Research Projects

1.  OR titled “Framework for TB care in Prisons”.

A project titled “Framework of TB care in prisons” is being managed by NDTB and the State TB Cell. Aim of this project is to estimate the burden of TB among prison inmates at Tihar Jail, frame the operational modalities for early detection of TB and drug resistant TB at Tihar Jail. Lastly, to mobilize standardized TB care practices among the jail inmates (during their stay in prisons and adequate referral thereafter). Talks are on with the Tihar jail officials to take up this project.

2.  Active Case Finding Campaign of Tuberculosis among People Who use  intravenous Drugs in New Delhi.

Objective of the OR is a) Early suspect of TB b) Early diagnosis c)Treatment preparedness d)Link to Treatment and Care. Targeted Population : Person who Inject drugs in the area of Delhi of Jamuna Bazar, Hanuman Mandir, CP of New Delhi. Estimated number of population will be from field area of two target intervention centres of DSACS project which is approximately 1500. Activities proposed: a)Training/Orientation for the team b) Community meeting on TB awareness c) 4’s TB Screening on of 1500 PWID in two given sites d) Accompanied referral who is suspected for TB e)Treatment preparedness and treatment follow ups for TB positive clients.

3. Mapping of anti mycobacterial drug resistant hotspots under Revised National Tuberculosis Control Programme (RNTCP) in Delhi state.

Objective of the OR is a) To estimate the prevalence of 1st & 2nd line drug resistance in PTB cases in Delhi state. b)To analyze the effect of drug resistance in the treatment outcome of the corresponding patients. c)To map the hotspots of drug resistance pattern in Delhi state. Retrospective data from 25 chest clinics of Delhi state for 2015 will be collected. The patient recruitment, diagnosis and treatment were done as per RNTCP guidelines. Resistance pattern of 1st/2nd line will be collected. Data analysis: will be done using SPSS v20. GIS mapping: ArcGIS software will be used for mapping of drug resistant hotspots.

Effect of counselling intervention on outcome among MDR TB patients in Delhi.

Objective of the OR is Effect of the counseling intervention will be assessed by a) Treatment adherence among DRTB patients. b) Loss to follow up among DR TB patients c)To provide psycho social support to DRTB patients and their family members d)Early detection of TB among household of patients. e) Linkage the patient with existing social support services. Methodology would be a) Baseline data will be collected from RNTCP records of three years. b)Trained counsellar will be recruited at LN DRTB Centre. c) The counsellar will provide concurrent facility and home based counseling to all MDR TB patients currently on treatment using a pre-structured module. d) Counselor would also liaison with district/sub-district RNTCP staff. e) counsellar will interact with MDR TB patients once in 15 days in IP & once for 1 month in CP.

5.  Delhi TB warm line consultation service

An expert consultation platform with an integrated IT support system which proposes to address provider’s clinical and programmatic TB questions. Specifically targeting private physicians and complicated drug-resistant TB is the TB ‘Warm Line. It is a telephone /email / web page based support line, answered by medical professional who answer complicated queries, offer referrals and comprehensive feedback to every caller. This is a non-crisis and non-emergency telephone/email service with a 24 hour turn-around-time for call back. Aim: The Warm line system, envisions TB notification and appropriate TB care for all the patients and their families residing in Delhi. Objectives are

(1)       To provide timely and appropriate expert opinion to private sector providers as per Standards for TB Care in India.

(2)       To improve patient care and outcomes through access to expert consultation.

(3)       To boost private sector notification through engaging the private sector through the provision of expert consultation and

(4)       To link private providers to the ECHO platform for clinical consultation, training and education.

6.   “Comparative yield of Mycobacterium tuberculosis by molecular diagnostics in individual respiratory specimens versus pooled specimens for diagnosis of pulmonary tuberculosis in children”

It will be a Comparative cross-sectional study. 200 Children aged 1 mo- 14 y, suspected to suffer from pulmonary tuberculosis will be included in the study. Inclusion criteria would be :-1. Fever or persistent cough or both for 2 weeks, with or without a) 5% weight loss in past 3 months,b) History of contact with suspected or diagnosed case of active TB, AND 2. Radiological abnormality in the chest skiagram. Exclusion criteria (any) a) Active sputum expectoration, b) Arterial oxygen saturation less than 92 % on room air. 12 months - Period which may be needed for enrolling the case.3 months - Period which may be needed for collecting and analysing the data.

