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Pediatric Tuberculosis: The EssentialsWith Dr. Ann Loeffler
October 8, 2014
Curry International Tuberculosis Center1
Pediatric Tuberculosis: The Essentials October 8, 2014
Ann M Loeffler, MD
Randall Children’s Hospital at Legacy Emanuel
Portland, Oregon
Curry International TB Center
Disclosures
• Nothing to disclose
Learning Objectives• Explain the key differences in clinical presentation, infectiousness, and
diagnosis (including interpretation of x‐rays) in children versus adults to best evaluate and ensure timely diagnosis in this population
• State the differences in treatment of TB and LTBI in children as compared to adults to achieve optimum pediatric patient outcomes
• List techniques to make children's medication dosing more effective and implement these techniques in their pediatric patients
• Monitor pediatric TB patients, including interpreting lab results, assessing the weight of infant patients, and determining clinical progress in pre‐verbal patients for optimum pediatric patient outcomes
• Address some of the challenges of working with parents of children with TB disease or LTBI and identify strategies to overcome them
Pediatric Tuberculosis: The EssentialsWith Dr. Ann Loeffler
October 8, 2014
Curry International Tuberculosis Center2
Why do kids get their own talk?
• They’re so darn cute
Why else?
• They are disproportionately affected by TB
– Higher case rates considering their overall risk of exposure
– Infants and toddlers at particular risk
• 40% of exposed babies will develop disease
• 25% of exposed toddlers will develop disease
– High rates of disseminated disease
• Among infants < 1 yr of age – 8.2% had meningeal disease
– 4.7% had miliary disease
AND
• A new diagnosis of LTBI or TB disease in a young child reflects recent transmission
• Recent transmission is a public health opportunity
Pediatric Tuberculosis: The EssentialsWith Dr. Ann Loeffler
October 8, 2014
Curry International Tuberculosis Center3
Reasons for TB Diagnosis
• Symptomatic– Children with symptoms concerning for TB undergo evaluation– 52% of US kids with TB diagnosed because of symptoms or
abnormal chest radiograph– 80% of all US cases
• Contact investigation Child d b th h k t d TB– Children screened because they have known or suspected TB exposure
– 43% of US kids with TB diagnosed during CI– 4.6% of all US cases (n = 444)
• Universal or targeted screening– Asymptomatic children undergo TST / IGRA– Just a few percent of adults and children diagnosed with TB this
way
General Screening
• Few children require routine TST / IGRA
• Targeted testing
– Test children likely to be infected
– Test adults who are likely to develop disease if infected
– Treat all children deemed to have LTBI
– Treat adults at risk of progression to TB disease
– Don’t test folks who you won’t treat if positive
Pediatric Tuberculosis: The EssentialsWith Dr. Ann Loeffler
October 8, 2014
Curry International Tuberculosis Center4
US Pediatric TB Cases by Case Verification Criterion*, 1993–2012
N=19,840
ProviderDiagnosis
23%
Laboratory Confirmed
26%
Clinical Case 51%
*Based on the public health surveillance definition for TB [MMWR 1997:46(No. RR-10):40-41]
51%
26%
23%
Age < 1 n=1,992
20%
54%
25%
Age 1–4 n=9,692
US Pediatric TB Cases by Case Verification Criterion by Age Group, 1993–2012
N=19,840
16%
60%
24%
Age 5–9 n=4,474
37%
46%
16%
Age 10–14 n=3,682
Laboratory Confirmed
Clinical Case
Provider Diagnosis
Pediatric Tuberculosis: The EssentialsWith Dr. Ann Loeffler
October 8, 2014
Curry International Tuberculosis Center5
TB Diagnosis ‐ Adults
Suspicious symptoms or radiographic changes
– Collect sputum (high quality x 3)
• If smear or NAAT positive OR
• Suspicious exposure history / demographics OR
• Classic radiographic findings / symptoms OR• Classic radiographic findings / symptoms OR
• High risk contacts ‐‐‐‐‐
Start TB treatment
Otherwise, consider awaiting more data / culture results
TB Diagnosis ‐ Children
• Screened during contact investigation– TST / IGRA
– Immediate History and Physical exam
– Immediate chest radiograph (2 views please) if:• Less than five years of age OR• Less than five years of age OR
• Immunocompromised OR
• Signs or symptoms of TB disease OR
• Positive TST / IGRA
– Treat for TB disease if abnormal chest radiograph typical for TB disease, even if asymptomatic, even if TST / IGRA negative (ideally after culture collection)
Not TB Disease
• Calcified granulomata OR pulmonary vessels on end
• Isolated calcified lymph nodes
• Isolated pleural thickeningp g
• Most “peribronchial thickening”
• Most “hilar fullness” not confirmed on lateral
Pediatric Tuberculosis: The EssentialsWith Dr. Ann Loeffler
October 8, 2014
Curry International Tuberculosis Center6
