Diabetes Mellitus, Smoking Status, and Rate of Sputum Culture Conversion in Patients with Multidrug-Resistant Tuberculosis: A Cohort Study from the Country of Georgia
Introduction Diabetes mellitus (DM) is a risk factor for active tuberculosis (TB) but little is known about the effect of DM on culture conversion among patients with multidrug-resistant (MDR)-TB. The primary aim was to estimate the association between DM and rate of TB sputum culture conversion. A secondary objective was to estimate the association between DM and the risk of poor treatment outcomes among patients with MDR-TB. Materials and Methods A cohort of all adult patients starting MDR-TB treatment in the country of Georgia between 2009–2011 was followed during second-line TB therapy. Cox proportional models were used to estimate the adjusted hazard rate of sputum culture conversion. Log-binomial regression models were used to estimate the cumulative risk of poor TB treatment outcome. Results Among 1,366 patients with sputum culture conversion information, 966 (70.7%) had culture conversion and the median time to conversion was 68 days (interquartile range 50–120). The rate of conversion was similar among patients with MDR-TB and DM (adjusted hazard ratio [aHR] 0.95, 95%CI 0.71–1.28) compared to patients with MDR-TB only. The rate of culture conversion was significantly less in patients that currently smoked (aHR 0.82, 95%CI 0.71–0.95), had low body mass index (aHR 0.71, 95%CI 0.59–0.84), second-line resistance (aHR 0.56, 95%CI 0.43–0.73), lung cavities (aHR 0.70, 95%CI 0.59–0.83) and with disseminated TB (aHR 0.75, 95%CI 0.62–0.90). The cumulative risk of poor treatment outcome was also similar among TB patients with and without DM (adjusted risk ratio [aRR] 1.03, 95%CI 0.93–1.14). Conclusions In adjusted analyses, DM did not impact culture conversion rates in a clinically meaningful way but smoking did.
References
[1]
Harries AD, Lin Y, Satyanarayana S, Lonnroth K, Li L, et al.. (2011) The looming epidemic of diabetes-associated tuberculosis: learning lessons from HIV-associated tuberculosis. Int J Tuberc Lung Dis 15: 1436–1444, i.
[2]
IDF (2013) Diabetes Atlas, 6th Edition. Brussels: International Diabetes Federation.
[3]
Magee MJ, Blumberg HM, Narayan KM (2011) Commentary: Co-occurrence of tuberculosis and diabetes: new paradigm of epidemiological transition. Int J Epidemiol 40: 428–431. doi: 10.1093/ije/dyq268
[4]
WHO (2012) Global tuberculosis report 2012. Geneva: World Health Organization.
[5]
Stevenson CR, Critchley JA, Forouhi NG, Roglic G, Williams BG, et al. (2007) Diabetes and the risk of tuberculosis: a neglected threat to public health? Chronic Illn 3: 228–245. doi: 10.1177/1742395307081502
[6]
Kapur A, Harries AD (2013) The double burden of diabetes and tuberculosis - Public health implications. Diabetes Res Clin Pract.
[7]
Dooley KE, Chaisson RE (2009) Tuberculosis and diabetes mellitus: convergence of two epidemics. Lancet Infect Dis 9: 737–746. doi: 10.1016/s1473-3099(09)70282-8
[8]
Baker MA, Harries AD, Jeon CY, Hart JE, Kapur A, et al. (2011) The impact of diabetes on tuberculosis treatment outcomes: A systematic review. BMC Med 9: 81. doi: 10.1186/1741-7015-9-81
[9]
Jeon CY, Murray MB (2008) Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies. PLoS Med 5: e152. doi: 10.1371/journal.pmed.0050152
[10]
WHO (2013) Global tuberculosis report 2013. Geneva: World Health Organization.
[11]
Fitzpatrick C, Floyd K (2012) A systematic review of the cost and cost effectiveness of treatment for multidrug-resistant tuberculosis. Pharmacoeconomics 30: 63–80. doi: 10.2165/11595340-000000000-00000
[12]
Chiang CY, Van Weezenbeek C, Mori T, Enarson DA (2013) Challenges to the global control of tuberculosis. Respirology.
[13]
Gandhi NR, Nunn P, Dheda K, Schaaf HS, Zignol M, et al. (2010) Multidrug-resistant and extensively drug-resistant tuberculosis: a threat to global control of tuberculosis. Lancet 375: 1830–1843. doi: 10.1016/s0140-6736(10)60410-2
[14]
Singh R, Gothi D, Joshi J (2007) Multidrug resistant tuberculosis: Role of previous treatment with second line therapy on treatment outcome. Lung India 24: 54–57. doi: 10.4103/0970-2113.44211
[15]
Aragon J, Litonjua A, Tupasi T, Quelapio I (2003) Prevalence of type 2 diabetes among multi-drug resistant tuberculosis (MDR-TB) patients seen in Makati Medical Center under the directly observed therapy plus (DOTS PLUS) program. Phil J Internal Medicine 41: 7–10.
