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ADC Online First, published on April 20, 2013 as 10.1136/archdischild-2013-303672
1
Infectious Diseases Unit,
Department of General
Medicine, The Royal Children’s
Hospital Melbourne, Parkville
Victoria, Australia
2
Infectious Diseases Unit,
University Children’s Hospital
Basel, Switzerland
3 assay (TST/IGRA) whether a CXR identifies findings
Department of Paediatrics,
The University of Melbourne,
Parkville, Victoria, Australia
4
Infectious Diseases &
Microbiology Group, Murdoch
Children’s Research Institute,
The Royal Children’s Hospital
Melbourne, Parkville, Victoria,
Australia
5
Medical Imaging Department,
The Royal Children’s Hospital
Melbourne, Parkville, Victoria,
Australia
Correspondence to
Professor Nigel Curtis,
Department of Paediatrics, The
University of Melbourne,
The Royal Children’s Hospital
Melbourne, 50 Flemington Rd,
Parkville, VIC 3052, Australia;
nigel.curtis@rch.org.au
Received 11 January 2013
Revised 8 March 2013
Accepted 11 March 2013
To cite: Gwee A,
Pantazidou A, Ritz N, et al.
Arch Dis Child Published
Online First: [ please include
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doi:10.1136/archdischild-
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Gwee A, etArticle
Copyright al. Arch Dis Child 2013;0:1–4.
author (or their doi:10.1136/archdischild-2013-303672
Original article
To x-ray or not to x-ray? Screening asymptomatic
children for pulmonary TB: a retrospective audit
Amanda Gwee,1 Anastasia Pantazidou,1 Nicole Ritz,1,2 Marc Tebruegge,1,3
Tom G Connell,1,3,4 Tim Cain,3,5 Nigel Curtis1,3,4
ABSTRACT
Objective Recent studies found that a chest x-ray
(CXR) has limited value in the assessment of
asymptomatic adults with tuberculosis (TB) infection. We
aimed to determine in asymptomatic children with a
positive tuberculin skin test and/or interferon-γ release
suggestive of pulmonary TB.
Design, setting and patients All children with TB
infection (defined as TST ≥10 mm and/or positive IGRA)
presenting to The Royal Children’s Hospital Melbourne
during a 54-month period were included. All CXRs were
reviewed by a senior radiologist blinded to the clinical
details. The medical records of those with radiological
abnormalities suggestive of TB were examined to identify
those who were asymptomatic when the CXR was done.
Demographical data were also collected.
Results CXRs were available for 268 of 330 TB-
infected children, of whom 60 had CXR findings
suggestive of TB. Of the 57 for whom clinical details
were available, 26 were asymptomatic. Of these
asymptomatic children with radiological abnormalities
suggestive of TB, 6 had CXR findings suggestive of
active TB, 14 had CXR findings suggestive of prior TB
and 6 had isolated non-calcified hilar lymphadenopathy.
The six with findings suggestive of active TB represented
2.6% (95% CI 0.9 to 5.5%) of asymptomatic TST/IGRA-
positive children with evaluable CXRs. One child with
isolated hilar lymphadenopathy had microbiologically-
confirmed TB.
Conclusions In contrast to the results from studies in
adults, a CXR identified a small but noteworthy number
of children with findings suggestive of pulmonary TB in
the absence of clinical symptoms.
INTRODUCTION
In a child at risk of tuberculosis (TB), a positive
tuberculin skin test and/or interferon-γ release assay
(TST/IGRA) does not distinguish between latent TB
infection (LTBI) and active TB.1 2 Although pul-
monary TB is usually symptomatic, current guide-
lines recommend that asymptomatic children who
have a positive TST/IGRA are screened with a chest
x-ray (CXR) to exclude asymptomatic pulmonary
TB.3–5 This distinction is important, as active TB
requires treatment with at least three anti-
mycobacterial antibiotics, whereas LTBI can be
treated with isoniazid alone, or a combination of
isoniazid and rifampicin.6
Recent studies in adults, however, question the
need for a CXR in TST/IGRA-positive individuals
who are asymptomatic.7 8 The diagnostic yield of a
CXR in this setting has not been specifically investi-
gated in children. We reviewed the CXRs of
employer) 2013. Produced by BMJ Publishing Group Ltd (& RCPCH) under licence.
What is already known about this topic
Studies in adults found that a CXR has limited
