Pediatric TB Basics and Evaluation and Management of Exposed Neonates Ann M. Loeffler, MD Randall Children s Hospital, Portland OR & Curry International TB Center, Oakland CA September, 2017
No Disclosures Objectives: Describe the basic differences between pediatric and adult TB in order to optimize patient outcomes Assess the risk of transmission to a neonate following an exposure in a nursery / NICU and identify those who will need evaluation Evaluate a neonate for evidence of TB disease following a known exposure
Pediatric Tuberculosis Basics When it comes to tuberculosis - Children are really and truly not just small adults!
1) Young children are more likely to get disease TB infected adults have a 5 10% lifetime risk of developing TB disease (aka active TB ) Increased risk with HIV, cancer, immunosuppression, diabetes, renal failure Babies less than one year of age have a 40% chance of developing disease! The risk gradually declines until age 5 yrs Adolescents have a higher risk again The same immunocompromising conditions increase risk of TB in children as adults 9/12/2017 RANDALL CHILDREN'S HOSPITAL 4
2) Children have different radiographic abnormalities Adults commonly have apical and cavitary disease > Streaky fibrotic changes might indicate scarring Children can have disease in any lobe of the lung > 25% have more than one lobe affected Children VERY commonly have intrathoracic lymph node swelling > Perihilar, mediastinal, paratracheal, subcarinal nodes > Often seen best or confirmed on the lateral view > Can cause airway compression with post obstructive infiltrate, collapse or hyperinflation > Can erode through the airway and cause endotracheal disease / bronchogenic spread Young children are more likely to have miliary disease Children rarely have cavitary disease or pleural disease 9/12/2017 RANDALL CHILDREN'S HOSPITAL 5
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ME 9/12/2017 RANDALL CHILDREN'S HOSPITAL 8
3) Children with TB often have subtle or no symptoms Most US children with TB are asymptomatic Often identified during a contact investigation The chest x-ray findings have NO correlation with signs and symptoms If a child has no symptoms and an impressive radiograph, it s more likely that they have TB disease Infants and adolescents with TB are most likely to have signs and symptoms fever and cough 9/12/2017 RANDALL CHILDREN'S HOSPITAL 9
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4) Most young children are not contagious In general, young children are not contagious with their TB disease This is because they have few organisms in their lung lesions Most of what you see on X-ray is the immune response not lots of germs like in adult cavities There have been a few newborns with TB who have been contagious Adolescents and teenagers can be contagious 9/12/2017 RANDALL CHILDREN'S HOSPITAL 12
5) It s hard to collect sputum from children 25 50% of children have culture proven tuberculosis Older children can undergo sputum induction with 7% hypertonic saline and are taught to cough into a cup In some places, younger children inhale the aerosolized hypertonic saline and as they cough, folks thread a tube into the back of their throat and collect sputum I generally prefer gastric aspiration for young children and get about 40% yield http://www.currytbcenter.ucsf.edu/products/pediatrictuberculosis-guide-gastric-aspirate-procedure/video 9/12/2017 RANDALL CHILDREN'S HOSPITAL 13
Nicholas Loeffler in his first acting role Neutralize the specimen with bicarbonate promptly 9/12/2017 RANDALL CHILDREN'S HOSPITAL 14
6) Kids have more extrapulmonary TB 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. 9/12/2017 RANDALL CHILDREN'S HOSPITAL 15
7) It s really hard to get the meds in In the US, TB drugs don t come in kid-friendly formulations The liquid INH which is commercially made causes belly ache and diarrhea is > 50% of kids (better tolerated in babies) INH crushed into sugary liquid breaks down and is not effective 9/12/2017 RANDALL CHILDREN'S HOSPITAL 16
7) It s really hard to get the meds in Try crushed or fragmented pills / capsules layered into soft foods For babies, can put it into some breastmilk, formula or water preferably just before dosing. Put it in a small volume so they don t have to drink a whole bottle to get the dose down It doesn t dissolve well, so use a medicine dropper or med syringe with a bigger opening Try puffing in their face to elicit a swallow. http://www.currytbcenter.ucsf.edu/products/pediatric-tuberculosisonline-presentation/resources (and here on the webinar!) 9/12/2017 RANDALL CHILDREN'S HOSPITAL 17
All doses are once daily / close to the same time 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!! 9/12/2017 RANDALL CHILDREN'S HOSPITAL 18
Vitamin B 6 (pyridoxine) supplementation Not needed for most children Exceptions > Exclusively breastfed babies > HIV Infected > Milk & meat deficient diets > Symptoms of peripheral neuropathy / CNS side effects Doses (all once daily; can give with INH): > Babies ¼ of a 25 mg tablet = 6.25 mg > Toddlers ½ of a 25 mg tablet = 12.5 mg > Older kids 25 mg tablet 9/12/2017 RANDALL CHILDREN'S HOSPITAL 19
8) X-rays often get worse before they get better 9/12/2017 RANDALL CHILDREN'S HOSPITAL 20
Is she clinically improving? Is she getting the right drugs? Is she getting the right doses? Is she missing doses? Do we have the right diagnosis? 9/12/2017 RANDALL CHILDREN'S HOSPITAL 21
6 months into treatment 9/12/2017 RANDALL CHILDREN'S HOSPITAL 22
