Paediatric tuberculosis

1. CHILDHOOD
TUBERCULOSIS
Arun George

2. Tuberculosis

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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. Magnitude
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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:
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15-25 per 1000 population
15 million infected, 25% sputum positive
3 to 4 million infected are children

4. Epidemiology
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Agent : Mycobacterium tuberculosis, M. bovis
Reservoir : Infected patient
Mode of infection : Droplet infection, dust, ingestion,
skin, mucous membrane, skin
Host Factors
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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. Portal of entry for tuberculosis
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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. 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. Primary infection
Children vs. Adults
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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. Progressive primary tuberculosis
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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. Progressive pulmonary disease
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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. Symptoms of childhood
tuberculosis
1.
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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. Pulmonary lesions in tuberculosis
- the primary complex

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. 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. 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. Symptoms
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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. 
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. Miliary tuberculosis
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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. Miliary tuberculosis
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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. Miliary TB

20. Cutaneous Tuberculosis
1.
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2.
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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. TB verrucosa cutis

22. Erythema nodosum

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. Ocular Tuberculosis
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Primary tuberculous conjunctivitis (after trauma)
Yellowish – gray nodules on palpebral conjunctiva
with preauricular adenopathy
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Phlyctenular conjunctivitis (Hypersensitivity)
Nodules on limbus recurring in crops for weeks
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Tubercles of choroid (with miliary TB)

25. Choroidal tubercles

26. Tuberculous otitis media
Primary with Preauricular adenitis
 Metastatic spread with primary elsewhere
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Symptoms: Painless otorrhea, may be bloodstained
 Complications: Secondary infection
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Deafness
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TB meningitis
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27. GI and Abdominal TB
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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. 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. Renal tuberculosis
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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. Caseous renal tuberculosis

31. Skeletal tuberculosis
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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. Genital tuberculosis
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Uncommon before puberty
Usually due to lympho-hematogenous spread
Occasionally by direct extension from
adjacent lesion of bone, gut, or urinary tract

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. 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. 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. 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. Diagnosis of TB meningitis
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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. 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. Direct tests for tuberculosis
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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. Culture
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LJ medium
BACTEC radiometric assay
Septichek AFB system
MGIT – mycobacterial growth indicator tube
system

41. 
PCR – rapid results
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Serodiagnosis – ELISA
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QuantiFERON- TB test (QFT) – for diagnosing
latent TB. Based on IFN-gamma released from
sensitized lymphocytes.
ELISPOT

42. Positive Mantoux

43. Mantoux Test
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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. Observation and Inference
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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. False Negatives
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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. False positive
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Atypical mycobacteria
BCG vaccine
Infection at site of test

47. Guidelines for presumptive diagnosis
of tuberculosis
Pediatr Infect Dis J 1993;12: 499-504)
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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. 
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. Radiology
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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. Treatment for TB
1st line anti-tuberculous drugs
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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. 
2nd Line drugs
Drug resistant cases or when first line drugs cant be used
 Eg. Cycloserine, ethionamaide, PAS, kanamycin
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Other drugs
Strictly for drug resistant cases
 Eg. Quinolones, rifamycin, amikacin, imipenem,
ampicillin
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52. Phases of Treatment
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Intensive Phase
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Continuation Phase
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Eliminate bacterial load
Prevent emergence of drug resistant strains
Atleast 3 Bactericidal Drugs used
Continue and complete therapy
Atleast 2 Bactericidal drugs used
Steroids
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Anti inflammatory effect – millary, peritonitis, pericarditis
TB meningitis

53. RNTCP Treatment

54. Treatment policies in children
with tuberculosis (IAP)
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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. 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. Drug Resistance
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Natural or Primary
Acquired
Initial
Multidrug resistance (MDR)

57. Treatment of resistant
tuberculosis
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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.

59. References
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Nelson’s textbook of paediatrics
OP Ghai – Essential Paediatrics
Preventive and Social Medicine – Park & Park
The Internet…