1. What data in particular will be shared?
   Response - All of the individual participant data collected during the trial, after de-identification.
   


2. What additional supporting information will be shared?
   Response -  Study Protocol
   Response - Clinical Study Report
   
   
3. Who will be able to view these files?
   Response - Researchers who provide a methodologically sound proposal.
   


4. For what types of analyses will this data be available?
   Response - Any purpose.
   


5. By what mechanism will data be made available?
   Response - Proposals should be directed to [harshith.beeravolu@gmail.com].
   


6. For how long will this data be available start date provided 04-05-2025 and end date provided 04-12-2025?
   Response - Beginning 9 months and ending 36 months following article publication.
   


7. Any URL or additional information regarding plan/policy for sharing IPD? 
   Additional Information - NIL

Datta Meghe Institute of Higher Education and Research

Jawaharlal Nehru Medical College,

Sawangi (Meghe), Wardha

Department of Respiratory Medicine

TO STUDY THE PATTERN OF DRUG RESISTANCE IN PATIENTS PRESENTING WITH EXTRA PULMONARY TUBERCULOSIS AT AVBRH

CANDIDATE

Dr. Beeravolu Harshith Reddy

Department of Respiratory Medicine

Datta Meghe Institute of Higher Education and Research

GUIDE

Dr. Babaji Ghewade

Professor and HOD

Department of Respiratory Medicine

Datta Meghe Institute of Higher Education and Research

HEAD OF THE DEPARTMENT

Dr. Babaji Ghewade

Professor & HOD

Department of Respiratory Medicine

Datta Meghe Institute of Higher Education and Research

TITLE

TO STUDY THE PATTERN OF DRUG RESISTANCE IN PATIENTS PRESENTING WITH EXTRA PULMONARY TUBERCULOSIS AT AVBRH

By-

Dr. Beeravolu Harshith Reddy

Junior Resident,

Dept. of Respiratory Medicine,

J.N.M.C., Sawangi(Meghe),

Wardha , Maharashtra

Guide –

Dr. Babaji Ghewade

Professor and HOD

Dept of Respiratory Medicine

J.N.M.C., Sawangi (Meghe)

Wardha, Maharashtra

Date of Submission :

