PEDIATRIC

TUBERCULOSI
S

Tuberculosis
an infectious disease caused by the bacteria
Mycobacterium tuberculosis
transmitted through coughing, sneezing and
spitting
commonly affects the LUNGS but it could also
affect other organs such as the kidney, bones, liver
and others
curable and preventable; however, incomplete or
irregular treatment may lead to drug-resistant TB
or even death

Etiology
Mycobacterium tuberculosis complex
Mycobacterium tuberculosis
Mycobacterium bovis
Mycobacterium canetti
Mycobacterium africanum
Mycobacterium microti

Tubercle Bacilli
non spore forming, non motile, pleomorphic,
weakly Gram+ 1-5um, slender and slightly bent,
obligate aerobes
Hallmark: ACID FASTNESS- ability to form stable
mycolate complexes with arylmethane dyes
(crystal violet, carbolfuschin, auramine, and
rhodamine)

Pediatric (vs Adult) TB

1. The diagnosis of TB is more difficult in children due to
non-specific or complete absence of symptoms and
difficulty in confirming the diagnosis microbiologically.
2. Young children suffer more extrapulmonary and
disseminated TB than adults.
3. Treatment of TB in children is challenging due to the
lack of pediatric drug formulations and challenges in
monitoring for toxicity.

4. Children should be TB skin tested only if they have risks

for TB infection, are likely to progress to active TB, or are
suspected of having active TB. Unlike adults, all children
should be treated for latent TB infection if identified
because the therapy is very safe in young people, they
were likely to have been infected relatively recently, and
they have a long time to reactivate their latent infection.
5. Young children are not contagious with active TB and
acquired their disease from shared airspace with
adolescents or adults with pulmonary TB or ingestion of
unpasturized milk products (M. bovis).

Transmission
By inhalation of airborne mucus DROPLET NUCLEI,
particles 1-5m dmcontaining M. tuberculosis
Rarely by direct contact with infected discharge or
contaminated fomite
Chance of transmission increases:
Positive acid smear of sputum
Extensive upper lobe infiltrate and cavity
Copious production of thin sputum
Severe ad forceful cough
Poor air circulation

 No transmission within several days to 2 weeks

beginning adequate chemotherapy
YOUNG CHILDREN with TB RARELY infect other
children and adults
Tubercle bacilli are sparse in the
endobronchialsecretions of children
Cough is often absent or lacks in tussiveforce

 Tubercle bacilli multiply initially within the alveoli

and alveolar ducts
Bacilli in nonactivated macrophages carried to
lymphatic vessels to regional lymph nodes
Tissue reaction in the lung parenchyma and LN
intensifies over the next 2 to 12 weeks as the
organism proliferates and hypersensitivity
develops

Parenchyma often heals by FIBROSIS or

CALCIFICATION after undergoing CASEOUS
NECROSIS AND ENCAPSULATION

PATHOGENESIS
Primary Complex (Ghon Complex)
-local infection at the portal of entry and the
regional lymph nodes that drain the area
-LUNGS -portal entry in >98%
-hilar lymph nodes are usually involved
-upper lobe focus-paratracheal nodes

PRIMARY COMPLEX
tubercle bacilli are carried to most tissues of the
body through the blood and lymphatic vessels
seeding of the organs of the reticuloendothelial
system is common, bacterial replication is more
likely to occur in organs with conditions that favor
their growth, such as the lung apices, brain,
kidneys, and bones

DISSEMINATED TUBERCULOSIS
The number of circulating bacilli is large and the
hosts cellular immune response is inadequate
More often the number of bacilli is small, leading to
clinically inapparent metastatic foci in many organs

The time between initial infection and clinically

apparent disease is variable
DISSEMINATED AND MENINGEAL TB
-early manifestations, within 2-6 mos
SIGNIFICANT LN or ENDOBRONCHIAL TB
-within 3-9mos
BONES AND JOINTS LESIONS
-several years
RENAL LESIONS
-after decades of infection

EXTRA-PULMONARY MANIFESTATIONS
more common in children than adults
develop in 25-35% of children with TB
10% in immunocompetent adults

tubercle bacilli replicate in

both free alveolar
spaces and inactivated
alveolar macrophages

tubercle bacilli replicate in

both free alveolar
spaces and inactivated
alveolar macrophages

lymphocytes that recognize

mycobacterial antigens proliferate
and secrete lymphokines
and other mediators that attract
other lymphocytes
and macrophages to the area

tubercle bacilli replicate in

both free alveolar
spaces and inactivated
alveolar macrophages

lymphocytes that recognize

mycobacterial antigens proliferate
and secrete lymphokines
and other mediators that attract
other lymphocytes
and macrophages to the area

Certain lymphokines activate

macrophages, causing them
to develop high concentrations
of lytic enzymes that enhance their
mycobactericidal capacity.

