TUBERCULOSIS

IN INFANCY AND
CHILDHOOD
Epidemiology
• TB is the leading cause of death from an infectious disease
• Estimated new cases of TB globally is 126:100,000
• More than half in Asia and Aftia
• 1.1-1.3 miliion of 9.6 million cases are co-infected with HIB
National Profile
• TB is the sixth leading cause of morbidity and mortality in the Philippines
• 9th out of the 22 highest TB burden counties
• One of the highest burdens of multi-drug resistant TB
• TB in children
• 500,000 children become ill with TB every year
• 70-80% pulmonary
TB and HIV co-infection
• HIV is the most significant risk factor for the progression o dormant TB infection to
clinical disease
• HIV + individuals are 20-30 times more likely to develop TB than those without
Mode of Transmission
• Airborne
• Carried by droplet nuceli measuring 1-5 microns in diameter
• From people who have pulmonary or laryngeal TB
• Particles can remain suspended in the air for several hours
• Ingestion of contaminated, unpasteurized dairy products from infected cattle
• Skin inoculation from contamination of an abrasion
Infectiousness of TB patients
• Related to the number of tubercle bacilli expelled into the air
• Infectiousness of TB patients depends on
• Susceptibility (immune status) of exposed individuals
• Environmental factors
• Proximity, frequency, and duration of exposure to an infectious source
• Considered infectious if
• They are coughing, AFB +, undergoing procedures \
• Not receiving therapy
Risk of progression to active disease
• Determined by age
• Time after exposure and initial infection
• Nutritional status
• Intercurrent disease
• Immunosuppresion
[MICROBIOLOGY]
Morphology
• Mycobacterium tuberculosis
• Aerobic, non-motile, slightly curved or straight bacilli
• Obligate aerobes
• Trehalose dimycolate (cord factor) and sulfatides associated with virulence
• Man-LAM (mannan-capped lipoarabinomannan) responsible for enhanced bacilli
survival and entry into macrophages
Laboratory diagnosis
• Demonstration of organism by culture is the gold standard
• Gastric aspirate assumes greater importance for children
• Acid fast staining techniques
• ZN technique or hot method uses carbolfuschin and will appear as red rods against a
blue background
• Kinyoun or cold method uses phenol with carbolfuschine
• Auramine-o stain uses auramine and appears as fluorescing under a fluorescence
microscope
Laboratory diagnosis
• Culture media
• Solid media – egg or agar bases
• L0wenstein-Jensen is the most popular
• Liquid media
• BACTEC

