European Journal of Cardiovascular Medicine

Drug-resistant TB continues to be a public health crisis. Drug-resistant TB requires an understanding of the causes and their effective response. In 2020, 2.1 million people (71% of all of TB) were diagnosed with bacteriologically confirmed pulmonary TB which was resistant to rifampicin, from 61% (2.2/3.6 million) in 2019 and 50% (1.7/3.4 million) in 2018 1. It indicates a clear increase in the percentage of R/R / MDR TB worldwide. As per the national drug resistance survey 2014-2016 data, in India, MDR-TB amongst new cases were estimated at 2.84% and amongst re- treatment cases at 11.6% with total giving to 6.19% of MDR cases 2. Undernutrition and TB forms a vicious cycle, in which undernutrition predisposes the patients for getting infected with TB and if infected with TB it further exacerbates undernutrition as loss of appetite is a predominant symptom of TB3.A third of all AIDS deaths worldwide in 2018 were caused by HIV-associated TB, which claimed around 251000 lives. A whopping 84% of all TB/HIV deaths occurred in Africa. PLHIV-positive individuals have a 29-fold (26-31) increased risk of contracting tuberculosis compared to PLHIV-negative individuals. Adults and children living with HIV are hospitalized and die from TB most frequently, accounting for 20% of all HIV-related deaths worldwide.3 and as a result, of CD4 cell depletion TB can reactivate, exogenous TB bacteria can re- infect, or can become a progressive primary illness in HIV4.

Tobacco usage is connected to 38% of TB deaths. Smokers have a three times higher prevalence of tuberculosis than non-smokers. Smokers have a 3– 4 times higher risk of dying from TB than non-smokers do. In India, smoking is a factor in 50% of male TB fatalities between the ages of 25 to 69.

In comparison to non-smokers, smoking doubles the likelihood of contracting TB infection, developing the disease, experiencing recurrence of the infection, and dying from TB. Abuse of alcohol has long been linked to poor clinical results and noncompliance with therapy for tuberculosis. Alcohol abusers are more likely to stop their tuberculosis treatment early, according to numerous researches.  Alcohol is shown to reduce the ability of lymphocytes to present TB antigens, which in turn lowers antigen-specific T-cell activation. Moreover, chronic alcohol intake may inhibit cytokine formation, which has a very important role in communication between different cells for the activation, proliferation, and migration of cells, and in regulating inflammation and healing mechanisms5,6,7.

Active TB cases are significantly associated to be having anemia and that most of TB related anemia is mostly because of chronic inflammation and not because of iron deficiency. Pulmonary cavitation is one of the most frequently observed clinical characteristics in TB, accounting for 44% of adults with pulmonary TB at the time of diagnosis 8. The presence of cavitary disease is associated with treatment failure and relapse among pulmonary TB patients. Many studies showed that the presence of pulmonary cavitation is linked to the development of drug resistance during treatment 9. As per India TB report 2022, in Andhra Pradesh 1026 patients were started on shorter injectable containing regimen. Cure rate was 46% (470 patients), treatment completed was 25%, and a total of 71% had success rate,13% had died,1% had failed treatment, 6% were lost to follow up and 6% came under regimen changed.3 As India is towards “End TB strategy”, prevention of drug resistance is of very much importance, which can be achieved only by early detection, isolation and at the earliest initiation of appropriate regimen and completion of treatment. These are vital keys to interrupt on-going transmission, to prevent death and reduce chances of post-TB sequelae. As Shorter MDR regimen is among the latest additions to the MDR TB regimen, effectiveness of the regimen is to be studied among various populations and should be followed up for better outcome. As the total duration of shorter MDR TB regimen is only 9-11 months, there is more adherence to the regimen compared to twenty months of conventional MDR regimen. But whether the new regimen is as effective as it claims to be needs further studies. And also, as per 2020 PMDT guidelines, the patients with RR TB will be considered for shorter MDR TB regimen after ruling out the exclusion criteria for shorter MDR TB regimen. Hence this study was planned to study the clinical social profile of MDR/ RR TB patients and their outcomes after treated with this shorter MDR regimen.

