TB

Soumaya Hadhood
Prof. Of Pediatrics
Sohag University
 Definition
Tuberculosis is a granulomatous disease that may
involve any tissue of the body. It is especially
prevalent in populations suffering of poor nutrition,
overcrowding and insufficient health care.

Etiology
It is caused by the acid- fast, alcohol-fast
Mycobacterium tuberculosis.

Detected by
1. Arylmethane dye
2. Culture
3. PCR
 Predisposing Factors
1.Exposure to infected adult
2.Low socioeconomic status,
overcrowding with poor air
circulation→ repeated exposure
to infection.
3.Poor nutrition, inadequate health
care→ low body resistance.
 Modes of transmission

Air borne infection: by droplet or dust

inhalation. The route of entry is the
lungs or tonsils.
Alimentary infection: by ingestion of infected milk or a contaminated
matter. The route of entry is the tonsils or small intestine.
Wound infection: by handling a contaminated material. The route of
entry is the skin.

Incubation Period
It ranges from 4-6 weeks (from time of
infection to development of a positive
tuberculin test).
 .In contrast to adults, children are
generally not infectious.

Children usually acquire TB from an

infected adult in the same household.
Pathology and Pathogenesis
Primary sites of infection are the lungs,
tonsils, intestine and skin.

Latent TB : It is characterized by positive

tuberculin test and absence of clinical and
radiological manifestations. 5-10% of
infected INFANTS AND YOUNG
CHILDREN develop tuberculosis disease if
infection is left untreated.

active TB Tuberculous disease occurs

when clinical or radiological manifestations
of T.B appear.
There is an important distinction

between latent TB (an asymptomatic

infection state) and TB disease
(active TB). Latent TB is more likely

to progress to active TB in infants and

young children compared with adults
Asymptomatic children with a positive

tuberculin skin test (TST) or

interferongamma release assays
result (i.e. latent TB) should be given
chemoprophylaxis (isoniazide for 9
moths) to prevent future conversion to
active TB.
Symptomatic

When the host’s cellular immune

system responds to the infection (3–6

weeks), mycobacterial replication

diminishes but systemic symptoms
develop:
fever
• anorexia and weight loss
• cough
• chest Xray changes
The primary complex (The lung lesion
plus the lymph node )usually heals
and may calcify. The inflammatory
reaction may lead to local
enlargement of peribronchial lymph
nodes, which may cause bronchial
obstruction, with collapse and
consolidation of the affected lung.
Pleural effusions may also be
present. Further progression may be
halted by the host’s immunological

response, or there may be local

dissemination to other regions of the
lung.
Dormancy and dissemination

Both asymptomatic and symptomatic

infections may become dormant but

subsequently reactivate and spread

by lymphohaematological routes
Lymphohematogenous dissemination
through the lung to extrapulmonary
sites including the brain and
meninges, eyes, bones , joints, lymph
nodes, kidneys intestine larynx and
skin is more likely to occur in infants.
Reactivation (Post-primarTB)
This may present as localized disease
or may be widely disseminated (called
miliary TB), to sites such as bones,
joints, kidneys, pericardium, and CNS.
Infants and young children are
particularly prone to tuberculous
meningitis. This was always fatal before
antimicrobial therapy was available,and
is still associated with significant
morbidity and mortality if treatment is not
initiated early.
PULMONARY TUBERCULOSIS

Primary Pulmonary Disease

Definition
It is the type of T.B which follows the first
infection of the lung with tubercle bacilli.
This type is called childhood type as it is
frequent in children.
Mode of infection
Droplet infection. The source is usually an
adult contact who is suffering from open
pulmonary T.B.
Formation of the primary pulmonary complex
An initial lesion occurs in the lung that takes the
form of a small focus, about one cm. in diameter,
situated subpleurally and consists of tubercles
showing central caseation. This primary lesion is
called Gohn's focus".
The draining lymphatic vessels show multiple
tubercles along their course "tuberculous
lymphangitis".
Many tubercles appear in the draining hilar lymph
nodes which become enlarged and undergo rapid
caseation "tuberculous lymphadenitis".
The triad of Gohn's focus, tuberculous lymphangitis
and tuberculous lymphadenitis is called the "primary
pulmonary complex
Chest Xray of pulmonaryTB.There is
marked left hilar lymphadenopathy
Fate of primary pulmonary complex
It depends on the virulence of the organism
and the state of immunity of the patient
which is affected by genetic factors,
nutritional status, age and presence of
other infections as measles, whooping
cough or recurrent streptococcal infections.
Good immunity + mild infection → healing
by fibrosis and calcification.
Low immunity + severe infection→ spread.
Clinical picture

