EDITORIALS

lung biopsies from patients with idiopathic interstitial pneumonias. Chest 10. Lakhani P, Sundaram B. Deep learning at chest radiography: automated
2004;125:522–526. classification of pulmonary tuberculosis by using convolutional neural
6. Kim EJ, Elicker BM, Maldonado F, Webb WR, Ryu JH, Van Uden JH, networks. Radiology 2017;284:574–582.
et al. Usual interstitial pneumonia in rheumatoid arthritis-associated 11. Lee JG, Jun S, Cho YW, Lee H, Kim GB, Seo JB, et al. Deep learning
interstitial lung disease. Eur Respir J 2010;35:1322–1328. in medical imaging: general overview. Korean J Radiol 2017;18:
7. Putman RK, Gudmundsson G, Axelsson GT, Hida T, Honda O, Araki T, 570–584.
et al. Imaging patterns are associated with interstitial lung 12. Walsh SL, Mackintosh JA, Calandriello L, Silva M, Sverzellati N, Larici
abnormality progression and mortality. Am J Respir Crit Care Med AR, et al. Deep learning-based outcome prediction in progressive
2019;200:175–183. fibrotic lung disease using high-resolution computed tomography.
8. Handa T, Tanizawa K, Oguma T, Uozumi R, Watanabe K, Tanabe N, et al. Am J Respir Crit Care Med 2022;206:883–891.
Novel artificial intelligence-based technology for chest computed 13. Walsh SLF, Calandriello L, Silva M, Sverzellati N. Deep learning for
tomography analysis of idiopathic pulmonary fibrosis. Ann Am Thorac classifying fibrotic lung disease on high-resolution computed
Soc 2022;19:399–406. tomography: a case-cohort study. Lancet Respir Med 2018;6:
9. Bratt A, Williams JM, Liu G, Panda A, Patel PP, Walkoff L, et al. Predicting 837–845.
usual interstitial pneumonia histopathology from chest CT imaging with
deep learning. Chest 2022 [online ahead of print]: S0012-3692(22)00590-6. Copyright © 2022 by the American Thoracic Society

The Value of Chest Radiography in Tuberculosis Preventive

Treatment Screening in Children and Adolescents

Despite existing guidelines and strong commitments to increase (or on the basis of known exposure to a bacteriologically confirmed
tuberculosis preventive treatment (TPT) uptake, the World Health infectious TB case, if a test for infection is unavailable) should receive
Organization (WHO) estimates that less than one-third of young TPT once TB disease has been excluded (2). The role of chest
children (,5 yr) who had household contact with an infectious radiography in this older age group requires better evidence as this is
tuberculosis (TB) case received TPT in 2020 (1). Increased TB a group that, compared with young child contacts, are more likely to
transmission resulting from COVID-19 health system disruption have coprevalent subclinical bacteriologically positive TB detectable
accentuates the threat posed to vulnerable young children and people by chest radiography (8). Therefore, they are at greater risk of
living with HIV, who are key TPT target groups. Recently, WHO suboptimal outcomes and drug resistance acquisition if not
extended TPT recommendations to HIV-uninfected older children appropriately treated.
and adolescents (5–19 yr) who are household TB contacts, and
coverage in this group is currently estimated to be less than 5%
globally (1, 2).
Barriers to implementation of child TB contact screening and Assessing the Value of Chest Radiograpy for
management include the need for pragmatic screening options to Tuberculosis Contact Screening
deliver community-based TPT (3). Chest radiography has a critical
role, both to support a clinical diagnosis of TB and to rule out active In this issue of the Journal, Huang and colleagues (pp. 892–900)
disease before initiating TPT; but access to chest radiography is a evaluated the diagnostic and prognostic value of chest radiography in
major hurdle in resource-limited settings (4). It has been children exposed to TB in Peru and measured the efficacy of
demonstrated that symptom-based TB contract screening is safe, isoniazid preventive therapy (IPT) in those with radiographic
and that chest radiography adds little value in asymptomatic young abnormalities (9). They enrolled 4,468 children with household
children who receive TPT (5–7). However, despite the available exposure to bacteriologically confirmed TB who had symptom
evidence, many clinicians remain uncomfortable providing TPT assessment and chest radiography done. The majority (56%) of
without a chest radiograph to rule out TB disease, given that chest contacts were 6 years of age or older, and only 0.1% were HIV
radiography is routinely performed before TPT commencement in positive. Chest radiography was limited to an anteroposterior film,
settings without resource constraints. and these were interpreted by experienced readers blinded to the
The value of chest radiography also requires further clarification clinical presentation. Those without coprevalent TB (at baseline) were
in older children and adolescents, since the WHO now recommends followed for 1 year to assess disease progression (incident TB) risk as
that older child and adolescent TB contacts with evidence of infection well as the protective efficacy of IPT.
Asymptomatic children with abnormal chest radiographs were
found to be 25 times more likely to have coprevalent TB and 26 times
This article is open access and distributed under the terms of the more likely to be diagnosed with incident TB during follow-up than
Creative Commons Attribution Non-Commercial No Derivatives asymptomatic children with normal chest films (9). The authors
License 4.0. For commercial usage and reprints, please e-mail concluded that chest radiography is strongly supported as a routine
Diane Gern ([email protected]).
screening tool for the evaluation of child TB contacts, where this is
Originally Published in Press as DOI: 10.1164/rccm.202205-1023ED readily available, given that even atypical radiographic findings in
on June 2, 2022 asymptomatic children may indicate incipient or subclinical disease.

