For training purpose only, please do not quote. Mahato RK, Laohasiriwong W, Koju R. The role of Diabetes mellitus comorbidity on Tuberculosis treatment outcomes in Nepal: A prospective cohort study. (Original research). SEEJPH 2022, posted: 20 March 2022. DOI: 10.11576/seejph-5329 P a g e 1 | 13 ORIGINAL RESEARCH The role of Diabetes mellitus comorbidity on Tuberculosis treatment outcomes in Nepal: A prospective cohort study Roshan Kumar Mahato1, Wongsa Laohasiriwong1, Rajendra Koju2 1 Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand; 2 Kathmandu University School of Medical Sciences, Department of Internal Medicine, Dhulikhel Hospital, Kathmandu University Hospital, Nepal. Corresponding author: Assist Prof. Dr. Roshan Kumar Mahato; Address: Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand; E-mail: mahatoroshank@kusms.edu.np Mahato RK, Laohasiriwong W, Koju R. The role of Diabetes mellitus comorbidity on Tuberculosis treatment outcomes in Nepal: A prospective cohort study. (Original research). SEEJPH 2022, posted: 20 March 2022. DOI: 10.11576/seejph-5329 P a g e 2 | 13 Abstract Aim: The Objective of this study was to assess the effect of Diabetes Mellitus (DM) on treatment outcomes of tuberculosis (TB) patients in the Central Development Region of Nepal. Methods: A prospective cohort study was conducted in central Nepal. The study population of n=408 was consecutively recruited from treatment centers of all 19 districts of central Nepal. The TB cases (n=306) and TB with DM (n=102) cases were followed up for the estimation of blood glucose level, HbA1c level, and sputum examination on 2, 5, and 6 months after TB treatment started. The Generalized Estimating Equation (GEE) was performed to identify the risk ratio among TB and TB with DM cases on treatment outcome. Results: Our study identified that the magnitude of treatment failure among the tuberculosis cases was 19.7% (95% CI: 17.44-21.95). The GEE analysis observed that factors associated with the treatment failure had uncontrolled DM (HbA1C ≥7 %) (adj.RR=5.24, 95% CI: 2.58-10.62, P value <0.001), aged ≥ 45 (adj.RR= 6.13, 95% CI: 2.55-14.76, P value <0.001), had inadequate financial status (adj.RR= 2.33, 95% CI: 1.07-5.06, P value 0.033) and had prior TB (adj.RR=2.33, 95% CI: 1.09-4.97, P value 0.028) respectively. Conclusion: The prevalence of worsening TB treatment among patients with TB and DM was significantly higher than those who had TB only. Poor glycaemic control, increasing age, inadequate financial status, and previous history of tuberculosis were strong predictors of worsening tuberculosis treatment outcomes. Keywords: Central Nepal, Generalized Estimating Equation, Glycaemic control, Tuberculosis with Diabetes mellitus. Conflict of interest: None declared. Ethical approval: The Ethics Committee in Human Research of Khon Kaen University, Khon Kaen, Thailand (HE612209), the Nepal Health Research Council (2640) and Institutional Review Committee (Protocol approved number 01/18), Kathmandu University School of Medical Sciences, Dhulikhel, Nepal had approved to conduct this study. Acknowledgment: The author wishes to thank the National Tuberculosis Centre, Nepal, for providing the approval to conduct this study. We would like to express our sincere gratitude to the Faculty of Public Health, Khon Kaen University, for their sincere guidance and support during the study period. Mahato RK, Laohasiriwong W, Koju R. The role of Diabetes mellitus comorbidity on Tuberculosis