Innitial tuberculosis infection

pathologic events depend on the balance among:
mycobacterial antigen load
cell-mediated immunity (intracellular killing)
tissue hypersensitivity (extracellular killing)

small antigen load

+
high degree of tissue sensistivity
=
solid granuloma formation
(lymphocytes, macrophages, fibriblasts)

small antigen load

+
high degree of tissue sensistivity
=
solid granuloma formation
(lymphocytes, macrophages, fibriblasts)

high antigen load

+
high degree of tissue sensistivity
=
caseous granuloma formation
(less organized, tissue necrosis is incomplete

high antigen load

+
low degree of tissue sensistivity
=
dissemination of infection
+
local tissue destruction

3 Major Clinical Stages

Expos
ure

had significant contact ("shared the air")

with an adult or adolescent with infectious
tuberculosis but lacks proof of infection
(-) TST/IGRA, CXR is normal, PE is normal,
lacks s/sx of disease

Infecti
on

an individual inhales droplet nuclei

containing M. tb which survive
intracellularly within the lung and assoc
lymphoid tissue
hallmark: + TST or IGRA

Diseas
e

s/sxs or radiographic manifestations

caused by M. tb are apparent

EXPOSURE

TST/IGRA

S/SX

PHYSICAL
EXAM

RADIOGR
APH

(-)

NORMAL

NORMAL

NORMAL

INFECTION

(+)

NORMAL

NORMAL

NORMAL or
granuloma/
calcificatio
ns

DISEASE

(+)

APPARENT

APPARENT

APPARENT

Clinical Manifestation
symptoms and physical signs of primary PTB in
children inadequate/limited considering the
degree of radiographic changes
most common symptoms:
Nonproductivecough and mild dyspnea

Less often:
Systemic complaints: fever, night sweats, anorexia, and
decreased activity

DIAGNOSTIC TOOLS
TUBERCULIN SKIN TEST
Mantoux Test intradermal injection of 0.1 mL purified
protein derivative stabilized with Tween 80
T cells sensitized by prior infection are recruited to the
skin
Release lymphokines that induce induration through
local vasodilation, edema, fibrin deposition and
recruitment of other inflammatory cells
Induration measured by 48-72 hrs after
Tuberculin sensitivity develops 3 wksto 3 mos after
inhalation

 INTERFERON-y RELEASE ASSAYS (IGRA)

2 blood tests that detect IFN-y generation by the
patients's T cells in repsonse to specific M.tb antigens

CASE FINDING
the identification and diagnosis of TB cases among
individuals with signs and symptoms presumptive of
tuberculosis
current approach includes passive and intensified case
finding
Available tests utilized
-direct sputum smear microscopy
-TB culture and drug susceptibility test
-tuberculin skin test and
-rapid molecular diagnostic tests

PRESUMPTIVE TB
A. For patients 15 years old and above, a presumptive TB has any of
the ff:
1. Cough of at least 2 weeks duration with or without the ffsymptoms
Significant and unintentional weight loss
Fever
Bloody sputum
Chest/back pains not referable to any musculoskeletal disorders
Easy fatigability
Night sweats
Shortness of breath or DOB

2. Unexplained Cough of any duration in:

Close contact of a known active TB case
High-risk clinical groups
High-risk populations

B. For patients below 15 years old, a presumptive PTB has

any of the ff:
1. At least three (3) of the following clinical criteria:
Coughing/wheezingof 2 weeks or more, espif unexplained
Unexplained fever of 2 weeks or more after common causes
such as malaria or PNA have been excluded
Loss of weight/failure to gain weight/weight faltering/loss of
appetite
Failure to respond to 2 weeks of appropriate antibiotic therapy
or lower respiratory tract infection
Failure to regain pervious stat of health2 weeks

2. Any one (1) of the above signs and symptoms

(e.g., clinical criteria) in achild who is a close
contact of a known active TB case.

C. CXR findings suggestive of PTB, with or

without symptoms, regardless of age.

TREATMENT
Basic principles in management of TB in children and
adolescents are the same in adults
Recommendations by CDC and American Academy of Pediatrics:
standard therapy of intrathoracic tb (pulmonary diseaseand/or
hilar LAD) in children,
6 more gimen of isoniazid and rifampin supplemented in the
1st 2 moof treatment by pyrazinamide and ethambutol
2HRZE/4HR
several clinical trials show this regimen yields a success
rateapproaching 100%, with an incidence of clinically significant
adverse reactions of <2%.

 experts recommend that all drug administration be

directly observed, meaning that a healthcare
worker is physically present when the medications
are administered to the patients
When DOT is used, intermittent (twice or thrice
weekly) administration of drugs after an initial
period as short as 2 wk of daily therapy is as
effctive in children as daily therapy for the entire
course

Extrapulmonary TB
Tx is same as for pulmonary tuberculosis
bone and joint, disseminated, and CNS
tuberculosistreated for 9-12 mo.
Surgical debridement in bone and joint disease
and ventriculoperitonealshunting in CNS disease
may be necessary adjuncts to medical therapy.

TB in HIV-infected children
optimal tx of tuberculosis in HIV-infected children
has not been stablished
Data for children are limited; most experts believe
that HIV-infected children with drug susceptible
tuberculosis should receive the standard 4-drug
regimen for the 1st 2 mo followed by isoniazid and
rifampin for a total duration of at least 9 mo
Have more frequent adverse effects

TREATMENT INITIATION
1.Inform px that he/she has TB disease and motivate
him/her to undergo tx.
2.For patients less than 18 years old, talk to the
parent/guardian regarding the need for the child to
undergo treatment. Provide, as necessary, the
following key messages for TB patients and their
families:
Need for at least 6-8 months of supervised, well
documented TB txwith good compliance
Free anti-TB drugs in DOTS program

Public health facilities offer free bacteriology

service
Schedule of ff-upDSSM for monitoring
Tracing mechanism if lost to ff-up by which the px
will b contacted
How to address possible adverse drug rxns
Relevance of contact investigation
Cough etiquette and other pertinent infection
control measures

FOLLOW-UP and MONITORING

Ask for the patients Form 5. NTP ID Card and inquire how
he/shehas been since the last clinic visit.
Ask the patient about the following:
General well-being
Progression or resolution of symptoms
Adverse drug reactions or side effects
Compliance to treatment and DOTS
Any problem or concerns regarding the treatment so far.