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. 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
4. 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
5. 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.
6. 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.
7. 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
8. Symptoms of childhood
tuberculosis
1. Failure to thrive } &
2. Intermittent fever } are the commonest symptoms
3. Pleural effusion
4. Ascites
5. Abdominal mass (Painless)
6. Limp / Arthritis
7. Painless lymphadenopathy
8. Persistent skin ulcer
9. Sterile pyuria
10. Meningitis
10. 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
11. 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
12. 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
13. 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
14. 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.
15. Miliary tuberculosis
most common within 1st3 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
16. 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).
18. Cutaneous Tuberculosis
1. 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
2. Associated with Hematogenous dissemination
- Papulonecrotic tuberculids
papules with soft centers on trunk, thighs and face
- Tuberculosis verrucosa cutis
Large tuberculids on arms and legs
3. Associated with hypersensitivity to tuberculin
- Erythema nodosum
painful indurated nodules on shins, elbows, forearms that
subside in 2-3 weeks
24. Tuberculous otitis media
Primary with Preauricular adenitis
Metastatic spread with primary elsewhere
Symptoms: Painless otorrhea, may be blood-
stained
Complications: Secondary infection
Deafness
TB meningitis
25. 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
26. 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
27. 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
29. 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)
30. Genital tuberculosis
Uncommon before puberty
Usually due to lympho-hematogenous spread
Occasionally by direct extension from
adjacent lesion of bone, gut, or urinary
tract
31. 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
32. 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 4thventricles 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.
33. Stages of TB meningitis
Stage I Irritability, anorexia, personality change
Stage II
Occasional vomiting, fever
Poor school performance
Focal neurological signs, cranial nerve palsies,
Seizures, hemiplegia, squint
Stage III Loss of consciousness, Coma, Papilloedema
Decerebrate rigidity
34. 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
36. 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
37. 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
38. Culture
LJ medium
BACTEC radiometric assay
Septichek AFB system
MGIT – mycobacterial growth indicator tube
system
39. PCR – rapid results
Serodiagnosis – ELISA
QuantiFERON- TB test (QFT) – for diagnosing
latent TB. Based on IFN-gamma released from
sensitized lymphocytes.
ELISPOT
41. 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
42. 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
43. 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
45. 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
46. History of contact = any child who lives in a
household with an adult taking ATT or has
taken therapy in the past 2 years
47. 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
48. Treatment for TB
1stline anti-tuberculous drugs
Isoniazid (INAH)
Rifampicin
Pyrazinamide
Ethambutol
Streptomycin
5 mg/kg/day H
10 mg/kg/day R
25 mg/kg/day Z
20 mg/kg/day E
20mg/kg/day S
49. 2ndLine 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
50. Phases of Treatment
Intensive Phase
Eliminate bacterial load
Prevent emergence of drug resistant strains
Atleast 3 Bactericidal Drugs used
Continuation Phase
Continue and complete therapy
Atleast 2 Bactericidal drugs used
Steroids
Anti inflammatory effect – millary, peritonitis, pericarditis
TB meningitis
53. 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
55. 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 2ndline
drug.
56.
57. References
Nelson’s textbook of paediatrics
OP Ghai – Essential Paediatrics
Preventive and Social Medicine – Park & Park
The Internet…