childhood tuberclusis

1. Childhood Tuberculosis
Epidemiology
Etiology
Transmission and Pathogenesis
C/ms
Diagnosis
Management

2. Epidemiology
 Worldwide:
Eight million (3million children) new cases
each
Three million(1.3million children) deaths
year
95% occurs in developing countries with
high HIV/AIDS, limited diagnostic and
therapeutic facilities

3.  Latent TB infection(LTBI)-occurs after
inhalation of infected droplet nuclei with
M.TB
This stage is characterized by:
Reactive Tuberculin skin test
Absence of clinical and
Radiological evidence of active

4. TB(Disease)- apparent signs/symptoms or
radiologic changes of active TB
Untreated infants with LTBI have 40%
liklihood of developing disease compared
with only 5-10% in adults
The greatest risk of progression occurs
during the 1st 2yr after infection

5.  Risk for progression to TB from LTBI
increases in:
Infants & children below 5yrs of age
(especially <2yrs)
Co-infected with HIV
Persons with skin conversion in the past
1-2yr
Immunocompromization (malignancy,
drugs, DM, malnutrition)

6.  Key risk factors for TB:
Strong contact with newly
diagnosed smear +ve case
Age below 5yrs
HIV infection
Severe malnutrition

7. The global burden of TB is increasing
due to:
oHIV epidemics
oPoverty
oCrowding
oInefficient TB control programs
oInadequate health coverage & poor
access to health services

8. Etiology
Mycobacterium Tuberculous
complex:
M.TB
M. Bovis
M. Africanum
M. Microti
M. Canetti

9. M. tuberculosis
• Most important cause
• Non-spore forming
• Non-motile
• Obligate aerobe
• Slow-growing
• Grow best at 37-41o
C
• Cell wall with high lipid content which gives “acid-fast”
staining properties (resistance to decolorization with
acid alcohol)

10. Transmission and pathogenesis
Incubation period from infection to
development of +ve tuberculin test is 2-
6wks
Transmission is person to person
(usually by air borne mucus droplet
nuclei)

11. Risk of transmission is dependent on
:
Index case
Smear positive TB
Extensive upper lobe infiltrate &
cavity
Copious production of sputum

12.  Environment:
• Poor ventilation
• Overcrowding
• Intimacy
Young children (<7yrs) rarely infect
others b/c:
• Sparse bacilli
• Cough is often absent or lacks the
tussive force to suspend infectious
particles of correct size

13. Immunity
 Cell-mediated immunity develops 2-12wk after
infection, along with tissue hypersensitivity
 After inhalation into the alveolus, bacillus is
ingested by macrophages but may not be killed
 Alveolar macrophages present the antigen to T-
lymphocytes, producing DTH, which together with
newly activated macrophages causes IC killing of
bacilli & granuloma formation
 Bacilli multiply, from granulomas, spread to local
LNs, & disseminate to extrathoraxic organs
lymphohematogenously.

14.  The pathologic events in the initial
tuberculous infection depend on the balance
between:
Mycobacterial antigen load
Cell-mediated immunity(enhance IC killing)
Tissue hypersensitivity(promotes extracellular
killing)
 When Ag load is small & tissue
hypersensitivity is high:

15.  When both (Ag & sensitivity) are high:
• granuloma is less organized
• Tissue necrosis is incomplete
• Results in formation of caseous
material
 When degree of tissue sensitivity is low
(infants, low immunity)
• Diffuse reaction
• Infection is not well contained

16. Factors that predispose to serious
disease:
• Young age
• Genetic factors
• Immunosuppression (AIDS,
malnutrition, measles, pertussis,
malignancy, steroids)

17. Tuberculin skin test
 0.1ml of PPD, volar surface of arms
 T-cells sensitized by prior infection are
recruited to the skin; release lymphokines
that induce indurations through local
vasodilatation, edema, fibrin deposition and
recruitment of other inflammatory cells to the
area
 Amount of induration is measured 48-72hrs

18.  Positive test:
> 10mm (immunocompetent) if
<5 = -ve, if b/n 5 -10 infection
by other weak type or prior
BCG vaccine
> 5mm (immunocompromised)

