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Tuberculosis in children

Pediatrics. Tuberculosis in children. Zhi-min Chen Dept. Pediatric Pulmonology Email: zmchen@zju.edu.cn. Etiology: Tubercle bacillus. Oder Actinomycetales Family mycobacteriaceae Genus Mycobacterium(M.) Species M. tuberculosis M. bovis Non-TB M. Characteristics. Acid-fastness

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Tuberculosis in children

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  1. Pediatrics Tuberculosis in children Zhi-min Chen Dept. Pediatric Pulmonology Email: zmchen@zju.edu.cn

  2. Etiology: Tubercle bacillus OderActinomycetales Family mycobacteriaceae Genus Mycobacterium(M.) Species M. tuberculosis M. bovis Non-TB M.

  3. Characteristics • Acid-fastness • Slow-growing • Unusual resistance • Multi-Drug Resistance strain(MDR)

  4. Source of infection Open Pulmonary Tuberculosis (adult) • acid-fast smear of sputum(+) • copious production of thin sputum • severe and forceful cough • extensive upper lobe infiltrate or cavity Young children with TB rarely infect others

  5. Route of transmission • By respiratory tract: airbone mucus droplet nuclei contaminated dust • By alimentary tract raw milk contaminated food • By others: (Placenta,skin) Transmission rarely occurs by direct contact with an infected discharge or contaminated fomite!

  6. High-risk population • Genetic background: twin racial difference HLA BW35 • Environmental factors: socioeconomic status overcrowding poor nutrition inadequate health care

  7. TBinfection and TB disease • TB infection: • inhalation of infective droplet nuclei containing TB • A reactive tuberculin skin test and the absence of clinical and radiographic manifestations • TB disease: • Signs and symptoms, or radiographic changes become apparent

  8. Infection, disease or not • Virulence of the TB strain • The size of inoculin • The hypersensitivity of the individual tissues • Nutritional or social status • Immunologic status • Genetic background

  9. Pediatrics Primary PulmonaryTuberculosis

  10. Spreading of M.tuberculosis Initial focus (local infection at the portal of entry) Draining lymphatic vessles Regional lymph nodes Blood Other tissues of the body

  11. Primary pulmonary tuberculosisClinical types Initial focus • Primary complex lymphangitis Lymphadenitis • Bronchial lymph node tuberculosis

  12. Primary pulmonary tuberculosisClinical manifestation • Surprisingly meager(subclinical) • Infants more likely to develop signs and symptoms • Nonproductive cough and mild dyspnea as the most common symptoms

  13. Primary pulmonary tuberculosisLess common symptoms • Systemic complaints fever, night sweats, failure-to-thrive, anorexia, etc. • Bronchial irritation or obstruction localized wheezing

  14. Prognosis • Improve or dissolve • Completely resolution • Induration • Calcification • Local progress • Exacerbation

  15. Tuberculous meningitis • Most common in children of 6mo~4yr • Usually develops during the lymphohematogenous dissemination of the primary infection • High mortality and high morbidity

  16. Tuberculous meningitis: Clinical manifestation • Stage 1: Prodromal stage • Stage 2: Transitional stage • Stage 3: Terminal stage

  17. Stage 1: Prodromal stage • Lasts 1~2wk • Nonspecific symptoms: character alteration, fever, headache, malaise, irritability, drowsiness • Focal neurologic signs absent

  18. Stage 2: Transitional stage • Increased intracranial pressure: headache, projectile vomiting, papilledema • Meningeal irritation: nuchal rigidity, Kernig’s sign, Brudzinski’s sign • Toxic appearance: fever, anorexia, nausea • Others: cranial nerve palsies, convulsion

  19. Stage 3: Terminal stage • 1~3wk • Exacerbation of neurologic symptoms • Very thin with scaphoid abdomen • Electrolyte imbalance SIADH Cerebral salt losing syndrome

  20. Diagnosis • Laboratory study • Clinical diagnosis

  21. Diagnosis • Laboratory study • detection of M. tuberculosis • Smear acid-fast staining • Culture (BACTEC, liquid, coloricmetric) • PCR and Gene probe

  22. Diagnosis • Laboratory study • Isolation of M. tuberculosis • Serology: limited value • LAM antibody • 38kDa antibody • 16kDa antibody • … …

  23. Diagnosis • Laboratory study • Isolation of M. tuberculosis • Serology • Pathology: biopsy and histology • Caseous necrosis and encapsulation

  24. Diagnosis • Laboratory study • Others • INF-γ Releasing Assays( IGRAs)- promising • INF-γ produced by T-cell responses to M.tb-special antigens called early secreted antigenic target 6 (ESAT-6) and culture filtrate protein10. • Commercial kits: Quantiferon-TB Gold In-tube (QFT) and The T-Spot TB (T-Spot) test

  25. Typical CSF picture of tuberculous meningitis, but NOT specific • Pressure • Appearance ground-glass • Cell counts 50~500×106/L, L. predominates • Protein • Glucose <40mg/dl，or CSF/blood <50% • Chloride

  26. Diagnosis • Laboratory Study • Clinical diagnosis • History • Clinical manifestation • Tuberculin test • Roentgenographic examination • Therapeutic trial

  27. Diagnosis • Laboratory Study • Clinical diagnosis • History: usually need chest film or CT of her parents or family members • Clinical manifestation • Tuberculin test • Roentgenographic examination • Therapeutic trial

  28. Diagnosis • Laboratory Study • Clinical diagnosis • History • Clinical manifestation: Not specific • Tuberculin test • Roentgenographic examination • Therapeutic trial

  29. Diagnosis • Laboratory Study • Clinical diagnosis • History • Clinical manifestation • Tuberculin test: more valuable • Roentgenographic examination • Therapeutic trial

  30. Tuberculin test：principle & method • Based on delayed type hypersensitivity( type IV) • Two antigen preparations: Old tuberculin, OT Protein purified derivative, PPD • Intradermal injection of 0.1ml containing 5 tuberculin units of PPD (Mantoux test)

  31. Tuberculin skin test:result evaluation • The amount of induration should be measured by a trained person 48~72hours after administration • Intensity: – or ±: <5mm negative or doubtful + : 5~9mm suspicious ++ : 10~19mm positive +++ : >=20mm strong-positive ++++ : blister,ulcer,lymphangitis,double rings

  32. What does it mean: Positive result • Previous infection with TB • Previous vaccination with BCG • Active tuberculosis • <=3 year without prior vaccination • > = 15mm • conversion occurring within 2 years

  33. What does it mean: Negative result • Not infected with TB • False-negative : incubation period immunosuppression or immunodeficiency technical error or improper reagents

  34. Diagnosis • Laboratory Study • Clinical diagnosis • History • Clinical manifestation • Tuberculin test • Roentgenographic examination • Therapeutic trial

  35. Diagnosis • Laboratory Study • Clinical diagnosis • History • Clinical manifestation • Tuberculin test • Roentgenographic examination • Therapeutic trial

  36. Prevention of TB • Avoiding contact with those with open pulmonary tuberculosis • BCG (Bacillus Calmette-Guerin) vaccination • Chemoprophylaxis

  37. Treatment • Antituberculosis therapy: • early, dosage, combination, regular, whole course • intensification stage and consolidate stage • directly observing therapy shortcourse (DOTS) • Corticosteroids • Symptomatic management • Supportive care

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