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Childhood TB

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Paediatric tuberculosis

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Childhood TB

  1. 1. CHILDHOOD TUBERCULOSIS Arun George
  2. 2. Tuberculosis    Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis characterized by vague constitutional symptoms and a protracted course of illness with remissions and exacerbations. Tuberculosis is the reaction of tissues of the human host to the presence and multiplication of Mycobacterium tuberculosis. The clinical states arising from TB infection are the outcome between the capacity of the host to contain and eliminate the organism versus the capacity of the organism to multiply and proliferate.
  3. 3. Magnitude   1/3rd of the world’s population is or has been infected with tubercle bacilli. India accounts for one third of the word TB burden Prevalence of the disease in India:    15-25 per 1000 population 15 million infected, 25% sputum positive 3 to 4 million infected are children
  4. 4. Epidemiology     Agent : Mycobacterium tuberculosis, M. bovis Reservoir : Infected patient Mode of infection : Droplet infection, dust, ingestion, skin, mucous membrane, skin Host Factors      Age : all ages affected, congenital is rare Sex : Girls > boys at Puberty Malnutrition : more succeptible Intercurrent infections : eg measles, whooping cough Environment : overcrowding, inadequate ventillation, damp, insanitary and unhygenic conditions
  5. 5. Portal of entry for tuberculosis     Inhalation of Tubercle bacilli in >95% (M.TB) Ingestion of milk containing Bovine Tubercle bacilli (M. bovis) Contamination of superficial skin or mucous membrane lesion with tubercle bacilli Congenital infection when mother has lymphohematogenous spread during pregnancy OR tuberculous endometritis
  6. 6. Primary tuberculous infection Primary Focus (Ghon’s focus)  at the site of first implantation  usually single and Subpleural  in most, - heals and disappears, or  - fibroses or calcifies. Primary Complex:  primary focus + Hilar lymphnodes + draining lymphatics  complications arise more commonly from regional adenitis than from the primary focus
  7. 7. Primary infection Children vs. Adults   In adults, - regional lymphadenitis less marked - bronchial erosion less frequent - less risk of dissemination Thus, adult primary infection tends to be more local and pulmonary.
  8. 8. Progressive primary tuberculosis    Progression of TB depends on the age of the child, number of tubercle bacilli, and host resistance. Apparently healed focus or nodes may contain viable organisms for many years. During 1st 4-8 weeks, organisms are disseminated in the blood stream.
  9. 9. Progressive pulmonary disease    Progressive primary infection: Progression of recently acquired pulmonary primary infection Endogenous exacerbation: reactivity of organisms and breakdown of primary lesions acquired > 5 years previously Exogenous exacerbation: Re-infection by newly acquired bacilli in persons with healed primary lesions
  10. 10. Symptoms of childhood tuberculosis 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Failure to thrive } & Intermittent fever } are the commonest symptoms Pleural effusion Ascites Abdominal mass (Painless) Limp / Arthritis Painless lymphadenopathy Persistent skin ulcer Sterile pyuria Meningitis
  11. 11. Pulmonary lesions in tuberculosis - the primary complex
  12. 12. Complications of the primary focus 1. Rupture of focus into pleural space causing serous effusion 2. Rupture of focus into bronchus causing cavitation 3. Enlarged focus, sometimes laminated or “coin” shadow
  13. 13. Complications of regional nodes 1. Incomplete (ball-valve) bronchial obstruction, emphysema of middle & lower lobes 2. Complete bronchial obstruction, collapse of right lower lobe 3. Erosion of node into bronchus & segmental consolidation 4. Rupture of node into pericardium: tuberculous pericardial effusion
  14. 14. Sequelae of bronchial complications 1. Stricture of bronchus at site of erosion 2. Cylindrical bronchiectasis in area of old collapse 3. Wedge shadow: contracture & fibrosis of segmental lesion 4. Linear scar of fibrosis following segmental lesion
  15. 15. Symptoms  Primary complex – mild fever, anorexia, weight loss, decreased activity, cough  Progressive primary complex – high grade fever, cough. Expectoration and hemoptysis – usually associated with cavity and ulceration of bronchus. Abnormal chest signs – decreased air entry, dullness, creps
  16. 16.  Endobronchial tb – wheeze!! Fever, troublesome cough, dyspnea, wheezing and cyanosis  Pleural effusion – follows a rupture of a subpleural focus. Also by hematogenous spread from primary focus. Occurs coz of hypersensitivity to tuberculoproteins. Fever, cough, dyspnea, pleuritic chest pain.