INTRODUCTION

Extrapulmonary tuberculosis EPT can affect all organs. • Its diagnosis is often challenging, especially when the lung is not involved. Some EPT locations, such as when the central nervous system is involved, are a medical emergency, and some have implications for treatment options and length Pathophysiology: Extrapulmonary tuberculous disease occurs as result of contiguous spread of tubercle organisms to adjoining structures, such as pleura or pericardium, or by lympho haematogenous spread during primary or chronic infection. Prevalence : Extrapulmonary TB may occur in multiple sites, with relative frequencies of 42 percent for lymphatic, 18 percent for pleural, 12 percent for bone or joint, 6 percent for genitourinary, 6 percent for meningeal, 5 percent for peritoneal, and 11 percent for other sites. Involvement of the meninges is more common in young children than in other age groups present in approximately 4 percent of children with TB, and the incidence of TB in the remainder of the extrapulmonary sites increases with age. Extra pulmonary tuberculosis is usually paucibacillary, and any treatment regimen effective in pulmonary tuberculosis is likely to be effective in the treatment of extra pulmonary tuberculosis as well. For the purposes of treatment, extra pulmonary tuberculosis can be classified into severe and non-severe forms. Severe forms include meningeal tuberculosis, spinal tuberculosis, neuro-tuberculosis, abdominal tuberculosis, bilateral pleural effusion, pericardial effusion, and bone and joint tuberculosis involving more than one site. Extra pulmonary tuberculosis of other sites is classified as non-severe. There are few reports of the use of short-course chemotherapy in the treatment of assessing the efficacy of treatment of extra pulmonary tuberculosis has led to varying durations of treatment, and there have been relatively few controlled clinical trials. Assessing the efficacy of treatment of extrapulmonary tuberculosis has led to varyingdurations of treatment, and there have been relatively few controlled clinical trials. The principles involved in the diagnosis and management of extrapulmonary tuberculosis have therefore evolved mainly from experience gained in randomized controlled clinical trials on pulmonary tuberculosis. However, studies on extrapulmonary tuberculosis tuberculosis of the spine, tuberculous lymphadenitis, abdominal tuber-culosis, and brain tuberculoma have clearly established the efficacy of short-coursetreatment 6–9 months in both children and adults , with the overall favourableresponse varying from 87 percent to 99 percent. Intermittent regimens have beenshown to be as effective as daily regimens. For the severe forms, it is preferable to treat with four drugs in the initial intensivephase and, if required, the total duration of treatment can be extended to 9 months,especially in tuberculous meningitis and neuro-tuberculosis. Steroids should be givenin case of tuberculous meningitis with neurological impairment, massive pleural effusion, or tuberculous pericarditis. Lymph nodes can enlarge, persist, and becomesuperinfected with bacteria in the course of tuberculosis treatment. Generally, nomodification or prolongation of the tuberculosis treatment regimen is indicated. Even though treatment gives good results in most forms of extrapulmonary tuberculosis, there are a few exceptions, such as meningitis and spinal tuberculosis, in which the outcome depends on early diagnosis. In tuberculous meningitis, even with short-course treatment the outcome is related to the stage of the diseaseat the time treatment is started; only a minority of patients with severe disease recover completely. Predictors of poor outcome are younger age and advanced stage; neurological sequelae are directly related to the stage of the disease and the duration ofsymptoms before admission. Similarly, in patients with spinal tuberculosis, the time taken for neurological recovery is not related to the type of treatment regimen but appears to be influenced by factors such as initial motor power, presence or absence of other infections. The long-term efficacy of short-course treatment regimens of 6–12 months’ duration in various forms of extrapulmonary tuberculosis has been studied .were followed up systematically for 5–10 years. Relapse rates during long-term followup were less than 4 percent in all studies reviewed, demonstrating the adequacy of shortcourse treatment regimens for extrapulmonary tuberculosis.

RATIONALE

1. Hard to Diagnose: Detecting EPTB (TB outside the lungs) is tough. It often shows vague symptoms and needs invasive tests for confirmation. Delayed or wrong diagnosis can lead to wrong treatment, causing drug resistance.
2. Treatment Challenges: Treating EPTB requires long courses of antibiotics. This increases the chance of treatment being stopped early due to side effects, patient not following instructions, or problems in healthcare systems. Stopping treatment too soon can lead to drug resistance.
3. Limited Treatment Choices: There aren’t many antibiotics for EPTB compared to regular TB. Using fewer options increases the risk of resistance if not used carefully.
4. Weakened Immune System: Many EPTB patients have other health problems that weaken their immune system. This makes antibiotic treatment less effective and raises the risk of resistance.
5. Sharing Resistance: EPTB patients might pick up drug-resistant TB strains from others with TB. This happens because of contact with people who have drug-resistant TB and can lead to patients developing resistance themselves.
6. Spreading Resistance: Drug-resistant TB can spread in communities or healthcare settings, especially where infection control isn’t good enough. This makes it easier for EPTB patients to get infected with drug-resistant strains.

To prevent drug resistance in EPTB, it’s important to diagnose it early, make sure patients complete their treatment, improve access to effective drugs, and strengthen infection control measures. Also, research for better diagnostics, drugs, and vaccines is crucial

.

AIMS AND OBJECTIVES

AIM:

To Study The Pattern of Drug Resistance In Extra Pulmonary Tuberculosis At AVBRH.

OBJECTIVES:

• To study the clinical profile of Extra Pulmonary Tuberculosis at AVBRH

• To study the pattern and prevalence of drug resistance in EPTB.