19. • False positive result:
• BCG
• 50% never develop the reaction
• Reactivity usually wanes in 2-3yrs
• If > 10mm , it is taken as +ve
• BCG is not a contraindication to PPD
test

20.  False Negative:
• Young age(below 3months)
• Malnutrition
• Immunosuppression
• Viral infections (measles, mumps, varicella,
influenza)
• Vaccination with live-viruses (within 6wks)
• Overwhelming TB

21. Pathogenesis
 The 1o complex of TB includes local infection at
the portal of entry (Ghon Focus) & regional LNs
 Lung is portal of entry in more than 98% of cases
 Bacilli multiply initially within alveoli & alveolar
ducts
 Most are killed, some survive within inactivated
macrophages
 Macrophages carry the bacilli to regional LNs by
lymphatic vessels
 If lung is portal of entry, hilar LNs are often

22.  Tissue reaction in the lung parenchyma & LNs
intensifies over the next 2-12wks
The parenchymal lesion of 1o complex often heals
completely by fibrosis or calcification
Occasionally may continue to enlarge & result in focal
pneumonitis & pleuritis
If caseation is intense, center of the lesion liquefies &
empties into the bronchus leaving a residual cavity
The infection of regional LNS develop some fibrosis &
encapsulation, but healing is usually incomplete
Viable M.TB can persist for decades within
parenchymal or LN foci

23.  If hilar & Para tracheal LNs enlarge(as part of
host inflammatory reaction), they may ecroach
on a regional LN and bronchus (partial
obstruction bronchus)
 distal hyperinflation and complete obstruction
results in atelectasis
Inflamed caseous nodes can attach to the
bronchial wall & erode through it, causing
endobronchial TB or a fistula tract
During the development of 1o complex, bacilli are

24. • Bacterial replication occurs in organs with
conditions that favor their growth:
• Lung apices
• Brain
• Kidneys
• Bones
• Disseminated TB occurs if:
• Circulating number of bacilli is large and
• Host immune response is inadequate

25.  The time b/n initial infection & clinically apparent disease is
variable:
Disseminated & meningeal TB are early manifestations
(2-6mo after infection)
TB LAP & endobronchial TB(3-9mo)
Bones & joints take several years
Renal TB takes decades after infection
 Pulmonary TB that occurs more than a year after 1o
infection is usually due to endogenous regrowth of bacilli
persisting in partially encapsulated lesions
 Common site of reactivation is the apex of upper
lobes(oxygen & blood flow good)

26. Clinical manifestations
 Primary Pulmonary Disease
70% of lung foci are subpleural & localized
pleurisy is common
All lobar segments of the lung are at equal
risk of initial infection
Enlarged LNs_ atelectasis
 Subcarinal LAP may cause esophageal
compression & rarely
bronchoesophageal
 May have lobar pneumonia without
impressive hilar LAP

27.  Erosion of a parenchymal lesion into blood or lymphatic
vessel may result in dissemination of bacilli & a military
pattern (small nodules distributed on CXR)
 Signs and symptoms of Primary Pulmonary Disease:
 Surprisingly minimal out of proportion of X-ray findings
 More than 50% with moderate to severe CXR findings
have no physical signs
 Infants are more likely to experience S/Sx
 Systemic (fever, night sweat, anorexia, decreased activity)
 Failure to thrive
 If bronchial obstruction, localized wheezes or decreased
breath sounds
 In young children (<3yr), milliary TB may occur

28.  Dx of primary pulmonary TB:
 Most specific is isolation of M.TB
• Sputum (>7yr) for AFB stainig &
culture
• Early morning gastric aspirate (young
age)
Yield is low (25-50% positive with
3cultures)
Negative culture never exclude
pulmonary TB
If PPD is reactive, abnormal CXR &
contact Hx, adequate evidence

29. Extrapulmonary
• Occurs in 25-30% 0f children
• Increases in HIV infection

30. Progressive primary pulmonary
TB
 Occurs when the primary infection is
not contained & produces
bronchopneumonia or lobar pneumonia
(usually middle, lower) & cavitations
 High grade fever, severe cough with
sputum, weight, night sweats
 Reduced breath sounds, rales,
dullness over the cavity
 TST is reactive

