- Pulmonary tuberculosis is caused by infection with Mycobacterium tuberculosis or Mycobacterium bovis bacteria. It is transmitted through inhalation of droplets from an infected person. - Diagnosis involves the Mantoux tuberculin skin test, sputum smears and cultures, and chest x-rays. Treatment depends on whether a person has latent infection, active disease, or a history of previous treatment. - For new cases of active pulmonary TB, treatment typically involves two months of four drugs followed by four months of two drugs. For latent infection, nine months of isoniazid is usually recommended. Preventive therapy aims to reduce the risk of developing active TB in the future.

1. Pulmonary Tuberculosis in Childhood 2010 http://crisbertcualteros.page.tl

2. Pulmonary Tuberculosis Etiology: 1.1 Mycobacterium tuberculosis 1.2 Mycobacterium bovis , rarely

3. Epidemiology WHO: > 2 Billion are infected with TB worldwide : 1.77M died from TB in 2007 Person w/ TB Disease infect 10-15 people/year WHO: Philippines is among the 22 high burden countries for TB is the 6th leading cause of illness and the 6th leading cause of deaths among Filipinos. Mostly: 15-54 years old

4. Mode of transmission: Inhalation of droplet nuclei by coughing, sneezing & talking Occ’l: ingestion of contaminated milk (M. bovis) Direct contamination of open wounds

5. Period of communicability: Children with active PTB are rarely contagious because of the nature of pulmonary lesion, the low bacterial output and sputum is often swallowed. A patient is non-infectious within 2-4 weeks of starting adequate therapy

6. Risk Factors Age: < 5 years old Household contact w/ newly dx smear (+) case HIV infection Immunocompromised state (severe malnutrition)

7. Portal of Entry Usually respiratory tract (inhalation of aerosolized particles containing 1-3 tubercle bacilli) Rarely: skin, GIT, mucous membrane, transplacentally from mother to fetus or via infected amniotic fluid

8. Incubation Period From 3weeks to 3 months

9. CLASSIFICATION Class I (TB exposure) (+) exposure (-) Mantoux tuberculin test (-) signs and symptoms suggestive of TB (-) chest radiograph

10. CLASSIFICATION Class II (TB infection) (±) exposure (+) Mantoux tuberculin test (-) signs and symptoms suggestive of TB (-) chest radiograph

11. CLASSIFICATION Class III (TB disease) three /more of the ff. criteria: (+) HX of exposure to an active TB disease pt. (+) Mantoux tuberculin test (+) s/s suggestive of TB Cough/wheezing > 2 weeks; fever > 2 weeks Painless cervical and/or other LAD Poor weight gain; failure to return to normal after an infection or failure to respond to approriate antibiotic therapy Abnormal Chest radiograph Laboratory findings suggestive of TB (histological, cytological, biochemical, immunological or molecular)

12. CLASSIFICATION Class IV (TB inactive) A child/adolescent with/without previous TB and any of the ff: (±) previous chemotherapy (+) radiographic evidence of healed/calcified TB (+) Mantoux tuberculin test (-) signs and symptoms suggestive of TB (-) smear/culture for M. tuberculosis

13. Clinical Forms of Tuberculosis Pulmonary/Intrathoracic TB Asymptomatic / Latent infection: Primary TB/primary complex Primary focus, lymphangitis and regional lymphadenitis Most common clinical symptoms Non-productive cough Mild dyspnea Cervical lymphadenopathies

14. Clinical Forms of Tuberculosis Pleurisy with effusion Accompanies primary focus Considered a component of the primary complex Onset: abrupt Fever, chest pain, shortness of breath Dullness to flatness and diminished breath sounds Obliteration of costophrenic sulcus on CXR (minimal) Layering of fluid density (moderate effusion) Occupy one hemithorax (massive effusion)

15. Clinical Forms of Tuberculosis Progressive primary tuberculosis More severe fever, malaise, cough, weight loss Classical signs of cavitation Crepitant rales, diminished breath sounds, lymphadenopathy Endobronchial TB Bronchial obstruction due to enlargement of peribronchial lymph nodes Sudden death by asphyxia Emphysema Atelectasis

16. Clinical Forms of Tuberculosis Miliary TB Generalized hematogenous tuberculosis due to massive invasion of the blood stream by the tubercle bacilli Arises from a discharge of a caseous focus often from a lymph node into the pulmonary vein High fever, cough, dyspnea Crepitant rales, splenomagaly, hepatomegaly, signs of meningeal irritation CXR: millet seed densities all over the lung fields

17. Clinical Forms of Tuberculosis Chronic TB Reinfection or adult TB Apical or infraclavicular infiltrates often with cavitation and no hilar lymphadenopathy Persistent cough, prlonged fever, chest pain, hemoptysis and supraclavicular adenitis Tuberculoma Pericardial TB: due to direct spread from the mediastinal glands

18. Clinical Forms of Tuberculosis Extrapulmonary TB TB of the cervical lymph nodes/Scrofula Involved LN are painless, firm, discrete, movable becoming adherent to each other and anchored to the surrounding tissues and skin as they enlarge Scofuloderma (when left untreated and ruptures resulting in a draining sinus tract TB of the CNS TB meningitis TB abscess

19. Clinical Forms of Tuberculosis Skeletal TB TB of the bones and joints TB of the spine or Pott’s Gastrointestinal TB TB enteritis TB peritonitis Hepatobiliary TB TB of the pancreas Cutaneous TB Ocular TB GUT TB TB of the Middle Ear

