Childhood Tuberculosis Following Household Exposure: Risk Factors and Clinical Outcomes from a Retrospective Cohort

Abstract

Background: Tuberculosis (TB) remains a major cause of morbidity and mortality, with children primarily infected through close contact with adults. Data on household transmission in children in Türkiye are limited.

Objective: This study aimed to determine the prevalence of latent t.u.berculosis infection (LTBI) and active TB disease among pediatric household contacts of adults with pulmonary multidrug-resistant (MDR) or drug-susceptible (DS) TB and identify risk factors associated with TB infection.

Methods: This retrospective study included children (0–18 years) exposed to adult pulmonary TB at a tertiary center (2018–2024). Demographic, clinical, and diagnostic data were collected. Pediatric cases were classified as latent or active TB, and index case resistance as MDR or DS. The risk factors for active TB were evaluated.

Results: A total of 124 household contacts were evaluated. The median age of the contacts was 111 months (IQR 47-151), and 65 (52.4%) were female. Bacillus Calmette-Guérin (BCG) coverage was 92.7%. LTBI was detected in 7 (5.6%) and active TB in 11 (8.8%) children. The absence of BCG vaccination (p = 0.027) and longer time to presentation (p = 0.002) were significantly associated with TB. Exposure to an MDR-TB index case significantly increased TB risk (42.9% vs 6.9%, p = 0.016). On multivariate analysis, MDR-TB contact (OR: 8.5; 95% CI: 1.39–52.4) and lack of BCG vaccination (OR: 6.3; 95% CI: 1.09–36.2) were independent predictors of disease.

Conclusion: A substantial proportion of pediatric household contacts of TB patients developed infection or disease, with delayed evaluation, MDR-TB exposure, and absence of BCG vaccination significantly increasing the risk of progression.

Keywords

• Pediatric tuberculosis
• Household contact
• Multidrug-resistant tuberculosis
• Tuberculosis risk factors

References

1. Goletti D, Meintjes G, Andrade BB, Zumla A, Shan Lee S. Insights from the 2024 WHO Global Tuberculosis Report - More Comprehensive Action, Innovation, and Investments required for achieving WHO End TB goals. Int J Infect Dis. 2025;150:107325. doi:10.1016/ j.ijid.2024.107325 google scholar
2. WHO. WHO consolidated guidelines on tuberculosis: Module 5: Management of tuberculosis in children and adolescentss. Geneva: World Health Organization; 2022. (Cited 2025 May 13) . Available from https://www.who.int/publications/i/item/ 9789240053072 google scholar
3. Republic of Türkiye, Ministry of Health Tuberculosis Control in Türkiye 2021 Report [Internet]. Ankara: Ministry of Health of Türkiye; 2022 [cited 2025 Aug 5]. Available from: https://hsgm.saglik.gov.tr/depo/birimler/tuberkuloz-db/Dokumanlar/Raporlar/ Turkiyede_Verem_Savasi_2021_Raporu.pdf google scholar
4. Schaaf HS, Michaelis IA, Richardson M, Booysen CN, Gie RP, Warren R et al. Adult-to-child transmission of tuberculosis: household or community contact? Int J Tuberc Lung Dis. 2003;7(5):426-31. PMID: 12757042. google scholar
5. Uplekar M, Weil D, Lonnroth K, Jaramillo E, Lienhardt C, Dias HM, et al. for WHO's Global TB Program. WHO's new end TB strategy. Lancet. 2015;385(9979):1799-1801. doi: 10.1016/ S0140-6736(15)60570-0. Epub 2015 Mar 24. PMID: 25814376. google scholar
6. WHO. WHO consolidated guidelines on tuberculosis: Module 4: treatment–Tuberculosis care and support. Geneva: World Health Organization; 2022. (cited 2025 April 12). Available from https://iris.who.int/bitstream/handle/10665/353399/9789240047716-eng.pdf?sequence=1) google scholar
7. Triasih R, Rutherford M, Lestari T, Utarini A, Robertson CF, Graham SM. Contact investigation of children exposed to tuberculosis in South East Asia: a systematic review. J Trop Med. 2012;2012:301808. doi:10.1155/2012/301808) google scholar
8. Yaşar Durmuş S, Tanır G, Aydın Teke T, Kaman A, Yalçınkaya R, Üner Ç et al. Tuberculosis contact-tracing results in childhood: a retrospective study in a tertiary-care children’s hospital in Turkey Paediatr Int Child Health. 2023 Feb-May;43(1-3):5-12. doi: 10.1080/20469047.2023.2252167. Epub 2023 Sep 6. PMID: 37671805. google scholar

