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Pediatrics : TB in Children Clara Rivera, MD Tuberculosis s WHO r 8M new cases each year r 3M deaths each year s

s 11.23.2007

Etiology: Mycobacterium tuberculosis r Mycobacterium tuberculosis Acid-fast bacilli, obligate aerobes, slow-growing Mycolic acid (lipid-rich cell wall resistant to bactericidal action of antibiotics) r Mycobacterium bovis Causes primary pulmonary as well as primary gastrointestinal TB Transmission r Airborne: inhalation of droplet nuclei produced by an adult or adolescent with contagious, cavitary PTB About 3,000 TB bacilli are expelled during coughing, sneezing, talking for 45 minutes r Marker of contagiousness: (+) Bacilli in sputum r Index of sensitivity: AFB smear r Children < 12 years old with primary PTB are not contagious (TB without cough) Pulmonary lesions are small Cough is minimal or non-existent Little or no expulsion of bacilli r Paucibacillary : TB in children r Bacilli coughed out sterilized in the sun or survive and persist in moist, dark areas Incubation period r 2-12 weeks from infection to development of a (+) skin test r Risk of developing TB disease is highest during the 6 months after infection & remains high for 2 years r Many years may elapse between latent TB & disease Predisposing factors r Relative virulence of the invading organism & the number of bacilli in the inoculum r Living in overcrowded condition & with little resistance to MTB r Chronic illness r Malnutrition r Fatigue r Physical trauma: Causes a tuberculous focus to rupture r Quiescent tuberculous lesion: Activated by measles, varicella, pertussis, HIV, severe viral pneumonia & corticosteroid Immunopathogenesis: r Bacilli ingested by alveolar macrophage stage of symbiosis, proliferation of macrophages as well as TB bacilli in susceptible patients, the caseation necrosis is walled off by partially activated or nonactivated macrophages thus larger granuloma r In resistant patients, lesions are smaller because it is walled off by fully activated macrophages Importance of better immunization status TB bacilli can be effectively engulfed r Stage of symbiosis: multiplication of TB bacilli but asymptomatic r Renal TB takes a long time before symptoms manifest compared to skeletal, miliary and meningeal types Lesions of Tuberculosis r Primary focus: Primary lesion r Primary complex: Primary focus, regional lymph nodes & connecting lymphatic vessels r Gohn complex: Calcified primary focus