814 American Journal of Respiratory and Critical Care Medicine Volume 206 Number 7 | October 1 2022
EDITORIALS

Table 1. Overview of the Benefits and Risks Associated with Chest Radiograph and Symptom-based Screening of Child and
Adolescent Tuberculosis Contacts

CXR-based Screening Symptom-based Screening

Benefits
 May detect incipient and sub-clinical disease in children who are  Can be applied independent of local resources, also in a
minimally or asymptomatic. decentralized fashion, and facilitates TPT access.
 Provides greater assurance that disease has not been missed  WHO endorsed in resource-limited settings.
prior to commencing TPT—this is particularly important in older
children and adolescents.
 Deeply engrained “standard of care” in well-resourced settings
with perceived “medicolegal” risk, if omitted.
Risks
 Could pose a major barrier to TPT provision in resource-limited  May miss early or subclinical disease—this should be
settings. adequately treated by combination TPT regimens at least in
 May detect and treat irrelevant chest radiograph abnormalities. young children (,5 yr).
 May reduce the impetus to increase child CXR access as a
matter of urgency; every effort should still be made to increase
children’s access to high-quality chest radiography.

Definition of abbreviations: CXR = chest X-ray; TB = tuberculosis; TPT = TB preventative treatment.

Asymptomatic should exclude any current symptoms potentially suggestive of TB, irrespective of duration.

The group that were asymptomatic with an abnormal chest Closing the TPT Gap
radiograph contributed to 28 (28.9%) of 97 coprevalent or incident
TB cases. However, the overall yield in asymptomatic child contacts It is important to remember that the main focus of TPT provision in
was very low: 0.79% for coprevalent disease and 0.76% for incident vulnerable young children is to prevent severe TB disease and death,
disease (not reported by age group). In the context of a resource- which provides a strong imperative to improve TPT access.
limited setting, such a low yield may not support routine chest Symptom-based TB screening approaches recognize “real-life”
radiography for all child contacts, especially not those who are resource constraints in many high–TB incidence settings, as well as
completely asymptomatic. IPT was also found to be highly effective in key differences in the TB risk and disease spectrum among young
preventing disease progression, with 82% efficacy against incident TB children, adolescents, and adults. Arguably, the exclusion of
documented among ‘asymptomatic’ children who had an abnormal coprevalent TB is less relevant in asymptomatic young children in
chest radiograph at baseline. whom the treatment of infection with 3RH and of nonsevere disease
Clearly, these important findings require careful with a new 4-month treatment regimen (2RHZ/2RH) is now very
consideration for programmatic implementation. This study did similar (2, 11, 12). The situation in older child and adolescent
have some limitations inherent to TB diagnosis in young contacts is different and therefore better age-disaggregated data
children. The symptom definitions used for screening were not (differentiating 5–9, 10–14, and 15–19 yr age groups) on TB
optimized for sensitivity (10). The specific radiographic screening and management approaches, including the utility of chest
abnormalities suggestive of TB were not reported, including by radiography, are required. Table 1 provides an overview of the
age group. In the absence of microbiological confirmation, the benefits and risks associated with chest radiograph and symptom-
case definitions used were heavily dependent on chest based screening of child and adolescent TB contacts.
radiograph interpretation and therefore open to strong Closing persistent gaps in child TB prevention and detection
incorporation bias. The most common radiographic abnormality is essential to meet targets formulated at the United Nations high-
reported in asymptomatic young child contacts is perihilar level meeting on the fight against TB. (13) In the end, TPT
lymph node enlargement (7, 8). However, accurate detection of implementation and scale-up will only be achieved if it is
this pathology by radiography can be challenging, leading to perceived as a priority by TB programmes and major donors, as
overdiagnosis of TB as well as underdetection, especially if lateral demonstrated by the high TPT coverage in HIV programmes. This
chest radiograph views are not performed. Lastly, 6 months of will require practical implementation plans, reliable drug supply
isoniazid monotherapy may be less effective in programmatic and effective monitoring and evaluation systems. High TPT uptake
practice than 3 months of rifampicin and isoniazid (3RH), which and completion rates have been reported in young child TB
is associated with higher uptake and completion and is now the contacts using decentralized, community-based approaches that
preferred WHO TPT regimen for HIV-uninfected child contacts limit the use of chest radiography to symptomatic contacts (6, 7, 14,
(2). Although the numbers were small, it appears as if the few 15). These prospective implementation studies have demonstrated
children who developed incident TB despite receiving IPT were effectiveness and safety with high retention to follow-up following
successfully treated with standard first-line therapy, reflecting the TPT completion. However, there is a need for stronger evidence in
low risk of drug resistance acquisition in young children older child and adolescent TB contacts to identify and support
receiving TPT, even if early paucibacillary disease is missed. pragmatic and safe TPT implementation strategies. 䊏

