AN EPIDEMIOLOGICAL STUDY OF DRUG RESISTANT TUBERCULOSIS CASES REGISTERED UNDER DOTS PLUS CENTER IN A RURAL BASED TERTIARY CARE HOSPITAL

Background: Drug resistance in tuberculosis is a global problem and India is no exception to this. However, this rise is mainly among the previously treated cases as previous antituberculosis therapy is the single most important risk factor for the development of drug resistance. The worldwide prevalence of drug resistant tuberculosis is on the rise and multiple studies give varying data regarding the epidemiology of drug resistant tuberculosis. This study was taken up to determine the demographic profile of a patient, previous history of anti tubercular drug intake and pattern of drug resistant. Design: Prospective observational study. Methods and Materials: Patient who are Sputum positive, diagnosed drug resistant tuberculosis and fulfill the inclusion and exclusion criteria, admitted from March 2015 February 2016 in DOTS PLUS centre, BMCH, Burdwan. To accomplish the objectives, information was collected by personal interviews using pre-designed, pre-tested proforma. Data, so collected, was analyzed and tabulated using appropriate statistical software. Results: More than 2/3rd were males and majority were in age group 18-55 years, educated up to primary level, living in overcrowded and ill-ventilated houses belongs to upper lower and lower class (IV & V) on Kuppuswamy‘s SES 2014. Initially almost all had pulmonary TB. At the start of category II, maximum number of patients was relapse cases. The prime cause being financial crunch and lack of knowledge. Resistance to both rifampicin and isoniazide (MDR) was found in more than 2/3rd of cases. 3 patients (3%) were reactive for HIV in the study. Conclusion: In general even after considering so many diversified variables it could be stated that most of the patients perceived some degree of improvement in their condition following treatment.


Introduction
Tuberculosis (TB) is one of the oldest diseases known to mankind since time immemorial and continues to be a major public health problem even in today's modern world. It is a preventable and curable disease, but still million of people suffer every year and a number of them die from this disease, resulting in a heavy impact on social and economic development. Its causative organism Mycobacterium tuberculosis was one of the disease is clearly understood. A vaccine against tuberculosis has been available for close a century. Effective treatment against the disease has been available for sixty years. Yet the disease is close to its highest level ever and so, the World Health Organisation declared tuberculosis as a global public health emergency in 1993.
(1-4) Tuberculosis primarily affect the lung but can affect part of the body such as intestine, bones, joints, meninges, lymph glands, skin and other tissues of the body. Pulmonary tuberculosis account for over eighty percent of the total cases suffering from tuberculosis. Transmission occurs by airborne spread of infection droplets and droplet nuclei containing the tubercle bacilli, When a person inhale, those micro particle get lodge in the terminal bronchiole and the alveoli to infect a person.(5) The source of infection is a person with sputum smear positive pulmonary tuberculosis.(6) Each sputum positive case can infect 10-15 individual in a year, if not treated.(7) In recent years, international attention has turned toward the evolving burden of drug resistance. Multidrug resistant tuberculosis (MDR TB) has emerged in epidemic proportions in the wake of widespread HIV infection in the world's poorest populations, including subSaharan Africa. Extensively drugresistant TB (XDR TB) was first reported in 2006 but has now been documented on six continents. These trends are critically important for global health, since drug-resistant TB mortality rates are high and second and third-line agents for the treatment of drugresistant TB are less potent and less tolerable than first-line therapies. Drug resistant tuberculosis (DR-TB) poses a great threat to the eradication of TB. Therefore, preventing the disease is the key to saving lives and resources. Social and behavioral variables play a big part in this prevention. It is important to determine the social factors that may lead to DR-TB in order to set up prevention programs and more efficient treatment regimens. 3 Globally, 5% of TB cases were estimated to have had MDR-TB in 2015 (3.9% of new and 21% of previously treated TB cases).Drug resistance surveillance data show that an estimated 480 000 people developed MDR-TB in 2015 and 210 000 people died. Extensively drugresistant TB (XDR-TB) has been reported by 117 countries in 2015. On average, an estimated 9% of people with MDR-TB have XDR-TB. (8) India has highest burden of both TB and MDR TB and second highest of HIV associated TB based on es mates reported in global TB eport 201 . An es mated 1,000 cases of TB emerge annually from the no ed cases of pulmonary TB in India . Based on sub-na onal surveys carried out in three state of India , 3% among new TB cases and 12%-17% among previously treated TB cases have MDR-TB.