TB Presentation

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Pediatric Tuberculosis

Ann M. Loeffler, MDPediatric TB Consultant

Francis J. Curry National Tuberculosis Center

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IntroductionBasic situations in which children areevaluatedDiagnosis and treatment of latent TB

infection (LTBI)Tuberculosis (TB) treatment strategies

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Reasons for complacencePediatric TB is uncommon in the U.S.In 2004, 961 pediatric TB cases in the U.S.

Young children with TB are usually not

contagiousAdults with TB are relatively easy to identify

More symptomatic and can produce sputum

Children with TB are difficult to diagnose

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Reasons to learn about pediatric TBWorldwide, 500,000 children die annuallyfrom TBChildren represent up to 30% of TB cases

globally, compared to 7% in U.S.Children age 0-4 are more likely to develop TBonce infected and are more vulnerable todisseminated TBChildren serve as indicators of contagious

adolescents or adults with TB

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Three basic situations1. General pediatric care for healthy children

Screen for TB risk factors

2. Child contacts to adults with potentially

contagious TBEvaluation and intervention required

3. Children with signs or symptoms of TB orradiographic changes

High index of suspicion required

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Quiz question

Which situation yields the most cases of TBin children?

Screening of healthy, asymptomatic childrenScreening of children exposed to contagiousadults with TB

Evaluation of children with symptomsconcerning for TB

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How are most cases found?From various studies published in the U.S.:

26-80% of children with TB identified duringcontact investigations3-25% of cases identified by routine screening17-44% of cases presented because of

symptomsIn developing countries, no screening of

asymptomatic children.

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Routine pediatric care:No more universal testing

It is not cost-effective to routinely skin testhealthy children without risk for TB infection or

disease!Preferred strategy: “targeted testing”

Test only children more likely to be exposed to TB

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Advantages of targeted testing

Up to 85% of positive results will be FALSEpositives in areas of low TB prevalenceMore expense, anxiety, and unnecessary

evaluations and treatmentTST is not free, not without discomfort, and notso easy to place and interpret

Families often do not return for TST reading

TST = tuberculin skin test

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Statistics about TB risk inU.S. children30% of children with TB are born outside U.S.50% are Hispanic

10% are Asian26-80% of pediatric cases are identified during

evaluation of contacts of adults with TB

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Questions validated to predict risk

Was your child born in Latin America, Asia,Eastern Europe, or Africa?Since last TST, has child traveled outsidethe U.S.?Since last TST, has child been exposed toanyone with TB or with a (+) TST?

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Questions to predict risk – local epidemiology

Since last TST, has child consumedunpasteurized dairy products from Mexico?

Since last TST, has child been around peoplewho have been incarcerated, homeless or inshelters, or people who have HIV, or use illegal

drugs?Since last TST, has child lived with new personwho was born or traveled outside U.S.?

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Targeted TB skin testing

Don’t skin test someone you won’t treat if TST ispositive

If child has no TB exposure risks, don’t skin test!“A decision to test is a decision to treat.”

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TST basicsStore PPD in the bottle, clearly labeled inrefrigerator; discard open bottles after 1 monthProviders who administer TST should be trainedand evaluated on TST techniqueInject 0.1 ml of PPD material intradermally into

volar aspect of forearmCorrect placement yields pale, distinct wheal,raised for several minutes

PPD = purified protein derivative

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Reading TST resultsA trained professional should read TST results48 to 72 hours after placementA positive test has distinct induration, not just

erythema:Bend arm at elbow; look with indirect lightFeel gently with your non-dominant hand or run penacross the induration

Measure and record result in millimeters of indurationperpendicular to long axis of arm

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TST interpretation>5 mm is (+) only if child is:

immunocompromiseda contact to a known or suspected case of TBhas clinical or radiographic evidence of TB or old TB

>10 mm is (+) for child with intermediate risk:age <4 years

medical conditions predisposing them to TB orincreased risk of TB exposure

>15 mm is (+) if child has no risk (should not be

skin tested!)

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What about BCG?BCG vaccine is routinely given to newborns/infants inmost areas of the worldIgnore history of BCG when placing or interpreting TSTIncreased risk of positive TST results being caused by

BCGBCG received as an older infant or child (>1 month of age)Multiple BCG dosesBCG in recent past

Treat LTBI or TB based on breakpoints from last slide

BCG = bacille Calmette-Guérin vaccineLTBI = latent TB infection

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If TST is negativeDocument results as millimeters of indurationin the chart and vaccine recordAdvise family to return to clinic if induration

increases in next few daysA (+) TST can be read up to 7 days after placement

Repeat questionnaire procedure at next well-child visitRepeat TST only if child has new risk factor

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TB or LTBI?TB: child has metabolically active M.tuberculosis bacteria in some part of the body

Many children are asymptomatic at time of TBdiagnosis in U.S.