treatment outcomes in Nepal: A prospective cohort study. (Original research). SEEJPH 2022, posted: 20 March 2022. DOI: 10.11576/seejph-5329 P a g e 3 | 13 Introduction Nepal is passing through a phase of epidemiological transition from a higher prevalence of communicable diseases to non- communicable diseases (NCDs). It is currently suffering from a double burden of diseases. Various small studies from different parts of the country on diverse populations have shown varying prevalence rates of type 2 diabetes mellitus ranging from 6.3 to 8.5%. However, a systematic review and meta- analysis from 2000 to 2014 illustrate that the prevalence of type 2 diabetes reached a minimum of 1.4% to a maximum of 19.0%. The pooled prevalence of type 2 diabetes was 8.4% (95% CI: 6.2-10.5%). In addition, prevalence of type 2 diabetes in urban and rural populations was 8.1% (95% CI: 7.3- 8.9%) and 1.0% (95% CI: 0.7-1.3%), respectively (1). TB patients beginning TB treatment with Diabetes comorbidity experience tardy regain of body mass and haemoglobin (2,3), which are essential for the profound recovery from both diseases (4). In addition, previous studies have revealed that Diabetes may weaken sputum conversion (2,5-7), cure and increase the risk of relapse (4,8,9), and raise the risk of anti-TB drug resistance as well (10,11). Furthermore, a recent study observed that TB with DM was associated with some critical socio- demographic factors, including age, unemployment, literacy, and polluted environment (12). A study from Nepal has also illustrated the prevalence of Diabetes among Tuberculosis patients, which was 9.1% among older age TB patients, tobacco users, people with high-income status, and a history of high blood pressure (8,13). Therefore, this present study aimed to identify the role of DM on the treatment response among TB patients in the Central Development Region of Nepal. Methods A prospective cohort study was conducted by administrating a structured questionnaire among the TB and TB with DM cases. In addition, we examined their blood glucose level, HbA1c level, and sputum grade 2, 5, and 6 months after starting treatment of TB to identify the treatment outcome of TB. Study population A total sample of 408 patients was estimated to be required by taking reference of risk ratio 2.93 of non-cure rate (28.65%) among the TB DM cases from a previous study (5). 408 TB cases were collected from the National Tuberculosis Centre and treatment centers of all 19 districts of the (Central Development Region) CDR, Nepal, and were examined for a blood glucose level. After that, 102 TB patients with Diabetes were considered cases, and 306 non-diabetes Tuberculosis patients were considered controls. Since six patients died and one got severe cancer during the study period, finally, 401 TB cases were followed up to identify treatment outcomes. Simultaneously, Body Mass Index (BMI) and blood glucose level were measured, and the sputum status was checked to determine treatment outcomes in two, five, and six months after starting treatment. The respondents who met the essential requirement for their family within the year of treatment were considered to have a good financial status. Data Collection The data was collected by using a structured questionnaire (Annex I). In addition, signs and symptoms of the tuberculosis cases were documented before the beginning of TB treatment, and additional history was obtained for the presence of DM or DM treatment, previous