Screening and Treating Pediatric TB

1. Screening and Treating Pediatric TB David Hilmers, MD January 9, 2006

2. Epidemiology • Worldwide • 8 million new cases (all ages) each year • 3 million deaths per year • US • 1000 kids develop active TB each year • Highest rates in minorities • Texas is among highest states for new cases

3. Stages of TB • 1. Exposure • Contact with someone with pulmonary TB • Asx and has negative PPD • 2. Latent infection • TB present only in lungs • Asx • CXR with only calcifications/granulomas • Positive PPD • 3. TB disease • Clinical manifestations • Radiographic evidence of disease

4. Transmission • Spread via respiratory route when someone with TB sneezes, laughs, talks • Kids get TB from adults and are less contagious because of lower TB burden • After growing in alveolar macrophages, 103 –104 organisms needed for + PPD • Spread via lymphatics to lymph nodes and to distant sites through bloodstream • If intact cellular immunity, spread is limited by production of granulomas = latent TB infection

5. Latent Infection • 40% of infants develop TB disease within 2-12 months after initial infection • Targeted PPD testing recommended now • Risk factors include: • Foreign traveler, immigrant • Exposure to high-risk individual or one with TB • Consuming raw milk or unpasteurized cheese • Living in jail or shelter • Having been exposed to HIV-positive person or drug user

6. Latent Infection Diagnosis • Medical history for sxs and exposures; attempt to find source case • PEX for signs of disease and CXR • Gastric aspirates in early am x 3 • TB skin test still best method (sensitivity 80-96%) • Shows delayed hypersensitivity reaction induced by antigenic components of M. TB • Interpretation of results (next slide)

8. Treatment of Latent TB • INH drug of choice if susceptible or susceptibility unknown • Evaluate for risk factors for INH-induced hepatitis, LFT’s NOT necessary • Daily rifampin is acceptable if sensitive and if INH not tolerated or INH resistance • B6 not needed unless there is risk factor for B6 deficiency (diabetes, uremia, HIV, alcoholism, low B6 in diet) or if breastfeeding • What is the duration of treatment? • 9 months

9. TB disease • Test high-risk kids with PPD, 10% of immunocompetent kids with dz have false neg • TB of superficial lymph nodes is most common extrapulmonary manifestation • Fever is common but other systemic signs are often absent • CXR may show LAD, atelectasis, consolidation, densities, effusions or mass • Cavities are rare • Try to isolate by gastric aspirates but yield is only 50%

11. Clinical Forms • Pulmonary • Disseminated most commonly miliary TB with massive release of bacilli into blood affecting at least 2 organs • CNS TB from formation of caseous granulomas in cerebral cortex during lymphohematogenous dissemination • Skeletal TB (Pott’s if in spine) also from lymphohematogenous dissemination

13. Treatment • Drug susceptible • 2 months of INH, RIF, and PZA • 4 months of INH and RIF qD or twice weekly • If areas of low-resistance • 1 month of INH and RIF daily • 8 months of INH and RIF qD or twice weekly • Extrapulmonary TB treated the same except tuberculous meningitis • TB meningitis • 2 months INH, RIF, PZA, and either ethambutol or streptomycin • 7-10 months INH and RIF qD or twice weekly

14. Treatment Complications • Few side effects, most common is hepatotoxicity from INH • NO LFT’s needed at baseline unless sxs develop (abdominal pain, icterus, e.g.) or if coexisting conditions (HIV, drug abuse) or hepatotoxic meds (anticonvulsants) • INH can cause peripheral neuropathy, neuritis, ataxia, seizures • RIF can cause hepatitis and may inhibit effectiveness of OCP’s, should use alternate form of birth control • Streptomycin affects the vestibular and auditory portions of 8th cranial nerve • Ethambutol can cause optic neuritis

15. But I’ve had the BCG vaccine! • 16 yo female from Guatemala presents with fever, cough, and malaise for several weeks. You are concerned about pulmonary TB. Her shot record indicates she received the BCG vaccine. Do you place a PPD on this patient? • Yes

16. BCG Vaccination • Attenuated strain of M. bovis • Used world-wide except in US • Efficacy is 52%, seemingly more effective in extrapulmonary TB • Given in US only if negative PPD and cannot be treated for LTBI but are at high risk of continuous exposure to TB • In patients who have had BCG vaccine, PPD should be interpreted similarly to those who have not been vaccinated

17. Case 1 • A 9 month old male, born in the US to a family from Mexico, has been visiting his grandmother who has been recently dx’d with pulmonary TB. • He is asymptomatic, has a normal exam. His PPD and CXR are negative. • Does he require any further testing? • Yes, repeat PPD in 12 weeks. After exposure, it can take 2-12 weeks for bacteria to grow to significant levels to cause an immune response/PPD conversion

18. Case 2 - Serial Testing • 2a - 26 yo intern had a PPD placed but missed his/her f/u for reading due to falling asleep post-call. The intern did take note that the test was negative. They return to Occupational Health the next week to have the PPD placed again. Can serial TB testing induce a positive PPD? • Depends…did the intern have a past positive ppd.

19. Booster Effect • PPD skin sensitivity persists throughout life • Over time, the size of the skin test can decrease and may disappear. • If a PPD comes back small or absent in a previously infected person, then there can be an accentuation of a response on repeat testing. • This can be misinterpreted as a skin test conversion if the history is not correctly taken. • Repeated testing on persons with no cellular immunity to the antigens in PPD will not induce a conversion.

20. How well do you know TB? • What does PPD stand for? • purified protein derivative • What does BCG stand for? • bacillus Calmette-Guerin - named after the two French investigators who developed the vaccine