MD/ Ph.D Thesis/ M.Sc. Dissertation conducted

1.    Clinical correlates of drug sensitivity pattern in children with tuberculosis : A  cross sectional study

(MD Thesis of PG student of Department of Pediatrics, Lady Harding Medical College, New Delhi)

 Childhood TB can be used as a sentinel marker to evaluate the effectiveness of a TB control programme It is seen that the pattern of drug resistance in children in a community generally mirrors that of the adult population. Children rarely have acquired resistance because childhood TB is usually pauci bacillary with small organism load. Hence it is unlikely that resistant mutants will occur and be selected.. Surveillance of drug resistance is therefore essential because trends in primary drug resistance or initial drug resistance provide an indication of the effectiveness of the treatment regimen .It is evident from the literatures that there is paucity of information on drug sensitivity pattern of isolates from children with TB especially in India. Therefore this study was carried out to observe pattern of drug sensitivity and emerging drug resistance in children with TB. Children with 0-14 years of age diagnosed with TB (free from known immunodeficiency and serious illness) were included in the study. Mycobacteriological examination like Xpert MTB Rif, Line Probe Assay and MGIT Culture and DST were carried out.  Results analysed  and thesis submitted.

2.  To study the role of Cartridge Based Nucleic Acid Amplification Test (CBNAAT) in early diagnosis of pulmonary tuberculosis and primary drug resistance in HIV positive patients

(MD Thesis of PG student of Department of Medicine, PGIMER, Dr. Ram Manohar Lohia Hospital, New Delhi)

Studies have shown that pulmonary TB (PTB) in HIV positive patients remains the most common opportunistic infection in India ranges from 17% to 23%. Sputum microscopy in HIV positive patients is found to be less reliable in diagnosis of TB. Further, increasing number of patients with drug resistant tuberculosis (DR-TB) creates more challenges in its treatment. Conventional diagnosis of DR-TB relies on bacterial culture and drug susceptibility testing, a slow and cumbersome process. Thus, it is very important to identify PTB at an earliest so that it can be managed appropriately. Cartridge Based Nucleic Acid Amplification Test (CBNAAT) is one of a recently developed diagnostic modality which can simultaneously detect TB and perform drug susceptibility testing of one of the key drug – Rifampicin within few hours.  So, the present study was carried out to study role of Cartridge Based Nucleic Acid Amplification Test (CBNAAT) in early diagnosis of pulmonary tuberculosis and primary drug resistance in HIV positive patients. 100 HIV positive subjects greater than 18 years of age presented with symptoms/ x-ray suggestive of TB were included in the study. Mycobacteriological examination like Xpert Rif and MGIT Culture of all the subjects were done. Results generated,  analysis done and thesis submitted.

3Rapid screening of second line anti tuberculosis drugs resistance among MDR TB suspects by Liquid DST (MGIT 960) and comparative evaluation with Solid Proportion Method.

(PhD thesis submitted to Department of Life Science, Jaipur National University, Jaipur, Rajasthan)

 Diagnosing XDR-TB earlier among MDR-TB will lead to more rapid implementation of the best therapy for given patients. Therefore this study was initiated with the objectives, a) Screening of Kanamycin and Ofloxacin resistance in suspected MDR TB cases by Liquid DST method (MGIT 960) and Standard proportion method (Solid LJ DST), b) Comparison of sensitivity and specificity of Liquid DST (MGIT 960) for Kanamycin and Ofloxacin with Standard proportion method (Solid LJ DST), c) Evaluation of Diagnostic accuracy of both the methods in discordant results for the detection of XDR-TB, d) Detection of mutations imparting discordant resistance by DNA sequencing.

In this study, all  specimens from MDR TB suspects were subjected to sputum-smear microscopy for acid-fast bacillus (AFB) by fluorescence microscopy. All sputum smear positive specimens were tested for primary drug susceptibility by Line Probe Assay (LPA) method while sputum negative samples were directly cultured on MGIT system and when culture become positive these samples were subjected to LPA.

