Module 10A - March 2010
Diagnosing
Tuberculosis in
Children
Project Partners
Funded by the Health Resources and Services Administration (HRSA)
Module Overview
 Clinical presentations of TB in children
 Diagnosing TB in children
International Standards 2, 3, and 6
Learning Objectives
Upon completion of this session,
participants will be able to:
Name several common presentations of
childhood tuberculosis
Accurately classify different presentations
of pediatric TB
Describe the 7 recommended steps
involved in diagnosing TB in children
Introduction
 The WHO estimates 1 million cases of
childhood TB (<15 years of age) annually
 Children can present with TB at any age
 The frequency of childhood TB is
influenced by:
• The intensity of the TB epidemic locally,
• The age structure of the population,
• The availability of diagnostic tools, and
• Whether TB contact investigation is routinely
conducted
Introduction (2)
 TB transmission to a child usually results
from exposure to an infectious adult or
adolescent, often within the household
 Very young children (<3 years of age) and
those with weakened immune systems
are at great risk for disease progression
 For infants, the time span between
infection and disease can be as short as
several weeks
Clinical
Presentations
of TB in
Children
Clinical Presentations of TB in Children
 Pulmonary (PTB) or extra-pulmonary TB
(EPTB)
 Most children with TB have PTB, but they
are more likely
than adults to
have EPTB
 Many children
with EPTB also
have PTB
EPTB in Children
 The most common type of EPTB seen in
children is intrathoracic
 Other forms of EPTB seen in children
include:
• TB lymphadenopathy (e.g., cervical lymphadenitis)
• Central nervous system TB (e.g., meningitis)
• Disseminated TB (e.g., miliary TB)
• TB effusions (pleural, pericardial, peritoneal)
• Spinal TB (Pott’s disease)
Uncomplicated Primary TB
Primary TB Disease:
 Often unilateral lymphadenopathy, hilar or
mediastinal, without obvious parenchymal
involvement
• Most frequent presentation in children (70-80%)
• Classify as EPTB
Uncomplicated Primary TB (2)
Primary TB Disease:
 Sometimes typical “primary complex”,
combining hilar and mediastinal
lymphadenopathy and a small opacity in the
lung, 3-10 mm in diameter (“primary lesion”)
• It is less frequent (20%, usually children < 5
years)
• Classify as PTB
Complicated Primary Disease
Primary TB Disease:
 Lobar or segmental opacity in the lung,
combined with unilateral lymphadenopathy
on the same side
• Classify as PTB
Acute Disseminated Primary TB
Acute Disseminated Primary TB
(often in children aged under 5 years)
Miliary with or without meningitis
• Classify as PTB
Post-primary PTB
Post-primary PTB (usually in children aged
over 10 years) is:
 Without cavitation,
smear-negative
classified as PTB
 With cavitation,
smear-positive is also
classified as PTB
Post-primary EPTB
Post-primary EPTB examples include:
 Most TB bone and joint disease
 Renal tuberculosis
 Some cervical lymph node TB (scrofula)
Presentations of HIV/TB
 The natural history of TB in a child with
HIV depends on the stage of HIV disease
 In early HIV infection, the signs of TB are
similar to those of an HIV-uninfected child
 As HIV infection progresses,
dissemination of TB becomes more
common
• Meningitis
• Miliary TB
• Widespread tuberculous lymphadenopathy
Presentations of HIV/TB (2)
 Older HIV-infected children with TB may
have clinical presentations similar to that
seen in HIV-infected adults
 Children with TB/HIV co-infection have:
• Longer hospital stays, and
• higher mortality despite initiation of
appropriate anti-TB medications
 It is essential to have a high index of
suspicion for TB disease in HIV-infected
children
TB Diagnostic Gold Standard
 A definitive diagnosis of TB disease
requires isolation of M. tuberculosis from
any of the following:
• Expectorated or induced sputum
• Bronchoalveolar lavage fluid, aspirated
gastric fluid, or pleural fluid
• Biopsied lung, peripheral lymph node, or
other tissue
ISTC Standard 2
All patients (adults,
adolescents, and
children who are
capable of producing
sputum) suspected of
having pulmonary TB
should have at least two
sputum specimens
submitted for microscopic
examination in a qualityassured laboratory.
When possible, at least one early morning
specimen should be obtained.
