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 lymph adenitis)

Central nervous system TB Disseminated TB TB effusions Spinal TB

(e.g., meningitis) (e.g., miliary TB) (pleural, pericardial, peritoneal) (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 quality assured 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.

2.

3.

4.

5.

6.

7.

Symptom and contact history Clinical exam (including growth assessment) Mantoux tuberculin skin test (TST) result Bacteriological confirmation (when possible) Chest radiograph Other specific evaluation indicated by disease site or co-morbidity 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 smear negative 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 smear positive 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 protein derivative (PPD) S,

or

purified • 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 HIV related 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