  17. 17. Miliary tuberculosis    most common within 1st 3 to 6 months after infection due to heavy hematogenous spread of tubercle bacilli Onset: Insidious, with Fever and weight loss Palpable liver and/or spleen Tachypnoea with normal chest findings
  18. 18. Miliary tuberculosis       Hematogenous dissemination leads to progressive development of small lesions throughout the body, with tubercles in the lung, spleen, liver, bone marrow, heart, pancreas brain, choroid, skin Radiologic diagnosis: “Snow storm” appearance (Multiple small lung nodules 1mm size and above in both lung fields).
  19. 19. Miliary TB
  20. 20. Cutaneous Tuberculosis 1.   2.   3.  Associated with primary complex (Direct inoculation into Traumatized Area) - Painless nodule, leading to non healing ulcer with regional lymphadenitis - Scrofuloderma over ruptured caseous lymph node Associated with Hematogenous dissemination - Papulonecrotic tuberculids papules with soft centers on trunk, thighs and face - Tuberculosis verrucosa cutis Large tuberculids on arms and legs Associated with hypersensitivity to tuberculin - Erythema nodosum painful indurated nodules on shins, elbows, forearms that subside in 2-3 weeks
  21. 21. TB verrucosa cutis
  22. 22. Erythema nodosum
  23. 23. Tuberculosis of superficial lymph nodes (scrofula) Tonsillar / submandibular (Spread from paratracheal nodes)  Supraclavicular (From primary lesion in upper lobe)  Axillary / epitrochlear (From skin lesion on hand)  Inguinal (From ulcer on sole of foot) 
  24. 24. Ocular Tuberculosis  Primary tuberculous conjunctivitis (after trauma) Yellowish – gray nodules on palpebral conjunctiva with preauricular adenopathy  Phlyctenular conjunctivitis (Hypersensitivity) Nodules on limbus recurring in crops for weeks  Tubercles of choroid (with miliary TB)
  25. 25. Choroidal tubercles
  26. 26. Tuberculous otitis media Primary with Preauricular adenitis  Metastatic spread with primary elsewhere  Symptoms: Painless otorrhea, may be bloodstained  Complications: Secondary infection  Deafness  TB meningitis 
  27. 27. GI and Abdominal TB  Hematogenous spread from lungs or swallowing of infected sputum. Painless ulcer in gingivolabial sulcus with submental or submandibular adenopathy  Ulcer on tonsil  Esophageal diverticulum secondary to rupture of mediastinal nodes into lumen 
  28. 28. Tuberculous toxemia  Present with colicky abdominal pain, vomiting and constipation.  Abdomen feels doughy.  Rolled up omentum and enlarged lymph nodes may appear as irregular nodular masses with ascites  Tuberculous enteritis Ulcers, mesenteric adenitis, peritonitis Adhesions, subacute intestinal obstruction, Hepatosplenomegaly 
  29. 29. Renal tuberculosis     Tubercles in glomeruli lead to shedding of tubercle bacilli into tubules Caseous mass / Cavity between cortex and pyramids TB of bladder (Tuberculous cystitis) Symptoms: dysuria, hematuria, pyuria with TB bacilli
  30. 30. Caseous renal tuberculosis
  31. 31. Skeletal tuberculosis     Bones involved in order of frequency: Vertebrae > knee > hip > elbow Upper extremities and non-weight-bearing bones (skull, clavicle) rarely involved Tuberculous spondylitis most commonly Thoracic / Lumbar / Both (Decreasing frequency) X-ray findings: Narrowing of disc space, Collapse of vertebral body Extensive destruction with kyphosis (Pott disease) Complications:Para vertebral abscess (Pott abscess) Psoas Abscess. Paraplegia, Quadriplegia (cervical)
