Tuberculosis in Infancy & Chidhood


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Tuberculosis in Infancy & Chidhood
PPS guideline on TB in Infancy & Childhood 3rd edition 2010

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  • While it is considered a disease of the urban poor today, tuberculosis has claimed the lives of numerous noted personalities around the world through the centuries. The most famous Filipino who contracted and later died of tuberculosis is probably Manuel L. Quezon, the first President of the Philippine Commonwealth. According to the WHO, >2 Billion people – one third of the world’s total population – are infected with TB bacilli. One in every 10 of those people will become sick with active TB in his lifetime. A total of 1.77 million people died from TB in 2007 (including 456,000 people with HIV), equal to about 4,800 deaths a day. The Philippines is among the 22 high burden countries for tuberculosis, according to the WHO. TB is the 6th leading cause of illness and the 6th leading cause of deaths among Filipinos. According to the 2nd National Prevalence Survey done in 1997, most TB patients belong to the economically productive age-group (15-54 years old).
  • When the infectious droplet nuclei are inhaled & reached the terminal air passages.
  • The time bet entry & the development of tissue hypersensitivity manifested as reactive tuberculin skin test
  • Establishing a definite dx of childhood TB is difficult because specimens are hard to obtain& contain few mycobacteria leading to delays in treatment or overdiagnosis.
  • Tuberculosis in Infancy & Chidhood

    1. 1. Pulmonary Tuberculosis in Childhood 2010 <ul><li> </li></ul>
    2. 2. Pulmonary Tuberculosis <ul><li>Etiology: </li></ul><ul><li>1.1 Mycobacterium tuberculosis </li></ul><ul><li>1.2 Mycobacterium bovis , rarely </li></ul>
    3. 3. Epidemiology <ul><li>WHO: > 2 Billion are infected with TB worldwide </li></ul><ul><li> : 1.77M died from TB in 2007 </li></ul><ul><li>Person w/ TB Disease infect 10-15 people/year </li></ul><ul><li>WHO: </li></ul><ul><li>Philippines is among the 22 high burden countries for TB </li></ul><ul><li>is the 6th leading cause of illness and the 6th leading cause of deaths among Filipinos. </li></ul><ul><li>Mostly: 15-54 years old </li></ul>
    4. 4. Mode of transmission: <ul><li>Inhalation of droplet nuclei by coughing, sneezing & talking </li></ul><ul><li>Occ’l: ingestion of contaminated milk (M. bovis) </li></ul><ul><li>Direct contamination of open wounds </li></ul>
    5. 5. Period of communicability: <ul><li>Children with active PTB are rarely contagious because of the nature of pulmonary lesion, the low bacterial output and sputum is often swallowed. </li></ul><ul><li>A patient is non-infectious within 2-4 weeks of starting adequate therapy </li></ul>
    6. 6. Risk Factors <ul><li>Age: < 5 years old </li></ul><ul><li>Household contact w/ newly dx smear (+) case </li></ul><ul><li>HIV infection </li></ul><ul><li>Immunocompromised state (severe malnutrition) </li></ul>
    7. 7. Portal of Entry <ul><li>Usually respiratory tract (inhalation of aerosolized particles containing 1-3 tubercle bacilli) </li></ul><ul><li>Rarely: skin, GIT, mucous membrane, transplacentally from mother to fetus or via infected amniotic fluid </li></ul>
    8. 8. Incubation Period <ul><li>From 3weeks to 3 months </li></ul>