value in detecting asymptomatic pulmonary TB in
patients with a positive TST/IGRA.
What this study adds
In children with a positive TST/IGRA, a CXR
identified a small but not insignificant proportion
of asymptomatic children with CXR findings
suggestive of pulmonary TB.
asymptomatic children with a positive TST/IGRA
to determine what proportion had abnormal CXR
findings suggestive of pulmonary TB.
METHODS
We retrospectively identified all children
(0–18 years of age) who attended The Royal
Children’s Hospital Melbourne (RCH) over a
54-month period (October 2006–March 2011) who
had a positive TST (defined as ≥10 mm induration
at 48–72 h, placed and read by specialist nurses spe-
cifically trained and certified in this procedure)
and/or positive IGRA result (QuantiFERON-TB
Gold or Gold In-Tube assay). In our hospital, the
majority of children who have a TST/IGRA com-
prise new arrivals from high TB prevalence coun-
tries and contacts of pulmonary TB. Data were
obtained from two databases: (1) the RCH
Immunisation Centre TST result database and
(2) the Victorian Infectious Diseases Reference
Laboratory (VIDRL) Mycobacterial Laboratory
database. VIDRL is the sole provider of IGRA
testing for the RCH. All IGRA were carried out rou-
tinely according to the manufacturer’s instructions.
All CXRs that were obtained within 6 months of
the positive TST/IGRA in children who fulfilled the
inclusion criteria were reviewed by a senior consult-
ant radiologist, who was aware of the TST/IGRA
results but evaluated the CXRs blind to any other
clinical data. Features suggestive of active TB
(defined as cavitation, consolidation, pleural effu-
sion and miliary disease) or prior TB (defined as
pleural thickening, fibrous scarring, calcified lymph
node and calcified granuloma) were documented.7
Non-calcified hilar lymphadenopathy was docu-
mented as a separate category.
1
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Original article
The medical records of children with a CXR finding suggest-
ive of TB were then retrieved to determine whether the patient
was asymptomatic or had symptoms suggestive of pulmonary
TB (cough or other respiratory symptoms, fever, weight loss or
failure to thrive, night sweats). Demographical information,
including BCG immunisation status and country of origin, was
also collected, as well as the results of additional investigations
and treatment details for all asymptomatic children.
RESULTS
We identified 330 children with TB infection on the basis of a
positive TST and/or IGRA (figure 1). Of these, 268 children
(81.2%) had a CXR that was available for review, of which 60
(22.4%) were reported as abnormal with non-calcified hilar
lymphadenopathy, or findings suggestive of prior or active TB as
defined in the Methods section.
CXR findings
Of the 60 children with CXR findings suggestive of TB, 31 had
symptoms suggestive of pulmonary TB, 26 were asymptomatic
Figure 1 Overview of study.
2 Gwee A, et al. Arch Dis Child 2013;0:1–4. doi:10.1136/archdischild-2013-303672
and for 3 children, clinical details were not available. Therefore,
overall, there were 234 evaluable CXRs in TST/IGRA-positive
children (excluding the 31 symptomatic children and 3 lost to
follow-up).
Of the 26 asymptomatic children with CXR findings suggest-
ive of TB, 6 had CXR findings suggestive of active TB (repre-
senting 2.6% (95% CI 0.9% to 5.5%) of the 234 total CXRs),
14 had CXR findings suggestive of prior TB and 9 had non-
calcified hilar lymphadenopathy (in 6 of whom this was the
only abnormality) (figure 1 and table 1). Of the six children
with CXR findings suggestive of active TB, three had a house-
hold contact with sputum smear-positive pulmonary TB
(table 2). Only one of these six children had gastric aspirates
performed, and these were negative for acid-fast bacilli. Among
the six children with isolated non-calcified hilar lymphadenop-
athy, one had gastric aspirates taken which revealed acid-fast
bacilli, and a PCR test for Mycobacterium tuberculosis was posi-
tive. This was a 19-month-old non-BCG-immunised boy whose
father had pulmonary TB. One other child with isolated non-
calcified hilar lymphadenopathy had a gastric aspirate and
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Original article

