Introduction - Department of Health Research

Annual Report 2011-20121

DEPARTMENT OF HEALTH RESEARCH

The President notified the creation of the Department of Health Research under the Ministry of Health & Family Welfare through an amendment to the Government of India (Allocation of Business) Rules, 1961 on the 17th September, 2007.

The Department of Health Research was formally launched on 5th October, 2007 by the Minister for Science & Technology and Earth Science in a function presided over by the Minister for Health & Family Welfare, in the presence of the Minister of State for Health & Family Welfare.

The first Secretary of the Department who is also the Director General of the Indian Council of Medical Research, was appointed in November, 2008.

The following work has been allocated to the Department of Health Research:

1. Promotion and co-ordination of basic, applied and clinical research including clinical trials and operational research in areas related to medical, health, biomedical and medical profession and education through development of infrastructure, manpower and skills in cutting edge areas and management of related information thereto.

2. Promote and provide guidance on research governance issues, including ethical issues in medical and health research.

3. Inter-sectoral coordination and promotion of public - private - partnership in medical, biomedical and health research related areas.

4. Advanced training in research areas concerning medicine and health, including grant of fellowships for such training in India and abroad.

5. International co-operation in medical and health research, including work related to international conferences in related areas in India and abroad.

6. Technical support for dealing with epidemics and natural calamities.

7. Investigation of outbreaks due to new and exotic agents and development of tools for prevention.

8. Matters relating to scientific societies and associations, charitable and religious endowments in medicine and health research areas.

9. Coordination between organizations and institutes under the Central and State Governments in areas related to the subjects entrusted to the Department and for the promotion of special studies in medicine and health.

10. Administering and monitoring of Indian Council of Medical Research.

Of the work allocation given above, the work relating to ICMR was the only ongoing scheme to have been transferred to the Department. There was almost no systematic

Introduction



work on the remaining areas allocated, although some ad hoc work was taken up during emergencies like the H1N1 out break. This has necessitated the taking up of new schemes in view of the major gap in programmes and infrastructure that exists today with respect to health research.

Since the creation of the Department wide scale consultations have been initiated in order to finalize and firm up the interventions and policies required in order to establish and facilitate a vibrant, well functioning and relevant health Research system.

During the year under report, the Indian Council of Medical Research that serves as the fulcrum for the Department of Health Research, continued and intensified its research and development for the benefit of the Indian public. More importantly, the proposed seamless integration between the ICMR (generation of new knowledge) and the DHR (putting this new knowledge to public good) has started in right earnest. Some of these areas where there has been tangible progress include the setting of virology laboratories and networks, translational research to convert the new leads to products, processes and devices, setting up of data repositories on medical and health research for wide public access as part of the national knowledge policy. The DHR has initiated action on three of the four areas approved by the Government viz., Infrastructure Development for Health Research, Grant-in-Aid for Health Research and Human Resources Development for Health Research. Other areas like Mapping of Health Research Institutions, Establishment of Laboratories for Managing Epidemics, Knowledge Management Policy, Health Research Policy, Accreditation of Health Research Institutes are in various stages of implementation.



Infrastructure Development for Health Research

Objectives:The objectives of the present scheme are to:

bridge the gap in the infrastructure which is inhibiting health research in the Medical • Colleges by assisting them to establish multidisciplinary research laboratory and animal house facility with a view to improving the health research and health services.

create infrastructure for transfer of technology to the end users which would ensure • an interface between the new technologies developers (Researchers in the Medical Institutions; State or Centre), health systems operators (Centre or state health services) and the beneficiaries (community Rural, Urban slums)

ensure the geographical spread of health research infrastructure by selecting judiciously • the institutions to be supported under the scheme.

this scheme, with the components detailed below, is essential since there are no other • schemes at present, which address these issues either in the Ministry of Health & Family Welfare or in other Ministries.

Components : 1. Establishment of Modern Biological Lab/ Multidisciplinary research units in Government

Medical Colleges and institutions

2. Establishing Animal House facilities in Govt. Medical Colleges

3. Developing of Model Rural Health Research Units (MRHRU) in states

Setting up of modern biological labs/ multi-disciplinary research units in State Govt. medical colleges - At present there are about 300 medical colleges in the country of which 143 are in Govt. sector. In order to revitalize medical colleges as centres for bio medical research, it is proposed to provide financial assistance upto Rs. 5 crores to each medical college for setting up appropriate infrastructure for medical research, depending on the infrastructure gap/ requirement of the institution This will include funds for civil works, equipments and furniture considering the availability of existing infrastructure in each of the Medical College, the requirements in terms of equipments, civil work for medical colleges etc. will vary. During the project period of 3 years, it is proposed to take up 100 State Government Medical Colleges. The project will be extended thereafter to cover the remaining government medical colleges and others.

Apart from this, the non-recurring grant will also be extended for a period of 5 years for engaging trained technical man power on contractual basis, for training, consumables and contingency expenditure.



Departments of Health Research will establish the Model Rural Health Research Units at least one per state. In bigger states, there will be more than one such unit. They will function under the Department of Health Research and would continue to develop specific models for transferring the technology, as the development of technology in the health system is a continuous process and there is a need to review and modify the models depending on the new available technology. They will also generate state/area/disease specific data, which would be a great input for improving the general health system. It was proposed to establish 50 such units during project period.

Achievements : 1. The scheme has been approved in principle by the planning commission and

expenditure finance concurrence (EFC) has been prepared. The EFC document was revised / improved thrice in the light of comments received from the Ministry, the last revision done in January 2012.

2. As per comments of Integrated Finance Division (IFD) of ministry of Health & Family Welfare, Government of India, the EFC for the period of one year was prepared and has been submitted to IFD for their approval.

3. In the meantime, the preparatory budget for the infrastructure scheme is being sought from the IFD so that the startup activities for establishing MRUs at the State Medical Colleges and MRHRUs at state level can be undertaken.

4. 60 medical colleges from 20 different states have sent their applications for establishing multi-disciplinary research unit (MRU). 31 medical colleges have been selected to be taken up into the first phase. These medical colleges were also contacted for sending their faculty applications to apply to the fellowship scheme of Human Resource Development under DHR so that faculty become active and develop projects.

5. The DHR has received willingness and proposals from 5 states namely Himachal Pradesh, Rajasthan, Bihar, Tamil Nadu and Maharashtra to establish MRHRU in their states. State Governments have sent the names of the nominees responsible for coordinating with the department for establishing the units. A workshop has been proposed to initiate the proposals through MRHRU of these states.



Human Resource Development for Health Research

Objectives: The objectives of the present scheme are to:

increase the availability of personnel for health research through scholarships, fellowships • and career advancement scheme etc. thereby providing an incentive for people to take up medical and health research

assist in the creation of a cadre of skilful researchers in fields such as clinical trials; • Toxicology; Good Clinical Practices (GCP); Good Laboratory Practices (GLP); Quality Control (QC) & Quality Assurance (QA); Genomics; Proteomics; Geriatrics; Modern Biology; Biotechnology; Stem cells; Genetics; Drugs chemistry; any other specialized area of medicine and operational research.

create and support multidisciplinary and multi-sectoral teams of researchers working in • medical colleges, universities, research institutes and NGOs

this scheme, with the components detailed below, is essential since there are no other • schemes at present, which address these issues either in the Ministry of Health & Family Welfare or in other Ministries. To create synergy, an Expert group has been constituted to identify the areas in which the DHR will complement the efforts of other scientific agencies in order to avoid any duplication of effort.

Components:Programme to create researchers in high focus, high skill areas. •

Programme to promote medical research as a career among young scientists and medical • students.

Programme to promote research in young and mid career faculty of medical colleges.•

Creation of a national initiative in partnership with relevant stakeholders to attract and • retain the young to a career in health research.

Development of human resource policy with focus on career development scheme for • young researchers.

Strengthening research through the establishment of online courses and web portal on • health research for students, faculty and other researchers.

Details :Development of researchers in critical and high focused areas - • This would be done through the adoption of a multi pronged strategy.



Through the identification of institutions working in identified areas, and by • providing access to researchers to work in frontline areas in such state- of- the- art facilities. Under this programme, selected researchers would be placed in state-of-the-art facilities both within and outside India, as required in cutting edge areas, so as to enhance their skills and knowledge and to ensure a core group with skills in important areas. In order to implement this scheme, Department of Health Research would identify state of the art facilities within and outside India. It will provide funds to the institutions in India for up gradation of facilities & consumables etc. and to the researchers; to develop core teams in selected areas.

To provide technology support to investigators who plan to work on frontline areas • of medical and health research, mechanisms will be built to make such facilities available to them locally or anywhere within the nation.

Programme to promote medical research as a career among young scientists and medical • students: This will be ensured through the provision of fellowships and scholarships as follows:

Fellowships for training: Researchers in identified advanced fields would be • provided fellowships so as to enhance their skills in deficit areas. DHR would provide fellowships for trainings in frontline and emerging areas for training within India and abroad. These fellowship trainings will be preferably for relatively young investigators who are working on health related areas and where the plans for utilizing the training are well focused and concrete.

Provision of scholarships at the Post graduate level: Support for producing man • power in newer areas which are essential for development of health research like Postgraduate degrees in clinical research, health technology, Regenerative Medicine, Ethics in medical research, patents relating to health, etc.

For the creation of a national initiative in partnership with relevant stakeholders to • attract and retain the young to a career in health research:

Institution of a young Researcher programme: The Young Researcher Programme • is designed for highly qualified and motivated individuals skilled in areas relevant to bio medical research, who wish to take up medical research as a career option. The programme would be open for potential researchers who have completed their undergraduate medical degree or post graduate degrees in medical and biomedical fields. This is proposed to be achieved by providing special training programmes.

Selected researchers would participate in specially designed orientation and given • an opportunity for on-the-job learning and mentoring. They would be provided an opportunity to participate in seminars, short trainings and workshops. They would also be provided specialized training through scholarships where required.

At the end of their training/ fellowship, selected researchers would be provided • startup grants to enable them to take up projects based on their training.

As highlighted above the proposed programme would identify young and mid • career researchers in medical colleges & other health research institutions and then provide support through fellowships and subsequently a start up grant so as to attract and retain the young in a career of health research.



Achievements:1. The scheme was approved by the Integrated Finance Division (IFD) of Min. of Health

and Family Welfare in Jan. 2012 for the current financial year (2011-2012). Applications were invited from the young and middle level faculty of various Medical Colleges of the country for fellowships in identified high focused areas under three different categories. These are: i) Long Term Fellowship (6 to 12 months) in Foreign Institutes, ii) Long Term Fellowships (6-12 months) in Indian Institutes and iii) Short Term Fellowship (1-3 months) in Indian Institutes. The application format was put on the DHR website and advertized in news papers for inviting applications from the interested faculty. Applications for the above stated three categories will be reviewed and finalized before the end of March 2012.

2. The DHR has been entrusted to promote human resource development for health research. One of the methodologies to undertake this activity is to make an attempt to provide training courses / programmes (both conventional and online) in the recognized institutions in the following priority areas of research identified by the DHR viz., Toxicology, Genomics, Proteomics, Geriatrics, Stem Cell Research, Clinical Trials, Good Clinical Practices (GCP), Biotechnology, Genetics, Operational Research, Health Informatics, Medical Ethics, Health Economics and any other area that the medical college/institute needs support. The DHR invited applications from various medical and biomedical scientific institutions which could provide training courses / programmes (both conventional and online in these areas) for short term and long term durations. The application format was put on the DHR website inviting applications from the institutions having necessary infrastructure and faculty. The financial assistance of Rs. 10 lacs from the DHR is to be utilized to strengthen their existing facilities. In future, it is proposed to provide a one-time non-recurring support for upgradation of facilities too. The stay and other expenses of the medical teachers/scientists sponsored will be borne by DHR as a part of fellowship.



Grant-in-Aid for Health Research

Objectives of the Scheme:i. To support and encourage clinical and translational science by catalyzing the application

of new knowledge and techniques to clinical practice and public health; knowledge management.

ii. To support studies addressing the problems of technology access to marginalized and underprivileged groups by focusing on issues pertaining to gender and health, tribal health, maternal and child health.

iii. To create synergy among various stakeholders – national and international agencies, investigators, institutions, regulators, NGOs and civil society for acceleration of knowledge generation, its translation and implementation.

Components:Financial support will be intended for the following projects/activities for the purpose of development of leads/products etc.:

i) To map the health research institutes in the country, research done by them, publications, technologies etc. There is a need to create collated data with regard to various institutions involved in health research, research publications and technologies etc. so as to analyze, identify the available material /lead that could be developed further to products in close coordination with the industry and also to undertake further research in identified projects for creation of additional data/information for development of leads for further processing.

ii) To evaluate the health research undertaken by various scientific departments including ICMR with a view to ensure that they are aligned to National Health Policy, National Health Research Policy, National Technology Policy etc. A unit will be established for evaluating and recommending technologies for improving the health care. Critical funding will be provided to the identified areas for further development.

iii) To establish a mechanism for coordination between the academia and the industry so that the leads could be translated into products and processes fast. Start up funds, when required, will also be provided for encouraging Public Private Partnership mode by focusing on proposals which have a promise of developing a product or process.

iv) To attract health research personnel (NRI, PIO, OCI) serving abroad in critical areas to come back to India for undertaking research in identified areas by extending financial support .

v) To support programmes in Medical Colleges for carrying out innovative research.



Under this component of the scheme, a start up fund will be provided to various scientific departments, industry in either in isolation or with academia, individuals including NRI,PIO,OCI, institutions etc. for development of leads, translation of leads/ product development. Further in order to promote/encourage translational research National Awards in various fields relating to translational research will be instituted.

In addition financial support will be extended to the following :

(i) Projects jointly developed in coordination with other Agencies like DST, DBT, DARE/ ICAR, DSIR/CSIR, Department of Space, Ministry of Environment & Forest, National Disaster Management Authority, DRDO, National Knowledge Network (Department of Information Technology) etc, in identified areas. For example, joint projects with DBT would be on diagnostics & vaccine developments and developments of guidelines for application of new generation technology; with DARE/ ICAR on zoonosis & nutrition; with Department of Space focus will be on technologies like use of GIS & remote sensing in relation to human health; with Department of Environment would be on climate change and health as well as impact of transgenic/ recombinant technology; with DSIR/ CSIR would be technology development & drug discovery; with DST would be for developing basic technology/ knowledge in areas pertaining to basic biology, polymers, devices, bio-instrumentation and other life science related areas like nanotechnology etc. While DHR will coordinate & fund the application side of investigations with special focus on human health, the other relevant areas of technology will be funded by respective agency.

(ii) To researchers to pursue research in areas which are very relevant to our country with special focus on knowledge management, technology access to marginalized and under privileged section of society.

(iii) To support to programme for Gender and Health: The vulnerability of women to various situations and circumstances are different as compared to men. A gender based analysis on a continuing basis is critical to establish gender based issues like Vulnerability to disease, access to testing and health services, mobility, care and support. There is therefore a need to understand these differences and respond with public health interventions that are specific to the situation of women, which includes access to services including testing, adherence to treatment, expenditure on treatment, differences in biological vulnerability, socio cultural factors like education & access to information, mobility, care & support services. Under the scheme the project will be supported for analyzing existing data, studies to cover the gap, vote to examine the current situation and changes over time on gender specific issues relating to women and health.

(iv) To develop and establish for preventive, diagnosis and treatment of diseases: While the profile of disease burden in the country is changing over time, the treatment especially in the primary and secondary sectors has not kept pace. It has therefore become critical to study the existing practice and to evolve suitable protocols and systems in order to have more evidence based treatment and diagnosis which is practicable at different levels within the country. Financial support will be extended for undertaking such studies and for devising diagnostic and treatment protocols. Various scientific professional associations/societies/bodies will also be involved for this purpose so as to address such vital issue in an impartial manner.



(v) Support to Scientific/Professionals/Association/Bodies: Financial support to scientific societies/associations etc. will be provided to create expert groups, to develop guidelines, to evaluate any technology that the specialty feels important and provide developmental grants for implementing the recommendations, emanating from these expert groups/workshops. Support will also be extended to print the proceedings, guidelines and recommendations emerging for such scientific events as well as specially constituted expert groups.

(vi) Financial support will also be extended for

participation in conferences abroad of non-ICMR researchers for presenting research • papers, chairing the session or delivering a key note address in international scientific events (conferences, seminars/symposia/workshop) for promoting the research activities and researchers for sharing of experiences among scientists from various countries.

organizing international conference/seminars/symposia/workshop in India for • sharing of knowledge and expertise of developed and developing countries for transfer of technology, for dealing with various emerging/re-emerging challenges.

Achievements:1. In accordance with the scheme approved, a notice seeking proposals in the areas of

Translational research, Gender & Health, Technology access to marginalized and under privileged sections of society, Comparative/cost effective analysis for public health choice and development of guidelines/protocols for prevention, diagnosis and treatment of diseases, which could be executed and completed in one year, was placed on the website of DHR and ICMR for submission of proposals on a prescribed format.

2. Under this scheme, proposals in various areas will be considered by Department of Health Research. All these proposals will be reviewed technically by Expert Committee of ICMR/DHR in accordance with the ICMR guidelines under two tier review system.

3. The basic criteria for evaluating the project proposals was relevance of the topic to national health priorities and/or possible advancement of knowledge in identified areas.



Establishment of a Network of Laboratories for Managing Epidemics

Objectives:Create infrastructures for timely identification of viruses and other agents causing • morbidity significant at public health level and specific agents causing epidemics and/or potential agents for bioterrorism.

Develop capacity for identification of novel and unknown viruses and other organisms • & emerging-reemerging viral strains and develop diagnostic kits

Provide training to health professionals. •

Undertake research for identification of emerging and newer genetically active/ modified • agents.

This scheme, with the components detailed below, is essential since there are no other schemes at present, which address this issue of infrastructure development and these aspects either in the Ministry of Health & Family Welfare or in other Ministries. This will be complementary to the Integrated Disease Surveillance Project and will strengthen the activity by capacity development & active research on these aspects

Components:1. Establishing a net-work of laboratories for diagnosis of the viral and other infectious

diseases

2. Setting up of revolving fund for facilitating a rapid mobilization of outbreaks/ disaster response (technology component) to infectious disease out-breaks or natural or man-made disaster.

Details:1. Establishing a network of laboratories for diagnosis of the viral and other infectious

diseases

As has been stated viral diagnosis today is a major health problem and outbreaks of new viral agents is a common phenomena. The inadequacy of specialized laboratories in the country especially of secondary and tertiary level has been noticed in the past as well as during the recent HINI crises that gripped the nation. In the context of biological agents being used as weapons for man-made disaster and also out breaks of new viral agents, it is considered necessary to establish a net work of laboratories for viral diagnosis. Such network and active research programme will be important to generate evidence for interventions for various viral infections which are endemic to the Country. For this purpose it is considered essential



to establish net work of laboratories across the country, with NICD and NIV, having bio-safety laboratory III, acting as the apex laboratories. These labs will supplement the activities of the Integrated Disease Surveillance Project coordinated by NCDC, Delhi with special focus on viruses and will also be expected to deal with all common viruses like:

1) Viruses transmitted by respiratory route: Measles, Rubella, Mumps, Influenza viruses (A, B and C), Parainfluenza virus, Adenoviruses, Respiratory Syncitial Virus, Rhinoviruses, Polio, Coronaviruses.

2) Viruses transmitted by intestinal route: Hepatitis A, E, Rotavirus, Astroviruses, Calciviruses, Norwalk viruses, Enteroviruses.

3) Vector Borne Disease Viruses: Dengue, Chikungunya, Japanese encephalitis, West Nile, Kyasanur Forest Disease, Chandipura.

4) Zoonotic viruses: Rabies, Nipah virus, Hanta virus

5) Viruses transmitted by body fluids: HIV, Hepatitis B and C.

Priority will be given to develop infrastructure and expertise for diagnosis of viruses with a potential to cause outbreaks and/or which are responsible for significant disease burden like Measles, Influenza viruses (A, B and C), Respiratory Syncitial Virus, Polio, Hepatitis A, E, Rotavirus, Enteroviruses, Dengue, Chikungunya, JE etc.. These laboratories will be expected to develop expertise for diagnosis of specific viruses circulating in their geographic area.

At present, there are only 2 laboratories well equipped to deal with all kinds of viruses viz. NIV, Pune and NCDC, Delhi. These labs will continue to act as Apex laboratories. In addition three levels of laboratories are proposed to be established.

(i) Regional laboratories

(ii) State level laboratories

(iii) District level laboratories

(i) Regional laboratories

It is proposed to establish 6 regional laboratories to deal with all kinds of viruses and other organisms causing infections, i.e. one each in North, South, East, West, Central and North-Eastern parts of India and preferably at ICMR institutes. They will be expected to carry out serology, RT-PCR, isolation, fluorescence microscopy, tissue culture and sequencing for viruses listed above or any other new viral pathogen. These labs will also be expected to develop capacity for identification of novel/unknown viruses and other organisms and emerging-reemerging viral strains etc. & develop diagnostic kits. They will receive unidentified samples from the State level labs for identification and characterization. These labs will also provide necessary training to those deployed in State level labs & support to them in building capacity. They will be responsible to do research apart from providing diagnostic facility and training. In addition, they will be equipped with facilities to identify viruses and other organisms which have the potential of being used as agents of bioterrorism.

It is proposed to create state-of-art facilities in these Regional labs so that it could achieve the objectives in research, continuous monitoring and surveillance of existing as well as new viral and other strains and handling viruses etc. with a potential of being used as agents of bioterrorism, capacity building, diagnosis, development of diagnostic kits etc.



These facilities will be created in the identified institutions under the Ministry of Health and Family Welfare and will function directly under the Department of Health Research for better coordination and would undertake continuous monitoring, surveillance, focused research on emerging and reemerging agents and development of diagnostic kits. These laboratories will be manned by regular scientific/ technical staff.

(ii) State Level Laboratories:

It is proposed to establish one lab in each State & Union Territory preferably in Govt. Medical College/ hospital. These labs will be equipped with BSL2 facility and expected to carry out serology, RT-PCR, isolation, fluorescence microscopy, tissue culture and sequencing for all enlisted viruses. These laboratories are also expected to be involved in basic as well as applied research on viruses, development of kits and diagnostic reagents and identification of unknown/referred samples from the Sub-state level laboratories.

(iii) District level Laboratories:

It is proposed to create 200 district level labs. State Govt. will be requested to identify 1 such lab to cover a cluster of 3-4 districts depending upon their requirement preferably in Govt. Medical Colleges. These labs will be equipped with facility to carry out serology, PCR and fluorescence microscopy for the listed viruses. With the available infrastructure, these labs are expected to identify all common viruses by using immunological and molecular tools. The viruses which cannot be identified by these labs will be referred to the state/regional labs for identification. These labs will also be involved in diagnosis of common diseases other than that of viral etiology, which are prevalent in their respective region. This will facilitate early diagnosis of all the identified viruses so that the intervention/treatment if available could be provided without losing valuable time. It will also strengthen the surveillance/ monitoring of viral diseases.

Achievements :1. The scheme has been approved in principle by the Planning Commission and EFC

documents are under processing.

2. To cope with emergent situation and urgency, ICMR has in the meantime started a Virology Diagnostic Laboratory (VDL) Network Programme in the extramural ad-hoc mode. The VDL Network program involves identification of candidate institutions / research centers/laboratories, which are in need of the facility and accept the offer to open/ establish/ upgrade the viral diagnostic laboratory. ICMR invites the Research Proposals from the selected laboratories / institutions in the format of Ad Hoc Research Project and funds are facilitated by ICMR as for Extra-mural Projects. The initial support by ICMR is ensured for Infrastructure development and functioning of the VDL for a period of five years, after which the state government/health authorities are required to absorb the facility (including its trained manpower) and maintain it at their end.

In the first phase, four Grade 1 Virology laboratories were established at Regional Medical Research Centres at Port Blair and Bhubaneswar, Chhatrapati Shahuji Maharaj Medical University (Formerly KGMU), Lucknow and Kasturba Medical College, Manipal as extramural project of ICMR.

In the second phase, four more labs – three Grade 1 labs at Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, SMS Medical College, Jaipur, Field Station of



National Institute of Virology at Allappuzzha, Kerala and one Grade III lab at Pt. Jawahar Lal Nehru Memorial Medical College, Raipur (Chhattisgarh) have been sanctioned and nearly established.

During 2011-12, six more Institutes have been identified for establishment of VDLs at PGIMER, Chandigarh, Rajindra Institute of Medical Sciences, Ranchi; Rajendra Memorial Research Institute of Medical Sciences, Patna; Andhra Medical College, Vizag; King Institute of Preventive Medicine, Chennai and Regional Medical Research Center for Tribals (RMRCT) ICMR, Jabalpur. These institutions are in various stages of establishment and action will be taken by the end of March 2012.

Three institutions identified in recent past are – Virus Unit of ICMR, Kolkata; Osmania Medical College, Hyderabad; and Government Medial College, Goa. Visit by experts of ICMR is planned for evaluation of two more medical institutions at BJ Medical College, Ahmedabad; and Government Medical College, Agartala, Tripura. States like Chhattisgarh and Jharkhand are receiving special attention for this purpose.



Knowledge Management (KM) envisages capturing, creating, sharing and managing knowledge. KM comprises of three components (i) people who create, share and use knowledge as part of their daily work and help shape a knowledge sharing organizational culture (ii) Processes which include methods to acquire, create, organize, share and transfer knowledge to fit different situations and (iii) The technology including the mechanisms to store and provide access to data, information, and knowledge that must be integrated with the way people work, and address their real needs.

The implementation of any KM policy in Health sector will have essential ingredients and processes for improving the health of people by imparting benefits of various health programs to the targeted communities and improving the quality of education and research which will lead to evidence based policy. However, KM in health sector faces three major challenges:

Unsatisfactory quality of dataWith good quality data better policies can be framed, better decisions can be made thus improving the implementation of Health care programs and quality of medical research.

Non- availability of data for knowledge generationMost of the data being captured may not be available in a suitable form for creating databases. Availability of digitized data in unified format helps in improving data quality and developing standards for knowledge generation.

Inadequate dissemination of knowledgeThere is a serious unavailability of information and knowledge to end-users which include health professionals, researchers, patients and students. Dissemination of quality information and knowledge through agencies like DAVP and appropriate media such as Internet, Information Kiosks etc. can provide relevant information to the end-users.

Health professionals should take advantage of the data, experience, and expertise available in their own and other organizations to create and share their own knowledge with others.

The policy would catalyze creation of knowledge and translation of that knowledge from research settings to real world application in order to improve the health of common man specially marginalized sector of our society.

The focus of this policy would be creating an environment for connecting knowledge related activities in health into a coherent action plan.

Knowledge Management Policy



MissionTo develop an efficient Health Knowledge Management System for collection, dissemination and utilization of knowledge for improving the quality of Health Services, Education and Research.

PoliciesService delivery

In order to create harmony among various health service providers and to impart their knowledge and services to the public at all times, the following essential components are proposed:

Empowering end user for better access to Health Service by :

1. Making available updated information about the service infrastructure such as manpower, equipment, medicines etc. available at different levels e.g. sub-centre, Primary Health Centre, Community Health Centre, District Hospital, Zonal Hospital, medical college and other tertiary care hospital etc.

2. Providing online information about functional status of the infrastructure i.e. availability of doctors, medical supplies including devices, vacant beds, surgical/ medical/ diagnostics facilities etc. at a given time.

3. Providing information about geographical locations and other logistics of various health service providers.

4. Promoting overall user awareness about available information sources by training of end users.

5. Promoting access to financial resources including insurance.

6. Ensuring access to all sections of society.

Enriching health professionals with knowledge about available resources around them by standardizing and linking functional, infrastructural and logistic information available with different healthcare service providers in Government and private sectors.

Increasing accountability of healthcare professionals and services towards human life by

1. Developing a well defined referral system for efficient utilization of resources between Central, state and other public/private healthcare providing institutes.

2. Creating a mandatory forward and back referral pathway over a period of 5-10 years. Responsibilities of every individual in the pathway to be enforced to ensure perfect accountability involving human life.

Connectingremoteareasanddifficultterrainsbyeffectiveuseoftelemedicine

Expert opinions of specialists need to be ensured on a structured fixed time interval basis as well as on emergency basis. The existing satellite connections and the optical-fibre-based National Knowledge Network (NKN) would be valuable in this context.

Efficientlyhandlinghealthaspectsofdisasters by using Data Mining and Business Intelligence tools on available data for quickly finding information about available resources around disaster site and mobilizing these resources.



Establishing an user friendly but informative electronic medical record system.

This record system should be in a standardized, internationally compatible format.

Education

In order to improve the quality of medical education uniformly across the country with help of knowledge network, following policy guidelines are proposed:

Sharing knowledge by :

1. Establishing an efficient physical network, connecting all medical/dental/ nursing/ other health related professional colleges

2. Creating tele-education portal to house resources which can be accessed online

3. Creating and networking digital / resource libraries for educational materials such as lectures, slides, video clippings etc. which can be accessed online as well as offline

4. Organizing prescheduled interactive lectures and practical sessions by prominent teachers through tele - education through national and international networks.

Developing unified high quality standards in health education across the country

Updating knowledge of health professionals by conducting online continued medical education/ special training programmes.

Evaluating quality of in-service health personnel by conducting online examinations

Training in-service health personnel by organizing localized interactive training courses

Enforcing regulations for tele-education applications by following existing guidelines of regulatory bodies like Medical Council of India, Medical Universities, Dental Council of India, Nursing Council , Pharmacy Council, various councils for alternate medical systems, other relevant bodies for Physiotherapy and other disciplines.

Research

Knowledge is both a key input for and output of health research. For increasing use of knowledge in medical research, both clinical research and basic research, following measures are proposed:

Creating information culture by adopting recent advances in Information and • Communication Technologies. Improving interaction between National and International researchers and stakeholders working in different subject areas by developing collaborative networks and alliances

Creating an information system and a policy framework to facilitate Indian medical • researchers abroad to return and join Indian medical research institutions.

Enhancing research to policy through collaborations and exchange of information • between researchers and health professionals ; between researchers and other stake holders involved in policy making ( political leadership, planners and civil servants etc)

Enhancing public-private partnership in health Preparing national information system of • research funding by different funding agencies.

Developing database of research resources such as manpower, equipment etc. available • with different laboratories/medical / dental colleges/ universities etc.



Developing disease database including clinical, epidemiological, genetic, biological • and social parameters.

Achieving high impact of research by effectively communicating research outcomes.

Balancing between responsibility to share information for betterment of health of people • and protecting intellectual property generated through research.

Empowering health research institutions to use tools of Knowledge Management for • improving quality research as per the guidelines of Medical Council/ Dental Council of India.

Providing access to research data to other scientists and students for secondary analysis by • taking care of ethical , copyright and IPR issues . Managing research priorities based on periodical in-depth analysis of existing research data.

Creating a National Health Knowledge Repository for free access to all researchers.•

Encouraging the use of knowledge management for creation of different application • groups and development of various disciplines like biomedical engineering.

Strategy for implementing Knowledge Management Policy

Broad strategy for implementing knowledge management policy for health is given below:

There will be three important components/ tiers : policy framing, strategy planning and • monitoring.

An expert advisory group should be constituted under the chairmanship of the Secretary, • Department of Health Research with following mandate:

To examine the policy document and modify it if necessary•

To decide the priority areas•

To classify the priority areas into short term, midterm and long term goals for • Implementation

To constitute three technical sub committees in the areas Service Delivery, Education • and Research to manage knowledge network for help with following mandate:

To carry out feasibility study/ studies , pilot study/ studies, model projects and preparing • proposal

To define parameters to be included in feasibility study•

To liaison between the study group and other stakeholders of the proposed•

knowledge network to facilitate preparation of feasibility report•

To examine the feasibility study report and present it to the Secretary, Department of • Health Research

To devise a strategy for implementation along with other stake holders•

Monitor implementation of work•

Funding of the different components of Knowledge Management Network

i) The responsibility of different stakeholders in providing infrastructure, manpower and other resources needs to be defined by consultative process among centre, state, other public and private stakeholders.



ii) While the network connectivity may be provided by central systems, department of information technology, UGC etc, the local supplementary support could be provided by State systems.

iii) A dedicated system will be required for keeping it functional all the times. For this IT connectivity will have to be ensured along with funds allocated for this purpose.

iv) A strategic plan for providing financial support for development of modules, appropriate software, professionals for data analysis on specific areas, mechanisms of review will have to be drawn for estimating the financial inputs.

Establishment of an Appropriate Authority

For developing and implementing a comprehensive plan for utilization of knowledge network for health service delivery, medical education and research, an Appropriate Authority under the Department of Health Research in the Ministry of Health and Family Welfare, Govt. of India may be desirable. Such an authority with committed resources will be responsible for strategic planning, for implementation and review of the progress from time to time. This Authority /Cell may establish units in the states for action at the local level.

Achievements The Policy is under the consideration for Government approval. Action has been initiated for setting up of necessary infrastructure for implementation.



The establishment of a Department of Health Research (DHR) in the Ministry of Health is recognition by the GOI of the key role that health research should play in the nation. The weakness of the publicly funded health structures and the research infrastructure is a key limiting factor in realizing the full benefits of this commitment to research. The fact that the almost 300 medical colleges in the country are not contributing of their best to health research is highlighted by the fact that in 2007, 96% of the research publications in India emanated from 9 medical colleges. Much of this published research is not on priority health concerns and the translational of key research findings into policy which could improve the health of the people is very limited and needs to be enhanced. Epidemiological know-how, surveillance technology and diagnostic services which are essential for determining health priorities are very poorly developed. There is also a compelling need to build multidisciplinary research blending physical, medical and social sciences. Besides, there is also an equal urgency to establish regulations, strict ethical norms and transparency, standardize methodology and international standards of research. Such capacity is necessary for undertaking operational research as also large-scale evaluation of diagnostics and trials of drugs, devices of both modern and traditional systems of medicine. It is in this context that the DHR has formulated a draft National Health Research Policy.

Vision of National Health Research PolicyTo maximize the returns on investments in health research through creation of a health research system to prioritize, coordinate, facilitate conduct of effective and ethical health research and its translation into products, policies and programmes aimed at improving health especially of the vulnerable populations.

Objectives of the National Health Research PolicyThe broad objectives of the National Health Research Policy are:

i. Identify priorities for effective and ethical health research to enable the achievement of the objectives of NHP 2002, NRHM, Bharat Nirman and National Food security Act as well as global commitments such as MDG and IHR, ensuring that the results of health research are translated into action.

ii. Foster inter-sectoral coordination in health research including all departments within the Government, Private Sector and the Academia to promote innovation and ensure effective translation to encourage/ accelerate indigenous production of diagnostics, vaccines, therapeutics, medical devices etc.

iii. Focus on the marginalized, the vulnerable and the disadvantaged sections of society.

iv. Strengthen national networks between research institutes, academia and service institutes, and encourage PPP.

National Health Research Policy



v. Put in place strategies and mechanisms for assessing the costeffectiveness and cost benefits of interventions for health.

vi. Develop and manage human resources and infrastructure for health research and ensure that international collaborative research contributes to national health.

Prescription of the NHRP1. Create a National Health Research System

2. Establish a National Health Research Management Forum

3. Operationalize a 10-point action programme

National Health Research System (NHRS)In order to achieve intersectoral coordination and to make national priorities for health research a new architecture of national health research system is envisaged. Health research system is a concept that integrates and coordinates the objectives, structures, stakeholders, processes, cultures and outcomes of health research towards development of equity in health and in national health system. It is a system for planning, coordinating, monitoring and managing health research resources and activities, and for promoting research for effective and equitable national health development Health Research in the country would be developed into a National Health Research System (NHRS) wherein all research agencies, cutting across Ministries and sectors identify priority areas of research and coordinate with each other to avoid duplication, fragmentation, redundancy and gaps in knowledge, in order to enable the results of research to transform health as a major driving force for development.

Goals of the NHRS1. To generate and communicate knowledge that helps to form the national `health plan

and guides its implementation, and thus contribute, directly or indirectly, to equitable health development in the country;

2. To adapt and apply knowledge generated elsewhere to national health development; and

3. To contribute to the global knowledge base on issues relevant to the Country

Functions of NHRSThe National Health Research System would be responsible for:

1. Developing National Health Research Plan

The DHR is responsible for the National Health Research Plan for a National Plan aligned with the Five Year Plans of GOI and its implementation and monitoring.

2. Set priorities

A Priority Research Agenda will be developed in tune with the National Programmes, and relevant to national and local needs.

3. Engage with Private Sector

The private sector, pharmaceutical industry, biotechnology and biomedical technology



oriented Industries, private educational institutions, hospitals and nursing homes, research foundations and institutions, private practitioners, NGO’s and CBO’s working on a not- for-profit basis etc. are now major stake holders in Health care research and delivery. The National Health Research System would recognise their important role in health research and shall foster their participation in the system as partners. These engagements have to be concurrent and intense rather than linear and loose.

4. Strengthen International Linkages

In the current global scenario International collaborative efforts are recognised as one of the factors in successful research because of the complimentarity of technology transfer, capacity building and access to diseased populations. There are a large number of potential partners and in the choice of partners the priorities of the National Health Research Plan and national interest shall be paramount. Linkages with International Developmental partners and WHO and other UN Agencies shall be further developed and strengthened to ensure that India plays a legitimate role as an emerging economy.

5. Ensure Ethical Research

The Bill on Research on Human Subjects and establishment of the National Biomedical Research Authority therein along with the guidelines developed by other agencies shall regulate all research. The Health Research System shall review these Guidelines from time to time, and harmonise them with International Guidelines. Facilitation of training in ethical research shall be the responsibility of the DHR. A major achievement has been the establishment of a National Clinical Trial Registry and all clinical trials are mandated to be registered by the DCGI.

6. Ensure Targeted Financing

The National Health Research System shall be responsible for ensuring equity in resource mobilisation and allocation of public funds. It shall endeavor to ensure that the allocation/ expenditure on health research is at least 2% of the allocation / expenditure on health. International funds will also be mobilised in keeping with the priorities. The NHRS would track the resources available and spent on research in the country and monitor its impact on health. Though a minimum of 2% of health expenditure has been achieved, this may be too small a figure considering that the allocation for health itself is meagre in relation to the population and health concerns of the country.

7. Monitor and Evaluate impact of health research.

To ensure that resources are used efficiently and in line with agreed priorities there is a need for continuous monitoring and evaluation. The health research system will develop explicit policies and procedures for reviewing proposals, and for monitoring and evaluating the output and impact of those that are funded. Indicators will be developed to monitor the development and effectiveness of the health research system. Indicators would also be defined for assessing health status, health system effectiveness, efficiency and affordability, in order to capture the contribution of research in reducing inequities. Direct indicators of National Development, would serve as indirect indicators of the efficacy of Health System research as a vehicle of development. Set mechanisms to ensure that best practices are encouraged, and practices are evidence based.

8. Partnership with State health system.

Encourage health research within States. Help set state level health research system by strengthening partnership between central and state systems.



9. Assess Health Research System

The health research system would need to be assessed periodically to provide evidence that it is functioning optimally.

The NHRS shall be managed by a National Health Research Management Forum (NHRMF).

The National Health Research Management Forum (NHRMF) The National Health Research Policy envisages a System wherein all present and prospective players have their own space. However, an overarching National Health Research Management Forum is proposed, having representation of all key stakeholders, the DHR as its Secretariat, and the following functions / terms of reference:

i) To advise on and evolve national health research policies and priorities and to evolve mechanisms and action plans for their implementation;

ii) To develop a 5 year projection of the plans for health research and to prepare an annual National health research plan;

iii) To do a mid-Plan appraisal for course correction, as needed

iv) To promote the development of health research activities in the country;

v) To review biomedical & health research management, and suggest strategies to overcome problems in implementation of policies;

vi) To suggest mechanisms to nurture a scientific environment to attract talent and to develop human resources for biomedical and health research; and

vii) To facilitate utilisation and dissemination of research results and advocacy for health research.

Structure of NHRMFThe NHRMF will be Chaired by the Minister of Health & Family Welfare and co-chaired by Minister of Science & Technology. The Minister(s) of State for Health would be the Vice-chairperson(s). The Secretariat shall be in the DHR and its Secretary shall be the Member-Secretary. All Secretaries of various

Departments in S&T would be the members, DGHS and 8-10 eminent scientists/ public health experts (numbers flexible) as well selected representatives from State Governments would be the other members. These experts would also be the Chairmen of the various working groups which would be constituted to address the following areas:

1. Development and evaluation of interventions for promotion, restoration, maintenance and protection of health.

2. Human resource management and infrastructure development

3. Knowledge management

4. Encouragement to translational research and originality in basic science research, and innovations

5. Optimizing intra- and inter-sectoral networks, coordination and collaboration especially with private sector and industry.



6. Track current resource flow and future requirements to address priority areas of health research.

7. Establishment of priorities for health research.

8. Implementation of health research policy, planning, monitoring and evaluation.

Responsibilities of NHRMFStewardship

This would encompass a range of activities for the national health system intended to ensure quality leadership, productivity, strategic direction and coherent action. Sub-functions would include Strategic Vision, Policy Formulation, Priority Setting, Performance and Impact Assessment” Promotion and Advocacy, and the setting of norms, standards and frameworks for the sound practice of research. Provide best practices for research management.

Financing

The essential functions of the System as regards finances would be to address issues related to resource generation, targeted allocation and judicious utilisation. On the basis of recommendations of the National Health Research Management Forum, funds would be allocated in ways that are consistent with national priorities. External Partners would be apprised of these priorities, while a national capability to monitor where and how research funds are being spent, and the quantities involved, would be created and put in place. Ensure that funds are spent where the burden of disease is. Efforts would be made to invest at least 2% of national health expenditure in research and research capacity strengthening.

Knowledge Generation

The research system would generate knowledge relevant to the Indian health situation, appraise the measures available for dealing with health problems, and suggest the actions likely to produce the greatest improvement in health.

Utilisation and Management of Knowledge

The Research System fully endorses the principle that the research process does not end with Knowledge Generation, but includes the translation of results into policy or action, or absorption into the existing knowledge / technology base. For this to happen, links will be strengthened between researchers, policy makers, health and development workers, non-governmental organisations, communities, and media. Vertical and horizontal connectedness will be improved upon. More specifically, for better utilisation and management of knowledge, an information culture would be fostered, supported by enhanced use of information technologies currently and likely to be available. A synergy with Knowledge Management Policy would be made.

Capacity Development

A long-term approach to the development and maintenance of research capacity will be adopted. Efforts will be focussed on both the quantity and quality of skills available / needed, including research techniques, research priority setting, research management, use of research (‘demand’ side), policy and systems analysis, communications, development of partnerships including medical colleges and rural health research centres. A situation analysis done periodically would ensure a phased and realistic plan for constructive and sustained capacity development. Thus, both the ‘Supply’ and ‘Demand’ sides of the research system needs will be addressed. Encourage policy research.



The 10-point Action Programme -

1. Harmonize optimally National policies in a variety of areas (education, social sciences, population, agriculture, nutrition, science, etc) to facilitate intersectoral collaboration and partnership, so that maximum developmental returns can occur from health research.

2. Ensure true inter-sectorality of health research and harness the resources in areas such as social sciences, economics and traditional systems of medicine.

3. Facilitate priority setting to guide the direction of health research and prepare Five-year Plan and strategy documents

4. Encourage the development of fundamental and basic research in areas relevant to health to ensure that a national critical mass of scientists who can contribute the benefits of modern technology to health research is created.

5. Foster translational research to ensure that the products of basic research can be appropriately utilized in health systems and services.

6. Establish linkages between health research and national health programmes to identify key operational issues and facilitate the operationalization of evidence based programmes and to obtain feedback for the optimization of health research

7. Build and integrate capacity for research in National Health Programs, research institutions and in the private sector (profit and non-profit organizations) both in rural and urban research settings utilizing as far as possible areas of excellence already available in the country.

8. Ensure that the global knowledge base is available for national programmes, and that research is channelled in relevant directions without unnecessary duplication by the optimal use of information, communication and networking technology.

9. Manage global resources and transnational collaborations optimally to ensure that collaborative health research primarily facilitates the development of national health systems and services.

10. Generate the evidence-base for health systems and services, to be significant promoters of equity and contribute to national development so that health research becomes a poverty reduction tool.

AchievementThe Policy is under the consideration of the Government for approval. Action has been initiated for setting up of necessary infrastructure for implementation.



During the year under report, The Directory of Health Research Institutions, supported by the WHO is being updated. This data base of more than 800 Health Research Institution from India. The institutions belong to ICMR, CSIR, DST, DRDO, DSIR, Department of Biotechnology, Ministry of Health & Family Welfare, Department of AYUSH, Department of Pharmaceuticals, Ministry of Social Justice & Empowerment, and Medical Colleges with active research activity, NGOs and Private Organizations. A CD with “user friendly software” is available for users. The database can be searched on the DHR web site (http://202.141.106.123/httpdocs/DHRI/DHRIDefault.aspx).

