Over the past year, the institute has consolidated its research efforts towards developing shorter, more effective regimens for pulmonary tuberculosis in HIV uninfected adults and towards defining the optimal treatment regimens for HIV-associated TB. The Clinical Research division also launched a new randomized clinical trial to shorten chemotherapy in TB lymphadenitis, enrolling patients with confirmed TB lymphadenitis. 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 in defining predictive markers for immune reconstitution syndrome, a debilitating condition commonly occurring in HIV-infected patients with advanced immunodeficiency, initiating TB and ant-HIV treatment together. Further, an NIH-funded multicentric study to identify host genetic and nutritional risk factors for metabolic syndrome and lipodystrophy in children with HIV infection, has been enrolling at 5 sites across south India. The study will look at polymorphisms in lipid metabolizing genes in HIV+ children, for the first time in India. A recently completed study also found that both iron deficiency anemia and anemia of chronic inflammation are common among these children and that iron supplementation along with antiretroviral treatment was effective in overcoming the anemia.
The clinical division has expanded its collaborative work and now has agreements with three medical colleges/research institutes, apart from the ongoing collaboration with the Tamil Nadu state government medical colleges, TNSACS and Corporation of Chennai. Patients attending these centres are screened and enrolled into clinical studies, and faculty from these centres are included as co-investigators. NIRT was identified by NACO as a centre of excellence for research and will use secondary program data for analysis.
Socio-behavioural research studies have focused on health seeking behavior and practices of vulnerable populations – both for HIV and TB. Different strategies to reduce sexual risk taking behavior among men who have sex with men, including the use of mobile technology are being explored. Further, a randomized clinical trial is testing cognitive behavioural therapy to reduce alcohol dependence and thus improve TB treatment outcomes. A study of migrant brick kiln workers was completed and showed that the prevalence of chest symptoms was high and awareness of TB was low in this group. Community involvement in TB control is being explored via the use of Self-help groups to improve case finding as well as directly observed treatment.
Clinical pharmacologic studies have been done to study adequacy of first line anti-TB drug levels in HIV infected and uninfected children with TB and the results have been communicated to the TB program managers. Further, a pilot study was undertaken in collaboration with GHTM, Tambaram to study Rifabutin levels in patients on 2 nd line ART. This is likely to lead to a larger, multicentric study across NACO sites in different states, to define optimal Rifabutin dosages in Indian patients. 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. These studies throw light on the need for higher/lower dosages than those recommended for Caucasian populations and will have practical implications for management of patients in India.
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 the state. Apart from drug resistance surveillance in the HIV population, the lab is engaged in research on subtype C strain and also HIV-2. Unique HIV-1 subtype C recombinants have been recently identified. Molecular characterization of HIV-1 subtype C isolates showed that the majority used CCR5 as co-receptor and have rev genes of variable length. Ongoing work will determine the functional significance of the C-terminus heterogeneity of HIV-1 subtype C rev, by cloning the rev proteins into a vector and co-transfection experiments.
The Department of Bacteriology has been busy performing the duties of a Supranational and National Reference laboratory for mycobacteriology. Reference panels are developed and shipped to Intermediate Reference laboratories, where on-site evaluations and external quality assurance are provided by NIRT. Further characterization of the new molecule “transitmycin” has been done and the substance will now be produced in bulk at > 97% purity in order to undertake further toxicity and efficacy experiments. Work is ongoing to improve the sensitivity of the luciferase reporter phage assay both for rapid drug susceptibility testing from clinical specimens as well as a rapid diagnostic test. The department also took on the added responsibility of performing line probe assays for patients with suspected MDRTB, to support the TB program in Tamil Nadu. Second line DST is performed on MDRTB specimens received from 9 states.
Biostatistics has always been an important pillar, lending support to the multifarious research activities of the institute, both clinical and basic science. Apart from these supporting activities and involvement in data management, the department also has multiple research interests, especially in the areas of modeling, neural networks, survival analysis and geospatial mapping.
Research in the Immunology department covers different aspects of the immunology and molecular biology of TB. Focus areas include antigen detection as a diagnostic test for TB, the role of host genetics (cytokine polymorphisms, Vitamin D receptor polymorphisms) in susceptibility to TB among HIV+ and HIV- individuals, cell mediated immune responses in pleural TB and identification of virulence genes in M.tuberculosis . In collaboration with JALMA, newer vaccine candidates are being tested in guinea pigs and mice. 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. The polarization of the immune response towards a Th2 phenotype leads to increased susceptibility to TB in people with latent TB infection. Further, a study of the impact of type 2 diabetes mellitus on the immune response to TB has shown that the inflammatory response is heightened, leading to potentially more severe forms of TB.
Prevalence surveys for TB, which were earlier conducted in Tiruvallur district, have been completed in Chennai city. The prevalence of TB was similar to that seen in earlier surveys (~330/100,000) and was higher in slum compared to non-slum areas and in men compared to women.
The institute conducted several workshops during the year, including a dialogue with private practitioners on how best to manage TB in the private sector – topics discussed included diabetes and TB, childhood TB and extrapulmonary TB as well as the role of newer diagnostic tools. An Indo-US Science and Technology funded workshop examined the link between nutrition, TB and HIV and came up with four high priority research questions. Around World TB day 2013, a CME program on drug resistant TB was conducted in collaboration with the Institute of Thoracic Medicine and Madras Medical College. Our scientists served as faculty at many conferences and workshops around the country.
Research priorities for the future include testing new drugs and adjunctive therapies for tuberculosis, shortening treatment for TB in children, testing of new diagnostics, pharmacokinetic and pharmacogenetic studies, testing of new compounds against TB and HIV, studying risk factors for recurrence and behavioural interventions to reduce HIV risk behavior as well as improve TB treatment outcomes.
Dr. Soumya Swaminathan |
