Development of treatment-decision algorithms for children evaluated for pulmonary tuberculosis: an individual participant data meta-analysis

Gunasekera, Kenneth S.; Marcy, Olivier; Muñoz, Johanna; López-Varela, Elisa; Sekadde, Moorine Penninah; Franke, Molly F; Bonnet, Maryline; Ahmed, Shakil; Amanullah, Farhana; Anwar, Aliya; Augusto, Orvalho; Aurílio, Rafaela Baroni; Banu, Sayera; Batool, Iraj; Brands, Annemieke; Cain, Kevin P.; Carratalá-Castro, Lucía; Caws, Maxine; Click, Eleanor S.; Cranmer, Lisa M; García‐Basteiro, Alberto L.; Hesseling, Anneke C.; Huynh, Julie; Kabir, Shahjahan; Lecca, Leonid; Mandalakas, Anna M.; Mavhunga, Farai; Myint, Aye Aye; Myo, Kyaw; Nampijja, Dorah; Nicol, Mark P.; Orikiriza, Patrick; Palmer, Megan; Sant’Anna, Clemax Couto; Siddiqui, Sara; Smith, Jonathan; Song, Rinn; Thuong, Nguyen Thuy Thuong; Vibol, Ung; Zalm, Marieke M. van der; Verkuijl, Sabine; Viney, Kerri; Walters, Elisabetta; Warren, Joshua L.; Zar, Heather J.; Marais, Ben J.; Graham, Stephen M.; Debray, Thomas P. A.; Cohen, Ted; Seddon, James A.

doi:10.1016/s2352-4642(23)00004-4

Cited by 11 publications

(4 citation statements)

References 22 publications

(24 reference statements)

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“…13 For contacts younger than 5 years, we modelled a household visit with symptom screening, in which symptomatic children would be referred to a health facility for diagnosis using chest x-ray. 13 , 33 Those with a chest x-ray suggestive of tuberculosis would initiate treatment for tuberculosis disease, and children with a negative symptom screening or negative chest x-ray would be eligible to initiate TPT. For contacts aged 5 years and older, we modelled a household visit with symptom screening as well as facility-based chest x-ray; in a sensitivity analysis, we included symptom screening only.…”

Section: Methodsmentioning

confidence: 99%

Impact and cost-effectiveness of short-course tuberculosis preventive treatment for household contacts and people with HIV in 29 high-incidence countries: a modelling analysis

Ryckman,

Weiser,

Gombe

et al. 2023

The Lancet Global Health

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Section: Methodsmentioning

confidence: 99%

Impact and cost-effectiveness of short-course tuberculosis preventive treatment for household contacts and people with HIV in 29 high-incidence countries: a modelling analysis

Ryckman,

Weiser,

Gombe

et al. 2023

The Lancet Global Health

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“…An alternative explanation is that a significant proportion of children classified as unconfirmed TB, despite fulfilling international diagnostic criteria for pediatric TB [36] and receiving treatment for TB based on independent assessment by experienced clinicians, did not have TB disease. The limitations of the currently applied criteria for unconfirmed TB in children are well recognized [46,47]. Despite lacking specificity for pulmonary TB, these guidelines are meant to reduce the number of missed TB diagnoses in young children, given the high risk of severe TB disease during early life.…”

Section: Discussionmentioning

confidence: 99%

Production of Proinflammatory Cytokines by CD4+ and CD8+ T Cells in Response to Mycobacterial Antigens among Children and Adults with Tuberculosis

