High Incidence of Multidrug-resistant Tuberculosis in Bhutan: A Cohort Study Based on National TB Surveillance Data

Overview

Journal IJID Reg

Specialty Infectious Diseases

Date 2024 Nov 8

PMID 39512908

Authors

Thinley Dorji

Karchung Tshering

Lila Adhikari

Thinley Jamtsho

Pavitra Bhujel

Pema Lhaden

Norelle L Sherry

Chantel Lin

Kristy Horan

Sonam Wangchuk

Patiyan Andersson

Benjamin P Howden

Affiliations

Soon will be listed here.

Abstract

Objectives: The emergence of multidrug-resistant tuberculosis (MDR-TB) has made the elimination of TB difficult. Currently, there are limited data on MDR-TB and other drug-resistant TB in Bhutan. We aimed to estimate the incidence and explore the potential risk factors associated with MDR/pre-extensively drug-resistant (pre-XDR)-TB using comprehensive national TB data.

Methods: We used the data from the Tuberculosis Information Surveillance System of the National Tuberculosis Reference Laboratory to analyze the resistance pattern and epidemiologic data for all TB cases tested for resistance for the year 2018-2021. Multiple logistic regression was performed to identify risk factors associated with MDR/pre-XDR-TB.

Results: Of the 2,290 samples tested for drug resistance, 10.6% (n = 243) was MDR-TB, 3.5% (n = 81) was isoniazid-resistant TB, and 0.61% (n = 14) was pre-XDR-TB. A high incidence of MDR/RR-TB/pre-XDR-TB was documented among patients in Thimphu, Samtse, and Sarpang districts. MDR/pre-XDR-TB was more likely documented among patients aged 18-39 years (adjusted odds ratio [aOR] 2.79; 95% confidence interval [CI] 1.46-6.07), female sex (aOR 1.37; 95% CI 1.01-1.86), and patients previously treated for TB (aOR 2.98; 95% CI 1.99-4.42).

Conclusions: Given the high burden of MDR-TB in some districts, decentralization of diagnostic facilities for more rapid characterization could improve early recognition of drug-resistant cases and assist in management. Comprehensive follow-up and monitoring of high-risk groups should be performed.

References

Shivekar S, Kaliaperumal V, Brammacharry U, Sakkaravarthy A, Vidya Raj C, Alagappan C . Prevalence and factors associated with multidrug-resistant tuberculosis in South India. Sci Rep. 2020; 10(1):17552. PMC: 7567814. DOI: 10.1038/s41598-020-74432-y. View

Siu G, Zhang Y, Lau T, Lau R, Ho P, Yew W . Mutations outside the rifampicin resistance-determining region associated with rifampicin resistance in Mycobacterium tuberculosis. J Antimicrob Chemother. 2011; 66(4):730-3. DOI: 10.1093/jac/dkq519. View

Lomtadze N, Aspindzelashvili R, Janjgava M, Mirtskhulava V, Wright A, Blumberg H . Prevalence and risk factors for multidrug-resistant tuberculosis in the Republic of Georgia: a population-based study. Int J Tuberc Lung Dis. 2008; 13(1):68-73. PMC: 2645031. View

Adhikari L, Wangchuk S, Bhujel P, Zangmo S, Lhaden P, Dorji U . Epidemiological and laboratory characteristics of multidrug-resistant tuberculosis patients in Bhutan, 2015-2019. IJID Reg. 2022; 3:228-233. PMC: 9216444. DOI: 10.1016/j.ijregi.2022.04.012. View

Tomasicchio M, Theron G, Pietersen E, Streicher E, Stanley-Josephs D, van Helden P . The diagnostic accuracy of the MTBDRplus and MTBDRsl assays for drug-resistant TB detection when performed on sputum and culture isolates. Sci Rep. 2016; 6:17850. PMC: 4748215. DOI: 10.1038/srep17850. View

Rifat M, Milton A, Hall J, Oldmeadow C, Islam M, Husain A . Development of multidrug resistant tuberculosis in Bangladesh: a case-control study on risk factors. PLoS One. 2014; 9(8):e105214. PMC: 4138182. DOI: 10.1371/journal.pone.0105214. View

Makhado N, Matabane E, Faccin M, Pincon C, Jouet A, Boutachkourt F . Outbreak of multidrug-resistant tuberculosis in South Africa undetected by WHO-endorsed commercial tests: an observational study. Lancet Infect Dis. 2018; 18(12):1350-1359. DOI: 10.1016/S1473-3099(18)30496-1. View

