4- Tuberculosis  In adults, you predominantly see cavitary TB in the

Dr. Carolie Lisa C. Sibulo apex why? Because of high ventilation perfusion at
D2017 the apex

 TB in children is usually subtle unlike TB in adults Transmission

which usually presents with hemoptysis
 TB is the most common among the top 5 diseases in  Person to person transmission by droplet of mucus
our country; so we’re very popular in WHO that become airborne when an infected individual
 Based on statistics, Philippines ranks 4 for TB coughs, sneezes, or laughs
 Still ranks as 1 of the 3 most important infectious  By direct contact with infected discharges (sputum,
diseases in the world in case of morbidity and saliva, urine or drainage from sinuses or abscess)
mortality; others are diarrhea and pneumonia  Children < 12 years old with 1˚ PTB are NOT
 Among developing countries still it is very common; contagious: (usually asked to pediatricians)
once a Filipino migrant goes to Canada or States, o TB bacilli are sparse in the endobronchial
they will screen them well for TB secretions
 Resurgence of TB in developed countries due to o Cough is minimal or non-existent
increased incidence of HIV o Little or no expulsion of bacilli; Children and
 TB is preventable and curable disease and yet it adolescent with adult type cavitary or endo-
remains a major health problem and 1 of the deadliest bronchial pulmonary TB can transmit the
disease worldwide disease
o ↑ transmission: (+) AFB smear, extensive
 Treatment is challenging because of multiple agents
upper lobe infiltrate or cavity, copious
 Give at least 4 drugs even in children
sputum, forceful coughing
 Why? to prevent multiple drug resistance
 Usually acquires the TB from an adult; look for the
 Causative agent? mycobacteria source. So screen for the family members. Start from
 Who discovered mycobacteria in 1882? Robert the household, screen also the yaya and caregivers
Koch, a German microbiologist. That’s why the other
name of TB is Koch’s infection. He also discovered Dissemination of Tuberculosis
anthrax, cholera, and formulated the Koch’s postulate.
 Koch’s postulate
o The microorganism must be found in
abundance in all organisms suffering from
the disease, but should not be found in
healthy organisms.
o The microorganism must be isolated from a
diseased organism and grown in pure
culture.
o The cultured microorganism should cause
disease when introduced into a healthy
organism.
o The microorganism must be reisolated from
the inoculated, diseased experimental host
and identified as being identical to the
original specific causative agent.
Droplets
Etiology
 Droplets may remain suspended for hours to days in
an enclosed house with poor ventilation
 Mycobacteria
 Sunlight can sterilized the droplet with MTB
 Classified into: Ingestion of unpasteurized milk
o M. tuberculosis complex
 Gastrointestinal TB
 M. tuberculosis
 In histopath you will see granuloma
 M. bovis
Handling specimens
 M. africanum
 M. microti
Incubation Period
 M. canetti
o Nontuberculous mycobacteria: may have
positive skin test  The incubation period from the time that the TB
 M. tuberculosis is the most important cause of TB bacillus enters the body until cutaneous sensitivity
disease in humans develops has been found to be 3 weeks to 3 months,
however the incubation period maybe shorter if the
 Non-spore forming, non-motile, pleomorphic, weakly
inoculum is large
gram (+) curve rods 1-5 um mm long, slow growth
with generation time of 12- 24 hours  The end of the incubation period coincides with the
onset of the tuberculin hypersensitivity
 Obligate aerobes that grow in synthetic media (LJ)
culture media

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 o Only positive is the exposure!

Tuberculin Skin Test (-)

Chest X-ray (-)
Signs and Symptoms (-)

 TB Infection- the child inhaled the droplets of TB

bacilli  established within the lungs and lymphoid
tissue
o Other name LTBI
o Give INH for 9 mos to prevent the
development of the disease
o However if resistant to INH, give 2 drugs:
INH and Rifampicin

Tuberculin Skin Test (+)