Morrow,

Liu,

Kiguli

et al. 2023

Pathogens

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of pediatric morbidity and mortality. Young children are at high risk of TB following Mtb exposure, and this vulnerability is secondary to insufficient host immunity during early life. Our primary objective was to compare CD4+ and CD8+ T-cell production of proinflammatory cytokines IFN-gamma, IL-2, and TNF-alpha in response to six mycobacterial antigens and superantigen staphylococcal enterotoxin B (SEB) between Ugandan adults with confirmed TB (n = 41) and young Ugandan children with confirmed (n = 12) and unconfirmed TB (n = 41), as well as non-TB lower respiratory tract infection (n = 39). Flow cytometry was utilized to identify and quantify CD4+ and CD8+ T-cell cytokine production in response to each mycobacterial antigen and SEB. We found that the frequency of CD4+ and CD8+ T-cell production of cytokines in response to SEB was reduced in all pediatric cohorts when compared to adults. However, T-cell responses to Mtb-specific antigens ESAT6 and CFP10 were equivalent between children and adults with confirmed TB. In contrast, cytokine production in response to ESAT6 and CFP10 was limited in children with unconfirmed TB and absent in children with non-TB lower respiratory tract infection. Of the five additional mycobacterial antigens tested, PE3 and PPE15 were broadly recognized regardless of TB disease classification and age. Children with confirmed TB exhibited robust proinflammatory CD4+ and CD8+ T-cell responses to Mtb-specific antigens prior to the initiation of TB treatment. Our findings suggest that adaptive proinflammatory immune responses to Mtb, characterized by T-cell production of IFN-gamma, IL-2, and TNF-alpha, are not impaired during early life.

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“…Similar challenges in terms of inter-overserver agreement and therefore sensitivity and specificity of chest x-ray results can also be encountered in other paediatric lung infections such as community acquired pneumonia (pCAP). Moreover, definitive proof of TB by detection of sputum smear positive tuberculosis can only be detected in 5-10 % of the children [5] and positive cultures from sputum, gastric aspirates or bronchoalveolar lavage can only be found in 30-40 % [6,7]. Therefore, the radiological diagnosis plays an essential role in the decision whether or whether not a child with a proven tuberculosis infection has got pulmonary TB disease.…”

Section: Introductionmentioning

confidence: 99%

TB or not TB? Diagnostic Sensitivity, Specifity and Interobserver Agreement in the Radiological Diagnosis of Pulmonary Tuberculosis in Children

Brinkmann,

Hofgrefe,

Ahrens

et al. 2024

Klin Padiatr

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Background The differentiation between latent tuberculosis infection (LTBI) and tuberculosis (TB) relies on radiological changes. Confirming the diagnosis remains a challenge because typical findings are often missing in children. This study evaluates diagnostic sensitivity, specifity and interobserver agreement on the radiological diagnosis of TB by chest-x-rays in accordance to professional specialization and work experience. Methods Chest x-rays of 120 children with proven tuberculosis infection were independently evaluated by general radiologists, paediatric radiologists and paediatric pulmonologists. Results were compared to a reference diagnosis created by group of experienced paediatric radiologists and paediatric pulmonologists. Primary endpoints were diagnostic sensitivity and specificity and interobserver variability defined as Krippendorfs alpha of thesel groups compared to the reference diagnosis. Results Of the 120 chest x-rays 33 (27,5%) were diagnosed as TB by the reference standard . Paediatric pulmonologist had the highest diagnostic sensitivity (90%) but were less specific (71%) whereas general radiologist were less sensitive (68%) but more secific (95%). The best diagnostic accuracy was achieved by pediatric radiologists with a diagnostic sensitivity of 77% and specificity 95% respectively. Conclusions We demonstrated significant interobserver variability and relevant differences in sensitivity and specificity in the radiological diagnosis of TB between the groups. Paediatric radiologists showed the best diagnostic performance. As the diagnosis of pulmonary TB has significant therapeutic consequences for children they should be routinely involved in the diagnostic process.

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Development of treatment-decision algorithms for children evaluated for pulmonary tuberculosis: an individual participant data meta-analysis

Cited by 11 publications

References 22 publications

Impact and cost-effectiveness of short-course tuberculosis preventive treatment for household contacts and people with HIV in 29 high-incidence countries: a modelling analysis

Impact and cost-effectiveness of short-course tuberculosis preventive treatment for household contacts and people with HIV in 29 high-incidence countries: a modelling analysis

Production of Proinflammatory Cytokines by CD4+ and CD8+ T Cells in Response to Mycobacterial Antigens among Children and Adults with Tuberculosis

TB or not TB? Diagnostic Sensitivity, Specifity and Interobserver Agreement in the Radiological Diagnosis of Pulmonary Tuberculosis in Children

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