The setting of the study was at department of Respiratory Medicine and department of General Medicine, Government General Hospital, Government Medical College, Machilipatnam. A one-year observational study was conducted during the period from January 2023 to December 2023 Objectives: 1. To know the socio-demographic profiles of the study subjects 2. To study the Risk factors, Drug resistance pattern and Treatment outcome of patients on MDR Shor term regimen. After receiving the Ethical committee clearance from the institution the study was began and the required data of MDR TB patients who were registered and had MDR short term treatment regimen during the period from January 2019 to December 2022 was collected retrospectively from the available hospital records like case sheets and patient registers etc; pertaining to their Sociodemographic profiles, Risk factors, Drug resistance pattern and treatment outcome etc;as study variables and the data was analysed and evaluated accordingly. Finally, the collected data was analyzed by using appropriate statistical tools like percentages, proportions, measures of central tendency, measures of dispersion, standard error of mean and tests of significance etc; with the help of computer software. The study results were compared and discussed in the light of published material of various similar studies belongs to different authors and there by conclusions and recommendations was framed.

Table no. 1: Age and Sex wise distribution of study subjects

 Mean  ± 2 SD = 44.89 ± 30.62 - 59.16,  P < 0.01

• Among the total study subjects 28% were male and 27.39% were female
• It was observed that the burden of the disease was more between 21-60 years of age (79.59%) with the Mean age was 52 years
• And also it was noticed that the disease burden was more among males when compared to females significantly

Table 2. Distribution of Risk factors among the study subjects

                                                 P < 0.05

• Regarding the Risk factors it was observed that Malnutrition was 48.28% followed by Previous h/0 TB 67.35%, Anaemia 59.5%, Alcoholism 40%,Diabetes 37.41%, Smoking23.8% and HIV +ve 17.68% distributed respectively.

Table 3. Distribution of Drug resistance Pattern among the Study subjects

• With reference to Drug resistance pattern maximum Rifampicin Resistance (RR) 76.87% followed by Multi drug resistance (MDR) R/R +H(B) 21% and Extensive Drug Resistance (XDR) R/R +H(B) + FQR 2% was noticed among the study subjects

Table no. 4: Evaluation of treatment outcome

• In this study regarding the treatment outcome about 46.9% were Cured followed by 20.4% were treatment completed, 19% were died during the course of treatment, 7.4% were lost to follow up, 5.4% treatment changed and 0.68% were Treatment failure as observed in this study.

In the present study out of total 147 study subjects 73.28% were male and 27.39% were female which was correlated with the findings of the other studies like Trubnikov et al10, Anh et al 11, Koirala et al12, Trebucq et al13, Abidi et al14 etc;but the other studies du Cross et al15 and Nunn et al16 reported the almost equal distribution. The mean age of the study subjects in the present study was 44.89 years and majority of the study subjects were belong to age group between 21-60 years (79.59%) which was on a par with the figures of the studies conducted by Wahid et al 17, Trubnikov et al 10, Anh et al11, Koirala et al12, Trebucq et al13 , Abidi et al14 and this age is both economically and reproductively productive age group which has a major impact on the socioeconomic condition of the family as well as the society.

