Pediatric Tuberculosis: The Essentials 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 1
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 2
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 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 3
US Pediatric TB Cases by Case Verification Criterion*, 1993 2012 N=19,840 Provider Diagnosis 23% Laboratory Confirmed 26% Clinical Case 51% *Based on the public health surveillance definition for TB [MMWR 1997:46(No. RR-10):40-41] US Pediatric TB Cases by Case Verification Criterion by Age Group, 1993 2012 Age < 1 23% n=1,992 N=19,840 Age 1 4 25% n=9,692 20% 51% 26% 54% Age 5 9 n=4,474 Age 10 14 n=3,682 24% 16% 16% 37% 60% 46% Laboratory Confirmed Clinical Case Provider Diagnosis 4
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 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 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 thickening Most peribronchial thickening Most hilar fullness not confirmed on lateral 5
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 6
Paratracheal node Treat for LTBI Other diagnosis confirmed, Course inconsistent with TB Clinically and radiographically Normal Consistent with TB Positive TB skin test Abnormal More consistent with other diagnosis Collect cultures and Patient t very stable? start 4 drug TB therapy NO YES TB still possible? Reassess weekly *** Cultures only help if they are positive* Consider culture collection (NO INH!!!) Treat other diagnosis 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 7
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 pansusceptible M 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 8
Pediatric TB Drug Dosing Drugs Dosage forms Daily dose mg/kg Isoniazid Rifampin Tablets 100 & 300 mg; Syrup 10mg/ml Capsules 150 & 300 mg; Syrup; IV Twice weekly dose Maximum dose 10 15 mg/kg 20 30 mg/kg Daily 300mg Twice weekly DOT 900 mg 10 20 mg/kg 10 20 mg/kg 600 mg Pyrazinamide Tablets 500 mg 30 40 mg/kg 50 mg/kg 2000 mg Ethambutol Tablets 100, 20 mg/kg 50 mg/kg 2500 mg 400 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 drugs Vitamin i B 6 supplementation ti is probably bbl 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 9
LTBI Latent TB Infection LTBI M tuberculosis complex infection positive TST or IGRA result, no physical findings of disease, 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 DOT Rifampin / pyrazinamide for 2 months LTBI Treatment Never start LTBI treatment until TB disease is ruled out This is not always comfortable Collect cultures, evaluate contacts t and start t multidrug treatment if you can t wait http://www.currytbcenter.ucsf.edu/pediatric_tb/ Two months of 4 drugs is treatment for LTBI 10
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 11
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 12
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 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 child 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 use anxiolytics sooner in the future (or call an experienced adult clinician) 13
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 cream topping Nutella Baby foods Jelly, maple syrup Whipped cream / chocolate whipped cream Savory foods (some kids don t like sweet things) Time for questions 14
Thank you for your care of the children 15