(9) The disease is not only medical problem or a public health problem but is also a critical social problem of great magnitude. Base line and adequate information on epidemiology, past history of anti tubercular drug and pattern of drug resistance is required for its control and effective treatment. Drug resistance in tuberculosis is a global problem and India is no exception to this. However, this rise is mainly among the previously treated cases as previous anti-tuberculosis therapy is the single most important risk factor for the development of drug resistance. The worldwide prevalence of drug resistant tuberculosis is on the rise and multiple studies give varying data regarding the epidemiology of drug resistant tuberculosis. This study was taken up to determine the demographic profile of a patient, previous history of anti tubercular drug intake and pattern of drug resistant AIMS and OBJECTIVES: 1. To find out the association of Drug resistant TB with demographic, environmental and socioeconomic factor.
2. To assess present and past history of anti tubercular drug 3. To determine the pattern of drug resistance in them.

MATERIALS and METHODS:
The present study entitled " An epidemiological study of drug resistant tuberculosis cases registered under dots plus center in a rural based tertiary care hospital" was undertaken as a mandatory research activity for M.D  Data collection techniques The subjects were explained about the purpose of study. Data was collected by interview method using the pre designed, pre tested questionnaire after taking informed consent from each study subject.
Data entry and analysis Proper template was generated for data entry in MS-Excel. Data entry was done and 10% of data were randomly checked to assure the quality of data entry under the supervision of Guide. The data were analysed by using software-Statistical Package for Social Science (SPSS) 20.0 VERSION. Frequency tables were generated to see the distribution of variable.
• Joint family-It consists of a number of married couples and their children who lives together in the same household and all the property is held in common.(34) • Nuclear family-It consists of married couple and their children whlie they are still regarded as dependents.
• Overcrowding-It refers to the situation where more people are living within a single dwelling than there is space for, so that the movement is restricted, privacy hampered, hygiene impossible, rest and sleep difficult. The present study entitled an epidemiological study of drug resistant tuberculosis cases registered under dots plus centre in a rural based tertiary care hospital was carried out in Burdwan Medical Collage and Hospital, Burdwan.  Out of 100 patients, majority patients were male (82%) while less than one fourth (18%) were females. This could be due to more exposure of males to outside environment and female often used to ignore their initial symptom due to their responsibilities towards their families as well as children.
Majority (59%) patients were Hindu followed by Muslim (29%) patients. Only some of the patients were belonged to Christian (4%) and other (8%). This finding is almost in accordance with the religion wise distribution of population in the state.
As far as area is concerned majority (65%) patients were belonged to rural area and less number (35%) ware belonged to urban area. This could be due to the fact that 68.13% of people live in the rural area and 31.87% of people live in urban area in the West Bengal state .  On the basis of occupation majority 22% of patients were unemployed followed by industrial/factory labour 19% and farmer 18%. 12% patients were housewives and 10% were in self employed. Only few patients were student (8%), daily wages and in private job 4% each.3% patient having govt. job.
On the basis of marital status, more than half (65%) were married patients followed by unmarried (30%) patients. 5% patients were widow/widower. This may be attributed to the fact that married people used to consult health care centre early by their counterparts so as to live a healthy life. Married women reported abandonment, isolation within the household and a lack of proper care from family members, particularly in-laws.
More than one third (78%) of the patients belonged to joint family and rest (22%) were from nuclear family. The reason for this is that still in India, joint family system is more common. Depending on the type of house, majority 37% patients were living in kuccha house followed by patients living in pakka house 36%. Only 26% patients were living in semipakka house. Kachha and semipakka house denotes lower socioeconomic status of the family which led to under nutrition, poverty. These factor's indirectly responsible for occurrence of the tuberculosis.