Chest X-ray (-)
So from the time of inhalation, it takes about 3 weeks to be Signs and Symptoms (-)
positive; once you become positive you will be positive for a
long period of time; you will have fever from 1-2 weeks after  Tuberculosis Disease
inhalation during night o Signs and symptoms:
 Afternoon lysis of fever
Disseminated TB  Cough of more than 2 weeks
 Lesser than 5 years old are more prone  Night sweats
 TB in other organs like brain, meningeal, military,  Weight loss
some children may have pleural effusion  Failure to thrive
 Did not respond well to usual
Primary complex starts with the site of the infection, as TB antibiotics given to pneumonia
bacilli is inhaled, alveolar macrophages engulf the bacteria   Di na nanunumbalik ang sigla
recruit more macrophages  cellular proliferation  initial site o Laboratory findings:
of infection  lymphadenopathy  lymphangitis  that  Sputum
comprises your primary complex  cannot collect sputum
because children cannot
Endobronchial TB expectorate
 Sometimes bronchial lymph nodes become affected  Age of children that can
 enlarged  encroached 1 portion of bronchus  expectorate: 7-8 years old
 Gastric AFB
increase the diameter
 Clinical signs and symptoms: unilateral wheezing,  Alternative specimen
hx of on and off coughing for more than 2 weeks,  Early morning
fever  Insert NGT  aspirate the
contents of the stomach
Skeletal TB  Yield: 33%
 Usually seen in lumbosacral thoracic spine  Cultures: LJ media
 Pott’s disease  IGRA- interferon gamma releasing
assay
Renal TB
 Slowest to acquire TB from time of infection, based on Tuberculin Skin Test (+)
timetable Chest X-ray (+)
 Common presentation: asymptomatic bacteriuria Signs and Symptoms (+)
 Longest incubation period: 1-5 years
Clinical Manifestations of Primary Pulmonary TB
Classification of Tuberculosis
 The hallmark of Primary Pulmonary TB
 TB Exposure- the child has significant contact with o Ghon Complex
an adult or adolescent with infectious pulmonary TB  Primary lung focus
o Remember Children < 5 years should be  Lymphangitis
treated with INH to prevent the rapid  One sided regional lymphadenitis
dissemination of TB which can occur before most often on the right
Skin Test becomes positive  Pleurisy
o For example yung yaya positive sputum, eh
naexposed na yung bata sa yaya. Positive History (+) exposure to an adult with
sputum AFB measures the infectivity of TB
the individual: meaning nakakahawa siya! S and Sx Pulmonary symptoms are
Lalo na pag plus 3! often meager, fever, night

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 sweats, anorexia, decrease  On rare occasion, the enlarging primary focus may
activity, poor weight gain rupture:
Mantoux Positive o Pneumothorax
Chest X-ray Ghon complex o Bronchopleural fistula
Treatment 2 months of intensive therapy o Caseous pyopneumothorax
with INH RIF PZA ETB o Tuberculous pericarditis/ mediastinitis
4 months INH and RIF  Clinical sign and symptoms:
o High fever
o Malaise
o Weight loss
o Egophony
 Prognosis
o Good with appropriate treatment

(+) Haziness and infiltrates

Progressive Primary Tuberculosis

 A serious complication of primary complex

 Seen in an older child/ adolescent with a history of
primary infection Kinakain yung lungs mo, magiging butas butas; eroding into
 The primary focus instead of resolving or calcifying the bronchus  hemoptysis (in adults)
develops a large caseous center
Reactivation Tuberculosis
 It has to have a cavitary lesion before you can say it
is a progressive primary TB
 Pulmonary TB in adults usually represents
 The center liquefies and empties into a bronchus to
endogenous reactivation of a site of TB infection
create a primary cavity
established previously in the body
 TB bacilli may spread to other parts of the lung
 The most common sites
creating multiple cavities can spread hematogenously
o Original parenchymal focus
or lymphohematogenously; depends on the immunity
o Lymph nodes
of the child, kung medyo immunocompromised, TB
o Apical seedings (Simon foci)
bacilli may rapidly spread  milliary or meningitis
Lymphohematogenous (Disseminated) Disease

Miliary TB

 Bacilli spreads via lymphatics to capillaries of most

organ system (oxygenated: liver, spleen, bone
marrow, and brain)
 Infants and young children affected as a complication
of primary TB occurring within 6 months of the
primary infection
 Reactivation of LTBI with subsequent caseation
necrosis
 Signs and symptoms
o Fever
o Chills
o Tachypnea
o Dyspnea
Active tb infiltrates on the right upper lobe; if initial lesion not o Organomegaly (hepatomegaly,
treated  may progress on cavitation splenomegaly)
o Skin lesions: possibility of HIV