    9. 9. CLASSIFICATION <ul><li>Class I (TB exposure) </li></ul><ul><ul><ul><li>(+) exposure </li></ul></ul></ul><ul><ul><ul><li>(-) Mantoux tuberculin test </li></ul></ul></ul><ul><ul><ul><li>(-) signs and symptoms suggestive of TB </li></ul></ul></ul><ul><ul><ul><li>(-) chest radiograph </li></ul></ul></ul>
    10. 10. CLASSIFICATION <ul><li>Class II (TB infection) </li></ul><ul><ul><ul><li>(±) exposure </li></ul></ul></ul><ul><ul><ul><li>(+) Mantoux tuberculin test </li></ul></ul></ul><ul><ul><ul><li>(-) signs and symptoms suggestive of TB </li></ul></ul></ul><ul><ul><ul><li>(-) chest radiograph </li></ul></ul></ul>
    11. 11. CLASSIFICATION <ul><li>Class III (TB disease) </li></ul><ul><ul><li>three /more of the ff. criteria: </li></ul></ul><ul><ul><ul><li>(+) HX of exposure to an active TB disease pt. </li></ul></ul></ul><ul><ul><ul><li>(+) Mantoux tuberculin test </li></ul></ul></ul><ul><ul><ul><li>(+) s/s suggestive of TB </li></ul></ul></ul><ul><ul><ul><ul><li>Cough/wheezing > 2 weeks; fever > 2 weeks </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Painless cervical and/or other LAD </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Poor weight gain; failure to return to normal after an infection or failure to respond to approriate antibiotic therapy </li></ul></ul></ul></ul><ul><ul><ul><li>Abnormal Chest radiograph </li></ul></ul></ul><ul><ul><ul><li>Laboratory findings suggestive of TB (histological, cytological, biochemical, immunological or molecular) </li></ul></ul></ul>
    12. 12. CLASSIFICATION <ul><li>Class IV (TB inactive) </li></ul><ul><ul><li>A child/adolescent with/without previous TB and any of the ff: </li></ul></ul><ul><ul><ul><li>(±) previous chemotherapy </li></ul></ul></ul><ul><ul><ul><li>(+) radiographic evidence of healed/calcified TB </li></ul></ul></ul><ul><ul><ul><li>(+) Mantoux tuberculin test </li></ul></ul></ul><ul><ul><ul><li>(-) signs and symptoms suggestive of TB </li></ul></ul></ul><ul><ul><ul><li>(-) smear/culture for M. tuberculosis </li></ul></ul></ul>
    13. 13. Clinical Forms of Tuberculosis <ul><li>Pulmonary/Intrathoracic TB </li></ul><ul><ul><li>Asymptomatic / Latent infection: </li></ul></ul><ul><ul><li>Primary TB/primary complex </li></ul></ul><ul><ul><ul><li>Primary focus, lymphangitis and regional lymphadenitis </li></ul></ul></ul><ul><ul><ul><li>Most common clinical symptoms </li></ul></ul></ul><ul><ul><ul><ul><li>Non-productive cough </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Mild dyspnea </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Cervical lymphadenopathies </li></ul></ul></ul></ul>
    14. 14. Clinical Forms of Tuberculosis <ul><ul><li>Pleurisy with effusion </li></ul></ul><ul><ul><ul><li>Accompanies primary focus </li></ul></ul></ul><ul><ul><ul><li>Considered a component of the primary complex </li></ul></ul></ul><ul><ul><ul><li>Onset: abrupt </li></ul></ul></ul><ul><ul><ul><li>Fever, chest pain, shortness of breath </li></ul></ul></ul><ul><ul><ul><li>Dullness to flatness and diminished breath sounds </li></ul></ul></ul><ul><ul><ul><li>Obliteration of costophrenic sulcus on CXR (minimal) </li></ul></ul></ul><ul><ul><ul><li>Layering of fluid density (moderate effusion) </li></ul></ul></ul><ul><ul><ul><li>Occupy one hemithorax (massive effusion) </li></ul></ul></ul>