TB treatment, TB contacts, other comorbidities, and medication used. Similarly, the patients were followed monthly during the intensive phase and bi-monthly after that. History, physical examination, blood testing, and microscopic examination were repeated after the intensive phase (at two months), five months, and at the end of treatment (at six months). TB program- specific definitions were used to classify Mahato RK, Laohasiriwong W, Koju R. The role of Diabetes mellitus comorbidity on Tuberculosis treatment outcomes in Nepal: A prospective cohort study. (Original research). SEEJPH 2022, posted: 20 March 2022. DOI: 10.11576/seejph-5329 P a g e 4 | 13 treatment response and outcome. TB registerswere cross-checked to ensure the quality of collected data. Statistical analysis All collected data were entered in Epi-Data (Version 3.1) and transferred to STATA (Version 13, Stata Corporation, College Station, TX USA) for analysis. The data collected after the respondents' follow-up in 2, 5, and 6 months were analysed using GEE to identify the risk ratio amongst the TB and TB with DM cases on treatment outcomes. Results Table 1 illustrates the characteristics of TB and TB with DM patients at 2, 5, and 6 months of the treatment period. The respondents (TB and TB with DM) aged ≥ 45 years old seemed to raise the non-curing rate from 43.30% at two months, 45.88% at five months, and 51.90% at six months of treatment. In addition, the tuberculosis patients living in rural areas were observed to fail sputum conversion at six months of treatment compared with two months of treatment, i.e., 12.50% to 11.49%, respectively. Table 1. Characteristics of TB patients at 2, 5 and 6 months of treatment (n=401) Characteristics 2 Months 5 months 6 months Cured Not cured Cured Not cured Cured Not cured Gender Male 185 (60.86) 64 (65.98) 192 (60.76) 57 (67.06) 192 (59.63) 57 (72.15) Female 119 (39.14) 33 (34.02) 124 (39.24) 28 (32.94) 130 (40.37) 22 (27.85) Age (years) <45 204 (67.11) 55 (56.70) 213 (67.41) 46 (54.12) 221 (68.63) 38 (48.10) ≥ 45 100 (32.89) 42 (43.30) 103 (32.59) 39 (45.88) 101 (31.37) 41 (51.90) Marital status Single 106 (34.87) 26 (26.80) 109 (34.49) 23 (27.06) 114 (35.40) 18 (22.78) Married 198 (65.13) 71 (73.20) 207 (65.51) 62 (72.94) 208 (64.60) 61 (77.22) Place of residence Urban 266 (87.50) 81 (83.51) 278 (87.97) 69 (81.18) 285 (88.51) 62 (78.48) Rural 38 (12.50) 16 (16.49) 38 (12.03) 16 (18.82) 37 (11.49) 17 (21.52) Employment Unemployed 69 (22.70) 27 (27.84) 71 (22.47) 25 (29.41) 70 (21.74) 26 (32.91) Employed 235 (77.30) 70 (72.16) 245 (77.53) 60 (70.59) 252 (78.26) 53 (67.09) Financial Status Adequate 216 (71.05) 66 (68.04) 225 (71.20) 57 (67.06) 223 (72.36) 49 (62.03) Inadequate 88 (28.95) 31 (31.96) 91 (28.80) 28 (32.94) 89 (27.64) 30 (37.97) History of Prior TB No 243 (79.93) 69 (71.13) 247 (78.16) 65 (76.47) 256 (79.50) 56 (70.89) Yes 61 (20.07) 28 (28.87) 69 (21.84) 20 (23.53) 66 (20.50) 23 (29.11) Treatment category Cat I 254 (83.55) 73 (75.26) 262 (82.91) 65 (76.47) 272 (84.47) 55 (69.62) Cat II & Cat III 50 (16.45) 24 (24.74) 54 (17.09) 20 (23.53) 50 (15.53) 24 (30.38) Drug resistant Status None 274 (90.13) 82 (84.54) 284 (89.87) 72 (84.71) 291 (90.37) 65 (82.28) Any or Multi drug resistance 30 (9.87) 15 (15.46) 32 (10.13) 13 (15.29) 31 (9.63) 14 (17.72) Initially Screened for DM No 285 (93.75) 88 (90.72) 298 (94.30) 75 (88.24) 307 (95.34) 66 (83.54) Yes 19 (6.25) 9 (9.28) 18 (5.70) 10 (11.76) 15 (4.66) 13 (16.46) History of