Updation and analysis of the Database of Research Papers published by ICMR institutes in Scholarly Journals with Value addition has been completed for all the institutes/RMRC till 2010 and as part of ICMR centenary celebrations a “Compendium of ICMR Research Papers (1919-2010)- A consolidation” have been published. Along with this two more publications namely “ICMR’s Most Cited Research Papers : A Chronicle (1950-2010)” and Citation Classics of ICMR’s research Papers (1950-2010) –Five Most Cited Papers in Priority Area of the Council”. The PDFs of the documents can be accessed on ICMR website http://icmr.nic.in/Publications/centenary_books/compendium/index.htm,

http://icmr.nic.in/Publications/centenary_books/Most%20Cited%20Rearch%20Papers/index.htm, “http://icmr.nic.in/Publications/centenary_books/citations_classic/index.htm. respectively.

Mapping of Health Research Institutes



The DHR has been given the mandate of developing guidelines for accreditation of Health Research Institutes. The institutions engaged in research activities related to basic, applied, epidemiological and translational research may get recognition under this scheme. Two meetings with experts have been held and the draft guidelines and format for application form developed.

AchievementApproval of the competent authority has been accorded and process initiated for actual implementation for according recognition to Health Research Institutions.

Accreditation of Health Research Institutes



IntroductionThe Indian Council of Medical Research (ICMR) completed hundred years in 2011. The Centenary Year was launched by Hon’ble Union Minister of Health & Family Welfare Shri Ghulam Nabi Azad at a function held at New Delhi on 15 November 2010 and the concluding ceremony was held on 15th November 2011. A series of events were organized on this occasion by the ICMR Headquarters and its Institutes/Centres. In 1911, officers of the then Indian Medical Services had the vision and foresight to create Indian Research Fund Association. Soon after Independence, it was rechristened as Indian Council of Medical Research.

The Council has blossomed into a vibrant network of 32 permanent Institutes/ Centres and over 70 field stations, employing over 5000 personnel including 750 scientists.

The ICMR has evolved over the years in line with changing health research needs, effectively addressing the new challenges that have emerged as a result of the economic, demographic, nutritional and epidemiological transition of the country. With the changing health challenges, the demands on the ICMR are also increasing. The Mission of ICMR continues to be is to promote the better health through research.

The Council has accepted a twin track approach to meet its objectives –intramural (through its Institutes) and extramural research (through grants-in-aid to projects in non-ICMR institutions).

The permanent Institutes of ICMR are mission-oriented discipline/disease-specific laboratories strategically located in different parts of the country. Extramural research is promoted basically to strengthen the biomedical expertise and infrastructure especially in medical colleges and the university system, aimed at developing and fostering a culture of research in academia. Currently, the ICMR spends over 25% of its budget on the extramural research programme.

The research priorities of the Council coincide with health policy and priorities of the country. The Council works very closely with the national programmes, which have well designed targets for control, elimination and eradication of diseases. The ICMR is actively engaged in various aspects of research for control of communicable diseases (HIV/AIDS, tuberculosis, malaria and others); infectious diseases targeted for elimination (kala-azar, lymphatic filariasis, leprosy) and those targeted for eradication (yaws, poliomyelitis); non-communicable diseases (cardio vascular diseases, neurological disorders, metabolic diseases, cancers, injuries, etc.); and improving maternal and child health including nutrition. The Council also carry out basic, applied, operational, social and behavioral, and health systems research etc.

The majority of the research activities of the Council are directed towards diseases that have significant links with poverty. The Council has a special focus on health of marginalized and

Indian Council of Medical Research



under privileged section of society and is responsive to issue of equity, gender, ethnicity, race and caste.

The ICMR has provided critical research support whenever the health needs of the country demanded rapid responses. With globalization, international collaborative research has also increased. The Council has played an important role in defining the limits of collaborative research and ensuring that such research is conducted in an ethically acceptable manner.

Closing Ceremony of Centenary Celebrations of ICMRThe Centenary celebrations of ICMR were concluded on November 15th 2011. Many events were organized during the year.

For the Centenary celebration a special centenary logo of ICMR was conceived and developed which was used in all activities of ICMR.

The ICMR conceived and developed a centenary calendar depicting electron micrographs of important microorganism (viruses, bacteria, cells) taken from various ICMR laboratories across the country.

The Department of Post and Telecommunications released a Rs.5.00 commemorative postal stamp on ICMR to commemorate its centenary. The stamp was unveiled and released by Sri Kapil Sibal, Hon’ble Minister for Post & Telecommunications and HRD, Govt. of India on November 8, 2011.

The Ministry of Finance, Govt. of India issued Commemorative Rs.5.00 and Rs.100.00 coins on ICMR. The coins were released by Hon’ble Minister of Health and Family Welfare, Govt. of India in a ceremony organized on November 15, 2011.

The ICMR also organized a day long medical symposium on the occasion of year long closing ceremony of ICMR centenary celebrations. Many distinguished medical professionals, academicians, scientists highlighted the contributions of ICMR in the field of medical/health research on this occasion. Notable among these were Prof. P.N. Tandon, Prof. Manju Sharma, Lt. Gen. (Retd.)Dr. D. Raghunath, Prof. V.I. Mathan, Prof. K.K. Talwar, Prof. N.K. Ganguly, Dr. Hamida Saiyed, Prof. S.E. Hasnain, Dr. S.P. Tripathy, Dr. G.V. Satyavati, Dr. R.K. Srivastava & Maj. Gen. R.K. Bansal.

Following books/documents published by the ICMR were also released on the occasion:- 1. Compendium of ICMR Research Papers (1919-2010)- a consolidation.2. ICMR’s Most Cited Research Papers: A Chronicle (1950-2010).3. Citation Classics of ICMR’s research Papers (1950-2010) – Five Most Cited Papers in

Priority Area of Council.4. Bibliographic Details of Ten Most Cited Papers (Categorized under priority areas of the

Council).5. Directory of Health Research Institutions of India.

The ICMR also prepared DVD’s on research activities and contributions of ICMR Institutes/Centres. An album containing a set of Nine DVD’s was also released by Hon’ble Minister of Health & Family Welfare on this occasion.

All the ICMR Institutes/Centres also organized many seminars/symposia/conferences brought out publications, and organized scientific lectures in connection with the celebration the ICMR Centenary.

ICMR Centenary Celebrations

Release of Commemorative Postal Stamp by Shri Kapil Sibal, Hon’ble Minister for Post & Telecommunications and

Presentation of ICMR Awards, November 8, 2011

Closing Ceremony of ICMR Centenary Celebrations and Release of Commemorative Coins, November 15, 2011



Communicable Diseases

INtRAMURAL RESEARCH

NAtIONAL INStItUtE FOR RESEARCH IN tUBERCULOSIS, CHENNAI

Clinical StudiesShortening the duration of tB treatment

A randomized clinical trial to study the efficacy and safety of 3- and 4-month moxifloxacin regimens in pulmonary TB patients is ongoing.

Comparison of daily vs intermittent anti-tB regimens in HIV-infected tB patients

A randomized controlled clinical trial comparing daily and intermittent 6 – month in reducing failures & emergence of acquired rifampicin resistance in patients with HIV and pulmonary TB was initiated by NIRT. The trial has important translational value and implication in the programme.

trial of a new drug in the management of MDR tBA

Phase II, placebo-controlled, double-blind, randomized trial to evaluate the anti-bacterial activity, safety, and tolerability of TMC207 in subjects with sputum smear-positive pulmonary infection with multi-drug resistant M. tuberculosis (MDR-TB) is ongoing.

Evaluation of a Diagnostic Algorithm for HIV positive smear negative tB suspects

A prospective cohort study was undertaken to determine the utility of initial chest X ray and sputum culture in TB diagnostic algorithm among HIV-infected chest symptomatics who were sputum smear negative. Patient enrollment took place in Chennai and Pune during 2007-2009. Chest X ray abnormalities among HIV-infected chest symptomatics were not specific for TB. Conventional sputum culture was specific but failed to detect all cases of clinically diagnosed TB and took several weeks, highlighting the need for newer rapid tests for TB diagnosis.

tB treatment outcomes among HIV co-infected tuberculosis patients treated with once-daily antiretroviral therapy

A randomised clinical trial was conducted in NIRT to evaluate the safety and efficacy of once-daily antiretroviral therapy when administered with rifampicin containing thrice-weekly anti-tuberculosis treatment among HIV co-infected TB patients. TB outcomes were better in those who received efavirenz than nevirapine.

Socio-Behavioral StudiesAddressing psychosocial needs and HIV risk in MSMs in India: A study to examine the behavioral risk factors among MSMs was conducted. The qualitative study showed more than three quarters of the respondents remained unreached in any HIV prevention intervention program. This study explored the possibility of providing an intervention that targets psychosocial problems concurrent with HIV risk reduction behaviors among the MSM population.

Community based approach in designing an AIDS program for mothers living with HIV: The study has provided multidimensional portrayal of the impact of HIV/AIDS on mothers



living with HIV. The salient finding was the stigma experienced from health care providers. The study also covered their perceptions of a feasible intervention program and the focus areas for the intervention.

Vaccine trial: A Phase I HIV Vaccine trial was initiated at NIRT along with the National AIDS Research Institute, Pune. This heterologous prime boost trial was completed and clinical trial report was submitted.

Epidemiological studies: Studies were carried out to estimate prevalence of PTB in Chennai city , Effect of albendazole dose and interval on Wuchereria bancrofti microfilarial clearance in India and to estimate tobacco use in urban, semi-urban and rural areas from Tamil Nadu. The data analysis is being carried out.

Bacteriological studiesMycobacteriophage Genome Database: An exclusive user friendly database on mycobacteriophages with exhaustive information catalogued on a single platform after analysis was developed and functions assigned to the proteins by in silico approach. The data mining and genome annotation has been completed for 64 mycobacteriophages and linked to the database. This includes 7325 protein sequences and their functions.

Novel brominated antibiotic from marine Streptomyces sp R2 effective against M. tuberculosis and HIV: Novel marine Streptomyces sp R2 isolated from Coral reef deposit off Rameswaram coastal area exhibited promising activity against M. tuberculosis and HIV. The active pigmented compound was identified as a low molecular weight brominated molecule with a novel simple structure, the details of which are filed for Indian and PCT patents. Similar studies are on with compounds isolated from rare actinomycetes.

RNtCP-related activities: Serving as Supra national reference laboratory and working closely with IRLs to monitor RNTCP activities in India, working on accreditation of laboratories for Culture & DST and support second line drug DST for MDR TB.

Pharmacokinetics and Quality assurance of anti-tB drugs in children: Studies are ongoing to determine the pharmacokinetics of anti-TB drugs in children receiving treatment according to RNTCP guidelines to provide useful information to the programme regarding the adequacy of the existing drug dosages in children and to check for content of certain anti-TB drugs stored at different TB treatment centers of the RNTCP in Tamil Nadu.

Immunological studiesSeveral T cell antigens have been identified from the secreted proteome of M. tuberculosis, that specifically recognize only the healthy household contacts and thus are useful in diagnosis of latent TB infection.

Functional genomics of M. tuberculosis has shown that serine threonine kinase PknE contribute to resistance of host microbicidal responses by modulating the adaptive response genes in M. tuberculosis.

Recombinant BCG based epitope vaccine with immunodominant epitopes has been observed to elicit THI type of immune response and protective immunity.

Molecular epidemiology has been utilized to unravel genetic diversity, transmission and evolution of M. tuberculosis strains in India.

Immunogenetic studies in the south Indian population have shown CCL5 gene haplotype



A-C-C and the diplotype G/A-T/C to be associated with resistance to pulmonary TB, and G/A genotype of In2+5887 and G/G genotype of 3’UTR+12197 polymorphisms of CXCL12 gene to be associated with susceptibility to pulmonary TB among females.

Studies on the role of matrix metallo proteinases (MMPs) in tuberculous pleuritis have shown MMP-7 and -9 levels to be significantly higher in blood compared to pleural fluid in both TB and non-TB groups, suggesting that MMPs play a major role in inflammatory responses and possess all characteristics to act as a valuable biomarker.

Studies comparing the differential capacity of vaccine strains [Mycobacterium bovis (BCG) and Mycobacterium w (Mw)] and laboratory strain H37Rv to activate and enhance neutrophil functions have shown H37Rv to be highly effective in modulating neutrophil functions.

NAtIONAL JALMA INStItUtE FOR LEPROSY AND OtHER MYCOBACtERIAL DISEASES, AGRADuring the year the Institute focused its activities on leprosy, tuberculosis and on the Model Rural Health Research Unit at Ghatampur.

Partnerships were established with many national agencies like DBT, DST, Central TB Division and Central Leprosy Division of Ministry of Health and Family Welfare, Government of India, CSIR, ICAR and International agencies like WHO and through intramural and extramural grants from ICMR .The studies and research outputs could be implemented with the help of State Government health facilities and their partnership. Joint collaborative projects are being envisaged with Agra college (Dr Bhim Rao Ambedkar University) and Sauji Maharaj University of Kanpur.

Studies on leprosy- Studies in progress on leprosy include assessing early nerve damage, molecular tests for early diagnosis, studies on basic, clinical, therapeutics, serological tests for early diagnosis and predictors of reactions. Molecular tools to study the continued transmission in leprosy were also initiated in selected areas of UP, Chattisgarh and Tamil Nadu.

National Sample Survey to assess the disease burden in leprosy: The National Sample Survey to assess the leprosy burden and stigma prevailing in the society was undertaken along with NIMS, New Delhi, Central Leprosy Division, States and Union territories with active co-operation of health staff of the selected districts and cities. The results of the National Sample survey which has been completed in 97/of the 99 districts is being electronically entered and analyzed. Information will be useful for highly endemic areas and to the Central Leprosy Division of the Government of India to treat back log cases The interim report has been presented to the Ministry of Health & Family Welfare while detailed data analysis is ongoing.

Tuberculosis: Studies on understanding the new targets for drug resistance using molecular and proteomic approaches, identifying new antigens for early diagnosis continued. In partnership with the State TB Demonstration Centre at Agra and the RNTCP programme of the Government of India the Drug Resistance Surveillance studies are ongoing in 35 districts of Western UP and Bundelkhand region.

Programmes of National Reference Laboratory (NRL) for tuberculosis : Resource and manpower development has been undertaken and the Intermediary Reference Laboratories



(IRL) of Uttarakhand and Lucknow, Central UP have been accredited for performing drug resistance and sensitivity tests. The IRl’s of Himachal Pradesh and Assam are in the process of accreditation and manpower has already been trained so that they are able to take care of programme needs in these areas. Laboratories of several Medical Colleges e.g. Ajmer, Ahmadabad, Jaipur, AIIMS, and Laboratories of LRS New Delhi, have already been accredited in Line Probe Assay (LPA) for detection of MDR tuberculosis.

Training and human resource development: Partners in NLEP and RNTCP programmes of the country undertake training and re-orientation of program managers, doctors and laboratory staff routinely conduct summer training for 2 weeks each year to about 150-160 MSc students of life sciences on biosafety and laboratory techniques of several colleges (UP, MP, Delhi etc). Project training of 4-6 months duration, for 60-80 students/year as an essential part of MSc curriculum is undertaken every year. ASHA and other health workers have been trained in diagnosis and treatment of leprosy and tuberculosis in several districts like Unnao, Ramabai Nagar, Kanpur, Banda. Undertake MD thesis of students of SN Medical College, Agra (average 2-4/year). This year in addition one candidate each from Dr Rajendra Prasad Medical College, Tanda, HP and Medical College Safai, Etawah, UP have been registered with the Institute.

Evaluation of alternate regimens against leprosy : The Institute participated in multicentric clinical trial to provide uniform MDT for all type of leprosy patients initially .The safety and acceptability of the patients was established before it was adopted by the WHO as UMDT for all type of leprosy patients. The safety and efficacy of addition of (MIP) immunotherapy to chemotherapy (MDT) was established at the Institute in highly bacillated leprosy cases initially. The therapy has been approved by DGCI and marketed and is being used by medical practioners. The addition has also been seen to be safe and beneficial in Borderline patients (BT,BB,BL).The same is now being tried in tuberculosis with DOTS in a randomized double blind study in Category I and II cases of pulmonary TB, with NJIL&OMD as one of the centers.

National Facility: The BSL-3 facility for animal experimentation is a national facility for guinea pig aerosol infection for TB studies and have collaborated with several colleges e.g. PGIMER, ICGEB, AIIMS, NII, South Campus Delhi University, Kolkatta University, Sagar University, Jiwaji University, DRDO and companies like Piramal and Roche. The mouse foot pad laboratory is also being used as national facility for drug resistance studies in leprosy using this model. The Mycobacterial repository at the Institute has several well characterized strains from 37 medical colleges of the country and these are shared with researchers.

Model Rural Health Research Unit: The main focus here is on training and utilization of health services of the area for early detection and completing treatment of identified tuberculosis patients in the area. Strengthening the linkages with the health facilities of CHC, PHC’s, District hospitals and Medical College of the area for improving the deliverables.

NAtIONAL INStItUtE OF CHOLERA AND ENtERIC DISEASES, KOLKAtAThe establishment of the Global V. cholerae Data-base (GVD) with the collaboration of Centers for Disease Control and Prevention, Atlanta, USA and the Pulse Net Asia Pacific PFGE network aims to profile the pathogen through pulsed-field gel electrophoresis (PFGE) generated by the participating countries and to have a real-time linked system for the early



recognition of clusters of cholera that may flare into outbreaks. The PFGE profiles of several strains of V. cholerae isolated from many cholera outbreaks occurred recently have been uploaded by the institute.

The Live Oral Recombinant Cholera Vaccine Strain VA1.4 developed by the NICED in collaboration with the IICB, Kolkata and IMTech, Chandigarh was constructed from a clinical O1 V. cholerae strain negative for CT and enterotoxins like Zot and ACE. The ctxB encoding the highly immunogenic but nontoxic B subunit was introduced and the recombinant strain elicited high antitoxic and antibacterial immunity in human volunteers without causing diarrhea.

In a study 100% protection was achieved by oral administration of heat killed Shigella flexneri 2a in rabbit model of shigellosis. The responsible immunogen was found to be a 34 kDa outer membrane protein which has all the properties of becoming a subunit vaccine such as antigenically conserved, cross reactive and surface exposed. Furthermore, it also showed that 34 kDa OMP recognized TLR2 as a receptor on macrophages. Moreover, p38 MAP kinase has been found to be the important regulator of cytokines such as G-CSF, IL-1β, IL-6, TNF-α, IFN-γ and IL-12p70.

Schematic model showing predicted role of Hsp90 in NSP3 dimerization

Major events in the evolution of V.cholerae 01 El Tor variant and O139 CTX prophases in Kolkata



Detection of NDM-1 by phenotypic and genotypic methods



In a neonatal intensive care unit New Delhi metallo β-lactamase (NDM-1) in E. coli and Klebsiella pneumoniae in gut and blood isolates of neonates with sepsis was Identified and characterized.

Rotavirus-host interaction studies confirmed importance of cellular chaperone protein Hsp90 for folding and stability of RV protein NSP3 suggesting that virus utilizes cellular chaperone machinery for maturity and folding of viral proteins.

Studies on cag pathogenicity island of Helicobacter pylori strains from duodenal ulcer patients and asymptomatic subjects from Kolkata showed that although the cag PAI is an important virulence component for infection, the determination of the direction of disease development (gastritis, ulcers, or cancer) is likely to involve a highly complex interplay of many bacterial and/or host factors.

Curcumin showed immense therapeutic potential against Helicobacter pylori infection as it was highly effective in eradication of H. pylori from infected mice as well as in restoration of H. pylori-induced gastric damage and H. pylori eradication by curcumin involves significant downregulation of MMP-3 and -9 in H. pylori infected mice.

Baseline assessment identified elements for intervention development and were translated in formulating intervention packages for HIV stigma reduction. Genetic Characterization of HIV strain among IDUs in Nagaland was reported for the first time.

Curcumin: A potent antibacterial agent to eradicate Helicobacter pylori



NAtIONAL INStItUtE OF MALARIA RESEARCH, NEW DELHI

Epidemiology The therapeutic efficacy of antimalarials used in the programme was monitored and it was found that the same (artesunate+ sulphadoxine pyrimethamine for falciparum malaria and chloroquine for vivax malaria) are efficacious.

Pharmacovigilance of antimalarials revealed that there were minimum and non serious adverse events.

Based on the results of the phase II and III clinical trials carried out by NIMR, an application for marketing the fixed dose combination arterolane maleate and piperaquine phosphate has been filed with the DCGI.

Projection of malaria intensity using PRECIS model of climate change has been made for India with emphasis on Himalayan, Northeastern, Western Ghats and Coastal regions.

Epidemic thresholds for prediction of dengue outbreak in Delhi have been developed by various methods. It will be further backed up with thresholds of vector density.

With the help of GIS, 15 years district-wise malaria data were analysed to identify hotspot, endemic and epidemic prone areas for focused interventions.

Parasite BiologyA novel mechanism of activation of cysteine proteases of P.falciparum was identified. This information can be exploited to design small chemical molecules to inhibit these crucial enzymes of P . falciparum

CSR specific PCR assay to P. vivax and P. falciparum was evaluated. This is a single step assay and there are less chances of contamination or error and there is reduced cost and time.

Variations were found in PfHRP2 and PfHRP3 genes of P. falciparum. This had an impact on the sensitivity of malaria rapid diagnostic tests. Further, the gene was also lacking in few isolates.

Vector Biology and ControlInsecticide resistance in vectors was monitored in 156 districts in 13 states so far including all seven North Eastern states.

Presence of kdr mutations (1014F & 1014S) was mapped using PCR-based assays developed by NIMR. Both the alleles are present in Orissa and Chattishgarh in low frequencies. Indiscriminate use of pyrethroids may results in fixation of these two kdr alleles.

Field evaluation of different LLINs like PermaNet, Oyset net, Interceptor was carried out in different eco-epidemiological settings.

Technical support to the programmeProvided technical expertise in the form of inputs in national drug policy for malaria, insecticide policy etc. through operational research projects.

NIMR field units are also involved in outbreak investigations, monitoring of the intervention strategies, and development of action plan.



Infrastructure developmentThe construction of Animal Facility Building is in progress and facility will be functional by end of 2012

Human resource developmentTraining imparted to 29 Vector Borne Disease Consultants, 15 Laboratory Technicians and medical doctors. Training was also imparted to researchers on cultivation of malaria parasites.

The institute is recognized by various universities for Ph.D. programmme. Besides this, it also provides an opportunity to M.Sc. students to carry out their dissertation work.

Ten field units have trained biologists, entomologists, clinicians, laboratory technicians as per the need of the state governments.

Other achievementsThe institute has been identified as the sentinel site for dengue and chikungunya testing in Delhi.

NIMR is in the process of being designated as WHOPES collaborating centre for Phase I testing and evaluation of public health pesticides.

The NIH initiated two International Centers of Excellence for Malaria Research at NIMR: Center for the Study of Complex Malaria in India and Malaria Evolution in South Asia.

VECtOR CONtROL RESEARCH CENtRE, PUDUCHERRY

Lymphatic filariasisA cluster design based Lot Quality Assurance Sampling (LQAS) method was developed and validated against simple random sampling based LQAS through mass blood/antigenemia surveys in two Primary Health Centres, Tanjavur district, Tamil Nadu, where eight rounds of MDA with DEC + albendazole have been completed. The performance (in terms of estimating prevalence, precision, detecting hotspots) of cluster design was found to be cost-effective. The design has been incorporated in the revised guidelines of WHO for transmission assessment surveys to stop / continue the LF elimination programme.

Antigenemia prevalence in children (2-8 years) has been identified as a useful indicator for monitoring infection in sentinel and spot-check sites in place of operationally constrained microfilaria survey. Prevalence of antigenemia at 2.5% level has been determined as the threshold for stopping MDA.

Annual assessment of post intervention situation in the villages in Tamil Nadu that received ten rounds of MDA with DEC only or five rounds of MDA supplemented with one year of DEC salt distribution showed continued absence of transmission of Wuchereria bancrofti, with no resurgence even after five years of stopping intervention.

Clinical trials on the efficacy of different regimens of drug combinations given to microfilaria positives showed that the rate of clearance of microfilaraemia was significantly higher (80%) in sequential administration of DEC + albendazole at 90 days post treatment, compared to co-administration of DEC with doxycycline or DEC with albendazole. Side reactions and change in antigenemia rates were comparable.



A total of 75 substituted naphthoquinone analogues were synthesized so far and 14 have been identified to have macrofilaricidal activity by in vitro screening against Setaria digitata.

In silico and in-vivo studies have shown that Albendazole, currently used in the elimination of lymphatic filarisis programme is wolbachicidal and therefore filaricidal.

Six genes from Wuchereria bancrofti and its symbiont Wolbachia from different endemic regions were analysed for polymorphism. 16SrDNA gene was found highly variable among parasite populations suggesting a high intra-specific variability of Wolbachia endosymbiont.

Malaria Socio-behavioural survey in Kalahandi district of Odisha state revealed that long lasting insecticide nets (LLINs) were acceptable to the community as 91% of the households were regularly using the nets. The community does not show preference (124/150) to indoor residual spraying (IRS) primarily due to bad smell of the insecticide, which could partially contribute to low coverage and incomplete spraying.

A part of Glutathione S Transferase enzyme gene {GST (epsilon) E2} involved in the development of vector resistance to DDT has been characterized for the first time in Indian Anopheles culicifacies. Analysis of partial GST E2 gene sequence revealed two coding regions and one non-coding region. The translated product showed substitution of four amino acid residues when compared to An. culicifacies in Iran. The information has given a lead to the development of a marker to measure the expression status of epsilon GST (E2) enzyme protein in different populations on An. culicifacies.

A comprehensive vector map showing the prevalence of Anopheles species, relative abundance of the major malaria vectors, Anopheles fluviatilis and An. culicifacies, their sibling species composition in different ecotypes and seasons in relation to malaria incidence has been developed for eight southern districts of Odisha state. The density of Anopheles fluviatilis was higher in hill top/foot hill villages with higher malaria incidence. The plain villages recorded very low density with correspondingly lower incidence of malaria although the density of An. culicifacies was highest in this ecotype. An. fluviatilis remains susceptible to all insecticides in public health use and An. culicifacies was resistant to DDT and malathion. The information facilitated providing evidence based recommendations on vector control strategy for malaria control in these districts.

Construction of bed dams with sluice gate across stream has resulted in a significant reduction of larval density of Anopheles fluviatilis, the major malaria vector in a tribal village endemic for Plasmodium falciparum. This could be a potential component of integrated vector management for the control of fluviatilis transmitted falciparum malaria.

Dengue / Chikungunya / JEA community based IVM strategy was demonstrated in collaboration with Rubber Research Institute (Ministry of Commerce), Kottayam for the prevention of Aedes albopictus breeding, the vector of dengue/chikungunya in organized and un-organized rubber plantation sectors in Kottayam district, Kerala. Through continued source reduction measures by the community as well as workers in plantation areas, a significant reduction in the vector population was achieved. Monitoring of vector abundance showed low level vector density throughout the year (40-50% reduction during the peak season). During an outbreak investigation in Northern states of Kerala, natural infection of chikungunya virus was detected in Aedes albopictus.



Development of Microbial / chemical agents for vector controlAn aqueous suspension formulation of Pseudomonas fluorescens, a mosquito pupicidal bacterium was developed and laboratory evaluation has shown that the formulation is active against Anopheles stephensi, Culex quinquefasciatus and Aedes aegypti mosquitoes. The pupicidal metabolite from Pseudomonas fluorescens (VCRC B426) has been identified as a Rhamnolipid.

Fly ash based Bti (VCRC B17) formulations - water dispersible powder, slow release floating briquettes and slow release submerged granules developed in collaboration with Neyveli Lignite Corporation (NLC) were found effective against mosquito vectors in different breeding habitats.

Bacillus amyloliquefaciens, a potential mosquito pupicidal has been isolated from soil samples from Mangrove forest.

Nanoparticles for the public health organophosphorus larvicides, temephos and pirimiphos-methyl were developed and characterized by Scanning Electron Microscope and Particle Size Analyzer.

Translational researchProduction of mosquitocidal metabolite of B. subtilis has been up-scaled to pilot level with a satisfactory level of yield and quality and the material can be taken up for field testing.

A simplified process for the production and purification of Thrombinase, a fibrinolytic enzyme, has been developed that resulted in the reduction of number of steps and time, and increase in yield.

A combination of four terpenes present in the fruit extract of Trachyspermum ammi, which exhibited better macrofilaricidal activity (0.3mg/ml at 24 hrs incubation) against S. digitata was identified by in vitro screening.

RAJENDRA MEMORIAL RESEARCH INStItUtE OF MEDICAL SCIENCES, PAtNAThe RMRIMS, Patna continued the research activities through 46 intramural and 20 extramural projects on different aspects of visceral leishmaniasis (VL). Some of the major achievements are as follows:

EpidemiologyIn comparison with the potentiality of snowball technique as a surveillance tool for impact assessment of VL elimination programme, with household (HH) survey in two highly endemic blocks demonstrated that though snowball technique is cheaper than HH survey but has missed more than 50% of VL cases whereas concordance between HMIS and HH survey was about 85-100%, HH survey was recommended as baseline survey tool.

Overall quality of life (QOL) of VL patients was found significantly lower as compared to healthy control from similar socio-economic background. In spite of better health care facility at Govt. Health units, still about 52% of VL patients utilized private health facility that caused 7-8 time higher financial burdens on the family.



A door-to-door survey in two highly VL-endemic blocks revealed high prevalence of PKDL (about 7 per 10,000 population). It attracts need for active surveillance of PKDL to achieve VL elimination goal.

Camp approach, that was found best tool for active surveillance of VL, was implemented through State Govt. machinery on experimental basis under supervision.

DiagnosisA novel non invasive method for diagnosis of VL using rk-39 testing of sputum samples (Sensitivity 92.3%) has been developed field trial is under progress. Four commercially available rk-39 and rk-16 based RDTs (Dia-med IT Leish, Signal KA, Crystal KA, CTK biotech) were evaluated for sensitivity, specificity and thermal stability. In Indian sub-continents, all RDTs showed >95% sensitivity and specificity. PCR based diagnosis of VL from urine showed preliminary encouraging result.

Treatment Successful completion of Phase III clinical trial on amphomule revealed initial cure of 94.4% and final cure of 88.6% without any major toxicity. Combination therapy of amphotericin B and miltefosine was found highly effective for PKDL treatment as popular and nodular lesions disappeared after 28 days without any AE/ SAE. AmBbisome was tried for VL treatment in HIV co-infected patients and 92.7% survival rate was observed after 2 years follow up.

Basic Research Four plants’ extract exhibited in vitro antileishmanial effect (<12µg/ml) and however, one plant extract showed insecticidal effect on P.argentipes.

Hypocholesterolemia in VL patients was found positively correlated with Hb% and parasite load. Study on trace elements revealed more decreased Zinc level (P=0.007) and increased Mg (P=0.002) in chronic VL infection than acute ones.

Presence of mild to moderate level of microalbuninuria in 82% of VL cases and increased levels in PKDL cases, may be included as one of the parameters to assess and control the progression of renal disease.

Study on mechanism of amphotericin B (AmB) resistance in clinical isolates of L. donovani revealed three synergistic mechanisms: 1) Altered sterol composition of the membrane, 2) Drug efflux mechanism and 3) Improved ROS scavenging machinery (thiol metabolic pathway). Microarray analysis revealed 41 differentially expressed genes; 3 fold up-regulated in AmB resistant strain. Functional characterization and validation revealed ascorbate peroxidase and MDR1 its involvement in AmB resistance mechanism.

Various recombinants fusion proteins involved in Fe-S clusters assembly and thiol metabolic pathways in L. donovani were cloned, expressed and purified. Catalytic component (IscS) and scaffold component (IscU) interaction, their complex formation and localization in mitochondria of L. donovani’s were proved. For the first time, TryS and TryR interaction and their localization was proved. The purified proteins involved in thiol metabolism recognize antibodies in human VL patients sera can be explored as diagnostic markers against Leishmaniasis.



In a study to understand the immune cell participation in the pathogenesis of PKDL, lower expression of cytokine IFN-γ and elevated level of IL-4, IL-10 & TGF-β was observed suggesting high inflammatory response at the site of PKDL lesions. Increased secretion of CCR4, CCR5 & CCR7 in tissue suggests more trafficking of immune cells during PKDL infection.

Vector ControlThe developed monitoring and evaluation (M&E) toolkit was applied at the ground level to identify improvement and short falls in IRS operation. Meetings and workshops were organized involving ACMOs, DMOs and MIs of 26 districts to share and exchange of views on Toolkit.

The customized GIS software has been developed to delineate the sandfly density and validated with the ground data. Developed Land surface temperature model from the satellite imagery to estimate the surface temperature of ground. Moran’s I statistics was used to estimate the spatial autocorrelation of VL disease distribution.

Bioinformatics Structure modeling of various novel target proteins of L. donovani were modeled and screened through docking analysis. The ligand protein interaction revealed saframycin A may arrest the growth of L. donovani. Novel sequence has been submitted to NCBI. LeishMICROSATdb database containing the whole genomic sequences of different Leishmania strains was developed. Other relational databases like LEISHPROT, cpdbldv, CALP, JEVBase and chpvdb were developed.

CENtRE FOR RESEARCH IN MEDICAL ENtOMOLOGY, MADURAI

Japanese EncephalitisJE virus activity was monitored longitudinally in the endemic villages of Cuddalore district, Tamil Nadu. During 2010-11 a total of 9692 mosquitoes representing 25 different species belonging to five genera were collected in 76 man-hours. Culex tritaeniorhynchus with PMH density 69.08 (54.17%) was the pre-dominant species followed by Culex gelidus with PMH density 35.20 (27.60%). The abundance of Cx. gelidus was relatively higher followed by Cx. tritaeniorhynchus which may play a significant role in the maintenance of the JEV in nature. A remote sensing/GIS study has revealed a strong correlation between breeding source and vector breeding. JE vector abundance was also monitored through environmental determinants using Remote Sensing (RS) & Geographical Information Systems (GIS) after mosquito collection during dusk hours in two villages from 3 different crop areas, viz., Double crop, Single crop, Rain-fed crop of rice cultivation. In the double crop area, Cx. gelidus was the most dominant species constituting 52.60% followed by Cx. tritaeniorhynchus (33.34%), Cx. fuscocephala (0.85%), Cx. vishnui (0.77%), Cx.infula (0.02%)and other culicines (7.67%). In the single crop area, Cx. tritaeniorhynchus was the dominant species comprised of 75.46 % followed by Cx. gelidus (5.73%), Cx. vishnui (1.64%), Cx. fuscocephala (2.68%), Cx. infula (1.81%) and others (3.79%). The collections from the rain-fed crop area showed Cx. tritaeniorhynchus to be the dominant species constituting 64.14% followed by Cx. vishnui (4.95%), Cx. gelidus (5.07%), Cx. fuscocephala



(4.10%) and others (2.97%). The JE vectors Cx. vishnui subgroup of mosquitoes contributed maximum from single crop area (77.51%), and in rain fed area (69.09%), compared to only 34.11% in double crop area. The secondary vector Cx. gelidus contributed 52.60% from double crop area when compared to other two areas.

A study was carried out in Tanjavur district, and in the non-endemic area .The entomological surveillance was initiated in three index areas which were hyperendemic (Villupuram district), moderately endemic (Cuddalore district) and non-endemic (Thanjavur district). A total of 24816 mosquitoes from 25 different species, belonging to six genera were collected spending 252 man hours from the afore mentioned areas. Among Cx. vishnui subgroup of mosquitoes collected, Cx. tritaeniorhynchus was the pre dominant vector species comprised of 86.84% of the total. PMH density of Cx. vishnui subgroup species was relatively high in the non-endemic areas (PMH 218.36) when compared to moderately (PMH 68.58) and hyper (PMH 75.7) endemic areas, indicating on an average three-fold increase in vector abundance in the non-endemic areas. In moderately endemic and non-endemic areas, the PMH density of Cx. vishnui subgroup mosquito species started increasing from the month of August onwards and reached the peak density during the month of November but in the hyper endemic areas the peak got extended up to January coinciding with the northeast monsoon. The paddy cultivation correlated with the abundance of Cx. vishnui subgroup species in higher density in hyper-endemic areas where three paddy crops per year are cultivated but in both of other two areas only 1-2 crops are cultivated. Out of a total of 597 pools consisting of 26754 mosquitoes screened for JEV by antigen capture ELISA, seventeen pools were found positive: 9 from non-endemic, 5 from hyperendemic and 3 from moderately endemic. Of the 17 positive pools 15 belonged to Cx. tritaeniorhynchus and one each from Cx. gelidus and Cx. fuscocephala. Most of the positive pools were from the non-endemic area, Thanjavur district.

Dengue A study was conducted to explore “Eco-Bio-Social” factors in dengue vector population in Chennai city, - an ideal urban situation for perpetual dengue infection, and to find out a model for effective control of the disease by integrating eco-bio-social components. In the baseline entomological survey (larva and pupal survey) cement cistern/tanks, drums (50 lit – 200 lit) were found most productive for the dengue vector, Aedes aegypti, in both dry and wet seasons. The stakeholders who had different degree and types of relationship with the dengue/mosquito problem in the community were identified to understand the dengue problem in local social system and to develop strategies to involve them in dengue control in Chennai city. After the intervention, Ae. aegypti indices (Breteau and house indices), in addition to pupae per person index; got reduced significantly in intervention clusters where the community based environmental management strategy was implemented compared with clusters that had the routine vector control programme alone. The environmental friendly methods with active women group participation in the intervention households had good effect.

Filariasis The impact of mass drug administration (MDA) using diethylcarbamazine (DEC) with and without albendazole under filariasis elimination campaign on geohelminth infection. was estimated in 18 villages of Tirukoilur taluk, Villupuram District, Tamil Nadu during



post MDA VII. Reductions in soil transmitted helminth prevalence and egg intensities at 6 months post-treatment period in DEC+ALB arm was similar to that observed for the previous MDAs demonstrating an impact on all 3 helminths, while DEC alone showed effect only on Ascaris. The above indices estimated during post MDAs demonstrates the added advantage of addition of albendazole along with DEC in the LF elimination programme. In the MDA alone villages (without vector control), the transmission was observed in 5 of the 8 months monitored during post-VC period, and the overall TII value was 0.0997. The costing data was consolidated for the three different strategy arms. Addition of VC, was found to be costly in the first year of implementation, and is assumed to be cost effective for elimination of LF in the subsequent years if the population continues to work with self-sufficiency.

During January-November 2011, 5330 vector mosquitoes were collected in the two intervention MDA+EPS and MDA+EPS+PIC arms (24 villages) as compared to 6370 in MDA alone arm (12 villages), kept as control. The overall per man hour density was 12.06, 4.87 and 5.22 in MDA alone, MDA+EPS and MDA+PIC+EPS arms respectively and there was >84% reduction in PMH in both the VC . The infection rate (0.32%) and the infectivity rate (0.04%) were significantly reduced in the MDA+EPS arm villages, with the transmission intensity index of 0.0019.

Molecular biologyVirological studies of investigation of an outbreak of suspected virus infection in certain districts of Tamil Nadu were carried out. Chikungunya virus was isolated in outbreak occurred in Thirunelveli district. Viral isolation and molecular diagnosis confirmed the involvement of Chikungunya virus (CHIKV) in the episode. The phylogenetic analysis of the virus based on partial sequence of the immunodominant envelop gene (E1) showed that the virus belong to the Central-East African strain. Further to characterize the virus, complete sequencing of the viral genome is being carried out.

NAtIONAL INStItUtE OF VIROLOGY, PUNE

Encephalitis The NIV plays a crucial role in the preparation and supply of diagnostic kits for Japanese Encephalitis, Dengue and Chikungunya to the national program. This year, 2828 MAC ELISA kits (JE, 237; Dengue, 1849; and Chikungunya, 742) were supplied. A candidate JEV vaccine strain was transferred to Bharat Biotech India Ltd (BBIL). The formalin-inactivated Vero cell vaccine lots were prepared at BBIL. The genetic stability of the strain was determined. The Phase I trial was conducted using 2-3 doses of the vaccine. Sero-conversion (≥4-fold increase in titer) in subjects administered with two and three doses were 90.48% and 96% respectively. No sero-conversion was observed with placebo dose. Phase II/III trials were completed recently and further analysis is in progress.

JEV genotype III (GIII) is circulating in India since its first detection. Vaccination with SA14-14-2 (GIII) is underway. NIV has demonstrated the recent introduction of JEV GI strain in the country and its increasing association with the human cases. Based on the neutralization studies using anti-SA14-14-2 human sera and vaccination / challenge studies in mice, it was demonstrated that SA14-14-2 vaccine could confer efficient protection against both GI and GIII strains.



High Containment Laboratory & Virus RepositoryNosocomial CCHFV outbreak occurred in January 2011 in a tertiary care hospital in Ahmedabad, India, resulting in 5 deaths, two being treating medical professionals. Virus was isolated from one case. The ‘S’ gene sequencing of CCHFV showed highest homology (98%) with the Tajikistan strain. About 17% domestic animals from Kolat, Ahmedabad were positive for IgG antibodies. Two pools of Hyalomma anatolicum anatolicum species from domestic animals from Kolat were positive for CCHFV in qRT-PCR and virus isolation. Only one of the hospital contacts out of 64 found IgM antibodies positive. All 90 samples collected from rodents were negative for CCHFV. Two patients from Rajkot, Gujarat, referred during March 2010 were also diagnosed a to have CCHFV infection. An IgM antibody capture ELISA was standardized for the detection of antibodies against CCHFV.

A new cell line was developed from the embryonic tissues from Pipistrellus ceylonicus bat and characterized. A diagnostic PCR developed for Bat AdV showed 4/176 samples from Maharashtra to be positive for this novel adenovirus.

EpidemiologyAn immunogenicity study of single 0.5 ml intramuscular dose of pandemic influenza vaccine among health care staff in Pune showed persistence of protective antibody levels at 12 months. A community based surveillance study of influenza, dengue and rotavirus diarrhoea is ongoing in Janata Vasahat, Parvati, Pune since July 2010. Under the project, a total of 477 throat swabs were collected from study area. Pandemic influenza A(H1N1) 2009 virus was detected in 3 cases, type B in 29 and A(H3N2) in 54 cases.

Hepatitis: HEV-infected pregnant women in different trimesters were shown to behave differently with respect to immunologic parameters. Association of TLR4 polymorphism with hepatitis E was shown. As a part of the multi-centric ICMR task force project for assessing efficacy of different drugs for chronic hepatitis B, molecular parameters were studied for sequential samples for ~200 patients. Full genome sequences were determined for responder and non-responder patients.

HA, NP and M2 protein/DNA based candidate vaccine(s) for H5N1 influenza were tested along with different adjuvants in mouse model. Significant level of protection was obtained with some candidates when immunized mice were challenged with the lethal



virus. Importantly, adjuvanted conserved recombinant proteins based on the Navapur strain offered significant protection against the Jamshetpur strain belonging to a different clade.

An adult mouse model was developed for Chikungunya. The recombinant E2 protein-based and formalin/BPL-inactivated whole virus vaccines were highly immunogenic and produced long-lasting sterilizing immunity in mice.

Both SOLiD and Ion Torront platforms are being used to identify Gorakhpur agent in the samples collected during the current season. In the absence of the permission of CPCSEA (pending for last 8 months), the transmission experiments in rhesus monkeys could not be initiated.

Entomology / Chikungunya Venereal transmission of chikungunya virus in Aedes aegypti was confirmed in the laboratory. Similarly, the persistence of chikungunya virus in the infected and desiccated Aedes aegypti mosquito was also confirmed. Potent siRNAs were developed and exhibited excellent protection in-vitro and in a murine model.

Dengue In the light of the importance of the molecular evolution of dengue virus in the spread and increase in the disease severity observed in the last two decades, we identified a new lineage in the genotype III of DENV-3 and a new genotype for DENV-4. The studies also indicated that the South of India and Sri Lanka provided a fertile ground for evolutionary events for both viruses. The currently circulating viruses of DENV-3 belong to lineages C & E of genotype III while DENV-4 viruses belong to lineage C of genotype I. The role of inflammatory cytokines is known in the dengue disease pathogenesis. To understand the role of host genetics in disease manifestation seen in India, Cytokine gene polymorphism



was studied. Combined genotypes of TNF-α, IFN-γ and IL-10, were significantly associated with DHF. Studies on dengue prevalence in the rural population on the outskirts of Pune revealed that the prevalence of dengue was higher in the peri-urban village compared to a rural village.

