childhood tuberculosis

1. CLINICAL ASPECTS OF
PAEDIATRIC TUBERCULOSIS
Dr . Arun Kumar.T
Karpagam Faculty of Medical Sciences and Research

2. Primary infection
• Compared to adults, children:
– TB infection occurs for first time
– Tend to develop primary active TB more often after
initial infection (0-4yrs)
– Are more likely to have extrapulmonary disease,
especially TB meningitis (0-4yrs)
– More lymphnode involvement
– Are more likely to have disseminated TB infection
– Are less contagious
• Paucibacillary disease (fewer organisms)
• Cannot cough/spread infection as well

3. Children vs. Adults
 Cavitatory TB uncommon
 Majority of deaths by EPTB
 Are more difficult to diagnose
• May not show typical symptoms

4. Children vs. Adults
 In adults,
- regional lymphadenitis less marked
- bronchial erosion less frequent
- less risk of dissemination
- infectious
- Cause of death - PTB
 Thus, adult primary infection tends to be
more local and pulmonary.

5. Risk factors in children
 Age < 1yr
 Steroid therapy
 Malnutrition
 Intercurrent infections: Measles,whooping
cough
 Immunocompromised state
 Environment : overcrowding, inadequate
ventillation, damp, insanitary and unhygenic
conditions

6. TB infection and disease
 Infection (LTBI)
 Contact w/ infectious pulmonary TB (adult)
 Child asymptomatic
 TST +, CXR normal
 Disease
 Contact w/ infectious pulmonary TB
 TST+/-
 Child symptomatic or CXR positive for TB

7. TB overview: infection and
disease
– Risk of infection depends on disease burden in the
index case, proximity and duration of exposure
– Household exposure from adult with active disease
is strongest source

8. Primary tuberculosis
 Primary TB infection -acquiring TB directly after
exposure to someone with active disease
 Inhaled TB bacilli penetrate into lungs and settle- ”set up
shop”
 Parenchymal (Ghon) focus develops- At the site of first
implantation
- usually single and Subpleural
- mostly - heals and disappears, or fibroses or calcifies
 Bacilli drain to regional nodes
 Upper lobes to paratracheal nodes
 Middle and lower lobes to hilar nodes

9. Primary tuberculous infection
 Infection is contained in a small area without spread or replication
(latent TB infection or LTBI)
 These individuals are not infectious to anyone
 Primary Complex: primary focus + lymphangitis +lymphadenitis.
 complications arise more commonly from regional adenitis than
from the primary focus

10. Progressive primary complex
 Progressive primary infection: Progression of
recently acquired pulmonary primary infection
 Progression depends on 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.

11. Progressive primary complex
 Incomplete bronchial obstruction with ball valve
thrombus leads to Obstructive emphysema.
 Aspiration of caseous material results in
bronchopneumonia, consolidation.
 Complete obstruction results in collapse of lung
distal to the obstruction or collapse consolidation.

13. Secondary tuberculosis(adult type
of TB)
 All active tuberculosis which occur after primary
infection due to Endogenous reactivation or
Exogenous reinfection
 Cavity formation seen in lung apices.
 Cavitating tuberculosis seen in younger children
due to high adult TB incidence in community.

14. Clinical features
 Physical manifestations differ by age of onset
 Less compared to degree of radiographic
changes
 Majority develop no signs or symptoms
 Young infants & adolescents more likely to have
significant symptoms.
 Infants --- smaller airways
 School age children often have clinically silent
disease

16. 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, crepts

17. Symptoms
 Pleural effusion
-follows a rupture of a subpleural focus.
-Also by hematogenous spread from primary
focus.
Fever, cough, dyspnea, pleuritic chest pain.

18. 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.
 Pleural effusion
 Miliary tb – millet sized lesions

19. Extrapulmonary tuberculosis
 Includes TB adenitis(75%) , TB meningitis(13%) ,
TB effusions (pleural, pericardial & peritoneal),
bone & joint TB, miliary TB, abdominal TB,
ocular TB, cutaneous TB, genito-urinary TB.

20. Tuberculous adenitis

21. Tuberculous adenitis
 Commonest form of EPTB
 LNTB is local manifestation of systemic disease
 Isolated cervical lymphadenopathy more
common in 2/3 rd with Painless, matted nodes.
 Lymphnode abscess can burst & lead to non
healing TB sinus and ulcer
 FNAC
 Excision biopsy confirmatory

23. Tuberculous meningitis
 TB meningitis seen in 1/300 Primary infections
 Rupture of a subcortical caseous focus (Rich’s)
into the subarachnoid space.
 Inflammatory meningeal exudates, ependymitis,
vasculitis, encephalitis & diturbance of CSF
circulation & absorption.
 Cerebral endarteritis narrows lumen, reduces blood
flow, leads to cerebral thrombosis and infarction.
 Hydrocephalus

24. CN palsy 3, 6, 7
Involvement of cranial nerves III VI VII and optic
chiasma

25. Tuberculous meningitis
 Risk factors :
Age < 5 years,
contact with an adult suffering from
tuberculosis,
PEM grade III and IV, and
HIV infection