Smoking Never 166 (54.61) 53 (54.64) 174 (55.06) 45 (52.94) 183 (56.83) 36 (45.57) Ever Smoke but now quitted 138 (45.39) 44 (45.36) 142 (44.94) 40 (47.06) 139 (43.17) 43 (54.43) Mahato RK, Laohasiriwong W, Koju R. The role of Diabetes mellitus comorbidity on Tuberculosis treatment outcomes in Nepal: A prospective cohort study. (Original research). SEEJPH 2022, posted: 20 March 2022. DOI: 10.11576/seejph-5329 P a g e 5 | 13 Characteristics 2 Months 5 months 6 months Cured Not cured Cured Not cured Cured Not cured History of alcohol consumption Never 186 (61.18) 52 (53.61) 195 (61.71) 43 (50.59) 204 (63.35) 34 (43.04) Ever Drunk but now quitted 118 (38.82) 45 (46.39) 121 (38.29) 42 (49.41) 118 (36.65) 45 (56.96) Type of house Cement 250 (82.24) 76 (78.35) 261 (82.59) 65 (76.47) 268 (83.23) 58 (73.42) Mud/Brick 54 (17.76) 21 (21.65) 55(17.41) 20 (23.53) 54 (16.77) 21 (26.58) Type of the floor Cement 265 (87.17) 80 (82.47) 276 (87.34) 69 (81.18) 284 (88.20) 61 (77.22) Mud/Brick 39 (12.83) 17 (17.53) 40 (12.66) 16 (18.82) 38 (11.80) 18 (22.78) Type of wall Cement 250 (82.24) 76 (78.35) 261 (82.59) 65 (76.47) 269 (83.54) 57 (72.15) Mud/Brick 54 (17.76) 21 (21.65) 55 (17.41) 20 (23.53) 53 (16.46) 22 (27.85) Blood Glucose level < 200 mg/dl 240 (78.95) 66 (68.04) 246 (77.85) 60 (70.59) 254 (78.88) 52 (65.82) ≥ 200mg/dl 64 (21.05) 31 (31.96) 70 (22.15) 25 (29.41) 68 (21.12) 27 (34.18) Blood Glucose level of TB DM only < 200 mg/dl 46 (71.88) 18 (58.06) 55 (78.57) 9 (36.00) 54 (79.41) 10 (37.04) ≥ 200mg/dl 18 (28.13) 13 (41.94) 15 (21.43) 16 (64.00) 14 (20.59) 17 (62.96) HbA1c Level of TB DM only < 7% 52 (81.25) 22 (70.97) 63 (90.00) 11 (44.00) 60 (88.24) 14 (51.85) ≥7% 12 (18.75) 9 (29.03) 7 (10.00) 14 (56.00) 8 (11.76) 13 (48.15) BMI (Kg/m2) of TB DM only <18.5 28 (43.75) 15 (48.39) 30 (42.86) 13 (52.00) 28 (41.18) 15 (55.56) ≥18.5 36 (56.25) 16 (51.61) 40 (57.14) 12 (48.00) 40 (58.82) 12 (44.44) The increasing blood glucose levels among the TB with DM cases at 2, 5, and 6 months of the treatment period revealed a curing failure with 41.94%, 64.00%, and 62.96%, respectively. Similarly, an uncontrolled HbA1c level is also responsible for increasing the no-curing rate from 2 months (29.03%) to 5 months (56.00%). On the other hand, a raising BMI (Body Mass Index) level from low to normal was observed that enhanced the TB curing rate from 2 months (56.25%) to 6 months (58.82%) (Table 1). Risk factors of the failure of treatment outcome: using the Generalized Estimating Equations model (GEE) In this study, we analysed the risk factors for failure in treatment outcomes using the GEE model for repeated measures of the outcomes. It could identify that uncontrolled Diabetes during the treatment period (≥7 %) was one of the major risk factors of failure in TB treatment outcome (adj.RR=5.24, 95% CI: 2.58-10.62, P-value <0.001) as well as other risk factors including; age ≥ 45 yrs. (adj.RR=6.13, 95% CI: 2.55-14.76, P-value <0.001), inadequate financial status (adj.RR=2.33, 95% CI: 1.07-5.06, P-value 0.033) and history of prior tuberculosis (adj.RR=2.33, 95% CI: 1.09-4.97, P-value 0.028) respectively (Table 2). Table 2. Risk Factors of Failure of Treatment Outcome among TB Patients Using the Generalized Estimating Equations Model Factors 2 months 5 Months Six months Adj. (RR) 95% CI P-Value n % * n % * n % * HbA1c Level <0.001 < 7 % 22 70.97 11 44.00 14 51.85 1 1 ≥7 % 9 29.03 14 56.00 13 48.15 5.24 2.58-10.62 Mahato RK, Laohasiriwong W, Koju R. The role of