TUBERCULOSIS

IN CHILDREN
By- Dr. Toshi Harne
14-07-2020
Tuberculosis is a chronic infectious disease
caused by MYCOBACTERIUM TUBERCULOSIS
 INTRODUCTION
• Tuberculosis (TB) is one of the most common causes
of mortality worldwide.
• An estimated 6.3 million new cases of TB were seen
in 2016, of which 1.3 million died due to TB in 2016.
Children represent about 11% of all TB cases.
• Approximately 67 million children are infected with
TB (latent TB) and are therefore at risk of developing
disease in the future.
• Despite the best of efforts, childhood TB is still
underreported in most of the countries.
ESTIMATED NEW TB CASES (all forms)
PER 1,00,000 POPULATION PER YEAR
 EPIDEMIOLOGY
• Incidence of TB cases varies among different populations and
regions from under 10 per 100,000 population in most high-
income countries to 150–300 in most of the 30 high-burden
countries.
• The World Health Organization (WHO) South-East Asia Region
(WHO-SEAR) accounted for 45% of the incident cases.
• TB is the ninth leading cause of death worldwide; it is the
main cause from a single infectious agent.
• About 82% of TB deaths among human immunodeficiency
virus (HIV)-negative people occurred in the WHO African
Region and the WHO-SEAR in 2016; these regions accounted
for 85% of the combined total of TB deaths in HIV-negative
and HIV-positive people.
• India accounted for 33% of global TB deaths among
HIV-negative people, and for 26% of the combined
total of TB deaths in HIV-negative and HIV-positive
people.
• The incidence of drug-resistant TB has increased over
the past few years and is a challenge for the whole
world due to diagnostic and therapeutic challenges.
• In 2016, worldwide estimates for multidrug-resistant
(MDR)/rifampicin (RIF)-resistant TB in new, and
previously treated cases were 4.1% and 19%,
respectively.
Uttar Pradesh, with 17% of population of the country, is the largest
contributor to the TB cases in with 20% of the total notifications,
accounting to about 4.2 Lakh cases (187 cases/lakh population).
Problem of TB in India (WHO SEAR REPORT
2015-2016)
• Estimated incidence -
2.8 MILLION CASES – 167 (156-179) per 1 lac
population annually – 75 new smear positive
PTB cases/1lakh population per year
• Estimated mortality –
480,000 deaths due to TB each year – Over
1000 deaths a day – 2 deaths every 3 minutes
In Chhattisgarh,
The TB suspect examined per lac population has increased from 452/lac in year
2013 to 652/lac in the year 2015.

Chhattisgarh has initiated the mandatory

TB notification from private practitioners
& chemists. TB notification from private
sector has increased from 3/lac in the
year 2013 to 30/lac in 2016.
 PATHOGENESIS
• Mycobacterium tuberculosis (MTB) bacilli are acid-fast,
nonspore-forming, nonmotile, pleomorphic, weakly gram-
positive curved rods 1–5 μm long, typically slender, and slightly
bent.
• They may appear beaded or clumped under microscopy.
• They are obligate aerobes that grow in synthetic media
containing glycerol as the carbon source and ammonium salts
as the nitrogen source.
• Other closely related mycobacteria, such as Mycobacterium
bovis, Mycobacterium africanum, and Mycobacterium microti,
along with MTB form the MTB complex.
• The characteristic property is acid-fastness, which is imparted
by the ability to form stable mycolate complexes with
 The spectrum of affliction by MTB includes exposure, infection, and
disease.
• Exposure means that the child had significant contact with a person
with infectious TB but lacks proof of infection.
• Infection occurs when an individual inhales droplets, which contain
mycobacteria, which survive intracellularly in lung and lymphoid
tissue. In this stage, child is asymptomatic and has a normal
physical examination.
• Disease occurs when the signs or symptoms or radiographic
manifestations become apparent.