  32. 32. Genital tuberculosis    Uncommon before puberty Usually due to lympho-hematogenous spread Occasionally by direct extension from adjacent lesion of bone, gut, or urinary tract
  33. 33. Genital tuberculosis Salpingitis  Endometritis  Oophoritis  Cervicitis  Infertility is commonest sequel  in males:  Primary tuberculosis of penis after circumcision with inguinal adenopathy  Epididymitis / Epididymo – orchitis in early childhood 
  34. 34. Tuberculous meningitis TB meningitis seen in 1/300 Primary infections Pathophysiology: Rupture of a subcortical caseous focus (Rich’s) into the subarachnoid space. Inflammatory exudates form about base of brain and along cerebral vessels as they pass over hemispheres. Raised intracranial pressure due to increased secretion of CSF Adhesions along base and roof of 4th ventricles lead to obstruction to CSF flow and hydrocephalus, involvement of cranial nerves III VI VII and optic chiasma. Cerebral endarteritis narrows lumen, reduces blood flow, leads to cerebral thrombosis and infarction.
  35. 35. Stages of TB meningitis Stage I Irritability, anorexia, personality change Occasional vomiting, fever Poor school performance Stage II Focal neurological signs, cranial nerve palsies, Seizures, hemiplegia, squint Stage III Loss of consciousness, Coma, Papilloedema Decerebrate rigidity
  36. 36. Complications of TB meningitis Hydrocephalus Subdural effusion Late: Hemiplegia / Paraplegia Intellectual impairment Blindness Deafness Intracranial calcifications leading to hypothalamic and pituitary dysfunction - Growth failure - Diabetes insipidus - Failure of development of secondary sexual characteristics
  37. 37. Diagnosis of TB meningitis       Signs of meningeal irritation X-ray chest CT scan – basal exudates, inflammatory granulomas etc Tuberculin testing Retinoscopy for choroidal tubercles Lumbar puncture Elevated CSF pressure(30 – 40cm h2o) Cobweb Coagulum/ pellicle on standing 100 – 500 WBCs / cu.mm >40 mg% protein Low / Normal sugar AFB smear & culture
  38. 38. Prognosis in TB meningitis 100% mortality in 3-4 weeks without treatment 100% survival with treatment started in Stage I 75% survival with treatment started in Stage II Stage III – variable survival, all will have sequelae
  39. 39. Direct tests for tuberculosis     Ziehl-Neelsen staining for AFB in clinical specimens (sputum, gastric juice, biopsy) AFB culture on Lowenstein-Jensen solid medium (4 weeks) PCR amplification of targeted mycobacterial DNA sequences DNA probes: fluorescence in situ hybridization assays
  40. 40. Culture     LJ medium BACTEC radiometric assay Septichek AFB system MGIT – mycobacterial growth indicator tube system
  41. 41.  PCR – rapid results  Serodiagnosis – ELISA  QuantiFERON- TB test (QFT) – for diagnosing latent TB. Based on IFN-gamma released from sensitized lymphocytes. ELISPOT
  42. 42. Positive Mantoux
  43. 43. Mantoux Test       MC used test for establishing diagnosis of TB in children Delayed type hypersensitivity reaction 0.1 ml of 5 TU PPD is injected intradermally into the volar aspect of the forearm (or 2 TU of PPD RT 23) A weal of 5 mm should be raised Reaction is read after 48 – 72 hrs Look for induration and erythema
  44. 44. Observation and Inference     48-72 hours later  diameter of induration is measured transversely to the long axis of the forearm. Induration > 10mm is suggestive of natural infection. 5-10 mm  borderline; considered positive in immunocompromised host <5mm  Negative mantoux test does not rule out TB
