European Journal of Cardiovascular Medicine

Tuberculosis is a major public health problem in India TB is one of the top 10 causes of death, and the leading cause from single infectious agent (Mycobacterium Tuberculosis), ranking above HIV/AIDS. The disease can affect anyone anywhere, but most people who develop TB (about 90%) are adults, the male: female ratio is 2:1, and case rate at national level vary from less than 50 to more than 5000 per 1 million population per year. Worldwide around 10 million people fall ill with tuberculosis each year. Almost 90% of cases each year are in high TB burden countries. Globally, an estimated 1.7 billion people are infected with M. tuberculosis and are thus at risk of developing the disease¹.As per Global TB report 2019 the estimated incidence of TB in India was approximately 26.9 lakh cases. Newly diagnosed and retreatment cases of TB in India were 87% and 13% respectively².As per current policy, to provide appropriate regimen based on the Drug Susceptibility Test (DST), universal DST is being offered to notified TB patients (including private sector TB patients) to assess the presence of Rifampicin resistance at the time of TB diagnosis³. Both type 2 diabetes (T2DM) and tuberculosis (TB) are prevalent in India. Prediabetes and T2DM are increasing in urban and rural India at a similar pace⁴ due to rapid changes in lifestyle and physical inactivity. India is reported to have the highest burden of TB globally, with 2.4 million cases reported in the National TB Program of India in 2019^5. It is estimated that in 2021, India had 74.2 million diagnosed and undiagnosed adult patients with DM (between 20 and 79 years) and these are likely to rise to 124.9 million in 2045. Alarmingly, there are around 39.4 million (53.1%) undiagnosed cases present in India.⁶ There is a bidirectional relationship between DM and infections, and it is true for TB as well.⁵ It is estimated that 15% of adult TB cases are attributable to DM, which is nearly the same for the HIV-TB association^.7,8,9 No authentic data on the overall number of patients with TB-DM comorbidity are available from India. TB cases in India were attributable to the following risk factors: undernutrition, alcohol use disorders, tobacco smoking, diabetes, and HIV.¹⁰ This study was planned to study the treatment outcome in new and previously treated patients in field condition at NTRD DOTS Area under RNTCP. This study also focused on identifying various risk factor and comorbidities associated with unsuccessful outcome.

Study Area:

Study was conducted in field condition in NITRD DOTS area (Ladosarai, Mehrauli, Chhatarpur, Khanpur, Tigri) New Delhi.

Study Period:

Study period from 1^st September 2019 to 31 March 2020. Patient’s enrolment was done from 1^st September to 31^st October and then follow up till end of treatment.

Study Design

The study was prospective Observational.

Study Population And Sample Size:

When we look at data from the previous year from there five DOTS centers of NITRD, approx.  8-10 sputum smear positive patients per month in each DOTS area of NITRD were diagnosed as sputum positive PTB (new and previously treated).  As we enrolled patient from 1^st September to 31^st October (2 month)). So, the on the basis of these previous year data our sample size were 100 patients.

Inclusion Criteria:

All newly diagnosed and previously treated sputum smear positive pulmonary tuberculosis patient who are registered under RNTCP in NITRD DORS AREA.

Exclusion Criteria:

1. All drug resistant (INH and RMP) cases of pulmonary Tuberculosis.
2. Refusal to participate in study.

Methodology:

Patient were enrolled in study who full fill the inclusion criteria.

Patients were enrolled from five DOTS area of NITRD (Lado Sarai, Chhatarpur, Khanpur, Tigre, Mehrauli, New Delhi) for study.

 Sputum smear Microscopy, CBNAAT, LPA and drug sensitivity testing were carried out in all enrolled cases of PTB to look for drug resistant. We enrolled only sputum smear positive drug sensitive PTB patients. Detail History were taken including of Diabetes mellitus.

Patients were interviewed two-time; first interview was carried out at the end of intensive phase and second interview was carried out at the end of the treatment to see outcome.

