10) printablePEDS Loeffler

Pediatric Tuberculosis Page 1 of 18

PEDIATRIC TUBERCULOSIS

Ann M. Loeffler, M.D.

Faculty ConsultantCurry International TB Center

Objectives

At the end of this session, participants will be ableto describe:

• how pediatric patients differ from adults in p ppresentation of tuberculosis (TB) disease

• the treatment regimens for latent TB infection (LTBI) and TB disease in children

Children are not just small adults

Pediatric TB and LTBI are sentinel events

Screening for LTBI

Likelihood of TB disease Likelihood of TB disease

Class 1 exposure

Signs and symptoms

Radiographic findings


Children are not just small adults (2)

Pulmonary vs. extrapulmonary

Contagion

B i l i di i Bacteriologic diagnosis

Treatment regimens

Dosing difficulties

Pediatric tuberculosis

TST conversion and TB disease in a young child represent recentchild represent recent infection and therefore active transmission within the community:

“Sentinel event”

Screening for LTBIScreening for LTBI


Why is screening for LTBI different for adults than kids?

1. Kids have fewer side effects from INH treatment than do adults

2. Most positive TSTs in adults are caused by previous BCG vaccinationBCG vaccination

3. Adults are more likely to get TB disease if they are infected

4. Adults don’t mind when we place a TST

Screening for latent TB infection

Adults

Screen only those at high risk of developing TB disease

Children

Screen those likely to have LTBI

Treat all LTBI identified

• INH less toxic

• Children more likely to be infected recently

Screening for latent TB infection (2)

Adults

www.thoracic.org

Statements

1999 − Targeted tuberculin testingand treatment of LTBI

Children – AAP guidelines http://pediatrics.aappublications.org/content/114/Supplement_4/1175.full.pdf


IGRA in children Limited data in youngest children

National guidelines support use in children 5 years and older

IGRAs appear to have improved specificity vs. TSTIGRAs appear to have improved specificity vs. TST

Just like TST, may have decreased sensitivity in TB disease, immune compromise/young age

Rare false positives; indeterminates may be more likely in children

Use with caveats

Which children are most likely to developmost likely to develop

TB disease once infected?

Which children are NOT at increased risk of TB disease?

1. Infants

2. School-aged kids

3. HIV-infected

4. Malnourished children


Host factors predisposing to disease

Young age

• 40% of infected babies <1 year develop TB disease

• higher risk continues until school-aged

Adolescence

Malnutrition

Underlying conditions/intercurrent illnesses: HIV, measles, pertussis, DM, immunosuppression

How do we evaluate and treat children exposed to adolescents

and adults with potentiallyand adults with potentially contagious TB?

Class 1 exposure

Exposure to an adult with TB disease:

• TST placement

• chest radiograph (PA and c es ad og ap ( a dlateral)

• physical exam to rule out extrapulmonary TB

• if no evidence of TB disease, initiate “window prophylaxis”


Window prophylaxis

The practice of treating high-risk individuals

• with negative TST

• no evidence of TB disease

• exposed to a likely contagious case of TB

• with INH (unless source case resistant)

Window prophylaxis (2)

Repeat TST 8-10 weeks • after source case non-

contagiouscontact with source case• contact with source case broken

• if TST reliable (6-12 months of age/immunocompetent)

Stop prophylaxis if TST negative and no other source case!!

What kinds of findings

do we expect for a child

with TB disease?


All children with TB disease have symptoms (cough, fever, or weight loss)

1. TRUE

2. FALSE

Signs and symptoms of tuberculosis

Most US children with TB are asymptomatic

The chest x-ray findingsThe chest x ray findings have NO correlation with signs and symptoms

Infants and adolescents are most likely to have signs and symptoms

Which chest X-ray finding is more common in children than adults?

1. Enlarged lymph nodes (intrathoracic lymphadenopathy)

2 Pleural effusion2. Pleural effusion

3. Apical disease

4. Cavitary disease


Chest radiographs

Characteristic: Adults Children

Location Apical Anywhere(25% multilobar)

Adenopathy Rare Usual (30-90%)(except HIV)

Cavitation Common Rare (except adolescents)

Signs and symptoms Consistent Relative paucity

Extrapulmonary tuberculosis

>25% of children have extrapulmonary TB

• 67% lymphatic – mediastinal and scrofula• 13% meningeal• 6% pleural• 6% pleural• 5% miliary• 4% bone and joint• 5% others

intra-abdominal ears and mastoids skin, laryngeal, kidneys, etc.

Scrofula

Enlarging nodes

Not particularly painful

Skin becomes dusky and thin over time Skin becomes dusky and thin over time

May eventually suppurate and drain

Differential diagnosis: bacterial; cat scratch disease, non-tuberculous mycobacteria


Scrofula (2)

More likely to be TB:

• cervical chain

• slightly older child

• exposure to TB

• consistent demographics

• larger TST reaction

• (in my experience) responds beautifully to TB therapy

Scrofula management

Skin test child and family

If most likely TB – treat empirically if you have culture material from elsewherematerial from elsewhere

If most likely non-tuberculous mycobacteria or diagnosis not clear – seek complete excision with AFB culture and path

AFB culture should be collected into syringe or cup without formalin – NOT ON SWAB!

How do we

bacteriologically confirmbacteriologically confirm

TB disease in a child?


What specimens may grow M. tuberculosis in children with TB?