InfluenzaInfluenza surveillance activity was carried out to identify circulating strains in community which showed A (H3N2) and Type B (predominantly Victoria lineage) to be co-circulating. Seventy five Isolates were submitted to WHO collaborating centre for vaccine selection. Studies on influenza disease burden in rural communities showed that overall, 7.1% of all hospital admissions were influenza-positive (19.6% during peak influenza activity). The annual incidence of influenza was significantly higher in May 2009 – April 2010 than during May 2010 – April 2011 (4.37 vs 3.78/1000, p=0.031), however the incidence of pH1N1 did not differ in 2009-10 and 2010-11 (2.03 and 2.17, respectively). A multiplex RT PCR for the detection of 15 different respiratory disease viruses in clinical samples was developed. Respiratory syncytial virus, metapneumovirus, parainfluenza virus-3 and rhinovirus were predominantly found in pediatric patients. Partial molecular characterization of RSV, HMPV and rhinovirus were carried out.

Electron Microscopy and HistopathologyThe dengue 2 virus (DENV) infection of a novel human endothelial cell line of hepatic origin (SK Hep1) was conclusively demonstrated that correlated with changes in cellular adhesion molecules, primarily ICAM family. Further, the expression of envelope glycoprotein of the virus could also alter endothelial cell ultrastructure and endomembrane organization implicating strongly the role of intracellular membranes and lipid changes in the cellular stress response of endothelial cells to DEN. Using high resolution electron tomography, we could demonstrate that dengue virus infection induces the phenomenon of autophagy in a human endothelial cell line.

Immunhistochemical analysis of the biopsied brain and heart tissues from representative fatal cases of acute encephalitis syndrome from Gorakhpur, Uttar Pradesh, showed evidence of inflammatory cytokines in tissues confirming encephalo-myocarditis-like profile in the cases.

Bioinformatics Evolutionary dynamics of pandemic H1N1 2009 virus strains with emphasis on the Indian isolates over the period from May 2009 to October 2010 was studied in terms of molecular clock and selection pressure in the HA gene. Other major contributions include studies on the genetic diversity of Influenza A/H3N2 viruses in Indian 2004-2011, evolutionary dynamics of Dengue type I viruses over the last 50 years in India with reference to global dynamics and molecular characterization of Chandipura viruses of epidemic strains in India and comparison with other rhabdoviruses. Antigenic variability of HA and NA proteins of H3N2 viruses (1968-2009) has been studied in the light of antigen-antibody interactions. Future projects to be taken up include molecular evolution of Dengue types III and IV and standardization of protocols for phylogeography, molecular clock studies of CCHF viruses from the recent outbreak in Gujarat, India (2011) and molecular dynamics studies of NA-drug interactions for Influenza viruses.



NIV UNITSBangalore Unit: As a part of the AFP surveillance for global poliomyelitis eradication programme, none of the 9764 stool specimens tested from 4888 AFP cases from Uttar Pradesh, Karnataka and Kerala states showed the presence of wild poliovirus. Importantly, 1537 were Non-Polio-Enteroviruses while 2956 could not be identified. As a part of the Measles surveillance for global Measles elimination programme, of the 37 outbreaks investigated from Karnataka and Kerala states, etiology of measles and rubella was confirmed for 20 (54.1%) and 6 (16.2%) outbreaks respectively while 11 (29.7%) were mixed Measles and Rubella outbreaks. WHO Profiency tests for Measles and Rubella FTA Practice Panels were passed, 3/110 Measles virus isolation negative TCF’s were Rubella-RNA positive by RT-PCR and were Genotype 2B.

Gorakhpur Unit: In order to understand the prevalence of JE virus, using the population proportional sampling method, 2220 samples from the age group 1-15 years were collected from 28 blocks in seven districts of eastern UP of Gorakhpur and Basti Division. The results indicated consistent circulation of JE virus in the region. Children in the age group 1-15 yrs were vaccinated with attenuated SA 14-14-2 vaccine during December 2010. Along with the seroprevalence studies Serologic response of 575 children revealed that 88% of vaccines seroconverted within one month increasing to 94% after six months.

Kerala unit: This unit was identified as a Referral centre for ICMR-CDC Influenza surveillance network and a Grade I virology Laboratory by ICMR. In addition to provide virological diagnosis, an outbreak of Influenza in Alappuzha district was attributed to H3N2. Etiology of an outbreak of encephalitis in adults was confirmed to be West Nile virus.

ENtEROVIRUS RESEARCH CENtRE, MUMBAI

Poliomyelitis Surveillance The EVRC continued to test clinical samples of cases of acute flaccid paralysis for detection of wild poliovirus transmission in India and neighboring countries. A total of 11202 and 8676

Wild polioviruses detected in weekly sewage samples from 3 slum areas in Mumbai during 2008 to 2011. None of the samples in 2010-2011 contained wild poliovirus.



stool samples of 5595 and 4318 AFP cases reported in Maharashtra, MP, Chatisgarh and Goa in 2010 and 2011 were tested for detection of wild and vaccine derived polioviruses. Polioviruses were isolated from 232 and 233 cases in 2010 and 2011 respectively. In addition, polioviruses isolated in other national polio network laboratories and those from Bangladesh, Sri Lanka and Myanmar were received for confirmation of the laboratory results or further characterization. In 2011, poliomyelitis due to WPV was confirmed only in one cases reported in Howrah District, West Bengal (date of onset 13 January 2011). The type 1 wild poliovirus isolated from this case showed close genetic linkage with virus transmission detected in Delhi in the previous year. As of end of 2011, India has remained polio-free for 11 months.

Dendrogram showing close similarity of VP1 sequences of the wild poliovirus type 1 isolated in Tajikistan and India (western Uttar Pradesh). The importation of wild poliovirus type 1 in polio free region of Europe caused more than 450 polio cases.

Environmental samples surveillance Testing sewage samples collected from three high-risk slum areas in Mumbai for wild poliovirus continued for the 11th year. In addition, ERC oversees the sewage samples testing in Delhi done at NCDC Delhi. In 2011, sewage samples collection in Patna, Bihar and Kolkata, West Bengal was initiated.

Detection of VDPVAn outbreak of type 2 circulating vaccine derived poliovirus (type 2 cVDPV) was reported in India in 2009. Five type 2 VDPV cases were reported in 2010 and six type 2 and one type 3 VDPV were isolated in 2011. Since 2009 VDPV have been isolated from sewage samples in Mumbai and Delhi. Two VDPVs (one each of type 1 and type 3) were isolated from sewage samples in Mumbai in 2009 and one type 2 VDPV in 2011. Four type 2 VDPVs were isolated from sewage samples in Delhi in 2010 and two VDPVs (one each of type 1 and type 2) were isolated in 2011.



Rapid diagnosis of poliovirus infectionSensitive and specific rapid diagnosis methods are needed for wild poliovirus detection and control. Presently virus culture followed by real time PCR identification of poliovirus is used as the method of choice in Global Polio Laboratory Network. Flow cytometry and PCR methods were compared for detection of poliovirus infections in cell cultures inoculated with clinical samples. Stool samples which were earlier tested by the standard routine method and known to have not produced poliovirus CPE within 48h post inoculation were retested by Flowcytometry at 20 h and 40 h after inoculation in cell cultures. In 90% (27/30 specimens) samples poliovirus specific fluorescence was detected before onset of visible CPE. Flowcytometry method has the potential for rapid detection of poliovirus infection.

NPEV in AFP casesEnteroviruses may cause a variety of diseases including paralysis, meningitis, encephalitis, gastroenteritis, respiratory diseases, cardiovascular diseases, diabetes and exanthemas. Enterovirus isolation rates from stool samples of AFP cases varies greatly (5 to 40%) depending upon local hygiene and sanitation conditions. During 2010 and 2011, Non-polio Enteroviruses were isolated from 27.04% (1513/5595 cases) and 25.57% (1104/4318 cases) of AFP cases reported in Maharashtra, MP, Chastisgarh and Goa. NPEV were isolated from 22.4% (320/1428) AFP cases reported in Mumbai during 2008 to 2010. Fifty six Enterovirus types were identified by partial VP1 gene sequencing of 244 isolates. E3, E6, E11, E26, E30, EV76 and CAV4 were the most frequent isolates. New Enterovirus types detected in Mumbai were EV73- EV77, EV80, EV89, EV90, EV93, EV101 and EV107. Association of NPEV with AFP is being evaluated.

Detection of non-cultivable EnterovirusesPolio Laboratories use RD (human rhabdomyosarcoma) and L20B (human PVR expressing murine cells) for isolation of polioviruses from stool specimens of AFP cases. RD cells are susceptible to a large number of Enterovirus types but not all. An attempt was made to use molecular techniques to detect and identify EV otherwise not detected by the currently used virus isolation algorithm. Total 360 culture negative stool samples were tested by real time EV specific RT-PCR and partial VP1 sequencing, 23.3% (84/360) samples yielded Enteroviruses including CVA1, CVA19 and CVA22 which do not grow in RD cells.

Non-Polio Enteroviruses outbreak investigationsHand Foot and Mouth Disease outbreak has been reported in Thane, Maharashtra since 2006 .Outbreaks were reported in the same district in 2009, 2010 and 2011 and in January in Wellington, Tamil Nadu and Agartala, Tripura in April 2010. Virus culture and molecular typing methods identified CVA6 as the etiological Enterovirus of HFMD outbreak in Thane in 2009, CVA16 in Wellington and Thane in 2010, CVA6 in Agartala and CVA16 in 2011 outbreak in Thane. EV71 was isolated from one case of HFMD in Thane in 2011.

Enteroviruses in Herpangina cases in ThaneHerpangina is characterized by ulcers and lesions in the mouth with sore throat and fever. Cases are reported among children during the summer months. A toal of 78 cases of



herpangina (64% below 3 years of age) were tested for Enteroviruses in throat swabs and stool samples. EV was detected in 69.2% cases with high predominance of CVA10 and CVA4. Other viruses isolated infrequently were CVA2, CVA6, CVA8, CVA21, CBV4, and E12. CVA4 and CVA10 appear to be the main cause of herpangina. Assay for detection of polymorphism in poliovirus receptor (CD155): Human cell surface molecule CD155 serves as the poliovirus receptor. It has been postulated that mutation at the 67th amino acid from Alanine to Threonine (Ala67Thr) increases susceptibility to polio paralysis. We developed new specific primers and standardized an SNP assay for detecting genetic polymorphism at this site. Preliminary results showed higher frequency of mutation at the site in a small number of Indian subjects tested during the assay standardization process. A project is being formulated to test genetic variation CD155 among confirmed poliomyelitis patients and controls in collaboration with National Polio Surveillance Project.

Population Immunity against Polioviruses in high risk blocks of UP and BiharPolio eradication requires high population immunity to stop wild poliovirus transmission. In 2009, ERC participated in a 5 arm vaccine trial to evaluate performance of bivalent OPV containing poliovirus type 1 and type 3. bOPV was found to be superior to trivalent OPV and not inferior to mOPV. bOPV was introduced in polio program for supplementary immunization in December 2009. Population immunity surveys were undertaken in highest risk areas in Uttar Pradesh and Bihar (10 blocks each) in 2010 and 2011. Polio 1 antibody seroprevalence among children 6 to 7 months age (n=1200) was more than 95% and polio 3 antibody prevalence between 70 to 85% in 2011. Results indicated that high population immunity against polio 1 was maintained and immunity levels increased against type 3 following introduction of bOPV.

Evaluation of mucosal immunity against poliovirus infection following OPV and IPV immunization Maintaining high sero prevalence against all three poliovirus types is essential to reach zero polio status. Maintaining high levels of gut immunity (mucosal immunity) is necessary to break all transmission chains of wild polioviruses. A WHO collaborative project is underway to evaluate mucosal immunity in children immunized with OPV and IPV (in previously OPV immunized children) in Moradabad district Uttar Pradesh. A total of 990 children have been enrolled in the study. Challenge virus excretion, crevicular fluid polio specific sIgA response, sIgA in fecal samples and serological investigations are being done. ERC is performing serology, virus isolation and quantification for 2935 sera and 4871 stool samples collected from 990 study participants.

Investigation of immunodeficiencyPolio eradication has been found difficult in Uttar Pradesh and Bihar due to several reasons. Lower antibody prevalence in children in these States could be due to many reasons including failure to vaccinate, vaccine failure, malnutrition and immunodeficiency. Low levels of serum IgG and IgA are markers of humoral immunodeficiency. Samples collected from apparently healthy children participants of polio-antibody sero-prevalence study in Moradabad and AFP cases reported in 25 districts in western Uttar Pradesh were studied. The mean IgG levels of normal children and AFP cases were 11.63±0.174g/L and 9.58± 0.011g/L, respectively. Though IgG levels differed significantly (P<0.0001) which could be



because of the large sample sizes the proportion of children with hypogammaglobulinemia remained same (0.7% in both groups). Around 8% healthy children and 9.5% AFP cases showed IgG levels less than 5g/L. Similarly IgA concentrations were found to be within normal range (1.2± 0.026g/L) in both groups. The results showed that immunodeficiency was not the main cause for high endemicity of polio in western UP.

VDPV in immunodeficient AFP casesVaccine derived polioviruses were isolated in 2009 in India for the first time. Low OPV immunization coverage and immunodeficiency are the recognized causes of development VDPV in any community. We initiated testing serum IgG and IgA concentration of VDPV cases for humoral immunodeficiency since 2009. In 2011, VDPV were isolated two hypogammaglobulinemic and one agammaglobilinemic patients. A gammablobulinemia was confirmed by absence of B lymphocytes by Flowcytometry at National Institute of Immunohematology (NIIH).

The Centre continued to supply cell lines to the National and Reference Laboratories in SEAR. The Centre also performed mycoplasma screening for cell culture contamination for the polio network labs in SEAR on regular basis and conducted training programmes on use of real time RT-PCR techniques , GLP and Poliovirus isolation, environmental sample collection, processing and poliovirus isolation etc.

ICMR VIRUS UNIt, KOLKAtA

Studies on Viral HepatitisThe natural history of hepatitis B virus (HBV) infection is modified in HIV coinfection. However, HBV genetic evolution during HIV associated immune suppression remains largely undefined. Furthermore, increased use of antiretroviral therapy (ART) in HIV-HBV coinfection might trigger the appearance of new group of HBV mutants, underscoring the importance of the study. Blood samples from 610 ART-naïve HIV patients coming to ART center of Calcutta School of Tropical Medicine, Kolkata was screened for the presence of HBsAg and 92 (15.08%) were found to be positive for HBsAg. Among them 73 HIV patients (Mean age 34.7 + 7.24 ) were detected positive for both HBsAg (14.71%) and HBV DNA and 11 ART treated patients were also included in the study. HBV genotype/subgenotype and mutations in surface and polymerase gene were investigated by nested-PCR followed by sequencing. Among HIV-HBV coinfected patients from eastern India, HBV/D was predominant (67.12%). Among the four HBV/D subgenotypes present, HBV/D2 was significant (68.08%, P<0.001), and had very high hepatitis B early antigen (HBeAg) positivity (83.33%). Immune escape mutations, premature stop codon (C69stop), lamivudine resistant triple mutation and corresponding vaccine escape mutation (E164D) were also found. HBV/D2 isolated from patients with CD4 count <300 cells/mm3 showed higher viral load and lowest genetic diversity compared to HBV/D2 isolates in patients with CD4 count ≥300 cells/mm3; as well as compared to non-HBV/D2 isolates in patients from both the groups. Compared to other subgenotypes, non-synonymous changes in overlapping pool gene were highest in HBV/D2 samples. HBV/D3 isolates from eastern Indian HIV patients showed sequence almost 100% similarity with western Indian HBV/D3 consensus sequence.

PCR amplification system was standardized to amplify the whole HCV envelope gene using genotype specific primers by nested PCR with Expand long template PCR system



(Roche). Analysis of envelope gene sequence data showed 51% to 91% homology among Gen-3 and 74% to 88% homology among Gen-1. Envelope protein amino acid sequence analysis showed 58% to 92% and 59% to 86% homology to Gen-3 and Gen-1 respectively. Interestingly, higher conservancy within HCV envelope gene was observed among HCV Gen-3 than Gen-1.To clone entire open reading frame and most part of the non-coding regions of HCV RNA genome, 9.28kb HCV RNA genome of a genotype 3a was successfully amplified by long template nested RT-PCR. Sequencing of PCR amplified product of 5’UTR (99%) and NS5B (96%) regions showed homology to amplified HCV genome.

Studies on Arbovirus InfectionDuring this year, a total of 796 acute sera samples, suspected Dengue and Chikungunya cases, were referred for the detection of respective IgM antibody from different medical colleges in Kolkata and also by the District health authority of different districts adjacent to Kolkata. A total of 118 and 256 samples were positive for Dengue and Chikungunya respectively. Among them, 59 samples were detected to have dual infections with both Dengue and Chikungunya viruses. Interestingly, in all the samples the O.D value of the Chikungunya IgM antibody was at least four times higher than the O.D value of the Dengue IgM antibody. Among 151 acute cases having history of fever up to 48 hours, 52 cases were identified as Chikungunya and 16 were identified as Dengue by RT-PCR method. Of them, only in 16 cases Chikungunya could be isolated in cell culture. In addition, blood samples from 82 AES cases were collected from different District hospitals and different medical colleges in West Bengal. These were referred for the detection of JEV. Out of 79 sera samples, 22 were positive to JE IgM antibody and all of them were negative to Dengue IgM antibody. Viral RNA could be detected by RT-PCR only from 2 IgM positive and 12 acute samples, nonreactive by ELISA method.

Studies on herpes simplex virus infectionEvaluation of anti-herpes virus activity of bioactive alkaloid, its characterization, synthesis and mechanism of action was also carried out. Out of 397 samples (348 M, 49 F) collected 290 were infected with HSV-2, and 52 with HSV-1, of which thirteen were infected with only HSV-1, and 98 were reactive to HIV-1.Analysis of samples collected from Medical College, revealed that 231 (58.2%) samples were sero-reactive to HSV-2 IgG and 59 (14.86%) to HSV-2 IgM antibody. While 37 (9.32%) were reactive to HSV-1 IgG and 15 (3.78%) HSV-1 IgM antibody. On the other hand 98 (24.68%) samples were reactive to HIV-1 antibody by double ELISA and Tridot test . Further analysis showed that 39 (9.82%) samples are reactive to both HSV-1 and HSV-2 IgG antibody. While 34 (8.56%) HIV-1 antibody positive samples were also reactive to HSV-2 IgG antibody, 14 (3.53%) HSV-2 IgM seropositive samples showed HIV-1 antibody positivity.

Out of 74 genital samples along with 16 oral samples the vesicle fluid was aspirated and used for viral isolation; while the vesicle base was aseptically unroofed and scrapped, taken on a slide, air dried, fixed, and stained with Giemsa. The Stained preparations demonstrated typical enlarged multinucleated giant cells with intra-nuclear inclusion bodies in 24 cases under light microscope. The Gram staining revealed the presence of Gram positive bacteria in 15, and Gram-negative bacteria in 9 samples. The HSV specific IFA test revealed that 15 samples were infected with HSV-2, while only one was found to be HSV-1. However, none of the damaged sample yielded any positive result. Only 9 (6+3) HSV-2 and one HSV-1



was isolated from the genital samples; while two HSV-1 was isolated from the oral blister samples could be cultured. Detection of viral DNA in the samples was done by the primers of TK and Pol gene, while quantitation was done by RT-PCR in 4 samples.

Studies on Human Cytomegalovirus Infection Blood samples was collected from 100 AIDS patients showing symptoms of active HCMV infection with varying CD4 counts and compared with 100 healthy non-HIV controls. The serum levels of the cytokines-IL6,IFN gamma and TGF Beta1 in each case of these HCMV infected AIDS patients and healthy volunteers were determined using specific ELISA kits. The serum levels of IL6,IFN gamma and TGF Beta1 were found to be highest amongst these AIDS patient groups infected with HCMV with CD4<50. In case of AIDS patients suffering from HCMV coinfection, a furthur increase in the level of IL6, IFN gamma and TGF Beta1 were recorded compared to the HCMV noninfected study subjects. Among 100 renal transplant patients admitted and visiting the OPD of Department of Nephrology, SSKM, Kolkata showing signs of active HCMV infection; at various times after their allograft transplant had increased levels of serum IL6, CRP and TGF Beta1 indicating HCMV by increasing the serum levels of these parameters are inducing renal allograft rejection.

NAtIONAL AIDS RESEARCH INStItUtE, PUNE

HIV Epidemiology & PreventionNARI’s second phase I HIV Vaccine Trial using a ‘Prime and Boost’ A phase 1 vaccine trial with DNA vaccine and a Modified Vaccinia Ankara (MVA) vector based vaccine in a prime and boost strategy was conducted at NARI with intention to further improve the strength of immune response and broadening spectrum of specificity of response. The prime boost strategy with DNA/MVA was found to be safe; however priming with the DNA vaccine helped only marginally to boost the immune response after the MVA boost. The cellular immune response is being further characterized for its poly-functionality and ability to lyse virally infected cells.

‘Early ART’ for HIV Prevention A Randomized Control Trial was conducted to evaluate the effectiveness of Antiretroviral Therapy plus HIV Primary Care versus HIV Primary Care Alone to Prevent the Sexual Transmission of HIV-1 in Serodiscordant Couples (HPTN 052) .175 HIV-1 discordant couples at high CD4 cell counts were enrolled at NARI and 1763 couples worldwide. The data analyzed and released in April 2011 showed a 96% reduction in HIV transmission and a 41 % decrease in clinical events in the arm that received ART immediately i.e. at CD4 count > 350 cells/mm3, indicating both personal and public health benefits from such therapy.

Social/sexual networks of married Men having Sex with Men (MSM) in Mumbai The study aimed to identify social/sexual networks of married men having sex with men in Mumbai and to find its association with sexual risk behavior, HIV infection, STIs and other antecedent determinants. Among 307 participants enrolled using Respondent driven sampling, the HIV-1 prevalence rate was 10% (95% CI 6.8-14.0%). About 3% (95% CI 1.4-



5.6%) participants were found to have Syphilis, about 10% had either Neisseria gonorrhoeae (NG) or Chlamydia trachomatis (CT) infection. Of those who were HIV infected, only 25% reported that they knew that they were infected. Married MSM do not reveal their bisexual orientation to both- male and female partners. This is likely to pose challenges in reaching out to their partners for accessing preventive and treatment related services.

Feasibility Study of HIV Database-Cancer Registry Matching in Pune IndiaDuring October 2011, the computerized ‘registry linkage (match)’ in a new first of its kind record linkage study in India was successfully conducted. This pilot study addressed the feasibility of matching two different databases (HIV database and cancer registry) in Pune to look at the association between HIV and Cancers at population level, and will provide important data. The match was conducted between 37541 HIV records in the HIV database and 31889 records in the cancer database for Pune for the years 1996-2008. A good number of records were matched highlighting the feasibility of this approach in the Indian setting and further analysis for associations is ongoing.

Adolescent Reproductive and Sexual Health Education (ARSHE): an intervention studyAdolescent Reproductive and Sexual Health Education (ARSHE) module the outcome of a multi-centric ICMR task force study has been initiated.

Clinical Care and TreatmentOptimization of Care and treatment is an important agenda for NARI. In 2011 studies focused on ‘optimal ART regimens’. Two important clinical trials, 1. A trial to study the effect of ART on Neurocognitive impairment and to study association of biomarkers with neurocognitive impairment and 2. A clinical trial to compare the Nevirapine (NVP)-based Vs Efavirenz (EFV)-based ART regimens in ‘HIV-Tb’ co-infection, continued during this year. One study for evaluating diagnostic algorithms for improvement of diagnosis of TB in HIV infected participants was completed during the year while second study to evaluate Inf-γ ELISPOT assay for diagnosis of childhood tuberculosis is ongoing. Analysis of data from the Government NACO ART centre showed that ‘First line treatment under National ART programme’ was effective and clinical and immunological response was correlated with adherence. A qualitative study has been initiated to understand the dynamic phenomena of policy development process in the case of HIV-TB co-infection in India.

Improving the quality of life among people living with HIV/AIDS through Sudarshan Kriya Yoga- A Pilot Study with intramural funding The study aims to study the impact of Sudarshan Kriya Yoga Meditation, a low-cost intervention on the quality of life of people living with HIV and changes in their social skills. This project seeks to implement and evaluate rigorously a three phase protocol designed for improvement in quality of life in people living with HIV. The enrollment in the study is over. The observation period has been extended one year.



Biology of HIV Infection Research programmes on multiple facets of the biology of HIV were carried out. 1. Co-receptor usage by HIV-1 strains was studied and identified clones of HIV-1 viruses that use multiple co-receptors. 2. Env clones obtained from recently infected individuals were analyzed for the neutralization properties. Analysis of neutralization sensitive and resistant clones revealed the influence of single amino acid substitution on the neutralization sensitivity. 3. Studies on identifying broadly cross-reactive neutralizing antibodies and CTL epitopes have been initiated under Indo-South Africa Collaborative project. 4. Studies on Innate immune response revealed the qualitative and quantitative defects in NK cells in HIV infected individuals. A new beginning has been made to study the mucosal immune response in HIV infection.

Innate and acquired immune response at cervico-vaginal level in HIV infected women A study was undertaken to characterize anti-HIV immune response at cervico-vaginal level and the innate factors in HIV infected and uninfected women. Levels of various innate immune factors such as cytokine, chemokines and anti-microbial factors were estimated using the Bioplex assay. In HIV positive women the virus load in cervicovaginal secretions had strong negative correlation with colonization of lactobacilli indicating role of lactobacilli in control of virus in reproductive tract.

STIs and Opportunistic Infections Data from an important operations research study among FSW, MSM and Clients regarding STI presumptive treatment package of the Avahan intervention helped make key recommendations for the programme. Additionally important information related to quinolone resistance of N.gonorrhoeae was generated and provides key data to GASP programs. Studies on Candida species as well as a study comparing microbiological yield from IS and Bronchoalvelor lavage (BAL) samples and detection of Pneumocystis jeroveci by staining techniques and Polymerase Chain Reaction (PCR) have provided important data.

Evaluating Essential Sexually Transmitted Infection Service Package for Sex Workers in India This multi-centric collaborative study evaluated the Essential Service Package (ESP) offered by Bill & Melinda Gates Foundation’s funded Avahan, STI/HIV prevention project. Female Sex workers (FSW, N=444) and Men having sex with Men (MSM, N=530) were recruited and were given a single round of treatment for asymptomatic infection at the first clinic visit and monthly STI screening and syndromic management of symptomatic STIs (except Male STI patients). The study found that the presumptive treatment in this study did not appear to have a desired impact on STI prevalence among these populations. The percentage of asymptomatic infections, increasing over time, among FSW and MSM cohorts seemed to indicate that the syndromic approach which was part of ESP missed most infections.

Quinolone resistance mutations in Neisseria gonorrhoeae Isolates of Neisseria gonorrhoeae were studied for resistance mutations. 64 strains were processed for detection of mutations in mtrR efflux system. Mutation patterns of 10 strains



in the gyr A, par C enzymes and 68 strains in MtrRCDE efflux system were analysed. The results indicate that mutations in quinolone target enzymes and MtrRCDE efflux system may have resulted in a high level resistance that was seen in these isolates.

Characterization of oral Candida isolates from HIV-infected and healthy individualsA significant role of biofilm formation in pathogenesis of non-albicans Candida was seen. Increased expression of virulence factors in isolates from HIV positive individuals compared to HIV negative ones was seen which supported the concept preferential strain selection, the molecular dissection of which could open new approaches for therapeutic interventions.

Product Development and TestingAn exploratory approach for development and screening of candidate microbicide agents in collaboration with renowned national institutes has led to standardization of anti-HIV testing algorithm using various in vitro models and has created complete bioactivity profile of more than 75 natural products. This has resulted in identification of lead compounds (herbal extracts) which can be further purified and taken up for anti-HIV microbicide /drug development.

Contribution to National programme and Services Provided NARI works closely with the National AIDS Control Programmes provides technical inputs and support to the various activities of the programme. NACO’s NACP Phase IV Planning process through various technical working groups. NARI participated in the following activities: 1. HIV Sentinel Surveillance 2010-11: Module development and HSS in Western India; 2. HIV Drug Resistance Surveillance and Monitoring; 3. NARI ART Link Centre: (Over 2000 patients registered and 1600 patients on ART), 4.Quality Control for Serological Diagnosis of HIV: (Apex laboratory for India and NRL); 5. EQAS for CD4 count estimating laboratories linked to NACO centers; 6. Consortium of National Reference Laboratory for kit quality testing (NRLonQ)

NAtIONAL INStItUtE OF EPIDEMIOLOGY, CHENNAINIE has been collaborating with several National and International partners with respect to research, Public Health training and consultancy.

Some research projects that are ongoing and/or completed include:

Uniform Multi-Drug Therapy regimen for all types of leprosy patients [WHO sponsored • multi-centric trial].

Awareness, social acceptance and community views on leprosy and its relevance for • leprosy control, Tamil Nadu – Intramural ICMR funded study.

Prevalence of HIV/STI and associated risk factors among wives of truck drivers in • Namakkal, Tamil Nadu.

A longitudinal study (2007-2011) on nutritional status of HIV-positive and HIV-negative • injection drug users in Chennai –– Collaboration with Tufts University.



Risk of STD and HIV among the STD clinic attendees with pre-marital sexual behaviour, • Chennai.

Impact assessment of collective HIV prevention response in Tamil Nadu and Maharashtra • (BMGF funded ongoing collaborative study).

Cardiovascular disease risk factors: a cohort study in a rural population in Tamil Nadu, • 2005 onwards.

Hypertension: local concepts, patterns of illness experience, meaning and health seeking • behavior in an urban and a rural population in Tamil Nadu, 2009-11.

Cross- sectional survey on the use of Household pesticides and related factors in a village • of Tamil Nadu, India.

Evaluation of Comprehensive Emergency Obstetric and Neonatal Care (CEmONC) • centers of Tamil Nadu.

Rate of Caesarean Section in Thiruvannamalai District, Tamil Nadu.•

End line evaluation of hypertension opportunistic screening and management in two • districts in Tamil Nadu- Tamil Nadu Health Systems project, 2010-11.

ICMR School of Public Health: Master of Applied Epidemiology: 9th cohort (14) scholars have graduated; Master of Public Health: 2nd cohort (15) Scholars have graduated

NIE has been identified as coordinating center for 2 national level surveillance programs:

Rotavirus [ICMR Task Force] and •

Bacterial Meningitis and Pneumonias [Ministry of Health and Family Welfare]•

The NIE has also been Identified as partner Institute for District Level Household and Facility Survey 4 (DLHS 4) – Clinical, Anthropometric and Biochemical assessment component in TN, Puducherry & Andaman & Nicobar Islands (NIHFW).

Concurrent evaluation of non-communicable disease program: Tamil Nadu Health Systems Project [World Bank-TNHSP funded project] - Monitoring and evaluation of screening and management of hypertension and cancer cervix in two districts of Tamil Nadu provided evidence to scale up the interventions to the entire state.

NIE is a Regional Institute for coordinating, monitoring and training for HIV sentinel surveillance for 6 southern states of India.

The National Nutrition Monitoring Bureau- Tamil Nadu unit started at NIE in January 2011.

Model Rural Health Research Unit - Place identified: Maranhalli, Dist Dharmapuri. Partnership with Govt. Medical College [Directorate of Medical Education, TN], and Dept. of Public Health, Tamil Nadu.

REGIONAL MEDICAL RESEARCH CENtRE, BHUBANESWAR

Filariasis An alternate regimen to MDA for LF Elimination

A community based study with three alternate doses of DEC (100 mg./200 mg. / 300 mg) is



ongoing.Single annual dose uniformly to all age groups, demonstrated that at the lowest dose i.e 100 mg. DEC the side reaction frequency is lowest while maintaining the mf clearance effect as compared to higher doses. The other study undertaken as a four arm randomized open clinical trial revealed that double dose of Albendazole (800 mg ) along with DEC given bi annually has greater effect on Mf & adult worm clearance compared to current MDA regimen using only 450 mg Albendazole.

An advocacy tool for improving MDA compliance

A study was conducted to look for sub clinical lymphatic pathology in children (5-18 Years) with W. bancrofti infection. Lymphoscintography of the limbs clearly demonstrated lymphatic pathology & lymphatic flow obstruction in infected but asymptomatic children as young age 5 yrs., which is a fore runner of adult disease. More importantly the standard dose of DEC + Albendazole given annually have found to reverse the pathology within 12-18 month . This evidence has been seen for the first time in W. bancrofti infection globally.

Effect of maternal infection on neonatal immune responses in filariasis

The study demonstrated transplacental transfer of circulating filarial antigens from mother to cord blood samples. The observation of placental transfer of filarial antigens has important implications for the global effort to eradicate lymphatic filariasis. Results also showed increased levels of (Th-2) IL-10 and down regulation of (Th-1) IFN-γ in cord blood of children born to filarial infected mothers indicative of increased susceptibility to filarial infection. High level of T- Regulatory cells and increased production of IL-10 in cord blood from infected mothers indicate that increased T-regulatory cells could down regulate inflammatory responses and susceptible to filarial infection.

Studies also demonstrated that genetic polymorphism of Endothelin-1 and TNF receptor II associated with development of hydrocele and elephantiasis respectively in human lymphatic filariasis. This adds to the present knowledge on mechanism of differential pathway of these clinical manifestations .

MalariaDevelopment of an adjunct therapy as a tool to combat complications in severe malaria

A hospital based study has shown that endothelial dysfunction is one of the key events in the pathogenesis of cerebral malaria, while it was shown that increased level of NOx gives protection against it. This was based on the flowcytometric analysis of circulating microparticles level, quantitative assay of plasma NOx and genetic variants of nitric oxide synthase (NOS) genes associated with NO production. Further studies are being carried out to use NOx which show high potential in reducing severity as an adjunct therapy against cerebral malaria.

Diarrhoeal DisordersPilot Introduction of Oral Cholera Vaccine in Odisha

For the first time Oral cholera vaccine Shanchol was introduced in public heath setting in phase IV trial mode in collaboration with State Health Department, NICED and IVI, Korea. The population under coverage was 51464 people of Satyabadi block, Puri district, Odisha. A total of 31551(61%) received either one or two doses, two-complete doses of vaccine was



received by 46.2% individuals. No serious adverse event among the vaccine recipients was reported. The post vaccination surveillance initiated in July 2011( after one month) and rectal swab collected from all diarrhea cases in both vaccinated and non vaccinated population in area surveyed. None of the vaccination people found to have V. cholerae positives while one non-vaccinated person was detected positive. At the same time 86(4.8%) of 1784 cases of diarrhea in periphery area found positive for V. cholerae. However, non O1/O139 positivity marked in 12/ 63((19%) environmental water sample collected from the study area. This indicates the vaccine has potential for prevention of cholera.

Etiology of diarrhea in three tribal districts of Orissa

The RMRC continued active surveillance of the population and the water samples indicated presence of Cholera in Koraput, Raygada and Gajapati districts. Out of total samples Vibrio cholerae O1 were 18.8%, Shigella species 4.5%, Salmonella 1.2%.The Vibrio cholerae strains were resistant to tetracycline, erythromycine, co-trimoxazole, ampicillin, furozolidone, nalidixic acid. There was a cholera epidemic reported in Rayagada district, where the RMRC field unit has been established, during July to October, 2010 accounting for high morbidity and mortality affecting 8 out of 11 blocks. Similarly, there was a cholera outbreak in 2 blocks of Mohona block of Gajapati district during August, 2010. V.cholerae were isolated from open well and tube wells of Mohona block from where the community drinking water. Immediate reporting during surveillance helped the district to take prompt action to overt another epidemic. The causative organism was the hybrid strain of V.cholerae.This indicates that the hybrid strain has spread over other areas in comparison to 2007 cholera epidemic in tribal areas.

Nutritional Studies and Tribal HealthStrategies to control anaemia among tribal adolescent girls in Gajapati district, Orissa

In a randomized clinical trial undertaken using 5-arm regimens indicated that combination of 5 regimens showed significant improvement in haemoglobin and reduction in anaemia prevalence (in Saura tribe) as compared to current regimen used in national programme (Hb 1.67 vs 1.1). This study shows the improvements in parameters like iron, vitamins B11 and B12. The results of the clinical trial have been communicated to the Women and Child Development Department, government of Orissa that included nutrition education to the existing programme. The study also developed a training module of nutrition education to the Anganwadi Workers in the area.

Virology Grade I virology laboratory has been established at the centre. Network has been established with different health facilities & Medical Colleges (both Govt. and Private) in the state to receive information and clinical specimens for investigation. More than 5000 cases of suspected viral disease have been investigated with immediate reporting to the hospitals and state public health system to support case management / outbreak control. Viral investigations covered around 50 viruses including respiratory viruses (Influenza, Para Influenza, Adeno, RSV, Measles, Varicella) enteric transmitted viruses (Hepatitis A, E , Rota, Adeno, Entero, HFMD) Arbo viruses (Dengue, Chik & JE) and parenterally transmitted viruses (HBV, HCV, HDV). Among the salient observations: (a) Rota virus prevalence of 40% causing diarrhoea among children within 6 months to 5 yrs due to genotypes P P[4] & P[9] and G-type G2, G4 & G9 (b)Adeno (18%), Rhino (15.4%) as the major respiratory viral agents, besides



H1N1 causing respiratory infection. Identification of Boca and Parecho causing respiratory infections which are not usually found, (c) HEV infection as the cause of Hepatitis in 31 % of cases next to HAV are to be noted. HBV genotype D and HCV genotype 1b were found to be circulating genotype in the region. HSV I & II were found to be the common cause of (9.39% & 5.74 %) encephalitis, though in many cases cause could not be ascertained.

REGIONAL MEDICAL RESEARCH CENtRE , JABALPUR

Malaria Plasmodium vivax and P. falciparum are highly prevalent (Pf:Pv 50:50) in central India posing a challenge to accurate diagnosis. The studies were conducted by this centre to evaluate bivalent kits (HRP2 + pLDH)under different field conditions of high temperature, humidity etc. The bivalent kits showed > 90% sensitivity and specificity for P. falciparum and marginally lesser for P. vivax suggesting its potential role in epidemiological surveillance The NVBDCP has accepted the recommendations of centre and has replaced the monovalent RDTs with bivalent kits for malarial diagnosis in various states of India. The studies also revealed that at high temperature i.e. at 45oC up to 100 days, there is no change in diagnostic performance of these RDTs.

The Centre has also established a clinic at Jagdalpur and Kanker in Chhattisgarh (CG) state, which are highly malarious districts in the state and consequently the burden of cerebral and severe malaria is known, for developing evidence based appropriate intervention measures.

The studies conducted by the centre on malaria in pregnancy have helped program and recommendations are partially accepted by the NVBDCP for implementation in program.

Virology The Centre has been recognized by the NVBDCP as Apex Referral Lab for Dengue and Chikungunya for MP and CG. This Centre is also part of Virology Network of the Council and is in the process of establishment of grade II virology laboratory for molecular and serological diagnosis of viruses. The studies conducted on dengue suspected samples have first time demonstrated the presence of dengue virus 1 and dengue virus 4 in this part of country. The centre also gave diagnosis for H1N1 P 09 (Swine flu) in this period for the state of MP.

HaemoglobinopathiesHaemoglobinopathies are a major problem in MP especially in tribal areas. Sickle cell prevalence ranged from 5-30% in various tribal districts. Unfortunately facilities for diagnosis and treatment are not available in most government health facilities in the state. On the recommendation of RMRCT, State Government has agreed to establish clinics for diagnosis and management of haemoglobinopathies and create public awareness at district level. The RMRCT will be involved in training both medical and paramedical staff of the state for diagnosis and management of different haemoglobinopathies.

Protection provided by haemoglobinopathies in uncomplicated and severe P. falciparum malaria – A cohort studyA study was carried out in 10 villages of Baiga Chak of Dindori district of MP where the prevalence of malaria is very high (50%), to examine the protective phenomenon of common



haemoglobinopathies against P. falciparum malaria. Sickle haemoglobin, β-thalassaemia trait, G-6-PD deficiency, raised level of foetal haemoglobin (HbF) showed significant protection against P.falciparum infection. Among these sickle cell trait and raised HbF provides maximal protection (33% & 40% respectively). Children with sickle cell trait (<14 years) showed maximum protection against P.falciparum infection (44%). Persons with two gene deletion (-α/-α) showed higher protection against malaria as compared to persons with one gene deletion (-α/αα). Alpha thalassaemia did not show this kind of protective effect in children (<14 yrs), but showed a higher degree of protection against malaria in adult population (14+ years). Sickle haemoglobin and α-thalassaemia also significantly lowered the parasite counts in P.falciparum infection compared to normal.

FluorosisFluorosis is a major public health problem in 26 out of 50 districts of Madhya Pradesh (MP). The model for intervention suggested by this centre i.e. inclusion of safe drinking water with calcium and vitamin C supplementation is now accepted in National Programme for Fluorosis Prevention and Control. This model is again successfully tested in Seoni district of MP.

Tuberculosis The Center’s laboratory is accredited as Intermediate Reference Lab for TB for MP by RNTCP. Additionally the centre is providing technical assistance to Jan Swasthya Sahyog, Bilaspur CG. Initial results have revealed high levels of MDR TB (30%) in the retreatment cases. The state tuberculosis officer and other concerned officials were informed for their necessary action.

REGIONAL MEDICAL RESEARCH CENtRE, PORt BLAIRThe centre elucidated the role of macrophages in the pathogenesis of chikungunya infection and generated preliminary evidence in the role of the cytokines IL6, MIP1A, MIP1B and MCP in pathogenesis of chronic arthritis following CHIKV infection, which could lead to research on new treatment modalities for post-CHIKV chronic arthritis.



The occurrence of dengue haemorrhagic fever and dengue shock syndrome and the existence of multiple serotypes of dengue virus in Port Blair has been shown. These findings have great public health importance as DHF and DSS have not been reported from Andaman and Nicobar Islands earlier.

The RMRC showed the occurrence hepatitis B infection by viruses with mutant surface antigen among the Nicobarese of Car Nicobar, which will have implications on the on-going programme of universal immunization against hepatitis B in Nicobar District.

The centre detected emergence of resistance to newer fluoroquinolones and third generation cephalosporins among Shigellae the presence of Plasmid Mediated Quinolone Resistance (PMQR), genes in Shigella Isolates, a seldom reported phenomenon in India. The findings will have implications on the study of development and spread of drug resistance among bacterial enteric pathogens.

The disease burden due to Leptospirosis was estimated. This is the first systematic effort to estimate the disease burden in India. The disease outcomes of survived patients were graded as mild, severe with pulmonary involvement, severe with hepato-renal involvement and severe with both pulmonary and hepato-renal involvement. Disability factors of 0.1, 0.4, 0.2 and 0.4 were assigned to these outcome grades respectively. YLL, YLD and DALY due to leptospirosis was estimated following standard procedure. Based on the data on duration of illness of each patient and the severity grade of the disease, the total days lost to disability to these 722 patients were 654.4 (YLD=1.8 years). DALY due to leptospirosis, which is the sum of YLL and YLD, was estimated as 657.6 years. The total population of South Andaman District as per 2011 census was 2,37,586 and therefore DALY per 1,000 population due to leptospirosis was estimated as 2.8 years.

Preliminary laboratory based observations indicate that two isolates of pseudomonas and bacillus spp show inhibitory potentials against leptospires. This could be an important milestone in the control of Leptospirosis if the findings are confirmed.

The RMRC showed persistence of microfilaraemia in diurnally sub-periodic form of filariasis, post six rounds of MDA. Findings have implications for putting an alternate strategy to hasten the process of elimination.

The prevalence study of non-communicable disease risk factors among the populations of Andaman and Nicobar Islands identified Nicobarese as a high NCD risk community

Land and building for establishing Field Station at Kamorta have been allotted by the Andaman and Nicobar Administration. Renovation of the laboratory-cum-residential accommodation has been completed and will be inaugurated shortly.

Construction of the Phase II of the Centre’s building initiated. Renovated and modernized laboratories and established Grade I virology laboratory with BSL III facilities. New equipment including Real Time PCR and Flow Assisted Cell Sorter installed.