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Chest X-ray Millet seed
Mandatory Lumbar tap For CSF examination
Mantoux test (+) but may be negative
Why? In disseminated form,
Skin Test may be falsely
negative
Treatment 2 months of INH RIF PZA
Streptomycin or Ethambutol
10 months of INH RIF
Add steroid to mitigate
alveolocapillary block
You nead to complete the tx
for 1 year
 Prognosis: Guarded
o Death occurs in 4-12 weeks if untreated
usually 2˚ to meningitis
o Fever resolves in 2-3 weeks of
chemotherapy
o X-ray lesions improve in 5-10 weeks
 It is infrequent in children < 6 years old and rare in
children < 2 years old
 Frequently associated with reactivation TB
S and Sx Onset is acute with high fever
and chest pain, dyspnea and
tachypnea
CXR Unilateral pleural effusion or
bilateral
 May resolve spontaneously with anti-TB drugs
 Adjunctive treatment with corticosteroids when there
are signs of pleurisy has been shown to accelerate
both the resolution of the symptomatology and
reabsorption of pleural effusion
TB of the Cervical Lymph Nodes
Scrofula
 This is the most common form of extra pulmonary TB
in children referred to as scrofula
 Often unilateral but bilateral involvement may occur
due to crossover drainage patterns of lymphatic
vessels in the chest and lower neck
 If left untreated, may lead to caseation necrosis of the
lymph node which may rupture and result in a sinus
draining tract
 Scrofula is infectious! Don’t ever touch!
 Produces a disfiguring scar (scrofuloderma)

Congenital Tuberculosis

 RARE
 Pathogenesis
o Transplacental spread
o Aspiration of infected amniotic fluid
 Clinical picture
nd rd
o Signs and symptoms begin in the 2 or 3
Millet seeds: Maliliit na lesions which is extensively seen in the
week of life similar to bacterial sepsis
lung parechyma
 Tuberculin test may be negative in the first 6-8 weeks
Endobronchial TB of life
o if due to aspiration – Miliary pattern
o if due to transplacental spread
 Extrabronchial or Extraluminal
(hematogenous)- Hepatic Calcifications
 As the nodes enlarge, they impinge and compress on
 Prognosis
the regional bronchus causing inflammation of the
o Mortality rate is high
wall and obstruction of the lumen (RML) usually right
middle lobe causes atelectasis on that side
Diagnosis of TB
S and Sx Pertussoid cough, tachypnea,
 Skin tests (positive 3 weeks to 3 months)
wheezes on the affected side
 Interferon- γ release assays
Chest X-ray Collapsed consolidation or
emphysema  Chest X-ray
Mantoux test (+)  Chest CT scan
Treatment 2 months of intensive therapy  Mycobacterial culture
with INH RIF PZA ETB  Newer tests (Nucleic acid probes, ELISA, PCR etc.)
4 months INH and RIF  Initial kahit Chest X-ray and Skin Test lang, ok na!
Add steroids for 6- 12 weeks
Tuberculin Skin Test
Pleural Effusion
 Based on a delayed type of hypersensitivity reaction
 A component of primary complex (DTH), manifested as an indurated area at the site of
 It occurs months to years after primary infection the intradermal injection which usually begins within 5
to 6 hours of administration, as previously sensitized

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 lymphocytes, monocytes and macrophages infiltrate  Induration of ≥ 15 mm
the site o No risk factors
 An immediate wheal and flare reaction may occur but o Positive at all times!
usually disappears by 24 hours and should not be
interpreted as a positive reaction Mantoux Test Interpretation
 Only the area of induration should be measured after
48 to 72 hours False Negative Reactions False Positive Reactions
1. Viral, Bacterial, Fungal, 1. Exposure to NTM
Early TB infection (test earlier
than 3 weeks), Severe TB
disease
2. Live virus vaccines 2. BCG vaccines
MMR, Varicella
3. Metabolic, Malignancies 3. Transfusion with whole
blood from donors with known
positive TST
4. Corticosteroids, 4. Inexperienced or biased
Immunosuppressive drugs reader
5. Technical factors and 5. Increasing mm induration
interpretation

Interferon- γ Release Assays

 Give 5 TU purified protein derivative
 Make sure you have an induration of 8 mm
 If you inject too deeply, walang induration
 Bevel up
 Use Tuberculin syringe or Insulin syringe
 Inject only the bevel not the whole needle
 Measure perpendicular to the long axis
 Using the ball point technique, measure the induration
 T- SPOT.TB- measures the number of lymphocytes/
monocytes producing IFN- γ
 QuantiFERON-TB test- measures whole blood
concentration IFN γ
Recommendations for Use of the Tuberculin Skin Test and
an Interferon- γ Release Assay in Children