Song W, Li S, Liu J, Fu Q, Xu T, Tao N . Impact of alcohol drinking and tobacco smoking on the drug-resistance of newly diagnosed tuberculosis: a retrospective cohort study in Shandong, China, during 2004-2020. BMJ Open. 2022; 12(7):e059149. PMC: 9341182. DOI: 10.1136/bmjopen-2021-059149. View

Lohiya A, Suliankatchi Abdulkader R, Rath R, Jacob O, Chinnakali P, Goel A . Prevalence and patterns of drug resistant pulmonary tuberculosis in India-A systematic review and meta-analysis. J Glob Antimicrob Resist. 2020; 22:308-316. DOI: 10.1016/j.jgar.2020.03.008. View

10.

Chung-Delgado K, Guillen-Bravo S, Revilla-Montag A, Bernabe-Ortiz A . Mortality among MDR-TB cases: comparison with drug-susceptible tuberculosis and associated factors. PLoS One. 2015; 10(3):e0119332. PMC: 4366185. DOI: 10.1371/journal.pone.0119332. View

11.

Alao M, Ibrahim O, Akinboro A, Oladipo T, Chan Y, Ogunbosi B . Trends in rifampicin resistance among patients with presumptive TB in the pre-COVID and COVID-era. J Clin Tuberc Other Mycobact Dis. 2022; 29:100335. PMC: 9617635. DOI: 10.1016/j.jctube.2022.100335. View

12.

Tembo B, Malangu N . Prevalence and factors associated with multidrug/rifampicin resistant tuberculosis among suspected drug resistant tuberculosis patients in Botswana. BMC Infect Dis. 2019; 19(1):779. PMC: 6728949. DOI: 10.1186/s12879-019-4375-7. View

13.

Hazra D, Chawla K, Shenoy V, Pandey A, S N . The aftermath of COVID-19 pandemic on the diagnosis of TB at a tertiary care hospital in India. J Infect Public Health. 2021; 14(8):1095-1098. DOI: 10.1016/j.jiph.2021.07.001. View

14.

Sharma S, Kohli M, Yadav R, Chaubey J, Bhasin D, Sreenivas V . Evaluating the Diagnostic Accuracy of Xpert MTB/RIF Assay in Pulmonary Tuberculosis. PLoS One. 2015; 10(10):e0141011. PMC: 4619889. DOI: 10.1371/journal.pone.0141011. View

15.

Gurung M, Pelzom D, Dorji T, Drukpa W, Wangdi C, Chinnakali P . Current tobacco use and its associated factors among adults in a country with comprehensive ban on tobacco: findings from the nationally representative STEPS survey, Bhutan, 2014. Popul Health Metr. 2016; 14:28. PMC: 4977656. DOI: 10.1186/s12963-016-0098-9. View

16.

Dorji T, Wangdi K . Treatment outcome of tuberculosis patient of Samtse General Hospital, Bhutan. Nepal J Epidemiol. 2020; 10(3):888-896. PMC: 7538015. DOI: 10.3126/nje.v10i3.28397. View

17.

Orvankundil S, Jose B, Yacoob F, Sreenivasan S . Culture positivity of smear negative pulmonary and extrapulmonary tuberculosis- A study from North Kerala, India. J Family Med Prim Care. 2019; 8(9):2903-2907. PMC: 6820437. DOI: 10.4103/jfmpc.jfmpc_424_19. View

18.

Gygli S, Borrell S, Trauner A, Gagneux S . Antimicrobial resistance in Mycobacterium tuberculosis: mechanistic and evolutionary perspectives. FEMS Microbiol Rev. 2017; 41(3):354-373. DOI: 10.1093/femsre/fux011. View

19.

Kamolwat P, Nateniyom S, Chaiprasert A, Disratthakit A, Mahasirimongkol S, Yamada N . Prevalence and associated risk factors of drug-resistant tuberculosis in Thailand: results from the fifth national anti-tuberculosis drug resistance survey. Trop Med Int Health. 2020; 26(1):45-53. DOI: 10.1111/tmi.13502. View

20.

Kendall E, Fofana M, Dowdy D . Burden of transmitted multidrug resistance in epidemics of tuberculosis: a transmission modelling analysis. Lancet Respir Med. 2015; 3(12):963-72. PMC: 4684734. DOI: 10.1016/S2213-2600(15)00458-0. View