Diabetes mellitus comorbidity on Tuberculosis treatment outcomes in Nepal: A prospective cohort study. (Original research). SEEJPH 2022, posted: 20 March 2022. DOI: 10.11576/seejph-5329 P a g e 6 | 13 Factors 2 months 5 Months Six months Adj. (RR) 95% CI P-Value n % * n % * n % * Age (years) <0.001 <45 55 56.70 46 54.12 38 48.10 1 1 ≥ 45 42 4330 39 45.88 41 51.90 6.13 2.55-14.76 Financial Status 0.033 Adequate 66 68.04 57 67.06 49 62.03 1 1 Inadequate 31 31.96 28 32.94 30 37.97 2.33 1.07-5.06 History of Prior TB 0.028 No 69 71.13 65 76.47 56 70.89 1 1 Yes 28 28.87 20 23.53 23 29.11 2.33 1.09-4.97 Discussion The prevalence of DM with TB will continue to increase, given the projected global expansion of DM. However, to our knowledge, this is the first study on this region that has been performed to identify the treatment outcomes of tuberculosis cases associated with DM. The data presented in this prospective cohort study show that a total of 401 respondents from both TB and TB with DM cases were observed until the last month of the tuberculosis treatment period, of which 79 or 19.7% (95% CI: 15.79-23.61) were not cured. A study conducted in Taiwan observed similarly 17.0% of treatment failure (14). A study conducted in the urban setting of Indonesia revealed that 22.2% of the DM patients with TB had positive sputum smears after the treatment period (15). In Pakistan, nearly one-third (33.6%) of study participants who had a previous history of tuberculosis was not cured (16). In addition, more than two-thirds of the respondents were delayed in seeking treatment (≥ 7 days). In addition, most of the respondents who failed to cure visited more than two health facilities for their diagnosis. This might be due to some health providers being unable to diagnose TB as well as Diabetes in the same place. In our setting, we determined the role of DM and other risk factors on TB treatment outcome 2, 5 & 6 months of comprehensive treatment of our tuberculosis cohort. The sputum conversion guides the duration of TB treatment and infectivity of the patient but delayed conversion is also associated with an increased risk of relapse. While most studies outside the Middle East (16) have shown no relationship between DM and conversion at the end of 2 months, we considered a more extended observation period of 6 months. Up to one-third of the world's population is infected with Mycobacterium tuberculosis; however, not all of those infected develop active TB because, usually, the immune system contains the germ. However, in some people, the bacteria remain dormant. They could become active, causing disease at later stages, especially those with risk factors such as old age, Diabetes, and other immunosuppressive treatments (7). So, after controlling the confounding factors, uncontrolled DM and five more risk factors showed an effect on the failure of TB treatment. The respondents who had uncontrolled DM with ≥7 % of HbA1c on two months of treatment were more than five times at risk of failing therapy. A systematic review found that uncontrolled DM (HbA1c ≥7) was a significant risk factor for positive sputum culture after two months (17). Another multicentre study conducted in South Korea revealed similar findings (18). Therefore, close monitoring of blood glucose and clinical conditions of TB patients with DM during the treatment period is crucial (19). Respondents aged ≥ 45 years had a greater risk of deteriorating TB treatment outcomes. A similar result has