31. Reactivation pulmonary TB
 Rare in children
 Most frequent site are the original parenchymal
focus, LNS or the apical segments (Simon foci)
established during the hematogenous phase of
early infection
 Usually there is little/no LAP & no extrathoracic TB
b/c of the established immune response
preventing spread
S/Sx: related with cavitation & endobronchial
spread
 Fever, night sweat, malaise, weight loss
 Productive cough, heomptysis

32. Milliary TB
 Wide spread hematogenous dissemination
with infection of multiple organs
 Diagnosed when > 2organs are involved
 Commonly involved organs are: lungs, liver,
spleen & BM
 Lesions are of roughly same size as that of a
millet seed
 Development of disseminated TB depends
on:
 Number of bacilli released from primary focus

33. S/Sx:
Fever, weakness, malaise, anorexia,
weight loss, LAP,
 night sweats & Hepatosplenomegally
Diffuse bilateral pneumonitis &
meningitis may be noted
Anemia, monocytosis,
thrombocytopenia & abnormal LFT are
common
TST is positive in only 60% of cases
Liver & BM Biopsy may be needed for

34. Extrapulmonary Tuberculosis (EPTB)
 Every organ can be affected by tuberculosis
 Common forms of extra pulmonary TB in children:
 TB Lymphadenitis
• TB of Superficial LNs (Scrofula) is most common
form of EPTB
• Tonsilar, anterior cervical, submandibular &
supraclavicular nodes are involved secondary to
extension of lesions of upper lung lobes &
abdomen
• Inguinal, epitrochlear or axillary are associated
with skin or bone TB

35. Diseaes is usually unilateral
Initially firm, discrete, non-tender, multiple nodes
involved and mass of matted nodes will be formed
Systemic symptoms (except fever) are rare
TST is usually reactive
CXR is normal in 70% of cases
If untreated
• May resolve spontaneously
• Progress to caseation & necrosis (common)
Capsule will be ruptured & spread to adjacent
nodes
Rupture usually results in draning sinus tract

36.  Dx of Tb lymphadenitis is biopsy.
 Culture yield is 50%
Pleural Disease
• TB effusion can be localized or generalized
• Usually is a hypersensitivity response to TB
antigens
• May result from discharge of bacilli into the
pleural space from a subpleural pul. Focus
or caseated LN

37.  Asymptomatic local pleural effusion is so frequent in
primary TB which is basically a component of the
primary complex
 Large effusions occur months to yrs after primary
infection
 TB effusion is infrequent in children below 6yrs
 Usually unilateral
 Rare in disseminated TB
 Radiologic finding is more extensive than physical
findings

38.  TST is positive in 70-80% of cases
 Scoliosis is one of the complications
 Prognosis is excellent
 Pleural fluid & membrane examination
 Pleural tap (Thoracentesis)
• Fluid is usually yellow (sometimes tinged with
blood)
• Sp.gr is 1.02-1.025
• Glucose is low
• AFB is rarely positive
• Culture is positive only in 30%

39. CNS TB
 Most serious complication of dissemination (fatal
if no Rx)
 TB meningitis
 Usually arises from the formation of a metastatic
caseous lesions (cerebral cortex or meninges)
that develop during the lymphohematogenous of
primary infection
 Initial lesion enlarges & discharges small no. of
bacilli into suabarachnoid space
 The resulting gelatinous exudate infiltrates
corticomeningeal vessels
inflammation & obstruction (cerebral cortex
infarction)

40.  The exudate also interferes with the CSF flow in &
out of the ventricle (at the level of basilar cisterns)_
Communicating hydrocephalus
 The combination of vasculitis, infarction,
cerebral edema, and hydrocephalus results in
severe damage (gradual, rapid)
 Electrolyte abnormalities (abnormal
metabolism, SIADH) also contributes to the
pathogenesis of TB meningitis
 Most common b/n 6mo-4yrs

41. Clinical features
Rapid or slowly progressing
Mostly slow progression having 3
stages;
Stage I (1-2wks):
 Non-specific symptoms (fever,
headache, irritability, malaise)
 Focal neurologic deficits are rare
 Stagnation or loss of developmental
milestones

