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PEDIATRIC TUBERCULOSIS

Ann M. Loeffler, M.D.

Faculty ConsultantCurry International Tuberculosis Center

Objectives

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

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

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

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Children are not just small adults

Pediatric TB and LTBI are sentinel events

Screening for LTBI

Likelihood of TB disease

Class 1 exposure

Signs and symptoms

Radiographic findings

Children are not just small adults (2)

Pulmonary vs. extrapulmonary

Contagion

Bacteriologic diagnosis

Treatment regimens

Dosing difficulties

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Pediatric tuberculosis

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

“Sentinel event”

Screening for LTBI

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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 TST / IGRAs in adults are caused by previous BCG vaccination

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

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

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

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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;

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IGRA in children Limited data in youngest children

National guidelines support use in children 2 years and older – preferred for BCG recipients

“some data support their use for even younger children”

IGRAs appear to have improved specificity vs. TST

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

Rare false positives; indeterminates may be more likely in young children

IGRA in children – California DPH

IGRA is preferred over the tuberculin skin test for foreign-born children ≥2 years of age.

IGRAs can be used <2 years of age (lack of data)

In BCG vaccinated immunocompetent children with a positive TST, it may be appropriate to confirm a positive TST with an IGRA.

If IGRA is not done the TST result should be considered the definitive result.

https://archive.cdph.ca.gov/programs/tb/Documents/TBCB-CA-Pediatric-TB-Risk-Assessment.pdf

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Which children are most 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

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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 potentially contagious TB?

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Class 1 exposure

Exposure to an adult with TB disease:

• TST placement or IGRA; chest radiograph (PA and lateral)

• 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 / IGRA no evidence of TB disease

• exposed to a likely contagious case of TB

• with INH (unless source case resistant)

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Window prophylaxis (2)

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

contagious• contact with source case

broken• if TST / IGRA reliable (6-12 months

of age/immunocompetent)

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

What kinds of findings

do we expect for a child

with TB disease?

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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 findings have NO correlation with signs and symptoms

Infants and adolescents are most likely to have signs and symptoms

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

1. Enlarged lymph nodes (intrathoracic lymphadenopathy)

2. 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

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Extrapulmonary tuberculosis

>25% of children have extrapulmonary TB

• 67% lymphatic – mediastinal and scrofula• 13% meningeal• 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

May eventually suppurate and drain

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

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Scrofula (2)

More likely to be TB:

• cervical chain

• slightly older child

• exposure to TB

• consistent demographics

• larger TST reaction / positive IGRA

• (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 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!

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How do we

bacteriologically 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

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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 empties

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

Pediatric on-line course: resources

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Gastric aspirate collection

Have everything ready

Have helper if possible

Restrain the child well (or not)

• mark tube length to stomach with pen

• insert at least 10 French catheter through nose

• stay away from septum

• aim straight at the bed

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Gastric aspirate collection (2)

If insignificant yield:

• put any yield in sterile container

• check tube position in stomach by instilling air and listening 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

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Gastric aspirate collection (3)

Put all yield in sterile cup or tube

Immediately transport to lab for neutralize OR

Neutralize 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%

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How do we treat LTBI and TB disease

in children?

Which LTBI treatment regimen is not recommended for children?

1. INH for 9 months

2. Rifampin for 4 months

3. Rifampin and pyrazinamide for 2 months

4. INH for 6 months

5. 3 and 4

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Treatment of latent TB infection

Regimen Adults Children

INH and rifapentine

weekly x 12 doses DOT

> 2 yrs; weekly x 12 doses DOT

Rifampin 4 months 4 months

Isoniazid 6-9 months 9 months

Drug/regimen Children

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

Isoniazid – thrice weekly DOPT 20-30 mg/kg/dose up to 900 mg

Isoniazid – weekly with rifapentine 25 mg/kg in patients 2-11 yrs up to 900 mg; 15 mg/kg for > 12 yrs

Rifapentine Wt: 10 – 14 .0 kg = 300 mg14.1 – 25.0 kg = 450 mg 25.1 – 32.0 kg = 600 mg 32.1 – 49.9 kg = 750 mg

Up to 900 mg

Rifampin – daily or

Thrice wkly DOPT

15-20 mg/kg/dose up to 600 mg

(up to 30 mg / kg for infants / toddlers / extensive disease)

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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

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 !!

Isoniazid (INH) dosing

Pediatric TB:

• A decision to treat is a decision to treat

• Most often, once TB treatment is begun, it must be completed

• Unlike adults – positive cultures rarely available

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

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Clinically and radiographically

Normal AbnormalConsistent with TB More consistent with other

diagnosis

Patient very stable?

Positive TB skin test

Treat for LTBI

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 good, and isolate presumed sensitive, two drugs for four more months

• miliary or CNS disease – one year

• Daily or three times weekly dosing in the continuation phase

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Dosing difficulties

Avoid liquid suspensions

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

• Babies tolerate it better

• others custom made─

poor stability, poor homogeneity

Dosing difficulties (2)

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

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Dosing difficulties (3)

Use thick, strong flavored vehicles:• jelly

• Nutella

• chocolate whipped cream

• syrup

• chocolate sauce

• baby foods

Give a spoonful of vehicle before and after drug dose

Dosing difficulties (4)

Small amounts of non-sugary liquids

Rarely, dose infants in their sleep

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Conclusions – pediatric TB

Large global problem

Focal U.S. problem

Higher rates of progression to TB – requires aggressive 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 (emphasis on short course)

Similar to adult TB regimens

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

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10 year old Ethiopian adoptee MDR-TB

KH head CT

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