Isolated calcifications without parenchymal changes or enlargement of lymph nodes is LTBI. It is not TB disease
Hilar nodes
Lymph nodes in the hilum or mediastinum are seen as fullness in the infrahilar window
Pediatric Tuberculosis: The EssentialsWith Dr. Ann Loeffler
October 8, 2014
Curry International Tuberculosis Center7
Paratracheal node
Clinically and radiographically
Normal Abnormal
Consistent 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*
Contagion
• Adults with pulmonary or laryngeal TB are contagious until proven otherewise
– Increased contagion with cavitary TB, smear positivity, lots of cough
– Other factors associated with transmission
• Young children are not contagious with TB
– Rare newborn have transmitted to others
– Older kids with extensive parenchymal disease, cavitary disease, lots of cough might transmit
Pediatric Tuberculosis: The EssentialsWith Dr. Ann Loeffler
October 8, 2014
Curry International Tuberculosis Center8
TB Treatment
• Treatment of pediatric TB disease is not very different than adult TB treatment
• Any drug used in adults can be used in children
• Weight based dosing is key in children
• Drug metabolism is typically faster in children and so their relative doses might seem high
• BUT – do not exceed adult maximum unless you are monitoring drug levels (RARE)
Pediatric TB Treatment
• Four drug initial therapy for most children
• “Some experts would administer 3 drugs (isoniazid, rifampin, and pyrazinamide) as the initial regimen
if a source case has been identified with known– if a source case has been identified with known pansusceptibleM tuberculosis,
– if the presumed source case has no risk factors for drug‐resistant M tuberculosis, or
– if the source case is unknown but the child resides in an area with low rates of isoniazid resistance.”
2012 AAP RedBook
Pediatric Tuberculosis: The EssentialsWith Dr. Ann Loeffler
October 8, 2014
Curry International Tuberculosis Center9
Pediatric TB Drug Dosing
Drugs Dosage forms Daily dose mg/kg
Twice weekly dose
Maximum dose
Isoniazid Tablets 100 & 300 mg;Syrup 10mg/ml
10‐15 mg/kg 20‐30 mg/kg Daily 300mg Twice weekly
DOT 900 mg
Rifampin Capsules 150 & 300 mg;
10‐20 mg/kg 10‐20 mg/kg 600 mg
Syrup; IV
Pyrazinamide Tablets 500 mg 30‐40 mg/kg 50 mg/kg 2000 mg
Ethambutol Tablets 100,400 mg
20 mg/kg 50 mg/kg 2500 mg
2012 AAP RedBook
Treatment Regimens
• Drug susceptible disease: the same as adults:
– 2 months of 3 – 4 drugs by DOT
– 4 months of 2 drugs (INH & RIF) by DOT
• INH monoresistant
– Rifampin, pyrazinamide and ethambutol for 6 + months
• Susceptible M. bovis:
– 2 months of INH, RIF, EMB, followed by 7‐10 mo of isoniazid and rifampin
Labs / pyridoxine• All individuals with TB disease should be HIV tested (HIV is now rare in US children)
• Other labs are not routine in children unless they have underlying liver problems or take other hepatotoxic drugsVit i B 6 l t ti i b bl t• Vitamin B 6 supplementation is probably not necessary in children whose diet includes milk and meat (except HIV infected or exclusively breastfeeding or adolescence)
• Many health departments prefer to use vitamin B6: Dose 25 mg tab:– ¼ tab for babies; ½ tab for toddlers; 1 tab for older
Pediatric Tuberculosis: The EssentialsWith Dr. Ann Loeffler
October 8, 2014
Curry International Tuberculosis Center10
LTBI
• Latent TB Infection ‐ LTBI
–M tuberculosis complex infection
• positive TST or IGRA result,
• no physical findings of disease, p y g ,
• chest radiograph findings that are normal or reveal evidence of healed infection (eg, calcification in the lung, hilar lymph nodes, or both)
2012 AAP RedBook
Pediatric LTBI Treatment
• Isoniazid for 9 months (270 doses)
• Rifampin for 6 months (likely will change to 4 months)
• Isoniazid and rifapentine weekly for 12 doses by p y yDOT
• Rifampin / pyrazinamide for 2 months
LTBI Treatment
• Never start LTBI treatment until TB disease is ruled out
• This is not always comfortable
C ll t lt l t t t d t t• Collect cultures, evaluate contacts and start multidrug treatment if you can’t wait http://www.currytbcenter.ucsf.edu/pediatric_tb/
• Two months of 4 drugs is treatment for LTBI
Pediatric Tuberculosis: The EssentialsWith Dr. Ann Loeffler
October 8, 2014
Curry International Tuberculosis Center11
LTBI Adherence
• Ensure adherence
– Treat only those who truly have LTBI
– Be very compelling with the family
– A little well placed guilt can be a good thing
– Set up convenient monitoring and medication delivery systems
– Use quick and easy clinic forms: www.currytbcenter.ucsf.edu/pediatric_tb“Resources”
– Consider intermittent treatment by DOT
Treatment: Ensure Adherence
• Sticker and calendar system
• Incentives
• Close monitoring – at least monthly in person for several months to reinforce adherence and screen for side effects.