42. Stage II:
 Lethargy
 Nuchal rigidity
 Seizures
 Hypertonia
 Vomiting
 Cranial nerve palsies
 Positive Kernig & Brudzinski sign

43. Stage III:
 Coma
 Hemi-or para-plegia
 Hyperetension
 Decerebration
 Deterioration of vital signs
Prognosis is dependent on stage of TB
meningitis
 Stage I_ almost all survive without sequelae
 Stage II_10-20% mortality and sequelae
 Stage III_ 50% mortality and almost all remain
with sequelae

44.  Common permanent disabilities:
Blindness
Deafness
Paraplegia
Diabetes Insipides
Mental retardation
Prognosis is worse in infants

45.  Dx: high degree of suspicion
TST is positive in 50%
CXR is normal in 20-50%
CSF ANALYSIS
• WBC(10-500/mm3)
• Increased protein (400-5,000mg/dl)
• Glucose is usually < 40mg/dl
• AFB & culture yield is dependent on volume of
CSF
CT/MRI of the brain

46. Tuberculoma
 Presents as brain tumor
 In children most common infratentorially (base of
the brain near the cerebellum)
 Lesions are most often singular
 S/Sx:
 headache, seizure, fever
 TST is usually reactive
 CXR is usually normal
 Dx: CT/MRI- discrete lesions with significant
surrounding edema and ring enhancement

47. Perinatal TB
Can be congenital
Commonly acquired postnatal
Clinically
similar to sepsis & other neonatal
problems
May manifest early but common time
is 2-3wks of age (respiratory distress,
poor feeding, fever,
hepatosplenomegally, FTT, abdominal
distension)

48. • Dx and Mx of Perinatal TB
If mother has active TB:
Screen the newborn (S/Sx, gastric aspirate,
CXR)
If positive,antiTB
If negative,INH for 3months
At 3months, PPD
o if +ve, continue for 6-9mon
o If non-reactive, give BCG and DIC INH
Isolation of the newborn:
 Seriously sick mother
 Previous Rx for TB
 Suspected drug resistant TB

49. Diagnosis of TB in children
 Acid Fast Staining/culture (sputum, gastric
aspirate, LN, fluid) is definitive
Smear +ve TB:
The criteria are:
1. Two or more initial sputum smear examinations positive
for AFB; or
2. One sputum smear examination positive for AFB plus
CXR abnormalities consistent with active pulmonary TB,
as determined by a clinician; or
3. One sputum smear examination positive for AFB plus
sputum culture positive for M. tuberculosis.

50. Smear -ve TB:
 Pulmonary TB, sputum smear negative
A case of pulmonary TB that does not meet the
definition for smear positive pulmonary TB;
Such cases include :
cases without smear results, which should be
exceptional in adults but relatively more
frequent in children.

51.  Diagnostic criteria for sputum smear negative pulmonary
TB should include:
1. At least three sputum specimens negative for acid fast
bacilli; and
2. Radiological abnormalities consistent with active
pulmonary TB; and
3. No response to a course of broad spectrum antibiotics;
and
4. Decision by a clinician to treat with a full course of anti-
TB chemotherapy

52.  If AFB is negative, Dx is based on:
Contact with patient(adult) with pulmonary
TB
S/Sx suggestive of TB
X-Ray finding consistent with TB
Positive TST
 If 3 are fullfilled, TB is likely Dx
 If severe malnutrition or immunosuppression,
2 criteria are enough

53. Management of childhood TB
Principles :
Chemotherapy/Anti-TB drugs
Nutritional rehabilitation
Screening of the family(index
case, other contacts)
Follow up (Adherence, response,
drug side effect)

54. Anti-TB drugs
 The main objectives of anti-TB treatment are to:
1. Cure the patient (by rapidly eliminating most of the
bacilli);
2. Prevent death from active TB or its late effects;
3. Prevent relapse of TB (by eliminating the dormant
bacilli);
4. Prevent the development of drug resistance (by
using a combination of drugs);
5. Decrease TB transmission to others