LTBI: organism is dormant; physical exam andradiograph are normalTo decide, perform focused history, physical

exam, and chest radiograph

TB = tuberculosis disease LTBI = latent TB infection

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Focused Physical ExamTemperature and growth parametersAlertness and meningeal signsPeripheral lymph nodesAbdomenPalpate back and extremities

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Lung findingsLung findings are relatively modest, even withabnormal chest radiographInfants and adolescents most likely to have

rales, decreased breath sounds, and increasedwork of breathing

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Chest radiographTwo-view chest radiograph helps identifycommon abnormality: IntrathoraciclymphadenopathyMention symptoms and possibility of TB onradiology order formSame-day interpretation by

radiologist experienced withpediatric TB is idealWait until TB is ruled out beforestarting treatment

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LTBI (latent TB infection)Normal chest radiograph and physical exam,(+) TST = diagnosis of LTBIWhy treat all children who have LTBI?

LTBI treatment is less toxic in children than in adultsYoung children are more likely to develop TB onceinfected than are adultsYoung children were infected recently, increasingrisk of progression to TB

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Summary:Screening well childrenNo more universal TB skin testingTargeted testing: Review TB exposure andpopulation risk factors; TST only for childrenwith new exposure risks since last TSTIf (+) TST, conduct focused history and physical

exam to discern TB from LTBI

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Child contact to a TB caseContact investigation: Evaluation of contacts toa contagious TB caseYoung children are high priority for evaluation

More likely to develop TBMay develop TB within weeks of infectionContacts < age 5: immediate chest

radiographs, history, and physical examDo not wait for (+) TST result before performingevaluation on young child,immunocompromised or symptomatic individual

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Treatment of contactsIf (+) TST, begin 9-month course of INH for LTBI

If (-) TST, consider INH treatment as “windowprophylaxis”Repeat TST after 8-10 weeks of no further exposureto contagious caseIf TST still (-), child is immunocompetent, and nonew TB symptoms, stop INHIf exposure to contagious case has continued, or if

another adult in proximity has TB, repeat evaluationand/or extend treatmentIf (+) TST upon repeat testing, complete 9 months ofINH

INH = isoniazid

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Child contacts > 4 yrTST and symptom reviewIf (-) TST and no symptoms, chestradiograph not imperative

Individualize use of window prophylaxis; local healthdepartment can advise youRepeat TST 8-10 weeks after contact is broken or

source case is deemed non-contagiousIf (+) TST, obtain chest radiograph if not performedinitially

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Summary:Child contactPrompt TST and symptom reviewfor all individuals with significant exposure to contagiousTB case

Children under 5Chest radiograph even before TST is readIf no TB, start window prophylaxis, independent of TST result

8-10 weeks after exposure is ended, repeat TST. If (-)TST, stop window prophylaxis (assumingimmunocompetence)

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Symptoms and abnormalradiographs

Difficult to distinguish community-acquiredpneumonia or asthma from TB onradiographic findingsSymptoms often subtle or even absentDifficult to confirm microbiologically

Children cannot produce sputa easilySputa from young children usually

smear (-)

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Circumstances that increaseTB suspicion

Exposure to person with TBSeveral people in child’s environment with (+)TSTsRadiographic changes common in pediatric TB,including intrathoracic adenopathy and calcified

granulomataA relative paucity or chronicity of symptoms incomparison to radiographic changes

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TST results are not definitiveA positive TST does not confirm thediagnosis of TBA negative TST does not exclude TB

TST results are merely one factor in theequation

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Algorithm forDiagnosis

Positive TB skin test

Clinically and radiographically

Treat for LTBI

Other diagnosisconfirmed; courseinconsistent with TB

Note: Cultures only help if they are positive.See the next few slides for more algorithm details.

Reassess weekly

TB still possible?

Collect cultures & start4-drug TB therapy

Consider culturecollection(no INH!)

Treat other

diagnosis

Patient very stable?

More consistent with otherdiagnosis

Consistentwith TB

Abnormal

YES

NO

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Findings more consistent with another

diagnosis…

Consider culturecollection(no INH!)

Treat otherdiagnosis

Patient very stable?

More consistent with otherdiagnosis

abnormal

YES

Chest radiograph

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If radiograph normalizes without TBtreatment…

Consider culturecollection(no INH!)

Treat otherdiagnosis

Treat for LTBI

Other diagnosis

confirmed; courseinconsistent with TB

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If findings do not normalize…

Consider culturecollection(no INH!)