Ethical consideration:

For all cases, informed consent in English and Hindi were taken after thoroughly explaining them about the study. Only patients giving consent were enrolled in the study. There was no financial burden to the patients for participation in the study.

Data entry and statistical analysis:

The collected data was transformed into variables, coded and entered in Microsoft Excel. Data was analyzed and statistically evaluated using SPSS-PC-20 version. Quantitative data was expressed in mean ± standard deviation while qualitative data were expressed in percentage and statistical differences between the proportions were tested by chi square test or fisher exact test. ‘P’ value less than 0.05 was considered statistically significant.

Demographic data:

The mean age± standard deviation of our study sample was 33.52±15.90 years respectively. When classified according to age the maximum patients 39(39%) belonged to age group 11-25 years, followed by 32 patients belongs to age group 26-40 years ,16 patients belonged to age group 41-55 years,12 patients belonged to age group 56-70 years, 1 patient belonged to age group >70 years (Table 1, Fig 1). In our study, out of enrolled 100 patients 60 (60%) were males 40 (40%) were females (Table 2, Fig 2)

Table 1: Age wise distribution of PTB study subjects (n=100)

Figure1: Age wise distribution of PTB study subjects (n=100)

Table2: Gender wise distribution of PTB study subjects

Figure 2: Gender wise distribution of PTB study subjects

Distribution of Diabetes mellitus in study patients: Among 100 enrolled patients 83 (83%) had no history of diabetes while17(17 %) patients had history of diabetes (Table 3, Fig 3)

Table 3: Diabetes status in PTB study subjects

Figure 3:  Distribution of Diabetes mellitus in study patients:

Sputum at the end of 2 months in newly diagnosed and previously treated pulmonary tuberculosis subjects: Among newly diagnosed patients (n=77), 13(16.9%) patients remain sputum smear positive at the end of 2 month of treatment, rest 64(83.1%) became sputum smear negative at the end of intensive phase. Among previously treated patients (n=23), 4(17.4%) patients remain sputum smear positive at the end of intensive phase, 19(82.6%) patients became sputum smear negative at the end of intensive phase. In our study we found no statistically significant difference in sputum smear conversion at the end of 2 month in new and previously treated PTB patients (P value=0.95). As shown in the form of (Table 4, fig 4).

Table 4: Sputum at the end of 2 months in newly diagnosed and previously treated PTB subjects

Figure 14:  Sputum at the end of 2 months in newly diagnosed and previously treated PTB subjects

Association of diabetes mellitus with sputum conversion at 2 months: Among 100 study participants  17 (17%) patients had history of DM, out of which sputum smear was positive at the end of 2 month in 7 (41.2%) patients and 10 (58.8%) patients became sputum smear negative at the end of 2 month of treatment .83 (83%) patients had no history of DM  , out of which 10(12%) patients remain sputum smear positive at the end of 2 month and 73 (88%) patients became sputum smear negative at the end of 2 month of treatment .In our study we found statistically significant relation between   history of DM with delayed sputum smear conversion in pulmonary tuberculosis patients (P value=0.01) (Table 5, Fig 5)

Table 5: Association of Diabetes with sputum conversion at 2 months

Figure 5: Association of Diabetes with sputum conversion at 2 months

This study was planned to study the treatment outcome in new and previously treated patients in field condition at NTRD DOTS Area under RNTCP. This study also focused on identifying various risk factor and comorbidities (Diabetes) associated with unsuccessful outcome. 100 patients registered for study from NITRD DOTS area between 1^st September to 31^st October and followed patient till the end of the treatment.

The mean age± standard deviation of our study sample was 33.52±15.90 years respectively. When classified according to age the maximum patients 39(39%) belonged to age group 11-25 years, followed by 32(32%) patients belongs to age group 26-40 years ,16(16%) patients belonged to age group 41-55 years,12(12%) patients belonged to age group 56-70 years, 1(1%) patient belonged to age group >70 years. Joseph N, Nagraj k, et al.¹¹ conducted study, the mean age of all patients in their study was 38.78±14.17.