As overcrowding is important risk factor for tuberculosis. It was also concluded from present study that overcrowding is present in about 66% of the study population. In crowded house a greater degree of shared air space increases exposure to M. tuberculosis. Which can even be more increase by limited air movement in closed space-so a greater risk of infection.
Crowding also has been reported to increase the risk of tuberculosis.
Smoking has direct relation with the progression of the disease of tuberculosis. In the present study more than one third 36% of the patients were present smoker followed by past smoker (17%).There were 47% patients were non smoker.  In above table shows past history of TB was present in majority of cases 96% cases. Only 4% patients were not having past history of TB. In only few 21% patients, family/neighbour/work place history of past/present TB present, which is also an important risk factor for tuberculosis. This may be due to the fact that patients hide their family status of tuberculosis due to social stigma.

DISCUSSION:
This study was taken up to determine the prevalence and the clinical profile of Drug Resistant TB cases in the patients coming to Burdwan medical college. In this study, the patients were analyzed based on their age, gender, presenting socioeconomic status, habits, past treatment history, the clinical symptoms at presentation and the drug susceptibility. Age Analysis of the 100 culture-confirmed TB cases showed that Drug resistant was more frequent among patients aged 18 to 45 years (71%). Bhatt Get al Found (83.7%) MDR-TB was more frequent among patients aged 16 to 45 years. In this study the mean age of MDR TB patients was 33.64 ± 11.03 years. whereas in our study it was 35.58±13.6 (18-72). The mean age group and the minimum and maximum age limits were found to be higher in our study population. Gender in our study of 100 patients, 82 were male and 18 were female. The male: female ratio is 4.51:1. In the study by Sharma et al the male to female ratio of the MDR TB patients in a cat II pts. was 3.4:1.However in another study done by Dholakia N male to female ratio was 1:1.Hence there is a lot of variability but a slight male preponderance is obvious taking into the account the various studies including ours. Religion in a study conducted by Bhatt G et al in Ahmadabad found that 76.1% patients were Hindu. 4.9% Muslim. In our study majority (59%) patients were Hindu followed by Muslim (29%) patients. Only some of the patients were belonged to others (8%) and Christian (4%). This finding is almost in accordance with the religion wise distribution of population in the state. Area wise distribution of patients most of the Drug resistant tuberculosis patients are resides in rural (65%) area, 35% patients are resides in urban area. In West Bengal most population come from rural area, about 65. 68 %. 13% population resides in rural area, so data may varies in various studies. Xiaochun He at al found 70.8% people resides in rural area. Occupation wise distribution Labour (19%) and Farmers (18%) were more vulnerable for drug resistant TB. Tuberculosis is a chronic disease so most of the patients were unemployed (22%). Marahatta SB at al found most of the drug resistant patients were self employed (30%), Himansh Karmkar et al found farmers (21.3%) were more with drug resistant TB. Distribution of patients on basis of marital status Drug resistant were found in 65% married patient in our study. This may be attributed to the fact that married people used to consult health care centre early by their counterparts so as to live a healthy life. Married women reported abandonment, isolation within the household and a lack of proper care from family members, particularly in-laws. Bhatt G et al found in their study that 67.9% were married. Distribution of DR-TB patients on basis of type of family and environment 78% of the patients belonged to joint family and rest 22% were from nuclear family. The reason for this is that still in India, joint family system is more common in India. Depending on the type of house, majority 37% patients were living in kaccha house followed by patients living in pakka house 36%. Only 26% patients were living in semipakka house. Kachha and semipakka house denotes lower socioeconomic status of the family which led to under nutrition, poverty. These factors indirectly responsible for occurrence of the tuberculosis. 