been observed by studies conducted in Indonesia (15), Taiwan (14), and Malaysia (2). Similarly, Mahato RK, Laohasiriwong W, Koju R. The role of Diabetes mellitus comorbidity on Tuberculosis treatment outcomes in Nepal: A prospective cohort study. (Original research). SEEJPH 2022, posted: 20 March 2022. DOI: 10.11576/seejph-5329 P a g e 7 | 13 inadequate financial status was also associated with failure of treatment. However, a study conducted in Kuala Lumpur, Malaysia, revealed no significant difference in the economic situation between both groups (2). Furthermore, history of prior tuberculosis is doubling the effect of the non-curing rate of tuberculosis, supported by a study conducted in Malaysia: the authors observed that patients with a previous history of tuberculosis treatment were found to be three times more likely to have sputum smear non- conversion compared with those without prior exposure to tuberculosis (2). So, the reason might be a previous infection may induce initial cavitation and increase the extent of residual lesions of the lung (20). Conclusion This study outcome was a stepping-stone towards getting free of TB despite being diabetic. Our study observed that poorly controlled DM, increasing age, inadequate financial status, and previous history of tuberculosis were strong predictors of tuberculosis treatment failure. Therefore, a regular DM screening program would enhance TB control and reduce the burden of TB in Nepal. The National Tuberculosis Program (NTP) should establish a policy on collaboration with the private sector by setting up a referral system and providing basic knowledge on tuberculosis and Diabetes. References 1. Gyawali B, Sharma R, Neupane D, Mishra SR, Van Teijlingen E, Kallestrup P. Prevalence of type 2 diabetes in Nepal: a systematic review and meta-analysis from 2000 to 2014. Glob Health Action 2015;8:29088. 2. Shariff NM, Safian N. Diabetes mellitus and its influence on sputum smear positivity at the 2nd month of treatment among pulmonary tuberculosis patients in Kuala Lumpur, Malaysia: A case control study. Int J Mycobacteriol 2015;4:323-9. 3. Lee PH, Lin HC, Huang AS, Wei SH, Lai MS, Lin HH. Diabetes and risk of tuberculosis relapse: nationwide nested case-control study. PloS One 2014;9:e92623. 4. 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The effect of type 2 diabetes mellitus on the presentation and treatment response of pulmonary tuberculosis. Clin Infect Dis 2007;45:428-35. 16. Alkabab YM, Al-Abdely HM, Heysell SK. Diabetes-related tuberculosis in the Middle East: an urgent need for regional research. Int J Infect Dis 2015;40:64-70. 17. Baghaei P, Marjani M, Javanmard P, Tabarsi P, Masjedi MR. Diabetes mellitus and tuberculosis facts and controversies. J Diabetes Metab Disord 2013;12:58. 18. Yoon YS, Jung J-W, Jeon EJ, Seo H, Ryu YJ, Yim J-J, et al. The effect of Diabetes control status on treatment response in pulmonary tuberculosis: a prospective study. Thorax 2017;72:263-70. 19. Workneh MH, Bjune GA, Yimer SA. Diabetes mellitus is associated with increased mortality during tuberculosis treatment: a prospective cohort study among tuberculosis patients in South-Eastern Amahra Region, Ethiopia. Infect Dis Poverty 2016;5:22. 