• Conventional culture media

• Examined for growth twice a week for the first four weeks starting from Day 3 to 5
postinoculation and after once a week until the eight week
• DNA fingerprinting
• Uses the restriction fragment-length polymorphism
Laboratory diagnosis
• Nucleic acid amplification tests (NAAT)
• Amplifies nucleic acid sequences allowing direct detection
• With rapid detection of drug resistance
• PCR commonly used NAAT
• Xpert MTB/RIF assay
• Rapid diagnostic tool which detects M. tuberculosis complex and rifamipicin resistance
• Recommended initial diagnostic test in suspected cases of MDR-TB or HIV-associated TB
• Can be used on unprocessed sputum, gastric lavage or aspirate, CSF, lymph node and
other tissues
• Inadequate data for stool, blood, and urine specimens
[PATHOGENESIS]
Pathogenesis
• Infected nuclei deposited in the alveoli
• 5-200 inhaled bacilli are necessary for a successful infection
• Transplacental infection through umbilical vein with primary hematogenous TB,
aspiration/ingestion of infected amniotic fluid in utero, inhalation of TB bacilli soon
or after delivery
• Incubation period of 3-12 weeks
Primary tuberculosis
• Inhalation -> scavenged by alveolar macrophages -> if not destroyed, bacilli
undergo unrestrained replication
• Bacteria carried to regional or hilar lymph nodes -> disseminated via lymphatics or
blood stream to other sites
• Logarithmic increase is inhibited by development of cell-mediated immunity and
delayed-type hypersensitivity
• Ghon focus is a casueous granuloma
• Usually located peripherally in any part of the lungs close to the pleura
• Soft semi-solid core surrounded by epitheloid macrophages, Langerhans giant t-cells
and lymphocytes
Progressive primary tuberculosis
• Occurs when the immune system is weakened and fails to control the
multiplication of TB bacilli
• Primary focus enlarges into a large caseous center then liquefies to form a primary
cavity allowing TB bacilli to multiply extensively
• Enlarging focus causes erosion of infected debris into a bronchi causing
intrapulmonary spread
• Miliary TB occurs refers to infection at disseminated sites where multiple small
yellow nodular lesions are produced in several organs like the lungs, lymph nodes,
kidney, adrenal, bone marrow, spleen and liver
Timetable of tuberculosis
[CLINICAL MANIFESTATIONS]
Overview
• Primary infection
• Most are asymptomatic
• Disease
• Low grade fever
• Lassitude
• Easy fatigability
• Anorexia
• Weight loss
• Malaise
• Night sweats
Spectrum of infection
TB Exposure TB Infection TB Disease
Exposure + + +
Signs and symptoms - - +
Tuberculin skin test - + +
Chest xray - - May be positive
Direct sputum smear - - May be positive
microscopy (DSSM)
Other diagnostics - May be positive May be positive
[CLINICAL FORMS]
A. Pulmonary/Endothoracic Tuberculosis
1. Asymptomatic or latent TB
• infection associated with tuberculin hypersensitivity and a positive tuberculin test
but with no striking clinical or roentgenographic manifestations. Occasionally, low
grade fever is found, usually by chance
2. Primary (childhood) TB
• Non-productive cough, mild dyspnea, cervical lymphadenopathies are the most
common clinical symptoms and signs
• Spontaneous healing occurs
A. Pulmonary/Endothoracic Tuberculosis
3. Pleurisy with effusion
• an early complication of primary infections
• pleural effusion may be localized or generalized, unilateral or bilateral
4. Progressive primary tuberculosis
• When the primary pulmonary focus, instead of resolving or calcifying, enlarges
steadily and develops a large caseous center
• More severe fever, cough, malaise and weight loss as well as classical signs of
cavitation
A. Pulmonary/Endothoracic Tuberculosis
5. Endobronchial TB
• moderately high fever, anorexia, night sweats, loss of weight and paroxysmal
cough ending in cyanosis
• Crepitant rales and expiratory wheezes are likewise noted
6. Miliary TB
• arises from the discharge of a caseous focus, often from a lymph node, into the
blood vessel (such as a pulmonary vein)
• Most common during the first 3-6 months after infection in infants
A. Pulmonary/Endothoracic Tuberculosis
7. Chronic pulmonary TB
• characterized by apical or infraclavicular infiltrates often with cavitation and no hilar
lymphadenopathy
• Clinical manifestations include chronic or persistent cough, prolonged fever, chest pain,
hemoptysis and supraclavicular adenitis. Most of these features, though, improve within
several weeks of starting effective treatment, but the cough may persist for several months
• 8. Tuberculoma
• Asymptomatic rounded lesions
• The presenting symptoms are usually nonspecific
• a pericardial friction rub may be appreciated.
• The diagnosis is established by examination of the pericardial fluid, which is usually
sanguineous, with a predominantly lymphocytic cellular reaction.
A. Pulmonary/Endothoracic Tuberculosis
9. Pericardial tuberculosis
• secondary to direct spread from mediastinal glands by direct invasion or by lymphatic
spread
• The diagnosis is established by examination of the pericardial fluid, which is usually
sanguineous, with a predominantly lymphocytic cellular reaction
B. Extrapulmonary tuberculosis
1. Tuberculosis of the cervical lymph nodes (scrofula)
• Through direct extension from a primary pulmonary infection