More than 150 floral and faunal species are endemic to these islands. Digital database on plant resources of these islands indicates over 200 plant species, herbs, shrubs, trees, climbers, epiphytes and lithophytes under different families with medicinal values. Traditional healers in Car Nicobar and Mayabunder were interviewed and usages of 142 medicinal plants that are being prescribed to cure 52 different ailments were documented. All these plants were collected for preparation of herbarium and plant parts, known to possess medicinal values, for undertaking laboratory studies. Community Bio-diversity registers (CBDRs) for Karen’s and Nicobarese have been prepared and circulated. This digitizing of information will facilitate in protecting intellectual property rights of the indigenous tribes. Copies of these CBDRs



will be given to the respective traditional knowledge healer/folk healers, Tribal Chieftains and Tribal Council. Preliminary assessment of extracts from various plants, seaweeds and sponges, show some activity against the human pathogens. However, further studies on active compounds would throw light on the activity against different pathogens.

NAtIONAL INStItUtE OF MEDICAL StAtIStICS, NEW DELHIDuring the reporting period January – December 2011, the Institute handled seven (1 completed and 6 ongoing) scientific projects, organized training programmes, CTRI dissemination workshops and dissemination of the research carried by the scientists of the Institute as described below.

Projects carried out were:

Endline evaluation of home base management of young infants in five states of India. •

NACO’s HIV Sentinel Surveillance and estimation of HIV burden in the country 2010 in • conjunction with NIHFW, WHO and UNAIDS;

Estimation and Prediction of HIV/AIDS in India using Deterministic Asian Epidemic • Model (AEM): A case of Mumbai.

The Prevention of HIV/STI among Married Women in Urban India in a slum population • of Mumbai.

Knowledge Network of Research on HIV/AIDS in India.•

Clinical Trial Registry – India (CTRI).•

Estimation of maternal mortality ratio in Orissa and Rajasthan. •

The Institute conducted a number of capacity building workshops:

1. Workshop on the use of “R” software for biomedical researchers of the country at NIHFW, New Delhi.

2. Workshops on Statistical Methods and Computing in Clinical Trials at NIOH Ahmedabad and RMRI Patna for the benefit of the researchers in the respective regions.

3. Orientation course on research and statistical methods was conducted for the post graduate students and young faculty of Safdarjung hospital as a part of training medical students in research issues.

4. Summer training programs for the post graduate students in Statistics/Biostatistics for various universities such as Banaras Hindu University, University of Delhi and IIT etc.

5. The Institute served as faculty for the various programs on Research Methodology being conducted by Department of Health Research and other departments such as NIHFW, Central Statistical Organization, Department of AYUSH, NIPCCD etc.

6. The Institute provided assistance to students and faculty of various medical Institutions on design and analysis of the studies. More than 60 students and faculty approached the Institute for advice on statistical issues from the local medical colleges.

7. The Institute advised on the epidemiological studies conducted by Calicut Medical College on Endosulfan affected population at Kasragod district of Kerala.

8. The Institute rendered statistical assistance to the programs of CCRAS and CCRH.



9. Ph.D. programme: The Institute is recognized for the Ph.D. program in Medical Statistics by GGSIP University, New Delhi.

It is conducting advance course in Medical Statistics for the students registered for • the program.

The Institute is also involved in the teaching of Research Ethics for the University. •

10. The Institute conducted a number of dissemination workshop on Clinical Trial Registration in different parts of the country including Delhi for members of the ethics committee and others researchers working in the area of clinical trials.

ExtRAMURAL RESEARCH The ICMR’s extramural research programme in the area of communicable diseases contributed significantly towards better management of diseases of public health importance, such as tuberculosis and multi-drug resistant TB, and leprosy, and thus accelerating disease control/ elimination/ eradication efforts. It also supported towards improved control strategies for diseases like malaria, JE, dengue, leprosy, filariasis, kala-azar, HIV/AIDS, including HIV-TB. Through these as well as its research on tribal health, the Division has ensured that research on the health of the poor, marginalized and special population groups have been at the centre of its priorities.

Ongoing initiatives Vector-borne diseases (VBDs) continued to emerge as a serious public health problem in India. Japanese encephalitis (JE) and malaria now occur in epidemic form almost on an annual basis causing considerable morbidity and mortality. Chikungunya and dengue are spreading rapidly to newer areas, with outbreaks occurring more frequently and explosively. Therefore, sharing the resources and working under collaborative mode was felt necessary to solve the problem at national and state level. To accomplish this and to co-ordinate all research activities on vectors; Vector Science Forum (VSF) was established by Secretary DHR and DG, ICMR with Terms of References to provide a platform where researchers/institutes working on Vectors/Vector-borne Diseases can share information available with them and also discuss the current findings and future trends in the diseases, identify neglected aspects/gap areas of vector research to help develop better control strategies and identify the cutting edge areas of science which could be translated to the field.

Subsequently under the forum 1st call for proposal has been made in identified priority areas in basic and applied research in vector borne disease including diseases which are occurring where not much information is available. The shortlisted projects have been funded. Besides this two brain storming meeting have been organized involving experts, researchers, programme officials from Directorate of NVBDCP and states to identify gap areas in knowledge of vectors and vector control of malaria, filarial, leishmaniasis, Dengue , Chikungunya and JE and to make the programme a science backed program.

In the meeting discussions were held according to the ecological sites of the vectors and research areas were identified in each area and concluded with the commitment to partner with programme people to accelerate development of improved methods of pathogen detection, treatment and vector identification and control of vector borne diseases. In a



view to develop human resource, NIMR (New Delhi), VCRC (Puducherry), CRME (Madurai) and RMRC (Dibrugarh) together along with Programme people have developed a course curriculum to organise a training programme (short and long term) for hands on experience training in entomology.

During the Brain storming meeting, the VSF website was launched by Secretary DHR and DG, ICMR. The link is available on ICMR website. This was developed for sharing of knowledge and is being updated regularly.

Another major initiative launched was establishing a Tribal Health Research Forum. This was established to synergize and intensify the research efforts of ICMR Institutes/ centres engaged in area of Tribal Health. The Forum on Tribal Health Research meets on the eve of international Day of the World’s Indigenous People at RMRCT, Jabalpur under the Chairmanship of the, Secretary DHR and DG , ICMR. In the Forum, scientists from various ICMR Institutes and Headquarters, engaged in research on tribal population participate to work towards translating the identified leads to public health benefit. The forum meets quarterly in other ICMR Institutes by rotation.

Virology Diagnostic LaboratoriesRecognizing the need for strengthening diagnostic facilities for diagnosis of viral infections, the Department of Health Research is strengthening virology laboratories in various parts of the country in a phased manner. Three categories of Laboratories having following capacities are being established:

Grade I laboratory (highest facility under this system) will be equipped with facilities to • carry out work on Serology, Tissue Culture, Virus Isolation, PCR/RT-PCR, Fluorescence Microscopy and Sequencing of all major respiratory, enteric, blood borne, vector borne, zoonotic viruses and especially viruses which have the potential to cause outbreaks. It is proposed to set up one Grade I lab in each state.

Grade II will be equipped to carry out serology, PCR, fluorescence microscopy for • immuno-detection. 1-2 labs will be established in each state.

Grade III laboratories will carry out serology for viruses (ELISA based diagnosis) and • PCR. 2-3 labs will be established in each state.

So far Grade I laboratory has been established at Chattarapathi Shahuji Maharaj Medical University, Lucknow; ICMR’s Regional Medical Research Laboratory, Bhubaneswar; ICMR’s Regional Medical Research Laboratory, Port Blair; Kasturba Medical College, Manipal; ICMR’s NIV field Unit, Alapuzzha, Kerala; SMS Medical College, Jaipur; Rajiv Gandhi Centre for Biotechnology at Thiruvnanathapuram, Kerala. Another 4 Grade I labs have been approved for establishment in 2011-12 at Post Graduate Institute of Medical Education and Research, Chandigarh; and Kings Institute of Preventive Medicine, Chennai and at ICMR’s Virus Unit at Kolkatta. Grade II laboratory has been established at Pt.JLM Medical College, Raipur, Chattisgarh and have been approved for establishment in 2011-12 at Andhra Medical College, Vishakapatanam, ICMR’s Regional Medical Research Centre for Tribals at Jabalpur, Rajendra Institute of Medical Sciences, Ranchi; Rajendra Memorial Institute of Medical Sciences, Patna; Osmania Medical College, Hyderabad and Goa Medical College, Goa.



Antimicrobial ResistanceThe major problem of the emergence of resistant bacteria is due to misuse and overuse of antibiotics by doctors as well as patients. Other practices contributing towards resistance include the addition of antibiotics to the feed of livestock. Also unsound practices in the pharmaceutical manufacturing industry can contribute towards the likelihood of creating antibiotic resistant strains. In view of considerable number of reports on antimicrobial resistant bacteria from different parts of the country and a report in the Lancet wherein Carbapenams resistance in Enterobacteriacae (E.coli & Klebsiella), an expert group had been set up to identify priority areas of research. Based on the recommendations a Call for proposals was put up.A total of 187 concepts were received out of which 69 have been selected for the development of full proposals. Of the 69 full proposals, 29 proposals have been approved for funding. In addition to the ICMR is proposing to set up antimicrobial surveillance networks in Enterobacteriacae causing sepsis; fungal pathogens; Gram negative non-fermenters; Salmonella; Diarrhoeagneic organisms and Methicillin resistant Staphylococcus auerues. The process of establishing these networks through developmentof a uniform protocol for each of these networks is currently in process.

The ICMR funded a total of 252 ad-hoc research, 88 Task Force and 1 centre for advanced research and 116 Fellowships (new and ongoing) in this financial year up to March 2012

Highlights of some major extramural projects completed

HIVA study on Social / Sexual Networks of High Risk Married MSM in Mumbai completed at National AIDS Research Institute, Pune, indicated that the overall HIV prevalence rate in MSM is about 10% and it does not differ by marriage status. It also reveals that there is a relatively higher prevalence of sexually transmitted infections among MSM compared to heterosexual population and these married MSM do not reveal their sexual orientation to both- male as well as female partners. Condom use is low among these MSM especially married MSM. Married MSM do not have many term by which they can be identified. Only 25% of those who were infected by HIV knew that they were infected.- a finding that is being reported for the first time and has an immense bearing on programmatic strategies. These findings will lead to many more studies on MSM especially those related to reaching their female partners in future.

Another study entitled Raising HIV Awareness among Non-infected Indian (RHANI) wives: HIV risk reduction intervention for at risk wives in India completed at National Institute for Research in Reproductive Health, Mumbai has shown that participants (N=220) aged 18-40 years faced victimization from spousal violence for past 30 day drunken significantly decreased, with greater impact seen for those who attended more versus fewer sessions of the six weeks intervention programme. This program was delivered to women in a single slum in Mumbai, but has the potential to be used in any community setting that reach wives at risk for HIV from husbands.

A study on the microbicidal effect titled Curcumin: A multi mechanism HIV microbicide completed at University of Hyderabad has shown the potential utility of nanoformulated curcumin as an intravaginal anti-HIV microbicide. This study may lead to development of novel antiviral microbicide formulation that would greatly reduce the risk of infection following vaginal (or, potentially, rectal) exposure. Significantly, in contrast to current



methods for reducing the risk of HIV transmission, such an approach would be under the control of the receptive, at-risk partner.

LeprosyThe Leprosy Mission Trust (TLM), India in New Delhi carried out a study of post elimination Leprosy situation in selected endemic States of Uttar Pradesh, Chhattisgarh and West Bengal in India. A population–based Leprosy Registry was established which has shown that 10 to 20% of the leprosy patients seem to prefer private practitioners. 40 to 60% attend the government primary health centers. TLM referral hospitals have taken care of the balance of 20 to 50%. 70 to 90% of the grade-2 patients come to TLM hospitals for care. Household sample survey indicates that the new case detection rate is about 5.6/10000. The national leprosy prevalence rate is 1/10,000. This study has shown the new case detection rate of about 2 to 9 per 10,000 populations in low, moderate and high endemic districts. About 14 to 20% of the patients were Multi bacillary (MB) in the three endemic districts. The disability adjusted life years for leprosy indicated that 83.23% were unskilled leprosy patients. Most of the patients were farmers, or labourers and a few were beggars.

TuberculosisAn investigation of Geo-spatial hotspots for the occurrence of tuberculosis in Kumaon region of Uttaranchal using GIS and spatial scan statistic carried out at Kumaon university, Almora showed a significant difference for T.B. incidence rate in the three districts. Crowding & urbanization was found to affect U.S. Nagar having maximum T.B. incidence rate. A significant association was also found between T.B. incidence and dimensions of method of cooking, nutrients in diet & liquor consumption suggesting that good habits regarding these dimensions will help in reducing the incidence rate of T.B.

Genotyping of M. tuberculosis isolated from an endemic area, carried out at AIIMS, New Delhi has shown that Mx. Test was positive in 97.5% of index PTB patients & 71.3% household contacts. Genotyping showed a great diversity among MTB isolates. Among the 46 ST, 6 predominant shared types alone were responsible for 62.55% of total 486 M. tuberculosis strains isolated, indicating high transmissibility & adaptability of these ST in Delhi/North Indian population. Analysis of transmission in household showed contacts in 83.87% household matched index PTB cases. ST26 was responsible for transmission in 35.48% household. Beijing ST1 was responsible for transmission in 6.45% household. While ST138 (EAI) and ST25 (CAS) was found to be responsible for transmission in 3 (4.84%) household. Undefined strains were responsible for transmission in 9 household.

Other Microbial InfectionsStudies carried out at the Centre for Advanced Research in Medical Mycology under Prof. Arunaloke Chakrabarti from PGIMER, Chandigarh has identified a common 45KD immuno dominant protein antigen from five medically important Zygomycetes, which holds great promise in the diagnosis. For identification of medically important zygomycetes in the tissue of experimental animals and in tissue samples from patients with invasive zygomycosis, different segments (ITS, 28s, 18s) of rDNA were evaluated to develop a PCR-RFLP method using MspI, AluI, MSeI and MboI digestion. Notable were the development of microsatellite typing technique for the molecular typing of Rhizopus oryzae; a microsatellite panel and an amplified fragment length polymorphisms technique for rapid and high-resolution genotyping



of A. flavus; and an amplified fragment length polymorphism (AFLP) molecular typing of A. elegans using Mse I and HpyCH41V. A multilocus sequence typing (MLST) for typing of Aspergillus flavus using eight housekeeping genes was also developed. The pathogenesis of penicilliosis, fungal rhinosinusitis and zygomycosis were also studied and novel protein / antigens as biomarkers for paranasal sinus mycoses were identified. In addition, ten training workshops were organized over the last five years (2006-2010). The Centre also trained 62 faculty/Scientists and 55 technicians during five years. External Quality Assurance Programme (started from June, 2009) involved fifteen laboratories from Delhi, Bangalore, Hyderabad, Pune, Mumbai and Chennai were initiated; 12 laboratories performed good, 2 excellent, while 1 was satisfactory.

A Centre of Advanced Research on Liver Diseases was established (November 2010) at the All India Institute of Medical Sciences, New Delhi. The results of the completed project suggest that co-infection of genotype A and D of Hepatitis B virus are more frequently present in HBV related hepatocellular carcinoma. Immunohistochemical studies of liver tissue in case of HEV infection revealed that CD8 and Granzyme positive cells are present indicating that in HEV infection the liver injury may be immune mediated rather than the cytopathic effect of the virus (as believed till date). Genotyping and phylogenetic analysis of HEV RNA +ve samples from human (n=124), monkey (n=5) and swine (n=4) in whom has been done. This analysis revealed that all samples belonged to genotype 1 HEV virus. Earlier studies reported that the swine HEV is genotype 4 and human genotype is genotype 1.This raises a possibility of HEV being a zoonotic disease. Patients with pre-existing chronic liver disease are more prone to contract HEV infection than those with normal liver. Whenever super infection of HEV occurs in patients with underlying chronic liver disease, they rapidly decompensate and die. HEV is hyperendemic in India and therefore patients with chronic liver disease, alcoholics and fatty liver are more prone to develop life threatening liver diseases due to super infection with HEV.

Diarrhoeal DiseasesQuinolone resistant strain of Salmonella enterica serotype typhi with mutations in gyrase gene under experimentally controlled selective pressure of ciprofloxacin and the active role of efflux pump in quinolone resistance was carried out at AIIMS. The study showed that while antibiotic resistance can be selected during antibiotic treatment, the efflux pump does not have any role in ciprofloxacin resistance in Salmonella Typhi.

A study on molecular analysis of the development of the intestinal bacterial flora in the neonates in south India carried out by CMC Vellore, showed that immediately after birth, Lactobacilli were prominent, but their relative abundance decreased from the second day onwards, indicating prominence of other bacteria. Bifidobacterium species and Enterobactericeae became prominent from the third day of life. Enterococci were somewhat less abundant. Bacteria belonging to the Bacteriodes-Prevotella-Porphyromonas group were low in abundance, in contrast to the situation in adolescence and adulthood. Similarly, bacteria belonging to the Clostridium coccoides cluster were low in abundance in the children until the age of six months. Bacterial colonization of the intestine occurred earlier in babies born through the normal vaginal route, and was delayed by a day or two in neonates delivered by Caesarean section.

The prevalence, characterization and epidemiological typing of shiga toxin producing E. coli (STEC) isolated from meat products, unpasteurized milk, cattle and children in north



India was studied by PGIMER, Chandigarh. The researchers concluded that STEC isolates belong to diverse serotypes and genotypes and have many virulence factors. The survey showed that STEC strains could not be implicated as a major causal agent of diarrhea, but were present in the food chain in north India. The exact potential of these organisms as food borne pathogen remains yet to be demonstrated.

Tribal HealthFive-arm randomized field trial in Serango ICDS sector covering 4 Gram Panchayats and 20 Anganwadi Centers in Gajapati district of Orissa was carried out by RMRCT, Jabalpur. Arm 1 included weekly iron, folic acid and vit.B12, six months of de-worming and monthly nutritional education for one year. Arm 2 excluded nutritional education. Arm 3 excluded vitamin B12 therapy. Arm 4 consisted of iron, folic acid and de-worming; while Arm 5 comprised of only iron and folic acid therapy. There were significant improvements in hemoglobin for arm-1 (1.6 g/dl) and arm-2 (1.4 g/dl). The prevalence of anaemia was reduced to a greater degree in arm-1 (51%) compared to the other arms. There were considerable improvements in the mean levels of iron indicators (ferritin, C-reactive protein, transferring receptor), folic acid, and vitamin B12. Arm-1, with all five interventions, proved to be most effective for reduction of anaemia as compared to others.

Parasitic infection in tribals and their domestic animals of southern Rajasthan was carried out Government Meera Girls College ,Udaipur. Nine species of intestinal parasites of intestinal parasites viz., Entamoeba histolytica, E. coli, Taenia solium (tape worm), Hymenolepis nan (dwarf tape worm), H. diminuta, Ascaris lumbricoides (round worm), Ancylostoma duodenale (hook worm), Trichuris trichiura (whip worm) and Strongyloides stercoralis (thread worm) were detected and identified. Among these, Entamoeba histolytica was most common in tribal subjects and showed the highest (23.66%) incidence of parasitic infection.

The CRME, Madurai conducted an epidemiological survey of vector borne diseases and control strategies for tribal health development through remote sensing (RS) and GIS for Sitheri hills of Tamil nadu. It was found that the density of vectors increased in response to rainfall and High Normalized Difference Vegetation Index (NDVI) values generally corresponded with higher rainfall. So, vector abundance was positively correlated with rainfall and NDVI value. Entomological survey and spatial analysis revealed a total of 2533 female mosquito specimens contributing to 19 species belonging to 7 genera. The abundance map indicated the highest and lowest abundance of vectors in Sitheri hills such as S. ammapalayam and S. suriyakadai respectively. The vector surveillance map also revealed the highest and lowest percentage of dengue and chikungunya surveillance in Sitheri hills.

Vector-borne DiseasesMalaria Parasite bank is facility being funded by ICMR in extra mural mode to NIMR, New Delhi as a long term project. It is serving as a national resource for Plasmodium isolates in the country. Till now a total of 1075 isolates of human malaria parasites (P. falciparum, P. vivax and P. malariae) have been collected and cryopreserved in parasite Bank. The facility is also utilized by various universities, Institutions and research organizations.

An Integrated Disease Vector Control (IDVC) project is being continued by ICMR as a long term project in extramural mode at 10 field stations located in different malaria endemic regions of India. These sites provide support to the local public health authorities and serve



as a testing site for new molecules for vector control and antimalarials. The field stations also provide technical support to Dt of NVBDCP as their regular activity for training, monitoring and evaluation in high risk malaria districts, rapid diagnostic kits etc.

The RMRIMS, Patna undertook the validation of sandfly distribution and kala-azar disease prevalence through remote sensing (RS) & GIS in endemic foci of kala-azar in one endemic and one non-endemic district of Bihar and Jharkhand respectively. The proportion of P. argentipes in both endemic and non-endemic areas was significantly much higher to the proportion of Sergentomiya and P. papatasi. While mud plastered walls, mixed dwellings and area were strongly associated with the presence of vectors; in-room temperature and relative humidity were the best predictors for vector distribution. Soil pH and moisture content was higher in the endemic sites compared to non-endemic sites. Software was also developed to identify the kala-azar ‘risk’ and ‘non-risk’ areas based on environmental parameters.

A study under taken at the University of Delhi evaluated the potential of cyclopoid copepod as an effective bio control agent for the control of disease vectors. Female cyclopoid exerted higher mortality on the larvae of Ae. aegypti than males. At higher larval density (≥30L/250 ml water), the presence of alternate pray, either Ceriodaphnia cornuta or Brachionus calyciflorus facilitated higher removal of Ae. aegypti larvae. The most predaceous cyclopoid, Mesocyclops aspericornis was not susceptible to Bti or to Temephos at the diagnostic doses of respective insecticides. Studies supported to CDRI, Lucknow evaluated DNA based tools for antimicrobial drug screening against Plasmodium falciparum. The findings revealed that the MSF assay is most suitable assay for bio evaluation of new molecules and RPNI medium gas potential to be used for chemo sensitivity studies.

Viral diseasesA study of hepatitis B resistance patterns in patients with chronic infection during therapy with nucleoside analogues carried out in Institute of Post graduate Medical Education and Research in Kolkata showed that at the end of one year follow up, only 20% of treatment naïve patients responded to combination therapy (TDF with either LMV/dLT) as evident from undetectable viral load while 40% showed a very slow decline in viral load and the remaining 40% continued to have HBV DNA comparable to their baseline and hence are non responders. Thus overall the response of the patients to the combination therapy was not satisfactory. Baseline complexity of HBV thus seems to be an early predictor of treatment response. The other group of patients namely LMV non-responders, who were given TDG as add-on therapy and had a complex baseline LMV resistant mutational pattern, showed a relatively better response since in 70% of them there was a slow but gradual decreasing trend in viral load although non achieved complete clearance after 1 year follow-up.

Another study to assess utility of HCV core antigen as screening tests for diagnosis of HCV core antigen conducted at AIIMS showed that HCV core antigen is not superior test compared to 3rd Generation anti-HCV test for diagnosis of HCV infection in patients on haemolysis.



Non-Communicable Diseases

INtRAMURAL RESEARCH

INStItUtE OF CYtOLOGY AND PREVENtIVE ONCOLOGY, NOIDAThe Institute is adopting multi-disciplinary approach to find the role of causative factors, like environmental, behavioural, genetic as well as their interaction for the prevention of cancers. The main focus is on translation of aetiological factors for the prevention and early detection of cancers.

Epidemiological Studies and Screening Activities for Cervical Cancer

Development of cost cutting measures for cytology screening for the resource limited settings; bacterial vaginosis and its association with cervical neoplasia. Screening for cancer cervix by combined aided visual test in a rural setting at Dadri with about 6000 women were screened during the first year of the project; and CARE-HPV vs. other options for screening in a rural community – a demonstration ICPO-PATH Collaborative Project. About 5000 women have already been tested. Sensitiviity of CARE-HPV have been found to be around 73%. Sensitivity for cytology was 54.5% and that of VIA 27.3% only. On the other hand specificity of the three techniques was in the range of 87% to 96%.

In the field of molecular screening for cervical cancer, the ICPO has been recognized as a National Referral Centre for HPV & Cervical Cancer Screening. More efficient methods of comprehensive genotyping PGMY-reverse line blot assay have been established. Samples have been received from CNCI, Kolkata for HPV confirmation. In addition, further these samples are being tested for comprehensive genotyping and viral load assessment. In addition, serological assays for HPV type 16 & 18 have been standardized. The ICPO has developed Multiplex PCR to detect various HPV types in one PCR reaction. The results showed that in a single test number of HPV strains can be detected with equal sensitivity. Study is being undertaken for detection of variant HPV types in Indian population for the purpose of developing HPV vaccines under an Indo-German Project.

Studies on therapeutic strategies for HPV infection include, 1) Transcriptional targeting of human papillomavirus by herbal derivatives, with evaluation of antiviral and anticancer properties of crude extract of B. pinnata on cervical cancer cells; The different fractions of the extract were tested for its biological activities against cervical cell lines. Fraction 4 was found to have anti-cancer properties. 2) Identification and characterization of stem cells in precancer and cancer of the uterine cervix. study is being performed to ascertain whether functionally equivalent stem cells may also be detected in human cervical cancers.

Molecular Oncologic Studies of cervical cancer include, 1) Role of transcription factor STAT3 in HPV 16 induced cervical carcinogenesis; Inhibition of STAT3 is accompanied by decrease in DNA binding activity of STAT3 transcription factor as well as reduction in phosphorylated STAT3. In addition, selective suppression of STAT 3 increases the accumulation of P53 and Hytophosphorylation of pRb in Siha cell line. Further it was shown 1) that suppression of STAT3 induces apoptosis in cervical cancer cell line. 2) Development of cervical cancer gene data base; 3) Cycline D1 Gene Polymorphism in cervical cancer and precancer; SNP at G870A in Cyclin D1 gene showed as a risk factor whereas SNP at G1722C showed a productive role in HPV associated cervical cancer in India. 4) Single nucleotide polymorphism of cytokine genes in human papillomavirus (HPV) mediated cervical cancer; Analysis of preliminary results show that carrier genotype frequencies (CA/AA) are more



common in controls (84%) then in cases (59%). Larger sample size is being investigated to reach at final conclusion.

The ICPO has been selected as one of the trial sites for HPV vaccine. ICPO is also involved in an Indo- German programme for development of Chimeric DNA – Based Vaccine against Human Papillomavirus Type 16.

Since there is an urgent global need for harmonization of laboratory assays for HPV DNA diagnostics and serology for HPV surveillance for implementation and monitoring of Vaccine response, ICPO has been recognized as WHO’s Regional HPV Reference Laboratory to strengthen HPV-LabNet programme in South East Asian countries since 2007. More efficient methods of comprehensive genotyping PGMY-reverse line blot assay have been established. In addition, serological assays for HPV type 16 & 18 have been standardized.

Studies on oral cancers include, 1) Field trial of a magnifying device (magnivisualizer, under patenting) for detection of precancerous and early cancerous lesions of oral cavity among chronic tobacco users in NOIDA and Ghaziabad; and 2) Role of HPV in oral carcinogenesis. Uptil now 677 driver and conductors from UP Roadways have been examined with an ordinary torch and magnivisualizer. Magnivisualizer could detect 122 lesions (18%) and while torch could pick up only 82 (12.1%) oral lesions. Magnivisualizer afforded much better differentiation compared to the torch light (96.7% vs. 63.4%)

Prevalence and molecular characterization of H.pylori genotypes in patients with duodenal ulcers and gastric carcinoma are being carried out in J&K (high risk zone for stomach cancer) and Delhi (low risk zone). A total of 205 endoscopic directed biopsies from J&K Region showed a frequency of 41%, 40%, 49% for gastric cancer, gastric ulcer, non-ulcer dyspepsia. Normal tissue showed a frequency of 29%. In Delhi region, results from 57 biopsies showed a frequency of 23% for cancer, 64% for ulcers and only 5% in normal tissue. The study is in progress.

During the year under report, a total of 38 papers were published with an average impact factor of 2.5. Five students completed their MD/MS/DNB Thesis while four were pursuing their thesis work. Five Ph.D. students completed their thesis work while 13 were undertaking the thesis work. A total of 33 students participated in the summer training programmes and 40 participated in the biostatistics training courses.

NAtIONAL INStItUtE FOR RESEARCH IN ENVIRONMENtAL HEALtH, BHOPALThe ICMR set up its 31st permanent Research centre National Institute for Research in Environmental Health at Bhopal, on 11th October, 2010.

To fulfill its short, medium and long term goals, the National Institute for Research in Environmental Health will have a divisional structure e.g. Clinical Division, Biomedical Division and Comparative Medicine Experimental Station.

Clinical Division of the institute shall function from Kamla Nehru Hospital in the space which has been provided by the Government of Madhya Pradesh. This division shall operate clinics of General Medicine, Respiratory Medicine, Ophthalmology, Paediatric, Obstetrics & Gyanaecology, Nephrology, Neurology, Psychiatric and Dermatology. State of the art laboratories fully equipped with required equipment and essentials are proposed to be established in the field of Microbiology, Molecular-biology, Biochemistry, Pathology, PFT,



Pharmacology & Toxicology and Radiology. Biomedical Research Division comprising of Laboratories, Public Health Division, Rapid Response Division, Allied services and Comparative Medicine Experimental Station shall come up separately in a new building in land (20 Acres) allotted to ICMR by the Government of Madhya Pradesh.

For realization of the main goal, some of the focused activities undertaken are as under:

Engagement of Scientific, Technical & Ministerial Staff: 44 staff working with Centre for • Rehabilitation Studies of Madhya Pradesh Government has been engaged for continuation of the ongoing studies and to initiate the newer one.

Renovation work: Renovation work at Kamla Nehru Hospital for functioning of Clinical • Division of NIREH was initiated and is at an advanced stage of completion. Clinical Division is expected to start functioning from renovated building from mid 2012.

Engagement of Scientific Consultants: Consultants in Epidemiology, Pathology, • Biochemistry, Dermatology, Ophthalmology, Neurosciences and Infrastructure Development have been engaged to give impetus to scientific activities of the institute.

Updation of original cohort (1985): As NIREH started functioning for future research, the • original cohort (1985) was considered as a very important source of information. It was decided to update all vital information like exact status of cohort population, mortality list, chronic ill patient and death list and pregnancy outcome. Population based long term epidemiological studies which have been carried out continuously since 1985, further continued with same protocol of the study.

The Institute is continuing the long term epidemiological studies. The 44th round of six monthly detailed surveys has been completed.

Preparation of Research proposals on Congenital malformation Registry, Pulmonary • disorders, biochemical markers in MIC affected people, Long Term Effect of MIC on Ocular Health, Gene expression through micro array technique, Mental Health Research are some of the new projects which are under various stages of preparation and finalization.The Vision Document of NIREH has been drafted by a committee for setting institute’s • short term, medium term and long term goals. The Vision document has been finalized and endorsed by Scientific Advisory Committee (SAC) meeting held on 19th Oct., 2011 at Bhopal. A Task Force group was constituted to study the work done so far and suggest present • activities and future need of research. The draft Task force Report was presented during Scientific Advisory Committee (SAC) meeting held on 19th Oct., 2011 at Bhopal. The report will be finalized and submitted by Chairman Task Force group after incorporating the suggestions of Task Force members. The Scientific Advisory Committee has been constituted to assess ongoing research • activities and examine & scrutinize research proposals to be undertaken. The Scientific Advisory Committee (SAC) meetings were held on 20th July,2011 and 19th Oct.,2011. Five research projects were developed by Consultants of NIREH, Bhopal.

REGIONAL MEDICAL RESEARCH CENtRE, DIBRUGARH The focus of research work of RMRC, Dibrugarh continued to be on Cancers, Cardiovascular diseases and hypertension, Haemoglobinopathies among the non-communicable diseases



and Mosquito borne diseases, HIV and drug abuse, Trematode infections, among the communicable diseases.

Cancers A total of 5 studies were pursued during the year on lung, breast, oral and stomach cancers. In the case-control study on risk factors for primary lung cancer 110 cases and 220 controls in Manipur and 97 cases and 129 controls in Mizoram were recruited. Family history of lung cancer was found in 6.4% cases and 0.5% controls. Tobacco smokers and alcohol takers were found more prone to develop lung cancer. Presence of kitchen inside the living room in Mizoram and presence of GSTM1 null genotype in Manipur were found area specific risk factors for lung cancer. In the case-control study of genetic and molecular epidemiology of oral cancer in Assam and Meghalaya states epidemiological information was collected from 173 cases and equal number of controls in Assam. Majority of the cases were from rural areas (58.5%) followed by semi-urban (34.8%) and urban areas (6.7%), 94.9% reported chewing habits and 56.3% used betel nut with lime and tobacco. Studies on Genetic and molecular epidemiology of breast cancer in Mizoram, Tripura, Assam and Meghalaya revealed betel nut chewing with or without tobacco as an important risk factor. No association of family history or genetic polymorphism of BRCA1 and XRCC1 genes with increased risk of breast cancer was found. While family history was found associated, age at menarche was not found associated with breast cancer. Study on genetic and molecular epidemiology of stomach cancer in Mizoram revealed significant association of consumption of Tuibur (tobacco smoke infused water) in males and smoking of Meizol (a locally made cigarette) in females with the stomach cancer. Consumption of smoked dried vegetables, smoked fish, preserved meat and fish were other significant risk factors. While GSTM1, GSTT1 and CYP2E1 polymorphisms were not significantly associated, mutations in P53 at codon 72 of exon 4 increased 4.7 times risk of stomach cancer. Persons with variant allele of CYP2E1 and smoked meiziol had very high risk of stomach cancer. Estimation of cancer disease burden through 12 population based cancer registries in north-east India was continued.

HaemoglobinopathiesThe study on prevalence of HbE and thalassaemia in malaria endemic zones of Assam and Arunachal Pradesh was completed during the year. In malaria endemic zones of Assam significantly higher Hb F level in subjects carrying heterozygous βE–globin gene, increased prevalence of Hb E-homozygous, 619 bp deletion and common mutation pattern of IVS 1-5 (G-C) was recorded. In Arunachal Pradesh, the gene frequency for βE-globin gene was 0.078 in malaria endemic areas and 0.056 in non-endemic areas. In malaria endemic areas, Hb E homozygous state was not observed and 15.6% subjects were heterozygous Hb E. Screening of 177 blood samples showed hyperbilirubinemia in 4% subjects in another study.

Mosquito–borne diseasesThe Indo-Myanmar-UK collaborative study to determine geographical and genomic barriers to gene flow in An. baimaii was continued. Genotyping of 144 individuals of An. baimaii, representing 8 NE Indian populations, using 7 nuclear markers revealed higher genetic diversity in this vector from NE India as compared to from neighbouring SE Asian countries. Ongoing study on Ecological succession of anophelines recorded 42 mosquito species under 11 genera In Tripura and 19 species of mosquitoes under 5 genera in Mizoram state. In a study on Morphological variation and molecular characterization of An. minimus species



complex in Assam and Arunachal Pradesh no variations in the wing characters among the An. minimus A individuals from various parts of Assam and Arunachal Pradesh was noted. A WHOPES sponsored Phase III evaluation of Deltamethrin SC 62.5 g ai/L for indoor residual spraying against An minimus was pursued during the year to determine and compare the persistence of insecticidal activity on common indoor surfaces and evaluate the efficacy on vectorial potential of a new insecticide Deltamethrin SC at 20 and 25 mg ai/m2 doses with Deltamethrin WG (250g ai/kg) at 25 mg ai/m2 dose.

Trematode/Cestode infectionsThe completed study on the prevalence and molecular diagnosis of human paragonimiasis in north-eastern region of India recorded 1.9% prevalence of paragonimiasis in the community, highest being in Arunachal Pradesh (3.7%) followed by Meghalaya (1.8 %) and Assam (1.1%). In this study 4 types of lung flukes-3 belonging to Westermani complex (P. westermani genotype 1, P. westermani genotype 2, P. siamensis like) and P. heterotremus were detected. Prevalence of Paragonimus metacercarial infection in crabs varied from 0.7 to 18.4%. Near complete mitochondrial genome sequencing of P. westermani genotype 1 was accomplished. In a highly endemic focus of human paragonimiasis in Arunachal Pradesh, the intervention undertaken during 2003-2005 through praziquantal treatment and creating community awareness, resulted in significant decrease in the egg positivity from 20.9 to 4.3% and sero-positivity from 51.7 to 7.9% in children below 15 years.

Bacterial diseasesA total of 130 isolates of Streptococcus pneumoniae in 21 serotypes (Type 33, 23, 19, 8 being the most common) were found in Dibrugarh district of Assam. Penicillin resistance

Near complete mitochondrial genome of P.westermani genotype 1 from NE India



was seen among 14.3% isolates, 97.1% isolates were sensitive to erythromycin, 48.6% isolates showed intermediate resistantance to ciprofloxacin, 11.5% to trimethoprim-sulphamethoxazole and 5.7% to tetracycline. As many as 57.7% isolates were resistant to trimethoprim-sulphamethoxazole and 7.1% to tetracycline. Study on prevalence of anti-tuberculosis drug resistance, risk factors for tuberculosis and status of HIV/AIDS in the tea garden workers of Assam , covering 5079 households in 9 tea gardens, was completed during the year. In this study 164 new AFB positive cases (prevalence <3 per thousand) were detected with overall 9.1% prevalence of MDR which was 3% in new cases.

Viral diseaseIn the completed study on molecular epidemiology of measles in NE India measles seropositivity was found 42.0% with D4 and D8 circulating genotypes of Indian origin. About 58% measles cases occurred in children with vaccination history. The completed investigation on the prevalence of occult Hepatitis B infection in Upper and Lower Dibang Valley districts of Arunachal Pradesh found 9.9% HBsAg positivity and 6.6% prevalence of occult infection with C1, C2 and D circulating genotypes. Only 57.8% subjects had protective HBsAb antibody level of >10mlU/ml. Whole genome sequencing was accomplished for 6 samples of HBV. Phase II monitoring of multisite monitoring of human influenza viruses in Dibrugarh district revealed 9.5% PCR positivity of influenza A virus mainly comprising of H3 (97%), Type B and pandemic H1N1 virusus. In a pilot study screening of 250 influenza negative nasal/throat swab samples from the cases with influenza like illness resulted in detection of Respiratory Syncytial Virus (3%), human Metapneumo virus (7.6%), type-3 para-influenza virus (2.4%) and Adeno virus (4.0%) in children below 5 years of age. The completed study on sexual behaviour and contraceptive usage in HIV positive people in Assam revealed 20% decrease in penovaginal sex and an increase in condom usage from 4.6 to 83.6% with overall contraceptive prevalence rate among married and unmarried respondents being 92% and 79% respectively after knowing their HIV status.

Other ActivitiesThe completed task force study on Epidemiology of musculo-skeletal conditions in India screened 10,032 individuals (males 4988, females 5044), aged >18years, from urban (4,999) and rural (5033) areas of Dibrugarh district. In this study, 14.04% in urban area (9.6% males, 18.4% females) and 9.97% in rural area (5.6% males, 14.4% females) were found positive for musculo-skeletal conditions with 43.5% screened positives having had joint pain. The

Whole genome sequence of HBV from NE India Hepatitis B vaccination in Upper Dibang Valley, Arunachal Pradesh by RMRC staff



Registry of People with Diabetes in young age enrolled 715 persons and found the onset of diabetes in 4.9% by the age of 10 years and family history of diabetes in 43%. In a study in Assam overall 71.5% adolescent girl students were found anaemic and haemoglobin type (Hb E) emerged as the important non-nutritional determinant of anaemia.

Other than the regular research activities, the Centre investigated the outbreaks of diarrhoeal diseases in Sonitpur district and bacterial skin infections in Dibrugarh district of Assam. A workshop on Tribal Health Research to celebrate the International Day of the World’s Indigenous people on 9th August 2011 and an International workshop on Basis of immunology and immunopathology of Infectious Diseases (12-23 September, 2011) in collaboration with the Centre for Infection and Immunity, Lille, CNRS, Institut Pasteur de Lille, University Lille, France and University Pierre and Marie Curie, Paris, France as a part of commemoration of centenary celebrations of ICMR was organized. Further, during the year a total of 22 research publications came out from the Centre with average impact factor of 2.5.

DESERt MEDICINE RESEARCH CENtRE, JODHPURDesert Medicine Research Centre (DMRC) continued to contribute its inputs to improve the health of the people of desert and non-desert parts of Rajasthan by generating new knowledge through biomedical research, providing advance molecular diagnostic facilities for the diagnosis of pandemic influenza 2009 (H1N1) and dengue viruses and by developing trained manpower in the state.

Research and public health contribution through newly created BSL-2 level laboratory equipped to diagnose the genes of Swine flu viruses in human swab samples, continued to carry out further research on swine flu and providing reference molecular diagnosis of H1N1 viruses in suspected samples referred by local medical college hospital. Re-mergence of suspected cases of swine flu was studied and out of 36 swab samples referred by local medical college hospital 4 were tested positive for Swine Flu, pin pointing sporadic but epidemiologically significant persistence of swine flu virus in the community.

During the period under review there has been an outbreak of Dengue in Jodhpur town. The research team of DMRC collected 324 serum samples from medical college hospitals of Jodhpur. To characterize the outbreak as being caused by dengue virus, Real Time PCR (RT-PCR) was performed on selected samples, using primers and probes obtained from National Institute of Virology, Pune. The tests performed established that the present outbreak was caused by dengue virus. Studies showed that number of cases which showed negative test results for IgM and IgG antibodies showed positive results for RT-PCR. The studies showed that present practice of detection of dengue through IgM and IgG antibodies need to be advanced to molecular diagnosis of virus for pathogen characterization and subsequent better case management in the hospitals. The observations also showed correlation of molecular presence of dengue virus from human patients and from mosquito collected from the houses of the patients. Screening of houses of 27 patients tested RT-PCR +ve, 19 houses showed mosquitoes carrying the dengue virus. Out of 27 houses +ve for human dengue, 19 showing presence of virus in mosquito fauna with a high vector infectivity rate which is likely to continue across generations of mosquitoes through transovarial transmission of virus.

Outbreak of malaria in and around a desert town was investigated and an approach to demonstrate integration of vector control and parasite containment simultaneously in all the affected villages was implemented and check over disease transmission was achieved in collaboration with state health department.



translational Research - DMRC has started three new translational research projects including study of field efficacy of application of latex of Calotropis procera against dengue vectors. Centre has generated virus activity among mosquito larvae in 8 district towns of the state, developing an early warning system of virus activity through study in 5761 houses covering 31,609 containers. The elimination of infected foci in collaboration with state health department is in progress. The field efficacy of anti larval activity of latex of C. procera was tested and the product was found useful in controlling breeding of dengue vectors. A real time IT based intelligent health informatics system was developed with reference to malaria. The developed system was found to be faster, cost effective, more advantageous and an adjunct to the existing health information system.

Studies on Non-Communicable diseases and Nutrition – The DMRC continued its studies on the prevalence of diabetes mellitus in Raika population. A total of 827 households were covered and 1858 individuals were interviewed and examined. Total 656 (63.1%) gave history of drinking camel milk. Among them, only 131 (20.0%) drank camel milk during last 12 months. The duration of drinking camel milk up to 4 years was 45.7%, followed by 5-14 years (25.7%) and 15 years and above (28.6%). A total of 6 diabetics were detected among Raika subjects studied, out of which 4 were males and 2 females. Their age was between 41-70 years. Studies on nutritional values of pearl millets was made and high iron contents of the millets was reported to serve as possible supplement to compensate iron deficiency among local population. Nutrition monitoring survey on the NNMB pattern was continued into its 5th phase covering 600 households involving population of 2797 individuals in Jodhpur district, Rajasthan. Main morbidities observed were acute respiratory infections and fever. Regarding nutritional deficiency signs discoloration (8.1%) were observed. Night blindness and Bitot’s Spots were 0.8 and 2.2%, and dental caries 27.9%, and dental fluorosis24.9%. Underweight in preschoolars was 59.3% and stunting was 51.7%. In children aged 1-3 years, average energy intake was 840.53 Kcals. Trends revealed that there is gradual decline in stunting and underweight in preschoolars over the 4 phases of the study.

Contributions in developing trained manpower in the state - The Centre has a laboratory equipped with the state of art facilities in bio-medical research. More than 15 students were imparted training as a part of their post graduate curriculum. A number of students continued the studies leading to Ph. D. and for post doctoral research.