20. Magee MJ, Foote M, Maggio DM, Howards PP, Narayan KM, Blumberg HM, et al. Diabetes mellitus and risk of all-cause mortality among patients with tuberculosis in the state of Georgia, 2009-2012. Ann Epidemiol 2014;24:369-75. ________________________________________________________________________________________________ © 2022 Mahato et al; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Mahato RK, Laohasiriwong W, Koju R. The role of Diabetes mellitus comorbidity on Tuberculosis treatment outcomes in Nepal: A prospective cohort study. (Original research). SEEJPH 2022, posted: 20 March 2022. DOI: 10.11576/seejph-5329 P a g e 9 | 13 ANNEX I: QUESTIONNAIRE FOR PARTICIPANTS “The role of diabetes mellitus co-morbidity on tuberculosis treatment outcomes in Nepal: A Prospective Cohort Study” General information: CRF Number: Date of the interview: |……..| …......| ………...| [Day | Month | Year] Name of district: _____________________ Part A: Socio-demographic characteristics Code A1 Gender ☐ 1. Male ☐ 2. Female A1 A2 Your age ………….. Years old (full Year) What is your date of births? |……..| …......| ………...| [Day | Month | Year] A2….... A3 Number of household members in your family?................... A3…… A4 Marital status ☐ 1. Single ☐ 2. Married ☐ 3. Separated ☐ 4. Divorced A4 A5 Place of residence ☐ 1. Urban ☐ 2. Rural ☐ 3. Homeless/displaced A5 A6 What is your educational attainment? ☐ 1. No formal education ☐ 2. Primary ☐ 3. Secondary ☐ 4. High school or equivalence ☐ 5. Bachelor or equivalence ☐ 6. Higher than Bachelor degree A6 A7 What is your main occupation? ☐ 1. None ☐ 2. Housewife ☐ 3. Student ☐ 4. Farmer ☐ 5. Unskilled worker ☐ 6. Employee ☐ 7. Business ☐ 8. Government officer ☐ 9. Other please specify ………………… A7 A79xxx A8 What is your average family monthly income ………………. NPR A8…… A9 What is your average monthly income ……………………… NPR A9…… A10 What is your average monthly expense ………………………NPR A10…. A11 What is your financial situation? ☐ 1. Not Enough ☐ 2. Not Enough with debt A11 Mahato RK, Laohasiriwong W, Koju R. The role of Diabetes mellitus comorbidity on Tuberculosis treatment outcomes in Nepal: A prospective cohort study. (Original research). SEEJPH 2022, posted: 20 March 2022. DOI: 10.11576/seejph-5329 P a g e 10 | 13 Part A: Socio-demographic characteristics Code ☐ 3. Enough with no saving ☐ 4. Enough with saving Part B: Health Status and History of Disease B1 Height ………… cm B1…... B2 Weight …………kg B2…... B3 Systolic Blood Pressure …….mmHg B3…... B4 Diastolic Blood Pressure …….mmHg B4…... B5 What are the signs/ symptoms that make you to see the health personnel? (Can choose more than one options) ☐ 1. Cough ☐ 2. Fever ☐ 3. Loss of Weight ☐ 4. Haemoptysis ☐ 5. Chest pain ☐ 6. Other please specify ………………… B51 B52 B53 B54 B55 B65xx B6 History of Prior TB ☐ 1. No ☐ 2. Yes B6 B7 If yes, where did you get the initial TB diagnosis? ☐ 1. Public Centre ☐ 2. Private Centre B7 B8 Who made your initial TB diagnosis? ☐ 1. Paramedic's ☐ 2. Medical Officer ☐ 3. Chest specialist ☐ 4. Other please specify ………… B8 B9 Family history of TB ☐ 1. No ☐ 2. Yes B9 B10 Date of first TB diagnosis? |……..| …......| ………...| [Day | Month | Year] B10 B11 How long does it take to get diagnosed with TB since having signs/ symptoms of TB………….(days) B11…. B12 Number of health facilities visited before initial TB diagnosis …….. B12…. B13 Which of the following investigations was performed to diagnose TB? (Can choose more than one options) ☐ 1. Sputum examination ☐ 2. X-ray ☐ 3. Gene-Xpert ☐ 4. PCR ☐ 5. Mountex Test ☐ 6. Other please specify ………………… B13 1 B132 B133 B134 B135 B136x B14 Sputum grade ☐ 1. + ☐ 2. ++ ☐ 3. +++ B14 B15 Type of TB ☐ 1. Positive sputum ☐ 2. Negative sputum ☐ 3. Extra pulmonary B15 Mahato RK, Laohasiriwong W, Koju R. The role of Diabetes mellitus comorbidity on Tuberculosis treatment outcomes in Nepal: A prospective cohort study. (Original research). SEEJPH 2022, posted: 20 March 2022. DOI: 10.11576/seejph-5329 P a g e 11 | 13 Part B: Health Status and History of Disease B16 Treatment of category ☐ 1. Cat I ☐ 2. Cat II ☐ 3. Cat III B16 B17 Stage of treatment period |……..