Childhood TB

Abdulwahhab S

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Learning objectives
 At the end of this lesson, learners will be able to:
 Define tuberculosis
 Describe the pathophysiology of Tuberculosis
 Describe clinical manifestations of tuberculosis
 Describe diagnostic methods of tuberculosis in
children
 Explain the management of tuberculosis in children

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Tuberculosis (TB)
Definition
 Tuberculosis (TB) is an infectious disease caused by
Mycobacterium tuberculosis, a rod-shaped bacillus
called “acid-fast” due to its staining characteristics
in laboratory.
 Occasionally the disease can also be caused by
Mycobacterium bovis and Mycobacterium
africanum.
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Epidemiology
 Tb is a major public health problem throughout the
world.
 The World Health Organization estimates that 8 to
10 million people develop tuberculosis in the world
every year and 3 to 5 million die from tuberculosis.
 Approximately 1.3 million cases of tuberculosis and
400,000 tuberculous-related deaths occur annually
among children younger than 15 years.

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Cont’d
 The global burden of TB is increasing due to:
 HIV epidemics

 Poverty

 Crowding

 Inefficient TB control programs

 Inadequate health coverage & poor access to

health services

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Etiology
 Mycobacterium Tuberculous complex:
 M.TB
 M.Bovis

 M.Africanum
 M.Microti
 M.Canetti

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Cont’d
 All belong to the order Actinomycetales and family Mycobacteriaceae

 M.TB

 Most important cause

 Non-spore forming

 Non-motile

 Obligate aerobe

 Slow-growing

 Grow best at 37-41oC

 Cell wall with high lipid content which gives “acid-fast” staining
properties (resistance to decolorization with acid alcohol)

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Transmission &
Pathogenesis
 Incubation period from infection to
development of +ve tuberculin test is 2-
6wks
 Transmission is person to person (usually by
air borne mucus droplet nuclei)

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Cont’d
 Risk of transmission is dependent on :
 Index case;
 Smear positive TB
 Extensive upper lobe infiltrate & cavity
 Copious production of sputum
 Severe & forceful cough
 Not treated
 Environment:
 Poor ventilation
 Overcrowding
 Intimacy

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Cont’d
 Young children (<7yrs) rarely infect others b/c:
 Sparse bacilli
 Cough is often absent or lacks the tussive force
to suspend infectious particles of correct size
 M.bovis may penetrate the GI mucosa or invade
the lymphatic tissue of oropharynx when large
numbers are ingested.

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Cont’d
 The pathologic events in the initial tuberculous
infection depend on the balance between:
 Mycobacterial antigen load
 Cell-mediated immunity(enhance IC killing)

 Tissue hypersensitivity(promotes
extracellular killing)

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Cont’d
 When Ag load is small & tissue hypersensitivity is
high
 granuloma formation (from organization of
lymphocytes, macrophages and fibroblasts)
 When both (Ag & sensitivity) are high:

 granuloma is less organized

 Tissue necrosis is incomplete

 Results in formation of caseous material

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Cont’d
 When degree of tissue sensitivity is low
(infants, low immunity)
 Diffuse reaction
 Infection is not well contained

 Results in local tissue damage and

dissemination

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Cont’d
 Factors that predispose to serious disease:
 Young age
 Genetic factors

 Immuno suppression (AIDS, malnutrition,

measles, pertussis, malignancy, steroids)

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Pathogenesis
 The 1o complex of TB includes local infection at the portal of
entry & regional LNs
 Lung is portal of entry in more than 98% of cases
 Bacilli multiply initially within alveoli & alveolar ducts
 Most are killed, some survive within nonactivated macrophages
 Macrophages carry the bacilli to regional LNs by lymphatic
vessels
 If lung is portal of entry, hilar LNs are often involved but
paratracheal LNs may be involved(upper lobe)

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Cont’d
 Tissue reaction in the lung parenchyma & LNs intensifies over the
next 2-12wks
 The parenchymal lesion of 1o complex often heals completely
by fibrosis or calcification.
 Occasionally may continue to enlarge & result in focal
pneumonitis & pleuritis
 If caseation is intense, center of the lesion liquefies & empties
into the bronchus leaving a residual cavity
 The infection of regional LNs develop some fibrosis &
encapsulation, but healing is usually incomplete.
 Viable M.TB can persist for decades within parenchymal or LN
foci

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Cont’d
 If hilar & Para tracheal LNs enlarge (as part of host
inflammatory reaction), they may encroach on a
regional LN bronchus partial obstruction
bronchus distal hyperinflation
complete obstruction results in atelectasis
 Inflamed caseous nodes can attach to the
bronchial wall & erode through it, causing
endobronchial TB or a fistula tract.
 During the development of 1o complex, bacilli
are carried to most tissues of the body through
the blood & lymphatic vessels; common seeding
is in the organs of Reticuloendothelial System.
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Cont’d
 Bacterial replication occurs in organs with conditions that favor
their growth:
 Lung apices
 Brain
 Kidneys
 Bones
 Disseminated TB occurs if:
 Circulating number of bacilli is large and
 Host immune response is inadequate