9. Eriksen J, Chow JY, Mellis V, Whipp B, Walters S, Abrahamson E et al. Protective effect of BCG vaccination in a nursery outbreak in 2009: time to reconsider the vaccination threshold? Thorax. 2010 Dec;65(12):1067-71. doi: 10.1136/thx.2010.140186. Epub 2010 Oct 28. PMID: 21030395. google scholar
10. Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV et al. Efficacy of the BCG vaccine in the prevention of tuberculosis Meta-analysis of the published literature. JAMA. 1994;271(9):698-702. PMID: 8309034. google scholar
11. Trunz BB, Fine PEM, Dye C. Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of costeffectiveness. Lancet. 2006;367(9517):1173–1180. google scholar
12. World Health Organization. BCG vaccine: WHO position paper, February 2018-Recommendations. Vaccine. 2018 Jun 7;36(24):3408-3410. doi: 10.1016/ j.vaccine.2018.03.009. Epub 2018 Mar 30. PMID: 29609965. google scholar
13. Martinez L, Cords O, Horsburgh CR, Andrews JR; Pediatric TB Contact Studies Consortium. The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis. Lancet. 2020;395(10228):973-984. doi:10.1016/ S0140-6736(20)30166-5 google scholar
14. Seddon JA, Shingadia D. Epidemiology and disease burden of tuberculosis in children: a global perspective. Infect Drug Resist. 2014;7:153-165. Published 2014 Jun 18. doi:10.2147/ IDR.S45090 google scholar
15. Perez-Velez CM, Marais BJ. Tuberculosis in children. N Engl J Med. 2012;367(4):348-361. doi:10.1056/NEJMra1008049 google scholar
16. Marais, BJ, Gie RP, Schaaf HS., Hesseling, AC, Enarson, DA, Beyers N (2004). The natural history of childhood intrathoracic tuberculosis: A critical review of the literature from the prechemotherapy era Int J of Tuberc Lung Dis, 8(4), 392-402. google scholar
17. Marais, BJ, Gie RP, Hesseling AC, Schaaf HS, Lombard C, Enarson DA. (2006). A refined symptom-based approach to diagnose pulmonary tuberculosis in children Pediatrics, 118(5), e1350-e1359. google scholar
18. Becerra MC, Huang CC, Lecca L, Bayona J, Contreras C, Calderon R et al. Transmissibility and potential for disease progression of drug resistant Mycobacterium tuberculosis: prospective cohort study. BMJ. 2019 Oct 24;367:l5894. doi: 10.1136/bmj.l5894. PMID: 31649017; PMCID: PMC6812583. google scholar
19. Teixeira L, Perkins MD, Johnson JL, Keller R, Palaci M, do Valle Dettoni V et al. Infection and disease among household contacts of patients with multidrug-resistant tuberculosis Int J Tuberc Lung Dis. 2001;5(4):321-8. PMID: 11334250. google scholar
20. Javaid A, Khan MA, Khan MA, Mehreen S, Basit A, Khan RA et al. Screening outcomes of household contacts of multidrug-resistant tuberculosis patients in Peshawar, Pakistan Asian Pac J Trop Med. 2016 Sep;9(9):909-912. doi: 10.1016/j.apjtm.2016.07.017. Epub 2016 Jul 26. PMID: 27633308. google scholar
21. Dayal R, Agarwal D, Bhatia R, Bipin C, Yadav NK, Kumar S et al. Tuberculosis burden among household pediatric contacts of adult tuberculosis patients Indian J Pediatr. 2018 Oct;85(10):867-871. doi: 10.1007/s12098-018-2661-9. Epub 2018 Mar 20. PMID: 29557089. google scholar
22. Seddon JA, Hesseling AC, Godfrey-Faussett P, Fielding K, Schaaf HS. Risk factors for infection and disease in child contacts of multidrug-resistant tuberculosis: a crosssectional study. BMC Infect Dis. 2013 Aug 26;13:392. doi: 10.1186/1471-2334-13-392. PMID: 23977834; PMCID: PMC3765928. google scholar
23. Schaaf HS, Marais BJ. Management of multidrug-resistant tuberculosis in children: a survival guide for pediatricians. Paediatr Respir Rev. 2011;12(1):31-38. doi:10.1016/ j.prrv.2010.09.010, google scholar