- Not all infected individuals have the same risk of developing

disease.
- An immunocompetent adult with untreated TB infection has
approximately a 5–10% lifetime risk of developing disease.
- In contrast, an infected infant has a 40% chance of developing
disease within 9–12 months.
• Lung is the portal of entry in majority of cases.
• Bacilli enter alveolar passage in an aerosol droplet and
interact with macrophages or type II pneumocytes
and are phagocytosed in a process initiated by
bacterial contact with macrophage mannose and/or
complement receptors.
• On entry into a host macrophage, MTB initially resides
in an endocytic vacuole called the phagosome. If the
normal phagosomal maturation cycle occurs, i.e.
phagosome-lysosome fusion, these bacteria may
encounter a hostile environment that includes acidic
pH, reactive oxygen intermediates, lysosomal
enzymes, and toxic peptides.
• Interferon-gamma (IFN-ɣ) plays a key role for a
protective immune response. IFN-ɣ, produced mainly by
CD4+ (cluster of differentiation), CD8+ T cells, and the
natural killer cells, synergizes with tumor necrosis factor-
α and activates macrophages to kill intracellular bacilli.
• Bacteria may evade destruction by preventing
phagosome-lysosome fusion and cause macrophage
necrosis.
• These bacilli, which survive within macrophage, are
carried to regional lymph nodes.
• The primary complex (Ghon complex) of TB includes
local infection at the portal of entry and the regional
lymph nodes that drain the area.
• There is tissue reaction at initial foci over next
2–12 weeks; and hypersensitivity develops,
which heal by calcification or fibrosis.
• Occasionally, this portion may continue to
enlarge and lead to focal pneumonitis and
pleuritis, and if caseation is intense then may
lead to cavitation.
• During the development of the primary
complex, tubercle bacilli are carried to most
tissues of the body through the blood and
lymphatic vessels.
• Disseminated TB occurs if host cellular immunity is
inadequate.
• Bacterial replication is more likely to occur in organs with
conditions that favor their growth, such as lung apices,
brain, kidneys, and bones.
• The time between initial infection and apparent disease is
variable.
• Pulmonary TB that occurs after 1 year of primary infection
is due to endogenous growth of bacilli.
• This reactivation of TB is rare in children but common in
adults and adolescents.
• Occasionally reinfection can occur in immunocompromised
individuals or those living in highly endemic areas.
 DIFFERENCES BETWEEN TUBERCULOSIS IN
ADULTS AND CHILDREN

• Childhood TB is not simply a reflection of the adult spectrum of

disease.
• Characteristics of TB in children include the paucibacillary nature;
preponderance of primary focus and lymph node disease; higher
chance of dissemination into serious manifestations, such as
 Miliary TB,
 TB meningitis (TBM),
 Spinal TB; and
 Higher burden of extrapulmonary TB (EPTB).

Challenges in diagnosis due to inability to expectorate sputum; and

difference in pharmacokinetic or pharmacodynamics characteristics
of antitubercular drugs.
 PULMONARY TUBERCULOSIS
Intrathoracic involvement in children is varied and may include
the following:
• Primary focus: Primary focus or Ghon focus that results from
primary infection is usually a single focus of parenchymal
involvement with or without pleural component. The primary
focus along with the draining regional lymph node is called the
primary or Ghon complex. This may get complicated and result
in cavitation or intrabronchial spread.
• Lymph node disease: As a result of primary infection,
parahilar and paratracheal nodes may be involved;
complications may include airway involvement leading to
alveolar collapse or pneumonia.
• Pleural or pericardial effusion: This represents a
hypersensitivity reaction resulting in straw-
colored fluid with high lymphocyte count. If
mycobacterium bacilli grow in pleural space,
localized empyema is formed. Pericardial effusion
may lead to constrictive pericarditis.
• Miliary disease: This results from hematogenous
dissemination of bacilli; < 2 mm nodules are seen
on chest X-ray extending up to the periphery.
• Adult-type cavitory lesion: This is usually seen
around 8–10 years of age and beyond.
CLINICAL FEATURES
 Clinical Features
• Pulmonary TB can present with :-
• Cough and/or fever for more than 2 weeks, not
responding to a course of antibiotic for 7–10 days
• Weight loss (more than 5% of the highest recorded
weight in the past 3 months) or not gaining weight
• Poor appetite
• Lethargy or easy fatigability
• and night sweats.
There may be history of contact with an open case
of TB within the last few years.
DIAGNOSIS
Diagnostic algorithm for Paediatric Pulmonary Tuberculosis
Tuberculin Skin Test (Mantoux Test)