    15. 15. Clinical Forms of Tuberculosis <ul><ul><li>Progressive primary tuberculosis </li></ul></ul><ul><ul><ul><li>More severe fever, malaise, cough, weight loss </li></ul></ul></ul><ul><ul><ul><li>Classical signs of cavitation </li></ul></ul></ul><ul><ul><ul><li>Crepitant rales, diminished breath sounds, lymphadenopathy </li></ul></ul></ul><ul><ul><li>Endobronchial TB </li></ul></ul><ul><ul><ul><li>Bronchial obstruction due to enlargement of peribronchial lymph nodes </li></ul></ul></ul><ul><ul><ul><ul><li>Sudden death by asphyxia </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Emphysema </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Atelectasis </li></ul></ul></ul></ul>
    16. 16. Clinical Forms of Tuberculosis <ul><ul><li>Miliary TB </li></ul></ul><ul><ul><ul><li>Generalized hematogenous tuberculosis due to massive invasion of the blood stream by the tubercle bacilli </li></ul></ul></ul><ul><ul><ul><li>Arises from a discharge of a caseous focus often from a lymph node into the pulmonary vein </li></ul></ul></ul><ul><ul><ul><li>High fever, cough, dyspnea </li></ul></ul></ul><ul><ul><ul><li>Crepitant rales, splenomagaly, hepatomegaly, signs of meningeal irritation </li></ul></ul></ul><ul><ul><ul><li>CXR: millet seed densities all over the lung fields </li></ul></ul></ul>
    17. 17. Clinical Forms of Tuberculosis <ul><ul><li>Chronic TB </li></ul></ul><ul><ul><ul><li>Reinfection or adult TB </li></ul></ul></ul><ul><ul><ul><li>Apical or infraclavicular infiltrates often with cavitation and no hilar lymphadenopathy </li></ul></ul></ul><ul><ul><ul><li>Persistent cough, prlonged fever, chest pain, hemoptysis and supraclavicular adenitis </li></ul></ul></ul><ul><ul><li>Tuberculoma </li></ul></ul><ul><ul><li>Pericardial TB: due to direct spread from the mediastinal glands </li></ul></ul>
    18. 18. Clinical Forms of Tuberculosis <ul><li>Extrapulmonary TB </li></ul><ul><ul><li>TB of the cervical lymph nodes/Scrofula </li></ul></ul><ul><ul><ul><li>Involved LN are painless, firm, discrete, movable becoming adherent to each other and anchored to the surrounding tissues and skin as they enlarge </li></ul></ul></ul><ul><ul><ul><li>Scofuloderma (when left untreated and ruptures resulting in a draining sinus tract </li></ul></ul></ul><ul><ul><li>TB of the CNS </li></ul></ul><ul><ul><ul><li>TB meningitis </li></ul></ul></ul><ul><ul><ul><li>TB abscess </li></ul></ul></ul>
    19. 19. Clinical Forms of Tuberculosis <ul><ul><li>Skeletal TB </li></ul></ul><ul><ul><ul><li>TB of the bones and joints </li></ul></ul></ul><ul><ul><ul><li>TB of the spine or Pott’s </li></ul></ul></ul><ul><ul><li>Gastrointestinal TB </li></ul></ul><ul><ul><ul><li>TB enteritis </li></ul></ul></ul><ul><ul><ul><li>TB peritonitis </li></ul></ul></ul><ul><ul><ul><li>Hepatobiliary TB </li></ul></ul></ul><ul><ul><ul><li>TB of the pancreas </li></ul></ul></ul><ul><ul><li>Cutaneous TB </li></ul></ul><ul><ul><li>Ocular TB </li></ul></ul><ul><ul><li>GUT TB </li></ul></ul><ul><ul><li>TB of the Middle Ear </li></ul></ul>
    20. 20. Diagnostic Tests <ul><li>Mantoux Test/Tuberculin skin test </li></ul><ul><ul><li>Standard method for screening </li></ul></ul><ul><ul><li>(+) if ≥ 10 mm induration size, regardless of BCG status </li></ul></ul><ul><ul><li>(+) if ≥ 5mm plus hx of close contact with TB, clinical findings suggestive of TB, CXR suggestive of TB & immunocompromised conditions </li></ul></ul><ul><ul><li>(+) if ≥ 15mm for population with no risk factors </li></ul></ul><ul><ul><li>A dose of 0.1 ml of 2-TU PPD-RT23/ 0.1 ml of 5-TU PPD-S </li></ul></ul><ul><ul><li>Provides a general measure of a person’s cellular response </li></ul></ul>