NAtIONAL CENtRE FOR DISEASE INFORMAtICS AND RESEARCH, BANGALORE The National Centre for Disease Informatics (NCDIR) was given status of a new permanent institute of the Indian Council of Medical Research in March 2011. The new centre was the

Serological and molecular diagnostic tests performed on dengue in DMRC



outcome of the sustained and successful run of the National Cancer Registry Programme since December 1981. The main objective of the NCDIR is to sustain and develop a national research data-base on cancer, diabetes, CVD and stroke through recent advances in electronic information technology with a national collaborative network, so as to undertake aetiological, epidemiological, clinical and control research in these areas. The following are the current thrust areas of NCDIR:

Cancer Registries - National Cancer Registry Programme (NCRP)• Patterns of Cancer Patient Care and Survival• Development of Software Applications Programmes•

The NCRP, as of now, has a network of 27 population based, 9 hospital based cancer registries and 17 centres collaborating in the study on Patterns of Care and Survival Studies. The first meeting of the Scientific Advisory Committee (SAC) was held on 15th September 2011 at Bangalore. The major achievements are listed below:

Collection of disease data in a systematic way & providing actual incidence (not estimates) • as per international standards and quoted. Sustained programme for over 25 years providing valid estimates of the burden and • patterns of cancer.The cancer atlas project helped map patterns of cancer in a cost effective way using • recent advances in information technology. This gave a new concept in data collection and broadened the field of disease informatics. It identified many researchable areas; motivated pathologists and clinical oncologists across country to collaborate and participate in cancer research; with minimum effort provided critical base line information at district level. Finally, it opened the entire North Eastern states for cancer registration and research.Some major contributions of the NCRP are the following:•

Epidemiological and other Research - i) Identification of geographic areas for site specific research; ii) Identification of variation in sites of tobacco related cancers vis-à-vis geographic areas; and iii) laid a foundation for studies in molecular epidemiologyCancer Control – i) Identified especially through the cancer atlas different sites for priority towards cancer control; ii) Provide an idea of the magnitude and trends over time in different sites of cancer; and iii) Provided information for doing evidence based cancer control activities through specific indicators.Patient Care – i) Identification of deficiencies in cancer patient care in the Indian setting in terms of standardised recording of clinical information, compliance to treatment and follow-up; ii) Identification of proportion of patients presenting at late stage; and iii) Laid a framework towards clinical evaluation and multi-centric trials.The NCRP through its network of cancer registries has several national and international publications in Descriptive and Analytical Epidemiology that are of national relevance and importance.

ExtRAMURAL RESEARCH

Cardiovascular DiseasesThe key areas of work undertaken in the field of Cardiovascular Diseases include Jai Vigyan Mission Mode Project on Community Control of RF/RHD, foetal origin of heart diseases,



management of acute coronary events (MACE) registries, school based interventions to reduce cardiovascular risk factors in children and Biobank linked to MACE registries.

Jai Vigyan Mission Mode Project on “Community Control of RF/RHD” had four arms including epidemiology and molecular typing of rheumatogenic strains, RF/RHD registries and research towards development of a vaccine against streptococci. A model of surveillance provided by community-based registries by four nodal registries has been replicated successfully in other parts of the country. The epidemiological component has been completed at a centre in North India (PGIMER, Chandigarh) and another in South India (CMC, Vellore). A survey in school children (5-14 years) under registry component and a passive population based registry has been undertaken by Chandigarh, Vellore and Kochi and Indore. Satellite registry at Mumbai and another one covering a tribal population Wayanad have completed data collection under Kochi nodal registry; Shimla, Jammu, Jodhpur under Chandigarh nodal centre and; Dibrugarh under Vellore nodal centre. The data from these registries indicated shift to lower prevalence rates of RF RHD in these parts of the country. The Group A Streptococcus (GAS) strains circulating in the community collected by the satellite registries from children with symptomatic and asymptomatic sore throat have been subjected to molecular typing. A comprehensive report is under preparation in a close collaboration between ICMR and Chandigarh centre. The translation of this project’s methodology by Punjab NRHM for screening all school children in government and government aided hospitals and providing them surgeries, cost of which will be borne by Punjab state, as well as taking up of this program on pilot basis in 4 states by Himachal Pradesh’s NRHM have been landmark achievements of this project. The program in Punjab has entered the fourth year.

The objective of the study “Relation of candidate gene variants regulating triglyceride metabolism to serial changes in childhood body mass index and coronary artery disease risk factors in young adulthood” was to determine the frequency of polymorphisms in APOA-V gene, hepatic lipase and PPAR γ in subjects of Delhi cohort and their relation to changes in body mass index (at different stages of growth). The risk allele of APOA5 (-1131C) resulted in 23.6 mg/dl higher triglycerides as compared to normal allele (P < 0.001). Risk allele of HL (-514T) was associated with significantly higher HDL2 levels (P = 0.002). None of the polymorphisms had any significant relationship with birth weight or serial changes in anthropometry from birth to adulthood in this cohort. Proposal for a follow up study to cover the four generations of the New Delhi birth cohort subjects and their spouses has been approved in principle by Task Force group.

A feasibility study for Web Based Management for Acute Coronary Events (MACE) Registry network is ongoing in 13 centres located in 12 different states of the country. Phase I objectives are to establish multicentric hospital based registry of acute coronary events and to develop an efficient electronic data management system amenable to be an ultimately web based system and test its feasibility. The Nodal centre at ICMR, which is responsible for development and operationalization of eCRF through establishment of information systems and secure storage of data, has developed a new website for MACE registry with questionnaire modified as per the feedback from PIs of feability study centres. The questionnaire has been designed to include various range checks and validity checks. The new questionnaire has been provided to all participating centres and experts for validation. Software is being developed to analyze the data and provide results to centres through a secure web based system. Few tables on patient demographics, mode of payments, drug prescription have already been generated. Data collection on 6 month follow up is ongoing.



A pilot study in two centres, PGIMER, Chandigarh and AIMS, Kochi in the area “School Based Interventions to Reduce the Risk of CVD Risk Factors in children” aims to develop a model for prevention of CVDs in school settings and assessing the effect of the lifestyle intervention programmes on the health behavior, anthropometric and biochemical measurements of school going children.

A project “Designing a biobank for biological samples collected from a mega study on acute coronary events in Indians” is ongoing under ICMR INSERM (Indo French) collaboration. A protocol for undertaking a pilot study for a MACE registry based Biobank has been designed with French investigator’s support. The pilot study has been initiated in June 2011 in 2 clinical centres and a laboratory at ICPO where data and biological samples will be stored. A ‘Manual of Operations’ developed for the biobanking facility is being validated.

Robust biomarkers for cardiovascular diseases need to be developed. These must be quantifiable and correlate well with clinical and biochemical measures of disease progression, and should be relatively inexpensive and noninvasive so that they can be measured serially over time. A multicentric project for developing biomarkers to identify individuals at risk and stages of heart disease is proposed to be initiated.

DiabetesThe ICMR’s Advanced Centre for Genomics in Type 2 Diabetes Mellitus aims to undertake both research and training components. For research component, two proposals entitled, Study of genes related to maturity onset diabetes of the young (MODY) and early onset diabetes, and Study of genes implicated in ion channel dysfunction in diabetes, are underway so as to determine the prevalence of MODY in different regions of India and screen the known gene variants in unrelated diabetic subjects and normal glucose tolerant subjects so as to find the association with the disease. The Centre completed its term in September 2011. It has been observed that about 9% of clinically diagnosed MODY patients had HNF1A (MODY 3) gene mutations and 3.4% of clinically diagnosed MODY patients had HNF4A gene (MODY 1) mutations. The novel HNF1A gene mutation Arg263His was found in diabetic members and not with the NGT members in the large family proving its co-segregation with diabetes. The mutant R263H showed completely lack DNA binding activity which was revealed by transactivation assay and subcellular localization studies. Discovery of the R201C mutation in one of the PNDM patients made it possible to switch over this patient from insulin therapy to oral sulfonylurea.

The multicentric task force project entitled Registry of People with Diabetes in India with Young Age at Onset, is continuing at nine centres with aim to understand magnitude of problem, disease pattern or types including the geographic variation and incidence and prevalence rate of complications. The training workshops were held at the Centres at a regular interval. The data set of approximately 6000 subjects (age ≤25 years) is available with information on varied parameters such as duration and type of disease, treatment pattern, family history, complications, immunology profile, etc. Out of 1407 subjects enrolled so far, majority of the subjects are with type 1 diabetes (88.4%) followed by type 2 diabetes (8.5%). Majority of the subjects are in the age group of 10-14 years. Most common type reported so far is type 1 diabetes followed by type 2 diabetes & MODY and most common complications are retinopathy and neuropathy.



The Task Force Project on Genomics of Type 1 Diabetes is ongoing at three centres viz Delhi, Chennai and Kashmir with the aim of undertaking genomic characterization of multiple autoimmune favoring HLA-DR3+ve haplotypes in type 1 diabetes (T1D) in these ethnic groups of India. Important findings of the study revealed that T1D shows a strong association with DR3 in all the three population groups, the strongest being in the North Indian and Kashmiri population. T1D patients from South India also revealed a positive association with DR4, similar to that observed in the North American and North European

Caucasoid populations.

The preliminary studies on the effect of camel milk in type 1 diabetes in population of north-west Rajasthan (Raika community) indicated its important role in glycemic control, lipid profile and quality of life. The Task Force project on “Camel Milk and Diabetes,” was constituted and two projects viz effect of camel milk on glucose metabolism in adults and the hypoglycemic/insulin like activity in camel milk using an animal model was completed in collaboration with National Institute of Nutrition, Hyderabad and SP Medical College, Bikaner. The findings of pilot study provided useful information and have been able to give lead regarding the effect of camel milk on biochemical parameters such as blood glucose, insulin, HbA1c, etc.

North India South India

Clinical Classification of Young Diabetics Registered at AIIMS Collaborating Centre

Under Task Force on Genetic Basis of Resistance to Diabetes; two projects entitled, “HLA profiling in Raika Community of Rajasthan,” and “Understanding genetic basis of resistance to diabetes in the Raika community,” were initiated. The frequency of the HLA-DRBI*03 allele in Raika and Non-Raika population was found to be significantly higher in comparison to the north Indian



population. As per published literature, Raika is the only population in the world that has such a high frequency of DRB1*03 allele and associated HLA-A and B alleles that confer risk of Type1 Diabetes in India and in most populations. Although there was high occurrence of autoimmunity favoring HLA alleles and haplotypes among both Raika and non-Raika communities, this did

not have a comparable incidence of Type 1 Diabetes and/or other autoimmune diseases in the two groups. During the personal interviews and clinical examination, none of the individuals presented history of any other autoimmune diseases. The data has been sent for publication. The projects on Understanding Genetic Basis of Resistance to Diabetes in Raika community aimed to (i) evaluate association between genetic polymorphism of candidate genes implicated in type 2 diabetes in the Raika community and (ii) compare the susceptible genetic polymorphism in Raika community and non- Raika communities residing in the same geographical area. The genotype analysis of selected SNP analysis in the Raika and Non-Raika samples showed significant difference in allele frequencies for genetic variants. This suggested the protection of Raika community against type 2 diabetes might be because of the higher prevalence of protective alleles.

The Task Force project on ICMR- Indian National Diabetes Study-Phase I, aims ot understand prevalence of diabetes and pre-diabetes along with its association with the genetic aspects is about to complete and data analysis is in the process at three states and one Union Territory. Of the 16,607 individuals selected for the study, 14,277 (86%) individuals participated. The overall weighted prevalence of diabetes (both known and newly diagnosed) in Tamilnadu was 10.4%, Jharkhand,

Prevalence* of diabetes in urban and rural population

Agewise prevalence of diabetes in urban and rural population



5.3%, Chandigarh, 13.6% and Maharashtra, 8.4%. The prevalence of prediabetes was 8.3%, 8.1%, 14.6% and 12.8% respectively.

Mental HealthCurrent research in mental health is focusing on Suicide to study prevalence of suicidal ideation and suicidal attempt in the community and to find correlates of suicidal ideation, the protective and risk factors attributing to suicide attempt and course of suicidal ideation, besides studying the pathways to suicidal attempt among the ideators. The study has been carried out at Delhi and Vellore. Vellore centre study results have indicated that suicidal ideation is widely prevalent in urban as well as rural Indian community. Suicidal ideation was found to be associated with both psychiatric as well as multiple psycho-social factors. High levels of psychosocial stress and lack of formal education was found to increase significantly the risk for suicidal ideation. It is proposed to initiate studies on Common Mental Disorders (CMD).

Neurological Sciences A prospective longitudinal study of stroke in Kolkata aims to determine the natural course and outcome of the stroke patients and to measure the impact of economic and psychological burden on the family members of stroke sufferers. It is a community-based, two-stage, door-to-door study in an urban population in the city of Kolkata, selected through stratified random sampling. An incidence rate of 140.61 (114.46-170.98) stroke cases/100,000/ year was observed in this prospective longitudinal study of stroke in Kolkata. Of the stroke survivors, 12.54% suffered from dementia. Financial worry was reported to be most prominent in stroke care givers, particularly among the lower-economic group.

A prospective population based pilot urban stroke registry aims to evaluate the feasibility of establishing a population based stroke registry for finding the burden of stroke, stroke types and risk factors for stroke in urban city of Ludhiana and to collect the methodology for data collection from city births and deaths division, selected health care institutions and scan centres. The methodology for collection of data from various clinical sub-centres and scan centres has been standardized. The registry has enrolled 1465 patients. The case fatality rate post discharge was 9.7%. It was concluded that population based Stroke Registry is feasible in urban population and main sources of data collection are hospitals and scan centres.

A protocol for ‘Rural Population based Registry at Bangalore proposes to develop a methodology (including instrument development) for acquiring data on first stroke cases from selected health care institutions and from community in a defined geographical area of one Taluk in a rural setting has been recommended by Task Force Group. A plan of action for developing population based stroke registry in a rural area that could be expanded at the District level for larger integration at the national level is in process.

Non-Communicable Disease SurveillanceThe ICMR was identified by the Ministry of Health and Family Welfare, Govt. of India to coordinate the implementation of the Non-communicable Disease Risk Factor surveys under the Integrated Disease Surveillance Project (IDSP) in 29 States/UTs over a period of 3 years beginning in 2007. The 1st Phase of the surveys was done in 7 States (Kerala, Tamil Nadu, Mizoram, Uttaranchal, Maharashtra, Madhya Pradesh, Andhra Pradesh) and their reports have been finalized. A dissemination workshop with the key stakeholders was held



on 15th December 2010 in New Delhi, and State level dissemination with key stakeholders was held in January 2011 in Trivandrum, Kerala.

The component of non-communicable disease surveillance planned periodic community based surveys of population aged 15-64 to provide data on the risk factors. Two types of questionnaires - one at household level and another for individual level were used for the survey. A total of 5000 households were contacted in urban and rural area of each of the seven states. The overall household response for the survey ranged from 88.6% in Kerala to 99.9% in Madhya Pradesh and Maharashtra. The percentage of current daily smokers varied between a low 9% in Maharashtra and high 42% in Mizoram. The average age of onset of smoking ranged from 17 years in Mizoram to 20 years in Maharashtra, Kerala and Tamil Nadu and in rest of the states it was 19 years. In Andhra Pradesh, Kerala, Tamil Nadu and Uttarakhand, 4-12% respondents were current daily users of smokeless tobacco. In rest of the states, it ranged from 32-48%. The mean age of initiation of alcohol consumption regularly in the age group 15-34 years was 20-22 years in all the seven states. The present survey found that the mean time spent on work related physical activity ranged from a low 128 minutes per day in Maharashtra to a high 293 minutes per day in Madhya Pradesh. By categories of hypertension, 17-21% of the respondents in all the states were found in stage I or stage II hypertension.

The grade I overweight was only 7% in Madhya Pradesh closely followed by 9% in Mizoram, 11% in Uttarakhand and Maharashtra where as it was 15% in Andhra Pradesh, 18% in Tamil Nadu and 22% in Kerala. The obesity of grade 2 and above was around 5% in Tamil Nadu, Andhra Pradesh and Kerala and it was around 2 to 3% in rest of the states.

OpthalmologyA Task Force Project on epidemiology of anophthalmia and or micropthalmia in children aged 0-5 years in selected districts of Bihar has been initiated from March 2011at RMRIMS,Patna. In phase I identification and mapping of cases of Anophthalmia and or Microphthalmia from the primary health centres and subcentres of the districts of Bhojpur, Buxar and Rohtash has been done. In phase II, the risk factors (clinical and environmental) associated with this problem will be identified retrospectively using a case control approach. A questionnaire for this purpose has been finalized and data collection has been initiated .

Environmental and Occuptaional HealthUnder the Centre for Advanced Research on Indoor Air Pollution with a mother-child cohortat the Sri Ramachandra University, Chennai, Enrollment of the rural component is in full swing and 358 individuals have been listed. For the urban component the number is still small (55) since it was started recently and there has been several unwilling for participation. The reasons are being investigated. A mobile laboratory has also been fabricated under this CAR which has the necessary equipments for air monitoring installed in the modified bus.

Community based survey on non-communicable disease surveillance



Obesity and Metabolic SyndromeAn ICMR task force project on Childhood Obesity is ongoing at 5 sites across the country (Delhi, Hyderabad, Jamnagar, Srinagar, Shillong). The study aims at developing reference curves for estimating body fatness in children and correlating it to cardiometabolic outcomes and identifying determinants of childhood obesity through qualitative research methods. Under the ICMR-CIHR, Canada, Memorandum of Understanding, three projects are ongoing on Childhood Obesity.

OtorhinolaryngologyTo augment research in the area of Otorhinolaryngology, a Call for Proposals was floated on ICMR website encouraging a multicentric, multidisciplinary approach. A total of 31 concept proposals were received. The protocol for the NTF project- Prevalence and epidemiological survey of hearing impairment in six regions of India has been finalized. The proposed task force related to issue of Congenital Deafness-Deaf and Dumb people in Dhadkai village of Doda district of Jammu will involve detailed genetic studies for carrier state detection for the whole population of the village.

Oral HealthUnder the task force project on Dento-Facial anomalies and congenital birth defects of face including cleft lip and palate, during the prepilot phase of the study, the data collection tool has been prepared and has been tested for the pilot and main study. To understand the logistics and feasibility of the multicentric pilot project, a pilot proposal in three centers has also been developed to study the spectrum of the disease, clinical profile, type of treatment provided etc.



Reproductive Health

INtRAMURAL RESEARCH

NAtIONAL INStItUtE FOR RESEARCH IN REPRODUCtIVE HEALtH, MUMBAIThe Institute has been pursuing basic, clinical, operational and epidemiological research with the focus on betterment of reproductive health. Institute has been engaged in generating new knowledge, development of indigenous products like diagnostic kits on early detection of pregnancy, infections, functional ability of sperm, etc.

Fertility RegulationActive immunization with Peptide1 for 80kDa HSA elicited gradual increase in antibody • titer in male bonnet monkeys (n = 4) and induced infertility due to loss of sperm motility. The animals are being monitored for regain of fertility following decline in antibody titer. The study suggests the potential of synthetic peptide 1 of 80kDa HSA for development of antifertility vaccine for males.

Preliminary results from a study on determinants of high vasectomy acceptance in • Jawhar block of Thane district of Maharashtra suggested the significant contribution of the health system in mobilizing the community and increased awareness about health and importance of family planning.

An intervention study was carried out to • enhance young couple’s contraceptive knowledge and acceptance of spacing methods through a gender-equity focused family planning intervention delivered by the village health care providers. Respondents included young husbands (n=30), young wives (n=20), village health providers (n=12) and mothers-in-law (FGDs=4). The results indicated poor knowledge, myths and misconceptions of couples on family planning and reproductive health issues. Gender inequality and domestic violence was common. The existing village health care providers hardly discuss these issues with couples. Intervention model and evaluation tools have been developed.

Infertility and Reproductive DisordersAntibodies against Alpha Actinin 4 (• α-ACTN4), Heat Shock 70 Protein 5 (HSPA5) and Actin beta (ACTB) were identified in women showing primary ovarian insufficiency and undergoing IVF-ET. Active immunization of female mice using peptides derived from these proteins showed 25 – 43% reduction in fertility. These peptides could be used in diagnostics and therapeutic management of ovarian autoimmune disease.

Follicle stimulating hormone (FSH) is used for super ovulation in women during the • in-vitro fertilization protocol. Polymorphism at A-29 position of FSH receptor gene was

Focus Group Discussion with Mothers-in-law (Thane District, Maharashtra)



found to be associated with poor ovarian response and lower expression of the receptor in the granulosa cells of women responding poorly to FSH. These findings suggest that the FSH receptor polymorphism could be developed as a molecular marker for predicting ovarian response to FSH treatment in women.

Studies undertaken to investigate the variants of gene related to insulin resistance in • women with Polycystic Ovary Syndrome (PCOS) showed significant association of a C/T polymorphism of insulin receptor gene with PCOS in lean women and also with insulin resistance and hyperandrogenemia. Frequency of a common variant in peroxisome proliferator activated receptor; gamma (PPRγ) which preserves insulin sensitivity is significantly low in PCOS women. Proteomic based investigations demonstrated that several extra cellular matrix (ECM) proteins, which are important dynamic factors in folliculogenesis and ovulation are dysregulated in PCOS. This may contribute to oocyte maturation and competence in PCOS.

Collectins (SP-A, SP-D and MBL) have been localized in the glandular epithelium of • human endometrium with higher expression during the secretory phase. SP-D was found to be regulated by estrogen in mouse endometrium. Differential expression of SP-D mouse endometrium during early pregnancy suggests its possible role in implantation.SP-D and MBL were found to be differentially expressed in full term and first trimester human and murine placenta thereby suggesting their role in parturition and recurrent miscarriages.

A community based study is being carried out to estimate prevalence of PCOS among • adolescents and young girls in Mumbai using both Rotterdam and AES criteria. Preliminary analysis of 448 cases reveals that about 5% of adolescents and young girls have PCOS, based on AES criteria and 12.2% by Rotterdam criteria.

Using sera of women with endometriosis, three cognate endometrial antigens were • identified namely, Tropomyosin 3, Stomatin like protein 2 and Tropomodulin 3. The peptide ELISA using the dominant epitopes of these identified antigens shows higher sensitivity, specificity and diagnostic accuracy than CA 125 and other reported immune markers in early detection of endometriosis, thereby suggesting that these can be new markers for early diagnosis of endometriosis.

Mesenchymal stem cells isolated from human endometrial and endometriotic tissue • showed differential expression of pattern recognition proteins.

In the area of endometrial biology, studies were conducted to elucidate the mechanisms • contributing to endometrial receptivity and decidualization. Proteomics based investigation revealed differential abundance of the select proteins in human uterine fluid during the transition from day 2 to 6 post ovulation. Some of these proteins were found to be conserved as these proteins showed the same expression pattern from the pre-receptive to receptive phase in rat uterine fluid. Studies are being conducted to assess the role of these proteins in implantation using a rat model.

Investigations carried out to understand the role of HOXA10 in endometrial decidualization • revealed differential regulation of several pathways. Further studies highlighted that HOXA10 regulates trophoblast invasion via the stat signalling pathway. Currently studies are being carried out to investigate the role of HOXA10 in immunomodulation.

Genomic imprinting, an epigenetic phenomenon whereby expression of gene/• chromosomal region depends on its parental origin, is important for embryo growth



and development. Studies were undertaken to examine DNA methylation status of imprinted genes involved in embryo growth in spermatozoa of the male partners as well as abortus of women undergoing Recurrent Spontaneous Abortion (RSA) of unknown etiology. Differentially Methylated Region (DMR) of one of the imprinted gene cluster, namely IGF2-H19, i.e. H19-DMR was found to be significantly hypomethylated. Since IGF2 is major growth modulator for early embryo development, it is likely that aberrant imprinting could be a cause of RSA.

A simple and cost effective Resazurin Reduction Test (RRT) has been developed to assess • the quality and fertilizing ability of spermatozoa in human and animals. The test is being commercialized through National Research and Development Corporation (NRDC), New Delhi.

Oct-4 a transcriptional regulatory factor plays an indispensable role in self-renewal and • differentiation of spermatogonial stem cells (SSCs). SSCs development and self-renewal is also dependent on the expression of Gfra-1 and Ret tyrosine kinase (Ret) (receptors for GDNF) in these cells. Oct-4 silencing in SSCs led to suppression of expression of Gfra-1 and Ret1 genes and the failure of SSCs differentiation.

Studies were carried out on the directed differentiation of two in-house derived human • embryonic stem cell line (KIND1 & KIND2) to pancreatic and tripotent cardiovascular progenitors. Gradual transition of embryonic stem cells line generated at the Institute into definitive endoderm, primitive gut tube and finally pancreatic progenitors was monitored by the expression of lineage specific gene transcripts.

A novel population of pluripotent very small embryonic-like stem cells (VSELs) were • reported in cord blood, bone marrow and mammalian testis and ovary. These are a unique stem cell population, more primitive to the adult stem cells and may have better regenerative potential. The VSELs were also detected in testicular biopsies of azoospermic men with childhood cancer. Studies are ongoing to restore fertility in cancer survivors by targeting these VSELs.

The institute along with three WHO Collaborating Centers (CCs) at AIIMS (Delhi) PGIMER • (Chandigarh) and MGIMS (Wardha) on reproductive health developed Guidelines on Prevention and Management of Infertility in the Public Health Care System. The guidelines were disseminated to the Ministry, Government of India, and other WHO Collaborating Centers of South East Asia Regional Office (SEARO) at the Regional networking meeting of WHO Collaborating Centers.

OsteoporosisOsteoporosis is emerging as an important and challenging public healthcare issue globally. • Estrogen plays a pivotal role in maintenance of bone mass in women. Polymorphisms in the genes that encode enzymes that catalyze estrogen biosynthetic pathways were observed to be associated with bone mineral density in two ethnic groups. The frequencies of polymorphic genotypes varied between the ethnic groups reflecting ethnic ancestry.

STI/ HIVHIV has been shown to bind human Mannose Receptor (hMR) and enter into sperm and • vaginal epithelial cells which are devoid of conventional CD4 receptor. Vaginal epithelial cells showed higher expression of hMR during periovulatory phase as compared to that



in pre and post ovulatory periods. The entry inhibitors targeting hMR and CD4 receptor have been formulated and showed prevention of HIV entry into vaginal epithelial cells, in-vitro. The formulation will be tested using rhesus monkey model at NIN, Hyderabad.

Env gene of HIV1C in PBMCs, spermatozoa, vaginal epithelial and cervical cells showed • the presence of distinct variants in the same individual. These variants differed in infectivity as well as affinity to host cell receptors. The study suggests the distinct HIV variants in PBMCs and urogenital cells may influence the sexual transmission and pathogenesis of HIV as well as response to antiretroviral drug therapy (ART). Full length sequencing of HIV variants in PBMCs and urinogenital cells is being carried out to identify the drug resistant mutations and their association with ART and sexual transmission of HIV.

Human surfactant protein D (SP-D), with established role in host defense against • various bacteria, fungi and viruses, is being evaluated for its role in host defense against HIV. Recombinant human SP-D (rhSP-D) retains its anti-HIV activity in presence of vaginal fluid and seminal plasma. An aqueous gel formulation of rhSP-D showed significant anti-HIV activity in TZMbl reporter cells.

SsALF-24 (hemocytes of Indian • mud crab, Scylla serrata) and rabbit vaginal fluid hemoglobin -α chain like peptide (RVFHbαP) (rabbit vaginal fluid) appear to have anti-bacterial and anti-HIV activities. These peptides did not adversely affect various Lactobacilli strains. In vitro safety studies revealed that these peptides found to be safe to human vaginal epithelial cells. In vivo toxicity studies in rabbit are ongoing.

Innate immune mechanisms of human vaginal epithelial cells were investigated with an • aim to development safe microbicide. Vaginal cells were found to express TLR7, TLR9 and RIG-1 which, involved in the recognition of nucleic acids of viral pathogens. Further studies revealed that repeated stimulation of these cells with ligand of TLR9 induces tolerance. Microarray results revealed the increase of downstream signaling pathways elicited by the ligands of these receptors.

Analysis of results on 35 mother-child pairs enrolled during the year revealed, controlled • viral load in 58.3% of women with anti-retroviral therapy (ART) compared to 30.7% of women with prophylactic treatment (PT, single dose of nevirapine during delivery). This highlights initiation of ART in pregnant women to control their viral load and thus to inhibit mother to child HIV transmission. Initial analysis on the polymorphism in cytokine and HLA genes revealed some significant association of genetic polymorphism with HIV transmission. These factors can be exploited as possible markers for prediction of perinatal HIV transmission. Further interim analysis of polymorphism of HLA, cytokine gene in 42 sero-discortant revealed association of specific alleles with HIV transmission.

Study of 1728 unregistered hospital deliveries from selected hospitals (Thane Civil • hospital, Nasik Civil hospital, Rajawadi hospital, Kurla Bhabha Hospital, Bandra Bhabha hospitals and Bhagavati hospital) in Maharashtra shows that the Prevalence of HIV is

Anti-HIV activity of rhSP-D gel formulation in TZMbl reporter cells



0.4 percent. According to MSACS report for the second quarter (April to June 2011) prevalence of HIV in ANC mothers is 0.2 percent. Prevalence of HIV in unregistered hospital deliveries is higher than the prevalence of HIV in ANC mothers.

RHANI wives study developed and tested the feasibility and acceptability of an intervention • for women at risk from HIV. During the year 2011-2012, survey was completed. Both unprotected marital sex and marital sexual coercion at last sex significantly decreased, with greater impact seen for those women who attended more versus fewer sessions of the six weeks intervention programme. This program was delivered to women in a single slum in Mumbai, but has the potential to be used in any community setting that reach wives at risk for HIV from husbands.

In response to this study an operational research study has been initiated to link up • ICTC and family planning services to improve correct and consistent use of condoms and promote dual contraceptive use i.e. condoms with other contraceptives. The study is using an experimental and control design model in hospital setup and will enroll and follow up 300 HIV positive women for one year to see the contraceptive uptake and consistent use.

In order to strengthen the established ARSH services as per the National Standards • of ARSH Implementation Guide in Karjat Block of Raigad district, NIRRH continued providing its technical support to the Government of Maharashtra by optimizing linkages of health and non-health related sectors. Linkages of school health services with ARSH clinics and involvement of NGOs, ASHAs and ICDS for demand generation activities and referrals was enhanced. Incentives were provided to ASHAs for adolescent client referral. ARSH services at PHC were extended up to sub center level. Quality of care was reinforced by introduction of Job Aids for service providers and monitoring by introducing Supervisory Checklist. With these interventions, approximately 7000 adolescents and young people availed services from 8 facilities in the block compared to 2222 in the previous year.

Reproductive CancersIn order to study function of CRISP-3 in prostate cancer, CRISP-3 expression was knocked • down stably in LNCaP cells. These cells are being studied for growth invasion. A 2.5 kb upstream region of human CRISP-3 gene was cloned to design a construct for genome wide shRNA screen to identify novel regulators of CRISP-3 expression.

One hundred and forty five women with cervical cancer and 35 healthy women were • screened for HPV. HPV was detected in 98.6% of women with cervical cancer whereas, in 10% of women with healthy cervix as per Pap test. HPV type 16 was the most prevalent (23.1%) HPV type in cervical cancer cases. Interim analysis of Human leucocytes antigen (HLA) revealed significant association of HLA allele as well as haplotype with cervical cancer. More participants are being enrolled to confirm these observations.

Studies conducted in previous year demonstrated the role of androgen receptor (AR) • in regulating the expression of a C- Myc (a known regulator of telomerase) in prostate cancer cells. However inhibition of C- Myc following silencing of AR expression did not lead to a significant decrease in telomerase activity or cell proliferation. Transcriptome analysis of AR silenced cells revealed that AR regulates the expression of positive as well as negative regulators of telomerase in prostate cancer cells.



In the reporting year, studies were also initiated to investigate whether there exist estrogen • binding protein(s) on the surface of prostate cancer cell lines. Estrogen binding protein(s) were localized on the cell surface of the prostate cancer cells. Further stimulation of these membrane bound estrogen binding protein with a cell impermeable estradiol conjugate revealed alteration in the phosphorylation pattern of cellular proteins. It is anticipated that elucidation of the role of cell surface estrogen binding proteins will help in the development of estrogen based therapies for prostate cancer.

The study on enhancing knowledge and promoting health seeking behavior of couples • on STIs and cervical cancer in urban slums is in second phase. During 2011–12; baseline data was collected from 1020 couples from intervention area through seven focus group discussions. Knowledge about cervical cancer as well as Pap smear test was poor among both husbands as well as wives but as compared to husbands, wives had better knowledge. Intervention programmes being conducted in the intervention area include dissemination of information on RTIs/STIs and cervical cancer through inter-personal communication, smaller group meetings and educational programmes. Orientation programmes for Community Health Volunteers, Medical and Para-medical staff as well as for Private General Medical Practitioners were also conducted.

National Centre for Primate Breeding and Research National Centre for Primate Breeding and Research (NCPBR) is being established to • provide pathogen free non-human primates for biomedical research in the field of reproductive health. Presently, construction of Quarantine Building, Corals, Corn-cribs etc. (Phase-I) is in the advanced stage. Installation of various services of the Quarantine building is in progress. The phase-I will be completed by December 2013 so as to achieve the primary objective of primate breeding.

National Centre for Preclinical Reproductive and Genetic ToxicologyThe man• date of the Centre is to provide services to public and private sectors, conduct workshops and research in the area of toxicology. In the reporting year the centre has provided services to private agencies as well as academic Institutions for testing their products for safety and efficacy. During the reporting year centre could provide services to Solumics Ltd., Mumbai; Dhootpapeshwar Ltd., Panvel; Zydus Research Centre, Ahmedabad and academic institutions such as Institute of Chemical Technology and Bombay Veterinary College, Mumbai.

The centre is also conducting research in the area of endocrine disruptors. Bisphenol-A • (BPA) a chemical commonly used in making of polycarbonate plastic and epoxy resin. BPA was found to be genotoxic but not mutagenic. Neonatal as well as perinatal exposure of male rats to BPA led to impairment in Hypothalamus–pituitary-testis axis affecting their fertility during adulthood.

GENEtIC RESEARCH CENtRE, MUMBAI

Genetic Clinic Services Services provided: Prevention of birth defects, Genetic Screening, Post natal screening.

ICMR Genetic Research Center has been registered with the Government of Maharashtra • as an independent prenatal diagnostic center (MOH/FS/53/PNDT/2011).



Genetic screening is the ‘the testing of apparently healthy people in the population • to identify those at increased risk of genetic disease themselves or whose children (including future children) may be at increased risk of disease. Genetic screening includes carrier, prenatal and newborn screening. Carrier screening is often considered by couples who want to have children, but who are concerned that they may “carry” gene for a certain disorder that has a potential to affect their children. Newborn screening identifies biochemical or other inherited conditions in newborns that may result in mental retardation or other compilcations. Newborn screening is an effective measure in preventing mental retardation.

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, primarily affecting • females and characterized by developmental regression, epilepsy, stereotypical hand movements, and motor abnormalities. Its prevalence is about 1 in 10,000 female births. Rett Syndrome is caused by mutations within methyl CpG-binding protein 2 (MECP2) gene, Over 200 individual nucleotide changes which cause pathogenic mutations have been reported. However, eight most commonly occurring missense and nonsense mutations account for almost 70% of all cases. A total of 70 individuals with Rett syndrome phenotype were screened and 20 different MECP2 mutations and polymorphisms were identified in 28 patients (40%). Of the 20 mutations, 7 (35%) frameshift, 6 (30%) nonsense, 14 (70%) missense mutations and one duplication (5%) was identified. The most frequent pathogenic changes were: p.Thr158Met (10.7%), p.Arg133Cys (7.1%), p.Arg306Cys (7.1%) missense and p.Arg168Stop (10.7%), p.Arg255Stop (7.1%) nonsense mutations.

Although SRY is the most important testis-determining gene, mutations in the SRY have • been found to account only for 15% cases of CGD and less than 1% of cases of partial forms (46,XY DSD). Hence, majority of these patients may have mutations in other genes involved in the sex-differentiation pathway. Various autosomal and sex-linked genes, besides SRY, have been shown to have a role in testicular development. Mutations and deletions in SRY, mutations in Desert Hedgehog (DHH), and Steroidogenic factor 1 (NR5A1) account for majority of these cases. DAX1 and WNT4 duplications also account for about 1% of cases.

We have identified mutations in the Desert hedgehog (DHH) gene in two cases of complete • gonadal dysgenesis. The mutations found in these two patients were a homozygous deletion (c.271_273delGAG) that resulted in deletion of one amino acid (p.D90del) and a homozygous duplication (c.57-60dupAGCC) that resulted in premature termination resulting in non-functional DHH protein. The structure-function implications of the p.D90del mutation were predicted using computational tools. Structural studies on the p.D90del mutant revealed that the mutation could seriously perturb the interaction of DHH with its binding partners.

Genetic Research Center has established DNA based tests for common genetic • disorders, primarily included into inborn errors of metabolism category. These include lysosomal storage disorders like Tay Sachs disease (HEXA gene), Sandhoff disease (HEXB), Gaucher disease (GBA), Pompe disease (GAA), metachromatic leukodystrophy (ARSA), Krabbe disease (GALC), Hunter disease (IDUS); organic acidemias like maple syrup urine disease (BCKDHA, BCKDHB, DBT), glutaricaciduria type 1 (GCDH), propionic acidemia (PCCA, PCCB), tyrosinemia (FAH), HMG CoA lyase deficiency (HMGCL). Other leukodystrophies include X-linked adrenoleukodystrophy (ABCD1 gene), megalencephalic leukoencephalopathy with subcortical cysts (MLC1). Skeletal dysplasias and genodermatoses were also included. A total of 550 new patients were



referred for clinical opinion during this year. Molecular diagnosis was provided for 206 patients. These patients and their families have availed genetic counseling and accurate recurrence risk prediction, (Table)

table: Summary of Molecular Diagnosis for Single gene Disorders at GRC

Name of disease Name of gene/s to be sequenced

Sensitivity of test to diagnose

mutations

Basis of diagnosis Number of patients (2011-12)

Lysosomal storage diseases1. Tay Sachs disease2. Sandhoff disease3. Gaucher disease4. Metachromatic

leukodystrophy5.Pompe disease6. Hunter disease

HEXAHEXBGBAARSA

GAAIDUS

>95%>95%>95%>95%

>95%>95%

Clinical, biochemical (deficiency of respective enzymes)

3315104

22

Organic acidemias1. Glutaricaciduria type 1 2. Maple syrup urine disease 3. HMG CoA lyase deficiency 4. Propionic acidemia5. Tyrosinemia

GCDHBCKDHA, BCKDHBHMGCLPCCA, PCCBFAH

>95%>95%>95%>95%>95%

Clinical, abnormal newborn screen (Tandem MS/MS, GCMS)

715226

Other metabolic conditions1. Glycogen storage disease

type 1a2. Glycogen storage disease

type 1b3. Glycogen storage disease

type 34. Glycogen storage disease

type 45. Wilson disease

G6PC

G6PT

AGL

GBE1*

AtP7B

>90 %

>90 %

>90 %

>90 %

>90 %

Clinical, pathological, biochemical,

1

1

10

-

10

Leukodystrophies1. X-linked

adrenoleukodystrophy2.Megalencephalic

leukodystrophy

ABCD1

MLC1

>95 %

>90 %

Clinical, MRI brain, biochemical

2

5

Genetic Skin diseases1.Ichthyosis

a. Lamellar ichthyosisb. ChanarinDorfman

syndromec. SjogrenLarrson syndrome

2. Progeria (HGPS And MADS)

3. Cutis laxa4. Infantile systemic

hyalinosis

TGM1CHD7

FALDHLMNA

ATP6V0A2CMG2

Clinical, pathological, biochemical

Clinical, radiological, biochemical

10

2

22

Skeletal dysplasia1. Achondroplasia and

related disorders2.Filaminopathies3. Osteopetrosis

FGFR3

FLNA, FLNBTCIRG1, CLCN7

>95%

>90%>95%

Clinical, radiological

10

59

Neuromuscular conditions1.Duchenne muscular

dystrophy2.Spinal muscular atrophy

DMD

SMN1

>90% (multiplex plus MLPA)>95% (PCR- RFLP, MLPA)

Clinical, biochemical

35

5



ExtRAMURAL RESEARCHReproductive HealthA randomized controlled trial is being undertaken at four centers to compare the probability of success of the three vas occlusion techniques namely (a) Cautery and excision with fascial interposition; (b) Cautery and excision without fascial interposition; and (c) Ligation and excision with fascial interposition. The study also addresses the safety and surgical difficulties associated with the three techniques of vas occlusion, the probability of success at 24 weeks and the predictive value of semen analysis at 8 and 12 weeks. A total of 430 participants have been enrolled and are being followed up at one week, 8 weeks, 12 weeks and 52 weeks of the procedure. No failures have been reported with any of the three techniques.

Phase-III Clinical Trial with an Intra-vasal Injectable Male Contraceptive – RISUG® is on going at 4 centers. Sixty four subjects who received the RISUG injection under this trial have been followed up to 3 years. No side effects have been noticed in any of the subjects and the clinical efficacy of the drug is maintained. Four new centers i.e. AIIMS, New Delhi, Guwahati Medical College, Guwahati, MCS & Hospital Patna, Sub Divisional Hospital, Kharagpur have been included. A new prototype of RISUG Syringe has been developed and after testing at various levels it has been approved by the Monitoring Committee to include it in the trial. After the training of the investigators, the prefilled new RISUG injection syringes have been sent to all the participating centers for use.

A post-marketing, multicentric surveillance study is being carried out to assess the efficacy of Centchroman - a non-steroidal oral contraceptive pill. Side effects on non-reproductive and reproductive organs including occurrence of ovarian cysts and return of fertility after discontinuation are being evaluated. This is being compared with Copper-T 380. A total of 2182 cases have been enrolled- 1008 centchroman users and 1174 IUD users. The interim analysis indicates among Centchroman users followed up for 11, 964 woman-months of use, a total of 67 method/user failures were reported. The continuation rate with Centchroman was 96.6, 93.1 and 85.4 per 100 users at 3, 6 and 12 months of use respectively.

Phase III clinical trial with subdermal contraceptive single rod implant Implanon a long term contraception method for 3 years of use is being evaluated through 22 centres for its efficacy, side effects, continuation rate, return of fertility and menstrual bleeding pattern (Fig.2). A total of 3161 women have been enrolled in the study so far and have been observed for 94,129 woman months of use. The cutoff date for the analysis is October, 2011. Total 2017 women have completed 36 months of use giving a continuation rate of 64.5% at 36 months of use. No Pregnancy (method failure) has been reported till date. Majority of the discontinuations were due to menstrual disruptions 7.4 per 100 users at 12 months increasing to 19.5 per 100 users at the end of 36 months (Fig 3). Amenorrhea contributed to discontinuation in 0.9 and 3.3 per 100 users at 12 and 36 months respectively. None of the Implanon users had any infection at site of insertion during use. Migration of the device from the site of insertion (subdermal in the inner aspect of upper arm) was reported in few women. Discontinuations due to personal reasons, medical reasons, were 3.2 and 4.2 per 100 users respectively at 36 months of use. The menstrual pattern revealed that 12.2 % women have normal bleeding in the first three months which increased to 22.4 % women at 36 months of Implanon use. Frequent/prolonged bleeding decreased from 11.7 % to 6.9 % women and reduced/infrequent bleeding decreased from 76.1% women to 70.0% women by 36 months of use indicating that there was some improvement in menstrual pattern with duration of use. Of the 3018 women who discontinued Implanon use due to various reasons including



discontinuations after 3 years of use of the device, 1732 women accepted another method of contraception following discontinuation of Implanon. Return of fertility is being observed in ex-Implanon users exposed to the risk of pregnancy. Preliminary analysis of the 470 Ex-Implanon users exposed to the risk of pregnancy indicates that 304 women conceived within 12 months of discontinuation till the reporting period.

Single Rod, 4 cm Implanon Device Reasons for discontinuation

Sexual Behavior and Contraceptive Use among HIV Positive People is being carried out at three centers to explore the changes and factors that influence the sexual behavior and contraceptive use among people aware of their HIV positive status and also explored the perspectives of the health care providers and program managers regarding this issue. The interim results indicated out of a total of 1055 participants enrolled at Mumbai, Dibrugarh and Aizawl, risky behaviors reduced at all sites however, in Aizawl, other forms of sex such as oral and anal sex increased by 2.7%, 30%, respectively. The major reasons for not availing contraceptives from public sector in all the centers were mainly related to quality of condoms not being good, providers not friendly and felt shy to access service.