• Involved superficial lymph nodes are painless,10 firm,13 discrete and movable,
becoming adherent to each other and anchored to the surrounding tissues and
skin as they enlarge
• If left untreated, it may either resolve or may progress to caseation and necrosis of
the lymph node, which can rupture and result in a draining sinus tract.
B. Extrapulmonary tuberculosis
2. Tuberculosis of the central nervous system
• may develop three to six months after initial infection
• It is frequently seen in the first six years of life, though rare in the first four months.
It may accompany miliary tuberculosis in approximately 50% of cases
• Meningitis is always secondary to a tuberculous process elsewhere in the body, the
primary lesion being in the lungs or in peribronchial and mediastinal lymph nodes
in 95% of cases
• the tubercle bacilli reach the central nervous system via the bloodstream during its
lymphohematogenous spread
B. Extrapulmonary tuberculosis
2. Tuberculosis of the central nervous system
• Usually gradual occurring over a period of 3 weeks
• an early stage of irritability
• apathy, vomiting, irritability and headache
• the pressure or convulsive stage
• meningeal signs such as lethargy, neck stiffness, seizures and cranial nerve palsies
• the paralytic or terminal stage
• posturing, profound neurologic and sensorial changes with deterioration of vital
signs, and eventually death
B. Extrapulmonary tuberculosis
2. Tuberculosis of the central nervous system
• The spinal fluid is usually clear but with an increased opening pressure
• Contains 50-500 WBC/mm, with polymorphonuclears predominant in the early
phase and lymphocytes later in the disease process
• CSF sugar is low and protein markedly elevated at which time the fluid develops
pellicle on standing
• AFB +
B. Extrapulmonary tuberculosis
2. Tuberculosis of the central nervous system
• Tuberculoma/TB abscess
• Tuberculomas occur most often in children younger than 10 years and are located
at the base of the brain around the cerebellum. Manifestations include headache,
convulsions, fever and signs and symptoms referrable to a tumor or brain abscess
B. Extrapulmonary tuberculosis
3. Skeletal tuberculosis
• results from lymphohematogenous seeding of the bacilli during the primary
infection or may develop as a direct extension from a caseous regional lymph node
or by extension from a neighboring infected bone
• Usually starts in the long bone
• Signs and symptoms include "night cries" and restless sleep, daily low-grade fever
and peculiar position (such as torticollis with cervical lesions) or gait. Physical
examination findings include marked "guarding" because of dorsal muscle spasm,
gibbus, or reflex changes including clonus
B. Extrapulmonary tuberculosis
4. Gastrointestinal TB
• occur after ingestion of tubercle bacilli or as part of generalized lympho-
hematogenous spread
• Involvement of the intestinal tract commonly the ileocecal area19 with extension
to the mesenteric lymph nodes and peritoneum results from ingestion of bronchial
secretions containing tubercle bacilli from a caseous pulmonary focus. The bacilli
are taken up by the lymphoid tissues, giving rise to local ulcers followed by
mesenteric lymphadenitis and sometimes peritonitis
B. Extrapulmonary tuberculosis
5. Cutaneous TB
• may be caused by direct inoculation of tubercle bacilli into a traumatized area. The
wound is slow to heal, painless with regional lymphadenitis.
6. Ocular TB
• involves the conjunctiva and the cornea in the form of conjunctivitis and
phlyctenular keratoconjunctivitis
B. Extrapulmonary tuberculosis
5. Genitourinary TB
• Occurs up to 15-20 years after primary infection
• Hematogenous spread can give rise to tubercles in the glomeruli, with resultant
caseating sloughing lesions which discharge TB bacilli into the tubules
• should be suspected in the presence of destructive pulmonary tuberculosis with
persistent, painless, sterile pyuria with associated albuminuria and hematuria
6. Genital TB
• arise as a metastatic lesion during lymphohematogenous spread or by direct
extension from an adjacent lesion
B. Extrapulmonary tuberculosis
5. Tuberculosis of the middle ear
• Differential for chronic otitis media in TB patients, or in those who have no
evidence of TB elsewhere and whose otitis do not improve with the conventional
medical treatment
• Always unilateral and involves the pre-auricular lymph nodes or the anterior
cervical chain
• Patients typically have a chronic tympanic membrane perforation and ear
drainage associated with progressive and profound hearing loss
• Facial nerve paralysis is highly suggestive of the disease
DIAGNOSTIC TEST
Diagnostic Tests
• Mantoux Test / Tuberculin skin test
• Standard method for screening
• (+) if ≥ 10mm induration size, regardless of BCG status
• (+) if ≥ 5mm plus hx of close contact with TB, clinical findings suggestive of TB, CXR
suggestive of TB and immunocompromised conditions
• (+) if ≥ 15mm for population with no risk factors
• A dose of 0.1 ml of 2-TU PPD-RT23 / o.1ml of 5-TU PPD-S
• Provides a general measure of a person’s cellular response
Diagnostic Tests
• Mantoux Testing / Tuberculin skin test
• Features of reaction
• Delayed course reaching a peak of more than 24h after injection of antigen
• Indurated character
• Occasional vesiculation and necrosis