Diagnosed MDR specimens were further tested for drug susceptibility testing (DST) by MGIT 960 as well as by LJ proportion method for two  second line drugs namely ofloxacin and kanamycin.

Study completed and results analysed. It was found that liquid culture system is more rapid and sensitive.  Because of this, the XDR cases detected were put on treatment earlier.

4 GENETIC POLYMORPHISM OF RARE MUTATIONS IN RIFAMPICIN RESISTANCE OF MYCOBACTERIUM TUBERCULOSIS INFECTED PATIENTS

PhD thesis submitted to School of Life Sciences at Jaipur National University, Jaipur, India

 Genetic polymorphism is the occurrence of two or more alleles at one locus in the same population, and each with appreciable frequency.It is therefore important to identify the genetic origins of M. tuberculosis inter strain pathobiological differences in order to progress the eventual association of strain genotypes with patient clinical phenotypes. Several studies showed frequency of mutations outside RRDR region (hot spot) and it is also present in Indian M. tuberculosis isolates but their role and impact in polymorphism is not yet well studied. Therefore, in the present study  attempts were made to rapidly screen drug resistance among smear positive sputum samples  obtained from different parts of Delhi by the use ofLine probe assay( LPA).

 The results were compared with that of the phenotypic drug susceptibility test (MGIT 960 DST) to demonstrate the sensitivity, specificity, accuracy  and turn around time of LPA . The virulence of Mycobacterium tuberculosis and its genetic polymorphism prevalence in clinical isolates was studied through band pattern analysis in DNA strips of Line Probe Assay. DNA Sequencing was performed to confirm the mutationsreported in this study which also confirmed Novel mutations.. The presence of uncommon mutations confirmed genetic polymorphism that may require treatment targeted at both drug-resistant and drug-susceptible phenotypes for the better management of patients with MDR-TB.

5. Drug susceptibility testing of Multi-drug resistant and mono rifampicin resistant M. tuberculosis isolates against 2nd line anti tuberculosis drugs and molecular epidemiology of XDR strains using Spoligotyping.

PhD thesis submitted to School of Life Sciences at Jaipur National University, Jaipur, India

Tuberculosis is a disease as old as mankind, probably older. The resurgence of interest in this disease may, therefore, seem strangely out of place. The emergence of DR-TB has jeopardized global TB control achievements and threatened the accomplishments of the WHO End TB Strategy. Antimicrobial resistance (AMR) has become one of the dominating, and most pressing, global concerns in public health. Multidrug-resistant TB (MDR-TB, defined as resistance to, at least, rifampicin and isoniazid) and rifampicin-resistant TB (RR-TB) are especially devastating. Globally, the treatment success rate among patients with MDR-TB varies between 49% and 65%, which could worsen with increased resistance to second line drugs. This study was conducted with the intention of knowing the baseline pattern of drug resistance among the presumptive DR-TB patients who had not been previously exposed to second line drugs in form of anti-tuberculous therapy and to perform the molecular epidemiology of XDR-TB isolates identified using Spoligotyping.

Sputum samples from presumptive drug resistant TB cases were tested for susceptibility against Isoniazid and Rifampicin using Line probe assay. The MDR-TB and RR-TB isolates identified were further tested for susceptibility against second line anti-tuberculosis drugs (kanamycin, capreomycin, levofloxacin, moxifloxacin, Linezolid, and Clofazimine). All the XDR strains identified were subjected to genotyping using Spoligotyping.

6. Diagnosis of MDR & XDR-TB in Smear Negative pulmonary and Extra pulmonary specimens from drug resistant TB suspects

(Ph.D thesis of student Maharaj Vinayak Global University, Jaipur)

 A lot of work has been done to detect drug resistance on smear positive TB patients but sparse data is available on smear negative pulmonary cases . Due to low mycobacterial load in early stage of infections, such patients are declared as smear negative even though they are actually positive. Such patients continuously spread infection in their close vicinity.  Therefore, this study was initiated with aim to determine the recovery of M. tuberculosis in smear negative samples through liquid culture using MGIT 960 and also to determine the number of drug resistant cases through Line Probe Assay (LPA) on cultures.  DST for number of second line drugs using MGIT was also done on positive cultures. 