• Tuberculin skin test (TST) is an intradermal skin test

with 5 TU of purified protein derivative (PPD)-S or 2
TU of PPD RT 23 or equivalent, read after 48–72
hours.
• An induration of 10 mm or more is considered
positive. In immunocompromised individuals,
induration of 5 mm or more is considered positive.
• Positive TST merely indicates presence of tubercular
infection and not disease; hence, it can only aid in
diagnosis of TB disease and not confirm it.
 Imaging
• Chest X-ray:
Radiological features highly suggestive of TB
include hilar or paratracheal lymph nodes
with or without parenchymal involvement,
miliary pattern, fibrocavitary lesion.
If left untreated, miliary nodules may coalesce
and may reach 3–5 mm in size, radiologically,
described as a “snow-storm” appearance.
PRIMARY TB

The most common

abnormality in children is
lymph node enlargement,
which is seen in 90-95% of
cases.
Chest X-ray showing bilateral
infiltrates.
GHON COMPLEX

• Typically of primary
tuberculosis in a child.
•Parenchymal
involvement is more in
adults.
Airspace consolidation is
usually unilateral, is
evident radiographically in
approx 70 % of children
with primary TB
POST- PRIMARY TUBERCULOSIS

Focal or patchy heterogeneous

consolidation involving the
apicoposterior segment of the upper
lobes and the superior segments of
the lower lobes.
Pleural Effusion in TB

Pleural effusion is usually

unilateral and due to
subpleural infection.

Pleural effusions are more

common in adults with
primary tuberculosis (40%)
CAVITATION

X-ray showing cavitatory

consolidation in right
upper lung zone and
multiple ill-defined
nodules in both lungs
ATELECTASIS
(Volume Loss)

Shows a right upper lobe

airspace opacity adjacent to the
trachea.
In adition, there elevation of the
minor fissure.
RANKE COMPLEX

The Combination of calcific

lesions of the lung and
lymph node is referred to as
the “ Ranke complex”.
HEALED TB

Calcified nodule consistent

with a calcified granuloma.
In addition there is bilateral
apical pleural thickening.
Contrast-enhanced computed tomography
(CECT) chest:
• Computed tomography (CT) chest may be done in cases where the chest
X-ray is not conclusive.
• CECT chest enables evaluation of parenchymal lesion; identification of
necrosis in lymph nodes; description of pleural, airway, and
diaphragmatic pathologies; and evaluating visualized bones.
• CECT features suggestive of TB include necrotic lymph node with a low-
density center surrounded by rim enhancement (rim sign), 2–4 mm
centrilobular nodules, and tree-in-bud appearances (sharply marginated
linear branching opacities around terminal and respiratory bronchioles)
indicating endobronchial spread, thick-walled cavity surrounded by
parenchymal lesion indicating active disease.
• CT may also be useful in undertaking guided aspiration/biopsy from
mediastinal nodes for cyto/histopathology and microbiological diagnosis
CECT show tuberculous
nodes that show central
areas of low attenuation
suggestive of caseous
necrosis and peripheral rim
enhancement.
 Tools for microbiological confirmation of Tuberculosis

A. Sputum Smear Microscopy (for AFB):

• • Zeihl-Neelsen Staining
• • Fluorescence staining
B. Culture:
• • Solid (Lowenstein Jensen) media
• • Automated Liquid culture systems e.g. BACTEC MGIT 960, BacT Alert or Versatrek
etc.
C. Drug Sensitivity Testing:
• • Modified Proportionate Sensitivity Testing (PST) for MGIT 960 system
• • Economic variant of Proportion sensitivity testing (1%) using LJ medium
D. Rapid molecular diagnostic tests:
• • Line Probe Assay (LPA) for MTB complex and detection of RIF & INH resistance (FL
LPA) and FQ and SLI resistance (SL LPA)
• • Nucleic Acid Amplification Test (NAAT) (CBNAAT/Truenat)
Diagnostic algorithm for Paediatric Pulmonary Tuberculosis
Anti-tubercular therapy
Category-based treatment for tuberculosis
in children.
Category of treatment Inclusion criteria Treatment regimen

