Pediatric Tuberculosis 1 PEDIATRIC TUBERCULOSIS Ann M. Loeffler, M.D. Faculty Consultant Curry International Tuberculosis Center Objectives At the end of this session, participants will be able to 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 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
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Pediatric Tuberculosis 1
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
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
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Children are not just small adults (2)
Pulmonary vs. extrapulmonary
Contagion
Bacteriologic diagnosis
Treatment regimens
Dosing difficulties
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
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 5 years and older
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 children
Use with caveats
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.
• (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
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
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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
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
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)
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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 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
Isoniazid 9 months 9 months
Isoniazid 6 months ---------
Rifampin 4 months 6 months
270 doses of INH in a one year period
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
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
10-20 mg/kg/dose up to 600 mg
Pediatric Tuberculosis 15
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
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*
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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
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
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
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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