ISTC Standard 3
For all patients (adults,
adolescents, and
children) suspected of
having EPTB, appropriate
specimens from the
suspected sites of
involvement should be
obtained for microscopy,
culture and
histopathological
examination.
ISTC Standard 6
In all children suspected of having
intrathoracic (i.e., pulmonary, pleural, and
mediastinal or hilar lymph node) TB,
bacteriological confirmation should be
sought through examination of sputum (by
expectoration, gastric washings, or induced
sputum) for smear microscopy and culture.
ISTC Standard 6 (2)
In the event of negative bacteriological
results, a diagnosis of TB should be
based on:
 The presence of abnormalities consistent
with TB on chest radiography
 A history of exposure to an infectious case
 Evidence of TB infection (positive tuberculin
skin test or interferon gamma-release assay),
and
 Clinical findings suggestive of TB
Diagnosing
TB in Children
Diagnosing TB in Children
 Diagnosing tuberculosis in children is
particularly problematic
 Children <5 years of age rarely
expectorate sputum for evaluation
• Even when specimens are obtained they are
rarely smear-positive for AFB on routine
microscopy
Diagnostic Approach
The diagnostic TB workup in a child should
include all of the following:
1. Symptom and contact history
2. Clinical exam (including growth assessment)
3. Mantoux tuberculin skin test (TST) result
4. Bacteriological confirmation (when possible)
5. Chest radiograph
6. Other specific evaluation indicated by
disease site or co-morbidity
7. HIV testing
1. Careful History: Contact
Contact History
 A close contact is defined as living in the
same household or in frequent contact
with someone with sputum smear-positive
TB
 Persons with TB who are sputum smearnegative but culture-positive are also
infectious, but to a much lesser degree
1. Careful History: Contact (2)
 Children (especially <5 years of age) who
have been in close contact with a smearpositive TB case must be screened for TB
 After TB is diagnosed in a child or
adolescent, an effort should be made to
detect the adult source case(s), especially
within the household
 Children whose sputum is smear-positive
or with a visible cavity on CXR should be
considered infectious
1. Careful History: Symptoms
 Children with
symptomatic
disease develop
chronic
symptoms in
most cases
 The most
frequent symptoms are chronic and
unremitting cough, fever, and weight loss
1. Careful History: Symptoms (2)
The specificity of symptoms for the
diagnosis of TB depends on how strict the
definitions of the symptoms are:
Chronic cough: an unremitting cough that is
not improving and has been present for 2-3
weeks
Fever: of 38°C for 14 days after common
causes such as malaria or pneumonia have
been excluded
Weight loss or failure to thrive: always ask and
look at the child’s growth chart
2. Clinical Exam
 There are no specific features on clinical
examination that can confirm that the
presenting illness is due to PTB
 Some less common signs are highly
suggestive of EPTB and the threshold to
initiate treatment should be lower
 Other signs are common and should
initiate investigation as to the possibility of
childhood TB
2. Clinical Exam (2)
Physical signs highly suggestive of EPTB:
 Gibbus, especially
of recent onset
(vertebral TB)
 Non-painful
enlarged cervical
lymphadenopathy
with fistula
formation
2. Clinical Exam (3)
Physical signs requiring investigation to
exclude EPTB:
Meningitis not responding to antibiotic treatment,
with sub-acute onset or  intracranial pressure
Pleural or pericardial effusion
Distended abdomen with ascites
Non-painful enlarged lymph nodes without fistula
formation
Non-painful enlarged joint
Signs of tuberculin hypersensitivity: phlyctenular
conjunctivitis, erythema nodosum
3. Mantoux TST
 Using the test: The Mantoux TST should be
standardized for each country using either:
• 5 tuberculin units (TU) of tuberculin purified
protein derivative (PPD) S, or
• 2 TU of tuberculin PPD RT23
 A positive Mantoux TST occurs when a child
is infected with M. tuberculosis
 In children, the TST can also be used as an
adjunct in diagnosing TB when used in
conjunction with history, physical exam and
other diagnostic tests
3. Mantoux TST (2)
 A TST should be regarded as “positive”
as follows:
• High-risk children: TST ≥5mm induration
– Close contact to person with active PTB
– HIV-infected children
– severely malnourished children, i.e., those with
clinical evidence of marasmus or kwashiorkor)
– Chest X-ray consistent with TB disease
• All other children: TST ≥10mm induration is