Fatigue, irritability and under nutrition

with or without fever and cough.

paroxysmal cough similar to

whooping cough may be present
 EXTRAPULMONARY
TUBERCULOSIS
Lymph Node Disease
Definition
Tuberculosis of the superficial lymph nodes,
often referred to as scrofula, is the most
common form of Extrapulmonary T.B in
children.
Mode of infection
anterior cervical, submandibular and
supraclavicular nodes become involved
secondary to primary T.B of the upper lung
fields , tonsils .
T.B of the skin or skeletal system is usually
associated with affection of the inguinal,
epitrochlear or axillary lymph nodes.
 Tuberculous Mediastinal
Lymphadenitis
Definition
The hallmark of primary T.B in the lung is the
relatively large size of the regional lymphadenitis
compared with the relatively small size of the initial
lung focus.
Clinical picture
Minimal general symptoms of T.B, but paroxysmal
cough similar to whooping cough may be present
cyanosis and engorged neck veins due to
compression of large blood
Obstructive Emphysema: Due to partial
bronchial obstruction. Clinical signs include
decreased air entry, localized or even
generalized wheezes and hyperinflated
lungs.

Atelectasis (collapse); Due to complete

bronchial obstruction . Clinical signs
include signs of local collapse and shifted
mediastinum to the affected side

Atelectasis + pneumonic consolidations:

Due to complete obstruction of bronchi with
erosion of the walls and pouring of caseous
material into the collapsed part. If the
poured caseous material contains TB
bacilli there is more severe toxemic
manifestations.
 Endobronchial TB

It occurs when the inflamed caseous nodes

attach to the endobronchial wall and erode
through it causing a fistula tract or
endobronchial T.B. Clinically it presents
with wheezy chest.
Chest X-ray shows enlarged mediastinal
lymph nodes and radiographic signs of
collapse, consolidation or emphysema
 Pleural Effusion
Asymptomatic local pleural effusion is so frequent
in primary T.B that it can be considered a
component of the primary complex .
Tuberculous pleural effusion occurs when T.B
bacilli reach the pleural space from a subpleural
pulmonary focus or a caseated lymph node. .
o Symptoms of T.B pleurisy are of sudden
onset and include low to high fever, shortness of
breath and chest pain on deep inspiration.
o On clinical examination, there are diminished
breath sounds
o Pleural effusion is usually unilateral but may
be bilateral.
Radiographic abnormalities are more extensive
than would be suggested by symptoms or physical
findings
Clinical picture

The disease is usually unilateral, but bilateral

involvement may occur.
The onset is acute with high fever, rapid
enlargement of lymph nodes, tenderness and
fluctuance with overlying cellulitis or skin
discoloration.
The nodes are firm, discrete,non-tender and often
feel fixed to the underlying or overlying tissues.
Later on, the lymph nodes tend to become matted
together and may liquify and rupture into the
overlying skin forming chronic sinuses.
Abdominal and Gastrointestinal
Disease

Definition
Abdominal T.B includes Tabes
mesenterica, T.B enteritis and T.B
peritonitis.
Mode of infection
Ingestion of T.B bacilli (bovine or human).
Swallowing sputum containing the
organism from tuberculous lesion in the
lung.
Hematogenous dissemination.
Tabes Mesenterica
Mesenteric glands in the right iliac fossa are affected
first.
The glands enlarge, become adherent to intestinal
loops,
They heal by fibrosis and calcification or liquify and
discharge their content in the peritoneum or spread by
blood leading to tuberculomata or miliary T.B.
Clinical Picture
General manifestations of T.B.
Attacks of abdominal pain, failure to thrive, mild attacks
of diarrhea alternating with constipation, passage of
fatty stools due to obstruction of lacteals.
Presence of palpable glands in the abdomen (multiple,
firm, slightly mobile and slightly tender)
Tuberculous Enteritis
The jejunum and ileum near Peyer’s patches and the
appendix are the most common sites of involvement.
There are shallow ulcers that spread in a circular
direction following the line of lymphatics.

