Determinants of treatment outcome in children with multidrug-resistant tuberculosis: a tertiary care hospital experience
Abstract
This study aimed to analyze the significant factors associated with unsuccessful treatment outcomes among multidrug-resistant tuberculosis in children under 18. This observational study was conducted at the Bahawal Victoria Hospital, Bahawalpur, Pakistan, at the Programmatic Management Unit of the National Tuberculosis Control Program of Pakistan. The data were collected retrospectively using the Electronic Nominal Recording Reporting System records for all the eligible drug-resistant tuberculosis patients registered at the study sites between June 2014 and September 2022. Multivariate binary logistic regression analysis was used to analyze the factors significantly associated with unsuccessful treatment outcomes. This study included 88 children. Of the 88 patients, 64 (72.8%) completed their treatment successfully. A total of 13 patients (14.8%) died, 2 (2.3%) had treatment failure, and 9 (10.2%) were lost to follow-up. Factors significantly associated with unsuccessful treatment outcomes included a history of use of second-line drugs and those with favorable interim treatment outcomes (negative association). The overall treatment success rate among the children was 72.8%, which can be further improved by reducing loss to follow-up and rational use of second-line drugs in treating drug-sensitive tuberculosis. This can be done by devising a careful, targeted treatment regimen and patient education.
Ethics Approval
Consent for publication was provided by the ethical review committee of QAMC/BVH under the reference no. QAMC/BVH-00921.
References
- Adu PA, Spiegel JM, Yassi A. Towards TB elimination: how are macro-level factors perceived and addressed in policy initiatives in a high burden country? Global Health 2021;17:11. DOI: https://doi.org/10.1186/s12992-020-00657-1
- Bhargava A, Bhargava M. Tuberculosis deaths are predictable and preventable: comprehensive assessment and clinical care is the key. J Clin Tuberc Other Mycobact Dis 2020;19:100155. DOI: https://doi.org/10.1016/j.jctube.2020.100155
- WHO. Global tuberculosis report 2020. Available from: https://www.who.int/publications/i/item/9789240013131.
- WHO. Global tuberculosis report 2013. Available from: https://www.who.int/publications/i/item/9789241564656.
- Dodd PJ, Sismanidis C, Seddon JA. Global burden of drug-resistant tuberculosis in children: a mathematical modelling study. Lancet Infect Dis 2016;16:1193-201. DOI: https://doi.org/10.1016/S1473-3099(16)30132-3
- Jenkins HE, Tolman AW, Yuen CM, et al. Incidence of multidrug-resistant tuberculosis disease in children: systematic review and global estimates. Lancet 2014;383:1572-9. DOI: https://doi.org/10.1016/S0140-6736(14)60195-1
- MacNeil A, Glaziou P, Sismanidis C, et al. Global epidemiology of tuberculosis and progress toward achieving global targets - 2017. MMWR Morb Mortal Wkly Rep 2019;68:263-6. DOI: https://doi.org/10.15585/mmwr.mm6811a3
- Hassan B, Ahmed A, Li B, et al. A comprehensive study capturing vision loss burden in Pakistan (1990-2025): findings from the Global Burden of Disease (GBD) 2017 study. PloS One 2019;14:e0216492. DOI: https://doi.org/10.1371/journal.pone.0216492
- Abubakar M, Ahmad N, Ghafoor A, et al. Treatment outcomes of extensively drug-resistant tuberculosis in Pakistan: a countrywide retrospective record review. Front Pharmacol 2021;12:640555. DOI: https://doi.org/10.3389/fphar.2021.640555
- Rashid A, Sheokand S, Fatima R, et al. Maximizing tuberculosis services through private provider engagement - a case study from Pakistan. J Clin Tuberc Other Mycobact Dis 2025;39:100506. DOI: https://doi.org/10.1016/j.jctube.2024.100506
- Ahmad N, Ahuja SD, Akkerman OW, et al. Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis. Lancet 2018;392:821-34. DOI: https://doi.org/10.1016/S0140-6736(18)31644-1
- Jenkins HE, Yuen CM. The burden of multidrug-resistant tuberculosis in children. Int J Tuberc Lung Dis 2018;22:3-6. DOI: https://doi.org/10.5588/ijtld.17.0357
- Zignol M, Sismanidis C, Falzon D, et al. Multidrug-resistant tuberculosis in children: evidence from global surveillance. Eur Respir J 2013;42:701-7. DOI: https://doi.org/10.1183/09031936.00175812
- WHO. WHO consolidated guidelines on tuberculosis. Module 4: treatment-drug-resistant tuberculosis treatment, 2022 update. Available from: https://www.who.int/publications/i/item/9789240063129.