    21. 21. Diagnostic Tests <ul><li>Mantoux Testing/Tuberculin skin test </li></ul><ul><ul><li>Features of reaction </li></ul></ul><ul><ul><ul><li>Delayed course reaching a peak of more than 24h after injection of antigen </li></ul></ul></ul><ul><ul><ul><li>Indurated character </li></ul></ul></ul><ul><ul><ul><li>Occasional vesiculation and necrosis </li></ul></ul></ul><ul><li>A pale wheal of 6 to 10mm in diameter should be evident after injection </li></ul><ul><li>Read within 48-72hrs from the time of administration </li></ul>
    22. 22. Diagnostic Tests <ul><li>Mantoux Testing/Tuberculin skin test </li></ul><ul><ul><li>False positive </li></ul></ul><ul><ul><ul><li>Nontuberculous mycobacteria </li></ul></ul></ul><ul><ul><ul><li>BCG vaccination </li></ul></ul></ul><ul><ul><ul><ul><li>Reaction develops 6-12 weeks after vaccination </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Wanes after 5 years from immunization </li></ul></ul></ul></ul><ul><ul><li>False negative </li></ul></ul><ul><ul><ul><li>Anergy </li></ul></ul></ul><ul><ul><ul><li>Very young age (< 6 months) </li></ul></ul></ul><ul><ul><ul><li>Recent TB infection or overwhelming TB disease </li></ul></ul></ul><ul><ul><ul><li>Live-virus vaccination </li></ul></ul></ul><ul><ul><ul><ul><li>postpone for at least 4 – 6 weeks after immunization or do it on the same day of vaccination </li></ul></ul></ul></ul>
    23. 23. Diagnostic Tests <ul><li>AFB smears </li></ul><ul><ul><li>Provides presumptive DX of active TB </li></ul></ul><ul><ul><li>Gives a quantitative estimation of bacilli on the smear </li></ul></ul><ul><ul><li>Implies infectiousness of the patient </li></ul></ul><ul><ul><li>Low sensitivity (51.8 – 53.1%) </li></ul></ul><ul><ul><li>High specificity (97.5 – 99.8%) </li></ul></ul><ul><ul><li>10 4 bacilli/ml of sputum : lowest concentration that can be detected </li></ul></ul>
    24. 24. Diagnostic Tests <ul><li>Culture : gold standard </li></ul><ul><ul><li>Solid media: </li></ul></ul><ul><ul><ul><li>4-6 wks for isolation </li></ul></ul></ul><ul><ul><ul><li>2-4 wks for susceptibility testing </li></ul></ul></ul><ul><ul><li>Liquid media </li></ul></ul><ul><ul><ul><li>Bactec : as few as 7 to 10 days; carbon-14 (marker of bacterial growth) </li></ul></ul></ul><ul><ul><ul><li>Middlebrook broth </li></ul></ul></ul><ul><ul><ul><li>Septi-check AFB </li></ul></ul></ul>
    25. 25. Diagnostic Tests <ul><li>Specimens used for demonstration of tubercle bacilli: </li></ul><ul><ul><li>Sputum </li></ul></ul><ul><ul><ul><li>for older children able to expectorate </li></ul></ul></ul><ul><ul><ul><li>Series of three early morning specimens on different days before starting chemotherapy </li></ul></ul></ul><ul><ul><ul><li>Make sure brought up from the lungs </li></ul></ul></ul>
    26. 26. Diagnostic Tests <ul><ul><li>Gastric aspirate </li></ul></ul><ul><ul><ul><li>For infants and children who cannot expectorate even with aerosol inhalation </li></ul></ul></ul><ul><ul><ul><li>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 </li></ul></ul></ul>
    27. 27. Diagnostic Tests <ul><ul><ul><li>Bronchial washings </li></ul></ul></ul><ul><ul><ul><li>Urine </li></ul></ul></ul><ul><ul><ul><ul><li>First morning-voided midstream specimen </li></ul></ul></ul></ul><ul><ul><ul><li>Other body fluids and tissues </li></ul></ul></ul><ul><ul><ul><ul><li>Bone marrow, lung and liver biopsy in patients with hematogenous spread/disseminated disease must be considered </li></ul></ul></ul></ul>