Table 1 Chest x-ray findings in 26 asymptomatic children with
radiological abnormalities suggestive of TB.
CXR abnormality
Suggestive of active TB
Cavitation
Consolidation
Pleural effusion
Miliary disease
Non-calcified hilar lymphadenopathy
Suggestive of prior TB
Pleural thickening
Fibrous scarring
Calcified granuloma
Calcified lymph node
Note: Some children had more than one abnormality.
lymph node biopsy, which did not find evidence of M tubercu-
losis. The remaining four did not have any microbiological
investigations.
Treatment of asymptomatic children
Of the six children who had CXR findings suggestive of active
TB, five children were treated for pulmonary TB and one child
was treated for LTBI. The latter was a 15-month-old girl who
had consolidation on CXR. Her only identifiable risk factor was
birth in a high-TB-prevalence country (Burma). At follow-up,
3 months after completing a 6-month course of isoniazid pre-
ventive therapy, she remained well. Of the 14 children who had
CXR findings suggestive of prior TB, in three cases, the phys-
ician made the decision to treat for active TB. Of the six chil-
dren who had isolated non-calcified hilar lymphadenopathy, one
child was treated for active TB (this was the 19-month old boy
who had positive gastric aspirates for M. tuberculosis).
Overall, of the 26 asymptomatic children with CXR findings
suggestive of TB for whom records were available, 17 were
treated for LTBI: five had a household contact with pulmonary
TB, one had a school contact with smear-positive pulmonary
TB, and one had a non-household contact with smear-positive
pulmonary TB. The remaining nine children were treated for
active TB, of which eight (88.9%) had a known household
contact with pulmonary TB.
DISCUSSION
Our data show that a routine CXR in asymptomatic children
with a positive TST and/or IGRA does identify children with
n (%) CXR abnormalities suggestive of pulmonary TB despite the
absence of clinical features. Importantly, the proportion (2.6%,
95% CI 0.9% to 5.5%) of asymptomatic children identified in
0 (0)
our study whose CXR findings were suggestive of pulmonary
6 (23)
TB is not insignificant.
0 (0)
Our findings contrast with two studies in adults in which CXR
0 (0)
screening failed to identify any cases of active TB among asymp-
9 (35)
tomatic healthcare workers.7 8 However, an important difference
between these studies in adults and our study is that our patients
0 (0)
had a TST/IGRA as a result of identified risk factors for TB,
7 (27)
whereas the previous studies screened low-risk populations.
7 (27)
There are also important differences between a study of this kind
0 (0)
in adults and children. Children have a higher risk of progression
to active TB. Moreover, those who have a positive TST/IGRA are
more likely to have been recently infected, which also increases
their risk of progression to active TB.
The value of CXR screening has also been raised in studies in
selected paediatric populations. In a study of asylum seekers in
Switzerland, 2 of 16 TST-positive children who were screened
with a CXR had radiological abnormalities (not further speci-
fied), but neither was treated for pulmonary TB.9 In an Italian
study of asylum seekers, none of the 68 TST-positive children
had radiological evidence of active TB, although 7 (10.3%) had
CXR abnormalities suggestive of prior TB (treatment outcomes
were not reported in this study).10 A study of internationally
adopted children in the USA reported that while 3 (3.3%) of the
90 asymptomatic TST-positive children had radiological findings
consistent with pulmonary TB, none were treated for active TB
and none of these 3 children developed active TB during a 2-year
follow-up period.11 However, our results are consistent with
studies in a different context in Brazil and South Africa that
found that children with active TB can be asymptomatic, includ-
ing up to 47% of those with culture-positive pulmonary TB.12 13
Our study also highlights differences in the classification and
management of asymptomatic children with isolated hilar lymph-
adenopathy. Mediastinal and hilar lymphadenopathy with or
without parenchymal abnormalities (Ghon focus) is a common
form of TB in children.14 15 Two studies in adults did not con-
sider hilar lymphadenopathy in their definitions of active or
prior TB,7 8 16 while another16 classified hilar lymphadenopathy
as a sign of active disease. Similarly, some paediatric studies have
classified hilar lymphadenopathy in an asymptomatic child as