• A pale wheal of 6 to 10mm in diameter should be evident after injection

• Read within 48 – 72hrs from the time of administration
Diagnostic Tests
• Mantoux Testing / Tuberculin skin test
• False positive
• Nontuberculous mycobacteria
• BCG vaccination
• Reaction develops 6 – 12weeks after vaccination
• Wanes after 5 years from immunization

• False negative
• Anergy
• Very young age (<6months)
• Recent TB infection or overwhelming TB disease
• Live-virus vaccination
• Postpone for at least 4 – 6weeks after immunization or do it on the same day of vaccination
Diagnostic Tests
• AFB smears
• Provides presumptive DX of active TB
• Gives a quantitative estimation of bacilli on the smear
• Implies infectiousness of the patient
• Low sensitivity (51.8 – 53.1%)
• High specificity (97.5 – 99.8%)
• 104 bacilli / ml of sputum: lowest concentration that can be detected
Diagnostic Tests
• Culture: gold standard
• Solid media
• 4 – 6weeks for isolation
• 2 – 4weeks for susceptibility testing

• Liquid media
• Bactec: as few as 7 to 10 days; carbon-14 (marker of bacterial growth)
• Middlebrook broth
• Septi-check AFB
Diagnostic Tests
Specimens used for demonstration of tubercle bacilli:
• Sputum
• For older children able to expectorate
• Series of three early morning specimens on different days before starting chemotherapy
• Make sure brought up from the lungs
Diagnostic Tests
• Gastric aspirate
• For infants and children who cannot expectorate even with aerosol inhalation
• 5 – 10ml of gastric contents aspirated early in the morning after the person has fasted
for at least 8 – 10hours preferably before the child arises and peristalsis empties the
stomach of respiratory secretions swallowed overnight
Diagnostic Tests
• Bronchial washings
• Urine
• First morning-voided midstream specimen
• Other body fluids and tissues
• Bone marrow, lung, and liver biopsy in patients with hematogenous spread /
disseminated disease must be considered
Diagnostic Tests
• Radiographic findings
• No pathognomonic findings in childhood TB
• Lateral projections are important wherein partially calcified mediastinal nodes may be
visible
• Most common cause of calcification in children
• Uniform stippling of both lungs found in miliary tuberculosis
• Lobar of lobular consolidations
• Common findings: Enlarged retrocardiac lymphadenopathy (70%), hilar adenopathy
with pulmonary infiltrates (20%), and pleural effusion
TREATMENT
Initial Empiric Therapy of Tuberculosis in
Infants, Children, and Adolescents
Category Regimen Remarks
Class I (TB Exposure) 3 months INH Immediate prophylaxis
• <5 years controversial for those ≥ 5 years
• ≥5 years but is recommended by some
experts specially if with risk
factors like malnutrition,
immunocompromised states.
Initial Empiric Therapy of Tuberculosis in
Infants, Children, and Adolescents
• Extrapulmonary 2 months HRZ + E or S ffd by 10 • Corticosteroids (usually
A) severe, life-threatening months HR ± E/S given once prednisone at 1mk day for 6 –
disease: disseminated / daily or as DOT 3x weekly 8weeks with gradual
miliary, meningitis, bone / tapering) beneficial for the
joint disease Same regimen as pulmonary following: meningitis,
B) Other extrapulmonary sites disease pericarditis, pleuritis,
endobronchial TB, miliary TB
Initial Empiric Therapy of Tuberculosis in
Infants, Children, and Adolescents
Class II TB infection In the presence of primary INH
• PPD conversion within past 1 9 months INH resistance, use Rifampicin
– 2 years (-) CXR
• PPD (+) not due to BCG, (-) 9 months INH
CXR, (-) previous treatment
• PPD (+) with stable healed 9 months INH
lesion, (-) previous treatment
Initial Empiric Therapy of Tuberculosis in
Infants, Children, and Adolescents
Class II TB infection
• PPD (+) with stable / healed
lesion, (+) previous
treatment, at risk of
reactivation due to:
• Measles, pertussis, etc. 1 – 2 months
• Conditions / drugs For the duration of the
inducing immunosuppression
immunosuppression
(IDDM leukemia chronic
dialysis)
• HIV infection / persons at 12 months INH
risk for infection but HIV
status unknown
Initial Empiric Therapy of Tuberculosis in
Infants, Children, and Adolescents
Class III (active TB disease) Intensive Continuation
New smear (-) PTB 2 months HRZ once daily 4 months HR given once daily or
Less form of extra PTB 6 months HE

New smear (+) PTB 2 HRZE 4HR or 6HE

New smear (-) PTB with
extensive parenchymal
involvement

Severe extrapulmonary TB
Severe concomitant HIV disease

TB meningitis 2 HRZS 4HR

Bone joint TB 2 HRZS 7-10HR

Initial Empiric Therapy of Tuberculosis in
Infants, Children, and Adolescents
Class III ( active TB disease) Intensive Continuation

Previously treated smear (+) 2HRZES / 1HRZE 5HRE

PTB; relapse tx after interruption
tx failure
Chronic MDR and XDR - TB Specially designed /
standardized regimens
Algorithm for Preventive Therapy of
Childhood Tuberculosis
TB Exposure Class I

yes
< 5 years old Start INH for 3months
no
yes
Radiologic findings and/or
Repeat Mantoux test yes
signs / symptoms TB Disease
after 3months (+) Multiple Drug Tx
suggestive of TB
no
no
Discontinue INH
If no BCG scar, give Latent TB infection
BCG after 2weeks Continue ≥ 6 INH
THANK YOU!