Perinatal Tuberculosis Like other infections of the newly born, TB can be > Congenital acquired in utero Hematogenous acquisition, often during maternal bacillemia Primary or disseminated TB in mom most common Tubercule can rupture into amniotic fluid and baby can swallow or inhale infected fluid into the lung > Natal acquired during the birth process Late swallowing or inhaling of amniotic fluid or urogenital secretions > Postnatal Inhalation of tubercle bacilli when mom or another caregiver has contagious pulmonary / laryngeal TB
Perinatal TB infection Much more common than congenital TB More pulmonary, miliary and disseminated disease Source case > Mother > Father > Other household > Nursery contacts High risk / rapid progression with HIV co-infection
TB Exposures Like all TB exposures, variables predict transmission > Smear / cavitary status of source case > Duration of exposure > Volume of shared air / air exchange rate / pattern > Virulence of the individual strain > Cough hygiene of the source case or aerosolizing procedures Nursery / NICU exposures > Infants with TB disease > Mother / visitor with TB disease > Health care worker with TB disease Young children with TB are not contagious > Except when they are 13 cases of < 10 yr old transmitters reported before 2006; 5 were < 1 yr of age and 3 were congenitally infected 9/12/2017 RANDALL CHILDREN'S HOSPITAL 25
Nursery Exposures - HCW 1974 Light Am Rev Resp Dis 109:415-419 > Nurse s aid with pulmonary TB 259 low risk infants skin tested / followed. None converted their TST 139 higher risk infants skin tested / treated with INH. None converted their TST 1976 Steiner Am Rev Resp Dis 113:267-72 > Nurse s aid with pulmonary TB 2 infants who had been in the nursery developed miliary TB 1647 infants skin tested / evaluated all neg TST / no evidence of disease 1978 Burk South Med J 71:7-10 > Nurse with pulmonary TB 514 infants evaluated none converted their TST or developed TB disease 9/12/2017 RANDALL CHILDREN'S HOSPITAL 26
Nursery Exposures - HCW 1998 Kim Pediatric Rad 28:836-40 > 5 Korean babies 2 3 months of age were diagnosed with culture proven TB disease > Source was likely nursery exposure 1998 Nivin Clin Infect Dis 26:303-7 > 3 of 184 exposed infants developed MDR-TB > Median hospital stay 5 days > Dx TB 4-15 months after birth > One mother also diagnosed with MDR 12 months later >? Source - HCW or non-compliant adult patient 9/12/2017 RANDALL CHILDREN'S HOSPITAL 27
Nursery Exposures - HCW 2003 CDC MMWR 12/23/2005 1280-3 > Nurse diagnosed with TB disease 78% of coworkers had prior positive TST and none tx for LTBI Remaining co workers all TST negative Extensive outreach found only 36% of 600 infants and 24 % of 900 women 5 of 227 infants were TST positive (one had received BCG) 9 of 216 women converted TST (assoc with foreign birth; not contact with RN) 2008 Ohno J Infect Chemother 14:66-71 > Nurse developed 3+ smear pos TB > 1 mother and 2 co-workers could have been infected > Babies received window prophylaxis and all TST neg 2011 Borgia Euro Surveill 16:pii=19984 > Italian nurse diagnosed with pulmonary TB > 1 infant diagnosed with TB disease > 9% of infants had positive QFT-TB; none positive TST and no TB disease 9/12/2017 RANDALL CHILDREN'S HOSPITAL 28
Nursery Exposures mother 2006 Berkowitz Infect Contr Hosp Epi 27:604-11 > HIV infected, smear negative mom diagnosed with TB disease > Decision model developed to compare use of INH prophylaxis for exposed infants with no prophylaxis > Risk of infection estimated at 1 in 1000 based on Light, Steiner, Burk, Myers and Spark reports > Prophylaxis indicated if risk of infection > 2/10,000 > $930,000 / death prevented for SAT > $21,000,000 / death prevented for DOPT
Guam Memorial Hospital Nursery Exposure Baby Algorithm And at least 8-10 weeks after exposure ended 9/12/2017 RANDALL CHILDREN'S HOSPITAL 30
Teaching Points Young children are more likely to develop TB disease if infected Young children may have no symptoms or subtle symptoms Chest radiographic changes might include airspace disease in any lobe / lymph node disease / miliary disease Young children are rarely contagious with TB It s hard to dose children with TB medicines It s hard to collect sputum from young children Children more often have extrapulmonary TB Their chest radiographs often worsen on therapy due to the immune reconstitution phenomenon
Teaching Points Gastric aspirates have great yield in babies > Gastric aspirate video and instructions Nicholas Loeffler http://www.currytbcenter.ucsf.edu/pediatric_tb/resources.cfm Consider INH prophylaxis once active disease has been ruled out (probably not necessary most of the time) Use B6 if breastfed baby INFECTION CONTROL
Teaching Points TB has been transmitted in nurseries and NICUs from: > Babies with congenital tuberculosis > Health care workers > Moms > Unknown source (? Other adult patients or visitors) Contact investigation should be customized > Multidisciplinary team convened > Closest contacts and highest risk contacts prioritized > Risk of transmission assessed based on smear positivity, cavitation, duration of symptoms, ventilation, duration of exposure, etc. > Window prophylaxis should be considered if significant risk discerned > Window prophylaxis should be continued until at least 8 10 weeks of age and the child is at least 6 months of age. THEN repeat a TST, and if negative, stop the therapy. > Watch the child monthly for signs / symptoms of TB disease or toxicity > Reinforce adherence 9/12/2017 RANDALL CHILDREN'S HOSPITAL 33
Thank you!