– Consider phone monitoring after several months for LTBI
Monitoring
• Monitor weight at each visit
– Usually the weight increases impressively and doses may need to be adjusted
– Failure to gain weight is concerning for:
/• Drug toxicity / side effects
• Failure to appropriately treat TB disease
• Monitor activity / energy / sleep
– Children sometimes become annoyingly more active on appropriate treatment
Pediatric Tuberculosis: The EssentialsWith Dr. Ann Loeffler
October 8, 2014
Curry International Tuberculosis Center12
Toxicity is rare in kids
• Never give more than one month of meds at a time
• No routine LFT measurements except underlying liver disease; other hepatotoxic meds, HIV, adolescent girls, alcohol use, symptoms
• Transient transaminase elevation is COMMON!
– Address ALT more than 3 x ULN if symptomatic
– Address ALT more than 5 x ULN if asymptomatic
• Most liver toxicity will occur in the first few months –but families must be able to recite the symptoms: Loss of appetite, malaise, abdominal pain, nausea and vomiting, jaundice (a later finding – don’t wait)
• Families should stop treatment and seek care if three days of these symptoms and not improving
Toxicity ‐ Treatment
• Sometimes the report of side effect actually reflects the parents’ discomfort with the diagnosis or value in treatment– Ideally, the family will share their opinions so that you can address their concerns
• Most reported side effects are trivial (to us, not to parents) and can usually be worked around with some creativity and reassurance– Try benadryl for mild, non‐urticarial rash
– Try bedtime dosing with food for stomach upset
– Avoid liquid suspension
– Consider brief drug holiday
Isoniazid Suspension
• Avoid liquid suspension except in young babies
– The commercially available product is suspended in sorbitol.
– Sorbitol is a huge molecule which pulls fluid into the intestinal lumen
– Half of older kids have stomach upset, cramping & diarrhea with liquid INH
– Babies tend to do fine (the dose is smaller) – dose needs to be adjusted frequently for weight gain
Pediatric Tuberculosis: The EssentialsWith Dr. Ann Loeffler
October 8, 2014
Curry International Tuberculosis Center13
Other Suspensions
• Avoid liquid suspension except in young babies
– Pharmacies can compound the INH (and other TB drugs) into “extemporaneous” solutions, usually with “simple syrup”with “simple syrup”
– These medications have unknown stability and poor homogeneity
– INH breaks down into hydrazine (rocket fuel component) in sugary liquid
• Suspend at the time of delivery if this is the preferred method
Medication Delivery
• Every single child is different
• Every single child / parent dynamic is different
• I like to empower the family and public health team to find the best delivery system for that y ychild and at that time
• This may mean that the parents take the lead or take the back seat
Advanced Medication Delivery
• I prefer to avoid the liquid products
• I like to teach older kids to swallow the pills or fractions of pills
• I have failed a couple of teens lately and will p yuse anxiolytics sooner in the future (or call an experienced adult clinician)
Pediatric Tuberculosis: The EssentialsWith Dr. Ann Loeffler
October 8, 2014
Curry International Tuberculosis Center14
Sandwich Technique
• My favorite system is the sandwich technique (also works for clindamycin):
– Layer soft, tasty vehicle with fragments of pills, powder from pills or capsules
• Fragments of pills have less bad taste than pulverized powder
• Some kids taste the product less if they take a popsicle first or eat some of the untainted food first
Vehicles (not trucks, boats, trains..)
• Yummy foods ‐ have to be able to swallow without mushing around in the mouth too much
– Some folks swear by Hershey’s chocolate ice icream topping
– Nutella
– Baby foods
– Jelly, maple syrup
– Whipped cream / chocolate whipped cream
– Savory foods (some kids don’t like sweet things)
• Time for questions
Pediatric Tuberculosis: The EssentialsWith Dr. Ann Loeffler
October 8, 2014
Curry International Tuberculosis Center15
Thank you for your care of the children