Treat otherdiagnosis

Reassess weekly

TB still possible?

Collect cultures & start4-drug TB therapy

Consistentwith TB

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OK to overtreat in uncertainsituations

If patient is not stable: Submit specimens forcultures and start TB therapy; sometimesdiagnosis becomes clear over timeSometimes diagnosis doesn’t become certain;complete treatment for TB

Weigh all likely diagnoses, consider risks andbenefits, and make best judgment afterdiscussion with family and expert resources

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When TB is most likely diagnosis…

Consider culturecollection(no INH!)

Treat otherdiagnosis

Positive TB skin test

Clinically and radiographically

Collect cultures & start4-drug TB therapy

Consistentwith TB

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ScrofulaScrofula: peripheral mycobacterial lymph

nodesTypically enlarge over several weeks; nottender unless they enlarge quicklyOverlying skin discolors, first pink, thendusky or purplish

Different from pyogenic lymph nodesChildren with TB scrofula

often have (+) TST

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Scrofula in briefTB scrofula

Tends to occur in children over 5Associated with TB exposure or risk factors: Travel toendemic areas and consumption of unpasteurized dairyproducts ( M. bovis )

Most often in cervical chains (could be anywhere)Associated with larger TST induration

Non-tuberculous or atypical mycobacterial scrofula

More likely in children < 5More frequently in submandibular and submental chains.Cat Scratch Disease

More common in axilla and groinExposure to kittens and history of scratches common

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Clinical suspicion, negative TST

A negative TST never rules out TB20% of culture-proven pediatric TB cases areTST (-) when initially evaluated

Pursue diagnosis and treatment of TB:Known source caseRadiographic abnormalities most consistent with TB

Clinical findings are subtle or more modest thanradiographic findingsIntrathoracic lymphadenopathy

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QuantiFERON ®

-TB Gold testNew option for clarifying dx of TB infectionAliquots of whole blood are exposed to TB-specific proteins and controls

Plasma is tested for levels of gamma-interferonTest is (+) if the lymphocytes have recognizedTB proteins and produced gamma-interferon

well above the level in control tubeQFT-G can distinguish true TB infections fromthose caused by NTM or BCG exposure

QFT-G = QuantiFERON ®

-TB Gold NTM = nontuberculous mycobacteria

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Limitations of QFT-GCDC advises caution when interpreting QFT-G inchildren and immunocompromisedStudy results regarding children are mixed

QFT-G most useful in identifying true infection inhealthy asymptomatic BCG-vaccinated individualsIn pediatric TB suspects and high-risk contacts < 5,

use QFT-G in confusing situations as one morepiece of informationNeither negative TST nor QFT-G ever rules out TB

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QuantiFERON ®

-Gold In TubeNext generation QuantiFERON ®

Blood is collected into tubes coatedwith stimulating proteinsNo need to transport blood within 12 hours to labOne pediatric study:

Good correlation with TST

Both QFT-G In Tube and TST were (-) in severalchildren with TB

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T-SPOT. ®

TB

Quite promising for childrenGamma-interferon release assay

Requires separation of peripheral bloodmononuclear cells from whole bloodTechnically more challenging than QFT-Gtests

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Culture collectionSputum: Older children can collect sputumby induction or in showerGastric aspirate

Highest yield specimen for infants~ 50% yield in children with TB

Other specimens: Cerebrospinal fluid, lymphnode tissue, blood, urine, bone biopsy,synovial fluidSubmit large volume specimens in sterile

container without formalin

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Summary: DiagnosisNot everyone with (+) TST has TB

Not everyone with TB has (+) TSTConsider TB exposure, TST results,signs/symptoms, and radiographic featuresTest for other likely diagnosesConsider a therapeutic trial of bronchodilator

therapy or single course of antibioticsUtilize dedicated TB clinic or expert pediatric TBconsultants

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Reporting casesDetermine local requirements for reportingpatients to local health department (LHD)Report suspected cases of TB to LHD within 1

working dayNo universal reporting requirement for LTBI

LTBI = latent TB infection

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Treatment of LTBI

All children with LTBI should be treated270 doses of isoniazid (INH)

Minimum 9 monthsGoal is to finish 270 doses within 12months

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Tips for completing therapyGive a big pep talk at beginning of therapyExplain:

Benefit of treatment

Consequences if child were to activate the TBUse INH tablets, not liquid, to avoid abdominalpain and diarrhea

Minimize GI side effects by giving drug withsnack and/or at bedtime

Provide calendar and stickers

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Monthly visits during therapy

Ensure adherenceMonitor for toxicityArrange for quick nurse visits

Only dispense bottles of 30 INH doses; no refillsWhen child has finished 9 bottles, course is doneProvide toy or incentive to keep child engagedOr offer incentive at end of therapy (movie tickets,fast food voucher, toy, etc.)