Regarding the Risk factors it was observed that Malnutrition was 48.28% followed by Previous h/0 TB 67.35%, Anaemia 59.5%, Alcoholism 40%, Diabetes 37.41%, Smoking 23.8% and HIV +ve 17.68% distributed respectively. The following studies like Wahid et al17, Soeroto et al18, Anh et al11, Koirala et al12, Trubucq et al13, Abidi et al14 etc. were reported similar results regarding Malnutrition and Previous h/o TB except Trubnikov et al10 which showed lesser percent than our study but with reference to HIV + ve percentage among the study subjects, all the above studies published the similar result except Das PK et al19 4.9%,Koirala  et al12 4.3% and Anh et al11 1% respectively as lesser percentage when compared to other studies. Commonly Tuberculosis risk is two to three times higher in people with diabetes. Diabetes patients may experience unusually severe and frequent symptoms of TB. And alsoby delaying Sputum conversion and being linked to higher rates of demise, failure, and relapse beyond the end of treatment, DM also has a negative impact on the effectiveness of TB treatments. The increased probability of getting TB and poor treatment response appear to be strongly correlated with insufficient glycaemic management3. Diabetes mellitus as a comorbid condition may cause reactivation of the infection in previously treated TB cases and patients with latent TB infection. Among 147 total MDR/ RR TB cases, about (37.41%) were Diabetics whereas the studies by Trebucq et al13 28.1%, Soeroto et al18 25.4%, Das P K et al19 reported17.24% and Koirala et al12 reported 9%. And also Diabetes mellitus as a comorbid condition may cause reactivation of the infection in previously treated TB cases and patients with latent TB infection. And in addition to this our study reported 23.8% 0f smoking rate which was high whereas Wahid et al reported low smoking rate in his study because of presence of more number of females as study subjects and also might be due to sociocultural factors. Chronic tobacco exposure and other pollutants, impairs the normal clearance of secretions on the tracheobronchial mucosal surface and may thus allow the Mycobacterium tuberculosis, to escape the first level host defence mechanisms20.And regarding Alcoholism about 40% of our study subjects were habituated to alcohol because of more number of male study subjects in the study where as Trubnikov et al10 reported 18.95%. Abuse of alcohol has long been linked to poor clinical results and noncompliance with therapy for tuberculosis as alcohol abusers are more likely to stop their tuberculosis treatment early, according to numerous researches. In our study about 59.5% were anaemic which correlates with the figures of Soeroto et al18 and Trubnikov et al10. Anemia among pulmonary TB patients is thought to result from chronic Inflammation, as well as increased blood loss due to hemoptysis (blood in sputum), decreased RBC production, and poor appetite and food intake, leading to poor nutrient status21.

In this study regarding the treatment outcome, about 46.9% were Cured followed by 20.4% were treatment completed, 19% were died during the course of treatment, 7.4% were lost to follow up, 5.4% treatment changed and 0.68% were Treatment failure as observed in this study which was a similar outcome as compared to Wahid et al17, Koirala et al12, Trebucq et al13, Nunn et al16 and Abidi et al14, Aung et al22 and Anh et al11 which were all showied that treating with shorter MDR regimen was associated with very high success rates compared to previous regimens.

LIMITATIONS

The study was a hospital based and conducted in a small group of patients. Further due to impact of Covid pandemic patients coming to hospital rates were decreased. The socioeconomic status of the study population was not taken in this study. Only limited comorbidities are compared like smoking, alcoholism, Diabetes, anaemia, HIV and undernutrition. Information regarding remaining comorbidities like, Thyroid disease, Renal failure and Hepatic failure was not obtained. Glycaemic control in patients with Diabetes was not recorded, which might give information regarding DR TB disease control. And CD4 counts were not assessed in HIV patients which might have given more information regarding the immune suppression and outcome of MDR TB.

As the distribution of the disease was observed more among the male and middle & older age group study subjects, it is very important to target our intervention and preventive strategies among these groups to control the incidence and prevalence of the drug resistance TB. And also, as the risk factors and social determinants in this study were strongly associated with the study subjects, People belonging to poor socioeconomic background and other vulnerable groups are at increased risk of being exposed to poor living/working conditions and immunocompromising conditions (such as HIV, undernutrition, smoking, and drug & alcohol abuse), and having poor access to diagnosis and treatment. Poor adherence due to social and economic constraints, as well as poverty and socioeconomic inequalities are determinants that cut across all levels of the two pathways to drug-resistant TB and in addition to this in this study previous h/o TB (recurrence) was also observed at high percentage, measures to be taken to improve the drug complience and proper followup of the cases until declared as cured is very much essential.

Regarding treatment the Shorter MDR regimen is a very effective regimen for RR / MDR TB patients if used with proper inclusion and exclusion criteria and it helps in minimizing the morbidity of the MDR TB patients by limiting the duration of treatment and ensuring better compliance than longer regimens. Even though the regimen has many serious side effects like ototoxicity, renal toxicity but frequent monitoring of these side effects helps in attaining better outcomes without complications. As per new guidelines Injectables in the regimen are to be phased out from the regimen as they need medical assistance for administration and requires more resource utilisation and also the new oral bedaquiline containing shorter MDR regimen is supposed to be having better outcome than injectable containing shorter MDR regimen which needs to be validated by doing similar studies among different population groups. Further comprehensive and effective implementation of the WHO-recommended Stop TB strategy (developed from the DOTS framework), is an important approach for preventing drug-resistant tuberculosis.

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