 Most widely used method to determine  TST preferred (Instruct the mother to comeback within
o Latent TB infection 48 hours after skin test), IGRA acceptable (but quite
o Infected persons expensive)
o Those who do not have the disease  > 5 years with BCG and those unlikely to return for
 A measure of a person’s cellular immune TST reading
responsiveness
 Features includes: TST and IGRA should be considered when:
o Delayed course
o Indurated character  Initial and repeat IGRA are indeterminate
o Occasional vesiculation and necrosis  Once negative ang IGRA, negative na talaga
 Initial test (-)
Cut-off size for a Positive Mantoux Test  Clinical suspicion and risk of progression is high

 Induration ≥ 5 mm Radiologic Findings in PTB

o Contact with infectious cases
o Abnormal chest radiograph
o HIV-infected and other immune-suppressed
patients (those who are taking steroids ex:
patients with leukemia)
 Induration ≥ 10 mm
o Persons from high prevalence countries (like
in the Philippines)
o Low income populations
o Use of IV street drugs
o Locally identified high-risk populations
o Infants
o Other medical risk factors
o BCG-vaccinated child, especially in a
country with a high prevalence of
tuberculosis (BCG: does not protect infant
from acquiring primary infection, but
prevention of military or disseminated type of
TB)
 Parenchymal involvement
 Lymph node involvement
 Airway involvement
 Pleural involvement
Lymph Node Involvement
 Hilar or paratracheal lymph node enlargement is the
radiologic finding that clearly differentiates primary
from post-primary tuberculosis
 Usually unilateral
 Highly suggestive is the large size of the adenitis
relative to the insignificant size of the primary lung
focus
Resolution of Radiographic Changes
 When do you request for a repeat X-ray?

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 Corticosteroids
Pulmonary infiltrates Usually clears in 2-9 months
Hilar adenopathy Usually clears in 2-3 years  Should never be used except under cover of effective
Pleural effusion Complete resorption in about anti- tuberculous drugs
6- 12 weeks  To reduce inflammatory reaction that is contributing to
Give steroids to hasten the tissue damage or its impairing function
absorption  Dose: Prednisone 1-2 mg/k/d for 4 to 6 weeks with
Hyperaeration in Improve as early as 3 weeks gradual withdrawal
endobronchial TB
Military TB After several months REMEMBER!!! Indications for steroids:
 Miliary
Treatment: Common Side Effects  Endobronchial
 Pleural Effusion
 Isoniazid  Pericardial Effusion
o Peripheral neuropathy  TB meningitis
 Rifampicin
o Red orange discoloration of urine, sweat,
tears
 Pyrazinamide
o Hyperuricemia
o Joint pains secondary to accumulation of uric
acid
 Ethambutol
o Optic neuritis

Mycobacteriology of Childhood TB

Obtain cultures
 Lowenstein- Jensen
 Bactec Method
o Sputum, gastric lavage, bronchoalveloar
lavage, body fluid
Positive lang sa exposure: lesser than 5 years old, give INH
Nucleic- Acid Amplification
initially, >5 don’t give INH, after taking 3 mos of INH, you have
to screen, if negative discontinue INH, if positive, > 10 mm
 PCR induration, request for an x-ray , if with s and sx of TB and
o Gene-xpert MTB/RIF is a real time PCR positive x-ray, start with multiple drug therapy, Give HRZE for 2
assay for M. TB that detects rifampin months extensive therapy and HR 4 months ; if no s and sx,
resistance negative x-ray but with TB infection, latent TB infection na,
complete tx for 9 months.
CT Scans
“Tuberculosis can be controlled… although not enough
 Chest CT Scan may show enlarged or prominent attention has been directed to prevention of tuberculosis in
mediastinal or hilar adenopathy not demonstrable on children; therein lies the fountainhead of tuberculosis” – Mita
chest x-ray Pardo de Tavera (1975)
 Can demonstrate endobronchial disease, pericardial
invasion, early cavitation or bronchiectasis

Relative Bactericidal Activity of First Line Anti-

Tuberculosis Drugs

Drugs Rapidly Slowly Slowly

growing growing growing
extracellular extracelluar intracellular
organisms organisms organisms
(neutral ph) (neutral ph) (acid ph)
H ++ +/- +
R ++ + +
Z 0 0 +++
E +/- 0 +/-