26. 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

27. Complications of TB meningitis
 Hydrocephalus
 Subdural effusion
 Hemiplegia / Paraplegia
Late :
 Intellectual impairment
 Blindness
 Deafness
 Intracranial calcifications leading to
 hypothalamic and pituitary dysfunction
 Growth failure
 Diabetes insipidus
 Failure of development of secondary sexual
 characteristics

28. 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

29. 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

30. Tuberculomas
 Infratentorial tuberculomas
 Solitary
 A ring enhancing lesion is not pathognomonic of
tuberculoma
 A larger lesion >20 mm, disc lesion or ring lesion with
thicker rim and central nodule favors tuberculoma;
while multiple, smaller, thin rim with epicentric nodule
favor NCC
 MR spectroscopy may help in diagnosis of tuberculoma
as it shows lipid peak.
 D/D Neurocysticercosis, fungus, other tumours.

31. Tuberculomas

32. 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
Generalized lymphadenopathy,
Papulonecrotic skin lesions, choroid tubercles
Tachypnoea with normal chest findings

33. 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).

34. Miliary TB

36. Choroidal tubercles

37. Cutaneous Tuberculosis
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

38. TB verrucosa cutis
Large tuberculids on arms and legs

39. Erythema nodosum
painful indurated nodules on shins, elbows, forearms

40. 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., cough>2wks, 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

41.  History of contact = any child who lives in a
household with an adult taking ATT or has
taken therapy in the past 2 years

42. Early morning Gastric aspirate
 Fasting for about 6 hours (at night)
 Appropriate size intra-gastric tube is passed
 Initially the aspirate is drawn from the stomach and
further washing with 15-30 mL saline is taken.
 The contents are transferred to the laboratory
 This specimen can also be collected as an ambulatory
procedure after 4-6 hours fasting with some loss of yield

43. Sputum collection in children
 Induced sputum can be done in children as young as 1
month
 6h fasting
 Pre-treat with inhaled albuterol by MDI
 3% hypertonic saline given by jet nebulizer for 15
minutes followed by chest percussion
 Samples are collected from throat or nasopharynx using
collector attached to a suction at one end and catheter
to the other.
 The suction catheter provokes cough and the
secretions brought up are collected via suction

45. Treatment for TB
1st line anti-tuberculous drugs
 Isoniazid (INAH) 5 mg/kg/day H
Rifampicin 10 mg/kg/day R
 Pyrazinamide 25 mg/kg/day Z
Ethambutol 20 mg/kg/day E
 Streptomycin 20mg/kg/day S

46. 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

47. RNTCP Treatment

48. Summary and Pearls
• Clinical manifestations in pediatric TB may be non-
specific
• TB is much more difficult to diagnose in children
• Undiagnosed or untreated TB in a child is potentially
serious,
– More likely to develop severe or disseminated disease
• Diagnosis of TB in a child is a sentinel event
– Contact investigation is critical

49. CONGENITAL TB
 Congenital infection by vertical transmission is
rare with only 358 cases reported till 1995 and
another 18 cases reported from 2001 to 2005
 High neonatal mortality (up to 60%) and
morbidity warrant early diagnosis and treatment
of newborns suffering from TB

50. Mother to child transmission
of TB
 Vertical transmission:
 Transplacental transmission through Umbilical
veins(occurs in late pregnancy)
 Aspiration & swallowing amniotic fluid (occurs
in perinatal period)
 Transmission through breast milk does not
occur
 Horizontal transmission in postpartum period is
by droplet infection from mother or family
members

51. High risk factors
 Extra Pulmonary, miliary and Meningeal TB in
Mother
 Untreated Mothers.

52. Diagnosis
 Cantwell criteria: Presence of proven tuberculous
disease and at least one of the following;
 (i) lesions in the newborn baby during first week of life;
 (ii) a primary hepatic complex or caseating hepatic
granulomata;
 (iii) tuberculous infection of the placenta or the maternal
genital tract; and
 (iv) exclusion of the possibility of postnatal transmission
by investigation of contacts, including hospital staff

53. Clinical Manifestations Of Congenital
T.B:
 Median Age of Presentation:- 24 days ( 1to 84
days)
 FETAL:- IUGR,LBW ,increased risk of mortality
 Neonate:- Irritability, Poor Feeding, lethargy
(100%) ,Failure to thrive, fever(100%),
Cough(88.9%),respiratory distress (66.7)
Apnea,Vomiting,cyanosis,seizures,petechiae(<1
0%case)

54. Examination
 Hepatosplenomegaly (100%)
 Splenomegaly (77.8%)
 Abdominal distension(77.8%)
 Lymphadenopathy(38%)
 Babies develop meningitis septicemia, pneumonia,
DIVC, ascitis, parotitis, osteomyelitis, otitis media,
paravertebral abscess, cold abscess, skin lesions

55. INVESTIGATIONS
Conventional Method:-
 Morphological & histological examination of placenta.
 Screening of house hold contact
 Poor response to conventional treatment
 Detection of AFB in gastric aspirates,Sputum(induced),
tracheal aspirates,ear discharge,Skin lesions, ascitic
fluid,CSF,pleural fluid
 Broncho Alveolar Lavage - By PCR (diagnostic)

56.  Chest radiography & computed tomography –
may show scattered infiltrates,
bronchopneumonia,
consolidation or periportal hypodensity (non
specific)
 Mantoux test-(supportive evidence)
Poor utility
Used after 3 months of age
PPD 2TU

57. Newer methods
 Gene expert (real time PCR )
 LED Fluoreseance microscopy and liquid based
mycobacteria growth indicator tube (MGIT)
 RIGAs, QuantiFERON –TB Gold assay and T-Spot –
Inconsistent result in newborn.