• To study the correlation of co-morbidities with resistance in EPTB

REVIEW OF LITERATURE

S. Thaseen et al. Has conducted a study and concluded that Point estimates for RMP resistance in new EPTB cases of 2.7 percent (95 percent CI 0.9–6.2) was lower than the prevalence in new PTB cases of 4.2 percent (95 percent CI 3.2– 5.3) but this difference was not significant. A good correlation was reported between culture-based phenotypic and genotypic DST. However, caution is warranted for treatment decisions based on RMPresistance results using Xpert in clinical specimens from new EPTB cases with a very low level of bacterial load. If feasible, culture-based DST should be applied for the diagnosis and confirmation of drug resistance.(1)

Emmanuel Miiro et al.DR-epTB is common and people with DR-epTB tend to be young with HIV co-infection and/or diabetes mellitus. Adenitis is the commonest form of DR-epTB. DR-epTB posts worse treatment outcomes compared to pulmonary TB and drug-susceptible EPTB. There is a need for site- specific treatment regimens and outcome definitions for DR-epTB.(2)

Radha Gopalaswamy et al. The “End TB Strategy”, established by the WHO, aims to reduce TB deaths by 95 percent and new cases by 90 percent in 2035. Achieving this goal involves applying improved diagnosis, treatment, and better vaccines to fight against TB. In addition to PTB, it is imperative to address the impact of EPTB and its rising drug resistance on global health and the economy to control these diseases worldwide. An early and accurate diagnosis and drug susceptibility testing are essential to initiate the correct treatment regimen without delay(3)

Getu Dirba et al.In conclusion, our systematic review showed a high proportion of RIF, INH, and MDR-TB among EPTB patients in Ethiopia. The review showed that the prevalence of extrapulmonary DR-TB has continued to become a serious public health problem in Ethiopia. To our knowledge, this finding could help the programmatic management of the disease within the context of the National TB Control program. Clinicians should request drug susceptibility testing for all patients with presumptive EPTB to detect drug resistance. Our findings highlight the need for more studies evaluating drug resistance in EPTB patients(4)

Unnati Desai et al. EP DR-TB is a heterogeneous subgroup consisted of 4.4 percent among our DR-TB cases. The treatment completion rate was very high (81.6 percent). Thus, we identify a subgroup with a good prognosis. We document the efficacy of shorter regimens in EP TB.(5)

MATERIALS AND METHODOLOGY

• Study Setting : The Study Will Be Conducted In AVBRH, A Tertiary Care Hospital, Attached To Jawaharlal Nehru Medical College , Situated In Rural Area Of Sawangi (Meghe ), Wardha, Central India

• Study Design-:Observational And Cross Sectional Study

• Study Duration: January 2024 to December 2025

• Study Population: Patients Referred To Dots Centre/Respiratory Medicine OPD At AVBRH With Extra Pulmonary Tuberculosis

• Study Setting : AVBRH

• Sample Size : 45

Cochran formula for sample size estimation:

Z equals one point nine six  

P equals Proportion of EPTB patients had DR -epTB  

equals thirteen percent equals zero point one three  

d equals Desired error of margin equals ten percent equals zero point one zero  

n equals one point nine six squared times zero point one two times one minus zero point one two  

divided by zero point one zero times zero point one zero  

equals forty point five six  

equals forty five participants needed in study  

Study Reference: Emmanuel Miiro et al  

Formula Reference: Cochran W.G. et al(one thousand nine hundred seventy seven)  

Statistical Methods: Student’s t test, One way ANOVA  

Software Used : SPSS twenty seven point zero version  

Study Design : Cross sectional observational study design  

INCLUSION CRITERIA  

• All adult greater than eighteen years patients presenting with extra pulmonary tuberculosis.  

EXCLUSION CRITERIA  

• Not willing to give consent  

• Non-compliant patient.  

BUDGET / SOURCE OF FUNDING  

No Separate Funding Is Required However Will Apply For Thesis Grant under NTEP/ICMR