Patterns of First-Line Anti-Tuberculosis Drug Resistance and Multidrug-Resistant Tuberculosis and Their Association with Diabetes Co-Morbidity: A Cross-Sectional Study at the NTBLTC, Saye, Zaria, Northern Nigeria
Abstract:
Drug-resistant tuberculosis threatens global tuberculosis control, and diabetes mellitus is a plausible but incompletely characterised driver of both active and resistant disease in high-burden settings. This study characterised first-line anti-tuberculosis drug-resistance patterns, including multidrug-resistant tuberculosis, and examined their association with diabetes co-morbidity among presumptive tuberculosis patients at a national reference centre in northern Nigeria. A facility-based, descriptive cross-sectional study enrolled 200 consecutive presumptive-TB adults at the National Tuberculosis and Leprosy Training Centre, Saye, Zaria. Tuberculosis was diagnosed using Ziehl–Neelsen smear microscopy, the Xpert MTB/RIF assay, and Löwenstein–Jensen culture with first-line drug-susceptibility testing by the proportion method; a single fasting plasma glucose measurement classified diabetes status. Associations were assessed using chi-square or Fisher exact tests and logistic regression at a significance threshold of 0.05. Bacteriologically confirmed tuberculosis was identified in 26.0% of participants and diabetes in 17.0%. Among 48 culture-positive isolates with valid drug-susceptibility testing, isoniazid resistance was most frequent (22.9%), followed by rifampicin (16.7%), streptomycin (14.6%), and ethambutol (10.4%); across all 52 confirmed cases, rifampicin resistance was 17.3% (9/52) and multidrug-resistant tuberculosis 11.5% (6/52). Any first-line resistance and multidrug resistance were more than twice as frequent among the 13 tuberculosis patients with diabetes than among the 39 without (46.2% versus 20.5% and 23.1% versus 7.7%, respectively), although these differences did not reach statistical significance (Fisher exact p = 0.086 and p = 0.157). Diabetes independently predicted confirmed tuberculosis (adjusted odds ratio 2.34, 95% CI 1.08–5.05), alongside prior tuberculosis treatment and low body-mass index. Because diabetes was based on a single fasting plasma glucose measurement obtained during acute illness, stress hyperglycaemia cannot be excluded. These findings reveal a substantial resistance burden at referral level and a consistent but statistically unconfirmed resistance signal associated with diabetes. Routine drug-susceptibility testing and bidirectional tuberculosis–diabetes screening are warranted, and larger studies are needed to confirm the resistance association.References:
[1]. World Health Organization. Global tuberculosis report
2023. Geneva: World Health Organization; 2023. Available from: who.int.
[2]. World Health Organization. Global tuberculosis report
2022. Geneva: World Health Organization; 2022. Available from: who.int.
[3].
Jeon CY, Murray
MB. Diabetes mellitus increases the risk of active tuberculosis: a systematic
review of 13 observational studies. PLoS Med. 2008;5(7):e152. Available from: https://doi.org/10.1371/journal.pmed.0050152
[4].
Dooley KE,
Chaisson RE. Tuberculosis and diabetes mellitus: convergence of two epidemics.
Lancet Infect Dis. 2009;9(12):737–46. Available from: https://doi.org/10.1016/S1473-3099(09)70282-8
[5].
Baker MA, Harries
AD, Jeon CY, et al. The impact of diabetes on tuberculosis treatment outcomes:
a systematic review. BMC Med. 2011;9:81. Available from: https://doi.org/10.1186/1741-7015-9-81
[6].
Restrepo BI.
Diabetes and tuberculosis. Microbiol Spectr.
2016;4(6):10.1128/microbiolspec.TNMI7-0023-2016. Available from: https://doi.org/10.1128/microbiolspec.TNMI7-0023-2016
[7].
Tegegne BS, Mengesha MM, Teferra AA, et al. Association between diabetes mellitus and
multidrug-resistant tuberculosis: a systematic review and meta-analysis. Syst
Rev. 2018;7:161. Available from: https://doi.org/10.1186/s13643-018-0828-0
[8].
Liu Q, Li W, Xue M, et al. Diabetes mellitus and the risk of multidrug-resistant tuberculosis: a
meta-analysis. Sci Rep. 2017;7:1090. Available from: https://doi.org/10.1038/s41598-017-01213-5
[9].
Nijland HM, Ruslami R, Stalenhoef JE, et al. Exposure to rifampicin is strongly reduced in patients
with tuberculosis and type 2 diabetes. Clin Infect Dis. 2006;43(7):848–54.
Available from: https://doi.org/10.1086/507543
[10].
Ruslami R, Nijland HM, Adhiarta IGN, et al. Pharmacokinetics of antituberculosis drugs in patients
with tuberculosis and type 2 diabetes mellitus. Antimicrob Agents Chemother.
2010;54(3):1068–74. Available from: https://doi.org/10.1128/AAC.00447-09
[11]. World Health Organization. Collaborative framework for
care and control of tuberculosis and diabetes. Geneva: World Health
Organization; 2011.
[12].
Lönnroth K,
Roglic G, Harries AD. Improving tuberculosis prevention and care through
addressing the global diabetes epidemic: from evidence to policy and practice.