Clinical picture
Chronic diarrhea with loose, slightly offensive stools
that may contain blood and mucus.
Low grade fever, loss of weight, abdominal pain and
tenderness.
The picture is non specific, but the disease should be
suspected in any child with chronic gastrointestinal
complaints and a reactive tuberculin test.
Tuberculous Peritonitis
Generalized peritonitis arise from subclinical or
miliary Hematogenous dissemination.
Localized peritonitis is caused by direct extension
from an abdominal lymph node, intestinal focus or
genitourinary T.B.

Clinical picture
Generalized (ascitic) peritonitis usually presents
with low grade fever, ascites, abdominal
enlargement, pain and tenderness.

Localized (plastic) peritonitis usually presents with

fever, anorexia, weight loss, swollen and doughy
abdomen. The omentum may be felt as a sausage
shaped mass across the epigastrium.
Central Nervous System Disease

Definition : It is the most serious

complication of T.B. in children and is fatal
without effective treatment. It may occur in
two forms, T.B. meningitis or tuberculoma.
Mode of infection :Lymphohematogenous
spread of the primary infection, leading to
formation of Metastatic caseous lesions in
the cerebral cortex or the meninges.
Tuberculous Meningitis

Clinical picture
It is most common in children between 6
months and 4 years of age.
The clinical progression of T.B. meningitis
may be rapid in infants and young
children.
Fever, vomiting, headache, lethargy and
irritability,increased intracranial tension,
Meningeal irritation, seizures, and coma.
Tuberculoma

Clinical picture
It usually presents clinically as a brain
tumor.
Lesions may be multiple, but often are
infratentorial, located at the base of
the brain near the cerebellum.
There is fever, headache and
convulsions.
Miliary Tuberculosis
Definition
It occurs when massive numbers of tubercle bacilli
are released into the blood stream, causing
disease in two or more organs.
Clinical picture
It occurs within 2-6 months of the initial infection.
It is most common in infants and malnourished or
immunosuppressed patients.
The onset is sometimes explosive, and the patient
becomes gravely ill in several days.
More often, the onset is insidious with early
systemic signs, including anorexia, weight loss,
and low–grade fever.
Lymphadenopathy and HSM usually develop
within several weeks.

The lungs then become filled with tubercles,

and dyspnea, cough or wheezing occurs.

Chest x-ray shows lesions smaller than 2-3

mm which coalesce to form large lesions and
sometimes extensive infiltrates (miliary
shadows or snow storm appearance)

Meningitis may be found with chronic or

recurrent headache.
Peritonitis with abdominal pain or tenderness
may also occur.
Choroid tubercles seen on fundoscopic
examination occur in about 50% of patients
and are highly specific for the diagnosis of
miliary tuberculosis.
DIAGNOSIS OF TUBERCULOSIS

History : history of contact with an adult with open

TB.
Physical examination
General toxemic manifestations as loss of body
weight, fever, night sweat, anorexia, easy
fatigability.
Signs of obstructive emphysema, collapse,
consolidation collapse, effusion or
bronchopneumonia depending on the underlying
pathology.
T.B. must be put in D.D. of any chronic chest
condition.
Diagnosis of TB in children is even
more difficult than in adults. The
clinical features of active TB are often
nonspecific, such as prolonged fever,
malaise, anorexia, weight loss, or
focal signs of infection (e.g. lymph
node swelling
(about three-quarter) of cases with
active TB have pulmonary TB;
extrapulmonary disease is less
common, and includes TB
lymphadenitis, enteritis, osteoarticular
TB, genitourinary TB, and TB
meningitis.
 gastric washings on three
consecutive mornings can be used to
identify M.
tuberculosis originating from the lung,
using special staining techniques for
acid–fast bacilli (Ziehl–Neelsen stains
or auramine stains) and
mycobacterial cultures
Investigations
Tuberculin test:
It is an allergic skin test detecting
the state of hypersensitivity to the
tuberculoprotein of the TB bacilli.
It depends on the proper function
of T- lymphocytes (i.e. delayed
hypersensitivity test).

It becomes positive 3 – 8 weeks

after onset of T.B. infection.
·
Technique: Intradermal injection of 0.1 ml
of the purified protein derivative (PPD) of
T.B. containing 5 tuberculin units into the
cleansed skin of the flexor or extensor
surface of the forearm. The injection is
made with a short sharply beveled needle
with special tuberculin syringe.
Example of a positive TST (24mminduration) A
TST is positive if the palpable induration is 5 mm
or more in diameter irrespective of whether or not
had BCG immunization (NICE guidelines,
2016).Only the induration should be measured
(not the surrounding erythema
A positive tuberculin reaction

indicates that the person has been

.

infected with the TB bacilli and is

hypersensitive to the

tuberculoprotein. However, it does

not mean an active lesion .