regarded as positive (whether or not they
have been BCG vaccinated)
3. Mantoux TST (3)
 The TST is useful in HIV-infected children
to identify those with dual TB/HIV
infection and as an aid in the diagnosis of
TB
 There can be false-positive TST results
as well as false-negative TST tests
 A negative Mantoux TST never rules
out a diagnosis of TB in a child
4. Bacteriological Confirmation
 It is always preferable to make a
diagnosis of TB based on bacteriology
using whatever specimens and laboratory
methods are available
 Samples might include sputum, gastric
aspirate and other material (e.g., lymph
node biopsy)
 Fine needle aspiration of enlarged lymph
glands for both histology and staining for
AFB has been shown to be a useful test
with a high bacteriological yield
4. Bacteriological Confirmation (2)
 All specimens that are obtained should be
sent for mycobacterial culture whenever
possible
 A bacteriological diagnosis is especially
important for children who have one or
more of the following:
• Suspected drug resistance
• HIV infection
• Complicated or severe cases of disease
• An uncertain diagnosis
4. Bacteriological Confirmation (3)
The more common ways of obtaining
sputum for microscopy include:
 Expectoration
 Gastric aspirates
 Sputum induction
5. Chest Radiograph
Investigations Relevant for Suspected PTB
Children with PTB frequently
have CXR changes suggestive
of TB
Persistent opacification in the
lung with enlarged hilar or
subcarinal lymph node is common
Adolescent with TB often have CXR changes similar
to adults (large pleural effusions and apical infiltrates
with cavity formation being the most common)
Adolescents may also develop primary disease, with
hilar adenopathy and collapse lesions visible on CXR
5. Chest Radiograph (2)
Investigations Relevant for Suspected
EPTB
 Most useful EPTB application is for
diagnosing intrathoracic lymphadenopathy
• Lateral view may be helpful in diagnosing if
frontal view is difficult to interpret
 In most other cases, TB will be suspected
from the clinical picture and confirmed by
histology or other special investigations
6. Other Tests
Serological and nucleic acid amplification
(e.g., polymerase chain reaction [PCR])
tests are not currently recommended for the
routine diagnosis of childhood TB
 They have been inadequately studied in
children and they have performed poorly in
the few studies that have been done
 This is an area that requires further research,
as they may prove to be useful in the future
6. Other Tests (2)
 Many experts recommend that all children
with miliary TB (or suspected of having
miliary TB) should undergo lumbar
puncture to evaluate for the presence of
meningitis
 Note: Other specialised tests, such as
computerized chest tomography and
bronchoscopy, are not recommended for
the routine diagnosis of TB in children
7. HIV Testing
 In areas with a high prevalence of HIV
infection in the general population, counseling
and testing for HIV should be included as part
of routine care and management of children in
which TB is diagnosed
 In areas with lower prevalence rates of HIV,
HIV counseling and testing is indicated when:
• a TB patient has symptoms and/or signs of HIVrelated conditions, and
• a TB patient has history suggestive of high risk of
HIV exposure
Summary
 TB infection in a child can progress rapidly to
TB disease
 Diagnosing TB, particularly PTB, in children is
difficult and should include the 7 diagnostic
elements discussed
 Not all children with TB disease have a
positive TST and not all children with a
positive TST and radiographic abnormalities
have TB disease
 Attempts should be made to obtain and send
sputum and/or other sample for AFB smear
and TB culture on children with suspect TB
Summary: ISTC Standards Covered*
Standard 2: All TB suspects should have at
least 2 sputum specimens obtained for
microscopic examination (at least one early
morning specimen if possible).
Standard 3: Specimens from suspected
extrapulmonary TB sites should be obtained
for microscopy, culture, and
histopathological exam.
* Abbreviated versions
Summary: ISTC Standards Covered* (2)
Standard 6: The diagnosis of intrathoracic TB
in symptomatic children with negative sputum
smears should be based on:
• The presence of abnormalities consistent with TB
on chest radiography
• A history of exposure to an infectious case
• Evidence of TB infection (positive tuberculin skin
test or interferon gamma-release assay), and
• Clinical findings suggestive of TB
Specimens should be obtained for microscopy and
for culture and histopathological examination
* Abbreviated versions