This study has been completed and data analysed. The results revealed that there were MDR TB cases identified among the smear negative cases. Some of them turned out to be XDR TB cases. Spoligotyping was done for these cases and the results showed that majority of the strains belong to the commonly identified group.

Ongoing thesis work

7. Role of Polymerase Chain Reaction (PCR) and Mycobacteria Growth Indicator Tube (MGIT) in The Diagnosis Of Cutaneous Tuberculosis

(MD thesis of student from Department of Microbiology, Maulana Azad Medical College, New Delhi)

There is paucity of data on comparative study between conventional diagnostic methods, Histopathology, Mycobacteria Growth Indicator Tube (MGIT) and Polymerase Chain Reaction (PCR) for diagnosis of cutaneous tuberculosis in literature till date from India. Therefore this study was started with objectives to identify Mycobacterium tuberculosis from cutaneous tuberculosis case by Polymerase Chain Reaction (PCR), Mycobacteria Growth Indicator Tube (MGIT)and conventional diagnostic methods and also to compare the results of Polymerase Chain Reaction (PCR) with Mycobacteria Growth Indicator Tube (MGIT) as reference standard.

All patients attending the Dermatology out-patient/in-patient departments of Lok Nayak Hospital with clinical features suggestive of cutaneous tuberculosis will be entitled to be enrolled in this study as per the  inclusion and exclusion criteria and saples from these cases will be subjected to Z-N Microscopy, Solidculture using the LJ media, Liquid culture using the MGIT960 system ,in house polymerase chain reaction and histo pathological investigations.

 

8. A Study of Uterine and Tubal Factors in Causation Of Infertility In Women With Extra genital Tuberculosis.

(MD thesis of student for Department of obstetrics and gynaecology, Lady Harding Medical College & Associated Hospitals, New Delhi)

 

Genital tuberculosis is an important cause of infertility in women. Female genital tuberculosis is always secondary to primary foci elsewhere in the body. This may remain asymptotic and latent for long period contributing towards infertility. The diagnosis is often difficult due to its paucibacillary nature. Many studies have associated symptomatic genital tuberculosis with infertility, however there is paucity of literature on impact of extra genital tuberculosis on fertility of women. India being a developing country has a high prevalence of pulmonary tuberculosis. Hence this study was srarted with objectives (i)To study the uterine and tubal factors contributing to infertility in women with extragenital tuberculosis.(ii) To assess women with past history of extragental tuberculosis for uterine and tubal factor infertility.(iii)To assess women without any history of extragental tuberculosis for uterine and tubal factory infertility.

 All women presenting the infertility clinic will be subjected to routine infertility work up. This will include detailed history and examination, blood investigations (CBC with peripheral smear with ESR), Mantoux test, chest X-ray, husband semen analysis, pre-menstrual endometrial biopsy, ultrasound pelvis and Day 21 progestrone. All women will be screened for any evidence of extra genital TB through history and investigations like smear microscopy, culture and histo pathololg will be done Clinical samples will be sent for GeneXpert testing and also for liquid culture.

9. ToStudy The Association Between Clinic-Demographic Profile And Drug Resistance in Musculo-Skeletal Tuberculosis.

(Ph.D thesis of student Maulana Azad Medical College, New Delhi)

There is paucity of data regarding the pattern of drug resistance in cases of musculoskeletal TB in India, especially new cases. There is paucity of data regarding the pattern of drug resistance in musculoskeletal tuberculosis in India. Therefore this study was started with objectives (i)To estimate the prevalence of drug resistance in musculoskeletal tuberculosis(ii)To compare and associate clinical features in patients with or without drug resistance in musculoskeletal tuberculosis.(iii)To compare and associate social-demographic profile in patients with or without drug resistance in musculoskeletal tuberculosis.

 A total of 100 patients will be included in the study. All cases selected as per the above inclusion and exclusion criteria will undergo the following evaluations like Demographic profile, Clinical symptoms, Clinical signs, Haematological investigation, Radiological investigations, Liquid culture, DST, Lowenstein Jensen medium (solid culture)