Clinical forms r Pulmonary or Endothoracic TB Asymptomatic or Latent TB infection (LTBI) : hallmark is (+) TST Primary pulmonary TB Progressive primary TB Endobronchial TB Reactivation TB Miliary TB Pleurisy with effusion r Extrapulmonary TB Latent Tuberculosis Infection (LTBI) r M. tuberculosis infection in a person who has a positive TST result, no physical findings of the disease & chest radiograph findings that are normal or reveal evidence of healed infection (Granulomas or calcifications in the lung, hilar lymph nodes or both) r Such patients are non-infectious Primary Pulmonary TB r Involves a primary complex & its progression r Most frequent: Presence of enlarged lymph nodes without primary focus visible radiographically r Can impinged on tracheobronchial tree resulting to either atelectasis (complete obstruction) or air trapping (partial obstruction) Progressive primary tuberculosis r With local progression of the primary complex Caseation enlarges, liquefies & disseminates its contents into the bronchi New foci r Pneumonia atelectasis, air trapping, stenosis, brochiectasis r Retractions, wheezes, crackles, localized decreased breath sounds r Bronchiectasis sicca: bronchiectasis but with minimal secretions (dry bronchiectasis) r Importance of getting the apico-lordotic posture on x-ray to see the apical infiltrates better Reactivation TB r Rare in childhood, more in adolescents r More common in children who acquire initial infection after 7 years old r CXR: extensive infiltrates or thick-walled cavities r History of fever, cough, hemoptysis, weight loss r PE: minor or absent Endobronchial TB r Extrabronchial or extraluminal r Hyperemic & edematous lymph nodes impinge upon the wall of a bronchus occlude the lumen usually the right middle lobe bronchus r Occurs more frequently r Adherence of lymph nodes with spread of the disease through the airway wall Ulceration of mucosa Granulation tissue Obstruct lumen usually the right middle lobe or right upper lobe bronchus (Right Middle Lobe Syndrome: atelectasis plus consolidation) r Treatment: Add prednisone 1-2 mg/kg/day for 6-12 weeks Miliary TB r Infants & young children affected as a complication of primary TB r Can be misdiagnosed as only acute pneumonia r Bacilli spreads via lymphatics to capillaries of most organ system (Oxygenated: Liver, spleen, marrow & brain) r Mandatory tests include lumbar tap & fundoscopy r Size of millet lesion varies with the hosts immune status, the larger lesions are found in imunocompromised patients r Death occurs in 4-12 weeks if untreated usually secondary to meningitis r Fever resolves in 2-3 weeks of chemotherapy r X-ray lesions improve in 5-10 weeks Lesions take awhile before disappearing in other types of TB (2-3 years)
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It is important to keep this in mind so as not to interpret CXR as still positive even after treatment There is no need to repeat treatment as long as patient is well r Treatment: Add prednisone to mitigate capillary block s Pleural effusion r Most common age group affected are school-age children (>5 years old) r Older children, unilateral r Either as a hypersensitivity reaction or as an extension of subpleural focus or TB of the spine r Onset is acute with high fever & chest pain r Serous pleural effusion & a (+) PPD Extrapulmonary TB r Extrapulmonary: Refers to tuberculosis of other organs other than the lungs (Pleura, lymph nodes, abdomen, genitourinary tract, skin, joints & bone & meninges) Classification (Stages) r TB exposure: (+) exposure to an adult or adolescent with active TB Treat with H for 3 months then work up after 3 months (repeat Mantoux and CXR) If after work up, the results are positive then treat the disease Otherwise, discontinue the drugs r TB infection (+) Mantoux test With or without exposure, normal chest x-ray, no signs & symptoms r TB disease: 3 or more of the following Exposure to an adult/ adolescent with active TB (+) Mantoux test Signs & symptoms suggestive of TB (Any 1 or 2 or more are considered positive) * Cough of more than 2 weeks duration * Fever of more than 2 weeks duration (usually low-grade) * Painless cervical &/or other lymphadenopathies * Failure to make a quick return to normal health after an infection (Measles, tonsillitis, whooping cough) * Failure to respond to appropriate antibiotic therapy Abnormal chest x-ray suggestive of TB Laboratory findings suggestive of TB (Histological, cytological, biochemical, immunological &/or molecular) Diagnosis of Childhood Tuberculosis r Tuberculin skin test (TST) For determining latent TB infection in infected persons, those who do not have the disease A measure of a persons cellular immune responsiveness Features include * Delayed course * Indurated character * Occasional vesiculation and necrosis The only recommended TST method is the intradermal injection of 5 tuberculin units (TU) of purified protein derivative (PPD) form M. tuberculosis administered by the Mantoux technique Results read after 48-72 hours, must be recorded as millimeters (mm) of induration The results are interpreted in the context of the patients risk of M. tuberculosis (Exposure to TB disease or risk of progression to TB disease)3 cut off levels ( 5, 10, 15 mm) are used to improve the sensitivity & specificity of the TST
2