Research is ongoing at 3 sites to describe fertility desires and contraceptive practices among HIV positive individuals and to examine the role of ART and other potential predictors on these desires and practices. This would provide critical insights into the provision and implementation of programs focused on the prevention of heterosexual and parent to child transmission of HIV as well as the refinement of policies aimed at integrating family planning and HIV prevention, care and support in India. A total of 54 in depth interviews with PLHA and Health Care Providers have been completed. Key findings from PLHA indicate that Women and Men living with HIV need access to both family planning and HIV treatment services. Inequities in gender-based power continue to constrain women’s ability to make child bearing decisions in the face of HIV infection and there is a need to provide women and men with more comprehensive information about their health status and safe child bearing. From Providers majority opined that PLHA have the right to bear children. Among those who opined otherwise, most of them tended to overestimate the risk of transmission. In phase II, cross sectional survey on 750 different categories of participants is ongoing.

A community based survey in 13 states is being carried out to study the prevalence of primary infertility, childlessness and secondary infertility in urban and rural India and to identify the possible risk factors for infertility. A total of 13,000 urban households and 27,300 rural households will be surveyed. Currently 10,292 urban households and 24,494 rural households have been surveyed. The interim analysis indicates that the primary infertility in urban area and rural area ranges from 0.7% to 7.8% and 2.0% to 7.6% respectively.



Environmental and Reproductive healthTo study the effect of Non-ionizing Electro Magnetic Field (EMF) on neurological, reproductive, cardiovascular, ENT diseases and cancer, a multi-centric study is being carried out in Delhi. To collect and record laboratory and clinical examinations data from various disciplines 24 proforma’s were developed in consultation with the investigators which were approved by the Expert Committee. To find out the contact persons who are interested to participate in this study a web based mechanism was developed and based on that a data base of 2,500 companies, govt. organization has been prepared. Simultaneously a note indicating possible adverse health effect of RFR emitted from cell phone and importance of this study was prepared. This note was sent to all the identified companies with the request to participate in this nationally relevant project. Based on the frequent reminders to these companies and individuals around 600 contact nos. were identified. The scientists of the project are contacting these 600 numbers with an intercom telephone facility provided to them. Nearly 200 subjects have been enrolled in the study.

Women’s Health Obstructed labour contributes to 5% maternal mortality and severe morbidity like genital fistula in the survivors. However, with an increase in institutional deliveries and use of caesarean section, the proportion of genital fistulae due to gynecological surgeries is on the rise. Socio-demographic data on genital fistula was collected from the gynecology and surgery departments of 23 medical colleges all over the country. Nearly 240 fistula cases were enrolled in a period of one year with highest burden (n=32) being reported from Patna. At onset of fistula, the mean age ±SD were 35.73 ± 10.40 years and the mean parity ± SD was 3.31 ± 1.97. Nearly 70% women with fistula were from rural background. The commonest cause of fistula was abdominal hysterectomy (50%) while injury during childbirth was the causative factor in 37% cases. Repair results of 194 cases indicated that surgery was successful in 81.4% cases.

A study on reduction of maternal mortality and morbidity through promotion of evidence based intra partum and early post partum care was carried out in one district one each of Tamil Nadu (Thiruvallur), Orissa (Cuttack), Uttar Pradesh (Allahabad), Gujarat (Baroda) and Rajasthan (Jaipur) so as to cover the different geographical regions of the country and include both good and poor performers based on the maternal health indicators. Data was collected on facility preparedness for maternity care services using IPHS standards from 56 facilities including medical colleges (MCs), district hospitals (DHs), FRUs/CHCs and PHCs. Findings of preliminary analysis indicate that all surveyed health facilities provided out-patient and in-patient care including 24 hour maternity services but comprehensive emergency obstetric care (CEmOC) services were available in only one third FRU/CHCs and very few PHCs. Even though nearly 90% FRUs/CHCs and 50% PHCs had operation theater buildings, operation theaters were not functional commonly due to lack of trained anesthetist, equipment and power supply. Caesarean section facilities were absent in most rural facilities of Allahabad and Jaipur. Regular blood supply was available in all MCs, 83% DHs and only 19% CHCs/FRUs. However, all facilities in Thiruvallur including FRU/CHCs reported availability of regular blood supply. Facilities for carrying out routine laboratory tests were available in all MCs and DHs and 90% of rural facilities but blood sugar testing and blood grouping were available in only 53% and 73.3% rural sites. Rapid pregnancy test was available in 73.3% facilities surveyed. HIV testing was available in all MCs, 83.3% DHs and 75.6% rural sites. Services for routine investigations at Cuttack lagged behind other sites.



Graphical representation of infrastructure and services available at different levels of facilities.

A study was conducted in two districts each in three states [Maharashtra, Rajasthan and Odisha] of India to understand the competency of AYUSH providers in providing Skilled Birth Attendance (SBA) services. The study used mixed methods approach to evaluate knowledge, skills, training needs and acceptability of AYUSH providers regarding SBA service provision. A total of 73 interviews [37 Ayush providers (APs) and 36 program managers] were conducted. The program mangers interviewed were working in the capacity of state AYUSH director, District health officers/ chief medical officers, and SBA master trainers. APs demonstrated adequate knowledge, competency and confidence to provide SBA services. Their skills could be enhanced by more hands-on practice during training, providing them opportunity to practice their skills and a continued education through mentor-mentee relationship with trainers and supportive supervision by program managers. Some constructive steps from leadership are needed to create enabling environment to build their morals and provide healthy work environments.

Post-partum period is associated with various physical problems and psychosocial stresses. However, not much data is available on the impact of various medical interventions and post-partum quality of life remains poorly studied. Quality of life was assessed using the Mother Generated index and depression was evaluated using the EPDS in a three-stage cluster randomized sampling survey in Delhi. In stage I, twenty of the 150 wards were selected by probability-proportionate-to-size (systematic method). In stage II, three colonies each from the twenty wards were chosen from a MCD list of colonies in Delhi by simple random sampling. In stage III, a house-to-house survey was initiated in the chosen colonies to recruit a minimum of 30 subjects. The survey team visited a total of 1,18,446 houses (60 colonies, 20 each from the higher, middle and lower income groups; 344 to 6759 houses per cluster) and identified 2286 women who have delivered within the last six months. The mother generated index was poorer amongst multi mothers and with higher socioeconomic

Matemity care & services

Miscellaneous facilities

Newborn facilities & services

Biowaste disposal in facilities



class (Primary index score HSEC- 2.6, MSEC- 2.7, LSEC- 2.8), (Secondary index score HSEC-4.0, MSEC-4.2, LSEC-4.5) while depression was more prevalent and severe amongst the higher classes - depression (HSEC- 25.8% (21.8 – 30.2), MSEC- 20.4 % (13.5 – 29.6), LSEC –21.2 % (11.8-35.2); suicidal thoughts (HSEC- 8.7% (5.7 -13.2) , MSEC- 7.1 %(2.6-18.0), LSEC – 3.0% (0.4-18.6). Sleep deprivation, adverse impact on social life and difficulty in managing increased responsibilities were the most commonly reported issues (74.7%, 26.8% and 20.7% respectively). Weight gain and physical problems were given the highest spending points (2.97 and 2.91 respectively). The study documented the wide variety and wide prevalence of physical problems, quality of life and depression related issues suffered by women in the post-partum period. The needs of post-partum mothers could be addressed through implementation of a wide based practicable maternal education and social support model

A study was carried out to estimate oxidative stress in pregnant women on daily versus weekly iron supplementation. A total of 162 primipara women were enrolled at 2 sites and 80 placentae were studied. The preliminary analysis indicated an equivalent rise in hemoglobin in both daily and weekly iron supplementation groups. However, the oxidative stress in daily arm was non-significantly higher than that in the weekly arm. There was no correlation (r=0.534) of number of iron tablets consumed with level of hemoglobin in both the groups.

Polycystic ovarian syndrome (PCOS) is the commonest endocrine disorder among women of reproductive age group. Metabolic disorders, cardiovascular risks and diabetes are common in women with PCOS. A study aimed at finding out whether relationship between B cell dysfunction and insulin resistant is causal or coincidental was carried out at 2 sites. Glucose test abnormalities and quantitative estimation of B cell dysfunction versus insulin resistance were studied in 203 cases of PCOS and 120 controls. The mean age + SD was 24.8±5.5 years (range 18 to 45). Of these 27% were overweight and 40% obese. Majority 67% had normal glucose tolerance while impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes was noted in 7%, 16% and 9% cases respectively. Family history of diabetes was positive in nearly one-third cases. Age was not significantly different in NGT and glucose intolerant groups. BMI was significantly higher in the glucose intolerant groups. HOMA-IR increased and WBISI decreased from NGT to DM. Beta cell secretion as measured by IGI 120 was not significantly different. Disposition index decreased significantly from NGT to newly diagnosed DM cases. Age, BMI, waist circumference, hip circumference, waist to hip ratio, systolic and diastolic blood pressure were higher in normoglycemic PCOS cases compared to healthy controls. Insulin and C-peptide levels at various time points were significantly higher in cases. TSH, total testosterone and DHEAS levels were also higher in cases. Total cholesterol, TG and LDL cholesterol were higher and HDL levels were lower in cases compared to controls. AUC of insulin, C-peptide, insulinogenic index and HOMA-IR were significantly higher in cases (after adjusting for age and BMI). WBISI was significantly

Haemoglobin levels in daily vs weekly iron supplementation



lower in cases. There were significantly higher fasting insulin, HOMA-IR and lower DI 120 in PCOS subjects with positive family history of T2DM compared to PCOS subjects without family history of T2DM. Higher plasma insulin, C-peptide, HOMA-IR and lower WBISI among subjects with PCOS compared to healthy controls. These differences were higher among PCOS subjects with family history of T2DM.

Child HealthEffectiveness of package of home based newborn care interventions were evaluated at five rural sites in the state of Bihar, Maharashtra, Orissa, Rajasthan and Uttar Pradesh. The interventions included health education to pregnant women, essential newborn care to all babies, care at birth, post natal home visits, early identification of morbidities in young infants (upto 60 days) using simple algorithm, and treatment of babies if referral is refused. The interventions were provided by extensively trained village level workers called Shishu Rakshaks (SR) in one arm, in another arm by anganwadi workers and there was a comparison arm where services were as per governmental programme. The interventions were provided by village level worker. Each intervention arm covered population of two primary health center. The early neonatal mortality rate in population clusters receiving intervention package delivered by Shishu Rakshak was 21% lower as compared to population in control clusters. The young infant mortality rate, post-neonatal mortality rate and infant mortality rate were also significantly lower(by 25%, 42% and 29% respectively) in the SR arm when compared to comparison arm. Decline in IMR, NMR post-neonatal mortality rate and young infant mortality rate in the AWW arm was not statistically insignificant.

In a randomized controlled trial the effect of Probiotics VSL#3 on prevention of sepsis in LBW infants during 0-2 month period was studied at two sites. A total of 1340 LBW infants were enrolled. There were 77 hospitalizations and 3 deaths in the study. Preliminary analysis indicated overall low infection and death rates. A statistical plan of analysis has been prepared and approved by the DSMB. Analysis as per this SAP will be carried out after data entry and validation is completed.

It is well known that morbidity and mortality is higher in low birth weight babies. Kangaroo mother care (KMC) has been found to be useful in reducing morbidity and mortality in preterm low birth weight babies in hospital settings. A pilot study on feasibility and acceptability of KMC for low birth weight (<2000 gms) babies in the community (urban, rural and rural tribal setting) was carried out in 100 subjects at three sites in Orissa, Maharashtra and Gujarat.

There is limited pharmacokinetic data on the use of the fixed dose formulations based on weight-band dosing in HIV-infected children. There are concerns about the possibility of sub-therapeutic blood levels of the antiretrovirals, The trough and the peak nevirapine levels (2 hours after dosing) in HIV infected children receiving nevirapine-based antiretroviral therapy using the FDCs (fixed dose combinations) were studied and to correlated with the clinical and immunological status of HIV infected children receiving nevirapine-based antiretroviral therapy using the FDCs. Children (n=79) HIV-1 infected children receiving nevirapine based ART were enrolled. There was no difference in the nevirapine levels in children who were underweight compared with those who had weight for age > -2 z. Similarly, the plasma levels were comparable in children who were receiving ART for < 12 months duration compared with those who were receiving it for longer durations. The study concluded that the current dosing schedule used in the treatment of pediatric HIV leads to adequate plasma levels of Nevirapine as most of the children had viral suppression.



A community-based longitudinal study was conducted in urban slums of Chandigarh to study the correlates of improvident maternity. Couples (n=667) with wives in reproductive age group were enrolled. Results indicated that improvident maternity rate is high (43.6%) in the slum population and differentials in fertility behavior of women and their spouses existed. Following intervention, the contraceptive prevalence rate was increased from 57.7% to 68.1% in the study group and from 56.7% to 62.6% in control group. Unmet need of contraception showed decrease from 41.2% to 29.6% in the study group and from 38.0% to 35.5% in the control group. Larger reduction in the proportions of undesired pregnancy was also observed in the study group as compared in the control group. Spousal relationships of more than 90% were reportedly good inspite of male dominance at both the occasions in both groups. Health education was helpful in reduction of improvident maternity, increasing contraceptives awareness as well as practice and also in promoting better spousal communications regarding reproductive issues, son preference etc. Interventions in the form of health education may have some positive role in reducing improvident maternity by modifying reproductive behavior of couples. Efforts should be made to address issues related with differentials in fertility preferences of women and men and to develop strategies related with aversion of unwanted births and attaining other outcome parameters in the domain of reproductive and child health.

Detection of minimal residual disease (MRD) in B cell lineage acute lymphoblastic leukemia (ALL) at the end of induction by flow cytometry was studied. Thirty -two cases were identified as B lineage ALL. Of these, 22 cases were CD34 negative therefore had no MRD. 8 out of the 32 B-lineage ALL cases were positive for MRD. Therefore MRD was seen in 25 % of MRD. The study indicates that when MRD exists at the end of the induction protocol, the treatment protocol should be intensified if the follow up shows relapses.

Anaemia is a leading cause of morbidity and mortality in children. The effect of mode of delivery of iron and/or iron and zinc supplement on iron status markers and potential markers of iron toxicity in children aged 24-36 months was studied. The results indicated that impact of tablets of iron and zinc was better than iron alone in improving iron status of study subjects. This is contrary to the conventional wisdom that zinc may interfere with iron absorption but is consistent with the results of recent large trials that there may be interaction at mechanistic and utilization pathways independent of absorption issues. The impact on iron status markers also indicated that all three forms of delivery i.e. (a) Dispersible tablet, (b) Dispersible tablet with zinc (10 mg), and (c) Fortified biscuit improved the iron status and delivery through biscuits and tablets with zinc were marginally better in terms of change in iron status both in comparison to control group at 30 days as well as in comparison corrected for baseline levels.

Efficacy of daily iron (20 mg) folic acid (IFA) Supplementation in correction of iron deficiency anemia amongst 36-59 months old children was studied in a community based cluster randomized trial. Group A (n=112) received 20 mg iron with 100 mcg folic acid, group B (n=114) received 40 mg iron with 200 mcg folic acid and group C (n=110) 40 mg iron with 200 cg folic acid weekly. IFA supplementation was completed in 336 children. Daily IFA supplementation when administered under supervision were found to be superior (P<0.001) to weekly dosing (40 mg) in improving haemoglobin levels in children in the age group of 36-59 months.



National Retinoblastoma Registry was established to collect descriptive data on all newly diagnosed cases of retinoblastoma occurring in the country. A total of 1561 cases have been registered. The mean age and median age at presentation was 24.97±23.61 months and 19 months respectively. The male: female Ratio was 1.28: 1.0; family history of retinoblastoma and other cancers was seen in 2.56% cases each. The unilateral retinoblastoma was seen in 66.8% (n=1043) cases whereas 32.2% (n=503) had bilateral disease .

Enrolled cases were grouped according to IIRS grouping (Group A- E) for intraocular disease and 72.3 % of the cases were in high stage of disease (Group D and E). The Chantada clinical staging indicated 30.7 % cases with extra ocular disease. Diagnosis of retinoblastoma was based on clinical examination, ultrasound and examination under anaesthesia and CT Scan findings. Enucleation was the preferred treatment for intraocular retinoblastoma. Eye was preserved with chemotherapy followed by focal therapy in 260 cases. Only focal therapy was given in 12 cases. For extra ocular disease, the preferred treatment was enucleation with secondary chemotherapy, only chemotherapy and enucleation with chemotherapy and radiotherapy. The cumulative survival of 50% had not been reached for any of the cases enrolled.

An assessment of Wastage Multiplier Factor (WMF) and Percent (%) Wastage of vaccines at the point of administration of vaccine during routine immunization under the Universal Immunization Programme (UIP), Government of India (GOI) was studied at 5 sites in 10 districts of four states of India. The estimated % wastage and its range, the estimated WMF and its range for DPT, DT, TT, OPV, BCG and Measles was respectively 38.9 (12.8-69.7), 1.64 (1.15-3.31); 39.1 (27.3-61.4), 1.64 (1.38-2.59); 48.0 (20.9-67.1), 1.92 (1.26-3.04); 52.7 (22.1-75.7), 2.12 (1.28-4.12); 49.3 (30.3-70.2), 1.97 (1.43-3.36); 38.7 (20.8-50.1), 1.39 (1.26-2.00) (Table). The estimated % wastage of five of the six vaccines namely, DPT, DT, TT, OPV and Measles was found to be significantly higher than what is assumed in the UIP (P<0.0001). Among all the other reasons for wastage of vaccines, “Residual vaccine left in the vial” was the most frequently reported reason for wastage of vaccines. Therefore, vials of variable size with house to house campaign were recommended to minimize wastage of vaccines in UIP.

table. Percent wastage and WMF of vaccines as adopted in the UIP and as estimated in the ICMR study

Vaccine % wastage WMF

Adopted in the national programme

(UIP)

Estimated in the ICMR Study

Adopted in the national programme

(UIP)

Estimated in the ICMR Study

DPT 25 38.9* 1.33 1.64*

DT 25 39.1* 1.33 1.64*

TT 25 48.0* 1.33 1.92*

OPV 25 52.7* 1.33 2.12*

BCG 50 49.3 2.0 1.97

Measles 25 38.7* 1.33 1.39*

*P<0.001

Distribution of cases according to site of disease



DiabetesCorrelation between first trimester glucose screening and serum insulin levels with development of gestational diabetes mellitus after 24 weeks of pregnancy was studied in 298 non-diabetic pregnant women using a 3 hour, 100 gm oral glucose tolerance test (OGTT). Insulin sensitivity was estimated using the established Matsuda and DeFronzo insulin sensitivity index for oral glucose tolerance tests (ISOGTT), homeostasis model assessment- insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI). These values were compared with the results of second trimester OGTT. The overall prevalence of GDM was 13.42%; of these, 24 (60%) were diagnosed to have GDM in first trimester (GDM 1) and 16 (40%) in late second and early third trimester (GDM 2). First trimester fasting plasma insulin value greater than 7.45µU/ml was able to predict GDM in later gestation with a sensitivity and specificity of 80% and 57.4% respectively. The NPV for this parameter was found to be 0.97. First trimester ISOGTT values of less than 5.5 had sensitivity and specificity of 71% and 62.5%, respectively for prediction of GDM in later trimester. The study concluded that first trimester hyperinsulinemia preceded the onset of hyperglycemia between 24th -28th weeks of gestation. First trimester insulin indices had modest sensitivity and specificity for prediction of GDM after 24 weeks of gestation.

ICMR-INSERM workshop on Gene environment interactions in diabetes; epigenetics, nutrition and drugs was organized at Jodhpur in Oct, 2011 and key areas for collaborative research were identified. These included clinical phenotypes of inflammation in diabetes; preclinical models; biomarkers in diabetes and diabetes complications; and new drugs. A Diabetes diagnostics programme support has been initiated under which various Pharmaceuticals/ R&D organizations, Universities/ Academic institutions and individual researchers were invited to develop alternate cost effective technologies for blood glucose estimation. Seven projects have already been supported and 5 are in the process.

The role of chronic environmental stress in abnormalities of glucose tolerance, insulin sensitivity and pancreatic beta cell function was studied. Stress scale questionnaires - Presumptive Stressful Life Events Scale (PSLES), Perceived Stress Scale (PSS) and Sense of Coherence (SOC) - were administered to 500 Normal Glucose Tolerance (NGT) and 500 Newly Detected Diabetes Mellitus (NDDM) subjects. Insulin resistance and pancreatic β-cell function were determined by homoeostasis model assessment (HOMA). Endocrinological stress response was assessed by salivary cortisol, salivary alpha amylase, serum prolactin, serum testosterone, and serum DHEA-S in 125 subjects of each group in whom inflammatory markers and oxidative stress markers were also estimated. Stress questionnaire scores were significantly higher in NDDM subjects as compared to NGT with respect to PSLES-lifetime (P=0.000), PSLES-1yr (P=0.000) as well as PSS (P=0.000) indicating higher prevalence of stress in them. SOC score (P=0.000) were lower in the NDDM group suggesting that NDDM subjects did not cope well as NGT subjects with stress.

Salivary cortisol 10pm, post dexa cortisol and salivary alpha amylase, were significantly higher (P=0.000; P=0.001; P=0.038; p=0.000; P=0.014 respectively) and Serum testosterone (male) were significantly lower (P=0.014; P=0.000 respectively) in NDDM subjects as compared to NGT subjects. There was no significant difference in serum prolactin, serum DHEA-S between the two groups. Inflammatory markers - serum hsCRP, leptin, adiponectin and oxidative stress markers were significantly different between the two groups. Stress scales such as PSLES, PSS as well as salivary cortisol (post dexa) were significantly correlated with BMI as well as waist circumference (WC) while coping scale SOC was inversely correlated with WC and waist–hip ratio (WHR). Furthermore, PSLES, PSS and SOC as well



as cortisol 10 pm and cortisol (post dexa) were significantly associated with all glycemic parameters. In addition, there was an inverse correlation between SOC and hsCRP, leptin, lipid peroxidation (MDA) and positive correlation between SOC and adiponectin. PSS was positively associated with alpha amylase, hsCRP and MDA level and inversely associated with GSH. Cortisol 10 pm as well as post dexa cortisol were positively associated with MDA level and inversely associated with GSH.

The results of the present study indicate that NDDM subjects display higher chronic environmental stress and poor stress coping that could lead to central adiposity, insulin resistance, pancreatic β-cell dysfunction and glucose intolerance. The effects of stress appear to be both due to a chronically activated HPA axis as well as hyperactive sympathetic pathway .The effects of the activated stress pathways in causing diabetes could be mediated by the oxidative stress pathway. These findings provide unequivocal evidence that supports a significant role of stress in the development of type 2 diabetes mellitus.

Indo-US collaboration in MCHDRA joint Indo-US programme on Maternal & Child Health and Human Development Research (MCHDR) has been ongoing. Under this programme 8 workshops in areas of mutual scientific interest were held in India since its inception in the year 2000. Till date thirteen projects have been completed and 8 are currently ongoing. A call for proposals was placed under which 19 proposals and 9 applications for the conference grants were received.



Nutrition

INtRAMURAL RESEARCH

NAtIONAL INStItUtE OF NUtRItION, HYDERABAD

Community StudiesCreating enabling environment in schools for promoting physical activity, consumption of healthy foods and lifestyles by employing a multi-component health and nutrition intervention targeted not only at school children, but also their teachers, school managements and district educational officers, resulted in a significant increase in the health and nutrition knowledge of the adolescents. In addition, there were favorable changes in their nutritional status, with lesser number of children moving from overweight to obese category and more number of children from overweight category becoming normal as compared to the control group.

Responding to a request from them the state administration of Madhya Pradesh, a study was carried out to assess the health and nutritional status of <5 year children and infant and young child feeding practices among <3 year children in the rural areas at the district level. Data was collected from all 50 districts. The study revealed that about 52% of the rural children (< 5years) were underweight, 49% were stunted and 26% were wasted respectively. These figures are lower than those reported in the National Family Health Survey (NFHS-3) in 2006. Over 78% of pregnant women underwent antenatal check-up (ANC) at least once during their pregnancy, while one third of them had three ANCs (36.4%). The proportion of newborns, who were given pre-lacteals was only 16.1% as against 58.7% reported in NFHS-3 survey. Almost all the mothers fed colostrum to their newborns. The study provided information at district level for the government to take up appropriate corrective and educational/communication strategies.

A study was conducted to assess the nutritional and health status of street children (n=260) of 8-17 years in Hyderabad. About 24% were smokers, 13% were consuming alcohol, 3% were smoking Ganja, 5% were inhaling whitener and 36% were consuming other tobacco products such as ghutkha. About 18% had dental flurosis, 2% each had Bitot spots and angular stomatitis, while 16% children had skin ailments. The overall prevalence of thinness, stunting and anaemia were about 25%, 47% and 50% respectively.

Basic StudiesEndocrinology and Metabolism

As part of studies on developmental origins of adiposity and insulin resistance (IR), the role

A set of posters developed and distributed to schools as part of educational intervention on obesity and lifestyle factors



of peri/postnatal Manganese (Mn) status and high fat feeding in causing IR in later life were explored. Maternal Mn restriction transiently altered the body composition of male and female rat offspring. It also modulated adipocyte function and played an important role in muscle function. This study has for the first time demonstrated that maternal Mn restriction predisposes the offspring to increased central adiposity, fat deposition in liver, induction of a proinflammatory state and altered

glucose tolerance specially when fed high fat diets.

The effect of different methods of cooking on phenolic content and antioxidant activities of 11 commonly consumed pulses and legumes in India were studied. Nine out of 11 legumes samples showed a maximum of 20% increase or decrease in their total phenolic content (TPC) during different types of cooking. Interestingly, during conventional and pressure cooking, whole Bengal gram and Rajmah showed 27 and 54% increase in their TPC respectively.

Micronutrient Research A study was conducted to assess folic acid, vitamin B12 status and its association with leptin and anthropometric indices of adiposity among urban adolescent boys belonging to low and middle income groups. Vitamin B12 deficiency of 39% and folic acid deficiency of 17% were found among the adolescent boys. An age independent significant increase in body weight, body mass index (BMI) and fat free mass, waist circumference, sub-scapular skin fold thickness and decrease in HDL cholesterol were observed in the folic acid deficient group. Interestingly, vitamin B12 deficient group showed a significant increase in body fat percentage and fat mass compared to sufficient group after controlling for age and economic status. It was also found that the dual deficiencies lead to a lower HDL cholesterol levels in the adolescents. Leptin showed a positive relationship with body fat but showed no significant relationship with the two nutrients.

Measuring iron dialyzability is used as surrogate of estimating iron bioavailability in foods. Considering that the existing conventional colorimetric method is not sensitive to detect low level of iron present in plant sources, a sensitive and rapid method of detection of dialyzable

Map of Madhya Pradesh showing districts-wise Prevalence of underweight

The effect of different methods of cooking on phenolic content and antioxidant activities of 11 commonly consumed pulses and legumes were studied



iron was developed using a combination of fluorescent probe Phen Green and a 6 well plate. This method was validated against the 59Fe tracer and the conventional colorimetric methods. Both the isotopic and florescent probe methods seem to be promising for rapid screening of dialyzable iron for selecting foods for dietary diversification.

Ocular BiochemistryDiabetic retinopathy (DR) is one of the common complications of diabetes. Based on a hospital based case-control study, it was previously reported that vitamin-B12 deficiency could be an independent risk factor for DR. This year, an animal experiment was conducted to understand the role of vitamin-B12 in the development of DR. The results indicate a role for vitamin-B12 in retinal structure and function both in neuronal and vascular component, particularly under hyperglycemic conditions. Further, supplementation of vitamin B12 has resulted in beneficial outcomes in normalizing neuronal, vascular and inflammatory mediators under hyperglycemic conditions in the retina.

Accumulation of advanced glycation endproducts (AGE) due to non-enzymatic glycation has been implicated in diabetic complications. Studies have demonstrated the antiglycating potential and mechanism of action of two such molecules, ellagic acid (EA) and rutin using various protein glycations systems. While the antiglycating action of EA seems to involve predominantly inhibition of Nε-(carboxyethyl) lysine (CEL) through scavenging of dicarbonyl compounds, rutin scavenges free radicals directly and also chelates the metal ions by forming complexes with them. Inhibition of glycosylated Hb formation in human blood under high glucose conditions signifies the antiglycating potential of EA. These findings establish the antiglycating potential of these flavonoids and their in vivo utility for controlling AGE-mediated diabetic pathologies.

Previously retinal degeneration in a spontaneously developed novel obese rat model was reported, while WNIN/Ob rats develop retinal degeneration progressively. Studies during the current year have shown that supplementation of 26-52 mg/kg diet vitamin A alleviated the obesity-associated retinal changes in WNIN/Ob rat model, which may have implications for treatment of retinal degeneration associated with obesity.

Lipid ChemistryA study on exploration of basal glucocorticoid levels and their possible role in obesity and insulin resistance using WNIN/Ob and WNIN/GR-Ob rat models was completed. The results from this study suggest that 11β-HSD1 plays an important role in the development

Retinal morphology. Hematoxylene and Eosine stained retinal sections of Group I (normal), group II (B12 deficiency), group III (diabetic), group IV (diabetic with B12 deficiency), group V (diabetic with B12 supplementation)



of obesity, dyslipidemia and insulin resistance in WNIN/Ob obese rats. Further, this study supported the hypothesis that inhibition of 11β-HSD1 as a key strategy to treat metabolic syndrome. This perhaps is the first study to link 11β-HSD1 to adipose tissue fibrosis and tissue glycogen content under obese condition. Feeding of diet rich in vitamin A decreased 11β-HSD1 activity in visceral fat and liver of WNIN/Ob obese rats, which is associated with decreased adiposity. Feeding of diet-rich in n-6 polyunsaturated fatty acids decreased hepatic 11β-HSD1 activity and increased enzyme activity in adipose tissue of WNIN/Ob lean rats.

Stem Cell ResearchA study that looked into the synergistic effects of amyloid peptides and lead on human neuroblastoma cells concluded that amyloid peptides and Pb at micro molar concentrations exert neurotoxic effects by inducing oxidative stress and inflammation resulting in the apoptosis.

A study attempted to explore the feasibility of using umbilical cord serum as a potential source for the growth and maintenance of pancreatic culture rat islets and assessment of their marker functions in comparison to fetal calf serum - in vivo and in vitro. The study suggested that that hUCBS can be explored as an alternate serum supplement for FCS, making it more feasible in cell systems of human derived origin and can also find its application for the human transplantation programmes.

Pancreatic exocrine tissue as a source of progenitors/stem cells to generate insulin secreting cells was examined and the methodology has been standardized for acinar cultures. Pyridoxal-phosphate (PLP) addition was protective to acinar cells and demonstrated antioxidant effects with the addition of H2O2. PLP modulated the regulation of the transcriptional factors such as Ngn3. PDX-1, which are the master regulators for acinar lineage to beta cell formation.

National Food and Nutrient Data centerA National Food and Nutrient Data Center (NFNDC) has been planned with an aim to provide data on the nutrients and bioactive substances in foods consumed in India. To this end, the equipment required for the analysis of nutrients and bioactive substances in foods have been procured and installed. Method standardization and validation for over 150 nutrients and bioactive substances in foods has been completed. Using the National Nutrition Monitoring Bureau data, key foods in the Indian diet have been identified. A probability proportional to size national sampling plan has been developed for collection of key foods from different regions of the country. The first phase of sampling and analysis plan is in progress.

Clinical Studies A study conducted in collaboration with London School of Hygiene and Tropical Medicine, (LSHTM), UK, aimed to examine the effect of nutritional shortage/ supplementation in early life and adulthood on the amount and distribution of body fat, and the development of type-2 diabetes and coronary diseases. The study conducted among two cohorts from a previous study. Preliminary analysis of the data has shown that modest protein-calorie supplementation in early life was not associated with higher lean body mass (LBM).

Micro-Biology and ImmunologyA study was carried out on molecular characterization of reshuffled bile salt hydrolase (Bsh) and effect of dietary inclusion of Bsh+ and Bsh- indigenous probiotic - Lactobacillus



plantarum strains of human origin on cholesterol metabolism of rats. Bile salt hydrolase active (Bsh+) L. plantarum strain 21 reduced serum total cholesterol, LDL, VLDL and triglyceride levels in comparison to Bsh inactive L. plantarum strain 37. Bsh active strain 21 colonized successfully into the cecum and large intestine of the respective animal groups. Bile salt hydrolase activity helps the lactobacilli to colonize in rat gut and hence can be considered as a probiotic marker. Strains 37 and 83 exhibited negligible Bsh activity compared to 21 while no significant difference was observed among their acid and bile tolerance abilities (P>0.05).

A study that looked in to the immune Status of WNIN Mutant Obese Rats with reference to leptin and obesity, found that in euglycemic WNIN/Ob rat, Cell mediated immune response to hepatitis B vaccine was impaired in obese animals. Though leptin receptor expression was intact in both the obese and lean animals, leptin signaling (JAK2 protein expression) was impaired in obese animals. In Impaired glucose tolerant WNIN/GR-Ob model too the cell mediated immune response to hepatitis B vaccine was impaired in obese animals, whereas, the leptin receptor expression is impaired in obese animals.

A study that aimed to assess the role of probiotics on growth and morbidity in children found that after supplementation of probiotics for 9 months there was a gradual reduction in the incidence of diarrhea in the groups supplemented with L.paracasei and B.lactis as compared to the placebo group. There was no difference in the prevalence of respiratory tract infections in all the three groups even after supplementation. There was consistent weight gain and linear growth.

Extension & Training A project that assessed the intra and extra individual factors on food consumption pattern among rural population in Tamil Nadu using a diagnostic model approach, was carried out in two phases. In phase-I, the factors affecting food habits and food intakes in the village population were identified and education materials were developed accordingly. In phase-II, PG students from a local university were trained to educate and measure the changes among women. The study concluded that continuous and repeated exposure to nutrition communication, clubbed with inter-personal communication/group discussions have brought about a positive modification in the dietary practices of rural. In order to ensure sustainability of such programmes, collaboration with Social Work and Women Studies departments in Universities can be helpful.

When the influence of mass media advertisements on family food purchasing patterns and efficacy of behavior change intervention, were studied, it was observed that the time spent on television viewing by women and children certainly have an influence on their food purchasing pattern and snacking habits. A total of 1602 food advertisements appeared during the study period in television channels, popular among the study groups. Advertisements on chocolates and confectionary products were highest in number followed by health drinks and grain-based products/snacks. Advertisement of chocolates/sweets, biscuits and snacks were mostly telecast on children’s channels and 63% of advertisements on healh drinks were seen on other channels. Advertisements on health drinks depicted these drinks as inevitable for child’s growth.

The institute has produced a wide range of nutrition education material like posters and films as part of different research studies. A book on the history of NIN was released during ICMR centenary year celebration. An educational film on ‘Dietary Guidelines’ produced earlier



in English was translated into 3 Indian languages. Several nutrition awareness programmes were conducted and popular radio talks were delivered.

The third batch of MSc (Applied Nutrition) programme affiliated to NTR University of Health Sciences, Andhra Pradesh was commenced and 16 students have been admitted. In addition, 13 participants were trained in the short-term PG Certificate Course in Nutrition.

FOOD AND DRUG tOxICOLOGY RESEARCH CENtRE, HYDERABADWhen the consumption of processed and non-processed foods in India was assessed it was found out that the consumption of different foodstuffs and nutrients among various age groups were below the recommended levels of ICMR. The consumption of processed foods was also considerably higher in some of the regions like West and South. The prevalence of undernutrition was higher among rural preschool children as compared to urban children. The prevalence of overweight and obesity and non-communicable diseases was higher among urban adults as compared to rural.

A study was conducted to understand the interaction of calcium and fluoride in biological system in terms of nutritional status and skeletal metabolism as well as to study the effect of rehabilitation (providing normal calcium diet and fluoride free water) on reversal of fluorosis. Nutritional status of low calcium and fluoride treated group was poor (in terms of body weight gain and body composition parameters). There was disturbance of calcium homeostasis in presence of fluoride in low as well as normal calcium treated rats. There was increased bone formation in presence of fluoride but quality of bone was poor in low calcium and fluoride group. Studies on effect of reversibility indicated that the nutritional status and calcium homeostasis of rats normalized to some extent after providing normal Ca diet and fluoride free water for 3 months. There was no improvement in bone strength in animals given normal calcium diet and fluoride free water for 3 months.

In a study that investigated whether silica (Si) and strontium (Sr) (with and without F) increases bone density secondary to kidney damage, it was observed that dietary intake and weight gain was reduced significantly in animals of Sr, Si + Sr, F + Sr and F+Si+Sr groups from 120 day to 180 day as compared to control. There was significantly low mineral apposition rate (MAR) and bone formation rate (BFR) in F+Sr group as compared to control. Sr and Sr+F treatment affected food intake and weight gain along with body composition and organ pathology.

Considering that food labelling is one of the important population-based approaches that can help consumers make healthy food choices by providing the necessary nutrition information on the pack, a consumer study was conducted in Hyderabad and Delhi to assess how many consumers among various age groups were using food labels. It was observed that only about 1/3rd of the consumers checked nutrition information and list of ingredients on labels. The reason cited for not checking the nutrient information was that the information was ‘too technical to understand’ and lack of nutrition knowledge. However, it was observed that women and adolescent girls who were concerned with ‘fat’ and ‘sugar’ intake were in the habit of checking the nutrition facts. A significantly greater number of consumers with higher education qualifications were checking the nutrition information. Only about 60% of the respondents checked the quality symbols.



Assessment of allergenicity potential of novel proteins expressed in genetically modified (GM) plants under varying conditions of digestion and thermal treatments looked into the digestive stability to pepsin in SGF at varying pH and pepsin activity levels and heat stability. Insect bioassay of heat treated Cry1Fa1 recombinant protein showed that at a temperature of 95°C the mortality among target insects fed was zero indicating heat liability of the recombinant protein at this temperature. SDS-PAGE analysis showed that the band intensity of protein sample heated at 95°C was less than the untreated control at 10% conc.

Preclinical ToxicologyMahyco has developed Bt Okra containing Cry 1Ac gene for insect tolerant trait. Its safety evaluated in WNIN rats by oral feeding for 90 days showed that there were no significant effects on body weight, serum immunologlobulins, clinical chemistry profile, hematological and histopathology due to transgenic okra.

GCSF (Granulocyte colony stimulating factor) was produced using recombinant DNA technology. Its safety was tested in Swiss Albino mice and New Zealand white rabbits at three dose levels namely therapeutic dose, average dose and high dose. In subchronic toxicity 5% mortality was observed in Swiss albino mice but not in rabbits. No other significant toxic effect was observed.

Red gram (tur dhal) was fortified with ferric ammonium citrate and fed to mice/rats in intended daily dietary intake levels. Acute toxicity tests (14 days) in Swiss Albino and Sprague Dawley rats were performed and no adverse effects were observed.

ExtRAMURAL RESEARCHOne of the important activities of the Division is to support individual scientists from different parts of the country. The proposals address varied interesting areas of research like nutrition profile of population of high and low altitude areas, non-alcoholic fatty liver disease, quality of life in patients with liver cirrhosis etc. Useful scientific contribution is being made via these studies.

A study entitled Nutrition Profile of Population of Kinnaur and Kangra districts of Himachal Pradesh to assess the impact of changes in lifestyle and dietary pattern in two different geographical districts of Himachal Pradesh; one at high altitude (HA) and other at low altitude (LA) revealed that mean hemoglobin level was 10.9 g/l and 11.5 g/l in adults residing in LA and HA area respectively. Further, no significant difference was found in mean cholesterol level in adults in LA (165.6 mg/dl) and HA (170.0 mg/dl) respectively. Breast feeding was

A report on “Consumer Behaviour and Practices Related to Use of Food Labels in India was submitted to WHO-India



found to be initiated within 24 hours in 97.3% cases in LA and 94.3% in HA. The practice of giving colostrum was found to be high in both HA (94.6) and LA (95.2%).

Another study in patients with Liver Cirrhosis revealed that such patients are malnourished and have poor Health Related Quality of Life (HRQOL). The intense dietary intervention improved their nutrition scores and that high protein diet, supplemented with formula feeds provide the best results in patients with advanced liver cirrhosis and severe malnutrition.

A study on usage trends, suitability and Toxicological implications of Anodized Polytetrafluoroethylene Coated Cookwares found that migrational aspects of leachable components from coating material are dependent upon the pH and temperature of surrounding medium and the storage (duration) time.

A study to assess the pulmonary function test (PFT) of 10-12 years old school going children and the effect of micronutrient intervention on respiratory profile of the children revealed that after the intervention, PFT values increased in both symptomatic and asymptomatic children.

Various fellowship proposals cover diverse areas like estimation of trans fatty acids, micronutrients analysis in pregnant women, impact of vitamin B12 supplementation on adolescent girls etc.

A study which aimed at evaluation of potential of selenium in regulating thyroid functions following lithium therapy, demonstrated that 8 weeks of lithium treatment to rats resulted in alterations in the physiological functions of thyroid, as evidenced by a significant decrease in the uptake 131 I at the time intervals of 2 hours and 24 hours.

A study which aimed at de-toxification of aflatoxin using potential food grade wild yeast revealed that among the 52 yeasts that were isolated, 38 showed the capacity to bind aflatoxins.

Another study that aimed at estimation of trans fatty acid (TFA) content in selected common Indian fast food items revealed that highest TFA was found in Mathari ranging from 4.2 to 14.58 g/100g and in balushahi i.e 0.89 g to 9.4/ 100 g food measured while TFA ranging from 2.2 g to 11.1g/100 g was estimated for Bhatura. The lowest TFA was for bread pakora ranging from 0.13 to 1.05 g/100g.

Centre for Promotion of Nutrition Research and Training with special focus on North-East, Tribal and Inaccessible populationThe laboratory at the Centre has been carrying out/ involved in various activities as per its mandate like analysis of human biological samples collected under Task Force studies or under collaborative mode for various micronutrients; facilitating researchers/ students for their PhD, DM, MD, MSc degrees; training to students/ staff for collection of biological samples, their packaging, labeling, transport and analysis, besides participation in various external quality assurance programmes.

During the year 2011-12, the laboratory at the Centre has carried out the analysis of around 4000 samples collected under a multi-centre study to assess nutrition profile of population of Dhar (M.P.) and under various collaborative research studies with Medical and Home Science colleges in the country. These studies have generated useful bio-chemical database on the prevalence of deficiencies of various micronutrients. The study in Dhar district has revealed that the prevalence of anaemia varied from 71.9% to 82.8% across different age



groups; deficiency of ferritin, folic acid and Vitamin B12 ranged between 10%-59%, 5%-14% and 10%-30% respectively. Further, the study revealed that 17%-25% of adults and elderly population had hypercholesteremia. Similarly, a collaborative study to assess Zinc status of low birth weight (<2000 g) infants revealed that 57.3% of Low Birth Weight infants and 42.7% of Normal Birth Weight infants had zinc deficiency at birth. Another study to assess prevalence of cobalamin and folate deficiency in children aged 6 to <60 months of age indicated that 38.38% and 63.22% children in Delhi were deficient in cobalamin (vitamin B12) and folate respectively.

Using the laboratory support, 1 DM, 1 MD and 5 MSc students have successfully completed their degrees. Currently, the Centre is facilitating 3 PhD scholars and 2 DM students working on diverse topics like impact of IFA and vitamin B12 supplementation to combat anaemia; micronutrient load during pregnancy and its correlation with birth outcome; biochemical profile of adult population; prevalence and electrophysiological characteristics of neuropathy in association with various diseases like childhood leukemia and stage V chronic kidney disease.

The laboratory has also enrolled in various external quality assurance programmes like CDC, Atlanta and Bio-Rad, India. Under the CDC Atlanta External Quality Assurance Programme for urinary Iodine, the laboratory has been awarded 100% performance score for the third consecutive year. In the Bio-Rad Clinical Chemistry Programme, the laboratory has been ranked as 6th out of 401 laboratories in the World, whereas under Bio-Rad Immunoassay Programme, the laboratory has secured 44th rank out of 1253 laboratories in the world and 8th rank out of 248 laboratories in India.

The Centre has been approached by various national and international agencies like WHO, CDC Atlanta, Society of Applied Sciences New Delhi and Global Alliance for Improved Nutrition (GAIN), Geneva for possible collaborations for biochemical analysis of various micronutrients in human biological samples.

NATIONAL NUTRITION MONITORING BUREAU (NNMB)The NNMB completed the third Rural Repeat Survey during 2011 looked into the diet and nutritional status of rural population and prevalence of hypertension and diabetes among adult population in all the 10 NNMB states. The preliminary results indicate that despite decline in the food and nutrient intakes over a decade, the prevalence of underweight (49% to 42%), stunting (53% to 45%) and wasting (23% to 20%) were declined from 1996-97 to 2010-11. Similarly, the prevalence of chronic energy deficiency (CED) among adults also has declined significantly from 46% to 36% in the above period. Hypertension (SBP ≥140 mm Hg and / or DBP≥90 mm Hg) was seen in over 20% of men and women and diabetes was over 7% among rural men and women.