Table 2 Details of the six asymptomatic children with CXR findings compatible with active TB
Age Country of birth, age arrived in BCG Microbiological
Sex (years) Australia (other risk factors) TB contact immunised CXR abnormality confirmation

M 1 Australia Grandmother: No Consolidation GA not done

smear-positive PTB Non-calcified hilar
lymph nodes
F 1 Burma, <1 year None known Yes Consolidation GA not done
F 5 Ethiopia (4 month visit to Ethiopia aged Sister: No Consolidation GA: no growth
5 years) lymph node TB
F 7 Kenya, 5 years Mother: Yes Consolidation GA not done
smear-positive PTB Non-calcified hilar
lymph nodes
M 8 Australia (parents from Somalia) Cousin: smear-positive PTB ‘stayed No Consolidation GA not done
with family for 1 week’
M 12 Philippines, 10 years None known Yes Consolidation GA not done
GA, gastric aspirates; PTB, pulmonary tuberculosis.

Gwee A, et al. Arch Dis Child 2013;0:1–4. doi:10.1136/archdischild-2013-303672 3

 Downloaded from http://adc.bmj.com/ on May 26, 2015 - Published by group.bmj.com
Original article
indicative of active TB,11 12 17 whereas others have suggested
that hilar lymphadenopathy is indicative of recent TB infection
but not pulmonary disease.18 19 Data from the latter studies
suggest that few children with isolated hilar lymphadenopathy
develop active disease. Notably, in our study, the one child with
isolated hilar lymphadenopathy who had a gastric aspirate had
microbiologically-confirmed TB despite the absence of clinical
symptoms.
In many instances, the decision to treat for LTBI or active TB
appears to have been influenced by factors other than the CXR
findings. In our study, eight of the nine children treated for
active TB had a household TB contact, and five of these did not
have CXR findings suggestive of pulmonary TB. Notably, only
three of the nine children had gastric aspirates taken and only
one child had microbiologically-confirmed pulmonary TB.
However, this is not surprising, as microbiological confirmation
is far less frequently achieved in children than in adults, and the
decision to treat a child for active TB consequently has to be
based on epidemiological risk factors, particularly a history of
exposure to an infected adult, in conjunction with TST/IGRA
results.20
Limitations of our study include its retrospective nature.
Although this resulted in a number of CXRs not being available
for review, this is unlikely to have introduced selection bias. Also,
all CXRs were interpreted by a single experienced consultant radi-
ologist, an approach that provides overall consistency, but does not
allow any conclusions regarding inter-observer variability.
CONCLUSION
Our data suggest that, in contrast to adults, a CXR remains a
valuable tool in the management of asymptomatic children with
a positive TST and/or IGRA, as this approach identifies a small,
but not insignificant proportion of children who have pulmon-
ary TB in the absence of clinical symptoms.
Acknowledgements We thank Dr David Leslie and Dr Norbert Ryan at the
Victoria Infectious Diseases Reference Laboratory for providing the interferon-gamma
release assay data.
Contributors AG, NR and NC were responsible for study concept and design; AG,
AP, MT, TC and NC were responsible for acquisition of data; AG, MT and NC were
responsible for analysis and interpretation of data; AG and NC were involved in
drafting the manuscript; critical revision of the manuscript for important intellectual
content was carried out by AG, AP, NR, MT, TGC, TC and NC; and NC supervised
the study.
Competing interests None.
Ethics approval From The Royal Children’s Hospital Human Research Ethics
Committee (HREC 31074).
Provenance and peer review Not commissioned; externally peer reviewed.
4 Gwee A, et al. Arch Dis Child 2013;0:1–4. doi:10.1136/archdischild-2013-303672
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 Downloaded from http://adc.bmj.com/ on May 26, 2015 - Published by group.bmj.com

To x-ray or not to x-ray? Screening

asymptomatic children for pulmonary TB: a
retrospective audit
Amanda Gwee, Anastasia Pantazidou, Nicole Ritz, Marc Tebruegge, Tom
G Connell, Tim Cain and Nigel Curtis

Arch Dis Child published online April 20, 2013

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