20. Diagnostic Tests Mantoux Test/Tuberculin skin test Standard method for screening (+) if ≥ 10 mm induration size, regardless of BCG status (+) if ≥ 5mm plus hx of close contact with TB, clinical findings suggestive of TB, CXR suggestive of TB & immunocompromised conditions (+) if ≥ 15mm for population with no risk factors A dose of 0.1 ml of 2-TU PPD-RT23/ 0.1 ml of 5-TU PPD-S Provides a general measure of a person’s cellular response

21. Diagnostic Tests Mantoux Testing/Tuberculin skin test Features of reaction Delayed course reaching a peak of more than 24h after injection of antigen Indurated character Occasional vesiculation and necrosis A pale wheal of 6 to 10mm in diameter should be evident after injection Read within 48-72hrs from the time of administration

22. Diagnostic Tests Mantoux Testing/Tuberculin skin test False positive Nontuberculous mycobacteria BCG vaccination Reaction develops 6-12 weeks after vaccination Wanes after 5 years from immunization False negative Anergy Very young age (< 6 months) Recent TB infection or overwhelming TB disease Live-virus vaccination postpone for at least 4 – 6 weeks after immunization or do it on the same day of vaccination

23. Diagnostic Tests AFB smears Provides presumptive DX of active TB Gives a quantitative estimation of bacilli on the smear Implies infectiousness of the patient Low sensitivity (51.8 – 53.1%) High specificity (97.5 – 99.8%) 10 4 bacilli/ml of sputum : lowest concentration that can be detected

24. Diagnostic Tests Culture : gold standard Solid media: 4-6 wks for isolation 2-4 wks for susceptibility testing Liquid media Bactec : as few as 7 to 10 days; carbon-14 (marker of bacterial growth) Middlebrook broth Septi-check AFB

25. Diagnostic Tests Specimens used for demonstration of tubercle bacilli: Sputum for older children able to expectorate Series of three early morning specimens on different days before starting chemotherapy Make sure brought up from the lungs

26. Diagnostic Tests Gastric aspirate For infants and children who cannot expectorate even with aerosol inhalation 5-10 ml of gastric contents aspirated early in the morning after the person has fasted for at least 8 – 10 hours preferably before the child arises and peristalsis empties the stomach of respiratory secretions swallowed overnight

27. Diagnostic Tests Bronchial washings Urine First morning-voided midstream specimen Other body fluids and tissues Bone marrow, lung and liver biopsy in patients with hematogenous spread/disseminated disease must be considered

28. Diagnostic Tests Radiographic Findings No pathognomonic findings in childhood TB Lateral projections are important wherein partially calcified mediastinal nodes may be visible Most common cause of calcification in children Uniform stippling of both lungs found in miliary tuberculosis Lobar or lobular consolidations Common findings: Enlarged retrocardiac lymphadenopathy (70%), hilar adenopathy with pulmonary infiltrates (20%), and pleural effusion

29. Initial Empiric Therapy of Tuberculosis in Infants, Children and Adolescents Category Regimen Remarks Class I (TB Exposure) <5 years > 5 years 3 months INH Immediate prophylaxis controversial for those > 5 years, but is recommended by some experts specially if with risk factors e.g. malnutrition, immunocompromised states.

30. Initial Empiric Therapy of Tuberculosis in Infants, Children and Adolescents Extrapulmonary Severe, life-threatening disease: disseminated/ miliary, meningitis, bone/joint disease Other extrapulmonary sites 2 months HRZ + E or S ffd by 10 months HR ± E/S given once daily or as DOT 3x weekly Same regimen as pulmonary disease Corticosteroids (usually prednisone at 1 mkday for 6-8 weeks with gradual tapering) beneficial for the following: meningitis, pericarditis, pleuritis, endobronchial TB, miliary TB

31. Initial Empiric Therapy of Tuberculosis in Infants, Children and Adolescents Class II TB infection PPD conversion within past 1-2 years, (-) CXR PPD (+) not due to BCG,(-)CXR, (-) previous treatment PPD(+)w/ stable healed lesion, (-) previous treatment 9 months INH 9 months INH 9 months INH In the presence of primary INH resistance, use Rifampicin

32. Initial Empiric Therapy of Tuberculosis in Infants, Children and Adolescents Class II TB infection PPD (+) with stable / healed lesion, (+) previous treatment, at risk of reactivation due to: Measles, pertussis, etc Conditions/drugs inducing immunosuppression (IDDM leukemia chronic dialysis) HIV infection/ persons at risk for infection but HIV status unknown 1-2 mos For the duration of immunosup-pression 12 Months INH

33. Initial Empiric Therapy of Tuberculosis in Infants, Children and Adolescents Class III (active TB Disease) New smear (-)PTB Less form of extra PTB New smear(+) PTB New smear(-) PTB w/ extensive parenchymal involvement Severe extrapulmonary TB Severe concomitant HIV disease TB Meningitis Bone joint TB Intensive 2 months HRZ once daily 2HRZE 2HRZS 2hrzs Continuation 4 months HR given once daily or 6 months HE 4HR or 6HE 4HR 7-10 HR

34. Class III (active TB Disease) Previously treated smear(+) PTB; relapse tx after interruptiontx failure Chronic MDR and XDR - TB Intensive 2HRZES/ 1HRZE Specially designed/ standardized regimens Continuation 5HRE

35. Algorithm for Preventive Therapy of Childhood Tuberculosis TB Exposure Class I yes <5years old Start INH for 3 months No Repeat Mantoux test Yes Radiologic findings Yes After 3 months(+) and /or, signs/symptoms TB Disease No suggestive of TB Multiple Drug Tx Discontinue INH NO If no BCG scar, Give BCG after 2 weeks Latent TB Infection Continue > 6 INH

36. Source: PPS Tuberculosis in Infancy and Childhood 3 rd Edition 2010 Salamat….