Basic Medical Sciences

INtRAMURAL RESEARCH

NAtIONAL INStItUtE OF IMMUNOHAEMAtOLOGY, MUMBAI

Service to the nationPrenatal diagnosis was offered to 84 families with hemophilia, 210 families with thalassemia & 3 families with congenital immunodeficiency.

A total of 15,280 patients were investigated for various hematological, autoimmune, transfusion medicine, transplantation, immunodeficiency related problems during the year under reporting. These patients were referred from medical colleges and hospitals from all over India.

Government Medical College, Nagpur has already developed capability to do prenatal diagnosis for sickle cell anemia under the mentorship of this Institute. There is a need for continuous help for this laboratory so that this investigation get strongly routed in that college and continue to help hundreds of affected people in that area.

NRS, Medical College, Kolkata, St’John’s Medical College, Bangalore and a centre in south.Gujarat i.e Valsad Ratdan Kendra is likely to develop full capability for prenatal diagnosis in hemoglobinopathies by the end of the year.

Translational Research ProgrammesWorkshops were held at Pune, Bangalore and Ludhiana on Screening and Molecular Diagnosis of Hemoglobinopathies for 14 medical colleges from these regions. Around 32-35 doctors and technicians were given hands-on training in the laboratory where DNA isolation, gel electrophoresis, characterization of mutations by reverse dot blot hybridization and ARMS and VNTR analysis for detection of maternal contamination in CVS samples was done.

A training workshop was conducted at the Institute on laboratory diagnosis of bleeding disorders entitled Education of laboratory workers for the Diagnosis of Haemophilia and other Bleeding Disorders with a view to establish full fledged diagnosis laboratories in selected centers in six states in Central and North East India from 5th to 7th July of 2011. Ten doctors and 10 laboratory technicians (one doctor and one Lab technician from each center) were selected from 6 states i.e. Orissa, Chhattisgarh, Madhya Pradesh, Manipur, Nagaland and Tripura. The Workshop included lectures on basic coagulation techniques, demonstration and hands on training for the laboratory technicians, though the emphasis was mainly on the laboratory techniques.

A workshop was conducted at Assam Medical College, Dibrugarh, Assam on Regional workshop and Hand-on Training on Karyotyping and FISH Technique from 9th to 15th August,2011. Lectures were given on basic genetic cytogenetic, genetic diseases and hematological malignancies. Twenty five candidates from Medical Colleges of North East region participated in this workshop. Hands on training were given on conventional cytogenetic, GTG banding, karyotying and FISH.

A workshop on Establishment of Red Cell Serology Techniques in the Blood Banks of the North eastern Region of India under the ICMR Translational Research project was held at



STNM hospital, Gangtok, Sikkim from 20th to 23rd March, 2012. The participants consisted of Blood Bank Medical officers and Laboratory Technicians from Gangtok, Namchi and Gaylzing districts of Sikkim. There were 17 participants. The workshop included lectures on basic blood group serology and hands on practicals on basic red cell serology techniques.

A workshop at Apollo Hospital, Bhubhaneshwar was held in February 2012 on Blood Coagulation Techniques for the Diagnosis of Bleeding Disorders and was attended by Dr.Bipn Kulkarni in which techniques on basic coagulation including PT, APTT, screening for factor inhibitors, factor assays using semi automated coagulometer was conducted.

The workshop on Molecular Analysis and Prenatal Diagnosis of Hemoglobinopathies under the ICMR Forum for Tribal Health Research was held from 11th to 14th October, 2011 at National Institute of Immunohaematology, Mumbai. There were 10 participants including scientists and technical persons from 5 ICMR centres who attended the workshop. The major part of training involved an interactive programme where practical demonstrations were given on the technology used for screening molecular analysis and prenatal diagnosis of hemoglobinopatheis alongside with discussions on possible problems and solutions for the same.

Annual training courses are conducted by the Institute on Transfusion Medicine and Blood Group Serology and Blood Bank Methodology for blood bank medical officers and technicians. Medical Officers from various blood banks across the country were trained from 12th July to 26th Aug 2011 and Technicians were trained from 12th July to 10th August, 2011.

Interaction with other medical colleges and ICMR Institutes Under Tribal Health Forum, feasibilities and preliminary work for establishing PND (Bhubhaneshwar and Jabalpur) and Neonatal screening (Bhubhaneshwar, Jabalpur, Nagpur, Valsad and Calicut) for hemoglobinopathies was initiated in several centres in the country.

With the support from National institute of Virology the work on impact of Dengue virus infection on various hematological parameters is in progress. The study highlighted the availability of a possible cell line for study of Arbo viruses infection in vitro. It has implication in quick screening for anti-arboviral compounds in novel drug development.

Seth G.S. Medical College and KEM Hospital has been one of the constant partners in research and patient care for NIIH.

Assam Medical College, Dibrugarh is twined with NIIH for development of cytogentics facility at the centre.

Government Medical College, Nagpur, CMC, Ludhiana, St John’s Medical College Bangalore, Valsad and Surat Raktdan Kendra, Valsad and Surat, NRS Medical College, Kolkata are already involved with NIIH in Community Control of hemoglobinopathies in all its facets. NIIH is actively monitoring these centres.

Transfusion Medicine Department at NIIH has initiated a human resource development and transfusion training programme with NEIGRIHMS (North Eastern Indira Gandhi Regional Institute for Health and Medical Sciences).

Hematogenetics department has initiated a twining programme with Agartala Medical College, Tripura on a project entitled New born screening and molecular characterization for red cell enzyme defects and hemoglobinopathies in Tripura.



New Techniques developedHbA2 immunoassay technique developed in this Institute is ready for trial for field application in 2 – 3 medical colleges.

Development of an ELISA based technique for detection of carriers of severe Glanzmann’s Thrombasthenia (GT) using a recombinant disintegrin protein.

Important leads with potential application in Community Control of ThalassemiaStudy showed a proportion of Beta thalassemia carriers with the common IVS 1 – 5 (GC) mutation having normal HbA2 levels. This complicates Beta-thalassemia screening programmes only on the basis of HbA2 levels.

Also demonstrated several mutations causing Beta-thalassemia in different parts of India. Some of these mutations are associated with normal HbA2

levels and some of them even do not change the red cell indices which are used for screening for thalassemia trait.

A proportion of normal HbA2 thalassemia carrier showed Beta globin gene mutations (10%) having borderline or low HbA2 levels.

All the above findings suggests Beta-thalassemia carrier screening only on the basis of HbA2 estimation may miss unusual carriers and emphasis the need for micromapping of beta thalassemia mutations in the country.

NAtIONAL INStItUtE OF PAtHOLOGY, NEW DELHI

TUMOR BIOLOGY

Breast CancerIn order to understand the mechanisms or pathways involved in early and late onset breast cancers, gene expression and methylation profiling of early onset and late onset cancer using illumine bead array has been done. Initial analysis of gene expression profiles showed that 172 genes are differentially expressed in early onset breast cancers compared to late onset breast cancers, genes belonging to several pathways involved in cell adhesion, cytokine receptor interaction, toll like receptor growth signaling pathway, cell cycle etc. Similarly, about 5600 CpG sites are differentially methylated in early onset breast tumors compared to late onset tumors, genes that are involved in Ion Channels, MAPK signaling pathway, Integrin signaling pathway etc. are differentially methylated in these patients. These differential genes will be validated in large number of cases using candidate gene approach, which might serve as new candidate biomarkers.

Two Breast Cancer Cell Lines, PCB20 (89 passages) and PCB36 (78 passages) have been established from patients with age of 38 and 39 years respectively using triple negative primary tumours. They have shown expression of epitelial markers, triple (ER, PR, ErbB2) negative, anchorage Independent growth, also have shown rapid population doubling time, which are suggestive of their epithelial and neoplastic origin. These cell lines have been screened for p53 exons 5-8 and BRCA1 genes. These cell lines are also analysed for copy number variations. To test tumorigenicity, SCID mice experiments have been initiated.



Studies on identification of predictive biomarker for neo-adjuvant chemotherapy in locally advanced breast cancer at NIOP have shown independent role of Androgen receptor for response to CAF regimn. Since the molecular mechanism of androgen receptor in AR (+)/AR (-) breast cancer, specially related to cellular survival, is not known, the knock down of androgen receptor gene using siRNA has been used in elucidating the role for the AR in androgen signaling pathway, and its importance as a clinically useful predictor to neo-adjuvant chemotherapy.

Urogenital MalignanciesIn the study to identify altered candidate genes that may serve as biomarkers, for improved diagnostic or prognostic application, or as novel targets for therapy of prostate cancer (CaP), genotyping for AR CAG, CYP19 TTTA and PSA -158 G/A polymorphism was done in 106 cancer prostate, 120 BPH cases and 106 normal healthy controls. Analysis of combined effects of AR CAG repeats and PSA -158 G/A genotypes on prostate cancer susceptibility showed that patients with short AR CAG (≤24) and GA or AA genotypes of PSA gene demonstrated a significant risk for CaP. In BPH cases significant increase in risk was found in patients having GA genotype of PSA irrespective of CAG repeat length of AR gene. Analysis of combined effects of AR CAG repeats and TP53 codon 72 genotypes showed that patients with short AR CAG (≤24) and Pro/Pro genotype of TP53 codon 72 polymorphism demonstrated a significant increased risk for CaP (p= 0.01) and BPH (p = 0.04). Also, the risk conferred to CaP was higher as compared to BPH. Interestingly, patients having longer AR CAG repeats (>24) with TP53 codon 72 Pro/Pro genotype demonstrated greater likelihood for developing BPH (p=0.02).The expression of six MMR genes, hMLH1, hMSH2, hPMS1, hPMS2, hMSH3 and hMSH6 was analysed in cases of CaP and BPH by Real Time qRT-PCR assays. All six MMR genes involved in mismatch repair system demonstrated downregulation when CaP was compared with BPH.

The study on characterization of the immune dysregulation in urinary bladder tumours with recurrence and metastasis showed that out of 84 genes studied, 14 genes are upregulated and 35 genes are downregulated in the Th1-Th2-Th3 array. The chemokine CCL11 and cytokine IL12, genes of the JAK-STAT pathway and MAP kinases are upregulated in tumour tissue when compared to the adjacent normal appearing mucosa. NFκB signaling pathway showed dysregulation of 20 genes in tumour compared to normal adjacent mucosa and these included MyD88, REL and the Jun-Fos pathway genes.

Cancer in north east-IndiaThe association between polymorphisms in three genes [CYP1A1 (Msp1 and Nco1), NAT2 and NQO1] encoding for xenobiotics metabolizing enzymes with risk of oral cancer in a population of northeast India showed no significant association with CYP A1 2A and CYP A1 2C genetic polymorphisms, marginal risk with homozygous variant AA genotypes of NAT2 Homozygous significantly higher risk with heterozygous variant of NQ01 serotypes. The cDNA microarray analysis showed several deregulated pathways oral cancer, the key genes involved in these metabolic pathways were analyzed using real time PCR.

Genotyping of EPHX1 gene exon 3 and exon 4 polymorphisms in lung cancer cases in NE region showed that mEH genotype (His113Tyr) which confers low enzyme activity decreases the risk of lung cancer whereas the fast activity genotype (Arg139Arg) increased the risk suggesting that although the products of hydrolysis are generally less reactive than



the parent epoxide, some resulting intermediates are precursors of highly reactive and carcinogenic compounds. The studies on gene expression profiling of lung cancers showed involvement of genes in glutathione metabolism, bisphenol A degradation, ABC transporters, phosphatidylinositol signaling system, calcium signaling pathway, Jak-STAT signaling pathway, ErbB signaling pathway, ECM-receptor interaction, cell cycle, focal adhesion, toll-like receptor signaling pathway to be upregulated and genes involved in regulation of actin cytoskeleton, TGF-beta signaling pathway were found to be downregulated in tumor with respect to the controls. These results are being validated by Real Time PCR.

Studies on gastric cancer in NE region showed significant association of VV genotype with risk factor for gastric cancer. No significant association had been found between NAT2 polymorphism and gastric cancer risk. Studies on gene expression profiling showed involvement of genes responsible for apoptosis, inflammatory response, immune response, angiogenesis, cell migration and cell proliferation to be significantly deregulated.

Incidence of breast cancer was found high in NE population and in previous study on the risk assessment of environmental and genotypic factors responsible for breast cancer in the northeast Indian population we have shown betel quid chewing to be the single factor imparting the main effect [testing accuracy of 0.6851 and cross validation consistency 10/10, p =0.05]. Mutation analysis by DHPLC of the BRCA2 gene showed only 4 samples to have mutations with 2 variants. Therefore we analysed the -26 G > A polymorphism in Exon2 by DHPLC .GA and AA genotype conferred 78% less and 83% less reduced risk to breast cancer which was insignificant.

Naso Pharyngeal Carcinoma (NPC) is a common malignancy in some regions of NE India, studies on molecular pathogenesis are ongoing.

Hematopoietic-Lymphoid MalignanciesAnalysis of FLT3/ITD and FLT3/D835 mutations in case of acute myeloid leukemia (AML) showed association with the age, leukocytosis and aberrant expression of CD7 although no influence of FLT3/ITD mutation was seen on the clinical outcome. In addition, analysis for the expression of genes commonly involved in drug resistance (MDR1, MRP, BCRP, LRP, DHFR and GST-pi) in cases of acute leukemia by Real-time RT- PCR (TaqMan probe assay) showed no statistically significant difference in the expression level of drug resistance gene between AML and ALL except DHFR whose expression was found to be significantly high in ALL (1.32 ± 1.55) compared to AML (0.48 ±0.26) (P=0.02).

Analysis of B-cell of Chronic lymphocytic leukemia(BCLL) patients showed that intracellular production of reactive oxygen species (ROS) and extracellular generation of ROS in B-cells enhances the proliferation, suggesting that ROS may have significant role in the pathogenesis of β cell chronic lymphocyte leukemia through activation and proliferation of β-cell.

PATHOLOGY OF INFECTIOUS DISEASES

ChlamydiasisTo investigate local immune response and whether IL-17A (IL-17) and IL-22 are produced in response to Chlamydia trachomatis infection, the levels of cytokines were determined in cervical washes from women with C. trachomatis infection and C. trachomatis negative controls. C. trachomatis infection appeared to activate local IL-17 and IL-22 production



more efficiently than IFN-γ production. In the cervical wash of infected women, median concentrations of IL- 17 and -22 were 5- and 3-fold higher, respectively, than in negative controls. The spontaneous intracellular expression of these cytokines was analysed by flow cytometry in blood and cervical cells and 26% of cervical mononuclear cells from infected women were shown to produce IL-22 and 12% to co-produce IL-17 and IL-22 .In addition, it was demonstrated that 20 to 25% of IL-22 producing and IL- 17-IL-22 co-producing cervical CD4+ T cells expressed the mucosal homing receptor CCR6. These results suggest that CCR6 is involved in the migration of these cells to the cervix and that IL-17 and IL- 22 might play a role in the immune response at the site of C. trachomatis infection. Study of expression patterns of Toll like receptor (TLR2, TLR4 and iNOS) in cervical monocytes upon C. trachomatis infection showed higher expression of TLR2 (P<0.05) in women with fertility disorders as compared to mucopurulant cervicitis (MPC) and asymptomatic carriers.

Decreased antibiotic susceptibility was observed in isolates obtained from recurrently infected patients towards the current first line drugs (azithromycin and doxycycline) for chlamydial infection treatment. Genotypic characterization of C. trachomatis isolates from recurrent infections showed no mutation (s) in heterotypic resistant isolates.

Study on the role of cox during Prostaglandin (PG) biosynthesis in spontaneously aborted (SA) tissues from women found infected with C. trachomatis showed increased expression of cox-2 and TNF-α in the SA group with C. trachomatis infection. Real-time PCR was standardized for studying quantitative expression of cox-2 in aborted tissues from women infected with C. trachomatis. Estimation of Superoxide Dismutase (SOD), Malondialdehyde (MDA) and Nitric Oxide (NO) has revealed that the level of MDA is significantly upregulated while SOD is significantly downregulated in SA presenting with vaginal bleeding in comparison with controls There was significantly decreased expression of Cu-Zn-SOD in C. trachomatis-infected SA while there was no significant difference in Mn-SOD between the two groups.

Intra-articular IgA anti-C. trachomatis antibodies were also detected in the three C. trachomatis positive patients. Further, PCR was standardized for MOMP gene. Both conventional and nested PCR confirmed the presence of MOMP gene in the synovial fluid of 2 ReA/UOA patients.

LeishmaniasisIn an attempt to establish rapid and accurate method to detect and quantify Leishmania parasite real-time assay was applied to estimate parasite load in clinical samples of Visceral Leishmaniasis (VL) and Post Kala-Azar Dermal Leishmaniasis (PKDL) patients. The mean parasite load in blood of VL patients was 8,372 parasites/ml. Parasite load was undetectable after treatment with amphotericin B, while a residual parasite burden was detected in a few patients following treatment with sodium antimony gluconate. Interestingly, circulating levels of IL-10 correlated significantly with parasite load (r = 0.82, P<0.0001) implicating IL-10 as a marker of disease severity. The mean parasite load in dermal lesions of PKDL patients was 9,502 parasites/mg tissue DNA at pre-treatment stage with no detectable parasites after therapy. Parasite burden was distinctly higher (P<0.0001) in nodular lesions compared to papular/macular lesions. Further, chronic PKDL lesions showed significantly (P = 0.0166) higher parasite load in comparison with acute lesions. Results indicate that chronic, nodular PKDL cases constitute the major parasite reservoir for anthroponotic transmission.

Over expression of H2A gene in a drug-sensitive laboratory strain as well as in a field isolate of L. donovani resulted in conversion of SAG-sensitive parasites into a resistant phenotype.



Moreover, H2A overexpression resulted in a significant decrease in susceptibility towards other anti-leishmanial drugs currently in use, i.e. amphotericin B and miltefosine, pointing to its role in drug resistance.

In India, Leishmania donovani is responsible for Visceral Leishmaniasis (VL) and Post Kala-azar Dermal Leishmaniasis (PKDL) while L. tropica is responsible for Cutaneous Leishmaniasis (CL) in humans. The molecular differences between the two species of Leishmania and within the same species causing distinct pathologies that govern the outcome of infection and pathogenesis in the human host are unknown. Quantitative expression of selected genes was evaluated directly in lesion tissues of VL, PKDL and CL patients. Assessment of in vivo mRNA level highlighted substantial differences in gene expression patterns, providing an indication of the genes involved in pathogenesis in the three different forms of leishmaniasis.

Study on localized and systemic immune response in CL revealed up-regulation of interferon-c (IFN-c), interleukin (IL)-1b, IL-8, tumour necrosis factor-a (TNF-α), IL-10 and IL-4 in dermal lesions at the pretreatment stage compared with healthy controls (P < 0.001) and a significant down-regulation after treatment (P < 0.05) indicating that the unfavourable clinical outcome in CL is not related to an inadequate T-helper 1 (Th1) cell response but rather to an impairment in multiple immune functions.

Comparative assessment of treatment regimes with Rifampicin (RFM) or Sodium Antimony Gluconate (SAG) revealed tissue cytokine levels to be significantly reduced after treatment with RFM (P < 0.005), while no significant decrease was evident in the levels of IFN-c, TNF-α and IL-10 (P > 0.05) as a result of treatment with SAG. Increased transcripts of monocyte chemoattractant protein-1 (MCP-1) (P < 0.001) and inducible nitric oxide synthase (iNOS) (P < 0.05) were evident before treatment in tissue lesions and remained high after treatment. Immunohistochemistry demonstrated strong expression of myeloperoxidase (MPO) and IL-8 and moderate expression of iNOS in dermal lesions. The expression levels of IL-8, MCP-1 and nitric oxide (NO) were high in patient sera before treatment, as determined using cytokine bead array and enzyme-linked immunosorbent assay (ELISA). At the post-treatment stage, the serum IL-8 levels had decreased; however, the levels of MCP-1 and NO remained high. These data suggest that IL-8 is an effector immuno-determinant in the progression of CL, whereas NO facilitates the parasite killing by macrophages via MCP-1-mediated stimulation.

The success of oral miltefosine in VL prompted a clinical, histopathological and parasitological study of this drug in PKDL. Twenty-six patients confirmed by slit-skin smear, histopathology and molecular tests were inducted in the study. They were advised miltefosine capsules 50 mg thrice daily after food. Treatment was for 60 days with a provision to increase by 30 days if a responder had not attained cure. Cure was ascertained by clinical and histopathological examination, and measuring parasite burden using real time PCR. Twenty-four patients having a wide range of parasite burden completed the study. Twenty three achieved cure giving an initial cure rate of 95.8% (efficacy as 79 to 99 at 95% confidence interval). Sixteen patients were cured with 50 mg thrice daily, 13 in 60 days and 3 within 90 days. In 7 cases, miltefosine had to be reduced to 50 mg twice daily due to gastrointestinal intolerance to a total of 180 capsules. Lesional parasites were undetectable at one month post-treatment. Treatment was safe with no relapses at 1 year of follow up. Oral miltefosine, 50 mg thrice daily for 60 days or twice daily for 90 days could be an effective treatment for PKDL.

A molecular assay based on slit aspirate sample for non-invasive diagnosis of PKDL has been developed with higher sensitivity in comparison with prevailing methods. Slit aspirates



of PKDL lesions were subjected to rk39 strip test and SYBR Green based Quantitative real time PCR (Q-PCR) assay for diagnostic purpose. rk39 strip test was 100% positive with both serum and slit aspirate of PKDL cases (n=36), while negative in all controls (n=24). Whilst LD body positivity in histopathology and slit smear was 27.3% and 50% respectively, parasite DNA was detectable by Q-PCR in all slit aspirates (n=36) and tissue biopsies (n=33) of PKDL cases and negative in corresponding controls (n=24). The parasite load in slit sample (mean=10,113 parasites/µl slit aspirate DNA) showed significantly (P<0.0001) high correlation (r=0.9273) with that in lesion biopsy (mean=11,742 parasites/µg tissue DNA). At 1 month post treatment, the parasite load was undetectable in a majority of the cases examined (17/19). Q-PCR assay detected Leishmania DNA in slit aspirates of all cutaneous leishmaniasis (CL) cases (n=11) while slit smear microscopy was positive in 10 of 11 cases. Slit aspirate Q-PCR assay provides a least invasive, simple, rapid and reliable assay for diagnosis of PKDL, subsequent to initial screening with slit aspirate rk39 strip test, with potential for field application and assessment of cure. The assay also shows promise for a reliable diagnosis of CL.

ADULT STEM CELL BIOLOGYSeveral stem cells are effectively established in vitro using feeder cells that are growth arrested either by gamma irradiation or by exposure to Mitomycin C (MMC), although there is no common consensus about their relative efficacy. We have earlier shown that the effectiveness of Mitomycin C (MMC) approach is dependant on the calculated availability of the drug to the cells present at the time of exposure and was found to be effective on NIH 3T3 fibroblasts in a ‘numerical’ dose-dependant manner. A culture system for the growth of stem cells. An Indian Patent was filed. The study is ongoing with standardizing the complex protocol for growing human Cultured Epidermal Autograft (CEA) using Swiss albino 3T3 fibroblasts, an established cell line popularly used to generate CEA for clinical application in burns patients. The basic experiments have been performed using variety of combinations of exposure cell and MMC-concentrations resulted in the identification of a narrow range of numerical doses. A significant empirical relationship between the concentrations of cells and MMC was derived by these experiments, although the range of concentrations was different from that observed with NIH 3T3 cells. It has been also hypothesized that the varied extent of attenuation of 3T3 fibroblasts through manipulation of arithmetically derived numerical doses of Mitomycin C (MMC) may lead to differential stimulation of epidermal keratinocyte proliferation and altered fibroblast-keratinocyte interactions that probably bring about qualitative and quantitative differences in morphogenesis of epidermis in vitro. It is known that fibroblasts from different body sites display different functional properties which may affect their suitability for dermal substitutes and the differentially growth arrested fibroblasts may similarly be functionally diverse exerting varied responses on keratinocytes.

So far, the basic methodology of preparing dermal equivalent with 3T3 fibroblasts as shown in the layout has been accomplished. Initially, an evaluation of various densities of 3T3 cells in collagen was verified. The stability of fibroblasts in the gelated collagen was verified by both MTT assay as well as periodical extraction of cells from dermal equivalents following by viable cell counts and the integrity of dermal equivalents is being verified by paraffin embedding followed by H & E staining. So far, we completed the cell extinction studies with differentially growth arrested feeders and observed the cell extinction trends in the 3-dimensional collagen matrix were comparable to those in monolayer experiments.



ENVIRONMENTAL TOXICOLOGYAnalysis of blood samples for the presence of fifteen different phthalates by Gas Chromatography showed presence of two or more phthalate compounds in 74% of infertile patients and 47.6% of control subjects indicating ubiquitous presence of these compounds in the environment. While Di-IsoHexyl Phthalate (DIHP) and DiMethyl Phthalate (DMP) were present in the infertile group, they were not observed in fertile controls. Further, Di-IsoDecyl Phthalate (DiDP), Di-IsoOctyl Phthalate (DIOP), IBCHP, DINP and BEHIP were observed in only 4.8% of control samples. On the other hand DBP, DEHP and BEHIP were present in 47.3%, 30.4% and 27.7% of infertile patients, respectively.

Biomonitoring for the pesticide exposure of tea garden workers in north eastern states of India using placenta and blood of women from Assam Medical College, Dibrugarh demonstrated presence of acephate, heptachlor, parathion, malathion, DDT, chlordane, ethion and phosalone in both blood (maternal and cord) and placental tissue. Further, apart from the exposed population, the pesticides have also been observed in probably directly un-exposed housewives which might have got exposure through use of chemicals for household cleaning and through dietary routes.

REGIONAL MEDICAL RESEARCH CENtRE, BELGAUM RMRC, Belgaum was established to conduct research on Herbal Medicines as a major thrust area. With limited staff, the Centre has achieved several milestones within a short period.

Elucidating anti-anrthritic potential of selected medicinal plants and their fractions Rheumatoid arthritis is a life style disease. It was aimed to develop an effective, safe and cost effective anti-arthritic agent, based on the leads obtained from traditional system. Petroleum ether, acetone, Hydroalcoholic (70:30) extracts were prepared from roots of Plumbago zeylanica and barks of Holoptelia integrifolia. In-vitro Cyclooxygenase I and cyclooxygenase II assay has been carried out for the extracts. The results indicated the inhibition of both Cox I and Cox II in both the plant materials. The acute toxicity studies were carried out as per the OECD guidelines. Further investigations are in progress.

Phytochemical screening and in vitro studies in Ancistrocladus heyneanus Wall. Ex Grah. and Achyranthes aspera Linn Two plants namely Ancistrocladus heyneanus and Achyranthes aspera were selected to investigate their distribution, identification elite populations, isolation of active constituents/fractions and their sustainable mode of production by tissue culture technique. Three sites were sampled with different geographical and seasonal distinction for phytochemical studies. Among the various extraction methods and plant material used, brown leaves of A. heyneanus showed good response to the continuous shaking extraction and ultrasonic extraction techniques with 95% aq. MeOH as solvent with 53.50 ppm yield.

In tissue culture studies of A. aspera, significant results with highest shoot / root length were obtained on MS + BAP 3 mg/l and MS + TDZ 0.5 mg/l (1.10 ± 1.79 cm/0.90 ± 1.45 cm respectively). In A. heyneanus, best response was observed on MS medium containing 2,4-D 2.0 mg/l + IAA 0.2 mg/l (60%). However, best response for callus growth was observed on MS medium fortified with 2.0 mg/l 2,4-D (100%) and the callus formed was healthier as



compared to other combinations in A. aspera. MS basal supplemented with 1.5 mg/l of 2,4-D initially showed callus growth which further produced somatic embryos within 2 weeks of inoculation (100% response).

Development and characterization of microsatellite (SSR) based molecular markers for identification, authentication and analysis of variations in the medicinal plant Saraca asoca (Roxb.) de Wilde.The study aims at studying population genetics in different populations of Saraca asoka (Roxb.) de Wilde from Western Ghats and characterization of genus specific genetic markers for plant, in comparison with common adulterants/substituents like M. ferrea and P. longifolia for correct identification and authentication. Total 160 samples (Leaves/ Bark) have been collected from ten different cohorts of S. asoca plants for population genetics studies. A total 10 samples each of P. longifolia as well as M. ferrea were also collected. Inter-simple sequence repeat (ISSR) and Random amplified polymorphic DNA (RAPD) fingerprinting has been used to type the individual plants following standard methods in PCR. Fingerprinting of all the samples is in progress. Genotyping and analysis will be carried out once the all the samples are fingerprinted using selected ISSR and RAPD primers.

Screening of antimicrobial effects of herbal formulations on highly virulent bacteria isolated from clinical casesEnteric infections was identified as a priority area of research for the Centre and it was recommended to initiate studies on herbal formulations traditionally used in the region for the treatment of cholera-like illness. The bark of Alseodaphne semecarpifolia and unripe fruit and leaves of Apama siliquosa have been reported to be useful in cholera like conditions in the region, which have been studied further.

For screening these plants for their antimicrobial activity, a highly virulent and toxigenic strain of Vibrio cholerae isolated from a clinical case recently from the region was chosen. The study also included other enteric pathogens common in the region like Shigella dysenteriae type 1, Shigella flexneri type 2, Enterotoxigenic Eschericiha coli (ETEC), Enterohaemorrhagiac Eschericiha coli (EHEC), Enteroinvasive Eschericiha coli (EIEC), Enteropathogenic Eschericiha coli (EPEC) and Enteroaggregative Eschericiha coli (EAggEC). Bark of Alseodaphne semicarpifolia as well as leaves of Apama siliquosa has been collected and extracts are being prepared. In vitro testing by agar cup and tube dilution methods are in progress.

Genetic profiling of the medicinal plant Ferronia elephantum Corr. (Rutaceae) showing difference in chemoprofilesFeronia elephantum Corr. (Rutaceae) is a widely used medicinal plant in the region. In one of the studies on chemoprofiling of different individuals of the same species, marked difference was noted in two plants. The plants were morphologically confirmed as Feronia elephantum Corr. However, keeping in view the difference in chemoprofiles, the plants were subjected to molecular genetic characterization in comparison with other individuals of the same species collected from the same locality.

The genetic studies showed that 3 individuals of Feronia elephantum had the same genetic pattern while the 4th one differed marginally. One individual was completely different. Phytochemical investications also revaled different chemoprofile despite being



morphologically identical with the other Feronia elephantum individuals. This study established the genetic diversity of the particular individual of Feronia elephantum from the others in the same population. Detailed botanical and phytochemical investigations are underway.

Status of Methicillin Resistant Staphylococcus aureus (MRSA) infections and estimation of frequency of Panton Valentine Leukocidin producing strains in BelgaumAn attempt was made to generate baseline data on the extent of MRSA infections and to estimate the frequency of potential PVL toxin producing MRSA and MSSA isolated from patients attending clinics and hospitals in Belgaum.

A total of 70 strains of Staphylococcus aureus isolated from samples obtained from various clinics, diagnostic laboratories and hospitals in and around the city of Belgaum were taken in the study. Twenty seven out of 70 isolates (38.6%) were confirmed as MRSA by PCR for mecA. The prevalence of PVL gene was 85.1% and 48.8% in MRSA and MSSA respectively. The overall prevalence of PVL gene was 62.85%. The study showed very high overall presence of MRSA amongst Staphylococcus aureus isolates in Belgaum. PVL positivity was high in MRSA strains as well in MSSA strains, much higher than most reported worldwide. In the backdrop of many bacterial strains gaining resistance to wide spectrum of antibiotics recently, the study warrants further epidemiological studies in hospitals and community levels in the region.

Study of cholera outbreak in Hubli, 2011A total of 9 suspected strains of Vibrio cholerae were received by RMRC for identification and characterization from KIMS, Hubli. These isolates were obtained from an outbreak of watery diarrhoea in Hubli. Five isolates were identified as Vibrio cholerae by standard biochemical and serological tests using commercial antisera. Multiplex PCR confirmed the stains as V.cholerae serotype O1 Ogawa biotype El Tor. All possessed the ctxA-tcpA virulence markers.

Investigation of an outbreak of Hepatitis E in Turmuri village on the outskirts of BelgaumAn outbreak of Hepatitis E was reported from Village Turmuri, located on the outskirts of Belgaum. Present studies were carried out to understand the epidemiology and to identify the potential sources of contamination. Blood samples collected from 11 patients were subjected to Enzyme Linked Immune Sorbent Assay (ELISA) and all were found positive for Hepatitis E by ELISA IgM. Serum samples have been stored at -20°C for further PCR based identifications and/or characterization.

Nine water samples were also collected aseptically from different drinking water sources. Analysis of water samples revealed that 7 of the 9 water samples collected were heavily contaminated with fecal coliforms indicating gross fecal contamination.

Phytochemical investigations and Screening of anti-diabetic activity of Feronia elephantum Corr. Bambusa arundinacea (Retz.) WilldThe dicloromethane extract of Feronia elephantum and Bambusa arundinacea were fractionated by using column chromatography and flash chromatography. The fractions



were further purified by using normal and reverse phase HPLC. Further, organic extract of F.elephantum was screened for anti-diabetic efficacy in Streptozotocin induced diabetic rats with standard protocol. Preliminary screening of organic extract and fractionated compounds of F. elephantum showed encouraging results.

ExtRAMURAL RESEARCHDuring the year, a total of 598 ad-hoc and 270 fellowship projects were ongoing in the following area: Allergy, Anatomy, Anthropology, Biochemistry, Biomedical Ethics, Bioinformatics, Cell & Molecular Biology, Genomics & Molecular Medicine, Stem Cell Research & Therapy, Haematology, Human Genetics, Immunology, Nanomedicine, Organ Transplantation, Pharmacology (incl.Clinical Pharmacology), Physiology, Toxicology, Traditional Medicine etc. Six Task Force studies initiated. Nine Centres of Advanced Research are ongoing.

Genomics and Molecular MedicineICMR Centre for Advanced Research in Cancer Genetics & Genomics at ACtREC, tata Memorial Centre, MumbaiThis is ongoing research programme under two subgroups: Genetics of germline mutations in hereditary or syndromic cancers and Genomics of somatic mutations & molecular alterations in common sporadic childhood cancers. Model of Comprehensive Cancer Genetics Unit comprising of a dedicated daily Cancer Genetics Clinic plus Cancer Genetics Lab has been established. Best international practices in pre-test counselling, genetic testing, post test counselling, screening & medical management tailored for Psycho-Social-Cultural dynamics unique to India. Total of 1085 families with inherited cancer predisposition enrolled so far of which 255 families enrolled during the period. With 1085 pedigrees, DNA Bank of 1176 cases & EBV cell lines from 450 cases, this is the largest collection of clinical & research resources in diverse hereditary cancers outside USA & Europe. The major finding is the identification of recurrent Founder mutations (some of these are Novel) in BRCA1, hMLH1 and XP genes (4284delAG BRCA1, 156delA hMLH1, R415X Homozygous mutation in XP-C, 4446delT APC gene). Deleterious mutations were identified in 68 families. 289 individuals from these families were subsequently tested and the same mutation identified in 165 family members. A total of 233 (68+165) individuals have been identified as carriers of deleterious mutations in a high penetrance gene and 124 individuals were found not to carry the family specific mutation. This information was used to counsel them about cancer prevention and prophylactic therapy. A unique Indian haplotype of the 2 most common Indian BRCA1 mutations (185delAG & 4284delAG), distinct from Jewish and other populations have been identified.

Satellite genetics clinic started outside TMC, Mumbai at Prince Ali Khan Hospital in August 2010 with weekly clinics. Awareness programme and increasing referral base through lectures were carried out in different parts of the country.

A workshop was conducted at AIIMS, New Delhi with 40 participants from AIIMS and other hospitals in Delhi to help them to establish a Cancer genetics unit. ‘Cloning and Characterization of novel mutations (S1722P in BRCA1 BRCT domain) identified in the ACTREC HBOC cohort using CD, MALDI-TOF-TOF’ is being done.

For chimerism analysis following allogeneic hematopoietic stem cell transplantation the methodologies were standardized and 60 donor – recipient pairs of which 54 were



assessed for chimerism. Slippage of chimerism occurred in 11 patients. The qualitative and quantitative chimerism studies done were useful in close monitoring and correlated with the clinical status.

Establishment of T-cell receptor gamma and delta gene rearrangement status as biomarker for diagnosis and prognosis of T cell Acute Lymphoblastic Leukemia (T-ALL) was studied.

Conclusions drawn from MicroRNA expression analyses of human cancers were that miRNAs are deregulated in cancer, and miRNA expression profile represents tumor biology better than the expression profile of protein coding genes.

Proteomic analysis of CSF samples from medulloblastoma patients to identify sensitive biomarkers, to detect, diagnose and monitor disease using a global approach was carried out with a aim to predict long term outcomes in medulloblastoma.

Creation of Genetic disease registry, DNA banking and EBV transformed cell lines from informative families of rare genetic disorders at SGPGI, LucknowDNA samples of 3531 individuals have been collected and DNA has been / is being extracted and stored at - 800 C. This includes samples from 1299 probands with various genetic disorders and clinical presentations with possibly genetic etiology. The number of samples from family members of the patients with genetic disorders is 1392. The clinical data including clinical presentation and detailed investigation reports is stored. From the samples collected mutations were detected in 44 patients with monogenic disorders have been identified. The samples of patients with mental retardation without cause were evaluated using newer molecular cytogenetic techniques namely MLPA and microarray. MLPA identified genomic deletions/ duplications in 11 of 200 patients with idiopathic mental retardation. Cytogenetic microarray was done in 60 patients with idiopathic mental retardation and identified abnormalities in 11 cases. There is no published data on MLPA and microarray for identification of deletions/ duplications from India. The research was also carried out on samples of patients with Age related macular degeneration, recurrent spontaneous abortions. Polymorphisms in VEGF and Apo E genes were studied in patients with recurrent spontaneous abortions and the data was published. The research has led to identification of mutations in Indian patients with monogenic disorders, establishment of new techniques like MLPA, Microarray, and a lot of patient data and samples for future research including gene mapping of rare syndromes. These results have been useful in providing genetic counseling and prenatal diagnosis to many families. The work has also greatly supported to the development of Medical Genetics in India.

Stem Cell ResearchTwo protocols have been developed in consultation with the experts, to initiate multi-centric clinical trials for Critical Limb Ischemia and Spinal Cord Injury.

National Apex Committee for Stem Cell Research and Therapy (NAC-SCRT) with the secretariat at ICMR was constituted to oversee/monitor activities at National level.

Proforma for registration of Institutional Committee for Stem Cell Research & Therapy (IC-SCRT) has been finalized and the registration process has been initiated.



Stem cell research is developing at a very fast pace. Understanding the implications of translation of this technology, after analyzing the outcome of the issues and suggestions received during the public consultations held in 5 regions of the country, the policy document is in the process of revision.

Community control of Thalassemia: Establishment of molecular characterization of haemoglobinopathies and prenatal diagnosis of Thalassemia and Sickle cell disease The objectives of this multicentric study are to establish molecular technology for characterization of mutations in hemoglobinopathies as well as facilities for first and second trimester prenatal diagnosis at 5 regional centres in Maharashtra, Gujarat, Karnataka, West Bengal and Punjab. Screening in antenatal clinics for identification of carriers and couples at-risk with a view to offer prenatal diagnosis to them is to be done at all the centres. Apart from providing training and assistance to establish these centres, National Institute of Immunohaematology would also conduct quality control programmes and monitor the accuracy of diagnosis at different centres.

All the centres are now able to carry out DNA isolation and PCR and are standardizing the other molecular techniques. They are also trying to procure the licenses from their respective State Governments for getting their centres approved for prenatal diagnosis. The staff medical officers, laboratory technicians and medical social workers at 5 centres have been given initial training given for their operation. The obstetricians and gynaecologists who will be doing the interventional procedures (CVS and Cordocentesis) have also been given a short training at NIIH Mumbai. Each centre is screening antenatal women and their husbands when needed to identify couples at risk for β-thalassemia major, Hb E, β-thalassemia and sickle cell anemia. A total of around 7000 women have been screened so far, the largest number being at Nagpur.

National Task Force on Inborn Metabolic Disorders: Newborn Screening for Congenital Hypothyroidism & Congenital Adrenal hyperplasia: A Multicentric StudyInborn metabolic disorders are common genetic conditions imposing a high burden on the health care infrastructure unless diagnosed and treated. National Task Force study group followed a common protocol for newborn screening of congenital hypothyroidism and congenital adrenal hyperplasia and has completed screening of over 90,000 newborns at various centres out of 1 lakh that has been planned. Treatment has been initiated in affected babies and appropriate counseling and management of disease carried out. The study is continuing at 11 centres which include, 5 newborn screening centres (All India Institute of Medical Sciences, New Delhi, Institute of Post Graduate Medicine & Research, Kolkata, KEM Hospital, Mumbai, Sandor Proteomics, Hyderabad, Mediscan centre, Chennai), 3 high risk screening centres (Maulana Azad Medical College, New Delhi, National Institute of Mental Health and Neurosciences, Bangalore, Sandor Proteomics, Hyderabad), one centre each for Quality Assurance, website and advocacy, Data Coordination and Central Coordination. The NTF group has also prepared a revised work manual with Standard Operating Procedures related to the study. A User friendly website which was prepared has been regularly updated with valuable information regarding ICMR Newborn Screening program as well as is an important resource for knowing more about various genetic diseases as well as centres involved in genetic research and diagnosis in the country.



Short Term StudentshipsShort Term Studentship program is one of the only program that supports undergraduate medical students in their research initiatives. During 2011 about 2215 students applied and 802 students were selected. Proposals were received from over 230 medical colleges from all parts of country and were categorized in 51 subject categories. These were reviewed online by about 75 subject experts from 26 ICMR Institutes. A total of 654 completed STS reports submitted online were evaluated by experts before their stipend and certificates are awarded to them.

National Task Force on ICMR Research Oriented Medical Education (NTF-ROME) at Moving Academy of Medicine and Biomedicine, PuneUnder this ongoing research programme 8 regional workshops were organized and were attended by over 400 students. Besides this four regional conferences were held during the year at Wardha, New Delhi, Belgaum and Thiruvanathapuram for STS awardees during 2010-2011. This task force is being centrally coordinated by Moving Academy of Medicine and Biomedicine, Pune with a view to encourage the undergraduate who are already receipient of ICMR,s Short Term Studentship, in their research aptitude through short term training courses.

Biomedical Ethics

International SIDCER Recognition program through joint efforts of ICMR-and FERCAP for Sanjay Gandhi Post Graduate Institute (SGPGIMS), Lucknow Under a major initiative to strengthen the status and functioning of the ethics committees in India and to assist them in raising their standards to the International level, the Council has conducted two training workshops namely Human Subject Protection Course (HSPC) and Standards Operating Procedures (SOP) Training at Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow. Both of these training programmes were attended by >70 members of institutional ethics committees from 12 medical colleges and research institutions from Lucknow and neighboring areas. Following this, a survey was conducted by International Team from Strategic Initiatives for Developing Capacity in Ethical Review (SIDCER) and an international recognition was granted to SGPGI Lucknow at the FERCAP Conference in Daegu, South Korea in November, 2011.

Center for Advanced Research in Yoga and Neurophysiology at Swami Vivekananda Yoga Research Foundation, BangaloreThis Centre was established with three main objectives aims at studying the neurophysiological correlates of four mental states associated with meditation. These were (i) Dharana, a form of meditative focusing, (ii) Dhyana an expansive state of mind in meditation, (iii) Ekagrata regular focusing or concentration which requires effort, and as a control state, (iv) Cancalata or random thinking. All the participants practiced meditation on the syllable OM. Their meditation practice was such that they practiced the Dharana phase before getting into the Dhyana phase. They could be considered experienced meditators as all of them had experience of meditation on OM for at least 3 years and in some cases for longer. In addition,



for a month prior to the present study all of them participated in a one month refresher course in OM meditation. During the month they were also given training sessions for Ekagrata.

The main assessments done were brainstem auditory evoke potentials, BAEPs, autonomic respiratory variables, functional magnetic resonance imaging (fMRI)] and polysomnography. Parts of the brain involved in meditation include Midbrain (Inferior colliculus) in Dhyana). Bilateral hippocampal activation during Dhyana while activation at Left hippocampus gyrus takes place during Ekagrata and Dharana. Regarding understanding the neurophysiological differences between the mental states. Delayed auditory information transmission at the peripheral relay centres during Cancalata, Ekagrata and Dharana was recorded by conducting brainstem auditory evoke potentials. During dhyana recruitment of more neurons at the inferior collicular level takes place. Autonomic and respiratory variables showed reduced psychophysiological arousal, increased skin resistance and decreased breath rate during Dhyana. Reduction in slow wave sleep was noted with Polysomnography.