Causes of false negative tuberculin test

a. If the test is done during the incubation period

before the development of the hypersensitivity.
b. Advanced TB e.g. miliary TB, or TB meningitis.
c. Severe malnutrition.
Temporary supression of tuberculin
reactivity in
d. Acute viral infections as measles, rubella,
mumps.
e.Corticosteroid administration.
f. Vaccination with live attenuated viral vaccines
g. Malignancy as lymphoma or the use of cytotoxic
drugs
Causes of false positive tuberculin
test
a. BCG vaccination.
b. Infection with atypical mycobacteria
which are not common in Egypt.
Interferone gamma release assays
They assess the response of T cells to
in vitro stimulation with a small number
of antigens expressed by M.
tuberculosis .
Have less false positive results from
non tuberculous mycobacterium and
BCG
USED IN ADULTS AND OLDER
CHILDREN NOT YET STUDIED IN
INFANTS
It is an invtro blood test
Neither IGRA nor the TST can
distinguish between latent TB and
active TB,so correlation with clinical
signs and symptoms is required.
Other investigations
Chest X-ray :
The findings depend on the lesion

1.segmental consolidation with

enlarged mediastinal lymph
nodes,
2.pleural effusion.
3. Cavities and apical disease are
unusual in children but common
in adults
4. miliary TB
Figure 1: Enlarged hilar lymph nodes on the right hand side. The lungs
appear normal. This is the commonest form of childhood TB.
Figure 2: Primary TB infection of the left
lower lobe
Figure 3: Enlarged hilar and paratracheal lymph nodes with TB pneumonia
of the right middle lobe. On careful inspection narrowing of the right
bronchus can be seen.
Figure 4: A large right sided pleural effusion seen in an
older child
Figure 5: Severe TB in an adolescent with scattered areas
of pneumonia and cavities in both upper lobes. This higly
infectious form of TB is usually seen in adults.
Figure 6: A typical example of miliary TB with fine
nodules visible in all the lobes of both lungs
 CSF examination
Done in case of T.B. meningitis or miliary T.B.
The CSF has the following criteria
Ø fluid is turbid with the so called ground
glass appearance.
Ø The pressure is increased.
Ø The cells are increased in number is with
(pleocytos with predominance of
lymphocytes.)
Ø The protein content increases while glucose
decreases.
Ø On standing, the CSF forms a fibrinous web
in which the TB bacilli can be demonstrated
by direct examination using auramine or
Ziehl- Neelsen stain, or by culture, or guinea
pig inoculation.
Direct detection of mycobacterium in
body fluids and discharges
(urine ,CSF, gastric wash) is best done
by staining specimens with auramine-
rhodamine and examining them with
fluorescence microscopy this method
is superior to the Zeil-Neelsen method
Although it is difficult to culture TB
from children, the rise of MDR-TB
makes it important to try to grow the
organism so that antibiotic sensitivity
can be assessed.
PCR-based methods for the detection
of M.tuberculosis are increasingly
being used in parallel with
mycobacterial cultures; however,
these methods only provide limited
information regarding drug resistance
and therefore cannot replace cultures.
PREVENTION :
1- BCG vaccine

Active immunization: BCG vaccine

BCG, which is a live vaccine, should not
be given to HIV-positive or other
immunocompromised children due to the
risk of severe local reactions and
dissemination.

It decreases disseminated TB in infants

BCG vaccine has been shown to
reduce the incidence of systemic TB,
but its protective effect is
incomplete(i.e. BCG-vaccinated
children can still acquire TB Infection
eg. Pulmonary TB)
2-Case finding and treatment

As most children are infected by a

household contact, it is essential to
screen other family members for TB
infection.
Children who are exposed to
individuals with pulmonary TB should
be assessed for evidence of latent TB
(by TST and IGRA).
3-ISONIAZIDE CHEMOPROPHYLAXIS

The latest NICE (National Institute for

Health and Care Excellence)
guidelines recommend that children
under 2 years of age who had close
contact with a sputum smear-positive
pulmonary TB person should be
started on prophylactic isoniazid;
3-ISONIAZIDE CHEMOPROPHYLAXIS

if the TST and the IGRA are negative

at 6 weeks, isoniazid should be
discontinued and the BCG vaccine
should be given (unless previously
immunized with BCG).
3-ISONIAZIDE CHEMOPROPHYLAXIS
All contacts below 5 years who have
negative tuberculin test should receive
INH for 3 months followed by
vaccination.

