A ten-year-long joint research programme between the United States and India has culminated in the development of a vaccine against a severe form of diarrhoea, called rotaviral infection, which claims lives of thousands of infants year after year.

In India alone, rotaviral infection accounts for about one- fourth of the diarrhoeal deaths. However, a majority of these would become preventable, once at the new vaccine developed under the Indo-US Vaccine Action Programme (VAP) reaches the market.

Billed to be one of the longest-running bilateral science and technology pact in the history of independent India, VAP was commenced in the mid-eighties as part of the famous Rajiv Gandhi-Reagan initiative on science and technology. The objective of the programme was to pool in efforts to develop vaccines and immunodiagnostics against infectious diseases which are a major health problem in India and to understand the basic biology of the microbes and epidemiology of diseases. So the collaborative efforts covered both basic and applied research. Initially the list of diseases identified was limited to acute respiratory diseases, pneumococcal pneumonia, hemophilus influenza, diarrhea due to rotaviruses, V.cholera or E. coli: hepatitis, polio, shigellosis and typhoid fever. As the programme progressed, the VAP portfolio was expanded to include canine rabies, HIV / AIDS, leishmaniasis and malaria as well. In all, two dozen projects were implemented in the first 10 years.

The most exciting of all the projects was the development of a set of rotaviral vaccines. Two candidate vaccines for rotaviral diarrhoea emerged from the concerted programme. Amng other significant achievements of the collaborative research were development of two diagnostic assays for Hepatitis C and several promising in relation to other diseases.

"The programme has addressed several national and international issues, with specific reference to disease burden, and developing simple and rapid diagnostic test methods and vaccines. It has played an important role in developing technologies for improvement of health-care system of the country", says Dr. Manju Sharma, secretary, Department of Biotechnology (DBT), which is the nodal agency for implementation of VAP from the Indian side.

More importantly, it created a vast body of knowledge and paved way for creation of useful infrastructure for in several of the Indian institutions participating in the programme.

"Training, transfer of technology, sharing of information, development of infrastructure - these are all permanent gains which will be useful in other projects as well", says Dr. V K Vinayak, adviser (medical) in the DBT. He points out that over 80 scientific papers were published since the inception of VAP, indicating the high level of basic research done.

Two Indian groups - at the All India Institute of Medical Sciences (AIIMS), New Delhi, and the Indian Institute of Science (IISc), Bangalore - were already engaged in studies on rotaviral strains, when VAP stepped in and gave further impetus to their work. The focus then shifted to development of candidate vaccines. The IISc group,along with a group from the Stanford University School of Medicine, isolated rotaviruses from asymptomatically infected newborn Indian children and characterizsd them. Similarly, the AIIMS group, working with the Center for Disease Control and Prevention, Atlanta, isolated and characterized rotaviral strains from newborns.

The two strains were then adapted for growth using tissue culture techniques at the National Institute of Allergy and Infectious Diseases of the National Institute of Health (NIH). After toxicology tests, U S Food and Drug Administration (FDA) clearance was obtained for limited trials of the vaccine. The first phase clinical trials have been conducted among adults, since infants cannot be given any new vaccine unless it has been tested in adultls. The results of this trial have shown the vaccine is safe. The second and third phase trials will now be conducted in India and the US simultaniously. Regulatory approvals are awaited from the Drug Controller of India for clinical trials in India.

The vaccine will have beneficial impact in India as well as the United States. "Although the problem is far less severe in the US (about 150 deaths occur due to rotaviral diarrhea annually), they are finding it cost-effective. The costs of hospitalization are so high that it may be cheaper to immunize all new-borns with this vaccine", says Dr. M K Bhan, the Indian collaborator from AIIMS. On the other hand, the problem is very serious in India, where one in every three kids admitted for dehydration suffers from rotaviral infection. About 25 per cent of the deaths relating to diarrhea ovvur because of this, accounting for over 200,000 deaths every year.

"The vaccine will drastically reduce the proportion of infant deaths. Of course, the number will depend on coverage of immunization and availabillity of the vaccine. Secondly, it will reduce the burden of admission for hospitalization and make available beds for other cases", says Dr. Bhan. And for the poor families, it could result in a great economic benefit.

But the availability of vaccine to poor people will depend on the costs, which at present seem to be high. The DBT is trying to involve Indian and American companies for commercial production of the vaccine. It has already organized one commercial colloquium in Bangalore for the purpose. The inclusion of the vaccine in the national immunization programme will also depend on cost. "International community will have to find ways to make it available cheaply. As a public health programme, it can't be used right now. A global initiative is needed to make it available at affordable price", feels Dr. Bhan.