In our study, among 100 patients, 60 (60%) were males 40 (40%) were females).  in a cross-sectional study conducted by Joseph N et al¹¹. at Mangalore, South India, in their study most of the patients were males (78.3%). In another retrospective study conducted by Sariem CN et al.¹² at north central Nigeria, in their study male patients were 58% and female patients were 42%.

DM is a well-known risk factor for tuberculosis .¹³ In our study among 100 enrolled patients 83 (83%) had no history of diabetes while17(17 %) patients had history of diabetes. Recent studies show that 10% -30% of patients with TB may also have Diabetes Mellitus.^14-17 Available evidence and modeling studies indicate that nearly 20% of all TB patients in India also suffer from Diabetes mellitus.³ In our study non has HIV.

In our study among newly diagnosed patients (n=77), 13(16.9%) patients remain sputum smear positive at the end of 2 month of treatment, rest 64(83.1%) became sputum smear negative at the end of intensive phase. Among previously treated patients (n=23), 4(17.4%) patients remain sputum smear positive at the end of intensive phase, 19(82.6%) patients became sputum smear negative at the end of intensive phase. In our study we found no statistically significant difference in sputum smear conversion at the end of 2 month in new and previously treated PTB patients. Similar results were found in a study conducted by Joseph N et al.¹¹ found that among new sputum smear positive cases 26.4% remain sputum positive at the end of intensive phase, 74% patients among NSP became sputum smear negative at end of IP. In retreatment cases 27% continued remain sputum smear positive at the end of IP and 73% patients among retreatment group became sputum smear negative at the end of IP.

Among 100 study participants 17 (17%) patients had history of Diabetes Mellitus (DM), out of which sputum smear was positive at the end of 2 month in 7 (41.2%) patients and 10 (58.8%) patients became sputum smear negative at the end of 2 month of treatment. 83 (83%) patients had no history of Diabetes Mellitus, out of which 10(12%) patients remain sputum smear positive at the end of 2 month and 73 (88%) patients became sputum smear negative at the end of 2 month of treatment. We found statistically significant relation between history of Diabetes Mellitus with delayed sputum smear conversion in pulmonary tuberculosis patient at the end of intensive phase (P value=<0.01). In a study conducted by Mi F et al.¹⁸ at China found that Diabetes mellitus in new sputum smear positive patients with Pulmonary Tuberculosis (PTB) was failure sputum smear conversion at 2 months. In their study 21.7% patient with DM remain sputum smear positive at end of 2 month while only 5.6 % patients without DM remain sputum smear positive at the end of 2 month (P value=<0.001). Another study conducted by Alisjahbana B et al.¹⁴ at Indonesia found that patients with DM with PTB have delayed conversion of sputum smear at 2 months in comparison with patients without DM with PTB (18.1% vs.10.0%).

LIMITATIONS OF OUR STUDY

Small sample size.

This was a prospective observational study in which we enrolled 100 patients, including 23 previously treated patients and 77 newly diagnosed sputum smear-positive patients, from five DOTS areas of NITRD, New Delhi. The history of Diabetes Mellitus and sputum smear conversion rates were assessed. We found that Diabetes Mellitus was significantly associated with delayed sputum smear conversion at the end of the second month of treatment. However, there was no statistically significant difference in sputum smear conversion rates between newly diagnosed and previously treated pulmonary tuberculosis groups at the end of the second month.