  45. 45. False Negatives        Test done in incubation period of TB For several weeks following measles During Corticosteroid therapy Overwhelming TB infection (milliary, meningits) Severe Malnutrition If given Sub Cutaneous instead of Intra dermal Inactive Tuberculin
  46. 46. False positive    Atypical mycobacteria BCG vaccine Infection at site of test
  47. 47. Guidelines for presumptive diagnosis of tuberculosis Pediatr Infect Dis J 1993;12: 499-504)  A combination of at least 3 of the following:  Symptoms/signs s/o TB: (fever > 1 mo., cough, weight loss)  History of close contact with TB  Positive tuberculin skin test (Mantoux > 10 mm)  sputum / gastric juice AFB +ve  lymph node / tissue biopsy positivity  Radiologic features suggestive of TB  Response to Anti TB Therapy
  48. 48.  History of contact = any child who lives in a household with an adult taking ATT or has taken therapy in the past 2 years
  49. 49. Radiology       In extra pulmonary tb, presence of lesions on chest radiograph supports diagnosis. Enlarged lymph nodes in hila, right paratracheal region Consolidation in progressive primary disease – heterogenous, poorly marginated with predilection to apical or posterior segments of upper lobe or superior segments of lower lobe. Bronchiectasis Pleural effusion Miliary tb – millet sized lesions
  50. 50. Treatment for TB 1st line anti-tuberculous drugs    Isoniazid (INAH) 5 mg/kg/day Rifampicin 10 mg/kg/day Pyrazinamide 25 mg/kg/day Ethambutol 20 mg/kg/day Streptomycin 20mg/kg/day H R Z E S
  51. 51.  2nd Line drugs Drug resistant cases or when first line drugs cant be used  Eg. Cycloserine, ethionamaide, PAS, kanamycin   Other drugs Strictly for drug resistant cases  Eg. Quinolones, rifamycin, amikacin, imipenem, ampicillin 
  52. 52. Phases of Treatment  Intensive Phase     Continuation Phase    Eliminate bacterial load Prevent emergence of drug resistant strains Atleast 3 Bactericidal Drugs used Continue and complete therapy Atleast 2 Bactericidal drugs used Steroids   Anti inflammatory effect – millary, peritonitis, pericarditis TB meningitis
  53. 53. RNTCP Treatment
  54. 54. Treatment policies in children with tuberculosis (IAP)         Preventive Therapy In Mantoux Positive : 6 HR Primary complex } Isolated LNE } 2 HRZ + 4 HR Pleural Effusion } Progressive Pulmonary Tuberculosis } Multiple LNE } 2 HRZE + 4 HR Miliary, Bone, Renal, Pericardial } 2 HRZE + 7HR TB Meningitis } 2 HRZE + 10 HRE + Prednisolone / Dexamethasone
  55. 55. The 5 components of DOTS Political & administrative commitment Diagnosis by good quality sputum microscopy Adequate supply of good quality drugs Directly observed treatment Systematic monitoring & Accountability
  56. 56. Drug Resistance     Natural or Primary Acquired Initial Multidrug resistance (MDR)
  57. 57. Treatment of resistant tuberculosis    INH-resistant TB: 18 RZE Rifampicin-resistant TB: 18 – 24 HZE Multidrug-resistant TB:  Treat for 24 mo. after culture conversion with regimen containing 3 second-line drugs, including IM aminoglycoside/ SM, one fluoroquinolone and one oral 2nd line drug.
  58. 58. References     Nelson’s textbook of paediatrics OP Ghai – Essential Paediatrics Preventive and Social Medicine – Park & Park The Internet…

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