1. Gastric aspirates

2. Induced sputum

3. Cerebrospinal fluid

4. Lymph node biopsy

5. All of the above

Bacteriologic diagnosis

Sputum can rarely be collected from children

Can try sputum induction in older children

Bronchoalveolar lavage is invasive, expensive and should be reserved for situations where the diagnosis is in question

Bacteriologic diagnosis (2)

Gastric aspirates

• people swallow mucus in their sleep

• collect gastric contents before the stomach• collect gastric contents before the stomach empties

• http://www.currytbcenter.ucsf.edu/pediatric_tb/

Pediatric on-line course: resources


Gastric aspirate collection

Have everything ready

Have helper if possible

Restrain the child wellRestrain the child well

• mark tube length to stomach with pen

• insert at least 10 French catheter through nose

• stay away from septum

• aim straight at the bed


Gastric aspirate collection (2)

If insignificant yield:

• put any yield in sterile container

• check tube position in stomach by instilling air and listening with stethoscopelistening with stethoscope

• instill 20 ml sterile water

• re-aspirate

• if no good mucous – advance and withdraw tube, roll the child, etc. looking for mucous

• continue to aspirate syringe as you withdraw tube

Gastric aspirate collection (3)

Put all yield in sterile cup or tube

Immediately transport to lab for neutralize OR Neutralize at bedsideNeutralize at bedside

Order AFB smear and culture

(Bicarbonate for neutralization − 2.5 grams NaHCO3 dissolved in 100 cc deionized water. Filter the solution through a 45um filter. Use 1.5 cc for each specimen. Lab should monitor and correct the pH)

Gastric aspirate yield

A negative culture does not rule out TB

First specimen is the very highest yield

Nearly 100% yield for <3-month-olds

• smear rarely positive after 3 months

Literature for 3 gastric aspirates: 40%


How do we treat LTBI and TB diseaseLTBI and TB disease

in children?

Which LTBI treatment regimen is not recommended for children?

1. INH for 9 months

2. Rifampin for 6 months

3 Rifampin and pyrazinamide for 2 months3. Rifampin and pyrazinamide for 2 months

4. INH for 6 months

5. 3 and 4

Treatment of latent TB infection270 doses of INH in a one year period

Regimen Adults Children

Isoniazid 9 months 9 months

Isoniazid 6 months ---------

Rifampin 4 months 6 months

Rifampin/

pyrazinamide

-------------- -----------


Latent TB infection drug doses

Drug/regimen Adults Children

Isoniazid – daily 300 mg or 5 mg/kg/dose 10-20 mg/kg/dose up to 300 mg

Isoniazid – twice weekly DOPT

900 mg or 15 mg/kg/dose 20-40 mg/kg/dose up to 900 mg

Rifampin – daily or

twice weekly DOPT

600 mg or 10 mg/kg/dose 10-20 mg/kg/dose up to 600 mg

Pyrazinamide

Vitamin B6 25 mg for medical risks only only for breastfed; malnourished, sx

Child’s weight INH daily dose (10-15mg/kg/d)

Kilograms Pounds Milligrams 100mg tabs

300 mg tabs

3-5 kg 6.6-11 # 50 mg ½

Isoniazid (INH) dosing

3 5 kg 6.6 11 # 50 mg ½

5-7.5 11-16.4 75 ¾

7.5-10 16.5-22 100 1

10-15 22-33 150 ½

15-20 33-44 200 2

Over 20 Over 44 300 1

Maximum dose 300 mg !!

Pediatric TB:

• A decision to treat is a decision to treat

• Most often, once TB treatment is begun, it must be completedbe co p eted

• Unlike adults – positive cultures rarely available

• Clinical or radiographic improvement on treatment may be attribute to TB treatment or spontaneous resolution of another process


Clinically and radiographically

Normal AbnormalConsistent with TB More consistent with other

diagnosis

P ti t t bl ?

Positive TB skin test

Treat for LTBI

C ll t lt d Patient very stable?Collect cultures andstart 4 drug TB therapy NO

YES

Consider culture collection

(NO INH!!!)Treat otherdiagnosis

Reassess weekly

Other diagnosis confirmed,Course inconsistent with TB

TB still possible?

*** Cultures only help if they are positive*

Treatment regimens

TB disease

• four drugs for two months

• if chest radiograph is not worse compliance• if chest radiograph is not worse, compliance good, and isolate presumed sensitive, two drugs for four more months

• miliary or CNS disease – one year

Dosing difficulties

Avoid liquid suspensions

• INH is only commercially available. High osmotic gload, stomach upset

• others custom made─

poor stability, poor homogeneity


Dosing difficulties (2)

Crush or fragment tablets, open capsules onto vehicle and layer with aand layer with a topping of the food


Use thick, strong flavored vehicles:• jelly

• NutellaNutella

• chocolate whipped cream

• syrup

• chocolate sauce

• baby foods

Give a spoonful of vehicle before and after drug dose


Small amounts of non-sugary liquids

Rarely, dose infants in their sleep


Conclusions – pediatric TB

Large global problem

Focal U.S. problem

Higher rates of progression to TB – requires aggressive evaluation for exposureaggressive evaluation for exposure

Children have:

• fewer signs and symptoms

• different radiographic findings

• more extrapulmonary TB

• less contagion

Conclusions – pediatric TB (2)

Gastric aspirates insensitive, but best culture method

Treatment regimens limited for LTBI, similar toTreatment regimens limited for LTBI, similar to adult TB regimens

Children are difficult to dose with TB meds; require patience and positive creativity

10 year old Ethiopian adoptee MDR-TB


KH head CT

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