Editorials 815
 EDITORIALS

4. Marais BJ, Ayles H, Graham SM, Godfrey-Faussett P. Screening and

Author disclosures are available with the text of this article at preventive therapy for tuberculosis. Clin Chest Med 2009;30:
www.atsjournals.org. 827–846, x.
5. Triasih R, Robertson CF, Duke T, Graham SM. A prospective evaluation of
the symptom-based screening approach to the management of children
Ben J. Marais, M.D., Ph.D.
who are contacts of tuberculosis cases. Clin Infect Dis 2015;60:12–18.
Sydney Institute for Infectious Diseases and the Children’s Hospital
6. Kruk A, Gie RP, Schaaf HS, Marais BJ. Symptom-based screening of child
Westmead
tuberculosis contacts: improved feasibility in resource-limited settings.
The University of Sydney
Pediatrics 2008;121:e1646–e1652.
Sydney, Australia
7. Triasih R, Robertson C, de Campo J, Duke T, Choridah L, Graham SM. An
and evaluation of chest X-ray in the context of community-based screening
of child tuberculosis contacts. Int J Tuberc Lung Dis 2015;19:
National Health and Medical Research Council (NHMRC), 1428–1434.
Centre for Research Excellence in Tuberculosis 8. Seddon JA, Chiang SS, Esmail H, Coussens AK. The wonder years: what
Camperdown, New South Wales, Australia can primary school children teach us about immunity to Mycobacterium
tuberculosis? Front Immunol 2018;9:2946.
Stephen M. Graham, M.D., Ph.D. 9. Huang CC, Tan Q, Becerra MC, Calderon R, Chiang SS, Contreras C,
et al. The contribution of chest radiography to the clinical management
National Health and Medical Research Council (NHMRC),
of children exposed to tuberculosis. Am J Respir Crit Care Med 2022;
Centre for Research Excellence in Tuberculosis
206:892–900.
Camperdown, New South Wales, Australia
10. Marais BJ, Graham SM. Symptom-based screening of child TB contacts:
Department of Paediatrics and Murdoch Children’s Research Institute, defining ‘symptomatic’. Int J Tuberc Lung Dis 2017;21:832–833.
University of Melbourne 11. WHO consolidated guidelines on tuberculosis. Module 5: management of
Melbourne, Australia tuberculosis in children and adolescents. Geneva: World Health
Organization; 2022. License: CC BY-NC-SA 3.0 IGO.14) Sx-based
and screening.
12. United Nations General Assembly (UNGA) high level meeting on the fight
Burnet Institute against TB political declaration. World Health Organization; 2019
Melbourne, Australia [accessed 2022 May 25]. Available from: https://www.who.int/
ORCID ID: 0000-0003-3404-2690 (B.J.M.). publications/m/item/political-declaration-of-the-un-general-assembly-
high-level-meeting-on-the-fight-against-tuberculosis.
13. Turkova A, Wills GH, Wobudeya E, Chabala C, Palmer M, Kinikar A,
et al.; SHINE Trial Team. Shorter treatment for nonsevere
tuberculosis in African and Indian children. N Engl J Med 2022;386:
911–922.
14. Schwoebel V, Koura KG, Adjobimey M, Gnanou S, Wandji AG, Gody JC,
References
et al. Tuberculosis contact investigation and short-course preventive
therapy among young children in Africa. Int J Tuberc Lung Dis 2020;
1. Global tuberculosis report 2021. Geneva: World Health Organization;
24:452–460.
2021. License: CC BY-NC-SA 3.0 IGO.
15. Kay AW, Sandoval M, Mtetwa G, Mkhabela M, Ndlovu B, Devezin T,
2. WHO consolidated guidelines on tuberculosis: module 1: prevention:
et al. Vikela Ekhaya: a novel, community-based, tuberculosis contact
tuberculosis preventive treatment. Geneva: World Health Organization;
management program in a high burden setting. Clin Infect Dis 2022;74:
2020.
1631–1638.
3. Marais BJ, Verkuijl S, Casenghi M, Triasih R, Hesseling AC, Mandalakas
AM, et al. Paediatric tuberculosis - new advances to close persistent
gaps. Int J Infect Dis 2021;113:S63–S67. Copyright © 2022 by the American Thoracic Society

816 American Journal of Respiratory and Critical Care Medicine Volume 206 Number 7 | October 1 2022