- Seddon JA, Hesseling AC, Godfrey-Faussett P, Schaaf HS. High treatment success in children treated for multidrug-resistant tuberculosis: an observational cohort study. Thorax 2014;69:458-64. DOI: https://doi.org/10.1136/thoraxjnl-2013-203900
- Chiang SS, Starke JR, Miller AC, et al. Baseline predictors of treatment outcomes in children with multidrug-resistant tuberculosis: a retrospective cohort study. Clin Infect Dis 2016;63:1063-71. DOI: https://doi.org/10.1093/cid/ciw489
- Dhakulkar S, Das M, Sutar N, et al. Treatment outcomes of children and adolescents receiving drug-resistant TB treatment in a routine TB programme, Mumbai, India. PLoS One 2021;16:e0246639. DOI: https://doi.org/10.1371/journal.pone.0246639
- Atif M, Fatima R, Ahmad N, Babar ZUD, et al. Treatment outcomes of extrapulmonary tuberculosis in Bahawalpur, Pakistan; a record review. J Pharm Policy Pract 2020;13:35. DOI: https://doi.org/10.1186/s40545-020-00227-1
- Khan FU, Khan A, Khan FU, et al., Assessment of adverse drug events, their risk factors, and management among patients treated for multidrug-resistant TB: a prospective cohort study from Pakistan. Front Pharmacol 2022;13:876955. DOI: https://doi.org/10.3389/fphar.2022.876955
- Mirzayev F, Viney K, Linh NN, et al. World Health Organization recommendations on the treatment of drug-resistant tuberculosis, 2020 update. Eur Respir J 2021;57:2003300. DOI: https://doi.org/10.1183/13993003.03300-2020
- Oliveira O, Gaio R, Correia-Neves M, et al. Evaluation of drug-resistant tuberculosis treatment outcome in Portugal, 2000-2016. PLoS One 2021;16:e0250028. DOI: https://doi.org/10.1371/journal.pone.0250028
- Ahmad R, Sulaiman SAS, Muttalif AR, et al. Treatment outcomes of childhood TB patients in four TB High Burden states of Malaysia: results from a multicenter retrospective cohort study. Antibiotics 2022;11:1639. DOI: https://doi.org/10.3390/antibiotics11111639
- Molla Y, Jerene D, Jemal I, et al. The experience of scaling up a decentralized, ambulatory model of care for management of multidrug-resistant tuberculosis in two regions of Ethiopia. J Clin Tuberc Other Mycobact Dis 2017;7:28-33. DOI: https://doi.org/10.1016/j.jctube.2017.03.001
- Djochie RDA, Anto BP, Opare-Addo MNA, Boakye-Yiadom J, et al. Factors influencing treatment success in drug-susceptible tuberculosis patients in Ghana: a prospective cohort study. PLOS Global Public Health 2025;5:e0004146. DOI: https://doi.org/10.1371/journal.pgph.0004146
- Javaid A, Ullah I, Masud H, et al. Predictors of poor treatment outcomes in multidrug-resistant tuberculosis patients: a retrospective cohort study. Clin Microbiol Infect 2018;24:612-7. DOI: https://doi.org/10.1016/j.cmi.2017.09.012
- Zwama G, Diaconu K, Voce AS, et al. Health system influences on the implementation of tuberculosis infection prevention and control at health facilities in low-income and middle-income countries: a scoping review. BMJ Global Health 2021;6:e004735. DOI: https://doi.org/10.1136/bmjgh-2020-004735
- Teo AKJ, Singh SR, Prem K, et al. Duration and determinants of delayed tuberculosis diagnosis and treatment in high-burden countries: a mixed-methods systematic review and meta-analysis. Respir Res 2021;22:251. DOI: https://doi.org/10.1186/s12931-021-01841-6
