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India Finds New Use for an Old Bug

Quietly and without fanfare, Indian scientists have been sequencing the genome of an organism called Mycobacterium-w (Mw). It is India's first sequencing effort of a complete// genome that holds promise in the treatment of several diseases, including tuberculosis and leprosy.

Recent evidence that a vaccine made from killed Mw drastically reduces treatment time of tuberculosis (TB) including the multi-drug resistant (MDR) variety is driving this project more than three decades after the discovery of the bug.

The organism Mw was discovered in late 1970s by a team led by biochemist Gursaran "Pran" Talwar, then head of the biochemistry division at the All India Institute of Medical Sciences (AIIMS) in New Delhi.

"Because we have not sequenced any genome so far, we decided to sequence Mw that was discovered in India," says Syed Hasnain, formerly director of the Centre for DNA Fingerprinting and Diagnostics (CDFD) in Hyderabad, one of the three laboratories involved in the sequencing project.

"The complete sequence will be available in about a month," Hasnain, now vice chancellor of the University of Hyderabad, told IANS. "Our data already suggests there may be surprises to the scientific community. I cannot say more until we publish the work."

Other labs participating in sequencing Mw are those of Akilesh Tyagi and Anil Tyagi in Delhi University.

The infrastructure built up in Delhi University for sequencing the chromosome number 11 of rice, as part of the global rice genome project, is used for cracking the genome of Mw, says Hasnain, who is coordinating the project.

The sequencing of Mw and a large-scale clinical trial with the Mw vaccine are two parts of a study funded by the Department of Biotechnology (DBT).

In the clinical trial being carried out in eight centres around the country, the Mw vaccine is given to tuberculosis patients already on drugs to see if the drug-v accine combination reduced the treatment time. And the results are reported to be amazing.

Hasnain says the ongoing clinical trials aim to find out the ability of the Mw vaccine in treating TB rather than preventing it. The trials are conducted on four categories of TB patients - from uncomplicated to chronic cases - including the hard to treat multi-drug resistant (MDR) cases.

Data from one of the centres shows that four shots of the vaccine at 15 days interval (given in addition to drugs) increase the cure rate to 82 percent even in MDR category. In uncomplicated cases (category 1), patients' sputum becomes completely negative for TB germs after just one shot.

Another important finding is that the vaccine induced sputum conversion after a single shot in 48 out of 50 AIDS patients suffering from tuberculosis.

According to Talwar, introducing the Mw vaccine for tuberculosis control programme should not face problems in India from regulatory angle because it is an already approved vaccine for leprosy and is commercially manufactured by Cadila Pharmaceuticals in Ahmedabad.

Talwar's group at AIIMS found the Mw organism among the collections in a tuberculosis hospital in Madras, now Chennai. The fact that it was a fast growing harmless organism that shared many of its antigens with M.leprae -- the organism that causes leprosy - led Talwar and his colleagues to use the organism for developing an anti-leprosy vaccine in 1981.

Ten years later the Indian health ministry launched a trial of the vaccine on a leprosy endemic population of 420,000 in Uttar Pradesh.

Although it was a leprosy vaccine trial, the last survey in 2001 sprang a surprise: the number of new TB cases in vaccinated group was less than half of that in the unvaccinated control group.

This unexpected observation prompted the DBT and the Indian Council of Medical Research to take a fresh look at Mw and the vacc ine's potential use against TB.

If the ongoing clinical trials turn out to be successful, Mw vaccine could emerge as an alternative to the currently used BCG vaccine, Talwar believes.

"One great advantage with Mw vaccine," he says, "is that it is made from killed organisms unlike the BCG vaccine that uses inactivated but live organisms."

While the BCG vaccine is used to immunize only infants, the Mw vaccine can be used in adults also, according to Talwar.


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