58. Management Of Congenital TB
 AIM - To ensure free survival of a newborn infant
 Diagnosis of active tubercular lesion
 Treatment of the neonate
 prevention of infection to the neonate from the
mother.

59. (i)Prevention of Transmission
(A)Maternal disease & therapy:
Transmission is less when mother complete
ATT Before delivery or
Have received ATT for at least 2 weeks before delivery.
 ATT drugs safe for fetus expect streptomycin in the first
trimester
 Safety of second line ATT drugs for resistant TB -
Insufficient evidence.

60. Prevention of transmission
(B) PROPHYLAXIS ( IAP guildelines )
 ISONIAZID for newborn at least 6 month (or)
 a minimum of three months until mother is Culture
negative
 DOSE:-10 mg/kg.

61. Prevention of transmission
(C)Nutrition and breast feeding
 Support for breast feeding.
 Expressed breast milk-when mother is sick or smear
positive or has MDR TB.
 Personal hygiene, hand washing, cough hygiene
 First line ATT is safe & excreted in breast milk

62. Prevention of transmission
(D) Isolation
 Isolation - sick mother, resistant TB, non adherent
therapy, received ATT for less then 2 weeks.

63. Prevention of transmission
 (E)Barrier Nursing
 Face Mask,
 Cough hygiene,
 Hand Washing ,
 Disinfecting nasal secretions & baby wipes.

64. TREATMENT
 American Academy of Pediatrics recommends treatment
with INH 10 to 15 mg/kg po,
Rifampin 10 to 20 mg/kg po,
Pyrazinamide 30 to 40 mg/kg po,
Aminoglycoside (amikacin or kanamycin) for 9-12
months.
 Regimen is modified as indicated based on results of
testing for resistance.
 Pyridoxine is given if the neonate is exclusively
breastfed.

65. (C)FOLLOW UP:-
DOTS recommends
 clinical surveillance during treatment &
 chest x-ray at the end of treatment.

66. (III)Long Term protection.
 IAP Recommendation
BCG (Bacillus Calmette Guerin) Vaccination
 No utility of BCG Vaccine in neonates with congenital
tuberculosis
 Advised at birth even with INH prophylaxis (IAP 2012).
 Need to conduct more studies to evaluate
immunogenicity of BCG Vaccine in infants receiving
INH prophylaxis.

67.  Congenital tuberculosis is diagnosed by Cantwell
criteria and treatment includes three or four anti-
tubercular drug regimen.
 Prophylaxis with isoniazid (3-6 months) is
recommended in neonates born to mother with TB
who are infectious.
 Breastfeeding should be continued in these neonates
and isolation is recommended only till mother is
infectious, has multidrug resistant tuberculosis or non
adherent to treatment.
 BCG vaccine is recommended at birth or after
completion of prophylaxis (3-6 months) in all neonates.

68. Peds TB Cases

69. Meron 4 ½ months old
 Well appearing, Normal PE (wt in 10%)
developmental screen.
 Screened for TB, Hepatitis, syphilis, HIV, parasites,
lead
 Vision/hearing screening: high frequency hearing loss
 Received BCG at birth
 TST 12 mm enduration, HIV –
 Hx repeated respiratory infections in orphanage,
treated w/ multiple antibiotics

70. Meron
 CXR 2 views
 Alert radiologist you are looking for TB

71. Meron
 Laboratory testing
 Microbiological testing
 Sputum, sputum induction (?)
 BAL (?)
 Gastric aspirates
 CBC, U/A & U/Cx, electrolytes & renal fct, LFT
Treatment? How many drugs?

72. Meron
 Gastric aspirate positive Mtb on second aspirate
 Started on 4 drug regime by DOT
 Resistant to INH, RIF. Sensitive to PZA, EMB,
SM
 MAC also grew on purity plates

73. Meron
 Use all first line drugs available (unless previously used
& associated w/ failing regime)
 Use injectable drug (SM, amikacin, capreomycin,
kanamycin) by Broviac
 Use fluroquinolone
 Use additional second line drugs to have 4-6 drugs in
the regime

74. Meron
 Treatment changed: aminoglycoside (by broviac x 4
mos), PZA, EMB, ethionamide and levofloxacin, Vit
B6 by DOT
 2 negative gastric aspirates on therapy
 Gained many pounds
 CXR normalized
 Normal growth and development