The annual one-month training program in “basic understanding of yoga techniques and training in neurophysiological techniques relevant to yoga research” was held for three consecutive years since 2007. The one-month training program has resulted in providing the participants (i) A basic idea of planning and conducting a research studies; and (ii) Exposure to sophisticated neurophysiological assessment methods. The annual training program has emerged as a sought after program among the neurophysiology and yoga research academicians

Research labs were established at – National Institute of Naturopathy (NIN), Pune, Maharashtra Zamorian’s Guruvayurappan College, Calicut, Kerala, Ghantali Mitra Mandali, Thane, Maharashtra and SDM College of Naturopathy & Yogic Sciences, Ujire. Ph.D. programs have been initiated at Vishwa Bharati University, Shanthiniketan, WB and Kalyani University, Kalyani, WB. Also initiated courses at Jadhavpur University, Kolkatta , Vardhaman university, WB and SVYASA University, Bengaluru .

The Center is compiling and publishing booklets to disseminate the scientific findings of the projects in English, Hindi and a regional language (in this case, Kannada) in a way which can be understood by laymen. So far three booklets are compiled and published for public distribution viz - The Path of meditation: descriptions from traditional texts, The Science of Meditation: Basis from scientific research and all one wants to know about SLEEP. The project has resulted in nine publications.

Advanced Centre of Reverse Pharmacology in traditional Medicine at Medical Research Centre, Kasturba Health Society, Mumbai The Centre was set up with the following ICMR advanced centre of reverse pharmacology in traditional medicine established at Medical Research Centre Kasturba Health Society, Mumbai. The objectives are : (1) to develop safe and scientifically investigated Ayurveda-inspired effective phyto-pharmaceutical products/ preventive- and/or therapeutic- modalities for identified disease conditions i.e. for malaria -Nyctanthes arbor-thrists, sarcopenia- Withania somnifera, cognition- Curcuma longa, diabetes mellitus- Enicostemma littorale, Osteoarthritis- Semicarpus anacardium, Antioxidant Activity- Anacardium occide, antioxidant activity - Anacardium occidentale and Hyperlipidemia - Allium sativum; (2) To initiate pharmacoepidemiology and vigilance studies in traditional medicine under which focus is on anti-rheumatic drugs /modalities and anti-diabetic medicinal plants in the field; (3) Innovative methods / instruments: Mobile phone camera for tele diagnosis of - Malaria



parasites and cervical cytology; Shat Kriyakul approach for diabetes mellitus and malaria pathogenesis and nestin-GF mice and neuro-plasticity and high specific CRP/TNF α assays in vitro; (4) awareness of reverse pharmacology (RP) by reviews, papers, chapters on RP, invited lectures/Orations on RP, Symposium of Reverse Pharmacology and training programme in reverse pharmacology; (5) Reverse pharmacology and translational research with following achievements: products in market / advanced stage (Zandopa (Mucuna pruriens), Trevol (Panchvalkal), Kvion (Vitamin K2-7 ), Picroliv (Picrorrhiza kurroa), AC-108 ( Chlorphenesin), DM-FN-02 (Enicostemma littorale) and mobile tele-diagnosis (which has appreciation by Gates Foundation). The long term goal is academic placement of reverse pharmacology in R & D network for the Golden Triangle and involve trans-disciplinary team: CSIR-NMITLI, institutes of integrated medicine, AYUSH/CCRAS Centres of Excellence and also MCI to be approached for RP

The work done include the first experiential study of antimalarial activity and clinical safety of the traditionally used paste formulation of leaves Nyctanthes arbor-tristis, the trials on Sudarshan Ghanavati (SG, a complex multi-ingredient formulation) initiated at KEM hospital, with a major component being Swertia chirata. A simple but elegant technique has been developed to transmit a microphotograph of the smear by using mobile telephone camera and several plants such as Bacopa monniera, Curcuma longa and Withania somnifera are being studied for their effects on rat hippocampal stem cells, during ageing.

CenterforAdvancedResearchinDNAfingerprintinganddiagnosticsofMedicinal plants from Eastern and North-Eastern India, Bose Institute, Kolkata in collaboration with Manipur University and Botanical Survey of India, KolkataThis Centre was set up with the objectives of DNA finger printing based plant identification for inventory of medicinal plants from North East region and DNA finger printing based authentication of the selected plants. The plant materials have been identified based on availability in the North Eastern Region. Of these, Curcuma and Zingiber has been taken up for DNA fingerprinting studies in the first phase DNA Extraction from rhizomes of these plants has been standardized. A method for extraction of DNA from leaf has also been standardized for Curcuma longa. Polymorphism among 16 varieties of Curcuma landraces was generated by AFLP using 8 sets of primers. Percentage of Polymorphism is very high comparable to other genomes used earlier

Evidence Based Medicine Centre at CMC, Vellore Increasing the capacity among health professionals (and health policy makers): understanding systemic reviews and their role in evidence based healthcare and 57 introductory workshops were conducted at Vellore and other parts of the country where 2230 participates attended the meeting. The workshops included beginners guide to EBM series for students, a workshop for medical journal editors, ethics committees and workshop on the WHO and evidence Informed Policy Network (EVIPNet) for health policy makers. Regarding protocol development and review completion seven workshop on following topics were held: interventional systematic review protocol development workshops, multiple treatment meta-analysis, evidence synthesis in social sciences, diagnostic accuracy systematic review and intervention systematic review completion workshop. A total of 47 new titles for systematic reviews were registered 32 protocols for systematic reviews were published and 9 systematic reviews completed .



National tumor tissue Repository (NttR) at tata Memorial Center, Mumbai Scientists working in the field of molecular biology, genetics, and immunology are hampered by the non-availability of sufficient and properly preserved tissues. In order to fulfill the ever growing requirement of human tissues to seek answers relating to genetic information, genetic engineering, targeted treatment or manipulation, to explore possibilities of cures and to unravel disease mechanisms, establishment of a tumour tissue repository has become the need of the hour the world over. No such facility existed before in India. ICMR National Tumor Tissue Repository (INTTR) was established at Tata Memorial Hospital (TMH), Mumbai and has developed a procurement model for supplying human tissues for research. The optimally banked tissues then can be made available to research workers requesting specific tissues for scientifically and ethically approved projects. The secondary objective is obtaining and providing a follow-up record of all patients whose tissues are maintained in Tumor Tissue Repository. Till date over 14,946 normal and tumor tissues have been collected from various anatomic sites viz. Breast and Axillary Nodes, Head Neck and regional nodes, gastrointestinal tract, urinary system including Geynec & regional nodes, thoracic system, bone and soft tissues. Total 19 research studies have been undertaken by the investigators on the basis of tissue disbursed.

Center for Clinical Pharmacodynamics at Nizam’s Institute of Medical Sciences, HyderabadThis center aims to develop a specialized facility for carrying out simple, non-invasive pharmacodynamics screening methods; to investigate the effect of drugs on cardiovascular and central nervous system functions and to conduct annual training programme in clinical pharmacodynamics methodologies. Standardization of thermal pain model using contact heat method on 24 healthy participants. This method is proposed to be used in future for the evaluation of analgesic agents.

Validation of radiant heat pain model by demonstrating the analgesic effect of tramadol, a double blind, placebo controlled, cross-over study, indicated that this study design was valid and capable of detecting an analgesic effect on thermal pain model using radiant heat pain method.

Effect of cold stimulation technique on pharmacodynamic responses in twenty four healthy participants showed an increase in skin conductance seems to be a good indicator of acute pain. As changes in skin impedance are found to be influenced by acute pain, monitoring of skin impedance, could be used as a pharmacodynamic parameter for evaluation of analgesic agents

In the study on evaluation of the effect of beta -1- blocker, nebivolol, on central aortic pressures and arterial stiffness in patients with essential hypertension, open label, single arm study. Seven patients completed the study and one patient was lost to follow-up. Nebivolol 5mg orally once daily had reduced not only peripheral brachial pressures, but also significantly reduced central aortic pressures, thereby reducing aortic stiffness, an independent predictor of all cause mortality in hypertensive patients.

Basic Research in AgeingA study on Influence of DNA repair gene polymorphisms on cancer and ageing at Manipal Life Sciences Centre have shown that the differences may be due to interaction of existing



and new mutations or polymorphisms in DNA repair genes which may modify DNA repair capacity. The comparison of the data of normal samples with the cancer samples with respect to DNA repair and polymorphisms may indicate the probable markers of ageing process.

Results of study on Neuro-immune interactions during aging and immunodeficiency carried out at University of Hyderabad, Hyderabad using multipoint age comparison approach showed an association of immunological and neurological changes with ageing.

Selenoproteins and antioxidants in the pathogenesis of Alzheimer’s disease study carried out at PSG College of Technology, Coimbatore have shown that the alteration in the levels of selenium in the Alzheimer’s patients leads to the decrease in the levels of selenoprotein P and alterations in the levels of selenoenzymes like thioredoxin reductase and glutathione peroxidase indicating the increased oxidative stress in the demented patients. As selenoprotein P also promotes the survival of neurons, the decrease in the levels of selenoprotein P could lead to neuronal death and decrease in cognitive function.

Study of Aging of microglia and associated disabilities of microglia in neuroprotection carried out at Jiwaji University, Gwalior demonstrated that shift in microglial morphology, immunophenotype and inflammatory profile with age have a bearing on spatial learning and memory as age advances. Such alterations (priming) possibly largely contribute to the neurodegenerative role of the microglia in the aging brain.

Reversing age related brain functions impairments by late onset dietary restriction : A study carried out at Guru Nanak Dev University, Amritsar have provided a scientific evidence for cognition and motor coordination enhancing properties of late onset short term intermittent fasting dietary restriction (IF-DR) regimen in aging rat brain. The life-style interventions such as dietary restriction could be used to improve mental health and also to improve quality of health during normal ageing.

Results of a study on health problems and care and support available to elderly during sickness in rural Tamil Nadu at Gandhgram Rural University showed that most of the elderly were living with their children and were maintaining cordial relationship with the family members. The life style index showed poor status for more than three fourth of elderly

Indigenous production of Shikimic Acid: a raw material for manufacture of Osetamiver In order to produce antiviral drug Tamiflu which reduces the severity of symptoms arising out of Avian Flu primarily caused by H5N1 and H1N1 viruses the division took initiative to produce shikimic acid, (the starting material for the production of Tamiflu) indigenously with the objective to make the country so as to make it self sufficient in production of shikimic acid to avoid or lessen the burden of import of the same.

Hairy Root Cultivation for Mass Scale Production of Shikimic Acid (Raw material for avian flu drug) at Indian Institute of Technology, Delhi Attempts have been made for induction of hairy root, callus micropropagation. Trial has been initiated for Calophyllum apetalum (having 4% shikimic acid), Pinanga dicksonii procured from TBGRI, Palode Trivendrum which are expected to transform to produce hairy roots. Hairy root culture for in vitro production of shikimic acid has been established.



Production of Shikimic Acid : A Potential Candidate for Developing Drug Formulation for Swine and Avian Flu, University of Delhi South Campus, Road, New DelhiAn efficient fermentation procedure for shikimic acid production and its purification has been successfully developed. Finally, 18g/L of shikimic acid is achieved by employing fermentation route for the production of this important molecule.

Commercial Potential of the Method for Domestic Production of Shikimic Acid at National Institute of Pharmaceutical Education and Research (Niper), Mohali, Punjab. Out of four plants studied accumulation of shikimic acid was found maximum in Ageratum conyzoides (1.25%). Two Indian patents have been filed on novel extraction method from Pinus roxburghi and Ageratum conyzoides to produce the shikimic acid.

Evaluation of Plant and Microbial Sources for Production of Shikimic Acid at National Chemical Laboratory, Pune.A complete method for extraction and purification of shikimic acid from plant leaves is studied and optimized using chemicals/resins available in the country.



International Health The International Health Division (IHD) co-ordinates international collaboration in biomedical research between India and other countries as well as with national and international agencies such as Ministry of Science & Technology, Indian and foreign missions, WHO etc. There are few specific agreements signed by the Ministry of Health and Family Welfare with other countries and rest are those signed directly by ICMR with international organizations/ institutions such as INSERM (France), German Federal Ministry of Education and Research (BMBF), Helmholtz Association (HGF) in Germany, National Institutes of Health(NIH)/Centers for Disease Control (CDC), (USA), Canadian Institutes of Health Research (CIHR) Canada, University of Sydney and George Institute for International Health, (Australia), Medical Research Council (MRC) and London School of Hygiene and Tropical Medicine (LSHTM) in UK, Karolinska Institute (KI) in Sweden etc.

Joint Working Group and Joint Steering Committee Meetings The regular meetings of Joint Working Group (JWG) or Joint Steering Committee (JSC) with various countries/international institutes/organizations were organized to review, develop and finalize joint collaborative programmes, decide future plans of action and identify priorities for bilateral cooperation. The JWG & JSC meetings under MoUs of ICMR with MRC (UK), ICMR-HGF (Germany), ICMR – INSERM (France), Indo-US Joint Statement on HIV / AIDS and Environmental and Occupational Health, were organized to review and work together on health issues of mutual importance during the year wherein number of collaborative research projects were approved and new modes of collaboration were identified. In addition to these meetings, the International Health Division has also represented ICMR in various Joint S&T Committee meetings with countries like Bulgaria, South Korea, Sweden, The Netherlands, Switzerland, Russia, Tunisia, Brazil etc. organized by Ministry of Science and Technology, Govt. of India.

Joint Collaborative WorkshopsDuring the year under review, The International Health Division also facilitated the organization of international workshops such as Indo-US workshop on Environmental and Occupational Health; ICMR – MRC (UK) Expert Panel on Non-Communicable Diseases; Indo-France workshop on Diabetes; ICMR – HGF (Germany) workshop on Translational Research in Infectious Diseases.

New Memorandum of Understanding and Letter of IntentMoUs such as ICMR-HGF (Germany), Indo-US Joint Statement on HIV / AIDS, ICMR – University of Minnesota (USA) were signed for renewal of collaboration. New MoUs with Global Alliance for Chronic Diseases (GACD), Foundation for Innovative New Diagnostics (FIND), Geneva as well as an ICMR – NIH Letter of Intent for collaboration in Diabetes Research were signed during 2011-12.

As a follow up of a Letter of Intent (LOI) between ICMR and INSERM for setting up of an International Associated Laboratory (IAL) in the field of Immunology / Haematology which was signed in December 2010 during the visit by delegation of His Excellency, the President of France to India, the collaborative project document for cooperation between labs of INSERM & ICMR was signed in October, 2011 at New Delhi for implementation. Further in response to another Letter of Intent (LOI) signed between ICMR and European



Union for collaboration in cancer and neurodegenerative diseases, a call for proposal was launched.

Exchange VisitsThe IHD supports and coordinates the international travel of Indian scientists engaged in approved bilateral research projects under various MoUs and joint statements with other countries. A total of 74 exchange visits of scientists / officials to and from India were arranged under various international collaborative programmes / projects.

Health Ministry’s Screening CommitteeThe research projects involving foreign assistance and/or collaboration in biomedical/health research are submitted by the Indian investigators to ICMR for approval of Govt. of India through Health Ministry’s Screening Committee (HMSC). The International Health Division of ICMR acts as the Secretariat for HMSC. The projects are peer reviewed by the concerned Technical Divisions at ICMR and then placed before the HMSC for consideration and decision. During the year 2011-12, four meetings of Health Ministry’s Screening Committee were organized wherein 140 projects for international collaboration / assistance with agencies from USA, Germany, France, Canada, Australia, UK, WHO, European Union and several other foundations and foreign universities were approved by the Committee. Of which, 33 projects were funded by ICMR under different bilateral collaborative programmes.

International Fellowship ProgrammeThe ICMR International Fellowship Programme for Indian biomedical scientists aims to augment capacity strengthening of institutions involved in basic, applied, epidemiological and clinical sciences through exposure of Indian researchers to the latest international advancements in knowledge, to understand the disease and find strategies for their prevention and cure. The ICMR International Fellowships have been awarded to six Senior and twelve Young Indian scientists during the year 2011-12.

Indo-German Science Centre for Infectious Diseases The mission of the virtual Indo-German Science Centre for Infectious Diseases (IG-SCID), established at ICMR is to coordinate joint research in identified areas of infectious diseases and to initiate proactive scientific cooperation with equal participation of Indian and German scientists. The Council has taken up a project entitled, Managing the Indo-German (ICMR-HGF) Science Centre for Infectious Diseases which is in operation with IHD. Under this programme four collaborative projects have been approved and funded.



Publication, Information and CommunicationDuring 2011-12, following activities were undertaken in the field of publication, information and communication:

PUBLICAtIONS

Indian Journal of Medical ResearchThe Indian Journal of Medical Research (IJMR) is one of the oldest (established in 1913) biomedical journals of the country, and is about to complete 99 years of its uninterrupted existence. The Journal is available full-text free on the website www.ijmr.org.in, and IJMR archive having full text articles since 1913 on http://ijmr.in. IJMR continued to publish quality original research articles as well as review articles in the area of biomedical research on topics of current interest after peer review. In addition, solicited review articles invited from eminent scientists from India and abroad were also published. The other regular features viz. Editorials, Commentaries and Letters to the Editor (Correspondence) were also continued. Articles under newly added sections viz. View Points, Perspectives, Systematic reviews with meta analysis, and Students’ IJMR were also published.

Since 2010, the IJMR has been switched over to Online Manuscript Management System and there has been a significant increase not only in the number of submissions but also in global representation. It has also led to a reduction in processing time of articles.

There has been a continuous increase in the number of hits, visits and downloads on the Journal’s website. The impact factor (IF) of the IJMR was 1.516 in 2009 and it rose to 1.826 in 2010. The IJMR is ranked among the top Indian biomedical journals.

Special issues on “Haemoglobinopathies” and “HIV/AIDS” were brought out in November and December 2011 respectively.

Annual ReportAnnual Reports of ICMR and Department of Health Research (DHR) (2010-11) were brought out during the year and can be accessed at the ICMR website, www.icmr.nic.in.

HINDI PUBLICAtIONS

ICMR Patrika / Other PublicationsThe articles published in ICMR Patrika during 2011-12 included : Nutraceuticals, Jalvayu Parivartan, Madhumeh, Tribal Health problems, etc. Besides, ICMR Patrika: Pragati ke 25 varsh and the theme articles on Council’s institutes viz. GRC, Mumbai, NIE, Chennai and RMRC, Belgaum were also published.

Pictorial Identification Key of Indian Anophelines in Regional LanguagesThe booklet entitled Pictorial Identification key of Indian Anophelines was originally prepared in English by NIMR. In coordination with National Book Trust, the booklet has



been translated into 3 regional languages viz. Telugu, Oriya and Bangla and made available to the NIMR for further use by its regional Field Units.

Public Information Campaign under Bharat Nirman Programmes The ICMR participated in a Public Information Campaign organized by the Press Information Bureau, Govt of India, Lucknow at Government Inter College compound, Jhansi during 21st to 24th June, 2011. An exhibition was organized for common man.

Hindi Day Symposium As a part of ICMR Centenary celebrations and on the occasion of Hindi day/ Hindi fortnight a symposium in Hindi was organized on the topic “ Jivan shaily se sambaddh rogon ka chikitsa-praband : ek update ( management of lifestyle diseases: An update)” at ICMR Hqrs on 21st September, 2011 in which three prominent doctors delivered lectures.

Video Films on Activities & Achievements of ICMRThe Unit prepared albums containing 9 DVDs ( Bilingual) each on activities and achievements of ICMR. Six films were on Communicable Diseases, Non-Communicable Diseases and Reproductive Health & Nutrition while 3 films are for common man, scientists and policy makers. The Album was released by Hon’ble Union Minister of Health & Family Welfare Shri Ghulam Nabi Azad during Council’s year long Centenary Celebrations held on 15th November, 2011.

INFORMAtION AND COMMUNICAtION

Library and Information ServicesAs part of modernization of ICMR Libraries the subscription for the ICMR e-consortia of core journals Lancet, Science, Nature, and NEJM for all ICMR Library & Information Centres has been reviewed by expert Committee and renewed for one more year as the usage is satisfactory among ICMR institutes. Subscription for full text electronic data base ProQuest Health & Medical Complete including ProQuest Medical Library (covers about 1900+ journals) has been renewed for one more year at four ICMR institutes as the usage of this database among ICMR institutes is found satisfactory. The subscription has been renewed for JCCC@ICMR (J-Gate Custom Content for Consortia) (provides access to content of about 1941 journals) and J-Gate as the usage of these databases also was found satisfactory. ICMR has continued as a member of ERMED Consortia, an initiative taken by DGHS and MOHFW to develop nationwide electronic information resources in the field of medicine for delivering effective health care. The consortium will be coordinated through its headquarter at National Medical Library. It provides easy access to 2745 medical journals from 9 leading publishers across the world and also makes online journals available to medical scholars working in the country through the electronic media.

Zonal Workshops/Training programmes were organized for ICMR scientists on Information Retrieval & Analytical Tools (Scopus & Science Direct) at ICMR institutes i.e. NIOP,Delhi; NICED,Kolkata; NARI,Pune; NITR,Chennai and for the Cochrane Library at NIOP, Delhi and NITR,Chennai.



Scientometric StudiesThe annual document ‘2010 Research Output of ICMR Institutes’ with analysis of publications from all the institutes including Regional Medical Research Centres was brought out. A total of 533 papers were published by the ICMR institutes during the calendar year 2010. The National Institute of Cholera and Enteric Diseases (NICED), Kolkata topped the tally with 87 papers followed by the National Institute for Tuberculosis Research (NIRT), Chennai (53), National Institute of Malaria Research (NIMR), New Delhi (51), National Institute of Nutrition (NIN), Hyderabad (38) and National Institute of Virology (NIV), Pune (32) . Of the 533 papers, 78.76 % were covered by SCI/JCR 2010, while 79.61% were covered during 2009. In this category of SCI/JCR 2010 covered papers, top five institutes were as follows : NICED, Kolkata (71), NIMR, New Delhi (45) ,NIRT, Chennai (39) , NIV , Pune (30) and National Institute for Research in Reproductive Health (NIRRH), Mumbai (27). The average IF/paper of the Council continues to remain over 2.000.

Bioinformatics CentreThe activities of BIC during 2011-12 can be organized into three categories viz., Research, Support and Services.

Research Activities

task-Force on Biomedical Informatics During 2011-12, to increase awareness of Informatics tools among medical professionals, the Centres conducted 12 workshops on a wide range of themes, from basic bioinformatics to advanced Next-Generation Sequence analysis. The Centres provided biomedical informatics services to medical researchers from host institute and regional medical colleges. Some of these services culminated to active collaborations. The Centres initiated/completed 42 collaborative research projects with researchers from host institute or regional medical colleges. The Centres developed 17 databases of clinical and biomedical data. Some of these databases were published in peer-reviewed journals and acknowledged by International community. During the year the Centres published 31 research publications in peer-reviewed journals including some of the highly reputed journals such as PNAS, Blood, Plos One etc.

Realizing the increased applications of high-through put technologies in medical research and the requirement of specialized infrastructure to meet increasing demand of analysis and storage of multi-dimensional biomedical data, a proposal for the second phase of this task-force have been prepared and will be submitted in 2012.

Data Repository and Business Intelligence Taking a leap forward to develop ICMR Research Data Repository, BIC drafted a RFP document for the project ‘ICMR data repository and Business Intelligence’. The mandate of the project is to create a data repository of all data generated by both intramural and extramural research. More than 200 scientists, IT professionals and managers working in the area were consulted for formulation of the project, the approach, the technical specifications, work flow etc. A pilot project is being initiated.



Support to ICMR staffStS portal - STS program is launched to provide support to young undergraduate medical students in pursuing short-term projects. BIC developed an online portal to fully automate receiving the project proposals, project review system and receiving completed reports and evaluation of reports by the experts. The web portal is available at http://icmr.nic.in/shortr.htm.

Management for Acute Coronary Events (MACE) Registry - BIC developed MACE registry as a part of an ongoing task-force project on Acute Coronary Systems (ACS). Registry facilitated online data entry and hierarchal editing of Acute Coronary Events from various collaborating centres across the country. It tracks outcome of patients with acute coronary syndrome including unstable angina, myocardial infarction etc. Currently 13 centres are feeding data into the registry.

ICMR Engineering work portal- ICMR Engineering work portal is a web based application for periodic information of the financial and physical progress of engineering related projects at ICMR Hqrds and Institutes. The system has been developed in consultation with Sr. DDG(A) and Executive Engineer and will be delivered to Executive Engineer and the administration after testing.

ServicesICMR website- BIC has developed and maintaining ICMR website. The site is constantly being upgraded with new and evolving technologies also every effort is made to weed out obsolete information and maintain correctness. During the year, the Cascading Style Sheet (CSS) approach and Templates are adopted for synchronization of WebPages. As per the webstat software hosted by NIC, average hit for the year 2010 is 27192 per day. It is widely seen across world (49 % in India, 51% abroad). Mass hit pages are IJMR, Ethical Guidelines, Bhopal Gas Tragedy, Circulars etc. Website is updated on regular basis. Announcements related to employment; call for proposals, tenders, workshops, press releases, scientists profile, ICMR institutes detail etc. are updated regularly. Photo gallery is restructured using programming script. Indian Journal of Medical Research, RTI, Library Bulletin are updated from time to time. General Circulars received by Admistration are also put in a database and displayed on the website. They can be searched by date or keyword. Pages for the newly added ICMR Insitutes, ISSRF conference, Vector Science Forum are added to the website. Database of extramural projects, publications etc. are consistently updated on the website.

Management Information System- BIC has developed and is maintaining Management Information System of Extramural Research activities of the Council. MIS has been upgraded in a major way and is now highly interactive and informative; efforts have been made to automate the entire process so that the Programme Officer can update information about a project at any given time. Reporting facilities have been considerably enhanced.

Video Conferencing- BIC established Video conferencing facilities between 8 ICMR institutes and the headquarters. The facility also provides access to video conferencing between ICMR institutes and with organizations outside the country.

Internet and Intranet Connectivity- The ICMR has a 5000 node network, which is centrally administered from the ICMR headquarters, the services include antivirus solutions, systems management and fault rectification, e-mail services. The connectivity to each of the locations of ICMR has been significantly enhanced with the establishment of 2X2 Mbps lines. The



ICMR intranet has been established and applications are being developed. Installation of the National Knowledge Networks (NKN) line (1 Gbps) at all the institutes of the Council will greatly enhance the Internet connectivity.

Dissemination of Biomedical InformationIndian Council of Medical Research participated in a state of art S & T Exhibition “Pride of India Science Exhibition” organized as part of 99th Session of Indian Science Congress at KIIT, University,Bhubaneswar during January 3-7,2012.The Council showcased research achievements, contributions and research activities in different priority areas of biomedical

sciences undertaken by ICMR institutes/centres spread across the country. Scientists of the Council explained the exhibits and answered the queries of the visiting delegates, students and scientists from various parts of the country as well as from abroad. Many senior scientists, academicians, policy makers visited ICMR pavilion and appreciated the research activities/contributions of ICMR.ICMR pavilion was adjudged the Most informative pavilion based on the feedback of visitors.

Web-based Extramural Project management SystemThe ICMR has shifted from manual receipt, processing and management of Extramural projects to web-based interactive system .The system has been developed by ICMR in technical collaboration with C-DAC,Noida .This system has started functioning w.e.f. January 2012.Now all function related to the processing of extramural ad hoc proposal ie submission, receipt, reviews by experts,sanction,release of funds, report submission, and final closure of the project would be through web-based system. All stake holders i.e. principal investigators,programme officers, experts,ICMR management and disbursing officers would be interacting through this web-based system ( available through the link available on the ICMR website. This system will eliminate the paper-based manual system which had been in operation in the Council so far.

In the new web-based system, extramural projects will be received in two stages- first as a concept proposal or preproposal and later for the selected preproposals the Principal Investigators would be requested to submit the detailed proposals. Every stakeholder is expected to log into system after registering.The access to senior officers of ICMR, Heads of Divisions, programme officers, experts and disbursing officers would be suitably provided after proper registration into the system.

Till March 31, 2012 around 400 pre proposals have been received through on line.



Other Areas

Tribal Health Research Forum The recently constituted Forum on Tribal Health Research, has undertaken research within various ICMR institutes on malarial infection and host genetic markers in a primitive tribal area in Madhya Pradesh - the effect of sickle cell gene, β-thalassemia, G6PD deficiency and α-thalassemia to offer protection against malaria, Impact of intervention on fluorosis (RMRCT, Jabalpur), Intervention strategies to control anemia among tribal adolescent girls in Orissa, Understand malaria - HIV interactions in malaria endemic regions, primarily HIV viral loads and CD 4 counts (Dibrugarh), Impact of dietary salt restriction in reduction of blood pressure in tea garden workers in Assam. Impart training and orientation - education department, district level department heads, supervisors, teachers and students (VCRC), Investigation of malarial outbreaks Risk factors of chronic non-communicable diseases, Nutritional status in preschool children of Nicobar island, Vector borne diseases, Traditional knowledge of healing and community biodiversity registers, Cardiomyopathies among Nicobarese (RMRC, Portblair).

The Forum has also initiated steps to develop multicentric studies for prenatal diagnosis and new born screening to reduce the incidence of various genetic diseases. NIIH, Mumbai as the lead center for these studies has already conducted, 6 training workshops covering various regions involving 95 participants from 34 medical colleges in its efforts to bring in non-ICMR institutes as partners in these studies in addition to training prospective of scientists and technical staff of various ICMR institutes.

To address the issue of hypertension, efforts are being made to undertake multi-centric studies on Role of diet and lifestyle on hypertension, Effect of nutrition and health education on blood pressure level among tribal adult population, Assessment of urine sodium output in relation to hypertension among tribals etc.

The Forum has made strides in involving more ICMR centers to widen its scope of activities on studies on nutritional status associated with the severity of vector and water borne disease, Exploration and experimental validation of ethno-medicine used to cure infectious diseases by tribal population.

Vector Science Forum (VSF)Vector Science Forum (VSF) was established by Secretary, DHR and DG, ICMR with Terms of References to provide a platform where researchers/institutes working on Vectors/Vector-borne Diseases can share information available with them and also discuss the current findings and future trends in the diseases, identify neglected aspects/gap areas of vector research to help develop better control strategies and identify the cutting edge areas of science which could be translated to the field.

Subsequently under the forum 1st call for proposal has been made in identified priority areas in basic and applied research in vector borne disease including diseases which are occurring where not much information is available. The shortlisted projects have been funded. Besides this two brain storming meeting have been organized involving experts, researchers, programme officials from Directorate of NVBDCP and states to identify gap areas in knowledge of vectors and vector control of malaria, filarial, leishmaniasis, dengue, chikungunya and JE and to make the programme a science backed program.



In the meeting discussions were held according to the ecological sites of the vectors and research areas were identified in each area and concluded with the commitment to partner with programme people to accelerate development of improved methods of pathogen detection, treatment and vector identification and control of vector borne diseases. In a view to develop human resource, NIMR, New Delhi, VCRC, Puducherry, CRME, Madurai, and RMRC, Dibrugarh together along with Programme people have developed a course curriculum to organise a training programme (short and long term) for hands on experience training in entomology. During the Brain storming meeting VSF website was launched by our Secretary, DHR and DG, ICMR. The link is available on ICMR website. This was developed for sharing of knowledge and is being updated regularly.

Translational Research/Intellectual Property Rights

Translational Programme of ICMRTranslational research is an important area of DHR. To start with the programme has been initiated as intramural programme of ICMR.

The concept of translational research at ICMR has received a greater impetus, especially since December, 2008 when formal structure was established to identify leads that could be translated into products, processes and technologies for improving the health care delivery services.

Translational research cells were established each at the 27 ICMR’s Institutes/Centres with appropriate expertise with a co-ordinating cell at ICMR Hqrs.

Of the 200 leads received from various ICMR’s Institutes/Centres, 102 flagship technologies / programmes were identified. Out of these 52 top priority technologies / programmes were short listed during phase I (2009-2010) and 23 in phase II (2010-2011) in addition to 3 HFM special initiative programmes to carry forward on a priority basis for their utilization into the health care system/clinical practice at the earliest. All these programmes are being monitored at quarterly intervals by the translational research cell at ICMR Hqrs.

These 75 leads/programmes in addition to 3 HFM special initiative programmes (diagnostics for diabetes mellitus, Production of H1N1 reagents and Indigenous H1N1 vaccines) are on development of new tools for vector control, diagnostic methods for various infectious diseases including dengue and chikungunya, lung fluke, tuberculosis; new treatment methods to improve the treatment of tuberculosis, leprosy, cancer, malaria, diabetes mellitus, prevention of occupational hazards etc. and vaccines for different infectious diseases. Out of these, 28 technologies may be ready within 1-2 years.

Keeping in view the importance of translational research and to process new projects on a fast track basis, fresh guidelines for funding of these projects were formulated and implemented.

Intellectual Property RightsDuring the year under review, a total of 8 patents filed of which 7 originated from intramural research done at ERC, MUMBAI; TRC Chennai, NIRRH Mumbai; and 1 extramural patent originating from research done at AIIMS Delhi. Two international filings as PCT have been filed from intramural research done at ERC, Mumbai; and NTRI, Chennai.

A total of 4 patents were granted in 2011 for research done at NIOP, New Delhi, ROHC Kolkata and University of Delhi, South Campus. A design application has been granted for



research done at ICPO Noida.

Initiatives have been taken by the Council to transfer its technologies for commercialization on a fast track mode. Memorandum of Understanding have been signed with the UCMS, New Delhi and the UCST Kolkata.

Few technologies like RDB Kit for detection of ß-Thalassemia, Magnivisualizer for visualizing the cancerous lesion, Non-invasive fertility assessment kit for estimation of Sex hormone and redesigned model of Cycle Rickshaw have already transferred to the different Indian companies. The ICMR has also received revenue on some of the technologies.

So for other technologies like Epidermal autologous grafting for burn patients , Monoclonal antibody based in kit for detection of cancer, negotiations are ongoing with interested companies. Some other technologies like hypoglyceinic compound for diabetes, ELISA based diagnostic kit for detection of kala azar, have also identified by the companies.

The ICMR has placed details about these technologies on the website for industrial partnership. We also collaborate with the outside technology transfer agencies like BCIL, NRDC for commercialization of technologies. A letter of consent signed with BCIL for partnering biotech based technology and also signed the MoU with NRDC for the technologies developed by the ICMR institutes or by others with ICMR support.

The ICMR also took participation and disseminate the technologies on various fora like FICCI, CII, NIAS to make aware the companies about ICMR technologies.

During the year, to streamline the process of regulation on Bti products for vector control, a committee has been formed to formulate robust, transparent and enforceable guidelines for introduction in the market. The SOP is under preparation with the active collaboration with other nodal Departments of the Government of India.

The ICMR renewed the agreement on a non-exclusive basis with NRDC, New Delhi to commercialize ICMR’s technologies. Few technologies like Resazurin reduction test, PCR based diagnostics kits for detection of food and water borne pathogens were transferred. A technology related to novel primer based diagnosis of pathogenic Mycobacterium was assigned to NRDC for industrial partnering. Apart from NRDC and BCIL the IPR Unit initiated tech. transfer exercise independently. Two technologies Magnivisualizer, a device developed by ICPO to visualize the cancerous lesion of uterocervix and RDB kit based on monoclonal antibody and nested PCR for parental diagnosis of haemoglobinopathies have been transferred for industrial collaborating.

During the year, brains storming interactive discussions were organized on current IP issues viz. Bayh-Dole Act, Modification in Drugs and Cosmetics Act, definition of spurious, counterfeit, misbranded drugs with participation from Govt. agencies, NGOs and law firms. Training of Women Scientists supported by TIFAC was continued during the year also.

Health Systems Research In order to improve and strengthen the Health System in India to meet the health needs of the people in the diverse and complex geographical, socio-economic, cultural, political, demographic and epidemiological environment studies on the following aspects were initiated.

Out of above research projects were invited on the following sub-areas: i) Delivery of RCH services – Public, Public –Private and NGO model; ii) Health Insurance for the population



living in rural areas and urban slums; iii) Strengthening research capacity and effective knowledge utilization; iv) Reduction of Gap in the Health System manpower and service delivery; and v) Reducing Gender discrimination and improving Adolescent Health and addressing other gender issues.

Two Taskforce projects on health issues of migrant’s population living in urban slums and other unorganized colonies were also initiated at Medical colleges situated in 13 states of India covering 6 metro cities.

The project - Rapid Appraisal of Rashtriya Swasthya Bima Yojna in Delhi – has been completed. This was a descriptive cross sectional study conducted in 8 districts of Delhi. One of the most problematic aspects of the implementation of the scheme in Delhi was poor status of BPL data. There was lack of cooperation among the Department of Labour, Nodal Insurance Company and TPA as a result the implementation of the scheme took a side track. Awareness about the scheme and its benefit were low among the target population. In conclusion, the RSBY was introduced for the poor population and the scheme aims to relieve them of the burden of health care costs. However, a significant proportion of the families availing benefits under the scheme have to incur out-of-pocket expenses.The empanelled hospitals/nursing homes do not admit RSBY patients with chronic ailments which require continuous treatment at the hospital.

Capacity building Five workshops were conducted on developing and using of Geographical Information System (GIS) for improving the functioning of health systems at NIE, Chennai. Workshops were also conducted on the application and use of Qualitative research in HSR at NIN, Hyderabad and RMRC, Bubaneswar.

Social & Behavioural ResearchThe Unit is involved in planning and carrying out targeted research on social and behavioural issues of high priority for health and which have important policy and programme implications for achieving the Plan targets. During the current year 14 research projects and one fellowship were carried out in the following four broad thrust areas, for which a new initiative was undertaken in the previous year:

Delivery and Utilization of Health Services and Newer Technologies • Gender Issues • Adolescent’s Behaviour & Health• Diseases with Stigma•

In order to cover the remaining aspects in the above thrust areas, during this year the concept proposals were again invited.

Health EquityEquity in health is not only an issue for equitable delivery, access and utilization of health services for social justice but also for better health of all in the society particularly the vulnerables, which should raise their productivity and quality of life. Social and behavioural research on all the related issues should guide the policy and programme formulation to achieve the goals of better health and social justice.



Life Style associated Diseases and HealthThe burden of diseases related to the life styles is on the rise. Some of the health issues in this area, where social & behavioural research has important role to play, are psychosocial health, alcoholism, drug addiction, cardiovascular diseases, cancer and obesity etc. among different population groups in different regions which have strong life-style associations. Social and behavioural research aims at diagnosing the problems and preventive interventions in these areas which will benefit the policy & programme and ultimately the community.

Through this new call for proposals in these above six priority areas, 83 concept proposals and 11 Adhoc proposals were received. The Project Review Group (PRG) recommended 32 concept proposals for submission of full proposals and 5 Adhoc proposals. After receiving and 2nd review by the PRG of full proposals a total of 23 proposals were recommended for funding and the same are in the process of being funded.

Medicinal Plants

Review Monographs on Indian Medicinal PlantsThe programme aims at consolidation of Indian research contributions (published information) at the various National laboratories/institutions across the country in the area of medicinal plants and present the compiled information in series on Reviews on Indian Medicinal Plants. Each Monograph includes regional names of the medicinal plant, its sanskrit synonyms as well as the Ayurvedic description (wherever available), ethnobotanical studies, apart from the habitat and the parts used, properties and uses on one hand, and the details of botanical, pharmacognostical, chemical, pharmacological and clinical data on the other, backed by complete references and bibliography on each aspect of the information cited, besides the colour photographs of important medicinal plants.

During the year Tenth volume (with botanical names Ec-Ex) has been published covering monographs on 422 medicinal plants species carrying multidisciplinary information as part of series on Reviews on Indian Medicinal Plants. The 11th volume (with botanical names F-G) is under preparation.

Earlier, 9 volumes of Reviews on Indian Medicinal Plants (with botanical names starting with A-D) covering multidisciplinary research data on about 2,154 plants covering about 40,814 citations were published.

Quality Standards of Indian Medicinal PlantsThe programme aims at development of Quality Standards of important Indian medicinal plants and preparation of monographs thereof. The programme is in progress at various national laboratories/Institutions in the country. The monographs are on the pattern of WHO guidelines and focus on the diagnostic features and phytochemical studies, including markers besides having information on pharmacological, clinical, toxicological aspects along with dosage, adulterants/substitutes etc.

The Quality standards of 70 medicinal plants were developed, monographs prepared, finalized, technically reviewed and published as Vol. 9 and 10 as part of series on Quality Standards of Indian Medicinal Plants. Earlier 8 volumes have been brought out containing



quality standards of a total of 274 plants. Monographs on another 35 plants are being finalized for 11th volume.

Generation of Phyto-chemical reference standards and Development of Repository of Reference Phyto-constituents of Important Indian Medicinal PlantsPhytochemical reference standards (PRS) are ideally those compounds in the plant which are therapeutically active. However, in many cases the therapeutic activity of the plant is attributed to a number of phytoconstituents present in the plants. Under such circumstances any compound that is unique to the plant or the major compound or the major chemical constituent can be regarded as the PRS.

During the year the second volume containing monographs of 30 important PRS entitled Phytochemical Reference Standards of Selected Indian Medicinal Plants was published. The monographs on 30 PRS are being prepared for incorporation in the third volume in this series.

The samples of marker compounds isolated along with the original spectroscopic data are being stored in the repository (quantity of each varying from 100mg to 1 g as per recommendations of the review committee) at RMRC, Belgaum.

Human Resource Planning & Development

Junior Research Fellowship (JRF)The Council has been awarding 150 JRFs selected through a National Level Junior Research Fellowship Examination since 2001 in Life Sciences and Social Sciences. This year one more Examination Centre viz., Varanasi has been added to the existing seven Centres (Chandigarh, Chennai, Delhi, Guwahati, Kolkata, Mumbai and Hyderabad). So far more than 820 candidates have joined the fellowship.

Financial Assistance for MD/MS/DM/MCH thesis in the priority areas of Biomedical Research (50 per year) To increase the competition in writing a good MD/MS/DM/MCH Thesis, the ICMR has started providing financial assistance of Rs.25000/- to the students who are in 2nd year of the above mentioned course. The Screening Committee has recommended the financial assistance to a total of 300 students out of 800 proposals received.

MD-Ph.D ProgrammeIn this programme 48 students have joined at 3 Universities i.e. King George Medical University, Lucknow, NIMHANS, Bangalore and Sri Ramachandra University, Chennai.

The programme provides the young medical graduates to do their Ph.D either directly after doing MBBS or after their MD course. The theme of this programme is to train these medical graduates in the highly specialized area so that after completing their Ph.D. they can join the different organizations to pursue their career as a Research Scientist. These all candidates were selected through the national Programme.



Financial support for participating in International Conference/training Programme/Workshops for non-ICMR scientistsThis programme was initiated about 2 years back to provide the international exposure to young and senior Indian scientists to expose them to recent advances in their respective fields. This year Council has received about 1200 proposals out of which about 450 have been granted the financial support. About 240 have availed this facility during 2011-12.

ICMR-Centenerary Post Doctoral FellowshipsThe Council has initiated this programme to provide the young scientists to work in the ICMR Institutes for two years. Fresh Ph.D. students are being selected twice every year i.e. in the month of December and June. So far 39 candidates have availed this PDF during the last 2 years.

ANNEXURE

Summary of Audit Observations Pertaining to Department of Health Research

IndIan CounCIl of MedICal ReseaRCh

Inordinate delay in creation of national facility for breeding of primates

A breeding centre for primates such as apes and monkeys to meet the needs of biomedical research could not be established even after 11 years due to inability of National Institute for Research in Reproductive Health (NIRRH) to ensure that the designs for the facility were prepared timely by the architect and that the building was constructed in time by executing agency. NIRRH also failed to effectively monitor and coordinate with different agencies implementing the project. Failure on part of NIRRH led not only to non-achievement of the objectives of establishing the facility but also blockade of funds of `14.15 crore and unfruitful expenditure of `8.90 crore already incurred on the project.

(Report No. 16 of 2011-12)Delay in commissioning of equipment Delay by National Institute of Occupational

Health in placement of the purchase order and poor planning in execution of construction of construction of instrumentation room led to non-commissioning of an equipment costing `2.20 crore to address the existence of pesticides and other contamination in soft drinks which adversely impact on the health of consumers.

(Report No. 16 of 2011-12)

Introduction - Department of Health Research

Documents

Transcript of Introduction - Department of Health Research