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Cont’d
 The time b/n initial infection & clinically apparent disease is variable:
 Disseminated & meningeal TB are early manifestations (2-6 month
after infection)
 TB LAP & endobronchial TB (3-9month)
 Bones & joints take several years
 Renal TB takes decades(10yrs) after infection

 Pulmonary TB that occurs more than a year after 1o infection is

usually due to endogenous regrowth of bacilli persisting in partially
encapsulated lesions
 Common site of reactivation is the apex of upper lobes (oxygen &
blood flow good)

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Clinical manifestations
 Pulmonary Tuberculosis:

 Most common clinical presentation

 Persistent respiratory symptoms and

 Poor weight gain or failure to thrive.

 A child may have nonproductive cough and/or mild

wheezes.
 Pulmonary TB in infants and HIV infected children
may present as acute pneumonia.
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Extra-pulmonary
Tuberculosis(EPTB):
 The most common forms of extrapulmonary disease
in children are TB of the superficial lymph nodes and
of the central nervous system (CNS).
 Children younger than 2 years of age are at risk of
disseminated disease causing miliary TB or TB
meningitis.
 The clinical presentation of extrapulmonary TB
depends on the site of disease.

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TB Lymphadenitis:
 Is the commonest form.
 Regardless of HIV status, the lymph nodes most
commonly involved are the cervical nodes.
 Generalized lymphadenopathy can occur in children with
 HIV infection,
 Reduced immunity and
 In symptomatic HIV infected children who are given
BCG vaccination.

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Tuberculosis of the Spine or
Joints:
 Is the second commonest form of childhood EPTB, and
may occur within the first few years following primary
infection.
 Usually affects weight bearing bones or joints.
 The most common sites are spine, hip, knee and
ankle.
 Early diagnosis of TB of the spine is essential to prevent
the disastrous consequence leading to paralysis.

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Miliary Tuberculosis:
 Presents with constitutional features rather than
respiratory symptoms.
 Early symptoms are vague and lack specificity.
 Lassitude, anorexia, failure to thrive and prolonged
unexplained fever are common.

 Therefore, a high index of suspicion is necessary.

 TB meningitis is the commonest cause of death if
miliary TB is untreated.

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CNS TB:
 Is the result of hematogenous spread of the bacilli to the CNS.

 The patient may present with constitutional features and chronic

meningitis and there is gradual onset and progression of

headache and decreased consciousness.

 Tuberculoma (a large solid lesion, rather like a malignant tumor)

 Present with focal neurological deficits, seizures and

obstructive hydrocephalus.

 Young children, especially those under 2 years of age, have the

highest incidence and the worst prognosis.

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Tuberculosis of the Serous
Membranes:
 Inflammatory tuberculous effusions may occur
in any of the serous cavities of the body,
 i.e. pleural, pericardial or peritoneal cavities.

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Perinatal TB
 Can be congenital

 Commonly acquired postnatal

 C/ms;
 Similar to sepsis & other neonatal problems.

 May manifest early but common time is 2-3wks of age (RD, poor feeding, fever,
HSM, FTT, abdominal distension)

Dx and Mx of Perinatal TB

 If mother has active TB:

 Screen the newborn (S/Sx, gastric aspirate, CXR)

 If positive, antiTB

 If negative, INH for 3 months

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Cont’d
 At 3months, PPD (purified protein derivative) skin
test.
 if +ve, continue for 6-9 months
 If non-reactive, give BCG and Dic. INH
 Isolation of the newborn:
 Seriously sick mother
 Previous Rx for TB
 Suspected drug resistant TB

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Diagnosis of TB in Children
 Key Features Suggestive of TB
 Chronic symptoms suggestive of TB
 Physical signs highly suggestive of TB

 X-ray suggestive of TB
 A positive tuberculin skin test

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Recommended Approach to
Diagnose TB in Children
 Clinical Assessment
 Typical Symptoms
 Cough, especially persistent and non-
improving
 Weight loss or failure to gain weight
 Fever and/or night sweats
 Fatigue, reduced playfulness, inactivity
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History of Contact
 Contact such as with a source case of Pulmonary TB
living in the same household or a chronic cougher.
 A source case with sputum smear-positive PTB is
more likely to infect contacts than cases with sputum
smear-negative PTB; however, cases with EPTB are
not infectious though.
 Children usually develop TB within 2 years after
exposure and most (90%) within the first year.

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Clinical Examination
 Special emphasis on weight measurement (look
for weight loss or poor weight gain), fever, signs
of respiratory distress and chest finding.
 Children can also present with acute severe
pneumonia (especially in infants and HIV-infected
children) as well as asymmetrical and persistent
wheeze.

