Director's Desk (2019-2020)
Over the past year, the institute has consolidated its research efforts towards developing shorter, more effective regimens for both drug-sensitive and drug resistant pulmonary tuberculosis.
The Clinical Research division launched a Phase 3 randomized TB preventive vaccine clinical trial under the guidance of ICMR, New Delhi. Eligible household contacts of newly diagnosed pulmonary TB patients are enrolled and vaccinated with one of the two new TB vaccine namely VPM1002 or MIP. Clinic also launched two new randomized drug trials to determine the effect of increased dosing of rifampicin and host-directed therapy of metformin when given daily along with first-line anti-tuberculosis drugs. The department also launched two trials for drug resistant TB using shorter MDR regimen (STREAM and BEAT studies). The institute thus continues its quest for better treatment options for all forms of TB and will pursue the investigation of new drugs as they become available.
Research is also ongoing for the management of minimal pediatric TB, TB meningitis in children, pediatric contact follow-up of MDR TB patients and pulmonary non-tuberculous mycobacteria. The clinical division has ongoing collaboration with the Tamil Nadu state government medical colleges, TNSACS and Corporation of Chennai. Patients attending these centers are screened and enrolled into clinical studies, and faculty from these centers are included as co-investigators.
Department of Epidemiology is involved with various prevalence surveys for TB. Earlier they were conducted in Tiruvallur district which have been completed in Chennai city also. The department is also involved in conducting a TB prevalence survey among homeless persons and in the prisons of Chennai city. Currently the department is involved in a nation-wide TB prevalence survey, initiated in 2019, where a total of 5,00,000 individuals from 625 clusters would be screened for tuberculosis utilizing mobile vans equipped with x-ray machines and CBNAAT.
Department of Statistics supports the various clinical and basic science research activities of the institute. Apart from these supporting activities and involvement in data management, the department also has multiple research interests, especially in the areas of modeling, survival analysis and geospatial mapping. Currently they are involved with estimation of the burden of TB in India.
Socio-behavioral research division conducted a targeted intervention to expand and strengthen TB control in tribal populations under RNTCP (TIE-TB project); evaluated 99DOTS novel strategy for monitoring adherence to TB medication and evaluated the acceptability and accuracy of MERM to monitor drug adherence in MDR-TB patients. They continue to be involved in estimating the burden of TB among tribal population and strategies to reduce sexual risk taking behavior among men who have sex with men. Community involvement in TB control is being explored including utilization of school students as TB ambassadors.
Department of Bacteriology continues to perform the duties of a Supranational and National Reference laboratory for mycobacteriology. Patent applied and we have obtained for expression and purification of Phage lysin to improve sensitivity of M.tb rapid diagnostics (Patent No. 269659). Further bioprocess development and preclinical evaluation of novel anti-TB antibiotic “transitmycin” is in progress. Multicentric validation of indigenous kit ‘TB-detect' and “TrueNAT' is in progress. Whole genome sequencing and Host directed autophagy stimulation studies focusing on novel diagnostics and therapeutics are in progress. Various indigenously developed technologies for the diagnosis of adult , and pediatric PTB as well as the screening and validation of medicinal plants to identify inhibitors of efflux pumps of M.tb . are in progress. Bacteriology laboratory automation system was installed.
Department of Biochemistry and Clinical Pharmacology was bifurcated in November 2018 into two new departments – Department of Clinical Pharmacology and Department of Biochemistry.
Clinical pharmacology department continues to conduct pharmacokinetic and bioavailability studies of first-line and second-line anti-TB drugs as well as anti-diabetic and anti-hypertensive drugs by HPLC. Pharmacogenetics is also expanding and we have developed molecular assays to test for genetic polymorphisms in drug metabolizing enzymes for many anti-TB and antiretroviral drugs. This department continues to generate evidence for the national programme in India
Biochemistry department plays a very vital role in supporting the various research projects conducted at NRT by providing high quality diagnostic and laboratory results. The laboratory participates in External Quality Assurance programs supported by Bio-Rad Pvt. Ltd. All staff in this department are GCLP certified. Currently, upgradation of clinical biochemistry data reporting is in progress.
The HIV laboratory performs three types of functions – providing all the basic support laboratory investigations for NIRT study patients, serving as a referral laboratory for NACO for the southern region (DNA and RNA PCR) as well as engaging in basic research. The HIV lab is a Regional Centre of Excellence for NACO and provides results for the early infant diagnosis program and also viral load results for patients failing first line ART, thus supporting the AIDS Control program in Tamil Nadu. Apart from drug resistance surveillance in the HIV population, the lab is engaged in research on HIV-1 subtype C strain and also HIV-2. They also recently completed analysis of humoral and cell mediated immune responses in HIV-1 subtype C phase 1 vaccine trial participants. HIV laboratory also hosts a biorepository for the samples from the Cohort for TB Research by Indo-US Medical Partnership and the REPORT consortium Research in the Immunology department covers different aspects of the immunology and molecular biology of TB. Focus areas include the role of host genetics (cytokine polymorphisms, Vitamin D receptor polymorphisms) in susceptibility to TB, early bactericidal activity of anti-TB drugs, whole genome sequencing and transcriptomic of M.tb from bovine and human origin, Crohn's disease and association of M.avium subspecies and Gene-knock out studies. They also carry out the characterization of mycobacterial intermediary metabolic enzymes as novel drug targets by comparative omics. They are part of many international collaborative projects like building laboratory capacity for next generation sequencing (with CDC, USA); anti-mycobacterial resistance in TB with a focus on newer diagnostic and therapeutic assays (Cambridge, UK).
The International Centre for Excellence in Research has focused on the immunological changes occurring when parasitic infections like filariasis occur along with latent or active TB. Further, immunology of extra pulmonary TB, diabetes and TB are also being studied.
The Electronic Data Processing division plays a pivotal role in the conduct of epidemiological surveys and provides data entry/verification support for several studies conducted at the institute. The unit also supports the LAN facility of NIRT.
A new Department of Health Economics was established in ICMR-NIRT, Chennai in July 2018. The mandate of this department is to conduct research on economic aspects of disease with special focus on TB. They also provide technical support to other departments involved with economic evaluation of various diagnostics and therapeutics. Their mandate also includes capacity building for health economic research and practice in the country by conducting various training and workshops. This year also saw the establishment of the Regional Resource Centre for Health Technology Assessment in India (HTA-In).
The institute conducted several workshops during the year, including Pediatric TB Symposium, International Workshop on Genomics of TB and HIV, Indo-UK Workshop on Challenges of TB Research Priorities in India. A new Online Course on TB for Doctors, “Manage TB” was launched in May 2018. Our scientists served as faculty at many conferences and workshops around the country.
Around World TB day 2019, a tribute was paid to all ex-staff of NIRT “Remembering our Heroes”. This programme was conducted to honor the Heroes of TCC, TRC & NIRT who made tremendous contribution in making NIRT what it is today.
Research priorities for the future include (1) testing new drugs and adjunctive therapies for tuberculosis, (2) shortening treatment for TB in children, (3) testing of new diagnostics, (4) pharmacokinetic and pharmacogenetics studies, (5) studying risk factors for recurrence and (6) behavioral interventions to improve TB drug adherence and treatment outcomes.
Dr. Srikanth Tripathy