Lancet Diabetes Endocrinol. 2014;2(9):730–39. Available from: https://doi.org/10.1016/S2213-8587(14)70109-3
[13].
Workneh MH, Bjune GA, Yimer SA. Prevalence and associated factors of tuberculosis and
diabetes mellitus comorbidity: a systematic review. PLoS One.
2017;12(4):e0175925. Available from: https://doi.org/10.1371/journal.pone.0175925
[14].
Alebel A,
Wondemagegn AT, Tesema C, et al. Prevalence of diabetes mellitus among
tuberculosis patients in sub-Saharan Africa: a systematic review and
meta-analysis. BMC Infect Dis. 2019;19:254. Available from: https://doi.org/10.1186/s12879-019-3892-8
[15].
Noubiap JJ,
Nansseu JR, Nyaga UF, et al. Global prevalence of diabetes in active
tuberculosis: a systematic review and meta-analysis of data from 2.3 million
patients. Lancet Glob Health. 2019;7(4):e448–60. Available from: https://doi.org/10.1016/S2214-109X(18)30487-X
[16].
Lawson L, Muc M,
Oladimeji O, et al. Tuberculosis and diabetes in Nigerian patients with and
without HIV. Int J Infect Dis. 2017;61:121–25. Available from: https://doi.org/10.1016/j.ijid.2017.06.014
[17].
Ekeke N, Ukwaja
KN, Chukwu JN, et al. Screening for diabetes mellitus among tuberculosis
patients in southern Nigeria: a multi-centre implementation study. PLoS One.
2017;12(5):e0177907. Available from: https://doi.org/10.1371/journal.pone.0177907
[18].
Ogbera AO, Kapur
A, Odeyemi K, et al. Screening for diabetes mellitus and human immunodeficiency
virus infection in persons with tuberculosis. J Diabetes Metab Disord.
2015;14:45. Available from: https://doi.org/10.1186/s40200-015-0169-7
[19].
Uloko AE, Musa BM, Ramalan MA, et al. Prevalence and risk factors for diabetes mellitus in
Nigeria: a systematic review and meta-analysis. Diabetes Ther.
2018;9(3):1307–16. Available from: https://doi.org/10.1007/s13300-018-0441-1
[20]. World Health Organization. WHO consolidated guidelines
on tuberculosis: Module 3 – Diagnosis: rapid diagnostics for tuberculosis
detection. Geneva: World Health Organization; 2021. Available from: who.int.
[21].
Boehme CC, Nabeta P, Hillemann D, et al. Rapid molecular detection of tuberculosis and rifampin
resistance. N Engl J Med. 2010;363(11):1005–15. Available from: https://doi.org/10.1056/NEJMoa0907847
[22].
Steingart KR, Schiller I, Horne DJ, et al. Xpert MTB/RIF assay for pulmonary tuberculosis and
rifampicin resistance in adults. Cochrane Database Syst Rev. 2014;1:CD009593.
Available from: https://doi.org/10.1002/14651858.CD009593.pub3
[23].
Zignol M, Dean
AS, Alikhanova N, et al. Population-based resistance of Mycobacterium
tuberculosis isolates to pyrazinamide and fluoroquinolones: results from a
multicountry surveillance project. Lancet Infect Dis. 2016;16(10):1185–92.
Available from: https://doi.org/10.1016/S1473-3099(16)30190-6
[24]. World Health Organization. WHO consolidated guidelines
on tuberculosis: Module 4 – Treatment: drug-resistant tuberculosis treatment.
Geneva: World Health Organization; 2020. Available from: who.int.
[25].
Gautam S,
Shrestha N, Mahato S, et al. Diabetes among tuberculosis patients and its
impact on tuberculosis treatment in South Asia: a systematic review and
meta-analysis. Sci Rep. 2021;11:2113. Available from: https://doi.org/10.1038/s41598-021-81057-2
[26].
Faustini A, Hall
AJ, Perucci CA. Risk factors for multidrug-resistant tuberculosis in Europe: a
systematic review. Thorax. 2006;61(2):158–63. Available from: https://doi.org/10.1136/thx.2005.045963
[27].
Pradipta IS,
Forsman LD, Bruchfeld J, et al. Risk factors of multidrug-resistant
tuberculosis: a global systematic review and meta-analysis. J Infect.
2018;77(6):469–78. Available from: https://doi.org/10.1016/j.jinf.2018.10.004
[28].
Song WM, Li YF,
Liu YX, et al. Diabetes mellitus and unfavourable treatment outcomes among
tuberculosis patients: a meta-analysis. J Infect. 2019;79(6):493–02. Available
from: https://doi.org/10.1016/j.jinf.2019.09.014
[29]. United States Agency for International Development.
Global tuberculosis strategy 2023–2030. Washington (DC): USAID; 2023. Available
from: usaid.gov.
[30]. Al-Rifai RH, Pearson F, Critchley JA, Abu-Raddad LJ.
Association between diabetes mellitus and active tuberculosis: a systematic
review and meta-analysis. PLoS One. 2017;12(11):e0187967. Available from: https://doi.org/10.1371/journal.pone.0187967