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Tuberculin Skin
Test(Mantoux test)
 Id, 0.1ml, 5TU of PPD/purified protein derivative/, volar
surface of arms
 T-cells sensitized by prior infection are recruited to the
skin; release lymphokines that induce indurations
through local vasodilatation, edema, fibrin deposition
and recruitment of other inflammatory cells to the area.
 Amount of induration is measured 48-72hrs after
administration.

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Cont’d
 TST is useful to support a diagnosis of TB in children
with suggestive clinical features who are sputum
smear-negative or who cannot produce sputum.
 A positive TST indicates infection:
 Positive in any child if ≥ 10 mm, irrespective of
BCG immunization; and also
 Positive if ≥ 5 mm in HIV-infected or severely
malnourished child.

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Cont’d
 A positive TST is particularly useful to indicate
TB infection when there is no known TB
exposure on clinical assessment, i.e. no
positive contact history.
 Caution: a positive TST does not distinguish
between TB infection and active disease.
 A negative TST does not exclude TB disease.

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Bacteriological Confirmation
 Children usually have paucibacillary pulmonary
disease (low organism numbers), as cavitating
disease is relatively rare.
 All attempts must be made to confirm diagnosis
of TB in a child using whatever specimens and
laboratory facilities are available.

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Chest X-Ray
 CXR remains an important tool for diagnosis of PTB in
children who are sputum smear negative or who cannot
produce sputum.
 The following abnormalities on CXR are suggestive of TB:
 Enlarged hilar lymph nodes and opacification in the
lung tissue
 Miliary mottling in lung tissue
 Cavitation (common with older children),Pleural or
pericardial effusion
 The finding of marked abnormality on CXR in a child with
no signs of respiratory distress (no fast breathing or
chest in-drawing) is supportive of TB

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Investigations for Common Forms
of Extrapulmonary TB in Children

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Cont’d
 Smear +ve TB:
 The criteria are:
 Two or more initial sputum smear examinations positive
for acid fast bacilli; or
 One sputum smear examination positive for acid fast
bacilli plus CXR abnormalities consistent with active
pulmonary TB, as determined by a clinician; or
 One sputum smear examination positive for acid fast
bacilli plus sputum culture positive for M. tuberculosis.

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Cont’d
 Smear -ve TB:

 Pulmonary TB, sputum smear negative

 A case of pulmonary TB that does not meet the

definition for smear positive pulmonary TB; Such
cases include :
 Cases without smear results, which should be
exceptional in adults but relatively more frequent
in children.
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Cont’d
 In keeping with good clinical and public health practice, diagnostic
criteria for sputum smear negative pulmonary TB should include:
 At least three sputum specimens negative for acid fast
bacilli; and
 Radiological abnormalities consistent with active pulmonary
TB; and
 No response to a course of broad spectrum antibiotics; and

 Decision by a clinician to treat with a full course of anti TB

chemotherapy.

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Cont’d
 If AFB is negative, Dx is based on:
 Contact with patient(adult) with pulmonary TB
 S/Sx suggestive of TB
 X-Ray finding consistent with TB
 Positive TST
 If 3 are fullfilled, TB is likely Dx
 If severe malnutrition or immunosupresion, 2
criteria are enough

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HIV Testing
 HIV counseling and testing is indicated for all
TB patients as part of their routine
management.

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Mx of Childhood TB
 Principles :
 Chemotherapy/Anti TB drugs
 Nutritional rehabilitation

 Screening of the family(index case, other

contacts)
 Follow up (Adherence, response, drug
side effect)

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Anti TB Drugs
 The main objectives of anti TB treatment are to:
 Cure the patient (by rapidly eliminating most of the
bacilli);
 Prevent death from active TB or its late effects;
 Prevent relapse of TB (by eliminating the dormant bacilli);
 Prevent the development of drug resistance (by using a
combination of drugs);
 Decrease TB transmission to others.

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Recommended treatment
regimen
 Anti-TB treatment is divided into two phases:
 an intensive phase and
 a continuation phase.

 During the intensive phase, TB in children

should be treated with four drugs regimen
(HRZE) for two months followed by two drug
regiment(HR) for four months.

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Second line anti TB drugs for
treatment of MDR-Tb in children
 Ethionamide or prothionamide
 Fluoroquinolones
 Ofloxacin
 Levofloxacin
 Moxifloxacin
 Gatifloxacin
 Ciprofloxacin
 Aminoglycosides
 Kanamycin
 Amikacin
 Capreomycin
 Cycloserine or terizidone

 paraAminosalicylic acid

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Steroids in TB
 Meningitis
 Pericarditis
 Adrenal insufficiency
 Airway obstruction (LAP, laryngeal TB)
 Bilateral pleural effusion with respiratory
problem
 Indications for prescribing steroids in renal TB:
 Severe bladder symptoms
 Tubular structure involvement (eg, ureter, fallopian
tubes, spermatic cord)

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Prevention of Childhood TB
 Case finding and treatment, which interrupts
transmission of infection between close
contacts
 Bacille Calmette-Guerin Vaccination
 INH prophylaxis

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