2. Tuberculosis August 17, 2010

5. Tuberculosis Mycobacterium tuberculosis – Fastidious, aerobic, acid-fast bacillus Tremendous increase in incidence over 25 yrs On average, adult pts infect 8 to 15 individuals prior to being diagnosed Increased risk – HIV, diabetes, renal failure – 9% of pts in US coinfected with HIV

6. Three Groups Exposed, but status unknown – Insufficient period of time to rely on TST Latent TB Infection – Positive TST but no signs or symptoms, nl CXR – 30% global population – 5-10% progress to disease TB Disease – Clinical or radiographic findings – Reportable

7. Resistance Drug-resistant TB (DR-TB) – Relapse after tx – Positive sputum smear after 2mos tx Multidrug-resistant TB (MDR-TB) – Resistance to at least 2 first line abx (1% in US) Extensively drug-resistant TB – Resistance to INH, rifampin, any fluoroquinolone, and any second line IV agent

8. Pathogenesis Lymphadenitis Ghon complex – Focus of infection with enlarged regional nodes Contained Spread rapidly Reactivated later in life Most clinical manifestations in children 1-2 yrs from initial infection

9. Clinical Manifestations Lung is most common site of infxn (80%) Tuberculous LAD (67%) Meningitis (13%) – Most commonly infants and toddlers Pleural, miliary, skeletal account for <6%

10. Pulmonary Disease Primary Parenchymal – Most common, Infants most likely to be symptomatic Cough, low-grade fever, wt loss – CXR: hilar or mediastinal adenopathy Collapse-consolidation pattern Progressive Primary Disease – Lung tissue destruction and cavitary lesion Reactivation disease – Immunocompromised adolescents or adults

12. Lymphatic Disease Most common extrapulmonary form of TB Usually cervical nodes Slightly older than pts with nontuberculous mycobacterial LAD 2-4cm, may have overlying violaceous skin color – Lack classic findings of pyogenic nodes CXR abnl in 33% Tx: 6 mos multidrug tx, +/- excision

13. CNS Disease 50% are <2y/o May include CNS vasculitis or increased ICP – Consider in cases of childhood stroke Tuberculomas in 5% of CNS TB – Single rim-enhancing lesion CSF: lymphocytes, low glucose, high protein TST in only 33% CXR in 90% Highest morbidity/mortality

17. Diagnosis TST, epidemiologic info, clinical/radiographic findings Children: vigorous response to few organisms – 30% with positive cx (AFB) TST (purified protein derivative or Mantoux) – Read at 48-72hrs – Delayed hypersensitivity rxn in those exposed – Negative in 15% of cases Interferon-gamma release assay (IGRA) Use CXR, CT not routine

20. Treatment TB Exposure – Contact with index case, but asymptomatic, neg TST and CXR – If < 4y/o or immunocompromised INH pending results of repeat TST (2-3 mos) LTBI – INH for 9mos – If intermittently dosed, used Directly Observed Tx

21. Treatment TB Disease – 4 drug Directly Observed Therapy – INH, rifampin, pyrazinamide, ethambutol – 6 months – If CNS involvement, 9-12 mos

22. What about infant of TB mom? Maternal LTBI… no workup or isolation for infant Maternal positive TST and CXR abnl but not consistent with TB – Maternal AFB sputum smear neg – No isolation or workup for infant – Tx maternal LTBI

23. What about infant of TB mom? Mom with CXR consistent with TB – Evaluate infant for TB CXR and PE – If infant is normal Separate from mother until she is being treated and infant starts INH Once on INH, separation unnecessary and may breastfeed

24. Health Care Workers Positive TST with normal CXR – Offer therapy for LTBI – Repeat screening should be done with CXR, not TST

25. Prevention Negative pressure and N95 use in children – Cavitary or extensive pulmonary involvement – AFB positive TB – Procedures such as intubation/bronchoscopy BCG vaccine in US – Children continually exposed to MDR-TB – Continually exposed to adults who have infectious TB who cannot be removed from setting