[16]
Tanrikulu AC, Hosoglu S, Ozekinci T, Abakay A, Gurkan F (2008) Risk factors for drug resistant tuberculosis in southeast Turkey. Trop Doct 38: 91–93. doi: 10.1258/td.2007.070131
[17]
Garcia F, Solis J, Calderon J, Luque E, Zacarias E (2007) Prevalence of diabetes mellitus and related risk factors in an urban population. Rev Soc Peru Med Interna 20: 90–94.
[18]
Fisher-Hoch SP, Whitney E, McCormick JB, Crespo G, Smith B, et al. (2008) Type 2 diabetes and multidrug-resistant tuberculosis. Scand J Infect Dis 40: 888–893. doi: 10.1080/00365540802342372
[19]
Harries AD, Murray MB, Jeon CY, Ottmani SE, Lonnroth K, et al. (2010) Defining the research agenda to reduce the joint burden of disease from diabetes mellitus and tuberculosis. Trop Med Int Health 15: 659–663. doi: 10.1111/j.1365-3156.2010.02523.x
[20]
Richards DC, Mikiashvili T, Parris JJ, Kourbatova EV, Wilson JC, et al. (2006) High prevalence of hepatitis C virus but not HIV co-infection among patients with tuberculosis in Georgia. Int J Tuberc Lung Dis 10: 396–401.
[21]
Tukvadze N, Kempker RR, Kalandadze I, Kurbatova E, Leonard MK, et al. (2012) Use of a molecular diagnostic test in AFB smear positive tuberculosis suspects greatly reduces time to detection of multidrug resistant tuberculosis. PLoS One 7: e31563. doi: 10.1371/journal.pone.0031563
[22]
IUATBLD (2000) Technical Guide: Sputum examination for tuberculosis by direct microscopy in low income countries. Paris: International Union Against Tuberculosis and Lung Disease.
[23]
Kleinbaum D, Klein M (2012) Survival Analysis: A Self-Learning Text. New York: Springer.
[24]
Greenland S, Pearl J, Robins JM (1999) Causal diagrams for epidemiologic research. Epidemiology 10: 37–48. doi: 10.1097/00001648-199901000-00008
[25]
Kurbatova EV, Gammino VM, Bayona J, Becerra MC, Danilovitz M, et al. (2012) Predictors of sputum culture conversion among patients treated for multidrug-resistant tuberculosis. Int J Tuberc Lung Dis 16: 1335–1343. doi: 10.5588/ijtld.11.0811
[26]
Restrepo BI, Fisher-Hoch SP, Smith B, Jeon S, Rahbar MH, et al. (2008) Mycobacterial clearance from sputum is delayed during the first phase of treatment in patients with diabetes. Am J Trop Med Hyg 79: 541–544.
[27]
Jimenez-Corona ME, Cruz-Hervert LP, Garcia-Garcia L, Ferreyra-Reyes L, Delgado-Sanchez G, et al. (2013) Association of diabetes and tuberculosis: impact on treatment and post-treatment outcomes. Thorax 68: 214–220. doi: 10.1136/thoraxjnl-2012-201756
[28]
Holtz TH, Sternberg M, Kammerer S, Laserson KF, Riekstina V, et al. (2006) Time to sputum culture conversion in multidrug-resistant tuberculosis: predictors and relationship to treatment outcome. Ann Intern Med 144: 650–659. doi: 10.7326/0003-4819-144-9-200605020-00008
[29]
Qazi F, Khan U, Khowaja S, Javaid M, Ahmed A, et al.. (2011) Predictors of delayed culture conversion in patients treated for multidrug-resistant tuberculosis in Pakistan. Int J Tuberc Lung Dis 15: 1556–1559, i.
[30]
Johnston JC, Shahidi NC, Sadatsafavi M, Fitzgerald JM (2009) Treatment outcomes of multidrug-resistant tuberculosis: a systematic review and meta-analysis. PLoS One 4: e6914. doi: 10.1371/journal.pone.0006914
[31]
Kurbatova EV, Taylor A, Gammino VM, Bayona J, Becerra M, et al. (2012) Predictors of poor outcomes among patients treated for multidrug-resistant tuberculosis at DOTS-plus projects. Tuberculosis (Edinb) 92: 397–403. doi: 10.1016/j.tube.2012.06.003
[32]
Shang S, Ordway D, Henao-Tamayo M, Bai X, Oberley-Deegan R, et al. (2011) Cigarette smoke increases susceptibility to tuberculosis–evidence from in vivo and in vitro models. J Infect Dis 203: 1240–1248. doi: 10.1093/infdis/jir009
[33]
Tachfouti N, Nejjari C, Benjelloun MC, Berraho M, Elfakir S, et al. (2011) Association between smoking status, other factors and tuberculosis treatment failure in Morocco. Int J Tuberc Lung Dis 15: 838–843. doi: 10.5588/ijtld.10.0437
[34]
Maciel EL, Brioschi AP, Peres RL, Guidoni LM, Ribeiro FK, et al. (2013) Smoking and 2-month culture conversion during anti-tuberculosis treatment. Int J Tuberc Lung Dis 17: 225–228. doi: 10.5588/ijtld.12.0426
[35]
Rothman K, Greenland S, Lash T (2008) Modern Epidemiology. Philadelphia: Lippincott Williams & Wilkins.