| …......| [Day | Month] B17 B18 In addition to tuberculosis, what other disease(s) has the patient been diagnosed? (Can choose more than one options) ☐ 1. None ☐ 2. Hypertension/ Cardiovascular ☐ 3. Diabetes ☐ 4. Diabetes ☐ 5. HIV/AIDS B181 B182 B183 B184 B185 B19 Do you have any type of drug resistant? ☐ 1. None ☐ 2. Any drug resistance ☐ 3. Multi drug resistance B19 B20 Have you been screened for Diabetes till date? (If No, then jump to Q C1) ☐ 1. No ☐ 2. Yes B20 B21 If you have DM, which type of DM you have? ☐ 1. Type 1 ☐ 2. Type2 B21 B22 Do you have any type of diabetic comorbidity? (Can choose more than one options) ☐ 1. None ☐ 2. Hypertension/ Cardiovascular ☐ 3. TB ☐ 4. Cancer ☐ 5. HIV/AIDS ☐ 6. Any other diseases, please specify ………………… B221 B222 B223 B224 B225 B226x B23 Do you have any type DM complication? (Can choose more than one options) ☐ 1. None ☐ 2. CVD ☐ 3. Nephropathy ☐ 4. Neuropathy ☐ 5. Retinopathy ☐ 6. Hearing Impairment ☐ 7. Any other diseases, please specify ………………… B231 B232 B233 B234 B235 B236 B237x B24 If, previously diagnosed date of first DM diagnosis? |……..| …......| ………...| [Day | Month | Year] B24 B25 If you have DM since how long you are getting treatment? ……………… months B25…. B26 Mode of DM treatment? (Can choose more than one options) ☐ 1. Dietary control ☐ 2. Oral glycaemic control ☐ 3. Insulin Injection ☐ 4. Health education ☐ 5. Health Counselling ☐ 6. Exercise B261 B262 B263 B264 B265 B266 Mahato RK, Laohasiriwong W, Koju R. The role of Diabetes mellitus comorbidity on Tuberculosis treatment outcomes in Nepal: A prospective cohort study. (Original research). SEEJPH 2022, posted: 20 March 2022. DOI: 10.11576/seejph-5329 P a g e 12 | 13 Part B: Health Status and History of Disease ☐ 7. Any other diseases, please specify ………………… B267x Part C: Behavioural and Environmental factors C1 History of smoking ☐ 1. Never ☐ 2. Currently ☐ 3. Ever smoke but now quitted C1 C2 If smoke, since how long …………months C2 C3 If quit, since how long …………months C3 C4 If currently smoke, specify amount of daily consumption …………. (number of cigarettes/day) C4…. C5 History of alcohol consumption ☐ 1. Never ☐ 2. Currently ☐ 3. Ever drunk but now quitted C5 C6 If currently drink, since how long …………months C6…. C7 If quit, since how long …………months C7…. C9 What type of house do you have? ☐ 1. Cement ☐ 2. Mud/Brick ☐ 3. Other please specify ………………… C33 C10 What is the type of the floor? ☐ 1. Cement ☐ 2. Mud/Brick ☐ 3. Other please specify ………………… C34 C11 What type of wall do you have? ☐ 1. Cement ☐ 2. Mud/Brick ☐ 3. Other please specify ………………… C35 Mahato RK, Laohasiriwong W, Koju R. The role of Diabetes mellitus comorbidity on Tuberculosis treatment outcomes in Nepal: A prospective cohort study. (Original research). SEEJPH 2022, posted: 20 March 2022. DOI: 10.11576/seejph-5329 P a g e 13 | 13 Chart assessment tool Date of assessment: |……..| …......| ………...| [Day | Month | Year] Name of the DOTS centre: _____________________ Description Initial 2 months 5 months 6 months Blood Glucose level Fasting Random HbA1c Level Sputum grade Weight Height SBP DBP