- Isaakidis P, Paryani R, Kan S, et al. Poor outcomes in a cohort of HIV-infected adolescents undergoing treatment for multidrug-resistant tuberculosis in Mumbai, India. PLoS One 2013;8:e68869. DOI: https://doi.org/10.1371/journal.pone.0068869
- Brode SK, Varadi R, McNamee J, et al. Multidrug‐resistant tuberculosis: treatment and outcomes of 93 patients. Can Respir J 2015;22:97-102. DOI: https://doi.org/10.1155/2015/359301
- Walker TM, Choisy M, Dedicoat M, et al. Mycobacterium tuberculosis transmission in Birmingham, UK, 2009-19: an observational study. Lancet Reg Health Eur 2022;17:100361. DOI: https://doi.org/10.1016/j.lanepe.2022.100361
- Connolly C, Keil R, Ali SH. Extended urbanisation and the spatialities of infectious disease: Demographic change, infrastructure and governance. Urban Stud 2021;58:245-63. DOI: https://doi.org/10.1177/0042098020910873
- Song WM, Li YF, Liu YX, et al. Drug-resistant tuberculosis among children: a systematic review and meta-analysis. Front Public Health 2021;9:721817. DOI: https://doi.org/10.3389/fpubh.2021.721817
- Peyrin-Biroulet L. Advances in inflammatory bowel diseases annual meeting abstracts, December 14-16, 2023, Orlando, Florida. 2023.
- Indriani L, Renitia GI, Setiani LA. Treatment duration and drug regimen correlation with side effects incidence in drug-resistant tuberculosis (DR-TB) patients at pulmonary hospital. JSFK 2023;10:320-6. DOI: https://doi.org/10.25077/jsfk.10.3.320-326.2023
- Tan MM, Jin X, Taylor C, et al. Long-term trajectories in weight and health outcomes following multidisciplinary publicly funded bariatric surgery in patients with clinically severe obesity (3 associated comorbidities): a nine-year prospective cohort study in Australia. J Clin Med 2022;11:4466. DOI: https://doi.org/10.3390/jcm11154466
- Edessa D, Adem F, Hagos B, Sisay M. Incidence and predictors of mortality among persons receiving second-line tuberculosis treatment in sub-Saharan Africa: a meta-analysis of 43 cohort studies. PLos One 2021;16:e0261149. DOI: https://doi.org/10.1371/journal.pone.0261149
- Prasad R, Singh A, Gupta N. Adverse drug reactions with first-line and second-line drugs in treatment of tuberculosis. Ann Natl Acad Med Sci 2021;57:15-35. DOI: https://doi.org/10.1055/s-0040-1722535
- Rivetti S, Romano A, Mastrangelo S, et al. Aminoglycosides-related ototoxicity: mechanisms, risk factors, and prevention in pediatric patients. Pharmaceuticals 2023;16:1353. DOI: https://doi.org/10.3390/ph16101353
- Howell P, Achar J, Huang GKL, et al. Treatment of rifampicin-resistant tuberculosis disease and infection in children: key updates, challenges and opportunities. Pathogens 2022;11:381. DOI: https://doi.org/10.3390/pathogens11040381
- Holtz TH, Sternberg M, Kammerer S, et al. Time to sputum culture conversion in multidrug-resistant tuberculosis: predictors and relationship to treatment outcome. Ann Int Med 2006;144: 650-9. DOI: https://doi.org/10.7326/0003-4819-144-9-200605020-00008
- Kurbatova E, Gammino VM, Bayona J, et al. Predictors of sputum culture conversion among patients treated for multidrug-resistant tuberculosis. Int J Tuberc Lung Dis 2012;16:1335-43. DOI: https://doi.org/10.5588/ijtld.11.0811
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