Clinical Features, Adverse Events and Treatment Outcomes of Multidrug/Rifampicin-resistant Tuberculosis in Children and Adolescents: An Eight-year Retrospective Cohort Study in Bandung, Indonesia

Heda M Nataprawira; Fajri Gafar; Chindy A Sari; Jan-Willem C Alffenaar; Ben J Marais; Rovina Ruslami; Dick Menzies

doi:10.1097/INF.0000000000004539

Clinical Features, Adverse Events and Treatment Outcomes of Multidrug/Rifampicin-resistant Tuberculosis in Children and Adolescents: An Eight-year Retrospective Cohort Study in Bandung, Indonesia

Pediatr Infect Dis J. 2024 Sep 23. doi: 10.1097/INF.0000000000004539. Online ahead of print.

Authors

Heda M Nataprawira¹, Fajri Gafar^{2

3

4}, Chindy A Sari¹, Jan-Willem C Alffenaar^{5

6

7}, Ben J Marais^{5

8}, Rovina Ruslami^{3

4}, Dick Menzies^{2

3}

Affiliations

¹ From the Division of Pediatric Respirology, Department of Child Health, Faculty of Medicine, Universitas Padjadjaran, Hasan Sadikin General Hospital, Bandung, Indonesia.
² Respiratory Epidemiology and Clinical Research Unit, Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
³ McGill International TB Centre, McGill University, Montreal, Quebec, Canada.
⁴ Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.
⁵ The University of Sydney Infectious Disease Institute (Sydney ID), Sydney, NSW, Australia.
⁶ School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
⁷ Westmead Hospital, Sydney, NSW, Australia.
⁸ The Children's Hospital at Westmead, Sydney, NSW, Australia.

PMID: 39312636
DOI: 10.1097/INF.0000000000004539

Abstract

Background: Data on childhood and adolescent multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) in Indonesia are lacking. We aimed to assess clinical features, adverse events (AEs) and treatment outcomes of childhood and adolescent MDR/RR-TB.

Methods: A retrospective cohort study was performed in children and adolescents aged <18 years treated for MDR/RR-TB at Hasan Sadikin General Hospital in Bandung, Indonesia, between June 2016 and March 2024. Multivariable logistic regression analyses were used to calculate adjusted odds ratios (aOR) for predictors of all-cause mortality.

Results: Among 84 included patients, 69 (82%) were adolescents aged 10-17 years, 54 (64%) were female, 54 (64%) were malnourished and 55 (65%) had culture-confirmed disease. Among 69 (82%) patients with known outcomes, 48 (70%) were successfully treated, 14 (20%) died (including 5 pretreatment deaths) and 7 (10%) were lost to follow-up (LTFU) (including 5 pretreatment LTFU). Predictors of all-cause mortality included shortness of breath on admission [aOR: 6.4, 95% confidence interval (CI): 1.3-49.1], high bacillary burden on Xpert MTB/RIF assay (aOR: 17.0, 95% CI: 1.6-260.5) and the presence of lung cavities on chest radiograph (aOR: 4.8, 95% CI: 1.1-23.3). Among 74 patients who initiated treatment, 39 (53%) had at least one grade 1-2 AE, and 4 (5%) had one grade 3-4 AE each, including hepatotoxicity, QT prolongation, hearing loss and rash/hyperpigmentation.

Conclusion: Younger children were underrepresented among those treated for MDR/RR-TB, indicating reduced access to care. Severe AEs were uncommon during MDR/RR-TB treatment. Baseline indicators of extensive disease were associated with all-cause mortality. The high proportion of pre-treatment mortality and LTFU may reflect complex patient pathways limiting access to care.