BREAK THROUGHS IN HEALTH SECTOR
 
Dr. Rajesh S Gokhale, National Institute of Immunology, New Delhi
 
 
 
Resisting Rotaviral diarrhea
 
Rotaviral diarrhoea contributes to 40% of the total dehydrating diarrhoea disease in young children, causing 150,000 deaths per year in India.

The first rotaviral diarrhoea vaccine specific to India has now completed the first phase of human clinical trial. Two candidate vaccines 116E and I1321 were developed under the Indo-US Vaccine Program. 116E was developed by Dr. M K Bhan and Dr.Pratima Ray

(All India Institute of Medical Sciences, New Delhi) & Dr. Nita Bhandari (Society of Applied Studies, New Delhi) in collaboration withDr. Roger I Glass, Center for Disease Control and Prevention, Atlanta, USA. I1321was developed by Dr. C.Durga Rao (Indian Institute of Science, Banglaore) in collaboration with Dr. Harry Greenberg (Stanford University, USA).
 
According to results of recent infant trials both candidate vaccines have been deemed safe and well tolerated. Vaccine take was reported in 74% of the recipients of candidate vaccine 116E wile in case of I1321 the same was 40%. M/s. Bharat Biotech International Ltd., Hyderabad has produced a prototype vaccine of 116E, the most promising candidate under GMP conditions. This will be followed by larger clinical trials. A double-blind, randomized placebo, controlled dose, escalating phase Ib/IIa study has been planned to evaluate the safety and immun-
ogenicity of live attenuated rotavirus vaccine 116E in healthy, non-malnourished infants, 8-20 weeks of age.
 
New pathway for combating Tuberculosis
 

Tuberculosis affects more than one third of the world's population and is a leading cause of morbidity and mortality across the globe. When Mycobacterium tuberculosis infects humans, it takes refuge in immune cells called macrophages. To survive, mycobacterium requires iron for sustenance. As free iron is not readily found in an intra cellular environment, most bacteria manufacture and secrete chemical compounds called siderophores that scavenge iron from the environment. Although siderophores were discovered over fifty years ago, the genes involved in adding the long lipid chain anchor that enables M. tuberculosis to do so more efficiently remained a mystery till now.
Mycobacteria evolve siderophores with lipid-chain tails that enable them to exploit the macrophage's lipid-trafficking system to capture iron more efficiently. Instead of using siderophores that diffuse freely, mycobacteria anchor siderophores to lipid membranes by means of a long fatty acid tail. After these siderophores bind to iron within the macrophage, the lipid tail makes the iron sticky enough to permit delivery to the very compartment in macrophages where the mycobacterium are lurking.

A team led by Dr. Rajesh S Gokhale from the National Institute of Immunology, New Delhi has identified five key genes that enable M.Tuberculosis to acquire the iron it needs for sustaining and promoting infection. They identified the location of four genes that produce the lipid tail. Since the gene required for the synthesis of siderophore core called mbt-1 functions the same way, the new locus and genes were named mbt-2 and mbt K, mbt L, mbt M and mbt N. Targeting these genes is a good strategy for preventing tuberculosis and other mycobacterial infections, because some of these genes are conserved across a number of related bacterial families, and are promising targets for drugs to treat tuberculosis and other bacterial diseases.