66% were lives in overcrowded area in our study, Bhatt G et al found overcrowding only in 47% patients. Regarding socio-economic factors, majority of Drug resistant TB patients were from low socioeconomic status, 42% patients belonged to upper lower class followed by lower middle 31%. About 18% belongs to lower class. It reveals that patients from low SES get easily reinfection from outside environment due to poverty and undernutrition. Bhatt  shown that there is about two-times increased risk of infection, progression to tuberculosis and death. Similarly alcohol consumption increases to about three-times the risk of disease associated with consumption >40 g per day. In our study more than one third 36% of the patients were present smoker, only 22% of the patients were alcoholics. Previous treatment history improper treatment in the past, poor patient compliance due to various factors and poor prescribing practices remain the most important risk factors for acquired drug resistance. In our study, among 100 Drug resistant TB pts. 46% were relapse, 35% were defaulters and 19% were failure. In the study done by Bhatt G et al found default in 30.9%, followed by relapse in (28.4%), failure in 22% cases. Clinical features the following symptoms were seen in the patients of the study group -Fever, Cough with or without Expectoration, Breathlessness, Chest Pain, Haemoptysis, and Weight Loss. Most common symptom is cough with or without expectoration is present in 74 patients, followed by fever present in 67 patients, shortness of breath present in 46 patients, 23 and 26 patients having hemoptysis and weight loss, 20 patient had also complaint chest pain. Bhatt G et al found 97.5% patients presented with cough with expectoration was the most common symptom, Other symptoms were fever (95.1%), anorexia and weight loss in (91.4%), breathlessness (38.3%), hemoptysis (23.5%) and chest pain (22.2%). In our study, 11 patients with mono resistance to Rifampicin, 77 patients resistant to R+H , 6 patients with resistant to H+R+S, 3 patients resistant to H+R+E and 1 patients with resistant to R+H+L+A(XDR).
Mono resistance to Streptomycin and Isoniazid was not detected in our study. Sharma et al found 36 patient were MDR, 3 patient were resistant to Rifampicin and 4 patient resistant to H+R+S in their study. (73) Various studies indicate varying data regarding the drug resistance pattern in India. Therefore a large scale nationwide study is required which will give the true picture of the magnitude of this drug resistance menace and also help the authorities in policy making and implementation of area specific programs.

Conclusion
 Most (87%) of the TB patients belonged to productive age group (18-55yrs). This may be attributed to the fact that productive age group people are the breed earners for their family.  When it comes to gender of the MTB TB patients, majority were males (82%) while more than one-fourth (18%) of the patients were females. This could be due to more exposure of males to working environment, which gives higher chances to come in contact with infectious TB patients.
 As far as religions wise distribution of MTB TB patients were concerned, more than half (59%) of the patients were Hindu followed by (29%) patients, belongs to Muslim.
 Majority (65%) of the TB patients belonged to rural background and (35%) of the patient were from urban area. In rural area, there is lack of qualified health care professionals and lesser availability of health services.
 As far as literacy status of the study population was concerned, majority (31%) of the patient had illiterate and lower education up to Middle school respectively. This finding reflect that people with lower literacy status were most vulnerable group.
 On the basis of occupations, self employed person (22%) followed by industrial/factory labours 19% and farmer 18%. 12% patients were housewives. Only few patients were student (8%), daily wages and in private job 4% each. 3% patient having govt. job. This reveals that farmers and labours were more vulnerable for getting infection with Tuberculosis  Depending upon the marital status of study population, married patients were TB patients in majority (65%) of the cases.
 On the basis of type of family, over two third (78%) of the patient belonged to joint family and rest (22%) were from nuclear family. It may be due to the fact that still in India, joint family system is more common.
 Out of 100 MDR TB patients, majority (42%) of the MDR TB patients belonged to Upper lower SES. As lower SES are most vulnerable group to be infected with tuberculosis infection due to poverty, ignorance and lack of health care services.
 Depending on the type of house, approximately half (37%) of the patients were residing in kaccha house followed by pakka house (36%). 27% residing in semipakka house.
 As overcrowding is important established risk factor tuberculosis. It was also evident from the