All contacts below 5 years who have

positive tuberculin test and were not
Given BCG should have an X-ray chest
and receive INH for 9 months
TREATMENT
General
Adequate nutrition is very important.
Careful follow up to promote adherence to
therapy and to monitor for toxic reactions to
medications.
Specific
Antituberculosis drugs
There are many antituberculosis drugs
which differ in their primary sites of activity
and their actions.
Triple or quadruple therapy
(rifampicin, isoniazid, pyrazinamide,
ethambutol) is the recommended
initial combination, unless MDR-TB is
strongly suspected (e.g. when a
household member has been recently
diagnosed with MDR-TB).
This is decreased to rifampicin and
isoniazid alone after 2 months, by
which time antibiotic sensitivities are
often known. Treatment for
uncomplicated pulmonary TB or TB
lymphadenitis is usually for 6 months;
longer treatment courses (12 months or
more) are required for osteoarticular TB,
TB meningitis, or disseminated disease.
In tuberculous meningitis,
dexamethasone is given initially, to
decrease the risk of long-term sequelae.
Asymptomatic children who are
Mantoux or IGRA positive and
therefore latently infected should also
be treated (e.g. with rifampicin and
isoniazid for 3 months or isoniazid
alone for 6-9 months) as this will
decrease the risk of reactivation (i.e.
conversion to active TB) later in life.
Antituberculosis drugs in
children
Isoniazid (INH)
Mode of action: Highly bactericidal for M.
tuberculosis
Dose : 10 mg/kg/day (maximum=300).
Side effects:Two principal toxic effects which are
rare in children
Peripheral neuritis (due to competitive inhibition of
pyridoxine utilization)
Hepatotoxicity : 3-10% of children may experience
transient rise of transaminases but clinically
significant hepatotoxicity is very rare.
Rifampin
Mode of action: Highly bactericidal for M.
tuberculosis
Dose :15 mg/kg/day (maximum =600 mg)
Side effects:
Orange discoloration of urine and tears.
GIT disturbances.
Hepatotoxicity (asymptomatic rise of
transaminases(
Pyrazinamide

Mode of action: bactericidal for bacilli inside

macrophages.

Dose : 25-30 mg/kg/day (maximum = 2 g)

Side effects:
Increase serum uric acid (but manifestations of
hyperuricemia are rare).
Streptomycin
Mode of action: bactericidal for extracellular bacilli.
Dose: 20-30 mg/kg/day I.M. (maximum = 1 g( for
1-2 months in severe disease
Its major use is when INH resistance is suspected
or when the child has a life threatening form of
T.B.

Side effects :
The major toxicity is dose-related damage to the
vestibular and auditory portions of the 8th crania!
nerve.
Nephrotoxicity is much less frequent.
Drug Regimens in the Treatment
of Tuberculosis
Pulmonary T.B.
9 months course
INH + Rifampicin daily for 9 months. OR
INH + Rifampicin daily for 2 months then
INH (in double dose i.e. 20-30 mg/kg) +
Rifampicin (in usual dose) twice weekly for
7 months.
6months course
INH + Rifampicin + Pyrazinamide daily for
2 months followed by INH + Rifampicin
daily for 4 months.
Extrapulmonary T.B (including T.B.
meningitis and miliary T.B)

12 months course
INH + Rifampicin + Pyrazinamide +
Streptomycin daily for 2 months
followed by INH + Rifampicin daily (or
twice weekly as mentioned before) for
the remaining 10months.
Corticosteroids in TB
Indications:

T.B. meningitis to reduce vasculitis, inflammation

and intracranial pressure.
Releive of bronchial obstruction by hilar adenopathy
Pericardial effusion to prevent constrictive
pericarditis.
T.B. pleural effusion.
Severe miliary T.B.
T.B. chorioretinitis.
Adrenal TB.
Dose: Prednisone is given 1 mg/kg/day in 2 divided
doses for 4-6 weeks then gradual tapering.
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