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Liver toxicity

Liver function testing (LFT) is no longer standard

Most children tolerate therapy wellLFT’s only for children with:

Underlying liver diseaseTaking other hepatotoxic medsSymptoms of hepatotoxicity

Watch for anorexia, malaise, abdominal painMake sure family stops treatment and returns forevaluation if symptoms develop

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B6 tableAGE OF CHILD PYRIDOXINE DOSE

Infant 6.25 mg ¼ of 25 mg tablet

Toddler 12.5 mg ½ of 25 mg tablet

School-aged 25 mg 25 mg tablet

Vitamin B6 (pyridoxine) dosing in children

Tablet can be crushed or fragmented into liquid orsoft vehicles.

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Summary: LTBI treatmentMost difficult thing: getting child to take all 270dosesLet family know what to expectTeach good tricks for dosingProvide incentivesEnsure families understand symptoms of

drug toxicityMonthly visits are important; keep them quick

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Treatment of TBSend child to TB clinic with pediatric expertise

Confer with local health department andpediatric TB consultantFour-drug empiric therapy using directly

observed therapy (DOT)DOT: Non-family member observes patient takingmedicationDOT can increase completion rates to 90% rangeCan take place at home, work, school, clinic, orstreet corner

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Four-drug treatment tableDRUG DAILY dose

in mg/kg/dose(maximum dose)

TWICE WEEKLYdose in mg/kg/dose(maximum dose)

Isoniazid 10-15 (300 mg)* 20-30 (900 mg)

Rifampin 10-20 (600 mg)* 10-20 (600 mg)

Pyrazinamide 20-40 (2 grams) 50 (2 grams)

Ethambutol # 15-25 (2.5 grams) 50 (2.5 grams)

American Academy of Pediatrics

* When using both INH and Rifampin DAILY, dose INH at 10/mg/kg/dose andRifampin no more than 15 mg/kg

# Consider risk and benefit of Ethambutol in children whose visual acuity cannot bemonitored.

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Course of treatment

Isoniazid

Rifampin

Ethambutol

0 1 2 3 4 5 6months

Initial Phase Continuation Phase

Ethambutol can be stopped if the patient or source case isolate is INH/RIF susceptible.

Pyrazinamide

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After 2 months of therapyAfter two months, regimen can be changed to INH

and RIF by DOT 2 to 3 times weekly if:Patient is doing well (gaining weight and not

worsening clinically or radiographically)Patient is taking and retaining each DOT dose,and appears to be absorbing the drugs

And there is no concern for drug resistance

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Assess the course of treatmentAt two months:

Repeat chest radiograph and assessthe situation.If adherence and response are goodand no particular concern for resistance,treat with INH and RIF for remainder of course

Total duration of therapy is six months, measured by

number of doses observedPatients receiving a typical regimen receive 40 daily dosesand 36 twice-weekly doses

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Challenges of treating childrenMicrobiologic confirmation is less common

Monitoring success by serial sputum isnearly impossibleMonitoring for toxicity is more difficultChildren tolerate regimens better than adultsINH liquid is poorly tolerated

Need to open capsules, crushtablets, hide drug into soft foodsor liquids

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Dosing tipsAnticipate trial-and-error period for 1-2 weeks

Don’t alienate child while figuring out agood systemPossible vehicles: Maple syrup, chili, nutella,spinach baby food, chocolate whipped creamLayer vehicle and drug on a spoonTeach child to take contents of spoonwithout chewingBe prepared to try new tricks or incentives

Never let child think the dose is optional

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Circumstances for prolongedtherapyIf disease is extensive or slow to respondIf patient has TB meningitis or osteomyelitis(treated for 12 mo)If TB isolate is drug-resistant

Includes treatment of M. bovis (inherently resistant

to PZA and often sluggishly responsive to therapy)If patient has been poorly adherent

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ConclusionPediatric TB is relatively uncommon in U.S. and

sometimes missedScreen healthy children with risk factorquestionnaires and reserve TST for those at risk

of exposureEvaluate children exposed to active cases of TBpromptly and thoroughly; they are at highest riskof infection and diseaseNot all children with TB have (+) TST and not allchildren with (+) TSTs and radiographicabnormalities have TB

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Next stepsProceed to the post-test

Peruse course resource materialsShare the resources with friends and colleagues

Call a pediatric TB expert for assistance

Thank you for your careof the children.