Intensive Continuation
phase phase
New cases (Category 1) • New smear-positive 2 HRZE 4 HRE
pulmonary tuberculosis
• New smear-negative
pulmonary tuberculosis
• New extrapulmonary
tuberculosis

Previously treated cases • Relapse, failure to 2 HRZES + 1 5 HRE

(Category 2) respond or treatment HRZE
after default
• Retreatment
 Range Average Maximum dose(mg)
mg/kg/day mg/kg/day

Rifampicin R 10-20 15 600

Isoniazid H 7-15 10 300
Pyrazinamide Z 30-40 35 2000
Ethambutol E 15-25 20 1500
Streptomycin S 15-20 20 1000
 Prophylaxis
• Isoniazid is prescribed for chemoprophylaxis at a dose of 10 mg/kg of
body weight/day, for 6 months.
Tuberculosis preventive therapy or chemoprophylaxis should be provided
in the following scenarios:
• All asymptomatic contacts, less than 6 years of age, of an open case of
TB (smear positive), after ruling out active disease. Status of BCG
vaccination or TST reading does not preclude one from receiving this
chemoprophylaxis.
• All HIV-infected children with a known exposure to an infectious TB
case, but with no active TB disease.
• All TST-positive children who are receiving immunosuppressive therapy.
• A child born to mother who was diagnosed to have TB in pregnancy,
after ruling out congenital TB. BCG vaccination can be given at birth
even if chemoprophylaxis is planned.
 Classification based on drug resistance
a. Mono-resistance (MR): A TB patient, whose biological specimen is resistant
to one first-line anti-TB drug only.
b. Poly-Drug Resistance (PDR): A TB patient, whose biological specimen is
resistant to more than one first-line anti-TB drug, other than both isoniazid
(INH) and Rifampicin (R).
c. Multi Drug Resistance (MDR): A TB patient, whose biological specimen is
resistant to both isoniazid and rifampicin, with or without resistance to other
first line drugs, based on the results from a quality assured laboratory.
d. Rifampicin Resistance (RR): resistance to rifampicin detected using
phenotypic or genotypic methods, with or without resistance to other anti-TB
drugs excluding INH. Patients, who have any Rifampicin resistance, should also
be managed as if they are an MDR TB case.
e. Extensive Drug Resistance (XDR): A MDR TB case whose biological specimen
is additionallyresistant to a fluoroquinolone (ofloxacin, levofloxacin, or
moxifloxacin) and a second-line injectable anti TB drug (kanamycin, amikacin, or
capreomycin) from a quality assured laboratory.
 BCG vaccine
Bacille Calmette–Guérin is the only vaccine for TB
disease used at present. The protection it provides
against pulmonary TB is variable; however, it has 60–
80% protective efficacy against more serious,
disseminated diseases in children such as Miliary TB
and TB meningitis.
When to give – BCG vaccine is given at birth or as early as
possible till 1year of age.

Route and site- BCG is given as intradermal injection (0.05-

0.1cc) in left upper arm.
 Evolution of TB Control in India
• 1950s-60s - Important TB research at TRC and NTI
• 1962 - National TB Programme (NTP) ( Designed for Domiciliary
Treatment, using self administered drug regimens)
• 1992- Programme Review - only 30% of patients diagnosed; of these,
only 30% treated successfully
• 1993 - RNTCP pilot began
• 1998 - RNTCP scale-up
• 2001 - 450 million population covered
• 2004 - >80% of country covered
• 2006 - Entire country covered by RNTCP on 24th march
• Since inception from 97-98 to Dec 2015 more than 19million patients
were initiated
National on treatment
TB Program- and More than 3.5 million additional lives
NTP (1962-1997)
have been
Revised saved.
National TB Control Program- RNTCP (1997-2020)
National TB Elimination Program- NTEP (2020-till date)
 REFERRENCES
• Nelson textbook
• IAP textbook
• GHAI textbook
• TBCINDIA.com
• WHO.com
THANK YOU