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 Pediatric Tuberculosis 1
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 Pediatric Tuberculosis 2
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 testing and treatment of LTBI Children AAP guidelines http://pediatrics.aappublications.org/content/114/supple ment_4/1175.full.pdf Pediatric Tuberculosis 3
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. https://archive.cdph.ca.gov/programs/tb/documents/tbcb-ca-pediatric-tb-risk-assessment.pdf Which children are most likely to develop TB disease once infected? Pediatric Tuberculosis 4
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 potentially contagious TB? Pediatric Tuberculosis 5
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) Window prophylaxis (2) Repeat TST / IGRA 8-10 weeks after source case noncontagious 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!! Pediatric Tuberculosis 6
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 findings have NO correlation with signs and symptoms Infants and adolescents are most likely to have signs and symptoms Pediatric Tuberculosis 7
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 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. Pediatric Tuberculosis 8
Enlarging nodes Scrofula Not particularly painful 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 / 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! Pediatric Tuberculosis 9
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 Pediatric Tuberculosis 10
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 Pediatric Tuberculosis 11
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) Pediatric Tuberculosis 12
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 Pediatric Tuberculosis 13
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 Isoniazid daily Isoniazid thrice weekly DOPT Children 10-20 mg/kg/dose up to 300 mg 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 mg 14.1 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 10-20 mg/kg/dose up to 600 mg Thrice wkly DOPT Pediatric Tuberculosis 14
Isoniazid (INH) dosing 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!! 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 Positive TB skin test Clinically and radiographically Treat for LTBI Other diagnosis confirmed, Course inconsistent with TB Normal Consistent with TB Collect cultures and start 4 drug TB therapy TB still possible? Reassess weekly *** Cultures only help if they are positive* Abnormal More consistent with other diagnosis Patient very stable? NO YES Consider culture collection (NO INH!!!) Treat other diagnosis Pediatric Tuberculosis 15
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 Pediatric Tuberculosis 16
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 nonsugary 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 Pediatric Tuberculosis 17
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 10 year old Ethiopian adoptee MDR-TB KH head CT Pediatric Tuberculosis 18