    28. 28. Diagnostic Tests <ul><li>Radiographic Findings </li></ul><ul><ul><li>No pathognomonic findings in childhood TB </li></ul></ul><ul><ul><li>Lateral projections are important wherein partially calcified mediastinal nodes may be visible </li></ul></ul><ul><ul><li>Most common cause of calcification in children </li></ul></ul><ul><ul><li>Uniform stippling of both lungs found in miliary tuberculosis </li></ul></ul><ul><ul><li>Lobar or lobular consolidations </li></ul></ul><ul><ul><li>Common findings: Enlarged retrocardiac lymphadenopathy (70%), hilar adenopathy with pulmonary infiltrates (20%), and pleural effusion </li></ul></ul>
    29. 29. Initial Empiric Therapy of Tuberculosis in Infants, Children and Adolescents Category Regimen Remarks <ul><li>Class I (TB Exposure) </li></ul><ul><li><5 years </li></ul><ul><li>> 5 years </li></ul>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. 30. Initial Empiric Therapy of Tuberculosis in Infants, Children and Adolescents <ul><li>Extrapulmonary </li></ul><ul><li>Severe, life-threatening disease: disseminated/ miliary, meningitis, bone/joint disease </li></ul><ul><li>Other extrapulmonary sites </li></ul>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 <ul><li>Corticosteroids (usually prednisone at 1 mkday for 6-8 weeks with gradual tapering) beneficial for the following: meningitis, pericarditis, pleuritis, endobronchial TB, miliary TB </li></ul>
    31. 31. Initial Empiric Therapy of Tuberculosis in Infants, Children and Adolescents <ul><li>Class II TB infection </li></ul><ul><li>PPD conversion within past 1-2 years, (-) CXR </li></ul><ul><li>PPD (+) not due to BCG,(-)CXR, (-) previous treatment </li></ul><ul><li>PPD(+)w/ stable healed lesion, (-) previous treatment </li></ul>9 months INH 9 months INH 9 months INH In the presence of primary INH resistance, use Rifampicin
    32. 32. Initial Empiric Therapy of Tuberculosis in Infants, Children and Adolescents <ul><li>Class II TB infection </li></ul><ul><li>PPD (+) with stable / healed lesion, (+) previous treatment, at risk of reactivation due to: </li></ul><ul><li>Measles, pertussis, etc </li></ul><ul><li>Conditions/drugs inducing immunosuppression (IDDM leukemia chronic dialysis) </li></ul><ul><li>HIV infection/ persons at risk for infection but HIV status unknown </li></ul>1-2 mos For the duration of immunosup-pression 12 Months INH
    33. 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. 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. 35. Algorithm for Preventive Therapy of Childhood Tuberculosis <ul><li>TB Exposure </li></ul><ul><li>Class I </li></ul><ul><li> yes </li></ul><ul><li><5years old Start INH for 3 months </li></ul><ul><li> No </li></ul><ul><li>Repeat Mantoux test Yes Radiologic findings Yes </li></ul><ul><li>After 3 months(+) and /or, signs/symptoms TB Disease </li></ul><ul><li> No suggestive of TB Multiple Drug Tx </li></ul><ul><li>Discontinue INH NO </li></ul><ul><li>If no </li></ul><ul><li>BCG scar, </li></ul><ul><li>Give BCG after 2 </li></ul><ul><li>weeks </li></ul>Latent TB Infection Continue > 6 INH
    36. 36. Source: <ul><li>PPS Tuberculosis in Infancy and Childhood </li></ul><ul><li>3 rd Edition 2010 </li></ul><ul><li>Salamat…. </li></ul>