1. World Health Organization (WHO), Global Tuberculosis Report 2019.World Health Organization,2019.
2. India TB. report 2018.New Delhi: Central TB division, Directorate General of Health Services, Ministry of Health and Family Welfare.2018.
3. India TB report 2020.New Delhi: Central TB division Directorate General of Health Services, Ministry of Health and Family Welfare.2020.
4. Ranasinghe P, Jayawardena R, Gamage N, Sivanandam N, Misra A. Prevalence and trends of the diabetes epidemic in urban and rural India: a pooled systematic review and meta‐analysis of 1.7 million adults. Ann Epidemiol. 2021. Jun;58:128‐148. doi: 10.1016/j.annepidem.2021.02.016 [DOI] [PubMed] [Google Scholar].
5. Government of India. India TB Report 2020.pdf. 2021. Accessed May 14, 2021. https://tbcindia.gov.in/WriteReadData/l892s/India%20TB%20Report%202020.pdf
6. pdf– IDF Diabetes Atlas. Accessed May 1, 2023. https://diabetesatlas.org/idfawp/resourcefiles/2021/07/IDF_Atlas_10th_Edition_2021.pdf
7. Fazaludeen Koya S, Lordson J, Khan S, et al. Tuberculosis and diabetes in India: stakeholder perspectives on health system chal lenges and opportunities for integrated care. J Epidemiol Glob Health. 2022;12(1):104-112. doi:10.1007/s44197-021-00025-1.
8. pdf– IDF Diabetes Atlas. Accessed May 1, 2023. https://diabetesatlas.org/idfawp/resourcefiles/2021/07/IDF_Atlas_10th_Edition_2021.pdf
9. Gupta R, Misra A. Epidemiology of microvascular complica tions of diabetes in South Asians and comparison with other ethnicities. J Diabetes. 2016;8(4):470-482. doi:10.1111/1753 0407.12378
10. Accessed February 3, 2023. https://worldhealthorg.shinyapps. io/tb_profiles/?_inputs_&entity_type=%22country%22&lan=%22EN%22&iso2=%22IN%22.
11. Joseph N, Nagaraj K, Bhat J, Babu RY, Kotian SM, Ranganatha YP, Hocksan AA, Shetty VV, Zaki NM, Swasthik KS, Hamzah NF. Treatment outcomes among new smear positive and retreatment cases of tuberculosis in Mangalore, South India–a descriptive study. The Australasian Medical Journal. 2011;4(4):162.
12. Sariem CN, Odumosu P, Dapar MP, Musa J, Ibrahim L, Aguiyi JC. Tuberculosis Treatment Outcomes: A Fifteen Year Retrospective Study in Jos North and Mangu, Plateau State, North–Central Nigeria.
13. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes care. 2004 May 1;27(5):1047-53.
14. Alisjahbana B, Van Crevel R, Sahiratmadja E, Den Heijer M, Maya A, Istriana E, Danusantoso H, Ottenhoff TH, Nelwan RH, Van Der Meer JW. Diabetes mellitus is strongly associated with tuberculosis in Indonesia. The International Journal of Tuberculosis and Lung Disease. 2006 Jun 1;10(6):696-700.
15. Kim SJ, Hong YP, Lew WJ, Yang SC, Lee EG. Incidence of pulmonary tuberculosis among diabetics. Tubercle and lung disease. 1995 Dec 1;76(6):529-33.
16. Restrepo BI, Fisher-Hoch SP, Crespo JG, Whitney E, Perez A, Smith B, McCormick JB. Type 2 diabetes and tuberculosis in a dynamic bi-national border population. Epidemiology & Infection. 2007 Apr;135(3):483-91.
17. Shetty N, Shemko M, Vaz M, D'souza G. An epidemiological evaluation of risk factors for tuberculosis in South India: a matched case control study. The International Journal of Tuberculosis and Lung Disease. 2006 Jan 1;10(1):80-6.
18. Mi F, Tan S, Liang L, Harries AD, Hinderaker SG, Lin Y, Yue W, Chen X, Liang B, Gong F, Du J. Diabetes mellitus and tuberculosis: pattern of tuberculosis, two‐month smear conversion and treatment outcomes in G uangzhou, C hina. Tropical Medicine & International Health. 2013 Nov;18(11):1379-85.