Basis of TST is Kochs phenomenon: hypersensitivity to a previously exposed individual r Targeted tuberculin skin testing Intended to identify children & adolescents at risk for LTBI who would benefit from treatment to prevent the progression to TB disease r Mantoux Test Based on a delayed type of hypersensitivity reaction (DTH), manifested as an indurated area at the site of intradermal injection which usually begins within 5-6 hours of administration, as previously sensitized lymphocytes, monocytes & macrophages infiltrate the site An immediate wheal & flare reaction may occur but usually disappear by 24 hours & should not be interpreted as a positive reaction Only the area of induration (not hyperemia) should be measured Mantoux test interpretation When wheal is not formed, the test was performed incorrectly. False negative Viral, bacterial, fungal, early TB infection, severe TB disease Live virus vaccine Metabolic False positive Exposure to NTM (nontuberculous mycobacteria) BCG vaccine Transfusions with whole blood from donors with known + TST Corticosteroids, Inexperienced or biased immunosuppressive drugs reader Technical Increasing mm induration BCG vaccine protects only against life-threatening forms of TB infection s How to measure the induration r Measure perpendicular to the long axis r Palpate to determine the margins of induration or use a ball point to measure the borders of resistance of the induration Interpretation of PPD r 5 mm Non-BCG vaccinated < 5 years old r 10 mm (high risk) BCG-vaccinated < 5 years old with (+) exposure r 15 mm: > 5 years old with or without BCG Boosting effect r Overtime the effect of DTH to mycobacterial antigens may wane & thus the TST could be negative. However, with subsequent TSTs, the DTH response may be stimulated by PPD & result in a + reaction: Boosting phenomenon r Increase in TST size caused by repetitive TST in an individual previously sensitized to mycobacterial antigens particularly BCG & NTM r Re-test after 1-3 weeks Chest x-rays r Considered essential to assess children & adolescents with positive TST for pulmonary TB r TB can also occur even if CXR is normal r LTBI: Chest xrays are usually normal but findings may include dense nodules with calcifications (gohn complex) calcified, non-enlarged regional lymph nodes or both or pleural thickening (scarring) r TB disease include enlargement of hilar, mediastinal or subcarinal lymph nodes & parenchymal changes such as segmental hyperinflation, atelectasis, alveolar consolidation, interstitial infiltrates, pleural effusion or a focal mass r Cavities are rare in young children, but may occur in adolescents with reactivation disease r Younger children are more likely to have intrathoracic lymphadenopathy than adolescents r 4607 children with TB disease in California
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6%: 0-4 years old 8%: 5 -14 years old 0.5%: Adolescents r Lateral chest x-rays improved the accuracy of detecting hilar adenopathy in children 1 month 12 years of age r 176 culture confirmed cases of TB disease 46% (81 of 176) had adenopathy visible on chest x-ray 49% (40 of 81) visible on both frontal & lateral view 24% (19 of 81) only on frontal view 27% (22 of 81) only on lateral view s CT scans r Chest CT scan may show enlarged or prominent mediastinal or hilar adenopathy not demonstrable on chest x-ray r Can demonstrate endobronchial disease, pericardial invasion, early cavitation or bronchiectasis Mycobacteriology of childhood TB r Obtain cultures Lowenstein-Jensen Bactec method (amplification technique, faster results) * Sputum, gastric lavage, bronchoalveolar lavage, body fluids New diagnostic tests for TB in children r Immunoassays for mycobacterial mycobacterial antigens (ELISA) r Polymerase chain reaction Guidelines for TB prophylaxis
Population at risk of infection/ disease *Newborn of an infected mother *PPD (-) infants & children under 5 years exposed to TB Duration of INH 3 months initially; after 3 months, if PPD (-) D/C H provided the infector is under therapy & give BCG; if PPD (+) continue H for 6 months more; if abnormal CXR; add 2 more drugs (R & Z) & treat as disease 12 months

Guidelines for TB treatment


Duration of treatment

PTB disease Susceptible Possible drug resistance Meningitis, miliary & bone/ joint TB Extrapulmonary TB except as above 6 months regimen: 2 months HRZ, then 4 months HR daily Add a 4th drug to the initial 3 drugs to complete the months regimen 2 months of HRZS then 10 months of HR Same regimen as PTB disease

Anti-TB Drugs r HRZ : hepatotoxic r S : ototoxic r E : ophthalmic neuritis r R: Best for rapidly growing, slowly growing extracellularly and slowly growing intracellularly Evaluation of response to treatment r In adults, repeat exam of sputum & culture at the end of the treatment for baseline comparison for future studies r In children, clinical & radiologic evaluation r For those with (+) CXR of TB disease, repeat in 2-3 months r For those with hilar adenopathies only, repeat at the end of therapy

antibodies

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Category Primary chemoprophylaxis

s Resolution of Radiographic Changes Pulmonary infiltrates Usually clears in 2-9 months Hilar adenopathy Usually clears in 2-3 years Pleural effusion Complete resorption in about 6-12 weeks Hyperaeration in endobronchial Improve as early as 3 weeks TB Miliary TB After several months

Secondary chemoprophylaxis

IV infection/ persons with risk factors for HIV whose HIV status is not known Recent tuberculin conversion (Within 12 years) with negative CXR PPD (+) not due to BCG with (-) CXR & no benefit of previous TB chemotherapy PPD with stable or healed parenchymal lesion & no previous chemotherapy PPD (+) with stable or healed TB with previous chemotherapy but are at risk for reactivation due to: measles/ pertussis, conditions/ drugs that induce immunosuppression (IDDM, chronic dialysis, leukemia)

9 months

9 months

9 months

1-2 months for the duration of immunosuppresion

Lala 3C-Med-2009

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